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Cervical adenocarcinoma is the second most common histology of cervical cancer and treatment can involve surgery, radiotherapy, systemic therapy, and any combination of the three. Photon external beam radiation therapy and brachytherapy have been the mainstay of radiation treatment options for cervical cancer. Here, we report a case of a 41-year-old patient who had a prior renal transplant and was diagnosed with early-stage, intermediate-risk adenocarcinoma treated with modified radical hysterectomy plus adjuvant proton-beam therapy and vaginal brachytherapy. Treatment was well tolerated with a disease-free interval of 14-months and preserved renal function., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Bakkum-Gamez is an editor for Gynecology Oncology Reports and is an inventor of Mayo Clinic intellectual property licensed to Exact Sciences (Madison, WI), and may receive royalties paid to Mayo Clinic]., (© 2024 The Authors.)

Background: The impact of induction type or high-risk viral discordance on older kidney transplant recipients is unclear. Herein, we analyzed the association between induction type, viral discordance, and outcomes for older recipients., Methods: We analyzed the Scientific Registry of Transplant Recipients standard analysis file for all primary kidney transplant recipients older than 55 y who were transplanted between 2005 and 2022. All transplants were crossmatch negative and ABO-compatible. Recipients were discharged on tacrolimus and mycophenolate ± steroids. Recipients were categorized into 3 groups by induction received: rabbit antithymocyte globulin (r-ATG; N = 51 079), interleukin-2 receptor antagonist (IL-2RA; N = 22 752), and alemtuzumab (N = 13 465). Kaplan-Meier curves were generated for recipient and graft survival, and follow-up was censored at 10 y. Mixed-effect Cox proportional hazard models examined the association between induction type, high-risk viral discordance, and outcomes of interest. Models were adjusted for pertinent recipient and donor characteristics., Results: Induction type did not predict recipient survival in the multivariable model, whereas Epstein-Barr virus high-risk discordance predicted 14% higher mortality (1.14 [1.07-1.21], P  < 0.01). In the multivariable model for death-censored graft survival, alemtuzumab, but not IL-2RA, was associated with an increased risk of graft loss (1.18 [1.06-1.29], P  < 0.01) compared with r-ATG. High-risk cytomegalovirus discordance predicted 10% lower death-censored graft survival (1.10 [1.01-1.19], P  < 0.02). Live donor and preemptive transplantation were favorable predictors of survival., Conclusions: In this large cohort of older transplant recipients, alemtuzumab, but not IL-2RA, induction was associated with an increased risk of graft loss compared with r-ATG. Cytomegalovirus and Epstein-Barr virus high-risk viral discordance portended poor graft and recipient survival, respectively., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Objective: To describe the outcomes of kidney transplant (KT) candidates with obesity undergoing sleeve gastrectomy (SG) to meet the criteria for KT., Methods: Retrospective analysis was conducted of electronic medical records of KT candidates with obesity (body mass index >35 kg/m 2 ) who underwent SG in our institution. Weight loss, adverse health events, and the listing and transplant rates were abstracted and compared with the nonsurgical cohort., Results: The SG was performed in 54 patients; 50 patients did not have surgery. Baseline demographic characteristics were comparable at the time of evaluation. Mean body mass index ± SD of the SG group was 41.7±3.6 kg/m 2 at baseline (vs 41.5±4.3 kg/m 2 for nonsurgical controls); at 2 and 12 months after SG, it was 36.4±4.1 kg/m 2 and 32.6±4.0 kg/m 2 (P<.01 for both). In the median follow-up time of 15.5 months (interquartile range, 6.4 to 23.9 months), SG was followed by active listing (37/54 people), and 20 of 54 received KT during a median follow-up time of 20.9 months (interquartile range, 14.7 to 28.3 months) after SG. In contrast, 14 of 50 patients in the nonsurgical cohort were listed, and 5 received a KT (P<.01). Three patients (5.6%) experienced surgical complications. There was no difference in overall hospitalization rates and adverse health outcomes, but the SG cohort experienced a higher risk of clinically significant functional decline., Conclusion: In KT candidates with obesity, SG appears to be effective, with 37% of patients undergoing KT during the next 18 months (P<.01). Further research is needed to confirm and to improve the safety and efficacy of SG for patients with obesity seeking a KT., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Cytomegalovirus (CMV) is a common cause of infection after transplantation, but few studies have evaluated its epidemiology, risk factors, and outcomes among pancreas transplant recipients. We performed a retrospective cohort study of adults who underwent pancreas transplantation from January 1, 2010, through December 31, 2020, at 3 sites in Arizona, Florida, and Minnesota. The primary outcome was clinically significant CMV infection (csCMVi), defined as CMV disease or infection requiring antiviral therapy. The secondary outcome was pancreas allograft failure. Among 471 pancreas transplant recipients, 117 (24.8%) developed csCMVi after a median of 226 (interquartile range 154-289) days. CMV donor (D)+/R- patients had a significantly higher incidence of csCMVi (hazard ratio [HR] 4.01, 95% confidence interval [CI] 2.10-7.64; P < .001). In adjusted analysis, a lower absolute lymphocyte count (ALC) was associated with a greater risk of csCMVi among seropositive recipients (HR 1.39 per 50% decrease, 95% CI 1.13-1.73; P = .002) but not among D+/R- patients (HR 1.04 per 50% decrease, 95% CI 0.89-1.23; P = .595). csCMVi, lower ALC, and acute rejection (P < .001) were independently associated with pancreas allograft failure. In conclusion, CMV D+/R- was associated with csCMVi in pancreas recipients, although ALC was associated with csCMVi only among seropositive patients. The development of csCMVi in pancreas recipients was associated with poor pancreas allograft outcomes., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: BK polyomavirus (BKV) infection is a common complication of kidney transplantation. While BKV has been described in non-kidney transplant recipients, data are limited regarding its epidemiology and outcomes in pancreas transplant recipients., Methods: We conducted a retrospective cohort study of adults who underwent pancreas transplantation from 2010-2020. The primary outcome was BKV DNAemia. Secondary outcomes were estimated glomerular filtration rate (eGFR) reduction by 30%, eGFR < 30 mL/min/1.73 m 2 , endstage kidney disease, and pancreas allograft failure. Cox regression with time-dependent variables was utilized., Results: Four hundred and sixty-six patients were analyzed, including 74, 46, and 346 with pancreas transplant alone (PTA), pancreas-after-kidney, or simultaneous pancreas-kidney transplants, respectively. PTA recipients experienced a lower incidence of BKV DNAemia (8.8% vs. 32.9%; p < .001) and shorter duration of DNAemia (median 28.0 vs. 84.5 days). No PTA recipients with BKV DNAemia underwent kidney biopsy or developed endstage kidney disease. Lymphopenia, non-PTA transplantation, and older age were associated with BKV DNAemia, which itself was associated with pancreas allograft failure (adjusted hazard ratio 2.14, 95% confidence interval 1.27-3.60; p = .004). Among PTA recipients, BKV DNAemia was not associated with eGFR reduction or eGFR < 30 mL/min/1.73 m 2 ., Conclusions: BKV DNAemia was common among PTA recipients, though lower than a comparable group of pancreas-kidney recipients. However, BKV DNAemia was not associated with adverse native kidney outcomes and no PTA recipients developed endstage kidney disease. Conversely, BKV DNAemia was associated with pancreas allograft failure. Further studies are needed to estimate the rate of BKV nephropathy in this population, and further evaluate long-term kidney outcomes., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Kidney transplant is the most common transplant operation performed in the United States. Although various approaches to pain management have been described, the optimal analgesic strategy remains undefined. Specifically, the role of intrathecal opioids in this patient population has not been comprehensively evaluated., Methods: Using a retrospective cohort design, data from kidney transplant operations at a single tertiary care medical center between August 1, 2017, and July 31, 2022, were extracted. Inverse probability of treatment weighting (IPTW) was used to assess differences in clinical outcomes based on the presence or absence of intrathecal opioid administration before surgical incision. The primary outcome was total opioid exposure expressed in milligram morphine equivalents (MME) in the first 72 hours postoperatively, with secondary outcomes including total MME (intraoperative plus postoperative MME, postoperative pain scores, and the presence of postoperative nausea/vomiting [PONV], pruritus, or adverse events)., Results: A total of 1014 kidney transplants in 1012 unique patients were included, with 411 (41%) receiving intrathecal opioids preoperatively. Hydromorphone was the intrathecal opioid used in all cases with median dose of 100 µg (interquartile range [IQR], 100, 100; range 50-200). Subjects receiving intrathecal opioids had significantly lower postoperative opioid requirements at 72 hours (30 [0-68] vs 64 [22, 120] MME), with ratio of geometric means in the IPTW analysis (ratio of geometric means 0.34, 95% confidence interval [CI], 0.26-0.43; P < .001). Similar findings were observed for total opioids (45 [30-75] vs 75 [60-90] MME; ratio of geometric means 0.58, 95% CI, 0.54-0.63; P < .001). Maximum reported pain scores in the intrathecal group were lower at 24 hours (4 [2-7] vs 7 [5, 8]; OR, 0.28; 95% CI, 0.21-0.37 for experiencing a higher pain score with intrathecal opioids, P < .001) and 72 hours (6 [4-7] vs 7 [5-8]; OR, 0.41; 95% CI, 0.31-0.54; P < .001). Patients receiving intrathecal opioids were more likely to experience PONV (225 of 411 [55%] vs 232 of 603 [38%]; OR, 2.16; 95% CI, 1.63-2.86; P < .001)., Conclusions: Intrathecal opioid administration was associated with improved pain outcomes in patients undergoing kidney transplantation, including lower opioid requirements and pain scores through 72 hours. However, this was accompanied by an increased risk of PONV., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Surgical-site infection (SSI) is the most common early infectious complication after pancreas transplantation (PT). Although SSI has been shown to worsen outcomes, little data exist to guide optimal choices in perioperative prophylaxis., Methods: We performed a retrospective cohort study of PT recipients from 2010-2020 to examine the effect of perioperative antibiotic prophylaxis with Enterococcus coverage. Enterococcus coverage included antibiotics that would be active for penicillin-susceptible Enterococcus isolates. The primary outcome was SSI within 30 d of transplantation, and secondary outcomes were Clostridioides difficile infection (CDI) and a composite of pancreas allograft failure or death. Outcomes were analyzed by multivariable Cox regression., Results: Of 477 PT recipients, 217 (45.5%) received perioperative prophylaxis with Enterococcus coverage. Eighty-seven recipients (18.2%) developed an SSI after a median of 15 d from transplantation. In multivariable Cox regression analysis, perioperative Enterococcus prophylaxis was associated with reduced risk of SSI (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.35-0.96; P  = 0.034). Anastomotic leak was also significantly associated with elevated risk of SSI (HR 13.95; 95% CI, 8.72-22.32; P  < 0.001). Overall, 90-d CDI was 7.4%, with no difference between prophylaxis groups ( P  = 0.680). SSI was associated with pancreas allograft failure or death, even after adjusting for clinical factors (HR 1.94; 95% CI, 1.16-3.23; P  = 0.011)., Conclusions: Perioperative prophylaxis with Enterococcus coverage was associated with reduced risk of 30-d SSI but did not seem to influence risk of 90-d CDI after PT. This difference may be because of the use of beta-lactam/beta-lactamase inhibitor combinations, which provide better activity against enteric organisms such as Enterococcus and anaerobes compared with