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With the rapid spread of SARS‐CoV2 has come a rapid proliferation of clinical research studies, resulting in considerable strain on research ethics committees (RECS), which need to review study proposals. RECs are pressured to move through the review process quickly so that studies can get underway to address the pandemic. These committees are also asked to increase efficiency without relaxing the standards for ethical review. RECs are accustomed to external pressure for approval from investigators; however, in the Covid‐19 era, this pressure is coming from not only the sponsors and investigators but also many other stakeholders, including world leaders, the community, the media, and professional organizations. Drawing on the authors' experiences on a central REC reviewing complex multicenter Covid‐19 studies, this commentary describes challenges that are inherent to Covid‐19 research studies, such as the difficulty of obtaining informed consent from patients ill with the highly infectious virus. The commentary recommends several steps that RECs can take to ensure ethical review of research studies during the Covid‐19 pandemic and future infectious disease outbreaks. [ABSTRACT FROM AUTHOR]

Renal transplantation between monozygous identical twins provides an opportunity to utilize minimal immunosuppression to maintain stable allograft function, thereby alleviating the toxicities of immunosuppressive therapy. Despite monozygosity, there is a possibility of discordant protein presentation in identical twins that could trigger alloimmune response and lead to graft injury. Therefore, the optimal immunosuppression regimen in this patient population is unknown, and the safety of immunosuppression withdrawal remains controversial. Herein, we describe two patients who underwent successful renal transplantation from monozygotic identical twin donors. Monozygosity was determined using short tandem repeat (STR) analysis. All immunosuppression was successfully discontinued at 2 days and 3 weeks, respectively, after transplantation. Both patients are alive with functioning renal grafts at 1 year and 5 years after transplant, respectively. These two cases suggest that immunosuppression can be withdrawn safely and rapidly in select monozygous identical twin renal transplant recipients. [ABSTRACT FROM AUTHOR]

Abstract: Background: The benefits of pancreas transplantation are often difficult to measure. Here, we sought to determine the difference in quality of life for diabetic patients with and without a functional pancreas transplant alone (PTA). Methods: Pancreas transplant alone cases from 1993 to 2015 were considered. An IRB‐approved survey inclusive of 15 questions spanning four domains was employed. Chi‐square, Fisher's exact, and the T test were used where appropriate. Results: A total of 137 PTAs were performed during the study period. Of those reached (n = 32), 94% responded to the survey. Self‐reported health scores were better (2.1 vs 3.0) for those with functioning pancreata (n = 18) vs those with a non‐functional pancreas (n = 14), respectively (P = .036). Those with a functional pancreas had a HgbA1c of 5.3, vs 7.7 for a non‐functional pancreas (P = .016). Significant hypoglycemia was reported in two of 18 with a functional transplant vs nine of 14 patients with a failed transplant (P = .003). Daily frustration with blood sugar affecting quality of life was significantly higher for patients with non‐functional pancreas grafts (P < .001). Conclusions: Pancreas transplantation alone is associated with better glucose control than insulin. In addition, recipients of functional PTAs have improved quality of life and better overall health scores than those with failed grafts. [ABSTRACT FROM AUTHOR]

More and more systems are becoming solely dependent on GPS or other Global Navigation Satellite Systems (GNSS) for their precise position, timing, and frequency information. Along with this explosive growth comes an increasing awareness of GNSS vulnerabilities such as interference, jamming, and spoofing. eLoran is a high-power, low-frequency, ground-wave radio broadcast system, capable of providing 10-meter positioning accuracy, Stratum-1 frequency distribution, and UTC timing well within 1 μs across very large areas (1,000 mi). Application of differential corrections for timing further improves the accuracy to better than 100 ns. eLoran is a proven technology, well established for providing services very similar to those delivered by GNSS, with characteristics and failure modes that are complementary to GNSS. This paper discusses the general concept of eLoran timing and UTC distribution, and the current prototype service. It highlights plans for an initial four-station CONUS-wide timing service, which can be expanded to provide increased coverage and redundancy and deeper penetration into buildings. Additional stations enable positioning and navigation services. Copyright © 2017 Institute of Navigation [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives Reducing preventable harm from repeat medication prescriptions is a patient safety priority worldwide. In the United Kingdom, repeat prescriptions items issued has doubled in the last 20 years from 5.8 to 13.3 items per patient per annum. This has significant resource implications and consequences for avoidable patient harms. Consequently, we aimed to test a risk management model to identify, measure, and reduce repeat prescribing system risks in primary care. Methods All 48 general medical practices in National Health Service (NHS) Lambeth Clinical Commissioning Group (an inner city area of south London in England) were recruited. Multiple interventions were implemented, including educational workshops, a web-based risk monitoring system, and external reviews of repeat prescribing system risks by clinicians. Data were collected via documentation reviews and interviews and subject to basic thematic and descriptive statistical analyses. Results Across the 48 participating general practices, 62 unique repeat prescribing risks were identified on 505 occasions (eg, practices frequently experiencing difficulty interpreting medication changes on hospital discharge summaries), equating to a mean of 8.1 risks per practice (range: 1-33; SD = 7.13). Seven hundred sixty-seven system improvement actions were recommended across 96 categories (eg, alerting hospitals to illegible writing and delays with discharge summaries) with a mean of 15.6 actions per practice (range: 0-34; SD = 8.0). Conclusions The risk management model tested uncovered important safety concerns and facilitated the development and communication of related improvement recommendations. System-wide information on hazardous repeat prescribing and how this could be mitigated is very limited. The approach reported may have potential to close this gap and improve the reliability of general practice systems and patient safety, which should be of high interest to primary care organisations internationally. [ABSTRACT FROM AUTHOR]

