Burden of Childhood Cancer and the Social and Economic Challenges in Adulthood: A Systematic Review and Meta-Analysis.

Importance: Significant advancements in pediatric oncology have led to a continuously growing population of survivors. Although extensive research is being conducted on the short-, medium-, and long-term somatic effects, reports on psychosocial reintegration are often conflicting; therefore, there is an urgent need to synthesize the evidence to obtain the clearest understanding and the most comprehensive answer. Objective: To provide a comprehensive review and analysis of the socioeconomic attainment of childhood cancer survivors (CCSs) compared with their unaffected peers. Data Sources: A systematic review and meta-analysis was conducted using data obtained from a comprehensive search of MEDLINE (via PubMed), Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) databases on October 23, 2021; the search was updated until July 31, 2023. Study Selection: Eligible articles reported on educational attainment, employment, family formation, quality of life (QoL), or health-risk behavior-related outcomes of CCSs, and compared them with their unaffected peers. Study selection was performed in duplicate by 4 blinded independent coauthors. Data Extraction and Synthesis: Data extraction was performed in duplicate by 4 independent authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Outcome measures were odds ratios (ORs) and mean differences with 95% CIs; data were pooled using a random-effects model. Results: The search identified 43 913 articles, 280 of which were eligible for analysis, reporting data on a total of 389 502 survivors. CCSs were less likely to complete higher levels of education (OR, 0.69; 95% CI, 0.40-1.18), had higher odds of health-related unemployment (OR, 2.94; 95% CI, 1.90-4.57), and showed lower rates of marriage (OR, 0.72; 95% CI, 0.63-0.84) and parenthood (OR, 0.60; 95% CI, 0.49-0.74) compared with population-based controls. Conclusion and Relevance: Study findings suggest that CCSs face several socioeconomic difficulties; as a result, the next goal of pediatric oncology should be to minimize adverse effects, as well as to provide lifelong survivorship support aimed at maximizing social reintegration.

Comparison of Executive Function Skills between Patients with Cerebral Palsy and Typically Developing Populations: A Systematic Review and Meta-Analysis.

Background: Children with CP show deficits in executive function compared to their typically developing peers, based on the majority of the available evidence. However, the magnitude of these deficits, as well as the proportions of the shortfalls in the three main components, have not yet been examined. This is the first meta-analysis to synthesize evidence on the magnitude of differences between patients with cerebral palsy (CP) and typically developing populations in different components of executive function skills (working memory, inhibitory control and cognitive flexibility), and thus makes recommendations on which areas of executive functioning are in greatest need of intervention. Methods: We conducted a systematic literature search of four databases for studies that measured executive functions in these two groups until 31 August 2023. We calculated the standardized mean difference (Hedges' g), an average effect size overall, and for the three components of executive function skills separately, we used several moderator analyses, including methodological differences between the primary studies. Results: Fifteen articles were included in the meta-analysis. The average mean difference in executive functioning overall was large (g+ = -0.82). Furthermore, large significant differences were found in working memory (g+ = -0.92) and inhibitory control (g+ = -0.82) and a moderate difference was identified in cognitive flexibility (g+ = -0.57). In addition, results of moderator analyses reveal the importance of a rigorous matching of control group participants and CP patients. Conclusions: The results demonstrate a severe impairment in all executive functions among CP patients compared to typically developing peers, which do not decrease over time.

Early onset of abnormal glucose tolerance in patients with cystic fibrosis: A systematic review and meta-analysis.

BACKGROUND: Despite translational evidences suggesting that cystic fibrosis-related abnormal glucose tolerance (CF-related AGT) may begin early in life and is known to be associated with increased morbidity and mortality, current guidelines recommend screening for AGT only from 10 years of age, thus missing the opportunity for early detection and intervention. METHODS: A systematic review and meta-analysis (PROSPERO number: CRD42021282516) was conducted on studies that reported data on the prevalence of AGT or its subtypes in CF populations. Pooled proportions, risk, and odds ratios with 95 % confidence intervals (CI) were calculated. One-stage dose-response random-effect meta-analysis was used to assess the effect of age on CF-related diabetes (CFRD). RESULTS: The quantitative analysis included 457 studies and data from 520,544 patients. Every third child with CF (chwCF) (0.31 [95 % CI 0.25-0.37]) and every second adult with CF (awCF) (0.51 [95 % CI 0.45-0.57]) were affected by AGT. Even in the 5-10 years of age subgroup, the proportion of AGT was 0.42 [95 % CI 0.34-0.51]. The prevalence of prediabetes remained unchanged (impaired glucose tolerance in chwCF:0.14 [95 % CI 0.10-0.18]) vs. awCF:0.19 [95 % CI 0.14-0.25]), whereas the proportion of CFRD increased with age (0-5: 0.005 [95 % CI 0.0001-0.15]; 5-10: 0.05 [95 % CI 0.01-0.27]; 10-18: 0.11 [95 % CI 0.08-0.14]; >18 years of age: 0.27 [95 % CI 0.24-0.30]). CONCLUSION: CF-related AGT is common under 10 years of age. Our study suggests considering earlier AGT screening, starting from 5 years of age. This highlights the imperative for additional research for guideline adjustments and provides the opportunity for early intervention.

