Incidence and predictors of heart failure with improved ejection fraction category in a HFrEF patient population.

AIMS: The aim of the study was to assess the incidence and predictive factors of the development of heart failure with improved ejection fraction (HFimpEF) category during a 1 year follow-up period in a heart failure with reduced ejection fraction (HFrEF) patient population managed in a heart failure outpatient clinic. METHODS AND RESULTS: The study evaluated data from patients enrolled in the Hungarian Heart Failure Registry (HHFR). The incidence and predictive factors of the development of the HFimpEF category after 1 year follow-up were assessed in the group of patients who had HFrEF at baseline. We evaluated the incidence and predictors of the development of HFimpEF after a 1 year follow-up in relation to time since diagnosis of HFrEF in patients diagnosed within 3 months, between 3 months and 1 year, and beyond 1 year. The predictive factors of the development of HFimpEF were analysed using univariate and multivariate logistic regression analysis. Of the 833 HFrEF patients enrolled in the HHFR, the development of HFimpEF was observed in 162 patients (19.5%) during 1 year follow-up. In the whole patient population, independent predictors of the development of HFimpEF were female gender [odds ratio (OR): 1.73; 95% confidence interval (CI): 1.01-2.96; P < 0.05], non-ischaemic aetiology (OR: 1.95; 95% CI: 1.15-3.30; P < 0.05), and left ventricular end-diastolic diameter (LVEDD) <60 mm (OR: 2.04; 95% CI: 1.18-3.51; P < 0.05). The 1 year incidence of HFimpEF decreased in relation to time since diagnosis of HFrEF. The incidence of HFimpEF was 27.1% in patients diagnosed within 3 months, 18.4% in patients diagnosed between 3 months and 1 year, and 12.2% in patients diagnosed beyond 1 year. Non-ischaemic aetiology (OR: 4.76; 95% CI: 1.83-12.4; P < 0.01) and QRS width (OR: 0.81; 95% CI: 0.71-0.94; P < 0.01) for patients diagnosed within 3 months, LVEDD (OR: 0.54; 95% CI: 0.32-0.90; P < 0.05) and left atrial diameter ≤45 mm (OR: 5.44; 95% CI: 1.45-20.4; P < 0.05) for patients diagnosed between 3 months and 1 year, and LVEDD < 67 mm (OR: 2.71; 95% CI: 1.07-6.88; P < 0.05) for patients diagnosed beyond 1 year were found to be independent predictive factors. CONCLUSIONS: In our study, in this HFrEF patient population managed in a heart failure outpatient clinic, the 1 year incidence of HFimpEF was found to be ~20%. The 1 year incidence of HFimpEF decreased in relation to time since diagnosis of HFrEF. The most important predictors of the development of HFimpEF were female sex, non-ischaemic aetiology, narrower QRS width, and smaller diameter of the left ventricle and left atrium.

Cardiovascular risk factors in coeliac disease (ARCTIC): a protocol of multicentre series of studies.

INTRODUCTION: There is only limited and controversial information available on the cardiovascular (CV) risk in coeliac disease (CD). In this study, we plan to investigate the body composition and CV risk-related metabolic parameters at the diagnosis of CD and on a gluten-free diet in a Hungarian cohort of patients with CD. METHODS AND ANALYSIS: This study consists of two case-control studies and a prospective cohort study, involving newly diagnosed and treated patients with CD with age and sex-matched non-CD control subjects with an allocation ratio of 1:1. CD-related symptoms, quality of life, quality of the diet and CV risk will be assessed with questionnaires. Our primary outcomes are body composition parameters, which will be estimated with InBody 770 device. Secondary outcomes are CV-risk related metabolic parameters (eg, serum lipids, haemoglobin A1c, homeostatic model assessment index, liver enzymes, homocysteine, interleukin 6, galectin-3) and enteral hormones (leptin, ghrelin, adiponectin) measured from venous blood samples for all participants. Fatty liver disease will be assessed by transabdominal ultrasonography. In statistical analysis, descriptive and comparative statistics will be performed. With this study, we aim to draw attention to the often neglected metabolic and CV aspect of the management of CD. Findings may help to identify parameters to be optimised and reassessed during follow-up in patients with CD. ETHICS AND DISSEMINATION: The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (27521-5/2022/EÜIG). Findings will be disseminated at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05530070.

