Frequency and predictors of decompressive craniectomy in ischemic stroke patients treated by mechanical thrombectomy in the ETIS registry.

BACKGROUND AND AIMS: Mechanical thrombectomy (MT) for patients with acute ischemic stroke (AIS) is usually performed in a comprehensive stroke center with on-site neurosurgical expertise. The question of whether MT can be performed in a primary stroke center without a neurosurgical facility is debated. In this context, there is a need to determine the frequency, delay and predictors of neurosurgical procedures in patients treated by MT. This study aims to determine these factors. METHODS: In total, 432 patients under 60years old, diagnosed with an acute ischemic stroke with a large vessel occlusion and treated by MT between January 2018 and December 2019 in six French stroke centers, were selected from the French clinical registry ETIS. Univariate and multivariate logistic regression models were used to identify predictive factors for decompressive craniectomy. RESULTS: Among the 432 included patients, 43 (9.9%) patients with an anterior circulation infarct underwent decompressive craniectomy. Higher admission NIHSS (OR: 1.08 [95% CI: 1.02-1.16]), lower ASPECT (OR per 1 point of decrease 1.53 [1.31-1.79] P<0.001) and preadmission antiplatelet use (OR: 3.03 [1.31-7.01]) were independent risk factors for decompressive craniectomy. The risk of decompressive craniectomy increases to more than 30% with an ASPECT score<4, an NIHSS>16, and current antiplatelet use. CONCLUSION: In this multicenter registry, 9% of acute ischemic stroke patients (<60years old) treated with MT, required decompressive craniectomy. Higher NIHSS score, lower ASPECT score, and preadmission antiplatelet use increase the risk of subsequent requirement for decompressive craniectomy.

TICI-RANKIN mismatch: Poor clinical outcome despite complete endovascular reperfusion in the ETIS Registry.

INTRODUCTION: Endovascular treatment (EVT) is a well-established technic for acute ischemic stroke, but despite a high recanalization rate of near 80%, at 3 months roughly 50% of patients have a poor functional outcome with a modified Rankin score (mRS) ≥3. The aim of this study was to determine predictive factors of poor functional outcomes in patients with complete recanalization after EVT, defined as modified thrombolysis in cerebral infarction (mTICI) 3. PATIENTS AND METHODS: This retrospective analysis based on the prospective multicenter ETIS registry (endovascular treatment in ischemic stroke) in France included 795 patients from January 2015 and November 2019 with acute ischemic stroke due to anterior circulation occlusion and prestroke mRS 0-1, treated with EVT and who achieved complete recanalization. Univariate and multivariate logistic regression models were used to identify predictive factors of poor functional outcome. RESULTS: 365 patients (46%) showed a poor functional outcome (mRS>2). In backward-stepwise logistic regression analysis, poor functional outcome was independently associated with older age (OR per 10-year increase, 1.51; 95%CI, 1.30 to 1.75), higher admission NIHSS (OR per 1 point increase, 1.28; 95%CI, 1.21 to 1.34), absence of prior intravenous thrombolysis (OR, 0.59; 95%CI, 0.39 to 0.90), and an unfavorable 24-hour NIHSS change (24h-baseline) (OR, 0.82; 95%CI, 0.79 to 0.87). We calculated that patients whose 24h NIHSS decreased by less than 5 points are more at risk of a poor outcome, with a sensitivity and a specificity of 65.0%. CONCLUSION: Despite complete reperfusion after EVT, half of patients had a poor clinical outcome. These patients, who were mainly older with a high initial NIHSS and an unfavorable post-EVT 24h NIHSS change, could represent a target population for early neurorepair and neurorestorative strategies.

Does ultrasound-guidance improve the outcome of botulinum toxin injections in cervical dystonia?

PURPOSE: Ultrasound-guided injections of botulinum neurotoxin in cervical dystonia have a number of theoretical advantages. However, their action has never been compared to that of non-guided injections. The objectives of the study were to compare the outcome of botulinum neurotoxin type A treatment in patients with idiopathic, focal cervical dystonia, according to two methods: inspection and palpation of anatomical landmarks (non-guided group) or ultrasound guidance (ultrasound-guided group). METHODS: We included consecutive patients in this single-center, prospective, real-life, non-randomized study. The outcomes were evaluated one month after the injections: Cervical Dystonia Impact Profile 58 (main outcome), Toronto Western Spasmodic Torticollis Rating Scale-2 (pain and disability subscores), Toronto Western Spasmodic Torticollis Rating Scale-PSYCH, patient-rated Clinical Global Impression - Improvement and adverse events. We used propensity score methods for statistical analysis; ten predefined confounding factors were used to build the propensity score. RESULTS: Sixty-three patients were included in the non-guided group, and 60 other patients in the ultrasound-guided group. We found no difference in main and secondary outcomes between the two study groups. CONCLUSION: This is the first direct comparison between ultrasound-guided and non-guided botulinum neurotoxin type A injections in patients with cervical dystonia. We hypothesize that ultrasound guidance made it possible to obtain the same results in the most severe (or the most demanding) patients as in the best responders. Further studies are still needed to assess the impact of botulinum neurotoxin injections into deep cervical muscles.

