Publications by authors named "Robert A Montgomery"

210 Publications

Post-Myocardial Infarction Ventricular Septal Rupture Bridged to Heartmate 3 with an Impella 5.5.

Ann Thorac Surg 2021 Jan 19. Epub 2021 Jan 19.

Department of Thoracic and Cardiovascular Surgery, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH. Electronic address:

Optimal timing of surgical repair for patients diagnosed with a post-myocardial infarction ventricular septal rupture (post-MI VSR) is controversial. Urgent surgical intervention to prevent hemodynamic decompensation must be balanced against delayed repair to allow for tissue stabilization and increased likelihood of a successful outcome. We report the use of an axillary Impella 5.5 temporary left ventricular assist device to aid in hemodynamic stabilization, shunt fraction reduction, and tissue maturation with eventual definitive surgical repair in a patient that presented with a post-MI VSR and cardiogenic shock.
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http://dx.doi.org/10.1016/j.athoracsur.2020.12.044DOI Listing
January 2021

Animal Behavioral Responses to the COVID-19 Quietus.

Trends Ecol Evol 2021 03 24;36(3):184-186. Epub 2020 Dec 24.

Research on the Ecology of Carnivores and their Prey (RECaP) Laboratory, Department of Fisheries and Wildlife, Michigan State University, East Lansing, MI 48824, USA.

Lockdown measures fundamentally reshaped human society during the COVID-19 pandemic. We present a framework featuring seven animal behavioral changes as a result of the calming effect of the lockdowns on human actions (COVID-19 quietus). We demonstrate how this framework can be used to quantify animal behavioral responses with implications for ecology and conservation.
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http://dx.doi.org/10.1016/j.tree.2020.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833595PMC
March 2021

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

Am J Transplant 2020 Dec 28. Epub 2020 Dec 28.

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
December 2020

Pancreas transplantation from hepatitis C viremic donors to uninfected recipients.

Am J Transplant 2020 Dec 21. Epub 2020 Dec 21.

Transplant Institute, NYU Langone Health, New York, New York, USA.

Despite utilization of hepatitis C viremic organs for hepatitis C naïve recipients (HCV D+/R-) in other solid organ transplants, HCV viremic pancreata remain an unexplored source of donor organs. This study reports the first series of HCV D+/R- pancreas transplants. HCV D+/R- had shorter waitlist times compared to HCV D-/R-, waiting a mean of 16 days from listing for HCV-positive organs. HCV D+/R- had a lower match allocation sequence than HCV D-/R-, and this correlated with receipt of organs with a lower Pancreas Donor Risk Index (PDRI) score. All HCV D+/R- had excellent graft function with a mean follow-up of 438 days and had undetectable HCV RNA levels by a mean of 23 days after initiation of HCV-directed therapy. The rates of infectious complications, reoperation, readmission, rejection, and length of stay were not impacted by donor HCV status. A national review of potential ideal pancreas donors found that 37% of ideal HCV-negative pancreas allografts were transplanted, compared to only 5% of ideal HCV-positive pancreas allografts. The results of the current study demonstrate the safety of accepting HCV-positive pancreata for HCV-naïve recipients and advocates for increased utilization of ideal HCV-positive pancreas allografts.
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http://dx.doi.org/10.1111/ajt.16465DOI Listing
December 2020

A Propensity-Matched Cohort Study of Tocilizumab in Patients With Coronavirus Disease 2019.

Crit Care Explor 2020 Nov 16;2(11):e0283. Epub 2020 Nov 16.

Department of Pulmonary and Critical Care Medicine, NYU Langone Health, New York, NY.

To determine the impact of tocilizumab, a monoclonal antibody against the interleukin 6 receptor, on survival in patients with coronavirus disease 2019.

Design: Observational cohort study of patients hospitalized with coronavirus disease 2019 between March 1, 2020, and April 24, 2020. A propensity-matched (1:1) analysis was used to compare patients who received tocilizumab to controls who did not. Competing risk survival analysis was used to determine the primary outcome of time to mortality, and adjusted log-linear and logistic regression for secondary outcomes.

Setting: Three hospitals within the NYU Langone Health system in New York.

Patients: Consecutive adult patients hospitalized with coronavirus disease 2019.

Intervention: Tocilizumab 400-mg IV once in addition to standard of care or standard of care alone.

Measurements And Main Results: Data from 3,580 severe acute respiratory syndrome coronavirus 2 positive qualifying hospitalized patients were included, of whom 497 (13.9%) were treated with tocilizumab. In the analysis of tocilizumab-treated patients and matched controls, fewer tocilizumab-treated patients died (145/497, 29.2%) than did controls (211/497, 42.4%). In the adjusted competing risk regression model, tocilizumab therapy was associated with improved survival relative to controls (hazard ratio = 0.24, 95% CI = 0.18-0.33, < 0.001). Tocilizumab-treated patients and controls had similar adjusted time to discharge from hospital (hazard ratio = 0.96, 95% CI = 0.78-1.17, = 0.67). However, they had longer adjusted ICU length of stay (rate ratio = 3.1, 95% CI = 2.5-3.7, < 0.001) and a higher adjusted infection rate (odds ratio = 4.18, 95% CI = 2.72-6.52, < 0.001) than controls.

