Calcium : A Crucial Potentiator for Efficient Enzyme Digestion of the Human Pancreas

Background: Effective digestive enzymes are crucial for successful islet isolation. Supplemental proteases are essential because they synergize with collagenase for effective pancreatic digestion. The activity of these enzymes is critically dependent on the presence of Ca2+ ions at a concentration of 5-10 mM. The present study aimed to determine the Ca2+ concentration during human islet isolation and to ascertain whether the addition of supplementary Ca2+ is required to maintain an optimal Ca2+ concentration during the various phases of the islet isolation process. Methods: Human islets were isolated according to standard methods and isolation parameters. Islet quality control and the number of isolations fulfilling standard transplantation criteria were evaluated. Ca2+ was determined by using standard clinical chemistry routines. Islet isolation was performed with or without addition of supplementary Ca2+ to reach a Ca2+ of 5 mM. Results: Ca2+ concentration was markedly reduced in bicarbonate-based buffers, especially if additional bicarbonate was used to adjust the pH as recommended by the Clinical Islet Transplantation Consortium. A major reduction in Ca2+ concentration was also observed during pancreatic enzyme perfusion, digestion, and harvest. Additional Ca2+ supplementation of media used for dissolving the enzymes and during digestion, perfusion, and harvest was necessary in order to obtain the concentration recommended for optimal enzyme activity and efficient liberation of a large number of islets from the human pancreas. Conclusions: Ca2+ is to a large extent consumed during clinical islet isolation, and in the absence of supplementation, the concentration fell below that recommended for optimal enzyme activity. Ca2+ supplementation of the media used during human pancreas digestion is necessary to maintain the concentration recommended for optimal enzyme activity. Addition of Ca2+ to the enzyme blend has been implemented in the standard isolation protocols in the Nordic Network for Clinical Islet Transplantation.Peer reviewe

Transplantation, Bioengineering, and Regeneration of the Endocrine Pancreas Chapter 48 - Treating diabetes with islet transplantation: Lessons learnt from the Nordic network for clinical islet transplantation

Transplantation, Bioengineering, and Regeneration of the Endocrine Pancreas, Volume 2, sets a new standard in transplant and regenerative medicine. The book details the state-of-the-art in modern islet auto-transplantation, also discussing current progress in regenerative medicine research in diabetes medicine. Regenerative medicine is changing the premise of solid organ transplantation, hence this volume catalogs technologies being developed and methods being implemented. Bioengineering and regenerating beta cells, clinical pancreas and islet transplantation, tissue engineering, biomaterial sciences, stem cell biology and developmental biology are all addressed and applied directly to diabetes medicine

Few Gender Differences in Attitudes and Experiences after Live Kidney Donation, with Minor Changes Over Time.

Background: We sought to study gender differences and differences over time with respect to demographics, relation to recipient,donor motives, and experiences of live kidney donation. Material/Methods: In all, 455 consecutive live kidney donors, representing all of the donors at our center between 1974 and 2008were considered for this study. There were 28 deceased donors and 14 donors who had moved abroad, leaving413 donors; 387 (94%) agreed to participate in this study. A questionnaire was sent and the answers wasanalyzed for gender differences and, where relevant, for changes over time. Results: In all sub-periods, female donors made up the majority (55–62%), except for sibling donors (45%) and childto-parent donors (40%). No significant gender differences were seen in perceived information given before donation.For males, it was more common that the recipient took the initiative to donate. For females, the motivationfor donating was more frequently to help the recipient and because others wanted them to donate.For males, it was more common to feel a moral obligation. Post-operatively, females more frequently felt sad and experienced nausea, and more frequently felt that the donation had a positive impact on their lifes. With the introduction of minimally invasive surgical techniques, donors experienced fewer problems from the operation, with no gender difference. Conclusions: Females donate more frequently than males, a difference that did not change over time. Only a few genderdifferences were seen in donor motives and the donation experience; however, these differences may be relevantto address the gender imbalance in kidney donations

Few Gender Differences in Attitudes and Experiences after Live Kidney Donation, with Minor Changes Over Time.

