The Hippo pathway governs cell growth, proliferation, and differentiation and is frequently deregulated in cancer. Yes-associated protein (YAP) is the central transcriptional coactivator of the Hippo pathway and interacts with β-catenin to coordinate YAP-Wnt signaling crosstalk. Both pathways are modulated by diverse upstream signals including mechanical cues, cell density, and cell polarity, yet how such signals are integrated remains poorly understood. Here, we demonstrate that Homer scaffolding proteins coordinate YAP and Wnt signaling downstream of the Crumbs polarity complex. Homers interact directly via their EVH1 domains with the Crumbs component PATJ and the NDR kinase scaffold Furry-like (FRYL). Homers antagonize FRYL to promote YAP activation while cooperating with FRYL to enhance Wnt/β-catenin signaling, revealing pathway-selective regulation. PATJ, in contrast, recruits Homers to the cortex and restrains YAP activity. We further show that Homers form biomolecular condensates in nonpolarized epithelial and colorectal cancer cells, whose assembly and signaling properties are differentially modulated by PATJ and FRYL. Whereas FRYL promotes the formation of cytoplasmic droplets, PATJ drives the assembly of phase-separated compartments at or near the plasma membrane. Collectively, our findings establish Homer-driven phase separation as a tunable signaling mechanism to translate polarity cues into transcriptional output.
Fusobacterium necrophorum is a recognized cause of brain abscesses and has been classically associated with Lemierre syndrome. We report a case of a 17-year-old male patient who presented with seizures, fever, and altered mental status following treatment for sinusitis. Neuroimaging revealed a right frontal lobe abscess requiring surgical drainage. Anaerobic cultures from the abscess fluid grew F. necrophorum, while a respiratory polymerase chain reaction (PCR) panel from a nasopharyngeal swab detected Mycoplasma pneumoniae. Anaerobic cultures also yielded Paenibacillus barengoltzii from a separate soft tissue specimen, though its clinical significance remained uncertain. The patient improved with surgical drainage and targeted antimicrobial therapy. This case highlights concurrent detection of F. necrophorum and M. pneumoniae in a central nervous system infection and underscores the uncertainty regarding the pathogenic role of M. pneumoniae in such presentations.
Radiographic assessment is central to the diagnosis of femoroacetabular impingement (FAI) syndrome. However, the relationship between specific bony morphology and symptom severity remains unclear. We sought to evaluate the relationship between FAI morphology, quantified through preoperative radiographic measures, and preoperative symptom burden in patients with FAI syndrome. We conducted a retrospective study of prospectively collected data that included a series of consecutive patients diagnosed with FAI syndrome who underwent hip arthroscopy by a single surgeon between January 2024 and October 2025. Inclusion criteria were (1) diagnosis of FAI syndrome and (2) availability of complete preoperative patient records, including X-ray images and preoperative patient-reported outcome measures. Exclusion criteria were (1) patients <14 or >60 years, (2) diagnosis that included FAI syndrome with concomitant intra-articular pathology, (3) hip surgery other than primary hip arthroscopy, (4) unavailable X-ray imaging, and (5) history of lower extremity osteotomy for abnormal rotational profile. Hip impingement measures were obtained on preoperative radiographs, including α angle, head-neck offset, anterior center-edge angle, and lateral center-edge angle, crossover sign, crossover ratio, and ischial spine sign. Preoperative symptom severity was assessed by the International Hip Outcome Tool-12 (iHOT-12). Multivariate models adjusted for demographics, mental health, physical activity, and corticosteroid injection history. Among 285 patients (median age 34.9 years, 75.4% female), the median iHOT-12 score was 37.5. Proximal femur measures and acetabular coverage were not correlated with iHOT-12. The presence of crossover or ischial spine signs was associated with higher iHOT-12 on bivariate analysis and remained predictive of higher iHOT-12 after adjustment for demographics and injection status in multivariate modeling. All other radiographic measures were non-significant after further adjustment for mental health and activity level. Radiographic measures of retroversion are associated with better preoperative symptoms in patients with FAI syndrome. Other radiographic measures of hip impingement showed no meaningful association with preoperative symptom severity. For patients with FAI syndrome, psychological and functional factors exerted a larger influence on symptom severity than did impingement severity as reflected on radiograph. Level IV: retrospective case series.