Conclusions: Tocilizumab therapy was associated with significantly improved survival in coronavirus disease 2019 patients. This survival benefit was associated with increased ICU length of stay and increased infection rate, even as more patients in the tocilizumab group were rescued from rapid death. A prospective, randomized, placebo-controlled trial is needed to confirm these findings.
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http://dx.doi.org/10.1097/CCE.0000000000000283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671881PMC
November 2020

Imlifidase desensitization in crossmatch-positive, highly-sensitized kidney transplant recipients: Results of an international phase 2 trial (Highdes).

Transplantation 2020 Oct 21. Epub 2020 Oct 21.

NYU Langone Transplant Institute, New York, New York, USA.

Background: Highly-HLA sensitized patients have limited access to life-saving kidney transplantation due to a paucity of immunologically suitable donors. Imlifidase is a cysteine protease that cleaves IgG leading to a rapid decrease in antibody level and inhibition of IgG-mediated injury. This study investigates the efficacy and safety of imlifidase in converting a positive crossmatch test to negative, allowing highly sensitized patients to be transplanted with a living or deceased donor kidney.

Methods: This open-label, single arm, phase 2 trial conducted at five transplant centers, evaluated the ability of imlifidase to create a negative crossmatch test within 24 hours. Secondary endpoints included post-imlifidase DSA levels compared to pre-dose levels, renal function, and pharmacokinetic/pharmacodynamic profiles. Safety endpoints included adverse events and immunogenicity profile.

Results: 89.5% of the transplanted patients demonstrated conversion of baseline positive crossmatch to negative within 24 hours after imlifidase treatment. DSA most often rebounded 3-14 days post-imlifidase dose, with substantial interpatient variability. Patient survival was 100% with graft survival of 88.9% at 6 months. 38.9% had early biopsy proven antibody mediated rejection with onset 2-19 days post-transplantation. Serum IgG levels began to normalize after ~3-7 days post-transplantation. Anti-drug antibody levels were consistent with previous studies. Seven adverse events in six patients were classified as possibly or probably related to treatment and were mild-moderate in severity.

Conclusions: Imlifidase was well tolerated, converted positive crossmatches to negative, and enabled patients with a median cPRA of 99.83% to undergo kidney transplantation resulting in good kidney function and graft survival at 6 months.
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http://dx.doi.org/10.1097/TP.0000000000003496DOI Listing
October 2020

Quantifying infection risks in incompatible living donor kidney transplant recipients.

Am J Transplant 2020 Sep 19. Epub 2020 Sep 19.

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

Desensitization has enabled incompatible living donor kidney transplantation (ILDKT) across HLA/ABO barriers, but added immunomodulation might put patients at increased risk of infections. We studied 475 recipients from our center from 2010 to 2015, categorized by desensitization intensity: none/compatible (n = 260), low (0-4 plasmaphereses, n = 47), moderate (5-9, n = 74), and high (≥10, n = 94). The 1-year cumulative incidence of infection was 50.1%, 49.8%, 66.0%, and 73.5% for recipients who received none, low, moderate, and high-intensity desensitization (P < .001). The most common infections were UTI (33.5% of ILDKT vs. 21.5% compatible), opportunistic (21.9% vs. 10.8%), and bloodstream (19.1% vs. 5.4%) (P < .001). In weighted models, a trend toward increased risk was seen in low (wIRR = 1.40 ,P = .3) and moderately (wIRR = 1.35 ,P = .2) desensitized recipients, with a statistically significant 2.22-fold (wIRR = 2.22 ,P = .002) increased risk in highly desensitized recipients. Recipients with ≥4 infections were at higher risk of prolonged hospitalization (wIRR = 3.57 , P < .001) and death-censored graft loss (wHR = 4.01 ,P = .03). Post-KT infections are more common in desensitized ILDKT recipients. A subset of highly desensitized patients is at ultra-high risk for infections. Strategies should be designed to protect patients from the morbidity of recurrent infections, and to extend the survival benefit of ILDKT across the spectrum of recipients.
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http://dx.doi.org/10.1111/ajt.16316DOI Listing
September 2020

Trajectories of glomerular filtration rate and progression to end stage kidney disease after kidney transplantation.

Kidney Int 2021 01 8;99(1):186-197. Epub 2020 Aug 8.

