Pharmacologic Management of Heart Failure with Preserved Ejection Fraction (HFpEF) in Older Adults.

There are several pharmacologic agents that have been touted as guideline-directed medical therapy for heart failure with preserved ejection fraction (HFpEF). However, it is important to recognize that older adults with HFpEF also contend with an increased risk for adverse effects from medications due to age-related changes in pharmacokinetics and pharmacodynamics of medications, as well as the concurrence of geriatric conditions such as polypharmacy and frailty. With this review, we discuss the underlying evidence for the benefits of various treatments in HFpEF and incorporate key considerations for older adults, a subpopulation that may be at higher risk for adverse drug events.

Substrate stiffness dictates unique doxorubicin-induced senescence-associated secretory phenotypes and transcriptomic signatures in human pulmonary fibroblasts.

Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood.

Novel Therapies for Right Ventricular Failure.

Purpose Of Review: Traditionally viewed as a passive player in circulation, the right ventricle (RV) has become a pivotal force in hemodynamics. RV failure (RVF) is a recognized complication of primary cardiac and pulmonary vascular disorders and is associated with a poor prognosis. Unlike treatments for left ventricular failure (LVF), strategies such as adrenoceptor signaling inhibition and renin-angiotensin system modulation have shown limited success in RVF.

Dihydropyrimidine enzyme activity and its effect on chemotherapy toxicity: importance of genetic testing.

Purpose: Patients with partial or complete DPD deficiency have decreased capacity to degrade fluorouracil and are at risk of developing toxicity, which can be even life-threatening.

Case: A 43-year-old man with moderately differentiated rectal adenocarcinoma on capecitabine presented to the emergency department with complaints of nausea, vomiting, diarrhea, weakness, and lower abdominal pain for several days. Laboratory findings include grade 4 neutropenia (ANC 10) and thrombocytopenia (platelets 36,000).

Pilomatrix carcinoma unveiled: a systematic review of clinical characteristics, pathogenesis, diagnostic puzzles, and management strategies.

Pilomatrix carcinoma (PC) is a rare malignant adnexal tumor originating from follicular matrix cells primarily impacting Caucasian males. This review provides a comprehensive analysis of scientific literature on PC through an exploration of 206 cases reported between 1980 and 2024. We discuss the epidemiology, clinical presentation, histopathology, and diagnostic challenges of PC, and explore various treatment methods for this rare malignancy as well as their associated outcomes.

Addressing Diabetes Distress in Primary Care: Where Are We Now, and Where Do We Need to Go?

Purpose Of Review: Addressing diabetes distress (DD), the emotional demands of living with diabetes, is a crucial component of diabetes care. Most individuals with type 2 diabetes and approximately half of adults with type 1 diabetes receive their care in the primary care setting. This review will provide guidance on addressing DD and implementing targeted techniques that can be tailored to primary care patients.

Cohort study on the Effect of various nicotine consumption modalities on Mohs surgery complications.

Knowledge on the effect of different nicotine consumption modalities on dermatologic surgical outcomes is limited, with conflicting conclusions. Cigarette smoking is known to adversely affect outcomes, but the impact of other nicotine consumption modalities like cigars, smokeless tobacco, and nicotine replacement therapy (NRT) is less understood. Our objective was to evaluate the impact of various nicotine consumption modalities on complication rates after Mohs micrographic surgery (MMS).

Robust discrimination between closely related species of salmon based on DNA fragments.

Closely related species of Salmonidae, including Pacific and Atlantic salmon, can be distinguished from one another based on nucleotide sequences from the cytochrome c oxidase sub-unit 1 mitochondrial gene (COI), using ensembles of fragments aligned to genetic barcodes that serve as digital proxies for the relevant species. This is accomplished by exploiting both the nucleotide sequences and their quality scores recorded in a FASTQ file obtained via Next Generation (NextGen) Sequencing of mitochondrial DNA extracted from Coho salmon caught with hook and line in the Gulf of Alaska. The alignment is done using MUSCLE (Muscle 5.

Epigenome-wide association study of perceived discrimination in the Multi-Ethnic Study of Atherosclerosis (MESA).

Perceived discrimination, recognized as a chronic psychosocial stressor, has adverse consequences on health. DNA methylation (DNAm) may be a potential mechanism by which stressors get embedded into the human body at the molecular level and subsequently affect health outcomes. However, relatively little is known about the effects of perceived discrimination on DNAm.

Timing of dietary effects on the epigenome and their potential protective effects against toxins.

Exposure to toxins causes lasting damaging effects on the body. Numerous studies in humans and animals suggest that diet has the potential to modify the epigenome and these modifications can be inherited transgenerationally, but few studies investigate how diet can protect against negative effects of toxins. Potential evidence in the primary literature supports that caloric restriction, high-fat diets, high protein-to-carbohydrate ratios, and dietary supplementation protect against environmental toxins and strengthen these effects on their offspring's epigenome.

Ascitic fluid amylase-to-serum amylase ratio to predict pancreatic duct leaks causing ascites.

Objectives: Pancreatic duct leaks can cause ascites, and fluid amylase can be used as a marker to suggest pancreatic duct leak; however, there is no reference parameter or cutoff value for diagnosis. We assessed whether a novel ratio of ascitic fluid to serum amylase can reliably predict pancreatic leaks and need for endoscopic retrograde cholangiopancreatography (ERCP).

Materials And Methods: Patients who had fluid amylase from ascitic fluid and serum amylase within one week of confirmed pancreatic leaks via ERCP were included along with appropriate medical and surgical controls.