Surgical volumes continue to shift from inpatient and hospital outpatient departments to independent and co-owned Ambulatory Surgery Centers (ASCs). Consumer preferences, payer pressure, lower cost, possibility of site-neutral payments, equivalent safety, and clinical innovation have caused this outmigration. Physicians have embraced the shift due to dissatisfaction with current employment models, more professional autonomy, a sense of purpose, the ability to drive efficiency and quality of care, and the option to invest and benefit financially. Vascular surgeons can utilize their existing experience delivering outpatient care to grow their practices. The unique challenges and business structure of this care model, regulatory roadblocks, arbitrary reimbursement adjustments, and new corporate entrants to ASCs need to be understood. New models of outpatient care will likely include shifting higher-acuity procedures to ASCs. The care will be delivered by independent vascular surgeons or through alignment between physicians and hospital systems to provide optimal care to patients in convenient, secure, and cost-effective settings.
To investigate whether lithium exposure in pregnancy is associated with spontaneous preterm birth, congenital malformations and abnormal fetal growth. Statewide retrospective cohort study. Victoria, Australia. 867 454 births (2009-2020), including 234 (0.03%) exposed to lithium during pregnancy. Inverse probability weighted regression adjustment to investigate the association between maternal lithium use and perinatal outcomes. Spontaneous preterm birth (< 37 weeks' gestation), large for gestational age (LGA) (birthweight > 90th percentile), macrosomia (birthweight > 4000 g), major congenital malformations, congenital cardiac malformations. Lithium use was associated a two-fold increased risk of spontaneous preterm birth compared with unexposed pregnancies (8.1% vs. 2.4%; adjusted relative risk [aRR] 2.18, 95% CI 1.45-3.30). Lithium was associated with an increased risk of an LGA infant (13.7% vs. 6.4%; aRR 1.94, 95% CI 1.36-2.76), and congenital cardiac malformations (3.0% vs. 0.8%; aRR 2.64, 95% CI 1.26-5.53). Lithium was not associated with an altered risk of major congenital malformations overall (aRR 1.51, 95% CI 0.92-2.50). Restricting the cohort to women with bipolar disorder or schizophrenia diagnoses, associations remained between lithium exposure and spontaneous preterm birth (aRR 1.88, 95% CI 1.06-3.32) and birth of an LGA infant (aRR 1.68, 95% CI 1.07-2.65). In our study, lithium exposure during pregnancy was associated with a two-fold increased risk of spontaneous preterm birth. Lithium use was also associated with an increased risk of cardiac malformations and having an LGA infant. These findings may be useful for shared decision-making around lithium use during pregnancy.
This study evaluated the effects of supplementation levels of a blend of vitamin B complex offered to weaned beef calves in a 42-day preconditioning program. Sixty-three Angus × Hereford calves were stratified by body weight (BW; 252 ± 3.7 kg) after weaning (d0) and allocated into 21 pens (3 calves/pen). Pens were randomly assigned to one of three treatments: (1) Control, (2) VitB1g, or (3) VitB2g. Calves assigned to vitamin B supplementation received vitamin B complex (1 vs. 2 g/calf daily; Vivalto, Selko USA; containing pantothenic acid [B5], pyridoxine [B6], folic acid [B9], biotin [B7], cyanocobalamin [B12]) mixed with 1.3 kg of dried distillers' grains (DDG), while calves in the Control group received only DDG. All calves had free-choice access to chopped alfalfa-grass hay and limited whole corn. Body weights and blood samples were collected from all calves on days 0, 1, 3, 7, 14, 21, and 42 relative to weaning to evaluate plasma cortisol and acute-phase proteins. Vitamin B7 concentration was measured on days 0, 14 and 42. Pen was the experimental unit, and data were analyzed as repeated measures using the MIXED procedure in SAS. No effects of treatment, day, and the interaction (P ≥ 0.23) were observed for any of the growth performance variables analyzed. At weaning, all calves had similar (P ≥ 0.91) plasma vitamin B7 concentrations, and with two weeks of supplementation, on d14, calves assigned to VitB2g treatment had greater (P ≤ 0.005) vitamin B7 concentration than calves assigned to VitB1g and Control treatments, which had similar vitamin B7 concentrations (P = 0.79). At the end of the preconditioning phase, on d42, calves assigned to VitB2g had greater (P ≤ 0.02) vitamin B7 concentrations than calves assigned to VitB1g and Control treatments, which continued to remain similar (P = 0.17). A tendency for a treatment × day (P = 0.08) for cortisol concentration was observed. Cortisol concentrations were similar at weaning (P ≥ 0.89). Interestingly, at the end of the supplementation, calves supplemented with vitamin B complex, regardless of vitamin level supplementation, had lower cortisol concentration (P ≤ 0.05) than calves assigned to the Control treatment. Collectively, these findings suggest that vitamin B complex supplementation during preconditioning enhances circulating vitamin B7 concentration, especially at 2 g/d, and may attenuate physiological stress responses in weaned beef calves.