Is There an Optimal Definition for a Positive Circumferential Resection Margin in Locally Advanced Esophageal Cancer?

BACKGROUND: Two definitions of a positive circumferential resection margin (CRM) in esophageal cancer coexist: one by the College of American Pathologists (CAP) (CRM = 0 mm) and another by the Royal College of Pathologists (RCP) (CRM ≤ 1 mm). This study aimed to evaluate the prognostic value of both definitions in esophageal cancer and to identify a new cutoff value for the CRM to predict survival. METHODS: Patients who underwent curative esophageal resection for locally advanced (≥ pT3) adenocarcinoma or squamous cell carcinoma were selected from 2007 to 2016. The CRM was reassessed using an ocular micrometer. Overall survival (OS) and disease-free survival were estimated with uni- and multivariate analyses. RESULTS: The study enrolled 283 patients: 48 with a positive CRM according to the CAP definition and 171 with a positive CRM according to the RCP definition. In the multivariate analysis, a positive CRM according to both definitions was significantly associated with a poor OS (CAP: hazard ratio [HR], 2.26, p < 0.001; RCP: HR, 1.42, p = 0.035). A CRM of 0 mm was predictive of a worse OS and DFS than a CRM of 1 mm or less (p < 0.0001), whereas no significant difference was found between a CRM greater than 1 mm and a CRM of 1 mm or less, indicating that the CAP definition was more accurate for predicting prognosis and recurrence. New cutoff CRM values of 100 µm in squamous cell carcinoma and 200 µm in adenocarcinoma were optimal for predicting OS. CONCLUSION: The CAP definition was more accurate for predicting prognosis and recurrence. The study identified a new cutoff value of CRM according to histologic type.

Longitudinal study of AMH variations in 122 Adolescents and Young Adults (AYA) and non-AYA lymphoma patients to evaluate the chemo-induced ovarian toxicity to further personalise fertility preservation counselling.

