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BACKGROUND AND OBJECTIVES: Gene-gene interactions likely contribute to the etiology of multifactorial diseases such as cerebral venous thrombosis (CVT) and could be one of the main sources of known missing heritability. We explored Factor XI (F11) and ABO gene interactions among patients with CVT. METHODS: Patients with CVT of European ancestry from the large Bio-Repository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) international collaboration were recruited. Codominant modelling was used to determine interactions between genome-wide identified F11 and ABO genes with CVT status. RESULTS: We studied 882 patients with CVT and 1,205 ethnically matched control participants (age: 42 ± 15 vs 43 ± 12 years, p = 0.08: sex: 71% male vs 68% female, p = 0.09, respectively). Individuals heterozygous (AT) for the risk allele (T) at both loci (rs56810541/F11 and rs8176645/ABO) had a 3.9 (95% CI 2.74-5.71, p = 2.75e-13) increase in risk of CVT. Individuals homozygous (TT) for the risk allele at both loci had a 13.9 (95% CI 7.64-26.17, p = 2.0e-15) increase in risk of CVT. The presence of a non-O blood group (A, B, AB) combined with TT/rs56810541/F11 increased CVT risk by OR = 6.8 (95% CI 4.54-10.33, p = 2.00e15), compared with blood group-O combined with AA. DISCUSSION: Interactions between factor XI and ABO genes increase risk of CVT by 4- to 14-fold.
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Sistema ABO de Grupos Sanguíneos , Fator XI , Trombose Venosa , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema ABO de Grupos Sanguíneos/genética , Epistasia Genética/genética , Fator XI/genética , Galactosiltransferases , Predisposição Genética para Doença/genética , Trombose Intracraniana/genética , Polimorfismo de Nucleotídeo Único , Trombose Venosa/genéticaRESUMO
INTRODUCTION: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. PATIENTS AND METHODS: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. RESULTS: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28-54) vs 45 (28-56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28-79) vs 68 (30-125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19-62) vs 53 (20-92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. DISCUSSION AND CONCLUSIONS: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.
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COVID-19 , Púrpura Trombocitopênica Idiopática , Trombose dos Seios Intracranianos , Trombocitopenia , Tromboembolia Venosa , Humanos , Feminino , Masculino , Adulto , Caracteres Sexuais , Mortalidade Hospitalar , Trombose dos Seios Intracranianos/epidemiologia , Progressão da Doença , VacinaçãoRESUMO
BACKGROUND: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. AIMS: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. METHODS: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). RESULTS: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20-37) versus 47 (IQR 32-58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11-40]) than in HICs (44/102 [43%, 95% CI 34-53], p = 0.039). CONCLUSIONS: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.
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Trombose dos Seios Intracranianos , Acidente Vascular Cerebral , Trombocitopenia , Vacinas , Humanos , Feminino , Adulto Jovem , Adulto , Vacinas contra COVID-19/efeitos adversos , Países em Desenvolvimento , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia , Trombose dos Seios Intracranianos/epidemiologia , Trombose dos Seios Intracranianos/etiologiaRESUMO
BACKGROUND: Vascular cognitive impairment (VCI) is the second most common cause of cognitive impairment worldwide and includes a spectrum from vascular cognitive impairment no dementia (VCIND) to vascular dementia (VaD). There is no specific pharmacological treatment approved for VCI. Physical activity has been indicated to be a promising preventive measure for cognition, with direct as indirectly benefits, while improving several modifiable vascular risk factors, so potentially effective when considering VCI. Our aim was to conduct a systematic review with a meta-analysis approaching the potential preventive role of physical activity on VCI. METHODS: A systematic search was conducted in 7 databases. A total of 6786 studies were screened and assessed for eligibility, culminating in the inclusion of 9 observational prospective studies assessing physical activity impact irrespectively the type for quality assessment and qualitative and quantitative synthesis. Quantitative synthesis was performed using the reported adjusted HRs. Physical activity was handled as a dichotomous variable, with two groups created (high versus low physical activity). Subgroup analyses were done for risk of bias, VaD and length of follow-up. RESULTS: There was considerable methodological heterogeneity across studies. Only three studies reported significant associations. The overall effect was statistically significant (HR 0.68, 95%CI 0.54-0.86, I2 6.8%), with higher levels of physical activity associated with a smaller risk of VCI overtime, particularly VaD. CONCLUSIONS: These findings suggest that physical activity is a potential preventive factor for vascular dementia. Insufficient data is available on VCIND. Randomized studies are desired to confirm these results.
