Emerging Conformational-Analysis Protocols from the RTCONF55-16K Reaction Thermochemistry Conformational Benchmark Set.

RTCONF55-16K is a new, reactive conformational data set based on cost-efficient methods to assess different conformational analysis protocols. Our reference calculations underpinned the accuracy of the CENSO (Grimme et al. J. Phys. Chem. A, 2021, 125, 4039) procedure and resulted in alternative recipes with different cost-accuracy compromises. Our general-purpose and economical protocols (CENSO-light and zero, respectively) were found to be 10-30 times faster than the original algorithm, adding only 0.4-0.7 kcal/mol absolute error to the relative free energy estimates.

The histologic fetal inflammatory response and neonatal outcomes: systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate the prognostic role of concomitant histological fetal inflammatory response with chorioamnionitis on neonatal outcomes through a systematic review and meta-analysis of existing literature. DATA SOURCES: The primary search was conducted on October 17, 2021, and it was updated on May 26, 2023, across 4 separate databases (MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, and Scopus) without using any filters. STUDY ELIGIBILITY CRITERIA: Observational studies reporting obstetrical and neonatal outcomes of infant-mother dyads with histological chorioamnionitis and histological fetal inflammatory response vs infant-mother dyads with histological chorioamnionitis alone were eligible. Studies that enrolled only preterm neonates, studies on neonates born before 37 weeks of gestation, or studies on neonates with very low birthweight (birthweight <1500 g) were included. The protocol was registered with the International Prospective Register of Systematic Reviews (registration number: CRD42021283448). METHODS: The records were selected by title, abstract, and full text, and disagreements were resolved by consensus. Random-effect model-based pooled odds ratios with corresponding 95% confidence intervals were calculated for dichotomous outcomes. RESULTS: Overall, 50 studies were identified. A quantitative analysis of 14 outcomes was performed. Subgroup analysis using the mean gestational age of the studies was performed, and a cutoff of 28 weeks of gestation was implemented. Among neonates with lower gestational ages, early-onset sepsis (pooled odds ratio, 2.23; 95% confidence interval, 1.76-2.84) and bronchopulmonary dysplasia (pooled odds ratio, 1.30; 95% confidence interval, 1.02-1.66) were associated with histological fetal inflammatory response. Our analysis showed that preterm neonates with a concomitant histological fetal inflammatory response are more likely to develop intraventricular hemorrhage (pooled odds ratio, 1.54; 95% confidence interval, 1.18-2.02) and retinopathy of prematurity (pooled odds ratio, 1.37; 95% confidence interval, 1.03-1.82). The odds of clinical chorioamnionitis were almost 3-fold higher among infant-mother dyads with histological fetal inflammatory response than among infant-mother dyads with histological chorioamnionitis alone (pooled odds ratio, 2.99; 95% confidence interval, 1.96-4.55). CONCLUSION: This study investigated multiple neonatal outcomes and found association in the case of 4 major morbidities: early-onset sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, and retinopathy of prematurity.

Dyspepsia-Like Symptoms in Helicobacter pylori-Negative Chronic Gastritis are Associated with ASCA-, ANCA-, and Celiac Seropositivity but Not with Other Autoimmune Parameters: A Single-Centre, Retrospective Cross-Sectional Study.

Introduction: Dyspeptic symptoms are frequent in the general population, with a high socioeconomic burden. Helicobacter pylori (H. pylori) might be a possible etiological factor; however, it is also common in H. pylori negative gastritis. Clarification of the underlying aetiology might be beneficial to set up the optimal treatment strategy for dyspepsia and chronic gastritis (CG) itself. We aimed to assess the prevalence of dyspeptic symptoms in patients with H. pylori negative CG and explore autoimmunity's possible role. Methods: This retrospective study included data from patients with H. pylori negative CG. Exclusion criteria were (1) acute gastritis; (2) reactive gastropathy; (3) subjects without any serology testing results; (4) H. pylori positivity; (5) presence of atrophy, intestinal metaplasia (IM), gastroesophageal reflux disease (GERD), ulcer, or cancer. The following endpoints were assessed (1) the rate of dyspepsia-like symptoms; (2) association between dyspepsia and autoimmune disease-related seromarker positivity (AISP); (3) frequency of other symptoms in CG and its association with AISP; (4) location of the inflammation and its association with AISP. Results: From a total of 285 patients, 175 were included in this study. Among these patients, 95 experienced dyspeptic symptoms (54.29%) and were associated more with AISP (p = 0.012), especially with celiac seropositivity (p = 0.045), anti-neutrophil cytoplasmic antibody (ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) positivity (p = 0.043). A significant association was not found with other tested autoimmune (AI)-related antibody positivity. Conclusion: Positivity of seromarkers of autoimmune diseases in chronic gastritis may predispose to have dyspeptic symptoms and may be the causative factor behind some cases of uninvestigated dyspepsia. These data suggest that further prospective studies are needed to clarify whether screening for autoantibodies in patients with dyspepsia is cost-effective and helps the earlier diagnosis of autoimmune diseases.

