Outcomes of critically ill solid organ transplant patients with COVID‐19 in the United States

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163464/2/ajt16280.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163464/1/ajt16280_am.pd

Management of new onset loss of sense of smell during the COVID-19 pandemic - BRS Consensus Guidelines

OBJECTIVES: The primary aim of the study is to provide recommendations for the investigation and management of patients with new onset loss of sense of smell during the COVID-19 pandemic. DESIGN: After undertaking a literature review, we used the RAND/UCLA methodology with a multi-step process to reach consensus about treatment options, onward referral, and imaging. SETTING AND PARTICIPANTS: An expert panel consisting of 15 members was assembled. A literature review was undertaken prior to the study and evidence was summarised for the panellists. MAIN OUTCOME MEASURES: The panel undertook a process of ranking and classifying appropriateness of different investigations and treatment options for new onset loss of sense of smell during the COVID-19 pandemic. Using a 9-point Likert scale, panellists scored whether a treatment was: Not recommended, optional, or recommended. Consensus was achieved when more than 70% of responses fell into the category defined by the mean. RESULTS: Consensus was reached on the majority of statements after 2 rounds of ranking. Disagreement meant no recommendation was made regarding one treatment, using Vitamin A drops. Alpha-lipoic acid was not recommended, olfactory training was recommended for all patients with persistent loss of sense of smell of more than 2 weeks duration, and oral steroids, steroid rinses, and omega 3 supplements may be considered on an individual basis. Recommendations regarding the need for referral and investigation have been made. CONCLUSION: This study identified the appropriateness of olfactory training, different medical treatment options, referral guidelines and imaging for patients with COVID-19-related loss of sense of smell. The guideline may evolve as our experience of COVID-19 develops

PARP-Inhibitors in BRCA-Associated Pancreatic Cancer

Recent data suggests that treatingpatients with pancreatic cancer that express mutations in BRCA1, BRCA2, and PALB2 with chemotherapy which targets the DNA repair defect in these cells, such as platinum based therapies or PARPi [poly (ADP-ribose) polymerase inhibitor], may be more beneficial in these patients. Moreover, further data also indicates the promise of combining PARPi with conventional chemotherapy. Authors summarize the data related to PARPi in BRCA-associated pancreatic cancer that was presented at the annual meeting of ASCO 2014. Enrolment on a clinical trial for patients who fit these criteria should be encouraged.Image: Schematic representation of PARP and BRCA mediated DNA repair

CMV specific T cell immune response in hepatitis C negative kidney transplant recipients receiving transplant from hepatitis C viremic donors and hepatitis C aviremic donors.

Kidney transplants (KT) from hepatitis C (HCV) viremic donors to HCV negative recipients has shown promising renal outcomes, however, high incidence of cytomegalovirus (CMV) viremia were reported. We performed a prospective cohort study of 52 HCV negative KT recipients from Methodist University Hospital including 41 receiving transplants from HCV aviremic donors and 11 from HCV viremic donors. CMV specific CD4+ and CD8 + T cell immunity was measured by intracellular flow cytometry assay. Primary outcome was the development of positive CMV specific CD4+ and CD8 + T cell immune response in the entire cohort and each subgroup. The association between donor HCV status and CMV specific CD4+ and CD8 + T cell immune response was analyzed by Cox proportional hazard models. Mean recipient age was 48 ± 13 years, with 73% male and 82% African American. Positive CMV specific CD4+ and CD8 + T cell immune response was found in 53% and 47% of the cohort at 1 month, 65% and 70% at 2 months, 80% and 75% at 4 months, 89% and 87% at 6 months, and 94% and 94% at 9 months post-transplant, respectively. There was no significant difference in the incidence of positive CMV specific T cell immune response between recipients of transplants from HCV aviremic donors compared to HCV viremic donors in unadjusted (for CD8+: HR = 1.169, 95%CI: 0.521-2.623; for CD4+: HR = 1.208, 95%CI: 0.543-2.689) and adjusted (for CD8+: HR = 1.072, 95%CI: 0.458-2.507; for CD4+: HR = 1.210, 95%CI: 0.526-2.784) Cox regression analyses. HCV viremia in donors was not associated with impaired development of CMV specific T cell immunity in this cohort

Association between ezetimibe usage and hepatitis C RNA levels in uninfected kidney transplant recipients who received hepatitis C infected kidneys.

