Evaluating the predictive value of late gadolinium enhancement assessed by cardiac magnetic resonance on sudden cardiac death in patients selected for implantable cardioverter defibrillator and cardiac resynchronization therapy implantation: a systematic review and meta-analysis.

AIMS: Late gadolinium enhancement (LGE) assessed by cardiovascular magnetic resonance (CMR) can evaluate myocardial scar associated with a higher risk of sudden cardiac death (SCD), which can guide the selection between cardiac resynchronization therapy with or without a defibrillator (CRT-P/CRT-D). Our aim was to investigate the association between LGE and SCD risk in patients with CRT using the LGE-CMR technique. METHODS AND RESULTS: We performed a systematic literature search using four databases. The target population was CRT candidates. The primary endpoint was SCD. The risk of bias was assessed using the QUIPS tool. Fifteen eligible articles were included with a total of 2494 patients, of whom 27%, 56%, and 19% had an implantable cardioverter defibrillator (ICD), CRT-D, and CRT-P, respectively. Altogether, 54.71% of the cohort was LGE positive, who had a 72% higher risk for SCD (HR 1.72; 95% CI 1.18-2.50) compared to LGE negatives. In non-ischemic patients, the proportion of LGE positivity was 46.6%, with a significantly higher risk for SCD as compared to LGE negatives (HR 2.42; 95% CI 1.99-2.94). The subgroup of CRT-only patients showed no difference between the LGE-positive vs. negative candidates (HR 1.17; 95% CI 0.82-1.68). Comparable SCD risk was observed between articles with short- (OR 7.47; 95% CI 0.54-103.12) vs. long-term (OR 6.15; 95% CI 0.96-39.45) follow-up time. CONCLUSION: LGE-CMR positivity was associated with an increased SCD risk; however, in CRT candidates, the difference in risk reduction between LGE positive vs. negative patients was statistically not significant, suggesting a role of reverse remodeling. LGE-CMR before device implantation could be crucial in identifying high-risk patients even in non-ischemic etiology.

Investigating the role of ultrasound-based shear wave elastography in kidney transplanted patients: correlation between non-invasive fibrosis detection, kidney dysfunction and biopsy results-a systematic review and meta-analysis.

INTRODUCTION: Interstitial fibrosis and tubular atrophy are leading causes of renal allograft failure. Shear wave elastography could be a promising noninvasive method for providing information on the state of the kidney, with specific regard to fibrosis but currently available data in the literature are controversial. Our study aimed to analyze the correlation between shear wave elastography and various kidney dysfunction measures. METHODS: This review was registered on PROSPERO (CRD42021283152). We systematically searched three major databases (MEDLINE, Embase, and CENTRAL) for articles concerning renal transplant recipients, shear wave elastography, fibrosis, and kidney dysfunction. Meta-analytical calculations for pooled Pearson and Spearman correlation coefficients (r) were interpreted with 95% confidence intervals (CIs). Heterogeneity was tested with Cochran's Q test. I2 statistic and 95% CI were reported as a measurement of between-study heterogeneity. Study quality was assessed with the QUADAS2 tool. RESULTS: In total, 16 studies were included in our meta-analysis. Results showed a moderate correlation between kidney stiffness and interstitial fibrosis and tubular atrophy, graded according to BANFF classification, on biopsy findings for pooled Pearson (r = 0.48; CI: 0.20, 0.69; I2 = 84%) and Spearman correlations (r = 0.57; CI: 0.35, 0.72; I2 = 74%). When compared to kidney dysfunction parameters, we found a moderate correlation between shear wave elastography and resistive index (r = 0.34 CI: 0.13, 0.51; I2 = 67%) and between shear wave elastography and estimated Glomerular Filtration Rate (eGFR) (r = -0.65; CI: - 0.81, - 0.40; I2 = 73%). All our outcomes had marked heterogeneity. CONCLUSION: Our results showed a moderate correlation between kidney stiffness measured by shear wave elastography and biopsy results. While noninvasive assessment of kidney fibrosis after transplantation is an important clinical goal, there is insufficient evidence to support the use of elastography over the performance of a kidney biopsy.

