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).

Network-driven cancer cell avatars for combination discovery and biomarker identification for DNA damage response inhibitors.

Combination therapy is well established as a key intervention strategy for cancer treatment, with the potential to overcome monotherapy resistance and deliver a more durable efficacy. However, given the scale of unexplored potential target space and the resulting combinatorial explosion, identifying efficacious drug combinations is a critical unmet need that is still evolving. In this paper, we demonstrate a network biology-driven, simulation-based solution, the Simulated Cell™. Integration of omics data with a curated signaling network enables the accurate and interpretable prediction of 66,348 combination-cell line pairs obtained from a large-scale combinatorial drug sensitivity screen of 684 combinations across 97 cancer cell lines (BAC = 0.62, AUC = 0.7). We highlight drug combination pairs that interact with DNA Damage Response pathways and are predicted to be synergistic, and deep network insight to identify biomarkers driving combination synergy. We demonstrate that the cancer cell 'avatars' capture the biological complexity of their in vitro counterparts, enabling the identification of pathway-level mechanisms of combination benefit to guide clinical translatability.

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.

Validation of artificial intelligence application for dental caries diagnosis on intraoral bitewing and periapical radiographs.

OBJECTIVES: This study aimed to assess the reliability of AI-based system that assists the healthcare processes in the diagnosis of caries on intraoral radiographs. METHODS: The proximal surfaces of the 323 selected teeth on the intraoral radiographs were evaluated by two independent observers using an AI-based (Diagnocat) system. The presence or absence of carious lesions was recorded during Phase 1. After 4 months, the AI-aided human observers evaluated the same radiographs (Phase 2), and the advanced convolutional neural network (CNN) reassessed the radiographic data (Phase 3). Subsequently, data reflecting human disagreements were excluded (Phase 4). For each phase, the Cohen and Fleiss kappa values, as well as the sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of Diagnocat, were calculated. RESULTS: During the four phases, the range of Cohen kappa values between the human observers and Diagnocat were κ=0.66-1, κ=0.58-0.7, and κ=0.49-0.7. The Fleiss kappa values were κ=0.57-0.8. The sensitivity, specificity and diagnostic accuracy values ranged between 0.51-0.76, 0.88-0.97 and 0.76-0.86, respectively. CONCLUSIONS: The Diagnocat CNN supports the evaluation of intraoral radiographs for caries diagnosis, as determined by consensus between human and AI system observers. CLINICAL SIGNIFICANCE: Our study may aid in the understanding of deep learning-based systems developed for dental imaging modalities for dentists and contribute to expanding the body of results in the field of AI-supported dental radiology..

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.

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.

A meta-analysis on first-trimester blood count parameters-is the neutrophil-to-lymphocyte ratio a potentially novel method for first-trimester preeclampsia screening?

Objective: Meta-analysis focusing on the role of first-trimester neutrophil-to-lymphocyte ratio (NLR) in the prediction of preeclampsia. Data sources: PubMed, Scopus, Web of Science, Cochrane Library, and Embase databases were queried from inception up to December 31, 2022. Study eligibility criteria: The study included all types of original research that was conducted in humans and values of NLR were measured during the first trimester, among patients who later developed preeclampsia, compared to the values of control groups. Study appraisal and synthesis methods: Two reviewers independently performed data abstraction and quality appraisal, and disagreements were resolved by consensus and, if necessary, by the opinion of a third reviewer. During the analysis, PRISMA and MOOSE guidelines were followed. All statistical analyses were made with R. Results: For the research on the predictive role of NLR values in the first trimester for preeclampsia, a total of 6 studies were selected for analysis, covering 2,469 patients. The meta-analysis revealed a 95% confidence interval (CI) for the effect size of 0.641 to 1.523, with a prediction interval of 0.027 to 2.137. Conclusion: Based on the analysis, NLR is a promising biochemical marker for future pieces of research that try to find new screening methods for first-trimester preeclampsia. We encourage other researchers to examine NLR's predictive value combined with other markers in preeclampsia screening, this way being able to find new and affordable protocols for first-trimester preeclampsia screening. Systematic review registration: identifier CRD42023392663.

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.

Supplementary Respiratory Therapy Improves Pulmonary Function in Pediatric Patients with Cerebral Palsy: A Systematic Review and Meta-Analysis.

