Long-term efficacy, safety and tolerability of secukinumab in children and adolescents with severe chronic plaque psoriasis: Two-year results from a Phase III double-blind, randomized controlled trial.

BACKGROUND: Secukinumab has previously demonstrated sustained efficacy and favourable safety for up to 52 weeks in paediatric patients (children and adolescents aged 6 to <18 years) with severe chronic plaque psoriasis (NCT02471144). OBJECTIVE: To investigate the long-term (104 weeks) efficacy and safety of secukinumab. METHODS: After 52 weeks, patients continued to receive secukinumab low dose (LD [75/150 mg]) or high dose (HD [75/150/300 mg]). Patients on etanercept (0.8 mg/kg) until Week 52 entered follow-up. Data for patients receiving secukinumab LD from the beginning and those switching to secukinumab LD from placebo ('Any secukinumab' LD) and patients receiving secukinumab HD from the beginning and those switching to secukinumab HD from placebo ('Any secukinumab' HD) are presented. ASSESSMENTS: Psoriasis Area and Severity Index (PASI) score, PASI (75/90/100) responses, Investigator's Global Assessment modified 2011 (IGA mod 2011) 0/1 response, Children's Dermatology Life Quality Index (CDLQI) score and CDLQI 0/1 response up to Week 104, and, safety up to Week 104 for all patients and up to 4 years for some patients (~320 patient-years [PY] of treatment). RESULTS: Secukinumab-treated patients showed sustained PASI 75/90/100 and IGA mod 2011 0/1 responses up to Week 104. Throughout the second year of treatment, efficacy was similar for the 'Any secukinumab' LD and HD groups for PASI 75 and IGA mod 2011 0/1 responses. PASI 90/100 responses were mostly comparable between the dose groups up to Week 88, but higher in the 'Any secukinumab' HD than the 'Any secukinumab' LD group at Week 104. Patients achieved a sustained CDLQI 0/1 response that was similar between the 'Any secukinumab' LD (61.1%) and HD (65.0%) groups. Safety data were consistent with the established safety profile of secukinumab. CONCLUSION: Secukinumab demonstrated sustained long-term efficacy (up to 2 years) and a favourable safety profile (~320 PY of treatment) in paediatric patients with severe chronic plaque psoriasis.

Predictors and Prognostic Implications of Hemorrhagic Transformation Following Cerebral Endovascular Thrombectomy in Acute Ischemic Stroke: A Multicenter Analysis.

PURPOSE: Hemorrhagic transformation (HT) following cerebral endovascular thrombectomy (EVT) for large vessel occlusion (LVO) in acute ischemic stroke is associated with poor outcome. Recent studies have shown that EVT can be efficacious in imaging-selected patients as late as 6-24 h from onset (late time window; LTW). We sought to determine predictors and prognostic implications of HT following EVT in LTW. METHODS: Consecutive patients undergoing EVT for LVO were recruited into a prospective multicenter database. HT was divided into petechial hemorrhagic-infarction and parenchymal hematoma (PH) type 1 or 2 defined as confluent hemorrhage covering < or > than 1/3 of the infarct volume, respectively. Multivariate analyses were performed to determine variables associated with HT subtypes. RESULTS: Among 611 patients included (mean age 70.5 ± 12.5 years; median NIHSS 16), 115 (18.8%) had HT and 33 of them (5.4%) had PH2. Independent PH2 predictors included failed recanalization (OR 7.0, 95% CI 2.3-21.6), longer time from symptom onset to admission (OR 1.002 per minute 95% CI 1.001-1.003) and hyperlipidemia (OR 3.12; 95%CI 1.12-8.7). HT was not associated with outcome. In contrast, PH2 patients had lower favorable outcome rates (14.3 vs 41.6%, p = 0.004) and higher mortality rates (39 vs 17%, p = 0.001). Patients who underwent EVT in the late versus early window had similar PH2 rates (4.5 vs 6.7%, p = 0.27). In multivariate models, PH2 tripled the odds of both 90-day poor outcome (OR 3.1, 95% CI 1.01-9.5) and 90-day mortality (OR 3.2, 95% CI 1.4-7.3). CONCLUSIONS: PH2 following EVT is associated with increased mortality and unfavorable outcome rates. Rates of PH2 are not different between LTW patients and those treated < 6 h from symptom onset.

Clopidogrel underactivity is a common in patients with acute symptomatic severe carotid stenosis.