Kidney transplantation (KT) from hepatitis C virus infected (HCV+) donors to HCV negative recipients achieve excellent graft function but have relatively higher rates of post-KT co-infections presumably due to prolonged HCV viremia in transmission-and-treat approach. Ezetimibe acts as an antagonist of Niemann-Pick C1-Like 1 receptor required for HCV entry and theoretically can reduce HCV viremia. However, no data is available to examine the role of ezetimibe as a bridge therapy between KT surgery and direct acting antiviral (DAA) initiation. A retrospective cohort study including 70 HCV+ to HCV negative KT recipients from Methodist University Hospital and Vanderbilt University Medical Center was performed to determine the association between ezetimibe usage and HCV viremia. Twenty patients received ezetimibe daily while 50 patients did not. Primary outcome of study was mean HCV RNA level at 1-2 weeks post-KT and before initiation of DAA. Median (IQR) viral load (VL) in log copies/ml was one log lower in ezetimibe group versus non-ezetimibe group (4.1 [3.7-5.3] vs. 5.1 [4.4-5.5], P = .01), and highest VL was also lower in ezetimibe group (4.2 [3.7-5.4] vs. 5.4 [4.7-5.9], P = .006). We concluded that ezetimibe bridge therapy might be associated with reduction in HCV VL while waiting for DAA initiation in HCV+ to HCV negative KT recipients

Comparison of Short-Term Outcomes in Kidney Transplant Recipients from SARS-CoV-2-Infected versus Noninfected Deceased Donors.

BACKGROUND: Acceptable posttransplant outcomes were reported in kidney transplant recipients from donors with coronavirus disease-2019 (COVID-19), however, there are no comparative studies with well-matched controls. METHODS: This multicenter, prospective observational study, which included three transplant centers in the US, enrolled 61 kidney recipients from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected deceased donors. Using optimal matching methods, we matched every recipient to three comparators receiving kidneys from SARS-CoV-2-negative deceased donors with otherwise highly similar characteristics within the same transplant centers to compare 6-month eGFR. RESULTS: Among recipients of SARS-CoV-2-infected donor kidneys, one recipient died with a functional graft within 6 months. Mean 6-month eGFR was not significantly different between SARS-CoV-2-infected and non-infected donor groups (55±21 and 57±25 mL/min/1.73m2; p=0.61). Six-month eGFR in recipients from SARS-CoV-2-infected donors who died from reasons other than COVID-19 was not significantly different from those from SARS-CoV-2-negative donors (58±22 and 56±25 mL/min/1.73m2; p=0.51). However, recipients from donors who died from COVID-19 had significantly lower 6-month eGFR that those from SARS-CoV-2-negative donors (46±17 and 58±27 mL/min/1.73m2; p=0.03). No donor-to-recipient SARS-CoV-2 transmission was observed. CONCLUSIONS: Six-month eGFR was not significantly different between recipients of kidneys from SARS-CoV-2-infected and non-infected donors. However, those receiving kidneys from donors who died from COVID-19 had significantly lower 6-month eGFR. Donor-to-recipient SARS-CoV-2 transmission was not observed

Data_Sheet_2_Unveiling APOL1 haplotypes in a predominantly African-American cohort of kidney transplant patients: a novel classification using probe-independent quantitative real-time PCR.PDF

IntroductionApolipoprotein-L1 (APOL1) is a primate-specific protein component of high-density lipoprotein (HDL). Two variants of APOL1 (G1 and G2), provide resistance to parasitic infections in African Americans but are also implicated in kidney-related diseases and transplant outcomes in recipients. This study aims to identify these risk variants using a novel probe-independent quantitative real-time PCR method in a high African American recipient cohort. Additionally, it aims to develop a new stratification approach based on a haplotype-centric model.MethodsGenomic DNA was extracted from recipient PBMCs using SDS lysis buffer and proteinase K. A quantitative PCR assay with modified forward primers and a common reverse primer enabled us to quantitatively identify single nucleotide polymorphisms (SNPs) and the 6-bp deletion. Additionally, we used Sanger sequencing to verify our QPCR findings.ResultsOur novel probe-independent qPCR effectively distinguished homozygous wild-type, heterozygous SNPs/deletions, and homozygous SNPs/deletions, with at least 4-fold differences. A high prevalence of APOL1 variants was observed (18% two-risk alleles, 34% one-risk allele) in our recipient cohort. Intriguingly, no significant impact of recipient APOL1 variants on transplant outcomes was observed up to 12-month of follow-ups. Ongoing research will encompass more time points and a larger patient cohort, allowing for a comprehensive evaluation of G1/G2 variant subgroups categorized by new haplotype scores, enriching our understanding.ConclusionOur cost-effective and rapid qPCR technique facilitates APOL1 genotyping within hours. Prospective and retrospective studies will enable comparisons with long-term allograft rejection, potentially predicting early/late-stage transplant outcomes based on haplotype evaluation in this diverse group of kidney transplant recipients.</p