The interplay of sex and genotype in disease associations: a comprehensive network analysis in the UK Biobank.

Background: Disease comorbidities and longer-term complications, arising from biologically related associations across phenotypes, can lead to increased risk of severe health outcomes. Given that many diseases exhibit sex-specific differences in their genetics, our objective was to determine whether genotype-by-sex (GxS) interactions similarly influence cross-phenotype associations. Through comparison of sex-stratified disease-disease networks (DDNs)-where nodes represent diseases and edges represent their relationships-we investigate sex differences in patterns of polygenicity and pleiotropy between diseases.

Onchocerciasis is not a major cause of blindness in two endemic villages in Sierra Leone.

Objective: Sierra Leone, a country where onchocerciasis is endemic in 14 of the 16 districts, was the focus of our investigation. Despite 17 rounds of annual ivermectin treatment since 2005, a report circulated by a local politician indicated an increase in cases of suspected onchocerciasis-related vision impairment in two villages (Mangobo and Petifu) in Tonkolili district. In response, the National Neglected Tropical Disease Program conducted a comprehensive investigation.

Enhancing prehospital decision-making: exploring user needs and design considerations for clinical decision support systems.

Background: In prehospital emergency care, providers face significant challenges in making informed decisions due to factors such as limited cognitive support, high-stress environments, and lack of experience with certain patient conditions. Effective Clinical Decision Support Systems (CDSS) have great potential to alleviate these challenges. However, such systems have not yet been widely adopted in real-world practice and have been found to cause workflow disruptions and usability issues.

Evaluation of macular retinal oximetry across different levels of diabetic retinopathy: a cross sectional study.

Background: This study evaluates retinal oxygen saturation and vessel density within the macula and correlates these measures in controls and subjects with type 2 diabetes (DM) with (DMR) and without (DMnR) retinopathy. Changes in retinal oxygen saturation have not been evaluated regionally in diabetic patients.

Methods: Data from seventy subjects (28 controls, 26 DMnR, and 16 DMR were analyzed.

Methods for modeling gestational weight gain: empirical application using electronic health record data from a safety net population.

Background: Understanding the risks and effects of gestational weight gain (GWG) is a prominent area of perinatal research but approaches for quantifying GWG are evolving and remain underdeveloped, especially in clinical settings for underserved demographic subgroups. To fill this gap, we demonstrated and compared six GWG metrics across pre-pregnancy BMI classifications: total GWG, trimester-specific linear rate of GWG, adherence to total and trimester-specific recommendations, area under the curve, and GWG for gestational age z-scores.

Methods: We used clinical data on 44,801 pregnant people from community-based health care organizations with extensive longitudinal measures and substantial representation of understudied subgroups.

Safety and Efficacy of Deutetrabenazine at High versus Lower Daily Dosages in the ARC-HD Study to Treat Chorea in Huntington Disease.

Background: Huntington disease (HD) is a progressive neurodegenerative disease that causes psychiatric and neurological symptoms, including involuntary and irregular muscle movements (chorea). Chorea can disrupt activities of daily living, pose safety issues, and may lead to social withdrawal. The vesicular monoamine transporter 2 inhibitors tetrabenazine, deutetrabenazine, and valbenazine are approved treatments that can reduce chorea.

High-Value Care Education in the USA: Lessons from a National Value Curriculum for Resident and Fellow Physicians.

Purpose: Physicians are estimated to be responsible for more than 50% of national healthcare costs and hold the greatest potential to improve value by orchestrating quality-driven programs to reduce unnecessary practices and variability. A physician's ability to practice cost-conscious care has been linked to their training, underscoring the importance of integrating cost-conscious practice into training.

Methods: The High Value Practice Academic Alliance was formed to help advance the value-improvement work of individual institutions through a national organization.

5-HT agonism as a neurotherapeutic for sarcopenia: preclinical proof of concept.

Sarcopenia, the pathological age-related loss of muscle mass and strength, contributes to physical decline, frailty, and diminished healthspan. The impact of sarcopenia is expected to rise as the aging population grows, and treatments remain limited. Therefore, novel approaches for enhancing physical function and strength in older adults are desperately needed.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.

Role of stereotactic radiosurgery for intracranial epidermoid tumors: a systematic review to assess its safety, efficacy, and complication profile.

Background: Even a gross total resection of a benign epidermoid tumor (ET) carries a high risk of recurrence. The management strategy mostly involves redo surgical excision but at a significant cost of morbidity and mortality. The role of adjuvant radiation therapies in this scenario is still undefined.

Performance of MR fusion biopsy, systematic biopsy and combined biopsy on prostate cancer detection rate in 1229 patients stratified by PI-RADSv2 score on 3T multi-parametric MRI.

Purpose: We analyzed the additional value of systematic biopsy (SB) to MR-Ultrasound fusion biopsy (MRgFbx) for detection of clinically significant prostate cancer (csPCa), as increased sampling may cause increased morbidity.

Materials And Methods: This retrospective study cohort was comprised of 1229 biopsy sessions between July 2016 and May 2020 in men who had a Prostate Imaging-Reporting and Data System (PI-RADSv2) category ≥ 3 lesion on 3 Tesla multiparametric MRI (3TmpMRI) and subsequent combined biopsy (CB; MRgFbx and SB) for suspected prostate cancer (PCa). Cancer detection rates (CDR) were calculated for CB, MRgFbx and SB in the study cohort and sub-cohorts stratified by biopsy history and PI-RADSv2 category.