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Disfunção Cognitiva , Demência Vascular , Humanos , Demência Vascular/diagnóstico , Demência Vascular/epidemiologia , Demência Vascular/prevenção & controle , Estudos Prospectivos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/prevenção & controle , Cognição , Exercício FísicoRESUMO
INTRODUCTION: High-quality evidence regarding the use of endovascular treatment (EVT) in patients with acute basilar artery occlusion (BAO) has been provided by recently completed randomized controlled clinical trials (RCTs). METHODS: We conducted a systematic review and meta-analysis including all available RCTs that investigated efficacy and safety of EVT in addition to best medical treatment (BMT) versus BMT alone for BAO. The random-effects model was used, while the fragility index (FI) was calculated for dichotomous outcomes of interest. RESULTS: Four RCTs were included comprising a total of 988 patients with acute BAO (mean age: 65.6 years, 70% men, median NIHSS: 24, 39% pretreatment with intravenous thrombolysis). EVT was related to higher likelihood of good functional outcome (RR: 1.54; 95% CI: 1.16-2.05; I2 = 60%), functional independence (RR: 1.83; 95% CI: 1.08-3.08; I2 = 79%) and reduced disability at 3 months (adjusted common OR: 1.96; 95% CI: 1.26-3.05; I2 = 59%) compared to BMT alone. Despite that EVT was associated with a higher risk for symptomatic intracranial hemorrhage (RR: 7.78; 95% CI: 2.36-25.61; I2 = 0%) and any intracranial hemorrhage (RR: 2.85; 95% CI: 1.50-5.44; I2 = 16%), mortality at 3 months was lower among patients that received EVT plus BMT versus BMT alone (RR: 0.76; 95% CI: 0.65-0.89; I2 = 0%). However, sufficient robustness was not evident in any of the reported associations (FI < 10) including the overall effect regarding the primary outcome. The former associations were predominantly driven by RCTs with recruitment limited in China. CONCLUSIONS: EVT combined with BMT is associated with a higher likelihood of achieving good functional outcomes and a lower risk of death at 3 months compared to BMT alone, despite the higher risk of sICH. An individual-patient data meta-analysis is warranted to uncover and adjust for potential sources of heterogeneity and to provide further insight.
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INTRODUCTION: Age-related white matter hyperintensities (ARWMHs) on brain magnetic resonance imaging have been associated with lower urinary tract symptoms/dysfunction (LUTS/LUTD), namely overactive bladder (OAB) and detrusor overactivity. We aimed to systematically review existing data on the association between ARWMH and LUTS and which clinical tools have been used for this assessment. MATERIALS AND METHODS: We searched PubMed/MEDLINE, Cochrane Library, and clinicaltrials.gov (from 1980 to November 2021) and considered original studies reporting data on ARWMH and LUTS/LUTD in patients of both sexes aged 50 or above. The primary outcome was OAB. We calculated the unadjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for the outcomes of interest using random-effects models. RESULTS: Fourteen studies were included. LUTS assessment was heterogeneous and mainly based on the use of nonvalidated questionnaires. Urodynamics assessment was reported in five studies. ARWMHs were graded using visual scales in eight studies. Patients with moderate-to-severe ARWMHs were more likely to present with OAB and urgency urinary incontinence (UUI; OR = 1.61; 95% CI: 1.05-2.49, p = 0.03), I2 = 21.3%) when compared to patients with similar age and absent or mild ARWMH. DISCUSSION AND CONCLUSIONS: High-quality data on the association between ARWMH and OAB is scarce. Patients with moderate to severe ARWMH showed higher levels of OAB symptoms, including UUI, when compared to patients with absent or mild ARWMH. The use of standardized tools to assess both ARWMH and OAB in these patients should be encouraged in future research.
