Introduction: The scope of the impact of the COVID-19 pandemic on living donor kidney transplantation (LDKT) practices is not well defined. Methods: We surveyed US transplant programs to assess practices, strategies, and barriers to living LDKT during the COVID-19 pandemic. After institutional review board approval, the survey was distributed from 9 May 2020 to 30 May 2020 by e-mail and postings to professional society list-servs. Responses were stratified based on state COVID-19 cumulative incidence levels. Results: Staff at 118 unique centers responded, representing 61% of US living donor recovery programs and 75% of LKDT volume in the prepandemic year. Overall, 66% reported that LDKT surgery was on hold (81% in "high" vs. 49% in "low" COVID-19 cumulative incidence states). A total of 36% reported that evaluation of new donor candidates had paused, 27% reported that evaluations were very much decreased (>0% to <25% typical), and 23% reported that evaluations were moderately decreased (25% to <50% typical). Barriers to LDKT surgery included program concerns for donor (85%) and recipient (75%) safety, patient concerns (56%), elective case restrictions (47%), and hospital administrative restrictions (48%). Programs with higher local COVID-19 cumulative incidence reported more barriers related to staff and resource diversion. Most centers continuing donor evaluations used remote strategies (video, 82%; telephone, 43%). As LDKT resumes, all programs will screen for COVID-19, although timeframe and modalities will vary. Recommendations for presurgical self-quarantine are also variable. Conclusion: The COVID-19 pandemic has had broad impacts on LDKT practice. Ongoing research and consensus building are needed to reduce barriers, to guide optimal practices, and to support safe restoration of LDKT across centers.

The scope of the impact of the Coronaviru s disease 19 (COVID‐19) pandemic on living donor kidney transplantation (LDKT) practices across the world is not well defined. We received survey responses from 204 transplant centers internationally from May to June 2020 regarding the impact of the COVID‐19 pandemic on LDKT practices. Respondents represented 16 countries on 5 continents. Overall, 75% of responding centers reported that LDKT surgery was on hold (from 67% of North American centers to 91% of European centers). The majority (59%) of centers reported that new donor evaluations were stopped (from 46% of North American centers to 86% of European centers), with additional 23% of centers reporting important decrease in evaluations. Only 10% of centers reported slight variations on their evaluations. For the centers that continued donor evaluations, 40% performed in‐person visits, 68% by video, and 42% by telephone. Center concerns for donor (82%) and recipient (76%) safety were the leading barriers to LDKT during the pandemic, followed by patients concerns (48%), and government restrictions (46%). European centers reported more barriers related to staff limitations while North and Latin American centers were more concerned with testing capacity and insufficient resources including protective equipment. As LDKT resumes, 96% of the programs intend to screen donor and recipient pairs for coronavirus infection, most of them with polymerase chain reaction testing of nasopharyngeal swab samples. The COVID‐19 pandemic has had broad impact on all aspects of LDKT practice. Ongoing research and consensus‐building are needed to guide safe reopening of LDKT programs.

Impacts of the prescription opioid epidemic have not yet been examined in the context of heart transplantation. We examined a novel database in which national U.S.transplant registry records were linked to a large pharmaceutical claims warehouse (2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016) to characterize prescription opioid use before and after heart transplant, and associations (adjusted hazard ratio, 95% LCL aHR 95% UCL ) with death and graft loss.Among 13 958 eligible patients, 40% filled opioids in the year before transplant. Use was more common among recipients who were female, white, or unemployed, or who underwent transplant in more recent years. Of those with the highest level of pretransplant opioid use, 71% continued opioid use posttransplant. Pretransplant use had graded associations with 1-year posttransplant outcomes; compared with no use, the highest-level use (>1000 mg morphine equivalents) predicted 33% increased risk of death (aHR 1.10 1.33 1.61 ) in the year after transplant. Risk relationships with opioid use in the first year posttransplant were stronger, with highest level use predicting 70% higher mortality (aHR 1.46 1.70 1.98 ) over the subsequent 4 years (from >1 to 5 years posttransplant). While associations may, in part, reflect underlying conditions or behaviors, opioid use history is relevant in assessing and providing care to transplant candidates and recipients. K E Y W O R D Sanesthesia/pain management, clinical research/practice, epidemiology, health services and outcomes research, heart transplantation, heart transplantation/cardiology, opioids, registries, risk assessment/risk stratification, risk factors, Scientific Registry for Transplant Recipients (SRTR)

