Islet Product Characteristics and Factors Related to Successful Human Islet Transplantation From the Collaborative Islet Transplant Registry (CITR) 1999–2010
Identifieur interne : 002234 ( Pmc/Corpus ); précédent : 002233; suivant : 002235Islet Product Characteristics and Factors Related to Successful Human Islet Transplantation From the Collaborative Islet Transplant Registry (CITR) 1999–2010
Auteurs : A N Balamurugan ; B. Naziruddin ; A. Lockridge ; M. Tiwari ; G. Loganathan ; M. Takita ; S. Matsumoto ; K. Papas ; M. Trieger ; H. Rainis ; T. Kin ; T W Kay ; S. Wease ; S. Messinger ; C. Ricordi ; R. Alejandro ; J. Markmann ; J. Kerr-Conti ; M R Rickels ; C. Liu ; X. Zhang ; P. Witkowski ; A. Posselt ; P. Maffi ; A. Secchi ; T. Berney ; P J O Onnell ; B J Hering ; F B BartonSource :
- American Journal of Transplantation [ 1600-6135 ] ; 2014.
Abstract
The Collaborative Islet Transplant Registry (CITR) collects data on clinical islet isolations and transplants. This retrospective report analyzed 1017 islet isolation procedures performed for 537 recipients of allogeneic clinical islet transplantation in 1999–2010. This study describes changes in donor and islet isolation variables by era and factors associated with quantity and quality of final islet products. Donor body weight and BMI increased significantly over the period (p < 0.001). Islet yield measures have improved with time including islet equivalent (IEQ)/particle ratio and IEQs infused. The average dose of islets infused significantly increased in the era of 2007–2010 when compared to 1999–2002 (445.4 ± 156.8 vs. 421.3 ± 155.4 ×103 IEQ; p < 0.05). Islet purity and total number of β cells significantly improved over the study period (p < 0.01 and <0.05, respectively). Otherwise, the quality of clinical islets has remained consistently very high through this period, and differs substantially from nonclinical islets. In multivariate analysis of all recipient, donor and islet factors, and medical management factors, the only islet product characteristic that correlated with clinical outcomes was total IEQs infused. This analysis shows improvements in both quantity and some quality criteria of clinical islets produced over 1999–2010, and these parallel improvements in clinical outcomes over the same period.
Url:
DOI: 10.1111/ajt.12872
PubMed: 25278159
PubMed Central: 4282081
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PMC:4282081Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Islet Product Characteristics and Factors Related to Successful Human Islet Transplantation From the Collaborative Islet Transplant Registry (CITR) 1999–2010</title>
<author><name sortKey="Balamurugan, A N" sort="Balamurugan, A N" uniqKey="Balamurugan A" first="A N" last="Balamurugan">A N Balamurugan</name>
<affiliation><nlm:aff id="au1"><institution>Schulze Diabetes Institute, Department of Surgery, University of Minnesota</institution>
<addr-line>Minneapolis, MN</addr-line>
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<author><name sortKey="Naziruddin, B" sort="Naziruddin, B" uniqKey="Naziruddin B" first="B" last="Naziruddin">B. Naziruddin</name>
<affiliation><nlm:aff id="au2"><institution>Baylor Annette C. and Harold C. Simmons Transplant Institute</institution>
<addr-line>Dallas, TX</addr-line>
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<author><name sortKey="Lockridge, A" sort="Lockridge, A" uniqKey="Lockridge A" first="A" last="Lockridge">A. Lockridge</name>
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<author><name sortKey="Tiwari, M" sort="Tiwari, M" uniqKey="Tiwari M" first="M" last="Tiwari">M. Tiwari</name>
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<author><name sortKey="Loganathan, G" sort="Loganathan, G" uniqKey="Loganathan G" first="G" last="Loganathan">G. Loganathan</name>
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<author><name sortKey="Takita, M" sort="Takita, M" uniqKey="Takita M" first="M" last="Takita">M. Takita</name>
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<author><name sortKey="Matsumoto, S" sort="Matsumoto, S" uniqKey="Matsumoto S" first="S" last="Matsumoto">S. Matsumoto</name>
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<author><name sortKey="Papas, K" sort="Papas, K" uniqKey="Papas K" first="K" last="Papas">K. Papas</name>
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<author><name sortKey="Trieger, M" sort="Trieger, M" uniqKey="Trieger M" first="M" last="Trieger">M. Trieger</name>
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<addr-line>Rockville, MD</addr-line>
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<author><name sortKey="Rainis, H" sort="Rainis, H" uniqKey="Rainis H" first="H" last="Rainis">H. Rainis</name>
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<author><name sortKey="Kin, T" sort="Kin, T" uniqKey="Kin T" first="T" last="Kin">T. Kin</name>
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<author><name sortKey="Kay, T W" sort="Kay, T W" uniqKey="Kay T" first="T W" last="Kay">T W Kay</name>
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<author><name sortKey="Wease, S" sort="Wease, S" uniqKey="Wease S" first="S" last="Wease">S. Wease</name>
<affiliation><nlm:aff id="au5"><institution>The EMMES Corporation</institution>
<addr-line>Rockville, MD</addr-line>
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<author><name sortKey="Messinger, S" sort="Messinger, S" uniqKey="Messinger S" first="S" last="Messinger">S. Messinger</name>
<affiliation><nlm:aff id="au8"><institution>Department of Public Health Services, University of Miami</institution>
<addr-line>Miami, FL</addr-line>
</nlm:aff>
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<author><name sortKey="Ricordi, C" sort="Ricordi, C" uniqKey="Ricordi C" first="C" last="Ricordi">C. Ricordi</name>
<affiliation><nlm:aff id="au9"><institution>Diabetes Research Institute, University of Miami</institution>
<addr-line>Miami, FL</addr-line>
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<author><name sortKey="Alejandro, R" sort="Alejandro, R" uniqKey="Alejandro R" first="R" last="Alejandro">R. Alejandro</name>
<affiliation><nlm:aff id="au9"><institution>Diabetes Research Institute, University of Miami</institution>
<addr-line>Miami, FL</addr-line>
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<author><name sortKey="Markmann, J" sort="Markmann, J" uniqKey="Markmann J" first="J" last="Markmann">J. Markmann</name>
<affiliation><nlm:aff id="au10"><institution>Department of Surgery, Massachusetts General Hospital</institution>
<addr-line>Boston, MA</addr-line>
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<author><name sortKey="Kerr Conti, J" sort="Kerr Conti, J" uniqKey="Kerr Conti J" first="J" last="Kerr-Conti">J. Kerr-Conti</name>
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<addr-line>Lille, France</addr-line>
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<author><name sortKey="Rickels, M R" sort="Rickels, M R" uniqKey="Rickels M" first="M R" last="Rickels">M R Rickels</name>
<affiliation><nlm:aff id="au12"><institution>Department of Medicine, University of Pennsylvania</institution>
<addr-line>Philadelphia, PA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liu, C" sort="Liu, C" uniqKey="Liu C" first="C" last="Liu">C. Liu</name>
<affiliation><nlm:aff id="au13"><institution>Department of Surgery, University of Pennsylvania</institution>
<addr-line>Philadelphia, PA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhang, X" sort="Zhang, X" uniqKey="Zhang X" first="X" last="Zhang">X. Zhang</name>
<affiliation><nlm:aff id="au14"><institution>Feinberg School of Medicine, Northwestern University</institution>
<addr-line>Chicago, IL</addr-line>
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<author><name sortKey="Witkowski, P" sort="Witkowski, P" uniqKey="Witkowski P" first="P" last="Witkowski">P. Witkowski</name>
<affiliation><nlm:aff id="au15"><institution>Department of Surgery, University of Chicago</institution>
<addr-line>Chicago, IL</addr-line>
</nlm:aff>
</affiliation>
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<author><name sortKey="Posselt, A" sort="Posselt, A" uniqKey="Posselt A" first="A" last="Posselt">A. Posselt</name>
<affiliation><nlm:aff id="au16"><institution>Department of Surgery, University of California, San Francisco</institution>
<addr-line>San Francisco, CA</addr-line>
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<author><name sortKey="Maffi, P" sort="Maffi, P" uniqKey="Maffi P" first="P" last="Maffi">P. Maffi</name>
<affiliation><nlm:aff id="au17"><institution>Vita-Salute, San Raffaele University</institution>
<addr-line>Milan, Italy</addr-line>
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<author><name sortKey="Secchi, A" sort="Secchi, A" uniqKey="Secchi A" first="A" last="Secchi">A. Secchi</name>
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<addr-line>Milan, Italy</addr-line>
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<author><name sortKey="Berney, T" sort="Berney, T" uniqKey="Berney T" first="T" last="Berney">T. Berney</name>
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<addr-line>Geneva, Switzerland</addr-line>
</nlm:aff>
</affiliation>
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<author><name sortKey="O Onnell, P J" sort="O Onnell, P J" uniqKey="O Onnell P" first="P J" last="O Onnell">P J O Onnell</name>
<affiliation><nlm:aff id="au19"><institution>National Pancreas Transplant Unit, University of Sydney at Westmead Hospital</institution>
<addr-line>Sydney, Australia</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hering, B J" sort="Hering, B J" uniqKey="Hering B" first="B J" last="Hering">B J Hering</name>
<affiliation><nlm:aff id="au1"><institution>Schulze Diabetes Institute, Department of Surgery, University of Minnesota</institution>
<addr-line>Minneapolis, MN</addr-line>
</nlm:aff>
</affiliation>
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<author><name sortKey="Barton, F B" sort="Barton, F B" uniqKey="Barton F" first="F B" last="Barton">F B Barton</name>
<affiliation><nlm:aff id="au5"><institution>The EMMES Corporation</institution>
<addr-line>Rockville, MD</addr-line>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Islet Product Characteristics and Factors Related to Successful Human Islet Transplantation From the Collaborative Islet Transplant Registry (CITR) 1999–2010</title>
<author><name sortKey="Balamurugan, A N" sort="Balamurugan, A N" uniqKey="Balamurugan A" first="A N" last="Balamurugan">A N Balamurugan</name>
<affiliation><nlm:aff id="au1"><institution>Schulze Diabetes Institute, Department of Surgery, University of Minnesota</institution>
<addr-line>Minneapolis, MN</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Naziruddin, B" sort="Naziruddin, B" uniqKey="Naziruddin B" first="B" last="Naziruddin">B. Naziruddin</name>
<affiliation><nlm:aff id="au2"><institution>Baylor Annette C. and Harold C. Simmons Transplant Institute</institution>
<addr-line>Dallas, TX</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lockridge, A" sort="Lockridge, A" uniqKey="Lockridge A" first="A" last="Lockridge">A. Lockridge</name>
<affiliation><nlm:aff id="au1"><institution>Schulze Diabetes Institute, Department of Surgery, University of Minnesota</institution>
<addr-line>Minneapolis, MN</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tiwari, M" sort="Tiwari, M" uniqKey="Tiwari M" first="M" last="Tiwari">M. Tiwari</name>
<affiliation><nlm:aff id="au1"><institution>Schulze Diabetes Institute, Department of Surgery, University of Minnesota</institution>
<addr-line>Minneapolis, MN</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Loganathan, G" sort="Loganathan, G" uniqKey="Loganathan G" first="G" last="Loganathan">G. Loganathan</name>
<affiliation><nlm:aff id="au1"><institution>Schulze Diabetes Institute, Department of Surgery, University of Minnesota</institution>
<addr-line>Minneapolis, MN</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Takita, M" sort="Takita, M" uniqKey="Takita M" first="M" last="Takita">M. Takita</name>
<affiliation><nlm:aff id="au2"><institution>Baylor Annette C. and Harold C. Simmons Transplant Institute</institution>
<addr-line>Dallas, TX</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Matsumoto, S" sort="Matsumoto, S" uniqKey="Matsumoto S" first="S" last="Matsumoto">S. Matsumoto</name>
<affiliation><nlm:aff id="au3"><institution>Research and Development Center, Otsuka Pharmaceutical Factory, Inc.</institution>
<addr-line>Tokushima, Japan</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Papas, K" sort="Papas, K" uniqKey="Papas K" first="K" last="Papas">K. Papas</name>
<affiliation><nlm:aff id="au4"><institution>Institute for Cellular Transplantation, University of Arizona</institution>
<addr-line>Tucson, AZ</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Trieger, M" sort="Trieger, M" uniqKey="Trieger M" first="M" last="Trieger">M. Trieger</name>
<affiliation><nlm:aff id="au5"><institution>The EMMES Corporation</institution>
<addr-line>Rockville, MD</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rainis, H" sort="Rainis, H" uniqKey="Rainis H" first="H" last="Rainis">H. Rainis</name>
<affiliation><nlm:aff id="au5"><institution>The EMMES Corporation</institution>
<addr-line>Rockville, MD</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kin, T" sort="Kin, T" uniqKey="Kin T" first="T" last="Kin">T. Kin</name>
<affiliation><nlm:aff id="au6"><institution>Clinical Islet Laboratory, University of Alberta</institution>
<addr-line>Edmonton, AB</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kay, T W" sort="Kay, T W" uniqKey="Kay T" first="T W" last="Kay">T W Kay</name>
<affiliation><nlm:aff id="au7"><institution>St. Vincent's Hospital</institution>
<addr-line>Melbourne, Australia</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wease, S" sort="Wease, S" uniqKey="Wease S" first="S" last="Wease">S. Wease</name>
<affiliation><nlm:aff id="au5"><institution>The EMMES Corporation</institution>
<addr-line>Rockville, MD</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Messinger, S" sort="Messinger, S" uniqKey="Messinger S" first="S" last="Messinger">S. Messinger</name>
<affiliation><nlm:aff id="au8"><institution>Department of Public Health Services, University of Miami</institution>
<addr-line>Miami, FL</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ricordi, C" sort="Ricordi, C" uniqKey="Ricordi C" first="C" last="Ricordi">C. Ricordi</name>
<affiliation><nlm:aff id="au9"><institution>Diabetes Research Institute, University of Miami</institution>
<addr-line>Miami, FL</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Alejandro, R" sort="Alejandro, R" uniqKey="Alejandro R" first="R" last="Alejandro">R. Alejandro</name>
<affiliation><nlm:aff id="au9"><institution>Diabetes Research Institute, University of Miami</institution>
<addr-line>Miami, FL</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Markmann, J" sort="Markmann, J" uniqKey="Markmann J" first="J" last="Markmann">J. Markmann</name>
<affiliation><nlm:aff id="au10"><institution>Department of Surgery, Massachusetts General Hospital</institution>
<addr-line>Boston, MA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kerr Conti, J" sort="Kerr Conti, J" uniqKey="Kerr Conti J" first="J" last="Kerr-Conti">J. Kerr-Conti</name>
<affiliation><nlm:aff id="au11"><institution>Lille University Hospital</institution>
<addr-line>Lille, France</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rickels, M R" sort="Rickels, M R" uniqKey="Rickels M" first="M R" last="Rickels">M R Rickels</name>
<affiliation><nlm:aff id="au12"><institution>Department of Medicine, University of Pennsylvania</institution>
<addr-line>Philadelphia, PA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liu, C" sort="Liu, C" uniqKey="Liu C" first="C" last="Liu">C. Liu</name>
<affiliation><nlm:aff id="au13"><institution>Department of Surgery, University of Pennsylvania</institution>
<addr-line>Philadelphia, PA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhang, X" sort="Zhang, X" uniqKey="Zhang X" first="X" last="Zhang">X. Zhang</name>
<affiliation><nlm:aff id="au14"><institution>Feinberg School of Medicine, Northwestern University</institution>
<addr-line>Chicago, IL</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Witkowski, P" sort="Witkowski, P" uniqKey="Witkowski P" first="P" last="Witkowski">P. Witkowski</name>
<affiliation><nlm:aff id="au15"><institution>Department of Surgery, University of Chicago</institution>
<addr-line>Chicago, IL</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Posselt, A" sort="Posselt, A" uniqKey="Posselt A" first="A" last="Posselt">A. Posselt</name>
<affiliation><nlm:aff id="au16"><institution>Department of Surgery, University of California, San Francisco</institution>
<addr-line>San Francisco, CA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Maffi, P" sort="Maffi, P" uniqKey="Maffi P" first="P" last="Maffi">P. Maffi</name>
<affiliation><nlm:aff id="au17"><institution>Vita-Salute, San Raffaele University</institution>
<addr-line>Milan, Italy</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Secchi, A" sort="Secchi, A" uniqKey="Secchi A" first="A" last="Secchi">A. Secchi</name>
<affiliation><nlm:aff id="au17"><institution>Vita-Salute, San Raffaele University</institution>
<addr-line>Milan, Italy</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Berney, T" sort="Berney, T" uniqKey="Berney T" first="T" last="Berney">T. Berney</name>
<affiliation><nlm:aff id="au18"><institution>Department of Surgery, Geneva University Hospital</institution>
<addr-line>Geneva, Switzerland</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="O Onnell, P J" sort="O Onnell, P J" uniqKey="O Onnell P" first="P J" last="O Onnell">P J O Onnell</name>
<affiliation><nlm:aff id="au19"><institution>National Pancreas Transplant Unit, University of Sydney at Westmead Hospital</institution>
<addr-line>Sydney, Australia</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hering, B J" sort="Hering, B J" uniqKey="Hering B" first="B J" last="Hering">B J Hering</name>
<affiliation><nlm:aff id="au1"><institution>Schulze Diabetes Institute, Department of Surgery, University of Minnesota</institution>
<addr-line>Minneapolis, MN</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Barton, F B" sort="Barton, F B" uniqKey="Barton F" first="F B" last="Barton">F B Barton</name>
<affiliation><nlm:aff id="au5"><institution>The EMMES Corporation</institution>
<addr-line>Rockville, MD</addr-line>
</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">American Journal of Transplantation</title>
<idno type="ISSN">1600-6135</idno>
<idno type="eISSN">1600-6143</idno>
<imprint><date when="2014">2014</date>
</imprint>
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<front><div type="abstract" xml:lang="en"><p>The Collaborative Islet Transplant Registry (CITR) collects data on clinical islet isolations and transplants. This retrospective report analyzed 1017 islet isolation procedures performed for 537 recipients of allogeneic clinical islet transplantation in 1999–2010. This study describes changes in donor and islet isolation variables by era and factors associated with quantity and quality of final islet products. Donor body weight and BMI increased significantly over the period (p < 0.001). Islet yield measures have improved with time including islet equivalent (IEQ)/particle ratio and IEQs infused. The average dose of islets infused significantly increased in the era of 2007–2010 when compared to 1999–2002 (445.4 ± 156.8 vs. 421.3 ± 155.4 ×10<sup>3</sup>
IEQ; p < 0.05). Islet purity and total number of β cells significantly improved over the study period (p < 0.01 and <0.05, respectively). Otherwise, the quality of clinical islets has remained consistently very high through this period, and differs substantially from nonclinical islets. In multivariate analysis of all recipient, donor and islet factors, and medical management factors, the only islet product characteristic that correlated with clinical outcomes was total IEQs infused. This analysis shows improvements in both quantity and some quality criteria of clinical islets produced over 1999–2010, and these parallel improvements in clinical outcomes over the same period.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Brandhorst, H" uniqKey="Brandhorst H">H Brandhorst</name>
</author>
<author><name sortKey="Brandhorst, D" uniqKey="Brandhorst D">D Brandhorst</name>
</author>
<author><name sortKey="Hering, Bj" uniqKey="Hering B">BJ Hering</name>
</author>
<author><name sortKey="Federlin, K" uniqKey="Federlin K">K Federlin</name>
</author>
<author><name sortKey="Bretzel, Rg" uniqKey="Bretzel R">RG Bretzel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lakey, Jr" uniqKey="Lakey J">JR Lakey</name>
</author>
<author><name sortKey="Warnock, Gl" uniqKey="Warnock G">GL Warnock</name>
</author>
<author><name sortKey="Rajotte, Rv" uniqKey="Rajotte R">RV Rajotte</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Goto, M" uniqKey="Goto M">M Goto</name>
</author>
