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Abstract Background There is currently a wide therapeutic arsenal for migraine patients, without a single first-line preventive drug and we choose the different available alternatives taking into account comorbidities, national guidelines, previous treatments and personal experiences. Our objective was to evaluate the differences in the use of migraine treatments between neurologists from different countries. Methods This is a multi-centre observational study carried out by neurologists from specialized headache units in seven countries, retrospective with consecutive inclusion of all patients presenting with a migraine diagnosis, over a period of three months. Results A total of 734 patients were recruited but only 600 were considered in the analysis in order to homogenize the patient cohorts from countries: 200 Spain (ES), 100 Italy (IT), 85 Russia (RUS), 80 Germany (DE), 60 Portugal (PT), 45 Poland (PL) and 30 Australia (AU). 85.4 % of patients were women with a mean age of 42.6 ± 11.8 years. Considering previous and current preventive treatment, the order of use was: antidepressants (69.3 %), antiepileptic drugs (54.7 %), beta-blockers and antihypertensive drugs (49.7 %), OnabotulinumtoxinA (44.0 %) and others (36.2 %). Statistically significant differences were found between all pharmacological classes: antidepressants were commonly used in all countries, with the exception of Poland (AU: 76.7 %, IT: 71.0 %, DE: 60.0 %, PL: 31.1 %, PT: 71.7 %, RUS: 70.6 %, ES: 78.5 %; p

Vault modelling in HBIM poses a significant challenge due to the geometrical complexity and lack of standardization of those elements. Starting from the definition of an ontology able to describe and manage different typologies of Italian Renaissance vaults, this paper presents two methods for their representation in the context of Ducal Palace of Urbino HBIM implementation. The first method is a simplified semi-automated scan-to-BIM procedure relying on Revit adaptive families; the second is a more complex parametric scripting in Dynamo VPL. The paper proposes a library of suitable vault families for the parametric modelling of Renaissance architecture and offers a comparison between the models generated and their respective surveyed point-clouds, with the aim of assessing the procedure. Revit adaptive families appeared to be the easiest to implement and the most efficient solution, while Dynamo allowed for greatest complexity thought showing limitations and implementation difficulties.

We used the mouse air pouch model of inflammation to study the interaction between cytokines, prostaglandin E2 (PGE2) and cell migration during the various phases of acute local inflammation induced by carrageenan. In serum, the levels of interleukin 1 (IL-1), interleukin 6 (IL-6), tumour necrosis factor (TNF), serum amiloid-A (SAA) and Fe++ were never different from controls, indicating that no systemic inflammatory changes were induced. Locally the exudate volume and the number of leukocytes recruited into the pouch increased progressively until 7 days after carrageenan. The same was true for PGE2 production. We could not measure IL-1 but the production of IL-6 and TNF reached a maximum after 5-24 h then quickly decreased. Anti-TNF antibodies inhibited cell migration by 50% 24 h after treatment. Pretreatment with interleukin 10 (IL-10) inhibited TNF production almost completely and cell migration by 60%. Carrageenan-induced inflammation was modulated by anti-inflammatory drugs. Pretreatment with dexamethasone (DEX) or indomethacin (INDO) inhibited cell migration and reduced the concentration of TNF in the exudate. Production of PGE2 or vascular permeability did not correlate with the number of cells in the pouch. Local TNF seems to play an important role in this model, particularly for leukocyte migration in the first phase of the inflammatory process. In conclusion, the air pouch seems to be a good model for studying the regulation of the early events of local inflammation, particularly the role of cytokines and cell migration.

Objectives: To study –238 and +489 TNF-α polymorphisms in severe-unresponsive (more than 6 swollen joints and still active disease despite at least 6 months of DMARDs combination therapy) and mild-responsive (less than 3 swollen joints and good response to MTX or other conventional DMARDs) rheumatoid arthritis (RA). Methods: We investigated 100 RA patients (56 with severe and 44 with mild disease activity) and 45 healthy blood donors (HBDs). Genotyping was performed by PCR-restriction fragment lenght polymorphism procedure. Several clinical and serological parameters were also examined. Results: Severe RA patients disclosed the –238 GG genotype in 100% of the cases versus 95.5% in the mild-responsive patients and 91.2% in the HBDs. The +489 GG genotype disclosed only a trend towards a prevalence in severe RA patients. However the +489 A allele seems to associates with early onset, longer disease duration and longer responsiveness to conventional therapy. Conclusion: The -238 AG genotype is absent in severe-unresponsive RA, but present in mild-responsive RA subjects. Thus –238 GG homozygosity associates with severity and unresponsiveness. In contrast the +489 polymorphism does not segregate differently between responsive and unresponsive RA patients.

