Interferon-α Inhibits NET Formation in Neutrophils Derived from Patients with Myeloproliferative Neoplasms in a Neutrophil Sub-Population-Specific Manner.

Neutrophils and neutrophil extracellular traps (NETs) contribute to thrombosis and hyperinflammation in myeloproliferative neoplasms (MPN). High-density neutrophils (HDNs) and low-density neutrophils (LDNs) have recently been characterized as distinct neutrophil sub-populations with distinct morphological and functional properties. We aim to study the kinetics of NET formation and inhibition with interferon-α (IFNα) in neutrophils derived from patients with MPN as compared to matched healthy controls.

Precision Oncology Approach for Urachal Carcinoma: A Clinical Case Report.

Urachal cancer (UrC) is a rare disease which is mostly diagnosed late due to symptoms caused by its local invasion to the urinary bladder. Given the lack of clinical trials and guideline recommendations for systemic treatment, a molecularly informed precision oncology approach is a viable option for UrC already in the early lines of systemic treatment. While single case experiences may provide valuable reference for later decision-making, well-documented clinical experience with off-label targeted treatments is limited to a few patients.

Machine Learning Models for 3-Month Outcome Prediction Using Radiomics of Intracerebral Hemorrhage and Perihematomal Edema from Admission Head Computed Tomography (CT).

: Intracerebral hemorrhages (ICH) and perihematomal edema (PHE) are respective imaging markers of primary and secondary brain injury in hemorrhagic stroke. In this study, we explored the potential added value of PHE radiomic features for prognostication in ICH patients. : Using a multicentric trial cohort of acute supratentorial ICH ( = 852) patients, we extracted radiomic features from ICH and PHE lesions on admission non-contrast head CTs.

Chemokine CXCL12 Activates CXC Receptor 4 Metastasis Signaling Through the Upregulation of a CXCL12/CXCR4/MDMX (MDM4) Axis.

Background: The metastasis-promoting G-protein-coupled receptor CXC Receptor 4 (CXCR4) is activated by the chemokine CXCL12, also known as stromal cell-derived factor 1 (SDF-1). The CXCL12/CXCR4 pathway in cancer promotes metastasis but the molecular details of how this pathway cross-talks with oncogenes are understudied. An oncogene pathway known to promote breast cancer metastasis in MDA-MB-231 xenografts is that of Mouse Double Minute 2 and 4 (MDM2 and MDM4, also known as MDMX).

Detecting Clinically Relevant Topological Structures in Multiplexed Spatial Proteomics Imaging Using TopKAT.

Novel multiplexed spatial proteomics imaging platforms expose the spatial architecture of cells in the tumor microenvironment (TME). The diverse cell population in the TME, including its spatial context, has been shown to have important clinical implications, correlating with disease prognosis and treatment response. The accelerating implementation of spatial proteomic technologies motivates new statistical models to test if cell-level images associate with patient-level endpoints.

Syphilis infection prevalence in the Middle East and North Africa: a systematic review and meta-analysis.

Background: Syphilis is a sexually transmitted infection (STI) that can be prevented and effectively treated; yet it continues to be a cause of morbidity and mortality worldwide. There is a limited understanding of the epidemiology of syphilis in the Middle East and North Africa (MENA) region.

Methods: A systematic review conducted up to April 30, 2024 assessed the prevalence of syphilis and followed PRISMA guidelines, without language and date restrictions.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Use of inpatient palliative care in metastatic testicular cancer patients undergoing critical care therapy: insights from the national inpatient sample.

To test for rates of inpatient palliative care (IPC) in metastatic testicular cancer patients receiving critical care therapy (CCT). Within the Nationwide Inpatient Sample (NIS) database (2008-2019), we tabulated IPC rates in metastatic testicular cancer patients receiving CCT, namely invasive mechanical ventilation (IMV), percutaneous endoscopic gastrostomy tube (PEG), dialysis for acute kidney failure (AKF), total parenteral nutrition (TPN) or tracheostomy. Univariable and multivariable logistic regression models addressing IPC were fitted.

MAT2A inhibitor AG-270/S095033 in patients with advanced malignancies: a phase I trial.

Homozygous MTAP deletion occurs in ~15% of cancers, making them vulnerable to decreases in the concentration of S-adenosylmethionine (SAM). AG-270/S095033 is an oral, potent, reversible inhibitor of methionine adenosyltransferase 2 A (MAT2A), the enzyme primarily responsible for the synthesis of SAM. We report results from the first-in-human, phase 1 trial of AG-270/S095033 as monotherapy in patients with advanced malignancies (ClinicalTrials.

Treatment of prehypertension among adults with HIV.

Objective: Elevated blood pressure (BP), even at prehypertensive levels, increases cardiovascular disease risk among people with HIV (PWH); yet international guidelines in low-income countries recommend treatment initiation at BP at least 140/90 mmHg. We determined the efficacy, feasibility, and acceptability of treating prehypertension in PWH in Haiti.

Design: An unblinded randomized clinical trial (enrolled April 2021-March 2022) with 12-month follow-up.

Long-Acting Injectable Antipsychotics in Adolescents with Bipolar Disorder.

Bipolar disorder often begins in adolescence or early adulthood, characterized by recurrent manic episodes that can lead to neurodegenerative brain changes and functional decline. While several oral second-generation antipsychotics are Food and Drug Administration (FDA)-approved for mania, adherence to maintenance treatment is frequently poor due to factors such as anosognosia, cognitive dysfunction, impulsivity, side effects aversion, and substance use. Long-acting injectable (LAI) antipsychotics, approved for adults with bipolar mania or schizoaffective disorder (bipolar type), offer a potential solution for adolescents with similar conditions.

