Prognostic, biological, and structural implications of FLT3-JMD point mutations in acute myeloid leukemia: an analysis of Alliance studies.

The FLT3 gene frequently undergoes mutations in acute myeloid leukemia (AML), with internal tandem duplications (ITD) and tyrosine kinase domain (TKD) point mutations (PMs) being most common. Recently, PMs and deletions in the FLT3 juxtamembrane domain (JMD) have been identified, but their biological and clinical significance remains poorly understood. We analyzed 1660 patients with de novo AML and found FLT3-JMD mutations, mostly PMs, in 2% of the patients.

A broad spectrum Shigella vaccine based on VirG multiepitope region produced in a cell-free system.

Dysentery caused by Shigella species remains a major health threat to children in low- and middle-income countries. There is no vaccine available. The most advanced candidates, i.

Evaluation of Drug-Drug Interactions in Pharmacoepidemiologic Research.

Drug-drug interactions (DDIs) represent a significant concern for clinical care and public health, but the health consequences of many DDIs remain largely underexplored. This knowledge gap underscores the critical need for pharmacoepidemiologic research to evaluate real-world health outcomes of DDIs. In this review, we summarize the definitions commonly used in pharmacoepidemiologic DDI studies, discuss common sources of bias, and illustrate through examples how these biases can be mitigated.

Venous Thromboembolism Occurrence and Association with Gastrointestinal Disorders in Children with Cystic Fibrosis: An Analysis from the TriNetX Research Network Global Multicenter Real-World Dataset.

The purpose of this study is to (1) estimate and compare the prevalence of venous thromboembolism (VTE) in children (age 0 to ≤21) with versus without cystic fibrosis (CF); (2) investigate putative associations between specific gastrointestinal (GI) manifestations and the development of VTE among children with CF. This was a multicenter case-control analysis among patients aged 0 to ≤ 21 years between 2010 and 2020, using the TriNetX Research Network. Data queries included ICD-9/10 (International Classification of Diseases-9th/10th Revision) diagnosis codes.

Effectiveness of Synchronous Postdischarge Contacts on Health Care Use and Patient Satisfaction : A Systematic Review and Meta-analysis.

Background: Postdischarge contacts (PDCs) after hospitalization are common practice, but their effectiveness in reducing use of acute care after discharge remains unclear.

Purpose: To assess the effects of PDC on 30-day emergency department (ED) visits, 30-day hospital readmissions, and patient satisfaction.

Data Sources: MEDLINE, Embase, and CINAHL searched from 2012 to 25 May 2023.

Factors associated with tuberculosis treatment initiation among bacteriologically negative individuals evaluated for tuberculosis: An individual patient data meta-analysis.

Background: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians' decisions to initiate TB treatment when initial bacteriological test results are negative.

Methods And Findings: We performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613).

Constitutive deletion of the obscurin-Ig58/59 domains induces atrial remodeling and Ca2+-based arrhythmogenesis.

Obscurin is a giant protein that coordinates diverse aspects of striated muscle physiology. Obscurin immunoglobulin domains 58/59 (Ig58/59) associate with essential sarcomeric and Ca2+ cycling proteins. To explore the pathophysiological significance of Ig58/59, we generated the Obscn-ΔIg58/59 mouse model, expressing obscurin constitutively lacking Ig58/59.

Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication of COVID-19 infection. Data on midterm outcomes are limited.

Objective: To characterize the frequency and time course of cardiac dysfunction (left ventricular ejection fraction [LVEF] <55%), coronary artery aneurysms (z score ≥2.

Cigar, Pipe, and Smokeless Tobacco Use and Cardiovascular Outcomes From Cross Cohort Collaboration.

Importance: Cardiovascular health outcomes associated with noncigarette tobacco products (cigar, pipe, and smokeless tobacco) remain unclear, yet such data are required for evidence-based regulation.

Objective: To investigate the association of noncigarette tobacco products with cardiovascular health outcomes.

Design, Setting, And Participants: This cohort study was conducted within the Cross Cohort Collaboration Tobacco Working Group by harmonizing tobacco-related data and conducting a pooled analysis from 15 US-based prospective cohorts with data on the use of at least 1 noncigarette tobacco product ranging between 1948 and 2015.

Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy: A Randomized Clinical Trial With Open-Label Extension.

Importance: There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN.

Objective: To present the long-term efficacy and safety of patisiran in adults with hATTR-PN.

Experience of The National Emergency Tele-Critical Care Network.

The COVID-19 pandemic exposed significant frailties of the U.S. healthcare system, especially inequities facing rural areas during surges when critical access and small community hospitals could not transfer patients to referral centers that were already overcapacity.

Electroconvulsive therapy in autism spectrum disorders: an update to the literature.

Purpose Of Review: Over the last quarter century, the clinical evidence surrounding the use of electroconvulsive therapy (ECT) in individuals with autism spectrum disorder (ASD) has expanded. This review provides the most up-to-date findings on the usage of ECT in ASD and discusses these results within the historical context and direct patient care experience.

Recent Findings: ECT is typically implemented for psychotropic-refractory catatonic, affective, psychotic, and combined pathology for individuals across the lifespan.

