Citations

Abstract Background Recent trials have furthered uncertainty regarding the endovascular benefit for medium vessel occlusions (MeVO). Stent retrievers (SR) were employed in the first attempt in most interventional arm participants. We sought to compare outcomes in acute MCA M2 occlusions between frontline aspiration and SR, and to delineate procedural and anatomical covariates associated with differential treatment effect. Methods Retrospective analysis of a multicenter stroke thrombectomy cohort identified cases of MT for M2 occlusions. Unmatched and propensity score-matched (PSM) cohorts were generated comparing frontline aspiration to standalone and combined SR. The primary outcome was functional independence (mRS 0–2) at 90 days. Recanalization, symptomatic intracranial hemorrhage (sICH), mortality, and the effect of M2 laterality, division occlusion and procedure time were assessed. Results About 1734 patients with M2 occlusions underwent either frontline aspiration (n = 711) or SR/combined (n = 958) thrombectomy between 2013 and 2024. PSM analysis favored aspiration for functional independence (49.9% vs 44.0%, OR 1.27 (1.03–1.57)), complete recanalization (61.2% vs 48.7%, OR 1.66 (1.34–2.05)), complete first pass effect (35.0% vs 27.6%, OR 1.42 (1.13–1.78)), and sICH (3.5% vs 6.2%, OR 0.55 (0.33–0.91)), with no difference in mortality. Frontline aspiration had significantly shorter procedural times (median 28 [IQR 15–49.5] vs 51 [IQR 35–78] minutes; p < 0.001). For every minute increase in procedure time, the probability of functional independence decreased significantly (p < 0.001) less with frontline aspiration (0.35%) compared to SR/combined (1.61%). Conclusion Frontline aspiration for M2 occlusions resulted in better clinical and angiographic outcomes compared to SRs. Future trials for MeVO with a focus on contact aspiration thrombectomy may succeed where recent trials have failed.

Abstract Objective To develop a comprehensive risk stratification model to identify patients at high risk of cesarean surgical site infection (cSSI) based on information available at the time of hospital discharge. Methods This is a retrospective cohort study based on datasets from two independent level IV academic medical centers to improve generalizability. The first study includes 2336 cesarean deliveries for analysis with 109 instances of cSSI (4.7%). The second study includes 2936 cesarean deliveries with 72 instances of cSSI (2.5%). The first study cohort was utilized for both model training and internal validation, using the 15 shared features present in both datasets. Random search with cross‐validation was used to choose the type of machine learning (ML) model and its hyperparameters, with area under the receiver operating characteristic curve (AUC) as the validation metric. The second study cohort was then used to evaluate testing accuracy (external validation) and generalization capability of this model. The predictive importance of each feature was evaluated using permutation importance applied to the second cohort. Risk stratification cutoff scores were defined based on centiles over the first patient cohort and evaluated on the second cohort. Results The ML model with the highest validation AUC was an XGBoost classifier. This trained model achieved an AUC of 0.78 on the training data and a 0.72 cross‐validated AUC. When tested on data from the second study cohort, it achieved an AUC of 0.69. The features showing the strongest predictive generalization, as measured by permutation importance, were length of hospital stay, primary indication for cesarean delivery, and estimated blood loss. Using the second cohort to test our model, the model shows a 22.7% positive predictive value (PPV) of cSSI among women in the highest risk group, and a 0.8% PPV among women in the bottom risk group, compared with 2.5% cSSI incidence for the study population at large. Conclusion We developed and validated a predictive ML model for cSSI with information available to healthcare professionals at the time of hospital discharge. This model suggests that the most predictive risk factors for cSSI include length of hospital stay, primary indication for cesarean delivery, and estimated blood loss. Additionally, the model provides reasonable risk stratifications for individual patients. This tool may be used for identifying subgroups at higher risk of cSSI and identifying those who may require closer surveillance or clinical intervention.