Background: We sought to study gender differences and differences over time with respect to demographics, relation to recipient,donor motives, and experiences of live kidney donation. Material/Methods: In all, 455 consecutive live kidney donors, representing all of the donors at our center between 1974 and 2008were considered for this study. There were 28 deceased donors and 14 donors who had moved abroad, leaving413 donors; 387 (94%) agreed to participate in this study. A questionnaire was sent and the answers wasanalyzed for gender differences and, where relevant, for changes over time. Results: In all sub-periods, female donors made up the majority (55–62%), except for sibling donors (45%) and childto-parent donors (40%). No significant gender differences were seen in perceived information given before donation.For males, it was more common that the recipient took the initiative to donate. For females, the motivationfor donating was more frequently to help the recipient and because others wanted them to donate.For males, it was more common to feel a moral obligation. Post-operatively, females more frequently felt sad and experienced nausea, and more frequently felt that the donation had a positive impact on their lifes. With the introduction of minimally invasive surgical techniques, donors experienced fewer problems from the operation, with no gender difference. Conclusions: Females donate more frequently than males, a difference that did not change over time. Only a few genderdifferences were seen in donor motives and the donation experience; however, these differences may be relevantto address the gender imbalance in kidney donations

Risk Factors for Developing BK Virus-Associated Nephropathy : A Single-Center Retrospective Cohort Study of Kidney Transplant Recipients

BACKGROUND BK virus (BKV) infection after kidney transplantation leads to BKV-associated nephropathy (BKVAN) in up to 10% of recipients, and is associated with an increased risk of allograft dysfunction or loss. The objective of this study was to estimate the incidence of BKVAN and to analyze whether enhanced induction is associated with an increased risk of BKVAN, possibly justifying more intensive surveillance. MATERIAL AND METHODS This was a single-center retrospective cohort study. All patients who underwent kidney transplantation or simultaneous pancreas and kidney transplantation at the Uppsala University Hospital in Sweden between 2005 and 2014 were included, a period when BKV screening was not yet implemented. The effect of enhanced induction, defined as treatment with thymoglobulin, rituximab, and/or eculizumab, often in combination with IVIg and glycosorb, immunoadsorption and/or plasmapheresis/apheresis, was analyzed in a multivariable Cox proportional hazards model together with sex, age, cytomegalovirus mismatch (donor+/recipient-) and rejection treatment as co-predictors. Further, the effects of BKVAN on graft survival was analyzed in a univariable Cox proportional hazards model. RESULTS In total 44 of 928 (4.7%) patients developed a biopsy-verified BKVAN 4.8 (1.5-34.2) months after transplantation. Male sex was identified as a risk factor (HR 2.02, P=0.04) but not enhanced induction. Patients with BKVAN experienced a significantly higher risk of graft loss (HR 4.37, P<0.001). CONCLUSIONS Male sex, but not enhanced induction, was found to be a risk factor for BKVAN development after kidney transplantation. BKVAN is associated with an increased risk of graft loss

Autologous regulatory T cells in clinical intraportal allogenic pancreatic islet transplantation

Allogeneic islet transplantation in type 1 diabetes requires lifelong immunosuppression to prevent graft rejection. This medication can cause adverse effects and increases the susceptibility for infections and malignancies. Adoptive therapies with regulatory T cells (Tregs) have shown promise in reducing the need for immunosuppression in human transplantation settings but have previously not been evaluated in islet transplantation. In this study, five patients with type 1 diabetes undergoing intraportal allogeneic islet transplantation were co-infused with polyclonal autologous Tregs under a standard immunosuppressive regimen. Patients underwent leaukapheresis from which Tregs were purified by magnetic-activated cell sorting (MACS) and cryopreserved until transplantation. Dose ranges of 0.14–1.27 × 106 T cells per kilo bodyweight were transplanted. No negative effects were seen related to the Treg infusion, regardless of cell dose. Only minor complications related to the immunosuppressive drugs were reported. This first-in-man study of autologous Treg infusion in allogenic pancreatic islet transplantation shows that the treatment is safe and feasible. Based on these results, future efficacy studies will be developed under the label of advanced therapeutic medical products (ATMP), using modified or expanded Tregs with the aim of minimizing the need for chronic immunosuppressive medication in islet transplantation

Healthcare Resource Use, Cost, and Sick Leave Following Kidney Transplantation in Sweden : A Population-Based, 5-Year, Retrospective Study of Outcomes: COIN

