Psychological intervention improves quality of life in patients with early-stage cancer: a systematic review and meta-analysis of randomized clinical trials.

The effectiveness of psychological interventions (PI) for malignant diseases is controversial. We aimed to investigate the effect of PI on survival and quality of life (QoL) in patients with cancer. We performed a systematic search of MEDLINE, Cochrane, and Embase databases to identify randomized controlled trials comparing PI to standard care (PROSPERO registration number CRD42021282327). Outcomes were overall survival (OS), recurrence-free survival (RFS), and different domains of QoL. Subgroup analysis was performed based on the provider-, type-, environment-, duration of intervention; cancer stage, and type. Pooled hazard ratios (HR) and standardized mean difference (SMD) with 95% confidence intervals (CI) were calculated using a random-effects model. The OS and RFS did not differ significantly between the two groups (OS:HR = 0.97; CI 0.87-1.08; RFS:HR = 0.99; CI 0.84-1.16). However, there was significant improvement in the intervention group in all the analyzed domains of QoL; in the global (SMD = 0.65; CI 0.35-0.94), emotional (SMD = 0.64; CI 0.33-0.95), social (SMD = 0.32; CI 0.13-0.51) and physical (SMD = 0.33; CI 0.05-0.60) domains. The effect of PI on QoL was generally positive immediately, 12 and 24 weeks after intervention, but the effect decreased over time and was no longer found significant at 48 weeks. The results were better in the breast cancer group and early stages of cancer. PIs do not prolong survival, but they significantly improve the QoL of cancer patients. PI should be added as standard of care 3-4 times a year, at least for patients with early-stage cancer.

Incidence of recurrent and chronic pancreatitis after acute pancreatitis: a systematic review and meta-analysis.

Background: Acute pancreatitis (AP) has a high incidence, and patients can develop recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) after AP. Objectives: We aimed to estimate the pooled incidence rates (IRs), cumulative incidences, and proportions of RAP and CP after AP. Design: A systematic review and meta-analysis of studies reporting the proportion of RAP and CP after AP. Data sources and methods: The systematic search was conducted in three (PubMed, EMBASE, and CENTRAL) databases on 19 December 2023. Articles reporting the proportion of RAP or CP in patients after the first and multiple episodes of AP were eligible. The random effects model was used to calculate the pooled IR with 95% confidence intervals (CIs). The I 2 value assessed heterogeneity. The risk of bias assessment was conducted with the Joanna Briggs Institute Critical Appraisal Tool. Results: We included 119 articles in the quantitative synthesis and 29 in the IRs calculations. Our results showed that the IR of RAP in adult patients after AP was 5.26 per 100 person-years (CI: 3.99-6.94; I 2 = 93%), while in children, it was 4.64 per 100 person-years (CI: 2.73-7.87; I 2 = 88%). We also found that the IR of CP after AP was 1.4 per 100 person-years (CI: 0.9-2; I 2 = 75%), while after RAP, it increased to 4.3 per 100 person-years (CI: 3.1-6.0; I 2 = 76%). The risk of bias was moderate in the majority of the included studies. Conclusion: Our results showed that RAP affects many patients with AP. Compared to patients with the first AP episode, RAP leads to a threefold higher IR for developing CP. Trial registration: Our protocol was registered on PROSPERO (CRD42021283252).

Early nutrition is safe and does not increase complications after upper gastrointestinal bleeding-a systematic review and meta-analysis of randomized controlled trials.

Despite a lack of evidence, patients are often not fed for 48-96 h after upper gastrointestinal bleeding (UGIB); however, many trials have demonstrated the benefits of early nutrition (EN). We conducted a meta-analysis of randomized controlled trials (RTCs) to evaluate the outcomes of EN compared to delayed nutrition (DN) after UGIB. The protocol was registered on PROSPERO (CRD42022372306). PubMed, Embase, CENTRAL, Scopus, and Web of Science were searched on the 27th of April 2024 to identify eligible RCTs. The primary outcomes were early (within 7 days) and late (within 30-42 days) mortality and rebleeding. Pooled risk ratios (RR), mean differences (MD), and corresponding 95% confidence intervals (CI) were calculated using a random-effects model. A total of 10 trials with 1051 patients were included in the analysis. Early mortality was not significantly different between the two groups (RR 1.20, CI 0.85-1.71, I2 = 0%), whereas late mortality was reduced to a clinically relevant extent in the EN group (RR 0.61, CI 0.35-1.06, I2 = 0%). When comparing the two groups, we found no significant difference in terms of early and late rebleeding (RR 1.04, CI 0.66-1.63, I2 = 0% and RR 1.16, CI 0.63-2.13, I2 = 0%, respectively). Our analysis also showed that the length of hospital stay was reduced in the EN group compared to the DN group (MD -1.22 days, CI: -2.43 to -0.01, I2 = 94%). In conclusion, compared with DN, EN (within 24 h) appears to be a safe intervention and could reduce the length of hospital stay without increasing the risk of complications after UGIB.