Objectives. To investigate the role of B-Lymphocyte stimulator (BLyS) in mixed cryoglobulinaemia syndrome (MCsn), a systemic vasculitis associated with a high risk to develop lymphoma, since BLyS up-regulation may favour both autoimmunity and lymphoproliferation.Methods. BLyS serum levels were analysed by enzyme-linked immunosorbent assay (positive when >0.85 ng/ml) in 66 patients with MCsn, 54 (81.8%) of whom were positive for hepatitis-C virus (HCV) infection. Thirty-three HCV-positive patients without MCsn were also studied. Patients were compared with 48 healthy blood donors (HBDs). BLyS modifications after antiviral therapy were also studied.Results. A significantly higher frequency of BLyS serum positivity was detected both in MCsn patients and in HCV-positive patients without MCsn (37.9 and 30.3%, respectively) when compared with HBDs (4.2%) (P < 0.0001 vs MCsn and P = 0.0026 vs HCV-positive patients without MCsn, respectively). BLyS appeared significantly higher in MCsn (3.70 ± 2.97 ng/ml) than in HCV-positive patients without MCsn (1.56 ± 0.63 ng/ml; P = 0.0044). BLyS expression did not correlate with rheumatoid factor levels, cryoglobulin levels or definite MCsn-related systemic features. High BLyS levels were significantly associated only with MCsn-related overt lymphoproliferative disorder. Finally, antiviral treatment significantly increased BLyS levels, independently from HCV-RNA negativization. However, BLyS normalization was noticed after both HCV-RNA negativization and suspension of antiviral therapy by preliminary data.Conclusions. BLyS is up-regulated and may play a pathogenetic role in a fraction of patients with MCsn, similarly to other autoimmune diseases. HCV infection likely represents the early event leading to BLyS up-regulation in this setting. BLyS is up-regulated during antiviral treatment. Overall, these data provide new insights for BLyS and virus-related autoimmunity, lymphoproliferation and possible treatment strategies. [ABSTRACT FROM AUTHOR]

Objective. To evaluate: (i) a correct equivalence ratio of clinical efficacy between low-dose deflazacort (DFZ) and methyl prednisolone (MP); and (ii) bone metabolic effects of low-dose DFZ and MP in the treatment of male RA and PsA. Methods. A total of 21 male patients with active RA or PsA, naive to steroid treatment were chosen for the study. Group I: 10 patients treated for 6 months with DFZ 7.5 mg, calcium, cholecalciferol and a DMARD; for the following 6 months with MP 4 mg, calcium, cholecalciferol and a DMARD. Group II: 11 patients treated for 6 months with MP 4 mg, calcium, cholecalciferol and a DMARD; for the following 6 months with DFZ 7.5 mg, calcium, cholecalciferol and a DMARD. At day 0, 90, 180, 240 and 360 evaluation of ACR improvement criteria; a blood sample for total and bone-specific ALP, calcium, phosphorus, PTH, SHBG, estradiol, ACTH, osteocalcin, LH, OPG; a sample of urine for calcium, phosphorus, creatinine and DPD. Results. 13/21 patients (6/10 Group I; 7/11 Group II) reached ACR 20 at 6 months; 14/21 (7/10 Group I, 7/10 Group II) at 12 months. Only at the third month we observed in Group II vs Group I a reduction of OPG (24% vs 6%, P = n.s.); ALP (P P = 0.006) decreased in both groups from the third month; DPD decreased in both groups only from the sixth month (P = 0.002). Conclusions. The correct equivalence ratio of DFZ to MP is 1.875:1, and of DFZ to prednisolone 1.5:1. We found a relative prevalence of bone resorption compared to bone formation in the first 6 months of treatment. The trend of OPG requires further investigation. [ABSTRACT FROM AUTHOR]