cephalosporin. Risk of SSI was also related to anastomotic leak from surgery, and SSI itself was associated with subsequent risk of a poor outcome. Measures to mitigate or prevent early complications are warranted., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Obesity is increasingly common in kidney transplant candidates and may limit access to transplantation. Obesity and diabetes are associated with a high risk for post-transplant complications. The best approach to weight loss to facilitate active transplant listing is unknown, but bariatric surgery is rarely considered due to patient- and physician-related apprehension, among other factors., Methods: We aimed to determine the magnitude of weight loss, listing, and transplant rates in 28 candidates with a mean BMI of 44.4±4.6 kg/m 2 and diabetes treated conservatively for 1 year post weight-loss consultations (group 1). Additionally, we evaluated 15 patients (group 2) who met the inclusion criteria but received bariatric intervention within the same time frame. All patients completed a multidisciplinary weight management consultation with at least 1 year of follow-up., Results: In the conservatively managed group (group 1), the mean weight at the time of initial consultation was 126.5±18.5 kg, and the mean BMI was 44.4±4.6 kg/m 2 . At 1 year post weight-loss consultation, the mean weight decreased by 4.4±8.2 kg to 122.9±17 kg, and the mean BMI was 43±4.8 kg/m 2 , with a total mean body weight decrease of 3% ( P =0.01). Eighteen patients (64%) did not progress to become candidates for active listing/transplantation during the follow-up time of 4±2.9 years, with 15 (54%) subsequently developing renal failure/diabetes-related comorbidities prohibitive for transplantation. In contrast, mean total body weight decreased by 19% at 6 months post bariatric surgery, and the mean BMI was 34.2±4 and 32.5±3.7 kg/m 2 at 6 and 12 months, respectively. Bariatric surgery was strongly associated with subsequent kidney transplantation (HR=8.39 [95% CI 1.71 to 41.19]; P =0.009)., Conclusions: A conservative weight-loss approach involving multidisciplinary consultation was ineffective in most kidney transplant candidates with diabetes, suggesting that a more proactive approach is needed., Competing Interests: H. Amer reports research funding from Kaneka Pharma and the US Department of Defense; honoraria from the Massachusetts Medical Society; and an advisory or leadership role for Transplantation (associate editor), the American Society of Transplantation (VCA advisory council co-chair), the American Society for Reconstructive Transplantation (board member), the International Society of Vascularized Composite Allotransplantation (councilor), and The Transplantation Society (education committee member). Y.C. Kudva reports consultancy for Medtronic and Novo Nordisk; research funding from Dexcom; and an advisory or leadership role for Diabetes Technology and Therapeutics. A. Kukla reports research funding as the site subinvestigator on the multicenter international study “A Research Study to See How Semaglutide Works Compared to Placebo in People with Type 2 Diabetes and Chronic Kidney Disease (FLOW)” sponsored by Novo Nordisk, and honoraria from UpToDate. M. Mundi reports research funding from Fresenius Kabi, Nestle, Realfood Blends, and VectivBio, and an advisory or leadership role for Baxter. C. Schinstock reports research funding from CSL Bering, Sanofi, and Veloxis; honoraria from CSL Bering and Veloxis; and an advisory or leadership role for Veloxis. All remaining authors have nothing to disclose. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Objective: To study the complications of hand-assisted laparoscopic living donor nephrectomy (HALLDN) with an emphasis on complications occurring early after hospital discharge up to 120 days after surgery., Patients and Methods: We retrospectively categorized complications using the Clavien-Dindo classification in 3002 HALLDNs performed at 1 center from January 1, 2000, through December 31, 2019. In addition to overall summaries, modeling was used to identify correlates of complications before and after living donation., Results: Of these donors, 87% were White, 59% were female, the mean age was 45 years (range, 18-77 years), 30.3% had a body mass index of at least 30, and 36.3% had previous abdominopelvic surgery. There were no deaths related to the surgery. The incidence of major complications (intraoperative complications plus Clavien-Dindo grade ≥III postoperatively) was 2.5% (n=74). The overall complication rate was 12.4% (n=371), including 15 intraoperative, 76 postoperative before discharge, and 280 after discharge to 120 days. Reoperation was required in 1.8% of patients (n=54), and all but 1 of these were incision-related problems. Seventy-six percent of all complications occurred after discharge, including 85% of the reoperations. For major complications, no risk factor was found. Risk factors for any complication included paramedian incision (hazard ratio [HR], 2.54; 95% CI, 1.49 to 4.34; P<.001); a history of abdominopelvic surgery (HR, 1.37; 95% CI, 1.07 to 1.76; P=.01), male sex (HR, 1.37; 95% CI, 1.07 to 1.76; P=.01), non-White race (HR, 1.40; 95% CI, 1.05 to 1.88; P=.02), and early era of the experience., Conclusion: Most major complications of HALLDN occur after discharge, suggesting that close follow-up is warranted and that the current literature may underestimate the true incidence., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Data on kidney transplantation outcomes among patients with monoclonal gammopathy of renal significance (MGRS) are lacking., Study Design: Case series of patients with MGRS, some of whom received clone-directed therapies before kidney transplantation., Setting & Participants: 28 patients who underwent kidney transplantation from 1987 through 2016 after diagnosis with MGRS-associated lesions including light-chain deposition disease (LCDD), C3 glomerulopathy with monoclonal gammopathy (C3G-MG), and light-chain proximal tubulopathy (LCPT)., Findings: Of the 19 patients with LCDD, 10 were treated before kidney transplantation and 9 were treatment-naive. Among the treated patients with LCDD, 3 (30%) experienced histologic recurrence, 2 (20%) grafts failed, and 2 (20%) died during a median follow-up of 70 (range, 3-162) months after transplant. In the treatment-naive LCDD group, 8 (89%) had histologic recurrence, 6 (67%) grafts failed, and 4 (44%) patients died during a median follow-up of 60 (range, 35-117) months. Of the 5 patients who had a complete response before transplant, none died, and only 1 experienced graft failure, 162 months after transplant. Of 5 patients with C3G-MG, 3 were treatment-naive before transplant. Both patients who were treated before transplant had histologic recurrence, and 1 experienced graft failure and died. Among the 3 patients with treatment-naive C3G-MG, histologic recurrence occurred in all, and graft loss and death were observed in 2 and 1, respectively. In the LCPT group (n=4), histologic recurrence was observed in all 3 patients who did not receive clone-directed therapies before transplant, and 2 of these patients died, 1 with a functioning kidney. The 1 patient with LCPT who received therapy before transplant did not have histologic recurrence or graft loss and survived., Limitations: Small sample size, nonstandardized clinical management, retrospective design., Conclusions: Recurrence is very common in all MGRS-associated lesions after kidney transplant. Achieving a complete hematologic response may reduce the risks of recurrence, graft loss, and death. More studies are needed to determine the effects of hematologic response on outcomes for each MGRS-associated lesion., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Achieving a functional or sterilizing cure for HIV will require identification of therapeutic interventions that reduce HIV reservoir size in infected individuals. Proteasome inhibitors, such as ixazomib, impact multiple aspects of HIV biology including latency, transcription initiation, viral replication, and infected cell killing through the HIV protease - Casp8p41 pathway, resulting in latency reversal and reduced measures of HIV reservoir size ex vivo., Methods: We conducted a phase 1b/2a dose escalating, open label trial of weekly oral ixazomib for 24 weeks in antiretroviral (ART)-suppressed, HIV positive adults (NCT02946047). The study was conducted from March 2017 to August 2019 at two tertiary referral centers in the United States. The primary outcomes were safety and tolerability of oral ixazomib. Secondary outcomes included changes in immunologic markers and estimates of HIV reservoir size after ixazomib treatment., Findings: Sixteen participants completed the study. Ixazomib up to 4mg weekly was safe and well-tolerated, yielding no treatment-emergent events above grade 1. In exploratory analyses, ixazomib treatment was associated with detectable viremia that was below the lower limit of quantification (LLQ) in 9 participants, and viremia that was above LLQ in 4 of 16 participants. While treatment was associated with reduced CD4 counts [baseline 783 cells/ mm 3 vs. week-24 724 cells/ mm 3 p=0.003], there were no changes in markers of cellular activation, exhaustion or inflammation. Total HIV DNA and proviral sequencing were not altered by ixazomib treatment. Intact proviral DNA assay (IPDA) identified intact proviruses in 14 patients pre-treatment, and in 10/14 of those subjects post treatment values were reduced (P=0.068), allowing a calculated intact proviral half life of 0.6 years (95% CI 0.3, 2.5), compared to 7.1 years (95% CI 3.9, 18, p=0.004) in historical controls. Differentiation Quantitative Viral Outgrowth Assays (dQVOA) identified measurable proviruses in 15 subjects pre-treatment; post-treatment values were numerically reduced in 9, but overall differences were not significantly different., Interpretation: Our study successfully met its primary endpoint of demonstrating the safety of ixazomib for 24 weeks in HIV infected persons. Exploratory analyses suggest that the effects observed ex vivo of latency reversal and reductions in HIV reservoir size, also occur in vivo. Future controlled studies of ixazomib are warranted., Funding: This study was funded by Millennium Pharmaceuticals Inc..; the Mayo Clinic Foundation; the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases, Division of AIDS, the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the National Institute on Drug Abuse. Mayo Clinic also acknowledges generous funding support from Mr. Joseph T. and Mrs. Michele P. Betten., Competing Interests: NWC was supported by R56 AI145407-01A. ADB was supported by R01 AI110173, R01 AI120698; Amfar (#109593). ML is supported by NIH grants AI130005, AI117841, AI152979, DK120387, DA047034, AI120008. RC is supported by NIH grants 1U01AI131566-0, 1R01HD097843-01,1R21HD103498-01. This project was conducted in part by Southern Research using federal funds from the Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health under contract HHSN272201500017C entitled “Quantitative Viral Outgrowth Assay (QVOA) Service Resource. This work was also supported by UM1AI164562, co-funded by National Heart, Lung and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute on Drug Abuse and the National Institute of Allergy and Infectious Diseases. ADB is a paid consultant for Abbvie, Gilead, Freedom Tunnel, Pinetree therapeutics Primmune, Immunome, MarPam, and Flambeau Diagnostics, is a paid member of the DSMB for Corvus Pharmaceuticals, Equilium, and Excision Biotherapeutics, has received fees for speaking for Reach MD and Medscape, owns equity for scientific advisory work in Zentalis and Nference, and is founder and President of Splissen therapeutics. Mayo Clinic has filed a patent on the use of ixazomib in HIV positive persons. GML is an employee of and owns equity in Accelevir Diagnostics. NWC received funding from Takeda (Millennium Pharmaceuticals Inc) to conduct the trial, including professional time. AJT receives honoraria from Uptodate.com for writing unrelated to this topic. JZ serves on the advisory board for ViiV. SK receives research support for clinical trials from Abbvie, Celgene, Janssen, Takeda, Adapative, KITE, Medimmune/ Astra Zeneca, Merck, Novartis, Roche and Sanofi. SK is an advisory board member for Abbvie, Celgene, Janssen, Takeda, Adaptive, KITE, and Medimmune/ Astra Zeneca. SK participates in an independent review committee for Oncopeptides., (© 2021 The Author(s).)

