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Abstract Objective To assess the localization and lateralization values of ictal emotional features and ictal defensive behaviors in pediatric and young adult patients with frontal lobe epilepsy (FLE). Methods Children and young adults with FLE were identified from a single institution's epilepsy surgery database. Two epileptologists determined by consensus the presence of ictal emotional features (positive‐ smile, laughter, humming, singing; negative‐ fear, crying, anger, disgust, contempt, sadness) and ictal defensive behaviors (freezing with a fearful facial expression, shielding the face with hands, burying the face in a pillow, or exhibiting hyperkinetic motor behaviors like attempting to escape from bed or resisting restraint) in each patient's first video EEG (vEEG). Historic seizure semiology and vEEG reports were compared with the consensus vEEG analysis. Longitudinal changes in ictal emotional features were defined by the emergence or resolution of ictal emotional features between historic seizure semiology and re‐review of presurgical vEEG analysis. Subgroup analyses were conducted according to the seizure lateralization (left vs. right) and sublobar localization (precentral, medial, lateral, extensive) based on surgical extent. Results Twenty‐three FLE patients were included (female 39%; mean age at vEEG analysis: 11.28 years, range 1.75–20.17). The inter‐rater reliability was very good for both ictal emotional features ( κ = 0.81, 95% CI: 0.59–1) and ictal defensive behaviors ( κ = 0.91, 95% CI: 0.79–1). Ictal emotional features were observed in 10 patients (43.4%), with negative emotions present in 70% (7/10) of these cases. vEEG reports lacked documentation of ictal emotional features in two patients. Although ictal emotional features showed no statistical correlation by sublobar regions, ictal defensive behaviors were consistently seen in medial compared to lateral FLE (100% vs. 16.6%; p = 0.004). Longitudinal changes in ictal emotional features were observed in 8 (34.7%) patients. Significance Ictal emotional features were common in pediatric and young adult FLE patients and were mainly negative. Ictal defensive behaviors were more likely associated with medial FLE. Longitudinal changes in ictal emotional features occurred in about a third of pediatric and young adult patients with FLE. Plain Language Summary This study examined emotional features and defensive behaviors during seizures in children and young adults with FLE. Negative emotions were commonly seen during seizures. Ictal defensive behaviors were more frequently observed in patients with medial FLE, and recognizing these signs could help clinicians localize the seizures. Changes in emotional features were seen over time in about one‐third of children and young adult patients.

Inverted papilloma (IP) is a benign neoplasm of the nasal cavity and paranasal sinuses, known for its variable risk of recurrence and potential for developing carcinoma. Emerging evidence has shown high rates of activating EGFR mutation, and a smaller subset is associated with low-risk human papillomavirus (lrHPV). While certain morphologic features, including an inverted growth pattern, are well-established, the presence of condylomatous features, such as large fungating lesions with thick undulating surface epithelium, hyperkeratosis, cytoplasmic clearing, raisinoid nuclei, and binucleation (koilocytic changes) in low-risk HPV-associated IP suggests that these tumors may be a distinct subtype of sinonasal papilloma (SP) with features similar to low-risk HPV-associated anogenital condylomas. This study presents a series of SP with condylomatous morphology and explores the association with lrHPV, the clinicopathologic features, and the rates of carcinoma development. In total, 17 cases of SP exhibiting condylomatous morphology were retrospectively identified. We performed lrHPV and high-risk HPV (hrHPV) RNA in situ hybridization and p16 immunohistochemistry and gathered detailed clinical and pathologic data along with treatment, disease follow-up, and outcomes. These condylomatous papillomas almost all developed in active smokers, were large, were primarily located in the nasal cavity (47%), and showed frequent transformation to invasive squamous cell carcinoma (29%). This malignant transformation rate is much higher than what has been reported for inverted, exophytic, and oncocytic papillomas. The tumors were almost uniformly associated with transcriptionally-active lrHPV (94%) and were consistently negative for p16 and hrHPV. This study shows that a subgroup of IPs with condylomatous morphology have a predilection for the nasal cavity, strong association with lrHPV, and high rates of carcinoma. These findings support the concept that these tumors are a distinct (fourth) type of SP with a higher risk of malignant transformation.

