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BMJ ; 372: m4933, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1007304
Transplant Proc ; 52(9): 2592-2595, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-720725


BACKGROUND: Kidney allograft biopsy is the gold standard for diagnosis of rejection. Under the current extraordinary circumstances of the coronavirus disease 2019 (COVID-19), in which social distancing is key to limiting the spread of the virus, the model used to provide care to transplant recipients has undergone a very rapid transformation. In the spirit of medical distancing, we have been using the donor-derived cell-free DNA (dd-cfDNA) test for screening for rejection. METHODS: This article describes our experience with this approach between March 15th and May 20th, 2020. RESULTS: This test was obtained for-cause in 23 patients and for monitoring in 9 patients. Normal results aided in forgoing biopsy in 63% of the patients for whom the test was obtained in the outpatient setting. The test is neither 100% sensitive nor specific for rejection; however, when used in combination with the available clinical information, it can be used for determining whether bringing in a transplant recipient into a medical facility is necessary. CONCLUSIONS: In the event COVID-19 becomes a long-term challenge for our community, noninvasive biomarkers such as the dd-cfDNA may become more relevant than ever in enhancing our ability to care for our transplant patients while maximizing the distancing measures.

Cell-Free Nucleic Acids/analysis , Coronavirus Infections/prevention & control , Disease Transmission, Infectious/prevention & control , Graft Rejection/diagnosis , Kidney Transplantation/adverse effects , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Adult , Allografts/chemistry , Betacoronavirus , Biomarkers/analysis , Coronavirus Infections/transmission , Female , Humans , Kidney/chemistry , Liquid Biopsy , Male , Middle Aged , Pneumonia, Viral/transmission , Transplantation, Homologous
J Immunother Cancer ; 8(2)2020 08.
Article in English | MEDLINE | ID: covidwho-712954


To report a multi-institutional case series of patients with advanced microsatellite instability high (MSI-H) prostate adenocarcinoma identified with clinical cell-free DNA (cfDNA) next-generation sequencing (NGS) testing and treated with immune checkpoint inhibitors. Retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) and MSI-H tumor detected by a commercially available cfDNA NGS assay Guardant360 (G360, Guardant Health) at eight different Academic Institutions in the USA, from September 2018 to April 2020. From a total of 14 MSI-H metastatic prostate cancer patients at participating centers, nine patients with mCRPC with 56% bone, 33% nodal, 11% liver and 11% soft-tissue metastases and a median PSA of 29.3 ng/dL, were treated with pembrolizumab after 2 lines of therapy for CRPC. The estimated median time on pembrolizumab was 9.9 (95% CI 1.0 to 18.8) months. Four patients (44%) achieved PSA50 after a median of 4 (3-12) weeks after treatment initiation including three patients with >99% PSA decline. Among the patients evaluable for radiographic response (n=5), the response rate was 60% with one complete response and two partial responses. Best response was observed after a median of 3.3 (1.4-7.6) months. At time of cut-off, four patients were still on pembrolizumab while four patients discontinued therapy due to progressive disease and one due to COVID-19 infection. Half of the patients with PSA50 had both MSI-H and pathogenic alterations in BRCA1 and BRCA2 in their G360 assays. The use of liquid biopsy to identify metastatic prostate cancer patients with MSI-H is feasible in clinical practice and may overcome some of the obstacles associated with prostate cancer tumor tissue testing. The robust activity of pembrolizumab in selected patients supports the generalized testing for MSI-H.

Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Microsatellite Instability , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Biomarkers, Tumor/genetics , Circulating Tumor DNA/blood , Coronavirus Infections , Humans , Liquid Biopsy , Male , Middle Aged , Mutation , Pandemics , Pneumonia, Viral , Prostatic Neoplasms/pathology
Eur Urol Focus ; 6(5): 1086-1096, 2020 Sep 15.
Article in English | MEDLINE | ID: covidwho-591878


CONTEXT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that erupted in December 2019 has affected more than a million people from over 200 countries, claiming over 70 000 lives (by April 7, 2020). As the viral infection is driven by increased angiotensin-converting enzyme-2 (ACE2) expression, with the kidney exhibiting the highest expression, it is crucial to gain insights into the mechanisms underlying renal cell carcinoma (RCC) and coronavirus disease 2019 (COVID-19). OBJECTIVE: This study considers up-to-date information on the biological determinants shared by COVID-19 and renal disease, and aims to provide evidence-based recommendations for the clinical management of RCC patients with COVID-19. EVIDENCE ACQUISITION: A literature search was performed using all sources (MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science). As of March 31, 2020, the Center for Disease Control reported that of the adults hospitalized for COVID-19 with underlying conditions in the USA, 74.8% had chronic renal disease. EVIDENCE SYNTHESIS: Evidence is discussed from epidemiological studies on SARS-CoV-2 pandemic and molecular studies on the role of kidney in facilitating routes for SARS-CoV-2 entry, leading to increased virulence of SARS-CoV-2 and clinical manifestation of symptoms in RCC. CONCLUSIONS: This analysis will advance our understanding of (1) the molecular signatures shared by RCC and COVID-19 and (2) the clinical implications of overlapping signaling pathways in the therapeutic management of RCC and COVID-19 patients. PATIENT SUMMARY: Amid the coronavirus disease 2019 (COVID-19) pandemic, patients diagnosed with renal cell carcinoma and infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may receive complimentary treatment modalities to enhance therapeutic response.

Betacoronavirus/metabolism , Carcinoma, Renal Cell/metabolism , Coronavirus Infections/metabolism , Kidney Neoplasms/metabolism , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism , Renal Insufficiency, Chronic/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Acute Kidney Injury/epidemiology , Acute Kidney Injury/metabolism , Acute Kidney Injury/therapy , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antibodies, Neutralizing/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Antiviral Agents/therapeutic use , Carcinoma, Renal Cell/epidemiology , Comorbidity , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Endothelin Receptor Antagonists/therapeutic use , Hospitalization , Humans , Ipilimumab/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/epidemiology , Liquid Biopsy , Nivolumab/therapeutic use , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Protein Kinase Inhibitors/therapeutic use , Renal Dialysis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , Serine Endopeptidases/metabolism , Severity of Illness Index , Sunitinib/therapeutic use