Université de Paris, INSERM, PARCC, Paris Translational Research Centre for Organ Transplantation, Paris, France; Kidney Transplant Department, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France. Electronic address:

Although the gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR), little is known about GFR trajectories after transplantation, their determinants, and their association with outcomes. To evaluate these parameters we examined kidney transplant recipients receiving care at 15 academic centers. Patients underwent prospective monitoring of estimated GFR (eGFR) measurements, with assessment of clinical, functional, histological and immunological parameters. Additional validation took place in seven randomized controlled trials that included a total of 14,132 patients with 403,497 eGFR measurements. After a median follow-up of 6.5 years, 1,688 patients developed end-stage kidney disease. Using unsupervised latent class mixed models, we identified eight distinct eGFR trajectories. Multinomial regression models identified seven significant determinants of eGFR trajectories including donor age, eGFR, proteinuria, and several significant histological features: graft scarring, graft interstitial inflammation and tubulitis, microcirculation inflammation, and circulating anti-HLA donor specific antibodies. The eGFR trajectories were associated with progression to end stage kidney disease. These trajectories, their determinants and respective associations with end stage kidney disease were similar across cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the seven randomized control trials. Thus, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring.
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http://dx.doi.org/10.1016/j.kint.2020.07.025DOI Listing
January 2021

Variability in the estimation of ungulate group sizes complicates ecological inference.

Ecol Evol 2020 Jul 10;10(14):6881-6889. Epub 2020 Jun 10.

Research on the Ecology of Carnivores and their Prey (RECaP) Laboratory Department of Fisheries and Wildlife Michigan State University East Lansing MI USA.

Foundational work has examined adaptive social behavior in animals in relation to the costs and benefits of group living. Within this context, a "group" of animals represents an organizational unit that is integral to the study of animal ecology and evolution.Definitions of animal group sizes are often subjective with considerable variability within and across species. However, investigations of both the extent and implications of such variability in the estimation of animal group sizes are currently lacking.Selecting ungulates as a case study, we conducted a literature review to assess prevailing practices used to determine group sizes among terrestrial Cetartiodactyla and Perissodactyla. Via this process, we examined group size definitions for 61 species across 171 peer-reviewed studies published between 1962 and 2018.These studies quantified group sizes via estimation of ungulate aggregations in space and time. Spatial estimates included a nearest neighbor distance ranging from 1.4 m to 1,000 m, and this variation was partially explained by a weak positive correlation (|| = .4,  < .003) with the body size of the ungulate research subjects. The temporal extent over which group size was estimated was even broader, ranging from three minutes to 24 hr.The considerable variability in ungulate group size estimation that we observed complicates efforts to not only compare and replicate studies but also to evaluate underlying theories of group living. We recommend that researchers: (a) clearly describe the spatiotemporal extents over which they define ungulate group sizes, (b) highlight foundational empirical and ecological rationale for these extents, and (c) seek to align such extents among individual species so as to facilitate cross-system comparisons of ungulate group size dynamics. We believe an integrative approach to ungulate group size estimation would readily facilitate replication, comparability, and evaluation of competing hypotheses examining the tradeoffs of animal sociality.
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http://dx.doi.org/10.1002/ece3.6463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391342PMC
July 2020

A Simple Prioritization Change to Lung Transplant Allocation May Result in Improved Outcomes.

Ann Thorac Surg 2021 02 17;111(2):427-435. Epub 2020 Jul 17.

Department of Cardiothoracic Surgery, New York University Langone Health, New York, New York.

Background: The lung allocation score (LAS) significantly improved outcomes and wait list mortality in lung transplantation. However, mortality remains high for the sickest wait list candidates despite additional changes to allocation distance. Regulatory considerations of overhauling the current lung allocation system have met significant resistance, and changes would require years to implement. This study evaluates whether a modest change to the current system by prioritization of only high-LAS lung transplant candidates would result in lowered wait list mortality.

Methods: The Thoracic Simulated Allocation Model was used to evaluate all lung transplant candidates and donor lungs recovered between July 1, 2009 and June 30, 2011. Current lung allocation rules (initial offer within a 250-nautical mile radius for ABO-identical then compatible offers) were run. Allocation was then changed for only patients with an LAS of50 or higher (high-LAS) to be prioritized within a 500-nautical mile radius with no stratification between ABO-identical and compatible offers. Ten iterations of each model were run. Primary end points were wait list mortality and posttransplant 1-year survival.

Results: A total of 6538 wait list candidates and transplant recipients were evaluated per iteration, for a total of 130,760 simulated patients. Compared with current allocation, the adjusted model had a 23.3% decrease in wait list mortality. Posttransplant 1-year survival was minimally affected.

