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Heart failure (HF) and cardiovascular diseases present public health challenges. Although great progress was achieved in their treatment, there is continuous need for new therapies. Urocortins of the corticotropin neuropeptide family were reported to exert beneficial effects in animal models of HF and cardiovascular diseases. We aimed to assess the available clinical evidence on the potential role of urocortins in HF and other cardiovascular diseases. We explored MEDLINE, Embase, CENTRAL, and Scopus databases. Twenty‐seven studies were included in the qualitative and 15 studies (2005 patients) in the quantitative syntheses. Available data allowed us to meta‐analyze the blood pressure (BP) lowering and heart rate (HR) increasing effects of urocortin 2 in HF with reduced ejection fraction. We applied meta‐regression to explore the association between left ventricular ejection fraction and serum urocortin 1 and urocortin 2 levels. Short‐term urocortin 2 infusion decreased mean arterial pressure in chronic HF with reduced ejection fraction (mean difference = −9.161 mmHg, 95% confidence interval [CI] −12.661 to −5.660 mmHg, p

A higher BMI has become acknowledged as one of the important risk factors for developing critical condition in coronavirus disease 2019 (COVID-19). In addition to BMI, body composition, and particularly visceral adiposity, might be an even more accurate measure to stratify patients. Therefore, the aim of this study was to evaluate the association between the distributions of computed-tomography-quantified fat mass and critical condition of patients with COVID-19.A systematic search was conducted in five databases for studies published until November 17, 2020. In the meta-analysis, pooled mean difference (standardized mean difference [SMD]) of visceral fat area (VFA; in square centimeters) was calculated between patients in the intensive care unit and those in general ward and between patients with the requirement for invasive mechanical ventilation (IMV) and those without the IMV requirement.The quantitative synthesis revealed that patients requiring intensive care had higher VFA values (SMD = 0.46, 95% CI: 0.20-0.71, P 0.001) compared with patients on the general ward. Similarly, patients requiring IMV had higher VFA values (SMD = 0.38, 95% CI: 0.05-0.71, P = 0.026) compared with patients without the IMV requirement.VFA values were found to be significantly higher in patients with critical condition. Therefore, abdominal adiposity seems to be a risk factor in COVID-19, and patients with central obesity might need special attention.

INTRODUCTION: With the aging of the population, the screening of frail patients, especially before high-risk surgery, come to the fore. The background of the frail state is not totally clear, most likely inflammatory processes are involved in the development. METHODS: Our survey of patients over age of 65 who were on cardiac surgery were performed with Edmonton Frail Scale (EFS). Patients’ demographic, perioperative data, incidence of complications and correlations of inflammatory laboratory parameters were studied with the severity of the frail state. RESULTS: On the basis of EFS, 313 patients were divided into non-frail (NF,163,52%), pre-frail (PF,89,28.5%) and frail (F,61,19.5%) groups. Number of complications in the three groups were different (NF:0.67/patient, PF:0.76/patient, F:1.08/patient). We showed significant difference between NF and F in both intensive care and hospital stay, but there was no statistical difference between the groups in hospital deaths (NF:5/163, PF:3/89, F:5/61). We also found a significant difference between NF and F patients in preoperative fibrinogen-, CRP- and white blood cell count levels. CONCLUSIONS: We first present the incidence of frailty in patients with heart surgery in a Central-European population. According to our results, inflammatory processes are likely to play a role in the development of the frail state.

Introduction Clostridioides difficile (formerly Clostridium) infection (CDI) is the most common cause of healthcare-associated diarrhea with high mortality and recurrence rate; furthermore, the treatment of recurrent cases is a challenge. In this network meta-analysis, we aimed to compare all available therapies against multiple recurrent CDI (mrCDI) and rank them by efficacy. Methods After a systematic search, randomized controlled trials (RCT) with any interventions against mrCDI were included. Data were extracted to the study database using Excel. Risk of bias assessment was performed with the Cochrane RoB 2 tool. The primary outcome was the clinical cure of CDI and the secondary outcome was the recurrence of CDI. A Bayesian method was performed to investigate the efficacy rank order of therapies. We registered our protocol with the Prospero Center for Reviews and Dissemination (registration no. CRD42020160365). Results Six RCTs with seven interventions were included in the quantitative synthesis. According to the surface under the cumulative ranking curve values, fecal microbiota transplantation (FMT) after a short course of vancomycin therapy (83%) shows the highest efficacy for clinical cure. Tolevamer and vancomycin + FMT seemed to be the most effective in preventing recurrence (87% and 75%, respectively). Conclusion Vancomycin + FMT is perhaps the most effective option for the treatment and prevention of mrCDI, while tolevamer is also effective in preventing recurrence. Electronic Supplementary Material The online version of this article (10.1007/s40121-020-00356-9) contains supplementary material, which is available to authorized users.

BACKGROUND: Hypertriglyceridemia is the third most common cause of acute pancreatitis (AP). It has been shown that hypertriglyceridemia aggravates the severity and related complications of AP; however, detailed analyses of large cohorts are contradictory. Our aim was to investigate the dose-dependent effect of hypertriglyceridemia on AP. METHODS: AP patients over 18 years old who underwent triglyceride measurement within the initial three days were included into our cohort analysis from a prospective international, multicenter AP registry operated by the Hungarian Pancreatic Study Group. Data on 716 AP cases were analyzed. Six groups were created based on the highest triglyceride level (

Aims Type-2 diabetes mellitus (T2DM) is a common health condition which prevalence increases with age. Besides lifestyle modifications, passive heating could be a promising intervention to improve glycemic control. This study aimed to assess the efficacy of passive heat therapy on glycemic and cardiovascular parameters, and body weight among patients with T2DM. Methods A systematic review and meta-analysis were reported according to PRISMA Statement. We conducted a systematic search in three databases (MEDLINE, Embase, CENTRAL) from inception to 19 August 2021. We included interventional studies reporting on T2DM patients treated with heat therapy. The main outcomes were the changes in pre-and post-treatment cardiometabolic parameters (fasting plasma glucose, glycated plasma hemoglobin, and triglyceride). For these continuous variables, weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated. Study protocol number: CRD42020221500. Results Five studies were included in the qualitative and quantitative synthesis, respectively. The results showed a not significant difference in the hemoglobin A1c [WMD −0.549%, 95% CI (−1.262, 0.164), p = 0.131], fasting glucose [WMD −0.290 mmol/l, 95% CI (−0.903, 0.324), p = 0.355]. Triglyceride [WMD 0.035 mmol/l, 95% CI (−0.130, 0.200), p = 0.677] levels were comparable regarding the pre-, and post intervention values. Conclusion Passive heating can be beneficial for patients with T2DM since the slight improvement in certain cardiometabolic parameters support that. However, further randomized controlled trials with longer intervention and follow-up periods are needed to confirm the beneficial effect of passive heat therapy.

Introduction: Minor physical anomalies (MPAs) may reflect basic neurobiological features underlying bipolar disorders (BPD), as they are sensitive physical indicators of morphogenetic failure of the brain. Despite several researches about the presence of MPAs in BPD, the results are still controversial.Objectives: The aim of the present meta-analysis was to assess the standardized weighted mean effect sizes of MPAs in BPD and to examine if MPAs may be found predominantly in the head and/or facial regions in BPD patients compared to controls (HC).Methods: Four studies, involving 155 patients with BPD, and 187 HC, were involved in the analysis after searching the literature. For the investigation of MPAs in the peripheral (MPA-P) and in the head and facial regions (MPA-CF), two studies involving 121 BPD patients, and 133 HC passed the inclusion criteria.Results: The number of the MPAs in the BPD group was significantly higher compared to HC. Another important finding of the present study is that BPD patients' MPA-P scores do not significantly differ from those of the HC. In contrast, BPD patients' MPA-CF scores were found to be significantly higher compared to HC subjects. It is important to note that there was a low number of eligible publications included, which caused higher heterogeneity.Conclusions: Low quality of evidence suggests that MPAs are more common in patients with BPD than in HC and the higher rate of MPAs is found predominantly in the head and facial regions.