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Sintomas do Trato Urinário Inferior , Bexiga Urinária Hiperativa , Incontinência Urinária , Substância Branca , Masculino , Feminino , Humanos , Substância Branca/diagnóstico por imagem , Incontinência Urinária/complicações , Sintomas do Trato Urinário Inferior/diagnóstico , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND PURPOSE: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish the superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to EVT versus medical management may differ between clinician specialties. METHODS: We conducted an international survey (January 18, 2022 to March 31, 2022) regarding management strategies in acute BAO prior to the announcement of two trials indicating the superiority of EVT, and compared responses between interventionalists (INTs) and non-interventionalists (nINTs). Selection practices for routine EVT and perceptions of equipoise regarding randomizing to medical management based on neuroimaging and clinical features were compared between the two groups using descriptive statistics. RESULTS: Among the 1245 respondents (nINTs = 702), INTs more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p < .01). A similar proportion of INTs and nINTs responded that they would not randomize a patient with BAO to EVT (29.4% vs. 26.7%), or that they would only under specific clinical circumstances (p = .45). Among respondents who would recommend EVT for BAO, there was no difference in the maximum prestroke disability, minimum stroke severity, or infarct burden on computed tomography between the two groups (p > .05), although nINTs more commonly preferred perfusion imaging (24.2% vs. 19.7%, p = .04). Among respondents who indicated they would randomize to medical management, INTs were more likely to randomize when the National Institutes of Health Stroke Scale was ≥10 (15.9% vs. 6.9%, p < .01). CONCLUSIONS: Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a BAO patient to medical treatment. There were small differences in preference for advanced neuroimaging for patient selection, although these preferences were unsupported by clinical trial data at the time of the survey.
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Arteriopatias Oclusivas , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Artéria Basilar/diagnóstico por imagem , Procedimentos Endovasculares/métodos , Resultado do Tratamento , Acidente Vascular Cerebral/terapia , Trombectomia/métodos , Estudos RetrospectivosRESUMO
The main goal of health services is for the elderly to maintain their mental and physical health and live at home independently for as long as possible. Various technical welfare solutions have been introduced and tested to support an independent life. The aim of this systematic review was to examine different types of interventions and assess the effectiveness of welfare technology (WT) interventions for older people living at home. This study was prospectively registered in PROSPERO (CRD42020190316) and followed the PRISMA statement. Primary randomized control trial (RCT) studies published between 2015 and 2020 were identified through the following databases: Academic, AMED, Cochrane Reviews, EBSCOhost, EMBASE, Google Scholar, Ovid MEDLINE via PubMed, Scopus, and Web of Science. Twelve out of 687 papers met the criteria for eligibility. We used risk-of-bias assessment (RoB 2) for the included studies. Based on the RoB 2 outcomes that showed a high risk of bias (>50%) and high heterogeneity of quantitative data, we decided to narratively summarize the study characteristics, outcome measures, and implications for practice. The included studies were conducted in six countries, namely the USA, Sweden, Korea, Italy, Singapore, and the UK. One was conducted in three European countries (the Netherlands, Sweden, and Switzerland). A total of 8437 participants were sampled, and individual study sample sizes ranged from 12 to 6742. Most of the studies were two-armed RCTs, except for two that were three-armed. The duration of the welfare technology tested in the studies ranged from four weeks to six months. The employed technologies were commercial solutions, including telephones, smartphones, computers, telemonitors, and robots. The type of interventions were balance training, physical exercise and function, cognitive training, monitoring of symptoms, activation of emergency medical systems, self-care, reduction of death risk, and medical alert protection systems. The latter studies were the first of their kind and suggested that physician-led telemonitoring could reduce length of hospital stay. In summary, welfare technology seems to offer solutions to supporting elderly people at home. The results showed a wide range of uses for technologies for improving mental and physical health. All studies showed encouraging results for improving the participants' health status.
