Reversal of inflammatory reprogramming by vasodilator agents in pulmonary hypertension.

Background: Pulmonary arterial hypertension (PAH) is a deadly disease without effective non-invasive diagnostic and prognostic testing. It remains unclear whether vasodilators reverse inflammatory activation, a part of PAH pathogenesis. Single-cell profiling of inflammatory cells in blood could clarify these PAH mechanisms.

Incidence and Risk Factors for Amiodarone-Induced Thyroid Dysfunction: A Nationwide Retrospective Cohort Study.

Background: Amiodarone is an effective anti-arrhythmic drug; however, it is frequently associated with thyroid dysfunction. The aim of this study was to investigate the incidence and risk factor of amiodarone-induced dysfunction in an iodine-sufficient area.

Methods: This retrospective cohort study included 27,023 consecutive patients treated with amiodarone for arrhythmia, using the Korean National Health Insurance database.

The Effects of Anti-Vascular Endothelial Growth Factor Loading Injections on Retinal Microvasculature in Diabetic Macular Edema.

Purpose: To evaluate changes in the retinal microvasculature using widefield swept-source optical coherence tomography angiography (SS-OCTA) following three anti-vascular endothelial growth factor (anti-VEGF) loading injections for diabetic macular edema (DME).

Methods: Thirty-four treatment-naïve patients with DME received an initial three loading injections, followed by injections on an as-needed basis. Macular ischemia was evaluated based on the foveal avascular zone (FAZ) area, perfusion density, and vessel density on a 3 × 3-mm SS-OCTA image.

Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma.

Background: Talquetamab (anti-G protein-coupled receptor family C group 5 member D) and teclistamab (anti-B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class-exposed relapsed or refractory multiple myeloma.

Methods: We conducted a phase 1b-2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. In phase 1, we investigated five dose levels in a dose-escalation study.

Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

Elevated IL-6 Expression in Autologous Adipose-Derived Stem Cells Regulates RANKL Mediated Inflammation in Osteoarthritis.

Interleukin-6 (IL-6) expression in mesenchymal stem cells (MSCs) has been shown to play a pivotal role in modulating cartilage regeneration and immune responses, particularly in the context of diseases that involve both degenerative processes and inflammation, such as osteoarthritis (OA). However, the precise mechanism through which IL-6 and other immune-regulatory factors influence the therapeutic efficacy of autologous adipose-derived stem cells (ASCs) transplantation in OA treatment remains to be fully elucidated. This study aims to investigate the relationship between IL-6 expression in autologous ASCs isolated from OA patients and their impact on immune modulation, particularly focusing on the regulation of Receptor Activator of Nuclear factor Kappa-Β Ligand (RANKL), a key mediator of immune-driven cartilage degradation in OA.

The Interplay Between Muscular Activity and Pattern Recognition of Electro-Stimulated Haptic Cues During Normal Walking: A Pilot Study.

This pilot study explored how muscle activation influences the pattern recognition of tactile cues delivered using electrical stimulation (ES) during each 10% window interval of the normal walking gait cycle (GC). Three healthy adults participated in the experiment. After identifying the appropriate threshold, ES as the haptic cue was applied to the gastrocnemius lateralis (GL) and biceps brachii (BB) of participants walking on a treadmill.

Maximizing the clinical utility and performance of cytology samples for comprehensive genetic profiling.

Comprehensive molecular profiling by next-generation sequencing has revolutionized tumor classification and biomarker evaluation. However, routine implementation is challenged by the scant nature of diagnostic material obtained through minimally invasive procedures. Here, we describe our long-term experience in profiling cytology samples with an in-depth assessment of the performance, quality metrics, biomarker identification capabilities, and potential pitfalls.

Child Neurology: Neurophysiologic and Anatomical Correlates in Startle Epilepsy: A Comprehensive SEEG Investigation for Successful Resective Surgery.

Startle epilepsy, characterized by startle-provoked epileptic seizures, was historically recognized as one of the reflex epilepsies but currently lacks classification as a specific epileptic syndrome because of insufficient characterization. This study presents an institutional experience and review of relevant literature focusing on the neurophysiologic and anatomical aspects of startle epilepsy. We describe a pediatric patient with an underlying structural etiology of left frontal encephalomalacia who continued to experience disabling seizures despite multiple antiseizure medications and previous palliative surgery.

Risk of Contrast-Induced Acute Kidney Injury in Computed Tomography: A 16 Institutional Retrospective Cohort Study.

Objectives: Concern about contrast-induced acute kidney injury (CI-AKI) may delay the timely administration of contrast media for computed tomography (CT). The precise causative effect of iodinated contrast media on CI-AKI and its relevant risk factors remains an area of ongoing investigation. Therefore, this study aimed to determine the risk of CI-AKI following contrast-enhanced CT and its predisposing risk factors.