Geno- and phenotypic characteristics and clinical outcomes of CACNA1C gene mutation associated Timothy syndrome, "cardiac only" Timothy syndrome and isolated long QT syndrome 8: A systematic review.

Background: Mutations in the CACNA1C gene-encoding for the major Ca2+ channel of the heart-may exhibit a variety of clinical manifestations. These include typical or atypical Timothy syndromes (TS) which are associated with multiple organ manifestations, and cardiac involvement in form of malignant arrhythmias, QTc prolongation, or AV block. "Cardiac only" Timothy syndrome (COTS) shows no extracardiac manifestation, whereas some CACNA1C gene mutations are associated with QTc prolongation alone (isolated long QT syndrome 8, LQT8). Methods: A systematic search of the literature reporting cases of CACNA1C gene mutation associated syndromes, including TS, COTS and isolated LQT8 via major databases published from 2004 through 2019 was performed. Detailed patient-level phenotypic and genotypic characteristics, as well as long-term outcome measures were collected and compared between pre-specified patient groups, defined both on phenotype and genotype. Results: A total of 59 TS, 6 COTS, and 20 isolated LQT8 index cases were identified. Apart of syndactyly or baldness, there were no major differences regarding clinical manifestations or outcome measures between TS subtypes, either defining TS subtypes on the genotype or based on the phenotype. Both subtypes were characterized by an extreme degree of QTc prolongation (median ≥600 ms) which were reflected in high major adverse cardiac event rate. On the other hand, there were marked differences between TS, COTS, and isolated LQT8. Timothy syndrome was characterized by a much earlier disease onset, much more pronounced QTc prolongation and much higher mortality rate than COTS or isolated LQT8. Similar differences were observed comparing CACNA1C exon 8/8A vs. non-exon 8/8A mutation carriers. TS showed a high degree of genetic homogeneity, as the p.Gly406Arg mutation either in exon 8 or exon 8A alone was responsible for 70% of the cases. Conclusions: Clinical phenotypes associated with mutations in the CACNA1C gene show important clinical differences. Timothy syndrome is associated with the most severe clinical phenotype and with the highest risk of morbidity and mortality. However, distinguishing TS subtypes, in any form, are not supported by our data. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020184737].

The Genetic Architecture of Hypertrophic Cardiomyopathy in Hungary: Analysis of 242 Patients with a Panel of 98 Genes.

Hypertrophic cardiomyopathy (HCM) is a primary disease of the myocardium most commonly caused by mutations in sarcomeric genes. We aimed to perform a nationwide large-scale genetic analysis of a previously unreported, representative HCM cohort in Hungary. A total of 242 consecutive HCM index patients (127 men, 44 ± 11 years) were studied with next generation sequencing using a custom-designed gene-panel comprising 98 cardiomyopathy-related genes. A total of 90 patients (37%) carried pathogenic/likely pathogenic (P/LP) variants. The percentage of patients with P/LP variants in genes with definitive evidence for HCM association was 93%. Most of the patients with P/LP variants had mutations in MYBPC3 (55 pts, 61%) and in MYH7 (21 pts, 23%). Double P/LP variants were present in four patients (1.7%). P/LP variants in other genes could be detected in ≤3% of patients. Of the patients without P/LP variants, 46 patients (19%) carried a variant of unknown significance. Non-HCM P/LP variants were identified in six patients (2.5%), with two in RAF1 (p.Leu633Val, p.Ser257Leu) and one in DES (p.Arg406Trp), FHL1 (p.Glu96Ter), TTN (p.Lys23480fs), and in the mitochondrial genome (m.3243A>G). Frameshift, nonsense, and splice-variants made up 82% of all P/LP MYBPC3 variants. In all the other genes, missense mutations were the dominant form of variants. The MYBPC3 p.Gln1233Ter, the MYBPC3 p.Pro955ArgfsTer95, and the MYBPC3 p.Ser593ProfsTer11 variants were identified in 12, 7, and 13 patients, respectively. These three variants made up 36% of all patients with identified P/LP variants, raising the possibility of a possible founder effect for these mutations. Similar to other HCM populations, the MYBPC3 and the MYH7 genes seemed to be the most frequently affected genes in Hungarian HCM patients. The high prevalence of three MYBPC3 mutations raises the possibility of a founder effect in our HCM cohort.