PARP inhibitor era in ovarian cancer treatment: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Ovarian cancer is the eighth leading cause of cancer-related death among women, characterized by late diagnosis and a high relapse rate. In randomized controlled trials, we aimed to evaluate the efficacy and safety of PARP inhibitors (PARPi) in treating advanced ovarian cancer. METHODS: This review was registered on PROSPERO (CRD42021283150), included all phase II and phase III randomized controlled trials (RCTs) assessing the effect of PARPi on ovarian cancer until the 13th of April, 2022. The main outcomes were progression- free survival (PFS), overall survival (OS), and adverse events (AEs). Pooled hazard ratios (HRs), and risk ratios (RRs) were calculated with 95% confidence intervals (95% CI). The random-effects model was applied in all analyses. RESULTS: In the meta-analysis, 16 eligible RCTs were included, with a total of 5,815 patients. In recurrent ovarian cancer, PARPi maintenance therapy showed a significant PFS benefit over placebo in the total population (HR 0.34, CI 0.29-0.40), BRCA mutant (HR 0.24, CI 0.18-0.31), germline BRCA mutant (HR 0.23, CI 0.18-0.30), and BRCA wild-type cases (HR 0.50, CI 0.39-0.65). PARPi monotherapy also improved PFS (HR 0.62, CI 0.51-0.76) compared with chemotherapy in BRCAm patients with recurrent ovarian cancer. The use of PARPi maintenance therapy resulted in an improvement in PFS over placebo in newly-diagnosed cancers in the overall population (HR 0.46, CI 0.30-0.71) and the BRCAm population (HR 0.36, CI 0.29-0.44). Although the risk of severe AEs was increased by PARPi therapy compared to placebo in most settings investigated, these side effects were controllable with dose modification, and treatment discontinuation was required in the minority of cases. CONCLUSIONS: PARPis are an effective therapeutic option for newly-diagnosed and recurrent ovarian cancer. Despite a minor increase in the frequency of serious adverse effects, they are generally well tolerated.

Ranking the dietary interventions by their effectiveness in the management of polycystic ovary syndrome: a systematic review and network meta-analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common condition in women, characterised by reproductive and metabolic dysfunction. While dietary approaches have been evaluated as a first-line treatment for patients with PCOS, there is limited evidence to support preference for a specific dietary composition. This systematic review and network meta-analysis was performed with the objective of comparing different dietary interventions in terms of positive impact. Metformin, the currently preferred treatment, was also compared. METHODS: The latest systematic search was performed on the 20th of March, 2023. Eligible randomised controlled trials (RCTs) included patients with PCOS and compared the dietary approach with another intervention or a standard diet. Outcomes were expressed via anthropometric measurements and hormonal, glycemic, and lipid levels. The Bayesian method was used to perform a network meta-analysis and to calculate the surface under the cumulative ranking curve (SUCRA) values in order to rank the dietary interventions. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. RESULTS: 19 RCTs were identified, comprising data from 727 patients who were variously treated with 10 types of dietary interventions and metformin. The Dietary Approaches to Stop Hypertension (DASH) diet was the most effective in reducing Homeostatic Model Assessment of Insulin Resistance (SUCRA 92.33%), fasting blood glucose (SUCRA 85.92%), fasting insulin level (SUCRA 79.73%) and triglyceride level (SUCRA 82.07%). For body mass index (BMI), the most effective intervention was the low-calorie diet (SUCRA 84.59%). For weight loss, the low-calorie diet with metformin (SUCRA 74.38%) was the most effective intervention. Metformin produced the greatest reductions in low-density lipoprotein cholesterol (SUCRA 78.08%) and total testosterone levels (SUCRA 71.28%). The low-carb diet was the most effective intervention for reducing cholesterol levels (SUCRA 69.68%), while the normal diet (SUCRA 65.69%) ranked first for increasing high-density lipoprotein cholesterol levels. CONCLUSION: Dietary interventions vary in their effects on metabolic parameters in women with PCOS. Based on our results, the DASH diet is the most effective dietary intervention for treating PCOS. Registration PROSPERO ID CRD42021282984.

The risk of developing splanchnic vein thrombosis in acute pancreatitis increases 3 days after symptom onset: A systematic review and meta-analysis.

