Citations

Abstract Background: Ovarian high-grade serous carcinomas (HGSC) comprise four distinct molecular subtypes based on mRNA expression patterns, with differential survival. Understanding risk factor associations is important to elucidate the etiology of HGSC. We investigated associations between different epidemiologic risk factors and HGSC molecular subtypes. Methods: We pooled data from 11 case–control studies with epidemiologic and tumor gene expression data from custom NanoString CodeSets developed through a collaboration within the Ovarian Tumor Tissue Analysis consortium. The PrOTYPE-validated NanoString-based 55-gene classifier was used to assign HGSC gene expression subtypes. We examined associations between epidemiologic factors and HGSC subtypes in 2,070 cases and 16,633 controls using multivariable-adjusted polytomous regression models. Results: Among the 2,070 HGSC cases, 556 (27%) were classified as C1.MES, 340 (16%) as C5.PRO, 538 (26%) as C2.IMM, and 636 (31%) as C4.DIF. The key factors, including oral contraceptive use, parity, breastfeeding, and family history of ovarian cancer, were similarly associated with all subtypes. Heterogeneity was observed for several factors. Former smoking [OR = 1.25; 95% confidence interval (CI) = 1.03, 1.51] and genital powder use (OR = 1.42; 95% CI = 1.08, 1.86) were uniquely associated with C2.IMM. History of endometriosis was associated with C5.PRO (OR = 1.46; 95% CI = 0.98, 2.16) and C4.DIF (OR = 1.27; 95% CI = 0.94, 1.71) only. Family history of breast cancer (OR = 1.44; 95% CI = 1.16, 1.78) and current smoking (OR = 1.40; 95% CI = 1.11, 1.76) were associated with C4.DIF only. Conclusions: This study observed heterogeneous associations of epidemiologic and modifiable factors with HGSC molecular subtypes. Impact: The different patterns of associations may provide key information about the etiology of the four subtypes.

Background: Many surgeons use body mass index (BMI) cutoffs when offering total hip arthroplasty (THA). However, little is known about who loses weight before THA, and if weight loss improves outcomes. This study determined how many patients lost weight before primary THA, identified predictors of preoperative weight loss, and evaluated whether preoperative weight loss was associated with improved outcomes. Methods: Among 53,038 primary THAs that were performed between 2002 and 2019, we identified 2,463 patients who had a BMI of ≥30 kg/m 2 (measured 1 to 24 months before surgery) and had their weight measured at the time of surgery. The mean age was 66 years; 47% were women. The mean BMI was 35 kg/m 2 . Nonparametric models evaluated potential associations with weight loss. Univariable and multivariable logistic regression and Cox proportional hazards models evaluated the impact of preoperative weight change on hospital length of stay, discharge disposition, operative time, periprosthetic joint infection (PJI), complications, revision, and reoperation. The mean follow-up was 5 years. Results: Overall, 17% of the patients gained >5 pounds (2.27 kg), 38% maintained their weight, 16% lost 5 to <10 pounds (4.54 kg), 17% lost 10 to <20 pounds (9.07 kg), and 12% lost ≥20 pounds before THA. Only 28% of patients with a preoperative BMI of ≥40 kg/m 2 achieved a BMI of <40 kg/m 2 by the time of surgery; those who did required a mean of 1.3 years to lose the weight. In multivariable analyses, there were no significant improvements in operative time, length of stay, and discharge disposition, or survivorship free of PJI, complication, revision, or reoperation for any weight-loss category when compared with those who maintained their weight. Conclusions: Only 12% of patients lost ≥20 pounds, and only 28% of patients with a BMI of ≥40 kg/m 2 achieved a BMI of <40 kg/m 2 before primary THA. There was no decrease in complications, revisions, or reoperations for any preoperative weight-loss category when compared with those who maintained their weight. While weight loss benefits overall health, the results of this study call into question whether preoperative weight loss alone is enough to reduce postoperative complications for most patients. Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