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Background: Endovascular treatment (EVT) for acute ischemic stroke (AIS) patients presenting with Alberta Stroke Program Early CT Score (ASPECTS) 0-5 has not yet proven safe and effective by clinical trials. Objectives: The aim of the study was to assess whether EVT in AIS patients presenting with low ASPECTS is beneficial. Design: Systematic review and meta-analysis of available studies in accordance with the PRISMA statement. Data sources and Methods: We have searched MEDLINE, the Cochrane Central Register of Controlled Trials, and reference lists of articles published until 28 May 2022 with the aim to calculate (1) modified Rankin scale (mRS) score 0-3 at 3 months, (2) mRS score 0-2 at 3 months, (3) symptomatic intracranial hemorrhage (sICH), and (3) mortality at 3 months. Results: Overall, 24 eligible studies were included in the meta-analysis, comprising a total of 2539 AIS patients with ASPECTS 0-5 treated with EVT. The pooled proportion of EVT-treated patients achieving mRS 0-3 at 3 months was calculated at 38.4%. The pooled proportion of EVT-treated patients achieving mRS 0-2 at 3 months was 25.7%. Regarding safety outcomes, sICH occurred in 12.8% of patients. The 3-month pooled mortality was 30%. In pairwise meta-analysis, patients treated with EVT had a higher likelihood of achieving mRS 0-3 at 3 months compared with patients treated with best medical therapy (BMT, OR: 2.41). sICH occurred more frequently in EVT-treated patients compared with the BMT-treated patients (OR: 2.30). Mortality at 3 months was not different between the two treatment groups (OR: 0.71). Conclusion: EVT may be beneficial for AIS patients with low baseline ASPECTS despite an increased risk for sICH. Further data from randomized-controlled clinical trials are needed to elucidate the role of EVT in this subgroup of AIS patients. Registration: The protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO; Registration Number: CRD42022334417.
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Rationale: Direct oral anticoagulants (DOAC) are highly effective in preventing ischaemic strokes in people with atrial fibrillation (AF). However, it is unclear how soon they should be started after acute ischaemic stroke (AIS). Early initiation may reduce early risk of recurrence but might increase the risk of haemorrhagic complications. Aim: To estimate the safety and efficacy of early initiation of DOACs compared to late guideline-based initiation in people with AIS related to AF. Methods and design: An international, multicentre, randomised (1:1) controlled, two-arm, open, assessor-blinded trial is being conducted. Early treatment is defined as DOAC initiation within 48 h of a minor or moderate stroke, or at day 6-7 following major stroke. Late treatment is defined as DOAC initiation after day 3-4 following minor stroke, after day 6-7 following moderate stroke and after day 12-14 following major stroke. Severity of stroke is defined according to imaging assessment of infarct size. Sample size: ELAN will randomise 2000 participants 1:1 to early versus late initiation of DOACs. This assumes a risk difference of 0.5% favouring the early arm, allowing an upper limit of the 95% confidence interval up to 1.5% based on the Miettinen & Nurminen formula. Outcomes: The primary outcome is a composite of symptomatic intracranial haemorrhage, major extracranial bleeding, recurrent ischaemic stroke, systemic embolism or vascular death at 30 ± 3 days after randomisation. Secondary outcomes include the individual components of the primary outcome at 30 ± 3 and 90 ± 7 days and functional status at 90 ± 7 days. Discussion: ELAN will estimate whether there is a clinically important difference in safety and efficacy outcomes following early anticoagulation with a DOAC compared to late guideline-based treatment in neuroimaging-selected people with an AIS due to AF.
