Intravenous thrombolysis in stroke patients under 55 years of age: is there a different effect according to etiology and severity?

The effect of intravenous thrombolysis (IVT) according to etiology and stroke severity in young patients with ischemic stroke (IS) has not been described previously. To analyze the effect of IVT in young patients with IS according to etiological subtype and stroke severity. Observational study with inclusion of IS patients under 55 years of age (2007–2012). Two groups were compared according to IVT treatment. Favorable outcomes were defined as 3 months modified Rankin Scale ≤2. Multivariate analyses were performed to determine those factors independently associated with favorable outcomes, and subgroup analyses were conducted to assess the effect of IVT according to etiological stroke subtype and severity on admission, adjusted for other prognostic variables. We evaluated 262 patients. 63 (24 %) received IVT. The mean age and the sex distribution were similar in the IVT treated and the non-treated groups. Multivariate analyses showed that IVT was associated with a higher probability of favorable outcome (OR, 95 % CI: 4.652, 1.294–16.722) whereas artery dissection (OR, 95 % CI: 0.191, 0.056–0.654) and NIHSS (OR, 95 % CI: 0.727, 0.664–0.797) were associated with a lower probability of a favorable outcome. The subgroup analysis showed that the beneficial effect of IVT on outcomes was significant in moderate-severe strokes (NIHSS ≥8) (OR, 95 % CI: 3.782, 1.095–13.069) and in cardioembolism (OR, 95 % CI: 41.887, 1.001–1751.596). In IS patients under 55 years of age, those with moderate-severe strokes benefit more from IVT than those with mild strokes. Cardioembolic infarctions may benefit more from IV tPA than other etiologies.     

Atrial fibrillation and stroke: clinical presentation of cardioembolic versus atherothrombotic infarction

The aim of the study was to compare demographic characteristics, anamnestic findings, cerebrovascular risk factors, and clinical and neuroimaging data of cardioembolic stroke patients with and without atrial fibrillation and of atherothrombotic stroke patients with and without atrial fibrillation. Predictors of early diagnosis of cardioembolic vs. atherothrombotic stroke infarction in atrial fibrillation patients were also determined. Data of cardioembolic stroke patients with (n=266) and without (n=81) atrial fibrillation and of atherothrombotic stroke patients with (n=75) and without (n=377) were obtained from 2000 consecutive patients included in the prospective Sagrat Cor-Alianza Hospital of Barcelona Stroke Registry. Risk factors, clinical characteristics and neuroimaging features in these subgroups were compared. The independent predictive value of each variable on early diagnosis of stroke subtype was assessed with a logistic regression analysis. In-hospital mortality in patients with atrial fibrillation was significantly higher than in non-atrial fibrillation patients both in cardioembolic (32.6% vs. 14.8%, P<0. 005) and atherothrombotic stroke (29.3% vs. 18.8%, P<0.04). Valvular heart disease (odds ratio (OR) 4.6; 95% confidence interval (95% CI) 1.19-17.68) and sudden onset (OR 1.8; 95% CI 0.97-3.63) were predictors of cardioembolic stroke, and subacute onset (OR 8; 95% CI 1.29-49.42), COPD (OR 5.2; 95% CI 1.91-14.21), hypertension (OR 3. 63; 95% CI 1.92-6.85), hypercholesterolemia (OR 2.67; 95% CI 1.13-6. 28), transient ischaemic attack (OR 2.49; 95% CI 1.05-5.90), ischaemic heart disease (OR 2.30; 95% CI 1.15-4.60) and diabetes (OR 2.26; 95% CI 1.14-4.47) of atherothrombotic stroke. In conclusion, some clinical features at stroke onset may help clinicians to differentiate cerebral infarction subtypes in patients with atrial fibrillation. Atrial fibrillation is associated with a higher in-hospital mortality both in cardioembolic and atherothrombotic stroke patients.     