The Effect of Resveratrol on the Cardiovascular System from Molecular Mechanisms to Clinical Results.

Cardiovascular diseases are the leading causes of death worldwide. The cardioprotective effects of natural polyphenols such as resveratrol (3,5,4-trihydroxystilbene) have been extensively investigated throughout recent decades. Many studies of RES have focused on its favorable effects on pathological conditions related to cardiovascular diseases and their risk factors. The aim of this review was to summarize the wide beneficial effects of resveratrol on the cardiovascular system, including signal transduction pathways of cell longevity, energy metabolism of cardiomyocytes or cardiac remodeling, and its anti-inflammatory and antioxidant properties. In addition, this paper discusses the significant preclinical and human clinical trials of recent years with resveratrol on cardiovascular system. Finally, we present a short overview of antiviral and anti-inflammatory properties and possible future perspectives on RES against COVID-19 in cardiovascular diseases.

Ultrafiltration is better than diuretic therapy for volume-overloaded acute heart failure patients: a meta-analysis.

Studies on the effectiveness of ultrafiltration (UF) in patients hospitalized with acute decompensated heart failure (ADHF) have led to heterogeneous study outcomes. This meta-analysis aimed to assess the impact of UF therapy in ADHF patients. We searched the medical literature to identify well-designed studies comparing UF with the usual diuretic therapy in this setting. Systematic evaluation of 8 randomized controlled trials enrolling 801 participants showed greater fluid removal (difference in means 1372.5 mL, 95% CI 849.6 to 1895.4 mL; p < 0.001), weight loss (difference in means 1.592 kg, 95% CI 1.039 to 2.144 kg; p < 0.001) and lower incidences of worsening heart failure (OR 0.63, 95% CI 0.43 to 0.94, p = 0.022) and rehospitalization for heart failure (OR 0.54, 95% CI 0.36 to 0.82, p = 0.003) without a difference in renal impairment (OR 1.386, 95% CI 0.870 to 2.209; p = 0.169) or all-cause mortality (OR 1.13, 95% CI 0.75 to 1.71, p = 0.546). UF increases fluid removal and weight loss and reduces rehospitalization and the risk of worsening heart failure in congestive patients, suggesting ultrafiltration as a safe and effective treatment option for volume-overloaded heart failure patients.

Resveratrol Improves Heart Function by Moderating Inflammatory Processes in Patients with Systolic Heart Failure.

The effects of resveratrol (RES) in heart failure have already been evaluated in animal models; however, in human clinical trials, they have not been confirmed yet. The aim of this study was to assess the effects of resveratrol treatment in systolic heart failure patients (heart failure with reduced ejection fraction or HFrEF). In this human clinical trial, 60 outpatients with NYHA (New York Heart Association) class II-III HFrEF were enrolled and randomized into two groups: receiving either 100-mg resveratrol daily or placebo for three months. At the beginning and at the end of the study echocardiography, a six-minute walk test, spirometry, quality of life questionnaire, lab test and RNA profile analysis were performed. The systolic and diastolic left ventricular function, as well as the global longitudinal strain, were improved significantly in the resveratrol-treated group (RES). Exercise capacity, ventilation parameters and quality of life also improved significantly in the RES group. In parallel, the cardiac biomarker levels (N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and galectin-3) decreased in the treated group. The level of inflammatory cytokines decreased significantly after RES supplementation, as a consequence of the decreased expression level of leucocyte electron transport chain proteins. The main findings of our trial are that RES treatment added to the standard heart failure therapy improved heart function and the clinical condition by moderating the inflammatory processes in patients with HFrEF.

