Publications by authors named "John Roberts"

609 Publications

Biliary obstruction following ureteral revision of a transplanted kidney.

Am J Transplant 2021 04;21(4):1657-1659

Division of Transplantation, Department of Surgery, University of California San Francisco, San Francisco, California.

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http://dx.doi.org/10.1111/ajt.16361DOI Listing
April 2021

Estimated Impact of Novel Coronavirus-19 and Transplant Center Inactivity on ESRD-related Patient Mortality in the United States.

Clin Transplant 2021 Mar 22:e14292. Epub 2021 Mar 22.

Department of Medicine - Med/Nephrology, Stanford University, Stanford, CA.

To predict if the COVID-19 pandemic and transplant center responses could have resulted in preventable deaths, we analyzed registry information of the U.S. ESRD patient population awaiting kidney transplantation. Data were from the Organ Procurement and Transplantation Network (OPTN), the U.S. Centers for Disease Control and Prevention, and the United States Renal Data System. Based on 2019 OPTN reports, annualized reduction in kidney transplantation of 25% to 100% could result in excess deaths of waitlisted (deceased donor) transplant candidates from 84 to 337 and living donor candidate excess deaths from 35 to 141 (total 119 to 478 potentially preventable deaths of transplant candidates). Changes in transplant activity due to COVID-19 varied with some centers shutting down while others simply heeded known or suspected pandemic risks. Understanding potential excess mortality for ESRD transplant candidates when circumstances compel curtailment of transplant activity may inform policy and procedural aspects of organ transplant systems allowing ways to best inform patients and families as to potential risks in shuttering organ transplant activity. Considering that more than 700,000 Americans have ESRD with 100,000 awaiting a kidney transplant, our highest annual estimate of 478 excess total deaths from postponing kidney transplantation seems modest.
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http://dx.doi.org/10.1111/ctr.14292DOI Listing
March 2021

Argentine Black and White Tegu (Salvator merianae) can survive the winter under semi-natural conditions well beyond their current invasive range.

PLoS One 2021 10;16(3):e0245877. Epub 2021 Mar 10.

U.S. Geological Survey, Fort Collins Science Center, Fort Collins, Colorado, United States of America.

The Argentine Black and White Tegu (Salvator merianae, formerly Tupinambis merianae) is a large lizard from South America. Now established and invasive in southern Florida, and it poses threats to populations of many native species. Models suggest much of the southern United States may contain suitable temperature regimes for this species, yet there is considerable uncertainty regarding either the potential for range expansion northward out of tropical and subtropical zones or the potential for the species establishing elsewhere following additional independent introductions. We evaluated survival, body temperature, duration and timing of winter dormancy, and health of wild-caught tegus from southern Florida held in semi-natural enclosures for over a year in Auburn, Alabama (> 900 km northwest of capture location). Nine of twelve lizards emerged from winter dormancy and seven survived the greater-than-one-year duration of the study. Average length of dormancy (176 d) was greater than that reported in the native range or for invasive populations in southern Florida and females remained dormant longer than males. Tegus grew rapidly throughout the study and the presence of sperm in the testes of males and previtellogenic or early vitellogenic follicles in female ovaries at the end of our study suggest the animals would have been capable of reproduction the following spring. The survival and overall health of the majority of adult tegus in our study suggests weather and climate patterns are unlikely to prevent survival following introduction in many areas of the United States far from their current invasive range.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245877PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946314PMC
March 2021

BK virus nephropathy in non-renal solid organ transplant recipients: Are we looking hard enough?

Clin Transplant 2021 Feb 21:e14265. Epub 2021 Feb 21.

Division of Nephrology, Duke University School of Medicine, Durham, NC, USA.

We retrospectively examined the clinical characteristics, pathological features, and outcomes of BK viremia and nephropathy in a population of non-renal solid organ transplant patients (NRSOT) referred for outpatient nephrology consultation over a period of 5 years. In the entire cohort of liver, heart, and lung transplant recipients referred to this clinic, 14% percent were found to have BK viremia with a median peak serum BK viral load of 35 500 copies/ml (range 250 to 21 100 000 copies/ml). BK viremia resolved in six of the seventeen patients (35%). Four out of five patients biopsied showed BK virus (BKV) nephropathy. Eleven out of seventeen patients with BK viremia developed advanced (stage 4 or 5) chronic kidney disease. Four patients developed rejection of their solid organ transplant within the first year post detection of BK viremia after immunosuppression reduction. We conclude that a multi-center study is required to evaluate whether implementation of a systematic BK screening program would be effective in early detection and management of this problem in the NRSOT population.
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http://dx.doi.org/10.1111/ctr.14265DOI Listing
February 2021

Current status of left lobe adult to adult living donor liver transplantation.

Curr Opin Organ Transplant 2021 Apr;26(2):139-145

Department of Surgery, University of California, San Francisco, California, USA.