Background: Experience with sequential hematopoietic stem cell transplant (HSCT) and kidney transplant (KT) is limited., Methods: We conducted a retrospective observational study of adult patients who underwent both HSCT and KT at our center, with a median follow-up of 11 y., Results: In our 54 patients cohort (94% autologous HSCT), 36 (67%) patients received HSCT first followed by KT, while 18 (33%) received KT before HSCT. In both groups, AL amyloidosis represented 50% of hematologic diagnosis. Only 4 patients expired due to hematologic disease relapse (2 patients in each group) and only 3 allografts were lost due to hematologic disease recurrence (HSCT first n = 1 and KT first n = 2). Overall 1, 5, and 10 y death-censored graft survival rates were 94%, 94%, and 94%, respectively, for the HSCT first group and 89%, 89%, and 75%, respectively, for the KT first group. Overall 1, 5, and 10 y patients survival rates were 100%, 97% and 90%, respectively, for the HSCT first group and 100%, 76%, and 63%, respectively, for the KT first group., Conclusions: Our study supports safety of sequential KT and HSCT, with improved overall patient survival compared to recipients of HSCT remaining on dialysis and good long-term kidney allograft outcome., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Longer survival using modern therapies has increased the number of patients with immunoglobulin light-chain amyloidosis receiving kidney transplantation. We evaluated 60 patients with immunoglobulin light chain amyloidosis who underwent kidney transplantation based on their hematologic response for outcomes of death, graft failure, and complications. Patient hematologic responses (light-chain in blood or urine) prior to kidney transplantation were three patients had no response, five had a partial response, six had a very good partial response, 37 had a complete response, and nine were treatment-naive patients (never treated for this disorder). After transplantation, seven of nine treatment-naive patients achieved a complete response. The median follow-up for the entire transplant cohort was 61 months. The estimated median overall survival from the time of kidney transplantation was 123 months for the entire group. Median overall survival was not reached for the very good partial response plus complete response groups, it was 47 months for no response plus partial response groups, and 117 months for the treatment-naive group (all significantly different). Median overall survival of very good partial response was 81 months, while the median was not reached in the complete response group (no significant difference). The time to amyloid recurrence was significantly longer in complete response compared to very good partial response (median 181 vs 81 months). Death-censored graft survival at one- and five-years was 98.3%, and 95.8%, respectively for all groups. Of the 60 patients, three had allograft failure, 19 died with a functioning graft, and 13 had an amyloid recurrence. Thus, outcomes after kidney transplant in patients with immunoglobulin light-chain amyloidosis seem acceptable if a very good partial response or complete response is achieved either before or after transplantation., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The changing paradigm of dental education in India has led its way to the development of Competency-Based Curriculum (CBC). This article describes the process of developing CBC in the specialty of Pediatric Dentistry under the initiative of Dental Council of India. Rationale behind CBC development is to bring uniform system of education for improving oral health outcomes of the society in long term. The process of CBC development was a collaborative teamwork, planned meticulously with predefined outline, tasks and timelines. Workflow involved identification of curricular content, defining program goals, outlining competencies, assigning them domains / levels of clinical competence, priority, educational strategies, assessment practices, integration and numbers needed for certification in selected competencies. Early clinical exposure was introduced in CBC. The final content was validated and submitted to the Council. CBC output can be summarized as competencies with fair share of all domains, levels, prioritization and integration. It is characterized by flexibility for choosing educational strategies and assessment practices. It opens up ways for global competition. However, it still has some inherent weaknesses like diverging learning paths, time constraints and number chasing. CBC can further have more academic flexibility and develop toward an outcome-based approach. Faculty preparedness and acceptability shall be the biggest challenges in CBC implementation besides resources' availability, support from leadership and acceptability from our primary stakeholders, our learners. CBC is the beginning of evidence-based delivery of education in dentistry. An effective implementation of CBC in current form would result in increased numbers of competent oral healthcare professionals for the society., (© 2021 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Background: Medical Council of India, introduced the Post Graduate (PG) curriculum as 'Competency Based Medical Education' (CBME). Feedback from the end users is a vital step in curriculum evaluation. Therefore, the primary objective of this study was to develop and validate a Structured Feedback Questionnaire (SFQ) for postgraduates, encompassing all the components of the PG-CBME curriculum., Methods: SFQ was developed with 23 Likert based questions and four open ended questions. Content validation was done by Lawshe method. After getting institutional ethics clearance and informed consent, SFQ was administered to 121 final year PGs (response rate 100%). We performed Principal component analysis (PCA), Structural equation modeling (SEM), Chi squared test (χ 2 /df); goodness-of-fit index (GFI); adjusted GFI; comparative fit index (CFI) and root mean square error of approximation (RMSEA). Cronbach's alpha was done for estimating the internal consistency., Results: The validation resulted in a three-factor model comprising of "curriculum" (42.1%), "assessment" (28%), and "support" (18.5%). Chi squared test (χ 2 /df ratio) < 2, CFI (0.78), GFI (0.72) and RMSEA (0.09) indicated superior goodness of fit for the three-factor model for the sample data. All the extracted factors had good internal consistency of ≥0.9., Conclusion: We believe that this 23 item SFQ is a valid and reliable tool which can be utilized for curriculum evaluation and thereby formulating recommendations to modify the existing curriculum wherever required, facilitating enriched program outcomes., Competing Interests: The authors have none to declare., (© 2021 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Female infertility continues to increase in prevalence annually and factors causing it need to be researched. As IL-6-174 G/C polymorphism is known to alter the plasma levels of IL-6, abnormal levels of IL-6 found in infertile females could be due to genetic reasons. With the understanding of the importance of IL-6 in reproductive physiology, several individual studies done so far to find the association of this polymorphism with female infertility related disorders were systematically combined for meta-analysis. Articles were searched using electronic data base sources and were included based on specific criteria. Finally, eight articles which includes polycystic ovarian syndrome (PCOS; n = 4), endometriosis (n = 3) and tubal damage (n = 1) were selected for the analysis. Results showed statistically significant heterogeneity across studies under the allele model (p < 0.0001, I 2 = 78 %) and dominant model (p < 0.00001, I 2 = 82%) but not under recessive model (p = 0.31, I 2 = 16%). This difference could be possibly due to variation in ethnicity, lifestyle, age or BMI related factors. The pooled odds ratio under the three genetic models were 0.87(CI = 0.75-1.02), 0.77 (CI = 0.63-0.94) and 1.05 (CI = 0.76-1.46) respectively. Sub group analysis showed statistical significant (P < 0.01) for PCOS under allele and dominant model, but not for endometriosis and tubal damage. By this meta-analysis, we can say that IL-6-174 G/C polymorphism can be considered as a potential genetic marker for PCOS but not for endometriosis and tubal damage disorders. However, more studies with adequate sample sizes are required to be done in endometriosis, tubal disease and other female infertility disorders to arrive at a definite conclusion., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: We examined the 10-year experience of Mayo Clinic's kidney paired donation (KPD).We aimed to determine the benefits for the recipients of enrolled ABO/HLA compatible pairs and determine the factors associated with prolonged KPD waiting time., Methods: We performed a retrospective study of 332 kidney transplants facilitated by the Mayo 3-site KPD program from September 2007 to June 2018., Results: The median (interquartile range) time from KPD entry to transplantation was 89 days (42-187 days). The factors independently associated with receiving a transplant >3 months after KPD entry included recipient blood type O and calculated panel reactive antibodies ≥98%. Fifty-four ABO/HLA compatible pairs participated in KPD for the following reasons: cytomegalovirus mismatch (18.5% [10/54]), Epstein-Barr virus (EBV) mismatch (EBV) (9.3% [5/54]), age/size mismatch (51.9% [28/54]), or altruistic reasons (20.3% [11/54]). Cytomegalovirus and EBV mismatch were avoided in 90% (9/10) and 100% (5/5) of cases. Recipients who entered KPD for age/size mismatch and altruistic reasons received kidneys from donors with lower Living Kidney Donor Profile Index scores than their actual donor (median [interquartile range] 31.5 [12.3-47]; P < 0.001 and 26 (-1 to 46); P = 0.01 points lower, respectively). Median time to transplant from KPD entry for compatible pair recipients was 70 days (41-163 days), and 44.4% (24/54) of these transplants were preemptive. All chains/swaps incorporating compatible pairs included ABO/HLA incompatible pairs., Conclusions: KPD should be considered for all living donor/recipient pairs because the recipients of these pairs can derive personal benefit from KPD while increasing the donor pool for difficult to match pairs.