Background and Purpose: Although there is extensive evidence about the safety of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP mAbs) in combination with traditional drugs, scarce data are available on the safety of their combination with other mAbs. This study aimed to evaluate the 6-month effectiveness and tolerability of anti-CGRP mAbs in combination with other mAbs for different diseases., Methods: Patients included in the Italian Headache Registry and treated concomitantly with an anti-CGRP mAb and another mAb were included. Effectiveness outcomes for migraine included reduction from baseline of monthly headache days (MHDs), Migraine Disability Assessment (MIDAS) score, Headache Impact Test-6 (HIT-6) scores, and Patients' Global Impression of Change (PGIC) scale. Adverse events (AEs) were recorded., Results: Thirty-eight patients were included. In 27 patients (71.1%), the anti-CGRP mAb was added to a previously ongoing mAb. Nine patients (23.7%) discontinued one of the two mAbs before the end of treatment (seven discontinued the anti-CGRP mAb and two the other mAb). One patient discontinued for AEs. Anti-CGRP mAbs were discontinued due to ineffectiveness (n = 5, 55.5%) and one each (11.1%) for clinical remission and lost to follow-up. MHDs significantly decreased from baseline to 3 months (p < 0.0001) and 6 months (p < 0.001), as did the MIDAS and the HIT-6 scores at 3 and 6 months (p < 0.001). For anti-CGRP mAbs, 27.4% of patients reported PGIC ≥ 5 at 3 months and 48.3% at 6 months. Mild AEs associated with introduction of a second mAb were detected in six patients (15.8%)., Conclusions: In this real-world study, anti-CGRP mAbs showed safety and effectiveness when administered concomitantly with other mAbs., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Guidelines help physicians to provide optimal care for stroke patients, but implementation is challenging due to the quantity of recommendations. Therefore a practical overview related to applicability of recommendations can be of assistance., Methods: A systematic review was performed on ischaemic stroke guidelines published in scientific journals, covering the whole acute care process for patients with ischaemic stroke. After data extraction, experts rated the recommendations on dimensions of applicability, that is, actionability, feasibility and validity, on a 9-point Likert scale. Agreement was defined as a score of ≥8 by ≥80% of the experts., Results: Eighteen articles were identified and 48 recommendations were ultimately extracted. Papers were included only if they described the whole acute care process for patients with ischaemic stroke. Data extraction and analysis revealed variation in terms of both content and comprehensiveness of this description. Experts reached agreement on 34 of 48 (70.8%) recommendations in the dimension actionability, for 16 (33.3%) in feasibility and for 15 (31.3%) in validity. Agreement on all three dimensions was reached for seven (14.6%) recommendations: use of a stroke unit, exclusion of intracerebral haemorrhage as differential diagnosis, administration of intravenous thrombolysis, performance of electrocardiography/cardiac evaluation, non-invasive vascular examination, deep venous thrombosis prophylaxis and administration of statins if needed., Discussion and Conclusion: Substantial variation in agreement was revealed on the three dimensions of the applicability of recommendations. This overview can guide stroke physicians in improving the care process and removing barriers where implementation may be hampered by validity and feasibility., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Randomized controlled trials (RCTs) proved the efficacy of short-term dual antiplatelet therapy (DAPT) in secondary prevention of minor ischemic stroke or high-risk transient ischemic attack (TIA). We aimed at evaluating effectiveness and safety of short-term DAPT in real-world, where treatment use is broader than in RCTs., Methods: READAPT (REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack) (NCT05476081) was an observational multicenter real-world study with a 90-day follow-up. We included patients aged 18+ receiving short-term DAPT soon after ischemic stroke or TIA. No stringent NIHSS and ABCD 2 score cut-offs were applied but adherence to guidelines was recommended. Primary effectiveness outcome was stroke (ischemic or hemorrhagic) or death due to vascular causes, primary safety outcome was moderate-to-severe bleeding. Secondary outcomes were the type of ischemic and hemorrhagic events, disability, cause of death, and compliance to treatment., Results: We included 1920 patients; 69.9% started DAPT after an ischemic stroke; only 8.9% strictly followed entry criteria or procedures of RCTs. Primary effectiveness outcome occurred in 3.9% and primary safety outcome in 0.6% of cases. In total, 3.3% cerebrovascular ischemic recurrences occurred, 0.2% intracerebral hemorrhages, and 2.7% bleedings; 0.2% of patients died due to vascular causes. Patients with NIHSS score ⩽5 and those without acute lesions at neuroimaging had significantly higher primary effectiveness outcomes than their counterparts. Additionally, DAPT start >24 h after symptom onset was associated with a lower likelihood of bleeding., Conclusions: In real-world, most of the patients who receive DAPT after an ischemic stroke or a TIA do not follow RCTs entry criteria and procedures. Nevertheless, short-term DAPT remains effective and safe in this population. No safety concerns are raised in patients with low-risk TIA, more severe stroke, and delayed treatment start., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AZ reports compensation from Angels Initiative, Boehringer-Ingelheim, Daiichi Sankyo, CSL Behring, Bayer, and Astra Zeneca; and he is member of ESO guidelines, ISA-AII guidelines, and IRETAS steering committee. RO reports compensations from Novartis and Allergan, Teva Pharmaceutical Industries, Eli Lilly and Company, SS reports compensations from Novartis, NovoNordisk, Allergan, AstraZeneca, Pfizer Canada, Inc, Eli Lilly and Company, Teva Pharmaceutical Industries, H. Lundbeck A/S, and Abbott Canada; employment by Università degli Studi dell’Aquila. MPa reports compensation from Daiichi Sankyo Company, Bristol Myers Squibb, Bayer, and Pfizer Canada, Inc. DT reports compensation from Alexion, AstraZeneca, Medtronic, and Pfizer. The other authors report no conflicts.

