Citations

BACKGROUND: Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS: This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS: In all, 4023 patients (mean age was 47.4 years; 44.5% were women) were included. By day 180, subsequent ischemic stroke occurred in 5.3% of the cohort. In adjusted Cox regression, factors associated with increased risk of subsequent ischemic stroke were prior history of ischemic stroke (adjusted hazard ratio [aHR], 7.31 [95% CI, 1.61–33.13]; P =0.010), presentation within 7 days from first symptoms (aHR, 3.04 [95% CI, 1.04–8.91]; P =0.043), infarct on baseline imaging (aHR, 9.85 [95% CI, 3.65–26.58]; P <0.001), and occlusive dissection (aHR, 2.34 [95% CI, 1.03–5.34]; P =0.043). Only patients with occlusive dissection demonstrated a reduced risk of subsequent ischemic stroke when treated with anticoagulation versus antiplatelets (aHR, 0.36 [95% CI, 0.16–0.80]; P =0.01). CONCLUSIONS: In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.

Background: The safety and cost of concomitant atrial fibrillation (AF) ablation and left atrial appendage occlusion (LAAO) procedure remain unknown. Objective: The study sought to determine real-world outcomes of AF patients who underwent LAAO with ablation. Methods: The National Inpatient Sample and International Classification of Diseases–Tenth Revision codes were used to identify patients who underwent LAAO with and without AF ablation during the years 2016-2022. The outcomes assessed included procedural complications and resource utilization. Results: LAAO with AF ablation was associated with a higher rate of overall complications (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.37-1.74), major complications (OR 1.38, 95% CI 1.18-1.60), non-home discharge (OR 1.55, 95% CI 1.23-1.96), prolonged length of stay >1 day (OR 3.21, 95% CI 2.92-3.52), and increased hospitalization costs as defined by median cost >$25,926 (OR 19.42, 95% CI 16.21-23.25) when compared to LAAO alone after adjustment for potential confounding variables. Patients who underwent LAAO with ablation were also more likely to receive pacemaker implantation (3.6 % vs 0.2%, P < 0.001) and experience acute kidney injury (3.9% vs 2.1%, P < 0.001) and non-ST elevation myocardial infarction (3.7% vs 1.5%, P < 0.001). Conclusion: In a large, contemporary, real-world study of LAAO procedures in the United States, concomitant AF ablation was associated with a higher rate of overall and major complications and an increased resource utilization.

Abstract Context Research and scholarship are core drivers of medicine in the modern era. Evidence-based practice continues to replace expert opinion and long-held practice beliefs. Involvement in the development and writing of these guidelines is critical for Doctors of Osteopathic Medicine (DOs) to maintain a seat at the academic table. According to the American Osteopathic Association (AOA), 11 % of practicing physicians in the US are DOs. This number is growing, as nearly 25 % of current medical students attend an osteopathic medical school. Without involvement in guideline development, DOs risk giving up control of their own practice of medicine. Objectives To quantify the contribution of DOs to the body of literature guiding practice, author information was extracted from all US-based guidelines published in the years 2021, 2022, and 2023 listed in the Emergency Care Research Institute (ECRI) Guidelines Trust database. Methods Authors of US-based guidelines listed in the ECRI Trust database from the years 2021–2023 were counted and categorized into one of three groups based on terminal degree: MD holders, DO holders, and Other-degree holders. Authors whose degrees could not be identified were counted as “Unidentifiable.” Additional data including sponsoring organization, organization type, and specialty were collected. Results A total of 674 guidelines were published by US organizations in 2021, 2022, and 2023, with 604 reporting author information. A total of 9,376 authors were counted. Of that, 7,253 held an MD (77 %), 110 held a DO (1.2 %), and 1,848 held another terminal degree (19.7 %); meanwhile, 1.66 % of counted authors did not have an identifiable degree. A total of 604 guidelines published by US organizations were identified. Of these, 88 (14.6 %) contained at least one DO author in their author list. Sixty-two unique specialties were identified, along with 130 unique sponsoring organizations. Of those specialties, 28 (44.4 %) had at least one DO author of at least one guideline. Of 130 sponsoring organizations, 44 (33.8 %) developed at least one guideline with at least one DO author. No osteopathic sponsoring organizations were identified. Conclusions Based on these results, we conclude that DOs are underrepresented in the development of guidelines.

