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Importance Total thyroidectomy is the established surgical standard for hereditary and sporadic medullary thyroid cancer (sMTC). However, for unilateral sporadic tumors, its benefit over lobectomy remains uncertain. Objective To compare oncologic outcomes between total thyroidectomy and lobectomy in patients with sMTC. Data Sources and Study Selection MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials were searched from inception to December 2025 to identify comparative studies on patients with sMTC who underwent total thyroidectomy or lobectomy. Data Extraction and Synthesis Reviewers working independently and in duplicate screened titles, abstracts, and full-text articles for eligibility using standardized instructions. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses ( PRISMA ) and Meta-Analysis of Observational Studies in Epidemiology ( MOOSE ) guidelines were used for reporting. Main Outcomes and Measures Primary outcomes were mortality, overall survival, structural recurrence, biochemical cure, and distant metastasis development. The secondary outcome was postoperative complications. Effect measures were calculated as odds ratios (ORs) or relative risks (RRs) with 95% CIs using a random-effects model. The risk of bias was assessed using the Newcastle-Ottawa Scale. Results Nine retrospective studies met inclusion criteria and comprised 1371 patients (295 of 397 patients [74.3%] with documented sex were female, and median age ranged from 45.0 to 58.2 years). A total of 531 patients (38.7%) underwent lobectomy and 840 (61.3%) underwent total thyroidectomy. Of 341 tumors, 280 (82.1%) lacked extrathyroidal extension, 284 of 401 tumors (70.8%) measured smaller than 2 cm (70.8%), and 197 of 343 tumors (57.4%) were node negative; central neck dissection was performed in 445 of 492 patients (90.4%). Multifocal disease was uncommon and reported in 30 of 330 patients (9.1%). Mortality did not differ at 5 years (RR, 0.30; 95% CI, 0.07-1.35) or beyond (RR, 1.00; 95% CI, 0.40-2.47). Overall survival at 5 years was similar (RR, 1.02; 95% CI, 0.94-1.11). Total thyroidectomy was not associated with lower structural recurrence rates at 5 years (OR, 0.45; 95% CI, 0.14-1.49), but it was associated beyond 5 years (OR, 7.26; 95% CI, 1.07-49.21). No differences were observed for biochemical cure at 5 years (OR, 0.86; 95% CI, 0.47-1.56) or beyond 5 years (OR, 0.87; 95% CI, 0.26-2.89). Distant metastasis development did not differ at 5 years (OR, 1.64; 95% CI, 0.09-31.52). Sensitivity analyses revealed no differences across any outcomes. Postoperative complications were more common in total thyroidectomy. Risk of bias was high in 4 studies, moderate in 4, and low in 1. Conclusions and Relevance Findings in this systematic review and meta-analysis, based on data from retrospective studies, suggest that thyroid lobectomy may be associated with oncologic outcomes comparable to total thyroidectomy in selected patients with sMTC.

Abstract INTRODUCTION The locus coeruleus (LC) degenerates early in Alzheimer's disease (AD). However, the extent of rostrocaudal degeneration across clinicopathologic heterogeneity remains underexplored in AD. METHODS Using digital pathology, we quantified LC neuronal density and area at three neuroanatomic levels in a large AD series. RESULTS Analysis of neuropathologic AD subtypes revealed greater middle LC vulnerability in hippocampal sparing AD compared to typical and limbic predominant AD. Regression analyses identified distinct predictor variables associated with the degeneration of rostral and middle LC. Age at onset predicted 24% of the variability in rostral LC neuronal density, whereas Braak stage, brain weight, Lewy body disease, and age at onset accounted for 15% of the variability in middle LC. Analyses of clinical presentations revealed lower rostral LC neuronal density in non‐amnestic compared to amnestic AD cases. DISCUSSION These insights demonstrate greater LC degeneration in atypical clinicopathologic forms of AD, including hippocampal sparing, young‐onset, and non‐amnestic presentations.