Uninterrupted or Minimally Interrupted Direct Oral Anticoagulant Therapy is a Safe Alternative to Vitamin K Antagonists in Patients Undergoing Catheter Ablation for Atrial Fibrillation: An Updated Meta-Analysis.

Adequate anticoagulation during catheter ablation (CA) for atrial fibrillation (AF) is crucial for the prevention of both thromboembolic events and life-threatening bleeding. The purpose of this updated meta-analysis is to compare the safety and efficacy of uninterrupted and minimally interrupted periprocedural direct oral anticoagulant (DOAC) protocols and uninterrupted vitamin K antagonist (VKA) therapy in patients undergoing CA for AF based on the latest evidence. Randomized controlled trials, prospective observational studies, and retrospective registries comparing DOACs to VKAs were identified in multiple databases (Embase, MEDLINE via PubMed, CENTRAL, and Scopus). The primary outcomes were stroke or transient ischemic attack (TIA), major bleeding, and net clinical benefit. Forty-two studies with a total of 22,715 patients were included in the final analysis. The occurrence of major bleeding was significantly lower in patients assigned to uninterrupted DOAC treatment compared to VKAs (pooled odds ratio (POR): 0.71, confidence interval (CI): 0.51-0.99). The pooled analysis of both uninterrupted and minimally interrupted DOAC groups also showed significant reduction in major bleeding events (POR: 0.70, CI: 0.53-0.93). The incidence of thromboembolic events was low, with no significant difference between groups. This updated meta-analysis showed that DOAC therapy is as effective as VKA in preventing stroke and TIA. Minimally interrupted DOAC therapy is a non-inferior periprocedural anticoagulation strategy; however, uninterrupted DOAC therapy showed superiority compared to VKA with regard to major, life-threatening bleeding. Based on our in-depth analysis, we conclude that both DOAC strategies are equally safe and preferable alternatives to VKAs in patients undergoing CA for AF.

Hemorheological Alterations in Patients with Heart Failure with Reduced Ejection Fraction Treated by Resveratrol.

OBJECTIVES: Several beneficial effects of resveratrol have already been published. This study evaluated the effect of resveratrol on the hemorheological parameters in patients with heart failure with reduced ejection fraction. METHODS: In our double-blind, placebo-controlled human clinical trial, we enrolled 60 outpatients with heart failure. Patients were randomized into two groups: receiving either 100 mg resveratrol capsule daily or placebo for 3 months. Hematocrit was determined by microhematocrit centrifuge. Plasma and whole blood viscosity was evaluated by capillary viscometer. Erythrocyte aggregation was measured by both LORCA and Myrenne aggregometers. LORCA ektacytometer was used for measuring erythrocyte deformability. Exercise capacity was assessed by a 6-minute walk test. RESULTS: Resveratrol treatment did not have any significant effect on hematocrit and viscosity. The erythrocyte deformability also remained unchanged. However, significant improvement of red blood cell aggregation was observed in the resveratrol group compared to baseline after 3 months. Furthermore, positive correlation was found between the exercise capacity and the hemorheological properties (Hct, WBV, and RBC aggregation and deformability) as well. CONCLUSION: These findings indicate that resveratrol can significantly reduce red blood cell aggregation, which may positively influence microcirculation, which may contribute to the improvement of tissue perfusion and oxygen supply in heart failure.

Surgical treatment of heart failure due to giant coronary artery fistula: a case report.

