Citations

Abstract Anaplastic large cell lymphomas (ALCLs) are CD30+ T-cell lymphomas that share pathologic features but differ in presentation, outcome, and genetics. Current classification incorporates clinical presentation and anaplastic lymphoma kinase (ALK) status but inadequately addresses molecular heterogeneity and therapeutic vulnerabilities. We studied 689 patients with ALCL in the LLMPP (Lymphoma/Leukemia Molecular Profiling Project) and performed expert consensus review, genetic subtyping (ALK, DUSP22, TP63, and triple negative), and immunohistochemistry for phosphorylated STAT3Tyr705. RNA sequencing with unsupervised gene expression profiling in 393 patients identified 2 main molecular types of ALCL that could be predicted with 91% accuracy based on the presence (type I) or absence (type II) of phosphorylated STAT3Y705 expression. Type I ALCLs included ALK+ ALCL and a subset of triple-negative ALCLs (TN-I); type II ALCLs included tumors with DUSP22 and/or TP63 rearrangements and the remaining triple-negative ALCLs (TN-II). Type I ALCLs were enriched for JAK-STAT3, whereas type II ALCLs were enriched for non–tyrosine kinase pathways, particularly epigenetic regulators such as EZH2. Immunohistochemistry showed overexpression of EZH2 and its trimethylated substrate H3K27. Prognosis in systemic ALCL was favorable for DUSP22-rearranged ALCL (5-year overall survival, 95%) and ALK+ ALCL (88%), intermediate for triple-negative ALCL (TN-I, 52% and TN-II, 37%), and poor for TP63-rearranged ALCL (0%). We introduce an integrated molecular classification that preserves currently diagnosed ALCL entities but identifies 4 molecularly distinct ALK− ALCL subtypes (DUSP22-rearranged, TP63-rearranged, TN-I, and TN-II). This classification can be easily implemented on paraffin tissue in routine practice or clinical trials, and stratifies ALCL into diagnostically, prognostically, biologically, and potentially therapeutically relevant subtypes.

Objective: Generative artificial intelligence is rapidly evolving and is now being explored in health care to support patient and clinician education. This study evaluated the accuracy, completeness, and readability of four large language models (LLMs): ChatGPT 3.5, Gemini, ChatGPT 4.0, and OpenEvidence in answering questions about menopause and hormone therapy. Methods: A total of 35 questions (20 patient-level, 15 clinician-level) were entered into each LLM. OpenEvidence was only used for clinician-level questions. Four blinded expert reviewers rated responses as accurate and complete, accurate but incomplete, or inaccurate. Readability of patient-level responses was assessed using the Flesch Reading Ease Score (FRES) and word count. Analysis used ANOVA for readability, odds ratios for accuracy comparisons. Results: For patient-level questions, ChatGPT 3.5 achieved the highest accuracy (70%), followed by ChatGPT 4.0 (60%) and Gemini (30%); Gemini had significantly lower odds of accuracy compared with ChatGPT 3.5 (OR=0.18, 95% CI=0.05-0.71; P =0.014). FRES scores differed significantly ( P <0.001): Gemini scored 38.9±7.3 (“difficult”), ChatGPT 3.5 scored 31.0±11.2, and ChatGPT 4.0 scored 26.5±8.6 (both “very difficult”). For clinician-level questions, ChatGPT 4.0 achieved the highest accuracy (67%), followed by ChatGPT 3.5 and OpenEvidence (60% each) and Gemini (47%); no significant differences were observed among models (all P >0.05). Conclusion: LLMs demonstrated limited accuracy and frequent incorrect or incomplete responses to menopause-related queries, highlighting the need to improve model performance to ensure accurate and reliable information for both patients and clinicians.

