A phase I study of temsirolimus in combination with metformin in patients with advanced or recurrent endometrial cancer.

Introduction: Molecular alterations in the PI3K/AKT and Ras/Raf/MEK/ERK pathways are frequently observed in patients with endometrial cancers. However, mTOR inhibitors, such as temsirolimus, have modest clinical benefits. In addition to inducing metabolic changes in cells, metformin activates AMPK, which in turn inhibits the mTOR pathway.

Direct Induction of Buprenorphine Extended-Release: A Case Report.

Buprenorphine has superior safety in opioid use disorder compared with alternatives due to its action as a partial opioid agonist, which limits its ability to cause respiratory depression. There is a risk of precipitated opioid withdrawal after buprenorphine exposure in someone using full opioid agonists. Buprenorphine induction strategies that avoid precipitated withdrawal remain a crucial component for starting buprenorphine in individuals actively using opioids.

Achieving the state of Georgia 25% HIV incidence reduction target among men who have sex with men in Atlanta through expanded use of multimodal pre-exposure prophylaxis: A mathematical model.

The US faces substantial demographic and geographic disparities in both HIV burden and access to pre-exposure prophylaxis (PrEP), an effective strategy to prevent HIV acquisition. Long-acting cabotegravir (CAB) is a novel, injectable PrEP option which demonstrated superior reduction in risk of HIV acquisition compared to daily-oral PrEP in the HPTN083 trial. We modelled the impact of increased PrEP initiations and the introduction of long-acting CAB on HIV incidence among men who have sex with men (MSM) in Atlanta, Georgia, a population with a high burden of HIV.

Ribosome customization and functional diversification among P-stalk proteins regulate late poxvirus protein synthesis.

Growing evidence suggests that ribosomes selectively regulate translation of specific mRNA subsets. Here, quantitative proteomics and cryoelectron microscopy demonstrate that poxvirus infection does not alter ribosomal subunit protein (RP) composition but skews 40S rotation states and displaces the 40S head domain. Genetic knockout screens employing metabolic assays and a dual-reporter virus further identified two RPs that selectively regulate non-canonical translation of late poxvirus mRNAs, which contain unusual 5' poly(A) leaders: receptor of activated C kinase 1 (RACK1) and RPLP2.

Registry versus claims-based index dates for studies of cancer diagnosis in administrative data.

Purpose: Studies of healthcare encounters leading to cancer diagnosis have increased over recent years. While some studies examine healthcare utilization before the cancer registry date of diagnosis, relevant pre-diagnosis interactions are not always immediately prior to this date due to date abstraction guidelines. We evaluated agreement of a registry date with a claims-based index and examined Emergency Department (ED) involvement in cancer diagnosis as an example of possible pre-diagnostic healthcare misclassification that could arise from improper date choice.

Antibody-Drug Conjugates in Breast Cancer: The Road Towards Biologically-Informed Selection and Sequencing.

Purpose Of Review: In this review, we discuss evidence supporting the use of antibody-drug conjugates (ADCs) in breast cancer treatment, describe novel ADCs and combination regimens under development, and examine our current understanding of resistance mechanisms and biomarkers to guide ADC selection and sequencing.

Recent Findings: Three ADCs have proven benefit in patients with metastatic breast cancer: trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG). There are over two hundred investigational ADCs on the horizon, as pre-clinical studies work to identify novel ADC targets and structures.

Resistance-Associated Substitution Testing Trends and Impact on HCV Treatment Outcomes in Canada: A CanHepC-CANUHC Analysis.

Resistance-associated substitutions (RASs) are mutations within the hepatitis C (HCV) genome that may influence the likelihood of achieving a sustained virological response (SVR) with direct acting antiviral (DAA) treatment. Clinicians conduct RAS testing to adapt treatment regimens with the intent of improving the likelihood of cure. The Canadian Network Undertaking against Hepatitis C (CANUHC) prospective cohort consists of chronic HCV patients enrolled between 2015 and 2023 across 17 Canadian sites.

Unusual outcome of treatment of thymoma with immunotherapy: case report.

Background: Thymoma is a rare mediastinal neoplasm originating from thymic epithelial cells, often associated with paraneoplastic syndromes. These syndromes can manifest as a range of autoimmune disorders, including myasthenia gravis, pure red cell aplasia, and aplastic anemia. Clinical trials involving the use of immune checkpoint inhibitors (ICIs) in thymoma have been complicated by a high incidence of immune-related adverse effects (irAEs).

T cell malignancies after CAR T cell therapy in the DESCAR-T registry.