Purpose Of Review: This review describes the history and current state of left lobe living donor liver transplantation (LDLT). The transplant community continues to face an organ shortage on a global scale, and the expansion of LDLT is attractive because it allows us to provide life-saving liver transplants to individuals without drawing from, or depending on, the limited deceased donor pool. Donor safety is paramount in LDLT, and for this reason, left lobe LDLT is particularly attractive because the donor is left with a larger remnant.

Recent Findings: This article reviews the donor and recipient evaluations for left lobe LDLT, discusses small for size syndrome and the importance of portal inflow modification, and reviews recipient outcomes in right lobe versus left lobe LDLT.

Summary: Left lobe LDLT was the first adult-to-adult LDLT ever to be performed in Japan in 1993. Since that time, the use of both right and left lobe LDLT has expanded immensely. Recent work in left lobe LDLT has emphasized the need for inflow modification to reduce portal hyperperfusion and early graft dysfunction following transplant. Accumulating evidence suggests, however, that even though early graft dysfunction following LDLT may prolong hospitalization, it does not predict graft or patient survival.
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http://dx.doi.org/10.1097/MOT.0000000000000863DOI Listing
April 2021

With the proven tenacity of waitlist mortality shouldn't we resist the urge to make mountains out of statistical molehills?

Liver Transpl 2021 Feb 9. Epub 2021 Feb 9.

Department of Surgery, Division of Transplant, University of California San Francisco, San Francisco, CA, USA.

The authors of Outcomes in living donor compared to deceased donor primary liver transplant in lower acuity MELD score < 30 present an analysis comparing outcomes based on graft type (1) . This type of analysis is challenging for a number of reasons, so the authors should be commended for their efforts. The finding of suboptimal outcome after left lobe LDLT in recipients with ascites is an important finding.
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http://dx.doi.org/10.1002/lt.26007DOI Listing
February 2021

Genetic variation of Ascosphaera apis and colony attributes do not explain chalkbrood disease outbreaks in Australian honey bees.

J Invertebr Pathol 2021 Mar 29;180:107540. Epub 2021 Jan 29.

Department of Pharmacy and Biomedical Sciences, La Trobe Institute of Molecular Science, La Trobe University, PO Box 199, Bendigo, Victoria 3552, Australia. Electronic address:

Chalkbrood infection caused by the fungus Ascosphaera apis currently has a significant impact on Australia's apicultural industry. We investigated the genetic variation of A. apis and colony and apiary level conditions to determine if an emerging, more virulent strain or specific conditions were responsible for the prevalence of the disease. We identified six genetically distinct strains of A. apis, four have been reported elsewhere and two are unique to Australia. Colonies and individual larvae were found to be infected with multiple strains of A. apis, neither individual strains, combinations of strains, or obvious colony or apiary characteristics were found to be predictive of hive infection levels. These results suggest that host genotype plays an important role in colony level resistance to chalkbrood infection in Australia.
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http://dx.doi.org/10.1016/j.jip.2021.107540DOI Listing
March 2021

A world-wide survey on kidney transplantation practices in breast cancer survivors: The need for new management guidelines.

Am J Transplant 2021 Jan 9. Epub 2021 Jan 9.

Division of General Surgery, Department of Surgery, University of California, San Francisco, California.

Kidney transplantation reduces mortality in patients with end stage renal disease (ESRD). Decisions about performing kidney transplantation in the setting of a prior cancer are challenging, as cancer recurrence in the setting of immunosuppression can result in poor outcomes. For cancer of the breast, rapid advances in molecular characterization have allowed improved prognostication, which is not reflected in current guidelines. We developed a 19-question survey to determine transplant surgeons' knowledge, practice, and attitudes regarding guidelines for kidney transplantation in women with breast cancer. Of the 129 respondents from 32 states and 14 countries, 74.8% felt that current guidelines are inadequate. Surgeons outside the United States (US) were more likely to consider transplantation in a breast cancer patient without a waiting period (p = .017). Within the US, 29.2% of surgeons in the Western region would consider transplantation without a waiting period, versus 3.6% of surgeons in the East (p = .004). Encouragingly, 90.4% of providers surveyed would consider eliminating wait-times for women with a low risk of cancer recurrence based on the accurate prediction of molecular assays. These findings support the need for new guidelines incorporating individualized recurrence risk to improve care of ESRD patients with breast cancer.
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http://dx.doi.org/10.1111/ajt.16483DOI Listing
January 2021

Opioid use prior to liver transplant is associated with increased risk of death after transplant.

Am J Surg 2020 Nov 20. Epub 2020 Nov 20.

Department of Surgery, University of California, San Francisco, San Francisco, CA, USA. Electronic address:

Background: Opioids are generally discouraged and used sparingly in liver transplant (LT) candidates prior to LT. This study examined the relationship between opioid use at the time of LT and graft and patient survival following transplantation.

Methods: A retrospective single center cohort study of LT recipients from June 2012 to December 2019 was performed. Primary outcomes were graft and patient survival, analyzed with the Kaplan-Meier method and Cox proportional hazards models; primary predictor was active opioid prescription at LT.