Abstract Background & Aims Central reading of endoscopy and histopathology is the current standard for disease activity assessment in inflammatory bowel disease (IBD) clinical trials but is limited by interreader and intrareader variability, operational delays, and cost. Artificial intelligence (AI) and machine learning (ML) offer the potential to improve accuracy, efficiency, and reproducibility. The International Organization for the Study of IBD (IOIBD) developed consensus statements on AI/ML use for endoscopic and histologic endpoint assessment in IBD trials. Methods As part of the IOIBD endpoints cluster initiative, a narrative, evidence-informed review with literature searches of Medline and Embase (January 2018-February 2025) identified studies applying AI/ML to endoscopy or histology in IBD. Relevant evidence informed 36 survey statements formulated by a steering committee. Seventy-two IOIBD members were invited to vote online; consensus required ≥80% agreement (score: 7-10 on a 10-point scale). Results Forty-five members completed the survey. Consensus was reached for 28 statements related to endoscopy, pathology, and trial design. Experts agreed that AI-based central reading could improve diagnostic accuracy, expedite processes, reduce costs, and enhance reproducibility. Combining human and AI assessments was favored over AI replacement. The key limitations identified included insufficient validation, generalizability concerns, and dependence on human-annotated training datasets. Conclusions This IOIBD consensus supports the integration of AI/ML into central reading for IBD clinical trials to improve objectivity, efficiency, and consistency, while maintaining human oversight. Further research should address validation, regulatory frameworks, and multimodal integration to enable broader adoption in both trials and clinical practice.

Abstract Background Intracranial mesenchymal tumors, FET::CREB fusion-positive (ICMT), show fusions involving FET RNA-binding protein family genes (EWSR1 or FUS) and CREB family of transcription factors (ATF1, CREB1, or CREM). The methylation signature(s), gene expression characteristics, and clinical behavior of this important tumor type require further characterization. Methods We study the methylation profiles of 81 ICMT cases (61 newly profiled cases and 20 cases from publicly available sources). Clinicopathologic and genomic data were recorded for each case when available. Results ICMT showed a relatively distinct methylation signature compared to related tumors. Among the 65 cases where fusion types were documented, the identified fusions included EWSR1::ATF1 (25 cases), EWSR1::CREB1 (12 cases), EWSR1::CREM (21 cases), FUS::CREM (3 cases), and SMARCA2::CREM (4 cases). We confirmed the prior description of 2 distinct subgroups of ICMT (subclasses A and B). The majority of the cases belonged to subclass A (n = 69; 85%), which showed a higher median age compared to subclass B patients (26 years vs. 15 years). Subclass B cases (n = 12; 15%) showed shorter progression-free survival (P < 0.01). Gene expression analysis of ICMT showed key overexpressed markers in ICMT, with significant CREM overexpression regardless of fusion type, when compared to either meningioma alone or a larger group of CNS tumors. Conclusions This work provides further characterization of ICMT as an important CNS mesenchymal neoplasm that is prone to tumor recurrence, showing 2 prognostically relevant methylation subclasses and warranting diagnostic distinction from other epigenetically and histologically related tumors. ICMTs show substantial overexpression of the CREM gene, independent of fusion type.

This scientific commentary refers to ‘Pure autonomic failure: a natural history study of the Queen Square cohort’ by Chiaro et al. (https://doi.org/10.1093/brain/awaf191).

Abstract Objective: Outpatient parenteral antimicrobial therapy (OPAT) is a mainstay of clinical infectious diseases practice, and OPAT-related publications continue to be prominent in journals. The objective of this article is to summarize ten clinically important OPAT-related publications from 2024. Design: Narrative review. Methods: Eighty-one articles were found in a literature search, and 56 met inclusion criteria. A survey containing 25 articles was sent to an email listserv of clinicians with OPAT experience. Results: This article summarizes the top 10 OPAT articles published in 2024, based on those survey results. Conclusions: Common themes from the top 10 OPAT articles published in 2024 included OPAT clinician workload, patient perspectives of OPAT, tools for OPAT work, and dalbavancin use.

