Glutathione overproduction mediates lymphoma initiating cells survival and has a sex-dependent effect on lymphomagenesis.

Lymphoid tumor patients often exhibit resistance to standard therapies or experience relapse post-remission. Relapse is driven by Tumor Initiating Cells (TICs), a subset of tumor cells capable of regrowing the tumor and highly resistant to therapy. Growing cells in 3D gels is a method to discern tumorigenic cells because it strongly correlates with tumorigenicity.

In Utero Exposure to Maternal SARS-CoV-2 Infection Is Associated With Higher Left Ventricular Mass in Toddlers.

The intrauterine environment plays a critical role in shaping chronic disease risk over the life course. We prospectively evaluated cardiometabolic outcomes in toddlers born to mothers with versus without prenatal severe acute respiratory syndrome coronavirus 2 infection. Children with in utero severe acute respiratory syndrome coronavirus 2 exposure had higher left ventricular mass in association with altered maternal immunologic indices.

Association of T-cell subtypes with macrophage-specific arterial infiltration in people with HIV.

People with human immunodeficiency virus (HIV, PWH) face an increased risk of cardiovascular disease (CVD) compared to the general population. We previously demonstrated that people with (versus without) HIV have higher macrophage-specific arterial infiltration in relation to systemic monocyte activation. We now show that select T lymphocyte subpopulations (naïve CD4 + , effector memory CD4 + , and central memory CD8 + ) are differentially associated with macrophage-specific arterial infiltration among participants with versus without HIV, with evidence of interaction by HIV status.

Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors.

Objective: Tesamorelin is the only FDA-approved therapy to treat abdominal fat accumulation in people with HIV (PWH). Phase III clinical trials were conducted prior to the introduction of integrase inhibitors (INSTIs), which are now a mainstay of HIV antiretroviral therapy.

Design: We leveraged a randomized double-blind trial of 61 PWH and metabolic dysfunction-associated steatotic liver disease to evaluate the efficacy and safety of tesamorelin 2 mg once daily vs.

The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants.

We describe humans with rare biallelic loss-of-function variants impairing pre-α T cell receptor (pre-TCRα) expression. Low circulating naive αβ T cell counts at birth persisted over time, with normal memory αβ and high γδ T cell counts. Their TCRα repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue αβ T cell development.

Delays in Accessing Healthcare Across the Gender Spectrum in the All of Us Research Program.

Background: Gender minorities and cisgender women face barriers to healthcare access. Prior work suggests cost may represent a particular barrier to accessing care for transgender and gender diverse (TGD) individuals.

Objective: To examine odds of delaying care for any reason and, secondarily, for 7 specific reasons among TGD individuals and cisgender women compared with cisgender men in the All of Us Research Program.

Epidemiology of obesity among people with HIV.

Purpose Of Review: People with HIV (PWH) on antiretroviral therapy (ART) globally are disproportionately affected by obesity, with prevalence rates highest among women with HIV. The purpose of this review is to discuss rates of obesity, factors associated with obesity, and adverse consequences of obesity among PWH.

Recent Findings: Among PWH on ART, rates of obesity have increased over the last several decades and tend to be higher than the general population.

Psychometric properties of the Global Psychotrauma Screen in the United States.

Background: Prior research assessing the psychometric properties of the Global Psychotrauma Screen provided support for its internal consistency reliability, construct validity, convergent validity, and divergent validity in several international samples, but not specifically in a U.S. subsample.

Brief Report: Use and Side Effects of Sodium-Glucose Transporter 2 Inhibitors Among US People With HIV With Clinical Indications.

Background: Sodium-glucose transporter 2 (SGLT2) inhibitors have been approved for treatment of diabetes mellitus (DM), chronic kidney disease, and heart failure, but little is known about prescription levels and safety profiles among people with HIV (PWH).

Methods: We leveraged data from the US Mass General Brigham electronic healthcare database to determine the use/uptake of SGLT2 inhibitors among PWH with type II diabetes (DM2) (with or without chronic kidney disease, proteinuria, or heart failure) and to assess rates of adverse events among PWH with DM2 taking SGLT2 inhibitors.

Results: Among eligible PWH with DM2 receiving care at US Mass General Brigham (N = 907), SGLT2 inhibitors were prescribed to 8.

Osteopontin Is an Integral Mediator of Cardiac Interstitial Fibrosis in Models of Human Immunodeficiency Virus Infection.

Background: People with human immunodeficiency virus (HIV) have heightened incidence/risk of diastolic dysfunction and heart failure. Women with HIV have elevated cardiac fibrosis, and plasma osteopontin (Opn) is correlated to cardiac pathology. Therefore, this study provides mechanistic insight into the relationship between osteopontin and cardiac fibrosis during HIV infection.

Accelerated Longitudinal Weight Gain Among Infants With In Utero COVID-19 Exposure.

