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Background The association between metabolic syndrome and increased cardiovascular disease (CVD) risk is well‐established. However, in patients with incident CVD, the relationship between obesity, metabolic health, and subsequent CVD and mortality outcomes are less well‐established. This study investigated the association between body mass index (BMI), metabolic health and the risk of subsequent cardiovascular mortality and morbidity outcomes in patients with incident CVD events. Methods This cohort study identified 130 685 patients from the nationwide Clinical Practice Research Datalink (CPRD GOLD) and Hospital Episode Statistics (HES) databases in the United Kingdom. Patients were ≥18 years with incident CVD [coronary heart disease (CHD), stroke, or peripheral vascular disease (PVD)] between 1 January 1998 and 31 December 2017. BMI (in kg/m2) was categorized as underweight (<18.5), normal (18.5–24.9), overweight (25.0–29.9) and obese (≥30). Within each BMI category, patients were grouped by increasing count of 1, 2 or 3 metabolic risk factors [RF] (dyslipidaemia, diabetes mellitus and hypertension) and were regarded as metabolically unhealthy while absence of these factors was considered metabolically healthy (MH). Multivariable Cox regression was used to assess the risk (hazard ratio with 95% confidence interval) of subsequent outcomes (non‐fatal CHD, stroke, PVD, incident heart failure, CVD‐mortality and all‐cause mortality) in BMI subgroups with incremental count of metabolic RFs. Results During a median follow‐up of 13.0 years, a higher BMI was associated with reduced risk for stroke, PVD, CVD‐mortality and all‐cause mortality within each metabolic risk category, while increasing metabolic RFs within each BMI subgroup accounted for increasing risks. When compared with patients with normal BMI and no RF, CVD‐mortality risk in overweight patients with no RF was 0.76 (0.70–0.84), and in obese patients with no RF was 0.85 (0.76–0.96). The respective risk for all‐cause mortality in patients with overweight and no RF was 0.69 (0.65–0.72), and in obese patients with no RF was 0.75 (0.70–0.79). Subsequent outcomes of stroke and PVD showed similar trends. In contrast, the risk of subsequent non‐fatal CHD events and incident HF increased with higher BMI and with incremental metabolic risk factors within each BMI category. Underweight was constantly associated with increased risk for all outcomes regardless of the presence of metabolic RFs except for non‐fatal CHD events. Conclusions In patients with incident CVD, overweight and obesity were related to a more favourable prognosis for subsequent stroke, PVD and mortality (CVD‐related and all‐cause) irrespective of the presence of other metabolic risk factors.

To evaluate the association of intracranial non-stenotic atherosclerotic plaque with cerebral small vessel disease (CSVD) imaging markers in a CSVD population using 3.0 T high-resolution magnetic resonance imaging (HRMRI), which was validated in embolic stroke of undetermined source (ESUS) cohort. We retrospectively recruited consecutive patients who were diagnosed with CSVD or ESUS from January 2015 to December 2019. All patients underwent intracranial HRMRI to assess intracranial non-stenotic atherosclerotic plaques. Baseline and imaging data were collected and were measured among all patients. Among 153 patients with CSVD, there were 59 with intracranial atherosclerotic plaque (IAP) and 94 with non-IAP, including 36 with intracranial atherosclerotic complicated plaque (IACP). Among 227 ESUS patients, there were 155 with IAP and 72 with non-IAP, including 127 with IACP. In the CSVD population, we found that: (1) CSVD burden was associated with IAP ( p  = 0.036) and IACP ( p  = 0.008); (2) IAP was associated with white matter hyperintensity (51% vs. 34%; P  = 0.039), and IACP was associated with lacunes (69% vs. 35%; P  = 0.009) and enlarge perivascular space (69% vs. 39%; P  = 0.022). A similar association of CSVD imaging markers with IAP or IACP was found in the ESUS population. Furthermore, the association of unilateral IAP or IACP with CSVD imaging markers of ipsilateral hemisphere was identified in the two cohorts. This is the first report that intracranial non-stenotic atherosclerotic plaque, especially complicated plaque, is closely associated with CSVD imaging markers, which provide further evidence for the association of large artery atherosclerosis with CSVD.