Contrast-enhanced endoscopic ultrasound likely does not improve diagnostic adequacy during endoscopic ultrasound guided tissue acquisition: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Solid pancreatic masses are sampled through tissue acquisition by endoscopic ultrasound (EUS). Inadequate samples may significantly delay diagnosis, increasing costs and carrying risks to the patients. AIM: assess the diagnostic adequacy of tissue acquisition using contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) compared to conventional EUS. METHODS: Five databases (PubMed, Embase, CENTRAL, Scopus and Web of Science) were searched in November 2023. Studies comparing diagnostic adequacy, accuracy and safety using CEH-EUS versus conventional EUS for tissue acquisition of solid pancreatic masses were included. Risk of bias was assessed using the Risk of Bias tool for randomized controlled trials (RoB2) and the Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool for non-randomized studies, level of evidence using the GRADE approach, Odds Ratios (RR) with 95 % Confidence Intervals (CI) calculated and pooled using a random-effects model. I2 quantified heterogeneity. RESULTS: The search identified 3858 records; nine studies (1160 patients) were included. OR for achieving an adequate sample was 1.467 (CI: 0.850-2.533), for randomized trials 0.902 (CI: 0.541-1.505), for non-randomized 2.396 (CI: 0.916-6.264), with significant subgroup difference. OR for diagnostic accuracy was 1.326 (CI: 0.890-1977), for randomized trials 0.997 (CI: 0.593-1.977) and for non-randomized studies 1.928 (CI: 1.096-3.393), significant subgroup difference (p = 0.0467). No differences were observed for technical failures or adverse events. Heterogeneity was low, risk of bias "low" to "some concerns" for most outcomes, mostly moderate for non-randomized studies. CONCLUSION: Non-randomized studies indicated differences in favor of contrast-enhanced EUS, randomized studies showed no difference in diagnostic adequacy, accuracy or sensitivity when using CEH-EUS.

Systematic review and meta-analysis: proton pump inhibitors slightly decrease the severity of chronic cough.

The Montreal consensus recognizes chronic cough as an extra-esophageal manifestation of gastroesophageal reflux disease. We performed a meta-analysis to assess the effects of acid-suppressive medications in adults with non-specific chronic cough. The protocol was registered on PROSPERO (CRD42022368769). Placebo-controlled randomized trials evaluating the impact of acid-suppressive medications on persistent cough were included. The systematic search was performed on the 1st of November 2022 in three databases. A random-effects model was used for the calculations. The effect size was the standardized mean difference (SMD) with 95% confidence interval (CI). A total number of 11 double-blinded placebo-controlled randomized trials were included in the meta-analysis. Data showed that compared to placebo, PPIs decreased the severity of cough (SMD 0.33; CI 0.05; 0.61). Therapeutic response was not different in patients with non-specific chronic cough only, compared to those with laryngopharyngeal reflux. Prolonged treatment durations did not result in greater symptomatic improvement, with SMD 0.33 (CI - 0.22; 0.88), 0.31 (CI - 1.74; 2.35), 0.32 (CI - 0.29; 0.93) and 0.34 (CI - 0.16; 0.85), following 4, 6, 8 and 12 weeks of treatment, respectively. The pooled analysis of the improvement in quality of life with PPIs found an SMD of 0.39 (CI - 0.51; 1.29). PPIs mildly decrease the severity of non-specific chronic cough, irrespective of treatment duration.

Morphology of the papilla can predict procedural safety and efficacy of ERCP-a systematic review and meta-analysis.

Endoscopic Retrograde Cholangiopancreatography (ERCP) is the primary therapeutic procedure for pancreaticobiliary disorders, and studies highlighted the impact of papilla anatomy on its efficacy and safety. Our objective was to quantify the influence of papilla morphology on ERCP outcomes. We systematically searched three medical databases in September 2022, focusing on studies detailing the cannulation process or the rate of adverse events in the context of papilla morphology. The Haraldsson classification served as the primary system for papilla morphology, and a pooled event rate with a 95% confidence interval was calculated as the effect size measure. Out of 17 eligible studies, 14 were included in the quantitative synthesis. In studies using the Haraldsson classification, the rate of difficult cannulation was the lowest in type I papilla (26%), while the highest one was observed in the case of type IV papilla (41%). For post-ERCP pancreatitis, the event rate was the highest in type II papilla (11%) and the lowest in type I and III papilla (6-6%). No significant difference was observed in the cannulation failure and post-ERCP bleeding event rates between the papilla types. In conclusion, certain papilla morphologies are associated with a higher rate of difficult cannulation and post-ERCP pancreatitis.

Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk.

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10-8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10-7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10-6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10-5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.

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.

One third of cases of new-onset diabetic ketosis in adults are associated with ketosis-prone type 2 diabetes-A systematic review and meta-analysis.

AIMS: Ketosis-prone type 2 diabetes was defined by the World Health Organization in 2019. According to the literature, the diagnosis is based on the presence of ketosis, islet autoantibody negativity and preserved insulin secretion. Our meta-analysis assessed the prevalence and clinical characteristics of ketosis-prone type 2 diabetes among patients hospitalised with diabetic ketoacidosis (DKA) or ketosis. METHODS: The systematic search was performed in five main databases as of 15 October 2021 without restrictions. We calculated the pooled prevalence of ketosis-prone type 2 diabetes (exposed group) within the diabetic population under examination, patients with ketoacidosis or ketosis, to identify the clinical characteristics, and we compared it to type 1 diabetes (the comparator group). The random effects model provided pooled estimates as prevalence, odds ratio and mean difference (MD) with 95% confidence intervals. RESULTS: Eleven articles were eligible for meta-analysis, thus incorporating 2010 patients of various ethnic backgrounds. Among patients presenting with DKA or ketosis at the onset of diabetes, 35% (95% CI: 24%-49%) had ketosis-prone type 2 diabetes. These patients were older (MD = 11.55 years; 95% CI: 5.5-17.6) and had a significantly higher body mass index (BMI) (MD = 5.48 kg/m2 ; 95% CI: 3.25-7.72) than those with type 1 diabetes. CONCLUSIONS: Ketosis-prone type 2 diabetes accounts for one third of DKA or ketosis at the onset of diabetes in adults. These patients are characterised by islet autoantibody negativity and preserved insulin secretion. They are older and have a higher BMI compared with type 1 diabetes. C-peptide and diabetes-related autoantibody measurement is essential to identify this subgroup among patients with ketosis at the onset of diabetes.

Obesity paradox in older sarcopenic adults - a delay in aging: A systematic review and meta-analysis.

The prognostic significance of obesity in sarcopenic adults is controversial. This systematic review and meta-analysis aimed to investigate the effect of additional obesity on health outcomes in sarcopenia. MEDLINE, EMBASE, Scopus and CENTRAL were systematically searched for studies to compare health outcomes of adults with sarcopenic obesity (SO) to those of sarcopenic non-obese (SNO) adults. We also considered the methods of assessing obesity. Of 15060 records screened, 65 papers were included (100612 participants). Older community-dwelling SO adults had 15% lower mortality risk than the SNO group (hazard ratio, HR: 0.85, 95% confidence interval 0.76, 0.94) even when obesity was assessed by measurement of body composition. Additionally, meta-regression analysis revealed a significant negative linear correlation between the age and the HR of all-cause mortality in SO vs. SNO community-dwelling adults, but not in severely ill patients. Compared with SNO, SO patients presented lower physical performance, higher risk for metabolic syndrome, but similar cognitive function, risk of falls and cardiovascular diseases. Age-related obesity, SO and later fat loss leading to SNO represent consecutive phases of biological aging. Additional obesity could worsen the health state in sarcopenia, but above 65 years SO represents a biologically earlier phase with longer life expectancy than SNO.

Anti-tumor necrosis factor alpha versus corticosteroids: a threefold difference in the occurence of venous thromboembolism in Inflammatory Bowel Disease - a systematic review and meta-analysis.

BACKGROUND, AIMS: Patients with inflammatory bowel disease (IBD) have a more than twofold higher risk of venous thromboembolic events (VTE) than the general population. The etiology is complex, and the role of medication is not precisely defined.We aimed to assess the effect of anti-tumor necrosis factor alpha (anti-TNFα) drugs and conventional anti-inflammatory therapy, namely corticosteroids (CS), immunomodulators (IM), and 5-aminosalicylates (5-ASA) on VTE in IBD. METHODS: A systematic search was performed in five databases on the 22nd of November 2022. We included studies reporting VTE in the distinct categories of medications, determined the proportions, and calculated the odds ratios (OR) with 95% confidence intervals (CI), using the random-effects model. The risk of bias was evaluated with the Joanna Briggs Institute Critical Appraisal Checklist and the Risk of Bias in Non-randomized Studies of Interventions tool. RESULTS: The quantitative analysis included 16 observational studies, with data from 91,322 IBD patients. Patients receiving anti-TNFα medication had significantly less VTE (proportion: 0.05, CI: 0.02-0.10), than patients treated with CS (proportion: 0.16, CI: 0.07-0.32), with OR=0.42 (CI: 0.25-0.71). IMs resulted in similar proportions of VTE compared with biologics (0.05, CI: 0.03-0.10), with OR=0.94 (CI: 0.67-1.33). The proportion of patients receiving 5-ASA having VTE was 0.09 (CI: 0.04-0.20), with OR=1.00 (CI: 0.61-1.62). CONCLUSIONS: Biologics should be preferred over corticosteroids in cases of severe flare-ups and multiple VTE risk factors, as they are associated with reduced odds of these complications. Further studies are needed to validate our data.