Coronary artery fistula is a rare congenital cardiac anomaly that is often found incidentally during computed tomography angiography. Coronary fistula between the left circumflex coronary artery and the coronary sinus is among the less common forms of coronary artery fistula. A 60-yea\r-old female patient presented to our outpatient cardiology department with symptoms of severe, de novo heart failure. Echocardiogram revealed severe mitral regurgitation and a dilated duct that turbulently accelerated colour Doppler flow behind the left ventricle with significant left-to-right shunt. Cardiac magnetic resonance imaging and computed tomography angiography revealed a massively dilated fistula between the left circumflex coronary artery and the coronary sinus with a diameter of 3-4 cm. The patient underwent combined heart surgery involving mitral ring annuloplasty and fistula ligation and was discharged in stable condition on guideline-based medical therapy. At 18 months of follow-up, minimal residual shunt flow and mild-to-moderate mitral regurgitation were found. We report a rare case of congenital coronary disorder resulting in heart failure and highlight the importance of complex non-invasive cardiac diagnostic procedures before planning and performing heart surgery.

Direct Anticoagulants and Risk of Myocardial Infarction, a Multiple Treatment Network Meta-Analysis.

We assessed the cardiovascular safety of long-term direct-acting oral anticoagulant (DOAC) treatment. A search of the medical literature was performed from inception until May 31, 2019. Inclusion criteria were (1) randomized trial that assessed the clinical efficacy and/or safety of 1 or more DOAC, (2) control group including oral anticoagulation and/or antiplatelet and/or placebo treatment, and (3) the incidence of acute coronary syndrome during follow-up was reported. Fixed-effect and random-effects models were applied. The analyzed outcomes were myocardial infarction (MI), major bleeding, and mortality. Twenty-eight randomized clinical trials (196 761 patients) were included. Rivaroxaban was associated with a 21% reduction in the relative risk of MI when compared to placebo (relative risk [RR]: 0.79 [95% credible interval, CrI: 0.65-0.94]) and a 31% reduction (RR: 0.70 [95% CrI: 0.53-0.89]) when compared to dabigatran. Apixaban resulted in 24% (RR: 0.76 [95% CrI: 0.58-0.99]) and vitamin K antagonists anticoagulation resulted in 19% (RR: 0.81 [95% CrI: 0.65-0.98]) risk reduction compared to dabigatran. The computed probability of being the first best choice of treatment was 61.8% for rivaroxaban. Cardiovascular safety shows considerable heterogeneity among oral anticoagulants. Treatment with rivaroxaban is associated with reduced rate of MI.

Anti-TNFα agents are the best choice in preventing postoperative Crohn's disease: A meta-analysis.

BACKGROUND: Despite the high rate of postoperative recurrence (POR) in Crohn's disease (CD), there is no widely accepted consensus on its prevention. AIM: To compare the efficacy of biological and conventional therapies in preventing POR of CD. METHODS: We searched four electronic databases up to April 2019 for articles that examined the efficacy of different preventive therapies against POR. Our PICO was: (P) adults with CD who underwent intestinal resection, (I) biological agents, (C) conventional therapies or a placebo, and (O) clinical, endoscopic, and histological POR. RESULTS: Anti-TNFα agents were significantly better in preventing clinical, endoscopic, severe endoscopic and histological POR compared to conventional therapies (OR: 0.508, 95% CI: 0.309-0.834, P = 0.007; OR: 0.312, 95% CI: 0.199-0.380, P < 0.001; OR: 0.195, 95% CI: 0.107-0.356, P < 0.001; and OR: 0.255, 95% CI: 0.106-0.611, P = 0.002, respectively), as well as in the subgroup of nonselected CD patients (OR: 0.324, 95% CI: 0.158-0.664, P = 0.002; OR: 0.225, 95% CI: 0.124-0.409, P < 0.001; and OR: 0.248, 95% CI: 0.070-0.877, P = 0.031, respectively). Infliximab and adalimumab proved to be equally effective in preventing endoscopic POR. CONCLUSION: Anti-TNFα agents are more effective in preventing clinical, endoscopic and histological POR than conventional therapies, even in nonselected CD patients.

The Effects of Bradykinin B1 Receptor Antagonism on the Myocardial and Vascular Consequences of Hypertension in SHR Rats.