Importance A greater proportion of older patients (age ≥65 years) are undergoing thyroidectomy amidst an aging population. Given the elusive results in the literature, clarifying whether older patients face different thyroidectomy safety profiles is crucial for optimizing risk assessment and patient counseling. Objective To evaluate the association between older age (age ≥65 years) and thyroidectomy safety by comparing endocrine-related complications, including recurrent laryngeal nerve injury, hypocalcemia, hematoma, and mortality in older compared with younger patients. Data Sources Ovid MEDLINE, CINAHL, Ovid Embase, and the Cochrane Library were systematically searched from inception to May 29, 2025; only English-language studies were included. Study Selection Cohort studies comparing thyroidectomy outcomes between older and younger patients and reporting endocrine-related complications were included. Two independent reviewers screened abstracts and full texts. Of 3192 studies identified, 11 met inclusion criteria. Data Extraction and Synthesis Two independent reviewers extracted data following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Risk of bias across studies was evaluated using the ROBINS-I (Risk of Bias in Nonrandomized Studies of Interventions) tool. Random-effects models were used to pool data. Main Outcomes and Measures Incidence of recurrent laryngeal nerve injury, hypocalcemia, and hematoma; odds ratios (ORs) with 95% CIs were calculated. Results The analysis included 11 studies with a total of 427 886 patients of whom 104 232 (24.4%) were older adults (≥65 years). Older adults had greater odds of overall recurrent laryngeal nerve injury (2.3% vs 1.0%; OR, 1.58; 95% CI, 1.15-2.16; I 2 = 76%), hematoma (2.4% vs 1.0%; OR, 2.32; 95% CI, 1.70-3.16; I 2 = 0%), and mortality at last follow-up (0.3% vs 0.01%; OR, 11.09; 95% CI, 1.77-69.52; I 2 = 90%) compared with younger patients. However, rates of overall hypocalcemia (OR, 0.80; 95% CI, 0.61-1.05; I 2 = 71%) and wound complications (OR, 1.38; 95% CI, 0.92-2.06; I 2 = 0%) were similar. Conclusions and Relevance This systematic review and meta-analysis found that thyroidectomy is safe in older patients, with only small absolute increases in recurrent laryngeal nerve injury, hematoma, and mortality despite statistical significance. These findings support individualized counseling and perioperative planning while acknowledging the overall safety of thyroidectomy in this population.

Background and Objectives: Cervical artery dissection (CeAD) is a leading cause of ischemic stroke in younger adults, yet sex-specific variations in its clinical presentation, imaging characteristics, and outcomes remain underexplored. We aimed to evaluate these differences using data from a large, multicenter registry. Methods: We analyzed data from the STOP-CAD registry, which includes patients with radiologically confirmed non-traumatic CeAD enrolled between 2015 and 2021 across multiple centers. Clinical and imaging characteristics were compared between men and women using multivariable logistic regression. Outcomes assessed included ischemic stroke recurrence at 180 days, excellent functional outcome (modified Rankin Scale [mRS] 0–1) at 90 days, symptomatic intracerebral hemorrhage (sICH), and mortality. Results: Among 4,023 patients with CeAD, 1,783 (44.6%) were women. Compared to men, women were younger (median age: 42 vs 50 years), more likely to have a history of migraine (26.9% vs 8.3%) and connective tissue disorders (14.3% vs 5.8%), and presented more frequently with non-ischemic symptoms such as headache, neck pain, or tinnitus (adjusted OR [aOR] 2.0; 95% CI, 1.8–2.3; p<0.001). Women had significantly higher odds of vertebral artery dissection (OR, 1.3; 95% CI, 1.2-1.5; p<0.001), multivessel involvement (OR, 2.1; 95% CI, 1.7-2.5; p<0.001), and pseudoaneurysm formation (OR, 1.3; 95% CI, 1.1-1.6; p=0.003). Despite these differences, there was no significant sex-based difference in key clinical outcomes: excellent functional recovery at 90 days (OR 0.94; 95% CI 0.76-1.15 p=0.542), ischemic stroke recurrence at 180 days (OR 0.56 CI 0.23-1.3 p=0.213), or mortality (OR 0.83; 95% CI 0.47-1.48, p=0.529). Conclusion: In this large international cohort, we observed women with CeAD were younger, more likely to present with non-ischemic symptoms with distinct imaging features. These underscore the need for heightened clinical suspicion of CeAD in women presenting with atypical symptoms, even in the absence of ischemic deficits or conventional vascular risk factors, and suggest that sex-specific phenotyping may enhance diagnostic accuracy and early management.

