Safety of topical estrogen therapy during adjuvant endocrine treatment among patients with breast cancer: A meta-analysis based expert panel discussion.

Importance: Endocrine treatments, such as Tamoxifen (TAM) and/or Aromatase inhibitors (AI), are the adjuvant therapy of choice for hormone-receptor positive breast cancer. These agents are associated with menopausal symptoms, adversely affecting drug compliance. Topical estrogen (TE) has been proposed for symptom management, given its' local application and presumed reduced bioavailability, however its oncological safety remains uncertain.

Impact of disease duration and surgical intervention on arousal networks in temporal lobe epilepsy.

Objective: Epilepsy is a common neurological disease affecting nearly 1% of the global population, and temporal lobe epilepsy (TLE) is the most common type. Patients experience recurrent seizures and chronic cognitive deficits that can impact their quality of life, ability to work, and independence. These cognitive deficits often extend beyond the temporal lobe and are not well understood.

Genomic Characterization and Prognostic Significance of Human Epidermal Growth Factor Receptor 2-Low, Hormone Receptor-Positive, Early Breast Cancers From the BIG 1-98 and SOFT Clinical Trials.

Purpose: To investigate whether hormone receptor-positive, human epidermal growth factor receptor 2-low (HR+HER2-low) versus HR+HER2-zero early breast cancers have distinct genomic and clinical characteristics.

Methods: This study included HR+, HER2-negative early breast cancers from patients enrolled in the phase III, randomized BIG 1-98 and SOFT clinical trials that had undergone tumor genomic sequencing. Tumors were classified HR+HER2-low if they had a centrally reviewed HER2 immunohistochemistry (IHC) score of 1+ or 2+ with negative in situ hybridization and HR+HER2-zero if they had an HER2 IHC score of 0.

Management of Insomnia in the General Hospital.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.

Successful Healing After Minimally Invasive Subtalar Fusion Following Comminuted Open Calcaneus Fracture: A Case Report.

Case: A 51-year-old male polytrauma patient presented with bilateral calcaneus fractures after a fall. This report describes treatment of his right comminuted Sanders IV calcaneus fracture with percutaneous open reduction internal fixation (ORIF) and minimally invasive surgery (MIS) primary subtalar fusion to restore alignment and preserve soft tissue.

Conclusion: Unlike traditional open approaches, which are prone to wound complications due to larger incisions, our approach of maintaining fracture alignment during joint preparation using an MIS burr for acute posttrauma subtalar arthrodesis and percutaneous ORIF appears to have reduced these risks, resulting in successful radiological healing and functional recovery at 1-year follow-up.

Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy.

Understanding how intratumoral immune populations coordinate antitumor responses after therapy can guide treatment prioritization. We systematically analyzed an established immunotherapy, donor lymphocyte infusion (DLI), by assessing 348,905 single-cell transcriptomes from 74 longitudinal bone marrow samples of 25 patients with relapsed leukemia; a subset was evaluated by both protein- and transcriptome-based spatial analysis. In acute myeloid leukemia (AML) DLI responders, we identified clonally expanded CD8 cytotoxic T lymphocytes with in vitro specificity for patient-matched AML.

Tumor localization strategies of multi-cancer early detection tests: a quantitative assessment.

Background: Multi-cancer early detection (MCED) tests may expand cancer screening. Characterizing diagnostic resolution approaches following positive MCED tests is critical. Two trials employed distinct resolution approaches: a molecular signal to predict tissue of origin (TOO) and an imaging-based diagnostic strategy.

Romosozumab Improves Tissue Thickness-Adjusted Trabecular Bone Score in Women With Osteoporosis and Diabetes.

Context: Trabecular bone score (TBS), a gray-level texture index derived from lumbar spine (LS) dual-energy x-ray absorptiometry (DXA) scans, is decreased in patients with diabetes and is associated with increased fracture risk, independent of areal bone mineral density (aBMD), but potentially influenced by abdominal fat tissue.

Objective: Evaluate effect of romosozumab (210 mg monthly) for 12 months followed by alendronate (70 mg weekly) for 24 months vs alendronate alone (70 mg weekly) for 36 months on LS aBMD and TBS in women with type 2 diabetes (T2D) enrolled in the ARCH study.

Methods: This post hoc analysis included women from ARCH who had T2D at baseline and LS DXA scans at baseline and ≥1 postbaseline visit (romosozumab-to-alendronate, n = 165; alendronate-to-alendronate, n = 195).

An alternatively translated isoform of PPARG proposes AF-1 domain inhibition as an insulin sensitization target.

PPARγ is the pharmacological target of thiazolidinediones (TZDs), potent insulin sensitizers that prevent metabolic disease morbidity but are accompanied by side effects such as weight gain, in part due to non-physiological transcriptional agonism. Using high throughput genome engineering, we targeted nonsense mutations to every exon of PPARG, finding an ATG in Exon 2 (chr3:12381414, CCDS2609 c.A403) that functions as an alternative translational start site.

Altered Effective Connectivity Within a Thalamocortical Corollary Discharge Network in Individuals With Schizophrenia.