Background Lecithin cholesterol acyl transferase ( LCAT) deficiency is a rare autosomal recessive disorder of lipoprotein metabolism that results in end-stage renal disease ( ESRD) necessitating transplantation. As LCAT is produced in the liver, combined kidney and liver transplantation was proposed to cure the clinical syndrome of LCAT deficiency. Methods A 29-year-old male with ESRD secondary to LCAT deficiency underwent a sequential kidney-liver transplantation from the same living donor (LD). One year following the kidney transplant, auxiliary partial orthotopic liver transplant ( APOLT) of a left lateral segment from the same donor was performed. Results At 5 years follow-up, there have been no major complications, readmissions, or rejection episodes. Serum lipid abnormalities recurred within the first year, but liver and kidney allograft function remains intact. Conclusion Few cases of sequential transplantation from the same LD have been performed in adults. This is the first APOLT and multi-organ transplant performed for LCAT deficiency. Sequential organ transplant from the same LD for ESRD secondary to a metabolic disorder of the liver is feasible in adults and should be further investigated. [ABSTRACT FROM AUTHOR]

Weir MR, Bartlett ST, Drachenberg CB. Eosinophilia as an early indicator of pancreatic allograft rejection. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01440.x. © 2011 John Wiley & Sons A/S. Abstract: Monitoring pancreas transplant recipients for rejection is an inexact science. Serial monitoring of urinary amylase has been used for patients with a bladder-drained pancreas. An increase in serum amylase and lipase has been utilized as an in vivo measure of pancreas rejection in patients with enteric pancreatic exocrine drainage. Decreases in urinary amylase or increases in serum amylase or lipase, respectively, in these two different types of surgical drainage would prompt a pancreas biopsy for histologic confirmation of rejection. Herein, we describe the case of an enteric-drained pancreatic transplant recipient who presented with peripheral eosinophilia at least one month before she developed increases in serum amylase and lipase. A pancreas allograft biopsy indicated eosinophilic acute cellular rejection. Peripheral eosinophilia may be a useful early indicator of pancreas graft rejection preceding changes in serum pancreatic enzymes by approximately one month. [ABSTRACT FROM AUTHOR]

OBJECTIVES To assess transplantation of high-risk kidneys with incidental renal masses (found occasionally during the routine evaluation of a living kidney donor) into recipients with limited life-expectancy on haemodialysis, as this offers a potential solution to the current organ deficit. PATIENTS AND METHODS We detected five small (<2.3 cm), incidental, enhancing renal masses during donor evaluation. All patients had a standard metastatic evaluation. After laparoscopic donor nephrectomy a back-table partial nephrectomy was performed and frozen-section analysis was used to confirm both the diagnosis and negative surgical margins before transplantation. RESULTS Renal cell carcinoma was found in three of the five masses (one each cystic, clear cell and papillary; Fuhrman grades II, II and III, respectively) and the other two patients had angiomyolipoma. There were no long-term complications in the transplanted kidneys. One patient developed delayed acute humoral rejection after transplantation and was treated appropriately. Both donor and recipient were followed with periodic imaging. At a median (range) last follow-up of 15 (1–41) months, four patients were alive and one had died from complications after a fall. The cancer-specific survival was 100%. There was no evidence of local recurrence in any patient at the last follow-up. CONCLUSION Live donor kidneys with incidental small renal masses might be acceptable for transplantation in high-risk recipients after careful back-table partial nephrectomy. [ABSTRACT FROM AUTHOR]

