Citations

Introduction Mechanical thrombectomy (MT) is a well‐established treatment for acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, its role in cervical artery dissection‐related (CeAD) LVO remains debated due to anatomical complexities and procedural challenges. This systematic review and meta‐analysis aims to evaluate the safety, efficacy, and clinical outcomes of MT in patients with AIS due to CeAD‐related LVO, compared with other AIS etiologies. Methods PubMed, Embase, and Scopus were systematically searched from inception through March 2025. Comparative observational studies evaluating the use of MT in adult patients with AIS due to LVO were included, specifically those comparing outcomes in those with CeAD versus non‐CeAD etiologies. Most studies were retrospective and multicentric. Eligible interventions included stent retriever thrombectomy, direct aspiration (ADAPT), or combined approaches. Results Nine studies with a total of 4889 patients were included, comprising 446 CeAD‐related and 4443 non‐CeAD LVO cases. MT for CeAD‐related AIS showed no statistically significant difference in successful recanalization compared with non‐CeAD cases (OR:0.81, CI: [0.63,1.04], p=0.10). However, CeAD patients had significantly higher rates of 90‐day functional independence (mRS 0‐2) (OR:2.17, CI: [1.55, 3.05], p < 0.0001) and lower 90‐day mortality (OR:0.34, CI: [0.22, 0.53], p < 0.0001). Rates of distal embolization (OR:1.60, CI: [0.69, 3.70], p = 0.27), symptomatic ICH (OR:0.84, CI: [0.51, 1.38], p=0.49), or iatrogenic dissection (OR:1.58, CI: [0.59, 4.22], p=0.36) did not differ significantly. Conclusions Mechanical thrombectomy in CeAD‐related LVO is safe and associated with clinical outcomes comparable to patients with non‐CeAD acute ischemic causes. They demonstrated a similar patient safety profile, such as functional outcomes and mortality.

Background Mechanical thrombectomy (MT) is a well-established treatment for acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, its role in cervical artery dissection-related (CeAD) LVO remains debated due to anatomical complexities and procedural challenges. This systematic review and meta-analysis aims to evaluate the safety, efficacy, and clinical outcomes of MT in patients with AIS due to CeAD-related LVO compared with other AIS etiologies. Methods PubMed, Embase, and Scopus were systematically searched from inception to March 2025. Comparative observational studies evaluating the use of MT in adult patients with AIS due to LVO were included, specifically those comparing outcomes in patients with CeAD versus non-CeAD etiologies. Results MT for CeAD-related AIS showed no statistically significant difference in successful recanalization compared with non-CeAD cases (OR 0.81 (95% CI 0.63 to 1.04), P=0.10). However, patients with CeAD-related AIS had significantly higher rates of 90-day functional independence (modified Rankin Scale score 0–2) (OR 2.17 (95% CI 1.55 to 3.05), P<0.01) and lower 90-day mortality (OR 0.34 (95% CI 0.22 to 0.53), P<0.01). Rates of distal embolization (OR 1.60 (95% CI 0.69 to 3.70), P=0.27), symptomatic intracranial hemorrhage (OR 0.84 (95% CI 0.51 to 1.38), P=0.49), or iatrogenic dissection (OR 1.58 (95% CI 0.59 to 4.22), P=0.36) did not differ significantly between patient groups. Conclusions MT in patients with CeAD-related LVO is safe, effective, and associated with improved functional outcomes and lower mortality compared with patients with non-CeAD acute ischemic causes.

Importance Treatment for cognitive dysfunction due to postacute sequelae of long COVID (ie, symptoms of fatigue, malaise, weakness, confusion that persist beyond 12 weeks after an initial COVID infection) remains a significant unmet need. Objective To test evidence-based rehabilitation strategies for improving cognitive symptoms in persons with long COVID. Design, Setting, and Participants This was a 5-arm, multicenter, randomized clinical trial of 3 remotely delivered interventions conducted between August 17, 2023, and June 10, 2024. The study took place at 22 trial sites and included the screening of individuals with cognitive long COVID. Interventions Participants were randomized to 1 of 5 arms: adaptive computerized cognitive training (BrainHQ [Posit Science]), cognitive-behavioral rehabilitation involving both group and individual counseling sessions (PASC-Cognitive Recovery [PASC-CoRE]) paired with BrainHQ, and transcranial direct current stimulation (tDCS) paired with BrainHQ. Two comparator arms were included as follows: unstructured computer puzzles and games (active comparator) and sham tDCS paired with BrainHQ. The interventions occurred 5 times per week over 10 weeks. Main Outcomes and Measures Cognitive and behavioral in-person assessments were performed at baseline, midintervention, at the end of intervention, and 3 months after the end of the intervention. The primary outcome measure was the modified Everyday Cognition Scale 2 (ECog2) completed at the end of the intervention compared to the baseline visit based on participant self-report looking back over the prior 7 days. Results A total of 378 individuals were screened, from which there were 328 participants (median [IQR] age, 48.0 [37.0-58.0] years; 241 female [73.5%]; race: 15 Asian [4.6%], 47 Black [14.3%], and 235 White [71.6%]; ethnicity: 52 Hispanic [15.9%]). None of the 3 active interventions demonstrated benefits on the modified ECog2 in the intention-to-treat population by the end of the intervention period. The adjusted differences in mean change were 0.0 (95% CI, −0.2 to 0.2) for BrainHQ vs active comparator, 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs active comparator, 0.0 (95% CI, −0.2 to 0.2) for tDCS-active + BrainHQ vs tDCS-sham + BrainHQ, and 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs BrainHQ alone. Secondary participant-reported outcomes and neuropsychological tests showed no differential benefits for any treatment arm. All 5 arms demonstrated some improvements over time on the modified ECog2 and on secondary outcomes. There were no serious adverse events attributable to the interventions. Conclusions and Relevance This phase 2 randomized clinical trial failed to demonstrate differential benefits for online cognitive training, a structured cognitive rehabilitation program, and tDCS for cognitive long COVID. Trial Registration ClinicalTrials.gov Identifier: NCT05965739 .