Network meta-analysis of randomized controlled trials on esophagectomies in esophageal cancer: The superiority of minimally invasive surgery.

BACKGROUND: Previous meta-analyses, with many limitations, have described the beneficial nature of minimal invasive procedures. AIM: To compare all modalities of esophagectomies to each other from the results of randomized controlled trials (RCTs) in a network meta-analysis (NMA). METHODS: We conducted a systematic search of the MEDLINE, EMBASE, Reference Citation Analysis (https://www.referencecitationanalysis.com/) and CENTRAL databases to identify RCTs according to the following population, intervention, control, outcome (commonly known as PICO): P: Patients with resectable esophageal cancer; I/C: Transthoracic, transhiatal, minimally invasive (thoracolaparoscopic), hybrid, and robot-assisted esophagectomy; O: Survival, total adverse events, adverse events in subgroups, length of hospital stay, and blood loss. We used the Bayesian approach and the random effects model. We presented the geometry of the network, results with probabilistic statements, estimated intervention effects and their 95% confidence interval (CI), and the surface under the cumulative ranking curve to rank the interventions. RESULTS: We included 11 studies in our analysis. We found a significant difference in postoperative pulmonary infection, which favored the minimally invasive intervention compared to transthoracic surgery (risk ratio 0.49; 95%CI: 0.23 to 0.99). The operation time was significantly shorter for the transhiatal approach compared to transthoracic surgery (mean difference -85 min; 95%CI: -150 to -29), hybrid intervention (mean difference -98 min; 95%CI: -190 to -9.4), minimally invasive technique (mean difference -130 min; 95%CI: -210 to -50), and robot-assisted esophagectomy (mean difference -150 min; 95%CI: -240 to -53). Other comparisons did not yield significant differences. CONCLUSION: Based on our results, the implication of minimally invasive esophagectomy should be favored.

Furtive small bowel perforation after blunt abdominal trauma / Lopakodó vékonybél-perforatio: sebészi csapda

A rare case of delayed jejunal perforation is reported, with a time window of approximately five hours. The diagnosis is challenging: there are no proper protocols, planned early physical examination checkups are advised. The forensic medical aspects of the occasional therapeutical delays are remarkable.

Selective intraoperative cholangiography should be considered over routine intraoperative cholangiography during cholecystectomy: a systematic review and meta-analysis.

BACKGROUND: Decades of debate surround the use of intraoperative cholangiography (IOC) during cholecystectomy. To the present day, the role of IOC is controversial as regards decreasing the rate of bile duct injury (BDI). We aimed to review and analyse the available literature on the benefits of IOC during cholecystectomy. METHODS: A systematic literature search was performed until 19 October 2020 in five databases using the following search keys: cholangiogra* and cholecystectomy. The primary outcomes were BDI and retained stone rate. To investigate the differences between the groups (routine IOC vs selective IOC and IOC vs no IOC), we calculated weighted mean differences (WMD) for continuous outcomes and relative risks (RR) for dichotomous outcomes, with 95% confidence intervals (CI). RESULTS: Of the 19,863 articles, 38 were selected and 32 were included in the quantitative synthesis. Routine IOC showed no superiority compared to selective IOC in decreasing BDI (RR = 0.91, 95% CI 0.66; 1.24). Comparing IOC and no IOC, no statistically significant differences were found in the case of BDI, retained stone rate, readmission rate, and length of hospital stay. We found an increased risk of conversion rate to open surgery in the no IOC group (RR = 0.64, CI 0.51; 0.78). The operation time was significantly longer in the IOC group compared to the no IOC group (WMD = 11.25 min, 95% CI 6.57; 15.93). CONCLUSION: Our findings suggest that IOC may not be indicated in every case, however, the evidence is very uncertain. Further good quality research is required to address this question.