Evaluation of the <Emphasis Type="Italic">F2R</Emphasis> IVS-14A/T PAR1 polymorphism with subsequent cardiovascular events and bleeding in patients who have undergone percutaneous coronary intervention

Abnormal platelet reactivity is associated with recurrent ischemia and bleeding following percutaneous coronary intervention (PCI). Protease-activated receptor-1 (PAR1), encoded by F2R, is a high affinity thrombin receptor on platelets and the target of the antiplatelet drug vorapaxar. The intronic single nucleotide polymorphism F2R IVS-14 A/T affects PAR1 receptor density and function. We hypothesized that carriers of the T allele, who have been shown to have decreased platelet reactivity, would be at lower risk for thrombotic events, but higher risk for bleeding following PCI. Using BioVU, the Vanderbilt DNA repository linked to the electronic medical record, we studied 660 patients who underwent PCI for unstable or stable coronary artery disease. Primary outcome measures were major adverse cardiovascular events (MACE, composite of revascularization, MI, stroke, death) and bleeding (assessed by Bleeding Academic Research Consortium scale) over 24 months. The minor allele (T) frequency was 14.8 %. There were no genotypic differences in the frequency of MACE (33.7, 28.8, and 31.6 % for A/A, A/T, and T/T respectively, P = 0.50) or bleeding (15.7, 14.7, and 18.8 % for A/A, A/T, and T/T respectively, P = 0.90). In a Cox regression model, fully adjusted for age, race, sex, BMI, and smoking status, carrying a T allele was not associated with MACE (HR 1.19, 95 % CI 0.89–1.59, P = 0.23) or bleeding (HR 0.73, 95 % CI 0.37–1.4, P = 0.34). In conclusion, in our population, F2R IVS-14 PAR1 variability does not affect risk of MACE or bleeding following PCI.     

Incidence and characteristics of spontaneous platelet macro-aggregation in acute ischemic stroke

Spontaneous platelet aggregation is a trigger for additional development of larger thrombi. Micro-aggregation is observed in 10% of diabetes approximately and blocked by P2Y12 inhibitors, whereas macro-aggregation is associated with overexpression of platelet α₂-adrenoreceptors and is not blocked by conventional anti-platelet medicines. We examined the incidence of spontaneous platelet macro-aggregation (SPMA) in acute ischemic stroke and analyzed its clinical characteristics. Out of 665 consecutive acute ischemic strokes, SPMA was found in 10 patients (1.5%, one tenth of micro-aggregation) despite no detection in 588 control subjects. Types of ischemic stroke were 4 atherothrombotic, 4 cardioembolic, and 2 lacunar strokes. Stroke with SPMA exhibited higher (worse) values of modified Rankin Scales (mRS) at discharge (3.00?±?0.53 vs 1.93?±?0.07, p?=?0.042 by Wilcoxon) compared with stroke without SPMA despite no difference at admission. The proportion of patients who were functionally independent (score 0–2 on the mRS) at discharge was lower in stroke with SPMA compared with stroke without SPMA (p?<?0.05 by chi-square test; OR 3.60, 95% CI 1.08–12.03; RR 2.04, 95% CI 1.05–2.86). It was intriguing that severe (high magnitude) SPMA was observed in 4 atherothrombotic stroke. Although anti-platelet therapy underwent, the proportion of atherothrombotic patients who were functionally improved and independent at discharge was lower in the presence of SPMA compared with the absence of SPMA (p?<?0.05 by chi-square test). The patients with SPMA were more likely to be older, having major disabilities, being less functionally improved during hospitalization, and being less functionally independent at discharge.

     

<Emphasis Type="Italic">PON1</Emphasis> Q192R genetic variant and response to clopidogrel and prasugrel: pharmacokinetics,pharmacodynamics, and a meta-analysis of clinical outcomes