Background Scleroedema adultorum of Buschke is a rare disorder characterized by fibromucinous thickening of the dermis that manifests mainly at the nape of the neck and on the upper back and shoulders. This study screened patients with diabetes mellitus for skin hardening caused by scleroedema adultorum of Buschke and characterized the clinical and laboratory findings in patients with newly identified cases, with a focus on lipid metabolism abnormalities and vascular complications. Methods Out of 113 consecutive patients with diabetes, 11 (9.7%) new scleroedema patients, all with type 2 diabetes, were found. Their clinical and laboratory data were compared to those of the rest of the screened patients and to those of a cohort of 15 patients with scleroedema and diabetes who were already being treated in a tertiary clinical centre at the University of Pécs. Results Higher proportions of patients with dyslipidaemia, hypertriglyceridemia (P P P = 0.021, P P P P = 0.003) were independent predictors of scleroedema in patients with diabetes mellitus. Conclusions Diabetes patients with scleroedema had more severe dyslipidaemia and higher occurrence of vascular complications compared to those without scleroedema. In addition to poorly controlled type 2 diabetes mellitus requiring insulin treatment, high non-HDL-C levels may be another contributing factor to the development of scleroedema. Trial registration NCT04335396.

The hunt for useful sepsis biomarkers is ongoing. Macrophage migration inhibitory factor (MIF) was implicated as a biomarker in sepsis, but its diagnostic and prognostic value has remained unclear in human studies. Here, we aimed at clarifying the value of MIF as a sepsis biomarker with the meta-analysis of clinical trials. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched until December 2019. From the included studies, blood MIF levels and indicators of disease severity were extracted in septic and control patient groups. Twenty-one eligible studies were identified, including data from 1876 subjects (of which 1206 had sepsis). In the septic patients, blood MIF levels were significantly higher than in healthy controls with a standardized mean difference (SMD) of 1.47 (95% confidence interval, CI: 0.96–1.97; p p p

In cases of difficult biliary cannulation, transpancreatic sphincterotomy (TPS) can be an alternative approach of biliary access. However, its success and safety profile have not been studied in detail. A systematic review and meta-analysis were performed to study the overall cannulation success and adverse events of TPS. These outcomes were also compared to other advanced cannulation methods. A systematic literature search was conducted to find all relevant articles containing data on TPS. Successful biliary cannulation and complications rates [post-ERCP pancreatitis (PEP), bleeding, and perforation rates] were compared in the pooled analyses of prospective comparative studies. The overall outcomes were calculated involving all studies on TPS. TPS was superior compared to needle-knife precut papillotomy (NKPP) and the double-guidewire method (DGW) regarding cannulation success (odds ratio [OR] 2.32; 95% confidence interval [CI] 1.37-3.93; and OR 2.72; 95% CI 1.30-5.69, respectively). The rate of PEP did not differ between TPS and NKPP or DGW; however, TPS (only retrospective studies were available for comparison) proved to be worse than needle-knife fistulotomy in this regard (OR 4.62; 95% CI 1.36-15.72). Bleeding and perforation rates were similar among these advanced techniques. There were no data about long-term consequences of TPS. The biliary cannulation rate of TPS is higher than that of the other advanced cannulation techniques, while the safety profile is similar to those. However, no long-term follow-up studies are available on the later consequences of TPS; therefore, such studies are strongly needed for its full evaluation.

Magnitude of gluten-specific T-cell responses in coeliac disease (CD) might be dependent on HLA-DQ2 gene dose. We aimed to investigate the effects of HLA-DQB1*02 allele dose on clinical outcomes.We reviewed the charts of all coeliac patients attending to three Hungarian university clinics after 1997 and included those patients, who (a) were diagnosed with CD, (b) underwent high-resolution HLA typing and (c) were ≥18 years at the time of data collection. HLA typing was performed to determine DQB1*02 allele dose. Patients were divided into risk groups by DQB1*02 allele dose, as follows: high-, intermediate- and low-risk groups corresponded to a double, single and zero doses, respectively. We used ANOVA and Pearson's chi-squared test to explore association between HLA risk and clinical variables.A total of 727 coeliac patients attended the clinics but only 105 (14.4%) patients were eligible for inclusion. High, intermediate and low HLA risk patients comprised 35.3%, 52.3% and 12.3% of the study population, respectively. Double dose of HLA-DQB1*02 was more frequent in patient with high tTGA level (>10 times the upper limit of normal; p = 0.045). Gene dose was not associated with younger age at diagnosis (p = 0.549), gender (p = 0.739), more severe diagnostic histology (p = 0.318), more frequent classical presentation (p = 0.846), anaemia (p = 0.611), metabolic bone disease (p = 0.374), dermatitis herpetiformis (p = 0.381) and autoimmune diseases (p = 0.837).Our study shows a significant gene dose effect in terms of tTGA level at diagnosis, but no significant association between HLA-DQB1*02 allele dose and the clinical outcomes in CD.