Prevalence of Autoimmune-phenomena behind Chronic Gastritis of Unknown Origin, and their Role in the Poor Histological Outcome of the Stomach: A Single-centre, Retrospective Cross-sectional Study.

BACKGROUND AND AIMS: The underlying aetiology of chronic gastritis (CG) often remains unknown due to its underrated significance in clinical practice. However, the role of chronic inflammation of the stomach in the development of atrophy, intestinal metaplasia (IM) and eventually of gastric cancer is well documented. We aimed to explore the possible aetiological factors of CG, determine the prevalence of systemic autoimmune disorders in patients with CG of unknown aetiology, and clarify the role of autoantibodies in the development of precancerous lesions in the stomach. METHODS: This is a retrospective, cross-sectional study, conducted from January 2016 to January 2020, including data from 175 patients with CG. Exclusion criteria were: (1) acute gastritis; (2) reactive gastropathy; (3) gastric cancer; (4) subjects without any serology testing results; and (5) Helicobacter pylori positivity. The primary endpoint was a composite endpoint involving gastric atrophy and IM. RESULTS: Fifty-five per cent of patients with CG had autoantibodies. Systemic lupus erythematosus (SLE)-related antibodies were positive in most of the cases, including antinuclear antibody (ANA) positivity, which was found in 19.13% of the patients. Autoimmune positivity was shown to be associated with precancerous lesions in the stomach (p<0.001): IM, atrophy and IM with atrophy. Anti-parietal cell antibody positivity seems to be a significant risk factor for IM and IM with atrophy. Autoimmune thyroiditis-related antibodies and ANA positivity by itself were only associated with atrophy; SLE-related antibodies and inflammatory bowel diseases related antibodies (ASCA and ANCA) correlated either with IM or with atrophy. No significant relation was found between any other investigated autoimmune disease-related antibodies and precancerous lesions. CONCLUSIONS: Autoimmune positivity often underlies gastritis of unknown aetiology and predisposes to precancerous lesions in the stomach. These antibodies can serve as non-invasive markers for the of optimal timing of an endoscopic follow-up strategy. Furthermore, CG can be an early symptom of a systemic autoimmune disorder.

Frailty and Emergency Surgery: Results of a Systematic Review and Meta-Analysis.

Background: Frailty, a "syndrome of loss of reserves," is a decade old concept. Initially it was used mainly in geriatrics but lately its use has been extended into other specialties including surgery. Our main objective was to examine the association between frailty and mortality, between frailty and length of hospital stay (LOS) and frailty and readmission within 30 days in the emergency surgical population. Methods: Studies reporting on frailty in the emergency surgical population were eligible. MEDLINE (via PubMed), EMBASE, Scopus, CENTRAL, and Web of Science were searched with terms related to acute surgery and frail*. We searched for eligible articles without any restrictions on the 2nd of November 2020. Odds ratios (OR) and weighted mean differences (WMD) were calculated with 95% confidence intervals (CI), using a random effect model. Risk of bias assessment was performed according to the recommendations of the Cochrane Collaboration. As the finally selected studies were either prospective or retrospective cohorts, the "Quality In Prognosis Studies" (QUIPS) tool was used. Results: At the end of the selection process 21 eligible studies with total 562.070 participants from 8 countries were included in the qualitative and the quantitative synthesis. Patients living with frailty have higher chance of dying within 30 days after an emergency surgical admission (OR: 1.99; CI: 1.76-2.21; p < 0.001). We found a tendency of increased LOS with frailty in acute surgical patients (WMD: 4.75 days; CI: 1.79-7.71; p = 0.002). Patients living with frailty have increased chance of 30-day readmission after discharge (OR: 1.36; CI: 1.06-1.75; p = 0.015). Conclusions: Although there is good evidence that living with frailty increases the chance of unfavorable outcomes, further research needs to be done to assess the benefits and costs of frailty screening for emergency surgical patients. Systematic Review Registration: The review protocol was registered on the PROSPERO International Prospective Register of Systematic Reviews (CRD42021224689).

