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Importance The choice of induction agent during rapid sequence intubation (RSI) of critically ill adults may affect clinical outcomes. Although ketamine and etomidate are frequently used for RSI, their comparative effectiveness remains controversial. Objective To compare the safety of etomidate vs ketamine for emergency RSI in critically ill adults. Design, Setting, and Participants This cohort study used a target trial emulation with observational data collected between March 1, 2022, and April 30, 2024, from 18 emergency departments across Brazil, with data from the Brazilian Airway Registry Cooperation. Adults who underwent RSI and received either etomidate or ketamine as a sole hypnotic agent were included; those with preintubation cardiac arrest or immediate postintubation transfer were excluded. Exposure Administration of etomidate or ketamine as the induction agent for RSI. Main Outcomes and Measures The primary outcome was 28-day in-hospital mortality. Secondary outcomes included 7-day in-hospital mortality, first-attempt intubation success, and major adverse events (new hemodynamic instability, severe hypoxemia, and cardiac arrest) within 30 minutes after intubation. Inverse probability of treatment weighting was used to adjust for confounding. Risk ratios (RRs) and risk differences (RDs) with 95% CIs were used to compare outcomes between groups. Results Among 1810 patients (median age, 64 years [IQR, 50-74 years]; 1048 men [57.9%]), 514 received ketamine and 1296 received etomidate. The median shock index was higher in the ketamine group than the etomidate group (0.81 [IQR, 0.65-1.01] vs 0.76 [IQR, 0.59-0.99]), and preintubation vasopressor use was more common in the ketamine group than the etomidate group (191 of 514 [37.2%] vs 391 of 1296 [30.2%]). Weighted 28-day mortality was higher with etomidate than ketamine (60.5% [95% CI, 57.2%-63.8%] vs 54.4% [95% CI, 45.0%-63.9%]; RR, 1.14 [95% CI, 1.03-1.27]; RD, 7.6% [95% CI, 2.0%-13.3%]). Seven-day mortality was also higher with etomidate than ketamine (35.2% [95% CI, 32.0%-38.3%] vs 30.1% [95% CI, 23.5%-36.7%]; RR, 1.19 [95% CI, 1.04-1.35]). New hemodynamic instability within 30 minutes after intubation was more frequent with ketamine (24.2% [95% CI, 20.4%-28.0%] vs 18.9% [95% CI, 16.7%-21.0%]; RR, 0.78 [0.64-0.95]). There were no statistically significant differences in the other secondary outcomes. Conclusions and Relevance In this cohort study of critically ill adults undergoing RSI, etomidate use was associated with higher in-hospital mortality at 7 and 28 days compared with ketamine. These findings highlight the need for definitive randomized clinical trials to compare both agents.

Abstract Introduction While most patients with Peyronie’s disease (PD) present with dorsal or lateral curvature, a significant number have ventral curvature (VC). These patients face limited treatment options, as they were excluded from initial clinical trials of collagenase clostridium histolyticum (CCH) due to safety concerns related to the proximity of the injection site to the urethra. However, urethral involvement is rare, as PD plaques develop in the tunica albuginea rather than the corpus spongiosum surrounding the urethra. Moreover, multiple prospective and retrospective studies have demonstrated favorable outcomes with CCH treatment in men with VC. Objective To evaluate the effectiveness and safety of CCH in men with PD and VC in a multicenter, real-world, retrospective study. Methods This is an ongoing phase 4, multicenter, retrospective review of medical records from 15 US physician sites. Eligible patients consisted of patients who are: age ≥18 years with a diagnosis of VC in PD with a palpable plaque that was treated with CCH from 2014 to the study start date at each site. Patients missing baseline (BL; pretreatment) or final (last measurement within 6 months of final CCH treatment) penile curvature measurements were excluded. Effectiveness endpoints included percentage change in VC from BL to last visit, mean change in VC (in degrees) from BL to last visit, and proportion of patients with ≥30% improvement in VC from BL to last visit. Safety was assessed as proportions of patients reporting treatment-related adverse events (TRAEs) throughout the study period. Results As of April 22, 2025, there were 116 patients with mean (SD) age of 58 (10.3) years who were eligible for analysis. Mean baseline VC decreased from 58 degrees to 37 degrees at last visit (37% improvement). An improvement in VC of ≥30% was seen in 73/116 (63%) of patients, with 81/116 (69.8%) experiencing ≥20% improvement. At least 1 TRAE was reported by 12 (10%) patients. TRAEs were mild-to-moderate in severity in 9 (75%) patients and unknown in 3 patients, with most events (14/17 [82%]) related to injection site reactions. As of the data cut, there were no treatment-related serious or treatment-related severe AEs, no reports of urethral involvement or injury, and no reports of corporal rupture. Conclusions Men with PD who present with ventral curvature represent an underserved patient population. Concerns about potential urethral injury pose a significant barrier to both minimally invasive and surgical treatments, thereby limiting available therapeutic options. These updated results from a multi-institutional real-world clinical cohort align with previous findings, and demonstrate that the clinical effectiveness and safety profile of CCH is consistent with the profile of CCH seen in other clinical presentations of PD. Disclosure Yes, this is sponsored by industry/sponsor: Endo USA, Inc Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo USA, Inc.