STUDY QUESTION: What is the influence of age and chemotherapy regimen on the longitudinal blood anti-Müllerian hormone (AMH) variations in a large series of adolescents and young adult (AYA) (15-24 years old) and non-AYA (25-35 years old) lymphoma patients? SUMMARY ANSWER: In case of alkylating regimen treatment, there was a deep and sustained follicular depletion in AYA as well as non-AYA patients; however in both groups, the ovarian toxicity was extremely low in cases of non-alkylating treatments. WHAT IS KNOWN ALREADY: AMH is now well-recognised to be a real-time indicator of ovarian follicular depletion and recovery in women treated by chemotherapy. Its longitudinal variations may discriminate between highly and minimally toxic protocols regarding ovarian function. It has been shown, in different cancer types, that age, type of chemotherapy regimen and pre-treatment AMH levels are the main predictors of ovarian recovery. Large studies on longitudinal AMH variations under chemotherapy in lymphoma patients are few but can provide the opportunity to assess the degree of follicle loss at a young age. STUDY DESIGN, SIZE, DURATION: This prospective cohort study was conducted in the Fertility Observatory of the Lille University Hospital. Data were collected between 2007 and 2016. Non-Hodgkin or Hodgkin lymphoma patients (n = 122) between 15 and 35 years old were prospectively recruited before commencing chemotherapy. Patients were treated either by a non-alkylating protocol (ABVD group; n = 67) or by an alkylating regimen (alkylating group; n = 55). PARTICIPANTS/MATERIALS, SETTING, METHODS: Serial AMH measurements were performed at baseline (AMH0), 15 days after the start of chemotherapy (AMH1), 15 days before the last chemotherapy cycle (AMH2), and at time 3, 6, 9, 12, 18 and 24 months from the end of chemotherapy. The whole study population was divided into two groups according to age: AYA (15-24; n = 65) and non-AYA (25-35; n = 57). All patients received a once monthly GnRH agonist injection during the whole treatment period. A linear mixed model was used to account for the repeated measures of single patients. MAIN RESULTS AND THE ROLE OF CHANCE: At baseline, non-AYA patients had higher BMI and lower AMH levels than AYA patients. All AYA and non-AYA patients having received ABVD protocols had regular cycles at 12 months of follow-up. In case of alkylating regimens, amenorrhoea was more frequent in non-AYA patients than in AYA patients at 12 months (37% vs 4%, P = 0.011) and at 24 months (24% vs 4%, P = 0.045). We distinguished a similar depletion phase from AMH0 to AMH2 between ABVD and alkylating groups but significantly different recovery phases from AMH2 to AMH + 24 months. AMH recovery was fast and complete in case of ABVD protocols whatever the age: AMH reached pre-treatment values as soon as the 6th month of follow-up in the AYA group (mean (95% CI) in log AMH M0 vs M6: 3.07 (2.86 to 3.27) vs 3.05 (2.78 to 3.31), P = 1.00) and in the non-AYA group (mean (95% CI) in log AMH M0 vs M6: 2.73 (2.40 to 3.05) vs 2.47 (2.21 to 2.74), P = 1.00). In contrast, no patients from the alkylating group returned to pre-treatment AMH values whatever the age of patients (AYA or non-AYA). Moreover, none of the AMH values post-chemotherapy in the non-AYA group were significantly different from AMH2. Conversely in the AYA group, AMH levels from 6 months (mean (95% CI) in log AMH: 1.79 (1.47 to 2.11), P < 0.001) to 24 months (mean (95% CI) in log AMH: 2.16 (1.80 to 2.52), P ≤ 0.001) were significantly higher than AMH2 (mean (95% CI) in log AMH: 1.13 (0.89 to 1.38)). Considering the whole study population (AYA and non-AYA), pre-treatment AMH levels influenced the pattern of the AMH variation both in alkylating and ABVD protocols (interaction P-value = 0.005 and 0.043, respectively). Likewise, age was significantly associated with the pattern of the recovery phase but only in the alkylating group (interaction P-value =0.001). BMI had no influence on the AMH recovery phase whatever the protocol (interaction P-value = 0.98 in alkylating group, 0.72 in ABVD group). LIMITATIONS, REASONS FOR CAUTION: There was a large disparity in subtypes of protocols in the alkylating group. The average duration of chemotherapy for patients treated with alkylating protocols was longer than that for patients treated with ABVD. WIDER IMPLICATIONS OF THE FINDINGS: These results make it possible to develop strategies for fertility preservation according to age and type of protocol in a large series of young lymphoma patients. In addition, it was confirmed that young age does not protect against ovarian damage caused by alkylating agents. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Agence Régionale de Santé Hauts de France and Agence Onco Hauts-de-France who provided finances for AMH dosages (n° DOS/SDES/AR/FIR/2019/282). There are no competing interests. TRIAL REGISTRATION NUMBER: DC-2008-642 and CNIL DEC2015-112.

Prognosis and risk factors associated with asymptomatic intracranial hemorrhage after endovascular treatment of large vessel occlusion stroke: a prospective multicenter cohort study.

BACKGROUND AND PURPOSE: Asymptomatic intracranial hemorrhage (aICH) is a common occurrence after endovascular treatment (EVT) for acute ischemic stroke (AIS). The aims of this study were to address its impact on 3-month functional outcome and to identify risk factors for aICH after EVT. METHODS: Patients with AIS attributable to anterior circulation large vessel occlusion who underwent EVT were enrolled in a multicenter prospective registry. Based on imaging performed 22-36 h post-EVT, we included patients with no intracranial hemorrhage (ICH) or aICH. Poor outcome defined as a 3-month modified Rankin Scale (mRS) score 4-6 and overall 3-month mRS score distribution were compared according to presence/absence of aICH, and aICH subtype using logistic regression. We assessed the risk factors of aICH using a multivariate logistic regression model. RESULTS: Of the 1526 patients included in the study, 653 (42.7%) had aICH. Patients with aICH had a higher rate of poor outcome: odds ratio (OR) 1.88 (95% confidence interval [CI] 1.44-2.44). Shift analysis of mRS score found a fully adjusted OR of 1.79 (95% CI 1.47-2.18). Hemorrhagic infarction (OR 1.63 [95% CI 1.22-2.18]) and parenchymal hematoma (OR 2.99 [95% CI 1.77-5.02]) were associated with higher risk of poor outcome. Male sex, diabetes, coronary artery disease, baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early Computed Tomography Score, number of passes and onset to groin puncture time were independently associated with aICH. CONCLUSIONS: Patients with aICH, irrespective of the radiological pattern, have a worse functional outcome at 3 months compared with those without ICH after EVT for AIS. The number of EVT passes and the time from onset to groin puncture are factors that could be modified to reduce deleterious ICH.