While guidelines support metformin as a therapeutic option for diabetic patients with mild-to-moderate renal insufficiency, the frequency and outcomes of metformin use in kidney transplant recipients are not well described. We integrated national U.S. transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2015). Associations (adjusted hazard ratio, aHR ) of diabetes regimens (with and excluding metformin) in the first year post-transplant with patient and graft survival over the subsequent year were quantified by multivariate Cox regression, adjusted for recipient, donor, and transplant factors and propensity for metformin use. Among 14 144 recipients with pretransplant type 2 diabetes mellitus, 4.7% filled metformin in the first year post-transplant; most also received diabetes comedications. Compared to those who received insulin-based regimens without metformin, patients who received metformin were more likely to be female, have higher estimated glomerular filtration rates, and have undergone transplant more recently. Metformin-based regimens were associated with significantly lower adjusted all-cause (aHR 0.41 ), malignancy-related (aHR 0.45 ), and infection-related (aHR 0.32 ) mortality, and nonsignificant trends toward lower cardiovascular mortality, graft failure, and acute rejection. No evidence of increased adverse graft or patient outcomes was noted. Use of metformin-based diabetes treatment regimens may be safe in carefully selected kidney transplant recipients.

Interleukin 13 (IL13) is secreted by multiple subsets of immune cells and acts directly on the gastric epithelium to promote neck cell expansion and metaplasia. Mice with autoimmune gastritis lacking the IL13 receptor do not develop neck cell expansion or metaplasia, and neutralization of IL13 inhibits and reverses disease development during chronic gastritis. BACKGROUND & AIMS:It is well established that chronic inflammation promotes gastric cancer-associated metaplasia, but little is known regarding the mechanisms by which immune cells and cytokines regulate metaplastic cellular changes. The goals of this study were to identify interleukin 13 (IL13)-producing immune cells, determine the gastric epithelial cell response(s) to IL13, and establish the role(s) of IL13 in metaplasia development. METHODS:Experiments used an established mouse model of autoimmune gastritis (TxA23), TxA23xIl4ra Q9 -/mice, which develop gastritis but do not express the IL4/IL13-receptor subunit IL4Ra, and TxA23xIL13-YFP Q10 mice, which express yellow fluorescent protein in IL13-producing cells. Flow cytometry was used to measure IL13 secretion and identify IL13producing immune cells. Mouse and human gastric organoids were cultured with IL13 to determine epithelial cell response(s) to IL13. Single-cell RNA sequencing was performed on gastric epithelial cells from healthy and inflamed mouse stomachs. Mice with gastritis were administered IL13neutralizing antibodies and stomachs were analyzed by histopathology and immunofluorescence. RESULTS:We identified 6 unique subsets of IL13-producing immune cells in the inflamed stomach. Organoid cultures showed that IL13 acts directly on gastric epithelium to induce a metaplastic phenotype. IL4Ra-deficient mice did not progress to metaplasia. Single-cell RNA sequencing determined that gastric epithelial cells from IL4Ra-deficient mice up-regulated inflammatory genes but failed to up-regulate metaplasia-associated transcripts. Neutralization of IL13 significantly reduced and reversed metaplasia development in mice with gastritis.CONCLUSIONS: IL13 is made by a variety of immune cell subsets during chronic gastritis and promotes gastric cancer-associated metaplastic epithelial cell changes. Neutralization of IL13 reduces metaplasia severity during chronic gastritis.