Introduction Hypoplastic left heart syndrome and Fontan procedure predispose to cardiac thrombus formation in the venous pathways due to the unique hemodynamic and hematologic disturbances inherent to the Fontan circulation. Systemic venous blood is routed passively to the pulmonary arteries without a subpulmonary pump, resulting in chronic low‐velocity flow, elevated central venous pressure, and venous stasis—all elements of Virchow's triad that favor clot formation 1 . Additionally, these patients exhibit reduced levels of protein C, coagulation factors II, V, VII, and X, plasminogen, and antithrombin III, along with increased levels of factor VIII 2,3 . Once a thrombotic event occurs, the rationale for lifelong anticoagulation is compelling. We report a case of an adult man that underwent Fontan palliation in infancy, with acute cerebral and renal infarcts, and discuss stroke and systemic embolism prevention. Case presentation A 22‐year‐old male with history of hypoplastic left heart syndrome status post Fontan procedure in infancy with congestive splenomegaly and liver disease presented with acute abdominal pain and was found to have bilateral renal infarcts. Anticoagulation was not initiated acutely and within 24 hours he developed left face and arm weakness, dysarthria and mild aphasia. Intravenous Tenecteplase was administered within 1 hour of symptom onset and was followed by symptoms’ complete resolution within 30 minutes of administration. Brain MRI confirmed scattered cerebral infarcts in the bilateral middle cerebral artery territories. Transthoracic echocardiogram showed atrial level shunting, expected due to fenestrated IVC to left atrium from prior Fontan procedure, and no evidence of atrial or ventricular thrombus. Due to the patient having evidence of multiple infarcts in multiple vascular beds within the brain and kidneys, an extensive hypercoagulable workup was undertaken which was unremarkable. The patient's stroke etiology was presumed to be cardioembolic from his altered cardiac anatomy with susceptibility to form venous thrombi and known surgically‐induced atrial level shunt. Low intensity heparin drip without bolus was started initially, and was transitioned to therapeutic apixaban upon discharge with proposed life long anticoagulation. Conclusions Subjects with hypoplastic heart syndrome display persistent unfavorable hemodynamics and procoagulant state after Fontan procedure. Either antiplatelet or anticoagulants are recommended after performing risk stratification. In high‐risk patients (recent thromboembolic event or stent, recurrent atrial arrhythmias, mechanical valve), therapeutic anticoagulation with either warfarin or direct oral anticoagulant is indicated, given increased vulnerability to recurrent events 1 . In intermediate‐risk subjects, antiplatelet or prophylactic doses of anticoagulation is indicated, whereas in low‐risk patients, antiplatelet agent is preferred.

Introduction/Purpose Vertebral artery dissection is a recognized cause of ischemic stroke in young and middle‐aged adults, often presenting with headache, neck pain, and focal neurologic deficits. Minor trauma, including neck manipulation, is a statistically significant risk factor for cervical artery dissection, with several case‐control and cohort studies demonstrating an association, particularly in younger patients. The vertebral arteries ascend through the transverse foramina of the cervical vertebrae, making them susceptible to mechanical stress from abnormal spinal curvature. Cervical scoliosis alters the bony alignment and curvature, causing the vertebral artery pathway to be elongated, kinked, or compressed, especially at the apex of the spinal curve. We suspect in patients with abnormal cervical biomechanisms the vertebral arteries are more vulnerable to injury during high velocity cervical manipulation. This case aims to highlight the risk of arterial dissection in a patient with scoliosis after undergoing neck manipulation. Materials/Methods A 37‐year‐old right‐handed male with a history of migraine headaches presented with acute onset diplopia and vertigo accompanied by nausea, vomiting, and right facial sensory loss on awakening. The patient reported recent chiropractic cervical manipulation days prior to symptom onset. Neurological examination revealed right‐sided facial sensory deficits, multidirectional nystagmus, and right homonymous hemianopia. CT angiography demonstrated right vertebral artery dissection in V2 and V3 and subtle luminal changes over the left V2 segment with scoliotic curve of the cervical spine and upper thoracic spine. MRI and MR angiography demonstrated multifocal acute infarcts in the posterior circulation and evidence of vertebral artery dissection. Additional workup included a lipid panel which showing an LDL of 137 mg/dL and a transthoracic echocardiogram revealing a bicuspid aortic valve. Results The patient was initiated on dual antiplatelet therapy with aspirin and clopidogrel for secondary prevention, consistent with American Heart Association guidance for extracranial cervical artery dissection, with plans to transition to single antiplatelet therapy after 3 months, assuming no recurrent events and stable follow up imaging. Ultimately, the patient had improvement in his visual symptoms including complete resolution of right homonymous hemianopia during his hospitalization. Given his elevated LDL, the patient was started on a high intensity statin therapy. Secondary prevention strategies included aggressive vascular risk factor modification, avoidance of further neck manipulation or trauma, and close outpatient follow‐up with repeat vascular imaging in 3 months. The patient was also referred to medical genetics to further evaluate possible underlying connective tissue disorders. He was counseled regarding the statistical association between cervical manipulative therapy and vertebral artery dissection, and the importance of prompt medical evaluation for any future neurological symptoms. Conclusions Cervical scoliosis is not a well‐established independent risk factor for vertebral artery dissection. However, when combined with cervical high velocity manipulations, the vertebral arteries are likely to be more vulnerable to injury and lead to dissections and strokes. Further research is warranted on this topic. Finally, early recognition and evidence‐based antithrombotic therapy are critical to optimizing outcomes in patients with arterial dissection.