The risk of T cell malignancies after chimeric antigen receptor (CAR) T cell therapy is a concern, although the true incidence remains unclear. Here we analyzed the DESCAR-T registry database, encompassing all pediatric and adult patients with hematologic malignancies who received CAR T cell therapy in France since 1 July 2018. Of the 3,066 patients included (2,536 B cell lymphoma, 162 B cell acute lymphoblastic leukemia (ALL) and 368 multiple myeloma), 1,680 (54.

GOLD grade-specific characterization of COPD in the COSYCONET multi-center trial: comparison of semiquantitative MRI and quantitative CT.

Objectives: We hypothesized that semiquantitative visual scoring of lung MRI is suitable for GOLD-grade specific characterization of parenchymal and airway disease in COPD and that MRI scores correlate with quantitative CT (QCT) and pulmonary function test (PFT) parameters.

Methods: Five hundred ninety-eight subjects from the COSYCONET study (median age = 67 (60-72)) at risk for COPD or with GOLD1-4 underwent PFT, same-day paired inspiratory/expiratory CT, and structural and contrast-enhanced MRI. QCT assessed total lung volume (TLV), emphysema, and air trapping by parametric response mapping (PRM, PRM) and airway disease by wall percentage (WP).

Does semaglutide reduce alcohol intake in Danish patients with alcohol use disorder and comorbid obesity? Trial protocol of a randomised, double-blinded, placebo-controlled clinical trial (the SEMALCO trial).

Introduction: Alcohol use disorder (AUD) is a massive burden for the individual, relatives and society. Despite this, the treatment gap is wide compared with other mental health disorders. Treatment options are sparse, with only three Food and Drug Administration (FDA)-approved pharmacotherapies.

Harmonization of alcohol use data and mortality across a multi-national HIV cohort collaboration.

Background: Alcohol use is measured in diverse ways across settings. Harmonization of measures is necessary to assess effects of alcohol use in multi-cohort collaborations, such as studies of people with HIV (PWH).

Methods: Data were combined from 14 HIV cohort studies (nine European, five North American) participating in the Antiretroviral Therapy Cohort Collaboration.

Effectiveness of bi-monthly long-acting injectable cabotegravir and rilpivirine as maintenance treatment for HIV-1 in the Netherlands: results from the Dutch ATHENA national observational cohort.

Background: Real-world data showing the long-term effectiveness of long-acting injectable cabotegravir and rilpivirine are scarce. We assessed the effectiveness of cabotegravir and rilpivirine in all individuals who switched to cabotegravir and rilpivirine in the Netherlands.

Methods: We used data from the ATHENA cohort, an ongoing observational nationwide HIV cohort in the Netherlands.

Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis.

Objective: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). S1P receptor expression on cardiac cells is involved in cardiac conduction. We report cardiovascular treatment-emergent adverse events (TEAEs) associated with S1P receptor modulators and other cardiovascular events in the etrasimod UC clinical programme.

Mortality of gastrointestinal cancers attributable to smoking, alcohol, and metabolic risk factors, and its association with socioeconomic development status 2000-2021: GI Cancer Mortality and Risk Factors.

Objective: Gastrointestinal (GI) cancers account for one-third of global cancer mortality, with nearly half being preventable. This study updates the global burden of GI cancers attributed to major risk factors: smoking, alcohol, and metabolic disturbances.

Methods: We utilized data from the Global Burden of Disease Study 2021 to examine trends in death and age-standardized death rates related to GI cancers caused by smoking, alcohol, high body mass index (BMI), and high fasting blood glucose (FBG) from 2000 to 2021.

Macronutrients in Human Milk Exposed to Antidepressant and Anti-Inflammatory Medications.

Importance: The association between maternal medications and the macronutrient composition of human milk has not been studied.

Objective: To compare macronutrient levels in milk samples from mothers treated with long-term medications with samples from untreated healthy and disease-matched control mothers (DMCs).

Design, Setting, And Participants: A cross-sectional study using samples collected between October 2014 and January 2024 from breastfeeding mothers in the US and Canada invited to participate to the Mommy's Milk Human Milk Research Biorepository at the University of California, San Diego.

Electrotherapy as treatment for chemotherapy-induced peripheral neuropathy - a randomized controlled trial.

Background: Electrotherapy has been investigated in chronic pain and diabetic peripheral neuropathy, however prospective trials in patients with chemotherapy-induced peripheral neuropathy (CIPN) are scarce.