Introduction: There is a lack of evidence for the optimal type of anesthesia technique in patients ⩾ 90 years with acute ischemic stroke undergoing mechanical thrombectomy (MT) as this subgroup of patients was often excluded or under-represented in previous trials. We aimed to compare outcomes between general anesthesia (GA) and non-GA techniques in patients ⩾ 90 years with large vessel occlusion (LVO) undergoing MT., Patients and Methods: Our study included patients ⩾ 90 years with anterior circulation LVO, NIHSS ⩾ 6, ASPECTS ⩾ 5 consecutively treated with MT within 6 h after stroke onset in three thrombectomy capable centers between January 1st, 2016 and March 30th, 2023. Inverse probability weighting (IPW) was used to reduce bias by indication of the anesthesia type on study outcomes. We used a weighted ordinal robust logistic regression analysis to explore the primary outcome of modified Rankin Scale (mRS) shift at 90 days in GA versus non-GA treated patients. Secondary outcomes included 90-day mortality, symptomatic intracranial hemorrhage (sICH) and TICI score of 2b, 2c, or 3., Results: We included 139 patients ⩾ 90 years treated with MT, 62 were in GA group and 77 in non-GA group. There was a significant shift for worse mRS scores at 90-day in non-GA treated patients (cOR 3.65, 95% CI 1.77-7.77, p  = 0.001). The weighted logistic regression showed that non-GA technique was an independent predictor of 90-day mortality (OR 7.49, 95% CI 2.00-28.09; p  = 0.003)., Conclusion: Our study indicated that nonagenarians with acute ischemic stroke treated with MT without GA have a worse prognosis than their counterparts undergoing MT with GA. Further studies in larger cohorts are warranted to evaluate the optimal type of anesthesia in this patient population., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SB is a key opinion leader for RAPIDAI. All other authors have no conflicts of interests.

We present haplotype-resolved reference genomes and comparative analyses of six ape species, namely: chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan, and siamang. We achieve chromosome-level contiguity with unparalleled sequence accuracy (<1 error in 500,000 base pairs), completely sequencing 215 gapless chromosomes telomere-to-telomere. We resolve challenging regions, such as the major histocompatibility complex and immunoglobulin loci, providing more in-depth evolutionary insights. Comparative analyses, including human, allow us to investigate the evolution and diversity of regions previously uncharacterized or incompletely studied without bias from mapping to the human reference. This includes newly minted gene families within lineage-specific segmental duplications, centromeric DNA, acrocentric chromosomes, and subterminal heterochromatin. This resource should serve as a definitive baseline for all future evolutionary studies of humans and our closest living ape relatives., Competing Interests: COMPETING INTERESTS E.E.E. is a scientific advisory board (SAB) member of Variant Bio, Inc. C.T.W. is a co-founder/CSO of Clareo Biosciences, Inc. W.L. is a co-founder/CIO of Clareo Biosciences, Inc. The other authors declare no competing interests.

Background and Purpose: Two early basilar artery occlusion (BAO) randomized controlled trials (RCTs) did not establish the superiority of endovascular thrombectomy (EVT) over medical management. Yet many providers continued to recommend EVT. The goal of the present article is to compare physicians' diagnostic and management strategies of BAO among middle-income and high-income countries (MICs and HICs, respectively)., Methods: We conducted an international survey from January to March 2022 regarding management strategies in acute BAO, to examine clinical and imaging parameters influencing clinician management of patients with BAO. We compared responses between physicians from HIC and MIC., Results: Among the 1245 respondents from 73 countries, 799 (64.2%) were from HIC, with the remaining 393 (31.6%) from MIC. Most respondents perceived that EVT was superior to medical management for acute BAO, but more so in respondents from HIC (98.0% vs. 94.2%, p < 0.01). MIC respondents were more likely to believe further RCTs were warranted (91.6% vs. 74.0%, p < 0.01) and were more likely to find it acceptable to enroll any patient who met a trial's criteria in the standard medical treatment arm (58.8% vs. 38.5%, p < 0.01)., Conclusions: In an area where clinical equipoise was called into question despite the lack of RCT evidence, we found that respondents from MIC were more likely to express willingness to enroll patients with BAO in an RCT than their HIC counterparts., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Alemseged reported research grants from Medical Research Future Fund, Australian Heart Foundation, Sylvia & Charles Viertel Charitable Foundation. Dr Fischer reported research grants from Medtronic; consultant for Medtronic, Stryker, CSL Behring; advisory board for Alexion/Portola. Dr Kaesmacher reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, Clinical Trials Unit Bern, and the Swiss National Science Foundation. Dr Nagel reported consultancy for Brainomix, speaker bureaus with Boehringer Ingelheim and Pfizer. Dr Nguyen reported research support from Medtronic and SVIN. Dr Puetz reported fees as lecturer for Daiichi Sankyo. Dr Sacco reported research grants from Novartis and Uriach; fees for advisor or speaker from Abbott, Allergan-Abbvie, AstraZeneca, Lilly, Lundbeck, Novartis, Novo Nordisk, Pfizer, Teva. Dr Siegler reported consulting from Ceribell and speakers’ bureau with AstraZeneca. Dr Thomalla reported fees as a consultant from Acandis, Alexion, Amarin, Bayer, Bristol Myers Squibb/Pfizer, Boehringer Ingelheim, Portola, and Stryker. Dr Yamagami reported research grants from Bristol-Myers Squibb, lecturer’s fees from Bayer, Daiichi-Sankyo, Stryker, Bristol-Myers Squib; advisory boards for Daiichi-Sankyo. Dr Banerjee reported consultancy for RapidAI. Dr Marto reports consulting fees from Amicus Therapeutics and Boehringer Ingelheim; speaker fees from Boehringer Ingelheim. Dr Kaiser reported grants from the Joachim Herz Foundation and the Else Kröner Fresenius Center for Digital Health.