Atrial fibrillation (AF) is the most common arrhythmia diagnosed in clinical practice. We aimed to measure the L-arginine pathway metabolites as well as their ratios in patients with different types of AF or sinus rhythm and to explore the relationship among the markers and clinical variables in the subacute phase of acute ischemic stroke (AIS).A total of 46 patients with AIS were prospectively enrolled. The patients were divided into three groups based on diagnosis of either sinus rhythm, paroxysmal or permanent AF. Plasma concentration of the L-arginine pathway metabolites were analyzed at post-stroke 24 hours in the three rhythm groups. Besides, clinical variables and laboratory data were recorded.Asymmetric dimetylarginine (ADMA) was significantly higher in patients with permanent AF compared to sinus rhythm (p0.001). Both ADMA (p0.001) and symmetric dimethylarginine (SDMA) (p0.002) at 24 hours were significantly higher among patients with permanent AF compared to those with paroxysmal AF. The L-arginine/SDMA (p0.031) ratios at 24 hours were significantly higher among patients with sinus rhythm compared to those with permanent AF. ROC analysis also revealed that plasma SDMA cut-off level over 0.639 μmol/L discriminated permanent AF from paroxysmal AF or sinus rhythm with a 90.9% sensitivity and 77.1% specificity. Neutrophil-lymphocyte ratio also showed significantly higher value in individuals with both paroxysmal and permanent AF (p=0.029).Plasma level of SDMA could discriminate permanent from paroxysmal AF in the subacute phase of ischemic stroke. In addition, an increased neutrophil-lymphocyte ratio may suggest inflammatory process in the evolution of atrial fibrillation.Bevezetés - A pitvari fibrilláció (PF) a klinikai gyakorlatban diagnosztizált leggyakoribb aritmia. Célul tűztük ki az L-arginin-útvonal metabolitjainak, valamint azok arányának mérését különböző típusú PF-ben szenvedő vagy sinusritmusban lévő betegeknél, és az akut ischaemiás stroke (AIS) szubakut fázisában, a fenti markerek és klinikai változók közötti kapcsolat elemzését. Módszerek - Összesen 46, AIS-ben szenvedő beteg bevo­nására került sor. A betegeket három csoportra osztottuk, sinusritmusban lévő, paroxysmalis vagy permanens PF-fel rendelkező csoportokra. Az L-arginin-útvonal metabolitjainak plazmakoncentrációját a három ritmuscsoportban az ictus kezdete után 24 órával mértük meg. Emellett a betegek klinikai és laboratóriumi adatait is rögzítettük. Eredmények - Az aszimmetrikus dimetil-arginin (ADMA) szintje szignifikánsan magasabb volt a permanens PF-ben szenvedő betegeknél a sinusritmushoz képest (p0,001). Huszonnégy órával a stroke kezdete után mind az ADMA (p0,001), mind a szimmetrikus dimetil-arginin szintje (SDMA) (p0,002) szignifikánsan magasabb volt a permanens PF-ben szenvedő betegeknél, mint paroxysmalis PF esetén. Az L-arginin / SDMA (p0,031) arány szignifikánsan magasabb volt a sinusritmusban lévő betegekhez képest, mint a permanensen pitvarfibrillálóknál. A reciever operating characteristic (ROC-) analízis alapján a plazma 0,639 μmol/l-nél nagyobb SDMA szintje (cut-off) 90,9%-os szenzitivitással és 77,1%-os specificitással megkülönbözteti a permanens PF-et a sinusritmustól, illetve a paroxysmalis PF-től. A neutrophyl-lymphocyta arány szignifikánsan magasabb értéket mutatott mind a paroxysmalis, mind a permanens PF-ben (p = 0,029). Következtetések - Az ischaemiás stroke szubakut fázisában az SDMA plazmaszintje alapján megkülönböztethető a paroxysmalis PF a permanens PF-től. Ezenkívül a megnövekedett neutrophyl-lymphocyta arány a gyulladásos folyamat szerepére világíthat rá a pitvarfibrilláció kialakulásában, fenntartásában.

ObjectiveThe 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.MethodsThe data search was performed in 3 major databases (PubMed, Embase, and Cochrane Library). The selecte

IntroductionThe impact of remote monitoring (RM) on clinical outcomes in heart failure (HF) patients with cardiac resynchronisation therapy-defibrillator (CRT-D) implantation is controversial. This study sought to evaluate the performance of an RM follow-up protocol using modified criteria of the PARTNERS HF trial in comparison with a conventional follow-up scheme.Material and methodsWe compared cardiovascular (CV) mortality (primary endpoint) and hospitalisation events for decompensated HF, and the number of ambulatory in-office visits (secondary endpoint) in CRT-D implanted patients with automatic RM utilising daily transmissions (RM group, n = 45) and conventional follow-up (CFU group, n = 43) in a single-centre observational study.ResultsAfter a median follow-up of 25 months, a significant advantage was seen in the RM group in terms of CV mortality (1 vs. 6 death event, p = 0.04), although RM follow-up was not an independent predictor for CV mortality (HR = 0.882; 95% CI: 0.25–3.09; p = 0.845). Patient CV mortality was independently influenced by hospitalisation events for decompensated HF (HR = 3.24; 95% CI: 8–84; p = 0.022) during follow-up. We observed significantly fewer hospitalisation events for decompensated HF (8 vs. 29 events, p = 0.046) in the RM group. Furthermore, a decreased number of total (161 vs. 263, p < 0.01) and unnecessary ambulatory in-office visits (6 vs.19, p = 0.012) were seen in the RM group as compared to the CFU group.ConclusionsFollow-up of CRT-D patients using automatic RM with daily transmissions based on modified PARTNERS HF criteria enabled more effective ambulatory interventions leading indirectly to improved CV survival. Moreover, RM directly decreased the number of HF hospitalizations and ambulatory follow-up burden compared to CRT-D patients with conventional follow-up.

With repeated positivity being an undiscovered and major concern, we aimed to evaluate which prognostic factors may impact repeated SARS-CoV-2 positivity (RSP) and their association with immunoglobulin detectability among recovered patients. A systematic literature search was performed on 5 April 2021. Cohort studies with risk factors for repeated RSP or information about the immunoglobulin response (immunoglobulin M (IgM) and/or immunoglobulin G (IgG)) were included in this analysis. The main examined risk factors were severity of the initial infection, body mass index (BMI), length of hospitalization (LOH), age, and gender, for which we pooled mean differences and odds ratios (ORs). Thirty-four cohort studies (N = 9269) were included in our analysis. We found that increased RSP rate might be associated with IgG positivity; IgG presence was higher in RSP patients (OR: 1.72, CI: 0.87–3.41, p = 0.117). Among the examined risk factors, only mild initial disease course showed a significant association with RSP (OR: 0.3, CI: 0.14–0.67, p = 0.003). Age, male gender, BMI, LOH, and severity of the first episode do not seem to be linked with repeated positivity. However, further prospective follow-up studies focusing on this topic are required.

Background: The most common pre-existing liver disease, the metabolic dysfunction-associated fatty liver disease (MAFLD) formerly named as non-alcoholic fatty liver disease (NAFLD), may have a negative impact on the severity of COVID-19. This meta-analysis aimed to evaluate if MAFLD or NAFLD are associated with a more severe disease course of COVID-19.Methods: A systematic search was performed in five databases for studies comparing severity, the rate of intensive care unit (ICU) admission, and mortality of COVID-19 patients with and without MAFLD or NAFLD. In meta-analysis, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.Results: Altogether, we included nine studies in our quantitative and qualitative synthesis. MAFLD was associated with an increased risk of severe COVID-19 compared to the non-MAFLD group (28 vs. 13%, respectively; OR = 2.61, CI: 1.75–3.91). Similarly, in the NAFLD vs. non-NAFLD comparison, NAFLD proved to be a risk factor as well (36 vs. 12%, respectively; OR = 5.22, CI: 1.94–14.03). On the other hand, NAFLD was not associated with an increased risk of ICU admission (24 vs. 7%, respectively; OR = 2.29, CI: 0.79–6.63). We were unable to perform meta-analysis to investigate the association of MAFLD with the rate of ICU admission and with mortality.Conclusion: In conclusion, patients with MAFLD and NAFLD showed a more severe clinical picture in COVID-19. Our results support the importance of close monitoring of COVID-19 patients with MAFLD. Further research is needed to explore the cause of increased severity of COVID-19 in MAFLD.