BACKGROUND: Despite medical advances, individuals with cerebral palsy (CP) face significant respiratory challenges, leading to heightened hospitalization rates and early mortality among this population. We hypothesize that integrating supplementary respiratory therapy into standard rehabilitation will result in significant improvements in pulmonary function, enhanced respiratory muscle strength, and an overall increase in the quality of life among pediatric patients with CP. METHODS: A systematic search of literature across five databases was conducted, and random-effects meta-analyses were performed to assess the impact of supplementary respiratory therapy on (a) pulmonary function: forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FVC/FEV1 ratio, peak expiratory flow (PEF), and (b) respiratory muscle strength: maximal inspiratory and expiratory pressure (MIP, MEP), and (c) quality of life. Certainty of evidence was determined by the GRADE assessment. RESULTS: Analysis of data from 11 eligible randomized controlled trials revealed clinically meaningful changes in pulmonary function. We found a relevant mean difference (MD) in absolute PEF of 0.50 L/s (95% confidence interval (CI): 0.19; 0.82 p = 0.0107). The certainty of the evidence ranged from moderate to high. CONCLUSIONS: This study presents current evidence on the impact of various supplementary respiratory therapies for CP patients classified under gross motor function classification level I-IV, demonstrating clinically meaningful improvements in pulmonary function and respiratory muscle strength. These improvements suggest the potential for an enhanced quality of life. Our findings hold the promise of serving as a foundational reference for potential revisions to conventional rehabilitation care, incorporating supplementary respiratory therapy.

Cellular forgetting, desensitisation, stress and ageing in signalling networks. When do cells refuse to learn more?

Recent findings show that single, non-neuronal cells are also able to learn signalling responses developing cellular memory. In cellular learning nodes of signalling networks strengthen their interactions e.g. by the conformational memory of intrinsically disordered proteins, protein translocation, miRNAs, lncRNAs, chromatin memory and signalling cascades. This can be described by a generalized, unicellular Hebbian learning process, where those signalling connections, which participate in learning, become stronger. Here we review those scenarios, where cellular signalling is not only repeated in a few times (when learning occurs), but becomes too frequent, too large, or too complex and overloads the cell. This leads to desensitisation of signalling networks by decoupling signalling components, receptor internalization, and consequent downregulation. These molecular processes are examples of anti-Hebbian learning and 'forgetting' of signalling networks. Stress can be perceived as signalling overload inducing the desensitisation of signalling pathways. Ageing occurs by the summative effects of cumulative stress downregulating signalling. We propose that cellular learning desensitisation, stress and ageing may be placed along the same axis of more and more intensive (prolonged or repeated) signalling. We discuss how cells might discriminate between repeated and unexpected signals, and highlight the Hebbian and anti-Hebbian mechanisms behind the fold-change detection in the NF-κB signalling pathway. We list drug design methods using Hebbian learning (such as chemically-induced proximity) and clinical treatment modalities inducing (cancer, drug allergies) desensitisation or avoiding drug-induced desensitisation. A better discrimination between cellular learning, desensitisation and stress may open novel directions in drug design, e.g. helping to overcome drug resistance.

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.

Beyond the Gut: A Systematic Review and Meta-analysis of Advanced Therapies for Inflammatory Bowel Disease-associated Extraintestinal Manifestations.

BACKGROUND AND AIMS: Extraintestinal manifestations are frequent in patients with inflammatory bowel disease and have a negative impact on quality of life. Currently, however, there is no evidence available to determine which drug should be recommended for these patients beyond anti-tumour necrosis factor [anti-TNF] treatment. We aimed to analyse the frequency of new extraintestinal manifestations and the behaviour of pre-existing extraintestinal manifestations during advanced therapy. METHODS: We conducted a systematic search on November 15, 2022, and enrolled randomized controlled trials, cohorts, and case series reporting the occurrence and behaviour of extraintestinal manifestations in patients with inflammatory bowel disease receiving advanced therapy [non-TNF inhibitor biologicals and JAK inhibitors]. Proportions of new, recurring, worsening, and improving extraintestinal manifestations were calculated with 95% confidence intervals [CIs]. The risk of bias was assessed with the QUIPS tool. RESULTS: Altogether, 61 studies comprising 13,806 patients reported eligible data on extraintestinal manifestations. The overall proportion of new extraintestinal manifestations was 8% [95% CI, 6-12%] during advanced therapy. There was no significant difference between the frequency of new extraintestinal manifestations during vedolizumab and ustekinumab therapy [11%, 95% CI, 8-15% vs 6%, 95% CI, 3-11%, p = 0.166]. The improvement of pre-existing manifestations was comparable between vedolizumab- and ustekinumab-treated patients, except for joint involvement [42%, 95% CI, 32-53% vs 54%, 95% CI, 42-65%, p = 0.029]. CONCLUSION: The proportion of new extraintestinal manifestations was low during advanced therapy. Furthermore, the improvement of pre-existing manifestations was comparable between advanced therapies, except for pre-existing joint manifestations.

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.

Molecular imaging of bacterial outer membrane vesicles based on bacterial surface display.