It is known that non-steroidal anti-inflammatory drugs increase cardiovascular (CV) morbidity and mortality. In this study, we examined whether a novel anti-inflammatory drug, bradykinin B1 receptor antagonist (FGY-1153) treatment could influence the development of hypertensive organ damages in spontaneously hypertensive rats (SHR). SHRs were treated with low (FGY-120) or high dose FGY-1153 (FGY-400) and with placebo (Control) for 26 weeks. Wistar-Kyoto rats were used as aged-matched, normotensive controls (WKY). Body weight, food consumption and blood pressure were measured regularly. Echocardiography was performed at the beginning and at the end of the study. Light and electron microscopic analysis of heart and great vessels were performed, and the extent of fibrotic areas was measured. The phosphorylation state of prosurvival Akt-1/glycogen synthase kinase (GSK)-3ß pathway and the activation of signaling factors playing part in the fibrotic processes - mitogen activated protein kinases (MAPKs), and TGF-ß/Smad2 - were monitored using Western-blot. Body weight and food consumption as well as the elevated blood pressure in SHRs was not influenced by FGY-1153 treatment. However, both doses of FGY-1153 treatment decreased left ventricular (LV) hypertrophy and diastolic dysfunction in hypertensive animals. Moreover systolic LV function was also preserved in FGY-120 group. Increased intima-media thickness and interstitial fibrosis were not significantly diminished in great vessels. FGY-1153 treatment inhibited the expression of TGFß and the phosphorylation of SMAD2 in the heart. Our results suggest that the tested novel anti-inflammatory compound has no deleterious effect on CV system, moreover it exerts moderate protective effect against the development of hypertensive cardiopathy.

Aging and Comorbidities in Acute Pancreatitis I: A Meta-Analysis and Systematic Review Based on 194,702 Patients.

Background: Acute pancreatitis (AP) is one of the most common cause of hospitalization among gastrointestinal diseases worldwide. Although most of the cases are mild, approximately 10-20% of patients develop a severe course of disease with higher mortality rate. Scoring systems consider age as a risk factor of mortality and severity (BISAP; >60 years, JPN>70 years, RANSON; >55 years, APACHE II >45 years). If there is a correlation between aging and the clinical features of AP, how does age influence mortality and severity? Aim: This study aimed to systematically review the effects of aging on AP. Methods: A comprehensive systematic literature search was conducted in the Embase, Cochrane, and Pubmed databases. A meta-analysis was performed using the preferred reporting items for systematic review and meta-analysis statement (PRISMA). A total of 1,100 articles were found. After removing duplicates and articles containing insufficient or irrelevant data, 33 publications involving 194,702 AP patients were analyzed. Seven age categories were determined and several mathematical models, including conventional mathematical methods (linear regression), meta-analyses (random effect model and heterogeneity tests), meta-regression, funnel plot and Egger's test for publication bias were performed. Quality assessment was conducted using the modified Newcastle-Ottawa scale. The meta-analysis was registered in the PROSPERO database (CRD42017079253). Results: Aging greatly influences the outcome of AP. There was a low severe AP incidence in patients under 30 (1.6%); however, the incidence of severe AP showed a continuous, linear increase between 20 and 70 (0.193%/year) of up to 9.6%. The mortality rate was 0.9% in patients under 20 and demonstrated a continuous linear elevation until 59, however from this age the mortality rate started elevating with 9 times higher rate until the age of 70. The mortality rate between 20 and 59 grew 0.086%/year and 0.765%/year between 59 and 70. Overall, patients above 70 had a 19 times higher mortality rate than patients under 20. The mortality rate rising with age was confirmed by meta-regression (coefficient: 0.037 CI: 0.006-0.068, p = 0.022; adjusted r2: 13.8%), and severity also (coefficient: 0.035 CI: 0.019-0.052, p < 0.001; adjusted r2: 31.6%). Conclusion: Our analysis shows a likelihood of severe pancreatitis, as well as, pancreatitis-associated mortality is more common with advanced age. Importantly, the rapid elevation of mortality above the age of 59 suggests the involvement of additional deteriorating factors such as co-morbidity in elderly.

The effect of serum triglyceride concentration on the outcome of acute pancreatitis: systematic review and meta-analysis.