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), which were originally developed for managing type 2 diabetes by enhancing insulin secretion and reducing appetite, have emerged as promising candidates in alcohol use disorder (AUD). These medications offer a dual mechanism of action that aligns with the multifaceted nature of addiction by targeting both peripheral metabolic and central reward pathways. This review focused on the current clinical trials and real-world evidence regarding the effects of GLP-1RAs as novel therapeutics for AUD. We also discussed early but encouraging results from clinical trials in AUD, observational and real-world evidence, safety profiles, psychiatric considerations, and future directions leading beyond GLP-1RAs. Methods: A comprehensive English-language literature search was conducted per PRISMA guidelines across PubMed, Medline, Google Scholar, Web of Science, and trial registries. Using targeted keywords, we identified relevant clinical and observational studies on GLP-1RAs for alcohol use disorder, excluding off-topic or non-English works and assessing all studies for eligibility. Results: Out of 1080 records identified, seven studies met the inclusion criteria. The findings from recent clinical trials, large-scale observational studies, and real-world evidence suggest that GLP-1RAs may significantly reduce alcohol consumption, cravings, and alcohol-related hospitalizations. Their central effect on reward processing, coupled with a generally favorable safety profile, supports their potential therapeutic role beyond metabolic disorders. Conclusions: Emerging evidence positions GLP-1RAs as a promising new pharmacologic approach for managing AUD. Ongoing and future research should prioritize larger, longer-duration randomized controlled trials that include diverse populations, with specific attention to treatment motivation, co-occurring psychiatric conditions, and long-term outcomes.

OBJECTIVE Coexisting medical conditions are increasingly prevalent in surgical populations. The impact of multiple comorbidities on patient-reported outcomes (PROs) and endotypes of frequently co-occurring conditions for cervical spondylotic myelopathy (CSM) remain unclear. This study explores whether CSM patients with multimorbidity have worse baseline and postoperative PROs and less functional improvement after surgery compared to those with few or no comorbidities. The authors also investigated whether distinct comorbidity endotypes exist among CSM surgical patients and whether they influence postoperative outcomes. METHODS The prospective Quality Outcomes Database (QOD) was used to assess patients undergoing surgery for CSM. Multimorbidity was defined as ≥ 2 chronic conditions, including diabetes, coronary artery disease, peripheral vascular disease, arthritis, chronic renal disease, chronic obstructive pulmonary disease, Parkinson’s disease, multiple sclerosis, depression, and anxiety. Baseline characteristics and 24-month PROs were assessed across multiple-comorbidity status, including modified Japanese Orthopaedic Association (mJOA), Neck Disability Index (NDI), visual analog scale for neck and arm pain, EQ-5D, and patient satisfaction scores. Clusters were identified from the full cohort using k-medoids, revealing subgroups with similar comorbidity endotypes. RESULTS The final cohort included 1141 CSM patients (83.1% reaching 24-month follow-up), with 761 (66.7%) having 0 or 1 comorbidity and 380 (33.3%) ≥ 2 comorbidities. The multimorbidity cohort was older (mean age 62.6 ± 11.2 vs 59.5 ± 12.0 years, p < 0.001), more likely to be female (52.9% vs 44.7%, p = 0.011), and had a higher BMI (mean 31.1 ± 6.7 vs 29.7 ± 6.2 kg/m 2 , p < 0.001). Multimorbidity patients exhibited worse mJOA, NDI, and EQ-5D scores at baseline and 24 months (p < 0.05). On multivariable analysis, the total number of comorbidities was not significantly associated with any PRO measures. Four comorbidity clusters were identified: low burden, arthritis, diabetes, and high burden. On one-way ANOVA, the baseline mJOA score was significantly different across clusters (p = 0.003). At 24 months, the mJOA score was significantly lower in the diabetes and high-burden endotypes. Twenty-four-month score change and minimal clinically important difference (MCID) achievement of all PROs remained similar across clusters (p > 0.05). CONCLUSIONS While patients with multimorbidity have worse baseline and postoperative PROs, they achieve similar functional and pain-related improvements following CSM surgery. Similarly, the comorbidity endotypes identified in this QOD cohort suggest that certain patterns of coexisting chronic conditions, such as overlapping diabetes and arthritis, are associated with different levels of disability but may not diminish the effectiveness of surgical intervention.

