Search

A letter to the editor is presented concerning making Pakistan's healthcare systems more responsive to women.

Dengue virus (DENV) is the most prevalent mosquito-borne Flavivirus that affects humans worldwide. Aedes albopictus, which is naturally infected with the bacteria Wolbachia, is considered to be a secondary vector of DENV. However, it was responsible for a recent DENV outbreak of unprecedented magnitude in Reunion Island, a French island in the South West Indian Ocean. Moreover, the distribution of the cases during this epidemic showed a spatially heterogeneous pattern across the island, leading to questions about the differential vector competence of mosquito populations from different geographic areas. The aim of this study was to gain a better understanding of the vector competence of the Ae. albopictus populations from Reunion Island for local DENV epidemic strains, while considering their infection by Wolbachia. Experimental infections were conducted using ten populations of Ae. albopictus sampled across Reunion Island and exposed to three DENV strains: one strain of DENV serotype 1 (DENV-1) and two strains of DENV serotype 2 (DENV-2). We analyzed three vector competence parameters including infection rate, dissemination efficiency and transmission efficiency, at different days post-exposition (dpe). We also assessed whether there was a correlation between the density of Wolbachia and viral load/vector competence parameters. Our results show that the Ae. albopictus populations tested were not able to transmit the two DENV-2 strains, while transmission efficiencies up to 40.79% were observed for the DENV-1 strain, probably due to difference in viral titres. Statistical analyses showed that the parameters mosquito population, generation, dpe and area of sampling significantly affect the transmission efficiencies of DENV-1. Although the density of Wolbachia varied according to mosquito population, no significant correlation was found between Wolbachia density and either viral load or vector competence parameters for DENV-1. Our results highlight the importance of using natural mosquito populations for a better understanding of transmission patterns of dengue., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hafsia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: Conflict of interest S.S.M. has received consulting fees from Nektar Therapeutics, Health & Wellness Partners, Medicure. P.A.R. has received consulting fees from AbbVie, BMS, Janssen, Novartis, BeiGene, Kite/Gilead, Intellia Therapeutics, Sana Biotechnology, CVS Caremark, Genmab, Pharmacyclics, Takeda, Karyopharm, Nektar Therapeutics, Nurix Therapeutics, and ADC Therapeutics. M.A.P. reports consulting fees from Adicet, Allovir, Caribou Biosciences, Celgene, Bristol-Myers Squibb, Equilium, Exevir, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, OrcaBio, Syncopation, VectivBio AG, and Vor Biopharma, is participating in DSMB of Cidara Therapeutics, Medigene, and Sellas Life Sciences, and is on the scientific advisory board of NexImmune and Omeros. M.B.G. has received institutional grant funding from Sanofi, Amgen, and Actinium and consulting fees from Sanofi, Novartis, and Allogene. M.L.P. has received royalties from Juno and Sers and consulting fees from Novartis, Cellectar, Synthekine, Kite, Seres, Magenta, WindMIL, Rheos, Nektar, Notch, Priothera, Ceramedix, Lygenesis, and Pluto. R.S. has received consulting fees from Mudexus and MyBiotics. G.S. has received research funding from Janssen, Amgen, Beyond Spring, and BMS and is on DSMB of ArcellX. E.H.Y. has received institutional grand funding from CSL Behring, Boehringer Ingelheim, BMS and Eli and Lilly and consulting fees from Pfizer. J.P.L. has received institutional grants from Genentech, Janssen, and Epizyme and consulting fees from Abbvie, Astellas, AstraZeneca, Bayer, Beigene, BMS, Calithera, Constellation, Caribou Biosciences, Eisai, Lilly, Epizyme, Genmab, Grail, Incyte, Jansssen, MEI Pharma, Merck, Mustang Bio, Novartis, Pfizer, Roche/Genentech, Seagen, Second Genome, Sutro, ADC Therapeutics, Miltenyi, and Karyopharm. T.G.N. has received consulting fees from BMS, Genentech, Abbvie, Roche, CRO Oncology, and Sanofi and participates in DSMB of Genentech and received research grant funding from AstraZeneca and BMS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: An unprecedent increase in the number of cases and deaths reported from dengue virus (DENV) infection has occurred in the southwestern Indian ocean in recent years. From 2017 to mid-2021 more than 70,000 confirmed dengue cases were reported in Reunion Island, and 1967 cases were recorded in the Seychelles from 2015 to 2016. Both these outbreaks displayed similar trends, with the initial circulation of DENV-2 which was replaced by DENV-1. Here, we aim to determine the origin of the DENV-1 epidemic strains and to explore their genetic characteristics along the uninterrupted circulation, particularly in Reunion., Methods: Nucleic acids were extracted from blood samples collected from dengue positive patients; DENV-1 was identified by RT-qPCR. Positive samples were used to infect VERO cells. Genome sequences were obtained from either blood samples or infected-cell supernatants through a combination of both Illumina or MinION technologies., Results: Phylogenetic analyses of partial or whole genome sequences revealed that all DENV-1 sequences from Reunion formed a monophyletic cluster that belonged to genotype I and were closely related to one isolate from Sri Lanka (OL752439.1, 2020). Sequences from the Seychelles belonged to the same major phylogenetic branch of genotype V, but fell into two paraphyletic clusters, with greatest similarity for one cluster to 2016-2017 isolate from Bangladesh, Singapore and China, and for the other cluster to ancestral isolates from Singapore, dating back to 2012. Compared to publicly available DENV-1 genotype I sequences, fifteen non-synonymous mutations were identified in the Reunion strains, including one in the capsid and the others in nonstructural proteins (NS) (three in NS1, two in NS2B, one in NS3, one in NS4B, and seven in NS5)., Conclusion: In contrast to what was seen in previous outbreaks, recent DENV-1 outbreaks in Reunion and the Seychelles were caused by distinct genotypes, all likely originating from Asia where dengue is (hyper)endemic in many countries. Epidemic DENV-1 strains from Reunion harbored specific non-synonymous mutations whose biological significance needs to be further investigated., (© 2023. The Author(s).)

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., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Disclosures: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

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., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 by the American Society of Nephrology.)

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., Competing Interests: Disclosures: All authors have no disclosures., (2020 by the Radiological Society of North America, Inc.)

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., Competing Interests: Dr. Thomas reports receiving research support from Biotronik and Medtronic, consulting fees from Medtronic, and speaker fees from Biotronik. Dr. Cheung reports receiving research support from Biotronik; consulting and speaker fees from Abbott Laboratories and Biotronik; and fellowship grant support from Abbott Laboratories, Biotronik, Boston Scientific, and Medtronic. The other authors report no conflicts of interest for the published content., (Copyright: © 2020 Innovations in Cardiac Rhythm Management.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The short arm of chromosome 8 is frequently deleted in advanced human colorectal cancers, suggesting the presence of one or more tumor suppressor genes having a major role in tumor progression and metastasis. Comprehensive sequencing of over 18,000 genes in colon and breast cancers identified somatic mutations in CUB and Sushi Multiple Domains 1 Gene (CSMD1)which is located on the p arm of chromosome 8. In this report, we describe a novel, robust, high-throughput gene mutation profiling strategy based on massively parallel picotiter plate pyrosequencing and have used this approach to identify additional somatic mutations to CSMD1 in early and late stage colorectal cancers. Using this strategy, we identified five nonsynonymous somatic mutations in CSMD1 among 26 colorectal cancers. Interestingly, these mutations occurred predominantly in advanced colorectal tumors,suggesting a role for CSMD1 in the development of late-stage metastatic disease.