Understanding the relationship between the structural and optical properties of lead halide perovskite quantum dots (QDs) requires precise control over their composition, size, surface passivation, and morphology. Although significant progress has been made in tuning the composition and size of perovskite QDs, less attention has been given to controlling their surface morphology, especially when the QDs are size-confined. Here, we present a synthesis of monodisperse, quantum-confined CsPbBr3 QDs with carefully controlled surface morphology. The exposure of surface facets is regulated by annealing the QDs with facet-selective dicationic ligands, which are designed to match the spacing of Cs+ vacancies on specific facets. Our QDs remain morphologically stable during purification and can self-assemble via drop-casting. By monitoring the circularity indices of QDs, we reveal that the evolution of surface facet exposure during annealing is driven thermodynamically. Our straightforward synthesis approach offers an additional degree of tuning freedom for perovskite QDs.
Our study aimed to determine the in-hospital mortality rate among granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) hospitalizations complicated with acute respiratory failure (ARF) in the US and determine prognostic factors during hospitalization. We performed a retrospective cohort analysis utilizing the National In-patient Sample (NIS) database to identify hospitalizations of patients with GPA or MPA associated with ARF from 2016 to 2021. The outcomes included in-hospital mortality, requirement of invasive procedures, and hospital length of stay. Univariable and multivariable analysis were used to identify prognostic factors associated with in-hospital mortality. We identified 21,430 weighted (4,283 unweighted) hospitalizations with diagnosis of GPA or MPA associated with ARF in the United States from 2016 to 2021. 78.3% of those were diagnosed with GPA, 19.2% with MPA, and 2.5% with both ICD-10 codes. The mean age was 63.7 years, 53.6% were female, and 73.3% were White. The rate of hemodialysis was 21.5%, plasmapheresis 7.4%, and extracorporeal membrane oxygenation in 0.5% of hospitalizations. The overall in-hospital mortality was 15.4%, compared to 35.9% in the subgroup requiring invasive mechanical ventilation (IMV). Independent prognostic factors associated with increased in-hospital mortality were higher age, acute kidney injury (AKI), sepsis, requirement of non-invasive mechanical ventilation, interstitial lung disease (ILD), history of stroke, shock, and requirement of IMV. GPA or MPA hospitalizations complicated with ARF were found to be associated with a high in-hospital mortality rate. At hospital-level prognostication assessment, we found that higher age, AKI, sepsis, shock, history of ILD, history of stroke, and requirement of mechanical ventilation were independently associated with increased in-hospital mortality.