Noninvasive ventilation improves the outcome in patients with pneumonia-associated respiratory failure: Systematic review and meta-analysis.

BACKGROUND: Noninvasive ventilation (NIV) is beneficial in exacerbations of chronic obstructive pulmonary disease (COPD), but its effectiveness in pneumonia-associated respiratory failure is still controversial. In the current meta-analysis, we aimed to investigate whether the use of NIV before intubation in pneumonia improves the mortality and intubation rates of respiratory failure as compared to no use of NIV in adults. METHODS: We searched three databases from inception to December 2019. We included studies, in which pneumonia patients were randomized initially into either NIV-treated or non-NIV-treated groups. Five full-text publications, including 121 patients, reported eligible data for statistical analysis. RESULTS: With NIV the overall hospital mortality rate seemed lower in patients with pneumonia-associated respiratory failure, but this was not significant [odds ratio (OR) = 0.39; 95% confidence interval (CI): 0.13-1.14; P = 0.085]. In the intensive care unit, the mortality was significantly lower when NIV was applied compared to no NIV treatment (OR = 0.22; 95% CI: 0.07-0.75; P = 0.015). NIV also decreased mortality compared to no NIV in patient groups, which did not exclude patients with COPD (OR = 0.25; 95% CI: 0.08-0.74; P = 0.013). The need for intubation was significantly reduced in NIV-treated patients (OR = 0.22; 95% CI: 0.09-0.53; P = 0.001), which effect was more prominent in pneumonia patient groups not excluding patients with pre-existing COPD (OR = 0.13; 95% CI: 0.03-0.46; P = 0.002). CONCLUSION: NIV markedly decreases the death rate in the intensive care unit and reduces the need for intubation in patients with pneumonia-associated respiratory failure. The beneficial effects of NIV seem more pronounced in populations that include patients with COPD. Our findings suggest that NIV should be considered in the therapeutic guidelines of pneumonia, given that future clinical trials confirm the results of our meta-analysis. AVAILABILITY OF DATA AND MATERIALS: All data and materials generated during the current study are available from the corresponding author on reasonable request.

Maternal overnutrition elevates offspring's blood pressure-A systematic review and meta-analysis.

BACKGROUND: Maternal overnutrition during pregnancy predisposes the offspring to cardiometabolic diseases. OBJECTIVES: This systematic review and meta-analysis aimed to investigate the association between maternal overnutrition and offspring's blood pressure (BP) and the effect of offspring's obesity on this association. DATA SOURCES: PubMed, EMBASE, Clinicaltrials.gov, CENTRAL. STUDY SELECTION AND DATA EXTRACTION: Human studies published in English before October 2021 were identified that presented quantitative estimates of association between maternal overnutrition just before or during pregnancy and the offspring's BP. SYNTHESIS: Random-effect model with the DerSimonian and Laird weighting method was used to analyse regression coefficients or mean differences. RESULTS: After selection, 17 observational studies (140,517 mother-offspring pairs) were included. Prepregnancy body mass index (ppBMI) showed positive correlation with BP in offspring (regression coefficient for systolic: 0.38 mmHg per kg/m2 , 95% confidence interval (CI) 0.17, 0.58; diastolic: 0.10 mmHg per kg/m2 , 95% CI 0.05, 0.14). These indicate 1.9 mmHg increase in systolic and 0.5 mmHg increase in diastolic BP of offspring with every 5 kg/m2 gain in maternal ppBMI. Results on coefficients adjusted for offspring's BMI also showed association (systolic: 0.08 mmHg per kg/m2 , 95% CI 0.04, 0.11; diastolic: 0.03 mmHg per kg/m2 , 95% CI 0.01, 0.04). Independent from ppBMI, gestational weight gain (GWG) showed positive correlation with systolic BP (systolic BP: 0.05 mmHg per kg, 95% CI 0.01, 0.09), but not after adjustment for offspring's BMI. Mean systolic BP was higher in children of mothers with excessive GWG than in those of mothers with optimal GWG (difference: 0.65 mmHg, 95% CI 0.25, 1.05). CONCLUSIONS: Independent from offspring's BMI, higher prepregnancy BMI may increase the risk for hypertension in offspring. The positive association between GWG and offspring's systolic BP is indirect via offspring's obesity. Reduction in maternal obesity and treatment of obesity in children of obese mothers are needed to prevent hypertension.