Introduction/Purpose Diabetic striatopathy (DS) is a rare neurologic complication of poorly controlled diabetes mellitus characterized by hemichorea/hemiballism and distinctive basal ganglia imaging abnormalities, most commonly T1 hyperintensity in the putamen or caudate nucleus. Emerging evidence suggests that DS may coexist with acute ischemic stroke, particularly in the context of intracranial atherosclerotic disease (ICAS), complicating both diagnosis and management. The pathophysiological interplay between chronic hyperglycemia and impaired regional perfusion is postulated to increase basal ganglia vulnerability to metabolic and ischemic injury, leading to the characteristic clinical and radiological features of DS. This case report aims to highlight the clinical course, diagnostic evaluation, and management of a patient presenting with DS and stroke secondary to ICAS. Materials/Methods A 68‐year‐old female with hypertension, hyperlipidemia, and newly diagnosed diabetes presented with a one‐month history of left arm choreiform movements, episodic dizziness, and blurred vision. Movements correlated with hyperglycemia (home blood glucose in the 400s) and resolved with dietary modification and improved glycemic control. Initial MRI revealed right M1 segment MCA occlusion with multiple subacute‐chronic infarcts in the right MCA territory and T1 hyperintensity in the right putamen, suggestive of DS. CT angiography head and neck demonstrated distal right M1 severe stenosis vs occlusion with distal reconstitution, atherosclerotic calcification in the right carotid siphon, and severe stenosis in the right V4 segment and left AICA. Laboratory evaluation showed LDL 103 mg/dL and HbA1c 10.7%. Cardioembolic evaluation with echocardiography, transcranial doppler, and prolonged cardiac monitoring was unremarkable. The patient was managed with dual antiplatelet therapy (aspirin and clopidogrel for 90 days, then aspirin monotherapy), high‐intensity statin, and intensive glycemic control per current consensus guidelines for ICAS and DS. Results The patient's involuntary movements resolved with improved glycemic control, consistent with DS. Follow‐up imaging at three months demonstrated interval resolution of right lentiform nucleus edema and enhancement, with residual mild T1 hyperintensity and curvilinear susceptibility artifact. No new infarcts were identified; prior right MCA territory infarcts appeared subacute/chronic. Persistent right distal M1 MCA stenosis was noted. The cessation of choreiform movements with normalization of blood glucose and the radiological evolution of basal ganglia changes supported the diagnosis of DS in the context of ICAS. Aggressive medical management, including dual antiplatelet therapy and statin, was implemented per American Heart Association (SAMMPRIS) recommendations for symptomatic ICAS. The patient remained neurologically stable without recurrent stroke or movement disorder. Conclusion This case illustrates the complex interplay between chronic hyperglycemia and intracranial atherosclerotic disease in the pathogenesis of both stroke and diabetic striatopathy. The combination of metabolic and vascular insults likely increases basal ganglia susceptibility to injury, manifesting as DS and ischemic stroke. Recognition of this association is critical for accurate diagnosis and optimal management, as DS may herald imminent cerebrovascular events. Aggressive risk factor modification and guideline‐directed medical therapy are essential for secondary prevention in ICAS, while glycemic control remains the cornerstone of DS management. Further research is needed to elucidate the mechanistic links and refine therapeutic strategies for these overlapping entities.