Results: 751 LT recipients were included; 16% had an opioid prescription at LT. Post-transplant death was significantly greater in opioid users (pvalue<0.001). In a multivariable Cox model examining predictors of death, opioid use remained associated with a significant increase in the risk of death (HR 2.4 CI 1.5-4.0, p < 0.001) even after controlling for other factors.

Conclusion: Opioid use at LT is associated with a markedly increased risk of death following transplant.
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http://dx.doi.org/10.1016/j.amjsurg.2020.11.039DOI Listing
November 2020

Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation.

Am J Transplant 2021 04 27;21(4):1612-1621. Epub 2021 Feb 27.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR =  1.68 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF =  2.09 ; PFNC =  2.40 ; PCC =  2.24 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR =  1.62 ) than CLDKT (aHR =  2.29 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.
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http://dx.doi.org/10.1111/ajt.16471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016719PMC
April 2021

Phase 1 study of belinostat (PXD-101) and bortezomib (Velcade, PS-341) in patients with relapsed or refractory acute leukemia and myelodysplastic syndrome.

Leuk Lymphoma 2020 Dec 28:1-14. Epub 2020 Dec 28.

Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.

We report the results of a phase 1 dose-escalation study of belinostat and bortezomib in adult patients with acute leukemia or MDS or CML with blast crisis. Thirty-eight patients received IV belinostat days 1-5 and 8-12 with IV bortezomib days 1, 4, 8, and 11 every 21 days. QTc prolongation was the only identified DLT. The RP2Ds were 1.3 mg/m bortezomib and 1000 mg/m belinostat. One patient with highly refractory rearranged biphenotypic AML with multiple karyotypic aberrations had a complete pathologic and karyotypic response. One patient with post-MPN AML remained on study with stable disease (SD) for 32 cycles. Whole-exome sequencing revealed no aberrations in the first patient and a hyper-mutator genotype in the second. Eighteen patients had a best response of SD. We conclude that this treatment strategy is feasible but has limited activity in this population. Nevertheless, the factors that predict exceptional responses to this strategy warrant further investigation.
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http://dx.doi.org/10.1080/10428194.2020.1861270DOI Listing
December 2020

Retransplantation After Living Donor Liver Transplantation: Data from the Adult to Adult Living Donor Liver Transplantation Study (A2ALL).

Transplantation 2020 Jun 22. Epub 2020 Jun 22.

Department of Surgery University of California, San Francisco San Francisco, CA, USA.

Background: The use of living donor liver transplantation (LDLT) for primary liver transplant (LT) may quell concerns about allocating deceased donor organs if the need for re-transplantation (re-LT) arises because the primary LT did not draw from the limited organ pool. However, outcomes of re-LT after LDLT are poorly studied. The purpose of this study was to analyze the Adult to Adult Living Donor Liver Transplantation Study (A2ALL) data to report outcomes of re-LT after LDLT, with a focus on long-term survival after re-LT.

Methods: A retrospective review of A2ALL data collected between 1998-2014 was performed. Patients were excluded if they received a deceased donor liver transplant. Demographic data, post-operative outcomes and complications, graft and patient survival, and predictors of re-LT and patient survival were assessed.

Results: Of the 1065 patients who underwent LDLT during the study time period, 110 recipients (10.3%) required re-LT. In multivariable analyses, HCV, longer LOS at LDLT, HAT, biliary stricture, infection, and disease recurrence were associated with an increased risk of re-LT. Patient survival among re-LT patients was significantly inferior to those who underwent primary transplant only at 1 (86 vs. 92%), 5 (64 vs. 82%), and 10 years (44 vs. 68%).

Conclusions: Approximately 10% of A2ALL patients who underwent primary LDLT required re-LT. Compared with patients who underwent primary LT, survival among re-LT recipients was worse at 1, 5, and 10 years after LT, and re-LT was associated with a significantly increased risk of death in MV modeling (HR 2.29, p<0.001).
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http://dx.doi.org/10.1097/TP.0000000000003361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942712PMC
June 2020

Reducing the Shortage of Transplant Kidneys: A Lost Opportunity for the US Health Resources and Services Administration (HRSA).

Am J Kidney Dis 2020 Nov 30. Epub 2020 Nov 30.

Department of Surgery, University of California San Francisco, San Francisco, CA.

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http://dx.doi.org/10.1053/j.ajkd.2020.10.007DOI Listing
November 2020

Albumin-Mediated Uptake Improves Human Clearance Prediction for Hepatic Uptake Transporter Substrates Aiding a Mechanistic In Vitro-In Vivo Extrapolation (IVIVE) Strategy in Discovery Research.

AAPS J 2020 11 16;23(1). Epub 2020 Nov 16.

Department of Pharmacokinetics and Drug Metabolism, Amgen Research, Amgen Inc, 360 Binney St, Cambridge, Massachusetts, 02142, USA.