There is limited evidence on the outcomes and safety of mechanical thrombectomy (MT) among patients with acute ischemic stroke (AIS) in the context of cardiac diseases. Our study reviews MT in AIS within the context of cardiac diseases, aiming to identify existing and emerging needs and gaps. PubMed and Scopus were searched until December 31, 2023, using a combination of cardiological diseases and "mechanical thrombectomy" or "endovascular treatment" as keywords. Study design included case reports/series, observational studies, randomized clinical trials, and meta-analyses/systematic reviews. We identified 943 articles, of which 130 were included in the review. Results were categorized according to the cardiac conditions. MT shows significant benefits in patients with atrial fibrillation (n=139) but lacks data for stroke occurring after percutaneous coronary intervention (n=2) or transcatheter aortic valve implantation (n=5). MT is beneficial in AIS attributable to infective endocarditis (n=34), although functional benefit may be limited. Controversy surrounds the functional outcomes and mortality of patients with AIS with heart failure undergoing MT (n=11). Despite technical challenges, MT appears feasible in aortic dissection cases (n=4), and in patients with left ventricular assist device or total artificial heart (n=10). Data on AIS attributable to congenital heart disease (n=4) primarily focus on pediatric cases requiring technical modifications. Treatment outcomes of MT in patients with cardiac tumors (n=8) vary because of clot consistency differences. After cardiac surgery stroke, MT may improve outcomes with early intervention (n=13). Available data outline the feasibility of MT in patients with AIS attributable to large-vessel occlusion in the context of cardiac diseases.

