Compositional and functional alterations of gut microbiota in patients with stroke

Background and aimsThere is accumulating evidence that gut microbiota plays a key role in cardiovascular diseases. Gut bacteria can transform dietary choline, l-carnitine, and trimethylamine N-oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver. However, the alterations of the gut microbiota in large artery atherosclerotic (LAA) stroke and cardioembolic (CE) stroke have been less studied.Methods and resultsWe performed a case–control study in patients with LAA and CE types of strokes. We profiled the gut microbiome using Illumina sequencing of the 16S ribosomal RNA gene (V4–V5 regions), and TMAO was determined via liquid chromatography–tandem mass spectrometry. Our results showed that the TMAO levels in the plasma of patients with LAA and CE strokes were significantly higher than those in controls (LAA stroke, 2931 ± 456.4 ng/mL; CE stroke, 4220 ± 577.6 ng/mL; healthy control, 1663 ± 117.8 ng/mL; adjusted p < 0.05). The TMAO level in the plasma of patients with LAA stroke was positively correlated with the carotid plaque area (rho = 0.333, 95% CI = 0.08–0.55, p = 0.0093). Notably, the composition and the function of gut microbiota in the LAA stroke group were significantly different from those in the control group (FDR-adjusted p-value < 0.05). There was no significant association between gut microbiota and CE stroke in our study.ConclusionThis study provides evidence for significant compositional and functional alterations of the gut microbiome in patients with LAA stroke. Gut microbiota might serve as a potential biomarker for patients with LAA stroke.     

Severity and outcomes according to stroke etiology in patients under 50 years of age with ischemic stroke

To analyze the association of stroke etiological subtypes with severity and outcomes at 3 and 12 months in patients ≤50 years. Observational study of patients admitted to a stroke unit (2007–2013). Variables: demographic data, vascular risk factors, comorbidities, severity on admission (NIHSS), and good functional outcome (mRS ≤ 1) at 3 and 12 months. We used multivariate analyses to evaluate the influence of stroke etiology on severity and outcomes. We included 214 patients, 58.3 % men, mean age 41.4 years. General linear models showed all etiologies were more severe than lacunar strokes (P < 0.05). Atherothrombotic strokes showed greater severity than those of undetermined and uncommon etiology, whereas cardioembolic strokes were more severe than cryptogenic. Taking into account specific etiologies, atherothrombotic strokes (B = 5.860; 95 % CI 2.979–8.751), cervical artery dissection (CAD) [B = 7.485; 95 % confidence interval (CI) 4.734–10.237], and atrial fibrillation (AF) strokes (B = 5.773; 95 % CI 2.704–8.132) were more severe than other etiologies. Logistic regression models showed that strokes of uncommon etiology, especially those not related to CAD, had a lower probability of good outcome at 3 months [odds ratio (OR) = 0.197; CI 95 % 0.044–0.873], whereas atherothrombotic strokes were associated with this probability at 12 months (OR = 0.187; 95 % CI 0.037–0.951; P = 0.007). In patients ≤50 years of age, strokes of atherothrombotic, cardioembolic (particularly those due to AF), and uncommon etiology had a greater severity than the rest. Furthermore, strokes of uncommon etiology, especially those different from CAD, decreased the probability of a good outcome at 3 months, as did atherothrombotic strokes at 1 year.     

Device-Related Thrombosis After Percutaneous Left Atrial Appendage Occlusion for Atrial Fibrillation

Background

Transcatheter left atrial appendage (LAA) occlusion is an alternative strategy for stroke prevention in patients with atrial fibrillation (AF).