Methods: Fifty-one patients with CIPN ≥ grade 1 subsequent to receiving platinum- and/or taxane-based chemotherapy types were randomized to 8 weeks of high tone external muscle stimulation (HTEMS) or transcutaneous electrical nerve stimulation (TENS). The primary outcome were changes in the EORTC-QLQ-CIPN20 questionnaire.

Immune complexes-mediated activation of neutrophils in systemic lupus erythematosus is dependent on RNA recognition by toll-like receptor 8.

Introduction: Neutrophil activation is important in systemic lupus erythematosus (SLE). We previously demonstrated that ribonucleoprotein (RNP) immune complexes (ICs) promoted neutrophil activation in a TLR7/8-dependent manner. However, it remains unclear if this mechanism occurs in patients.

Absence of Viral Replication Is Associated With Improved Outcome in Anti-HCV-Positive Patients With Hepatocellular Carcinoma.

Background And Aims: Presence of active hepatitis C virus (HCV) infection may influence the outcome of patients treated for hepatocellular carcinoma (HCC), although this issue has never been adequately assessed in a large series of patients. The aim of this study was to evaluate whether the presence of active HCV affects the survival of patients treated for HCC.

Methods: This study assessed the outcome of 3123 anti-HCV-positive patients with HCC, subdivided according to the presence of active HCV infection or previous sustained virological response (SVR).

Real-World Prevalence, Incidence and Management of Systemic Lupus Erythematosus in Germany: A Retrospective Claims Data Analysis.

Introduction: This study evaluated the prevalence and incidence of systemic lupus erythematosus (SLE) in Germany and explored real-world data on sequence of therapy (SOT; sequence of drugs as prescribed in clinical practice).

Methods: This retrospective, observational, longitudinal cohort study using German claims data from the WIG2 GmbH Scientific Institute for Health Economics and Health System Research database (January 2011-December 2019), extrapolated to the statutory health insurance (SHI)-insured population, evaluated prevalence and incidence in an epidemiological analysis group and SLE treatment patterns in an incident cohort (subgroup ≥ 18 years of age with incident disease and ≥ 24-month follow-up post index date). Analyses were descriptive.

Enhanced D614G and Omicron Variants Antibody Persistence in Infants at 2 Months of Age Following Maternal mRNA Booster Vaccination During Pregnancy or Postpartum.

Background: Following maternal COVID-19 vaccination, the persistence of antibodies in sera and breast milk for mothers and infants is not well characterized. We sought to describe the persistence of antibodies through 2 months after delivery in maternal and infant serum and breast milk following maternal COVID-19 mRNA vaccination and to examine differences by receipt of booster dose during pregnancy or postpartum.

Methods: This is a prospective cohort study with enrollment from July 2021 to January 2022 at 9 US academic sites.

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in treatment-naïve and treatment-experienced people with HIV: 12-month virologic effectiveness and safety outcomes in the BICSTaR Japan cohort.

BICSTaR (BICtegravir Single Tablet Regimen) is an ongoing, observational cohort study assessing the virologic effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in treatment-experienced (TE) and treatment-naïve (TN) people with HIV across 14 countries over 24 months. We present 12-month outcomes from participants in the BICSTaR Japan cohort. Retrospective and prospective data were pooled from people with HIV aged ≥20 years receiving B/F/TAF within routine clinical care in Japan.

Advancing Delirium Treatment Trials in Older Adults: Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS).

Objectives: To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults.

Design: A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs).

Costs of home-delivered antiretroviral therapy refills for persons living with HIV: Evidence from a pilot randomized controlled trial in KwaZulu-Natal, South Africa.

Antiretroviral therapy (ART) is needed across the lifetime to maintain viral suppression for people living with HIV. In South Africa, obstacles to reliable access to ART persist and are magnified in rural areas, where HIV services are also typically costlier to deliver. A recent pilot randomized study (the Deliver Health Study) found that home-delivered ART refills, provided at a low user fee, effectively overcame logistical barriers to access and improved clinical outcomes in rural South Africa.

Increased MASH-associated liver cancer in younger demographics.

Background: The incidence of cancer and the prevalence of metabolic disease and metabolic dysfunction-associated steatotic liver disease is increasing in young adults. However, updated global data on metabolic dysfunction-associated steatohepatitis (MASH)-associated primary liver cancer (PLC) in young adults remains scarce.

Methods: This study analyzed data from the Global Burden of Disease study between 2000 and 2021 to assess the age-standardized incidence, mortality, and disability-adjusted life years rates from MASH-associated PLC in young adults (15-49 y).