Background: Varied responses to acute migraine medications have been observed, with over one-third (34.5%) of patients reporting insufficient headache relief. Sumatriptan-naproxen sodium, a single, fixed-dose combination tablet comprising sumatriptan 85 mg and naproxen sodium 500 mg, was developed with the rationale of targeting multiple putative mechanisms involved in the pathogenesis of migraine to optimise acute migraine care., Methods: A narrative review of clinical trials investigating sumatriptan-naproxen sodium for both adults and adolescents was performed in March 2024., Results: Across a total of 14 clinical trials in nine publications, sumatriptan-naproxen sodium offered greater efficacy for 2-h pain freedom (14/14) and sustained pain-free response up to 24 h (13/14) compared with monotherapy and/or placebo for both adult and adolescent study participants with an acceptable and well-tolerated adverse effect profile. Clinical trial data also demonstrates the effectiveness of sumatriptan-naproxen sodium in participants with allodynia, probable migraine, menstrual-related migraine and those with poor responses to acute, non-specific, migraine medication., Conclusions: Multi-mechanistic therapeutic agents offer an opportunity to optimise acute medications by targeting multiple mediators involved in the pathogenesis of migraine. Sumatriptan-naproxen sodium resulted in greater initial and sustained pain freedom, compared with either sumatriptan, naproxen-sodium and/or placebo, for the treatment of single or multiple attacks of migraine across both adult and adolescent study populations., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: Mechanical thrombectomy (MT) is the standard treatment for acute ischemic stroke (AIS) due to anterior large vessel occlusion (LVO). Despite successful recanalization, some patients remain disabled after 3 months. Mechanisms that can cause futile recanalization (FR) are still largely unknown. We investigated if stress hyperglycemia might be associated with FR., Patients and Methods: This is a retrospective analysis of consecutive patients with successful recanalization treated in four participating centers between January 2021 and December 2022. According to the modified Rankin scale (mRS) status at 3 months, patients were divided into two groups: FR, if mRS score >2, and useful recanalization (UR), if mRS score ⩽2. Stress hyperglycemia was estimated by the glucose-to-glycated hemoglobin ratio (GAR) index., Results: A total of 691 subjects were included. At 3 months, 403 patients (58.3%) were included in the FR group, while the remaining 288 patients (41.7%) were included in the UR group. At the multivariate analysis, variables independently associated with FR were the following: age (OR 1.04, 95% CI 1.02-1.06, p  < 0.001), GAR index (OR 1.08, 95% CI 1.03-1.14, p  = 0.003), NIHSS at admission (OR 1.16, 95% CI 1.11-1.22; p  < 0.001), and procedure length (OR 1.01, 95% CI 1.00-1.02; p  = 0.009). We observed that the model combining age, GAR index, NIHSS at admission, and procedure length had good predictive accuracy (AUC 0.78, 95% CI 0.74-0.81)., Conclusions: Stress hyperglycemia predicts FR in patients with successful recanalization after MT. Further studies should explore if managing stress hyperglycemia may reduce futile recanalization. Additionally, we recommend paying close attention to AIS patients with a GAR index greater than 24.8 who exhibit a high risk of FR., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Infants with Down syndrome (DS) are at high risk of obstructive sleep apnoea (OSA) which is associated with neurocognitive dysfunction and behaviour problems. The aim of our study was to evaluate the effect of early OSA treatment in infants with DS on neurocognitive development and behaviour., Methods: In this prospective, interventional, non-randomised study, 40 infants with DS underwent polysomnography (PSG) every 6 months in room air between 6 and 36 months of age ( Screened Group ) and were compared to a control group of 40 infants with DS receiving standard of care and a single, systematic PSG in room air at 36 months of age ( Standard Care Group ). When present, OSA was treated. The primary endpoint was the total score of the Griffiths Scales of Child Development, Third Edition (Griffiths III) and its subscores at 36 months. Secondary endpoints included a battery of neurocognitive and behaviour questionnaires, and PSG outcomes., Findings: On the Griffiths III, the total score was significantly higher in the Screened Group compared to the Standard Care Group (difference: 4.1; 95%CI: 1.3; 7.6; p = 0.009). Results in Griffiths III subscores and secondary endpoints were in support of better neurocognitive outcomes in the Screened Group compared with the Standard Care Group. At 36 months, median (Q1; Q3) apnoea-hypopnea index was higher in the Standard Care Group (4.0 [1.5; 9.0] events/hour) compared to the Screened Group (1.0 [1.0; 3.0] events/hour, p = 0.006). Moderate and severe OSA were more frequent in the Standard Care Group as compared to the Screened Group (18.9% versus 3.7% for moderate OSA and 27.0% versus 7.4% for severe OSA)., Interpretation: Early diagnosis and treatment of OSA in infants with DS may contribute to a significantly better neurocognitive outcome and behaviour at the age of 36 months., Funding: The study was funded by the Jérôme Lejeune Foundation., Competing Interests: None of the authors had a conflict of interest to declare. A medical writer provided writing and editing assistance, which was funded through the Jérôme Lejeune Foundation., (© 2024 The Author(s).)

Background: The optimal treatment for acute minor ischemic stroke is still undefined. and options include dual antiplatelet treatment (DAPT), intravenous thrombolysis (IVT), or their combination. We aimed to investigate benefits and risks of combining IVT and DAPT versus DAPT alone in patients with MIS., Methods and Results: This is a prespecified propensity score-matched analysis from a prospective multicentric real-world study (READAPT [Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack]). We included patients with MIS (National Institutes of Health Stroke Scale score at admission ≤5), without prestroke disability (modified Rankin scale [mRS] score ≤2). The primary outcomes were 90-day mRS score of 0 to 2 and ordinal mRS distribution. The secondary outcomes included 90-day risk of stroke and other vascular events and 24-hour early neurological improvement or deterioration (≥2-point National Institutes of Health Stroke Scale score decrease or increase from the baseline, respectively). From 1373 patients with MIS, 240 patients treated with IVT plus DAPT were matched with 427 patients treated with DAPT alone. At 90 days, IVT plus DAPT versus DAPT alone showed similar frequency of mRS 0 to 2 (risk difference, 2.3% [95% CI -2.0% to 6.7%]; P =0.295; risk ratio, 1.03 [95% CI 0.98-1.08]; P =0.312) but more favorable ordinal mRS scores distribution (odds ratio, 0.57 [95% CI 0.41-0.79]; P <0.001). Compared with patients treated with DAPT alone, those combining IVT and DAPT had higher 24-hour early neurological improvement (risk difference, 20.9% [95% CI 13.1%-28.6%]; risk ratio, 1.59 [95% CI 1.34-1.89]; both P <0.001) and lower 90-day risk of stroke and other vascular events (hazard ratio, 0.27 [95% CI 0.08-0.90]; P =0.034). There were no differences in safety outcomes., Conclusions: According to findings from this observational study, patients with MIS may benefit in terms of better functional outcome and lower risk of recurrent events from combining IVT and DAPT versus DAPT alone without safety concerns., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05476081.