Increasing chest imaging utilization, including for screening, identifies more non-small cell lung cancer (NSCLC) at earlier stages. We suspected that a parallel increase in early detection and resection of small cell lung cancer (SCLC) was also occurring. We therefore reviewed our institutional experience to explore trends in surgically resected SCLC frequency and outcomes. A single-institution, retrospective review was performed of all SCLC cases resected between 2000-2022. We evaluated demographics, oncologic characteristics, overall survival (OS), and disease-free survival (DFS). Among 30 patients with resected SCLC, the majority underwent lobectomy (73%) and only 37% were known to have SCLC preoperatively. The frequency of resections increased over time with almost half (47%) occurring in the last four study years (2019-2022). This increase in SCLC resections coincided with increasing lung cancer screening (LCS) volume, with no change in thoracic surgical case volume. The 2019-2022 cohort was predominantly clinical stage I (86%) compared to 56% pre-2019 (I vs. II-IV, P=0.08), and also trended toward more screen-detected (43% vs. 13%, P=0.08) patients. Subgroup analysis showed encouraging OS outcomes following surgical resection for clinical and pathological stage I patients. There was a trend toward better OS among screen-detected patients (73% vs. 34%, log-rank P=0.07) that was significant in DFS (75% vs. 26%, P=0.02). The number of surgically resected SCLC patients at our institution has increased in recent years, as has the proportion of screen-detected and clinical stage I cases, alongside rising LCS volume. This may be an early signal of a broader trend toward increasing diagnosis of limited stage SCLC eligible for resection.
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease in which the earliest cellular events driving fibrosis remain poorly defined. Here, we analyzed lung samples from three independent and unique cohorts of patients with early disease and preserved lung function (Florence, NIH, Forli), applying an integrated multi-modal approach combining single-nucleus RNA sequencing, bulk transcriptomics, immunostaining, and spatial transcriptomics. Single nuclear RNA sequencing of samples obtained by diagnostic bronchoscopic cryobiopsy (Florence, n= 22) revealed that early IPF is characterized by a marked shift in alveolar epithelial composition, with loss of AT1 and AT2 cells and the emergence of aberrant basaloid cells and alveolar epithelial intermediate cells. These populations exhibited transcriptional programs associated with epithelial plasticity and profibrotic signaling and closely resembled those observed in end-stage IPF. Higher proportions of aberrant basaloid and alveolar epithelial intermediate cells were associated with subsequent disease progression, whereas AT2 cell abundance correlated with preserved lung function. Fibrotic CTHRC1+ fibroblasts are largely restricted to advanced disease, while endothelial remodeling and inflammatory fibroblast states are already evident in early IPF. Spatial transcriptomic analyses confirmed early disruption of the alveolar niche, with replacement of normal epithelial-capillary interactions by aberrant epithelial and venous endothelial cells (Forli, n= 24); the findings were replicated through single cell RNA sequencing of samples obtained by video assisted thoracoscopy two decades earlier (NIH n=9). Together, these findings identify that alveolar niche remodeling with loss of its normal components, and emergence of aberrant basaloid cells are features of early IPF, highlighting epithelial dysfunction as a key potential target for therapeutic interventions in early disease.
Coronary artery disease (CAD) is an important comorbidity that may increase perioperative cardiovascular risk in major noncardiac surgery. However, data evaluating its impact on outcomes following pancreatic cancer surgery remain limited. This study evaluated inpatient outcomes among patients undergoing pancreatic cancer resection with versus without CAD in the United States. We performed a retrospective analysis using the National Inpatient Sample (2016-2022). Adult hospitalizations with ICD-10 diagnosis codes for pancreatic cancer and procedure codes for pancreatic resection were identified and stratified by the presence of CAD. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, hospitalization cost, and complications such as shock, respiratory failure, acute kidney injury, and transfusion. A total of 49,395 hospitalizations were identified, including 6910 (14.0%) with CAD. Patients with CAD were older and had a greater comorbidity burden. In-hospital mortality was similar between groups (2.32% vs. 2.34%). Most complications were comparable, although shock was more frequent in CAD patients (6.66% vs. 5.44%). Length of stay was similar, while hospitalization costs were modestly higher in the CAD cohort. Pre-existing CAD was not associated with increased in-hospital mortality or longer hospitalization following pancreatic cancer surgery despite a greater comorbidity burden.