Background: Patients with cervical artery dissection (CAD) have a higher prevalence of cerebral aneurysms, likely due to underlying vasculopathies. Understanding risk factors and outcomes in this population may inform screening and management strategies. Methods: We conducted a post-hoc analysis of the STOP-CAD study, a multicenter international registry of patients with non-major trauma-related CAD across 63 centers. Cerebral aneurysms were identified based on medical history and intracranial vascular imaging obtained for dissection diagnosis. We compared demographic, clinical, laboratory, and imaging characteristics between patients with and without aneurysms. Variables with p<0.05 in univariate analysis were entered into a multivariable binary logistic regression to identify independent predictors. Clinical outcomes including ischemic stroke and symptomatic intracranial hemorrhage at follow-up were compared between both groups. Results: Out of 4023 patients included in the STOP-CAD study, 116 (2.9%) had at least one incidental cerebral aneurysm. In adjusted binary logistic regression, patients with cerebral aneurysm were more likely to have a history of migraine (aOR 1.78 95% CI 1.15-2.75, p=0.009), history of hypertension (aOR 1.65 95% CI 1.12-2.43, p = 0.010), known connective tissue disorder (aOR 3.47 95% CI 1.71-7.03), history of dissection (aOR 2.63 95% CI 1.31-5.28, p = 0.007), and a dissecting aneurysm at the site of the dissection (aOR 1.94 95% CI 1.25-3.01, p = 0.003). At follow-up, the presence of a cerebral aneurysm was not associated with ischemic stroke (7.8% vs. 5.6% p>0.1), but with a trend towards increased odds of symptomatic intracranial hemorrhage (3.4% vs. 1.2%, p = 0.062). Conclusions: Patients with CAD and concurrent incidental cerebral aneurysm were more likely to have a history of migraine headaches and markers of underlying vasculopathy and had a non-significantly increased risk of intracranial hemorrhage at follow-up. Further studies are needed to identify best practices for surveillance and risk stratification in this subgroup.

Background: Cervical artery dissection (CeAD) accounts for nearly 25% of all ischemic strokes in young adults. CeAD can lead to the development of dissecting aneurysms (DA). However, the incidence, risk factors and outcomes of CeAD patients with DA is not well established. This study aims to identify risk factors for developing DA, subsequent growth, and impact on patient outcomes. Methods: This is a secondary analysis of the Antithrombotics for Stroke Prevention in Cervical Artery Dissection (STOP-CAD), a multicenter cross-sectional international retrospective study. CeAD patients were stratified for the presence of DA. We used multivariable regression to identify factors associated with DA. Patients with DA were further analyzed for DA growth. The primary outcome was ischemic stroke after CeAD+DA diagnosis. Secondary outcomes included ischemic stroke after CeAD+DA with DA growth. Multivariable logistic regression analysis was used to assess the association between DA and risk factors. We also performed univariate Cox regression and generated Kaplan-Meier survival curves comparing study outcomes based on presence of DA and subsequent growth. Results: Of the 4023 patients included in the STOP-CAD study, 4008 were included in this analysis and 767 (19%) patients had DA (546 with DA on initial presentation). Patients with DA had a mean age of 46 [IQR 37-55] years and 50% (383) were women. In combined adjusted analyses, DA patients were more often non-Hispanic (aOR 0.63, 95% CI 0.41-0.94, p<0.02), more commonly had a history of migraine (aOR 1.27, 95% CI 1.01-1.59, p=0.037), connective tissue disorder (aOR 2.02, 95% CI 1.22-3.36, p=0.007), minor neck trauma (aOR 1.70, 95% CI 1.29-2.26, p<0.001) and were more likely to present with ischemic stroke (aOR 1.73, 95% CI 1.05-2.87, p=0.031). DA growth was noted in 55 out of 546 (10%) patients with DA on presentation. There was no significant difference in the risk of ischemic stroke by day 180 in patients with DA (hazard ratio [HR] 0.92 [95% CI, 0.65-1.30]; P =0.63) or DA growth (HR 2.40, [95% CI, 0.79-7.24]; P =0.12). Conclusion: In this subanalysis of STOP-CAD, nearly one in five patients with CeAD developed a DA. Factors associated with a higher likelihood of DA included non-Hispanic ethnicity, history of migraine, connective tissue disorder, minor neck trauma, and ischemic stroke at presentation. DA diagnosis and DA growth did not impact the risk of subsequent ischemic stroke at 6 months.