Background: Improved understanding of the impact of kidney transplantation on healthcare resource use/costs and loss of productivity could aid decision making about funding allocation and resources needed for the treatment of chronic kidney disease in stage 5. Material/Methods: This was a retrospective study utilizing data from Swedish national health registers of patients undergoing kidney transplantation. Primary outcomes were renal disease-related healthcare resource utilization and costs during the 5 years after transplantation. Secondary outcomes included total costs and loss of productivity. Regression analysis identified factors that influenced resource use, costs, and loss of productivity. Results: During the first year after transplantation, patients (N=3120) spent a mean of 25.7 days in hospital and made 21.6 outpatient visits; mean renal disease-related total cost was & euro;66,014. During the next 4 years, resource use was approximately 70% (outpatient) to 80% (inpatient) lower, and costs were 75% lower. Before transplantation, 62.8% were on long-term sick leave, compared with 47.4% 2 years later. Higher resource use and costs were associated with age <10 years, female sex, graft from a deceased donor, prior hemodialysis, receipt of a previous transplant, and presence of comorbidities. Higher levels of sick leave were associated with female sex, history of hemodialysis, and type 1 diabetes. Overall 5-year graft survival was 86.7% (95% CI 85.3-88.2%). Conclusions: After the first year following transplantation, resource use and related costs decreased, remaining stable for the next 4 years. Demographic and clinical factors, including age <10 years, female sex, and type 1 diabetes were associated with higher costs and resource use

Healthcare Resource Use, Cost, and Sick Leave Following Kidney Transplantation in Sweden : A Population-Based, 5-Year, Retrospective Study of Outcomes: COIN

Background: Improved understanding of the impact of kidney transplantation on healthcare resource use/costs and loss of productivity could aid decision making about funding allocation and resources needed for the treatment of chronic kidney disease in stage 5. Material/Methods: This was a retrospective study utilizing data from Swedish national health registers of patients undergoing kidney transplantation. Primary outcomes were renal disease-related healthcare resource utilization and costs during the 5 years after transplantation. Secondary outcomes included total costs and loss of productivity. Regression analysis identified factors that influenced resource use, costs, and loss of productivity. Results: During the first year after transplantation, patients (N=3120) spent a mean of 25.7 days in hospital and made 21.6 outpatient visits; mean renal disease-related total cost was & euro;66,014. During the next 4 years, resource use was approximately 70% (outpatient) to 80% (inpatient) lower, and costs were 75% lower. Before transplantation, 62.8% were on long-term sick leave, compared with 47.4% 2 years later. Higher resource use and costs were associated with age <10 years, female sex, graft from a deceased donor, prior hemodialysis, receipt of a previous transplant, and presence of comorbidities. Higher levels of sick leave were associated with female sex, history of hemodialysis, and type 1 diabetes. Overall 5-year graft survival was 86.7% (95% CI 85.3-88.2%). Conclusions: After the first year following transplantation, resource use and related costs decreased, remaining stable for the next 4 years. Demographic and clinical factors, including age <10 years, female sex, and type 1 diabetes were associated with higher costs and resource use

Does experience affect physicians’ attitude towards assisted suicide? A snapshot of Swedish doctors’ opinions

Introduction Assisted dying is a current and controversial topic that seems to be gaining more support among both physicians as well as the general public. This paper aims to provide a snapshot of Swedish physicians’ opinions regarding AS, including their opinion concerning experience and to evaluate whether a correlation between opinion and experience exists. Material and methods A poll was conducted through a panel of members of the Swedish Medical Association. The panel is representative of the association's members regarding age and gender. Results The response rate was 49% Of the respondents 41% stated that AS and/or euthanasia should be legalized. Doctors with great experience in working with dying patients express most strongly against AS and/or euthanasia. More than half of the respondents (54%) stated that AS if it would be legal, should be performed within specific health care units. Approximately the same proportion (48%) were willing to write a statement on health status, knowing that it would be used in decisions regarding AS. Similarly, 44% could not consider performing AS and 27% were indecisive on the question. A majority (41%) thought that a physician should be responsible for approving applications for AS. Discussion A few more physicians express a positive attitude toward AS than against it, but many cannot express a certain opinion. In our material, no side in the “debate” for or against AS reaches the majority. The most junior physicians are the most uncertain ones