Osimertinib long-term tolerability in patients with EGFRm NSCLC enrolled in the AURA program or FLAURA study.

Introduction: This post-hoc analysis of the registrational FLAURA study and AURA program reports long-term safety data in epidermal growth factor receptor-mutated (EGFRm), advanced non-small cell lung cancer (NSCLC) treated with osimertinib for ≥ 36 months.

Methods: Patients from FLAURA who received first-line osimertinib and from the AURA program (AURA, AURA2, AURA3) who received ≥ second-line osimertinib were included. Patients received osimertinib 80 mg once daily.

Evaluation of influenza antiviral prophylaxis for long-term care residents: a systematic review and meta-analysis.

Background: Influenza is a pervasive respiratory infection which disproportionately burdens long-term care residents. To limit outbreaks, guidelines recommend antiviral prophylaxis, particularly oseltamivir or zanamivir, despite acknowledging the inadequate supporting evidence. Therefore, we aimed to review the literature on the efficacy of oseltamivir, zanamivir, and baloxavir prophylaxis for influenza in long-term care.

Caregiving is Associated with Lower Brain Age in Humans.

Middle-aged adults who are parents have better average cognitive performance and lower average brain age compared with middle-aged adults without children, raising the possibility that caregiving slows brain aging. Here, we investigate this hypothesis in two additional groups of caregivers: grandmothers and caregivers for people living with dementia (PLWD). Demographic, questionnaire, and structural MRI data were acquired from n=50 grandmothers, n=24 caregivers of PLWD and n=37 non-caregiver controls, and BrainAge was estimated.

Copy Number Variation and Haplotype Analysis of 17q21.31 Reveals Increased Risk Associated with Progressive Supranuclear Palsy and Gene Expression Changes in Neuronal Cells.

Background: The 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents the strongest risk locus in progressive supranuclear palsy (PSP).

Objective: To investigate the association between CNVs and structural forms on 17q.

Antagonizing Il10 and Il4 signaling via intracerebral decoy receptor expression attenuates Aβ accumulation.

Multiple lines of evidence indicate that immune signaling can impact the pathological progression in Alzheimer's disease (AD), including amyloid deposition, tau aggregation, synaptic pathology and neurodegenerative trajectory. In earlier studies, we reported that intracerebral expression of the anti-inflammatory cytokines, Interleukin-10 (Il10) and Interleukin-4 (Il4), increased amyloid β (Aβ) burden in TgCRND8 mice, a preclinical model of AD-type amyloidosis. As both Interleukin-10 receptor (IL10R) and Interleukin-4 receptor (IL4R) are upregulated in an age-progressive manner in rodent models of AD and in specific regions of human AD brains, we hypothesized that a decoy receptor strategy specifically targeting Il10 and Il4 signaling could have a disease-modifying effect.

A cross-generational methylomic signature of infant maltreatment in newborn rhesus macaques.

Background: Early life adversity (ELA) result in detrimental physical and mental health outcomes. The impact of ELA can reverberate across generations, with epigenetic modifications being one of the proposed biological correlates of exposure to ELA. Here we bridge the translational gap between rodent models and clinical studies by utilizing a nonhuman primate model to study the cross-generational epigenetic and functional footprints of physical maltreatment and neglect.

Trainee Perception of Virtual Interviews and Associations of Virtual Engagement with Vascular Surgery Culture and Community.

Objectives: In recent years, the vascular surgery community has increased utilization of virtual interviews and virtual engagement, or use of online technologies for educational, networking, and mentorship activities. This study evaluates trainee preferences of virtual interviews and associations of virtual engagement with wellness.

Methods: De-identified data was collected from a confidential, voluntary survey of residents and fellows in vascular surgery programs administered following the 2023 Vascular Surgery In-Training Exam (VSITE).

Trend and Provider- and Organizational-Level Factors Associated With Early Palliative Care Billing Among Patients Diagnosed With Distant-Stage Cancers in 2010-2019 in the United States.

Purpose: Early integration of specialized palliative care (PC) is recommended by clinical guidelines for advanced-stage cancers, but real-world evidence of its use is limited. We examined the recent trend of early PC billing among Medicare beneficiaries with distant-stage cancers and associated provider- and organization-level factors.

Methods: Using SEER-Medicare data, we identified Medicare Fee-For-Service beneficiaries 65.

Pediatric cardiac patients with pulmonary hemorrhage supported on ECMO: An ELSO registry study.

Background: Pulmonary Hemorrhage (PH) is a rare but potentially devastating condition and pediatric cardiac patients are at increased risk for. ECMO may be used to safely support these patients, but data is limited.

Methods: Observational retrospective cohort study from the ELSO registry database in pediatric cardiac patients from birth to 18 years old with PH supported on ECMO from January 2011 through December 2020.

Contrasting genetic predisposition and diagnosis in psychiatric disorders: A multi-omic single-nucleus analysis of the human OFC.

Psychiatric disorders like schizophrenia, bipolar disorder, and major depressive disorder exhibit substantial genetic and clinical overlap. However, their molecular architecture remains elusive due to their polygenic nature and complex brain cell interactions. We integrated clinical data with genetic susceptibility to investigate gene expression and chromatin accessibility in the orbitofrontal cortex of 92 postmortem human brain samples at the single-nucleus (sn) level.

Newborn Screening for Sickle Cell Disease and Thalassemia.

Importance: Hemoglobin disorders are a considerable public health issue with more than 500 000 affected infants born annually worldwide. First introduced in the 1970s, newborn screening (NBS) for sickle cell disease (SCD) was included in the Recommended Uniform Screening Panel (RUSP) in 2006, a successful public health promotion and prevention practice that has led to improved childhood survival. Although SCD is the primary target, the screening process also detects many other hemoglobinopathies.