This study focused on exploring various in vitro to in vivo extrapolation (IVIVE) approaches with the primary goal of improving human hepatic clearance (CL) prediction for OATP substrates. To that effect, the impact of albumin-mediated uptake in human hepatocytes was investigated. In vitro hepatic uptake assay using suspended human hepatocytes was performed with 16 selected OATP substrates to determine the uptake CL in the absence and presence of 4% BSA and unbound hepatocyte to media partition coefficient (Kp). Substantial enhancement of the unbound uptake CL (PS) was observed in the presence of 4% BSA, demonstrating "albumin-mediated" uptake. Prediction of human hepatic CL was performed using two non-traditional IVIVE approaches: initial uptake CL (PS) and intrinsic metabolic CL (CL) corrected by Kp based on extended clearance concept. Compared to traditional IVIVE using CL only, the two tested IVIVE approaches significantly improved the prediction of human hepatic CL. Particularly, direct extrapolation from PS showed the most robust correlation with in vivo human hepatic CL for all 16 compounds with bias of 1.9-2.0 for two lots of human hepatocytes, respectively. In addition, PS and Kp were also determined in suspended cynomolgus monkey hepatocytes. Prediction of monkey hepatic CL was improved by both approaches, although with more bias compared to human. These results suggested supplementing 4% BSA in human hepatocyte uptake assay provides a useful tool to characterize hepatic uptake CL for OATP substrates, enabling more accurate human CL prediction without any empirical scaling factor (ESF).
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http://dx.doi.org/10.1208/s12248-020-00528-yDOI Listing
November 2020

A novel waitlist dropout score for hepatocellular carcinoma - identifying a threshold that predicts worse post-transplant survival.

J Hepatol 2021 Apr 11;74(4):829-837. Epub 2020 Nov 11.

Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.

Background & Aims: It has been suggested that patients with hepatocellular carcinoma (HCC) at high risk of wait-list dropout would have done poorly after liver transplantation (LT) because of tumour aggressiveness. To test this hypothesis, we analysed risk of wait-list dropout among patients with HCC in long-wait regions (LWRs) to create a dropout risk score, and applied this score in short (SWRs) and mid-wait regions (MWRs) to evaluate post-LT outcomes. We sought to identify a threshold in dropout risk that predicts worse post-LT outcome.

Methods: Using the United Network for Organ Sharing database, including all patients with T2 HCC receiving priority listing from 2010 to 2014, a dropout risk score was created from a developmental cohort of 2,092 patients in LWRs, and tested in a validation cohort of 1,735 patients in SWRs and 2,894 patients in MWRs.

Results: On multivariable analysis, 1 tumour (3.1-5 cm) or 2-3 tumours, alpha-fetoprotein (AFP) >20 ng/ml, and increasing Child-Pugh and model for end-stage liver disease-sodium scores significantly predicted wait-list dropout. A dropout risk score using these 4 variables (C-statistic 0.74) was able to stratify 1-year cumulative incidence of dropout from 7.1% with a score ≤7 to 39.5% with a score >23. Patients with a dropout risk score >30 had 5-year post-LT survival of 60.1% vs. 71.8% for those with a score ≤30 (p = 0.004). There were no significant differences in post-LT survival below this threshold.

Conclusions: This study provided evidence that patients with HCC with the highest dropout risk have aggressive tumour biology that would also result in poor post-LT outcomes when transplanted quickly. Below this threshold risk score of ≤30, priority status for organ allocation could be stratified based on the predicted risks of wait-list dropout without significant differences in post-LT survival.

Lay Summary: Prioritising patients with hepatocellular carcinoma for liver transplant based on risk of wait-list dropout has been considered but may lead to inferior post-transplant survival. In this study of nearly 7,000 patients, we created a threshold dropout risk score based on tumour and liver-related factors beyond which patients with hepatocellular carcinoma will likely have poor post-liver transplant outcomes (60% at 5 years). For patients below this risk score threshold, priority status could be stratified based on the predicted risk of wait-list dropout without compromising post-transplant survival.
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http://dx.doi.org/10.1016/j.jhep.2020.10.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979440PMC
April 2021

Expanding living donor liver transplantation: Report of first US living donor liver transplant chain.

Am J Transplant 2021 04 8;21(4):1633-1636. Epub 2020 Dec 8.

Department of Surgery, University of California, San Francisco, California, USA.

Living donor liver transplantation (LDLT) enjoys widespread use in Asia, but remains limited to a handful of centers in North America and comprises only 5% of liver transplants performed in the United States. In contrast, living donor kidney transplantation is used frequently in the United States, and has evolved to commonly include paired exchanges, particularly for ABO-incompatible pairs. Liver paired exchange (LPE) has been utilized in Asia, and was recently reported in Canada; here we report the first LPE performed in the United States, and the first LPE to be performed on consecutive days. The LPE performed at our institution was initiated by a nondirected donor who enabled the exchange for an ABO-incompatible pair, and the final recipient was selected from our deceased donor waitlist. The exchange was performed over the course of 2 consecutive days, and relied on the use and compliance of a bridge donor. Here, we show that LPE is feasible at centers with significant LDLT experience and affords an opportunity to expand LDLT in cases of ABO incompatibility or when nondirected donors arise. To our knowledge, this represents the first exchange of its kind in the United States.
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http://dx.doi.org/10.1111/ajt.16396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016700PMC
April 2021

Safety and cost-effectiveness of individualised screening for diabetic retinopathy: the ISDR open-label, equivalence RCT.