Introduction Although Valsalva maneuvers and strenuous exercise are commonly discouraged in patients with intracranial aneurysms (IAs), the cerebrovascular stress they induce remains poorly characterized. To our knowledge, no prior review has systematically quantified their effects on hemodynamic surrogates of rupture risk. Objective To characterize the acute intracranial hemodynamic effects of strenuous physical activity and Valsalva maneuvers in individuals with and without IAs. Methods We searched PubMed, Embase, Scopus, Web of Science, and Cochrane (February 2025; PROSPERO ID: CRD42025637608) following PRISMA. Eligible studies reported acute changes in SBP, ICP, central venous pressure (CVP), cerebrovascular transmural pressure (CVTMP), middle cerebral artery (MCA) velocity, or CFD‐derived parameters (wall shear stress [WSS], oscillatory shear index [OSI], relative residence time [RRT]) in response to physical exertion or Valsalva. Populations included individuals with or without IAs. Acute neurological symptoms were also reviewed. Results From 2,859 records, 14 studies met inclusion criteria. Eight studies assessed real‐time hemodynamic responses during exercise (91 participants without IAs). Three studies (n=39) showed that resistance exercise increased SBP (mean Δ+21.8 mmHg). Two studies (n=22) showed significant MAP elevation (mean Δ+24.7 mmHg). When combined with a Valsalva maneuver, SBP increased further (mean Δ+26 mmHg; range 20–30). Three studies (n=38) evaluating isolated Valsalva identified significant ICP elevation (mean Δ+15 mmHg; range 5.7–24.3), primarily driven by CVP increases (mean Δ+52.0 mmHg; range 39–56). Breath‐holding during exertion reduced MCA velocity (mean Δ–11.6 cm/s), while continuous ventilation preserved more stable flow. In seven patients, resistance exercise without Valsalva increased CVTMP by 24.5%. In contrast, Valsalva alone raised ICP and CVP without increasing SBP, yielding a CVTMP 11% lower than during exercise alone. These paired observations suggest that Valsalva may transiently offset exercise‐induced transmural stress by raising ICP alongside SBP. However, this effect may be time‐limited and reverse during early recovery—when SBP remains elevated as ICP quickly normalizes—potentially producing a CVTMP rebound above exercise‐only levels. Six CFD studies (11 aneurysms; diameter 6.3–23 mm; 2 ruptured) reported exercise‐related increases in time‐averaged WSS (mean +21.7%, range –4.4% to +50%) and peak WSS (mean +382.3%, range +100% to +628%). Exercise‐induced changes in heart rate and flow pulsatility led to complex redistributions of intra‐aneurysmal WSS, potentially exposing the aneurysmal wall to focal mechanical stress. Conclusion Resistance exercise, especially with breath‐holding, provokes dynamic, time‐sensitive cerebrovascular stress. Valsalva maneuver may transiently lower CVTMP during effort, yet its release with lingering SBP elevation can precipitate delayed transmural pressure surges. The proposed biphasic effect of Valsalva offers a novel conceptual framework for prospective. Our findings underscore the need to define safe, individualized activity thresholds for patients with IAs with patient‐specific validation integrating concurrent physiology and CFD to reduce the risk of IA growth and rupture.