BACKGROUND: Clopidogrel is commonly used for secondary stroke prevention in patients with large vessel stenosis. Reduced Clopidogrel high on treatment platelet reactivity (CR) can lead to Clopidogrel underactivity (CU) causing acute thrombosis. However, the prevalence of CU among patients with acute symptomatic carotid disease remains unknown. Therefore, we aimed to find the prevalence and identify the predictors for CU among patients with acutely symptomatic carotid stenosis. PATIENTS AND METHODS: Over the span of 14 months, CR was measured at the time of endovascular procedure in all patients undergoing angiography and stenting because of acute symptomatic carotid stenosis. Only patients treated per institutional protocol with a combination of Clopidogrel and Aspirin were included. CR was measured with VerifyNowP2Y12 reaction units (PRU) and CU was defined as PRU > 208. Patients with CU were compared to those without CU. RESULTS: Thirty-five patients were included (mean age 71.3 ± 10, 76% men) and twelve (34.3%, mean age 71.8 ± 8.4, 58% men) had CU at the time of endovascular intervention. On univariate analysis more severe carotid stenosis was seen in CU patients (92.6 ± 6.5% vs 81.6 ± 13.6%, p = 0.013) and percent stenosis was independently associated with CU on multivariate analysis (p = 0.023). CONCLUSIONS: CU is present in 1 of every 3 patients with acutely symptomatic carotid disease. The current results suggest that CR testing should become part of routine care in patients with acutely symptomatic carotid disease.

Meconium-stained amniotic fluid as a protective factor against childhood dermatitis and skin rash-related hospitalization in the offspring - a population-based cohort analysis.

BACKGROUND: Gut microbiome influences cutaneous diseases including atopic dermatitis. Possible impact of intrauterine exposure to meconium on the occurrence of dermatitis and skin rash was proposed. OBJECTIVE: We investigated the possible influence of intrauterine exposure to meconium-stained amniotic fluid (MSAF) on the occurrence of dermatitis and skin rash-related hospitalizations throughout childhood. METHODS: Singleton deliveries occurring between 1991 and 2014 at a single medical centre were divided into two study groups based on presence or lack of MSAF during delivery. Population-based cohort analysis, Kaplan-Meier survival analysis and Cox proportional hazards model were used to study the association between MSAF and cutaneous morbidity-related hospitalizations. RESULTS: A lower rate of the total dermatitis or skin eruption-related hospitalization was documented in the MSAF-exposed group; 0.78 per 1000-person years (0.9%, n = 312), as compared to 0.98 per 1000-person years in the unexposed group (1.0%, n = 1992) with a hazard ratio of 0.86 (95% CI 0.76-0.96, P = 0.011). The survival curve showed lower cumulative hospitalization rate in the MSAF-exposed group as compared to the unexposed group (log rank P = 0.01). The Cox analysis, controlled for confounders, demonstrated MSAF exposure to be an independent protective factor for dermatitis and skin rash-related hospitalizations during childhood (adjusted HR 0.878 (95% CI 0.779-0.990, P = 0.034). CONCLUSION: Fetal exposure to MSAF appears to be an independent protective factor for dermatitis and skin rash-related hospitalizations in the offspring throughout childhood and adolescence.

Atopic dermatitis and the metabolic syndrome: a cross-sectional study of 116 816 patients.

BACKGROUND: Data regarding the association between atopic dermatitis (AD) and the metabolic syndrome are controversial. OBJECTIVE: To evaluate the prevalence of the metabolic syndrome and its components in a large group of patients with AD compared to a matched reference group. METHODS: A cross-sectional study of AD patients diagnosed by a dermatologist between 1998 and 2016, and a matched comparison group was performed. We analysed the association between AD and metabolic syndrome, its components and possible complications for the entire study population, adults (age > 18) and adults with moderate-to-severe AD. RESULTS: The study included 116 816 patients with AD and 116 812 comparison enrollees. AD in the entire group of patients and in the adult patients was associated with a higher prevalence of dyslipidaemia and a lower prevalence of diabetes and metabolic syndrome. Moderate and severe AD were associated, respectively, with higher prevalence rates of the metabolic syndrome (17.0% vs. 9.4%), its components (obesity: 22.2% vs. 18.6%; diabetes: 15.9% vs. 9.2%; hypertension 27.9% vs. 15.3%; dyslipidaemia 47.1% vs. 28.5%, all P values < 0.001) and cardiovascular morbidity (all P values < 0.001). Multivariate analysis demonstrated a significant overrepresentation of the metabolic syndrome in moderate-to-severe AD (P = 0.04). CONCLUSIONS: Severely affected patients with AD may have one or more undiagnosed components of metabolic syndrome.