Diabetologia 2021 Jan 4;64(1):56-69. Epub 2020 Nov 4.

Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Member of Liverpool Health Partners, Liverpool, UK.

Aims/hypothesis: Using variable diabetic retinopathy screening intervals, informed by personal risk levels, offers improved engagement of people with diabetes and reallocation of resources to high-risk groups, while addressing the increasing prevalence of diabetes. However, safety data on extending screening intervals are minimal. The aim of this study was to evaluate the safety and cost-effectiveness of individualised, variable-interval, risk-based population screening compared with usual care, with wide-ranging input from individuals with diabetes.

Methods: This was a two-arm, parallel-assignment, equivalence RCT (minimum 2 year follow-up) in individuals with diabetes aged 12 years or older registered with a single English screening programme. Participants were randomly allocated 1:1 at baseline to individualised screening at 6, 12 or 24 months for those at high, medium and low risk, respectively, as determined at each screening episode by a risk-calculation engine using local demographic, screening and clinical data, or to annual screening (control group). Screening staff and investigators were observer-masked to allocation and interval. Data were collected within the screening programme. The primary outcome was attendance (safety). A secondary safety outcome was the development of sight-threatening diabetic retinopathy. Cost-effectiveness was evaluated within a 2 year time horizon from National Health Service and societal perspectives.

Results: A total of 4534 participants were randomised. After withdrawals, there were 2097 participants in the individualised screening arm and 2224 in the control arm. Attendance rates at first follow-up were equivalent between the two arms (individualised screening 83.6%; control arm 84.7%; difference -1.0 [95% CI -3.2, 1.2]), while sight-threatening diabetic retinopathy detection rates were non-inferior in the individualised screening arm (individualised screening 1.4%, control arm 1.7%; difference -0.3 [95% CI -1.1, 0.5]). Sensitivity analyses confirmed these findings. No important adverse events were observed. Mean differences in complete case quality-adjusted life-years (EuroQol Five-Dimension Questionnaire, Health Utilities Index Mark 3) did not significantly differ from zero; multiple imputation supported the dominance of individualised screening. Incremental cost savings per person with individualised screening were £17.34 (95% CI 17.02, 17.67) from the National Health Service perspective and £23.11 (95% CI 22.73, 23.53) from the societal perspective, representing a 21% reduction in overall programme costs. Overall, 43.2% fewer screening appointments were required in the individualised arm.

Conclusions/interpretation: Stakeholders involved in diabetes care can be reassured by this study, which is the largest ophthalmic RCT in diabetic retinopathy screening to date, that extended and individualised, variable-interval, risk-based screening is feasible and can be safely and cost-effectively introduced in established systematic programmes. Because of the 2 year time horizon of the trial and the long time frame of the disease, robust monitoring of attendance and retinopathy rates should be included in any future implementation.

Trial Registration: ISRCTN 87561257 FUNDING: The study was funded by the UK National Institute for Health Research. Graphical abstract.
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http://dx.doi.org/10.1007/s00125-020-05313-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716929PMC
January 2021

The Nephrology Clinician Educator: Pathway and Future.

Adv Chronic Kidney Dis 2020 07 24;27(4):312-319.e1. Epub 2020 Oct 24.

Department of Medicine, Division of Nephrology, Washington University in St. Louis, St. Louis, MO.

In the medical profession, teaching has always been a routine expectation for practicing physicians. While this remains true today, in recent years, we have seen the emergence of a well-defined career pathway for those practicing physicians who want to focus on education: the clinician educator. This is a physician who is highly active in the practice of teaching, science of learning, service as a role model for young physicians, and leading educational programs. In nephrology, one can have a fruitful and fulfilling career as a lifelong clinician educator. As career interest in our specialty wanes, the clinician educator is the professional well suited to reverse this trend. In this article, we will further define the clinician educator and map out a pathway of skills needed to thrive in this rewarding career. We also provide recommendations to both educators and leaders to ensure the clinician educator pathway continues to grow.
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http://dx.doi.org/10.1053/j.ackd.2020.05.004DOI Listing
July 2020

Contemporary Management of Hepatic Cyst Disease: Techniques and Outcomes at a Tertiary Hepatobiliary Center.

J Gastrointest Surg 2021 Jan 20;25(1):77-84. Epub 2020 Oct 20.

Department of Surgery, University of California San Francisco, 533 Parnassus Avenue, Room 370, San Francisco, CA, USA.

Background: Hepatic cyst disease is often asymptomatic, but treatment is warranted if patients experience symptoms. We describe our management approach to these patients and review the technical nuances of the laparoscopic approach.

Methods: Medical records were reviewed for operative management of hepatic cysts from 2012 to 2019 at a single, tertiary academic medical center.

