Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers.

Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.

Vitamin D Therapy May Induce Lipoma Involution: A Multi-case Report.

Benign lipomas are a common medical problem that is not known to regress spontaneously. In addition, vitamin D (VD) is a known regulator of adipocyte proliferation and differentiation. Thus, the purpose of this multi-case study was to determine if optimizing serum 1,25(OH)D3 (VD3) concentrations to the 40-60 ng/mL range would catalyze regression of benign subcutaneous lipomas.

Pancreaticoduodenectomy in trauma patients with grade IV-V duodenal or pancreatic injuries: a post hoc analysis of an EAST multicenter trial.

Introduction: The utility of pancreaticoduodenectomy (PD) for high-grade traumatic injuries remains unclear and data surrounding its use are limited. We hypothesized that PD does not result in improved outcomes when compared with non-PD surgical management of grade IV-V pancreaticoduodenal injuries.

Methods: This is a retrospective, multicenter analysis from 35 level 1 trauma centers from January 2010 to December 2020.

Systematic treatment and management of postpartum hypertension using remote patient monitoring.

Objective: To describe postpartum visit attendance and postpartum blood pressure control among patients enrolled in a remote patient monitoring program and compare these outcomes by race.

Study Design: A prospective cohort study of postpartum patients with a diagnosis of hypertensive disorders of pregnancy at the University of Chicago between October 2021 and April 2022. All patients received remote patient monitoring as routine care but consented separately for the use of their data.

Evaluating post-cardiac arrest blood pressure thresholds associated with neurologic outcome in children: Insights from the pediRES-Q database.

Background: Current Pediatric Advanced Life Support Guidelines recommend maintaining blood pressure (BP) above the 5th percentile for age following return of spontaneous circulation (ROSC) after cardiac arrest (CA). Emerging evidence suggests that targeting higher thresholds, such as the 10th or 25th percentiles, may improve neurologic outcomes. We aimed to evaluate the association between post-ROSC BP thresholds and neurologic outcome, hypothesizing that maintaining mean arterial pressure (MAP) and systolic blood pressure (SBP) above these thresholds would be associated with improved outcomes at hospital discharge.

Psychiatrists' Experiences, Training Needs, and Preferences Regarding Prescription and Management of HIV Pre-exposure Prophylaxis (PrEP) Within Psychiatric Care.

Background: People living with mental illness (PLWMI) experience a disproportionate prevalence and incidence of HIV. Preventing HIV among PLWMI is a priority for multiple domestic public health agencies. As key clinicians for this group, psychiatrists may have an important role to play in increasing PrEP use among PLWMI.

Common lipidomic signatures across distinct acute brain injuries in patient outcome prediction.

Lipidomic alterations have been associated with various neurological diseases. Examining temporal changes in serum lipidomic profiles, irrespective of injury type, reveals promising prognostic indicators. In this longitudinal prospective observational study, serum samples were collected early (46 ± 24 h) and late (142 ± 52 h) post-injury from 70 patients with ischemic stroke, aneurysmal subarachnoid hemorrhage, and traumatic brain injury that had outcomes dichotomized as favorable (modified Rankin Scores (mRS) 0-3) and unfavorable (mRS 4-6) three months post-injury.

Methotrexate induced hepatotoxicity in metabolic dysfunction-associated steatotic liver disease.

Hepatotoxicity is an under-recognized and potentially fatal side effect of high-dose methotrexate (HDMTX) chemotherapy, and this risk is compounded in children with metabolic dysfunction-associated steatotic liver disease and/or metabolic-associated steatohepatitis. We present the case of a 12-year-old obese, Hispanic male with elevated hepatic transaminases of unknown etiology at initiation of high-risk B-cell acute lymphoblastic leukemia chemotherapy. He developed acute kidney injury within 24 hours of receiving intravenous HDMTX which progressed to acute hepatic failure.

Sonopermeation With Size-sorted Microbubbles Synergistically Increases Survival and Enhances Tumor Apoptosis With L-DOX by Increasing Vascular Permeability and Perfusion in Neuroblastoma Xenografts.