Dietary supplementation of transient receptor potential vanilloid-1 channel agonists reduces serum total cholesterol level: a meta-analysis of controlled human trials.

Abnormal cholesterol level is a major risk factor in the development of atherosclerosis, which is a fundamental derangement in cardiovascular diseases. Any efforts should be undertaken to lower blood cholesterol levels. Among dietary interventions, capsaicinoid supplementation is also considered as a novel cholesterol-lowering approach, but human studies concluded contradictory results about its effectiveness. The present meta-analysis aimed at determining the effects of capsaicinoids on serum lipid profile in humans. We searched the PubMed, EMBASE, and CENTRAL databases from inception to February 2021. We included 10 controlled studies, which involved 398 participants. We found that dietary capsaicinoid supplementation alone or in combination with other substances significantly (p = 0.004 and 0.001, respectively) reduced serum total cholesterol level compared to controls with an overall standardized mean difference of -0.52 (95% confidence interval: -0.83, -0.21). Capsaicinoids also decreased low-density lipoprotein level significantly (p = 0.035), whereas no effect was observed on serum levels of high-density lipoprotein and triglycerides. Our findings provide novel quantitative evidence for the efficacy of dietary capsaicin supplementation in lowering serum total cholesterol and low-density lipoprotein levels in humans. To validate our conclusion, further randomized controlled trials in a diverse population of adult humans receiving dietary capsaicinoid supplementation are warranted.

Hypoalbuminemia affects one third of acute pancreatitis patients and is independently associated with severity and mortality.

The incidence and medical costs of acute pancreatitis (AP) are on the rise, and severe cases still have a 30% mortality rate. We aimed to evaluate hypoalbuminemia as a risk factor and the prognostic value of human serum albumin in AP. Data from 2461 patients were extracted from the international, prospective, multicentre AP registry operated by the Hungarian Pancreatic Study Group. Data from patients with albumin measurement in the first 48 h (n = 1149) and anytime during hospitalization (n = 1272) were analysed. Multivariate binary logistic regression and Receiver Operator Characteristic curve analysis were used. The prevalence of hypoalbuminemia (< 35 g/L) was 19% on admission and 35.7% during hospitalization. Hypoalbuminemia dose-dependently increased the risk of severity, mortality, local complications and organ failure and is associated with longer hospital stay. The predictive value of hypoalbuminemia on admission was poor for severity and mortality. Severe hypoalbuminemia (< 25 g/L) represented an independent risk factor for severity (OR 48.761; CI 25.276-98.908) and mortality (OR 16.83; CI 8.32-35.13). Albumin loss during AP was strongly associated with severity (p < 0.001) and mortality (p = 0.002). Hypoalbuminemia represents an independent risk factor for severity and mortality in AP, and it shows a dose-dependent relationship with local complications, organ failure and length of stay.

Prevalence and Prognostic Significance of Hyponatremia in Patients With Lung Cancer: Systematic Review and Meta-Analysis.

Background: The prevalence of hyponatremia is highly variable among patients with lung cancer. However, its prevalence and prognostic significance in subgroups of patients with lung cancer have not yet been evaluated in a meta-analysis. Methods: We have registered our meta-analysis and review protocol to the PROSPERO International Prospective Register of Systematic Reviews, with the following registration number: CRD42020167013. A systematic search was done in the following sources: MEDLINE, Embase, CENTRAL, Web of Science, ClinicalTrials.gov, a WHO Global Health Library. Results: We identified a total of 8,962 potentially eligible studies, and we included 31 articles in our evaluation. The prevalence of hyponatremia in patients with lung cancer varied between 3 and 94.8% with an average of 25% without any significant differences between the following subgroups: histotype, gender, age, Eastern Cooperative Oncology Group (ECOG) state, and the extent of disease. The overall survival (OS) was significantly lower in hyponatremic compared to normonatremic patients at 10 months [RR.59 (95% CI.47-0.74), p < 0.001] and at 20 months [RR.44 (95% CI.33-0.59), p < 0.001], with worse survival rates in non-small cell lung cancer (NSCLC) [RR.27 (95% CI.12-0.44), p < 0.001] than in small cell lung cancer (SCLC) [RR.42 (95% CI.27-0.57), p < 0.001]. If hyponatremia was corrected, OS at 10 months was significantly higher than in the uncorrected hyponatremia group [RR 1.83 (95% CI 1.37-2.44), p < 0.001], but, at 20 months, no statistically significant difference could be found between these subgroups [RR 2.65 (95% CI.94-7.50), p = 0.067]. Conclusions: Patients with lung cancer diagnosed with hyponatremia, especially patients with NSCLC, seem to have significantly lower survival rates than normonatremic patients. If hyponatremia remains uncorrected, the mortality rates might be even higher.

