BACKGROUND AND OBJECTIVES:Recent reports have suggested that levodopa exposure may contribute to freezing of gait (FOG), but this relationship remains controversial because of confounding by disease severity and duration. Our goal was to assess the relationship between levodopa use and FOG incidence and severity. METHODS:We studied 2 prospective, multicentric cohorts: NS-Park and Parkinson's Progression Markers Initiative (PPMI). Patients with ≥2 visits were selected. Three nested subcohorts were defined based on disease duration, baseline FOG, and levodopa exposure. FOG was assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II 2.13. Analyses included mixed-effects ordered logistic regression to evaluate FOG severity and Kaplan-Meier and Cox proportional hazards models to assess incident FOG. Models adjusted for disease duration, Hoehn and Yahr (H&Y) stage, and MDS-UPDRS Part III scores. RESULTS:A total of 25,602 patients with Parkinson disease from the NS-Park (mean age 68.3 ± 29.1, 42% female) and 1,441 from the PPMI (mean age 62.9 ± 9.8, 37% female) cohorts were included. In unadjusted analyses with the NS-Park cohort, levodopa use was associated with higher FOG severity and incidence, but this association was no longer statistically significant in the PPMI cohort. In mixed-effects ordinal logistic regression models adjusting for disease duration/severity, levodopa status showed a nonsignificant effect size on FOG (NS-Park odds ratio [OR] 1.84, 95% CI 0.94-3.61, p = 0.074; PPMI OR 0.76, 95% CI 0.38-1.51, p = 0.430), while disease duration (NS-Park OR 4.4, 95% CI 3.01-6.29, p = 6.0e-15; PPMI OR 6.97, 95% CI 5.05-9.63, p = 4.7e-32), Hoehn & Yahr stage (NS-Park OR 6.8, 95% CI 3.52-13.08, p = 1.059e-08; PPMI OR 1.5, 95% CI 0.96-2.22, p = 0.073), and MDS-UPDRS-III score (NS-Park OR 1.85, 95% CI 1.38-2.49, p = 4.34e-05; PPMI OR 2.00, 95% CI 1.67-2.39, p = 2.4e-14) were independently associated with greater FOG severity. No statistically significant association was observed between future levodopa exposure and de novo FOG incidence. In turn, FOG incidence was driven by the H&Y (NS-Park: hazard ratio [HR] 1.94, 95% CI 1.68-2.23; PPMI: HR 1.78, 95% CI 1.47-2.17) and MDS-UPDRS III (NS-Park: HR 1.40, 95% CI 1.07-1.83; PPMI: HR 1.26, 95% CI 1.17-1.36). DISCUSSION:No significant or consistent association between levodopa exposure and FOG severity or incidence was observed after adjustment for disease duration and severity, with the effect estimates significantly attenuated despite residual uncertainty.
Abstract Background and aims We aimed to assess the effect of DTAS for patients with acute severe neurological deficit highly suggestive of ischemic stroke due to a large vessel occlusion (ASND-LVO). Methods We did an open-label, multicentre, randomised controlled trial performed in 10 comprehensive stroke centres in France. We enrolled adult patients (85 years) with ASND-LVO (unilateral motor deficit with a score 5 plus a cortical symptom with a score 1 based on the NIHSS) admitted within 5 hours of symptom onset. Patients were randomised in (1:1) ratio to DTAS or conventional pathway. The primary outcome was functional independence defined as modified Rankin Scale score 0 to 2 at 90 days in the intention-to-treat population. Results 115 patients (57 in the DTAS and 58 in the conventional group) were randomised. The steering committee permanently stopped the trial for safety reasons. In the ITT analysis, the risk of symptomatic intracranial hemorrhage was increased in the DTAS group compared to the conventional group (5 15% of 34 vs 0 0% of 42; adjusted odds ratio OR 10·2; 95% confidence interval [CI] 1·18-1296). DTAS led to a non-significant lower rate of functional independence (20 36% of 56 vs 22 42% of 53; adjusted OR 0·73; 95% CI 0·32-1·69). Analysis in the modified intention-to-treat (patients with LVO) population yielded similar findings. Conclusions DTAS pathway are associated with an increased risk of symptomatic intracranial hemorrhage without evidence for a beneficial effect on functional outcome. Conflict of interest
Current triplet regimens associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab have dramatically improved the outcome of immune-mediated thrombotic thrombocytopenic purpura (iTTP). However, nearly half of the patients require extended caplacizumab treatment (i.e., > 30 days) due to persistent ADAMTS13 deficiency, raising cost and tolerance concerns. Therefore, we investigated whether anti-ADAMTS13 antibodies titer and their trajectory during the acute phase of the disease could predict ADAMTS13 improvement (i.e., activity ≥ 20% before day-30 post-TPE). From a cohort of 286 patients receiving the triplet regimen, we identified on diagnosis a cut-off value for anti-ADAMTS13 IgG antibodies of 90.5 U/mL, with a modest discriminating ability (AUC: 0.57) for predicting long-term response, precluding its use to guide therapeutic strategies. Nonetheless, the analysis of anti-ADAMTS13 IgG antibodies titer trajectory from diagnosis revealed that the proportion of iTTP patients with ADAMTS13 activity improvement was higher in patients who decreased (Dec+) their antibodies titer within the 7-14 days interval post-TPE compared to those without decrease (Dec-) (65% vs. 25% of cases, respectively, p < 0.001), a finding confirmed in a validation cohort (N = 51). These results highlight the possibility of intensifying immunosuppression in an early period post-TPE to shorten time to ADAMTS13 activity recovery. Close monitoring of anti-ADAMTS13 antibodies titer may guide immunomodulation strategies, including additional courses of B-cell depleting agents when appropriate.
Objectives: To identify risk factors for conversion, develop a predictive Conversion Risk Score (CRS), and assess the association between conversion and severe postoperative complications. Background: Conversion occurs in 15-30% of minimally invasive left pancreatectomies (MILP). Risk factors and potential negative impacts on postoperative outcomes are poorly described. Methods: Retrospective, nationwide, multicenter study including all MILP (laparoscopy and robot) performed between 2010 and 2021. Risk factors for conversion were identified by multivariate mixed model, and a CRS was developed on a “training-set” and validated (calibration diagrams and ROC curves) on a “validation-set.” The association between severe complications and conversion was assessed using a propensity score based on the main risk factors for severe complications: age, sex, BMI, ASA score, tumor malignancy, multi-organ resection, operative duration, blood loss, splenectomy. Results: 2104 patients included from 55 centers. Conversion occurred in 15.6% of MILP. Its risk factors were male sex (OR=1.67;P=0.048), BMI≥25 kg/m2 (OR=2.15;P=0.004), history of laparotomy (OR=2.9;P<0.001), initial pancreatitis (OR=3.58;P=0.007), tumor size≥40 mm (OR=2.12;P=0.003), planned splenectomy (OR=2.63;P<0.001), unplanned splenectomy (OR=4.05;P=0.028), portal vein resection (OR=36.3;P=0.002), multi-organ resection (OR=12.97;P<0.001). A predictive CRS was created based only on preoperatively available variables (the first six), with scores ranging from 0 to 7, corresponding to a conversion risk of 2% to 100%. No association was observed with tumor malignancy, robotic approach, or pancreatectomy volume. Conversion was significantly associated with severe complications [OR=1.80(1.16-2.54)], independent of other risk factors for complications. Conclusions: Conversion during MILP can be predicted by CRS, aiding surgeons in decision-making, given its significant association with severe complications.