Clopidogrel and prasugrel are antiplatelet therapies commonly used to treat patients with cardiovascular disease. They are both pro-drugs requiring biotransformation into active metabolites. It has been proposed that a genetic variant Q192R (rs662 A>G) in PON1 significantly alters the biotransformation of clopidogrel and affects clinical outcomes; however, this assertion has limited support. The relationship between this variant and clinical outcomes with prasugrel has not been studied. We genotyped PON1 Q192R in 275 healthy subjects treated with clopidogrel or prasugrel and 2922 patients with an ACS undergoing PCI randomized to treatment with clopidogrel or prasugrel in the TRITON-TIMI 38 trial. A meta-analysis was performed including 13 studies and 16,760 clopidogrel-treated patients. Among clopidogrel-treated subjects, there were no associations between Q192R and active drug metabolite levels (P = 0.62) or change in platelet aggregation (P = 0.51). Consistent with these results, in clopidogrel-treated patients in TRITON-TIMI 38, there was no association between Q192R and the rates of CV death, myocardial infarction, or stroke (RR 11.2 %, QR 8.6 %, and QQ 9.3 %; P = 0.66) or stent thrombosis (RR 2.4 %, QR 0.7 %, and QQ 1.6 %, P = 0.30), with patients with the putative at-risk Q variant having numerically lower event rates. Likewise, among prasugrel-treated subjects, there were no associations between Q192R and active drug metabolite levels (P = 0.88), change in platelet aggregation (P = 0.97), or clinical outcomes (P = 0.72). In a meta-analysis, the Q variant was not significantly associated with MACE (QQ vs. RR 1.22, 95 % CI 0.84–1.76) or stent thrombosis (QQ vs. RR OR 1.36, 95 % CI 0.77–2.38). Furthermore, when restricted to the validation studies, the OR (95 % CI) for MACE and stent thrombosis were 0.99 (0.77–1.27) and 1.23 (0.74–2.03), respectively. In the present study, the Q192R genetic variant in PON1 was not associated with the pharmacologic or clinical response to clopidogrel, nor was it associated with the response to prasugrel. The meta-analysis reinforced a lack of a significant association between Q192R and cardiovascular outcomes in clopidogrel-treated patients.     

Incidence and predictors of ischemic stroke during hospitalization for congestive heart failure

Heart failure (HF) increases the risk of ischemic stroke. Data regarding the incidence and predictors of ischemic stroke during hospitalization for HF are limited. The study population of this retrospective cohort study consisted of patients with congestive HF, consecutively admitted to our center from October 2010 to April 2014. We excluded patients complicated with acute myocardial infarction, infective endocarditis, and takotsubo cardiomyopathy. We also excluded those with dialysis or mechanical circulatory support. We investigated the incidence of ischemic stroke during hospitalization for HF. Thereafter, we divided the patients without oral anticoagulants at admission into two groups: patients with ischemic stroke and those without it, and explored the predictors of ischemic stroke. A total of 558 patients (287 without atrial fibrillation (AF), 271 with AF) were enrolled. The mean age was 76.8 ± 12.3 years, and 244 patients (44 %) were female. The mean left-ventricular ejection fraction was 47.4 %. Oral anticoagulants were prescribed in 147 patients (8 without AF, 139 with AF). During hospitalization (median length 18 days), symptomatic ischemic stroke (excluding catheter-related) occurred in 15 patients (2.7 % of the total, 8 without AF, 7 with AF). Predictors significantly associated with increased risk of ischemic stroke in patients without oral anticoagulants were as follows; short-term increases in blood urea nitrogen after admission (at day 3; odds ratio (per 1 md/dl): 1.06, 95 % confidence interval (CI) 1.01–1.11, p = 0.02, and at day 7; odds ratio: 1.03, 95 % CI 1.00–1.07, p = 0.03, respectively), and previous stroke (odds ratio; 3.33, 95 % CI 1.01–11.00, p = 0.04). The incidence of ischemic stroke during hospitalization for HF was high, even in patients without AF. Previous stroke and short-term increases in blood urea nitrogen was significantly associated with the incidence of ischemic stroke.     

Interleukin 12B gene polymorphisms and susceptibility to rheumatoid arthritis: a data synthesis

The aim of this study was to investigate the association of two common interleukin 12B (IL-12B) polymorphisms (rs3212227 and rs6887695) with rheumatoid arthritis (RA) susceptibility through meta-analyses. A systematic literature search of PubMed, Web of Science, Cochrane Library, and Embase databases was conducted on articles published before 28 February 2016. Then odds ratio (OR) with 95 % confidence interval (CI) was used to quantify the strength of association for homozygote, heterozygote, dominant, and recessive genetic models. Nine articles with a total of 17 case–control studies (12 for IL-12B rs3212227 polymorphism and 5 for IL-12B rs6887695 polymorphism) met our inclusion criteria. The pooled results demonstrated that IL-12B rs3212227 (homozygote model: OR?=?0.96, 95 % CI?=?0.81–1.15; heterozygote model: OR?=?1.07, 95 % CI?=?0.93–1.23; dominant model: OR?=?1.05, 95 % CI?=?0.91–1.20; recessive model: OR?=?0.93, 95 % CI?=?0.79–1.10) and rs6887695 (homozygote model: OR?=?1.01, 95 % CI?=?0.84-1.21; heterozygote model: OR?=?1.14, 95 % CI?=?0.86–1.51; dominant model: OR?=?1.14, 95 % CI?=?0.87–1.48; recessive model: OR?=?1.01, 95 % CI?=?0.85–1.21) polymorphisms may not be associated with RA risk. Our meta-analyses demonstrated that IL-12B rs3212227 and rs6887695 polymorphisms do not confer susceptibility to RA.     