BACKGROUND AND OBJECTIVES: Preventive treatment of unruptured intracranial aneurysms (UIAs) requires assessment of treatment risks vs expected benefit. Although established scores exist to estimate rupture and growth risk, currently, no externally validated tools exist to estimate the risks of microsurgical treatment of UIAs. Clinical prediction models based on machine learning enable generation of personalized risk estimates for each individual patient based on their specific patient and aneurysm characteristics. METHODS: Using data from 20 international centers from the prediction of adverse events after microsurgery for intracranial unruptured aneurysms study on patients treated microsurgically for UIAs, we developed and externally validated clinical prediction models for 3 outcomes measured at hospital discharge: poor neurological outcome (modified Rankin Score ≥3), new sensorimotor neurological deficits, and all-cause adverse events (Clavien-Dindo Grade ≥1). RESULTS: A total of 3705 patients were included. Data from 13 centers (2881, 78%) were used for model development. Fully trained models were evaluated on 824 patients (22%) from 7 additional centers. Average age was 56 ± 12 years, and 1049 (28%) were male. At discharge, poor neurological outcome was seen in 514 patients (14%). New sensorimotor deficits were observed in 534 patients (14%), and 894 patients (24%) experienced adverse events until discharge. At external validation, prediction of poor neurological outcome was achieved with good calibration and an area under the curve (AUC) = 0.70 (95% CI: 0.63-0.75). Similarly, new neurological deficits were predicted with good calibration and with an AUC = 0.69 (95% CI: 0.63-0.74). Prediction of all-cause adverse events only achieved an AUC = 0.59 (95% CI: 0.55-0.64) with fair calibration. The prediction model was integrated into a web application accessible at https://neurosurgery.shinyapps.io/PRAEMIUM/. CONCLUSION: The developed models for prediction of poor neurological outcome and new sensorimotor neurological deficits at discharge exhibit good calibration and fair discrimination based on a multinational external validation, indicating that the predicted probabilities correspond well to real-world risks and may thus be clinically useful in more objectively estimating the risk of microsurgical treatment.

Background Contact aspiration remains a frontline approach for mechanical thrombectomy (MT) in acute ischemic stroke (AIS). Early evidence correlates catheter size with procedural efficiency and clinical outcomes. Larger‐bore (LB) aspiration catheters may enhance clot ingestion, increase aspiration force, and facilitate faster and more complete recanalization. However, the transition from standard LB catheters (0.068‐0.072″) to super‐large‐bore (SLB, ≥0.080″) devices has raised questions regarding both safety and clinical benefit. Although the use of SLB catheters is increasing, comparative data on their performance versus LB catheters remain limited. This study aims to evaluate the safety and efficacy of SLB compared with LB catheters including data from a large multicenter international registry. Methods We retrospectively analyzed patients with AIS due to LVO treated at 46 international stroke centers between January 2013 and June 2025. Among eligible patients, propensity score matching (PSM) at a 5:1 ratio was used to balance baseline characteristics between those treated with standard LB catheters and those treated with SLB catheters. Safety endpoints included intraprocedural complications, symptomatic intracranial hemorrhage (sICH), distal embolization, and 90‐day mortality. Efficacy endpoints included functional independence at 90 days (modified Rankin Scale [mRS] 0‐2), successful recanalization (TICI ≥2b), first‐pass effect (TICI ≥2b on the first aspiration attempt), and procedural timing to TICI2b. Results A total of 3,100 patients were included (LB n=3,024; SLB n=67). After PSM (LB n=335; SLB n=67), safety outcomes were comparable between groups in terms of intraprocedural complications occurred (p=0.5), sICH (p>0.9), embolization to new territory (p=0.2), and 90‐day mortality (p>0.9). Efficacy outcomes were similarly consistent for functional independence (mRS 0‐2) (p>0.9), successful recanalization (p>0.9), first‐pass effect (p=0.5), and time to TICI ≥2b (27.6 vs. 24.5 minutes; p=0.9). These findings remained consistent in the subgroup with ICA and M1 occlusions, with no significant differences in safety (intraprocedural complications [p=0.4], sICH [p>0.9], embolization to new territory [p=0.6], or 90‐day mortality [p>0.9], nor in efficacy outcomes (functional independence at 90 days [p>0.9], successful recanalization [p=0.9], first‐pass effect [p=0.6], and time to TICI ≥2b [p=0.9]). Conclusion In this large multicenter analysis, the use of SLB aspiration catheters demonstrated comparable safety and efficacy to standard LB catheters for MT in AIS. Despite theoretical advantages in aspiration dynamics, SLB devices did not confer significant procedural or clinical benefit over LB catheters. These findings suggest that while SLB catheters are a feasible alternative, technical and clinical outcomes remain comparable to LB catheters. Further prospective studies are warranted to clarify potential clinical advantages. image