Background: Immunosuppressant therapeutic drug monitoring (TDM) usually requires outpatient travel to hospitals or phlebotomy sites for venous blood collection; however Mitra® Microsampling Device (MSD) sampling could allow self-collection and shipping of samples to a laboratory for analysis. This study examined the feasibility of using volumetric microsampling by MSD for TDM of tacrolimus (TaC) and cyclosporin A (CsA) in transplant patients, along with their feedback on the process., Methods: MSD was used to collect TaC and CsA from venous (VB) or capillary (CB) blood. The MSDs were rehydrated, extracted, and analyzed using on-line solid phase extraction coupled to tandem mass spectrometry (SPE-MS/MS). We report an abbreviated method validation of the MSD including: accuracy, precision, linearity, carry-over, and stability using residual venous whole blood (VB) samples. Subsequent clinical validation compared serially collected MSD + CB against VB (200 µL) from transplant patients., Results: Accuracy comparing VB vs. MSD+VB showed high clinical concordance (TaC = 89% and CsA = 98%). Inter- and intra-precision was ≤11.5 %CV for TaC and CsA. Samples were stable for up to 7 days at room temperature with an average difference of <10%. Clinical validation with MSD+CB correlated well with VB for CsA (slope = 0.95, r2 = 0.88, n = 47) and TaC (slope = 0.98, r2 = 0.82, n = 49). CB vs. VB gave concordance of 94% for CsA and 79% for TaC. A satisfaction survey showed 82% of patients preferred having the capillary collection option., Conclusion: Transplant patients favored having the ability to collect capillary samples at home for TaC/CsA monitoring. Our results demonstrate good concordance between MSD+CB and VB for TaC and CsA TDM, but additional studies are warranted., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: With advancements in surgical equipment and procedures, human-system interactions in operating rooms affect surgeon workload and performance. Workload was measured across surgical specialties using surveys to identify potential predictors of high workload for future performance improvement., Summary Background Data: Surgical instrumentation and technique advancements have implications for surgeon workload and human-systems interactions. To understand and improve the interaction of components in the work system, NASA-Task Load Index can measure workload across various fields. Baseline workload measurements provide a broad overview of the field and identify areas most in need of improvement., Methods: Surgeons were administered a modified NASA-Task Load Index survey (0 = low, 20 = high) following each procedure. Patient and procedural factors were retrieved retrospectively., Results: Thirty-four surgeons (41% female) completed 662 surgery surveys (M = 14.85, SD = 7.94), of which 506 (76%) have associated patient and procedural data. Mental demand (M = 7.7, SD = 5.56), physical demand (M = 7.0, SD = 5.66), and effort (M = 7.8, SD = 5.77) were the highest rated workload subscales. Surgeons reported difficulty levels higher than expected for 22% of procedures, during which workload was significantly higher (P < 0.05) and procedural durations were significantly longer (P > 0.001). Surgeons reported poorer perceived performance during cases with unexpectedly high difficulty (P < 0.001)., Conclusions: When procedural difficulty is greater than expected, there are negative implications for mental and physical demand that result in poorer perceived performance. Investigations are underway to identify patient and surgical variables associated with unexpected difficulty and high workload. Future efforts will focus on re-engineering the surgical planning process and procedural environment to optimize workload and performance for improved surgical care.