Results: Fifty-three patients (39 female) met the inclusion criteria with median age at presentation of 65 years. Fifty cases (94.3%) were performed laparoscopically. Fourteen patients carried diagnosis of polycystic liver disease. Dominant cyst diameter was median 129 mm and located within the right lobe (30), left lobe (17), caudate (2), or was bilobar (4). Pre-operative concern for biliary cystadenoma/cystadenocarcinoma existed for 7 patients. Operative techniques included fenestration (40), fenestration with decapitation (7), decapitation alone (3), and excision (2). Partial hepatectomy was performed in conjunction with fenestration/decapitation for 15 cases: right sided (7), left sided (7), and central (1). One formal left hepatectomy was performed in a polycystic liver disease patient. Final pathology yielded simple cyst (52) and one biliary cystadenoma. Post-operative complications included bile leak (2), perihepatic fluid collection (1), pleural effusion (1), and ascites (1). At median 7.1-month follow-up, complete resolution of symptoms occurred for 34/49 patients (69.4%) who had symptoms preoperatively. Reintervention for cyst recurrence occurred for 5 cases (9.4%).

Conclusions: Outcomes for hepatic cyst disease are described with predominantly laparoscopic approach, approach with minimal morbidity, and excellent clinical results.
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http://dx.doi.org/10.1007/s11605-020-04821-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850990PMC
January 2021

Homoconjugated Acids as Low Cyclosiloxane-Producing Silanol Polycondensation Catalysts.

ACS Omega 2020 Sep 21;5(38):24954-24963. Epub 2020 Sep 21.

Dow Inc., Core R&D, 633 Washington, Midland, Michigan 48667, United States.

Polycondensation of α,ω-disilanols is a foundational technology for silicones producers. Commercially, this process is carried out with strong Brønsted acids and bases, which generates cyclosiloxane byproducts. Homoconjugated acids (a 2:1 complex of acid:base or a 1:1 complex of acid:salt), a seldom used class of silanol polycondensation catalysts, were evaluated for their ability to polymerize α,ω-disilanols while forming low levels of cyclosiloxane byproducts. Homoconjugated acid catalysts were highly active for silanol polycondensation, even when made from relatively mild acids such as acetic acid. Both the acid and base (or cation) component of the homoconjugated species was important for activity and avoiding cyclosiloxane byproduct formation. Stronger acids and bases were found to positively affect reactivity, and the p of the acid was found to correlate with cyclosiloxane byproduct formation. The individual components of the homoconjugated species (the acid and base) were ineffective as catalysts by themselves, and compositions with fewer than 2 mol of acid to 1 mol of base were much less reactive. Homoconjugated trifluoroacetic acid tetramethylguanidinium and tetrabutylphosphonium complexes were found to be privileged catalysts, able to give high-molecular-weight siloxanes ( > 60 kDa) while generating less than 100 ppm of octamethylcyclotetrasiloxane byproduct. Finally, a mechanism has been proposed where silanols are electrophilically and nucleophilically activated by the homoconjugated species, leading to silanol polycondensation.
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http://dx.doi.org/10.1021/acsomega.0c03883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528505PMC
September 2020

Consensus-based perioperative protocols during the COVID-19 pandemic.

J Neurosurg Spine 2020 Oct 2:1-9. Epub 2020 Oct 2.

Departments of1Neurological Surgery.

Objective: During the COVID-19 pandemic, quaternary-care facilities continue to provide care for patients in need of urgent and emergent invasive procedures. Perioperative protocols are needed to streamline care for these patients notwithstanding capacity and resource constraints.

Methods: A multidisciplinary panel was assembled at the University of California, San Francisco, with 26 leaders across 10 academic departments, including 7 department chairpersons, the chief medical officer, the chief operating officer, infection control officers, nursing leaders, and resident house staff champions. An epidemiologist, an ethicist, and a statistician were also consulted. A modified two-round, blinded Delphi method based on 18 agree/disagree statements was used to build consensus. Significant disagreement for each statement was tested using a one-sided exact binomial test against an expected outcome of 95% consensus using a significance threshold of p < 0.05. Final triage protocols were developed with unblinded group-level discussion.

Results: Overall, 15 of 18 statements achieved consensus in the first round of the Delphi method; the 3 statements with significant disagreement (p < 0.01) were modified and iteratively resubmitted to the expert panel to achieve consensus. Consensus-based protocols were developed using unblinded multidisciplinary panel discussions. The final algorithms 1) quantified outbreak level, 2) triaged patients based on acuity, 3) provided a checklist for urgent/emergent invasive procedures, and 4) created a novel scoring system for the allocation of personal protective equipment. In particular, the authors modified the American College of Surgeons three-tiered triage system to incorporate more urgent cases, as are often encountered in neurosurgery and spine surgery.

Conclusions: Urgent and emergent invasive procedures need to be performed during the COVID-19 pandemic. The consensus-based protocols in this study may assist healthcare providers to optimize perioperative care during the pandemic.
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http://dx.doi.org/10.3171/2020.6.SPINE20777DOI Listing
October 2020

Treatment of immunocompromised COVID-19 patients with convalescent plasma.

Transpl Infect Dis 2020 Sep 29:e13477. Epub 2020 Sep 29.