BACKGROUND: Splanchnic vein thrombosis is a complication of acute pancreatitis (AP) and is likely often underdiagnosed. OBJECTIVES: We aimed to understand the time course and risk factors of splanchnic vein thrombosis in the early phase of AP. METHODS: A systematic search was conducted using the PRISMA guidelines (PROSPERO registration CRD42022367578). Inclusion criteria were appropriate imaging techniques in adult AP patients, studies that reported splanchnic vein thrombosis data from the early phase, and reliable information on the timing of imaging in relation to the onset of pancreatitis symptoms or hospital admission. The proportion of patients with thrombosis with 95% confidence intervals (CI) was calculated using random-effects meta-analyses, and multiple subgroup analyses were performed. RESULTS: Data from 1951 patients from 14 studies were analyzed. The proportion of patients with splanchnic vein thrombosis within 12 days after symptom onset was 0.13 (CI 0.07-0.23). The occurrence was lowest at 0.06 (CI 0.03-0.1) between 0 and 3 days after symptom onset, and increased fourfold to 0.23 (CI 0.16-0.31) between 3 and 11 days. On hospital admission, the proportion of patients affected was 0.12 (CI 0.02-0.49); it was 0.17 (CI 0.03-0.58) 1-5 days after admission. The prevalence in mild, moderate, and severe AP was 0.15 (CI 0.05-0.36), 0.26 (CI 0.15-0.43), and 0.27 (CI 0.17-0.4), respectively. Alcoholic etiology (0.31, CI 0.13-0.58) and pancreatic necrosis (0.55, CI 0.29-0.78, necrosis above 30%) correlated with increased SVT prevalence. CONCLUSION: The risk of developing splanchnic vein thrombosis is significant in the early stages of AP and may affect up to a quarter of patients. Alcoholic etiology, pancreatic necrosis, and severity may increase the prevalence of splanchnic vein thrombosis.

Persistently High Procalcitonin and C-Reactive Protein Are Good Predictors of Infection in Acute Necrotizing Pancreatitis: A Systematic Review and Meta-Analysis.

Infected necrotizing pancreatitis (INP) is associated with an increased risk of organ failure and mortality. Its early recognition and timely initiation of antibiotic therapy can save patients' lives. We systematically searched three databases on 27 October 2022. In the eligible studies, the presence of infection in necrotizing pancreatitis was confirmed via a reference test, which involved either the identification of gas within the necrotic collection through computed tomography imaging or the examination of collected samples, which yielded positive results in Gram staining or culture. Laboratory biomarkers compared between sterile necrotizing pancreatitis and INP were used as the index test, and our outcome measures included sensitivity, specificity, the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Within the first 72 hours (h) after admission, the AUC of C-reactive protein (CRP) was 0.69 (confidence interval (CI): 0.62-0.76), for procalcitonin (PCT), it was 0.69 (CI: 0.60-0.78), and for white blood cell count, it was 0.61 (CI: 0.47-0.75). After the first 72 h, the pooled AUC of CRP showed an elevated level of 0.88 (CI: 0.75-1.00), and for PCT, it was 0.86 (CI: 0.60-1.11). The predictive value of CRP and PCT for infection is poor within 72 h after hospital admission but seems good after the first 72 h. Based on these results, infection is likely in case of persistently high CRP and PCT, and antibiotic initiation may be recommended.

Comparison of Combined Parenteral and Oral Hormonal Contraceptives: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Delivering contraceptive hormones through a transdermal patch or a vaginal ring might have advantages over the traditional oral route. OBJECTIVES: To compare the effectiveness, compliance, and side effect profile of oral and parenteral drug administration methods. METHODS: We performed a systematic literature search in four medical databases-MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, and Scopus-from inception to 20 November 2022. Randomized controlled trials assessing the efficacy, compliance, and adverse event profile of combined parenteral and oral hormonal contraceptives were included. RESULTS: Our systematic search provided 3952 records; after duplicate removal, we screened 2707 duplicate-free records. A total of 13 eligible studies were identified after title, abstract, and full-text selection. We observed no significant difference in contraceptive efficacy (Pearl Index) between oral and parenteral drug administration (MD = -0.06, CI: -0.66-0.53; I2 = 0%). We found significant subgroup differences between parenteral methods in terms of compliance (χ2 = 4.32, p =0.038, I2 = 80%) and certain adverse events: breast discomfort (χ2 = 19.04, p =0.001, I2 = 80%), nausea (χ2 = 8.04, p =0.005, I2 = 75%), and vomiting (χ2 = 9.30, p =0.002; I2 = 72%). CONCLUSION: Both parenteral and oral contraceptives can be used as an effective contraceptive method, and the route of administration should be tailored to patient needs and adverse event occurrence.

Reducing the Risk of Birth Defects Associated with Maternal Influenza: Insights from a Hungarian Case-Control Study.