ABSTRACT Introduction Donation after circulatory death (DCD) allografts are underutilized in liver transplantation (LT) due to increased risk of complications. These risks stem from ischemic injury sustained during the total donor warm ischemia time (tDWIT), historically limited to 30 min. Normothermic machine perfusion (NMP) can mitigate these risks and facilitate LT of DCD grafts with extended tDWIT. We aimed to compare outcomes of DCD allografts with extended tDWIT preserved on NMP versus static cold storage (SCS). Methods This single‐center study included adult DCD LT with tDWIT ≥ 30 from 2019 to 2023. Outcomes of NMP and SCS were compared including EAD, IC, graft survival, and patient survival. Results Among 68 DCD LT with tDWIT ≥ 30, 64.7% ( n = 44) were preserved with NMP and 35.3% ( n = 24) with SCS. No differences in donor or recipient demographics were observed. The median tDWIT was 33 min for NMP and 30.5 min for SCS ( p < 0.01). Despite longer tDWIT, the NMP group had lower rates of EAD (4.5% vs. 66.7%, p < 0.01) and IC (2.3% vs. 29.2%, p < 0.01). One‐year graft survival was higher in NMP ( p < 0.01), and 1‐year patient survival was comparable between groups ( p = 0.18). Conclusion NMP challenges traditional tDWIT constraints and can increase the pool of viable DCD allografts for transplantation.

ABSTRACT Metabolic-associated steatohepatitis-driven hepatocellular carcinoma (MASH-HCC) incidence is rapidly rising worldwide. Lipid metabolic reprogramming is a hallmark of solid tumors to satisfy cancer high metabolic demand. However, it may confer sensitivity to ferroptosis, a cell death mode driven by iron-dependent lipid peroxidation. In this report, we describe the lipid metabolic landscape in MASH-HCC and characterize long chain acyl-CoA synthetases (ACSLs), a family of enzymes involved in synthesis of cellular lipids. Bulk RNA-sequencing, single-cell RNA-sequencing, spatial transcriptomics and immunohistochemistry analyses of human MASH-HCC were integrated to identify differentially expressed lipid metabolism genes. Ferroptosis in vitro was assessed in human HCC cell lines. A characterization of ACSLs was also conducted at the single-cell level in a diet-induced experimental murine model of MASH-HCC. Our analysis revealed that in human MASH-HCC, ACSLs exhibit a heterogeneous expression, with ACSL4 notably enriched in tumor tissues, contrasting with ACSL5 upregulation in non-cancerous MASH. We identified a unique lipid metabolic gene signature of MASH-HCC, which included genes associated with ferroptosis vulnerability. In vitro , ACSL4 upregulation was associated with increased ferroptosis sensitivity in human HCC cell lines. Lastly, single-cell RNA-sequencing revealed elevated ACSL4 expression in immune cells in a murine MASH-HCC model, suggesting a role of ACSL4 in shaping the tumor immune microenvironment. Overall, this report offers new insights into lipid metabolic landscape and ferroptosis sensitivity for novel MASH-HCC treatments. GRAPHICAL ABSTRACT

OBJECTIVE In this study, the authors aimed to establish a supervised machine learning (ML) model based on multiple tree-based algorithms to predict long-term biochemical outcomes and intervention-free survival (IFS) after endonasal transsphenoidal surgery (ETS) in patients with Cushing’s disease (CD). METHODS The medical records of patients who underwent ETS for CD between 2013 and 2023 were reviewed. Data were collected on the patient’s baseline characteristics, intervention details, histopathology, surgical outcomes, and postoperative endocrine functions. The study’s primary outcome was IFS, and the therapeutic outcomes were labeled as "under control" or "treatment failure," depending on whether additional therapeutic interventions after primary ETS were required. The decision tree and random forest classifiers were trained and tested to predict long-term IFS based on unseen data, using an 80/20 cohort split. RESULTS Data from 150 patients, with a median follow-up period of 56 months, were extracted. In the cohort, 42 (28%) patients required additional intervention for persistent or recurrent CD. Consequently, the IFS rates following ETS alone were 83% at 3 years and 78% at 5 years. Multivariable Cox proportional hazards analysis demonstrated that a smaller tumor diameter that could be detected by MRI (hazard ratio 0.95, 95% CI 0.90–0.99; p = 0.047) was significantly associated with greater IFS. However, the lack of tumor detection on MRI was a poor predictor. The ML-based model using a decision tree model displayed 91% accuracy (95% CI 0.70–0.94, sensitivity 87.0%, specificity 89.0%) in predicting IFS in the unseen test dataset. Random forest analysis revealed that tumor size (mean minimal depth 1.67), Knosp grade (1.75), patient age (1.80), and BMI (1.99) were the four most significant predictors of long-term IFS. CONCLUSIONS The ML algorithm could predict long-term postoperative endocrinological remission in CD with high accuracy, indicating that prognosis may vary not only with previously reported factors such as tumor size, Knosp grade, gross-total resection, and patient age but also with BMI. The decision tree flowchart could potentially stratify patients with CD before ETS, allowing for the selection of personalized treatment options and thereby assisting in determining treatment plans for these patients. This ML model may lead to a deeper understanding of the complex mechanisms of CD by uncovering patterns embedded within the data.

