Biomarkers and cardiovascular outcomes in chimeric antigen receptor T-cell therapy recipients.

AIMS: Chimeric antigen receptor T-cell therapy (CAR-T) harnesses a patient's immune system to target cancer. There are sparse existing data characterizing death outcomes after CAR-T-related cardiotoxicity. This study examines the association between CAR-T-related severe cardiovascular events (SCE) and mortality. METHODS AND RESULTS: From a multi-centre registry of 202 patients receiving anti-CD19 CAR-T, covariates including standard baseline cardiovascular and cancer parameters and biomarkers were collected. Severe cardiovascular events were defined as a composite of heart failure, cardiogenic shock, or myocardial infarction. Thirty-three patients experienced SCE, and 108 patients died during a median follow-up of 297 (interquartile range 104-647) days. Those that did and did not die after CAR-T were similar in age, sex, and prior anthracycline use. Those who died had higher peak interleukin (IL)-6 and ferritin levels after CAR-T infusion, and those who experienced SCE had higher peak IL-6, C-reactive protein (CRP), ferritin, and troponin levels. The day-100 and 1-year Kaplan-Meier overall mortality estimates were 18% and 43%, respectively, while the non-relapse mortality (NRM) cumulative incidence rates were 3.5% and 6.7%, respectively. In a Cox model, SCE occurrence following CAR-T was independently associated with increased overall mortality risk [hazard ratio (HR) 2.8, 95% confidence interval (CI) 1.6-4.7] after adjusting for age, cancer type and burden, anthracycline use, cytokine release syndrome grade ≥ 2, pre-existing heart failure, hypertension, and African American ancestry; SCEs were independently associated with increased NRM (HR 3.5, 95% CI 1.4-8.8) after adjusting for cancer burden. CONCLUSION: Chimeric antigen receptor T-cell therapy recipients who experience SCE have higher overall mortality and NRM and higher peak levels of IL-6, CRP, ferritin, and troponin.

Conflict Nephrology: War and Natural Disasters.

Access to care for patients with ESKD is frequently disrupted after natural disasters, public health crises, and human conflict. Emergency preparation can mitigate the risk of harm and improve outcomes. Before Hurricane Katrina in 2005, the United States was unprepared to assist patients facing disaster. We evaluate responses to Hurricane Katrina which caused unprecedented damage to health and property in the Gulf Coast. As a result of the multitude of identified problems with the national, local, and kidney-specific responses to Katrina, new systems were created that mitigated loss after Hurricane Sandy in 2012. The improved disaster response system was no match for the coronavirus disease 2019 pandemic; real-time changes worsened the effect on highly vulnerable populations, including patients with ESKD. Similarly, preparation can only mitigate the difficulties faced by patients with ESKD living in a war zone. Government agencies need to provide tools and dialysis centers need to educate patients. Beginning with steps implemented in the aftermath of Hurricane Katrina and augmented after Hurricane Sandy, every patient with ESKD and those who care for them must begin emergency preparations before the need arises. Recognizing that it is not possible to prepare for every possible emergency, our health care systems must be ready to adapt to our ever-changing world. After reviewing the responses to previous events, we suggest steps that should be considered to improve preparations for our uncertain future.

New insights into the microbiome in kidney transplantation.

PURPOSE OF REVIEW: Research in the past decade has revealed important implications for the microbiome in human health. Studies have defined a distinct gut microbiota in kidney transplant recipients and have recently linked the microbiota to infectious complications, similar to the allogeneic stem cell transplant population. RECENT FINDINGS: In this review, we focus on the metabolism of immunosuppressive medications by the gut microbiota and on the urinary microbiome in the setting of infectious and immunological complications. We highlight seminal studies showing the role of specific gut microbiota in the direct metabolism of tacrolimus into a lesser effective immunosuppressant as well as the role of the gut microbiota in the metabolism of mycophenolic acid (MPA) glucuronide. We describe distinct urinary microbiota patterns in kidney transplant recipients with interstitial fibrosis tubular atrophy, chronic allograft nephropathy, tolerance, and bacterial and viral complications. SUMMARY: The microbiota has important implications for immunosuppressive medications and immunological outcomes in kidney transplant recipients. Further research is needed to better delineate the impact of the metabolism of tacrolimus and MPA by gut bacteria and the role of the urine microbiota in the development of immunological and infectious complications.