Shivering is a common complication of targeted temperature management (TTM), which could undermine its neuroprotective benefits by increasing cerebral oxygen consumption and metabolic demand. Buspirone, a 5-HT1A receptor partial agonist, is incorporated into many antishivering protocols for TTM following cardiac arrest, despite limited evidence supporting its efficacy in critically ill patients. We conducted a targeted literature review using PubMed to assess the evidence in favor of the use of buspirone in antishivering protocols during TTM. Experimental, physiological, and clinical studies were reviewed with emphasis placed on study design, patient population, and relevance to critically ill individuals undergoing TTM. Experimental studies in animals and healthy human volunteers show that buspirone can modestly lower core temperature or shivering thresholds. Two small studies (n = 8 each) in healthy male volunteers demonstrated that buspirone reduced the shivering threshold by approximately 0.7°C. A retrospective cohort study (n = 131) in post-cardiac arrest patients showed a reduction in shivering with a multidrug protocol including buspirone, but the independent contribution of buspirone could not be isolated. No randomized controlled trials have evaluated buspirone's efficacy as a standalone antishivering agent in critically ill patients. Current evidence to support the buspirone's use in antishivering protocols is limited and largely extrapolated from noncritical care settings. Given that most patients undergoing TTM already receive sedatives and analgesics with more potent antishivering effects, the incremental benefit of buspirone remains unproven. Furthermore, it adds to the already high burden of polypharmacy in ICU patients and could, in theory, increase the risk of serotonin syndrome. Randomized trials comparing protocols with and without buspirone are needed to determine its clinical utility.
Antimicrobials are among the classes of pharmaceuticals most used by acute care surgeons, with many emergency general surgery conditions either related to infections or at high risk of infectious complications. As such, knowledge of proper use of antimicrobial agents, especially in this era of increasing antimicrobial resistance, is imperative for optimal outcomes. This review focuses on the advanced infectious diseases and antimicrobial utilization knowledge required to treat complicated and critically ill surgical patients. Overall concepts pertaining to antibiotics are discussed, followed by a more in-depth discussion of conditions common in emergency general surgery. Key themes include the importance of source control and accurate culture data, the frequent need for broad-spectrum, empiric antimicrobial therapy, subsequent careful de-escalation of antibiotics, and minimizing treatment duration. (J Trauma Acute Care Surg. 2026;101: 13-27. Copyright © 2026 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Surgery of Trauma.).
Laryngeal cancer incidence has risen globally, yet survival outcomes have shown limited improvement over recent decades. This study evaluated contemporary outcomes across multiple centres in Northern UK and examined stage- and treatment-specific survival. Multi-centre retrospective observational study. Data were collected for 2028 patients with biopsy-proven squamous cell carcinoma of the larynx treated with curative intent between 2015 and 2021 across six tertiary head and neck cancer centres (Newcastle, Glasgow, Liverpool, Sheffield, Leeds, and Middlesbrough). Overall survival (OS) and disease-specific survival (DSS) were estimated using Kaplan-Meier analysis and compared using log-rank testing. Median follow-up was 40 months (mean age 66.8 years; 81% male). Overall mortality was 41% and disease-specific mortality 20%. Five-year OS declined with advancing stage: 72.0% (T1), 54.5% (T2), 50.6% (T3), and 45.2% (T4). In unadjusted analyses, surgery in T1 disease was associated with higher survival (5-year DSS 93.6% vs. 88.5%), while in advanced disease chemoradiotherapy was associated with the highest DSS (5-year DSS 70.2%), although differences were not statistically significant. No significant differences in DSS were observed across year of diagnosis (2015-2021). Survival outcomes for laryngeal cancer remain poor and have shown limited improvement over time. These findings provide important real-world insights into contemporary outcomes and highlight the need for earlier detection, prevention strategies, and prospective collaborative research to improve future outcomes.