The important roles of bacterial outer membrane vesicles (OMVs) in various diseases and their emergence as a promising platform for vaccine development and targeted drug delivery necessitates the development of imaging techniques suitable for quantifying their biodistribution with high precision. To address this requirement, we aimed to develop an OMV specific radiolabeling technique for positron emission tomography (PET). A novel bacterial strain (E. coli BL21(DE3) ΔnlpI, ΔlpxM) was created for efficient OMV production, and OMVs were characterized using various methods. SpyCatcher was anchored to the OMV outer membrane using autotransporter-based surface display systems. Synthetic SpyTag-NODAGA conjugates were tested for OMV surface binding and 64Cu labeling efficiency. The final labeling protocol shows a radiochemical purity of 100% with a ~ 29% radiolabeling efficiency and excellent serum stability. The in vivo biodistribution of OMVs labeled with 64Cu was determined in mice using PET/MRI imaging which revealed that the biodistribution of radiolabeled OMVs in mice is characteristic of previously reported data with the highest organ uptakes corresponding to the liver and spleen 3, 6, and 12 h following intravenous administration. This novel method can serve as a basis for a general OMV radiolabeling scheme and could be used in vaccine- and drug-carrier development based on bioengineered OMVs.

Seroconversion after SARS-CoV-2 vaccination is protective against severe COVID-19 disease in heart transplant recipients.

BACKGROUND: Heart transplant (HTX) recipients are prone to develop complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Vaccination is often ineffective due to weaker immunogenicity. In this high-volume single-center study, we aimed to determine factors influencing seroconversion after vaccination and predictors of severe SARS-CoV-2 infection. METHODS: Two hundred twenty-nine HTX recipients were enrolled. Type of the first two vaccine doses included messenger RNA (mRNA), vector, and inactivated vaccines. We carried out analyses on seroconversion after the second and third doses of vaccination and on severity of infection. Antispike protein SARS-CoV-2 immunoglobulin G (IgG) was measured after the second and third vaccines and serostatus was defined. Effect of the first two vaccine doses was studied on patients who did not suffer SARS-CoV-2 infection before antibody measurement (n = 175). The effectivity of the third vaccine was evaluated among seronegative recipients after the second vaccine (n = 53). Predictors for severe infection defined as pneumonia, hospitalization or death were assessed in all patients who contracted SARS-CoV-2 infection (n = 92). RESULTS: 62% of the recipients became seropositive after the second vaccination. Longer time between HTX and vaccination (odds ratio [OR]: 2.35) and mRNA vaccine (OR: 4.83) were predictors of seroconversion. 58% of the nonresponsive patients became seropositive after receiving the third vaccine. Male sex increased the chance of IgG production after the third dose (OR: 5.65). Clinical course of SARS-CoV-2 infection was severe in 32%. Of all parameters assessed, only seropositivity before infection was proven to have a protective effect against severe infection (OR: 0.11). CONCLUSIONS: We found that longer time since HTX, mRNA vaccine type, and male sex promoted seroconversion after SARS-CoV-2 vaccination in HTX recipients. Seropositivity-but not the number of vaccine doses-seemed to be protective against severe SARS-CoV-2 infection. Screening of HTX patients for anti-SARS-COV-2 antibodies may help to identify patients at risk for severe infection.

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.

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.

Investigation of the effect of rifampicin resistance and risk factors on recovery rates after DAIR procedure in patients with prosthetic joint infection.

BACKGROUND: Rifampicin plays a key role in the management of prosthetic joint infections (PJIs), however, the emergence of rifampicin resistance is associated with less favourable clinical outcomes. The purpose of this study was to investigate the impact of rifampicin resistance and other patient-related factors on recovery rates among patients with PJI undergoing debridement, antibiotics and implant retention (DAIR). METHODS: We reviewed medical records and microbiology reports of 67 patients (37 males and 30 females) undergoing DAIR due to PJI between 2014 and 2021. Patient-related factors, co-morbidities and microbiological reports were collected and reviewed. Forty-four patients had hip, 21 had knee, 1 had shoulder and 1 had elbow joint infection. Obtained data were statistically analysed with a logistic regression model. RESULTS: Rifampicin-sensitive organism was isolated in 47 cases. Recovery rate was 72.3% in the sensitive and 76.9% in the resistant group. We found no significant effect of rifampicin resistance on the probability of recovery. Age and diabetes mellitus showed negative clinical impact on recovery. Staphylococcus aureus and coagulase-negative Staphylococci were predominant in the rifampicin-sensitive (66.6% of the isolates) and Gram-negative rods in the resistant group (65.2%). CONCLUSIONS: Based on our results, higher age and diabetes mellitus may have a clinically relevant negative impact on clinical outcome, however, this effect was not statistically significant. This may be due to the limited number of patients included in this study. We observed no clinically relevant effect of rifampicin-resistance, sex and body mass index (BMI) on recovery rates among patients undergoing DAIR due to PJI.