<author><name sortKey="Johansson, U" uniqKey="Johansson U">U Johansson</name>
</author>
<author><name sortKey="Eich, Tm" uniqKey="Eich T">TM Eich</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nano, R" uniqKey="Nano R">R Nano</name>
</author>
<author><name sortKey="Clissi, B" uniqKey="Clissi B">B Clissi</name>
</author>
<author><name sortKey="Melzi, R" uniqKey="Melzi R">R Melzi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kim, Sc" uniqKey="Kim S">SC Kim</name>
</author>
<author><name sortKey="Han, Dj" uniqKey="Han D">DJ Han</name>
</author>
<author><name sortKey="Kang, Ch" uniqKey="Kang C">CH Kang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="O Gorman, D" uniqKey="O Gorman D">D O'Gorman</name>
</author>
<author><name sortKey="Kin, T" uniqKey="Kin T">T Kin</name>
</author>
<author><name sortKey="Murdoch, T" uniqKey="Murdoch T">T Murdoch</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ponte, Gm" uniqKey="Ponte G">GM Ponte</name>
</author>
<author><name sortKey="Pileggi, A" uniqKey="Pileggi A">A Pileggi</name>
</author>
<author><name sortKey="Messinger, S" uniqKey="Messinger S">S Messinger</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Koh, A" uniqKey="Koh A">A Koh</name>
</author>
<author><name sortKey="Kin, T" uniqKey="Kin T">T Kin</name>
</author>
<author><name sortKey="Imes, S" uniqKey="Imes S">S Imes</name>
</author>
<author><name sortKey="Shapiro, Am" uniqKey="Shapiro A">AM Shapiro</name>
</author>
<author><name sortKey="Senior, P" uniqKey="Senior P">P Senior</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liu, X" uniqKey="Liu X">X Liu</name>
</author>
<author><name sortKey="Matsumoto, S" uniqKey="Matsumoto S">S Matsumoto</name>
</author>
<author><name sortKey="Okitsu, T" uniqKey="Okitsu T">T Okitsu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Niclauss, N" uniqKey="Niclauss N">N Niclauss</name>
</author>
<author><name sortKey="Bosco, D" uniqKey="Bosco D">D Bosco</name>
</author>
<author><name sortKey="Morel, P" uniqKey="Morel P">P Morel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name>
</author>
<author><name sortKey="Daneilson, Kk" uniqKey="Daneilson K">KK Daneilson</name>
</author>
<author><name sortKey="Ropski, A" uniqKey="Ropski A">A Ropski</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hilling, De" uniqKey="Hilling D">DE Hilling</name>
</author>
<author><name sortKey="Bouwman, E" uniqKey="Bouwman E">E Bouwman</name>
</author>
<author><name sortKey="Terpstra, Ot" uniqKey="Terpstra O">OT Terpstra</name>
</author>
<author><name sortKey="Marang Van De Mheen, Pj" uniqKey="Marang Van De Mheen P">PJ Marang-van de Mheen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kaddis, Js" uniqKey="Kaddis J">JS Kaddis</name>
</author>
<author><name sortKey="Danobeitia, Js" uniqKey="Danobeitia J">JS Danobeitia</name>
</author>
<author><name sortKey="Niland, Jc" uniqKey="Niland J">JC Niland</name>
</author>
<author><name sortKey="Stiller, T" uniqKey="Stiller T">T Stiller</name>
</author>
<author><name sortKey="Fernandez, La" uniqKey="Fernandez L">LA Fernandez</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Barton, Fb" uniqKey="Barton F">FB Barton</name>
</author>
<author><name sortKey="Rickels, Mr" uniqKey="Rickels M">MR Rickels</name>
</author>
<author><name sortKey="Alejandro, R" uniqKey="Alejandro R">R Alejandro</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Center, Cc" uniqKey="Center C">CC Center</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sabek, Om" uniqKey="Sabek O">OM Sabek</name>
</author>
<author><name sortKey="Cowan, P" uniqKey="Cowan P">P Cowan</name>
</author>
<author><name sortKey="Fraga, Dw" uniqKey="Fraga D">DW Fraga</name>
</author>
<author><name sortKey="Gaber, Ao" uniqKey="Gaber A">AO Gaber</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Socci, C" uniqKey="Socci C">C Socci</name>
</author>
<author><name sortKey="Davalli, Am" uniqKey="Davalli A">AM Davalli</name>
</author>
<author><name sortKey="Vignali, A" uniqKey="Vignali A">A Vignali</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ricordi, C" uniqKey="Ricordi C">C Ricordi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Movassat, J" uniqKey="Movassat J">J Movassat</name>
</author>
<author><name sortKey="Saulnier, C" uniqKey="Saulnier C">C Saulnier</name>
</author>
<author><name sortKey="Portha, B" uniqKey="Portha B">B Portha</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kitamura, T" uniqKey="Kitamura T">T Kitamura</name>
</author>
<author><name sortKey="Nakae, J" uniqKey="Nakae J">J Nakae</name>
</author>
<author><name sortKey="Kitamura, Y" uniqKey="Kitamura Y">Y Kitamura</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kuroda, Y" uniqKey="Kuroda Y">Y Kuroda</name>
</author>
<author><name sortKey="Kawamura, T" uniqKey="Kawamura T">T Kawamura</name>
</author>
<author><name sortKey="Suzuki, Y" uniqKey="Suzuki Y">Y Suzuki</name>
</author>
<author><name sortKey="Fujiwara, H" uniqKey="Fujiwara H">H Fujiwara</name>
</author>
<author><name sortKey="Yamamoto, K" uniqKey="Yamamoto K">K Yamamoto</name>
</author>
<author><name sortKey="Saitoh, Y" uniqKey="Saitoh Y">Y Saitoh</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tanioka, Y" uniqKey="Tanioka Y">Y Tanioka</name>
</author>
<author><name sortKey="Sutherland, De" uniqKey="Sutherland D">DE Sutherland</name>
</author>
<author><name sortKey="Kuroda, Y" uniqKey="Kuroda Y">Y Kuroda</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Matsumoto, S" uniqKey="Matsumoto S">S Matsumoto</name>
</author>
<author><name sortKey="Rigley, Th" uniqKey="Rigley T">TH Rigley</name>
</author>
<author><name sortKey="Qualley, Sa" uniqKey="Qualley S">SA Qualley</name>
</author>
<author><name sortKey="Kuroda, Y" uniqKey="Kuroda Y">Y Kuroda</name>
</author>
<author><name sortKey="Reems, Ja" uniqKey="Reems J">JA Reems</name>
</author>
<author><name sortKey="Stevens, Rb" uniqKey="Stevens R">RB Stevens</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Papas, Kk" uniqKey="Papas K">KK Papas</name>
</author>
<author><name sortKey="Colton, Ck" uniqKey="Colton C">CK Colton</name>
</author>
<author><name sortKey="Nelson, Ra" uniqKey="Nelson R">RA Nelson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Noguchi, H" uniqKey="Noguchi H">H Noguchi</name>
</author>
<author><name sortKey="Ueda, M" uniqKey="Ueda M">M Ueda</name>
</author>
<author><name sortKey="Hayashi, S" uniqKey="Hayashi S">S Hayashi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Matsumoto, S" uniqKey="Matsumoto S">S Matsumoto</name>
</author>
<author><name sortKey="Noguchi, H" uniqKey="Noguchi H">H Noguchi</name>
</author>
<author><name sortKey="Hatanaka, N" uniqKey="Hatanaka N">N Hatanaka</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kin, T" uniqKey="Kin T">T Kin</name>
</author>
<author><name sortKey="Mirbolooki, M" uniqKey="Mirbolooki M">M Mirbolooki</name>
</author>
<author><name sortKey="Salehi, P" uniqKey="Salehi P">P Salehi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Caballero Corbalan, J" uniqKey="Caballero Corbalan J">J Caballero-Corbalán</name>
</author>
<author><name sortKey="Eich, T" uniqKey="Eich T">T Eich</name>
</author>
<author><name sortKey="Lundgren, T" uniqKey="Lundgren T">T Lundgren</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Qin, H" uniqKey="Qin H">H Qin</name>
</author>
<author><name sortKey="Matsumoto, S" uniqKey="Matsumoto S">S Matsumoto</name>
</author>
<author><name sortKey="Klintmalm, Gb" uniqKey="Klintmalm G">GB Klintmalm</name>
</author>
<author><name sortKey="De Vol, Eb" uniqKey="De Vol E">EB De Vol</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kin, T" uniqKey="Kin T">T Kin</name>
</author>
<author><name sortKey="Senior, P" uniqKey="Senior P">P Senior</name>
</author>
<author><name sortKey="O Gorman, D" uniqKey="O Gorman D">D O'Gorman</name>
</author>
<author><name sortKey="Richer, B" uniqKey="Richer B">B Richer</name>
</author>
<author><name sortKey="Salam, A" uniqKey="Salam A">A Salam</name>
</author>
<author><name sortKey="Shapiro, Am" uniqKey="Shapiro A">AM Shapiro</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Salehi, P" uniqKey="Salehi P">P Salehi</name>
</author>
<author><name sortKey="Hansen, Ma" uniqKey="Hansen M">MA Hansen</name>
</author>
<author><name sortKey="Avila, Jg" uniqKey="Avila J">JG Avila</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stewart, Za" uniqKey="Stewart Z">ZA Stewart</name>
</author>
<author><name sortKey="Cameron, Am" uniqKey="Cameron A">AM Cameron</name>
</author>
<author><name sortKey="Singer, Al" uniqKey="Singer A">AL Singer</name>
</author>
<author><name sortKey="Dagher, Nn" uniqKey="Dagher N">NN Dagher</name>
</author>
<author><name sortKey="Montgomery, Ra" uniqKey="Montgomery R">RA Montgomery</name>
</author>
<author><name sortKey="Segev, Dl" uniqKey="Segev D">DL Segev</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gaber, Ao" uniqKey="Gaber A">AO Gaber</name>
</author>
<author><name sortKey="Fraga, Dw" uniqKey="Fraga D">DW Fraga</name>
</author>
<author><name sortKey="Callicutt, Cs" uniqKey="Callicutt C">CS Callicutt</name>
</author>
<author><name sortKey="Gerling, Ic" uniqKey="Gerling I">IC Gerling</name>
</author>
<author><name sortKey="Sabek, Om" uniqKey="Sabek O">OM Sabek</name>
</author>
<author><name sortKey="Kotb, My" uniqKey="Kotb M">MY Kotb</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Noguchi, H" uniqKey="Noguchi H">H Noguchi</name>
</author>
<author><name sortKey="Naziruddin, B" uniqKey="Naziruddin B">B Naziruddin</name>
</author>
<author><name sortKey="Jackson, A" uniqKey="Jackson A">A Jackson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kedinger, M" uniqKey="Kedinger M">M Kedinger</name>
</author>
<author><name sortKey="Haffen, K" uniqKey="Haffen K">K Haffen</name>
</author>
<author><name sortKey="Grenier, J" uniqKey="Grenier J">J Grenier</name>
</author>
<author><name sortKey="Eloy, R" uniqKey="Eloy R">R Eloy</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lacy, Pe" uniqKey="Lacy P">PE Lacy</name>
</author>
<author><name sortKey="Davie, Jm" uniqKey="Davie J">JM Davie</name>
</author>
<author><name sortKey="Finke, Eh" uniqKey="Finke E">EH Finke</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lafferty, Kj" uniqKey="Lafferty K">KJ Lafferty</name>
</author>
<author><name sortKey="Prowse, Sj" uniqKey="Prowse S">SJ Prowse</name>
</author>
<author><name sortKey="Simeonovic, Cj" uniqKey="Simeonovic C">CJ Simeonovic</name>
</author>
<author><name sortKey="Warren, Hs" uniqKey="Warren H">HS Warren</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cosimi, S" uniqKey="Cosimi S">S Cosimi</name>
</author>
<author><name sortKey="Marchetti, P" uniqKey="Marchetti P">P Marchetti</name>
</author>
<author><name sortKey="Giannarelli, R" uniqKey="Giannarelli R">R Giannarelli</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Markmann, Jf" uniqKey="Markmann J">JF Markmann</name>
</author>
<author><name sortKey="Tomaszewski, J" uniqKey="Tomaszewski J">J Tomaszewski</name>
</author>
<author><name sortKey="Posselt, Am" uniqKey="Posselt A">AM Posselt</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Brendel, Md" uniqKey="Brendel M">MD Brendel</name>
</author>
<author><name sortKey="Kong, Ss" uniqKey="Kong S">SS Kong</name>
</author>
<author><name sortKey="Alejandro, R" uniqKey="Alejandro R">R Alejandro</name>
</author>
<author><name sortKey="Mintz, Dh" uniqKey="Mintz D">DH Mintz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Korbutt, Gs" uniqKey="Korbutt G">GS Korbutt</name>
</author>
<author><name sortKey="Pipeleers, Dg" uniqKey="Pipeleers D">DG Pipeleers</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fraker, Ca" uniqKey="Fraker C">CA Fraker</name>
</author>
<author><name sortKey="Cechin, S" uniqKey="Cechin S">S Cechin</name>
</author>
<author><name sortKey="Alvarez Cubela, S" uniqKey="Alvarez Cubela S">S Alvarez-Cubela</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bucher, P" uniqKey="Bucher P">P Bucher</name>
</author>
<author><name sortKey="Mathe, Z" uniqKey="Mathe Z">Z Mathe</name>
</author>
<author><name sortKey="Bosco, D" uniqKey="Bosco D">D Bosco</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Brandhorst, H" uniqKey="Brandhorst H">H Brandhorst</name>
</author>
<author><name sortKey="Friberg, A" uniqKey="Friberg A">A Friberg</name>
</author>
<author><name sortKey="Nilsson, B" uniqKey="Nilsson B">B Nilsson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Iglesias, I" uniqKey="Iglesias I">I Iglesias</name>
</author>
<author><name sortKey="Valiente, L" uniqKey="Valiente L">L Valiente</name>
</author>
<author><name sortKey="Shiang, Kd" uniqKey="Shiang K">KD Shiang</name>
</author>
<author><name sortKey="Ichii, H" uniqKey="Ichii H">H Ichii</name>
</author>
<author><name sortKey="Kandeel, F" uniqKey="Kandeel F">F Kandeel</name>
</author>
<author><name sortKey="Al Abdullah, Ih" uniqKey="Al Abdullah I">IH Al-Abdullah</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Balamurugan, An" uniqKey="Balamurugan A">AN Balamurugan</name>
</author>
<author><name sortKey="He, J" uniqKey="He J">J He</name>
</author>
<author><name sortKey="Guo, F" uniqKey="Guo F">F Guo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Balamurugan, An" uniqKey="Balamurugan A">AN Balamurugan</name>
</author>
<author><name sortKey="Breite, Ag" uniqKey="Breite A">AG Breite</name>
</author>
<author><name sortKey="Anazawa, T" uniqKey="Anazawa T">T Anazawa</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Balamurugan, An" uniqKey="Balamurugan A">AN Balamurugan</name>
</author>
<author><name sortKey="Loganathan, G" uniqKey="Loganathan G">G Loganathan</name>
</author>
<author><name sortKey="Bellin, Md" uniqKey="Bellin M">MD Bellin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Robertson, Gs" uniqKey="Robertson G">GS Robertson</name>
</author>
<author><name sortKey="Chadwick, Dr" uniqKey="Chadwick D">DR Chadwick</name>
</author>
<author><name sortKey="Contractor, H" uniqKey="Contractor H">H Contractor</name>
</author>
<author><name sortKey="James, Rf" uniqKey="James R">RF James</name>
</author>
<author><name sortKey="London, Nj" uniqKey="London N">NJ London</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wei, Gh" uniqKey="Wei G">GH Wei</name>
</author>
<author><name sortKey="Sun, Wp" uniqKey="Sun W">WP Sun</name>
</author>
<author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Webb, Ma" uniqKey="Webb M">MA Webb</name>
</author>
<author><name sortKey="Dennison, Ar" uniqKey="Dennison A">AR Dennison</name>
</author>
<author><name sortKey="James, Rf" uniqKey="James R">RF James</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kaddis, Js" uniqKey="Kaddis J">JS Kaddis</name>
</author>
<author><name sortKey="Olack, Bj" uniqKey="Olack B">BJ Olack</name>
</author>
<author><name sortKey="Sowinski, J" uniqKey="Sowinski J">J Sowinski</name>
</author>
<author><name sortKey="Cravens, J" uniqKey="Cravens J">J Cravens</name>
</author>
<author><name sortKey="Contreras, Jl" uniqKey="Contreras J">JL Contreras</name>
</author>
<author><name sortKey="Niland, Jc" uniqKey="Niland J">JC Niland</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shimoda, M" uniqKey="Shimoda M">M Shimoda</name>
</author>
<author><name sortKey="Itoh, T" uniqKey="Itoh T">T Itoh</name>
</author>
<author><name sortKey="Sugimoto, K" uniqKey="Sugimoto K">K Sugimoto</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Friberg, As" uniqKey="Friberg A">AS Friberg</name>
</author>
<author><name sortKey="Korsgren, O" uniqKey="Korsgren O">O Korsgren</name>
</author>
<author><name sortKey="Hellgren, M" uniqKey="Hellgren M">M Hellgren</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="O Gorman, D" uniqKey="O Gorman D">D O'Gorman</name>
</author>
<author><name sortKey="Kin, T" uniqKey="Kin T">T Kin</name>
</author>
<author><name sortKey="Pawlick, R" uniqKey="Pawlick R">R Pawlick</name>
</author>
<author><name sortKey="Imes, S" uniqKey="Imes S">S Imes</name>
</author>
<author><name sortKey="Senior, Pa" uniqKey="Senior P">PA Senior</name>
</author>
<author><name sortKey="Shapiro, Am" uniqKey="Shapiro A">AM Shapiro</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stahle, M" uniqKey="Stahle M">M Stahle</name>
</author>
<author><name sortKey="Honkanen Scott, M" uniqKey="Honkanen Scott M">M Honkanen-Scott</name>
</author>
<author><name sortKey="Ingvast, S" uniqKey="Ingvast S">S Ingvast</name>
</author>
<author><name sortKey="Korsgren, O" uniqKey="Korsgren O">O Korsgren</name>
</author>
<author><name sortKey="Friberg, As" uniqKey="Friberg A">AS Friberg</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Niclauss, N" uniqKey="Niclauss N">N Niclauss</name>
</author>
<author><name sortKey="Sgroi, A" uniqKey="Sgroi A">A Sgroi</name>
</author>
<author><name sortKey="Morel, P" uniqKey="Morel P">P Morel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Itoh, T" uniqKey="Itoh T">T Itoh</name>
</author>
<author><name sortKey="Takita, M" uniqKey="Takita M">M Takita</name>
</author>
<author><name sortKey="Sorelle, Ja" uniqKey="Sorelle J">JA SoRelle</name>
</author>
</analytic>
</biblStruct>
</listBibl>
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</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Transplant</journal-id>
<journal-id journal-id-type="iso-abbrev">Am. J. Transplant</journal-id>
<journal-id journal-id-type="publisher-id">ajt</journal-id>
<journal-title-group><journal-title>American Journal of Transplantation</journal-title>
</journal-title-group>
<issn pub-type="ppub">1600-6135</issn>
<issn pub-type="epub">1600-6143</issn>
<publisher><publisher-name>BlackWell Publishing Ltd</publisher-name>
<publisher-loc>Oxford, UK</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25278159</article-id>
<article-id pub-id-type="pmc">4282081</article-id>
<article-id pub-id-type="doi">10.1111/ajt.12872</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Original Articles</subject>
</subj-group>
</article-categories>
<title-group><article-title>Islet Product Characteristics and Factors Related to Successful Human Islet Transplantation From the Collaborative Islet Transplant Registry (CITR) 1999–2010</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Balamurugan</surname>
<given-names>A N</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
<xref ref-type="corresp" rid="cor2">†</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Naziruddin</surname>
<given-names>B</given-names>
</name>
<xref ref-type="aff" rid="au2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lockridge</surname>
<given-names>A</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tiwari</surname>
<given-names>M</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Loganathan</surname>
<given-names>G</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Takita</surname>
<given-names>M</given-names>
</name>
<xref ref-type="aff" rid="au2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Matsumoto</surname>
<given-names>S</given-names>
</name>
<xref ref-type="aff" rid="au3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Papas</surname>
<given-names>K</given-names>
</name>
<xref ref-type="aff" rid="au4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Trieger</surname>
<given-names>M</given-names>
</name>
<xref ref-type="aff" rid="au5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rainis</surname>
<given-names>H</given-names>
</name>
<xref ref-type="aff" rid="au5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kin</surname>
<given-names>T</given-names>
</name>
<xref ref-type="aff" rid="au6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kay</surname>
<given-names>T W</given-names>
</name>
<xref ref-type="aff" rid="au7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wease</surname>
<given-names>S</given-names>
</name>
<xref ref-type="aff" rid="au5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Messinger</surname>
<given-names>S</given-names>
</name>
<xref ref-type="aff" rid="au8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ricordi</surname>
<given-names>C</given-names>
</name>
<xref ref-type="aff" rid="au9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Alejandro</surname>
<given-names>R</given-names>
</name>
<xref ref-type="aff" rid="au9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Markmann</surname>
<given-names>J</given-names>
</name>
<xref ref-type="aff" rid="au10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kerr-Conti</surname>
<given-names>J</given-names>
</name>
<xref ref-type="aff" rid="au11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rickels</surname>
<given-names>M R</given-names>
</name>
<xref ref-type="aff" rid="au12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Liu</surname>
<given-names>C</given-names>
</name>
<xref ref-type="aff" rid="au13">13</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>X</given-names>
</name>
<xref ref-type="aff" rid="au14">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Witkowski</surname>
<given-names>P</given-names>
</name>
<xref ref-type="aff" rid="au15">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Posselt</surname>
<given-names>A</given-names>
</name>
<xref ref-type="aff" rid="au16">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Maffi</surname>