Aims: The restoration of coronary circulation plays a crucial role in treating ST-segment elevation myocardial infarction (STEMI), however successful reperfusion with primary percutaneous coronary intervention (PPCI) may induce life-threatening arrhythmias. The relation between myocardial electrical instability, as a background factor in reperfusion arrhythmia, and magnesium administered periprocedurally is still questionable. Several randomized clinical trials have been conducted predominantly in the thrombolysis era. Due to the contradictory results of these studies, there is little evidence of the potential preventive effect of magnesium on reperfusion arrhythmias. The aim of our study is to review and meta-analytically analyze data from all studies published so far in the PPCI era, comparing STEMI patients who have undergone primary PCI and received either magnesium or a placebo before the reperfusion procedure.Methods and Results: Our meta-analysis follows the points in the PRISMA protocol and, meets all of their criteria. We conducted a search in five scientific databases using the following keyword combination: (myocardial infarction OR myocardial injury OR acute coronary syndrome OR acs OR stemi) AND magnesium. The 7,295 collected publications were filtered with the Endnote program by title, abstract and full-text based on predefined criteria. A statistical analysis was performed on three randomized-controlled trials using three common parameters, involving 336 patients Trial sequential analysis (TSA) was applied to assess the risk of random error associated with sparse data and multiple testing which can affect cumulative meta-analysis. The incidence of ventricular tachycardias (VTs) was not significantly increased in the non-magnesium control group. (OR: 1.36; CI: 0.619; −2.986, P = 0.263). For the ejection fraction (EF), a non-significant decrease was observed in the magnesium group by weighted mean difference calculation. (WMD: 7.262, 95% CI: −0.238; 0.053; P = 0.057). There was significant decrease in the infarct zone wall motion index (IZWMSI) in the magnesium treatment group. (WMD: 0.384, 95% CI: −0.042; 0.811, P = 0.015). Based on the TSA assessments, the results of all parameters are not significant, objectively demonstrating the lack of reasonable data pertaining to our question.Conclusions: The preventive effect of magnesium on reperfusion arrhythmia associated with primary PCI can still be considered contradictory based on previous studies. In our study, we found, that magnesium is ineffective with a very weak evidence, due to the small number of patients and the biases of the included studies, and a well-designed clinical trial is needed in this area, based on the TSA.

BackgroundThe epidemiology of esophageal cancer has changed dramatically over the past 4 decades in many Western populations. We aimed to understand the Hungarian epidemiologic trends of esophageal squamous cell cancer (SCC) and adenocarcinoma (AC).MethodsWe performed a cross-sectional study using data from esophageal cancer patients diagnosed between 1992 and 2018 at eight tertiary referral centers in four major cities of Hungary. We retrospectively identified cases in the electronic databases of each center and collected data on gender, age at diagnosis, year of diagnosis, specialty of the origin center, histological type, and localization of the tumor. Patients were grouped based on the two main histological types: AC or SCC. For statistical analysis, we used linear regression models, chi-square tests, and independent sample t tests.ResultsWe extracted data on 3,283 patients with esophageal cancer. Of these, 2,632 were diagnosed with either of the two main histological types; 737 had AC and 1,895 SCC. There was no significant difference in the gender ratio of the patients between AC and SCC (80.1 vs 81.8% males, respectively; p = 0.261). The relative incidence of AC increased over the years (p < 0.001, b = 1.19 CI: 0.84–1.54). AC patients were older at diagnosis than SCC patients (64.37 ± 11.59 vs 60.30 ± 10.07 years, p < 0.001). The age of patients at the diagnosis of primary esophageal cancer increased over time (p < 0.001, R = 0.119).ConclusionsThe rapid increase in the relative incidence of AC and simultaneous decrease of the relative incidence of SCC suggest that this well-established Western phenomenon is also present in Hungary.

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 p 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.

In Sub-Saharan Africa, African giant pouched rats (Cricetomys gambianus) are trained to identify TB patients by smelling sputum. We conducted a systematic review and meta-analysis of the data to see if this novel method is comparable to traditional laboratory screening and detection methods like Ziehl–Neelsen stain-based assays (ZN) and bacterial culture. The search and data processing strategy is registered at PROSPERO (CRD42019123629). Medline via PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched for the keywords “pouched rat” and “tuberculosis”. Data from 53,181 samples obtained from 24,600 patients were extracted from seven studies. Using sample-wise detection, the sensitivity of the studies was 86.7% [95% CI 80.4–91.2%], while the specificity was 88.4% [95% CI 79.7–93.7%]. For patient-wise detection, the sensitivity was 81.3% [95% CI 64.0–91.4%], while the specificity was 73.4% [95% CI 62.8–81.9%]. Good and excellent classification was assessed by hierarchical summary receiver-operating characteristic analysis for patient-wise and sample-wise detections, respectively. Our study is the first systematic review and meta-analysis of the above relatively inexpensive and rapid screening method. The results indicate that African giant pouched rats can discriminate healthy controls from TB individuals by sniffing sputum with even a higher accuracy than a single ZN screening.

Summary The disease course of COVID‐19 varies from asymptomatic infection to critical condition leading to mortality. Identification of prognostic factors is important for prevention and early treatment. We aimed to examine whether obesity is a risk factor for the critical condition in COVID‐19 patients by performing a meta‐analysis. The review protocol was registered onto PROSPERO (CRD42020185980). A systematic search was performed in five scientific databases between 1 January and 11 May 2020. After selection, 24 retrospective cohort studies were included in the qualitative and quantitative analyses. We calculated pooled odds ratios (OR) with 95% confidence intervals (CIs) in meta‐analysis. Obesity was a significant risk factor for intensive care unit (ICU) admission in a homogenous dataset (OR = 1.21, CI: 1.002‐1.46; I2 = 0.0%) as well as for invasive mechanical ventilation (IMV) (OR = 2.05, CI: 1.16‐3.64; I2 = 34.86%) in COVID‐19. Comparing body mass index (BMI) classes with each other, we found that a higher BMI always carries a higher risk. Obesity may serve as a clinical predictor for adverse outcomes; therefore, the inclusion of BMI in prognostic scores and improvement of guidelines for the intensive care of patients with elevated BMI are highly recommended.

Background: COVID-19 is a serious and potentially deadly disease Early diagnosis of infected individuals will play an important role in stopping its further escalation The present gold standard for sampling is the nasopharyngeal swab method However, several recent papers suggested that saliva-based testing is a promising alternative that could simplify and accelerate COVID-19 diagnosis Objectives: Our aim was to conduct a meta-analysis on the reliability and consistency of SARS-CoV-2 viral RNA detection in saliva specimens Methods: We have reported our meta-analysis according to the Cochrane Handbook We searched the Cochrane Library, Embase, Pubmed, Scopus, Web of Science and clinical trial registries for eligible studies published between 1 January and 25 April 2020 The number of positive tests and the total number of tests conducted were collected as raw data The proportion of positive tests in the pooled data were calculated by score confidence-interval estimation with the Freeman-Tukey transformation Heterogeneity was assessed using the I (2) measure and the χ(2)-test Results: The systematic search revealed 96 records after removal of duplicates Twenty-six records were included for qualitative analysis and 5 records for quantitative synthesis We found 91% (CI 80-99%) sensitivity for saliva tests and 98% (CI 89-100%) sensitivity for nasopharyngeal swab (NPS) tests in previously confirmed COVID-19 patients, with moderate heterogeneity among the studies Additionally, we identified 18 registered, ongoing clinical trials of saliva-based tests for detection of the virus Conclusion: Saliva tests offer a promising alternative to NPS for COVID-19 diagnosis However, further diagnostic accuracy studies are needed to improve their specificity and sensitivity

Disturbance of consciousness (DOC) may develop in acute pancreatitis (AP). In clinical practice, it is known that DOC may worsen the patient's condition, but we have no exact data on how DOC affects the outcome of AP.From the Hungarian Pancreatic Study Groups' AP registry, 1220 prospectively collected cases were analyzed, which contained exact data on DOC, included patients with confusion, delirium, convulsion, and alcohol withdrawal, answering a post hoc defined research question. Patients were separated to Non-DOC and DOC, whereas DOC was further divided into non-alcohol related DOC (Non-ALC DOC) and ALC DOC groups. For statistical analysis, independent sample t-test, Mann-Whitney, Chi-squared, or Fisher exact test were used.From the 1220 patients, 47 (3.9%) developed DOC, 23 (48.9%) cases were ALC DOC vs. 24 (51.1%) Non-ALC DOC. Analysis between the DOC and Non-DOC groups showed a higher incidence of severe AP (19.2% vs. 5.3%, p 0.001), higher mortality (14.9% vs. 1.7%, p 0.001), and a longer length of hospitalization (LOH) (Me = 11; IQR: 8-17 days vs. Me = 9; IQR: 6-13 days, p = 0.049) respectively. Patients with ALC DOC developed more frequently moderate AP vs. Non-ALC DOC (43.5% vs. 12.5%), while the incidence of severe AP was higher in Non-ALC vs. ALC DOC group (33.3% vs. 4.4%) (p 0.001). LOH showed a tendency to be longer in Non-ALC DOC compared to ALC DOC, respectively (Me:13; IQR:7-20 days vs. Me:9.5; IQR:8-15.5 days, p = 0.119).DOC during AP is associated with a higher rate of moderate and severe AP and increases the risk of mortality.