Epidemiology of acute kidney injury in patients with stroke: a retrospective analysis from the neurology ICU

Acute kidney injury (AKI) is proven to be an independent risk factor for adverse clinical outcomes in patients with stroke, but data about the epidemiology of AKI in these patients are not well characterized. Therefore, we investigated the incidence, risk factors, and the impact of AKI on the clinical outcomes in a group of Chinese patients with stroke. We retrospectively recruited 647 stroke patients from the neurology ICU between 2012 and 2013. AKI was identified according to the 2012 KDIGO criteria. Baseline estimated glomerular filtration rate (eGFR) was calculated using modified Chronic Kidney Disease Epidemiology Collaboration equation for Chinese patients. National Institutes of Health Stroke Scale (NIHSS) score was assessed for the stroke severity. A total of 135 (20.9%) patients developed AKI. Patients with AKI stages from 1 to 3 were 84 (62.2%), 26 (19.3%), and 25 (18.5%), respectively. Logistic regression analysis showed that independent risk factors for AKI were higher NIHSS score (OR, 1.027; 95% CI 1.003–1.051), lower baseline eGFR (OR, 0.985; 95% CI 0.977–0.993), the presence of hypertension (OR, 1.592; 95% CI 1.003–2.529), and infectious complications (OR, 3.387; 95% CI 1.997–5.803) (P < 0.05 for all). AKI patients were also significantly associated with all-cause mortality in the neurology ICU [OR and 95% CI of AKI-stage 1, AKI-stage 2, and AKI-stage 3 were 4.961 (2.191–11.232), 19.722 (6.354–61.217), and 48.625 (17.616–134.222), respectively (P < 0.001 for all)]. AKI is common among patients with stroke and is associated with worse clinical outcomes after stroke. Prevention of AKI seems to be very important among these patients, because they are exposed to many risk factors for developing AKI.     

Comparison of new adenosine diphosphate receptor antagonists with clopidogrel in patients with coronary artery disease: a meta-analysis

Recent data suggest the superiority of new adenosine diphosphate (ADP) receptor antagonists compared with clopidogrel in acute coronary syndrome patients. We aimed to assess the risks and benefits of new ADP receptor antagonists in patients with coronary artery disease (CAD). Relevant studies published through February 28, 2014 were searched and identified in the MEDLINE, EMBASE, and Cochrane databases. Summary estimates were obtained using a random-effects model. All nine published randomized controlled studies comparing new ADP receptor antagonists with clopidogrel in CAD were included. The database consisted of 66,900 patients; 33,782 on novel agents, and 33,118 on clopidogrel. New ADP receptor antagonists reduced the composite incidence of all-cause mortality, myocardial infarction or stroke (odds ratio [OR] 0.89, 95 % confidence interval [CI] 0.81–0.97, p = 0.01) but increased the incidence of non-coronary artery bypass grafting-related major bleeding (OR 1.24, 95 % CI 1.08–1.42, p = 0.003). The composite end point of the net rate of adverse clinical events, which was the combination of the primary efficacy end point and the primary safety end point, was significantly lower in the new agent group compared to the clopidogrel group (9.7 versus 10.6 %, OR 0.92, 95 % CI 0.85–1.00). Use of recently introduced new ADP receptor antagonists results in a reduction in adverse clinical outcomes but a substantial increase in bleeding. New agents revealed an improved combined efficacy and safety outcome compared to that of clopidogrel in patients with CAD.     