Diabetes Mellitus Increases the Risk of Hepatocellular Carcinoma After Direct-Acting Antiviral Therapy: Systematic Review and Meta-Analysis.

Background: Hepatitis C virus (HCV)-infected patients treated with direct-acting antivirals (DAAs) are still at risk of developing hepatocellular carcinoma (HCC) after sustained virologic response (SVR). This study aimed to investigate the role of diabetes mellitus (DM) as a potential predictive risk factor in developing de novo HCC in HCV-infected patients after DAA treatment. Methods: This study was registered on PROSPERO under registration number CRD42021230457. We performed a systematic search in four medical databases from inception through November 3rd, 2020. Studies were eligible if they reported on HCV-infected patients treated with DAAs and compared the frequency of de novo HCC in patients with and without DM. We calculated pooled odds ratios, unadjusted (UHR), and adjusted hazard ratios (AHR) with 95% confidence intervals (CIs) in meta-analysis. Results: We included 30 articles in our systematic review and meta-analysis. DM proved to be a significant risk factor of HCC in DAA-treated HCV patients in unadjusted (UHR = 1.44, CI: 1.15-1.79) and adjusted analyses (AHR = 1.31, CI: 1.06-1.62). In the group of patients achieving SVR after DAA therapy, DM increased the risk of HCC in unadjusted (UHR = 1.3, CI: 1.09-1.51) analysis; however, in adjusted results, the risk was non-significant (AHR = 1.07, CI: 0.89-1.28). In patients with advanced liver fibrosis, DM was a risk factor for HCC in adjusted (AHR = 1.36, CI: 1.03-1.8), but not in unadjusted analysis (UHR = 1.11, CI: 0.8-1.42). Conclusions: DM is an independent risk factor of de novo HCC after DAA treatment in HCV-infected patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=230457, identifier: CRD42021230457.

Increased Prevalence of Celiac Disease in Patients with Cystic Fibrosis: A Systematic Review and Meta-Analysis.

OBJECTIVES: Immune regulation seems to be altered in cystic fibrosis (CF), thus potentially predisposing patients to developing autoimmune diseases (AID). In this meta-analysis, we aimed to evaluate the prevalence of celiac disease (CeD) among CF patients as by far the most commonly reported autoimmune disease in this population and, secondly, to review the observations on other, less frequently studied autoimmune diseases. METHODS: We conducted a systematic literature search for studies that discussed AIDs among CF patients. Following standard selection and data collection, we calculated pooled raw prevalence with 95% confidence intervals (CI) for biopsy-verified CeD and seropositivity. RESULTS: Out of the 21 eligible studies, 15 reported on CeD. Pooled prevalence of biopsy-verified CeD was 1.8% (CI 1.1-2.7%) according to a homogeneous dataset from six prospective, consecutive screening studies, while it proved to be 2.3% (CI 1.1-4.7%) according to a heterogeneous dataset from the other studies. Tissue transglutaminase IgA positivity was detected in 4.5% of CF cases (CI 2.8-6.9%), while tissue transglutaminase IgA-endomysial antibody IgA double positivity was found in 2.4% of them (CI 1.5-3.9%). Findings on other AIDs were strongly limited. CONCLUSIONS: The pooled prevalence of CeD in CF seemed to be more than twice as high compared to the global prevalence; therefore, routine screening of CeD could be considered in CF.

Initial Renal Function (eGFR) Is a Prognostic Marker of Severe Acute Pancreatitis: A Cohort-Analysis of 1,224 Prospectively Collected Cases.