Conclusions: Without overhauling the entire system, simple prioritization changes to the allocation system for high-LAS candidates may lead to decreased wait list mortality and increased organ use. Importantly, these changes do not appear to lead to clinically significant changes in posttransplant 1-year survival.
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http://dx.doi.org/10.1016/j.athoracsur.2020.05.108DOI Listing
February 2021

Extracorporeal Membrane Oxygenation Support in Severe COVID-19.

Ann Thorac Surg 2021 Feb 17;111(2):537-543. Epub 2020 Jul 17.

Department of Cardiothoracic Surgery.

Background: Coronavirus disease 2019 (COVID-19) remains a worldwide pandemic with a high mortality rate among patients requiring mechanical ventilation. The limited data that exist regarding the utility of extracorporeal membrane oxygenation (ECMO) in these critically ill patients show poor overall outcomes. This report describes our institutional practice regarding the application and management of ECMO support for patients with COVID-19 and reports promising early outcomes.

Methods: All critically ill patients with confirmed COVID-19 evaluated for ECMO support from March 10, 2020, to April 24, 2020, were retrospectively reviewed. Patients were evaluated for ECMO support based on a partial pressure of arterial oxygen/fraction of inspired oxygen ratio of less than 150 mm Hg or pH of less than 7.25 with a partial pressure of arterial carbon dioxide exceeding 60 mm Hg with no life-limiting comorbidities. Patients were cannulated at bedside and were managed with protective lung ventilation, early tracheostomy, bronchoscopies, and proning, as clinically indicated.

Results: Among 321 patients intubated for COVID-19, 77 patients (24%) were evaluated for ECMO support, and 27 patients (8.4%) were placed on ECMO. All patients were supported with venovenous ECMO. Current survival is 96.3%, with only 1 death to date in more than 350 days of total ECMO support. Thirteen patients (48.1%) remain on ECMO support, and 13 patients (48.1%) have been successfully decannulated. Seven patients (25.9%) have been discharged from the hospital. Six patients (22.2%) remain in the hospital, of which 4 are on room air. No health care workers who participated in ECMO cannulation developed symptoms of or tested positive for COVID-19.

Conclusions: The early outcomes presented here suggest that the judicious use of ECMO support in severe COVID-19 may be clinically beneficial.
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http://dx.doi.org/10.1016/j.athoracsur.2020.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366119PMC
February 2021

Impact of ABO-Incompatible Living Donor Kidney Transplantation on Patient Survival.

Am J Kidney Dis 2020 11 12;76(5):616-623. Epub 2020 Jul 12.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD; Scientific Registry for Transplant Recipients, Minneapolis, MN. Electronic address:

Rationale & Objective: Compared with recipients of blood group ABO-compatible (ABOc) living donor kidney transplants (LDKTs), recipients of ABO-incompatible (ABOi) LDKTs have higher risk for graft loss, particularly in the first few weeks after transplantation. However, the decision to proceed with ABOi LDKT should be based on a comparison of the alternative: waiting for future ABOc LDKTs (eg, through kidney paired exchange) or for a deceased donor kidney transplant (DDKT). We sought to evaluate the patient survival difference between ABOi LDKTs and waiting for an ABOc LDKT or an ABOc DDKT.

Study Design: Retrospective cohort study of adults in the Scientific Registry of Transplant Recipients.

Setting & Participants: 808 ABOi LDKT recipients and 2,423 matched controls from among 245,158 adult first-time kidney-only waitlist registrants who did not receive an ABOi LDKT and who remained on the waitlist or received either an ABOc LDKT or an ABOc DDKT, 2002 to 2017.

Exposure: Receipt of ABOi LDKT.

Outcome: Death.

Analytical Approach: We compared mortality among ABOi LDKT recipients versus a weighted matched comparison population using Cox proportional hazards regression and Cox models that accommodated for changing hazard ratios over time.

Results: Compared with matched controls, ABOi LDKT was associated with greater mortality risk in the first 30 days posttransplantation (cumulative survival of 99.0% vs 99.6%) but lower mortality risk beyond 180 days posttransplantation. Patients who received an ABOi LDKT had higher cumulative survival at 5 and 10 years (90.0% and 75.4%, respectively) than similar patients who remained on the waitlist or received an ABOc LDKT or ABOc DDKT (81.9% and 68.4%, respectively).

Limitations: No measurement of ABO antibody titers in recipients; eligibility of participants for kidney paired donation is unknown.

Conclusions: Transplant candidates who receive an ABOi LDKT and survive more than 180 days posttransplantation experience a long-term survival benefit compared to remaining on the waitlist to potentially receive an ABOc kidney transplant.
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http://dx.doi.org/10.1053/j.ajkd.2020.03.029DOI Listing
November 2020

Outpatient management of kidney transplant recipients with suspected COVID-19-Single-center experience during the New York City surge.

Transpl Infect Dis 2020 Dec 6;22(6):e13383. Epub 2020 Jul 6.