Influenza viruses can cause several complications during pregnancy. Therefore, we aimed to investigate the effects of influenza on the development of congenital abnormalities (CAs) by analyzing the database of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA). In our multicenter, case-control, population-based study, we processed clinician-reported outcomes and diagnoses collected in the HCCSCA. The case group included newborns with different non-chromosomal birth defects, while the controls were newborns without CAs. Maternal influenza, as a risk factor for CAs, was analyzed by using a logistic regression model and odds ratios with 95% confidence intervals (CIs). Our results showed that maternal influenza in the first trimester was associated with increased odds of developing non-chromosomal CAs (OR: 1.41, CI: 1.28-1.55). There were increased odds of neural tube defects (OR: 2.22, CI: 1.78-2.76), orofacial clefts (OR: 2.28, CI: 1.87-2.78), and congenital heart defects (OR: 1.28, CI: 1.10-1.49) after influenza infection. In all cases, we found a protective effect of folic acid supplementation in the first trimester. In summary, the odds of non-chromosomal birth defects are higher after maternal influenza in the first trimester, and folic acid or pregnancy vitamin supplementation and antipyretic therapy may reduce the effect of maternal influenza during the first trimester.

Potential benefits of restrictive transfusion in upper gastrointestinal bleeding: a systematic review and meta-analysis of randomised controlled trials.

The optimal red blood cell (RBC) transfusion strategy in acute gastrointestinal bleeding (GIB) is debated. We aimed to assess the efficacy and safety of restrictive compared to liberal transfusion strategies in the GIB population. We searched PubMed, CENTRAL, Embase, and Web of Science for randomised controlled trials on 15.01.2022 without restrictions. Studies comparing lower to higher RBC transfusion thresholds after GIB were eligible. We used the random effect model and calculated pooled mean differences (MD), risk ratios (RR) and proportions with 95% confidence intervals (CI) to calculate the overall effect size. The search yielded 3955 hits. All seven eligible studies reported on the upper GIB population. Restrictive transfusion did not increase the in-hospital- (RR: 0.94; CI 0.46, 1.94) and 30-day mortality (RR: 0.71; CI 0.35, 1.45). In-hospital- and 28 to 45-day rebleeding rate was also not higher with the restrictive modality (RR: 0.67; CI 0.30, 1.50; RR:0.75; CI 0.49, 1.16, respectively). Results of individual studies showed a lower rate of transfusion reactions and post-transfusion intervention if the transfusion was started at a lower threshold. A haemoglobin threshold > 80 g/L may result in a higher untoward outcome rate. In summary, restrictive transfusion does not appear to lead to a higher rate of significant clinical endpoints. The optimal restrictive transfusion threshold should be further investigated.

Fatty Pancreas Is a Risk Factor for Pancreatic Cancer: A Systematic Review and Meta-Analysis of 2956 Patients.

Pancreatic cancer (PC) is one of the most lethal cancers worldwide. Recently, fatty pancreas (FP) has been studied thoroughly, and although its relationship to PC is not fully understood, FP is suspected to contribute to the development of PC. We aimed to assess the association between PC and FP by conducting a systematic review and meta-analysis. We systematically searched three databases, MEDLINE, Embase, and CENTRAL, on 21 October 2022. Case-control and cross-sectional studies reporting on patients where the intra-pancreatic fat deposition was determined by modern radiology or histology were included. As main outcome parameters, FP in patients with and without PC and PC in patients with and without FP were measured. Proportion and odds ratio (OR) with a 95% confidence interval (CI) were used for effect size measure. PC among patients with FP was 32% (OR 1.32; 95% CI 0.42-4.16). However, the probability of having FP among patients with PC was more than six times higher (OR 6.13; 95% CI 2.61-14.42) than in patients without PC, whereas the proportion of FP among patients with PC was 0.62 (95% CI 0.42-0.79). Patients identified with FP are at risk of developing PC. Proper screening and follow-up of patients with FP may be recommended.

At admission hemodynamic instability is associated with increased mortality and rebleeding rate in acute gastrointestinal bleeding: a systematic review and meta-analysis.

Background: Acute gastrointestinal bleeding (GIB) is a life-threatening event. Around 20-30% of patients with GIB will develop hemodynamic instability (HI). Objectives: We aimed to quantify HI as a risk factor for the development of relevant end points in acute GIB. Design: A systematic search was conducted in three medical databases in October 2021. Data sources and methods: Studies of GIB patients detailing HI as a risk factor for the investigated outcomes were selected. For the overall results, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated based on a random-effects model. Subgroups were formed based on the source of bleeding. The Quality of Prognostic Studies tool was used to assess the risk of bias. Results: A total of 62 studies were eligible, and 39 were included in the quantitative synthesis. HI was found to be a risk factor for both in-hospital (OR: 5.48; CI: 3.99-7.52) and 30-day mortality (OR: 3.99; CI: 3.08-5.17) in upper GIB (UGIB). HI was also associated with higher in-hospital (OR: 3.68; CI: 2.24-6.05) and 30-day rebleeding rates (OR: 4.12; 1.83-9.31) among patients with UGIB. The need for surgery was also more frequent in hemodynamically compromised UGIB patients (OR: 3.65; CI: 2.84-4.68). In the case of in-hospital mortality, the risk of bias was high for 1 (4%), medium for 13 (48%), and low for 13 (48%) of the 27 included studies. Conclusion: Hemodynamically compromised patients have increased odds of all relevant untoward end points in GIB. Therefore, to improve the outcomes, adequate emergency care is crucial in HI. Registration: PROSPERO registration number: CRD42021285727.