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have demonstrated benefits in heart failure with preserved ejection fraction (HFpEF), but their impact following acute myocardial infarction (AMI) is less well understood. Using the TriNetX Research Network (TriNetX) multi-center registry (2014–2022), we identified patients with heart failure with preserved ejection fraction (HFpEF)—defined as left ventricular ejection fraction (LVEF) >50% and New York Heart Association (NYHA) class II–IV—not previously treated with sodium-glucose co-transporter 2 inhibitors (SGLT2i) who experienced an acute myocardial infarction (AMI). Patients who initiated SGLT2i within 1-year post-AMI were compared with those who did not. Propensity score matching was used to balance cohorts ( n = 20,423 each; mean age 68.3 ± 11.0 years; 54.5% female) for demographics, comorbidities, and treatment variables. The primary outcome was a composite of major adverse cardiovascular events (MACE), including all-cause mortality, recurrent AMI, acute heart failure, and stroke. Secondary outcomes included cardiac arrest and major bleeding. SGLT2i use was associated with lower rates of MACE (3.7% vs 6.1%; P = .0005), all-cause mortality (0.9% vs 5.6%; P < .0001), and other adverse events at both 30 days and 1 year. In this large, propensity-matched cohort, SGLT2i use post-AMI in HFpEF patients was associated with favorable cardiovascular outcomes. Further studies are needed to confirm these associations.

Background: Levetiracetam administration via intravenous push (IVP) may improve outcomes in status epilepticus (SE) by decreasing time to administration. However, there is a paucity of literature describing the safety of IVP administration of higher loading doses used for early management of SE. Objective: The purpose of this evaluation was to investigate the safety of high-dose IVP levetiracetam. Methods: This was a retrospective, single-arm cohort study conducted at an academic medical center. Patients were included if they received IVP levetiracetam ≥3000 mg. The primary outcome was a composite of clinically significant adverse events (AEs) within 1-hour post-administration of levetiracetam: hypotension, hypertension, bradycardia, tachycardia, arrhythmia, and/or injection site reaction. Results: A total of 140 patients met inclusion criteria, receiving a median levetiracetam dose of 4000 mg (interquartile range [IQR] = 3000, 4500). Seventeen (12.1%) patients experienced a clinically significant AE. The most common clinically significant AE was hypotension (9.2% [10/109]), followed by tachycardia (3.6% [4/112]), arrhythmia (1.8% [2/112]), hypertension (0.9% [1/109]), and injection site reaction (0.7% [1/140]). Eighty percent [8/10] of patients who experienced clinically significant hypotension were on at least 1 medication with potential confounding hemodynamic effects. Conclusion and Relevance: In this retrospective, single-arm analysis, high-dose (≥3000 mg) IVP levetiracetam was relatively well-tolerated but associated with a higher rate of clinically significant hypotension than has been reported in the previous literature, although several confounding factors may have contributed to this outcome. Our findings support the continued use of high-dose IVP levetiracetam with appropriate hemodynamic monitoring; hemodynamic effects should be further explored in future studies.