<given-names>P</given-names>
</name>
<xref ref-type="aff" rid="au17">17</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Secchi</surname>
<given-names>A</given-names>
</name>
<xref ref-type="aff" rid="au17">17</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Berney</surname>
<given-names>T</given-names>
</name>
<xref ref-type="aff" rid="au18">18</xref>
</contrib>
<contrib contrib-type="author"><name><surname>O’Connell</surname>
<given-names>P J</given-names>
</name>
<xref ref-type="aff" rid="au19">19</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hering</surname>
<given-names>B J</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Barton</surname>
<given-names>F B</given-names>
</name>
<xref ref-type="aff" rid="au5">5</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<aff id="au1"><label>1</label>
<institution>Schulze Diabetes Institute, Department of Surgery, University of Minnesota</institution>
<addr-line>Minneapolis, MN</addr-line>
</aff>
<aff id="au2"><label>2</label>
<institution>Baylor Annette C. and Harold C. Simmons Transplant Institute</institution>
<addr-line>Dallas, TX</addr-line>
</aff>
<aff id="au3"><label>3</label>
<institution>Research and Development Center, Otsuka Pharmaceutical Factory, Inc.</institution>
<addr-line>Tokushima, Japan</addr-line>
</aff>
<aff id="au4"><label>4</label>
<institution>Institute for Cellular Transplantation, University of Arizona</institution>
<addr-line>Tucson, AZ</addr-line>
</aff>
<aff id="au5"><label>5</label>
<institution>The EMMES Corporation</institution>
<addr-line>Rockville, MD</addr-line>
</aff>
<aff id="au6"><label>6</label>
<institution>Clinical Islet Laboratory, University of Alberta</institution>
<addr-line>Edmonton, AB</addr-line>
</aff>
<aff id="au7"><label>7</label>
<institution>St. Vincent's Hospital</institution>
<addr-line>Melbourne, Australia</addr-line>
</aff>
<aff id="au8"><label>8</label>
<institution>Department of Public Health Services, University of Miami</institution>
<addr-line>Miami, FL</addr-line>
</aff>
<aff id="au9"><label>9</label>
<institution>Diabetes Research Institute, University of Miami</institution>
<addr-line>Miami, FL</addr-line>
</aff>
<aff id="au10"><label>10</label>
<institution>Department of Surgery, Massachusetts General Hospital</institution>
<addr-line>Boston, MA</addr-line>
</aff>
<aff id="au11"><label>11</label>
<institution>Lille University Hospital</institution>
<addr-line>Lille, France</addr-line>
</aff>
<aff id="au12"><label>12</label>
<institution>Department of Medicine, University of Pennsylvania</institution>
<addr-line>Philadelphia, PA</addr-line>
</aff>
<aff id="au13"><label>13</label>
<institution>Department of Surgery, University of Pennsylvania</institution>
<addr-line>Philadelphia, PA</addr-line>
</aff>
<aff id="au14"><label>14</label>
<institution>Feinberg School of Medicine, Northwestern University</institution>
<addr-line>Chicago, IL</addr-line>
</aff>
<aff id="au15"><label>15</label>
<institution>Department of Surgery, University of Chicago</institution>
<addr-line>Chicago, IL</addr-line>
</aff>
<aff id="au16"><label>16</label>
<institution>Department of Surgery, University of California, San Francisco</institution>
<addr-line>San Francisco, CA</addr-line>
</aff>
<aff id="au17"><label>17</label>
<institution>Vita-Salute, San Raffaele University</institution>
<addr-line>Milan, Italy</addr-line>
</aff>
<aff id="au18"><label>18</label>
<institution>Department of Surgery, Geneva University Hospital</institution>
<addr-line>Geneva, Switzerland</addr-line>
</aff>
<aff id="au19"><label>19</label>
<institution>National Pancreas Transplant Unit, University of Sydney at Westmead Hospital</institution>
<addr-line>Sydney, Australia</addr-line>
</aff>
</contrib-group>
<author-notes><corresp id="cor1">* <italic>Corresponding authors: Appakalai N. Balamurugan</italic>
, <email>isletologist@hotmail.com</email>
<italic>and Franca B. Barton</italic>
, <email>fbarton@emmes.com</email>
</corresp>
<corresp id="cor2">† Current address: Islet Cell Laboratory, Cardiovascular Innovation Institute, Department of Surgery, University of Louisville, Louisville, KY
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>11</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>02</day>
<month>10</month>
<year>2014</year>
</pub-date>
<volume>14</volume>
<issue>11</issue>
<fpage>2595</fpage>
<lpage>2606</lpage>
<history><date date-type="received"><day>03</day>
<month>3</month>
<year>2014</year>
</date>
<date date-type="rev-recd"><day>30</day>
<month>5</month>
<year>2014</year>
</date>
<date date-type="accepted"><day>18</day>
<month>6</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>© 2014 The Authors. <italic>American Journal of Transplantation</italic>
Published by Wiley Periodicals, Inc. <italic>on behalf of American Society of Transplant Surgeons</italic>
</copyright-statement>
<copyright-year>2014</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><license-p>This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.</license-p>
</license>
</permissions>
<abstract><p>The Collaborative Islet Transplant Registry (CITR) collects data on clinical islet isolations and transplants. This retrospective report analyzed 1017 islet isolation procedures performed for 537 recipients of allogeneic clinical islet transplantation in 1999–2010. This study describes changes in donor and islet isolation variables by era and factors associated with quantity and quality of final islet products. Donor body weight and BMI increased significantly over the period (p < 0.001). Islet yield measures have improved with time including islet equivalent (IEQ)/particle ratio and IEQs infused. The average dose of islets infused significantly increased in the era of 2007–2010 when compared to 1999–2002 (445.4 ± 156.8 vs. 421.3 ± 155.4 ×10<sup>3</sup>
IEQ; p < 0.05). Islet purity and total number of β cells significantly improved over the study period (p < 0.01 and <0.05, respectively). Otherwise, the quality of clinical islets has remained consistently very high through this period, and differs substantially from nonclinical islets. In multivariate analysis of all recipient, donor and islet factors, and medical management factors, the only islet product characteristic that correlated with clinical outcomes was total IEQs infused. This analysis shows improvements in both quantity and some quality criteria of clinical islets produced over 1999–2010, and these parallel improvements in clinical outcomes over the same period.</p>
</abstract>
<kwd-group><kwd>Clinical research/practice</kwd>
<kwd>diabetes: type 1</kwd>
<kwd>endocrinology/diabetology</kwd>
<kwd>health services and outcomes research</kwd>
<kwd>islet isolation</kwd>
<kwd>islet transplantation</kwd>
<kwd>Organ Procurement and Transplantation Network (OPTN)</kwd>
<kwd>pancreas/simultaneous pancreas-kidney transplantation</kwd>
<kwd>registry/registry analysis</kwd>
</kwd-group>
</article-meta>
</front>
<body><sec><title>Introduction</title>
<p>Over the last two decades, numerous studies have attempted to document the donor and procedural factors that significantly influence the success of pancreatic islet isolation and clinical transplantation <xref rid="b1" ref-type="bibr">1</xref>
–<xref rid="b12" ref-type="bibr">12</xref>
. The following donor variables are commonly identified in those studies: donor age, BMI, metabolic condition, pancreas characteristics, cause of death and cold ischemia time (CIT). Various evaluations of the procedures have been performed including processing times, pancreas preservation method, digestion enzyme selection and purification method. The most frequently used primary outcome in these studies pertained to islet yield as represented by total islet equivalent (IEQ) and IEQ/g pancreas or IEQ/kg of recipient body weight. These reports have laid a nearly unanimous emphasis on the importance of reaching a critical minimum islet mass to achieve transplant success.</p>
<p>Consistent results across the studies have been observed for some variables, such as age and BMI; however, controversial findings also have been reported <xref rid="b12" ref-type="bibr">12</xref>
,<xref rid="b13" ref-type="bibr">13</xref>
. The lack of a consistent or sufficiently detailed reporting of variables and outcome measures limits the efficacy of meta-analysis to resolve these debates. In addition, recent investigations have begun to highlight the importance of nonyield-based indicators in predicting the ultimate goal of any islet transplantation procedure, normalization of blood sugar control and a relief from diabetic symptoms in the transplant recipients <xref rid="b4" ref-type="bibr">4</xref>
,<xref rid="b10" ref-type="bibr">10</xref>
,<xref rid="b11" ref-type="bibr">11</xref>
.</p>
<p>The current investigation represents a comprehensive review of islet characteristics, analyzing data from 1017 clinical islet isolations conducted in North American and Juvenile Diabetes Research Foundation (JDRF) European and Australian centers through the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) - and JDRF-sponsored Collaborative Islet Transplant Registry (CITR) database. The CITR has collected data on donors; pancreas procurement, isolation and product characteristics; and baseline and follow-up on recipients of human allogeneic islet transplants from 1999 to the present. CITR operates with all sites and the Coordinating Center undergoing annual review of the research protocol by local Internal Review Boards. This collaboration, concomitant with the standardization of variable and outcome reporting, has produced the largest and most thorough collection on the production of human clinical-grade islets. We focus in this report on identifying the factors that significantly impacted the yield, purity and endocrine function of the final islet product and clinical outcomes, while recipient and management characteristics are reserved for a separate analysis.</p>
</sec>
<sec sec-type="methods"><title>Methods</title>
<p>This analysis comprises data from 1017 islet transplant alone (ITA), islet after kidney (IAK) and simultaneous islet and kidney (SIK) allogeneic transplants reported to CITR from 1999 to 2010. The analysis period was divided into 4-year eras: 1999–2002, 2003–2006, 2007–2010 as reported previously for clinical outcomes <xref rid="b14" ref-type="bibr">14</xref>
. For multiple-donor infusions given on the same day, the donor, pancreas and procurement characteristics were averaged or summed as appropriate to characterize the composite infused preparation.</p>
<p>Table <xref ref-type="table" rid="tbl1">1</xref>
organizes variables according to donor characteristics, procurement and processing characteristics, islet product characteristics and infusion characteristics. Data shown in Table <xref ref-type="table" rid="tbl4">4</xref>
on islet product characteristics comprises the primary outcomes of this analysis, while the others are investigated as possible factors associated with these outcomes. The variables themselves may vary according to calendar year of transplant (era), continent (North America vs. the JDRF sites in Europe and Australia), ITA versus IAK/SIK and many other factors that may or may not be captured in the data. Categorical variables and outcomes are described by their distribution: in particular many are characterized as either present (1) or absent (0); those comprising several distinct levels, including preservation solution, enzyme and gradient type, are reported and analyzed as class variables. Continuous variables are described by their mean and standard deviation. Not all variables were available for all preparations. Table <xref ref-type="table" rid="tbl1">1</xref>
shows the distribution of available data for each variable, excluding the missing data (i.e. treated as missing at random); hence, the percentage distributions are estimates of the actual distribution.</p>
<p>Associations between the variables and the outcomes were estimated by general linear models, first univariately, to identify all associations at p < 0.05, then by step-down multivariate modeling to isolate net effects after adjustment for confounders, with each islet infusion as an independent observation. For about 10% of all “infusions” islet products were derived from two to three donors administered on the same day; these are analyzed as composite infusions because clinical outcomes cannot be ascribed to one or the other donor products, but to the infusion of multiple products given on the same day. All variables in CITR including recipient and donor characteristics, islet procurement, processing and final product criteria, as well as medical management variables, were evaluated by comprehensive multivariate models for their association with clinical outcomes of islet transplantation including achievement and retention of insulin independence (≥14 days, but usually ranging many months or years), and retention of fasting C-peptide >0.3 ng/mL. These results are reported in the CITR 7th Annual Report <xref rid="b15" ref-type="bibr">15</xref>
, also based on the same data set as the present report. SAS V9.3 (SAS Institute, Cary, NC) was used for all computations. Definitions of the terminology shown in the tables and figures have been described in the annual report of CITR <xref rid="b15" ref-type="bibr">15</xref>
.</p>
</sec>
<sec sec-type="results"><title>Results</title>
<p>There were sufficient data available to report on 1017 islet preparations used for clinical allogeneic transplantation. These 1017 islet preparations were infused into 537 recipients: 167 (31%) patients received single infusion, 270 (50%) received two infusions, 92 (17%) received three infusions, 7 (1%) received four infusions, and 1 patient received six infusions. For each infusion event, a single donor pancreas was used 90% of the time, two pancreata were pooled for 9.3% of infusions and islets from three donors were combined for a single infusion in five instances.</p>
<sec><title>Changes in donor and islet isolation by era</title>
<p>Table <xref ref-type="table" rid="tbl1">1</xref>
shows the various characteristics of the 1017 donors and infusions, organized for comparison by era of 1999–2002, 2003–2006 and 2007–2010. Significant increase in body weight, BMI, use of steroid and insulin during treatment at last admission use were observed among donor characteristics (p < 0.001, <0.001, <0.05 and <0.05, Table <xref ref-type="table" rid="tbl1">1</xref>
). Pancreas preservation method significantly changed during the study period (p < 0.001, Table <xref ref-type="table" rid="tbl2">2</xref>
); the ratio of University of Wisconsin solution (UW) only and two layer method (TLM) decreased in 2007–2010 compared to the earlier eras (p < 0.001, Table <xref ref-type="table" rid="tbl2">2</xref>
). Time from death to cross-clamp, time from pancreas recovery to transplant and death to transplant were significantly prolonged (p < 0.001, Table <xref ref-type="table" rid="tbl2">2</xref>
).</p>
<table-wrap id="tbl1" position="float"><label>Table 1A</label>
<caption><p>Donor characteristics</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th rowspan="1" colspan="1"></th>
<th align="center" rowspan="2" colspan="1">Total (n = 1017)</th>
<th align="center" colspan="3" rowspan="1">Era</th>
<th align="left" rowspan="2" colspan="1">p-Value</th>
</tr>
<tr><th rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">1999–2002 (n = 257)</th>
<th align="center" rowspan="1" colspan="1">2003–2006 (n = 472)</th>
<th align="center" rowspan="1" colspan="1">2007–2010 (n = 288)</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">Age (years)</td>
<td align="right" rowspan="1" colspan="1">43.2 ± 12.2 (n = 846)</td>
<td align="right" rowspan="1" colspan="1">42.5 ± 12.2</td>
<td align="right" rowspan="1" colspan="1">43.3 ± 11.7</td>
<td align="right" rowspan="1" colspan="1">43.6 ± 13</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" colspan="5" rowspan="1">Gender, % (n)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Female donor only</td>
<td align="right" rowspan="1" colspan="1">37.3 (n = 379)</td>
<td align="right" rowspan="1" colspan="1">38.9 (n = 100)</td>
<td align="right" rowspan="1" colspan="1">36.9 (n = 174)</td>
<td align="right" rowspan="1" colspan="1">36.5 (n = 105)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Mixed-gender multiple-donor infusion</td>
<td align="right" rowspan="1" colspan="1">3.7 (n = 38)</td>
<td align="right" rowspan="1" colspan="1">5.4 (n = 14)</td>
<td align="right" rowspan="1" colspan="1">4.7 (n = 22)</td>
<td align="right" rowspan="1" colspan="1">0.7 (n = 2)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Male donor only</td>
<td align="right" rowspan="1" colspan="1">59 (n = 600)</td>
<td align="right" rowspan="1" colspan="1">55.6 (n = 143)</td>
<td align="right" rowspan="1" colspan="1">58.5 (n = 276)</td>
<td align="right" rowspan="1" colspan="1">62.8 (n = 181)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Body weight (kg)</td>
<td align="right" rowspan="1" colspan="1">87.6 ± 20.5 (n = 946)</td>
<td align="right" rowspan="1" colspan="1">84.1 ± 20.6</td>
<td align="right" rowspan="1" colspan="1">86.6 ± 19.8</td>
<td align="right" rowspan="1" colspan="1">93.5 ± 20.7</td>
<td align="right" rowspan="1" colspan="1"><0.001</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Height (cm)</td>
<td align="right" rowspan="1" colspan="1">173.4 ± 9.8 (n = 994)</td>
<td align="right" rowspan="1" colspan="1">172.5 ± 9</td>
<td align="right" rowspan="1" colspan="1">173.5 ± 9.9</td>
<td align="right" rowspan="1" colspan="1">174 ± 10.3</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">BMI (kg/m<sup>2</sup>
)</td>
<td align="right" rowspan="1" colspan="1">29.1 ± 6.3 (n = 944)</td>
<td align="right" rowspan="1" colspan="1">28.3 ± 6.5</td>
<td align="right" rowspan="1" colspan="1">28.7 ± 6.2</td>
<td align="right" rowspan="1" colspan="1">30.9 ± 6.1</td>
<td align="right" rowspan="1" colspan="1"><0.001</td>
</tr>
<tr><td align="left" colspan="5" rowspan="1">Ethnicity, % (n)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Non-Hispanic</td>
<td align="right" rowspan="1" colspan="1">90.9 (n = 538)</td>
<td align="right" rowspan="1" colspan="1">92.9 (n = 156)</td>
<td align="right" rowspan="1" colspan="1">89 (n = 251)</td>
<td align="right" rowspan="1" colspan="1">92.3 (n = 131)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Mixed-ethnicity multiple-donor infusion</td>
<td align="right" rowspan="1" colspan="1">1.9 (n = 11)</td>
<td align="right" rowspan="1" colspan="1">2.4 (n = 4)</td>
<td align="right" rowspan="1" colspan="1">2.5 (n = 7)</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Hispanic</td>
<td align="right" rowspan="1" colspan="1">7.3 (n = 43)</td>
<td align="right" rowspan="1" colspan="1">4.8 (n = 8)</td>
<td align="right" rowspan="1" colspan="1">8.5 (n = 24)</td>
<td align="right" rowspan="1" colspan="1">7.7 (n = 11)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" colspan="5" rowspan="1">Donor race, % (n)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> White</td>
<td align="right" rowspan="1" colspan="1">89.8 (n = 564)</td>
<td align="right" rowspan="1" colspan="1">93.9 (n = 168)</td>
<td align="right" rowspan="1" colspan="1">87.5 (n = 273)</td>
<td align="right" rowspan="1" colspan="1">89.8 (n = 123)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" colspan="5" rowspan="1">Cause of death, % (n)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Trauma</td>
<td align="right" rowspan="1" colspan="1">33.2 (n = 308)</td>
<td align="right" rowspan="1" colspan="1">32.9 (n = 76)</td>
<td align="right" rowspan="1" colspan="1">32 (n = 145)</td>
<td align="right" rowspan="1" colspan="1">35.8 (n = 87)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Cerebrovascular/stroke</td>
<td align="right" rowspan="1" colspan="1">58.4 (n = 541)</td>
<td align="right" rowspan="1" colspan="1">55.8 (n = 129)</td>
<td align="right" rowspan="1" colspan="1">61.1 (n = 277)</td>
<td align="right" rowspan="1" colspan="1">55.6 (n = 135)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" colspan="5" rowspan="1">History, % (n)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Hypertension</td>
<td align="right" rowspan="1" colspan="1">35.2 (n = 294)</td>
<td align="right" rowspan="1" colspan="1">36.7 (n = 65)</td>
<td align="right" rowspan="1" colspan="1">35.1 (n = 150)</td>
<td align="right" rowspan="1" colspan="1">34.2 (n = 79)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Alcohol use</td>
<td align="right" rowspan="1" colspan="1">18.6 (n = 145)</td>
<td align="right" rowspan="1" colspan="1">13.9 (n = 25)</td>
<td align="right" rowspan="1" colspan="1">22.2 (n = 91)</td>
<td align="right" rowspan="1" colspan="1">15.2 (n = 29)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" colspan="5" rowspan="1">Laboratory results</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Creatinine (mg/dL)</td>
<td align="right" rowspan="1" colspan="1">1.1 ± 0.6 (n = 809)</td>
<td align="right" rowspan="1" colspan="1">1.1 ± 0.8</td>