Reappraisal of heart rate variability in acute ischemic stroke

Cardiac autonomic dysfunction is a common complication after acute ischemic stroke (IS). Prior investigators have emphasized that infarction of brain stem or hemispheres with insular involvement is related to this dysfunction and may predict poor clinical outcome. From the viewpoint of stroke physicians, however, all stroke patients, particularly large-artery atherosclerosis (LAA) should be monitored for possible cardiac complications after acute IS. This study aimed to investigate cardiac autonomic impaction in patients with acute IS and to make the comparison between LAA and small-vessel occlusion (SVO) subtypes. Of the 126 acute IS patients prospectively enrolled in this study, 32 had LAA, 56 had SVO, and 38 had undetermined etiology according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Cardiac autonomic function of all patients was assessed by measuring heart rate variability (HRV). The low- and high-frequency components of HRV in all stroke patients were significantly lower than those of control subjects after comparing multivariable models, including additional adjustments for age, gender, and all risk factors. There were no significant differences on HRV between LAA and SVO although post hoc comparisons showed that stroke patients of SVO had increased sympathetic modulation and reduced vagal activity. In conclusion, in acute IS patients, both LAA and SVO are predisposed to have cardiac autonomic dysfunction, manifesting as abnormalities in HRV, whether in hemispheric or brain stem lesions. Stroke patients of SVO are at higher risks of cardiac abnormalities, which might suggest an early cardiac dysfunction because of long-term hypertension. The HF component of HRV thought to be for vagal control might be a cardinal marker for predicting cardiac autonomic dysfunction after acute IS. Short-term HRV spectral analysis is a convenient approach for stroke clinicians to assess autonomic function in acute stroke. Long-term follow-up for HRV and clinical outcome relative to LAA and SVO stroke subtypes is warranted, particularly when an abnormal HRV is found at admission.     

Left Atrial Appendage Dimensions Predict the Risk of Stroke/TIA in Patients With Atrial Fibrillation

Risk of Stroke/TIA in Patients With Atrial Fibrillation. Introduction: Most strokes in patients with atrial fibrillation (AF) arise from thrombus formation in left atrial appendage (LAA). Our aim was to identify LAA features associated with a higher stroke risk in patients with AF using magnetic resonance imaging and angiography (MRI/MRA). Methods: The study included 144 patients with nonvalvular AF who were not receiving warfarin and who underwent MRI/MRA prior to catheter ablation for AF. LAA volume, LAA depth, short and long axes of LAA neck, and numbers of lobes were measured. Results: Of the 144 patients, 18 had a prior stroke or transient ischemic attack (TIA) (13 and 5, respectively). Compared with patients who had no history of stroke/TIA, these patients were older, had higher prevalence of hypertension and hyperlipidemia and had higher LAA volume (22.9 ± 9.6 cm³ vs. 14.5 ± 7.1 cm³, P < 0.001). Their LAA depth (3.76 ± 0.9 cm vs. 3.21 ± 0.8 cm, P = 0.006) and the long and short axes of the LAA neck (3.12 ± 0.7 cm vs. 2.08 ± 0.7 cm, P < 0.001; 2.06 ± 0.5 cm vs. 1.37 ± 0.4 cm, P < 0.001, respectively) were larger. Using stepwise logistic regression model, the only statistically significant multivariable predictors of events were age (OR = 1.21 per year, 95% CI 1.06‐1.38, P = 0.004), aspirin use (OR = 0.039, 95% CI 0.005‐0.28, P = 0.001), and LAA neck dimensions (short axis × long axis) (OR = 3.59 per cm², 95% CI 1.93‐6.69, P < 0.001). Conclusion: LAA dimensions predict strokes/TIAs in patients with AF. LAA assessment by MRI/MRA can potentially be used as an adjunctive tool for risk stratification for embolic events in AF patients. (J Cardiovasc Electrophysiol, Vol. 22, pp. 10‐15, January 2011)     

The relationship between the autonomic nervous function and early renal dysfunction in elderly patients with mild-to-moderate essential hypertension