Prognostic Impact of Node-Spreading Pattern in Surgically Treated Small-Cell Lung Cancer: A Multicentric Analysis

Objective

Although surgery in selected small-cell lung cancer (SCLC) patients has been proposed as a part of multimodality therapy, so far, the prognostic impact of node-spreading pattern has not been fully elucidated. To investigate this issue, a retrospective analysis was performed.

Methods

From 01/1996 to 12/2012, clinico-pathological, surgical, and oncological features were retrospectively reviewed in a multicentric cohort of 154 surgically treated SCLC patients. A multivariate Cox proportional hazard model was developed using stepwise regression, in order to identify independent outcome predictors. Overall (OS), cancer-specific (CSS), and Relapse-free survival (RFS) were calculated by Kaplan-Meier method.

Results

Overall, median OS, CSS, and RFS were 29 (95 % CI 18–39), 48 (95 % CI 19–78), and 22 (95 % CI 17–27) months, respectively. Lymphadenectomy was performed in 140 (90.9 %) patients (median number of harvested nodes: 11.5). Sixty-seven (47.9 %) pN0-cases experienced the best long-term survival (CSS: 71, RFS: 62 months; p < 0.0001). Among node-positive patients, no prognostic differences were found between pN1 and pN2 involvement (CSS: 22 vs. 15, and RFS: 14 vs. 10 months, respectively; p = 0.99). By splitting node-positive SCLC according to concurrent N1-invasion, N0N2-patients showed a worse CSS compared to those cases with combined N1N2-involvement (N0N2: 8 months vs. N1N2: 22 months; p = 0.04). On the other hand, the number of metastatic stations (p = 0.80) and the specific node-level (p = 0.85) did not affect CSS. At multivariate analysis, pN+ (HR: 3.05, 95 % CI 1.21–7.67, p = 0.02) and ratio between metastatic and resected lymph-nodes (RL, HR: 1.02, 95 % CI 1.00–1.04, p = 0.03) were independent predictors of CSS. Moreover, node-positive patients (HR: 3.60, 95 % CI 1.95–6.63, p < 0.0001) with tumor size ≥5 cm (HR: 1.85, 95 % CI 0.88–3.88, p = 0.10) experienced a worse RFS.

Conclusions

In selected surgically treated SCLC, the long-term survival may be stratified according to the node-spreading pattern.

     

Correlates of Combination Antiretroviral Adherence Among Recently Diagnosed Older HIV-Infected Adults Between 50 and 64 years

Optimal adherence to combination antiretroviral therapy is essential to the health of older people living with HIV (PLWH), however, the literature on adherence and aging is limited. Using Medicaid data from 29 states (N = 5177), we explored correlates of optimal adherence among older PLWH. The prevalence of optimal adherence was low (32 %) in this study. Males were more adherent than females (APR = 1.11, 95 % CI 1.02–1.21, P = 0.0127); persons with three or more co-morbidities (APR = 0.67, 95 % CI 0.60–0.74, P < 0.001), two co-morbidities (APR = 0.86, 95 % CI 0.75–0.98, P = 0.0319) and one co-morbidity (APR = 0.82, 95 % CI 0.73–0.92, P = 0.0008) were less adherent than those without any co-morbidity; and residents of rural areas (APR = 0.90, 95 % CI 0.63–0.98, P = 0.0385) and small metropolitan areas (APR = 0.82, 95 % CI 0.72–0.94, P = 0.0032) were less adherent than residents of large metropolitan areas. There were no racial differences in optimal adherence. Targeted interventions that provide adherence support, case management, and peer navigation services may be of benefit in achieving optimal adherence in this population.     

Effect of anticoagulation on cardioembolic stroke severity,outcomes and response to intravenous thrombolysis