Background: Active antibody-mediated rejection (AMR) that occurs during the amnestic response within the first month posttransplant is a rare but devastating cause of early allograft loss after kidney transplant. Prior reports of eculizumab treatment for AMR have been in heterogeneous patient groups needing salvage therapy or presenting at varied time points. We investigated the role of eculizumab as primary therapy for active AMR early posttransplant., Methods: We performed a retrospective observational study of a consecutive cohort of solitary kidney transplant recipients who were transplanted between January 1, 2014, and January 31, 2018, and had AMR within the first 30 days posttransplant and treated with eculizumab ± plasmapheresis., Results: Fifteen patients had early active AMR at a median (interquartile range [IQR]) of 10 (7-11) days posttransplant and were treated with eculizumab ± plasmapheresis. Thirteen cases were biopsy proven, and 2 cases were presumed on the basis of donor-specific antibody trends and allograft function. Within 1 week of treatment, the median estimated glomerular filtration rate increased from 21 to 34 mL/min (P = 0.001); and persistent active AMR was only found in 16.7% (2/12) of biopsied patients within 4-6 months. No graft losses occurred, and at last follow-up (median [IQR] of 13 [12-19] mo), the median IQR estimated glomerular filtration rate increased to 52 (46-60) mL/min., Conclusions: Prompt eculizumab treatment as primary therapy is safe and effective for early active AMR after kidney transplant or abrupt increases in donor-specific antibodies when biopsy cannot be performed for diagnosis confirmation.

Background: Current therapy for Type 1 diabetes (T1D) is characterized by significant glucose variability (GV). Pancreas transplantation (PT) is performed in certain T1D patients with and without end-stage renal disease. To date, GV has been examined to a limited extent after PT., Methods: We investigated GV using continuous glucose monitoring (CGM) 3-6 weeks after PT., Results: Eleven patients had simultaneous kidney pancreas transplantation (SPK), nine pancreas after kidney (PAK), and six pancreas transplantation alone (PTA). Mean CGM showed no difference between SPK, 126.5 ± 13.9, PAK 119.9 ± 12.8, and PTA 131.1 ± 29 mg/dL (P value .6). Percentage of time in range (TIR, 70-180 mg/dL) was 92% for SPK, 93.4% in PAK, and 88.5% in PTA with only 0.3%, 1.5%, and 0.3% of time <70 mg/dL. Percentage >180 mg/dL was 7.9% for SPK, 4.9% PAK, and 11% in PTA. Other measures of GV were similar in the three cohorts. In six patients, CGM was performed before and after PT and improved significantly. GV was also better compared with a matched cohort of T1D patients., Conclusions: All 3 types of PT resulted in excellent glucose control 3-6 weeks post-procedure. CGM outcomes represent an important objective outcome after PT., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To identify preoperative factors predicting early admission (within 30 days) of adult kidney transplant recipients to the intensive care unit (ICU)., Patients and Methods: This is a single-center retrospective study of consecutive kidney transplant recipients between January 1, 2007, and December 31, 2016. Children (aged <18 years) and patients who underwent simultaneous multiorgan transplantation were excluded from the analysis. Associations between demographic, transplant-related, and comorbidity variables with ICU admission within 30 days of transplantation were analyzed using univariate and multivariate logistic regression models., Results: Of the 1527 eligible patients, 305 (20%) required early ICU admission. In univariate analysis, older age, higher body mass index (BMI), previous transplantation, myocardial infarction, congestive heart failure, obstructive pulmonary disease, longer ischemia time, pretransplant dialysis, and transplantation from a deceased donor were associated with increased odds of ICU admission. After multivariate adjustment, every 10-year increase in recipient age (odds ratio [OR], 1.26; 95% CI, 1.12-1.42; P <.001), 5-unit increase in BMI (OR, 1.11; 95% CI, 1.00-1.22; P =.049), pretransplant dialysis (OR, 1.57; 95% CI, 1.19-2.08; P =.002), and deceased donor transplantation (OR, 1.82; 95% CI, 1.29-2.55; P <.001) were associated with the increased risk of ICU admission. Preemptive transplantation (OR, 0.64; 95% CI, 0.48-0.84; P =.002) and living donor kidney transplantation (OR, 0.55; 95% CI, 0.39-0.77; P <.001) were associated with lower odds of ICU admission after transplantation., Conclusion: Recipient age, BMI, and the need for pretransplant dialysis are associated with a higher risk of early ICU admission after kidney transplantation, whereas living donor kidney transplantation and preemptive transplantation decrease these odds. Early referral of patients with end-stage renal disease for preemptive transplantation and living donor kidney transplantation can significantly reduce transplant-related ICU admissions.