Objective: This study investigated the relationship between autonomic nervous function and early renal dysfunction in elderly patients with mild-to-moderate essential hypertension (EH). Design: A total of 223 elderly patients with mild-to-moderate EH were enrolled. Urinary albumin excretion (UAE) and urinary creatinine (UCr) were measured in all elderly patients with mild-to-moderate EH, and urinary albumin to creatinine ratio (ACR) was calculated (ACR = UAE/UCr × 0.113). All patients were divided into two groups such as ACR normal group (109 cases) and abnormal ACR group (114 cases) according to the results of ACR. Synchronic 24-hour ambulatory blood pressure monitoring and 24-hour ambulatory electrocardiogram were detected for all patients to simultaneously monitor heart rate variability (HRV) and blood pressure variability (BPV). Results: The level of 24-hour SSD, dSSD, and nSSD and 24-hour PP (parameters of BPV) increased significantly (P < 0.028, P < 0.023, P < 0.027 and P < 0.019, respectively), while the level of RMSSD, pNN50, SDNN, and SDANN (parameters of HRV) decreased significantly(P < 0.048, P < 0.029, P < 0.025 and P < 0.022, respectively) in abnormal ACR group than in normal ACR group. Multiple logistic regression analysis showed that ACR was closely correlated with 24-hour SSD, 24-hour PP, SDANN, and SDNN (ß = 1.261, P = 0.000; ß = 1.121, P = 0.003; ß = ?1.741, P = 0.000 and ß = ?1.231, P = 0.002, respectively). Conclusions: HRV (SDANN, SDNN) and BPV (24-hour SSD, dSSD, nSSD) were significantly correlated to ACR in patients with mild-to-moderate EH. This result suggested that sympathetic activation was closely related with early renal dysfunction in elderly patients with mild-to-moderate EH.     

Association of insulin resistance and autonomic tone in patients with pregnancy-induced hypertension

Pregnancy-induced hypertension (PIH) remains the main cause of maternal and fatal mortality. Insulin resistance (IR) and autonomic nervous system (ANS) imbalance are two principal drivers of PIH development. Few previous researches investigated the association between IR and ANS imbalance in Chinese PIH patients. 120 pregnant women were enrolled in our study, sixty healthy pregnant women (control group), fourty one gestational hypertension (GH group) and nineteen preeclampsia patients (PE group). The homeostasis model assessment of IR (HOMA-IR) and markers of ANS (plasma biomarkers and heart rate variability (HRV) components) were collected. Body mass index (BMI), Ln(HOMA-IR), noradrenaline level, LnTP (total power), Ln SDNN (standard deviation of the normal-to-normal interval), LnLF (low frequency), LnLF/LnHF (low frequency/high frequency) were different in the GH and PE groups compared with the controls. Significant correlations were observed between Ln (HOMA-IR) and gestational duration (r = 0.237, P = 0.031), BMI（r = 0.314, P = 0.002), systolic blood pressure (r = 0.108, P = 0.016), noradrenaline (r = 0.451, P = 0.009), LnTP (r = ?0.269, P = 0.015) and LnLF/HF (r = 0.183, P = 0.026) in those PIH patients. Furthermore, BMI, noradrenaline and LnTP were independent determinants of Ln(HOMA-IR) in PIH patients by multiple regression analysis. Our finding verified both IR and ANS imbalance were more severe in PIH patients than healthy pregnant women. Moreover, IR had a close association with ANS parameters in PIH patients, suggesting that they probably had contributory effects on the occurrence and development of PIH. We propose that these parameters could be added to the traditional indexes for individualized treatment of PIH patients in the future.     

Relationship between the NF-κB1-94ins/del ATTG locus polymorphism and risk of hypertension in the Chinese Han population

Objective: The onset of essential hypertension is the result of a combination of genetic factors and the environment. The nuclear factor (NF)-κB1-94ins/del ATTG locus polymorphism is associated with the occurrence of various diseases. The purpose of this study was to find out the relationship between the NF-κB1-94ins/del ATTG locus polymorphism and the risk of hypertension in the Chinese Han population.

Methods: A total of 585 Chinese Han patients with essential hypertension and 585 Chinese Han healthy volunteers were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to analyze the genotype of the NF-κB1-94ins/del ATTG locus in all the subjects.