IntroductionAcute pancreatitis (AP) is a life-threatening inflammatory disease of the exocrine pancreas which needs acute hospitalisation. Despite its importance, we have significant lack of knowledge whether the lifestyle factors elevate or decrease the risk of AP or influence the disease outcome. So far, no synthetising study has been carried out examining associations between socioeconomic factors, dietary habits, physical activity, chronic stress, sleep quality and AP. Accordingly, LIFESPAN identifies risk factors of acute pancreatitis and helps to prepare preventive recommendations for lifestyle elements.Methods and analysisLIFESPAN is an observational, multicentre international case–control study. Participating subjects will create case and control groups. The study protocol was designed according to the SPIRIT guideline. Patients in the case group (n=1700) have suffered from AP (alcohol-induced, n=500; biliary, n=500; hypertriglyceridemiainduced, n=200; other, n=500); the control group subjects have no AP in their medical history. Our study will have three major control groups (n=2200): hospital-based (n=500), population-based (n=500) and aetiology-based (alcohol, n=500; biliary, n=500 and hypertriglyceridemia, n=200). All of them will be matched to the case group individually by gender, age and location of residence. Aggregately, 3900 subjects will be enrolled into the study. The study participants will complete a complex questionnaire with the help of a clinical research administrator/study nurse. Analysis methods include analysis of the continuous and categorical values.Ethics and disseminationThe study has obtained the relevant ethical approval (54175-2/2018/EKU) and also internationally registered (ISRCTN25940508). After obtaining the final conclusions, we will publish the data to the medical community and will also disseminate our results via open access.Trial registration numberISRCTN25940508; Pre-results.

BackgroundThe quadrivalent human papillomavirus (HPV) vaccine has been assumed to give protection against genital warts (GW) as well as cervical cancer. Our main question was whether HPV vaccine has any effects on the prevention of GW reported in randomised controlled clinical trials (RCTs) and time-trend analyses.MethodsThis meta-analysis was performed according to the PRISMA guidelines using the PICO format. We searched in three electronic databases (PubMed, Embase, Cochrane Trials), and assessed heterogeneity using the Q-test and I-squared statistics, meta-regression was also performed. Odds ratios (OR) and their confidence intervals (CI) were calculated. The sensitivity was tested by leave-one-out method. We evaluated the presence of publication bias using the funnel plot graph and the Copas selection model. The strength of evidence was assessed using the GRADE approach.ResultsEight RCTs (per-protocol populations) and eight time-trend ecological studies were included in this meta-analysis. A significant reduction (pooled OR = 0.03, 95% CI: 0.01–0.09; I-squared = 53.6%) of GW in young women was recorded in RCTs, and in time-trend analyses both in young women (pooled OR = 0.36, CI 95% = 0.26–0.51; I-squared = 98.2%), and in young men (pooled OR = 0.69, 95% CI = 0.61–0.78; I-squared = 92.7%). In subgroup analysis, a significant reduction of the number of GW events was observed especially in women under 21 years (pooled OR = 0.33, 95% CI = 0.17–0.63). Leave-one-out analysis showed that similar results could be obtained after excluding one study, meta-regression did not show significant difference.ConclusionsProphylactic, quadrivalent HPV vaccination can prevent GW in healthy women and men, therefore, it should be included in routine immunization programme.

Background: In steroid-refractory acute severe ulcerative colitis (ASUC), cyclosporine (CYS) or infliximab (IFX) may be considered as a second-line alternative to avoid colectomy. There are short-term data reported, but until now, there is no meta-analysis regarding long-term outcomes of CYS and IFX in patients with ASUC. Aim: To compare long-term efficacy and safety of CYS and IFX in a meta-analysis. Methods: Three electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials) were searched for studies which compared CYS vs. IFX in adults with ASUC. Long-term colectomy-free rate from 1 to 10 years during CYS or IFX therapy was collected, last updated up to 22nd May 2019. Primary outcome was long-term colectomy-free rate, secondary outcomes were adverse events (AE), serious adverse events (SAE), and mortality. Long-term colectomy-free survival and safety measures were pooled with the random-effect model. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. Results: Data from 1,607 patients in 15 trials were extracted. In the first 3 years, pooled OR for colectomy-free survival was higher with IFX than with CYS (OR = 1.59, 95% CI: 1.11-2.29, p = 0.012; OR = 1.57, 95% CI: 1.14-2.18, p = 0.006; and OR = 1.75, 95% CI: 1.08-2.84, p = 0.024; at 1, 2, and 3 years, respectively). However, the significant difference remained undetected from the fourth year of follow-up and in subgroup of RCTs (OR = 1.35, 95% CI: 0.90-2.01, p = 0.143; OR = 1.41, 95% CI: 0.94-2.12, p = 0.096; and OR = 1.34, 95% CI: 0.89-2.00, p = 0.157; at 1, 2, and 3 years, respectively). No significant difference was detected regarding adverse events, serious adverse events and mortality between the groups. The neutral associations proved to be underpowered with trial sequential analysis. Conclusion: However observational studies show IFX as a better choice, according to the RCTs, choosing either CYS or IFX as rescue therapy for ASUC, the long-term outcomes are not different, although further large RCTs are warranted.

Background Ovarian hyperstimulation syndrome (OHSS) is a rare, yet severe, iatrogenic complication of ovulation induction therapy during assisted reproductive procedures. Our group previously detected atypical cells in the ascitic fluid of OHSS patients, although no malignancy developed during follow up. Here, the aim was to perform a comparative analysis of the cytokines present in the abdominal fluid of patients affected by OHSS versus patients with advanced ovarian cancer, a benign adnexal mass, or ovarian endometriosis. Methods This prospective, non-randomized study was conducted at the Clinical Center of the University of Pecs Department of Obstetrics and Gynecology/Reproductive Center between October 2016 and March 2018. Abdominal fluid samples were obtained from 76 patients and subjected to Luminex analysis. The samples were collected from patients with OHSS (OHSS; n = 16), advanced ovarian cancer (OC; n = 22), a benign adnexal mass (BAM; n = 21), or ovarian endometriosis (EM; n = 17). Data were subjected to the non-parametric Kruskal-Wallis test and Spearman’s rank correlation coefficient to identify statistical differences between the four study groups. Results Leukocytosis and hemoconcentration were detected in the peripheral blood of OHSS patients. Abdominal fluid analysis further revealed significantly higher levels of interleukin (IL)-6, IL-8, IL-10, and transforming growth factor (TGF)-β in both the OHSS and OC groups compared to the BAM and EM groups. The highest concentration of vascular endothelial growth factor (VEGF) was detected in the OC group, while a significantly lower level was detected in the OHSS group. Moreover, VEGF levels in OC and OHSS groups were significantly elevated compared to the levels in the BAM and EM groups. Conclusions Vasoactive and hematogenic cytokines were present at higher levels in both the OHSS and OC abdominal fluid samples compared to the fluid samples obtained from the peritoneal cavity of the BAM patients. It is possible that these cytokines play an important role in the formation of ascites.