Elevated serum triglyceride concentration (seTG, >1.7 mM or >150 mg/dL) or in other words hypertriglyceridemia (HTG) is common in the populations of developed countries. This condition is accompanied by an increased risk for various diseases, such as acute pancreatitis (AP). It has been proposed that HTG could also worsen the course of AP. Therefore, in this meta-analysis, we aimed to compare the effects of various seTGs on the severity, mortality, local and systemic complications of AP, and on intensive care unit admission. 16 eligible studies, including 11,965 patients were retrieved from PubMed and Embase. The results showed that HTG significantly elevated the odds ratio (OR = 1.72) for severe AP when compared to patients with normal seTG (<1.7 mM). Furthermore, a significantly higher occurrence of pancreatic necrosis, persistent organ failure and renal failure was observed in groups with HTG. The rates of complications and mortality for AP were significantly increased in patients with seTG >5.6 mM or >11.3 mM versus <5.6 mM or <11.3 mM, respectively. We conclude that the presence of HTG worsens the course and outcome of AP, but we found no significant difference in AP severity based on the extent of HTG.

Pancreatitis-Associated Genes and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to evaluate the connection between pancreatic cancer (PC) and genetic variants associated with chronic pancreatitis via systematic review and meta-analysis. METHODS: The data search was performed in 3 major databases (PubMed, Embase, and Cochrane Library). The selected studies have looked into the presence of the pancreatitis-associated genes in patients with PC and in control subjects, the outcome being the frequency of the mutations in the 2 groups. For the binary outcomes, pooled odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: Ten articles proved to be eligible for the qualitative synthesis, and 8 articles were suitable for statistical analysis. Six case-control studies, comprising 929 PC cases and 1890 control subjects for serine protease inhibitor Kazal type 1 (SPINK1) mutations, and 5 case-control studies, comprising 1674 PC cases and 19,036 control subjects for CFTR mutations, were enrolled in our analysis. SPINK1 mutations showed no association with PC (OR, 1.52; 95% CI, 0.67-3.45; P = 0.315), whereas mutations in CFTR modestly increased the risk of PC (OR, 1.41; 95% CI, 1.07-1.84; P = 0.013). CONCLUSION: Our meta-analysis showed that mutations in CFTR modestly increase the risk of PC, whereas no association was found between SPINK1 and PC.

Helicobacter pylori infection reduces the risk of Barrett's esophagus: A meta-analysis and systematic review.

INTRODUCTION: The prevalence of Helicobacter pylori infection (HPI) has been decreasing in developed countries, with an increasing prevalence of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) at the same time. The aim of our meta-analysis was to quantify the risk of BE in the context of HPI. METHODS: A systematic search was conducted in 3 databases for studies on BE with data on prevalence of HPI from inception until December 2016. Odds ratios for BE in HPI were calculated by the random effects model with subgroup analyses for geographical location, presence of dysplasia in BE, and length of the BE segment. RESULTS: Seventy-two studies were included in the meta-analysis, including 84 717 BE cases and 390 749 controls. The overall analysis showed that HPI reduces the risk of BE; OR = 0.68 (95% CI: 0.58-0.79, P < .001). Subgroup analyses revealed risk reduction in Asia OR = 0.53 (95% CI: 0.33-0.84, P = .007), Australia OR = 0.56 (95% CI: 0.39-0.80, P = .002), Europe OR = 0.77 (95% CI: 0.60-0.98, P = .035), and North-America OR = 0.59 (95% CI: 0.47-0.74, P < .001). The risk was significantly reduced for dysplastic BE, OR = 0.37 (95% CI: 0.26-0.51, P < .001) for non-dysplastic BE, OR = 0.51 (95% CI: 0.35-0.75, P = .001), and for long segment BE, OR = 0.25 (95% CI: 0.11-0.59, P = .001) in case of HPI. CONCLUSIONS: This extensive meta-analysis provides additional evidence that HPI is associated with reduced risk of BE. Subgroup analyses confirmed that this risk reduction is independent of geographical location. HPI is associated with significantly lower risk of dysplastic, non-dysplastic, and long segment BE.