Our objective was to evaluate the effect of anticoagulation on cardioembolic stroke (CS) severity, outcomes, and response to intravenous thrombolysis (IVT). Observational study of CS patients admitted to a Stroke Center (2010–2013). The sample was classified into three groups based on pre-stroke oral anticoagulants (OAC) treatment (all acenocumarol) and the international normalized ratio (INR) on admission: (1) non-anticoagulated or anticoagulated patients with INR <1.5, (2) anticoagulated with INR 1.5–1.9 and (3) anticoagulated with INR ≥2. We compared demographic data, vascular risk factors, symptomatic intracranial hemorrhage, severity on admission (NIHSS) and 3 month outcomes (mRS). Overall 475 patients were included, 47.2 % male, mean age 75.5 (SD 10.7) years old, 31.8 % were on OAC. 76 % belonged to the INR <1.5 group, 13.3 % to the INR 1.5–1.9 and 10.5 % to the INR >2. 35 %of patients received IVT. Multivariate analyses showed that an INR ≥2 on admission was a factor associated with a higher probability of mild stroke (NIHSS <10) (OR 2.026, 95 % CI 1.006–4.082). Previous OAC in general (OR 2.109, 95 % CI 1.173–3.789) as well as INR 1.5–1.9 (OR 3.676, 95 % CI 1.510–8.946) were associated with favorable outcomes (mRS ≤2). OAC was not related to stroke outcomes in the subgroup of IVT patients. Therapeutic OAC levels are associated with lesser CS severity, and prior OAC treatment with favorable outcomes. In this study, OAC are not related with response to IVT.     

Volume elastic modulus of the brachial artery and coronary artery stenosis in patients with suspected stable coronary artery disease

This study aimed to examine the association between the non-invasive measurement of the brachial artery volume elastic modulus (V _E), an index of arterial stiffness, and the presence of coronary artery stenosis in patients with suspected stable coronary artery disease (CAD). A total of 135 patients with suspected stable CAD (87 men, mean age, 64 ± 12 years) underwent oscillometric measurement of the brachial artery to obtain V _E. Coronary angiography was thereafter carried out to diagnose CAD, defined as having ≥75 % stenosis in the epicardial coronary arteries. V _E was significantly higher in patients with CAD (1.94 ± 0.34 mmHg/%) than in those without CAD (1.71 ± 0.35 mmHg/%, P < 0.001). In multiple logistic regression analysis, V _E was an independent predictor for the presence of CAD (odds ratio 1.19 per 0.1 mmHg/% increase, 95 % CI 1.04–1.51) even after adjusting for multiple potential confounders including the Framingham risk score (FRS). The area under the curve of the receiver operating characteristic curve analysis for discriminating CAD increased significantly after the addition of V _E to the FRS (from 0.75 to 0.81, P = 0.034). The category-free net reclassification improvement and the integrated discrimination improvement by adding V _E to the FRS were 0.476 (95 % CI 0.146–0.806) and 0.086 (95 % CI 0.041–0.132), respectively. In conclusion, the brachial V _E was significantly associated with the presence of coronary artery stenosis. The additional measurement of V _E to the FRS improved the ability to identify patients with coronary artery stenosis among those with suspected stable CAD.     

Association Study Between Coronary Artery Disease and rs1333049 Polymorphism at 9p21.3 Locus in Italian Population

In this study, we verify the association between the rs1333049 single nucleotide polymorphism (9p21.3) within CDKN2A-CDKN2B and coronary artery disease (CAD) in an Italian population. We replicated rs1333049_G allele association with a significantly reduced risk of CAD (OR = 0.816; 95% confidence interval [0.705–0.945]; p = 0.0065) in 711 CAD patients and 755 normal healthy individuals. This effect is maintained even stratifying patients by gender and by risk factors. A significant association was found with age of CAD onset. Interestingly, we found a protective trend of association between the rs1333049_G allele and peripheral artery disease, a progressive atherosclerotic condition in which plaque builds up in the arteries that carry blood to the head, organs, and limbs (OR = 0.724; 95% CI [0.520–1.007]; p = 0.054). No genotype-phenotype association was found with more severe CAD clinical parameters. If certain genetic factors predispose individuals to adverse outcomes, the knowledge of a patient’s genotype may influence clinical management.     