<td align="right" rowspan="1" colspan="1">1.1 ± 0.6</td>
<td align="right" rowspan="1" colspan="1">1 ± 0.5</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Bilirubin (mg/dL)</td>
<td align="right" rowspan="1" colspan="1">0.9 ± 0.7 (n = 633)</td>
<td align="right" rowspan="1" colspan="1">0.9 ± 0.7</td>
<td align="right" rowspan="1" colspan="1">0.9 ± 0.6</td>
<td align="right" rowspan="1" colspan="1">0.9 ± 0.8</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> AST (U/L)</td>
<td align="right" rowspan="1" colspan="1">76.7 ± 202 (n = 655)</td>
<td align="right" rowspan="1" colspan="1">115.7 ± 342.1</td>
<td align="right" rowspan="1" colspan="1">63.1 ± 128.9</td>
<td align="right" rowspan="1" colspan="1">70.9 ± 154.5</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> ALT (U/L)</td>
<td align="right" rowspan="1" colspan="1">63.4 ± 165.1 (n = 720)</td>
<td align="right" rowspan="1" colspan="1">89.3 ± 286</td>
<td align="right" rowspan="1" colspan="1">52.3 ± 107.6</td>
<td align="right" rowspan="1" colspan="1">63.6 ± 127.2</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Lipase (U/L)</td>
<td align="right" rowspan="1" colspan="1">1.1 ± 1.9 (n = 631)</td>
<td align="right" rowspan="1" colspan="1">1 ± 1.7</td>
<td align="right" rowspan="1" colspan="1">1.1 ± 1.9</td>
<td align="right" rowspan="1" colspan="1">1 ± 2.2</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Amylase (U/L)</td>
<td align="right" rowspan="1" colspan="1">2.6 ± 5.1 (n = 726)</td>
<td align="right" rowspan="1" colspan="1">2.3 ± 3.7</td>
<td align="right" rowspan="1" colspan="1">2.5 ± 4.2</td>
<td align="right" rowspan="1" colspan="1">3.4 ± 8</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Preinsulin glucose (mg/dL)</td>
<td align="right" rowspan="1" colspan="1">125.5 ± 38.2 (n = 743)</td>
<td align="right" rowspan="1" colspan="1">129.5 ± 36</td>
<td align="right" rowspan="1" colspan="1">123.3 ± 38.5</td>
<td align="right" rowspan="1" colspan="1">126.1 ± 39.8</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Maximum blood glucose (mg/dL)</td>
<td align="right" rowspan="1" colspan="1">230.6 ± 83.5 (n = 773)</td>
<td align="right" rowspan="1" colspan="1">247 ± 98</td>
<td align="right" rowspan="1" colspan="1">228.7 ± 84.2</td>
<td align="right" rowspan="1" colspan="1">221.7 ± 67.5</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Max-Min glucose (mg/dL)</td>
<td align="right" rowspan="1" colspan="1">110.7 ± 86 (n = 670)</td>
<td align="right" rowspan="1" colspan="1">119.4 ± 98.6</td>
<td align="right" rowspan="1" colspan="1">109.5 ± 84.3</td>
<td align="right" rowspan="1" colspan="1">104.4 ± 75.1</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> HbA1c (%)</td>
<td align="right" rowspan="1" colspan="1">5.5 ± 0.5 (n = 161)</td>
<td align="right" rowspan="1" colspan="1">5.3 ± 0.4</td>
<td align="right" rowspan="1" colspan="1">5.4 ± 0.5</td>
<td align="right" rowspan="1" colspan="1">5.5 ± 0.5</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" colspan="5" rowspan="1">Treatment at last admission, % (n)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Vasopressors</td>
<td align="right" rowspan="1" colspan="1">96.7 (n = 816)</td>
<td align="right" rowspan="1" colspan="1">96.7 (n = 204)</td>
<td align="right" rowspan="1" colspan="1">97.7 (n = 432)</td>
<td align="right" rowspan="1" colspan="1">94.2 (n = 180)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Steroids</td>
<td align="right" rowspan="1" colspan="1">59 (n = 309)</td>
<td align="right" rowspan="1" colspan="1">65.5 (n = 78)</td>
<td align="right" rowspan="1" colspan="1">52 (n = 157)</td>
<td align="right" rowspan="1" colspan="1">71.8 (n = 74)</td>
<td align="right" rowspan="1" colspan="1"><0.05</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Insulin</td>
<td align="right" rowspan="1" colspan="1">42.6 (n = 321)</td>
<td align="right" rowspan="1" colspan="1">27.8 (n = 49)</td>
<td align="right" rowspan="1" colspan="1">43 (n = 166)</td>
<td align="right" rowspan="1" colspan="1">55.2 (n = 106)</td>
<td align="right" rowspan="1" colspan="1"><0.05</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Transfusion prerecovery</td>
<td align="right" rowspan="1" colspan="1">32.9 (n = 244)</td>
<td align="right" rowspan="1" colspan="1">34.8 (n = 65)</td>
<td align="right" rowspan="1" colspan="1">33.7 (n = 134)</td>
<td align="right" rowspan="1" colspan="1">28.8 (n = 45)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Transfusion intra-operatively</td>
<td align="right" rowspan="1" colspan="1">6.5 (n = 41)</td>
<td align="right" rowspan="1" colspan="1">9.1 (n = 15)</td>
<td align="right" rowspan="1" colspan="1">5.7 (n = 20)</td>
<td align="right" rowspan="1" colspan="1">5.1 (n = 6)</td>
<td rowspan="1" colspan="1"></td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="tbl2" position="float"><label>Table 1B</label>
<caption><p>Pancreas preservation and recovery</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th rowspan="1" colspan="1"></th>
<th align="center" rowspan="2" colspan="1">Total (n = 1017)</th>
<th align="center" colspan="3" rowspan="1">Era</th>
<th align="left" rowspan="2" colspan="1">p-Value</th>
</tr>
<tr><th rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">1999–2002 (n = 257)</th>
<th align="center" rowspan="1" colspan="1">2003–2006 (n = 472)</th>
<th align="center" rowspan="1" colspan="1">2007–2010 (n = 288)</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">Procurement/transplant centers related, % (n)</td>
<td align="center" char="." rowspan="1" colspan="1">61.5 (n = 551)</td>
<td align="center" char="." rowspan="1" colspan="1">60.6 (n = 157)</td>
<td align="center" char="." rowspan="1" colspan="1">61.3 (n = 284)</td>
<td align="center" char="." rowspan="1" colspan="1">63.2 (n = 110)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Pancreas preservation, % (n)</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td align="left" char="." rowspan="1" colspan="1"><0.001</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> UW only</td>
<td align="center" char="." rowspan="1" colspan="1">42.3 (n = 430)</td>
<td align="center" char="." rowspan="1" colspan="1">58.4 (n = 150)</td>
<td align="center" char="." rowspan="1" colspan="1">46 (n = 217)</td>
<td align="center" char="." rowspan="1" colspan="1">21.9 (n = 63)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> TLM only</td>
<td align="center" char="." rowspan="1" colspan="1">20.4 (n = 207)</td>
<td align="center" char="." rowspan="1" colspan="1">16.7 (n = 43)</td>
<td align="center" char="." rowspan="1" colspan="1">29.2 (n = 138)</td>
<td align="center" char="." rowspan="1" colspan="1">9 (n = 26)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> HTK only</td>
<td align="center" char="." rowspan="1" colspan="1">7 (n = 71)</td>
<td align="center" char="." rowspan="1" colspan="1">0 (n = 0)</td>
<td align="center" char="." rowspan="1" colspan="1">6.8 (n = 32)</td>
<td align="center" char="." rowspan="1" colspan="1">13.5 (n = 39)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Celsior</td>
<td align="center" char="." rowspan="1" colspan="1">2.3 (n = 23)</td>
<td align="center" char="." rowspan="1" colspan="1">1.9 (n = 5)</td>
<td align="center" char="." rowspan="1" colspan="1">1.7 (n = 8)</td>
<td align="center" char="." rowspan="1" colspan="1">3.5 (n = 10)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> UW+TLM</td>
<td align="center" char="." rowspan="1" colspan="1">3.8 (n = 39)</td>
<td align="center" char="." rowspan="1" colspan="1">3.9 (n = 10)</td>
<td align="center" char="." rowspan="1" colspan="1">4.7 (n = 22)</td>
<td align="center" char="." rowspan="1" colspan="1">2.4 (n = 7)</td>
<td align="left" char="." rowspan="1" colspan="1"><0.001</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Combinations/other</td>
<td align="center" char="." rowspan="1" colspan="1">4.8 (n = 49)</td>
<td align="center" char="." rowspan="1" colspan="1">4.7 (n = 12)</td>
<td align="center" char="." rowspan="1" colspan="1">4 (n = 19)</td>
<td align="center" char="." rowspan="1" colspan="1">6.3 (n = 18)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Missing/unknown</td>
<td align="center" char="." rowspan="1" colspan="1">19.5 (n = 198)</td>
<td align="center" char="." rowspan="1" colspan="1">14.4 (n = 37)</td>
<td align="center" char="." rowspan="1" colspan="1">7.6 (n = 36)</td>
<td align="center" char="." rowspan="1" colspan="1">43.4 (n = 125)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Time (hours)</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Admission to brain death</td>
<td align="center" char="." rowspan="1" colspan="1">50.3 ± 61.3 (n = 592)</td>
<td align="center" char="." rowspan="1" colspan="1">50 ± 57.3</td>
<td align="center" char="." rowspan="1" colspan="1">51.4 ± 66.8</td>
<td align="center" char="." rowspan="1" colspan="1">47.9 ± 51.1</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Death to cross-clamp</td>
<td align="center" char="." rowspan="1" colspan="1">18.4 ± 8.3 (n = 766)</td>
<td align="center" char="." rowspan="1" colspan="1">16.4 ± 6.6</td>
<td align="center" char="." rowspan="1" colspan="1">18.8 ± 8.6</td>
<td align="center" char="." rowspan="1" colspan="1">19.8 ± 9.2</td>
<td align="left" char="." rowspan="1" colspan="1"><0.001</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Cross-clamp to pancreas recovery</td>
<td align="center" char="." rowspan="1" colspan="1">0.8 ± 1.1 (n = 627)</td>
<td align="center" char="." rowspan="1" colspan="1">0.6 ± 0.4</td>
<td align="center" char="." rowspan="1" colspan="1">0.9 ± 1.4</td>
<td align="center" char="." rowspan="1" colspan="1">0.9 ± 0.5</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Death to pancreas recovery</td>
<td align="center" char="." rowspan="1" colspan="1">18.7 ± 8.6 (n = 571)</td>
<td align="center" char="." rowspan="1" colspan="1">16.6 ± 6.9</td>
<td align="center" char="." rowspan="1" colspan="1">19.2 ± 8.9</td>
<td align="center" char="." rowspan="1" colspan="1">19.7 ± 9.2</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Cold ischemia time</td>
<td align="center" char="." rowspan="1" colspan="1">7.6 ± 6.1 (n = 775)</td>
<td align="center" char="." rowspan="1" colspan="1">7.3 ± 3.5</td>
<td align="center" char="." rowspan="1" colspan="1">7.2 ± 3.2</td>
<td align="center" char="." rowspan="1" colspan="1">9.3 ± 11.6</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Pancreas recovery to transplant</td>
<td align="center" char="." rowspan="1" colspan="1">33.5 ± 20.5 (n = 629)</td>
<td align="center" char="." rowspan="1" colspan="1">25.3 ± 18.5</td>
<td align="center" char="." rowspan="1" colspan="1">33.3 ± 20.3</td>
<td align="center" char="." rowspan="1" colspan="1">41.4 ± 20.0</td>
<td align="left" char="." rowspan="1" colspan="1"><0.001</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Death to transplant</td>
<td align="center" char="." rowspan="1" colspan="1">52.9 ± 23.6 (n = 796)</td>
<td align="center" char="." rowspan="1" colspan="1">43.7 ± 22.1</td>
<td align="center" char="." rowspan="1" colspan="1">52.9 ± 23.4</td>
<td align="center" char="." rowspan="1" colspan="1">63.1 ± 21.6</td>
<td align="left" char="." rowspan="1" colspan="1"><0.001</td>
</tr>
</tbody>
</table>
<table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Percentage excluding missing cases</th>
<th rowspan="1" colspan="1"></th>
<th rowspan="1" colspan="1"></th>
<th rowspan="1" colspan="1"></th>
<th rowspan="1" colspan="1"></th>
<th rowspan="1" colspan="1"></th>
</tr>
<tr><th rowspan="1" colspan="1"></th>
<th align="center" rowspan="2" colspan="1">Total (n = 819)</th>
<th align="center" colspan="3" rowspan="1">Era</th>
<th align="left" rowspan="2" colspan="1">p-Value</th>
</tr>
<tr><th rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">1999–2002 (n = 220)</th>
<th align="center" rowspan="1" colspan="1">2003–2006 (n = 436)</th>
<th align="center" rowspan="1" colspan="1">2007–2010 (n = 164)</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">Pancreas preservation, % (n)</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td align="left" char="." rowspan="1" colspan="1"><0.001</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> UW only</td>
<td align="center" char="." rowspan="1" colspan="1">52.5%</td>
<td align="center" char="." rowspan="1" colspan="1">68.2%</td>
<td align="center" char="." rowspan="1" colspan="1">49.8%</td>
<td align="center" char="." rowspan="1" colspan="1">38.4%</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> TLM only</td>
<td align="center" char="." rowspan="1" colspan="1">25.3%</td>
<td align="center" char="." rowspan="1" colspan="1">19.5%</td>
<td align="center" char="." rowspan="1" colspan="1">31.7%</td>
<td align="center" char="." rowspan="1" colspan="1">15.9%</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> HTK only</td>
<td align="center" char="." rowspan="1" colspan="1">8.7%</td>
<td align="center" char="." rowspan="1" colspan="1">0.0%</td>
<td align="center" char="." rowspan="1" colspan="1">7.3%</td>
<td align="center" char="." rowspan="1" colspan="1">23.8%</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Celsior</td>
<td align="center" char="." rowspan="1" colspan="1">2.8%</td>
<td align="center" char="." rowspan="1" colspan="1">2.3%</td>
<td align="center" char="." rowspan="1" colspan="1">1.8%</td>
<td align="center" char="." rowspan="1" colspan="1">6.1%</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> UW+TLM</td>
<td align="center" char="." rowspan="1" colspan="1">4.8%</td>
<td align="center" char="." rowspan="1" colspan="1">4.5%</td>
<td align="center" char="." rowspan="1" colspan="1">5.0%</td>
<td align="center" char="." rowspan="1" colspan="1">4.9%</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Combinations/other</td>
<td align="center" char="." rowspan="1" colspan="1">6.0%</td>
<td align="center" char="." rowspan="1" colspan="1">5.5%</td>
<td align="center" char="." rowspan="1" colspan="1">4.4%</td>
<td align="center" char="." rowspan="1" colspan="1">11.0%</td>
<td rowspan="1" colspan="1"></td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tf1b-1"><p>HTK, histidine-tryptophan-ketoglutarate; TLM, two layer method; UW, University of Wisconsin solution.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>The pancreas digestion enzyme changed significantly during the study period; NB1 collagenase has primarily replaced Liberase HI in the most recent era (p < 0.001, Table <xref ref-type="table" rid="tbl3">3</xref>
). The proportion of <italic>in vitro</italic>
culture more than 6 h has increased significantly over the era (p < 0.001).</p>
<table-wrap id="tbl3" position="float"><label>Table 1C</label>
<caption><p>Islet processing</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th rowspan="1" colspan="1"></th>
<th align="center" rowspan="2" colspan="1">Total (n = 1017)</th>
<th align="center" colspan="3" rowspan="1">Era</th>
<th align="left" rowspan="2" colspan="1">p-Value</th>
</tr>
<tr><th rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">1999–2002 (n = 257)</th>
<th align="center" rowspan="1" colspan="1">2003–2006 (n = 472)</th>
<th align="center" rowspan="1" colspan="1">2007–2010 (n = 288)</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">Digestion enzyme, % (n)</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Collagenase</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"><0.001</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Liberase HI alone</td>
<td align="center" char="." rowspan="1" colspan="1">57.8 (n = 588)</td>
<td align="center" char="." rowspan="1" colspan="1">91.4 (n = 235)</td>
<td align="center" char="." rowspan="1" colspan="1">71.6 (n = 338)</td>
<td align="center" char="." rowspan="1" colspan="1">5.2 (n = 15)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Serva NB1 alone</td>
<td align="center" char="." rowspan="1" colspan="1">9.3 (n = 95)</td>
<td align="center" char="." rowspan="1" colspan="1">–</td>
<td align="center" char="." rowspan="1" colspan="1">3.6 (n = 17)</td>
<td align="center" char="." rowspan="1" colspan="1">27.1 (n = 78)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> ServaGMPColl+ServaNeutProtease</td>
<td align="center" char="." rowspan="1" colspan="1">4.7 (n = 48)</td>
<td align="center" char="." rowspan="1" colspan="1">–</td>
<td align="center" char="." rowspan="1" colspan="1">–</td>
<td align="center" char="." rowspan="1" colspan="1">16.7 (n = 48)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> CollagenaseP alone</td>
<td align="center" char="." rowspan="1" colspan="1">1.5 (n = 15)</td>
<td align="center" char="." rowspan="1" colspan="1">0.8 (n = 2)</td>
<td align="center" char="." rowspan="1" colspan="1">2.5 (n = 12)</td>
<td align="center" char="." rowspan="1" colspan="1">0.3 (n = 1)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Liberase MTF</td>
<td align="center" char="." rowspan="1" colspan="1">0.3 (n = 3)</td>
<td align="center" char="." rowspan="1" colspan="1">–</td>
<td align="center" char="." rowspan="1" colspan="1">–</td>
<td align="center" char="." rowspan="1" colspan="1">1 (n = 3)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Liberase-collagenase blend</td>
<td align="center" char="." rowspan="1" colspan="1">4.7 (n = 48)</td>
<td align="center" char="." rowspan="1" colspan="1">–</td>
<td align="center" char="." rowspan="1" colspan="1">9.7 (n = 46)</td>
<td align="center" char="." rowspan="1" colspan="1">0.7 (n = 2)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Other/other combination</td>
<td align="center" char="." rowspan="1" colspan="1">5.9 (n = 60)</td>
<td align="center" char="." rowspan="1" colspan="1">0.4 (n = 1)</td>
<td align="center" char="." rowspan="1" colspan="1">7.2 (n = 34)</td>
<td align="center" char="." rowspan="1" colspan="1">8.7 (n = 25)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Not yet reported</td>
<td align="center" char="." rowspan="1" colspan="1">15.7 (n = 160)</td>
<td align="center" char="." rowspan="1" colspan="1">7.4 (n = 19)</td>
<td align="center" char="." rowspan="1" colspan="1">5.3 (n = 25)</td>
<td align="center" char="." rowspan="1" colspan="1">40.3 (n = 116)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Thermolysin (in addition to other)</td>
<td align="center" char="." rowspan="1" colspan="1">7.3 (n = 63)</td>
<td align="center" char="." rowspan="1" colspan="1">–</td>
<td align="center" char="." rowspan="1" colspan="1">12.5 (n = 56)</td>
<td align="center" char="." rowspan="1" colspan="1">4 (n = 7)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Pulmozyme (in addition to other)</td>
<td align="center" char="." rowspan="1" colspan="1">45.4 (n = 391)</td>
<td align="center" char="." rowspan="1" colspan="1">14.7 (n = 35)</td>
<td align="center" char="." rowspan="1" colspan="1">54.6 (n = 245)</td>
<td align="center" char="." rowspan="1" colspan="1">63.4 (n = 111)</td>
<td align="left" char="." rowspan="1" colspan="1"><0.001</td>
</tr>
<tr><td align="left" colspan="6" rowspan="1">Purification gradient type, % (n)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Discontinuous</td>
<td align="center" char="." rowspan="1" colspan="1">5.8 (n = 49)</td>
<td align="center" char="." rowspan="1" colspan="1">9.8 (n = 21)</td>
<td align="center" char="." rowspan="1" colspan="1">5.9 (n = 26)</td>
<td align="center" char="." rowspan="1" colspan="1">1.1 (n = 2)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Continuous</td>
<td align="center" char="." rowspan="1" colspan="1">83.8 (n = 704)</td>
<td align="center" char="." rowspan="1" colspan="1">77.7 (n = 167)</td>
<td align="center" char="." rowspan="1" colspan="1">82.4 (n = 361)</td>
<td align="center" char="." rowspan="1" colspan="1">94.1 (n = 176)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Both</td>
<td align="center" char="." rowspan="1" colspan="1">10.2 (n = 86)</td>
<td align="center" char="." rowspan="1" colspan="1">12.6 (n = 27)</td>
<td align="center" char="." rowspan="1" colspan="1">11.4 (n = 50)</td>
<td align="center" char="." rowspan="1" colspan="1">4.8 (n = 9)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" colspan="6" rowspan="1">Islet culture (hours)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Culture time (0-max)</td>
<td align="center" char="." rowspan="1" colspan="1">17.7 ± 18.4 (n = 777)</td>
<td align="center" char="." rowspan="1" colspan="1">11.9 ± 18.1</td>
<td align="center" char="." rowspan="1" colspan="1">18 ± 17.9</td>
<td align="center" char="." rowspan="1" colspan="1">24.7 ± 17.5</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Cultured ≥6 h, % (n)</td>
<td align="center" char="." rowspan="1" colspan="1">26.5 (n = 269)</td>
<td align="center" char="." rowspan="1" colspan="1">14.4 (n = 37)</td>
<td align="center" char="." rowspan="1" colspan="1">14.4 (n = 68)</td>
<td align="center" char="." rowspan="1" colspan="1">56.9 (n = 164)</td>
<td align="left" char="." rowspan="1" colspan="1"><0.001</td>
</tr>
</tbody>
</table>
<table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Percentage excluding missing cases</th>
<th rowspan="1" colspan="1"></th>
<th rowspan="1" colspan="1"></th>
<th rowspan="1" colspan="1"></th>