162 Background: In preclinical studies, the tryptophan-metabolizing enzyme, Indoleamine 2, 3-dioxygenase 1 (IDO1), promotes resistance to radiation in colorectal cancer, and IDO1 inhibition with epacadostat improves tumor radiosensitivity. In a phase 1 trial, patients (pts) with locally advanced rectal cancer (LARC, n=17) were treated with epacadostat in combination with short course radiotherapy (SCRT) and CAPOX which was well-tolerated, and the recommended phase 2 dose (RP2D) of epacadostat was 400mg BID. Here we report efficacy and safety from the NCI-supported phase 2 (NCT03516708) multicenter, open-label trial (treatment cohort). Methods: Pts were treated with standard of care (SOC) SCRT, then SOC neoadjuvant chemotherapy (NAC) followed by SOC surgical resection or non-operative management (NOM). Epacadostat (400 mg BID) started with SCRT and continued until starting NAC (a minimum of 21 days). Eight pts were enrolled prior to discontinuation of epacadostat by Incyte in February/March 2025. The primary endpoint is Neoadjuvant Rectal (NAR) score. In patients who underwent NOM, we calculated MRI-based tumor regression grade (MR-TRG). Secondary endpoints are pathologic complete response (pCR) rate, complete clinical response (cCR) rate, and progression free survival (PFS). Results: Table 1 summarizes baseline characteristics and endpoints (primary and secondary). NOM was pursued in 7/8 (87.5%) pts, surgical resection was performed on 1/8 (12.5%). At median follow-up of 12 months, local tumor regrowth occurred in 1 pt initially treated with NOM (after tumor regrowth, he underwent salvage surgery and is currently on surveillance). Treatment with epacadostat was interrupted in 2/8 (25%) patients due to grade 3 maculopapular skin rash. Most frequent treatment-emergent adverse events (TEAEs) regardless of causality (all grades (G)/G3-4) were bloating (75%/0%), increased ALT (62.5%/0%), increased AST (50%/0%), nausea (50%/0%), and constipation (50%/0%). Grade 3 diarrhea and grade 3 non-cardiac chest pain occurred in 1 patient each (both unrelated to epacadostat). Conclusions: Epacadostat demonstrates promising efficacy and manageable safety in patients with LARC. The biomarker cohort and correlative studies are ongoing. Clinical trial information: NCT03516708 . Baseline characteristics and endpoints. Patient Age Sex Ethnicity Stage Surgery/NOM NAR MR-TRG cCR/pCR Recurrence 1 52 M Caucasian T3N1 NOM NA 2 Y/NA No 2 45 M Caucasian T3N1 NOM NA 3 Y/NA Local tumor regrowth 3 48 M Caucasian T3N2 NOM NA 3 Y/NA No 4 61 M Caucasian T4N2 NOM NA 3 Y/NA No 5 57 M Caucasian T3N0 NOM NA 1 Y/NA No 6 60 F Caucasian T3N1 Surgery 15 3 N/ypT3N0 No 7 67 M Caucasian T4N0 NOM NA 3 Y/NA No 8 51 M Caucasian T4N2 NOM NA P NA No

BACKGROUND: Patients with cervical artery dissection (CeAD) may experience a recurrent dissection, but its frequency, risk factors, and clinical implications are not well defined. We aimed to determine the risk, associated factors, and clinical impact of recurrent CeAD. METHODS: The STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection) was a multicenter international retrospective observational study of patients with CeAD treated between January 2015 and June 2022. Recurrent dissection was defined as a CeAD occurring at least 7 days after the diagnosis of the index event that affects a different artery or a different segment of the same artery. Patients were followed from day 7 up to 2 years. The absolute risk of recurrent CeAD over time was calculated using Kaplan-Meier survival estimates. Multivariable logistic and Cox regression models were used to assess predictors of CeAD recurrence. RESULTS: Of the 4023 patients included in STOP-CAD, 3836 (median age 46 years, 45% women) were eligible for this analysis. During a median (interquartile range) follow-up of 295 (97–720) days, 88 (2.29%) patients had a CeAD recurrence. Median time-to-recurrent CeAD was 53 (interquartile range, 18–157) days. The estimated risk of recurrent CeAD at 2 years was 3.22% (95% CI, 2.59%–4.00%). In multivariable analyses, younger age (adjusted odds ratios, 0.98 [95% CI, 0.96–0.99]), migraine (adjusted odds ratio, 1.88 [95% CI, 1.14–3.07]), and fibromuscular dysplasia (adjusted odds ratio, 2.90 [95% CI, 1.66–5.06]) were associated with CeAD recurrence, while presenting with an ischemic stroke was associated with a lower likelihood of recurrence (adjusted odds ratio, 0.47 [95% CI, 0.29–0.75]). These associations with CeAD recurrence over time were confirmed by Cox regression analyses. Among the 88 patients with recurrent CeAD, only 5 had accompanying ischemic events (3 strokes, 2 transient ischemic attacks). CONCLUSIONS: In this retrospective study, recurrent CeAD was uncommon, approximately half of the events were diagnosed within the first 2 months of the index event, and recurrent events rarely caused new ischemic events. Younger age, migraine, absence of ischemic stroke at presentation, and signs of fibromuscular dysplasia may help identify high-risk patients.