Paced QRS duration and myocardial scar amount: predictors of long-term outcome of right ventricular apical pacing

Long-term right ventricular apical pacing (RVAP) is reportedly associated with heart failure (HF) development. However, the predictors of pacing-induced HF (PHF) remained unclear. We retrospectively enrolled 234 patients without structural heart disease who underwent a permanent pacemaker implantation with RVAP between 1982 and 2004. RVAP-induced HF was defined as left ventricular ejection fraction decrease >5 % with HF symptom without other HF development etiology. The QRS duration of a paced beat (pQRSd) and myocardial scar score were analyzed from each patient’s 12-lead ECG. During a mean 15.6 years (range 3.3–30.0 years), 48 patients (20.5 %) patients developed RVAP-induced HF. The PHF group patients had a longer pQRSd (192.4 ± 13.5 vs. 175.7 ± 14.7 ms in non-PHF patients, p < 0.001) and a higher myocardial scar score (5.2 ± 1.9 vs. 2.7 ± 1.9, respectively p < 0.001). In multivariate Cox regression analysis, old age at implantation [Hazard ratio (HR) 1.62, 95 % confidential interval (CI) 1.22–2.16, p = 0.001], a longer pQRSd (HR 1.54, 95 % CI 1.15–2.05, p = 0.003), a higher myocardial scar score (HR 1.23, 95 % CI 1.03–1.49, p = 0.037), and a higher percentage of ventricular pacing (HR 1.31, 95 % CI 1.01–1.49, p = 0.010) were independent predictors of PHF. Based on the results of the receiver-operating characteristic (ROC) curve, the pQRSd cutoff was 185 ms (AUC 0.79, sensitivity 66.7 %, specificity 76.3 %) and myocardial scar score cutoff value was 4 (AUC 0.81, sensitivity 81.3 %, specificity 66.1 %). The pQRSd was positively correlated with scar score (r = 0.70, p < 0.001). pQRSd ≥185 ms and/or myocardial scar score ≥4 might be independent long-term prognostic markers of PHF.     

Effect of CPAP therapy on cardiovascular events and mortality in patients with obstructive sleep apnea: a meta-analysis

Purpose

Continuous positive airway pressure (CPAP) therapy may decrease the risk of mortality and cardiovascular events in patients with obstructive sleep apnea. However, these benefits are not completely clear.

Methods

We undertook a meta-analysis of randomized clinical trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database.

Results

Eighteen studies (4146 patients) were included. Overall, CPAP therapy did not significantly decrease the risk of cardiovascular events compared with the control group (odds ratio (OR), 0.84; 95 % confidence intervals (CI), 0.62–1.13; p = 0.25; I ² = 0 %). CPAP was associated with a nonsignificant trend of lower rate of death and stroke (for death: OR, 0.85; 95 % CI, 0.35–2.06; p = 0.72; I ² = 0.0 %; for stroke: OR, 0.56; 95 % CI, 0.18–1.73; p = 0.32; I ² = 12.0 %), a significantly lower Epworth sleepiness score (ESS) (mean difference (MD), ?1.78; 95 % CI, ?2.31 to ?1.24; p < 0.00001; I ² = 76 %), and a significantly lower 24 h systolic and diastolic blood pressure (BP) (for 24 h systolic BP: MD, ?2.03 mmHg; 95 % CI, ?3.64 to ?0.42; p = 0.01; I ² = 0 %; for diastolic BP: MD, ?1.79 mmHg; 95 % CI, ?2.89 to ?0.68; p = 0.001; I ² = 0 %). Daytime systolic BP and body mass index were comparable between the CPAP and control groups. Subgroup analysis did not show any significant difference between short- and mediate-to-long-term follow-up groups with regard to cardiovascular events, death, and stroke.

Conclusions

CPAP therapy was associated with a trend of decreased risk of cardiovascular events. Furthermore, ESS and BP were significantly lower in the CPAP group. Larger randomized studies are needed to confirm these findings.

     

Independent risk factors for mortality in critically ill patients with candidemia on Italian Internal Medicine Wards

Candida is an increasing cause of bloodstream infection and is associated with significant morbidity and mortality. The aim of our study is to analyze risk factors for short-term mortality in patients with bloodstream Candida spp. infections admitted to Internal Medicine Wards (IMWs). This was a retrospective case–control study between January 2012 and December 2014 from four University Hospitals in Italy, where patients with candidemia dying within 30 days from diagnosis were matched to control cases with candidemia who survived in the same period of time. Two-hundred and fifty cases of candidemia were registered during the 36 months of enrollment. Among these, 112 patients died (45%) within 30 days from the first blood culture’s positivity for Candida spp. At multivariate analysis, septic shock [odds ratio (95% CI) = 2.919 (1.62–5.35), p < 0.001] and concomitant chronic kidney failure [odds ratio (95% CI) = 2.296 (1.07–5.12), p = 0.036] were independent predictors of mortality. Low-dose chronic steroid therapy was protective [odds ratio (95% CI) = 0.461 (0.25–0.83), p = 0.011).     