The prevalence of diabetes mellitus (DM) and acute pancreatitis (AP) increases continuously, therefore, to understand the effects of preexisting diabetes on AP is crucially needed. Here, we performed a systematic review and meta-analysis in which AP patients including DM and non-DM groups were sorted. Several outcome parameters were analyzed, and the odds ratio (OR) and standardized mean difference with 95% confidence intervals (CIs) were calculated.We found 1417 articles, of which 9 articles involving 354,880 patients were analyzed. More complications were seen in diabetic patients than in non-DM patients (OR, 1.553 [95% CI, 1.266-1.904]; P < 0.001). Intensive care unit admission (OR, 1.799 [95% CI, 1.442-2.243]; P < 0.001) and renal failure (OR, 1.585 [95% CI, 1.278-1.966]; P < 0.001) were more frequent in DM patients. There was a tendency of higher mortality and local complications (OR, 1.276 [95% CI, 0.991-1.643]; P = 0.059; and OR, 1.267 [95% CI, 0.964-1.659]; P = 0.090, respectively) in preexisting DM. Length of hospitalization was longer in DM patients (standardized mean difference, 0.217 [95% CI, 0.075-0.360]; P = 0.003). Preexisting DM negatively influences the outcome of AP and increases the risk of renal failure, local complications, and mortality.

The diagnosis of thrombophilia is a cost-consuming and time-consuming process, as each defect should be separately investigated. The Coagulation Inhibitor Potential (CIP) assay is a promising new global test, sensitive for most of the hereditary thrombophilias, developed for manual methodology. We adapt the original method to an optical coagulation analyser. By this automation, the test will be easier, faster and more precise, and it also allows carrying out 18 measurements simultaneously. The CIP assay was performed in 126 healthy subjects and 193 patients with different types of hereditary thrombophilia conditions. Detected with conventional laboratory tests high-risk thrombophilia was present in 70 patients: deficiencies of antithrombin (AT) (n = 12), protein C (PC) (n = 14), protein S (PS) (n = 6), homozygous factor V Leiden (FVL) mutation (n = 9) and combined types (n = 29). Low-risk thrombophilia was present in 123 patients: heterozygous FVL (n = 115) and FII G2010A mutation (n = 8). Significantly lower median CIP values were found for AT-,PC-, PS deficiencies, homozygous and heterozygous FVL mutations and combined thrombophilias (P < 0.01) as compared with healthy controls. There was no significant difference between the heterozygous FIIG20210A (P = 0.669) thrombophilia group and the healthy controls. The best performance of the test was achieved at the cut-off value of 90.0 U (area: 0.981) with 96% sensitivity and 92% specificity in the high-risk thrombophilia group estimated by receiver operating characteristic analysis. The new method seems to be appropriate and reliable for the detection of AT-, PC- and PS deficiencies, homozygous FVL mutation and also for combined deficiencies. The automated CIP test is insensitive to FII G2010A mutation.

Aims: In this observational study, we investigated whether specialized care improves outcomes for acute pancreatitis (AP).Methods: Consecutive patients admitted to two university hospitals with AP were enrolled in this study between 1 January 2016 and 31 December 2016 (Center A: specialized center; Center B: general hospital). Data on demographic characteristics and AP etiology, severity, mortality and quality of care (enteral nutrition and antibiotic use) were extracted from the Hungarian Acute Pancreatitis Registry. An independent sample t-test, Mann–Whitney test, chi-squared test or Fisher’s test were used for statistical analyses. Costs of care were calculated and compared in the two models of care.Results: There were 355 patients enrolled, 195 patients in the specialized center (Center A) and 160 patients in the general hospital (Center B). There was no difference in mean age (57.02 ±17.16 vs. 57.31 ±16.50 P=0.872) and sex ratio (56% males vs. 57% males, P=0.837) between centres, allowing a comparison without selection bias. Center A had lower mortality (n=2, 1.03% vs. n=16, 6.25%, p=0.007), more patients received enteral feeding (n=179, 91.8%, vs. n=36, 22.5%, p

Background and Aims Inflammatory bowel disease [IBD] is associated with a 1.5- to 3-fold increased risk of venous thromboembolism [VTE] events. The aim of this study was to determine the risk of VTE in IBD as a complication of systemic corticosteroids and anti-tumour necrosis factor alpha [TNFα] therapies. Methods A systematic review and meta-analysis was conducted, which conforms to the Preferred Reporting Items for Systematic Reviews and Meta-analyses [PRISMA] statement. PubMed, EMBASE, Cochrane Library and Web of Science were searched for English-language studies published from inception inclusive of 15 April 2017. The population-intervention-comparison-outcome [PICO] format and statistically the random-effects and fixed-effect models were used to compare VTE risk during steroid and anti-TNFα treatment. Quality of the included studies was assessed using the Newcastle-Ottawa scale. The PROSPERO registration number is 42017070084. Results We identified 817 records, of which eight observational studies, involving 58518 IBD patients, were eligible for quantitative synthesis. In total, 3260 thromboembolic events occurred. Systemic corticosteroids were associated with a significantly higher rate of VTE complication in IBD patients as compared to IBD patients without steroid medication (odds ratio [OR]: 2.202; 95% confidence interval [CI]: 1.698-2.856, p < 0.001). In contrast, treatment with anti-TNFα agents resulted in a 5-fold decreased risk of VTE compared to steroid medication [OR: 0.267; 95% CI: 0.106-0.674, p = 0.005]. Conclusion VTE risk should be carefully assessed and considered when deciding between anti-TNFα and steroids in the management of severe flare-ups. Thromboprophylaxis guidelines should be followed, no matter the therapy choice.

AIM To understand the influence of chronic kidney disease (CKD) on mortality, need for transfusion and rebleeding in gastrointestinal (GI) bleeding patients. METHODS A systematic search was conducted in three databases for studies on GI bleeding patients with CKD or end-stage renal disease (ESRD) with data on outcomes of mortality, transfusion requirement, rebleeding rate and length of hospitalization (LOH). Calculations were performed with Comprehensive Meta-Analysis software using the random effects model. Heterogeneity was tested by using Cochrane’s Q and I2 statistics. Mean difference (MD) and OR (odds ratio) were calculated. RESULTS 1063 articles (EMBASE: 589; PubMed: 459; Cochrane: 15) were found in total. 5 retrospective articles and 1 prospective study were available for analysis. These 6 articles contained data on 406035 patients, of whom 51315 had impaired renal function. The analysis showed a higher mortality in the CKD group (OR = 1.786, 95%CI: 1.689-1.888, P < 0.001) and the ESRD group (OR = 2.530, 95%CI: 1.386-4.616, P = 0.002), and a rebleeding rate (OR = 2.510, 95%CI: 1.521-4.144, P < 0.001) in patients with impaired renal function. CKD patients required more unit red blood cell transfusion (MD = 1.863, 95%CI: 0.812-2.915, P < 0.001) and spent more time in hospital (MD = 13.245, 95%CI: 6.886-19.623, P < 0.001) than the controls. CONCLUSION ESRD increases mortality, need for transfusion, rebleeding rate and LOH among GI bleeding patients. Prospective patient registries and observational clinical trials are crucially needed.