To estimate the cost-effectiveness of immediate septoplasty compared with 6 months of medical management with the option for delayed septoplasty in individuals with nasal obstruction associated with septal deviation. Economic evaluation alongside a multicentre, open label, randomised controlled trial. 17 otolaryngology clinics in the UK, recruiting from January 2018 to December 2019. Adults aged≥18 years with symptoms of nasal obstruction associated with septal deviation with at least moderate symptoms of nasal obstruction (score>30 on the Nasal Obstruction and Symptom Evaluation scale). Participants were randomised to receive either septoplasty within 12 weeks of recruitment or 6 months of medical management (nasal steroid and saline spray) with the option for delayed septoplasty. Incremental cost per quality-adjusted life year (QALY) gained at 12 months. A UK National Health Service perspective was adopted, and surgery costs were estimated using a tariff and micro-costing. QALYs were estimated based on responses to the Short Form-36 (SF-36). Seemingly unrelated regression was used to estimate incremental costs and QALYs. A model-based analysis was used to extrapolate costs and effects to 24 months. Sensitivity analyses were used to illustrate uncertainty. In the within-trial analysis, immediate septoplasty was on average more costly (mean difference (95% CI) £1193 (£1018 to £1368)) and more effective (mean difference (95% CI) 0.044 QALYs (0.03 to 0.06)) when compared with 6 months of medical management with the option for deferred septoplasty. Immediate septoplasty had an incremental cost per QALY gained of £27 114 in the base case analysis, which decreased to £16 682 when micro-costing was used to estimate surgery costs. Immediate septoplasty had a 15% and 78% probability of being considered cost-effective at a £20 000 threshold for an additional QALY, respectively. In the model-based analysis, immediate septoplasty remained more costly and more effective than 6 months of medical management with the option for deferred septoplasty but had a 99% probability of being considered cost-effective at a £20 000 threshold for an additional QALY. Over a 24-month time horizon, immediate septoplasty would be cost-effective in the management of deviated nasal septum. ISRCTN16168569.
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Reversible cerebral vasoconstriction syndrome is a recently defined disease entity classically presenting with recurrent thunderclap headache. The pathology involves triggered cerebral arterial vasoconstriction, which can lead to complications including seizure, ischemic stroke, and intracranial hemorrhage. Diagnosis requires angiography, and treatment consists of vasodilatory therapy. We describe a case of reversible cerebral vasoconstriction syndrome following glucocorticoid burst therapy in a patient on multiple vasoactive medications, suggesting the possibility of compounding risk factors and triggers. As is common with this syndrome, the patient in our case required multiple hospital visits for diagnosis but ultimately experienced a positive outcome upon treatment. The presentation of reversible cerebral vasoconstriction syndrome can vary. Diagnosis requires a high degree of suspicion in patients with potential triggers to ensure early treatment and avoidance of poor outcomes.
Defining the core content for each scientific discipline in a modern preclinical medical education curriculum is critical to ensure optimal student learning and application of foundational knowledge for clinical practice. Attendees of the Association of Medical School Microbiology and Immunology Chairs (AMSMIC) Educational Strategies Workshop recently highlighted the need for updated medical microbiology learning objectives, given the shift in medical education toward less time for preclinical coursework and more integrated learning. Herein, we describe the process of developing a comprehensive, educator-driven set of knowledge objectives for medical microbiology. These objectives emphasize common pathogens, as well as pathogens associated with severe disease, organized by clinical presentation and disease processes. They also recognize newer pathogen identification methods used in clinical laboratories and provide flexibility to address emerging pathogens. Educators can use these objectives to refine curricula and define core content expected to appear on major medical licensure examinations.
Remediation during residency training remains underexplored despite unique challenges. Residencies face complex factors including increasing awareness of learning difficulties, greater diversity in training programs, and elevated rates of mental health concerns. Aiming to understand remediation best practices, this study leveraged behavioral science faculty (BSF), who often support early identification, intervention, and remediation for family medicine residency programs. BSF perceptions of the frequency of best practice implementation for early intervention and remediation within family medicine residency programs served as an initial step toward developing a questionnaire to help programs assess their process and infrastructure. Seventy BSF from university-based, university-affiliated, and community programs completed a national survey developed through a Delphi process identifying consensus-based best practices (CBBP). The questionnaire assessed the frequency with which BSF observed best practice implementation across their programs. Data were analyzed using χ2 tests, Fisher's exact tests, and factor analysis with Promax rotation to identify underlying dimensions of remediation practices. Implementation of CBBP varied across programs. Preliminary factor analysis revealed two factors that could be used for program evaluation. The two factors emerged as indicators of the remediation process. Organization and follow-up (Factor 1) reflected processes characterized by transparency, predictability, and follow-through. People and development (Factor 2) reflected a culture that normalizes challenges inherent in residency, understands key experiences, and develops faculty skill in effectively delivering feedback. Effective remediation requires organized processes and culture that support growth and psychological safety. This study presents a preliminary questionnaire assessing these practices from the BSF perspective.