Neurological improvement predicts clinical outcome after acute basilar artery stroke thrombectomy.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is the standard of care for patients with anterior circulation large vessel occlusion. Early neurological improvement (ENI), defined as a reduction of ≥ 8 on the National Institutes of Health Stroke Scale (NIHSS) compared with baseline score, or an NIHSS score of 0 or 1 at 24 h after MT, is a strong predictor of 3-month favorable outcome in such patients. The impact of ENI after MT in stroke patients with basilar artery occlusion (BAO) on 3-month outcome is not clear. We aimed to study the effects of ENI in patients with BAO. METHODS: We performed a retrospective analysis of a multicenter prospective cohort of all consecutive stroke patients with BAO who underwent MT. We compared clinical outcomes between BAO patient groups according to ENI status. Multivariate analyses were performed to determine the impact of ENI on favorable 90-day outcome (modified Rankin scale score 0-3) and to report factors contributing to ENI. RESULTS: A total of 237 patients were included. ENI was observed in 70 patients (30%). Outcomes were significantly better in ENI-positive patients, with 84% achieving favorable outcome (mRS score 0-3) at 3 months versus 30% for ENI-negative patients (P < 0.0001). In multivariate analysis, ENI was an independent predictive factor associated with higher rates of favorable outcome {odds ratio (OR) 18.12 [95% confidence interval (CI) 3.95-83.10]; P = 0.0001}. Higher number of passes [OR 0.62 (95% CI 0.43-0.89); P = 0.010] and need for stenting [OR 0.27 (95% CI 0.07-0.95); P = 0.041] were negatively associated with ENI. CONCLUSION: Early neurological improvement on day 1 following MT for BAO is a strong independent predictor of a favorable 3-month clinical outcome.

Impact of recanalisation by mechanical thrombectomy in mild acute ischemic stroke with large anterior vessel occlusion.

BACKGROUND: The net clinical benefit of mechanical thrombectomy (MT) in patients presenting acute anterior circulation ischemic stroke with large-vessel occlusion (AIS-LVO) and mild neurological deficit is uncertain. AIMS: To investigate efficacy and safety of MT in patients with acute AIS-LVO and mild neurological deficit by evaluating i) the influence of recanalisation on three-month outcome and ii) mortality, symptomatic intracerebral hemorrhage (sICH) and procedural complications. METHODS: We included consecutive patients with acute AIS-LVO and National Institute of Stroke Scale (NIHSS) score<8, treated by MT at Lille University Hospital. Recanalisation was graded according to modified thrombolysis in cerebral infarction (mTICI) score, mTICI 2b/2c/3 being considered successful. We recorded procedural complications and classified intra-cerebral hemorrhages (ICH) and sICH according with European Cooperative Acute Stroke Study (ECASS) and ECASS2 criteria. Three-month outcome was evaluated by modified Rankin scale (mRS). Excellent and favourable outcomes were respectively defined as mRS 0-1 and 0-2 (or similar to pre-stroke). RESULTS: We included 95 patients. At three months, 56 patients (59. 0%) achieved an excellent outcome and 69 (72, 6%) a favourable outcome, both being more frequent in patients with successful recanalisation than in patients without (excellent outcome 71, 1% versus 10, 5%, P<0.001 and favourable outcome 82.9% versus 31.6%, P<0.001). The difference remained unchanged after adjustment for age and pre-MT infarct volume. Similar results were observed in patients with pre-MT NIHSS ≤5. Death occurred in five patients (5.3%), procedural complications in 12 (12.6%), any ICH in 38 (40.0%), including 3 (3.2%) sICH. CONCLUSIONS: Achieving successful recanalisation appears beneficial and safe in acute AIS-LVO patients with NIHSS<8 before MT.

Two-layered susceptibility vessel sign is associated with biochemically quantified thrombus red blood cell content.

BACKGROUND AND PURPOSE: Better characterization of the thrombus could be useful to determine acute ischaemic stroke (AIS) aetiology and predict response to thrombolysis and endovascular therapy (EVT). To test the hypothesis that susceptibility vessel sign (SVS) on baseline magnetic resonance imaging (MRI) is related to red blood cell (RBC) content of AIS thrombi, the total haemoglobin contents (HbCs) of AIS thrombi retrieved by EVT from patients with or without SVS or two-layered SVS (TLSVS) were compared. METHODS: Baseline MRI of 84 anterior AIS patients was reviewed by neuro-radiologists blinded to clinical and biochemical data. Thrombi from these patients were retrieved by EVT and analysed for HbC by quantitative enzyme-linked immunosorbent assay and measurement of haem concentration. RESULTS: Susceptibility vessel sign and TLSVS were respectively observed in 85.7% and 50.0% of cases. The median HbC content was 253 µg/mg thrombus (interquartile range 177-333) and the median haem content was 219 µg/mg thrombus (131-264). Thrombus HbC and haem content were highly correlated with thrombus RBC content determined by flow cytometry (r = 0.94). Thrombi from patients with TLSVS weighed more [31.1 (16.5-68.3) mg vs. 17.7 (11.7-33.3) mg; P = 0.005] and had a higher HbC content [278 (221-331) µg/mg vs. 196 (139-301) µg/mg; P = 0.010] compared to thrombi from patients without TLSVS. There was no difference in thrombus weight or HbC content according to SVS status. CONCLUSIONS: Our study shows that TLSVS is significantly associated with a higher thrombus weight and RBC content, as determined by quantitative assays.