Background: The clinical characteristics and complications associated with de novo pseudoaneurysm formation beyond the acute phase of cervical artery dissection remain poorly defined. In this study, we examined the incidence, risk factors, and related ischemic and hemorrhagic events of post-acute de novo pseudoaneurysm formation. Methods: We analyzed data from the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection). A de novo pseudoaneurysm was defined as a new (not present on initial imaging) focal enlargement in the diameter of the artery, greater than the native lumen. The incidence of de novo pseudoaneurysm was assessed at 90 days, 180 days, and beyond 180 days of follow-up. Univariate and multivariate regression analyses were conducted to identify risk factors for post-acute de novo pseudoaneurysm formation. Kaplan-Meier survival estimates were used to compare ischemic and hemorrhagic events between patients with and without de novo pseudoaneurysms. Results: Among 4008 patients, 546 were excluded as they had dissecting pseudoaneursyms on initial presentation. Therefore, 3,462 patients were included in this analysis of whom 220 patients (6.35%) developed a de novo pseudoaneurysm over a maximum follow-up of 4.4 years. Of these, 127 (57.72%) were detected within the first 90 days, and 172 (78.18%) within the first 180 days. In multivariate regression analyses, in addition to hypertension, active smoking and Hispanic ethnicity, fibromuscular dysplasia (FMD) was an independent risk factor for post-acute de novo pseudoaneurysm formation (adjusted OR: 2.160; 95% CI: 1.408–3.315; p < 0.001). Notably, the presence of a de novo pseudoaneurysm was not associated with a significant increase in ischemic (hazard ratio [HR] 1.43 [95% CI, 0.89–2.30]; P=0.14) or hemorrhagic events (hazard ratio [HR] 1.42 [95% CI, 0.43–4.69]; P=0.57). Conclusion: De novo pseudoaneurysm formation following a diagnosis of a cervical artery dissection is not uncommon and most frequently occurs within the first 180 days. FMD was independently associated with this complication. The development of a de novo pseudoaneurysm did not significantly increase the risk of subsequent ischemic or hemorrhagic events.

Background and Objectives: Pregnancy and the postpartum period increase the risk of cervical artery dissection (CEAD), a notable cause of stroke in young women. We aimed to describe the clinical presentation, imaging findings, and outcomes of CEAD occurring during pregnancy or shortly after delivery. Methods: We analyzed data from the STOP-CAD registry, a large international multicenter study of patients treated with antithrombotic therapy for non-traumatic CEAD between 2015 and 2021. This sub-study focused on women who were pregnant or within 12 weeks postpartum at the time of symptom onset. We assessed baseline clinical features, imaging results, acute stroke treatments, and functional outcomes. Results: Among 1,783 women in the registry, 62 (3.5%) had pregnancy-associated CEAD, with a median age of 34 years (IQR, 30-38). One-third had a history of migraine (33.9%), one-fifth had hypertension (21.0%), while other vascular risk factors were rare. Recent minor neck trauma was reported in 17.7%. Ischemic stroke symptoms occurred in 25 (40.3%) patients, and 23 (37.1%) had acute infarcts on imaging. However, most (59.7%) presented with non-ischemic symptoms. Vertebral artery dissections were more common than carotid dissections (62.9% vs. 48.4%), and 33.9% had multivessel involvement. Among patients presenting with ischemic stroke symptoms, 4 received thrombolysis and 7 underwent thrombectomy. Remarkably, 92% had excellent functional recovery (modified Rankin Score 0–1) at 90 days, and there were no stroke recurrences at 180 days. Conclusion: Pregnancy- and postpartum-associated CEAD is uncommon and associated with ischemic stroke in nearly half of patients. A history of migraine and hypertension may be potential risk factors. Despite the severity of presentation, most patients had favorable outcomes with timely treatment.