Chronic urticaria and osteoporosis: a longitudinal, community-based cohort study of 11 944 patients.

BACKGROUND: Chronic urticaria (CU) carries many risk factors for osteoporosis, but data on the relationships between CU and osteoporosis are lacking. OBJECTIVES: To evaluate the association between CU and osteoporosis in a large community-based study. METHODS: A nationwide observational longitudinal cohort study was conducted. CU was defined as four pairs of urticaria diagnoses; each pair was recorded within a period of 6 weeks and was registered by physicians in a primary-care setting. Patients with CU and their age- and sex- matched controls were followed for the incidence of osteoporosis and other laboratory data between 2002 and 2017. Data regarding systemic steroid exposure and other relevant risk factors for osteoporosis were obtained. Analyses of risk for osteoporosis were performed in Cox regression models adjusted for age, sex, exposure to systemic corticosteroids, obesity, smoking and hyper- and hypothyroid disease. RESULTS: The study included 11 944 patients with CU and 59 829 controls. During the study's observation period, 1035 (8·7%) patients with CU were diagnosed with osteoporosis, compared with 4046 (6·8%) controls. The adjusted multivariate analysis demonstrated that CU was significantly associated with a higher risk for osteoporosis (hazard ratio 1·23, 95% confidence interval 1·10-1·37, P < 0·001). CONCLUSIONS: CU may impose a risk for osteoporosis. Appropriate targeted screening should be considered.

Chronic urticaria and the metabolic syndrome: a cross-sectional community-based study of 11 261 patients.

BACKGROUND: Emerging evidence suggests that chronic urticaria (CU) is associated with chronic, low-grade, inflammatory process. OBJECTIVE: To evaluate the association between CU and metabolic syndrome and its components in a large community-based medical database. METHODS: A cross-sectional study of CU patients and matched controls was performed. CU was defined as eight urticaria diagnoses (with each two diagnoses registered within a period of 6 weeks) from 2002 to 2012. Data regarding the prevalence of metabolic syndrome, its components and possible complications were collected. RESULTS: The study included 11 261 patients with CU and 67 216 controls. In a univariate analysis, CU was significantly associated with higher body mass index (BMI) and a higher prevalence of obesity, diabetes, hyperlipidaemia, hypertension, metabolic syndrome, chronic renal failure and gout. Multivariate analysis demonstrated a significant association between CU and metabolic syndrome (OR = 1.12, 95% CI 1.1-1.2, P < 0.001) and its components - obesity (OR = 1.2, 95% CI 1.1-1.3, P < 0.001), diabetes (OR = 1.08, 95% CI 1.01-1.15, P = 0.001), hyperlipidaemia (OR = 1.2, 95% CI 1.1-1.2, P < 0.001) and hypertension (OR = 1.1, 95% CI 1.1-1.2, P < 0.001). CONCLUSIONS: CU patients may have one or more undiagnosed components of metabolic syndrome despite their young age. Thus, appropriate targeted screening is advised.

Changes in headache frequency in premenopausal obese women with migraine after bariatric surgery: a case series.

BACKGROUND: The association between migraine and obesity gives the clinician with an exciting possibility to alleviate migraine suffering through weight-reduction gastric-restrictive operations. We hypothesized that bariatric weight-reduction intervention (gastric banding) will be associated with reduction of migraine burden in this population. METHODS: A total of 105 women between 18 and 50 years of age, admitted for bariatric surgery between April 2006 and February 2007, were screened for migraine. Twenty-nine with diagnosis of migraine were enrolled into the prospective phase. We followed the migraine pattern of these patients for 6 months post bariatric surgery. RESULTS: Baseline median migraine frequency was six headache days a month. Post bariatric surgery, the migraine-suffering women reported of a lower frequency of migraine attacks (p < 0.001), shorter duration of the attacks (p = 0.02), lower medication use during the attack (p = 0.005), less non-migraine pain (44.8 vs. 33%, p = 0.05), and post-bariatric surgery reduction in headache-related disability assessed by the MIDAS and HIT-6 scores. There was a reduction in migraine frequency among both episodic (from four to one episodes a month) and chronic (from 16.8 to 8.5 episodes per month) migraine patient cohorts separately and combined. CONCLUSIONS: Among migraine-suffering premenopausal obese women, we found a reduced frequency of migraine attacks and improvement of headache-related disability post bariatric surgery. Our findings should be interpreted cautiously. The absence of a control group and the non-blinded nature of our small study make it difficult to draw firm conclusions about the causal nature of the headache changes observed in this population. Further study is needed to evaluate the possible specific effects of surgical weight loss on migraine in obese women.