Poly (ADP-ribose) Polymerase Inhibitors Have Comparable Efficacy with Platinum Chemotherapy in Patients with BRCA-positive Metastatic Castration-resistant Prostate Cancer. A Systematic Review and Meta-analysis.

CONTEXT: Testing for mutations in Breast Cancer Gene 1/2 (BRCA) has emerged as a novel decision-making tool for clinicians. Patients with metastatic castration-resistant prostate cancer (mCRPC) harboring pathogenic BRCA mutations can benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) and platinum treatments, whereas the impact of the mutation on sensitivity to cabazitaxel and prostate-specific membrane antigen (PSMA)-ligand therapy is currently unknown. OBJECTIVE: To assess the efficacy of PARPi, platinum, cabazitaxel, and PSMA-ligand therapies in BRCA-positive mCRPC. EVIDENCE ACQUISITION: Databases were queried in February 2022. We performed data synthesis by using both proportional and individual patient data. For prostate-specific antigen (PSA) response rate (≥50% decrease from baseline [PSA50]) evaluation, we pooled event rates with 95% confidence intervals (CIs). Progression-free (PFS) and overall (OS) survival analyses with individual patient data were performed with the mixed-effect Cox proportional hazard model and single-arm random-effect analysis, providing pooled medians. EVIDENCE SYNTHESIS: We included 23 eligible studies with 901 BRCA-positive mCRPC patients. PSA50 response rates for PARPi and platinum were 69% (CI: 53-82%), and 74% (CI: 49-90%), respectively. Analyses of OS data showed no difference between PARPi and platinum treatments (hazard ratio: 0.86; CI: 0.49-1.52; p = 0.6). The single-arm OS and PFS analyses revealed similarities among different PARPis; pooled PFS and OS medians were 9.7 mo (CI: 8.1-12.5) and 17.4 mo (CI: 12.7-20.1), respectively. CONCLUSIONS: Our data revealed that different PARPis were similarly effective in terms of PFS and OS. Moreover, we found that PARPi and platinum therapy were comparable in terms of PSA50 response rate and OS, highlighting that platinum is a valid treatment option for BRCA-positive mCRPC patients. However, prospective interventional studies comparing these agents are essential to provide a higher level of evidence. PATIENT SUMMARY: In this report, we found that different poly (ADP-ribose) polymerase inhibitors had similar efficacy, and platinum was a valid treatment option in BRCA-positive metastatic castration-resistant prostate cancer patients.

One in four patients with gastrointestinal bleeding develops shock or hemodynamic instability: A systematic review and meta-analysis.

BACKGROUND: Hemodynamic instability and shock are associated with untoward outcomes in gastrointestinal bleeding. However, there are no studies in the existing literature on the proportion of patients who developed these outcomes after gastrointestinal bleeding. AIM: To determine the pooled event rates in the available literature and specify them based on the bleeding source. METHODS: The protocol was registered on PROSPERO in advance (CRD42021283258). A systematic search was performed in three databases (PubMed, EMBASE, and CENTRAL) on 14th October 2021. Pooled proportions with 95%CI were calculated with a random-effects model. A subgroup analysis was carried out based on the time of assessment (on admission or during hospital stay). Heterogeneity was assessed by Higgins and Thompson's I2 statistics. The Joanna Briggs Institute Prevalence Critical Appraisal Tool was used for the risk of bias assessment. The Reference Citation Analysis (https://www.referencecitationanalysis.com/) tool was applied to obtain the latest highlight articles. RESULTS: We identified 11589 records, of which 220 studies were eligible for data extraction. The overall proportion of shock and hemodynamic instability in general gastrointestinal bleeding patients was 0.25 (95%CI: 0.17-0.36, I2 = 100%). In non-variceal bleeding, the proportion was 0.22 (95%CI: 0.14-0.31, I2 = 100%), whereas it was 0.25 (95%CI: 0.19-0.32, I2 = 100%) in variceal bleeding. The proportion of patients with colonic diverticular bleeding who developed shock or hemodynamic instability was 0.12 (95%CI: 0.06-0.22, I2 = 90%). The risk of bias was low, and heterogeneity was high in all analyses. CONCLUSION: One in five, one in four, and one in eight patients develops shock or hemodynamic instability on admission or during hospitalization in the case of non-variceal, variceal, and colonic diverticular bleeding, respectively.