Bone Health Screening in Persons With Bleeding Disorders: A Survey of United States Haemophilia Treatment Centres.

Background: Despite reports of elevated rates of osteoporosis and fractures in persons with haemophilia (PwH) and von Willebrand disease (PwVWD), routine bone health screening using dual-energy X-ray absorptiometry (DEXA) scans is not consistently implemented for this population across all Haemophilia Treatment Centres (HTCs) in the United States.

Objectives: The primary aim of this study was to examine rates of screening for bone health in PwH and PwVWD with vitamin D levels and DEXA scans.

Methods: We conducted a survey of all federally funded HTCs nationwide from June 2023 to August 2023.

Global emergency medicine: A scoping review of the literature from 2023.

Objective: The Global Emergency Medicine Literature Review (GEMLR) highlights the highest-quality research addressing emergency care in resource-limited settings (ECRLS). This 18th edition reviews global emergency medicine (GEM) literature published during 2023.

Methods: A scoping review of GEM articles published in 2023 was performed using a systematic PubMed search and manual gray literature (GRAY) search.

Preference for Long-Acting Injectable PrEP Compared With Daily Oral PrEP Among Transgender Women in the U.S.: Findings From a Multisite Cohort.

Introduction: Pre-exposure prophylaxis (PrEP) use among transgender women in the U.S. has not reached levels optimal to change the trajectory of the HIV epidemic owing to multilevel barriers.

The Impact of Video-assisted Thoracoscopic Versus Percutaneous Tunneled Pleural Catheter Techniques on Pleurodesis Outcomes: A Retrospective, Single-center Study.

Background: Tunneled pleural catheters (TPCs) generate an inflammatory reaction, which, along with frequent drainage, aids in achieving pleurodesis enabling removal in 30% to 50% of patients. However, it is unknown whether the technique of TPC placement influences pleurodesis outcomes.

Methods: This is a retrospective, single-center study of patients who underwent TPC placement from 2010 through 2018.

Sequencing in over 50,000 cases identifies coding and structural variation underlying atrial fibrillation risk.

Atrial fibrillation (AF) is a prevalent and morbid abnormality of the heart rhythm with a strong genetic component. Here, we meta-analyzed genome and exome sequencing data from 36 studies that included 52,416 AF cases and 277,762 controls. In burden tests of rare coding variation, we identified novel associations between AF and the genes MYBPC3, LMNA, PKP2, FAM189A2 and KDM5B.

Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases.

Atrial fibrillation (AF) is the most common heart rhythm abnormality and is a leading cause of heart failure and stroke. This large-scale meta-analysis of genome-wide association studies increased the power to detect single-nucleotide variant associations and found more than 350 AF-associated genetic loci. We identified candidate genes related to muscle contractility, cardiac muscle development and cell-cell communication at 139 loci.

Modulation of the Renin-Angiotensin System against COVID-19: A path forward?

Soon after the pandemic outbreak in 2020, it was proposed that binding of SARS-CoV-2 to the angiotensin converting enzyme-2 may explain most of COVID-19's manifestations. Therefore, manipulation of the renin-angiotensin system (RAS) by using well known and commercialized blockers of its classical arm or by repurposing new stimulators of the alternative RAS pathway in clinical development was seen as a potentially effective strategy for the treatment of COVID-19. Moreover, this therapeutic approach had previously shown significant promise in the treatment of other respiratory viral respiratory infections and forms of acute respiratory distress syndrome.

Current controversies in the use of Oncotype DX in early breast cancer.

Multigene prognostic genomic assays have become essential tools in the management of early breast cancer (BC), providing information that help in risk-stratification, to provide risk-adapted decision-making of adjuvant treatments. Clinical practice guidelines recommend refining the prognostic information provided by clinical and pathology features with the use of genomic tests, such as Oncotype DX®, to classify cancers into risk groups and inform adjuvant treatment strategies. However, the clinical value (i.

Does joint hypermobility exacerbate altered landing and jumping strategies in adolescents with fibromyalgia syndrome compared to controls?

Background: Joint hypermobility is common in children and persists in various genetic and connective tissue disorders, including conditions characterized by chronic musculoskeletal pain (i.e. Juvenile Fibromyalgia Syndrome), which involves movement dysfunction.

Compromised Intestinal Barrier Resilience to Disruption in People with HIV.

People with HIV (PWH) experience chronic intestinal barrier dysfunction which contributes to chronic inflammation and its comorbidities. The mechanisms underlying this phenomenon remain unclear. We hypothesize that living with HIV compromises the intestinal barrier's resilience to injurious agents, increasing susceptibility to leakage upon exposure to disruptors.

Generation and modification of human locomotor EMG activity when walking faster and carrying additional weight.

In activities of daily living, people walk at different speeds with or without carrying additional loads. In this study, we sought to examine how human adults manage these commonly encountered additional demands during walking. We measured electromyography (EMG), triceps surae H-reflexes, joint motion and ground reaction forces (GRF) while participants walked at 1.

Divergent populations of HIV-infected naïve and memory CD4+ T-cell clones in children on antiretroviral therapy.

Background: Naïve cells comprise 90% of the CD4+ T-cell population in neonates and exhibit distinct age-specific capacities for proliferation and activation. We hypothesized that HIV-infected naïve CD4+ T-cell populations in children on long-term antiretroviral therapy (ART) would thus be distinct from infected memory cells.

Methods: Peripheral blood naïve and memory CD4+ T cells from 8 children with perinatal HIV on ART initiated at age 1.