Results: For the NF-κB1-94ins/del ATTG locus, the dominant (adjusted odds ratio [OR] = 1.31, 95% confidence interval [CI] = 1.13–1.54, P < 0.001), recessive (adjusted OR = 1.17, 95% CI = 1.02–1.32, P = 0.03) and additive (adjusted OR = 1.19, 95% CI = 1.03–1.36, P = 0.01) models showed significant increase in the risk of hypertension. The NF-κB1-94ins/del ATTG locus II genotype was an independent risk factor for hypertension (OR = 1.15, 95% CI = 0.78–1.69, P = 0.02). The interaction between the NF-κB1-94ins/del ATTG locus polymorphism and BMI, alcohol consumption, and diabetes significantly increased the risk of hypertension (OR = 1.71, 95% CI = 1.26–1.86, P < 0.01).

Conclusion: The NF-κB1-94ins/del ATTG polymorphism is an independent risk factor for essential hypertension. The NF-κB1-94ins/del ATTG locus, obesity, drinking, and diabetes also interact to yield a higher risk of hypertension.     

Comparison of oxidative stress biomarkers in hypertensive patients with or without hyperhomocysteinemia

Hyperhomocysteinemia is an independent risk factor for cardiovascular impairment in hypertension. Oxidative stress is important in the molecular mechanisms associated with hypertension, but there are few studies focusing on the comparison of oxidative stress biomarkers in hypertensive patients with or without hyperhomocysteinemia. The study included 50 newly diagnosed hypertensive patients with hyperhomocysteinemia, 50 newly diagnosed hypertensive patients without hyperhomocysteinemia, and 50 age-matched healthy controls. Serum levels of malondialdehyde, nitric oxide, 8-isoprostane-F2_ɑ, superoxide dismutase, catalase, and glutathione peroxides were compared. Levels of malondialdehyde and 8-isoprostane-F2_ɑ were higher in both hypertensive groups than in the control group (8.3 ± 1.8 μmol/L vs. 6.5 ± 1.3 μmol/L vs. 4.3 ± 1.2 μmol/L, P < 0.05; 23.5 ± 12.1 pg/mL vs. 17.4 ± 10.3 pg/mL vs. 13.9 ± 7.5 pg/mL, P < 0.05), while levels of superoxide dismutase and catalase were lower in both hypertensive groups than in the control group (120.5 ± 13.7 U/mL vs. 131.3 ± 18.2 U/mL vs. 149.1 ± 14.6 U/mL, P < 0.05; 23.8 ± 7.4 U/mL vs. 24.6 ± 9.2 U/mL vs. 33.5 ± 8.2 U/mL, P < 0.05). In hypertensive subgroups, serum malondialdehyde levels were higher in the hyperhomocysteinemia group than the other group (8.3 ± 1.8 μmol/L vs. 6.5 ± 1.3 μmol/L; P < 0.05), and superoxide dismutase activities were lower in the hyperhomocysteinemia group than the other group (120.5 ± 13.7 U/mL vs. 131.3 ± 18.2 U/mL; P < 0.05). Moreover, in hypertensive patients, homocysteine levels were significantly correlated with malondialdehyde (r = 0.39, P < 0.01), 8-isoprostane-F2ɑ (r = 0.47, P < 0.05), superoxide dismutase (r = ?0.51, P < 0.01), and catalase (r = ?0.51, P < 0.05), respectively. Our ?ndings demonstrated oxidative stress was more severe in hypertensive patients with hyperhomocysteinemia than those hypertensive patients without it. Besides, there were strong relationships between homocysteine activities and oxidative/antioxidative parameters, which indicated that homocysteine might aggravate the oxidative stress in hypertension to produce contributory effects on cardiovascular impairment.     

<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.     

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.     

CCL23: a new CC chemokine involved in human brain damage

Background

CCL 23 role in the inflammatory response after acute brain injuries remains elusive. Here, we evaluated whether CCL 23 blood levels associate with acquired cerebral lesions and determined CCL 23 predictive capacity for assessing stroke prognosis. We used preclinical models to study the CCL 23 homologous chemokines in rodents, CCL 9 and CCL 6.

Methods

Baseline CCL 23 blood levels were determined on 245 individuals, including ischaemic strokes (IS ), stroke mimics and controls. Temporal profile of circulating CCL 23 was explored from baseline to 24 h in 20 of the IS . In an independent cohort of 120 IS with a 3‐month follow‐up, CCL 23 blood levels were included in logistic regression models to predict IS outcome. CCL 9/CCL 6 cerebral expression was evaluated in rodent models of brain damage. Both chemokines were also profiled in circulation and histologically located on brain following ischaemia.