OBJECTIVE Objective values on procedural risk are essential to facilitate informed consent and optimize clinical decision-making in patients with unruptured intracranial aneurysms (UIAs). While robust heuristics, such as the PHASES (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage, and site of aneurysm) score, are established for predicting rupture risk, contemporary and granular benchmarks for procedural safety remain scarce. The multinational Prediction of Adverse Events After Microsurgery for Intracranial Unruptured Aneurysms (PRAEMIUM) study aims to comprehensively characterize contemporary adverse event rates following microsurgical treatment at high-volume expert centers, stratified by aneurysm location, morphology, and complexity factors to better inform individual risk/benefit analyses. METHODS A cohort study among 20 participating expert centers from 9 countries was established. Patients treated microsurgically for UIAs were included. The authors describe the epidemiology of treated patients and UIAs and a comprehensive adverse event profile using 3 outcomes measured at hospital discharge: 1) poor neurological outcome (modified Rankin Scale score ≥ 3), 2) new sensorimotor neurological deficits, and 3) all-cause adverse events (Clavien-Dindo grade ≥ 1). Subgroup reports were given for aneurysm location, morphology, and complexity factors (prior aneurysm treatment, calcifications, complex angioanatomy involving critical branch vessels or perforators, and thrombosis). The authors purposely chose discharge as the time point to capture early postoperative risks and complications in patients with asymptomatic UIAs, for whom preserving neurological function is paramount. RESULTS The cohort included 3705 patients (mean age 56 [SD 12] years, 28% male). Overall, at discharge 13.9% of patients (95% CI 12.8%–15.0%) had poor neurological functional outcomes, 14.4% (95% CI 13.3%–15.5%) had new sensorimotor deficits, and 24.1% (95% CI 22.8%–25.5%) experienced all-cause adverse events. Poor neurological outcomes ranged from 8.5% (M1 aneurysms) to 37.4% (posterior circulation aneurysms), neurological deficits from 9.3% (distal anterior cerebral artery [ACA] aneurysms) to 34.2% (posterior circulation aneurysms), and all-cause adverse events from 21.2% (distal ACA aneurysms) to 31.3% (posterior circulation aneurysms). Dissecting and fusiform aneurysms showed notably high rates of poor neurological outcomes (22.0%–33.3%), new deficits (25.4%–26.7%), and adverse events (26.7%–37.0%). Complexity factors significantly influenced outcomes, with prior treatment (22.9%, 19.7%, and 30.1%), calcification (16.3%, 18.1%, and 30.5%), complex angioanatomy (13.1%, 15.9%, and 26.9%), and thrombosis (19.6%, 23.9%, and 39.6%) notably increasing the risks for poor neurological outcomes, deficits, and adverse events, respectively. CONCLUSIONS This large international cohort provides contemporary benchmarks for microsurgical treatment of UIAs, emphasizing variability in outcomes based on aneurysm location, morphology, and complexity. The presented granular and quotable adverse event rates support informed patient counseling and individualized risk/benefit assessments in comparable high-volume centers.

Objective To assess the impact of renal replacement therapy in people with lupus nephritis (LN)–associated end‐stage kidney disease (ESKD) and support the development of the 2024 American College of Rheumatology LN treatment guidelines. Methods We conducted a systematic literature review and meta‐analysis to address three Population, Intervention, Comparison, and Outcome (PICO) questions related to renal replacement therapy for ESKD due to LN, including comparisons of kidney transplant versus dialysis, hemodialysis versus peritoneal dialysis, and preemptive kidney transplant versus no preemptive kidney transplant. Outcomes of interest included mortality, cardiovascular (CV) events, infections, lupus flares, disease‐related damage, graft failure, and quality of life. We conducted a meta‐analysis and analyzed hazard ratios for time‐to‐event analyses and risk ratios for dichotomous outcomes, as well as absolute risk estimates. Results Sixteen comparative observational studies addressed at least one of the three PICO questions. Kidney transplant was found to reduce the risks of all‐cause mortality, CV mortality, infection‐related mortality, and CV events compared with dialysis (high certainty). Dialysis modality (peritoneal vs hemodialysis) was not associated with mortality (high certainty) or with other outcomes of infection, CV complications, and systemic lupus erythematosus flares (low certainty). Preemptive kidney transplant was associated with lower risks of graft failure and mortality (low certainty). Conclusion This systematic review identified improved outcomes with kidney transplant versus dialysis for people with LN‐associated ESKD and potential benefits of preemptive kidney transplant. This evidence supports the use of kidney transplant as a preferred renal replacement therapy for people with LN‐ESKD.