Microscopic colitis is a risk factor for low bone density: a systematic review and meta-analysis.

Background: Microscopic colitis (MC) is a chronic inflammatory disease of the large bowel characterized by watery diarrhea, substantially decreasing the patient's quality of life. Scarce data suggest that MC is associated with low bone density (LBD). Objectives: We aimed to assess whether MC is a risk factor for LBD and the proportion of patients with MC having LBD. Design: A systematic review and meta-analysis of studies reporting bone density measurements in MC patients. Data Sources and Methods: We systematically searched five databases from inception to October 16, 2021 (Pubmed, Embase, Cochrane, Scopus, and Web of Science). We used the random-effect model to calculate pooled odds ratios (ORs) and pooled event rates with 95% confidence intervals (CIs). To ascertain the quality of evidence of our outcomes, we followed the recommendations of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group. Results: The systematic search yielded a total of 3046 articles. Four articles were eligible for quantitative synthesis. All of them used age- and sex-matched controls to evaluate LBD occurrence among patients with MC. The odds of having LBD were twofold increased (OR = 2.13, CI: 1.42-3.20) in the presence of MC, the odds of osteopenia occurrence were 2.4 (OR = 2.45, CI: 1.11-5.41), and of osteoporosis 1.4 (OR = 1.42, CI: 0.65-3.12). The proportion of LBD was 0.68 (CI: 0.56-0.78), osteopenia was 0.51 (CI: 0.43-0.58), and osteoporosis was 0.11 (CI: 0.07-0.16) among the MC population. Our findings' certainty of the evidence was very low following the GRADEPro guideline. Conclusion: Our data demonstrate that MC is associated with a twofold risk for LBD. Based on our findings, we suggest screening patients for bone mineral density upon diagnosis of MC. Further prospective studies with higher patient numbers and longer follow-up periods on this topic are needed. Registration: Our protocol was prospectively registered with PROSPERO (CRD42021283392).

Investigating microscopic colitis as a risk factor for having low bone density in a literature overview and statistical approach Microscopic colitis (MC) is an underdiagnosed chronic inflammatory large bowel disease, characterized by watery diarrhea, which substantially impacts the patient's quality of life. The etiology of MC is still unclear but is suspected to be multifactorial. Moreover, low bone density (LBD) has been associated with the disease. Scarce data investigate the relationship of MC with LBD, although they share common risk factors, like advanced age and female sex. LBD has two forms; the mild is osteopenia and the severe form is osteoporosis. The most severe complications of osteoporosis are osteoporotic fractures, which can culminate in a life-threatening state and amplify the hospital expenses burden. Our primary aim was to assess if MC increases the risk of LBD. Furthermore, we estimated the proportions of bone mineral changes in the MC population. Following a rigorous methodology, our data suggest that MC doubles the odds of LBD. Furthermore, we have shown that two-thirds of the MC population suffers from bone density decrease, half of them have osteopenia, and one in 10 MC patients has osteoporosis. In conclusion, we highly suggest screening patients with MC for bone mineral density at the moment of diagnosis.

Improved body composition decreases the fat content in non-alcoholic fatty liver disease, a meta-analysis and systematic review of longitudinal studies.