Prediction performance of scoring systems after out-of-hospital cardiac arrest: A systematic review and meta-analysis.

INTRODUCTION: Ongoing changes in post resuscitation medicine and society create a range of ethical challenges for clinicians. Withdrawal of life-sustaining treatment is a very sensitive, complex decision to be made by the treatment team and the relatives together. According to the guidelines, prognostication after cardiopulmonary resuscitation should be based on a combination of clinical examination, biomarkers, imaging, and electrophysiological testing. Several prognostic scores exist to predict neurological and mortality outcome in post-cardiac arrest patients. We aimed to perform a meta-analysis and systematic review of current scoring systems used after out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS: Our systematic search was conducted in four databases: Medline, Embase, Central and Scopus on 24th April 2023. The patient population consisted of successfully resuscitated adult patients after OHCA. We included all prognostic scoring systems in our analysis suitable to estimate neurologic function as the primary outcome and mortality as the secondary outcome. For each score and outcome, we collected the AUC (area under curve) values and their CIs (confidence iterval) and performed a random-effects meta-analysis to obtain pooled AUC estimates with 95% CI. To visualize the trade-off between sensitivity and specificity achieved using different thresholds, we created the Summary Receiver Operating Characteristic (SROC) curves. RESULTS: 24,479 records were identified, 51 of which met the selection criteria and were included in the qualitative analysis. Of these, 24 studies were included in the quantitative synthesis. The performance of CAHP (Cardiac Arrest Hospital Prognosis) (0.876 [0.853-0.898]) and OHCA (0.840 [0.824-0.856]) was good to predict neurological outcome at hospital discharge, and TTM (Targeted Temperature Management) (0.880 [0.844-0.916]), CAHP (0.843 [0.771-0.915]) and OHCA (0.811 [0.759-0.863]) scores predicted good the 6-month neurological outcome. We were able to confirm the superiority of the CAHP score especially in the high specificity range based on our sensitivity and specificity analysis. CONCLUSION: Based on our results CAHP is the most accurate scoring system for predicting the neurological outcome at hospital discharge and is a bit less accurate than TTM score for the 6-month outcome. We recommend the use of the CAHP scoring system in everyday clinical practice not only because of its accuracy and the best performance concerning specificity but also because of the rapid and easy availability of the necessary clinical data for the calculation.

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.

Nafamostat Reduces the Incidence of post-ERCP Pancreatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). As the management of pancreatitis is limited, clinical approaches focus on the prevention of post-ERCP pancreatitis (PEP). In theory, the serine protease inhibitor nafamostat can reduce circulating inflammatory mediators in pancreatitis. We aimed to investigate the effect of nafamostat in the prevention of PEP in this systematic review and meta-analysis. The protocol for this review was registered in PROSPERO (CRD42022367988). We systematically searched 5 databases without any filters on September 26, 2022. The eligible population was adult patients undergoing ERCP. We compared the PEP preventive effect of nafamostat to placebo. The main outcome was the occurrence of PEP. We calculated the pooled odds ratios (ORs), mean differences, and corresponding 95% confidence intervals (95% CIs) and multilevel model. The risk of bias was assessed using the Rob2 tool. Seven randomized controlled trials involving 2,962 patients were eligible for inclusion. Nafamostat reduced the overall incidence rate of PEP (20 mg, OR: 0.50, 95% CI: 0.30-0.82 and 50 mg, OR: 0.48, 95% CI: 0.24-0.96). However, the occurrence of mild PEP was significantly reduced only in the subgroup receiving 20 mg nafamostat (OR, 0.49, 95% CI: 0.31-0.77). Overall, nafamostat therapy reduced moderate PEP in high-risk patients (OR: 0.18, 95% CI: 0.0.4-0.84) and mild PEP in low-risk patients (OR: 0.32, 95% CI: 0.17-0.61). Nafamostat is an effective therapy in the prevention of mild post-ERCP pancreatitis. Further research is required to determine the cost-effectiveness of this therapy.

Discharge protocol in acute pancreatitis: an international survey and cohort analysis.

There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p < 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients' care.

Extended infusion of ß-lactams significantly reduces mortality and enhances microbiological eradication in paediatric patients: a systematic review and meta-analysis.