Somatic variant detection is an integral part of cancer genomics analysis. While most methods have focused on short-read sequencing, long-read technologies now offer potential advantages in terms of repeat mapping and variant phasing. We present DeepSomatic, a deep learning method for detecting somatic SNVs and insertions and deletions (indels) from both short-read and long-read data, with modes for whole-genome and exome sequencing, and able to run on tumor-normal, tumor-only, and with FFPE-prepared samples. To help address the dearth of publicly available training and benchmarking data for somatic variant detection, we generated and make openly available a dataset of five matched tumor-normal cell line pairs sequenced with Illumina, PacBio HiFi, and Oxford Nanopore Technologies, along with benchmark variant sets. Across samples and technologies (short-read and long-read), DeepSomatic consistently outperforms existing callers, particularly for indels., Competing Interests: Competing interests K.S., D.E.C., P.C., A. Kolesnikov, L.B., J.C.M., and A.C. are employees of Google LLC and own Alphabet stock as part of the standard compensation package. M.S.F. is a part of the speakers bureau for Bayer and PacBio.

Background: The superiority of endovascular thrombectomy (EVT) over medical management was not established in two early basilar artery occlusion (BAO) randomized controlled trials. Despite this, many clinicians recommended EVT for acute BAO under certain circumstances. This paper aims to compare physicians' diagnostic and management strategies of BAO according to gender., Methods: From January to March 2022 an international survey was conducted regarding management strategies in acute BAO. We compared responses between clinicians by identifying gender. Questions were designed to examine clinical and imaging parameters influencing management of patients with BAO., Results: Among the 1245 respondents from 73 countries, 311 (25.0%) identified as female. This figure was 13.6% amongst interventionists. Geographically, female respondents were lowest in Asia (14.5%) and North America (23.9%). The proportion of respondents identifying as female was consistent regardless of their years of experience. Female respondents were more likely to choose time of onset as time of first estimated stroke like symptom (48.0% vs. 38.5%, p  < .01), were less likely to favor thrombectomy in the V4 segment of vertebrobasilar artery occlusions (31.5% vs. 43.3%, p  < .01), and were less likely to find it acceptable to enroll all patients who met trial criteria in the standard medical treatment arm of a clinical trial (41.2% vs. 47.0%, p  = .01). Male respondents were more likely to agree that thrombolysis would not alter their decision on proceeding with EVT (93.7% vs. 88.3%, p  < .01)., Conclusions: Female clinicians appear to be significantly underrepresented in stroke medicine. This is most pronounced amongst interventionists and in Asia. Although male and female opinions were closely aligned on many aspects of BAO management, differences in opinion were observed in a number of significant areas which influence decision making.

Machine Learning models trained from real-world data have demonstrated promise in predicting suicide attempts in adolescents. However, their transportability, namely the performance of a model trained on one dataset and applied to different data, is largely unknown, hindering the clinical adoption of these models. Here we developed different machine learning-based suicide prediction models based on real-world data collected in different contexts (inpatient, outpatient, and all encounters) with varying purposes (administrative claims and electronic health records), and compared their cross-data performance. The three datasets used were the All-Payer Claims Database in Connecticut, the Hospital Inpatient Discharge Database in Connecticut, and the Electronic Health Records data provided by the Kansas Health Information Network. We included 285,320 patients among whom we identified 3389 (1.2%) suicide attempters and 66% of the suicide attempters were female. Different machine learning models were evaluated on source datasets where models were trained and then applied to target datasets. More complex models, particularly deep long short-term memory neural network models, did not outperform simpler regularized logistic regression models in terms of both local and transported performance. Transported models exhibited varying performance, showing drops or even improvements compared to their source performance. While they can achieve satisfactory transported performance, they are usually upper-bounded by the best performance of locally developed models, and they can identify additional new cases in target data. Our study uncovers complex transportability patterns and could facilitate the development of suicide prediction models with better performance and generalizability., (© 2024. The Author(s).)

Objective: The aim of this paper is to critically re-appraise the published trials assessing propranolol for migraine prophylaxis., Methods: We report methods and results following the Preferred Reporting Items for Systematic Reviews (PRISMA), by searching MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials of pharmacologic treatments for migraine prophylaxis. We included randomized trials that compared propranolol with placebo for migraine prophylaxis in adults. The outcomes of interest were informed by the Core outcome set for preventive intervention trials in chronic and episodic migraine (COSMIG) and include the proportion of patients who experience a 50% or more reduction in monthly migraine days, the reduction of monthly migraine days, and the number of adverse events leading to discontinuation. We assessed risk of bias by using a modified Cochrane RoB (risk of bias) 2.0 tool and the certainty of evidence by using the GRADE approach., Results: Our search yielded twenty trials (n = 1291 patients) eligible for data synthesis and analysis. The analysis revealed a moderate certainty evidence that propranolol leads to a reduction in monthly migraine days versus placebo (-1.27; 95% CI: -2.25 to -0.3). We found moderate certainty evidence that propranolol increases the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo with a relative risk of 1.65 (95% CI 1.41 to 1.93); absolute risk difference: 179 more per 1,000 (95% CI 113 to 256). We found high certainty evidence that propranolol increases the proportion of patients who discontinue due to adverse events compared to placebo with a risk difference of 0.02 (95% CI 0.00 to 0.03); absolute risk difference: 20 more per 1,000 (95% CI 0 to 30)., Conclusions: The present meta-analysis shows that propranolol has a prophylactic role in migraine, with an overall acceptable tolerability profile. Combining these results with its long-standing use and its global availability at a low cost confirms its role as a first line agent in the prophylaxis of migraine., (© 2024. The Author(s).)