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BACKGROUND: We identified risk factors, derived and validated a prognostic score for poor neurological outcome and death for use in cerebral venous thrombosis (CVT). METHODS: We performed an international multicenter retrospective study including consecutive patients with CVT from January 2015 to December 2020. Demographic, clinical, and radiographic characteristics were collected. Univariable and multivariable logistic regressions were conducted to determine risk factors for poor outcome, mRS 3-6. A prognostic score was derived and validated. RESULTS: A total of 1,025 patients were analyzed with median 375 days (interquartile range [IQR], 180 to 747) of follow-up. The median age was 44 (IQR, 32 to 58) and 62.7% were female. Multivariable analysis revealed the following factors were associated with poor outcome at 90- day follow-up: active cancer (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.62 to 27.14; P<0.001), age (OR, 1.02 per year; 95% CI, 1.00 to 1.04; P=0.039), Black race (OR, 2.17; 95% CI, 1.10 to 4.27; P=0.025), encephalopathy or coma on presentation (OR, 2.71; 95% CI, 1.39 to 5.30; P=0.004), decreased hemoglobin (OR, 1.16 per g/dL; 95% CI, 1.03 to 1.31; P=0.014), higher NIHSS on presentation (OR, 1.07 per point; 95% CI, 1.02 to 1.11; P=0.002), and substance use (OR, 2.34; 95% CI, 1.16 to 4.71; P=0.017). The derived IN-REvASC score outperformed ISCVT-RS for the prediction of poor outcome at 90-day follow-up (area under the curve [AUC], 0.84 [95% CI, 0.79 to 0.87] vs. AUC, 0.71 [95% CI, 0.66 to 0.76], χ2 P<0.001) and mortality (AUC, 0.84 [95% CI, 0.78 to 0.90] vs. AUC, 0.72 [95% CI, 0.66 to 0.79], χ2 P=0.03). CONCLUSIONS: Seven factors were associated with poor neurological outcome following CVT. The INREvASC score increased prognostic accuracy compared to ISCVT-RS. Determining patients at highest risk of poor outcome in CVT could help in clinical decision making and identify patients for targeted therapy in future clinical trials.
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Unruptured intracranial aneurysms (UIA) occur in around 3% of the population. Important management questions concern if and how to perform preventive UIA occlusion; if, how and when to perform follow up imaging and non-interventional means to reduce the risk of rupture. Using the Standard Operational Procedure of ESO we prepared guidelines according to GRADE methodology. Since no completed randomised trials exist, we used interim analyses of trials, and meta-analyses of observational and case-control studies to provide recommendations to guide UIA management. All recommendations were based on very low evidence. We suggest preventive occlusion if the estimated 5-year rupture risk exceeds the risk of preventive treatment. In general, we cannot recommend endovascular over microsurgical treatment, but suggest flow diverting stents as option only when there are no other low-risk options for UIA repair. To detect UIA recurrence we suggest radiological follow up after occlusion. In patients who are initially observed, we suggest radiological monitoring to detect future UIA growth, smoking cessation, treatment of hypertension, but not treatment with statins or acetylsalicylic acid with the indication to reduce the risk of aneurysm rupture. Additionally, we formulated 15 expert-consensus statements. All experts suggest to assess UIA patients within a multidisciplinary setting (neurosurgery, neuroradiology and neurology) at centres consulting >100 UIA patients per year, to use a shared decision-making process based on the team recommendation and patient preferences, and to repair UIA only in centres performing the proposed treatment in >30 patients with (ruptured or unruptured) aneurysms per year per neurosurgeon or neurointerventionalist. These UIA guidelines provide contemporary recommendations and consensus statement on important aspects of UIA management until more robust data come available.
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Introduction: There is uncertainty regarding the optimal timing for initiation of oral anticoagulation in patients with acute ischemic stroke (AIS) due to atrial fibrillation (AF). Methods: We performed a systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) and prospective observational studies to assess the efficacy and safety of early anticoagulation in AF-related AIS (within 1 week versus 2 weeks). A second comparison was performed assessing the efficacy and safety of direct oral anticoagulants (DOACs) versus vitamin-K antagonists (VKAs) in the two early time windows. The outcomes of interest were IS recurrence, all-cause mortality, symptomatic intracerebral haemorrhage (sICH) and any ICH. Results: Eight eligible studies (6 observational, 2 RCTs) were identified, including 5616 patients with AF-related AIS who received early anticoagulation. Patients that received anticoagulants within the first week after index stroke had similar rate of recurrent IS, sICH and all-cause mortality compared to patients that received anticoagulation within two weeks (test for subgroup differences p = 0.1677; p = 0.8941; and p = 0.7786, respectively). When DOACs were compared to VKAs, there was a significant decline of IS recurrence in DOAC-treated patients compared to VKAs (RR: 0.65; 95%CI: 0.52-0.82), which was evident in both time windows of treatment initiation. DOACs were also associated with lower likelihood of sICH and all-cause mortality. Conclusions: Early initiation of anticoagulation within the first week may have a similar efficacy and safety profile compared to later anticoagulation (within two weeks), while DOACs seem more effective in terms of IS recurrence and survival compared to VKAs.