<th rowspan="1" colspan="1"></th>
<th rowspan="1" colspan="1"></th>
</tr>
<tr><th rowspan="1" colspan="1"></th>
<th align="center" rowspan="2" colspan="1">Total (n = 857)</th>
<th align="center" colspan="3" rowspan="1">Era</th>
<th rowspan="1" colspan="1"></th>
</tr>
<tr><th rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">1999–2002 (n = 238)</th>
<th align="center" rowspan="1" colspan="1">2003–2006 (n = 472)</th>
<th align="center" rowspan="1" colspan="1">2007–2010 (n = 288)</th>
<th align="center" rowspan="1" colspan="1">p-Value</th>
</tr>
</thead>
<tbody><tr><td align="left" colspan="6" rowspan="1">Digestion enzyme, % (n)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Collagenase</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td align="left" char="." rowspan="1" colspan="1"><0.001</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Liberase HI alone</td>
<td align="center" char="." rowspan="1" colspan="1">68.6%</td>
<td align="center" char="." rowspan="1" colspan="1">98.7%</td>
<td align="center" char="." rowspan="1" colspan="1">75.6%</td>
<td align="center" char="." rowspan="1" colspan="1">8.7%</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Serva NB1 alone</td>
<td align="center" char="." rowspan="1" colspan="1">11.1%</td>
<td align="center" char="." rowspan="1" colspan="1">0.0%</td>
<td align="center" char="." rowspan="1" colspan="1">3.8%</td>
<td align="center" char="." rowspan="1" colspan="1">45.3%</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> ServaGMPColl+ServaNeutProtease</td>
<td align="center" char="." rowspan="1" colspan="1">5.6%</td>
<td align="center" char="." rowspan="1" colspan="1">0.0%</td>
<td align="center" char="." rowspan="1" colspan="1">0.0%</td>
<td align="center" char="." rowspan="1" colspan="1">27.9%</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> CollagenaseP alone</td>
<td align="center" char="." rowspan="1" colspan="1">1.8%</td>
<td align="center" char="." rowspan="1" colspan="1">0.8%</td>
<td align="center" char="." rowspan="1" colspan="1">2.7%</td>
<td align="center" char="." rowspan="1" colspan="1">0.6%</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Liberase MTF</td>
<td align="center" char="." rowspan="1" colspan="1">0.4%</td>
<td align="center" char="." rowspan="1" colspan="1">0.0%</td>
<td align="center" char="." rowspan="1" colspan="1">0.0%</td>
<td align="center" char="." rowspan="1" colspan="1">1.7%</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Liberase-collagenase blend</td>
<td align="center" char="." rowspan="1" colspan="1">5.6%</td>
<td align="center" char="." rowspan="1" colspan="1">0.0%</td>
<td align="center" char="." rowspan="1" colspan="1">10.3%</td>
<td align="center" char="." rowspan="1" colspan="1">1.2%</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Other/other combination</td>
<td align="center" char="." rowspan="1" colspan="1">7.0%</td>
<td align="center" char="." rowspan="1" colspan="1">0.4%</td>
<td align="center" char="." rowspan="1" colspan="1">7.6%</td>
<td align="center" char="." rowspan="1" colspan="1">14.5%</td>
<td rowspan="1" colspan="1"></td>
</tr>
</tbody>
</table>
</table-wrap>
<p>IEQ per islet particle number and IEQ infused were significantly higher during 2007–2010 when compared to 1999–2002 (p < 0.001 and <0.05, respectively, Table <xref ref-type="table" rid="tbl4">4</xref>
) although no significant change in total IEQ at particle count (completion of isolation) was seen. IEQ at count and IEQ infused correlated strongly with each other (r = 0.93, p < 0.0001, Figure S1). Purity of islets and the number of total β cells in 2007–2010 were significantly higher than the previous years (p < 0.01 and <0.05, respectively, Table <xref ref-type="table" rid="tbl4">4</xref>
). The stimulation index and viability declined over the periods (p < 0.001 and <0.01, respectively) but remained above 2.7 and 90.2%, respectively.</p>
<table-wrap id="tbl4" position="float"><label>Table 1D</label>
<caption><p>Islet product characteristics</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th rowspan="1" colspan="1"></th>
<th align="center" rowspan="2" colspan="1">Total (n = 1017)</th>
<th align="center" colspan="3" rowspan="1">Era</th>
<th align="left" rowspan="2" colspan="1">p-Value</th>
</tr>
<tr><th rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">1999–2002 (n = 257)</th>
<th align="center" rowspan="1" colspan="1">2003–2006 (n = 472)</th>
<th align="center" rowspan="1" colspan="1">2007–2010 (n = 288)</th>
</tr>
</thead>
<tbody><tr><td align="left" colspan="6" rowspan="1">Islet mass</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Total IEQs (×10<sup>3</sup>
) at time of particle count</td>
<td align="center" char="." rowspan="1" colspan="1">416 ± 156.9 (n = 773)</td>
<td align="center" char="." rowspan="1" colspan="1">417.5 ± 160.6</td>
<td align="center" char="." rowspan="1" colspan="1">413.7 ± 159.9</td>
<td align="center" char="." rowspan="1" colspan="1">419.2 ± 146.7</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> IEQ/islet particle ratio</td>
<td align="center" char="." rowspan="1" colspan="1">1.1 ± 0.6 (n = 655)</td>
<td align="center" char="." rowspan="1" colspan="1">1.1 ± 0.5</td>
<td align="center" char="." rowspan="1" colspan="1">1.1 ± 0.4</td>
<td align="center" char="." rowspan="1" colspan="1">1.3 ± 0.8</td>
<td align="left" char="." rowspan="1" colspan="1"><0.001</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> IEQs infused (×10<sup>3</sup>
)</td>
<td align="center" char="." rowspan="1" colspan="1">426.5 ± 157.1 (n = 1015)</td>
<td align="center" char="." rowspan="1" colspan="1">421.3 ± 155.4</td>
<td align="center" char="." rowspan="1" colspan="1">417.8 ± 157.6</td>
<td align="center" char="." rowspan="1" colspan="1">445.4 ± 156.8</td>
<td align="left" char="." rowspan="1" colspan="1"><0.05</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Packed cell volume infused (mL)</td>
<td align="center" char="." rowspan="1" colspan="1">3.9 ± 2.2 (n = 825)</td>
<td align="center" char="." rowspan="1" colspan="1">4.1 ± 2.1</td>
<td align="center" char="." rowspan="1" colspan="1">3.9 ± 2</td>
<td align="center" char="." rowspan="1" colspan="1">3.8 ± 2.8</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" colspan="6" rowspan="1">Islet quality</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Purity (%)</td>
<td align="center" char="." rowspan="1" colspan="1">61.8 ± 18.3 (n = 770)</td>
<td align="center" char="." rowspan="1" colspan="1">59 ± 19.1</td>
<td align="center" char="." rowspan="1" colspan="1">61.7 ± 18.5</td>
<td align="center" char="." rowspan="1" colspan="1">65.1 ± 16.4</td>
<td align="left" char="." rowspan="1" colspan="1"><0.01</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Embedded islets (%)</td>
<td align="center" char="." rowspan="1" colspan="1">15.7 ± 18.7 (n = 527)</td>
<td align="center" char="." rowspan="1" colspan="1">13.6 ± 17.7</td>
<td align="center" char="." rowspan="1" colspan="1">16.1 ± 19.5</td>
<td align="center" char="." rowspan="1" colspan="1">16.9 ± 18</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Stimulation index</td>
<td align="center" char="." rowspan="1" colspan="1">3.3 ± 3.3 (n = 693)</td>
<td align="center" char="." rowspan="1" colspan="1">3.8 ± 3.9</td>
<td align="center" char="." rowspan="1" colspan="1">3.2 ± 3.2</td>
<td align="center" char="." rowspan="1" colspan="1">2.7 ± 2.7</td>
<td align="left" char="." rowspan="1" colspan="1"><0.001</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Islet viability (%)</td>
<td align="center" char="." rowspan="1" colspan="1">91.2 ± 6.2 (n = 752)</td>
<td align="center" char="." rowspan="1" colspan="1">91.4 ± 6.9</td>
<td align="center" char="." rowspan="1" colspan="1">91.5 ± 6</td>
<td align="center" char="." rowspan="1" colspan="1">90.2 ± 5.9</td>
<td align="left" char="." rowspan="1" colspan="1"><0.01</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Total beta cells (×10<sup>6</sup>
)</td>
<td align="center" char="." rowspan="1" colspan="1">231.1 ± 191.5 (n = 228)</td>
<td align="center" char="." rowspan="1" colspan="1">196.2 ± 180</td>
<td align="center" char="." rowspan="1" colspan="1">235.6 ± 191.9</td>
<td align="center" char="." rowspan="1" colspan="1">318.9 ± 201.4</td>
<td align="left" char="." rowspan="1" colspan="1"><0.05</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Total beta cells (×10<sup>6</sup>
)/kg recipient</td>
<td align="center" char="." rowspan="1" colspan="1">3.6 ± 3.1 (n = 219)</td>
<td align="center" char="." rowspan="1" colspan="1">3 ± 2.8</td>
<td align="center" char="." rowspan="1" colspan="1">3.8 ± 3.2</td>
<td align="center" char="." rowspan="1" colspan="1">4.5 ± 2.8</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Total insulin content of islets (mg)</td>
<td align="center" char="." rowspan="1" colspan="1">3.5 ± 2.2 (n = 247)</td>
<td align="center" char="." rowspan="1" colspan="1">3.2 ± 2</td>
<td align="center" char="." rowspan="1" colspan="1">3.6 ± 2.4</td>
<td align="center" char="." rowspan="1" colspan="1">1.7 ± 0.5</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Total endotoxin infused (EU)</td>
<td align="center" char="." rowspan="1" colspan="1">22.7 ± 54.9 (n = 667)</td>
<td align="center" char="." rowspan="1" colspan="1">29.4 ± 60.7</td>
<td align="center" char="." rowspan="1" colspan="1">26.1 ± 60</td>
<td align="center" char="." rowspan="1" colspan="1">7.8 ± 26.7</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> Total endotoxin (EU)/kg recipient</td>
<td align="center" char="." rowspan="1" colspan="1">0.4 ± 0.8 (n = 651)</td>
<td align="center" char="." rowspan="1" colspan="1">0.5 ± 1</td>
<td align="center" char="." rowspan="1" colspan="1">0.4 ± 0.9</td>
<td align="center" char="." rowspan="1" colspan="1">0.1 ± 0.5</td>
<td rowspan="1" colspan="1"></td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tf1D-1"><p>IEQ, islet equivalent.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>The analysis of donor and isolation characteristics compared by continent (North America vs. European and Australian sites) and by type of transplantation (ITA vs. IAK/SIK) are shown in Tables S1–S5. Briefly, significant differences were seen in the following variables when the data were stratified by continent (p < 0.05): donor body weight, BMI, maximum blood glucose, donor steroid therapy, insulin therapy, transplant-center related pancreas procurement, pancreas preservation, time from death to cross-clamp, cross-clamp to pancreas recovery, death to transplant, pancreas digestion enzyme, islet culture over 6 h, total IEQ at count, IEQ/particle count, IEQ infused, purity, stimulation index, total insulin content of islets, number of islet infusion sequence and the number of total donor(s) per infusion. Analyzed by ITA versus IAK/SIK, the following variables showed significant differences: donor body weight, BMI, cause of death, HbA1c, donor steroid therapy, insulin therapy, time from death to cross-clamp, death to pancreas recovery, pancreas digestion enzyme, purification method, total IEQ at count, IEQ infused, packed cell volume, purity and ratio of embedded islets (Tables S1–S5).</p>
<table-wrap id="tbl5" position="float"><label>Table 1E</label>
<caption><p>Islet infusion</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th rowspan="1" colspan="1"></th>
<th align="center" rowspan="2" colspan="1">Total (n = 1017)</th>
<th align="center" colspan="3" rowspan="1">Era</th>
<th align="left" rowspan="2" colspan="1">p-Value</th>
</tr>
<tr><th rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">1999–2002 (n = 257)</th>
<th align="center" rowspan="1" colspan="1">2003–2006 (n = 472)</th>
<th align="center" rowspan="1" colspan="1">2007–2010 (n = 288)</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">Recipient infusion sequence #, % (n)</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td align="left" char="." rowspan="1" colspan="1"><0.05</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> 1st</td>
<td align="center" char="." rowspan="1" colspan="1">52.8 (n = 537)</td>
<td align="center" char="." rowspan="1" colspan="1">62.3 (n = 160)</td>
<td align="center" char="." rowspan="1" colspan="1">46 (n = 217)</td>
<td align="center" char="." rowspan="1" colspan="1">55.6 (n = 160)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> 2nd</td>
<td align="center" char="." rowspan="1" colspan="1">36.4 (n = 370)</td>
<td align="center" char="." rowspan="1" colspan="1">31.9 (n = 82)</td>
<td align="center" char="." rowspan="1" colspan="1">39.2 (n = 185)</td>
<td align="center" char="." rowspan="1" colspan="1">35.8 (n = 103)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> 3rd</td>
<td align="center" char="." rowspan="1" colspan="1">9.8 (n = 100)</td>
<td align="center" char="." rowspan="1" colspan="1">5.4 (n = 14)</td>
<td align="center" char="." rowspan="1" colspan="1">14 (n = 66)</td>
<td align="center" char="." rowspan="1" colspan="1">6.9 (n = 20)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> 4th–6th</td>
<td align="center" char="." rowspan="1" colspan="1">1 (n = 10)</td>
<td align="center" char="." rowspan="1" colspan="1">0.4 (n = 1)</td>
<td align="center" char="." rowspan="1" colspan="1">0.8 (n = 4)</td>
<td align="center" char="." rowspan="1" colspan="1">1.6 (n = 5)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" colspan="6" rowspan="1">Total donors/infusion, % (n)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> 1</td>
<td align="center" char="." rowspan="1" colspan="1">90.2 (n = 917)</td>
<td align="center" char="." rowspan="1" colspan="1">89.9 (n = 231)</td>
<td align="center" char="." rowspan="1" colspan="1">88.6 (n = 418)</td>
<td align="center" char="." rowspan="1" colspan="1">93.1 (n = 268)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> 2</td>
<td align="center" char="." rowspan="1" colspan="1">9.3 (n = 95)</td>
<td align="center" char="." rowspan="1" colspan="1">9.3 (n = 24)</td>
<td align="center" char="." rowspan="1" colspan="1">11.2 (n = 53)</td>
<td align="center" char="." rowspan="1" colspan="1">6.3 (n = 18)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1"> 3</td>
<td align="center" char="." rowspan="1" colspan="1">0.5 (n = 5)</td>
<td align="center" char="." rowspan="1" colspan="1">0.8 (n = 2)</td>
<td align="center" char="." rowspan="1" colspan="1">0.2 (n = 1)</td>
<td align="center" char="." rowspan="1" colspan="1">0.7 (n = 2)</td>
<td rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Any positive crossmatch, % (n)</td>
<td align="center" char="." rowspan="1" colspan="1">3.1 (n = 20)</td>
<td align="center" char="." rowspan="1" colspan="1">0.8 (n = 1)</td>
<td align="center" char="." rowspan="1" colspan="1">3.8 (n = 12)</td>
<td align="center" char="." rowspan="1" colspan="1">3.7 (n = 7)</td>
<td rowspan="1" colspan="1"></td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec><title>Variables associated with islet product characteristics</title>
<p>The donor and isolation factors associated with islet product characteristics are shown in Table <xref ref-type="table" rid="tbl6">6</xref>
and <xref ref-type="fig" rid="fig01">Figure 1</xref>
. Total IEQs at particle count was remarkably associated with donor body weight (<xref ref-type="fig" rid="fig01">Figure 1</xref>
A), BMI, donor steroid therapy at last admission and blood transfusion (<xref ref-type="fig" rid="fig01">Figure 1</xref>
B), time from death to cross-clamp, total number of donors per infusion and continent. IEQ/particle count was associated with donor BMI, donor steroid therapy, CIT (<xref ref-type="fig" rid="fig01">Figure 1</xref>
C), time from death to cross-clamp, pancreas digestion enzymes, era and continent. Packed cell volume correlated negatively with the number of islet infusions sequence (<xref ref-type="fig" rid="fig01">Figure 1</xref>
D). Islet purity was associated with donor steroid therapy, time from death to cross-clamp, pancreas digestion enzymes (<xref ref-type="fig" rid="fig01">Figure 1</xref>
E) and continents. The proportion of embedded islets correlated negatively with donor age (<xref ref-type="fig" rid="fig01">Figure 1</xref>
F). Stimulation index correlated negatively with donor HbA1c (<xref ref-type="fig" rid="fig01">Figure 1</xref>
G). Viability was negatively associated with Liberase HI (<xref ref-type="fig" rid="fig01">Figure 1</xref>
H), and associated with pancreas preservation method (<xref ref-type="fig" rid="fig01">Figure 1</xref>
I). Total β cell number per kilograms of recipient body weight correlated negatively with donor age (<xref ref-type="fig" rid="fig01">Figure 1</xref>
J), cause of death, steroid and insulin therapy (<xref ref-type="fig" rid="fig01">Figure 1</xref>
K), purification methods (<xref ref-type="fig" rid="fig01">Figure 1</xref>
L), islet culture time and era. Total insulin content correlated negatively with donor steroid therapy at the last admission, and correlated positively with total number of donors per infusion and continents. Significant changes were observed in endotoxin content during the analysis period; however, wide variation in data was also noted. This difference observed between sites from different continents could be due to changes in the methodology.</p>
<table-wrap id="tbl6" position="float"><label>Table 2</label>
<caption><p>Correlations between donor, procurement, processing characteristics (“factors”; rows) and islet product criteria (columns) in 1017 islet preparations of clinical allogeneic transplantation in CITR, 1999–2010</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Category</th>
<th align="center" rowspan="1" colspan="1">Factors</th>
<th align="center" rowspan="1" colspan="1">IEQ at count (1000s)</th>
<th align="center" rowspan="1" colspan="1">IEQ/particle count ratio</th>
<th align="center" rowspan="1" colspan="1">Purity (%)</th>
<th align="center" rowspan="1" colspan="1">Embedded islets (%)</th>
<th align="center" rowspan="1" colspan="1">Viability (%)</th>
<th align="center" rowspan="1" colspan="1">Total beta cells/kg recipient</th>
<th align="center" rowspan="1" colspan="1">Total insulin content (mg)</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">Donor characteristics</td>
<td align="left" rowspan="3" colspan="1">Age (years)</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">−0.183</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">−0.195</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.0052</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">480</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">204</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="left" rowspan="3" colspan="1">Donor BMI</td>
<td align="center" rowspan="1" colspan="1">0.265</td>
<td align="center" rowspan="1" colspan="1">0.193</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">733</td>
<td align="center" rowspan="1" colspan="1">620</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="left" rowspan="3" colspan="1">Trauma death (0 = no, 1 = yes)</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.198</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.0038</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">212</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="left" rowspan="3" colspan="1">Donor given steroids during hospital stay (0 = no, 1 = yes)</td>
<td align="center" rowspan="1" colspan="1">0.161</td>
<td align="center" rowspan="1" colspan="1">0.265</td>
<td align="center" rowspan="1" colspan="1">0.172</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.245</td>
<td align="center" rowspan="1" colspan="1">−0.257</td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.001</td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1">0.0001</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.0613</td>
<td align="center" rowspan="1" colspan="1">0.0079</td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">417</td>
<td align="center" rowspan="1" colspan="1">309</td>
<td align="center" rowspan="1" colspan="1">487</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">59</td>
<td align="center" rowspan="1" colspan="1">106</td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="left" rowspan="3" colspan="1">Donor given insulin during hospital stay (0 = no, 1 = yes)</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.255</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.0005</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">184</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Pancreas preservation and recovery</td>
<td align="left" rowspan="3" colspan="1">Hours from death to cross-clamp</td>
<td align="center" rowspan="1" colspan="1">0.157</td>
<td align="center" rowspan="1" colspan="1">0.189</td>
<td align="center" rowspan="1" colspan="1">0.156</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">653</td>
<td align="center" rowspan="1" colspan="1">548</td>
<td align="center" rowspan="1" colspan="1">653</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Islet processing</td>
