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Abstract Objective This study was undertaken to examine acute and chronic electroencephalographic (EEG) and seizure characteristics in new onset refractory status epilepticus (NORSE). Methods Multicenter inpatient and follow‐up clinical and EEG data were analyzed using International League Against Epilepsy definitions and American Clinical Neurophysiology Society (ACNS) EEG terminology. Results Forty‐four patients were included from the Yale NORSE/FIRES Biorepository (median age = 29 years, 33 female, 38 cryptogenic). Nine hundred twenty inpatient EEG days were reviewed (median = 13.5 days/patient). Presenting status epilepticus (SE) types included 24 convulsive SE (CSE), five focal–motor (FMSE), and 15 nonconvulsive (NCSE). Of 39 patients with post discharge follow‐up (median = 14.7 months), 61.5% ( n = 24) had seizures and required more antiseizure medications than seizure‐free patients (median = 4 vs. 1, p < .001). Inpatient EEG captured epileptiform discharges in all and periodic discharges in 38 patients. Seizures were captured in 38 patients: 33 electrographic (11 only electrographic) and 27 electroclinical. Total seizure burden ranged 6.5–29 615.0 min (median = 50.7). Seizures fulfilling ACNS EEG criteria for SE were captured in 20 patients; two had CSE and the remainder NCSE with coma, nine of whom also had FMSE. Inpatient seizure days (median = 50.0 vs. 15.5%, p = .004) and seizure burden (median = 42.9 vs. 0 min, p = .009) were higher in the first half of monitored days. Interictal findings were equally present and did not predict postdischarge seizures, whereas electroclinical seizures (90.9% vs. 45.5%, p = .037), seizure burden (median = 116.8 vs. 32.5 min, p = .045), and proportion of seizure days (36.3% vs. 20.0%, p = .037) did. Among 12 patients with follow‐up EEGs (median = 19.6 months post onset), posterior‐dominant rhythm (PDR) returned in nine; five had periodic discharges, and three had seizure captured. Significance Seizures are most commonly convulsive upon presentation and nonconvulsive or clinically subtle throughout the inpatient course in NORSE. Inpatient seizures, but not interictal abnormalities, occur earlier in the inpatient course and presence of electroclinical seizures, seizure burden, and proportion of seizure days but not interictal findings are associated with postdischarge seizures. Although return of PDR reflects neurological recovery, seizure persistence and EEG abnormalities post‐NORSE are common.

Myths and misconceptions about the evaluation and treatment of constipation persist. Many widely prevalent misconceptions about laxatives, specifically stimulant laxatives, interfere with the effective management of constipation. Although some of these myths and misconceptions have been dispelled in recent years, there is additional room for improving the awareness and understanding of the pathophysiology of constipation, the mechanisms of action and the efficacy and safety of available therapies. An evolution in our understanding of pathophysiology and the availability of new treatments requires that primary care practitioners be better positioned to treat this common disorder that reduces patients’ quality of life and negatively impacts the healthcare system. This review defines constipation and elucidates various factors that contribute to its aetiology, including lifestyle, dietary habits, medications and underlying medical conditions. This review addresses and refutes common myths and misconceptions about constipation, such as the belief that regular bowel movements must occur daily or the use of laxatives leads to dependence. This review also highlights the importance of distinguishing between normal and abnormal bowel habits and emphasises the need for individualised management approaches to address constipation effectively. Finally, the review discusses different classes of laxatives, dispelling misconceptions about their safety, efficacy and potential for misuse, with a specific focus on stimulant laxatives. In summary, this review enhances awareness and knowledge of this prevalent disorder, provides evidence-based insights into common myths and misconceptions surrounding constipation and promotes more informed decision-making regarding constipation and the use of laxatives.