The body composition of patients with celiac disease (CD), on which the effects of a gluten-free diet (GFD) are controversial, differs from that of the average population. In this study, we aimed to compare the body composition across CD patients before a GFD, CD patients after a one-year GFD and non-celiac control subjects. A systematic search was conducted using five electronic databases up to 15 July 2021 for studies that reported at least one of the pre-specified outcomes. In meta-analyses, weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated. A total of 25 studies were eligible for systematic review, seven of which were included in meta-analysis. During a ≥1-year GFD, fat mass of CD patients, compared to that at baseline, significantly increased (WMD = 4.1 kg, 95% CI = 1.5 to 6.6, three studies). In CD patients after a ≥1-year GFD, compared to non-celiac controls, fat mass (WMD = −5.8 kg, 95% CI = −8.7 to −2.9, three studies) and fat-free mass (WMD = −1.9 kg, 95% CI = −3.0 to −0.7, three studies) were significantly lower. In conclusion, body composition-related parameters of CD patients differ from that of the non-celiac control subjects even after a longstanding GFD.

Aims The aims of this study were to investigate the potential of β-catenin as a biomarker for predicting cancer-specific survival, and to find a reproducible mode of evaluation of immunohistochemistry. Methods and results β-Catenin expression was analysed by immunohistochemistry in a cohort of 488 patients with conventional renal cell carcinoma (RCC) operated on between 2000 and 2010. The association between β-catenin expression and cancer-specific survival was assessed with univariate and multivariate Cox regression models in relation to conventional clinical pathological prognostic factors, and by Kaplan–Meier survival analysis with the log rank test. The univariate Cox regression model revealed an association of cytoplasmic β-catenin positivity and pathological variables with cancer-specific death. The multivariate Cox regression model analysis of tumours without metastatic disease at the first presentation identified the T-classification (P < 0.001) and cytoplasmic β-catenin positivity as risk factors for postoperative tumour progression. Specifically, cytoplasmic β-catenin expression was an independent factor indicating an unfavourable prognosis, with a four-fold higher risk of cancer-specific death (relative risk 4.017; 95% confidence interval 2.489–6.482; P < 0.001). The median survival time for patients with tumours showing cytoplasmic accumulation of β-catenin was 48 months, whereas the overall survival time was 166 months. Conclusions Cytoplasmic β-catenin expression is an independent prognostic factor for conventional RCC, and may help to identify patients with a high risk of cancer-specific death and to direct optimized active surveillance or adjuvant therapy.

Background C-reactive protein level (CRP) and white blood cell count (WBC) have been variably used in clinical trials on acute pancreatitis (AP). We assessed their potential role. Methods First, we investigated studies which have used CRP or WBC, to describe their current role in trials on AP. Second, we extracted the data of 1435 episodes of AP from our registry. CRP and WBC on admission, within 24 hours from the onset of pain and their highest values were analyzed. Descriptive statistical tools as Kruskal-Wallis, Mann-Whitney U, Levene’s F tests, Receiver Operating Characteristic (ROC) curve analysis and AUC (Area Under the Curve) with 95% confidence interval (CI) were performed. Results Our literature review showed extreme variability of CRP used as an inclusion criterion or as a primary outcome or both in past and current trials on AP. WBC is rarely used as an inclusion criterion and never as a primary outcome. In our cohort, CRP levels on admission poorly predicted mortality and severe cases of AP; AUC:0.669 (CI:0.569-0.770); AUC:0.681 (CI:0.601-0.761), respectively. CRP levels measured within 24 hours from the onset of pain failed to predict mortality or severity; AUC:0.741 (CI:0.627-0.854); AUC:0.690 (CI:0.586-0.793), respectively. The highest CRP during hospitalization had equally poor predictive accuracy for mortality and severity AUC:0.656 (CI:0.544-0.768); AUC:0.705 (CI:0.640-0.769) respectively. CRP within 24 hours from the onset of pain used as an inclusion criterion markedly increased the combined event rate of mortality and severe AP (13% for CRP>25mg/l and 28% for CRP>200mg/l). WBC count, both on admission and within 24 hours from the onset of pain, proved to be a poor predictor of mortality and severity of AP AUC: 0.648 (CI: 0.546-0750) AUC: 0.630 (CI: 0.563-0.696) respectively. In addition, its elevation as an inclusion criterion also failed to increase the event rate of mortality and severity. Conclusion CRP within 24 hours from the onset of pain as an inclusion criterion elevates event rates and reduces the number of patients required in trials on AP. d in trials on AP.

Background Composition of pericardial fluid (PF) may reveal immunological processes influencing oxidative stress and microcirculation of different tissues of the heart and may play a role in the course of myocardial infarction, atherosclerosis, and aortic stenosis. Patients and methods We investigated lymphocyte populations, cardiovascular markers and immunoglobulin composition in PF and blood samples of patients undergoing CABG operation and compared them to those who had aortic valve surgery. Results The amount of CD8 + T, NK, memoT and activated T-cytotoxic cells were elevated in PF compared to blood, but naiveT and activated T-helper cell ratio were lower in PF. Amount of activated T-helper cells and regulatory T-lymphocytes were elevated in CABG participants in both PF and blood. INKT cells represented the only regulatory lymphocyte population reaching significantly higher concentration in PF than in blood. IL-6 and MCP1 level were elevated in PF compared to blood and MCP1 plasma level was markedly elevated in CABG group. Conclusions Our study describes a comprehensive immunological analysis of PF in humans for the first time. We showed that the investigated lymphocyte populations and cardiovascular markers in PF have significantly different distribution compared to blood, and lymphocyte populations show different compartmentization in coronary disease and aortic stenosis.

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.

Despite the high rate of postoperative recurrence (POR) in Crohn's disease (CD), there is no widely accepted consensus on its prevention.To compare the efficacy of biological and conventional therapies in preventing POR of CD.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.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.Anti-TNFα agents are more effective in preventing clinical, endoscopic and histological POR than conventional therapies, even in nonselected CD patients.

Background and aimsExperimental data suggest that the HLA-DQ2 gene dose has a strong quantitative effect on clinical outcomes and severity of celiac disease (CD). We aimed to conduct a meta-analysis with systematic review to investigate the association between HLA-DQB1*02 gene doses and the characteristics of CD.MethodsWe searched seven medical databases for studies discussing HLA-DQB1 gene dose in CD and various disease characteristics, such as clinical presentation, histology, age at diagnosis, and comorbidities. Odds ratios (OR, for categorical variables) and weighted mean differences (for age) were calculated to compare patients with a double dose of HLA-DQB1*02 versus those with single and zero doses. Heterogeneity was tested with I2-statistics and explored by study subgroups (children and adults).ResultsTwenty-four publications were eligible for meta-analysis. Classical CD was more frequent with a double versus single dose of the HLA-DQB1*02 allele (OR = 1.758, 95%CI: 1.148-2.692, I2 = 0.0%). In pediatric studies, gene dose effect was more prominent (OR = 2.082, 95%CI: 1.189-3.646, I2 = 0.0% and OR = 3.139, 95%CI: 1.142-8.630, I2 = 0.0% for the comparisons of double versus single and double versus zero dose, respectively). Atrophic histology was more prevalent with a double versus zero dose (OR = 2.626, CI: 1.060-6.505, I2 = 21.3%). We observed no gene dose effect regarding diarrhea, age at diagnosis, the severity of villous atrophy, and the association with type 1 diabetes mellitus.ConclusionA double dose of HLA-DQB1*02 gene seems to predispose patients to developing classical CD and villous atrophy. Risk stratification by HLA-DQB1*02 gene dose requires further clarification due to the limited available evidence.