<td align="left" rowspan="3" colspan="1">Liberase HI</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">−0.18454</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.171</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">639</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">743</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="left" rowspan="3" colspan="1">Serva NB1</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.2338</td>
<td align="center" rowspan="1" colspan="1">0.170</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">639</td>
<td align="center" rowspan="1" colspan="1">762</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="left" rowspan="3" colspan="1">Hours culture time</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.287</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">219</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Islet infusion</td>
<td align="left" rowspan="3" colspan="1">Total donors (1, 2, 3)</td>
<td align="center" rowspan="1" colspan="1">0.182</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.203</td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"><.0001</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.0013</td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">773</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">247</td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="left" rowspan="3" colspan="1">Era (1 = 1999–2002, 2 = 2003–2006, 3 = 2007–2010)</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.144</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.164</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.0002</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.0154</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">655</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">219</td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="center" rowspan="1" colspan="1"></td>
<td align="left" rowspan="3" colspan="1">Continent (0 = North America, 1 = Europe/Australia)</td>
<td align="center" rowspan="1" colspan="1">−0.265</td>
<td align="center" rowspan="1" colspan="1">−0.199</td>
<td align="center" rowspan="1" colspan="1">−0.319</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.189</td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1"><0.0001</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">0.0029</td>
</tr>
<tr><td rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">773</td>
<td align="center" rowspan="1" colspan="1">655</td>
<td align="center" rowspan="1" colspan="1">770</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">247</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tf2-1"><p>CITR, Collaborative Islet Transplant Registry; IEQ, islet equivalent.</p>
</fn>
<fn id="tf2-2"><p>Each cell describes, from top to bottom: correlation coefficient, Pr{Rho = 0|H<sub>0</sub>
} number of observations.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<fig id="fig01" position="float"><label>Figure 1</label>
<caption><p>Factors significantly associated with islet product characteristics. (A) Total islet equivalents (IEQs) at particle count versus donor body weight. (B) Total IEQs at particle count versus donor transfusion. (C) IEQ/islet particle ratio versus CIT, cold ischemia time (CIT). (D) Packed cell volume versus infusion number. (E) Purity versus digestion enzyme. (F) Embedded islets versus donor age. (G) Stimulation index versus donor HbA1c. (H) Viability versus digestion enzyme. (I) Viability versus pancreas preservation. (J) Total β cells/kg of recipient weight versus donor age. (K) Total β cells/kg of recipient weight versus donor insulin treatment. (L) Total β cells/kg of recipient weight versus purification type.</p>
</caption>
<graphic xlink:href="ajt0014-2595-f1"></graphic>
</fig>
</sec>
<sec><title>Donor and islet product characteristics associated with clinical outcomes</title>
<p>Of all the donor characteristics and islet product criteria assessed for their association with primary clinical end points, the only factor significantly associated with any primary outcome was total IEQs infused on achievement of insulin independence over one to several infusions (<xref ref-type="fig" rid="fig02">Figure 2</xref>
): when at least 600 000 total IEQs were infused, 75–80% of recipients achieved insulin independence compared to 55% achieving insulin independence with <600 000 IEQs infused (hazard ratio = 1.215, p = 0.035), regardless of the number of infusions. (Over the entire CITR period, of the 537 recipients, 31% received one infusion, 50% received two infusions and 17% received three infusions.) No other donor or islet product characteristics were related to this or any other clinical outcome including retention of insulin independence after achievement, or retention of fasting C-peptide >0.3 ng/mL (indicating a functioning graft).</p>
<fig id="fig02" position="float"><label>Figure 2</label>
<caption><p>Effect of total islet equivalents (1000 s) infused, over one to several infusions, on achievement of insulin independence (≥14 days) post–last infusion in clinical islet transplantation (hazard ratio = 1.215, p = 0.035; solid line: <600; dashes: 600 to <1000; dashes-dots: >1000).</p>
</caption>
<graphic xlink:href="ajt0014-2595-f2"></graphic>
</fig>
</sec>
</sec>
<sec sec-type="discussion"><title>Discussion</title>
<p>This report represents a comprehensive analysis of clinical-grade islet products from a total of 1017 isolations performed at CITR-participating North American, European and Australian centers. We found a significant increase in IEQs infused in the most recent era and that higher islet mass transplanted was independently associated with the clinical outcome of insulin independence rate. While there are some improvements in islet product criteria for islet transplantation, these criteria have been set so stringently high that it is not possible to compare clinical outcomes across low-, medium- and high-quality islet preparations, thus curtailing our ability to definitively state which specific product criteria influence clinical outcomes. Nonetheless, the improvements noted here in pancreatic islet yield and isolation in this duodecennium have paralleled the notable improvements in clinical outcomes of islet transplantation for the same period <xref rid="b14" ref-type="bibr">14</xref>
. Despite the strengths of this study including the largest collection of clinical islets for transplantation ever reported on, limitations are: nonuniformity of islet procurement and preparation methods across several nations in three continents and over a 12-year period; an estimated 80% availability of relevant data in the pertinent geographic regions and calendar time frame; a lack of low- to medium-quality islets for statistical comparison of outcomes.</p>
<p>Along with increasing IEQs infused by era, donor body weight, BMI and the frequency of steroid and insulin use in the last admission also showed significant gains by era <xref rid="b14" ref-type="bibr">14</xref>
. It is expected that higher body weight or BMI correlates with higher islet yield <xref rid="b1" ref-type="bibr">1</xref>
,<xref rid="b2" ref-type="bibr">2</xref>
,<xref rid="b4" ref-type="bibr">4</xref>
,<xref rid="b7" ref-type="bibr">7</xref>
,<xref rid="b11" ref-type="bibr">11</xref>
–<xref rid="b13" ref-type="bibr">13</xref>
. This could be due to increased islet mass <xref rid="b1" ref-type="bibr">1</xref>
,<xref rid="b11" ref-type="bibr">11</xref>
, larger islet size <xref rid="b11" ref-type="bibr">11</xref>
or more efficient digestion of fat-infiltrated pancreata <xref rid="b1" ref-type="bibr">1</xref>
. Some studies have found BMI to be a positive predictor of islet viability and insulin secretion <xref rid="b1" ref-type="bibr">1</xref>
,<xref rid="b16" ref-type="bibr">16</xref>
but we could not confirm those results here. Surprisingly, we found that as donor BMI rose, so did the infused endotoxin content. This could be a confounder of the data set in which endotoxin values were generally higher at North American sites, where average BMI has increased over time disproportionately to non-North American JDRF sites.</p>
<p>Reports on age-based yield effects in the literature have been mixed, associating younger donors with higher yields <xref rid="b9" ref-type="bibr">9</xref>
,<xref rid="b12" ref-type="bibr">12</xref>
,<xref rid="b13" ref-type="bibr">13</xref>
, lower yields <xref rid="b5" ref-type="bibr">5</xref>
or no effect <xref rid="b10" ref-type="bibr">10</xref>
. We found no direct correlation of donor age to IEQ-based measures. It is likely that the contradictory results of these studies are tied to varying degrees of postpurification recovery, as the correlation between young donor age and a high % of embedded islets, such as we observed here, is well established <xref rid="b2" ref-type="bibr">2</xref>
,<xref rid="b9" ref-type="bibr">9</xref>
,<xref rid="b12" ref-type="bibr">12</xref>
,<xref rid="b17" ref-type="bibr">17</xref>
,<xref rid="b18" ref-type="bibr">18</xref>
. A second confounding factor may be the variability in definition between “young” and “old.” Another study has instituted a maximum donor age of 50 years, which aligns with a recent observation that the most significant differences arise from segregating donor data above and below 45 years old <xref rid="b10" ref-type="bibr">10</xref>
. Given the clear benefits of lower donor age on islet functionality, future research efforts should focus on minimizing the loss of embedded islets during purification.</p>
<p>Apart from inherent donor characteristics, the data show a trend toward more intensive treatment—that is, more frequent use of steroids and insulin—during the terminal hospital stay, potentially representing recognition of benefits to subsequently donated tissue <xref rid="b7" ref-type="bibr">7</xref>
. Although some investigators have suggested that donor fluid resuscitation or blood transfusion may be detrimental to islet yield <xref rid="b6" ref-type="bibr">6</xref>
,<xref rid="b13" ref-type="bibr">13</xref>
, we found intraoperative transfusions correlated with higher IEQs at particle count. Donor steroid treatment pushed yields higher, which confirms similar results of an earlier study in which steroid use was associated with twice as many successful clinical isolations as nonsteroid treated donors <xref rid="b7" ref-type="bibr">7</xref>
. On the other hand, steroid use, in this investigation, was also correlated to reduced insulin and elevated endotoxin in the final islet product. The CITR database provided information on donor insulin treatment, which has not been previously considered as a clinical islet isolation variable. Nevertheless, we found that insulin use was correlated with higher beta cell/kg recipient. This finding is supported by preclinical research suggesting that insulin treatment can promote or maintain islet beta cell mass in rodents <xref rid="b19" ref-type="bibr">19</xref>
,<xref rid="b20" ref-type="bibr">20</xref>
. The impact of donor vasopressor treatment is unclear and has been correlated to reduced yield <xref rid="b2" ref-type="bibr">2</xref>
, elevated yield <xref rid="b7" ref-type="bibr">7</xref>
or no effect <xref rid="b9" ref-type="bibr">9</xref>
,<xref rid="b13" ref-type="bibr">13</xref>
. We found no significant impact of vasopressors on any of our outcome measures but it is conceivable that a more specific sub-categorization may be necessary to resolve this question.</p>
<p>Since its introduction more than two decades ago, TLM for packaging and transporting the pancreas to an isolation-capable facility has been vigorously debated. Early experiments on canine pancreata suggested that a bottom layer of oxygenated perfluorochemical could promote cellular respiration in otherwise ischemic tissue and thereby enhance the yield and viability of recovered islets <xref rid="b21" ref-type="bibr">21</xref>
,<xref rid="b22" ref-type="bibr">22</xref>
. Although clinical experiments initially supported these claims <xref rid="b23" ref-type="bibr">23</xref>
, a series of subsequent investigations found no benefit of TLM over simple UW cold storage <xref rid="b24" ref-type="bibr">24</xref>
–<xref rid="b28" ref-type="bibr">28</xref>
and modern literature reviews have tended to limit the benefits of TLM to long-distance travel <xref rid="b12" ref-type="bibr">12</xref>
,<xref rid="b29" ref-type="bibr">29</xref>
. The rise and fall of TLM popularity is reflected here in its peak usage between 2004 and 2006 with a significant decline into the modern era. We did not find any full group independent effects, but a small percentage (3%) of cases did see a benefit of TLM on total IEQs, potentially owing to longer transport conditions or to the increased attention and experience demanded of procurement staff to properly implement the technique. Given the cost and difficulty of the procedure and at least one study where TLM packaging was actively detrimental to postculture islet recovery <xref rid="b30" ref-type="bibr">30</xref>
, it seems appropriate that the trend toward simple cold storage continues. In that context, UW had historically dominated the choice of cold storage solution for the human pancreas but the less expensive histadine-tryptophan-ketoglutarate (HTK) has seen increasing use in North America. Several studies have reported no difference between UW and HTK on isolation outcome <xref rid="b1" ref-type="bibr">1</xref>
,<xref rid="b11" ref-type="bibr">11</xref>
,<xref rid="b25" ref-type="bibr">25</xref>
,<xref rid="b31" ref-type="bibr">31</xref>
but a few have correlated HTK use to diminished graft survival <xref rid="b32" ref-type="bibr">32</xref>
and reduced yield <xref rid="b13" ref-type="bibr">13</xref>
. The CITR data support the finding that HTK solution was associated with reduced islet viability and suggests that a thorough and specific analysis of HTK's influence on clinical outcomes is warranted.</p>
<p>Changes over time in postisolation processing seem largely focused on islet culture, which has increased dramatically in the last decade. Culturing islets provides a flexible time window for quality control testing, travel accommodations for recipients, recipient pretreatment with immunosuppression to avoid cytokine associated islet injury and the potential for storing or pooling islets for infusion into a compatible recipient <xref rid="b30" ref-type="bibr">30</xref>
,<xref rid="b33" ref-type="bibr">33</xref>
,<xref rid="b34" ref-type="bibr">34</xref>
. The benefits of culture to reducing immunogenicity have been known for some time <xref rid="b33" ref-type="bibr">33</xref>
,<xref rid="b35" ref-type="bibr">35</xref>
–<xref rid="b39" ref-type="bibr">39</xref>
but culturing has also been found to improve islet morphology, increase pellet purity and viability while reducing total tissue volume <xref rid="b30" ref-type="bibr">30</xref>
,<xref rid="b34" ref-type="bibr">34</xref>
. On the other hand, major islet losses can occur even over short periods <xref rid="b30" ref-type="bibr">30</xref>
,<xref rid="b33" ref-type="bibr">33</xref>
,<xref rid="b34" ref-type="bibr">34</xref>
as well as increased fragmentation <xref rid="b30" ref-type="bibr">30</xref>
,<xref rid="b33" ref-type="bibr">33</xref>
,<xref rid="b40" ref-type="bibr">40</xref>
,<xref rid="b41" ref-type="bibr">41</xref>
and diminished endocrine function <xref rid="b30" ref-type="bibr">30</xref>
,<xref rid="b33" ref-type="bibr">33</xref>
,<xref rid="b34" ref-type="bibr">34</xref>
. We found that a greater number of culture hours boosted yield and endocrine composition, although the average period here (∼18 h) was significantly shorter than the time periods examined in the studies listed. Whether an infusion of short-term cultured islets results in a better clinical outcome than freshly isolated islets still remains unresolved <xref rid="b33" ref-type="bibr">33</xref>
,<xref rid="b34" ref-type="bibr">34</xref>
. One promising future direction seems to be in the improvement of culture conditions to better promote islet survival and function. Fraker et al <xref rid="b42" ref-type="bibr">42</xref>
have recently developed a culturing device with a perfluorohydrocarbone-silicone membrane that maintains a more physiological oxygen supply to the islets, minimizing overnight losses and boosting viability.</p>
<p>The unavailability of Liberase HI for clinical digestion due to FDA recommendation in 2007, has led to major changes in isolation and transplant activity around the world. Numerous studies have examined the differences between Liberase and its most common replacement, Serva NB1, but results have been consistently contradictory. Compared to Liberase, NB1 has been found to improve yield <xref rid="b12" ref-type="bibr">12</xref>
,<xref rid="b16" ref-type="bibr">16</xref>
,<xref rid="b43" ref-type="bibr">43</xref>
, reduce yield <xref rid="b44" ref-type="bibr">44</xref>
, encourage viability and endocrine function <xref rid="b43" ref-type="bibr">43</xref>
,<xref rid="b44" ref-type="bibr">44</xref>
or diminish it <xref rid="b45" ref-type="bibr">45</xref>
, and to shorten digestion time <xref rid="b11" ref-type="bibr">11</xref>
,<xref rid="b16" ref-type="bibr">16</xref>
or prolong it <xref rid="b45" ref-type="bibr">45</xref>
. There does appear to be general agreement that Liberase results in higher endotoxin content <xref rid="b44" ref-type="bibr">44</xref>
–<xref rid="b46" ref-type="bibr">46</xref>
and less product purity <xref rid="b44" ref-type="bibr">44</xref>
than NB1, findings that we confirmed in this analysis. We also observed a clear differentiation on yield with Liberase and NB1 negatively and positively correlated to IEQ/particle ratio, respectively. Nevertheless, there is a growing trend towards the use of other digestion enzymes and combinations as various alternatives have become available. The University of Minnesota identified a higher proportion of intact C1 collagenase isoform in Liberase versus NB1, which could account for some of the negative reports on NB1 enzyme <xref rid="b47" ref-type="bibr">47</xref>
. It was subsequently shown that VitaCyte-HA collagenase contains the highest available intact C1 and when used in combination with NB1 neutral protease doubled the percentage of successful clinical islet isolations <xref rid="b47" ref-type="bibr">47</xref>
,<xref rid="b48" ref-type="bibr">48</xref>
.</p>
<p>Not surprisingly, the use of a discontinuous gradient for isopycnic density purification has almost disappeared, given the technical limitations of this system and its negative impact on yield <xref rid="b49" ref-type="bibr">49</xref>
,<xref rid="b50" ref-type="bibr">50</xref>
. Accordingly, we correlated a continuous gradient to higher particle count but more interestingly, we found that the use of a discontinuous gradient appeared to increase the beta cell content of the final product. This finding is consistent with another study showing improved islet morphology <xref rid="b4" ref-type="bibr">4</xref>
to suggest that an investigation of the circumstantial benefits of discontinuous gradient purification may be warranted before the technique is altogether abandoned. On the other hand, the necessity of any purification procedure continues to be debated, especially given the difficulty in obtaining critical minimum islet mass from deceased donors and the reported success of nonpurified islets in autologous islet transplant recipients <xref rid="b51" ref-type="bibr">51</xref>
.</p>
<p>Major differences of the present study from previous reports of pancreatic islet isolation include analysis of only clinical-grade islet products, changes over time and data reported from multiple countries on three different continents. Kaddis et al reported their analyses on donor and isolation characteristics of both clinical and research grade islets based on collaboration of multiple islet centers in North America (n of isolations = 1023), revealing that donor age, BMI, CIT, liver/pancreas enzyme, pancreas appearance and preservation method were independently related to islet isolation success <xref rid="b13" ref-type="bibr">13</xref>
,<xref rid="b52" ref-type="bibr">52</xref>
. In the present study focusing on clinical-grade islet products, the primary end point of islet yield was correlated with donor BMI, steroid therapy at terminal hospital stay, hours between death and cross-clamp, number of donors and continent. These findings confirm that donor and/or selection criteria for clinical isolation are well established.</p>
<p>Overall, findings in the present report with regard to donor characteristics of age and BMI are in agreement with previously published results. Evidence continues to build that simple cold storage in UW solution may be the best packaging method if applied with due care but the benefits of a postisolation culture period may be outweighed by losses if more physiological culture conditions are not developed and adopted. The debate over Serva NB1 as a substitute for Liberase HI continues but although the present results suggest general benefits from using NB1, the movement toward alternate enzymes and combinations may soon render this argument moot. Finally, purification technique seems to warrant additional study both to improve the recovery of high-functioning but frequently embedded islets from young donors and to evaluate whether some surprising viability benefits of a discontinuous density gradient justify the use of this procedure in specific situations.</p>
