TY - JOUR
T1 - Hospital time prior to death and pancreas histopathology
T2 - implications for future studies
AU - Kusmartseva, Irina
AU - Beery, Maria
AU - Philips, Tiffany
AU - Selman, Stephen
AU - Jadhav, Priyanka
AU - Wasserfall, Clive
AU - Muller, Axel
AU - Pugliese, Alberto
AU - Longmate, Jeffrey A.
AU - Schatz, Desmond A.
AU - Atkinson, Mark A.
AU - Kaddis, John S.
N1 - Funding Information:
The authors thank A. Posgai (Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA) for editing and formatting the manuscript. Some of the data from this study was previously presented at the 9th annual JDRF nPOD Scientific Meeting in February 2017. Organ Procurement Organizations (OPO) partnering with nPOD to provide research resources are listed at http://www.jdrfnpod.org/for-partners/npod-partners. Our deepest apologies go to those colleagues whose work was not cited, or cited and not discussed in detail. This research was performed with the support of the nPOD, a collaborative type 1 diabetes research project, and was sponsored by the JDRF (25-2013-268, 25-2012-380, and 25-2007-874 to MAA, including a subcontract to JSK). Funding was also provided by the National Institutes of Health Human Islet Research Network (NIH HIRN, U01DK104147 to JSK) and a program project grant (P01 AI42288 to MAA).
Funding Information:
Data availability Jupyter Notebooks have been prepared to allow reproduction of all aspects of this study, including the matching process, pilot data analysis, power calculations, dataset preparation, statistical analysis and figure generation. All referenced macros (adopted and developed), calculations, programming code and numerical dataset files (including individual-level donor data) are freely available on GitHub through Zenodo at https://doi.org/10.5281/zenodo.1034422 Funding This research was performed with the support of the nPOD, a collaborative type 1 diabetes research project, and was sponsored by the JDRF (25-2013-268, 25-2012-380, and 25-2007-874 to MAA, including a subcontract to JSK). Funding was also provided by the National Institutes of Health Human Islet Research Network (NIH HIRN, U01DK104147 to JSK) and a program project grant (P01 AI42288 to MAA).
Publisher Copyright:
© 2017, Springer-Verlag GmbH Germany.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Aims/hypothesis: Diabetes research studies routinely rely upon the use of tissue samples from human organ donors. It remains unclear whether the length of hospital stay prior to organ donation affects the presence of cells infiltrating the pancreas or the frequency of replicating beta cells. Methods: To address this, 39 organ donors without diabetes were matched for age, sex, BMI and ethnicity in groups of three. Within each group, donors varied by length of hospital stay immediately prior to organ donation (OpenSPiltSPi3 days, 3 to OpenSPiltSPi6 days, or ≥6 days). Serial sections from tissue blocks in the pancreas head, body and tail regions were immunohistochemically double stained for insulin and CD45, CD68, or Ki67. Slides were electronically scanned and quantitatively analysed for cell positivity. Results: No differences in CD45+, CD68+, insulin+, Ki67+ or Ki67+/insulin+ cell frequencies were found when donors were grouped according to duration of hospital stay. Likewise, no interactions were observed between hospitalisation group and pancreas region, age, or both; however, with Ki67 staining, cell frequencies were greater in the body vs the tail region of the pancreas (∆ 0.65 [unadjusted 95% CI 0.25, 1.04]; p = 0.002) from donors OpenSPiltSPi12 year of age. Interestingly, frequencies were less in the body vs tail region of the pancreas for both CD45+ cells (∆ −0.91 [95% CI −1.71, −0.10]; p = 0.024) and insulin+ cells (∆ −0.72 [95% CI −1.10, −0.34]; p OpenSPiltSPi 0.001). Conclusions/interpretation: This study suggests that immune or replicating beta cell frequencies are not affected by the length of hospital stay prior to donor death in pancreases used for research. Data availability: All referenced macros (adopted and developed), calculations, programming code and numerical dataset files (including individual-level donor data) are freely available on GitHub through Zenodo at https://doi.org/10.5281/zenodo.1034422.
AB - Aims/hypothesis: Diabetes research studies routinely rely upon the use of tissue samples from human organ donors. It remains unclear whether the length of hospital stay prior to organ donation affects the presence of cells infiltrating the pancreas or the frequency of replicating beta cells. Methods: To address this, 39 organ donors without diabetes were matched for age, sex, BMI and ethnicity in groups of three. Within each group, donors varied by length of hospital stay immediately prior to organ donation (OpenSPiltSPi3 days, 3 to OpenSPiltSPi6 days, or ≥6 days). Serial sections from tissue blocks in the pancreas head, body and tail regions were immunohistochemically double stained for insulin and CD45, CD68, or Ki67. Slides were electronically scanned and quantitatively analysed for cell positivity. Results: No differences in CD45+, CD68+, insulin+, Ki67+ or Ki67+/insulin+ cell frequencies were found when donors were grouped according to duration of hospital stay. Likewise, no interactions were observed between hospitalisation group and pancreas region, age, or both; however, with Ki67 staining, cell frequencies were greater in the body vs the tail region of the pancreas (∆ 0.65 [unadjusted 95% CI 0.25, 1.04]; p = 0.002) from donors OpenSPiltSPi12 year of age. Interestingly, frequencies were less in the body vs tail region of the pancreas for both CD45+ cells (∆ −0.91 [95% CI −1.71, −0.10]; p = 0.024) and insulin+ cells (∆ −0.72 [95% CI −1.10, −0.34]; p OpenSPiltSPi 0.001). Conclusions/interpretation: This study suggests that immune or replicating beta cell frequencies are not affected by the length of hospital stay prior to donor death in pancreases used for research. Data availability: All referenced macros (adopted and developed), calculations, programming code and numerical dataset files (including individual-level donor data) are freely available on GitHub through Zenodo at https://doi.org/10.5281/zenodo.1034422.
KW - Basic science
KW - Clinical science
KW - Human
KW - Imaging (MRI/PET/other)
KW - Islets
KW - Islets(all)
KW - Pathophysiology/metabolism
UR - http://www.scopus.com/inward/record.url?scp=85033437982&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85033437982&partnerID=8YFLogxK
U2 - 10.1007/s00125-017-4494-x
DO - 10.1007/s00125-017-4494-x
M3 - Article
C2 - 29128936
AN - SCOPUS:85033437982
VL - 61
SP - 954
EP - 958
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 4
ER -