Abstract Roux‐en‐Y gastric bypass (RYGB) surgery is a highly effective technique for treating obesity. However, it may result in nutritional deficiencies. Here we report the case of a 55‐year‐old woman presenting with chronic diarrhea lasting 2 years, accompanied by lower limb paresthesia, macrocytic anemia, leukopenia, and thrombocytopenia. Her medical history included hypothyroidism treated with levothyroxine, and RYGB surgery performed in 2014, with intermittent micronutrient supplementation. The patient developed copper and zinc deficiencies. To our knowledge, this is the first report of a patient presenting with both deficiencies simultaneously with pancytopenia 10 years after RYGB. This case underscores the need to verify adherence to existing preoperative screening recommendations involving preoperative micronutrient measurements to assess micronutrient deficiency risks and multidisciplinary postoperative follow‐up, the importance of monitoring micronutrient levels, close follow‐up of both symptomatic and asymptomatic patients and evaluating adherence to supplementation regimens.

Importance Clinical trials in cardiovascular medicine aim to deliver high-quality evidence with greater efficiency, including smaller sample sizes and shorter timelines. The selection of sensitive and reliable end points is central to this goal. Right ventricular (RV) structure and function play a critical role in many cardiovascular conditions; however, RV-specific parameters remain underused and inconsistently applied in interventional clinical trials. In this article, the current and emerging role of RV-focused imaging and hemodynamic parameters as end points in clinical trials are explored and a comprehensive framework for their development, validation, and broader implementation is proposed. Observations Across multiple disease domains, RV-focused parameters derived from echocardiography, cardiac magnetic resonance imaging, computed tomography, and right-sided heart catheterization demonstrate potential value in assessing the therapeutic effects of new medicines or devices across a wide range of conditions including heart failure, cardiomyopathies, valve diseases, pulmonary hypertension, and congenital heart conditions. However, their use is inconsistent, and feasibility challenges are common, particularly in multicenter clinical trial settings. Key limitations include variability in imaging acquisition, incomplete data capture, lack of standardized protocols, and insufficient validation linking short-term RV changes to long-term clinical outcomes. Emerging tools such as artificial intelligence may improve reproducibility and efficiency, while collaborative, multidisciplinary efforts are essential for advancing end-point development. Conclusions and Relevance RV-specific end points hold substantial promise for enhancing the sensitivity and mechanistic insight of clinical trials but remain inadequately integrated into current practice. Optimal end-point selection requires balancing clinical relevance, analytical validity, and operational feasibility, with consideration of disease-specific pathophysiology and trial design. Standardization of acquisition, validation of clinically meaningful changes, and centralized data analysis are important next steps. Broader adoption of robust RV metrics supported by technological innovation and cross-sector collaboration has the potential to improve trial efficiency, accelerate therapeutic development, and ultimately enhance patient outcomes.

Abstract Background In children with non-metastatic atypical teratoid/rhabdoid tumor (ATRT), proton therapy is increasingly utilized worldwide due to the radiosensitivity of afflicted young patients. General questions persist, however, surrounding dose and volume of radiotherapy. Methods Between 2009-2024, 39 children from a single institution with non-metastatic intracranial ATRT received focal proton therapy at a median age of 2.4 years (range 0.7-19). Twenty-two patients had supratentorial tumors and 27 had gross/near total resection prior to radiation. Most common chemotherapy regimens were ACNS0333 and SJYC07 (n = 10 each) and Dana-Farber (n = 6). Four patients received consolidative high-dose chemotherapy after radiation. The median radiation dose was 50.4 Gy (range, 50.4-54). The cumulative incidence method assessed freedom from selected endpoints.The Fine-Gray method assessed the level of statistical significance between levels of selected prognostic factors. Results With a median followup of 5.2 years (range 0.5-16.2), the 5-yr overall survival, progression-free survival, and local control was 63%, 64%, and 97%, respectively. Thirteen patients developed isolated leptomeningeal failure as first site of recurrence. Only subtotal resection was significantly associated with local recurrence (100% vs 92%, p &lt; 0.05). Patient age, tumor site, extent of resection, radiation dose, and chemotherapy regimen were otherwise not significantly associated with disease control or survival. Four patients experienced symptomatic radiation necrosis, including 1 death: Three of 4 cases received 54 Gy and consolidative intrathecal methotrexate (n = 2) or high dose ACNS0333 intravenous chemotherapy (n = 1, fatal) after radiation. The other patient received 50.4 Gy and necrosis was immediately preceded by ventriculoperitoneal shunt failure. Six patients developed hearing loss requiring aids. One patient developed radiation-induced meningioma a decade following treatment. Conclusion This represents the largest experience reporting 5-year outcomes following focal radiation in children with non-metastatic intracranial ATRT. When applied with a variety of modern chemotherapy regimens in real-world settings, focal proton therapy at a dose of 50.4 Gy may offer the best therapeutic ratio but does not eliminate serious toxicity. If avoidance of craniospinal radiation remains an ongoing priority, further improvement in survival will depend upon systemic therapy.