Klotho mutation does not accelerate intervertebral disc aging in mice.

Aging is a risk factor for several chronic conditions, including intervertebral disc degeneration and associated back pain. Disc pathologies include loss of reticular-shaped nucleus pulposus cells, disorganization of annulus fibrosus lamellae, reduced disc height, and increased disc bulging. Sonic hedgehog, cytokeratin 19, and extracellular matrix proteins are markers of healthy disc.

Aerodigestive Approach in Evaluating Pediatric Patients With Recurrent Croup.

Objective: To evaluate the effectiveness of coordinated endoscopy with otolaryngology, pulmonology, and gastroenterology in diagnosing and managing recurrent croup in pediatric patients.

Methods: We reviewed our REDCap Pediatric Aerodigestive Database for patients with recurrent croup who underwent coordinated endoscopy between January 2013 and July 2023. We reviewed patient demographics, comorbidities, surgical findings, treatments, and outcomes.

Association of corneal endothelial cell morphology with neurodegeneration in mild cognitive impairment and dementia.

Introduction: Corneal confocal microscopy (CCM) detects neurodegeneration in mild cognitive impairment (MCI) and dementia and identifies subjects with MCI who develop dementia. This study assessed whether abnormalities in corneal endothelial cell (CEC) morphology are related to corneal nerve morphology, brain volumetry, cerebral ischemia, and cognitive impairment in MCI and dementia.

Methods: Participants with no cognitive impairment (NCI), MCI, and dementia underwent CCM to quantify corneal endothelial cell density (CECD) and area (CECA), corneal nerve fiber morphology, magnetic resonance imaging (MRI) brain volumetry, and severity of brain ischemia.

Creation of a Multimodal Telemedicine Curriculum for Preclinical Medical Students.

Introduction: In 2020, the AAMC created telemedicine competencies to guide curriculum and assessment development. Most available curricula are designed for clinical medical students or graduate trainees, and few offer opportunities for individualized, timely feedback and participation in pediatric simulated encounters.

Methods: We designed a hybrid curriculum to provide preclinical medical students with the knowledge and skills necessary to perform telemedicine encounters.

The doctor will polygraph you now.

Artificial intelligence (AI) methods have been proposed for the prediction of social behaviors that could be reasonably understood from patient-reported information. This raises novel ethical concerns about respect, privacy, and control over patient data. Ethical concerns surrounding clinical AI systems for social behavior verification can be divided into two main categories: (1) the potential for inaccuracies/biases within such systems, and (2) the impact on trust in patient-provider relationships with the introduction of automated AI systems for "fact-checking", particularly in cases where the data/models may contradict the patient.

Discordance of 3rd and 4th generation QuantiFERON-TB Gold assays by pregnancy stages in India.

Background: Pregnancy and HIV affect CD4+ T lymphocytes and impact performance of QuantiFERON-TB Gold (QFT). We compared the results of QFT with QuantiFERON-TB Gold Plus (QFT-Plus), which also measures CD8+ responses to TB antigens, during pregnancy and postpartum.

Methods: We screened 516 pregnant women for TB infection (TBI) with IGRA.

Outcomes of Revision Cartilage Restoration Surgery for Failed Primary Treatment of Chondral or Osteochondral Defects of the Knee: A Systematic Review.

Background: Failure of primary cartilage restoration procedures of the knee that proceed to necessitating revision cartilage procedures represent a challenging clinical scenario with variable outcomes reported in previous literature.

Purpose: To perform a systematic review and meta-analysis of clinical outcomes and adverse events after revision cartilage restoration procedures of the knee for failed primary cartilage procedures.

Study Design: Systematic review and meta-analysis; Level of evidence, 4.

Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial.

Background: In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes.

Methods: In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 10 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone).

Trends in comorbidities and complications among patients undergoing elective total hip and knee arthroplasty in the USA.

Background: Demand for total hip and knee arthroplasty procedures continues to rise. Ongoing changes in surgical care and patient populations require continued monitoring of outcome trends. Using nationwide data from the USA, we aimed to describe updated trends in patient and peri-operative care characteristics as well as complications among total hip and knee arthroplasty recipients.

Effect of semaglutide 2.4 mg on use of antihypertensive and lipid-lowering treatment in five randomized controlled STEP trials.

Objective: The objective of this study was to assess antihypertensive and lipid-lowering treatment changes in participants receiving semaglutide 2.4 mg versus placebo across pooled populations from five Semaglutide Treatment Effect in People with Obesity (STEP) trials.

Methods: Efficacy and safety of semaglutide 2.

Consensus review and considerations on TMS to treat depression: A comprehensive update endorsed by the National Network of Depression Centers, the Clinical TMS Society, and the International Federation of Clinical Neurophysiology.

This article updates the prior 2018 consensus statement by the National Network of Depression Centers (NNDC) on the use of transcranial magnetic stimulation (TMS) in the treatment of depression, incorporating recent research and clinical developments. Publications on TMS and depression between September 2016 and April 2024 were identified using methods informed by PRISMA guidelines. The NNDC Neuromodulation Work Group met monthly between October 2022 and April 2024 to define important clinical topics and review pertinent literature.