Background: Based on cross-sectional studies, there is a link between body composition parameters and steatosis in non-alcoholic fatty liver disease (NAFLD). However, whether long-term changes in different body composition parameters will result in NAFLD resolution is unclear. Therefore, we aimed to summarize the literature on longitudinal studies evaluating the association between NAFLD resolution and body composition change. Methods: Based on the recommendations of the Cochrane Handbook, we performed a systematic search on September 26th, 2021, in three databases: Embase, MEDLINE (via PubMed), and Cochrane Central Register of Controlled Trials (CENTRAL). Eligible studies reported on patients with NAFLD (liver fat >5%) and examined the correlation between body composition improvement and decrease in steatosis. We did not have pre-defined body composition or steatosis measurement criteria. Next, we calculated pooled correlation coefficient (r) with a 95% confidence interval (CI). Furthermore, we narratively summarized articles with other statistical methods. Results: We included 15 studies in our narrative review and five in our quantitative synthesis. Based on two studies with 85 patients, we found a pooled correlation coefficient of r = 0.49 (CI: 0.22-0.69, Spearman's correlation) between the change of visceral adipose tissue and liver steatosis. Similarly, based on three studies with 175 patients, the correlation was r = 0.33 (CI: 0.19-0.46, Pearson's correlation). On the other hand, based on two studies with 163 patients, the correlation between subcutaneous adipose tissue change and liver steatosis change was r = 0.42 (CI: 0.29-0.54, Pearson's correlation). Furthermore, based on the studies in the narrative synthesis, body composition improvement was associated with steatosis resolution. Conclusions: Based on the included studies, body composition improvement may be associated with a decrease in liver fat content in NAFLD. Systematic review registration: Identifier: CRD42021278584.

Detailed Characteristics of Post-discharge Mortality in Acute Pancreatitis.

BACKGROUND & AIMS: The in-hospital survival of patients suffering from acute pancreatitis (AP) is 95% to 98%. However, there is growing evidence that patients discharged after AP may be at risk of serious morbidity and mortality. Here, we aimed to investigate the risk, causes, and predictors of the most severe consequence of the post-AP period: mortality. METHODS: A total of 2613 well-characterized patients from 25 centers were included and followed by the Hungarian Pancreatic Study Group between 2012 and 2021. A general and a hospital-based population was used as the control group. RESULTS: After an AP episode, patients have an approximately threefold higher incidence rate of mortality than the general population (0.0404 vs 0.0130 person-years). First-year mortality after discharge was almost double than in-hospital mortality (5.5% vs 3.5%), with 3.0% occurring in the first 90-day period. Age, comorbidities, and severity were the most significant independent risk factors for death following AP. Furthermore, multivariate analysis identified creatinine, glucose, and pleural fluid on admission as independent risk factors associated with post-discharge mortality. In the first 90-day period, cardiac failure and AP-related sepsis were among the main causes of death following discharge, and cancer-related cachexia and non-AP-related infection were the key causes in the later phase. CONCLUSION: Almost as many patients in our cohort died in the first 90-day period after discharge as during their hospital stay. Evaluation of cardiovascular status, follow-up of local complications, and cachexia-preventing oncological care should be an essential part of post-AP patient care. Future study protocols in AP must include at least a 90-day follow-up period after discharge.

Trichomonas vaginalis infection is associated with increased risk of cervical carcinogenesis: A systematic review and meta-analysis of 470 000 patients.

BACKGROUND: Trichomonas vaginalis infection is the most prevalent non-viral sexually transmitted infection (STI) in women and has been suggested as a risk factor for developing cervical cancer. OBJECTIVE: We aimed to investigate the associations between T. vaginalis infection and cervical carcinogenesis. SEARCH STRATEGY: A comprehensive systematic search was conducted in five databases on 21 October 2021. SELECTION CRITERIA: Studies assessing the relationship between T. vaginalis infection, HPV co-infections, cervical dysplasia, and cervical cancer were found eligible. DATA COLLECTION AND ANALYSIS: Summary estimates for pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated with a random-effects model. Statistical heterogeneity was measured with I2 and Cochran's Q tests. MAIN RESULTS: The 29 articles included 473 740 women, of whom 8518 were T. vaginalis-positive. Our results showed that T. vaginalis-infected women had 1.79 times higher odds of being diagnosed with HPV co-infection (95% CI 1.27-2.53; I2 95%). We also found that T. vaginalis infection was associated with high-grade squamous intraepithelial lesion diagnosis (OR 2.34, 95% CI 1.10-4.95; I2 75%) and cervical cancer (OR 5.23, 95% CI 3.03-9.04; I2 3%). CONCLUSIONS: Our results showed an association between T. vaginalis and cervical carcinogenesis in sexually active women.