Age and sex have effect on atherosclerosis. This study aimed to investigate their effect on non-stenotic intracranial atherosclerotic plaque (NIAP) in embolic stroke of undetermined source (ESUS) using high-resolution magnetic resonance imaging (HR-MRI). We retrospectively recruited consecutive ESUS patients who underwent intracranial HR-MRI to assess the plaque characteristics (remodeling index [RI], plaque burden [PB], fibrous cap [FC], discontinuity of plaque surface [DPS], intraplaque hemorrhage [IPH] and complicated plaque [CP]). We divided patients into three groups (< 60 years, 60–74 years, ≥ 75 years). 155 patients with ipsilateral NIAP were found from 243 ESUS patients, with 106 men (68.39%) and 49 women (31.61%). In total population or age group under 60 years, there were no significant differences in plaque characteristics between men and women (all p > 0.05). In age group of 60–74 years, men were associated with higher PB (66.27 ± 9.17% vs 60.91 ± 8.86%, p = 0.017) and RI (1.174 vs 1.156, p = 0.019), higher prevalence of DPS (82.50% vs 60.00%, p = 0.036) and complicated plaque (85.00% vs 63.33%, p = 0.036). For subjects ≥ 75 years old, PB were significantly higher in twomen vs men (68.85 ± 6.14% vs 62.62 ± 7.36%, p = 0.040). In addition, the probability for PB upper (≥ median PB), RI upper (≥ median RI) and vulnerable plaque increased as age increased, and its predictive power for index ESUS was higher in men than women. This study identified age-dependent sex differences in NIAP characteristics of ESUS patients, which will help us clarify their etiology.

Background The association between obesity, major adverse cardiovascular events (MACE), and mortality in patients with incident stroke is not well established. We assessed the relationship between body mass index (BMI) and MACE in patients with incident stroke. Methods The population‐based cohort study identified 30 702 individuals from the Clinical Practice Research Datalink (CPRD GOLD) and Hospital Episode Statistics (HES) databases from the United Kingdom. Individuals were aged ≥18 years with incident stroke between 1‐1‐1998 and 31‐12‐2017, a BMI recorded within 24 months before incident stroke, and no prior history of MACE. BMI was categorized as underweight (<18.5 kg/m2), normal (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), obesity class I (30.0–34.9 kg/m2), class II (35.0–39.9 kg/m2) and class III (≥40 kg/m2). MACE was defined as a composite of incident coronary heart disease, recurrent stroke, peripheral vascular disease (PVD), heart failure, and cardiovascular‐related mortality. Multivariable Cox regression was used to assess differences in MACE risk between BMI categories. Results At baseline, 1217 (4.0%) were underweight, 10 783 (35.1%) had a normal BMI, 10 979 (35.8%) had overweight, 5206 (17.0%) had obesity Class I, 1749 (5.7%) Class II, and 768 (2.5%) Class III. In multivariable analysis, higher BMI were associated with lower risk of subsequent MACE [overweight: HR 0.96, 95% CI 0.93–0.99)]; PVD [overweight: 0.65 (0.49–0.85); obesity Class III: 0.19 (0.50–0.77)]; cardiovascular‐related death [overweight: 0.80 (0.74–0.86); obesity Class I: 0.79 (0.71–0.88); Class II: 0.80 (0.67–0.96)]; and all‐cause mortality [overweight: 0.75 (0.71–0.79); obesity Class I: 0.75 (0.70–0.81); Class II: 0.77 (0.68–0.86)] when compared to those with normal BMI. The results were similar irrespective of sex, diabetes mellitus, smoking or cancer at time of incident stroke. Conclusions In patients with incident stroke, overweight or obesity were associated with a more favourable prognosis for subsequent MACE, PVD, and mortality, irrespective of sex, diabetes mellitus, smoking, or cancer at baseline. As with other cohort studies, our study demonstrates an association. Randomized control trials should be considered to robustly evaluate the impact of weight management recommendations on subsequent cardiovascular outcomes in stroke survivors.