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Cotinine, the primary metabolite of nicotine, is currently regarded as the best biomarker of tobacco smoke exposure. We aim to assess whether cotinine levels are associated with (1) intracranial aneurysm and (2) intracranial aneurysm rupture. METHODS: We performed a single-center case-control study. Cases were consecutive patients admitted with diagnosis of brain aneurysm (ruptured or unruptured). We randomly selected controls without intracranial aneurysm from the same source population that produced the cases. Smoking data were collected by questionnaire, and serum levels of cotinine were used as an objective measure of nicotine exposure. Logistic regression models were used to assess the relationship between cotinine levels and aneurysm rupture. RESULTS: We included 86 patients with intracranial aneurysm and 96 controls. Smoking status (p < .001), cotinine levels (p = .009), and female sex (p = .006) were associated with diagnosis of intracranial aneurysm. In the multivariate analysis, controlling for sex, smoker status and age, levels of cotinine were independently associated with aneurysm rupture (OR 1.53, 95% CI 1.10-2.13, p = .012). CONCLUSIONS: Our results suggest that high cotinine levels in smokers with brain aneurysm are significantly associated with high rupture risk, independently of smoker status, age, and sex.
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Aneurisma Roto , Aneurisma Intracraniano , Poluição por Fumaça de Tabaco , Aneurisma Roto/epidemiologia , Estudos de Casos e Controles , Cotinina , Feminino , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/epidemiologia , Nicotina , Fatores de RiscoRESUMO
The risk of recurrence after discontinuation of anticoagulation for a combined oral contraceptive (COC)-associated venous thromboembolism (VTE) is unclear. Therefore, we conducted a systematic review and meta-analysis to estimate the incidence of recurrent VTE among women with COC-associated VTE, unprovoked VTE and to compare the incidence of recurrent VTE between the two groups. The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase Classic +Embase and Medline ALL to July 2020 and citations from included studies were searched. Randomized controlled trials, prospective cohort studies and meta-analyses of these study types were selected. The analysis was conducted by random-effects model. Nineteen studies were identified including 1537 women [5828 person-years (PY)] with COC-associated VTE and 1974 women (7798 PY) with unprovoked VTE. Studies were at low risk of bias. The incidence rate of VTE recurrence was 1.22/100 PY [95% confidence interval (CI) 0.92-1.62, I2 = 6%] in women with COC-associated VTE, 3.89/100 PY (95% CI 2.93-5.17, I2 = 74%) in women with unprovoked VTE and the unadjusted incidence rate ratio was 0.34 (95% CI 0.26-0.46, I2 = 3%). The recurrence risk in women after COC-associated VTE is low and lower than after an unprovoked VTE.
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Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Anticoncepcionais Orais Combinados/efeitos adversos , Feminino , Humanos , Estudos Prospectivos , Recidiva , Fatores de Risco , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND AND PURPOSE: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. METHODS: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). RESULTS: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. CONCLUSIONS: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.
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OBJECTIVE: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. METHODS: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. RESULTS: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). CONCLUSIONS: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.