Background: Acute pancreatitis (AP) is a life-threatening disease. We aimed to explore the prognostic relevance of renal function based on estimated glomerular filtration rate (eGFR). Methods: A prospective registry of AP patients was established by the Hungarian Pancreatic Study Group. Data of 1,224 consecutive patients were collected between 2012 and 2017. Patients were divided into 3 groups according to their eGFR measured within 24 h of hospitalization: normal renal function: >90 mL/min, mild to moderate renal functional impairment: 30-90 mL/min and severe renal dysfunction: <30 mL/min. Associations of eGFR with outcome (survival, length of hospitalization, AP severity, blood glucose), inflammatory markers (erythrocyte sedimentation rate, white blood cell count), anemia and organ failure (heart, kidney, liver) were analyzed. Results: Death, longer hospitalization and severe AP, but not the cause of AP, were significantly associated with lower eGFR. The inflammatory markers (CRP, WBC count) but not anemia (Hb, Htk) were closely associated with severe renal dysfunction. Renal function was associated with heart and renal failure but not with other complications of AP such as respiratory failure, local pancreatic complications, diabetes or peptic ulcer. eGFR was not associated with liver damage (ALAT, γ-GT) or liver function (serum bilirubin) although biliary complications, alcohol and metabolic syndrome were the most common etiologies of AP. Conclusions: Our study suggests a useful prognostic value of initial eGFR in AP patients. Even mild eGFR reduction predicted mortality, severity of AP and the length of hospitalization. Thus, precise evaluation of renal function should be considered for assessing AP severity and outcome.

Orally Administered Probiotics Decrease Aggregatibacter actinomycetemcomitans but Not Other Periodontal Pathogenic Bacteria Counts in the Oral Cavity: A Systematic Review and Meta-Analysis.

Introduction: At the initial part of the gastrointestinal tract, multiple tissues serve the normal function of food delivery. Periodontal structures are integral elements of these. When they deteriorate, it is extremely challenging to regenerate and reconstruct them. The conventional intervention for periodontal disease is scaling and root planning with the aim of reducing pathogenic bacteria. However, periodontal pathogens can rapidly recolonize treated areas. Probiotics have been proposed as novel tools for managing oral health by suppressing pathogenic bacteria through their anti-inflammatory effect, but the available data are controversial. Aim: Therefore, we performed a meta-analysis to study the effect of probiotics on periodontal pathogenic bacteria. Methods: The study was registered in PROSPERO under registration number CRD42018094903. A comprehensive literature search from four electronic databases (PubMed, Cochrane CENTRAL, Embase, and Web of Science) yielded nine eligible records for statistical analysis. Studies measuring bacterial counts in saliva and supra- and subgingival plaque were included. Bacterial counts were analyzed using standard mean difference (SMD) and by a random effects model with the DerSimonian-Laird estimation. Results: The results showed a significant decrease in the overall count of Aggregatibacter actinomycetemcomitans in the probiotic-treated group compared to the control at 4 weeks (SMD: -0.28; 95% CI: -0.56--0.01; p = 0.045) but not later. Analyzing the bacterial counts in subgroups, namely, in saliva and supra- and subgingival plaque, separately, yielded no significant difference. Probiotics had no significant effect on the overall count of Porphyromonas gingivalis at 4 weeks (SMD: -0.02; 95% CI: -0.35-0.31; p = 0.914) or later. Subgroup analysis also revealed no significant difference between treatment and control groups nor did probiotics significantly decrease the overall and subgroup bacterial counts of Prevotella intermedia, Tannerella forsythia, and Fusobacterium nucleatum. Conclusion: Our data support the beneficial effect of probiotics in reducing A. actinomycetemcomitans counts, but not of other key periodontal pathogenic bacteria in periodontal disease patients. However, due to the complex mechanism associated with periodontal disease and the limitations of the available studies, there is a further need for well-designed randomized clinical trials to assess the efficacy of probiotics.

Therapeutic Approach of Chronic Pseudomonas Infection in Cystic Fibrosis-A Network Meta-Analysis.