Prophylactic administration of paracetamol (acetaminophen) has been reported to reduce body temperature in the first day after stroke and to reduce blood pressure on the first day. We aimed to validate these findings in the randomised PRECIOUS trial and to assess the effect of paracetamol on body temperature in the first seven days after stroke. PRECIOUS was an international, 3*2 factorial, randomised, controlled, clinical trial assessing preventive treatment with paracetamol, metoclopramide, and ceftriaxone in patients aged 66 years or older with acute stroke and a score on the National Institutes of Health Stroke Scale (NIHSS) ≥ 6. Paracetamol was given in a dose of 4g daily for four days. Vital signs were recorded at 12 hours intervals up to seven days. The primary outcomes of this study were body temperature and systolic and diastolic blood pressure at 24 hours after randomisation, analysed with linear regression. The presence of a subfebrile temperature or fever at 24 hours was a secondary outcome. We used data from 1419 of 1493 patients included in PRECIOUS. Paracetamol reduced mean body temperature by 0.1°C (95% CI, 0.0-0.2) at 24 hours after randomisation but did not lower systolic or diastolic blood pressure. Paracetamol reduced the occurrence of subfebrile temperatures or fever at 24 hours from 15.8% to 8.3% (p < 0.001). The effects of paracetamol on body temperature were consistent over the four days of treatment. Prophylactic use of paracetamol resulted in a modest reduction in mean body temperature and almost halved the rate of subfebrile temperatures or fever at 24 hours after stroke, but had no effect on blood pressure.

We systematically reviewed data about the effect of exogenous estrogens and progestogens on the course of migraine during reproductive age. Thereafter a consensus procedure among international experts was undertaken to develop statements to support clinical decision making, in terms of possible effects on migraine course of exogenous estrogens and progestogens and on possible treatment of headache associated with the use or with the withdrawal of hormones. Overall, quality of current evidence is low. Recommendations are provided for all the compounds with available evidence including the conventional 21/7 combined hormonal contraception, the desogestrel only oral pill, combined oral contraceptives with shortened pill-free interval, combined oral contraceptives with estradiol supplementation during the pill-free interval, extended regimen of combined hormonal contraceptive with pill or patch, combined hormonal contraceptive vaginal ring, transdermal estradiol supplementation with gel, transdermal estradiol supplementation with patch, subcutaneous estrogen implant with cyclical oral progestogen. As the quality of available data is poor, further research is needed on this topic to improve the knowledge about the use of estrogens and progestogens in women with migraine. There is a need for better management of headaches related to the use of hormones or their withdrawal.

Ischemic stroke (IS) is a severe complication and leading cause of mortality in patients under extracorporeal membrane oxygenation (ECMO). The aim of our narrative review is to summarize the existing evidence and provide a deep examination of the diagnosis and treatment of acute ischemic stroke patients undergoing ECMO support. The incidence rate of ISs is estimated to be between 1 and 8%, while the mortality rate ranges from 44 to 76%, depending on several factors, including ECMO type, duration of support and patient characteristics. Several mechanisms leading to ISs during ECMO have been identified, with thromboembolic events and cerebral hypoperfusion being the most common causes. However, considering that most of the ECMO patients are severely ill or under sedation, stroke symptoms are often underdiagnosed. Multimodal monitoring and daily clinical assessment could be useful preventive techniques. Early recognition of neurological deficits is of paramount importance for prompt therapeutic interventions. All ECMO patients with suspected strokes should immediately receive brain computed tomography (CT) and CT angiography (CTA) for the identification of large vessel occlusion (LVO) and assessment of collateral blood flow. CT perfusion (CTP) can further assist in the detection of viable tissue (penumbra), especially in cases of strokes of unknown onset. Catheter angiography is required to confirm LVO detected on CTA. Intravenous thrombolytic therapy is usually contraindicated in ECMO as most patients are on active anticoagulation treatment. Therefore, mechanical thrombectomy is the preferred treatment option in cases where there is evidence of LVO. The choice of the arterial vascular access used to perform mechanical thrombectomy should be discussed between interventional radiologists and an ECMO team. Anticoagulation management during the acute phase of IS should be individualized after the thromboembolic risk has been carefully balanced against hemorrhagic risk. A multidisciplinary approach is essential for the optimal management of ISs in patients treated with ECMO.