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) provide recommendations for the evaluation, diagnosis, and comprehensive care of patients with MDS based on a review of recent clinical evidence that has led to important advances in treatment or has yielded new information on biologic factors that may have prognostic significance in MDS. The multidisciplinary panel of MDS experts is convened at least on an annual basis. During the annual meeting, the panel evaluates new and emerging data to inform their recommendations. These NCCN Guidelines Insights review the recent updates, including treatment recommendations both for lower-risk and higher-risk MDS, preference stratification of therapeutic agents, and emerging data on novel therapeutics.

ABSTRACTIntroductionStudies demonstrate an overlap of constipation with gastroparesis and functional dyspepsia, but the impact of treatments that target constipation on improving upper gastrointestinal (UGI) symptoms is unexplored. We quantified the effects of constipation medication therapies on UGI and constipation symptom severity in subjects presenting with symptoms of gastroparesis.MethodsFifty‐six subjects with symptoms of gastroparesis underwent concurrent wireless motility capsule and gastric emptying scintigraphy and were recommended to receive either a new medication therapy for constipation or a change in constipation therapy based on investigator interpretation of test results. Gastroparesis Cardinal Symptom Index (GCSI), upper abdominal pain, and constipation scores were compared between baseline and 6 months. Data were compared between delayed or non‐delayed gastric emptying and the presence or absence of slow colonic transit.Key ResultsSubjects with slow colonic transit had improvements in GCSI (p = 0.007) and constipation scores (p = 0.004) after treatment with a new or changed constipation medication, with the delayed emptying subgroup driving GCSI improvements (p = 0.004). Reductions in nausea/vomiting (p = 0.02) and early satiety/fullness subscores (p = 0.002) with trends to improved bloating/distention subscores (p = 0.06) were observed in this subgroup, but upper abdominal pain was unchanged. Subjects with normal colonic transit showed no improvement in GCSI scores regardless of gastric emptying status (p > 0.05).Conclusions and InferencesIdentifying and treating delayed colonic transit in gastroparetic (delayed gastric emptying) subjects improves global UGI symptoms as well as selected individual symptoms. Evaluation of whole gut motility as well as recognizing and managing extragastric delay may promote improved outcomes in these patients.Trial RegistrationClinicalTrials.gov: NCT02022826

AbstractObjectiveTo assess relations between Ménière's disease and suicidality, measured by suicidal ideation, suicidal behaviors, and death by suicide.Data SourcesCINAHL, Cochrane Library, PubMed, PsycINFO, and SCOPUS databases were searched from inception through July 2, 2024.Review MethodsObservational studies related to suicidality in patients with Ménière's disease were included. Non‐English language papers, editorials, and studies on vestibular disorders not specified as Ménière's disease were excluded. The Risk Of Bias In Nonrandomized Studies‐of Exposure tool was used for cohort and qualitative studies, and the Joanna Briggs Institute critical appraisal checklist was used for case‐control studies.ResultsFour studies (n = 168,566) were included in our review. Two cohort studies found significantly increased adjusted hazard ratios of 2.1 (95% CI: 2.0‐2.2) for death by suicide and 7.6 (95% CI: 4.4‐13.3) for suicidal behaviors, respectively, in patients with Ménière's disease compared to the control population after their diagnosis. However, a case‐control study found no significant difference in the prevalence of suicidal ideation or behaviors prior to the date of diagnosis in patients with Ménière's disease compared to the control population (0.9% vs 0.8%; P = .44). In addition, one patient with Ménière's disease expressed suicidal ideation in the qualitative study.ConclusionPatients may experience variable responses to Ménière's disease. Thus, otolaryngologists should be mindful of the potential for suicidality in patients with Ménière's disease.