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Diabetologia

, Volume 61, Issue 4, pp 954–958 | Cite as

Hospital time prior to death and pancreas histopathology: implications for future studies

  • Irina Kusmartseva
  • Maria Beery
  • Tiffany Philips
  • Stephen Selman
  • Priyanka Jadhav
  • Clive Wasserfall
  • Axel Muller
  • Alberto Pugliese
  • Jeffrey A. Longmate
  • Desmond A. Schatz
  • Mark A. Atkinson
  • John S. Kaddis
Article

Abstract

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 (<3 days, 3 to <6 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 <12 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 < 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

Keywords

Basic science Clinical science Human Imaging (MRI/PET/other) Islets Islets(all) Pathophysiology/metabolism 

Abbreviation

nPOD

Network for Pancreatic Organ Donors with Diabetes

Notes

Acknowledgements

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.

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).

Duality of interest

MAA and AP serve as executive directors of the nPOD program and JSK directs its data management core. All other authors declare that there is no duality of interest associated with their contribution to this manuscript.

Contribution statement

IK conceived of the study, acquired and interpreted data and drafted and edited the manuscript. MB acquired and interpreted data. TP, SS and CW acquired data. AM analysed and interpreted data and edited the manuscript. PJ contributed to the conception of the study. AP, DS and JAL interpreted the data. MAA conceived of the study and edited the manuscript. JSK conceived of the study, analysed and interpreted the data and drafted and edited the manuscript. All authors critically reviewed the manuscript and approved the final version. JSK is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Supplementary material

125_2017_4494_MOESM1_ESM.pdf (626 kb)
ESM (PDF 625 kb)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Irina Kusmartseva
    • 1
  • Maria Beery
    • 1
  • Tiffany Philips
    • 1
  • Stephen Selman
    • 1
  • Priyanka Jadhav
    • 1
  • Clive Wasserfall
    • 1
  • Axel Muller
    • 2
  • Alberto Pugliese
    • 3
    • 4
  • Jeffrey A. Longmate
    • 5
  • Desmond A. Schatz
    • 1
    • 6
  • Mark A. Atkinson
    • 1
    • 6
  • John S. Kaddis
    • 2
  1. 1.Department of Pathology, Immunology, and Laboratory Medicine, College of MedicineUniversity of FloridaGainesvilleUSA
  2. 2.Department of Diabetes and Cancer Discovery Science, Diabetes and Metabolism Research InstituteCity of Hope/Beckman Research InstituteDuarteUSA
  3. 3.Diabetes Research Institute, Department of Medicine, Division of Diabetes, Endocrinology and MetabolismUniversity of Miami Miller School of MedicineMiamiUSA
  4. 4.Department of Microbiology and ImmunologyUniversity of Miami Miller School of MedicineMiamiUSA
  5. 5.Division of BiostatisticsCity of HopeDuarteUSA
  6. 6.Department of PediatricsUniversity of FloridaGainesvilleUSA

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