Early successful reperfusion after endovascular therapy reduces malignant middle cerebral artery infarction occurrence in young patients with large diffusion-weighted imaging lesions.

BACKGROUND AND PURPOSE: Malignant middle cerebral artery infarction (MMI) is a severe complication of acute ischaemic stroke (AIS). The aim of our study was to assess whether successful reperfusion after endovascular therapy (EVT) in AIS with clinical and imaging predictors of MMI decreased its occurrence. METHODS: Data were collected between January 2014 and July 2018 in a monocentric prospective AIS registry of patients treated with EVT. Patients selected were <65 years old with severe anterior circulation AIS with a National Institutes of Health Stroke Scale score >15, baseline Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score ≤ 6 and baseline diffusion-weighted imaging lesion volume >82 mL within 6 h of symptom onset. Successful reperfusion was defined as a Thrombolysis in Cerebral Ischemia score ≥ 2b. Occurrence of MMI was the primary endpoint. RESULTS: A total of 66 EVT-treated patients were included in our study. MMI occurred in 27 patients (41%). In unadjusted analysis, successful reperfusion was associated with fewer MMIs (31.8% vs. 65.0%; P = 0.015) and with more favorable outcome at 3 months (50% vs. 20%; P = 0.023). In multivariate analysis, successful reperfusion was associated with an adjusted odds ratio (95% confidence intervals) of 0.35 (0.10-1.12) for MMI and 2.77 (0.84-10.43) for 3-month favorable outcome occurrence. CONCLUSIONS: Early successful reperfusion performed in patients with AIS with clinical and imaging predictors of MMI was associated with decreased MMI occurrence. Reperfusion status might be considered in evaluating the need for craniectomy in patients with early predictors of MMI.

[Elaboration and psychometric properties of a well-being scale at work. The Serenat study among employees in occupational medicine unit]. / Élaboration et qualités psychométriques d'une échelle de bien-être au travail. Étude SERENAT auprès de salariés vus en médecine du travail.

BACKGROUND: Well-being at work is nowadays a major public health challenge. It includes, among others, absence of psychological (anxio-depressive) symptoms, perceived positive work conditions (environment and organization), happiness and good quality of life at work. Many studies have shown that social support and control at work protect mental health while high job demands and effort-reward imbalance are risk factors for anxiety and depression. There is currently no global indicator to measure both the state of mental health and social working conditions. The main objective of this work is to construct and explore the psychometric properties of scale of well-being at work called "Serenat" in order to validate it. METHODS: The Serenat Scale is a self-report questionnaire composed of 20 items. All items are scored on a four-point Likert scale ranging from 0 (strongly disagree) to 3 (strongly agree) resulting in a range of 0 to 60. It was constructed from data collected from the literature and from consultations in an Occupational Health Unit. From January 2014 to May 2017 193 subjects who have consulted an occupational doctor are included in this cross sectional survey. Validation included item quality and data structure diagnosis, internal consistency, intraobserver reliability evaluation and external consistency. RESULTS: The Serenat scale showed very good item quality, with a maximal non-response rate of 0.01 % per item, and no floor effect. Factor analysis concluded that the scale can be considered unidimensional. Cronbach's alpha of internal consistency was 0.89. The intraclass correlation coefficient for intraobserver reliability was 0.89. Serenat scale was correlated with HADS (r=-0.54; P<0.001), STAI-Y (r=-0.78; P<0.001) and BDI-13 (r=-0.57; P<0.001). CONCLUSION: Serenat's well-being at work scale shows good psychometric properties for final validation. It could be useful to occupational physicians for individual and collective screening. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02905071.

Unknown-onset strokes with anterior circulation occlusion treated by thrombectomy after DWI-FLAIR mismatch selection.