Introduction The risk of aneurysmal subarachnoid hemorrhage (aSAH) during exercise is not well quantified. We assessed temporal clustering of aSAH around physical exertion and around Valsalva‐like activities (defecation or urination). Objectives To estimate the proportion of aSAH cases temporally linked to strenuous activities using reported exposure‐to‐onset window uwing within‐person odds of rupture from case‐crossover studies. Methods We searched PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library from inception through January 2025, and hand‐searched reference lists (PRISMA‐aligned; PROSPERO CRD42025637608). Eligible studies reported the activity at aSAH onset or within a defined pre‐onset window. Exposures were analyzed separately (exertion; defecation/urination). Primary proportional estimates used each study's own exposure‐to‐onset window as reported. To improve comparability, subgroup analysis was performed with only a prespecified subset pooled consecutive case series that explicitly used a ≤2‐hour window between the index activity and aSAH. Within‐person odds ratios (ORs) were abstracted from case‐crossover studies. Risk of bias for observational exposure studies was assessed with ROBINS‐E by two independent reviewers. Results Sixteen studies (published 1980–2022) from 10 countries were included with 5,815 cases of aSAH (mean age 55 years; 60.6% female). Designs comprised 10 case series, 3 case reports, 2 case‐crossover studies, and 1 case‐control study. Activity‐at‐onset was recorded for 4,219/5,815 (72.6%); among these 4,219 patients, mean age was 52.7 years. Using each study's reported window, 308/4,219 (7.3%) aSAH occurred during or within the study‐defined window after physical exertion, and 387/4,219 (9.2%) during/within the window after defecation or urination 695/4,219 (16.5%) were temporally linked to either exposure. In the subset of 10 consecutive case series restricted to ≤2 hours, 275 (5.4%) were linked to exertion and 385 (7.6%) to defecation/urination (combined 660; 13.0%). Study‐specific proportions ranged from 0.8–21.3% for exertion and 2.0–15.4% for defecation/urination. Two case‐crossover studies reported higher within‐person odds of rupture after moderate‐to‐vigorous exertion (OR 2.4–2.7). Temporal clustering of aSAH around exertion or straining was observed in 13–17% of cases, depending on dataset and inclusion criteria. Conclusions Although this relatively high rate of temporal association between aSAH and exercise might suggest an increased risk of aneurysm rupture during strenuous activity, variable definitions and unstated exposure‐to‐onset windows do not permit causal inference. Prospective or registry‐embedded case‐crossover studies using standardized exposure definitions (intensity, duration) and objective exposure capture are needed to refine immediate‐risk estimates and identify patient‐level susceptibility modifiers.

Introduction Chronic internal carotid artery occlusion (CICAO) can result in recurrent ischemic events despite optimal medical therapy. Revascularization may serve as salvage treatment for symptomatic patients who fail medical management. Objective To evaluate the clinical outcomes of endovascular revascularization in patients with symptomatic CICAO. Methods We reviewed consecutive cases of symptomatic CICAO (symptoms ≥4 weeks) undergoing attempted endovascular revascularization between 2011 and 2024. Occlusions were classified as typical (complete) or atypical (pseudo‐occlusion or distal reconstitution via vasa‐vasorum). Outcomes included periprocedural complications (≤24 hours), technical failure, and new ischemic stroke or TIA during follow‐up. Functional status was assessed using the mRS before and after the procedure, with a favorable outcome defined as mRS ≤2. Results Twenty‐five patients were included (21 male; 84%), mean age 67.8 (range: 51‐81). Prior stroke was reported in 18 patients (72%) and TIA in in 13 (52%). Fourteen patients’ occlusion was at the level of the bifurcation (56%), nine at the cervical level (36%), one at the level of the mandible (4%) and one at the level of the common carotid artery (4%). The mean follow‐up duration was 23.1 ± 38.3 months. Dual antiplatelet therapy was used in 15 patients (60%), and single‐agent therapy in eight (32%). Technical treatment success, defined as adequate recanalization of the treated artery, was achieved in 20 (80%) patients, representing 13 of 18 patients from the typical group and all seven from the atypical group. Five patients (20%) failed the endovascular revascularization attempt and were treated with EC‐IC bypass instead (all from typical group). Periprocedural complications occurred in 11 patients (44%), affecting 10 of 18 patients (56%) with typical occlusion and 1 of 7 (14%) with atypical occlusion. During follow‐up, three patients (12%) experienced ischemic stroke and, three (12%) had TIA. Functional status changed in 16 patients (64%), with improvement in 12 and decline in four. Categorically, six patients (24%) transitioned to a favorable outcome (mRS ≤2), while three (12%) shifted to an unfavorable one (two had underlying malignancies). Conclusion Endovascular revascularization offers a salvage option for patients with symptomatic CICAO who fail medical therapy. While the procedure can reduce recurrent ischemia and improve functional outcomes, it carries procedural risks, especially in cases with typical occlusion. Patients with atypical occlusions showed higher success rates and fewer complications, suggesting they may benefit most from this approach. Careful patient selection remains critical, and further studies are needed to refine indications and improve safety.