New York University Grossman School of Medicine, New York, New York, USA.

Data describing the clinical progression of coronavirus disease 2019 (COVID-19) in transplant recipients are limited. In New York City during the surge in COVID-19 cases, a systematic approach to monitoring and triaging immunocompromised transplant patients was required in the context of strained healthcare resources, limited outpatient testing, and heightened hospital exposure risks. Public health guidance at the onset of the COVID-19 outbreak recommended outpatient monitoring of mildly symptomatic patients without specific recommendations for special populations such as transplant recipients. We developed and implemented a systematic monitoring algorithm for kidney transplant recipients at our transplant center who reported mild symptoms suggestive of COVID-19. We describe the outcomes of the first 44 patients monitored through this algorithm. A total of 44 kidney transplant recipients thought to be symptomatic for COVID-19 disease were followed for a minimum of 14 days. The majority of mildly symptomatic patients (34/44) had clinical progression of disease and were referred to the emergency department where they all tested PCR positive and required hospitalization. More than half of these patients presented with hypoxia requiring supplemental oxygen, 39% were intubated within 48 hours, and 53% developed acute kidney injury but did not require dialysis. There were 6 deaths. During surge outbreaks, kidney transplant patients with even mild symptoms have a high likelihood of COVID-19 disease and most will worsen requiring hospitalization for supportive measures. Earlier outpatient testing and hospitalization may improve COVID-19 outcomes among transplant recipients.
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http://dx.doi.org/10.1111/tid.13383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361210PMC
December 2020

COVID-19, Health, Conservation, and Shared Wellbeing: Details Matter.

Trends Ecol Evol 2020 09 4;35(9):748-750. Epub 2020 Jun 4.

Wildlife Conservation Research Unit, Department of Zoology, University of Oxford, The Recanati-Kaplan Centre, Tubney House, Abingdon Road, Tubney, Oxon OX13 5QL, UK.

Many have stridently recommended banning markets like the one where coronavirus disease 2019 (COVID-19) originally spread. We highlight that millions of people around the world depend on markets for subsistence and the diverse use of animals globally defies uniform bans. We argue that the immediate and fair priority is critical scrutiny of wildlife trade.
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http://dx.doi.org/10.1016/j.tree.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269933PMC
September 2020

The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection.

Am J Transplant 2020 09 28;20(9):2318-2331. Epub 2020 May 28.

Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.

The XV. Banff conference for allograft pathology was held in conjunction with the annual meeting of the American Society for Histocompatibility and Immunogenetics in Pittsburgh, PA (USA) and focused on refining recent updates to the classification, advances from the Banff working groups, and standardization of molecular diagnostics. This report on kidney transplant pathology details clarifications and refinements to the criteria for chronic active (CA) T cell-mediated rejection (TCMR), borderline, and antibody-mediated rejection (ABMR). The main focus of kidney sessions was on how to address biopsies meeting criteria for CA TCMR plus borderline or acute TCMR. Recent studies on the clinical impact of borderline infiltrates were also presented to clarify whether the threshold for interstitial inflammation in diagnosis of borderline should be i0 or i1. Sessions on ABMR focused on biopsies showing microvascular inflammation in the absence of C4d staining or detectable donor-specific antibodies; the potential value of molecular diagnostics in such cases and recommendations for use of the latter in the setting of solid organ transplantation are presented in the accompanying meeting report. Finally, several speakers discussed the capabilities of artificial intelligence and the potential for use of machine learning algorithms in diagnosis and personalized therapeutics in solid organ transplantation.
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http://dx.doi.org/10.1111/ajt.15898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496245PMC
September 2020

Poaching is Not One Big Thing.

Trends Ecol Evol 2020 06 20;35(6):472-475. Epub 2020 Mar 20.

Research on the Ecology of Carnivores and their Prey (RECaP) Laboratory, Department of Fisheries and Wildlife, Michigan State University, East Lansing, MI 48824, USA. Electronic address:

Among science and society, poaching is often depicted as one big dark conservation problem. In actuality, there are three main categories of poaching, with innumerable subcategories, including trophy, medicative, and consumptive poaching. Recognition of the complexity of poaching is vital to the effective alignment of conservation practice and social justice.
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http://dx.doi.org/10.1016/j.tree.2020.02.013DOI Listing
June 2020

Regulating the risk-reward trade-off in transplantation.

Am J Transplant 2020 08 15;20(8):2282-2283. Epub 2020 Apr 15.

NYU Langone Transplant Institute, New York, New York, USA.

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http://dx.doi.org/10.1111/ajt.15882DOI Listing
August 2020

A means to an end: the promise of tracking natriuresis with diuretic therapy.

Eur J Heart Fail 2020 08 2;22(8):1448-1450. Epub 2020 Apr 2.

Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA.

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http://dx.doi.org/10.1002/ejhf.1806DOI Listing
August 2020

Center-level Variation in HLA-incompatible Living Donor Kidney Transplantation Outcomes.

Transplantation 2021 02;105(2):436-442

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.

Background: Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remains unknown.

Methods: We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to Scientific Registry of Transplant Recipients for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences and to identify any center-level characteristics associated with improved post-ILDKT outcomes.

Results: After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (P < 0.01) and 4.4% of the differences in graft loss (P < 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates.

Conclusions: Unlike most aspects of transplantation in which center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.
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http://dx.doi.org/10.1097/TP.0000000000003254DOI Listing
February 2021

Successful A2 to B Deceased Donor Kidney Transplant after Desensitization for High-Strength Non-HLA Antibody Made Possible by Utilizing a Hepatitis C Positive Donor.

Case Rep Transplant 2020 13;2020:3591274. Epub 2020 Mar 13.

Transplant Institute, NYU Langone Health, New York, NY, USA.

Desensitization using plasma exchange can remove harmful antibodies prior to transplantation and mitigate risks for hyperacute and severe early acute antibody-mediated rejection. Traditionally, the use of plasma exchange requires a living donor so that the timing of treatments relative to transplant can be planned. Non-HLA antibody is increasingly recognized as capable of causing antibody-mediated renal allograft rejection and has been associated with decreased graft longevity. Our patient had high-strength non-HLA antibody deemed prohibitive to transplantation without desensitization, but no living donors. As the patient was eligible to receive an A2 ABO blood group organ and was willing to accept a hepatitis C positive donor kidney, this afforded a high probability of receiving an offer within a short enough time frame to attempt empiric desensitization in anticipation of a deceased donor transplant. Fifteen plasma exchange treatments were performed before the patient received an organ offer, and the patient was successfully transplanted. Hepatitis C infection was treated posttransplant. No episodes of rejection were observed. At one-year posttransplant, the patient maintains good graft function. In this case, willingness to consider nontraditional donor organs enabled us to mimic living donor desensitization using a deceased donor.
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http://dx.doi.org/10.1155/2020/3591274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094197PMC
March 2020

Positioning human heritage at the center of conservation practice.

Conserv Biol 2020 10 20;34(5):1122-1130. Epub 2020 Aug 20.

Conservation Solutions Afrika, Muthaiga Estate P.O. Box 880-10400, Nanyuki, Kenya.

Conservation projects subscribing to a community-based paradigm have predominated in the 21st century. We examined the context in which the phrase was coined and traced its growth over time. Community-based conservation first appeared in the literature in the early 1990s; but grew little until after the 5th World Parks Congress in 2003. Thereafter, publications describing community-based conservation approaches increased exponentially. The conference theme was Benefits Beyond Boundaries, and its goal was to provide an economic model based on revenue accrued from conservation fundraising and ecotourism to support ecosystems, wildlife, and people, particularly in the Global South. Such models tended not to incorporate, as a core principle, the heritage of local human communities. Human heritage varies substantially over time and space making generalization of conservation principles across scales challenging. Pitfalls that have grown out of the community-based conservation approaches in the Global South include fortress conservation, conservation militarism, consumptive and nonconsumptive ecotourism, and whiz-bang solutions. We propose 10 tenets in a human heritage-centered conservation framework (e.g., engage in conservation practices using local languages, thoughtfully propose and apply solutions consistent with human heritage, provide clear professional development pathways for individuals from local communities, and promote alternative revenue-generating programs centered in local communities, among others). Progressive philosophies can derive from authentic and ethical integration of local communities in conservation practice.
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http://dx.doi.org/10.1111/cobi.13483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540558PMC
October 2020

Characteristics that make trophy hunting of giant pandas inconceivable.

Conserv Biol 2020 08 15;34(4):915-924. Epub 2020 Apr 15.

Department of Fisheries and Wildlife, Michigan State University, 480 Wilson Road, 13 Natural Resources Building, East Lansing, MI, 48824, U.S.A.

In November 1928, Theodore Jr. and Kermit Roosevelt led an expedition to China with the expressed purpose of being the first Westerners to kill the giant panda (Ailuropoda melanoleuca). The expedition lasted 8 months and resulted in the brothers shooting a giant panda in the mountains of Sichuan Province. Given the concurrent attention in the popular press describing this celebrated expedition, the giant panda was poised to be trophy hunted much like other large mammals around the world. Today, however, the killing of giant pandas, even for the generation of conservation revenue, is unthinkable for reasons related to the species itself and the context, in time and space, in which the species was popularized in the West. We found that the giant panda's status as a conservation symbol, exceptional charisma and gentle disposition, rarity, value as a nonconsumptive ecotourism attraction, and endemism are integral to the explanation of why the species is not trophy hunted. We compared these intrinsic and extrinsic characteristics with 20 of the most common trophy-hunted mammals to determine whether the principles applying to giant pandas are generalizable to other species. Although certain characteristics of the 20 trophy-hunted mammals aligned with the giant panda, many did not. Charisma, economic value, and endemism, in particular, were comparatively unique to the giant panda. Our analysis suggests that, at present, exceptional characteristics may be necessary for certain mammals to be excepted from trophy hunting. However, because discourse relating to the role of trophy hunting in supporting conservation outcomes is dynamic in both science and society, we suspect these valuations will also change in future.
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http://dx.doi.org/10.1111/cobi.13458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522670PMC
August 2020

Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantion Society Working Group.