Renal Considerations in COVID-19: Biology, Pathology, and Pathophysiology.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.

Racial and Neighborhood-Level Disparities in COVID-19 Incidence among Patients on Hemodialysis in New York City.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected socially disadvantaged populations. Whether disparities in COVID-19 incidence related to race/ethnicity and socioeconomic factors exist in the hemodialysis population is unknown. METHODS: Our study involved patients receiving in-center hemodialysis in New York City. We used a validated index of neighborhood social vulnerability, the Social Vulnerability Index (SVI), which comprises 15 census tract-level indicators organized into four themes: socioeconomic status, household composition and disability, minority status and language, and housing type and transportation. We examined the association of race/ethnicity and the SVI with symptomatic COVID-19 between March 1, 2020 and August 3, 2020. COVID-19 cases were ascertained using PCR testing. We performed multivariable logistic regression to adjust for demographics, individual-level social factors, dialysis-related medical history, and dialysis facility factors. RESULTS: Of the 1378 patients on hemodialysis in the study, 247 (17.9%) developed symptomatic COVID-19. In adjusted analyses, non-Hispanic Black and Hispanic patients had significantly increased odds of COVID-19 compared with non-Hispanic White patients. Census tract-level overall SVI, modeled continuously or in quintiles, was not associated with COVID-19 in unadjusted or adjusted analyses. Among non-Hispanic White patients, the socioeconomic status SVI theme, the minority status and language SVI theme, and housing crowding were significantly associated with COVID-19 in unadjusted analyses. CONCLUSIONS: Among patients on hemodialysis in New York City, there were substantial racial/ethnic disparities in COVID-19 incidence not explained by neighborhood-level social vulnerability. Neighborhood-level socioeconomic status, minority status and language, and housing crowding were positively associated with acquiring COVID-19 among non-Hispanic Whites. Our findings suggest that socially vulnerable patients on dialysis face disparate COVID-19-related exposures, requiring targeted risk-mitigation strategies.

Tumor Lysis Syndrome.

Tumor lysis syndrome (TLS) is an oncologic emergency due to massive tumor cell lysis with the release of large amounts of potassium, phosphate, and nucleic acids into the systemic circulation. Clinical presentation is characterized by hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia. Acute kidney injury due to tumor lysis is potentiated by the precipitation of uric acid and calcium phosphate as well as renal vasoconstriction. Early recognition of tumor lysis can help prevent cardiac arrhythmias, seizures, and death. Management includes intravenous hydration to maintain urine flow, medications targeting hyperuricemia including rasburicase and allopurinol and in severe cases renal replacement therapy may be required.

Associations between the size and location of myocardial infarction and cerebral infarction.

BACKGROUND: Myocardial infarction (MI) is a known cause of cerebral infarction. We assessed whether the size and location of MI is associated with the risk of cerebral infarction. METHODS AND RESULTS: We performed a cross-sectional study of adults who underwent both brain MRI and delayed-enhancement cardiac MRI (DE-CMR) within 365 days of each other at Weill Cornell Medicine between 2014 and 2017 and had evidence of MI on DE-CMR. We used multiple logistic regression to evaluate associations between MI size and any cerebral infarction, apical MI location and any cerebral infarction, and MI size/location and cortical versus subcortical cerebral infarction. Models were adjusted for demographics, and the total number of vascular risk factors. Among 234 patients who underwent both DE-CMR and brain MRI within 365 days, 76 had evidence for MI on DE-CMR. Among these 76 patients, 51 (67.1%) had evidence of cerebral infarction. The size of MI (global MI burden) was not associated with any cerebral infarction (OR per 5% increase in MI size, 1.12; 95% CI, 0.85-1.47), but was associated with cortical cerebral infarction (OR per 5% increase in MI size, 1.30; 95% CI, 1.00.-1.68). Similarly, apical MI location was not associated with any cerebral infarction (OR 2.63, 95% CI, 0.78-8.87), but was associated with cortical cerebral infarction (OR, 3.67; 95% CI, 1.19-11.33). CONCLUSION: Among patients with MI on cardiac MRI, both size and apical location of MI were associated with cortical cerebral infarction. Our results may help stratify cardioembolic risk and inform antithrombotic treatment algorithms among patients with MI.