Metabolic-associated fatty liver disease is associated with acute pancreatitis with more severe course: Post hoc analysis of a prospectively collected international registry.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a proven risk factor for acute pancreatitis (AP). However, NAFLD has recently been redefined as metabolic-associated fatty liver disease (MAFLD). In this post hoc analysis, we quantified the effect of MAFLD on the outcomes of AP. METHODS: We identified our patients from the multicentric, prospective International Acute Pancreatitis Registry of the Hungarian Pancreatic Study Group. Next, we compared AP patients with and without MAFLD and the individual components of MAFLD regarding in-hospital mortality and AP severity based on the revised Atlanta classification. Lastly, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regression analysis. RESULTS: MAFLD had a high prevalence in AP, 39% (801/2053). MAFLD increased the odds of moderate-to-severe AP (OR = 1.43, CI: 1.09-1.89). However, the odds of in-hospital mortality (OR = 0.89, CI: 0.42-1.89) and severe AP (OR = 1.70, CI: 0.97-3.01) were not higher in the MAFLD group. Out of the three diagnostic criteria of MAFLD, the highest odds of severe AP was in the group based on metabolic risk abnormalities (OR = 2.68, CI: 1.39-5.09). In addition, the presence of one, two, and three diagnostic criteria dose-dependently increased the odds of moderate-to-severe AP (OR = 1.23, CI: 0.88-1.70, OR = 1.38, CI: 0.93-2.04, and OR = 3.04, CI: 1.63-5.70, respectively) and severe AP (OR = 1.13, CI: 0.54-2.27, OR = 2.08, CI: 0.97-4.35, and OR = 4.76, CI: 1.50-15.4, respectively). Furthermore, in patients with alcohol abuse and aged ≥60 years, the effect of MAFLD became insignificant. CONCLUSIONS: MAFLD is associated with AP severity, which varies based on the components of its diagnostic criteria. Furthermore, MAFLD shows a dose-dependent effect on the outcomes of AP.

Intravenous ferric carboxymaltose versus oral ferrous sulfate replacement in elderly patients after acute non-variceal gastrointestinal bleeding (FIERCE): protocol of a multicentre, open-label, randomised controlled trial.

INTRODUCTION: Acute gastrointestinal bleeding (GIB) is a life-threatening emergency with a critical economic burden. As a result of bleeding, anaemia often requires intravenous or oral iron supplementation. Elderly patients are even more prone to untoward outcomes after hospital discharge if iron supplementation is inefficient. There is a gap in current guidelines on which supplementation route clinicians should choose. We aim to investigate the effect of one dose of intravenous iron therapy versus 3-month oral iron administration on anaemia in an elderly population. METHODS AND ANALYSIS: The FIERCE study is an open-label, randomised controlled, two-armed trial. At least 48 hours after the acute non-variceal GIB treatment, patients will be recruited in participating centres. A random sequence generator will allocate the participants to group A (intravenous ferric carboxymaltose, 1000 mg) or group B (oral ferrous sulfate (FS), ca. 200 mg every day) with an allocation ratio of 1:1 on the day of the planned discharge from the hospital. Randomisation will be stratified for participating centres and the need for transfusion within the same hospitalisation before recruitment to the trial. Quality of life assessment, functional measurement and laboratory tests will be performed at baseline, 1 and 3 months±7 days after enrolment to the trial. The primary endpoint is a composite endpoint, including all-cause mortality, anaemia-associated unplanned emergency visit and anaemia-associated unplanned hospital admission within 3 months of enrolment in the trial. ETHICS AND DISSEMINATION: The study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (46395-5/2021/EÜIG). We will disseminate our results to the medical community and will publish our results in peer-reviewed journals. TRIAL REGISTRATION: The trial has been registered at ClinicalTrials.gov (NCT05060731).

No Association between Gastrointestinal Rebleeding and DOAC Therapy Resumption: A Systematic Review and Meta-Analysis.

BACKGROUND: There are recommendations for anticoagulation resumption after gastrointestinal bleeding (GIB), although data addressing this topic by direct oral anticoagulants (DOACs)-treated patients is lacking. We aim to determine the safety and efficacy of restarting DOACs after GIB. METHODS: Studies that reported rebleeding, thromboembolic events, and mortality after restarting or withholding DOACs were selected. The systematic research was conducted in five databases (MEDLINE, EMBASE, CENTRAL, Web of Science, and Scopus). The random effect model was implemented to calculate the pooled odds ratio (OR). The ROBINS-I tool was used for risk of bias assessment, and the certainty of the evidence was evaluated with the GRADE approach. RESULTS: Four retrospective cohort studies (1722 patients) were included in the meta-analysis. We did not find a significant increase in the risk of rebleeding in patients restarting DOACs after index GIB (OR = 1.12; 95% CI: 0.74-1.68). The outcomes of thromboembolic events and mortality data were not suitable for meta-analytic calculations. Single studies did not show statistically significant differences. Data quality assessment showed a serious overall risk of bias and very low quality of evidence (GRADE D). CONCLUSION: DOAC resumption after a GIB episode may not elevate the risk of rebleeding. However, the need for high-quality randomized clinical trials is crucial.