Memory T cells are heterogeneous in expression of lymph node homing receptors, delineating "central-memory" (T, CD62L/CCR7) and "effector-memory" (T, CD62L/CCR7) subsets that migrate to lymphoid and non-lymphoid tissues, respectively. It is not known how these subsets arise or how homing receptor expression and tissue origin determine their functional and migratory properties. Here, we investigated the role of CD62L expression in the generation, function, distribution and migration of heterogeneous memory CD4 T cells specific for influenza hemagglutinin (HA). We found that CD62L and CD62L memory subsets are generated independent of CD62L expression by the activated precursor, and both subsets distribute into spleen and lung. Functionally, spleen- and lung-derived CD62L memory subsets produce effector cytokines at similar kinetics but differ strikingly in cell surface phenotype and migration: the CD62L memory subset expresses a classic memory phenotype (CD45RB/CD44/CD11a), while the CD62L subset expresses an unconventional phenotype (CD45RB/CD44/CD11a), defining a new polyclonal memory subset. The CD62L subset also trafficked more efficiently than CD62L cells into lymph nodes; however, only lung but not spleen CD62L memory T cells homed to lung. Our results reveal novel phenotypic heterogeneity of memory CD4 T cells co-segregating with CD62L expression and tissue-specific tropism of non-lymphoid memory CD4 T cells. [ABSTRACT FROM AUTHOR]

The study was performed to compare the efficacy and side effects of azathioprine (AZA) and mycophenolate mofetil (MMF) in conjunction with cyclosporine or tacrolimus and steroids for the prevention of acute pancreas rejection during the first 6 months of pancreas transplantation. In this case-controlled study, MMF is compared with historical controls of AZA in the prevention of acute pancreas rejection. The primary measures of treatment efficacy were patient and pancreas survival rate at 6 months after transplantation. Secondary efficacy measures were the occurrence of biopsy proven pancreas rejections and the use of antilymphocyte preparations for rejection treatment. A total of 111 pancreas transplant patients (57 in the AZA group and 54 in the MMF group) were evaluated. The 6-month patient survival rate was 96% in the AZA group versus 97% in the MMF group (p = 0.57). The 6-month pancreas graft survival rate was 88% in the AZA group versus 91% in the MMF group (p = 0.29). However, biopsy-proven rejection episodes during the first 6 months of transplantation were significantly lower with MMF (46%) than with AZA (69%) (p = 0.01). In addition, patients in the AZA group received a greater number of full courses of antilymphocyte therapy as a rejection treatment (p = 0.004). Overall, the frequency of adverse events was similar, although the MMF group experienced higher incidences of gastrointestinal adverse events. In conclusion, compared with AZA, MMF significantly reduces the rate of biopsy-proven pancreas rejection during the first 6 months of transplantation and is well tolerated, except for gastrointestinal adverse events. [ABSTRACT FROM PUBLISHER]

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Background: Protease inhibitors (PI) pose a challenge post‐transplant due to significant drug interactions with calcineurin inhibitors, prompting many clinicians to convert patients to non‐interacting regimens prior to transplant. The purpose of this study was to examine the impact of PI‐based regimens on graft outcomes in HIV‐infected renal transplant recipients. Methods: In this retrospective cohort study, 50 HIV‐infected renal allograft recipients (27 receiving a PI regimen, 23 receiving a non‐PI regimen) transplanted between 2003‐2015 were analyzed. Results: Cumulative rejection rates at 12 and 36 months were 41% and 54% in the PI group vs 52% and 86% in the non‐PI group. At last follow‐up, the overall risk of acute rejection in the PI group was 46% lower compared with the non‐PI cohort (P = 0.12). Patients who received a PI‐based regimen had significantly reduced graft failure rates (P = 0.027). There was no difference between groups in the degree of interstitial fibrosis/tubular atrophy, arteriolar hyalinosis, arterial sclerosis, or glomerular sclerosis on available biopsies, despite longer follow‐up time in the PI group. Conclusions: Our study suggests that PI‐based antiretroviral therapy regimens are associated with improved graft survival and that patients can achieve adequate outcomes on a PI‐based regimen when necessary. Due to study limitations, further studies are needed to determine the optimal immunosuppression/antiretroviral therapy regimen post‐transplant. [ABSTRACT FROM AUTHOR]