Background And Hypothesis: Sequential saccade planning requires corollary discharge (CD) signals that provide information about the planned landing location of an eye movement. These CD signals may be altered among individuals with schizophrenia (SZ), providing a potential mechanism to explain passivity and anomalous self-experiences broadly. In healthy controls (HC), a key oculomotor CD network transmits CD signals from the thalamus to the frontal eye fields (FEF) and the intraparietal sulcus (IPS) and also remaps signals from FEF to IPS.

Benefit Design and Access to Dental Care Among Seniors With Medicare Advantage Dental Benefits.

Importance: Although Medicare Advantage plans frequently offer dental benefits, enrollees report lower rates of dental care use and higher rates of unmet dental need compared with individuals with employer-sponsored benefits. It is unknown which attributes of Medicare Advantage dental plans are associated with enhanced dental care access.

Objective: To determine attributes of Medicare Advantage dental plans associated with higher rates of dental care use and lower rates of unmet dental need.

Duration in Immigration Detention and Health Harms.

Importance: Length of custody is a mechanism by which carceral systems can worsen health. However, there are fewer studies examining US immigration detention, in large part because US immigration detention is largely privately operated and opaque by design.

Objectives: To examine the association between duration spent in US immigration detention with subsequent health outcomes.

COVID-19 Pandemic and Racial and Ethnic Disparities in Long-Term Nursing Home Stay or Death Following Hospital Discharge.

Importance: Long-term nursing home stay or death (long-term NH stay or death), defined as new long-term residence in a nursing home or death following hospital discharge, is an important patient-centered outcome.

Objective: To examine whether the COVID-19 pandemic was associated with changes in long-term NH stay or death among older adults with sepsis, and whether these changes were greater in individuals from racial and ethnic minoritized groups.

Design, Setting, And Participants: This cross-sectional study used patient-level data from the Medicare Provider Analysis and Review File, the Master Beneficiary Summary File, and the Minimum Data Set.

Tau Pathology Drives Disease-Associated Astrocyte Reactivity in Salt-Induced Neurodegeneration.

Dietary high salt intake is increasingly recognized as a risk factor for cognitive decline and dementia, including Alzheimer's disease (AD). Recent studies have identified a population of disease-associated astrocytes (DAA)-like astrocytes closely linked to amyloid deposition and tau pathology in an AD mouse model. However, the presence and role of these astrocytes in high-salt diet (HSD) models remain unexplored.

Automation of Ultrasonographic Optic Nerve Sheath Diameter Measurement: A Scoping Review.

Intracranial pressure (ICP) monitoring is a cornerstone of neurocritical care in managing severe brain injury. However, current invasive ICP monitoring methods carry significant risks, including infection and intracranial hemorrhage, and are contraindicated in certain clinical situations. Additionally, these methods are not universally available.

Inhibition of acyl-CoA synthetase long-chain isozymes decreases multiple myeloma cell proliferation and causes mitochondrial dysfunction.

Multiple myeloma (MM) is an incurable cancer of plasma cells with a 5-year survival rate of 59%. Dysregulation of fatty acid (FA) metabolism is associated with MM development and progression; however, the underlying mechanisms remain unclear. Herein, we explore the roles of long-chain fatty acid coenzyme A ligase (ACSL) family members in MM.

Frailty determinants in heart failure: Inflammatory markers, cognitive impairment and psychosocial interaction.

Aims: This study aimed to identify factors associated with frailty in heart failure (HF) patients, focusing on demographic, biochemical and health-related variables. It also explored the correlation between frailty and comorbidities such as malnutrition, cognitive impairment and depression, assessing how these factors interact to influence frailty risk.

Methods: A total of 250 HF patients (mean age 73.

Biodegradable polymeric microsphere formulations of full-length anti-VEGF antibody bevacizumab for sustained intraocular delivery.

Age-related macular degeneration (AMD) is one of the leading causes of central vision loss in the elderly population. Bevacizumab, a full-length humanized monoclonal anti-VEGF antibody, is commonly used off-label drug to treat AMD. However, the dosing regimen of bevacizumab and other anti-VEGF antibodies requires monthly intravitreal injections followed by regular intravitreal injections at 4-16-week intervals.

The impact of imprecise case definitions in electronic health record research: a melanoma case-study from the Million Veteran Program.

Cases for a disease can be defined broadly using diagnostic codes, or narrowly using gold-standard confirmation that often is not available in large administrative datasets. These different definitions can have significant impacts on the results and conclusions of studies. We conducted this study to assess how using melanoma phecodes versus histologic confirmation for invasive or in situ melanoma impacts the results of a genome-wide association study (GWAS) using the Million Veteran Program.

Effect of dietary phenolic compounds intake on mortality in the "Seguimiento Universidad De Navarra" (SUN) Mediterranean cohort.

Plant-based dietary patterns have been demonstrated to reduce the risk of non-communicable disease (NCD), including cardiovascular disease (CVD), type 2 diabetes, cancer, and all-cause mortality. Phenolic compounds (PC), abundant in plant-based foods, have been considered as instrumental in this attenuation of NCD risk. We evaluated the association between dietary intake of PC and the risk of all-cause mortality in a relatively young Mediterranean cohort of 18,173 Spanish participants in the "Seguimiento Universidad de Navarra" (SUN) project, after a median follow-up of 12.