Division of Infectious Disease, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Immunosuppressed patients such as solid organ transplant and hematologic malignancy patients appear to be at increased risk for morbidity and mortality due to coronavirus disease 2019 (COVID-19) caused by SARS coronavirus 2 (SARS-CoV-2). Convalescent plasma, a method of passive immunization that has been applied to prior viral pandemics, holds promise as a potential treatment for COVID-19. Immunocompromised patients may experience more benefit from convalescent plasma given underlying deficits in B and T cell immunity as well as contraindications to antiviral and immunomodulatory therapy. We describe our institutional experience with four immunosuppressed patients (two kidney transplant recipients, one lung transplant recipient, and one chronic myelogenous leukemia patient) treated with COVID-19 convalescent plasma through the Expanded Access Program (NCT04338360). All patients clinically improved after administration (two fully recovered and two discharged to skilled nursing facilities) and none experienced a transfusion reaction. We also report the characteristics of convalescent plasma product from a local blood center including positive SARS-CoV-2 IgG and negative SARS-CoV-2 PCR in all samples tested. This preliminary evidence suggest that convalescent plasma may be safe among immunosuppressed patients with COVID-19 and emphasizes the need for further data on the efficacy of convalescent plasma as either primary or adjunctive therapy for COVID-19.
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http://dx.doi.org/10.1111/tid.13477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537112PMC
September 2020

Complementary and Alternative Medicine Use in Psoriatic Arthritis Patients: a Review.

Curr Rheumatol Rep 2020 Sep 28;22(11):81. Epub 2020 Sep 28.

Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA.

Purpose Of Review: While complementary and alternative medicine (CAM) use is prevalent in the general population and is known to be used in systemic rheumatic disease such as rheumatoid arthritis and systemic lupus erythematosus, its use in psoriatic arthritis (PsA) is less well-studied. The purpose of this review was to identify published data describing the use of CAM in patients with PsA.

Recent Findings: PsA patients report frequent use of CAM. Diet is believed to affect disease activity, and dietary approaches are used by patients to mitigate symptoms. Dietary supplements have been studied, especially fatty acids, with some positive results. Herbal remedies show promise, but more and better studies are needed, including evaluating medical cannabis. Studies of some the most commonly used CAM, such as acupuncture and massage, are conspicuously absent. CAM use is common among patients with PsA. There is, however, a significant knowledge gap, and there is a critical need for rigorous research to ensure safe and effective use of CAM for these patients.
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http://dx.doi.org/10.1007/s11926-020-00956-xDOI Listing
September 2020

Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement.

Am J Transplant 2021 02 10;21(2):475-483. Epub 2020 Oct 10.

Department of Medicine, Mayo Clinic, Rochester, Minnesota.

Patients undergoing evaluation for solid organ transplantation (SOT) frequently have a history of malignancy. Only patients with treated cancer are considered for SOT but the benefits of transplantation need to be balanced against the risk of tumor recurrence, taking into consideration the potential effects of immunosuppression. Prior guidelines on timing to transplant in patients with a prior treated malignancy do not account for current staging, disease biology, or advances in cancer treatments. To update these recommendations, the American Society of Transplantation (AST) facilitated a consensus workshop to comprehensively review contemporary literature regarding cancer therapies, cancer stage specific prognosis, the kinetics of cancer recurrence, as well as the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis, treatment, and transplant recommendations for melanoma and hematological malignancies. Given the limited data regarding the risk of cancer recurrence in transplant recipients, the goal of the AST-sponsored conference and the consensus documents produced are to provide expert opinion recommendations that help in the evaluation of patients with a history of a pretransplant malignancy for transplant candidacy.
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http://dx.doi.org/10.1111/ajt.16324DOI Listing
February 2021

Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement.

Am J Transplant 2021 02 23;21(2):460-474. Epub 2020 Oct 23.

Department of Medicine, Mayo Clinic, Rochester, Minnesota.

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.
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http://dx.doi.org/10.1111/ajt.16318DOI Listing
February 2021

Is It Safe to Perform Lung Surgery During the Coronavirus Pandemic?

Cureus 2020 Aug 14;12(8):e9749. Epub 2020 Aug 14.

Thoracic Surgery, Delray Medical Center, Johns Hopkins University, Delray Beach, USA.

Background:  Coronavirus disease (COVID-19) patients are rapidly growing in our community. Patients with compromised lungs and older age are supposedly at high risk of poor outcomes with COVID-19. We aimed to evaluate the COVID-19 impact on lung surgery during this pandemic at our hospital.

Methodology: This is a retrospective study of all lung surgery patients at our hospital in Boca Raton over three months (February to April 2020). All patients who remained for at least one-day inpatient post-lung surgery were assessed to see if they had an increased incidence of coronavirus infection during the hospital stay or at the follow-up office visit.

Results: A total of 44 patients underwent thoracic surgery. It was found that there was no incidence of coronavirus infection in these patients.