Results

Baseline CCL 23 blood levels did not discriminate IS , but permitted an accurate discrimination of patients presenting acute brain lesions (P  = 0.003). IS exhibited a continuous increase from baseline to 24 h in circulating CCL 23 (P  < 0.001). Baseline CCL 23 blood levels resulted an independent predictor of IS outcome at hospital discharge (OR _adj: 19.702 [1.815–213.918], P  = 0.014) and mortality after 3 months (OR _adj: 21.47 [3.434–134.221], P  = 0.001). In preclinics, expression of rodent chemokines in neurons following cerebral lesions was elevated. CCL 9 circulating levels decreased early after ischaemia (P  < 0.001), whereas CCL 6 did not alter within the first 24 h after ischaemia.

Conclusions

Although preclinical models do not seem suitable to characterize CCL 23, it might be a novel promising biomarker for the early diagnosis of cerebral lesions and might facilitate the prediction of stroke patient outcome.

     

Hepatectomy with or without the thoraco-abdominal approach: impact on perioperative outcome

Background

Hepatectomy using the thoraco-abdominal approach (TAA) compared to the abdominal approach (AA) remains under debate. This study assessed the perioperative outcomes of patients operated with or without TAA.

Living or deceased organ donors in liver transplantation for hepatocellular carcinoma: a systematic review and meta-analysis

Background

The outcomes of living donor liver transplantation (LDLT) versus deceased donor liver transplantation (DDLT) for HCC patients were not well defined and it was necessary to reassess.

大动脉粥样硬化性脑梗死患者血脂性别差异的多中心横断面研究

目的研究大动脉粥样硬化性(LAA)脑梗死相关血脂指标的性别差异。方法选择中国国家卒中登记数据库中4189例首发脑梗死患者,依据TOAST病因学分型分为LAA组1919例、小血管闭塞(SVO)组716例和非LAA&SVO组1554例。分析TG、TC、HDL-C、LDL-C水平与LAA的相关性。结果 3组除TG外,女性TC、HDL-C、LDL-C水平均高于男性(P<0.01)。LAA组vs非LAA组,LAA组vs非LAA&SVO组的2个logistic回归模型分析均显示:TC、LDL-C水平与LAA发生相关。男性患者TG水平与LAA的相关性有显著意义,TG每升高1个四分位数区间,LAA组较非LAA组、非LAA&SVO组发生的可能性分别增加8.6%和15.0%。结论相较于其他缺血性脑卒中亚型,TC、LDL-C增高与LAA的发生密切相关;TG在预测颅内外LAA风险时,存在性别差异,对于男性除常规关注TC、LDL-C外,还需将TG考虑在内。     

Challenges in secondary stroke prevention: prevalence of multiple metabolic risk factors,including abnormal glycaemia,in ischaemic stroke and transient ischaemic attack

Background: Secondary prevention of ischaemic stroke (IS) and transient ischaemic attack (TIA) mandates identification and treatment of multiple metabolic risk factors. The aim was to determine the prevalence of abnormal glycaemia, hypertension and dyslipidaemia in patients presenting to an Acute Stroke Unit of a tertiary referral teaching hospital with IS or TIA. Methods: We reviewed the clinical characteristics of consecutive patients presenting with symptoms of acute stroke or TIA between 1 February 2006 and 30 June 2007 to determine the prevalence of diabetes, impaired fasting glucose (IFG), post‐stroke dysglycaemia (PSD), hypertension and dyslipidaemia. Results: Mean age ± SD of the 224 patients (84 female) was 71 ± 15 years. Seventy per cent (n= 157) of patients presented with IS and 30% (n= 67) with TIA. Of the cohort, 15% (n= 33) had previously diagnosed diabetes, 10% (n= 22) were diagnosed with diabetes during admission and 19% (n= 42) had IFG diagnosed during admission. A further 4% (n= 9) were classified as having PSD. Sixty‐two per cent (n= 139) of patients had previously diagnosed hypertension; another 7% (n= 15) were diagnosed during admission. Eighty‐eight per cent (n= 197) of patients had dyslipidaemia. Thirty per cent had all three risk factors concurrently. Conclusion: Abnormal glycaemia was present in almost half the patients presenting with IS/TIA, with the majority of cases undiagnosed. One‐third of patients had abnormal glycaemia, hypertension and dyslipidaemia concurrently. Patients presenting with stroke should be routinely screened for abnormal glycaemia in concert with other vascular risk factors.     