BACKGROUND AND PURPOSE: The DAWN trial recently showed compelling evidence in treating late window and wake-up stroke patients with thrombectomy using a clinical-imaging mismatch. The aim was to evaluate the results of thrombectomy for unknown-onset strokes (UOS) treated in our centres after a diffusion weighted imaging/fluid attenuated inversion recovery (DWI-FLAIR) mismatch based selection. METHODS: A multicentre, cohort study was performed of consecutive UOS treated by thrombectomy between 2012 and 2016. UOS with proximal anterior circulation occlusion discovered beyond 6 h from 'last seen normal' were compared with known-onset strokes (KOS) for whom thrombectomy was started within 6 h from onset. Time intervals were recorded from first time found abnormal. Results were adjusted for age, diabetes, hypertension, National Institutes of Health Stroke Scale, site of occlusion, DWI Alberta Stroke Programme Early CT Score, intravenous thrombolysis and use of general anaesthesia. RESULTS: Amongst 1246 strokes with anterior circulation occlusion treated by thrombectomy, 277 were UOS, with a 'last time seen well' beyond 6 h and DWI-FLAIR mismatch, and 865 were KOS who underwent groin puncture within 6 h. Favourable outcome was achieved less often in UOS than KOS patients (45.2% vs. 53.9%, P = 0.022). After pre-specified adjustment, this difference was not significant (adjusted relative risk 0.91; 95% confidence interval 0.80-1.04; P = 0.17). No differences were found in secondary outcomes. Time intervals from first found abnormal were significantly longer in UOS. CONCLUSION: Thrombectomy of UOS with anterior circulation occlusion and DWI-FLAIR mismatch appears to be as safe and efficient as thrombectomy of KOS within 6 h from onset. This pattern of imaging could be used for patient selection when time of onset is unknown.

Impact of intravenous thrombolysis and emergent carotid stenting on reperfusion and clinical outcomes in patients with acute stroke with tandem lesion treated with thrombectomy: a collaborative pooled analysis.

BACKGROUND AND PURPOSE: Tandem anterior circulation lesions in the setting of acute ischemic stroke (AIS) are a complex endovascular situation that has not been specifically addressed in trials. We determined the predictors of successful reperfusion and good clinical outcome at 90 days after mechanical thrombectomy (MT) in patients with AIS with tandem lesions in a pooled collaborative study. METHODS: This was a retrospective analysis of consecutive patients presenting to 18 comprehensive stroke centers with AIS due to tandem lesion of the anterior circulation who underwent MT. RESULTS: A total of 395 patients were included. Successful reperfusion (modified thrombolysis in cerebral infarction score 2b-3) was achieved in 76.7%. At 90 days, 52.2% achieved a good outcome (modified Rankin Scale score 0-2), 13.8% suffered a parenchymal hematoma and 13.2% were dead. Lower National Institutes of Health Stroke Scale score [odds ratio (OR), 1.26; 95% confidence intervals (CI), 1.07-1.48, P = 0.004], Alberta Stroke Program Early CT Score ≥7 (OR, 2.00; 95% CI, 1.07-3.43, P = 0.011), intravenous thrombolysis (OR, 1.47; 95% CI, 1.01-2.12, P = 0.042) and stenting of the extracranial carotid lesion (OR, 1.63; 95% CI, 1.04-2;53, P = 0.030) were independently associated with successful reperfusion. Lower age (OR, 1.58; 95% CI, 1.26-1.97, P < 0.001), absence of hypercholesterolemia (OR, 1.77; 95% CI, 1.10-2.84, P = 0.018), lower National Institutes of Health Stroke Scale scores (OR, 2.04; 95% CI, 1.53-2.72, P < 0.001), Alberta Stroke Program Early CT Score ≥7 (OR, 2.75; 95% CI, 1.24-6.10, P = 0.013) and proximal middle cerebral artery occlusion (OR, 1.59; 95% CI, 1.03-2.44, P = 0.035) independently predicted a good 90-day outcome. CONCLUSIONS: Intravenous thrombolysis and emergent stenting of the extracranial carotid lesion were predictors of a successful reperfusion after MT of patients with AIS with tandem lesion of the anterior circulation.

Exchangeable copper: a reflection of the neurological severity in Wilson's disease.

BACKGROUND AND PURPOSE: The severity of Wilson's disease (WD) is linked to free copper accumulating in the liver and brain. Exchangeable copper (CuEXC) is a new technique to determine plasmatic copper and is useful in the diagnosis of WD. It is hypothesized that it may also enable a good evaluation of extra-hepatic involvement and its severity. METHODS: Forty-eight newly diagnosed WD patients were prospectively evaluated using hepatic, neurological, ophthalmological and brain magnetic resonance imaging (MRI) scores. Three phenotypic presentations were distinguished: pre-symptomatic, hepatic and extra-hepatic. CuEXC was determined in addition to standard copper assays before decoppering therapy. Correlations between biological parameters and the different scores were determined and compared in the hepatic and extra-hepatic groups. RESULTS: Extra-hepatic patients had significantly higher CuEXC values than those with the hepatic form (P < 0.0001). The overall ability of CuEXC to separate the two forms was satisfactory, with an area under the curve of 0.883 (95% confidence interval 0.771-0.996) and an optimal threshold for extra-hepatic diagnosis of 2.08 µmol/l (sensitivity 85.7%; specificity 94.1%). In extra-hepatic patients, CuEXC was the only biological marker to be positively correlated with the Unified Wilson Disease Rating Score (r = 0.45, P = 0.016), the Kayser-Fleischer ring score (r = 0.46, P = 0.014) and the brain MRI score (r = 0.38, P = 0.048), but it was not correlated with the hepatic score. CONCLUSIONS: Exchangeable copper determination is useful when diagnosing WD as a value >2.08 µmol/l is indicative of the severity of the extra-hepatic involvement. In the case of purely hepatic presentation, atypical or mild neurological signs, it should encourage physicians to search for lesions in the brain and eyes.