Background: Real-world, observational studies have investigated the safety profile of Direct Oral Anticoagulants (DOACs) on Major Hemorrhage (MH) used for stroke prevention in Non-Valvular Atrial Fibrillation (NVAF). We performed a systematic review and meta-analysis to investigate the comparative safety of DOACs versus other DOACs and versus Vitamin K Antagonists (VKAs) adhering to PRISMA guidelines. We defined MH according to the International Society on Thrombosis and Haemostasis statement or as the composite outcome of intracranial, gastrointestinal, genitourinary, respiratory, cavitary and musculoskeletal bleeding in case of studies using International Statistical Classification of Diseases codes for patient selection. Methods: We systematically investigated two databases (Medline, Embase) until April of 2021, gathered observational studies and extracted hazard ratios (HRs) with 95% confidence intervals (CI) on our outcome of interest. Additional subgroup analyses according to DOAC dosing, prior diagnosis of chronic kidney disease, prior diagnosis of stroke, history of previous use of VKA, the users’ age, the users’ gender and study population geographic region were conducted. All analyses were performed with a random-effects model. Results: From this search, 55 studies were included and 76 comparisons were performed. The MH risk associated with Rivaroxaban use was higher than the risk with Dabigatran use (HR: 1.32, 95% CI: 1.21–1.45, I2: 12.39%) but similar to VKA use (HR: 0.94, 95% CI: 0.87–1.02, I2: 76.57%). The MH risk associated with Dabigatran use was lower than the risk with VKA use (HR: 0.75, 95% CI: 0.64–0.90, I2: 87.57%). The MH risk associated with Apixaban use was lower than the risk with Dabigatran use (HR: 0.75, 95% CI: 0.64–0.88, I2: 58.66%), with Rivaroxaban use (HR: 0.58, 95% CI: 0.50–0.68, I2: 74.16%) and with VKA use (HR: 0.60, 95% CI: 0.55–0.65, I2: 58.83%). Our aforementioned subgroup analyses revealed similar results. Conclusions: All in all, Apixaban was associated with a reduced MH risk compared to Dabigatran, Rivaroxaban and VKA. Dabigatran was associated with a reduced MH risk compared to both Rivaroxaban and VKA.

Risk stratification of coronavirus disease-19 (COVID-19) patients by simple markers is critical to guide treatment. We studied the predictive value of soluble interleukin-2 receptor (sIL-2R) for the early identification of patients at risk of developing severe clinical outcomes. sIL-2R levels were measured in 197 patients (60.9% males; median age 61 years; moderate disease, n = 65; severe, n = 132, intubated and/or died, n = 42). All patients received combined immunotherapies (anakinra ± corticosteroids ± intravenous immunoglobulin ± tocilizumab) according to our local treatment algorithm. The endpoint was the composite event of intubation due to severe respiratory failure (SRF) or mortality. Median (interquartile range) sIL-2R levels were significantly higher in patients with severe disease, compared with those with moderate disease (6 (6.2) vs. 5.2 (3.4) ng/mL, p = 0.017). sIL-2R was the strongest laboratory predictive factor for intubation/death (hazard ratio 1.749, 95%CI 1.041–2.939, p = 0.035) after adjustment for other known risk factors. Youden’s index revealed optimal sIL-2R cut-off for predicting intubation/death at 9 ng/mL (sensitivity: 67%; specificity: 86%; positive and negative predictive value: 57% and 91%, respectively). Delta sIL-2R between the day of event or discharge minus admission date was higher in patients that intubated/died than in those who did not experience an event (2.91 (10.42) vs. 0.44 (2.88) ng/mL; p = 0.08)). sIL-2R on admission and its dynamic changes during follow-up may reflect disease severity and predict the development of SRF and mortality.

Acute lower extremity proximal deep venous thrombosis (DVT) requires accurate diagnosis and treatment in order to prevent embolization and other complications. Point-of-care ultrasound (POCUS), a clinician performed, and clinician interpreted bedside ultrasound examination has been increasingly used for DVT evaluation mainly in the urgent and critical care setting, but also in the ambulatory clinics and the medical wards. Studies have demonstrated that POCUS has excellent diagnostic accuracy for acute proximal DVT when performed by well-trained users. However, there is significant heterogeneity among studies on the necessary extent of training and universally acceptable standardized education protocols are needed. In this review, we summarize the evidence that supports the use of POCUS to diagnose acute proximal DVT and focus on methodology and current technology, sensitivity and specificity, pre-test probability and the role of D-dimer, time and resources, education, limitations, and future directions.