Conclusion: With adequate precautions, older patients can undergo lung surgery during this pandemic. There was no incidence of COVID-19 found among the patients during the hospital stay or at the first follow-up in the office. Also, the postoperative course was not adversely affected.
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http://dx.doi.org/10.7759/cureus.9749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489776PMC
August 2020

Daily Cannabis Users with Sickle Cell Disease Show Fewer Admissions than Others with Similar Pain Complaints.

Cannabis Cannabinoid Res 2020 2;5(3):255-262. Epub 2020 Sep 2.

Department of Internal Medicine, Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut.

Previous studies have shown that cannabis use is common in adults with sickle cell disease (SCD), and that many patients report using cannabis to treat pain. We performed a cross-sectional study of adults with SCD and compared daily users of cannabis with others using validated patient-reported measures of pain and quality of life as well as opioid and health care utilization. Daily cannabis users with SCD had worse pain episode severity scores than others (56.7 vs. 48.8, =0.02) yet had 1.8 fewer annual admissions (=0.01) and 1.2 fewer annual emergency room (ER) visits (=0.01), and similar amounts of opioids dispensed to others after matching for age, gender, SCD genotype, hydroxyurea use, and pain impact scores. We show that people with SCD with more severe pain crisis are more likely to use daily cannabis, yet have lower rates of hospital admission and ER use as compared with others with similar disease severity and pain impact. Randomized controlled trials should be performed.
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http://dx.doi.org/10.1089/can.2019.0036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480712PMC
September 2020

Post-operative assessment in patients after liver transplantation: imaging parameters associated with 1-year graft failure.

Eur Radiol 2021 Feb 30;31(2):764-774. Epub 2020 Aug 30.

Department of Radiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.

Purpose: To identify post-liver transplant CT findings which predict graft failure within 1 year.

Materials And Methods: We evaluated the CT scans of 202 adult liver transplants performed in our institution who underwent CT within 3 months after transplantation. We recorded CT findings of liver perfusion defect (LPD), parenchymal homogeneity, and the diameters and attenuations of the hepatic vessels. Findings were correlated to 1-year graft failure, and interobserver variability was assessed.

Results: Forty-one (20.3%) of the 202 liver grafts failed within 1 year. Graft failure was highly associated with LPD (n = 18/25, or 67%, versus 15/98, or 15%, p < 0.001), parenchymal hypoattenuation (n = 20/41, or 48.8% versus 17/161, or 10.6%, p < 0.001), and smaller diameter of portal veins (right portal vein [RPV], 10.7 ± 2.7 mm versus 14.7 ± 2.2 mm, and left portal vein [LPV], 9.8 ± 3.0 mm versus 12.4 ± 2.2 mm, p < 0.001, respectively). Of these findings, LPD (hazard ratio [HR], 5.43, p < 0.001) and small portal vein diameters (HR, RPV, 3.33, p < 0.001, and LPV, 3.13, p < 0.05) independently predicted graft failure. All the measurements showed fair to moderate interobserver agreement (0.233~0.597).

Conclusion: For patients who have CT scan within the first 3 months of liver transplantation, findings of LPD and small portal vein diameters predict 1-year graft failure.

Key Points: •Failed grafts are highly associated with liver perfusion defect, hypoattenuation, and small portal vein. •Right portal vein < 11.5 mm and left portal vein < 10.0 mm were associated with poor graft outcome. •Liver perfusion defect and small portal vein diameter independently predicted graft failure.
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http://dx.doi.org/10.1007/s00330-020-07124-wDOI Listing
February 2021

Global allele polymorphism indicates a high rate of allele genesis at a locus under balancing selection.

Heredity (Edinb) 2021 Jan 27;126(1):163-177. Epub 2020 Aug 27.

Behaviour, Ecology and Evolution Laboratory, School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, 2006, Australia.

When selection favours rare alleles over common ones (balancing selection in the form of negative frequency-dependent selection), a locus may maintain a large number of alleles, each at similar frequency. To better understand how allelic richness is generated and maintained at such loci, we assessed 201 sequences of the complementary sex determiner (csd) of the Asian honeybee (Apis cerana), sampled from across its range. Honeybees are haplodiploid; hemizygotes at csd develop as males and heterozygotes as females, while homozygosity is lethal. Thus, csd is under strong negative frequency-dependent selection because rare alleles are less likely to end up in the lethal homozygous form. We find that in A. cerana, as in other Apis, just a few amino acid differences between csd alleles in the hypervariable region are sufficient to trigger female development. We then show that while allelic lineages are spread across geographical regions, allelic differentiation is high between populations, with most csd alleles (86.3%) detected in only one sample location. Furthermore, nucleotide diversity in the hypervariable region indicates an excess of recently arisen alleles, possibly associated with population expansion across Asia since the last glacial maximum. Only the newly invasive populations of the Austral-Pacific share most of their csd alleles. In all, the geographic patterns of csd diversity in A. cerana indicate that high mutation rates and balancing selection act together to produce high rates of allele genesis and turnover at the honeybee sex locus, which in turn leads to its exceptionally high local and global polymorphism.
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http://dx.doi.org/10.1038/s41437-020-00358-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853069PMC
January 2021