Cytomegalovirus (CMV) infection in solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients may increase the risk of rejection or allograft dysfunction, other infection(s), and morbidity and mortality. Treatment can be challenging due to medication-associated toxicities. Maribavir (MBV) is a promising option for the treatment of resistant or refractory (R/R) CMV infection in lieu of foscarnet (FOS), which has long been the recommended therapy for (val)ganciclovir-resistant infection.
View Article and Find Full Text PDFAneuploid epithelial cells are common in breast cancer; however, their presence in normal breast tissues is not well understood. To address this question, we applied single-cell DNA sequencing to profile copy number alterations in 83,206 epithelial cells from the breast tissues of 49 healthy women, and we applied single-cell DNA and assay for transposase-accessible chromatin sequencing co-assays to the samples of 19 women. Our data show that all women harboured rare aneuploid epithelial cells (median 3.
View Article and Find Full Text PDFThere is an increased risk of infection in patients with cancer that results in higher morbidity and mortality. Several risk factors can predispose these patients to infectious complications. Some such factors include immunocompromised states like neutropenia, allogeneic hematopoietic cell transplantation, and graft-versus-host disease, while others include immunosuppressive agents like corticosteroids, purine analogs, monoclonal antibodies, and other emerging cancer therapeutics like CAR T-cell therapy.
View Article and Find Full Text PDFBackground: A myriad of risk factors and comorbidities have been determined to influence COVID-19 mortality rates; among these is pneumonia. This study considers pneumonia as a risk factor for increased mortality in patients admitted with COVID-19 in a rural healthcare system. We predicted that the presence of pneumonia of any kind would increase mortality rates in patients admitted with COVID-19.
View Article and Find Full Text PDFDespite their relatively short lifespan, neutrophils are tasked with counteracting pathogens through various functions, including phagocytosis, production of reactive oxygen species, neutrophil extracellular traps (NETs), and host defense peptides. Regarding the latter, small cationic cathelicidins present a conundrum in neutrophil function. Although primarily recognized as microbicides with an ability to provoke pores in microbial cell walls, the ability of cathelicidin to modulate key neutrophil functions is also of great importance, including the release of chemoattractants, cytokines, and reactive oxygen species, plus prolonging neutrophil lifespan.
View Article and Find Full Text PDFRemdesivir is the first FDA-approved drug for treating severe SARS-CoV-2 infection and targets RNA-dependent RNA polymerase (RdRp) that is required for viral replication. To monitor for the development of mutations that may result in remdesivir resistance during prolonged treatment, we sequenced SARS-CoV-2 specimens collected at different treatment time points in two transplant patients with severe COVID-19. In the first patient, an allogeneic hematopoietic stem cell transplant recipient, a transient RdRp catalytic subunit mutation (nsp12:A449V) was observed that has not previously been associated with remdesivir resistance.
View Article and Find Full Text PDFBackground: Situs inversus totalis (SIT) is a rare genetic anomaly involving the mirror-image transposition of organs. This transposition can potentially make surgical treatments difficult because of the reversed anatomy and intraoperative confusion. The aim of this systematic review is to compare the perioperative outcomes and safety of robotic and laparoscopic gastrectomy in patients with SIT.
View Article and Find Full Text PDFThe field of transplant infectious diseases is rapidly evolving, presenting a challenge for clinical practice and trainee education. Here we describe the construction of transplantid.net, a free online library, crowdsourced and continuously updated for the dual purpose of point-of-care evidence-based management and teaching.
View Article and Find Full Text PDFThe structure of the genome shapes the distribution of genetic diversity and sequence divergence. To investigate how the relationship between chromosome size and recombination rate affects sequence divergence between species, we combined empirical analyses and evolutionary simulations. We estimated pairwise sequence divergence among 15 species from three different mammalian clades-Peromyscus rodents, Mus mice, and great apes-from chromosome-level genome assemblies.
View Article and Find Full Text PDFBackground: Mycoplasma hominis can cause significant infections after solid organ transplantation (SOT). Treatment should be guided by susceptibility testing, but conventional lab methods are laborious with prolonged turnaround time (TAT). This case series compares the phenotypic and genotypic susceptibility profiles of M.
View Article and Find Full Text PDFIntroduction: Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined.
Methods: We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90.
Despite efforts in understanding its underlying mechanisms, the etiology of chromosomal instability (CIN) remains unclear for many tumor types. Here, we identify CIN initiation as a previously undescribed function for APOBEC3A (A3A), a cytidine deaminase upregulated across cancer types. Using genetic mouse models of pancreatic ductal adenocarcinoma (PDA) and genomics analyses in human tumor cells we show that A3A-induced CIN leads to aggressive tumors characterized by enhanced early dissemination and metastasis in a STING-dependent manner and independently of the canonical deaminase functions of A3A.
View Article and Find Full Text PDFUnlabelled: Focal amplifications (FA) can mediate targeted therapy resistance in cancer. Understanding the structure and dynamics of FAs is critical for designing treatments that overcome plasticity-mediated resistance. We developed a melanoma model of dual MAPK inhibitor (MAPKi) resistance that bears BRAFV600 amplifications through either extrachromosomal DNA (ecDNA)/double minutes (DM) or intrachromosomal homogenously staining regions (HSR).
View Article and Find Full Text PDF-activating mutations are the most frequent driver mutations in papillary thyroid cancer (PTC). Targeted inhibitors such as dabrafenib have been used in advanced -mutated PTC; however, acquired resistance to the drug is common and little is known about other effectors that may play integral roles in this resistance. In addition, the induction of PTC dedifferentiation into highly aggressive -driven anaplastic thyroid cancer (ATC) has been reported.
View Article and Find Full Text PDFMortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020).
View Article and Find Full Text PDFPurpose: Diabetes mellitus (DM) is common among recipients of heart transplantation (HTx) but its impact on clinical outcomes is unclear. We evaluated the associations between pretransplant DM and posttransplant DM (PTDM) and outcomes among adults receiving HTx at a single center.
Methods: We performed a retrospective study (range 01/2008 - 07/2018), n = 244.
Measles is a worldwide viral disease that can cause fatal complications in immunocompromised hosts such as hematopoietic cell transplant (HCT) recipients. The live attenuated measles, mumps, and rubella (MMR) vaccine is generally contraindicated post-HCT due to the risk for vaccine-associated measles. This, combined with decreasing vaccination rates due to vaccine hesitancy and the coronavirus disease 2019 pandemic, raises significant concerns for a measles resurgence that could portend devastating consequences for immunocompromised hosts.
View Article and Find Full Text PDF