Impact of thrombolysis in acute ischaemic stroke without occlusion: an observational comparative study.

BACKGROUND AND PURPOSE: The impact of intravenous recombinant tissue plasminogen activator (IV-rtPA) in patients with acute ischaemic stroke (AIS) but no arterial occlusion is currently a matter of debate. This study aimed to assess functional outcome of such patients with respect to IV-rtPA use. METHODS: A retrospective case-control analysis was performed comparing the outcome of AIS patients without arterial occlusion with or without IV-rtPA use. Patients were selected from prospective consecutive observational registries of five European university hospitals. The primary study outcome was excellent outcome at 3 months after stroke, as defined by a modified Rankin Scale (mRS) 0-1. RESULTS: A total of 488 patients without arterial occlusion documented by angiography were included in the present study; 300 received IV-rtPA and 188 did not. No between-group difference was found for excellent outcome before and after adjustment for baseline characteristics (adjusted odds ratio for no IV-rtPA use 0.79, 95% confidence interval 0.51-1.24, P = 0.31). Similar results were found for favourable outcome (defined as a 90-day mRS of 0-2) whereas a higher rate of early neurological improvement was found in IV-rtPA-treated patients (adjusted odds ratio 1.99; 95% confidence interval 1.29-3.07, P = 0.002). Sensitivity analyses yielded similar results. CONCLUSIONS: Our study suggests that AIS patients without visible arterial occlusion treated with IV-rtPA may have no better outcome at 3 months than those untreated. However, only a randomized controlled trial would provide a definitive answer about the impact of rtPA in acute stroke patients without occlusion. Until then, these patients should be treated by rtPA as recommended.

[Physical fitness levels in French adolescents: The BOUGE program]. / Condition physique des enfants et adolescents en France de 2009 à 2013 et prévalence du risque de maladie cardiovasculaire à l'âge adulte - le programme « Bouge Une priorité pour ta santé ¼.

BACKGROUND: A high level of physical fitness is associated with cardiovascular health in adolescents. The aims of this study were to assess the levels of physical fitness of French adolescents and to determine the prevalence of these adolescents below the minimum level of cardiorespiratory fitness needed to guarantee future favorable cardiovascular profile. METHODS: Participants were 12,082 French children and adolescents (5975 boys, 6107 girls) aged to 9 from 16 years. Cardiorespiratory fitness, muscular endurance, speed, flexibility and speed agility were tested. The associations of physical fitness measures with adolescent's characteristics were analyzed using Student t test, one-way ANOVA, or Pearson correlations as appropriate. RESULTS: Boys were physically fitter than girls, expected for flexibility (P<0.0001). Subjects of normal weight adolescents had significantly better results than overweight or obese adolescents (P<0.05 for all comparisons), but also in comparison with underweight adolescents for muscular endurance, flexibility, cardiorespiratory fitness test (P<0.05). Our findings indicate that, on the basis of cardiorespiratory fitness, 16% of French boys and 7.7% of French girls have a risk of future cardiovascular disease (P<0.0001). This subgroup also performed poorly in all other tests of physical fitness used (P<0.0001). Aerobic fitness decreased significantly with the age (r=-0.168 for boys; r=-0.261 for girls). CONCLUSIONS: Our results indicate that the physical fitness of French adolescents must be improved to help protect against cardiovascular disease in adulthood, especially in boys. The study showed also a dramatically decrease of the cardiorespiratory fitness during the adolescence period. Developing and introducing a health promotion curriculum in the French schools is suggested to improve health and physical fitness.

Endothelial markers are associated with thrombolysis resistance in acute stroke patients.