BACKGROUND: Catheter ablation of ventricular arrhythmias, one of the most rapidly growing procedures in cardiac electrophysiology, is associated with magnetic resonance imaging–detected brain lesions in more than half of cases. Although a retrograde aortic approach is conventional, modern tools enable entry through a transseptal approach that may avoid embolization of debris from the arterial system. We sought to test the hypothesis that a transseptal puncture would mitigate brain injury compared with a retrograde aortic approach. METHODS: The TRAVERSE trial (Transseptal Versus Retrograde Aortic Ventricular Entry to Reduce Systemic Emboli) was a multicenter randomized controlled comparative effectiveness trial. Patients with left ventricular arrhythmias undergoing catheter ablation procedures were randomly assigned to a transseptal puncture approach compared (1:1) with a retrograde aortic approach. The primary outcome was the presence of an acute brain lesion detected by magnetic resonance imaging. Secondary outcomes included clinically manifest complications, procedural efficacy, and 6-month neurocognitive assessments. RESULTS: Among the 62 patients randomly assigned to a retrograde aortic approach with postoperative brain magnetic resonance imaging, 28 (45%) exhibited an acute brain lesion compared with 19 of the 69 (28%) of those randomized to a transseptal puncture ( P =0.036). No differences in clinically manifest complications or procedural efficacy were observed. More patients in the retrograde aortic arm were categorized as having a high likelihood of cognitive impairment at 6 months (33% compared with 19% of those in the transseptal arm), but substantial loss to follow-up was present. CONCLUSIONS: Among patients undergoing left ventricular catheter ablation procedures, a transseptal approach reduced the risk of acute brain lesions by nearly half compared with a retrograde aortic approach without sacrificing safety or efficacy. Given a likely embolic pathogenesis, the brain magnetic resonance imaging findings may reflect a propensity to other organ damage; these findings may extend to other procedures requiring left ventricular entry. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03946072.

Abstract Total wrist arthroplasty (TWA) is a motion-preserving treatment option for wrist arthritis. High-precision measurement methods for implant migration such as computed tomography motion-analysis (CTMA) can potentially detect poor implant fixation. The aim of this pilot study was to assess CTMA as a complementary method to diagnose aseptic loosening of TWA. Three patients with a TWA and wrist pain during activity underwent induced displacement CT (CTMA) with alternated provocations as a complement to plain radiographs. Two of the three patients had displacement of the carpal component on CTMA. The radial component was stable in all cases. The tool was adapted to clinical routine use. CT motion-analysis could be a valuable adjunct to plain radiographs in assessing component loosening in TWA.

Study Design Retrospective Cohort. Objectives Craniovertebral instability can arise from various congenital or acquired conditions, but definitive management often requires craniocervical fusion. This study evaluates whether postoperative clivo-axial angle (CXA) can predict distal junctional failure in patients undergoing craniocervical fusion. While postoperative alignment of the head and cervical spine can be quantified via the CXA, it is unclear whether the CXA can predict distal junctional failure. Methods All patients undergoing craniocervical decompression and fusion (CCF) for craniovertebral instability between 2012 and 2023 at a single institution were identified. Patients experiencing adjacent segment disease (ASD) were identified and compared to those without said pathology based on CXA, Grabb-Oakes line (pBC2), and the presence of cervical kyphosis, cervical disc degeneration, or subluxation on pre- and postoperative imaging. Statistical analysis included Shapiro-Wilk tests for normality, followed by independent t-tests or Mann-Whitney U tests with FDR adjusted P values as appropriate, and univariable logistic regression. Results 71 patients were included, of whom ten (14.3%) developed distal junctional kyphosis and 3 (4.3%) developed cervical spondylolisthesis. The median postoperative CXA was significantly lower in non-ASD patients (144° [IQR: 140-148°] vs 158° [IQR: 153-162°]; P < .001) and logistic regression showed that each 10° degree increase in CXA was associated with a 6.7-fold higher odds of ASD. Conclusions We found craniocervical alignment, as assessed by CXA, independently predicted distal junctional disease in patients undergoing craniocervical fusion, possibly due to low preoperative CXA in these patients. Large increases in CXA may contribute to postoperative instrumentation failure.

Background Improving safety in healthcare has been paramount for decades, yet despite major attention and investment, improvement has remained incremental. Patient safety is a major concern in US healthcare, leading to significant harm and economic losses annually. Accurately identifying safety events remains difficult due to methodological discrepancies and lack of standardisation. This study evaluated the feasibility of implementing a standardised case-review methodology and safety-event taxonomy across diverse hospital settings to assess opportunities for improvement (OFIs) and compare findings with traditional definitions. Methods This multicentre retrospective cohort study reports data from 103 hospitals across the USA and Canada between 2016 and 2023. A multivariable logistic regression was performed to test case reviews for differences in the presence of one or more OFIs across several hospital types (bed size, academic status, urban setting, trauma level and Centres for Medicare and Medicaid Services overall star rating) and patient characteristics (age, gender, length of stay, admission and discharge code status and mortality). Results 19 181 cases were reviewed across the Learning Health System Collaborative, with a median of 107 reviews per hospital. Mortality was the most common cohort selection, studied by 91 hospitals (88%). At least one OFI was identified in 12 714 cases (66.3%). The logistic regression analysis found that all hospital characteristics and patient age, length of stay, code status and discharge disposition were significantly associated with at least one OFI. Of the 46 444 OFIs identified, 41 439 (89%) were from categories focused on omissions of care. The categories of end-of-life, documentation and treatment/care alone accounted for 25 980 OFIs (56%). Conclusion The highest volumes of safety-related OFIs were associated with omissions of care, as opposed to the traditional definition of patient safety, which primarily includes outcomes from acts of commission.