Context: Since the initial outbreak of coronavirus disease 2019 (COVID-19), a novel population of children with in utero exposure to maternal infection has emerged whose health outcomes are largely unknown.

Objective: To compare longitudinal growth trajectories among infants with vs without in utero COVID-19 exposure.

Methods: We conducted a longitudinal cohort study leveraging a prospectively enrolled perinatal biorepository among 149 infants with in utero COVID-19 exposure and 127 unexposed controls.

Hormone Prescription and HIV Screening/Preventive Practices Among Clinicians Providing Care for Transgender Individuals.

Purpose: Through a survey-based approach, we sought to investigate regional differences in gender-affirming hormone therapy (GAHT) prescribing practices, as well as HIV screening and prevention practices among clinicians providing care to transgender individuals.

Methods: Our survey was disseminated between December 2019 and January 2021 to clinicians who prescribe GAHT within New England (United States). Between-group differences in GAHT prescribing and HIV screening/prevention practices were evaluated by practice setting and subspecialty.

Notch Partners in the Long Journey of T-ALL Pathogenesis.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disease that arises from the oncogenic transformation of developing T cells during T-lymphopoiesis. Although T-ALL prognosis has improved markedly in recent years, relapsing and refractory patients with dismal outcomes still represent a major clinical issue. Consequently, understanding the pathological mechanisms that lead to the appearance of this malignancy and developing novel and more effective targeted therapies is an urgent need.

Cardiac strain is lower among women with HIV in relation to monocyte activation.

Background: Women with HIV (WWH) face heightened risks of heart failure; however, insights on immune/inflammatory pathways potentially contributing to left ventricular (LV) systolic dysfunction among WWH remain limited.

Setting: Massachusetts General Hospital, Boston, Massachusetts.

Methods: Global longitudinal strain (GLS) is a sensitive measure of LV systolic function, with lower cardiac strain predicting incident heart failure and adverse heart failure outcomes.

Efficient preclinical treatment of cortical T cell acute lymphoblastic leukemia with T lymphocytes secreting anti-CD1a T cell engagers.

Background: The dismal clinical outcome of relapsed/refractory (R/R) T cell acute lymphoblastic leukemia (T-ALL) highlights the need for innovative targeted therapies. Although chimeric antigen receptor (CAR)-engineered T cells have revolutionized the treatment of B cell malignancies, their clinical implementation in T-ALL is in its infancy. CD1a represents a safe target for cortical T-ALL (coT-ALL) patients, and fratricide-resistant CD1a-directed CAR T cells have been preclinically validated as an immunotherapeutic strategy for R/R coT-ALL.

Plasma osteopontin relates to myocardial fibrosis and steatosis and to immune activation among women with HIV.

Objective: Women with HIV (WWH) have heightened heart failure risk. Plasma OPN (osteopontin) is a powerful predictor of heart failure outcomes in the general population. Limited data exist on relationships between plasma OPN and surrogates of HIV-associated heart failure risk.

Assessing and Addressing the Risk of Venous Thromboembolism Across the Spectrum of Gender Affirming Care: A Review.

Objective: Accumulating evidence demonstrates that gender affirming hormone therapy (GAHT) improves mental health outcomes in transgender persons. Data specific to the risks associated with GAHT for transgender persons continue to emerge, allowing for improvements in understanding, predicting, and mitigating adverse outcomes while informing discussion about desired effects. Of particular concern is the risk of venous thromboembolism (VTE) in the context of both longitudinal GAHT and the perioperative setting.

Proteomic Analysis of Hepatic Fibrosis in Human Immunodeficiency Virus-Associated Nonalcoholic Fatty Liver Disease Demonstrates Up-regulation of Immune Response and Tissue Repair Pathways.

Background: Human immunodeficiency virus (HIV)-associated nonalcoholic fatty liver disease (NAFLD) is characterized by a high prevalence of hepatic fibrosis as a strong clinical predictor of all-cause and liver-specific mortality risk.

Methods: We leveraged data from an earlier clinical trial to define the circulating proteomic signature of hepatic fibrosis in HIV-associated NAFLD. A total of 183 plasma proteins within 2 high-multiplex panels were quantified at baseline and at 12 months (Olink Cardiovascular III; Immuno-Oncology).

Therapeutic potential of an anti-CCR9 mAb evidenced in xenografts of human CCR9 tumors.

Relapsed or refractory T acute lymphoblastic leukemia (T-ALL) still carries poor prognosis. Aiming to improve outcomes, the therapeutic potential of an anti-CCR9 monoclonal antibody (mAb 92R), targeting the human chemokine-receptor CCR9 is analyzed on orthotopic xenotransplants. 92R mAb treatment of mice carrying human CCR9 T-ALL cell lines or primary T cell leukemias inhibits tumor growth and increases survival.