Introduction: Intracranial atherosclerosis (ICAS) is a leading cause of ischemic stroke (IS) worldwide and carries a high risk of recurrence. Current guidelines favor 90 days of dual antiplatelet therapy (DAPT) for severe symptomatic ICAS, but recurrence remain high. Limited data suggest possible benefit of single antiplatelet plus anticoagulation (SAPT+AC). We compared the effectiveness and safety of DAPT versus SAPT+AC. We hypothesized that DAPT would lower 90-day recurrent IS risk without significantly increasing bleeding. Methods: This substudy of the Biomarkers and Recurrence Risk in Symptomatic Intracranial Arterial Stenosis (BIORISK-ICAS) included patients from 35 centers (Jan 2019–Jun 2024) with symptomatic 50–99% ICAS in the intracranial internal carotid, vertebral, basilar, or M1 segment of the MCA, presenting ≤72 hours from last known well. The primary efficacy outcome was recurrent IS in the same vascular territory at 90 days; the primary safety outcome was severe bleeding (symptomatic intracranial hemorrhage or major extracranial bleeding). Categorical variables were compared using χ 2 and continuous variables with the Student's t test; multivariable Cox regression adjusted for key covariates. Results: Of 2050 BIORISK-ICAS patients, 1658 met criteria (DAPT n=1499; SAPT+AC n=159). Mean age was 67 vs. 73 years, and 44% were women. At 90 days, recurrent IS occurred in 121 DAPT patients (8.07%) vs. 13 SAPT+AC patients (8.17%); unadjusted HR 0.83 (95% CI, 0.50–1.36; p=0.46). After adjustment for age, diabetes, coronary heart disease, atrial fibrillation, active smoking, and borderzone infarct, the adjusted HR was 0.99 (95% CI, 0.52–1.86; p=0.97). Severe bleeding occurred in 34 DAPT patients (2.26%) and 5 SAPT+AC patients (3.14%); unadjusted HR 0.79 (95% CI, 0.28–1.85; p=0.50), adjusted HR 0.66 (95% CI, 0.21–2.09; p=0.47). Conclusions: In patients with symptomatic ICAS, DAPT and SAPT+AC were associated with similar risks of 90-day recurrent ischemic stroke and severe bleeding. Well-powered randomized trials are needed to determine the optimal antithrombotic regimen in this high-risk population.

Background and Objectives: Cervical artery dissection (CeAD) is a common cause of ischemic stroke in young adults. We aim to identify age-based differences in clinical presentation, imaging findings, and outcomes after CeAD. Methods: This was a sub-study using the STOP-CAD registry, a multicenter cross-sectional international retrospective study of patients diagnosed with CeAD and treated with an antithrombotic from January 1, 2015 to December 31, 2021. Baseline clinical and imaging characteristics were compared between younger and older adults with CeAD (≤45 versus >45 years of age) using multivariable logistic regression. We chose this age cut off due to its frequent usage in stroke in the young literature. Multiple logistic regression models were used to determine association between young age and outcomes after CeAD (ischemic stroke at 180 days, excellent functional outcome with modified Rankin Scale of 0-1 at 90 days, and mortality) after adjusting for sex, vascular risk factors, CeAD characteristics, and NIHSS on presentation. Results: Among 4023 CeAD patients included in the study, 1901 (47.3%) were ≤45 years of age. Patients were followed for a median of 307 days (IQR 102-831). Young adults with CeAD were more likely to be women (Odds Ratio [OR], 2.4; 95% CI, 2.1-2.9; p<0.001), of Hispanic ethnicity (OR, 1.8; 95% CI 1.3-2.5; p<0.001), have a history of migraines (OR, 1.6; 95% CI, 1.3-2.0; p<0.001) and recent neck trauma (OR, 1.6; 95% CI, 1.3-1.9; p<0.001) while having fewer traditional vascular risk factors. Young adults with CeAD had higher odds of a non-ischemic presentation (OR, 1.3; 95% CI, 1.1-1.5; p=0.013), vertebral artery dissection (OR 2.5; 95% CI, 2.2-3.0; p<0.001), and multivessel involvement (OR 1.5; 95% CI, 1.1-1.9; p=0.004). In adjusted analysis, younger age was not associated with an increased risk of recurrent ischemic stroke (adjusted Hazard Ratio [HR], 0.48; 95% CI 0.2-1.2; p=0.119). Younger age was associated with significantly greater odds of excellent functional outcome at 90 days (aOR, 1.48; 1.20-1.84, p<0.001) and lower risk of death at follow up (aHR, 0.37; 95% CI, 0.17-0.81; p=0.012) after CeAD. Conclusion: In a large international cohort, young adults with CeAD had a distinct clinical phenotype with higher odds of non-ischemic presentation, vertebral artery dissection, and multivessel involvement while having fewer traditional vascular risk factors. Young adults had a decreased odds of disability and mortality after CeAD.