The Association of Menopausal Age with Sex Hormones and Anthropometric Measures Among Postmenopausal Women in the Multi-Ethnic Study of Atherosclerosis Study.

We investigated associations of menopausal age category with body mass index (BMI), waist circumference, waist-hip ratio, and waist-height ratio. We also explored the moderating effect of anthropometric measures on associations of menopausal age category with prespecified sex hormones: estradiol, dehydroepiandrosterone (DHEA), sex hormone-binding globulin, bioavailable testosterone, and total testosterone-estradiol (T/E) ratio. In this cross-sectional study, we included 2,436 postmenopausal women from the Multi-Ethnic Study of Atherosclerosis who had menopausal age, anthropometric, and sex hormone data at baseline.

ZNFX1 functions as a master regulator of epigenetically induced pathogen mimicry and inflammasome signaling in cancer.

DNA methyltransferase and poly (ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon genes (STING)-dependent pathogen mimicry response (PMR) in ovarian and other cancers. Here, we showed that combining DNMTis and PARPis upregulates expression of the nucleic-acid sensor NFX1-type zinc finger-containing 1 protein (ZNFX1). ZNFX1 mediated induction of PMR in mitochondria, serving as a gateway for STING-dependent interferon/inflammasome signaling.

Liver Injury due to Intravenous Methylprednisolone in the Drug-Induced Liver Injury Network.

Background And Aims: Short courses of intravenous (iv) methylprednisolone (MP) can cause drug induced liver injury (DILI). The aim of this study was to assess the clinical features and HLA associations of MP-related DILI enrolled in the US DILI Network (DILIN).

Methods: DILIN cases with MP as a suspected drug were reviewed.

Treatment of focal anaplastic Wilms tumor: A report from the Children's Oncology Group AREN0321 and AREN03B2 studies.

Background: In the fifth National Wilms Tumor Study, patients received vincristine and dactinomycin (VA) without radiation for stage I focal anaplastic Wilms tumor (FAWT) and VA plus doxorubicin (DD4A) and radiation for stage II-IV FAWT. Four-year event-free survival (EFS) and overall survival (OS) for stage I FAWT were 67.5% and 88.

Association Between Positive Airway Pressure Therapy and Healthcare Costs Among Older Adults with Comorbid Obstructive Sleep Apnea and Common Chronic Conditions: An Actuarial Analysis.

Study Objectives: To determine the association between adherence to positive airway pressure and healthcare costs among a national sample of older adults with comorbid OSA and common chronic conditions.

Methods: Our data source was a random sample of Medicare administrative claims for years 2016-2019. Inclusion criteria included age >65 years and new diagnosis of OSA.

Impact of Neoadjuvant Chemotherapy on Perioperative Morbidity in Combined Resection of Rectal Cancer and Liver Metastases.

Background And Objectives: Little is known about the relationship between neoadjuvant chemotherapy (NAC) and perioperative morbidity for patients undergoing combined resection of rectal cancer and sLM. The purpose of this study is to determine the impact of NAC on 30-day morbidity for patients who undergo combined resection of primary rectal cancer and sLM.

Materials And Methods: A retrospective cohort study of patients undergoing combined resection of primary rectal cancer and sLM between 2016 and 2020 at participating NSQIP hospitals.

Transcranial Doppler Arterial Pressure Gradient Is Associated With Delayed Infarction After Subarachnoid Hemorrhage.

Background And Purpose: While the pulsatility index (PI) measured by transcranial Doppler (TCD) has broader associations with outcomes in neurocritical care, its use in monitoring delayed cerebral infarction (DCI) in patients with aneurysmal subarachnoid hemorrhage (SAH) is not endorsed by current clinical guidelines. Recognizing that arterial pressure gradient (ΔP) can be estimated using PI, we investigated the potential significance of TCD-estimated ΔP.

Methods: In this observational study of 186 SAH patients, we recorded the mean cerebral blood flow velocity (mCBFV) and PI values from the middle cerebral artery, along with corresponding blood pressures.

Prevalence and characteristics of group standardized letters of evaluation in emergency medicine: A cross-sectional observational study.

Background: The standardized letter of evaluation (SLOE) for emergency medicine (EM) is a well-established tool for residency selection. While previous work characterizes the utility and outcomes related to SLOE use, less is known about SLOE authorship patterns and trends.

Objective: The objective was to measure the prevalence of group SLOEs in EM over time, characterize the role groups represented in group SLOEs, and compare the rating practices of groups of authors versus single authors.

Evaluating Digital Rehabilitation Outcomes in Chronic Musculoskeletal Conditions Across Non-Obesity, Obesity, and Severe Obesity.

Background: Obesity is a known risk factor and aggravator of musculoskeletal (MSK) conditions. The rising prevalence of obesity calls for scalable solutions to address MSK conditions in this population, given their complex clinical profile and barriers to accessing care.

Purpose: To evaluate the engagement and clinical outcomes of a fully remote digital care program in patients with MSK conditions, focusing on those with and without comorbid obesity.

Trends in treatment and epidemiology of radial head fractures.

Objective: We aimed to assess the recent trends in the demographics of radial head and neck fractures and their management based on displacement.

Methods: TriNetX was queried for cases from 1 January 2017, through 31 December 2022. ICD diagnosis codes were used to define patient cohorts with radial head or neck fractures.