Background/Objectives: Endovascular treatment (EVT) is recommended for acute ischemic stroke due to large-vessel occlusion (LVO) and an Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6. Randomized controlled trials (RCTs) have recently become available on EVT effects in people with LVO-related large core stroke (ASPECTS 0-5). Here, we provide an updated meta-analysis of the EVT effect on functional neurological status in people with large-core stroke. Methods: The study followed the PRISMA guidelines. PubMed, EMBASE and Cochrane Central were searched for RCTs comparing EVT vs. best medical treatment (BMT) in large-core LVO stroke. The primary outcome was functional independence at 90 days (modified Rankin Scale; mRS 0-2). The secondary outcomes were symptomatic intracranial hemorrhage (sICH), good functional outcome (mRS 0-3) and excellent functional outcome (mRS 0-1). EVT vs. BMT was compared through random effect meta-analysis. Heterogeneity was assessed with the I 2 and Q test and risk of bias reported according to the RoB2 tool. Results: Six RCTs were included (n = 1656 patients). All studies had a moderate risk of bias, with blinding bias due to the nature of the intervention, potential allocation bias and incomplete outcome reporting. Functional independence was significantly more frequent in the EVT vs. BMT group (OR = 2.47, 95% CI = 1.52-4.03, p < 0.001). sICH rates (OR = 1.77, 95% CI = 1.01-3.11, p = 0.04) and good functional outcome (OR = 2.20; 95% CI = 1.72-2.81, p < 0.001) were more frequent in the EVT vs. BMT group, while the rates of mRS 0-1 did not differ. Conclusions: In patients with large-core stroke and LVO, EVT plus BMT as compared to BMT alone carries a significant increase in independent ambulation and good functional outcome at 3 months despite the marginal increase in sICH.

Introduction: There are limited data regarding cerebrospinal fluid (CSF) and plasma biomarkers among patients with Cerebral Amyloid Angiopathy (CAA). We sought to investigate the levels of four biomarkers [β-amyloids (Aβ42 and Aβ40), total tau (tau) and phosphorylated tau (p-tau)] in CAA patients compared to healthy controls (HC) and patients with Alzheimer Disease (AD)., Patients and Methods: A systematic review and meta-analysis of published studies, including also a 5 year single-center cohort study, with available data on CSF and plasma biomarkers in symptomatic sporadic CAA versus HC and AD was conducted. Biomarkers' comparisons were investigated using random-effects models based on the ratio of mean (RoM) biomarker concentrations. RoM < 1 and RoM > 1 indicate lower and higher biomarker concentration in CAA compared to another population, respectively., Results: We identified nine cohorts, comprising 327 CAA patients (mean age: 71 ± 5 years; women: 45%) versus 336 HC (mean age: 65 ± 5 years; women: 45%) and 384 AD patients (mean age: 68 ± 3 years; women: 53%) with available data on CSF biomarkers. CSF Aβ42 levels [RoM: 0.47; 95% CI: 0.36-0.62; p  < 0.0001], Aβ40 levels [RoM: 0.70; 95% CI: 0.63-0.79; p  < 0.0001] and the ratio Aβ42/Aβ40 [RoM: 0.62; 95% CI: 0.39-0.98; p  = 0.0438] differentiated CAA from HC. CSF Aβ40 levels [RoM: 0.73; 95% CI: 0.64-0.83; p  = 0.0003] differentiated CAA from AD. CSF tau and p-tau levels differentiated CAA from HC [RoM: 1.71; 95% CI: 1.41-2.09; p  = 0.0002 and RoM: 1.44; 95% CI: 1.20-1.73; p  = 0.0014, respectively] and from AD [RoM: 0.65; 95% CI: 0.58-0.72; p  < 0.0001 and RoM: 0.64; 95% CI: 0.57-0.71; p  < 0.0001, respectively]. Plasma Aβ42 [RoM: 1.14; 95% CI: 0.89-1.45; p  = 0.2079] and Aβ40 [RoM: 1.07; 95% CI: 0.91-1.25; p  = 0.3306] levels were comparable between CAA and HC., Conclusions: CAA is characterized by a distinct CSF biomarker pattern compared to HC and AD. CSF Aβ40 levels are lower in CAA compared to HC and AD, while tau and p-tau levels are higher in CAA compared to HC, but lower in comparison to AD patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.