Objective: Despite aggressive therapy, approximately 50% of patients with neuroblastoma (NB) fail to respond, and survivors endure lifelong toxicities. Sonopermeation increases drug uptake via cell bilayer disruption through focused ultrasound and microbubbles (MBs)-gas-filled, sound sensitive lipid spheres. MB response to a given ultrasound pulse (cavitation) varies according to MB size.

The Pseudoinflammatory Pattern Revisited.

In 1973, Dr. Martin C. Mihm, Jr.

Somatic co-alteration signatures are prognostic in high-grade TP53-mutated myeloid neoplasms.

To assess the relevance of co-occurring somatic mutations in TP53-mutated myeloid neoplasms with ≥10% blasts, we pooled 325 individuals from 10 centres. We focused on comparing three published somatic co-alteration signatures comprising (1) nine MDS-related genes ('ICC-MDSR'), (2) ICC-MDSR + additional secondary mutations-related genes ('Tazi signature') and (3) EPI6 (comprising six genes). Outcomes examined were 24-month overall survival (OS24) and front-line complete response (CR1).

Soluble Urokinase-Type Plasminogen Activator Receptor and Inflammatory Biomarker Response with Prognostic Significance after Acute Neuronal Injury - a Prospective Cohort Study.

Aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS), and traumatic brain injury (TBI) are severe conditions impacting individuals and society. Identifying reliable prognostic biomarkers for predicting survival or recovery remains a challenge. Soluble urokinase type plasminogen activator receptor (suPAR) has gained attention as a potential prognostic biomarker in acute sepsis.

NAFLD No More: A Review of Current Guidelines in the Diagnosis and Evaluation of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Purpose Of Review: Provide a concise update on metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), as well as a practical approach to screening and initial evaluation.

Recent Findings: Nomenclature changes have placed a greater focus on cardiometabolic risk factors in the definition of MASLD. Screening for MASLD is by stepwise noninvasive serum and imaging tests which can identify patients at risk for advanced fibrosis and liver-related complications.

Portal Hypertensive Gastropathy and MELD-Na Score Predict Recurrent Gastrointestinal Bleeding After TIPSS: An ALTA Group Study.

Background: Transjugular intrahepatic portosystemic shunt (TIPSS) is highly effective for treatment of variceal bleeding; however, factors contributing to rebleeding complications remain unclear.

Aims: In this study, we aim to determine risk factors for recurrent portal hypertensive gastrointestinal bleeding following TIPSS.

Methods: Utilising the Advancing Liver Therapeutic Approaches multicentre database, we retrospectively identified adult patients who underwent TIPSS for secondary prophylaxis of variceal bleeding and had a gastrointestinal rebleeding event within 1 year.

Renal denervation - radiofrequency vs. ultrasound: insights from a mixed treatment comparison meta-analysis of randomized sham controlled trials.

Background And Aims: Multiple randomized trials have shown that renal denervation (RDN) reduces blood pressure (BP) when compared with sham control but the antihypertensive efficacy of radiofrequency vs. ultrasound-based RDN is uncertain. We aimed to compare the outcomes of radiofrequency RDN (rRDN) and ultrasound RDN (uRDN), when compared with sham in patients with hypertension.

Residency Education Practices in Endoscopic Skull Base Surgery.

 There has been increased interest in how residents train in the subspecialty of skull base surgery. Examining which training methods are popular and effective to optimize residency learning is necessary, especially with new training adjuncts available to the modern trainee. In this study, we survey North American Skull Base Society (NASBS) members to analyze endoscopic skull base surgery education methods.

Fatal Pediatric Firearm Injuries: When and Where Are Children at Risk?

Objective: In 2022, firearms injured or killed more than 6000 American children. Significant disparities exist in injury risk. We hypothesized that analyzing an injury's time, date, and location could help identify additional risk and protective factors in the pediatric population.

Evaluation and treatment of rhinosinusitis with primary antibody deficiency in children: Evidence-based review with recommendations.

Background: There is clear evidence that prevalence of primary antibody deficiency (PAD) is higher in children with chronic rhinosinusitis (CRS) than in the general population. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on rhinosinusitis with PAD, summarize the existing evidence, and provide recommendations on the evaluation and management of rhinosinusitis in children with PAD.

Methods: The PubMed, Embase, and Cochrane databases were systematically reviewed from inception through December 2023.