Background Although intravenous thrombolysis (IVT) is safe and effective in populations with general stroke, its impact on cervical artery dissection–related acute ischemic stroke (CeAD‐AIS) remains unclear. This retrospective study used the National Inpatient Sample to compare outcomes in patients with CeAD‐AIS treated with and without IVT. Methods We included adult patients with concurrent CeAD and AIS diagnoses ( International Classification of Diseases, Tenth Revision [ ICD‐10 ], codes) hospitalized from 2016 to 2019. The primary outcome was home discharge; safety outcomes included inpatient death and intracerebral hemorrhage. We performed survey‐weighted multivariable logistic regressions comparing IVT versus no IVT, followed by interaction analyses to examine effect modifications based on age, medical history, stroke severity, carotid artery involvement, and endovascular treatment. Results Between 2016 and 2019, 1360 (12.1%) of 11 285 patients with CeAD‐AIS received IVT. IVT‐treated patients had higher median National Institutes of Health Stroke Scale scores (median [interquartile range], 8 [4–17] versus 3 [1–11]; P <0.001). Adjusted analyses showed IVT was associated with higher odds of home discharge (adjusted odds ratio [OR], 1.40 [95% CI, 1.01–1.92]; P =0.042), but not with inpatient death (adjusted OR, 1.29 [95% CI, 0.76–2.20]; P =0.347) or intracerebral hemorrhage (adjusted OR, 0.69 [95% CI, 0.32–1.48]; P =0.341). Stroke severity ( P for interaction=0.001) and carotid artery involvement ( P for interaction=0.021) significantly modified IVT's effect on home discharge, with IVT being associated with an increased likelihood of home discharge in patients with moderate to severe strokes (National Institutes of Health Stroke Scale score >4) and carotid artery involvement. Conclusions IVT improves the likelihood of home discharge in patients with CeAD‐AIS without increasing the risk of inpatient death or intracerebral hemorrhage.

ABSTRACTSeveral dynamic models predict mortality and corticosteroid response in alcohol‐associated hepatitis (AH), yet no consensus exists on the most effective model. This study aimed to assess predictive models for corticosteroid response and short‐term mortality in severe AH within a global cohort. We conducted a multi‐national study of patients with severe AH treated with corticosteroids for at least 7 days, enrolled between 2009 and 2019. Dynamic models—Lille‐4, Lille‐7, trajectory of serum bilirubin (TSB), and neutrophil‐to‐lymphocyte ratio (NLR)—were used to estimate 30‐ and 90‐day mortality. Lille‐7 demonstrated the highest accuracy for both 30‐ and 90‐day mortality.

Abstract INTRODUCTION Early‐onset and late‐onset Alzheimer's disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head‐to‐head comparison of cortical atrophy in EOAD and LOAD, using two large and well‐characterized cohorts (LEADS and ADNI). METHODS We analyzed brain structural magnetic resonance imaging (MRI) data acquired from 377 sporadic EOAD patients and 317 sporadicLOAD patients who were amyloid positive and had mild cognitive impairment (MCI) or mild dementia (i.e., early‐stage AD), along with cognitively unimpaired participants. RESULTS After controlling for the level of cognitive impairment, we found a double dissociation between AD clinical phenotype and localization/magnitude of atrophy, characterized by predominant neocortical involvement in EOAD and more focal anterior medial temporal involvement in LOAD. DISCUSSION Our findings point to the clinical utility of MRI‐based biomarkers of atrophy in differentiating between EOAD and LOAD, which may be useful for diagnosis, prognostication, and treatment. Highlights Early‐onset Alzheimer's disease (EOAD) and late‐onset AD (LOAD) patients showed distinct and overlapping cortical atrophy patterns. EOAD patients showed prominent atrophy in widespread neocortical regions. LOAD patients showed prominent atrophy in the anterior medial temporal lobe. Regional atrophy was correlated with the severity of global cognitive impairment. Results were comparable when the sample was stratified for mild cognitive impairment (MCI) and dementia.