Association of Striatal Dopamine Depletion and Brain Metabolism Changes With Motor and Cognitive Deficits in Patients With Parkinson Disease.

Background And Objectives: Parkinson disease (PD) shows degeneration of dopaminergic neurons in the substantia nigra and characteristic changes in brain metabolism. However, how they correlated and affect motor and cognitive dysfunction in PD has not yet been well elucidated.

Methods: In this single-site cross-sectional study, we enrolled patients with PD who underwent -(3-[F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (F-FP-CIT) PET, F-fluorodeoxyglucose (F-FDG) PET, the Movement Disorder Society-sponsored Unified PD Rating Scale examination, and detailed neuropsychological testing.

Long-Term Outcome of Rescue Stenting for Acute Intracranial Atherosclerotic Stenosis Related Large Vessel Occlusion in Anterior Circulation.

Background And Purpose: Rescue stent (RS) is an accepted rescue option after failed mechanical thrombectomy (MT) for acute ischemic stroke due to intracranial atherosclerotic stenosis (ICAS)-related large vessel occlusion (LVO). However, the long-term outcomes (≥ 12 months) of RS have not yet been elucidated.

Materials And Methods: We retrospectively analyzed the data of 154 patients with RS for ICAS-related LVO, which were identified from prospectively maintained multicenter database of RS after MT failure, to assess good outcome (mRS 0-2), mortality, stroke recurrence, symptomatic intracranial hemorrhage (SICH) and stent patency.

Effectiveness of a Novel Global Telemedicine Curriculum for Medical Students.

Background: The University of Pittsburgh School of Medicine collaborated with The Addis Clinic to create a global telemedicine elective for fourth-year medical students during the COVID-19 pandemic. The elective aimed to promote cross-cultural understanding by providing unique, hands-on telemedicine experience.

Aim: To assess the effectiveness of the telemedicine elective, four of five medical students and 11 of 12 Kenyan clinical officers completed one-on-one interviews and surveys.

Deep learning-based algorithm for automatic quantification of nigrosome-1 and Parkinsonism classification using susceptibility map-weighted MRI.

Background And Purpose: To develop and validate a deep learning-based automatic quantification for nigral hyperintensity and a classification algorithm for neurodegenerative parkinsonism using susceptibility map-weighted imaging (SMwI).

Materials And Methods: We retrospectively collected 450 participants (210 with idiopathic Parkinson's disease [IPD] and 240 individuals in the control group) for training data between November 2022 and May 2023, and 237 participants (168 with IPD, 58 with essential tremor, and 11 with drug-induced Parkinsonism) for validation data between July 2021 and January 2022. SMwI data were reconstructed from multi-echo GRE.

5'-tRNA halves generated by IRE1α are linked to the ER stress response.

Transfer RNA halves (tRHs) have various biological functions. However, the biogenesis of specific 5'-tRHs under certain conditions remains unknown. Here, we report that inositol-requiring enzyme 1α (IRE1α) cleaves the anticodon stem-loop region of tRNA to produce 5'-tRHs (5'-tRH-Gly) with highly selective target discrimination upon endoplasmic reticulum (ER) stress.

Multi-Ancestry Causal Association between Rheumatoid Arthritis and Interstitial Lung Disease: A Bidirectional Two-Sample Mendelian Randomization Study.

: Rheumatoid arthritis (RA) is associated with diverse extra-articular manifestations, including interstitial lung disease (ILD). No previous studies have examined the bidirectional relationship between RA and ILD using the Mendelian randomization (MR) analyses. Therefore, we aimed to investigate this subject using a two-sample bidirectional MR method.

Unravelling monocyte functions: from the guardians of health to the regulators of disease.

Monocytes are a key component of the innate immune system. They undergo intricate developmental processes within the bone marrow, leading to diverse monocyte subsets in the circulation. In a state of healthy homeostasis, monocytes are continuously released into the bloodstream, destined to repopulate specific tissue-resident macrophage pools where they fulfil tissue-specific functions.

Prognostic Value of Pulmonary Artery Systolic Pressure in Severe Rheumatic Mitral Stenosis.

Background: Current guidelines recommend intervention for asymptomatic rheumatic mitral stenosis (MS) with mitral valve area ≤1.5 cm based on indicators including pulmonary arterial systolic pressure (PASP) >50 mm Hg and new-onset atrial fibrillation; however, evidence supporting this is lacking.

Methods: This single-center retrospective study included patients with rheumatic MS between 2006 and 2022.