Pseudomonas infection is a major determinant of morbidity and mortality in cystic fibrosis (CF). Maintaining optimal lung function in CF patients carrying Pseudomonas remains a challenge. Our study aims to investigate the efficacy of antipseudomonal inhaled antibiotics in CF patients with chronic Pseudomonas infection. A Bayesian network meta-analysis of randomized controlled trials was conducted. The main outcomes were changes in: (a) forced respiratory volume (FEV1), (b) Pseudomonas aeruginosa sputum density, and (c) CF Questionnaire Revised Respiratory Symptom Score (CFQR-RSS) at 4 weeks follow-up. Eighteen trials which reported on treatment with aztreonam lysine, tobramycin, colistin, levofloxacin, fosfomycin/tobramycin, and amikacin in various dosages were eligible for inclusion. In terms of change in FEV1%, aztreonam lysine (t.i.d., 75 mg) with a 28-day run in the tobramycin phase, aztreonam lysine (b.i.d., 75 mg) with a 28-day run in the tobramycin phase had the highest probability of being the most effective treatment (SUCRAs were 77, 76%, respectively). Regarding change in Pseudomonas sputum density, aztreonam lysine (b.i.d., 75 mg) with a 28-day run in the tobramycin phase, aztreonam lysine (t.i.d., 75 mg) with a 28-day run in the tobramycin phase had the highest probability of being the most effective treatment (SUCRAs were 90, 86%, respectively). Regarding change in CFQR-RSS, aztreonam lysine (t.i.d., 75 mg) and aztreonam lysine (b.i.d., 75 mg) with a 28-day run in the tobramycin inhalation solution phase had the highest probability of being the most effective treatments (SUCRA:74% and 72%, respectively). Regarding changes in FEV1% and Pseudomonas sputum density, aztreonam lysine with a run in tobramycin phase may be the best treatment option in treating chronic Pseudomonas in CF. According to CFQR-RSS no significant differences were found. Given the limitations of the studies included, validation trials are called for.

Granulocyte and monocyte apheresis as an adjunctive therapy to induce and maintain clinical remission in ulcerative colitis: a systematic review and meta-analysis.

OBJECTIVE: The goal of treatment in ulcerative colitis (UC) is to induce and maintain remission. The addition of granulocyte and monocyte apheresis (GMA) to conventional therapy may be a promising therapeutic alternative. In this meta-analysis, we aimed to assess the efficacy and safety profile of GMA as an adjunctive therapy. DESIGN: Systematic review and meta-analysis. METHODS: We searched four databases (MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials) for randomised or minimised controlled trials which discussed the impact of additional GMA therapy on clinical remission induction and clinical remission maintenance compared with conventional therapy alone. Primary outcomes were clinical remission induction and maintenance, secondary outcomes were adverse events (AEs) and steroid-sparing effect. ORs with 95% CIs were calculated. Trial Sequential Analyses were performed to adjusts for the risk of random errors in meta-analyses. RESULTS: A total of 11 studies were eligible for meta-analysis. GMA was clearly demonstrated to induce and maintain clinical remission more effectively than conventional therapy alone (598 patients: OR: 1.93, 95% CI 1.28 to 2.91, p=0.002, I2=0.0% for induction; 71 patients: OR: 8.34, 95% CI 2.64 to 26.32, p<0.001, I2=0.0% for maintenance). There was no statistically significant difference in the number of AEs (OR: 0.27, 95% CI 0.05 to 1.50, p=0.135, I2=84.2%). CONCLUSION: GMA appears to be more effective as an adjunctive treatment in inducing and maintaining remission in patients with UC than conventional therapy alone. PROSPERO REGISTRATION NUMBER: CRD42019134050.

Macrophage migration inhibitory factor as a diagnostic and predictive biomarker in sepsis: meta-analysis of clinical trials.

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 < 0.001) and also higher than in patient groups with nonseptic systemic inflammation (SMD = 0.94; CI: 0.51-1.38; p < 0.001). Markedly greater elevation in blood MIF level was found in the more severe forms of sepsis and in nonsurvivors than in less severe forms and in survivors with SMDs of 0.84 (CI: 0.45-1.24) and 0.75 (CI: 0.40-1.11), respectively (p < 0.001 for both). In conclusion, blood MIF level is more elevated in systemic inflammation caused by infection (i.e., sepsis) compared to noninfectious causes. In more severe forms of sepsis, including fatal outcome, MIF levels are higher than in less severe forms. These results suggest that MIF can be a valuable diagnostic and prognostic biomarker in sepsis given that well-designed clinical trials validate our findings.