Transplantation 2020 05;104(5):911-922

Centre for Transplant and Renal Research, Westmead Institute of Medical Research, University of Sydney and Renal Unit, Westmead Hospital, NSW, Australia.

With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated rejection (AMR) has become more common and is a major cause of kidney graft loss. Currently, there are no approved therapies and treatment guidelines are based on low-level evidence. The number of prospective randomized trials for the treatment of AMR is small, and the lack of an accepted common standard for care has been an impediment to the development of new therapies. To help alleviate this, The Transplantation Society convened a meeting of international experts to develop a consensus as to what is appropriate treatment for active and chronic active AMR. The aim was to reach a consensus for standard of care treatment against which new therapies could be evaluated. At the meeting, the underlying biology of AMR, the criteria for diagnosis, the clinical phenotypes, and outcomes were discussed. The evidence for different treatments was reviewed, and a consensus for what is acceptable standard of care for the treatment of active and chronic active AMR was presented. While it was agreed that the aims of treatment are to preserve renal function, reduce histological injury, and reduce the titer of donor-specific antibody, there was no conclusive evidence to support any specific therapy. As a result, the treatment recommendations are largely based on expert opinion. It is acknowledged that properly conducted and powered clinical trials of biologically plausible agents are urgently needed to improve patient outcomes.
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http://dx.doi.org/10.1097/TP.0000000000003095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176344PMC
May 2020

Dynamic rodent behavioral response to predation risk: implications for disease ecology.

Oecologia 2020 Jan 7;192(1):67-78. Epub 2019 Dec 7.

Department of Fisheries and Wildlife, Michigan State University, 480 Wilson Road, Room 13 Natural Resources Building, East Lansing, MI, 48824, USA.

Prey modify their behavior in response to variation in predation risk, and such modifications can affect trophic processes such as disease transmission. However, variation in predation risk is complex, arising from direct risk from the predator itself and indirect risk due to the environment. Moreover, direct risk typically stems from multiple predators and varies over timescales (e.g., a predator nearby vs. its seasonal activities). We implemented a field-based experiment to disentangle these sources of risk and relate them to antipredator behavior in rodents. We modeled rodent occurrence and activity as a function of short- and long-term risk from a primary predator, red foxes (Vulpes vulpes), long-term risk from a second predator, coyotes (Canis latrans), and environmental variables. We found that long-term red fox activity strongly reduced rodent occurrence and that cues of nearby red fox presence decreased rodent activity by > 50%. In addition, this activity reduction was dynamic in that varied according to the background level of long-term red fox activity. Importantly, rodents did not respond to environmental variables (moonlight, temperature, and habitat) or long-term coyote activity. These results bear upon recent work that suggests predators can alter tick-borne disease dynamics via induced antipredator behavior of rodents, which are hosts for pathogens and ticks. Specifically, our study corroborates the hypothesis that red foxes act as important proximal agents in regulating tick-borne diseases by reducing rodent activity. More generally, this study highlights the need to consider the dynamic nature of prey antipredator response across landscapes with variable long-term predation risk.
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http://dx.doi.org/10.1007/s00442-019-04565-zDOI Listing
January 2020

Clinical outcomes after ABO-incompatible renal transplantation.

Lancet 2019 11;394(10213):1988-1989

New York University Langone Transplant Institute, New York, NY, USA.

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http://dx.doi.org/10.1016/S0140-6736(19)32490-0DOI Listing
November 2019

Managing highly sensitized renal transplant candidates in the era of kidney paired donation and the new kidney allocation system: Is there still a role for desensitization?

Clin Transplant 2019 12 26;33(12):e13751. Epub 2019 Nov 26.

The William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USA.