Association between NINJ2 gene polymorphisms and ischemic stroke: a family-based case–control study

Novel susceptibility genes related to ischemic stroke (IS) are proposed in recent literatures. Population-based replicate studies would cause false positive results due to population stratification. 229 recruit IS patients and their 229 non-IS siblings were used in this study to avoid population stratification. The family-based study was conducted in Beijing from June 2005 to June 2012. Association between SNPs and IS was found in the sibship discordant tests, and the conditional logistic regression was performed to identify effect size and explore gene–environment interactions. Significant allelic association was identified between NINJ2 gene rs11833579 (P = 0.008), protein kinase C η gene rs2230501 (P = 0.039) and IS. The AA genotype of rs11833579 increased 1.51-fold risk (95 % CI 1.04–3.46; P = 0.043) of IS, and it conferred susceptibility to IS only in a dominant model (OR 2.69; 95 % CI 1.06–6.78; P = 0.036]. Risk of IS was higher (HR 3.58; 95 % CI 1.54–8.31; P = 0.003) especially when the carriers of rs11833579 AA genotype were smokers. The present study suggests A allele of rs11833579 may play a role in mediating susceptibility to IS and it may increase the risk of IS together with smoking.     

Inulin-type fructans improve active ulcerative colitis associated with microbiota changes and increased short-chain fatty acids levels

The intestinal microbiota is involved in ulcerative colitis (UC) pathogenesis. Prebiotics are hypothesized to improve health through alterations to gut microbiota composition and/or activity. Our aim was therefore to determine if inulin-type fructans induce clinical benefits in UC, and identify if benefits are linked to compositional and/or functional shifts of the luminal (fecal) and mucosal (biopsy) bacterial communities. Patients (n = 25) with mild/moderately active UC received 7.5 g (n = 12) or 15 g (n = 13) daily oral oligofructose-enriched inulin (Orafti®Synergy1) for 9 weeks. Total Mayo score, endoscopic activity and fecal calprotectin were assessed. Fecal and mucosal bacterial communities were characterized by 16S rRNA tag sequencing, and short chain fatty acids (SCFA) production were measured in fecal samples. Fructans significantly reduced colitis in the high-dose group, with 77% of patients showing a clinical response versus 33% in the low-dose group (P = 0.04). Fructans increased colonic butyrate production in the 15 g/d dose, and fecal butyrate levels were negatively correlated with Mayo score (r = ?0.50; P = 0.036). The high fructan dose led to an increased Bifidobacteriaceae and Lachnospiraceae abundance but these shifts were not correlated with improved disease scores. In summary, this pilot study revealed that 15 g/d dose inulin type fructans in UC produced functional but not compositional shifts of the gut microbiota, suggesting that prebiotic-induced alterations of gut microbiota metabolism are more important than compositional changes for the benefits in UC. The findings warrant future well-powered controlled studies for the use of β-fructans as adjunct therapy in patients with active UC.     

Left Atrial Appendage Closure and Systemic Homeostasis: The LAA HOMEOSTASIS Study

Background

The impact of left atrial appendage (LAA) exclusion, comparing an epicardial LAA or an endocardial LAA device, on systemic homeostasis remains unknown.

Behavioral,socio-environmental,educational and demographic correlates of excess body weight in Italian adolescents and young adults

Background and Aims

Excess body weight (EBW) is the most prevalent nutritional disorder among adolescents worldwide. Identifying determinants of EBW may help find new intervention strategies. Behavioral, socio-economic, educational and demographic correlates of EBW were examined in a population of Italian adolescents, separately for males and females.