Repeated positivity and reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is a significant concern. Our study aimed to evaluate the clinical significance of repeatedly positive testing after coronavirus disease 2019 (COVID-19) recovery. We performed a systematic literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. With available individual patient data reporting on repeatedly SARS-CoV-2 positive (RSP) patients, case reports, and case series were included in this analysis. We performed a descriptive analysis of baseline characteristics of repeatedly positive cases. We assessed the cases according to the length of their polymerase chain reaction (PCR) negative interval between the two episodes. Risk factors for the severity of second episodes were evaluated. Overall, we included 123 patients with repeated positivity from 56 publications, with a mean repeated positivity length of 47.8 ± 29.9 days. Younger patients were predominant in the delayed (>90 days) recurrent positive group. Furthermore, comparing patients with RSP intervals of below 60 and above 60 days, we found that a more severe disease course can be expected if the repeated positivity interval is shorter. Severe and critical disease courses might predict future repeatedly positive severe and critical COVID-19 episodes. In conclusion, our results show that the second episode of SARS-CoV-2 positivity is more severe if it happens within 60 days after the first positive PCR. On the other hand, the second episode’s severity correlates with the first.

INTRODUCTION Hemorheology is the study of the flow properties of the blood and its elements, which, together with natural anticoagulants, are important determinants of cardiovascular events. This study aimed to assess hemorheological and natural anticoagulant profiles of patients with celiac disease (CeD) comprehensively. METHODS Our study is a case-control study (registered under ISRCTN49677481) comparing patients with CeD with age- and sex-matched control subjects (1:1). We measured erythrocyte deformability (ED) at high (3-30 Pa) and low shears (0.3-3 Pa), erythrocyte aggregation, whole blood viscosity, plasma viscosity, and natural anticoagulants (protein C, protein S, and antithrombin activity). Adherence to gluten-free diet was estimated through dietary interview and urine gluten immunogenic peptide (urine GIP) detection. RESULTS After matching, we analyzed the data of 100 study participants. ED at high shears was impaired in CeD (P < 0.05 for all shears, confirmed by random forest analysis) independently of findings on CeD-specific serological assessment and urine GIP detection but slightly dependently on dietary adherence (P = 0.025 for 30 Pa shear). ED at low shears seemed to be impaired only in urine GIP+ CeD patients (P < 0.05 for all comparisons with urine GIP- CeD patients and control subjects). All parameters describing erythrocyte aggregation and whole blood viscosity were shifted toward a prothrombotic direction in patients with CeD with poor dietary adherence compared with those with good dietary adherence. Plasma viscosity and activity of natural anticoagulants did not differ across groups. DISCUSSION We observed diet-dependent and diet-independent prothrombotic hemorheological alterations in CeD, which can contribute to the elevated cardiovascular risk. The untoward metabolic changes during gluten-free diet, which can further aggravate hemorheological status, may indicate the implementation of prevention strategies.(Equation is included in full-text article.).

To validate the Disease Activity Score 28 using ESR (DAS28-ESR) and CRP (DAS28-CRP), the Simplified Disease Activity Index and the Clinical Disease Activity Index used in RA for SSc patients.Seventy-seven SSc patients, 40 RA patients, 20 patients with primary RP (PRP) and 28 healthy volunteers were assessed. Besides the disease activity composite indices, the European Scleroderma Study Group Activity Index (EScSG-AI), the HAQ-DI, the Cochin Hand Function Scale and the Short Form Health Survey (SF36) were evaluated. The validation procedure included the assessment for truth, discrimination and feasibility.DAS28-ESR, DAS28-CRP, Simplified Disease Activity Index and Clinical Disease Activity Index showed significant correlation with EScSG-AI, HAQ-DI, Cochin Hand Function Scale and the physical component of SF36 (P0.001). All four indices discriminated patients with SSc from RA, PRS and healthy controls, respectively (P0.01). With the exception of DAS28-CRP, the other three indices also discriminated between subgroups of SSc based on value of EScSG-AI (⩽3 and3) (P0.05). All four disease activity composite indices showed a good inter- and intraobserver reliability based on repeated measures of two independent investigators (P0.001).All four disease activity composite indices were found to be valid measures for assessing arthritis in SSc. DAS28-ESR showed the best performance regarding reliability and construct validity.

Introduction We aimed to compare the antimicrobial efficacy of chlorhexidine (CHX) and sodium hypochlorite (NaOCl), 2 irrigants routinely used in root canal therapy of permanent teeth. Methods Electronic databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, were searched for randomized controlled trials published until March 2020. The meta-analysis of relative risk (RR) and standardized mean difference (SMD) was performed using a random effects model with a 95% confidence interval (CI). Subgroup analysis was performed for culture and molecular methods of bacterial detection. Results The literature search yielded 2110 records without duplicates. Eight studies were eligible for a systematic review. No significant differences in the incidence of samples with positive bacterial growth after irrigation (RR = 1.003; 95% CI, 0.729–1.380; P = .987) and mean bacterial number changes (SMD = 0.311; 95% CI, −0.368 to 0.991; P = .369) were observed between CHX and NaOCl in the culture and molecular subgroups. Heterogeneity in RR (I2 = 0%, P = .673) was low among studies, whereas considerable heterogeneity was observed in the analysis of SMD (I2 = 76.336%, P = .005). Conclusions Our findings suggest that both CHX and NaOCl can reduce bacterial infections after irrigation without any significant difference in antimicrobial efficacy between them. Although CHX and NaOCl showed similar efficacy, their molecular mechanisms were different. Therefore, they can be used as the main antibacterial root canal irrigants. However, our results were limited by inconsistencies among retrieved articles and a lack of clinically relevant outcomes. Further well-designed clinical studies are warranted to supplement our results.

Purpose To evaluate the effect of our current transition process on clinical outcomes in adolescent patients with inflammatory bowel diseases (IBD). Design and methods Two groups of patients with IBD diagnosed in pediatric care were compared retrospectively: Group A patients did not attend the transition process, while Group B patients entered the planned transition service. Outcomes at 1-year after transfer to adult care were evaluated. Results Forty-five patients with IBD diagnosed under the age of 18 years were identified of whom 35 had Crohn's disease and 10 had ulcerative colitis. Twenty-four patients were in Group A (without transition), and 21 patients in Group B (with at least one planned transition visit). Mean age at diagnosis was 15.1 ± 2.2 and 13.7 ± 3.0 years (p = 0.086), respectively. There were no significant differences in disease duration before transfer, Montreal classification at diagnosis, body mass index, anti-TNF therapy usage, and disease status at transfer between the two groups. A significantly higher number of Group B patients were in remission at 12 months after transfer when compared to patients in Group A (11 vs. 18, respectively, p = 0.037). There was a significant difference between groups regarding the number of scheduled visits within the examined period (9 vs. 16, p = 0.011, respectively). Conclusions Planned transition visits resulted in higher disease remission rate at 1-year follow-up after transfer from pediatric to adult health care system in adolescent patients with IBD. Practice implication Well-established transition programs in IBD are needed.