Background Spontaneous intracranial hypotension (SIH) results from cerebrospinal fluid (CSF) leakage due to spinal dural tears or CSF–venous fistulas. Orthostatic headache is the hallmark presentation, though severe downward displacement of the brainstem may lead to altered consciousness or coma. Definitive treatments include targeted epidural blood patches, venous embolization, or surgical repair. Methods This article reviews the role of the Trendelenburg position as a temporizing measure in the acute management of SIH. We describe the correct technique, physiologic rationale, and practical considerations for its application, with attention to both therapeutic and diagnostic utility. Discussion Positioning the patient with the feet elevated above the head can reduce brain sag and provide short-term symptomatic relief while awaiting definitive treatment. Although the Trendelenburg position is widely used in practice, supporting evidence remains limited, and clinicians must be aware of its benefits, indications, and inherent limitations. Its appropriate application may assist in stabilizing patients with acute or severe SIH, particularly those with impaired consciousness, until more definitive interventions are pursued.

Abstract Case Description: A 73-year-old female with history of stage IIIC high-grade mixed endometroid and serous ovarian cancer in remission presented with lower extremity weakness and paresthesias for several months ultimately wheelchair bound by presentation. Her exam was notable for severe proximal greater than distal lower extremity weakness, allodynia, absent patellar and Achilles reflexes, and diminished vibration and pinprick sensation. MRI demonstrated symmetric enhancement of the spinocerebellar tracts in the lateral cord from T6-T9. EMG showed a length-dependent axonal predominant sensorimotor neuropathy. The differential included metabolic, paraneoplastic, or inflammatory etiologies of her myelopathy. CSF studies revealed TNCs 30, elevated kappa free light chain, and negative cytology. Autoimmune/paraneoplastic myelopathy panels were negative. With her past history of cancer, FDG PET performed showed a right hypermetabolic chest wall and upper abdominal mass. Core needle biopsy demonstrated recurrence of high-grade carcinoma of mullerian origin consistent with recurrence of ovarian cancer. Her in-hospital treatment included 5 days of 1g IV methylprednisolone and seven sessions of PLEX. Her exam improved following PLEX with improvements in strength, sensation, and neurogenic bowel and bladder. She also started Carboplatin and Doxorubicin chemotherapy prior to discharge. She continued 60mg prednisone after discharge. She unfortunately had many hospitalizations for infections and anemia impacting her neurological recovery and strength has declined. Discussion: This case illustrates an interesting case of paraneoplastic myelopathy as the presenting symptom for relapsed ovarian cancer previously in remission for more than 10 years. The case shows the importance of keeping a paraneoplastic process on the differential when imaging findings and clinical syndrome are consistent with a paraneoplastic myelopathy even though the patient did not have a known, active cancer or positive antibodies identified. The work-up for malignancy is crucial as cancer-specific therapy is needed for hopeful symptom improvement.

Abstract Berubicin is a unique anthracycline engineered to have the ability to cross the blood-brain barrier (BBB). Herein we present the primary results from a large global trial of Berubicin vs. Lomustine randomizing patients with progressive disease after only one prior therapy, all being IDH WT and stratified for MGMT methylation. The primary endpoint was overall survival (OS), secondary endpoints included progression-free survival (PFS), overall response rates (ORR) of complete (CR) and partial (PR) responses. Eligibility was determined radiologically by central reads based on progression of disease, and in 2.5 years 252 patients were enrolled with 168 randomized to Berubicin and 84 to Lomustine. Safety assessment showed that Berubicin was well tolerated and myelosuppressive side effects were manageable with growth factors. Importantly, although anthracyclines are known to cause cardiotoxicity, evaluation with frequent troponin measurements, ECG and ECHO testing revealed no evidence of impact on cardiac function. The primary endpoint, OS, showed Berubicin and Lomustine had similar outcomes. Median overall survival for Berubicin was 8.7 months (6.7, 9.9) and for Lomustine was 9.3 months (6.7, 10.7) with a Hazard Ratio of 1.13 (p = 0.5351). PFS of Berubicin and Lomustine were also similar (1.5 vs, 1.6 months). There were no responses in the Lomustine arm and stable disease in 35.2% of patients while Berubicin had a response rate of 5.8% (PR) and stable disease of 33.6% with a combined disease control rate (DCR) of 39.4%. Additional data will be presented and discussed. Anthracyclines are characteristically used in combination for systemic therapy (e.g. leukemia, lymphoma, certain breast cancers), so there is promise that combination therapy will be the next pertinent approach to treatment of GBM. Evaluation of activity against a range of pediatric brain tumors is being pursued and preliminary results will be presented at the time of the conference.