Therapeutic Whole-Body Hypothermia Reduces Death in Severe Traumatic Brain Injury if the Cooling Index Is Sufficiently High: Meta-Analyses of the Effect of Single Cooling Parameters and Their Integrated Measure.

Therapeutic hypothermia was investigated repeatedly as a tool to improve the outcome of severe traumatic brain injury (TBI), but previous clinical trials and meta-analyses found contradictory results. We aimed to determine the effectiveness of therapeutic whole-body hypothermia on the deaths of adult patients with severe TBI by using a novel approach of meta-analysis. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to February 2017. The identified human studies were evaluated regarding statistical, clinical, and methodological designs to ensure interstudy homogeneity. We extracted data on TBI severity, body temperature, death, and cooling parameters; then we calculated the cooling index, an integrated measure of therapeutic hypothermia. Forest plot of all identified studies showed no difference in the outcome of TBI between cooled and not cooled patients, but interstudy heterogeneity was high. On the contrary, by meta-analysis of randomized clinical trials that were homogenous with regard to statistical, clinical designs, and precisely reported the cooling protocol, we showed decreased odds ratio for death in therapeutic hypothermia compared with no cooling. As independent factors, milder and longer cooling, and rewarming at <0.25°C/h were associated with better outcome. Therapeutic hypothermia was beneficial only if the cooling index (measure of combination of cooling parameters) was sufficiently high. We conclude that high methodological and statistical interstudy heterogeneity could underlie the contradictory results obtained in previous studies. By analyzing methodologically homogenous studies, we show that cooling improves the outcome of severe TBI, and this beneficial effect depends on certain cooling parameters and on their integrated measure, the cooling index.

[Hungarian Heart Failure Registry 2015-2016. Preliminary results]. / Magyar Szívelégtelenség Regiszter 2015­2016. Kezdeti eredmények.

Heart failure is associated with a poor prognosis despite significant advances in the pharmacological and device therapy and incurs very high cost because of frequent hospitalizations. Therefore, professional high-quality care is essential for both patients and the healthcare system. The best way to evaluate the quality of care for a particular disease is the use of disease-specific registries. Until now, there has not been a registry evaluating characteristics and management of heart failure patients in Hungary. For that reason, the Hungarian Society of Cardiology initiated the set-up of the Hungarian Heart Failure Registry. The Aim of this paper is to present the goals, methods and first year results of the Hungarian Heart Failure Registry. The goal of the Registry is to create a modern, web-based database that summarizes the data of large number of patients who are currently or were previously admitted to hospital or who are currently or were previously patients in an outpatient department due to severe heart failure (NYHA III-IV). Currently 17 cardiology departments participate in the development of the Registry. The planned number of patients is 2000. Initially follow-up was planned for one year (pilot study). After the evaluation of the relevant experiences of the pilot study, long-term follow-up is planned. The Registry collects information about the type of heart failure (heart failure with reduced - LVEF≤45% - vs. preserved - LVEF>45% - ejection fraction), etiology, co-morbidities, diagnostic methods, treatment as well as morbidity and mortality. After the first year, assessing the baseline parameters of 698 patients enrolled in the Registry we found that the majority of patients (87.8%) has heart failure with reduced ejection fraction and in 39.8% of the patients heart failure has an ischaemic origin. The most frequent co-morbidity was hypertension followed by diabetes, renal insufficiency and COPD. The patients were treated with ACE inhibitors or ARBs in 94.4%, with beta blockers in 95.9%, and mineralocorticoid receptor antagonists in 73.9%. The mean dose of neurohormonal antagonists was higher than half of the target dose defined by current guidelines. The use of cardiac resynchronisation therapy was 11.7% and implantable cardioverter defibrillator was 25.8%. The pharmacological and device therapy of patients who were enrolled in the Registry until now was fit the current guidelines' recommendations. This, however, does not mean that the management of heart failure is without problems in our country but that high quality patient care is available with adequate heart failure treatment in cardiology departments dedicated to heart failure care. Orv. Hetil., 2017, 158(3), 94-100.