Abstract Aim To identify patient factors, including gastrointestinal functions, that are predictive or associated with weight loss in response to once‐daily 3 mg liraglutide administered subcutaneously (SQ) or placebo in obesity. Methods One hundred and thirty‐six obese adults (87% female) were randomized in a placebo‐controlled, 16‐week trial of liraglutide, escalated to 3 mg administered SQ daily. Gastrointestinal functions were measured at baseline and 16 weeks: gastric emptying of solids (GET 1/2 ); fasting and postprandial gastric volumes; kcal ingested during ad libitum buffet meal and the nutrient drink test. GET 1/2 was also measured at 5 weeks. A multiple variable regression model examined variables associated with weight loss of more than 4 kg at 16 weeks. A parsimonious model using backward selection identified the final model. Results Weight loss of more than 4 kg at 16 weeks occurred in 71% of liraglutide‐ and 16% of placebo‐treated patients. In all participants combined, parameters univariately associated with a weight loss of more than 4 kg were GET 1/2 at 5 and 16 weeks, weight loss at 5 weeks and kcal intake during the buffet meal at 16 weeks. The final parsimonious model (area under the receiver operator characteristics [AUROC] curve = 0.832) identified that factors associated with more than 4‐kg weight loss were GET 1/2 at 5 weeks (OR = 2.505; 95% CI: 1.57‐3.997) per 50 minutes and kcal intake during ad libitum meal at 16 weeks (OR = 0.721; 95% CI: 0.602‐0.864) per 100 kcal. Among only the 60 liraglutide‐treated subjects, kcal intake at 16 weeks was associated with 4‐kg weight loss (AUROC = 0.757). Conclusions Slower GET 1/2 and weight loss at 5 weeks predicted a weight loss of more than 4 kg at 16 weeks in all participants. Among liraglutide‐treated adults, weight loss of more than 4 kg was associated with ad libitum meal kcal intake at 16 weeks.

Abstract Objective This study aimed to determine the effects of a long‐acting glucagon‐like peptide‐1 (GLP‐1) receptor agonist, liraglutide, and placebo subcutaneously over 16 weeks on weight and gastric functions and to evaluate associations of single‐nucleotide polymorphisms in GLP1R (rs6923761) and TCF7L2 (rs7903146) with effects of liraglutide. Methods The study conducted a randomized, parallel‐group, placebo‐controlled, 16‐week trial of liraglutide, escalated to 3 mg subcutaneously daily in 136 otherwise healthy adults with obesity. Weight, gastric emptying of solids (GES), gastric volumes, satiation, and body composition measured at baseline and after treatment were compared in two treatment groups using analysis of covariance. Results Liraglutide ( n = 59) and placebo ( n = 65) groups completed treatment. Relative to placebo, liraglutide increased weight loss at 5 and 16 weeks (both p < 0.05), slowed time to half GES (T 1/2 ) at 5 and 16 weeks (both p < 0.001), and increased fasting gastric volume ( p = 0.01) and satiation ( p < 0.01) at 16 weeks. GES T 1/2 was positively correlated with weight loss on liraglutide (both p < 0.001). After 16 weeks of liraglutide, GLP1R rs6923761 (AG/AA vs. GG) was associated with reduced percent body fat ( p = 0.062), and TCF7L2 rs7903146 (CC vs. CT/TT) was associated with lower body weight ( p = 0.015). Conclusions Liraglutide, 3 mg, induces weight loss with delay in GES T 1/2 and reduces calorie intake. Slowing GES and variations in GLP1R and TCF7L2 are associated with liraglutide effects in obesity.

SummaryBackgroundTradipitant, an NK1 receptor antagonist, improved symptoms in patients with gastroparesis. It is unclear whether these effects are mediated centrally (e.g., vomiting centre) or on gastric functions. As a class, NK1 antagonists may retard gastric emptying (GE) or increase fasting and postprandial gastric volumes (GV).AimTo evaluate the effects of tradipitant relative to placebo on gastric motor functions, satiation, postprandial symptoms, and pharmacokinetics.MethodsWe conducted a randomised, double‐blind, placebo‐controlled, single‐centre study of tradipitant 85 mg or matching placebo b.i.d. for 9 consecutive days in 24 healthy volunteers. During the last 2 days of treatment, participants underwent scintigraphic measurements of GE of 320 kcal egg meal, fasting and postprandial GV by SPECT, and satiation by nutrient drink ingested to maximum tolerated volume (MTV) and symptoms 30 min later. Treatments were compared by Wilcoxon rank sum test. The study had 80% power to detect group differences of 23.6% in GV and 29.2% in GE T1/2.ResultsThe two groups of healthy participants were well balanced based on demographic features, age, and BMI. There were nonsignificant positive correlations between blood levels of tradipitant and accommodation GV and GE at 4 h. There were no significant effects of tradipitant, 85 mg b.i.d. for 9 days compared to placebo on GE, GV, satiation, or symptoms 30 min after MTV.ConclusionTradipitant, 85 mg b.i.d., does not significantly affect gastric motor functions (GV or GE). Importantly, there was no retardation of GE by tradipitant, which is important in relation to its potential use in patients with gastroparesis.Clinic trials registryClinicalTrials.gov #NCT04849559.