Introduction Software packages for quantification of CT perfusion parameters allow quick visualization of perfusion deficits to support clinical decision making in acute ischemic stroke (AIS). Several packages are now commercially available for automated quantification of ischemic core, penumbra volumes, and mismatch ratios to indicate eligibility for reperfusion therapies. This study explored the agreement between two software packages, Brainomix 360 e‐CTP and Rapid CTP, in prospective, real‐world use. Methods Consecutive patients scanned for suspected stroke at three comprehensive stroke centers over 90 days from May to July 2024 were included in the study. Eligibility for the current analysis was limited to discharge diagnosis of AIS and CTP imaging processed by both Brainomix and Rapid software. Software processing was conducted in real time after image acquisition. The presence of large vessel occlusion (LVO) was determined from review of electronic medical records. CTP core (CBF<30%) and penumbra (Tmax>6s) volumes from Brainomix and Rapid were recorded for each case. Mismatch ratios were calculated (penumbra÷core volume); positive mismatch was defined according to DEFUSE‐3 criteria (core<70ml, penumbra>15ml, mismatch ratio > 1.8). The correlations and linear regressions between Brainomix and Rapid were computed for core, penumbra and mismatch ratios, and their concordance for mismatch positivity was assessed. Results 137 patients were scanned and received a final diagnosis of AIS. Of these, only 38 had imaging processed by both Brainomix and Rapid. Median age was 69 years (interquartile range: 57‐77.5y); 16 (42%) were female; 13 (34%) had LVO. Linear models between Brainomix and Rapid's outputs for CBF and Tmax volumes are shown in Figure 1a and 1b. The correlation between software outputs for CBF volume was r=0.70 (p<.001), and for Tmax volume was r=0.72 (p<.001). Mismatch ratios were calculated for the 13 cases with LVO (Figure 1c). The linear model between mismatch ratios was not significant, with four Rapid outputs showing infinite mismatch ratios (due to having CBF volumes of 0ml). Concordance between software for mismatch positivity was good; 8/13 cases showed mismatch on both softwares; 1 case showed mismatch on Brainomix only; 1 for Rapid only; and 3 cases showed mismatch on neither software. Conclusion This prospective study, despite limited sample size (N=38), showed good correlations between Brainomix 360 e‐CTP and Rapid CTP for calculation of both core and penumbra volumes. Although mismatch ratios showed less agreement, the categorization of mismatch positivity showed good concordance between software platforms. image

Introduction Post‐market and multicenter studies report low complete occlusion rates (41‐49%) and higher retreatment rates (13%) following WEB deployment, compared to 3.8% with microsurgical clipping. While retreatment after WEB has been shown to be technically feasible, data on final angiographic outcomes remain limited. We performed a retrospective analysis of prospective databases from 14 cerebrovascular centers in the US to compare the safety and efficacy of retreatment versus continued observation for residual and recurrent aneurysms after initial WEB deployment. Materials/Methods Multinomial logistic regression was used to identify baseline characteristics of untreated and residual/recurrent aneurysms that may act as confounders, which then underwent propensity scored matching (PSM). Results Among 211 patients (125 observed, 86 retreated), retreatment was more common in initially ruptured aneurysms (p<0.001), which showed higher recurrence (p=0.036) and sac‐dominant residuals (p=0.004). These were primarily due to WEB compression on follow‐up (p=0.001), rather than incomplete occlusion with an appropriately sized device (p<0.001). Retreatment was associated with significantly higher rates of complete angiographic occlusion at last follow‐up compared to observation alone (p<0.001), a finding that remained consistent across subgroups defined by initial unruptured status, residual type, and recurrence patterns (all p<0.05). Clipping demonstrated higher, though statistically insignificant, rates of complete occlusion; flow diversion and stent‐assisted coil embolization yielded comparable complete occlusion rates at follow‐up. After propensity score matching, retreatment remained significantly associated with higher rates of complete angiographic occlusion (all p<0.05), with comparable outcomes observed between clipping and various endovascular approaches as above. Conclusion Retreatment improved complete occlusion rates; however, no aneurysmal hemorrhages occurred in either group. Further intervention may be unnecessary when the WEB device—whether compressed or intact (BOSS 0/1)—adequately protects the dome. In cases where WEB compression significantly exposes the aneurysm wall, stent‐assisted coiling or flow diversion can be performed safely and successfully, depending on vascular anatomy and surgeon preference. image image