Predicting which renal allografts will fail and the likely cause of failure is important in clinical trial design to either enrich patient populations to be or as surrogate efficacy endpoints for trials aimed at improving long-term graft survival. This study tests our previous Birmingham-Mayo model (termed the BirMay Predictor) developed in a low-risk kidney transplant population in order to predict the outcome of patients with donor specific alloantibody (DSA) at the time of transplantation and identify new factors to improve graft loss prediction in DSA+ patients. We wanted define ways to enrich the population for future therapeutic intervention trials. The discovery set included 147 patients from Mayo Cohort and the validation set included 111 patients from the Paris Cohort-all of whom had DSA at the time of transplantation. The BirMay predictor performed well predicting 5-year outcome well in DSA+ patients (Mayo C statistic = 0.784 and Paris C statistic = 0.860). Developing a new model did not improve on this performance. A high negative predictive value of greater than 90% in both cohorts excluded allografts not destined to fail within 5 years. We conclude that graft-survival models including histology predict graft loss well, both in DSA+ cohorts as well as DSA- patients., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: To assess the frequency of renal transplantation in patients rendered surgically anephric during treatment of renal cancers as well as the clinicopathologic factors associated with receipt of transplantation., Methods: A retrospective review was conducted to identify patients rendered surgically anephric between 2001 and 2016 due to cancer in both renal units or cancer in an anatomically or functionally solitary kidney. Patient demographics, comorbidities, and cancer features were compared between patients who subsequently received a renal transplantation and those who did not. Time-to-event analysis was used to compare time to transplantation across varied identified parameters., Results: Among 27 patients rendered anephric, 4 (15%) received a renal transplantation over a median follow-up of 21.6 months (interquartile range 7.2, 53.3). All transplanted patients were less than 70 years of age and had cT1a renal parenchymal mass at the time of nephrectomy. No patient undergoing completion nephrectomy for upper tract urothelial carcinoma received transplantation. Patients who were evaluated by the transplant service prior to nephrectomy were more likely to eventually undergo transplantation (60% vs 5%; P < .01). On time-to-event analyses, a cT1a renal parenchymal mass (P < .01) and a pre-nephrectomy transplant evaluation (P < .01) were associated with receipt of a transplant., Conclusion: Patients rendered anephric via nephrectomy for cancer are more likely to receive renal transplantation if they are less than 70 years old, have a cT1a renal parenchymal mass, and receive transplant consultation before nephrectomy. These data may inform future patient counseling., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Although rare, major urologic complications (MUC) in kidney transplantation can cause significant morbidity, increased cost, and may even lead to graft loss. Ureteric stents are routinely used to prevent MUC, although complications related to their use have been reported. Here, we systematically reviewed the role of routine stenting in preventing MUC in kidney transplantation with extravesical ureteric implantation and performed a meta-analysis of 6 randomized controlled trials., Methods: A PubMed search was performed for studies on MUC and stents in kidney transplant recipients. Randomized controlled trials were shortlisted for the review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RevMan 5 was used for statistical analysis, and outcome analysis was done with Cochran-Mantel-Haenszel test using random effect model., Results: Six trials meeting the criteria were identified. Although stent use did not decrease the incidence of urinary leak (odds ratio [OR], 0.39; 95% CI, 0.14-1.11; P = .08) or obstruction (OR, 0.41; 95% CI, 0.13-1.24; P = .11), it was associated with a higher incidence of urinary tract infection (OR, 3.59; 95% CI, 1.33-9.75; P = .01)., Conclusion: In the present era of extravesical ureterovesical anastomosis, routine stenting has a limited role in decreasing major urologic complications and may be associated with higher incidence of urinary tract infections., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Despite substantial evidence demonstrating clear benefit, rates of preemptive kidney transplantation (PreKTx) remain low in the United States. Our goal was to identify barriers to PreKTx., Methods: Using a telephone-administered questionnaire including questions about barriers, timing of referral, timing of education, we retrospectively studied first living donor kidney transplant recipients (2006-2010) at Mayo Clinic, Rochester, MN. Of 235 patients, 145 (62%) responded to the questionnaire (74 PreKTx and 71 non-PreKTx). We compared categorical data with Fisher exact test and median times with Wilcoxon rank sum test., Results: Polycystic kidney disease (PCKD), longer median time between diagnosis and transplant, and time between education about transplant and transplant correlated with PreKTx ( P < 0.01). The presence of at least 1 patient-identified barrier (lack of referral, financial barriers, medical barriers, no identified living donor and donor evaluation delays) was associated with non-PreKTx (0.034) though no single barrier predominated. Age, education level, insurance status and source of referral (primary care, nephrology, and nonphysician referral) were not associated with the rate of PreKTx. Univariate logistic regression identified white race, PCKD, and increased time from diagnosis as factors favoring PreKTx; PCKD and increased time remained significant factors after multivariate analysis., Conclusions: Even among a patient population that is primarily white, educated, and has a spouse or first-degree relative donor, PreKTx rates remain concerningly low. Increased time between diagnosis or education and transplant are predictors of PreKTx. Greater emphasis on transplant education earlier in the stages of chronic kidney disease and community outreach from transplant centers may help to increase the rate of PreKTx., Competing Interests: The authors declare no funding or conflicts of interest.

Background: Notwithstanding 1 documented case of HIV-1 cure following allogeneic stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV-1 positive individuals have failed to cure HIV-1 infection. The aim of our study was to describe changes in the HIV reservoir in a single chronically HIV-infected patient on suppressive antiretroviral therapy who underwent allo-SCT for treatment of acute lymphoblastic leukemia., Methods and Findings: We prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable by multiple measures-including PCR measurements of both total and integrated HIV-1 DNA, replication-competent virus measurement by large cell input quantitative viral outgrowth assay, and in situ hybridization of colon tissue-the patient consented to an analytic treatment interruption (ATI) with frequent clinical monitoring. He remained aviremic off antiretroviral therapy until ATI day 288, when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to 1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA detected in circulating PBMCs before transplantation. The main limitations of this study are the insensitivity of reservoir measurements, and the fact that it describes a single case., Conclusions: allo-SCT led to a significant reduction in the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1 replication. Phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the PBMCs.

Aims: Short-term studies have reported left ventricular (LV) dilatation following surgical creation of arteriovenous fistulas (AVF) or arteriovenous grafts (AVGs), but chronic cardiac structural and functional changes have not been examined or related to clinical outcomes following AVF/AVG. We sought to characterize the long-term changes in cardiac structure and function in patients undergoing shunt creation for haemodialysis., Methods and Results: A retrospective analysis was performed of patients undergoing echocardiography before and after surgical AVF/AVG creation for the initiation of haemodialysis. 137 patients underwent echocardiographic examinations prior to AVF and 2.6 years (median) after AVF creation. Following AVF and dialysis initiation, there were reductions in blood pressure, body weight and estimated plasma volume coupled with modest reverse LV remodelling. In contrast, AVF/AVG creation was associated with significant right ventricular (RV) dilatation and deterioration in RV function. Incident heart failure (HF) developed in 43% of patients in tandem with greater RV remodeling. The development of RV dilation following surgical AVF/AVG was independently associated with increased risk of death [HR 3.9, 95% CI (1.7-9.2), P = 0.001]., Conclusion: In long-term follow-up, RV remodelling and dysfunction develop following AVF/AVG creation and dialysis initiation, despite improved control of LV pressure load through dialysis. Deleterious effects on right heart structure and function are coupled with development of incident HF and increased risk of death. Further study is required to identify patients at greatest risk for detrimental AVF/AVG changes who may benefit from alternate forms of dialysis or potentially ligation of existing AVF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

The treatment of patients with diabetes mellitus (DM) presents many challenges to care providers and represents a major proportion of healthcare expenditure worldwide. Successful pancreas transplantation provides durable glycemic control and improves survival for patients with diabetes. Progress in the field has mainly been based on large single center studies and the cumulative analyses of registry data from the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry. This review focuses on the outcomes of pancreas transplantation for patients with and without end stage renal disease. It describes the current state of pancreas transplantation, gaps in knowledge, and future studies needed to enable more patients to benefit from this treatment. A common theme that emerges is the need for multicenter randomized trials in pancreas transplantation to define clearly the efficacy, risks, and long term benefits., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Given high dialysis mortality rates for patients older than 60 years, accepting a kidney with a high Kidney Donor Profile Index (KDPI) score could enable earlier and potentially preemptive transplantation (preKT). However, evidence regarding the risks of high KDPI allografts in older patients is limited. Our objective was to determine the relative benefit for older patients of KDPI greater than 85% transplant either preemptively or not compared with remaining on the waitlist., Methods: United Network of Organ Sharing data from 2003 to 2012 for adult deceased donor kidney transplant candidates was analyzed to evaluate patient survival in patients older than 60 years for preKT and non-preKT KDPI greater than 85% transplants compared with candidates remaining on the waitlist including patients who received KDPI 0% to 85% transplants according to multivariate Cox regression models., Results: In the first year posttransplant for KDPI greater than 85% of transplants in recipients older than 60 years, preKT had a reduced mortality hazard (hazards ratio [HR], 0.61; 95% confidence interval [95% CI], 0.41-0.90) and non-preKT an increased mortality hazard (HR, 1.15; 95% CI, 1.03-1.27) compared with the waitlist including KDPI 0% to 85% transplant recipients. At 1 to 2 years and after 2 years, both KDPI greater than 85% groups had significant reductions in mortality (1-2 years: preKT HR, 0.38; 95% CI, [0.23-0.60] and non-preKT HR, 0.52; 95% CI, 0.45-0.61; and 2+ years: preKT HR, 0.50; 95% CI, 0.38-0.66 and non-preKT HR, 0.64; 95% CI, 0.58-0.70, respectively)., Conclusions: PreKT and non-preKT KDPI greater than 85% transplant was associated with lower mortality hazard after the first year compared with the waitlist including KDPI 0% to 85% transplants in patients older than 60 years. Further consideration should be given to increased utilization of high KDPI grafts in older patients with the goal of avoiding or limiting time on dialysis.