Association of serum uric acid and risk of hypertension in adults: a prospective study of Kailuan Corporation cohort

Whether hyperuricemia is an independent risk factor for hypertension in adults is still under debate. To determine the association between serum uric acid and risk of hypertension in the Chinese population, we conducted a prospective study using the “Kailuan Corporation cohort.” A total of 39,233 adult subjects with available data on serum uric acid were enrolled from 2006 to 2007. Subjects with established hypertension were excluded and were then grouped based on the gender and baseline quartile serum uric acid into F1–4 for women and M1–4 for men with F1 and M1 being the lowest quartiles. Incidence of newly described primary hypertension was reevaluated in 2010–2011. The median (interquantile range) baseline uric acid (UA) was 290 (243–344) μmol/L in men and 230 (194–274) μmol/L in women. During a 4-year follow-up period, 12,844 subjects (31.31 %) were newly diagnosed with hypertension. The incidence of hypertension was 14.36, 16.57, 19.06, and 22.35 % in F1 to F4 and 33.64, 33.97, 36.54, and 40.74 % in M1 to M4, respectively. Multiple logistic regression analysis showed that the odds ratios (ORs) of incident hypertension were 1.17 [95 % confidence interval (CI) 1.00–1.37, P = 0.055], 1.24 (95 % CI 1.06–1.45, P = 0.009), and 1.20 (95 % CI 1.02–1.41, P = 0.027) in F2 to F4 compared to the F1 and 0.98 (95 % CI 0.91–1.05, P = 0.534), 1.05 (95 % CI 0.98–1.13, P = 0.190), and 1.13 (95 % CI 1.05–1.22, P = 0.002) in M2 to M4 compared to the M1. Elevated level of serum uric acid is associated with an increased risk of hypertension in adults.     

Anti-IL-17 therapy in treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials

IL-17 has a role in inflammation in RA, and its levels in joints correlate with disease severity. Multiple RCTs have been performed to study effects of anti-IL-17 agents. The objective of this study was to perform a systematic review and meta-analysis to analyze the efficacy and safety of anti-IL-17 agents in the management of RA. This work is based on a systematic review of studies retrieved by a sensitive search strategy in PubMed, EMBASE and Cochrane CENTRAL from inception through 9/7/15. Study selection criteria were the following: adult patients (age ≥ 18 years) with RAs, random selection of patients for anti-IL-17 therapy and treatment response compared to placebo. We performed systematic literature review per PRISMA guideline and two investigators independently selected seven randomized clinical trials (RCTs) for meta-analysis. We used random effect model calculating odds ratio (OR) and 95 % confidence interval (CI) to measure the efficacy with ACR20/50/70 responses and the safety with adverse events. Seven studies with total of 1226 patients including 905 in anti-IL-17 group and 321 in placebo were included in the meta-analysis. Anti-IL-17 was effective in achieving ACR20 and ACR50 compared to placebo (OR 2.47, 95 % CI 1.29–4.72, P = 0.006, I ² 77 % and OR 2.94, 95 % CI 1.37–6.28, P = 0.005, I ² 64 %, respectively). Data analysis for ACR70 showed a favorable trend toward anti-IL-17 (OR 2.62, 95 % CI 1–6.89, P = 0.05, I ² 15 %). Subgroup analysis of ACR20 for individual anti-IL-17 agents showed that ixekizumab was more effective than placebo, while secukinumab showed a trend toward achieving the ACR20 response. However, brodalumab was not effective compared to placebo. Safety analysis did not show increased risk of any or serious adverse effects by anti-IL-17 compared to placebo (OR 1.23, 95 % CI 0.94–1.61, P = 0.13, I ² = 0 % and OR 1.28, 95 % CI 0.57–2.88, P = 0.55, I ² = 0 %, respectively). This meta-analysis concludes that anti-IL-17 is effective in the treatment of RA without increased risk of any or serious adverse effects; however, the results are limited by significant heterogeneity and small duration of studies.