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COVID-19 , Trombose Intracraniana , Trombose Venosa , Adenoviridae , Anticoagulantes/uso terapêutico , Vacinas contra COVID-19/efeitos adversos , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , SARS-CoV-2 , Vacinação/efeitos adversos , Trombose Venosa/complicaçõesRESUMO
BACKGROUND AND PURPOSE: Cerebral venous sinus thrombosis (CVST) has been reported as a rare adverse event in association with thrombosis-thrombocytopenia syndrome (TTS) following COVID-19 vaccination. METHODS: We performed a systematic review and meta-analysis of investigator-initiated registries including confirmed CVST cases, with the aim to calculate (1) the odds ratio of TTS-CVST versus non-TTS-CVST after vector-based vaccines and (2) after non-vector-based vaccines, (3) the in-hospital mortality ratio of TTS-CVST compared to non-TTS-CVST; and (4) the dependency or death at discharge among TTS-CVST compared to non-TTS-CVST cases. RESULTS: Two eligible studies were included in the meta-analysis, comprising a total of 211 patients with CVST associated with COVID-19 vaccination. Vector-based COVID-19 vaccination was associated with a higher likelihood of TTS-associated CVST than with non-TTS-CVST (OR: 52.34, 95% CI 9.58-285.98). TTS-CVST was also associated with higher likelihood of in-hospital mortality (OR: 13.29; 95% CI 3.96-44.60) and death or dependency at discharge compared to non-TTS-CVST (OR: 6.70; 95% CI 3.15-14.26). TTS-CVST was recorded with a shorter interval between vaccination and symptom onset [Mean Difference (MD):-6.54 days; 95% CI - 12.64 to - 0.45], affecting younger patients (MD:-9.00 years; 95% CI - 14.02 to - 3.99) without risk factors for thromboses (OR:2.34; 95% CI 1.26-4.33), and was complicated more frequently with intracerebral hemorrhage (OR:3.60; 95% CI 1.31-9.87) and concomitant thromboses in other sites (OR:11.85; 95% CI 3.51-39.98) compared to non-TTS-CVST cases. CONCLUSIONS: TTS-CVST following COVID-19 vaccination has distinct risk factor profile, clinical phenotype and prognosis compared to non-TTS-CVST. Further epidemiological data are required to evaluate the impact of different treatment strategies on outcome of TTS-CVST cases following COVID-19 vaccination.
Assuntos
COVID-19 , Trombose dos Seios Intracranianos , COVID-19/complicações , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Fatores de Risco , Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/epidemiologia , Trombose dos Seios Intracranianos/etiologia , Vacinação/efeitos adversosRESUMO
Importance: Tenecteplase is being evaluated as an alternative thrombolytic agent for the treatment of acute ischemic stroke (AIS) within ongoing randomized clinical trials (RCTs). In addition, nonrandomized clinical experiences with off-label use of tenecteplase vs alteplase for AIS treatment are being published. Objective: To evaluate the available evidence on the safety and efficacy of intravenous tenecteplase compared with intravenous alteplase provided by nonrandomized studies. Data Sources: Eligible studies were identified by searching MEDLINE and Scopus databases. No language or other restrictions were imposed. The literature search was conducted on October 12, 2021. This meta-analysis used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal. Study Selection: Nonrandomized studies (prospective or retrospective) comparing intravenous tenecteplase (at any dose) with intravenous alteplase in patients with AIS were included in the analysis. Data Extraction and Synthesis: The crude odds ratios (ORs) and 95% CIs were calculated for the association of tenecteplase vs alteplase with the outcomes of interest and adjusted ORs were extracted if provided. Estimates using random-effects models were pooled. Main Outcomes and Measures: The primary outcome was the probability of good functional outcome (modified Rankin scale [mRS] score, 0-2) at 90 days. Results: Six studies were identified including a total of 1820 patients (618 [34%] treated with tenecteplase). Patients receiving tenecteplase had higher odds of 3-month good functional outcome (crude odds ratio [OR], 1.22; 95% CI, 0.90-1.66; adjusted OR, 1.60, 95% CI, 1.08-2.37), successful recanalization (crude OR, 2.82; 95% CI, 1.12-7.10; adjusted OR, 2.38; 95% CI, 1.18-4.81), and early neurological improvement (crude OR, 4.88; 95% CI, 2.03-11.71; adjusted OR, 7.60; 95% CI, 1.97-29.41). No significant differences were detected in 3-month excellent functional outcome proportions (mRS score 0-1; crude OR, 1.53; 95% CI, 0.81-2.91; adjusted OR, 2.51; 95% CI, 0.66- 9.49), symptomatic intracranial hemorrhage (crude OR, 0.97; 95% CI, 0.44-2.16; adjusted OR, 1.16; 95% CI, 0.13-10.50), or parenchymal hematoma (crude OR, 1.20; 95% CI, 0.24-5.95). Conclusions and Relevance: Evidence from nonrandomized studies suggests tenecteplase is as safe as alteplase and potentially associated with improved functional outcomes compared with alteplase. Based on these findings, enrollment in the ongoing RCTs appears to be appropriate.