Purpose: To determine if patient aspirin exposure and timing affect bleeding risk after renal allograft biopsy., Materials and Methods: Review of 6,700 renal allograft biopsies (in 2,362 unique patients) was performed. Median patient age was 53.0 years [interquartile range 43.0, 62.0]; 56.2% of patients were male. Of biopsies, 4,706 (70.2%) were performed in patients with no aspirin exposure within 10 days of biopsy; 664 (9.9%), were performed within 8-10 days of aspirin exposure; 855 (12.8%), within 4-7 days; and 475 (7.1%), within 0-3 days. Follow-up to 3 months after the procedure was completed in all patients. Biopsies were categorized as protocol or indication; 19.7% were indication biopsies. Bleeding complications were graded based on SIR criteria. Logistic regression models examined the association between aspirin use and bleeding events., Results: Rate [95% confidence interval] of major bleeding complications was 0.24% [0.14, 0.39], and rate of any bleeding complication was 0.66% [0.46, 0.90]. Bleeding events were significantly associated with patients undergoing indication biopsies compared with protocol biopsies (odds ratio [OR] 2.27, P = .012). Patient factors associated with major bleeding complications in multivariate models included estimated glomerular filtration rate (OR 0.61, P = .016) and platelet count (OR 0.64, P = .033). Aspirin use was not significantly associated with increased risk of bleeding complication except for use of 325 mg of aspirin within 3 days of biopsy (any complication OR 3.87 [1.12, 13.4], P = .032; major complication OR 6.30 [1.27, 31.3], P = .024)., Conclusions: Renal allograft biopsy bleeding complications are very rare, particularly for protocol biopsies. Use of 325 mg of aspirin within 3 days of renal allograft biopsy was associated with increased bleeding complications., Competing Interests: None of the authors have identified a conflict of interest., (Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to investigate correlations between early subclinical findings (10- and 90-day histology and gene expression data) and late outcomes (transplant glomerulopathy and graft loss) in positive crossmatch kidney transplants (+XMKTx). We compared 34 +XMKTx (19 receiving eculizumab and 15 receiving standard of care without eculizumab) to 13 -XMKTx (between August 2001 and August 2011). At 10 days, light microscopy identified subclinical inflammation in only 18% of +XMKTx, while intragraft gene expression identified inflammation in 79% (gene sets for activated macrophages, dendritic cells, NK cells or T cells). Inflammation persisted at 90 days and was associated with the development of transplant glomerulopathy by 2 years and graft loss. In contrast, endothelial cell (EC) changes present at 90 days by either electron microscopy or gene expression were not associated with transplant glomerulopathy or graft loss in this cohort. Eculizumab treatment did not appear to alter inflammation or EC changes. Therefore, intragraft inflammation might be an appropriate surrogate marker of progression and also a target of therapy to prevent chronic antibody-mediated rejection., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Preemptive kidney transplantation (preKT) is associated with higher patient survival, improved quality of life, and lower costs. However, only a minority of patients receives preKT. The aim of this study was to examine changes over the past decade in rates of preKT, focusing on living donor kidney transplantation (LDKT) and specifically recipients who underwent kidney transplantation within 1 year of initiating dialysis., Methods: Using United Network of Organ Sharing data, we examined retrospectively all kidney transplant candidates (n = 369 103) and recipients (n = 141 254) from 2003 to 2012 in the United States focusing on LDKT (n = 47 108). Predictors of preKT were examined, and patient and graft survival were compared for preKT, pretransplant dialysis less than 1 year, and pretransplant dialysis recipients of 1 year or longer., Results: PreKT occurred in only 17% of recipients overall and 31% of LDKT recipients. Medicare patients (odds ratio [OR], 0.29; 95% confidence interval [95% CI], 0.28-0.31), diabetics (OR, 0.75; 95% CI, 0.69-0.80), and minorities (Hispanics OR, 0.62; 95% CI, 0.57-0.68 and African Americans OR, 0.58; 95% CI, 0.53-0.63) were less likely to receive preKT. Dialysis recipients for less than 1 year comprised 30% of nonpreemptive LDKT. Dialysis recipients of less than 1 year had similar patient survival to preKT (5 years: preKT, 94%; dialysis < 1 year, 94%; dialysis ≥ 1 year, 89%; P < 0.01), but decreased death-censored graft survival (5 years: preKT, 93%; dialysis < 1 year, 89%; and dialysis ≥ 1 year, 89%; P < 0.01)., Conclusions: PreKT remains an unrealized goal for the majority of recipients. Medicare patients, diabetics, and minorities are less likely to receive preKT. Almost one third of nonpreemptive LDKT recipients were dialyzed for less than 1 year, highlighting an important target for improvement.

Background: The natural course of native kidneys after renal transplantation (RT) or dialysis in patients with autosomal dominant polycystic kidney disease (ADPKD) remains poorly understood., Methods: We measured the total volumes of native kidneys and liver in 78 and 68 ADPKD patients, respectively, who had pre-transplant (within 2 years) and at least one post-transplant computed tomography (CT)/magnetic resonance imaging (MRI); in 40 patients with at least two post-transplant but no pre-transplant CT/MRIs; in 9 patients on chronic hemodialysis with at least one CT/MRI before and after beginning dialysis; and in 5 patients who had no image before and more than one image after dialysis. The last imaging was used in patients with multiple studies., Results: Mean total kidney volume (TKV) ( ± SD) prior to transplantation was 3187 ± 1779 mL in the 78 patients who had imaging before and after transplantation and decreased by 20.2, 28.6, 38.3 and 45.8% after 0.5-1 (mean 0.7), 1-3 (1.8), 3-10 (5.7) and >10 (12.6) years, respectively. In the multivariable analysis, time on dialysis prior to RT and time from baseline to transplantation were negatively associated with reduction in TKV, whereas estimated glomerular filtration rate (eGFR) after transplantation and time from transplantation were positively associated with percent reduction in TKV. In the 40 patients with imaging only after transplantation, TKV decreased by 3.2 ± 16.3% between 7.2 ± 6.0 and 11.2 ± 6.8 years after transplantation (P < 0.001). TKV was 11.2 ± 35.6% higher (P = NS) after a follow-up of 3.4 ± 2.0 years in the 9 patients with imaging before and after initiation of hemodialysis and 3.4 ± 40.2% lower (P = NS) in the 5 patients with imaging between 2.0 ± 2.1 and 3.5 ± 3.6 years after initiation of hemodialysis. In the 68 patients with liver measurements, volume increased by 5.8 ± 17.9% between baseline and follow-up at 3.7 ± 3.8 years after transplantation (P = 0.009)., Conclusions: TKV of native polycystic kidneys decreases substantially after RT. The reduction occurs mainly during the early post-transplantation period and more slowly thereafter., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Native nephrectomy (NNx) is often done in patients with autosomal dominant polycystic kidney disease (ADPKD). Controversy exists concerning the need and timing of nephrectomy in transplant candidates. We hypothesize that post-transplant NNx does not negatively impact patient and graft survival., Methods: Among 470 ADPKD transplant recipients included in the study, 114 (24.3%) underwent pre- (30.7%) or post-transplant (69.3%) NNx. Clinical data was retrieved from electronic records. Follow up was until death, graft loss or June 2014. Perioperative complications were compared between the surgical techniques (open or laparoscopic) and between the pre- and post-transplant nephrectomy groups. The effect of nephrectomy on graft survival was analyzed as a time-dependent covariate when performed post-transplant., Results: Mean age at transplant was 52.4 years, 53.8% were male, 93% white, 70% were from living donors and 56.8% were pre-emptive. Nephrectomy was done laparoscopically in 31% and 86% in the pre- and post- transplant nephrectomy groups, respectively. Complications were less common in those who underwent nephrectomy post-transplant (26.6% vs. 48%, p=0.03) but were similar regardless of surgical technique (open, 33.3% vs. laparoscopic 33%, p=0.66). Patient and graft survival were similar between those who underwent pre-transplant nephrectomy and the rest of the recipients. In the post-transplant nephrectomy group, nephrectomy did not affect patient (HR 0.77, CI 0.38-1.54, p=0.45) or graft survival (HR 1.0, CI 0.57-1.76, p=0.1)., Conclusions: Nephrectomy does not adversely affect patient or graft survival. Post-transplant nephrectomy is feasible when indicated without compromising long term graft outcome and has fewer complications than pre-transplant nephrectomy.