OBJECTIVE The optimal surgical treatment for lumbar spinal stenosis (LSS) with degenerative spondylolisthesis (DS) remains controversial. Posterior lumbar facet arthroplasty preserves motion after decompression and may address some of the limitations of fusion techniques. The Total Posterior Spine System (TOPS) investigational device exemption trial compared decompression with facet arthroplasty to decompression plus fusion (open with interbody). This study reports the 3-year outcomes from this trial. METHODS This randomized, controlled, multicenter trial enrolled 321 patients with LSS and grade I DS across 37 sites (2:1 randomization of arthroplasty to fusion). Eligible patients were 35–80 years old, had failed ≥ 6 months of nonsurgical treatment, and met thresholds for disability and leg pain. The primary endpoint was a composite clinical success score at 36 months, defined by four criteria: 1) no reoperation or lumbar injection, 2) no major device adverse events, 3) ≥ 15-point improvement in the Oswestry Disability Index (ODI), and 4) no new/progressive neurological deficit. Secondary outcomes included the ODI score, visual analog scale (VAS) scores for back and leg pain, the Zurich Claudication Questionnaire (ZCQ), device-related adverse events, and reoperations. RESULTS One hundred seventy-nine patients in the arthroplasty (TOPS) group and 74 in the fusion group were eligible for the 36-month analysis. The composite clinical success achievement rate was significantly higher in the arthroplasty group (76.0%) than in the fusion group (56.8%; p = 0.0038). The rate of reoperation or lumbar injection was significantly lower for the arthroplasty group (14.0%) compared to the fusion group (25.3%; p = 0.0222). Arthroplasty was associated with a significantly higher minimal clinically important difference (MCID) achievement rate for VAS back pain score compared with fusion (85.2% vs 72.2%; p = 0.041). Although there was no significant difference in ODI score, VAS leg pain score, or ZCQ component scores between groups, the arthroplasty group trended toward higher MCID achievement rates across all patient-reported outcome measures. There was no significant difference in reoperation failure rates between groups (5.8% for arthroplasty vs 9.5% for fusion; p = 0.329). CONCLUSIONS Decompression and dynamic stabilization with lumbar facet arthroplasty was associated with statistically significantly superior clinical outcomes and lower rates of secondary invasive procedures, including reoperations and injections, compared with decompression and fusion. Long-term follow-up is critical in defining the role of lumbar facet arthroplasty for the treatment of DS.

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressive neurodegenerative disease of motor neurons for which therapeutics are limited. Improved biomarkers are imperative to improve patient care and therapeutic development. Here, we employed 35-plex isobaric tandem mass tag labeling based on isobutyl-proline reporter group (TMTpro) to perform unbiased proteomic analysis of cerebrospinal fluid (CSF) and plasma from control (n= 28, n= 31) and sporadic ALS (sALS) (n= 39, n= 41), from the Target ALS Global Natural History Study (TALS GNHS). We identified 2,875 proteins in CSF and 1,118 proteins in plasma and identified known and novel differentially expressed proteins (DEPs) between controls and sALS, some of which were orthogonally validated using immunoassay. Comparison of TMTpro-MS and Olink proximity extension assay proteomics revealed common and non-overlapping differentially expressed proteins illustrating strengths unique to each platform. This initial cross-sectional proteomic study of biofluids from the TALS GNHS, with unrestricted availability of study results to the research community, highlights the potential of this resource as a potent platform for ALS biomarker discovery.