Low molecular weight heparin decreases mortality and major complication rates in moderately severe and severe acute pancreatitis-a systematic review and meta-analysis.

Background: Routine anticoagulation therapy in acute pancreatitis (AP) is not recommended by the guidelines in the field, although it is frequently used in clinical practice. Objectives: We aimed to analyze the efficacy and safety of adding anticoagulants therapy to AP management. Methods: The systematic search was performed in three databases on the 14th of October 2022 without restrictions. Randomized controlled trials (RCTs) and observational studies that reported the differences in the outcomes of AP for patients receiving anticoagulants (intervention group) in addition to the standard of care (SOC), compared to patients managed by SOC alone (control group), were eligible. A random-effects model was used to calculate the pooled odds ratios (OR) and mean differences (MD) with the corresponding 95%-confidence intervals (CI). We performed subgroup analysis for study design and disease severity, among other criteria. Results: Of the 8,223 screened records, we included eight in the meta-analysis. Except one, all studies reported on low-molecular-weight heparin (LMWH). Both RCTs and observational studies reported results in favor of the LMWH group. Subgroup RCTs' analysis revealed significantly decreased odds of mortality [OR 0.24; 95%CI 0.17-0.34] and multiple organ failure [OR 0.32; 95%CI 0.17-0.62] in the intervention group. Moreover, the need for endoscopic or surgical interventions [OR 0.41; 95%CI 0.28-0.61] were significantly reduced by LMWH. The subgroup analyzes for moderate and severe cases, respectively, yielded similar results. Due to limited data, we could no perform subgroup analysis for mild cases. Conclusion: LMWH therapy reduces major complication rates in moderate and severe AP. Across all identified RCTs, LMWH were initiated early after AP diagnosis and improved its prognosis.

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.

Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians.

BACKGROUND: The genomes of present-day non-Africans are composed of 1-3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50-60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations. RESULTS: The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19-1.54, P = 3.59 × 10-6), with a P-value close to a threshold that takes into account multiple testing. CONCLUSIONS: Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

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.

Probiotic supplementation during antibiotic treatment is unjustified in maintaining the gut microbiome diversity: a systematic review and meta-analysis.

BACKGROUND: Probiotics are often used to prevent antibiotic-induced low-diversity dysbiosis, however their effect is not yet sufficiently summarized in this regard. We aimed to investigate the effects of concurrent probiotic supplementation on gut microbiome composition during antibiotic therapy. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials reporting the differences in gut microbiome diversity between patients on antibiotic therapy with and without concomitant probiotic supplementation. The systematic search was performed in three databases (MEDLINE (via PubMed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL)) without filters on 15 October 2021. A random-effects model was used to estimate pooled mean differences (MD) with 95% confidence intervals (CI). This review was registered on PROSPERO (CRD42021282983). RESULTS: Of 11,769 identified articles, 15 were eligible in the systematic review and 5 in the meta-analyses. Quantitative data synthesis for Shannon (MD = 0.23, 95% CI: [(-)0.06-0.51]), Chao1 (MD = 11.59 [(-)18.42-41.60]) and observed OTUs (operational taxonomic unit) (MD = 17.15 [(-)9.43-43.73]) diversity indices revealed no significant difference between probiotic supplemented and control groups. Lacking data prevented meta-analyzing other diversity indices; however, most of the included studies reported no difference in the other reported α- and ß-diversity indices between the groups. Changes in the taxonomic composition varied across the eligible studies but tended to be similar in both groups. However, they showed a potential tendency to restore baseline levels in both groups after 3-8 weeks. This is the first meta-analysis and the most comprehensive review of the topic to date using high quality methods. The limited number of studies and low sample sizes are the main limitations of our study. Moreover, there was high variability across the studies regarding the indication of antibiotic therapy and the type, dose, and duration of antimicrobials and probiotics. CONCLUSIONS: Our results showed that probiotic supplementation during antibiotic therapy was not found to be influential on gut microbiome diversity indices. Defining appropriate microbiome diversity indices, their standard ranges, and their clinical relevance would be crucial.