Purpose: Among kidney transplant recipients with acute kidney injury, the differential diagnosis must be broadened to include conditions such as rejection, immunocompromised host infections, anatomic pathologies, and recurrent or de novo glomerular diseases. In this case report, we describe an unusual cause of acute renal allograft injury due to external compression of the allograft ureter., Methods: Retrospective review; case report., Results: The patient developed acute kidney injury of the renal allograft due to external compression of the allograft ureter coincident with a cecal volvulus. The patient underwent lysis of adhesions, right hemicolectomy, and end ileostomy creation with resolution of acute kidney injury., Conclusions: Cecal volvulus is an uncommon cause of bowel obstruction and is often associated with adhesions following abdominal surgery. To our knowledge, cecal volvulus has not previously been reported as a direct contributor to acute kidney injury. This case highlights the need for a systematic approach to the patient with acute kidney injury and the special considerations involved in the diagnosis of renal failure in the kidney transplant population.

The majority of kidney transplant recipients die from cardiovascular events. Physical activity may be a modifiable risk factor for cardiovascular disease following transplant. The goal of our study was to examine adherence to a physical activity intervention following kidney transplant and its impact on metabolic parameters. All patients who received a kidney transplant at our center between 12/2010 and 12/2011 received usual care (n = 162), while patients transplanted between 12/2011 and 1/2013 received a 90-day pedometer-based physical activity intervention (n = 145). Metabolic parameters were assessed at four and 12 months post-transplant. Baseline demographics and clinical management were similar between cohorts. Adherence to the prescription was 36.5%. Patients in the physical activity cohort had lower systolic and diastolic blood pressure four months post-transplant compared to the usual care cohort (122 ± 18 vs. 126 ± 16 mmHg, p = 0.049 and 73 ± 10 vs. 77 ± 9, p = 0.004) and less impaired fasting glucose (20.7% vs. 30.9%, p = 0.04). Twelve-month outcomes were not different between cohorts. Over one-third of our cohort adhered to a pedometer-based physical activity intervention following kidney transplant, and the intervention was associated with improved metabolic parameters. Further study of post-transplant exercise interventions and methods to optimize long-term adherence are needed., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pancreas transplantation can provide insulin independence, improved survival, and improved quality of life for patients with diabetes mellitus. However, there has been a steady decline in the number of pancreas transplants (either alone or with a kidney) performed in the United States over the past decade. This decline has occurred despite a steady increase in the number of diabetic patients with end stage renal disease on the kidney transplant alone waiting list. This paper will review the current status of pancreas transplantation, suggest possible explanations for the declining numbers of transplants, highlight current gaps in knowledge, and suggest possible future studies and developments aimed at increasing the application of this effective therapy., (Copyright© 2016 by the Terasaki Foundation Laboratory.)

Terminal complement blockade has been shown to decrease the incidence of early acute antibody-mediated rejection (eAMR) in the first month after positive cross-match kidney transplant recipients, yet some patients still develop eAMR. The current study investigated possible mechanisms of eAMR despite eculizumab treatment. Of the 26 patients treated with eculizumab, two developed clinical eAMR and another patient developed histologic signs of eAMR without graft dysfunction ('subclinical eAMR'). Twenty-three did not have histologic injury on early surveillance biopsies. All 26 patients had therapeutic levels of eculizumab and showed complete blockade of complement in hemolytic assays. High levels of donor-specific alloantibody (DSA) including total IgG, IgG3, and C1q+ DSA were present in patients with and without eAMR, and none correlated well with eAMR. In contrast, IgM DSA was present in only four patients after transplantation: the two patients with clinical eAMR, one patient with subclinical AMR, and one patient without eAMR (P = 0.006 correlation with eAMR). Both clinical eAMR episodes were easily treated with plasma exchange which removed IgM more completely and rapidly than IgG, resulting in normalization of function and histology. These data suggest a possible role of antidonor IgM DSA in the pathogenesis of eAMR in patients treated with terminal complement blockade (ClinicalTrials.gov Identifier: NCT00670774)., (© 2014 Steunstichting ESOT.)

Background: ABO-incompatible kidney transplantations (ABOiKTxs) seem to have better long-term outcomes than positive crossmatch kidney transplantations (+XMKTxs)., Methods: This study aimed to assess the differences in chronic injury on histologic findings on 1- and 5-year surveillance biopsies and the clinical outcomes in living-donor kidney transplantations performed between May 1999 and November 2006 including 102 +XMKTxs, 73 ABOiKTxs, and 652 conventional KTxs., Results: Although 5-year patient survival was similar between groups, graft loss between 1 and 5 years was similar in ABOiKTx (2.6% per year) and conventional KTx (1.7% per yr), and both were lower than that of +XMKTx (5.8% per year). At 5 years, renal function was similar in ABOiKTx and conventional KTx, and both were higher than that of +XMKTx, which had higher rates of inflammation and chronic glomerulopathy on both 1- and 5-year biopsies. Despite having evidence of less chronic injury, ABOiKTx showed a higher rate of intragraft complement activation (C4d deposition) at 5 years compared with +XMKTx (77.8% vs. 18.9%, P<0.001)., Conclusion: These data suggest that +XMKTxs have high rates of chronic inflammation at 1 and 5 years after transplantation, which may explain the higher rates of graft loss and lower renal function compared with other factors such as anti-donor antibody or intragraft complement deposition.

Background: Kidney paired donation (KPD) has emerged as a viable option for renal transplant candidates with incompatible living donors. The aim of this study was to assess the "performance" of a three-site KPD program that allowed screening of multiple donors per recipient., Methods: We reviewed retrospectively the activity of our KPD program involving three centers under the same institutional umbrella. The primary goal was to achieve a transplant that was both ABO compatible and had a negative or low-positive flow cytometric crossmatch (+XM)., Results: During the 40-month study period, 114 kidney transplant candidates were enrolled-57% resulting from a +XM and 39% resulting from ABO incompatible (ABOi) donors. Important outcomes were as follows: (1) 81 (71%) candidates received a transplant and 33 (29%) were still waiting; (2) 368 donors were evaluated, including 10 nondirected donors; (3) 82% (37/45) of ABOi candidates underwent transplantation; (4) 56% (36/65) of +XM candidates underwent transplantation (however, all but four of these had a cPRA less than 95%); (5) at the end of the study period, 97% (28/29) of +XM candidates still waiting had a cPRA greater than 95%., Conclusions: These data suggest evaluating large numbers of donors increases the chances of KPD. Patients with a cPRA greater than 95% are unlikely to receive a negative or low-positive +XM, suggesting the need for desensitization protocols in KPD.

Death with function (DWF) is a major cause of kidney allograft failure. Allograft dysfunction may contribute to DWF. The aim of this study was to examine the relationship between DWF and allograft function using estimated GFR (eGFR) and histology. We retrospectively analyzed 1842 kidney allografts transplanted at our center from 1996 to 2010. eGFR was estimated using the MDRD equation. Biopsies obtained 12 months posttransplant and within 1 year of DWF were analyzed. Proportional hazards models were used to examine the relationship between eGFR and DWF. During 68 ± 43 months of follow-up, 14% (n = 256) of recipients experienced DWF. Risk factors of DWF included increasing recipient age (hazard ratio [HR] = 2.07, confidence interval [CI] 1.77-2.43, p < 0.0001), diabetes (HR = 2.58, CI 1.81-3.69, p < 0.0001), prior dialysis (HR = 1.47, CI 1.05-2.06, p = 0.03) and eGFR <40 mL/min/1.73 m(2) (HR 2.26 per 10 mL/min/1.73 m(2) decrease in eGFR, CI 1.82-2.81, p < 0.0001). Prior to death, only 15.9% (n = 39) of DWF recipients had stage 4 chronic kidney disease (CKD) and only 4.9% (n = 12) had stage 5 CKD. Most biopsies performed within 1 year of DWF (68%) demonstrated benign histology and were comparable to biopsies from matched controls. In conclusion, allograft dysfunction is independently associated with DWF. However, the majority of DWF recipients have well-preserved allograft function and histology prior to death., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)