<p>Future directions to improve islet isolation outcomes include modification of pancreas preservation <xref rid="b53" ref-type="bibr">53</xref>
, development of new combinations of collagenase or neutral protease <xref rid="b48" ref-type="bibr">48</xref>
, optimization of digestion <xref rid="b54" ref-type="bibr">54</xref>
,<xref rid="b55" ref-type="bibr">55</xref>
and enhancing purification <xref rid="b56" ref-type="bibr">56</xref>
. Attempts to measure islet quantity and quality in objective ways such as digital image analysis, oxygen consumption rate and islet biomarkers should translate into improved clinical efficacy through more precise data analysis <xref rid="b24" ref-type="bibr">24</xref>
,<xref rid="b57" ref-type="bibr">57</xref>
,<xref rid="b58" ref-type="bibr">58</xref>
. The CITR should continue capturing these developments and trends. The ultimate success of any islet isolation and transplantation is, of course, in the benefit to the recipient. The range of measures pertaining to transplant outcome such as euglycemia will be the subject of a forthcoming analysis.</p>
</sec>
</body>
<back><ack><p>The CITR is funded by the NIDDK, National Institutes of Health and by a supplemental grant from the JDRF International. Additional data were made available through cooperative agreements with the U.S. United Network for Organ Sharing (UNOS), Alexandria, Virginia, the Administrative and Bioinformatics Coordinating Center of the City of Hope, Duarte, California (1999–2009) and the NIDDK-sponsored CIT (<ext-link ext-link-type="uri" xlink:href="http://www.citisletstudy.org">www.citisletstudy.org</ext-link>
), coordinated by the University of Iowa Clinical Trials and Data Management Center (2008–present).</p>
</ack>
<sec><title>Disclosure</title>
<p>The authors of this manuscript have no conflicts of interest to disclose as described by the <italic>American Journal of Transplantation</italic>
.</p>
</sec>
<ref-list><title>References</title>
<ref id="b1"><label>1</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brandhorst</surname>
<given-names>H</given-names>
</name>
<name><surname>Brandhorst</surname>
<given-names>D</given-names>
</name>
<name><surname>Hering</surname>
<given-names>BJ</given-names>
</name>
<name><surname>Federlin</surname>
<given-names>K</given-names>
</name>
<name><surname>Bretzel</surname>
<given-names>RG</given-names>
</name>
</person-group>
<article-title>Body mass index of pancreatic donors: A decisive factor for human islet isolation</article-title>
<source>Exp Clin Endocrinol Diabetes</source>
<year>1995</year>
<volume>103</volume>
<fpage>23</fpage>
<lpage>26</lpage>
<comment>(Suppl 2)</comment>
<pub-id pub-id-type="pmid">8839248</pub-id>
</element-citation>
</ref>
<ref id="b2"><label>2</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lakey</surname>
<given-names>JR</given-names>
</name>
<name><surname>Warnock</surname>
<given-names>GL</given-names>
</name>
<name><surname>Rajotte</surname>
<given-names>RV</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Variables in organ donors that affect the recovery of human islets of Langerhans</article-title>
<source>Transplantation</source>
<year>1996</year>
<volume>61</volume>
<fpage>1047</fpage>
<lpage>1053</lpage>
<pub-id pub-id-type="pmid">8623183</pub-id>
</element-citation>
</ref>
<ref id="b3"><label>3</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Goto</surname>
<given-names>M</given-names>
</name>
<name><surname>Johansson</surname>
<given-names>U</given-names>
</name>
<name><surname>Eich</surname>
<given-names>TM</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Key factors for human islet isolation and clinical transplantation</article-title>
<source>Transplant Proc</source>
<year>2005</year>
<volume>37</volume>
<fpage>1315</fpage>
<lpage>1316</lpage>
<pub-id pub-id-type="pmid">15848708</pub-id>
</element-citation>
</ref>
<ref id="b4"><label>4</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nano</surname>
<given-names>R</given-names>
</name>
<name><surname>Clissi</surname>
<given-names>B</given-names>
</name>
<name><surname>Melzi</surname>
<given-names>R</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Islet isolation for allotransplantation: Variables associated with successful islet yield and graft function</article-title>
<source>Diabetologia</source>
<year>2005</year>
<volume>48</volume>
<fpage>906</fpage>
<lpage>912</lpage>
<pub-id pub-id-type="pmid">15830183</pub-id>
</element-citation>
</ref>
<ref id="b5"><label>5</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname>
<given-names>SC</given-names>
</name>
<name><surname>Han</surname>
<given-names>DJ</given-names>
</name>
<name><surname>Kang</surname>
<given-names>CH</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Analysis on donor and isolation-related factors of successful isolation of human islet of Langerhans from human cadaveric donors</article-title>
<source>Transplant Proc</source>
<year>2005</year>
<volume>37</volume>
<fpage>3402</fpage>
<lpage>3403</lpage>
<pub-id pub-id-type="pmid">16298607</pub-id>
</element-citation>
</ref>
<ref id="b6"><label>6</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>O'Gorman</surname>
<given-names>D</given-names>
</name>
<name><surname>Kin</surname>
<given-names>T</given-names>
</name>
<name><surname>Murdoch</surname>
<given-names>T</given-names>
</name>
<etal></etal>
</person-group>
<article-title>The standardization of pancreatic donors for islet isolations</article-title>
<source>Transplantation</source>
<year>2005</year>
<volume>80</volume>
<fpage>801</fpage>
<lpage>806</lpage>
<pub-id pub-id-type="pmid">16210968</pub-id>
</element-citation>
</ref>
<ref id="b7"><label>7</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ponte</surname>
<given-names>GM</given-names>
</name>
<name><surname>Pileggi</surname>
<given-names>A</given-names>
</name>
<name><surname>Messinger</surname>
<given-names>S</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Toward maximizing the success rates of human islet isolation: Influence of donor and isolation factors</article-title>
<source>Cell Transplant</source>
<year>2007</year>
<volume>16</volume>
<fpage>595</fpage>
<lpage>607</lpage>
<pub-id pub-id-type="pmid">17912951</pub-id>
</element-citation>
</ref>
<ref id="b8"><label>8</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Koh</surname>
<given-names>A</given-names>
</name>
<name><surname>Kin</surname>
<given-names>T</given-names>
</name>
<name><surname>Imes</surname>
<given-names>S</given-names>
</name>
<name><surname>Shapiro</surname>
<given-names>AM</given-names>
</name>
<name><surname>Senior</surname>
<given-names>P</given-names>
</name>
</person-group>
<article-title>Islets isolated from donors with elevated HbA1c can be successfully transplanted</article-title>
<source>Transplantation</source>
<year>2008</year>
<volume>86</volume>
<fpage>1622</fpage>
<lpage>1624</lpage>
<pub-id pub-id-type="pmid">19077899</pub-id>
</element-citation>
</ref>
<ref id="b9"><label>9</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liu</surname>
<given-names>X</given-names>
</name>
<name><surname>Matsumoto</surname>
<given-names>S</given-names>
</name>
<name><surname>Okitsu</surname>
<given-names>T</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Analysis of donor- and isolation-related variables from non-heart-beating donors (NHBDs) using the Kyoto islet isolation method</article-title>
<source>Cell Transplant</source>
<year>2008</year>
<volume>17</volume>
<fpage>649</fpage>
<lpage>656</lpage>
<pub-id pub-id-type="pmid">18819253</pub-id>
</element-citation>
</ref>
<ref id="b10"><label>10</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Niclauss</surname>
<given-names>N</given-names>
</name>
<name><surname>Bosco</surname>
<given-names>D</given-names>
</name>
<name><surname>Morel</surname>
<given-names>P</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Influence of donor age on islet isolation and transplantation outcome</article-title>
<source>Transplantation</source>
<year>2011</year>
<volume>91</volume>
<fpage>360</fpage>
<lpage>366</lpage>
<pub-id pub-id-type="pmid">21344706</pub-id>
</element-citation>
</ref>
<ref id="b11"><label>11</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname>
<given-names>Y</given-names>
</name>
<name><surname>Daneilson</surname>
<given-names>KK</given-names>
</name>
<name><surname>Ropski</surname>
<given-names>A</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Systematic analysis of donor and isolation factor's impact on human islet yield and size distribution</article-title>
<source>Cell Transplant</source>
<year>2013</year>
<volume>22</volume>
<fpage>2323</fpage>
<lpage>2333</lpage>
<pub-id pub-id-type="pmid">23363652</pub-id>
</element-citation>
</ref>
<ref id="b12"><label>12</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hilling</surname>
<given-names>DE</given-names>
</name>
<name><surname>Bouwman</surname>
<given-names>E</given-names>
</name>
<name><surname>Terpstra</surname>
<given-names>OT</given-names>
</name>
<name><surname>Marang-van de Mheen</surname>
<given-names>PJ</given-names>
</name>
</person-group>
<article-title>Effects of donor-, pancreas-, and isolation-related variables on human islet isolation outcome: A systematic review</article-title>
<source>Cell Transplant</source>
<year>2014</year>
<volume>23</volume>
<fpage>921</fpage>
<lpage>928</lpage>
<pub-id pub-id-type="pmid">23635354</pub-id>
</element-citation>
</ref>
<ref id="b13"><label>13</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kaddis</surname>
<given-names>JS</given-names>
</name>
<name><surname>Danobeitia</surname>
<given-names>JS</given-names>
</name>
<name><surname>Niland</surname>
<given-names>JC</given-names>
</name>
<name><surname>Stiller</surname>
<given-names>T</given-names>
</name>
<name><surname>Fernandez</surname>
<given-names>LA</given-names>
</name>
</person-group>
<article-title>Multicenter analysis of novel and established variables associated with successful human islet isolation outcomes</article-title>
<source>Am J Transplant</source>
<year>2010</year>
<volume>10</volume>
<fpage>646</fpage>
<lpage>656</lpage>
<pub-id pub-id-type="pmid">20055802</pub-id>
</element-citation>
</ref>
<ref id="b14"><label>14</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barton</surname>
<given-names>FB</given-names>
</name>
<name><surname>Rickels</surname>
<given-names>MR</given-names>
</name>
<name><surname>Alejandro</surname>
<given-names>R</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Improvement in outcomes of clinical islet transplantation: 1999–2010</article-title>
<source>Diabetes Care</source>
<year>2012</year>
<volume>35</volume>
<fpage>1436</fpage>
<lpage>1445</lpage>
<pub-id pub-id-type="pmid">22723582</pub-id>
</element-citation>
</ref>
<ref id="b15"><label>15</label>
<element-citation publication-type="other"><person-group person-group-type="author"><name><surname>Center</surname>
<given-names>CC</given-names>
</name>
</person-group>
<article-title>Seventh annual report of the Collaborative Islet Transplant Registry</article-title>
<year>2011</year>
<comment>Available at: <ext-link ext-link-type="uri" xlink:href="http://www.citregistry.org/">http://www.citregistry.org/</ext-link>
. Accessed February 12, 2014</comment>
</element-citation>
</ref>
<ref id="b16"><label>16</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sabek</surname>
<given-names>OM</given-names>
</name>
<name><surname>Cowan</surname>
<given-names>P</given-names>
</name>
<name><surname>Fraga</surname>
<given-names>DW</given-names>
</name>
<name><surname>Gaber</surname>
<given-names>AO</given-names>
</name>
</person-group>
<article-title>The effect of isolation methods and the use of different enzymes on islet yield and in vivo function</article-title>
<source>Cell Transplant</source>
<year>2008</year>
<volume>17</volume>
<fpage>785</fpage>
<lpage>792</lpage>
<pub-id pub-id-type="pmid">19044205</pub-id>
</element-citation>
</ref>
<ref id="b17"><label>17</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Socci</surname>
<given-names>C</given-names>
</name>
<name><surname>Davalli</surname>
<given-names>AM</given-names>
</name>
<name><surname>Vignali</surname>
<given-names>A</given-names>
</name>
<etal></etal>
</person-group>
<article-title>A significant increase of islet yield by early injection of collagenase into the pancreatic duct of young donors</article-title>
<source>Transplantation</source>
<year>1993</year>
<volume>55</volume>
<fpage>661</fpage>
<lpage>663</lpage>
<pub-id pub-id-type="pmid">8456488</pub-id>
</element-citation>
</ref>
<ref id="b18"><label>18</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ricordi</surname>
<given-names>C</given-names>
</name>
</person-group>
<article-title>Islet transplantation: A brave new world</article-title>
<source>Diabetes</source>
<year>2003</year>
<volume>52</volume>
<fpage>1595</fpage>
<lpage>1603</lpage>
<pub-id pub-id-type="pmid">12829621</pub-id>
</element-citation>
</ref>
<ref id="b19"><label>19</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Movassat</surname>
<given-names>J</given-names>
</name>
<name><surname>Saulnier</surname>
<given-names>C</given-names>
</name>
<name><surname>Portha</surname>
<given-names>B</given-names>
</name>
</person-group>
<article-title>Insulin administration enhances growth of the beta-cell mass in streptozotocin-treated newborn rats</article-title>
<source>Diabetes</source>
<year>1997</year>
<volume>46</volume>
<fpage>1445</fpage>
<lpage>1452</lpage>
<pub-id pub-id-type="pmid">9287045</pub-id>
</element-citation>
</ref>
<ref id="b20"><label>20</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kitamura</surname>
<given-names>T</given-names>
</name>
<name><surname>Nakae</surname>
<given-names>J</given-names>
</name>
<name><surname>Kitamura</surname>
<given-names>Y</given-names>
</name>
<etal></etal>
</person-group>
<article-title>The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth</article-title>
<source>J Clin Invest</source>
<year>2002</year>
<volume>110</volume>
<fpage>1839</fpage>
<lpage>1847</lpage>
<pub-id pub-id-type="pmid">12488434</pub-id>
</element-citation>
</ref>
<ref id="b21"><label>21</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kuroda</surname>
<given-names>Y</given-names>
</name>
<name><surname>Kawamura</surname>
<given-names>T</given-names>
</name>
<name><surname>Suzuki</surname>
<given-names>Y</given-names>
</name>
<name><surname>Fujiwara</surname>
<given-names>H</given-names>
</name>
<name><surname>Yamamoto</surname>
<given-names>K</given-names>
</name>
<name><surname>Saitoh</surname>
<given-names>Y</given-names>
</name>
</person-group>
<article-title>A new, simple method for cold storage of the pancreas using perfluorochemical</article-title>
<source>Transplantation</source>
<year>1988</year>
<volume>46</volume>
<fpage>457</fpage>
<lpage>460</lpage>
<pub-id pub-id-type="pmid">3047936</pub-id>
</element-citation>
</ref>
<ref id="b22"><label>22</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tanioka</surname>
<given-names>Y</given-names>
</name>
<name><surname>Sutherland</surname>
<given-names>DE</given-names>
</name>
<name><surname>Kuroda</surname>
<given-names>Y</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Excellence of the two-layer method (University of Wisconsin solution/perfluorochemical) in pancreas preservation before islet isolation</article-title>
<source>Surgery</source>
<year>1997</year>
<volume>122</volume>
<fpage>435</fpage>
<lpage>441</lpage>
<comment>discussion 441–432</comment>
<pub-id pub-id-type="pmid">9288151</pub-id>
</element-citation>
</ref>
<ref id="b23"><label>23</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Matsumoto</surname>
<given-names>S</given-names>
</name>
<name><surname>Rigley</surname>
<given-names>TH</given-names>
</name>
<name><surname>Qualley</surname>
<given-names>SA</given-names>
</name>
<name><surname>Kuroda</surname>
<given-names>Y</given-names>
</name>
<name><surname>Reems</surname>
<given-names>JA</given-names>
</name>
<name><surname>Stevens</surname>
<given-names>RB</given-names>
</name>
</person-group>
<article-title>Efficacy of the oxygen-charged static two-layer method for short-term pancreas preservation and islet isolation from nonhuman primate and human pancreata</article-title>
<source>Cell Transplant</source>
<year>2002</year>
<volume>11</volume>
<fpage>769</fpage>
<lpage>777</lpage>
<pub-id pub-id-type="pmid">12588109</pub-id>
</element-citation>
</ref>
<ref id="b24"><label>24</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Papas</surname>
<given-names>KK</given-names>
</name>
<name><surname>Colton</surname>
<given-names>CK</given-names>
</name>
<name><surname>Nelson</surname>
<given-names>RA</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Human islet oxygen consumption rate and DNA measurements predict diabetes reversal in nude mice</article-title>
<source>Am J Transplant</source>
<year>2007</year>
<volume>7</volume>
<fpage>707</fpage>
<lpage>713</lpage>
<pub-id pub-id-type="pmid">17229069</pub-id>
</element-citation>
</ref>
<ref id="b25"><label>25</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Noguchi</surname>
<given-names>H</given-names>
</name>
<name><surname>Ueda</surname>
<given-names>M</given-names>
</name>
<name><surname>Hayashi</surname>
<given-names>S</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Comparison of M-Kyoto solution and histidine-tryptophan-ketoglutarate solution with a trypsin inhibitor for pancreas preservation in islet transplantation</article-title>
<source>Transplantation</source>
<year>2007</year>
<volume>84</volume>
<fpage>655</fpage>
<lpage>658</lpage>
<pub-id pub-id-type="pmid">17876281</pub-id>
</element-citation>
</ref>
<ref id="b26"><label>26</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Matsumoto</surname>
<given-names>S</given-names>
</name>
<name><surname>Noguchi</surname>
<given-names>H</given-names>
</name>
<name><surname>Hatanaka</surname>
<given-names>N</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Estimation of donor usability for islet transplantation in the United States with the Kyoto islet isolation method</article-title>
<source>Cell Transplant</source>
<year>2009</year>
<volume>18</volume>
<fpage>549</fpage>
<lpage>556</lpage>
<pub-id pub-id-type="pmid">19775516</pub-id>
</element-citation>
</ref>
<ref id="b27"><label>27</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kin</surname>
<given-names>T</given-names>
</name>
<name><surname>Mirbolooki</surname>
<given-names>M</given-names>
</name>
<name><surname>Salehi</surname>
<given-names>P</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Islet isolation and transplantation outcomes of pancreas preserved with University of Wisconsin solution versus two-layer method using preoxygenated perfluorocarbon</article-title>
<source>Transplantation</source>
<year>2006</year>
<volume>82</volume>
<fpage>1286</fpage>
<lpage>1290</lpage>
<pub-id pub-id-type="pmid">17130776</pub-id>
</element-citation>
</ref>
<ref id="b28"><label>28</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Caballero-Corbalán</surname>
<given-names>J</given-names>
</name>
<name><surname>Eich</surname>
<given-names>T</given-names>
</name>
<name><surname>Lundgren</surname>
<given-names>T</given-names>
</name>
<etal></etal>
</person-group>
<article-title>No beneficial effect of two-layer storage compared with UW-storage on human islet isolation and transplantation</article-title>
<source>Transplantation</source>
<year>2007</year>
<volume>84</volume>
<fpage>864</fpage>
<lpage>869</lpage>
<pub-id pub-id-type="pmid">17984839</pub-id>
</element-citation>
</ref>
<ref id="b29"><label>29</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Qin</surname>
<given-names>H</given-names>
</name>
<name><surname>Matsumoto</surname>
<given-names>S</given-names>
</name>
<name><surname>Klintmalm</surname>
<given-names>GB</given-names>
</name>
<name><surname>De Vol</surname>
<given-names>EB</given-names>
</name>
</person-group>
<article-title>A meta-analysis for comparison of the two-layer and university of Wisconsin pancreas preservation methods in islet transplantation</article-title>
<source>Cell Transplant</source>
<year>2011</year>
<volume>20</volume>
<fpage>1127</fpage>
<lpage>1137</lpage>
<pub-id pub-id-type="pmid">21092403</pub-id>
</element-citation>
</ref>
<ref id="b30"><label>30</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kin</surname>
<given-names>T</given-names>
</name>
<name><surname>Senior</surname>
<given-names>P</given-names>
</name>
<name><surname>O'Gorman</surname>
<given-names>D</given-names>
</name>
<name><surname>Richer</surname>
<given-names>B</given-names>
</name>
<name><surname>Salam</surname>
<given-names>A</given-names>
</name>
<name><surname>Shapiro</surname>
<given-names>AM</given-names>
</name>
</person-group>
<article-title>Risk factors for islet loss during culture prior to transplantation</article-title>