BACKGROUND AND PURPOSE: The endothelium is crucial in maintaining the haemostatic balance between pro- and anti-thrombotic factors. In this pilot study, the association of endothelial biomarkers with arterial recanalization and clinical outcome in the setting of acute ischaemic stroke (AIS) was evaluated amongst patients treated with recombinant tissue plasminogen activator (rt-PA). METHODS: Sixty-four AIS patients treated with rt-PA were prospectively recruited. Blood was collected before thrombolysis and analysed for von Willebrand factor (vWF), soluble thrombomodulin (sTM) and soluble endothelial protein C receptor (sEPCR). Complete recanalization was defined by a Thrombolysis in Myocardial Infarction Score of 3. Favourable clinical outcome was defined by a modified Rankin Score of 0-2 at 90 days. RESULTS: Amongst the 64 patients, 31 had no documented occlusion, 19 had persistent occlusion and 14 had complete recanalization. After adjustment for confounding factors, these patients presented lower sTM and sEPCR levels than patients with persistent occlusion (median sTM, 21 vs. 48 ng/ml, P = 0.008; median sEPCR, 78 vs. 114 ng/ml, P = 0.018), but similar levels compared with patients without occlusion. vWF levels did not differ between groups. None of these biomarkers was significantly associated with favourable outcome. CONCLUSIONS: Recanalization after thrombolytic therapy is associated with low sTM and sEPCR levels but not with vWF levels. If corroborated in further larger studies, these findings could be helpful in the identification of patients resistant to rt-PA thrombolysis who could benefit from a modified recanalization therapy.

Outpatient balloon catheter versus expectant management for post-term labor induction in nulliparous women: A randomized trial.

BACKGROUND: Increased use of labor induction has renewed interest in outpatient cervical ripening. Post-term pregnancy (i.e., ≥41 weeks) is a specific situation of increased neonatal risk, including greater risk of perinatal death and adverse perinatal outcomes. While a high proportion of these patients will need induction, outpatient management of this specific population has never been studied. Therefore, our objective was to compare two policies of management of post term pregnancies: the use of a transcervical Foley catheter for outpatient cervical ripening compared with expectant management. METHODS: Multicenter, randomized controlled open-label study comparing home induction with a Foley catheter versus expectant management. Inclusion criteria were nulliparous, live singleton fetus in a vertex position, post-term (at 41 + 4 days), requiring cervical ripening (Bishop score <6), intact membranes, and distance home-hospital within 40 min. The primary endpoint was change in Bishop score beetween randomization (41 + 4 days) and consultation (41 + 5 days). RESULTS: Forty-five women were included: 21 in the home induction group and 24 in the control group. The study was stopped due to low recruitment. The difference in Bishop score increases one day after randomization approached significance (p = 0.055), with home induction showing a larger change compared with expectant management (Cohen's d = 0.60; 95 % confidence interval [CI] -0.002 to 1.21). Regarding change in Bishop score, 81 % of home induction group patients had a better score at 41 + 5 days versus 52.2 % in the control group (relative risk = 1.55; 95 %CI 0.99 to 2.15). CONCLUSION: By specifically evaluating home induction in nulliparous women with post term pregnancies, we observed a Bishop score improvement in the home induction group. These data support further evaluation of induction methods and birth experiences in a larger cohort of this population. TRIAL REGISTRATION: The study was registered under European policy (number EudraCT 2015-A01298-41) and on www.clinitrials.gov (number NCT02932319). Date of registration: 13/10/2016, Date of initial participant enrollment: 31/03/2017.

Voice quality after surgery or radiotherapy for glottic T1 squamous cell carcinoma: Results of the VOQUAL study.

PURPOSE: Many series have compared voice quality after radiotherapy or surgery for cT1 glottic carcinoma. Different meta-analyses identify better results for radiotherapy while others do not identify any difference, some finally find a superiority of surgery. The purpose of this study was to compare the voice quality in the long term of patients who underwent transoral surgery versus exclusive irradiation for the treatment of cT1 glottic carcinoma. MATERIAL AND METHODS: The VOQUAL study was a pilot comparative multicenter cross-sectional study. The primary endpoint was the Voice Handicap Index comparison between two groups (radiotherapy or surgery). The voice assessment also consisted in the heteroevaluation of voice quality by the Grade, Roughness, Breathness, Asthenia, and Strain rating scale reported by Hirano. RESULTS: The study included 41 adult patients with cT1 carcinoma of the vocal cord treated by cordectomy or exclusive radiation in two oncologic centers. The median Voice Handicap Index value was 20 [8; 32.5] in the surgery group and 10 [4; 18.5] in the radiotherapy group. There was no statistically significant difference between the median values and the various components F, P and E of the questionnaire (P=0.1585). The median value of the numeric dysphonia Grade, Roughness, Breathness, Asthenia, and Strain scale was 2 [0; 5] in the surgery group and 2 [0.25; 3.75] in the radiotherapy group. There was no statistically significant difference between these values (P=0.78). CONCLUSION: Our study did not show any significant difference on the primary endpoints of Voice Handicap Index and Grade, Roughness, Breathness, Asthenia, and Strain scores. LEVEL OF EVIDENCE: III. CLINICAL TRIAL REGISTRATION: The VOQUAL study was registered on the ClinicalTrials.gov platform under the number NCT04447456, in July 2020.