ABSTRACTNodal follicular helper T‐cell (T FH) lymphoma of the angioimmunoblastic (AITL) subtype has a dismal prognosis. Using whole‐exome sequencing (n = 124), transcriptomic (n = 78), and methylation (n = 40) analysis, we identified recurrent mutations in known epigenetic drivers (TET2, DNMT3A, IDH2 R172 ) and novel ones (TET3, KMT2D). TET2, IDH2 R172 , DNMT3A co‐mutated AITLs had poor prognosis (p < 0.0001). Genes regulating T‐cell receptor (TCR) signaling (CD28, PLCG1, VAV1, FYN) or activation (RHOA G17V ) or regulators of the PI3K‐pathway (PIK(3)C members, PTEN, PHLPP1, PHLPP2) were mutated. CD28 mutation/fusion was associated with poor prognosis (p = 0.02). WES of purified, neoplastic T‐cell (CD3+PD1+) demonstrated high concordance with whole tumor biopsies and validated the presence of TET2 and DNMT3A in tumor and non‐lymphoid cells, but other mutations (CD28, RHOA G17V , IDH2 R172 , PLCG1) in neoplastic cells. Integrated DNA‐methylation and mRNA expression analysis revealed epigenetic alterations in genes regulating TCR, cytokines, PI3K‐signaling, and apoptosis. RNA‐seq analysis identified fusion transcripts regulating TCR‐activation (8%), revealed a restricted TCR‐repertoire (α = 87%, β = 72%), and showed the presence of Epstein–Barr virus transcriptome (73%). GEP demonstrated the association of B‐cells or dendritic cells in the tumor milieu with prognosis (p < 0.01). RNA‐seq and WES analysis of 12 AITL‐patient‐derived‐xenografts (PDX) showed that bi‐allelic TET2 and DNMT3A mutations or sub‐clonal mutations (PLCG1, PHLPP2) propagated in sequential passages, and gene signatures related to T FH and T CM (central‐memory) were well‐maintained through passages. Gene expression signatures associated with late PDX passages (3rd–5th) were enriched with proliferation and metabolic reprogramming‐related genes and predicted prognosis in an independent AITL series. Low PHLPP2 mRNA expression predicted poor prognosis (p = 0.05) and engineered PHLPP2 or TET2 loss in CD4+ T‐cells showed enhanced PI(3)K activation, thus uncovering a therapeutic target for clinical trials.

Background Given the low haemorrhagic risk of intracranial low-grade dural arteriovenous fistulas (dAVFs), the benefits of routine intervention remain controversial. This study compares patient outcomes treated with stereotactic radiosurgery (SRS) versus conservative management. Method Multicentre retrospective analysis of the Consortium for Dural Arteriovenous Fistula Outcomes Research and the International Radiosurgery Research Foundation data. Inclusion criteria were (1) intracranial low-grade dAVF diagnosed by catheter-based angiography, (2) no prior dAVF-related haemorrhage and (3) management with upfront SRS (intervention group) or conservative management (observation group). The primary outcome was symptomatic improvement. Secondary outcomes included dAVF obliteration, up-conversion, haemorrhage, improvement and favourable modified Rankin Scale (mRS) at follow-up. Results 304 patients with a mean age of 56 years (SD 13.5) and a follow-up of 46.7 months (SD 45.5) were included. 135 (44.4%) were managed conservatively and 169 (55.6%) had upfront SRS. Compared with the observation group, symptomatic and mRS Score improvement (≥1-point decrease in baseline score) was more likely in the intervention group (95.1% vs 58.5%; OR=13.75 (5.61–33.69) and 37.0% vs 24.0%; OR=1.85 (1.09–3.15), respectively). These findings remained significant after multiple imputation and propensity score matching. Remaining outcomes were similar between groups. The all-cause mortality rate was 5.4% (n=16), unrelated to the dAVF or treatment. Five (3.0%) SRS-related complications were reported and resolved during the follow-up period. Conclusions SRS was associated with increased symptomatic and mRS Score improvement for low-grade dAVFs compared with conservative management. SRS had a low complication risk and did not appear to alter dAVF obliteration or haemorrhage. Future prospective trials on SRS as a first-line intervention for symptomatic low-grade dAVFs should be considered.