Kidney paired donation (KPD) and the new kidney allocation system (KAS) in the United States have led to improved transplantation rates for highly sensitized candidates. We aimed to assess the potential need for other approaches to improve the transplantation rate of highly sensitized candidates such as desensitization. Using the UNOS STAR file, we analyzed transplant rates in a prevalent active waiting-list cohort as of June 1, 2016, followed for 1 year. The overall transplantation rate was 18.9% (11 129/58769). However, only 9.7% (213/2204) of candidates with a calculated panel reactive antibody ≥99.9% received a transplant, and highly sensitized candidates were less likely to receive a living donor transplant. Among candidates with a CPRA ≥ 99.5% (ie. 100%), only 2.5% of transplants were from living donors (13 total, 7 from KPD). Nearly 4 years after KAS (6/30/2018), 1791 actively wait-listed candidates had a CPRA of ≥99.9% and 34.6% (620/1791) of these had ≥5 years of waiting time. Thus, despite KPD and KAS, many sensitized candidates have not been transplanted even with prolonged waiting time. We conclude that candidates with a CPRA ≥ 99.9% and sensitized candidates with an incompatible living donor and prolonged waiting time may benefit from desensitization to improve their ability to receive a transplant.
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http://dx.doi.org/10.1111/ctr.13751DOI Listing
December 2019

Getting Comfortable with Risk.

N Engl J Med 2019 Oct;381(17):1606-1607

From the New York University Langone Transplant Institute, New York.

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http://dx.doi.org/10.1056/NEJMp1906872DOI Listing
October 2019

Patterns of livestock depredation and cost-effectiveness of fortified livestock enclosures in northern Tanzania.

Ecol Evol 2019 Oct 15;9(19):11420-11433. Epub 2019 Sep 15.

Research on the Ecology of Carnivores and their Prey Laboratory Department of Fisheries and Wildlife Michigan State University East Lansing MI USA.

Human-carnivore conflicts and retaliatory killings contribute to carnivore populations' declines around the world. Strategies to mitigate conflicts have been developed, but their efficacy is rarely assessed in a randomized case-control design. Further, the economic costs prevent the adoption and wide use of conflict mitigation strategies by pastoralists in rural Africa. We examined carnivore (African lion [], leopard [], spotted hyena [], jackal [], and cheetah []) raids on fortified ( = 45, total 631 monthly visits) and unfortified (traditional,  = 45, total 521 monthly visits) livestock enclosures ("") in northern Tanzania. The study aimed to (a) assess the extent of retaliatory killings of major carnivore species due to livestock depredation, (b) describe the spatiotemporal characteristics of carnivore raids on livestock enclosures, (c) analyze whether spatial covariates influenced livestock depredation risk in livestock enclosures, and (d) examine the cost-effectiveness of livestock enclosure fortification. Results suggest that (a) majority of boma raids by carnivores were caused by spotted hyenas (nearly 90% of all raids), but retaliatory killings mainly targeted lions, (b) carnivore raid attempts were rare at individual households (0.081 raid attempts/month in fortified enclosures and 0.102 raid attempts/month in unfortified enclosures), and (c) spotted hyena raid attempts increased in the wet season compared with the dry season, and owners of fortified bomas reported less hyena raid attempts than owners of unfortified bomas. Landscape and habitat variables tested, did not strongly drive the spatial patterns of spotted hyena raids in livestock bomas. Carnivore raids varied randomly both spatially (village to village) and temporally (year to year). The cost-benefit analysis suggest that investing in boma fortification yielded positive net present values after two to three years. Thus, enclosure fortification is a cost-effective strategy to promote coexistence of carnivores and humans.
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http://dx.doi.org/10.1002/ece3.5644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802044PMC
October 2019

Therapeutic Modulation of the Complement System in Kidney Transplantation: Clinical Indications and Emerging Drug Leads.

Front Immunol 2019 1;10:2306. Epub 2019 Oct 1.

NYU Langone Transplant Institute, New York, NY, United States.

The complement system is integral to innate immunity, and it is an essential deterrent against infections. The complement apparatus comprises of >30 fluid-phase and surface-bound elements that also engage with the adaptive immune system, clear harmful immune complexes, and orchestrates several salutary physiological processes. An imbalance in the complement system's tightly regulated machinery and the consequent unrestrained complement activation underpins the pathogenesis of a wide array of inflammatory, autoimmune, neoplastic and degenerative disorders. Antibody-mediated rejection is a leading cause of graft failure in kidney transplantation. Complement-induced inflammation and endothelial injury have emerged as the primary mechanisms in the pathogenesis of this form of rejection. Researchers in the field of transplantation are now trying to define the role and efficacy of complement targeting agents in the prevention and treatment of rejection and other complement related conditions that lead to graft injury. Here, we detail the current clinical indications for complement therapeutics and the scope of existing and emerging therapies that target the complement system, focusing on kidney transplantation.
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http://dx.doi.org/10.3389/fimmu.2019.02306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779821PMC
October 2020

Author Correction: 'Stealth' corporate innovation: an emerging threat for therapeutic drug development.

Nat Immunol 2019 Nov;20(11):1556

Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41590-019-0531-xDOI Listing
November 2019