<source>Transpl Int</source>
<year>2008</year>
<volume>21</volume>
<fpage>1029</fpage>
<lpage>1035</lpage>
<pub-id pub-id-type="pmid">18564983</pub-id>
</element-citation>
</ref>
<ref id="b31"><label>31</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Salehi</surname>
<given-names>P</given-names>
</name>
<name><surname>Hansen</surname>
<given-names>MA</given-names>
</name>
<name><surname>Avila</surname>
<given-names>JG</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Human islet isolation outcomes from pancreata preserved with histidine-tryptophan ketoglutarate versus University of Wisconsin solution</article-title>
<source>Transplantation</source>
<year>2006</year>
<volume>82</volume>
<fpage>983</fpage>
<lpage>985</lpage>
<pub-id pub-id-type="pmid">17038916</pub-id>
</element-citation>
</ref>
<ref id="b32"><label>32</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stewart</surname>
<given-names>ZA</given-names>
</name>
<name><surname>Cameron</surname>
<given-names>AM</given-names>
</name>
<name><surname>Singer</surname>
<given-names>AL</given-names>
</name>
<name><surname>Dagher</surname>
<given-names>NN</given-names>
</name>
<name><surname>Montgomery</surname>
<given-names>RA</given-names>
</name>
<name><surname>Segev</surname>
<given-names>DL</given-names>
</name>
</person-group>
<article-title>Histidine-tryptophan-ketoglutarate (HTK) is associated with reduced graft survival in pancreas transplantation</article-title>
<source>Am J Transplant</source>
<year>2009</year>
<volume>9</volume>
<fpage>217</fpage>
<lpage>221</lpage>
<pub-id pub-id-type="pmid">18986383</pub-id>
</element-citation>
</ref>
<ref id="b33"><label>33</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gaber</surname>
<given-names>AO</given-names>
</name>
<name><surname>Fraga</surname>
<given-names>DW</given-names>
</name>
<name><surname>Callicutt</surname>
<given-names>CS</given-names>
</name>
<name><surname>Gerling</surname>
<given-names>IC</given-names>
</name>
<name><surname>Sabek</surname>
<given-names>OM</given-names>
</name>
<name><surname>Kotb</surname>
<given-names>MY</given-names>
</name>
</person-group>
<article-title>Improved in vivo pancreatic islet function after prolonged in vitro islet culture</article-title>
<source>Transplantation</source>
<year>2001</year>
<volume>72</volume>
<fpage>1730</fpage>
<lpage>1736</lpage>
<pub-id pub-id-type="pmid">11740381</pub-id>
</element-citation>
</ref>
<ref id="b34"><label>34</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Noguchi</surname>
<given-names>H</given-names>
</name>
<name><surname>Naziruddin</surname>
<given-names>B</given-names>
</name>
<name><surname>Jackson</surname>
<given-names>A</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Fresh islets are more effective for islet transplantation than cultured islets</article-title>
<source>Cell Transplant</source>
<year>2012</year>
<volume>21</volume>
<fpage>517</fpage>
<lpage>523</lpage>
<pub-id pub-id-type="pmid">22793060</pub-id>
</element-citation>
</ref>
<ref id="b35"><label>35</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kedinger</surname>
<given-names>M</given-names>
</name>
<name><surname>Haffen</surname>
<given-names>K</given-names>
</name>
<name><surname>Grenier</surname>
<given-names>J</given-names>
</name>
<name><surname>Eloy</surname>
<given-names>R</given-names>
</name>
</person-group>
<article-title>In vitro culture reduces immunogenicity of pancreatic endocrine islets</article-title>
<source>Nature</source>
<year>1977</year>
<volume>270</volume>
<fpage>736</fpage>
<lpage>738</lpage>
<pub-id pub-id-type="pmid">413059</pub-id>
</element-citation>
</ref>
<ref id="b36"><label>36</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lacy</surname>
<given-names>PE</given-names>
</name>
<name><surname>Davie</surname>
<given-names>JM</given-names>
</name>
<name><surname>Finke</surname>
<given-names>EH</given-names>
</name>
</person-group>
<article-title>Prolongation of islet allograft survival following in vitro culture (24 degrees C) and a single injection of ALS</article-title>
<source>Science</source>
<year>1979</year>
<volume>204</volume>
<fpage>312</fpage>
<lpage>313</lpage>
<pub-id pub-id-type="pmid">107588</pub-id>
</element-citation>
</ref>
<ref id="b37"><label>37</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lafferty</surname>
<given-names>KJ</given-names>
</name>
<name><surname>Prowse</surname>
<given-names>SJ</given-names>
</name>
<name><surname>Simeonovic</surname>
<given-names>CJ</given-names>
</name>
<name><surname>Warren</surname>
<given-names>HS</given-names>
</name>
</person-group>
<article-title>Immunobiology of tissue transplantation: A return to the passenger leukocyte concept</article-title>
<source>Annu Rev Immunol</source>
<year>1983</year>
<volume>1</volume>
<fpage>143</fpage>
<lpage>173</lpage>
<pub-id pub-id-type="pmid">6443557</pub-id>
</element-citation>
</ref>
<ref id="b38"><label>38</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cosimi</surname>
<given-names>S</given-names>
</name>
<name><surname>Marchetti</surname>
<given-names>P</given-names>
</name>
<name><surname>Giannarelli</surname>
<given-names>R</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Preparation and long-term storage by culture or cryopreservation of purified bovine pancreatic islets</article-title>
<source>Transplant Proc</source>
<year>1995</year>
<volume>27</volume>
<fpage>3355</fpage>
<pub-id pub-id-type="pmid">8539992</pub-id>
</element-citation>
</ref>
<ref id="b39"><label>39</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Markmann</surname>
<given-names>JF</given-names>
</name>
<name><surname>Tomaszewski</surname>
<given-names>J</given-names>
</name>
<name><surname>Posselt</surname>
<given-names>AM</given-names>
</name>
<etal></etal>
</person-group>
<article-title>The effect of islet cell culture in vitro at 24 degrees C on graft survival and MHC antigen expression</article-title>
<source>Transplantation</source>
<year>1990</year>
<volume>49</volume>
<fpage>272</fpage>
<lpage>277</lpage>
<pub-id pub-id-type="pmid">2106179</pub-id>
</element-citation>
</ref>
<ref id="b40"><label>40</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brendel</surname>
<given-names>MD</given-names>
</name>
<name><surname>Kong</surname>
<given-names>SS</given-names>
</name>
<name><surname>Alejandro</surname>
<given-names>R</given-names>
</name>
<name><surname>Mintz</surname>
<given-names>DH</given-names>
</name>
</person-group>
<article-title>Improved functional survival of human islets of Langerhans in three-dimensional matrix culture</article-title>
<source>Cell Transplant</source>
<year>1994</year>
<volume>3</volume>
<fpage>427</fpage>
<lpage>435</lpage>
<pub-id pub-id-type="pmid">7827781</pub-id>
</element-citation>
</ref>
<ref id="b41"><label>41</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Korbutt</surname>
<given-names>GS</given-names>
</name>
<name><surname>Pipeleers</surname>
<given-names>DG</given-names>
</name>
</person-group>
<article-title>Cold-preservation of pancreatic beta cells</article-title>
<source>Cell Transplant</source>
<year>1994</year>
<volume>3</volume>
<fpage>291</fpage>
<lpage>297</lpage>
<pub-id pub-id-type="pmid">7921634</pub-id>
</element-citation>
</ref>
<ref id="b42"><label>42</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fraker</surname>
<given-names>CA</given-names>
</name>
<name><surname>Cechin</surname>
<given-names>S</given-names>
</name>
<name><surname>Alvarez-Cubela</surname>
<given-names>S</given-names>
</name>
<etal></etal>
</person-group>
<article-title>A physiological pattern of oxygenation using perfluorocarbon-based culture devices maximizes pancreatic islet viability and enhances beta-cell function</article-title>
<source>Cell Transplant</source>
<year>2013</year>
<volume>22</volume>
<fpage>1723</fpage>
<lpage>1733</lpage>
<pub-id pub-id-type="pmid">23068091</pub-id>
</element-citation>
</ref>
<ref id="b43"><label>43</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bucher</surname>
<given-names>P</given-names>
</name>
<name><surname>Mathe</surname>
<given-names>Z</given-names>
</name>
<name><surname>Bosco</surname>
<given-names>D</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Serva collagenase N B1: A new enzyme preparation for human islet isolation</article-title>
<source>Transplant Proc</source>
<year>2004</year>
<volume>36</volume>
<fpage>1143</fpage>
<lpage>1144</lpage>
<pub-id pub-id-type="pmid">15194398</pub-id>
</element-citation>
</ref>
<ref id="b44"><label>44</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brandhorst</surname>
<given-names>H</given-names>
</name>
<name><surname>Friberg</surname>
<given-names>A</given-names>
</name>
<name><surname>Nilsson</surname>
<given-names>B</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Large-scale comparison of Liberase HI and collagenase NB1 utilized for human islet isolation</article-title>
<source>Cell Transplant</source>
<year>2010</year>
<volume>19</volume>
<fpage>3</fpage>
<lpage>8</lpage>
<pub-id pub-id-type="pmid">19818208</pub-id>
</element-citation>
</ref>
<ref id="b45"><label>45</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Iglesias</surname>
<given-names>I</given-names>
</name>
<name><surname>Valiente</surname>
<given-names>L</given-names>
</name>
<name><surname>Shiang</surname>
<given-names>KD</given-names>
</name>
<name><surname>Ichii</surname>
<given-names>H</given-names>
</name>
<name><surname>Kandeel</surname>
<given-names>F</given-names>
</name>
<name><surname>Al-Abdullah</surname>
<given-names>IH</given-names>
</name>
</person-group>
<article-title>The effects of digestion enzymes on islet viability and cellular composition</article-title>
<source>Cell Transplant</source>
<year>2012</year>
<volume>21</volume>
<fpage>649</fpage>
<lpage>655</lpage>
<pub-id pub-id-type="pmid">22236690</pub-id>
</element-citation>
</ref>
<ref id="b46"><label>46</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Balamurugan</surname>
<given-names>AN</given-names>
</name>
<name><surname>He</surname>
<given-names>J</given-names>
</name>
<name><surname>Guo</surname>
<given-names>F</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Harmful delayed effects of exogenous isolation enzymes on isolated human islets: Relevance to clinical transplantation</article-title>
<source>Am J Transplant</source>
<year>2005</year>
<volume>5</volume>
<fpage>2671</fpage>
<lpage>2681</lpage>
<pub-id pub-id-type="pmid">16212626</pub-id>
</element-citation>
</ref>
<ref id="b47"><label>47</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Balamurugan</surname>
<given-names>AN</given-names>
</name>
<name><surname>Breite</surname>
<given-names>AG</given-names>
</name>
<name><surname>Anazawa</surname>
<given-names>T</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Successful human islet isolation and transplantation indicating the importance of class 1 collagenase and collagen degradation activity assay</article-title>
<source>Transplantation</source>
<year>2010</year>
<volume>89</volume>
<fpage>954</fpage>
<lpage>961</lpage>
<pub-id pub-id-type="pmid">20300051</pub-id>
</element-citation>
</ref>
<ref id="b48"><label>48</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Balamurugan</surname>
<given-names>AN</given-names>
</name>
<name><surname>Loganathan</surname>
<given-names>G</given-names>
</name>
<name><surname>Bellin</surname>
<given-names>MD</given-names>
</name>
<etal></etal>
</person-group>
<article-title>A new enzyme mixture to increase the yield and transplant rate of autologous and allogeneic human islet products</article-title>
<source>Transplantation</source>
<year>2012</year>
<volume>93</volume>
<fpage>693</fpage>
<lpage>702</lpage>
<pub-id pub-id-type="pmid">22318245</pub-id>
</element-citation>
</ref>
<ref id="b49"><label>49</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Robertson</surname>
<given-names>GS</given-names>
</name>
<name><surname>Chadwick</surname>
<given-names>DR</given-names>
</name>
<name><surname>Contractor</surname>
<given-names>H</given-names>
</name>
<name><surname>James</surname>
<given-names>RF</given-names>
</name>
<name><surname>London</surname>
<given-names>NJ</given-names>
</name>
</person-group>
<article-title>The optimization of large-scale density gradient isolation of human islets</article-title>
<source>Acta Diabetol</source>
<year>1993</year>
<volume>30</volume>
<fpage>93</fpage>
<lpage>98</lpage>
<pub-id pub-id-type="pmid">8219265</pub-id>
</element-citation>
</ref>
<ref id="b50"><label>50</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wei</surname>
<given-names>GH</given-names>
</name>
<name><surname>Sun</surname>
<given-names>WP</given-names>
</name>
<name><surname>Zhang</surname>
<given-names>J</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Comparison of continuous and discontinuous density gradient centrifugation for purification of human pancreatic islets</article-title>
<source>Nan Fang Yi Ke Da Xue Xue Bao</source>
<year>2007</year>
<volume>27</volume>
<fpage>1352</fpage>
<lpage>1354</lpage>
<pub-id pub-id-type="pmid">17884776</pub-id>
</element-citation>
</ref>
<ref id="b51"><label>51</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Webb</surname>
<given-names>MA</given-names>
</name>
<name><surname>Dennison</surname>
<given-names>AR</given-names>
</name>
<name><surname>James</surname>
<given-names>RF</given-names>
</name>
</person-group>
<article-title>The potential benefit of non-purified islets preparations for islet transplantation</article-title>
<source>Biotechnol Genet Eng Rev</source>
<year>2012</year>
<volume>28</volume>
<fpage>101</fpage>
<lpage>114</lpage>
<pub-id pub-id-type="pmid">22616483</pub-id>
</element-citation>
</ref>
<ref id="b52"><label>52</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kaddis</surname>
<given-names>JS</given-names>
</name>
<name><surname>Olack</surname>
<given-names>BJ</given-names>
</name>
<name><surname>Sowinski</surname>
<given-names>J</given-names>
</name>
<name><surname>Cravens</surname>
<given-names>J</given-names>
</name>
<name><surname>Contreras</surname>
<given-names>JL</given-names>
</name>
<name><surname>Niland</surname>
<given-names>JC</given-names>
</name>
</person-group>
<article-title>Human pancreatic islets and diabetes research</article-title>
<source>JAMA</source>
<year>2009</year>
<volume>301</volume>
<fpage>1580</fpage>
<lpage>1587</lpage>
<pub-id pub-id-type="pmid">19366778</pub-id>
</element-citation>
</ref>
<ref id="b53"><label>53</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shimoda</surname>
<given-names>M</given-names>
</name>
<name><surname>Itoh</surname>
<given-names>T</given-names>
</name>
<name><surname>Sugimoto</surname>
<given-names>K</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Improvement of collagenase distribution with the ductal preservation for human islet isolation</article-title>
<source>Islets</source>
<year>2012</year>
<volume>4</volume>
<fpage>130</fpage>
<lpage>137</lpage>
<pub-id pub-id-type="pmid">22627378</pub-id>
</element-citation>
</ref>
<ref id="b54"><label>54</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Friberg</surname>
<given-names>AS</given-names>
</name>
<name><surname>Korsgren</surname>
<given-names>O</given-names>
</name>
<name><surname>Hellgren</surname>
<given-names>M</given-names>
</name>
</person-group>
<article-title>A vast amount of enzyme activity fails to be absorbed within the human pancreas: Implications for cost-effective islet isolation procedures</article-title>
<source>Transplantation</source>
<year>2013</year>
<volume>95</volume>
<fpage>e36</fpage>
<lpage>e38</lpage>
<pub-id pub-id-type="pmid">23507655</pub-id>
</element-citation>
</ref>
<ref id="b55"><label>55</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>O'Gorman</surname>
<given-names>D</given-names>
</name>
<name><surname>Kin</surname>
<given-names>T</given-names>
</name>
<name><surname>Pawlick</surname>
<given-names>R</given-names>
</name>
<name><surname>Imes</surname>
<given-names>S</given-names>
</name>
<name><surname>Senior</surname>
<given-names>PA</given-names>
</name>
<name><surname>Shapiro</surname>
<given-names>AM</given-names>
</name>
</person-group>
<article-title>Clinical islet isolation outcomes with a highly purified neutral protease for pancreas dissociation</article-title>
<source>Islets</source>
<year>2013</year>
<volume>5</volume>
<fpage>111</fpage>
<lpage>115</lpage>
<pub-id pub-id-type="pmid">23756701</pub-id>
</element-citation>
</ref>
<ref id="b56"><label>56</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stahle</surname>
<given-names>M</given-names>
</name>
<name><surname>Honkanen-Scott</surname>
<given-names>M</given-names>
</name>
<name><surname>Ingvast</surname>
<given-names>S</given-names>
</name>
<name><surname>Korsgren</surname>
<given-names>O</given-names>
</name>
<name><surname>Friberg</surname>
<given-names>AS</given-names>
</name>
</person-group>
<article-title>Human islet isolation processing times shortened by one hour: Minimized incubation time between tissue harvest and islet purification</article-title>
<source>Transplantation</source>
<year>2013</year>
<volume>96</volume>
<fpage>e91</fpage>
<lpage>e93</lpage>
<pub-id pub-id-type="pmid">24342944</pub-id>
</element-citation>
</ref>
<ref id="b57"><label>57</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Niclauss</surname>
<given-names>N</given-names>
</name>
<name><surname>Sgroi</surname>
<given-names>A</given-names>
</name>
<name><surname>Morel</surname>
<given-names>P</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Computer-assisted digital image analysis to quantify the mass and purity of isolated human islets before transplantation</article-title>
<source>Transplantation</source>
<year>2008</year>
<volume>86</volume>
<fpage>1603</fpage>
<lpage>1609</lpage>
<pub-id pub-id-type="pmid">19077896</pub-id>
</element-citation>
</ref>
<ref id="b58"><label>58</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Itoh</surname>
<given-names>T</given-names>
</name>
<name><surname>Takita</surname>
<given-names>M</given-names>
</name>
<name><surname>SoRelle</surname>
<given-names>JA</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Correlation of released HMGB1 levels with the degree of islet damage in mice and humans and with the outcomes of islet transplantation in mice</article-title>
<source>Cell Transplant</source>
<year>2012</year>
<volume>21</volume>
<fpage>1371</fpage>
<lpage>1381</lpage>
<pub-id pub-id-type="pmid">22546320</pub-id>
</element-citation>
</ref>
</ref-list>
<glossary><def-list><def-item><term>BMI</term>
<def><p>body mass index</p>
</def>
</def-item>
<def-item><term>CIT</term>
<def><p>cold ischemia time</p>
</def>
</def-item>
<def-item><term>CITR</term>
<def><p>Collaborative Islet Transplant Registry</p>
</def>
</def-item>
<def-item><term>HTK</term>
<def><p>histidine-tryptophan-ketoglutarate</p>
</def>
</def-item>
<def-item><term>IAK</term>
<def><p>islet after kidney transplantation</p>
</def>
</def-item>
<def-item><term>IEQ</term>
<def><p>islet equivalent</p>
</def>
</def-item>
<def-item><term>ITA</term>
<def><p>islet transplant alone</p>
</def>
</def-item>
<def-item><term>JDRF</term>
<def><p>Juvenile Diabetes Research Foundation</p>
</def>
</def-item>
<def-item><term>NIDDK</term>
<def><p>National Institute of Diabetes and Digestive and Kidney Diseases</p>
</def>
</def-item>
<def-item><term>SIK</term>
<def><p>simultaneous islet and kidney transplantation</p>
</def>
</def-item>
<def-item><term>TLM</term>
<def><p>two layer method</p>
</def>
</def-item>
<def-item><term>UW</term>
<def><p>University of Wisconsin solution</p>
</def>
</def-item>
</def-list>
</glossary>
<sec sec-type="supplementary-material"><title>Supporting Information</title>
<p>Additional Supporting Information may be found in the online version of this article.</p>
<supplementary-material content-type="local-data" id="SD1"><label>Figure S1</label>
<caption><p><bold>Distribution of islet yields processed and infused.</bold>
Percent distribution of total islet yield (A) and the correlation between those at count and infusion (B) are shown. Data are based on 1017 clinical products in NIDDK-sponsored North American and JDRF European and Australian CITR sites participating in the Collaborative Islet Transplant Registry, 1999–2010. Linear regression (r = 0.93, p < 0.0001) is shown (B).</p>
</caption>
<media mimetype="pdf" mime-subtype="pdf" xlink:href="ajt0014-2595-SD1.pdf" xlink:type="simple" id="d35e5107" position="anchor"></media>
</supplementary-material>
<supplementary-material content-type="local-data" id="SD2"><label>Table S1</label>
<caption><p>Donor characteristics.</p>
<p><bold>Table S2:</bold>
Pancreas preservation and recovery.</p>
<p><bold>Table S3:</bold>
Islet processing.</p>
<p><bold>Table S4:</bold>
Islet product characteristics.</p>
<p><bold>Table S5:</bold>
Islet infusion.</p>
</caption>
<media mimetype="txt" mime-subtype="txt" xlink:href="ajt0014-2595-SD2.txt" xlink:type="simple" id="d35e5130" position="anchor"></media>
</supplementary-material>
</sec>
</back>
</pmc>
</record>
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