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) practice has continued to increase. We sought to understand current OPAT practices in a survey of U. S. clinicians.Figure 1Respondents rated their agreement with the following statement: “The OPAT program at my hospital receives adequate support in the following areas”Figure 2Factors present in providing safe OPAT services on a scale where 1 is “extremely challenging” and 5 is “not challenging at all” Methods A survey instrument was developed by ID physicians, pharmacists and Infectious Diseases Society of America (IDSA) Emerging Infections Network (EIN) staff, utilizing prior EIN OPAT surveys. The survey focused on respondents’ role, responsibilities, time devoted to OPAT, structure of OPAT provision, location where OPAT is received, institutional support and oversight, role of complex outpatient antimicrobial therapy (COpAT) including oral antimicrobials and long-acting injectable agents, and barriers to safe OPAT care. The confidential survey was distributed to adult EIN members from Feb to March 2025. Results Overall, 622 (38%) EIN members responded to the survey, of whom 469 with a role in managing OPAT patients were eligible to complete the survey. OPAT teams varied across programs with nearly all involving ID physicians (98%), majority involving ID/OPAT pharmacists (61%), nurses (60%), and nearly half involving administrative staff (48%) and advanced practice providers (APPs, 47%). ID consultation for OPAT enrollment was required in 60% of programs. Many programs (59%) report including COpAT. Response to outpatient lab results was largely managed by ID physicians (75%); however, multidisciplinary OPAT teams (37%), pharmacists (33%), and inpatient ID physicians (30%) were also frequently involved. Lab values were most often available via fax/email (43%) or electronic health record (EHR, 41%). Nearly 25% of programs “often/always” required proactive outreach to obtain safety labs. Overall, many programs lacked data analysis, administrative, information technology, and financial support (Figure 1). Challenges faced by OPAT programs included lack of leadership awareness of the value of OPAT (51%), difficulty managing patients with substance use disorder (50%), access to timely lab values (48%), personnel to retrieve missing lab values (46%), and struggles with the EHR (43%) (Figure 2). Conclusion Compared to EIN OPAT surveys in 2013 and 2019, programs have grown in size and composition, and expanded to COpAT. Similar problems persist regarding perceived lack of support. Disclosures Monica V. Mahoney, PharmD, BCPS, BCIDP, FCCP, FIDSA, FIDP, FMSHP, gsk: Advisor/Consultant|seqirus: Advisor/Consultant Philip M. Polgreen, MD, Eli Lily: Advisor/Consultant|Pfizer: Grant/Research Support Sara C. Keller, MD, MPH, MSPH, CorMedix: Grant/Research Support

ABSTRACT Obstructive sleep apnea (OSA) is a common, heritable disorder with diverse clinical presentations and etiologies. We conducted a genome-wide association meta-analysis of 492,107 individuals, including 46,028 OSA cases, identifying 14 genome-wide significant loci, eight of which are novel. Analyses adjusting for body mass index (BMI) revealed three loci independent of obesity, implicating alternative biological pathways contributing to disease. Integrative functional analyses, including chromatin interaction mapping, fine-mapping, and eQTL colocalization, prioritized candidate effector genes. Notably, implicated genes in chondrocytes were associated with craniofacial morphology in both mouse and human multivariate genotype-phenotype mapping, supporting a role for craniofacial structure in OSA risk. These findings highlight key genetic pathways (obesity-related, neurological, and craniofacial) underlying the development of OSA, offering new insights into its complex etiology.