Strategies to Prevent Cardiac Implantable Electronic Device Infection.

The association between the risk of mortality and cardiovascular implantable electronic device (CIED) infections has been well-established in the literature. As CIED implantations have increased in frequency in the past few decades, the incidence of CIED-related infections has also risen. Given the morbidity, mortality, and health-care costs associated with CIED infections, the prevention of device-related infection is a critical goal. Risk factors for developing CIED infections can be categorized as patient-, procedure-, or device-related. Numerous studies have highlighted different strategies for preventing CIED-related infections, which include patient optimization, device selection, and periprocedural preparation and treatment. Nonetheless, as the comorbidity burden of patients undergoing CIED implantation continues to increase, significant challenges in the successful elimination of CIED-related infections remain. This review provides a comprehensive overview of available evidence-based approaches and strategies to reduce the risk of CIED infections.

Imaging Utilization and Outcomes in Vulnerable Populations during COVID-19 in New York City.

BACKGROUND: Coronavirus disease 2019 (COVID-19) affects vulnerable populations (VP) adversely. PURPOSE: To evaluate overall imaging utilization in vulnerable subgroups (elderly, racial/ethnic minorities, socioeconomic status [SES] disadvantage) and determine if a particular subgroup has worse outcomes from COVID-19. MATERIALS/METHODS: Of 4110 patients who underwent COVID-19 testing from March 3-April 4, 2020 at NewYork-Presbyterian Hospital (NYP) health system, we included 1121 COVID-19 positive adults (mean age 59±18 years, 59% male) from two academic hospitals and evaluated imaging utilization rates and outcomes, including mortality. RESULTS: Of 897 (80%) VP, there were 465 (41%) elderly, 380 (34%) racial/ethnic minorities, and 479 (43%) SES disadvantage patients. Imaging was performed in 88% of patients and mostly portable/bedside studies, with 87% of patients receiving chest radiographs. There were 83% hospital admissions, 25% ICU admissions, 23% intubations, and 13% deaths. Elderly patients had greater imaging utilization, hospitalizations, ICU/intubation requirement, longer hospital stays, and >4-fold increase in mortality compared to non-elderlies (adjusted hazard ratio[aHR] 4.79, p<0.001). Self-reported minorities had fewer ICU admissions (p=0.03) and reduced hazard for mortality (aHR 0.53, p=0.004; complete case analysis: aHR 0.39, p<0.001 excluding "not reported"; sensitivity analysis: aHR 0.61, p=0.005 "not reported" classified as minorities) with similar imaging utilization, compared to non-minorities. SES disadvantage patients had similar imaging utilization and outcomes as compared to their counterparts. CONCLUSIONS: In a predominantly hospitalized New York City cohort, elderly patients are at highest mortality risk. Racial/ethnic minorities and SES disadvantage patients fare better or similarly to their counterparts, highlighting the critical role of access to inpatient medical care during the COVID-19 pandemic.

Cardiomyopathy Prevention in Cancer Patients.

Left ventricular systolic dysfunction (LVSD) and overt heart failure are well known manifestations of chemotherapy-induced cardiotoxicity. The development of LVSD is clinically significant because it can impact the delivery of lifesaving chemotherapy and increase the risk of developing heart failure, compromising quality of life and survival years after cure of the cancer. Cancer treatment-related cardiomyopathy is most commonly associated with anthracyclines and trastuzumab. Several interventions have been identified to prevent cancer-induced cardiomyopathy. Anthracyclines is a major culprit, and prevention strategies with limiting cumulative dose, continuous infusion, dexrazoxane, and liposomal formulation have been shown to decrease the risk of cardiotoxicity.