Background: Paediatric patients are often exposed to subtherapeutic levels or treatment failure of ß-lactams, and prolonged infusion may be beneficial. We aimed to investigate the efficacy and safety of extended infusion (EI; defined as ≥3 h) or continuous infusion vs. short, intermittent infusion (SI; defined as ≤60 min) of ß-lactams in patients <21 years of age. Methods: A systematic review and meta-analysis was conducted to compare EI and continuous infusion with SI of ß-lactams in children. A systematic search was performed in MEDLINE (via PubMed), Embase, CENTRAL, and Scopus databases for randomised controlled trials (RCTs) and observational studies published from database inception up to August 22, 2023. Any comparative study concerned with mortality, clinical efficacy, adverse events, or plasma concentrations of ß-lactams for any infection was eligible. Case reports, case series, and patients aged >21 years were excluded. Odds ratios (OR) and median differences with 95% confidence intervals (CI) were calculated using a random-effects model. Risk of bias (ROB) was assessed using ROB2 and ROBINS-I tools. The protocol was registered with PROSPERO, CRD42022375397. Findings: In total, 19,980 articles were screened, out of which 19 studies (4195 patients) were included in the meta-analysis. EI administration was associated with a significantly lower all-cause mortality in both RCTs and non-RCTs [OR 0.74; CI 0.55-0.99; I2 = 0%; CI 0-58%]. Early microbiological eradication was higher with EI [OR 3.18; CI 2.24-4.51; I2 = 0%; CI 0-90%], but the clinical cure did not differ significantly between the two groups [OR 1.20; CI 0.17-8.71; I2 = 79%; CI 32-93%]. Achieving the optimal plasma level (50-100% fT > MIC) appeared favourable in the EI group compared to the SI. No significant differences were observed in the adverse events. The overall ROB was high because of the small sample sizes and clinically heterogeneous populations. Interpretation: Our findings suggest that extended infusion of ß-lactams was associated with lower mortality and increased microbiological eradication and was considered safe compared to short-term infusion. Funding: None.

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

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

The Effect of Additional Whole-Body Vibration on Musculoskeletal System in Children with Cerebral Palsy: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Nowadays, whole-body vibration (WBV) has become increasingly popular as an additional therapy in the intervention of patients with cerebral palsy (CP). However, the impact of WBV remains a subject of debate. Consequently, a systematic review and meta-analysis were undertaken to evaluate the effects of WBV on the musculoskeletal system in children with CP. Randomized controlled trials (RCTs) were sought in the most frequent databases. The intervention studied was WBV combined with conventional physiotherapy (PT) compared with conventional PT as the control; the main outcomes were changes in the musculoskeletal system. Weighted mean differences with 95%CIs were calculated. A random-effects model was applied, and the publication bias was checked using funnel plots. On the basis of the inclusion and exclusion criteria, 16 articles, including 414 patients, were considered in the final analysis. The improvement in walking performance (speed and step length) was statistically significant (p < 0.05), and although there were no significant differences in the further outcomes, a clear positive tendency was visible in the case of improved muscle strength, decreased spasticity, enhanced gross motor functions, and overall stability. Based on the findings, a clear assessment of the usefulness of this intervention cannot be made; nonetheless, due to the promising results, it would be worthwhile to conduct additional RCTs to enhance the available evidence in this field. Due to the wide range of vibration configurations, including varying durations and intensities, it is suggested to establish guidelines and a strategy for the incorporation of this additional treatment.

Routine screening of abnormal vaginal flora during pregnancy reduces the odds of preterm birth: a systematic review and meta-analysis.

Prematurity is the leading cause of perinatal mortality and the morbidity among children under the age of 5. The prevalence of preterm birth is between 5 and 18% worldwide. Approximately 30% of preterm deliveries occur as a consequence of fetal or maternal infections. Bacterial vaginosis can increase the risk of ascending infections. However, there is no recommendation or protocol for screening of abnormal vaginal flora. The aim of this systematic review was to investigate the effectiveness of routine screening of abnormal vaginal flora during pregnancy care. We conducted our systematic search in the following databases: MEDLINE via PubMed, Embase, and Cochrane Library. Studies reporting on pregnant women with no symptoms of bacterial vaginosis were included in our analysis if they provided data on the outcome of their pregnancy. The intervention group went through screening of abnormal vaginal flora in addition to routine pregnancy care. Odds ratio (OR) with 95% confidence intervals (CIs) was used as effect size measure. From each study the total number of patients and number of events was extracted in both the intervention and control arm to calculate OR. Altogether we included 13 trials with 143,534 patients. The screening methods were Gram stain, pH screening, pH self-screening and pH screening combined with Gram stain. Regular screening of vaginal flora compared to no screening significantly reduces the odds of preterm birth before 37 weeks (8.98% vs 9.42%; OR 0.71, CI 0.57-0.87), birthweight under 2500 g (6.53% vs 7.24%; OR 0.64, CI 0.50-0.81), preterm birth before 32 weeks (1.35% vs 2.03%; OR 0.51, CI 0.31-0.85) and birthweight under 1000 g (0.86% vs 2.2%; OR 0.33, CI 0.19-0.57). In conclusion, the routine screening of abnormal vaginal flora might prevent preterm birth, extreme preterm birth, low birthweight deliveries and very low birthweight deliveries. Further research is needed to assess the problem more accurately.

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.

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.

Direct Oral Anticoagulants as the First Choice of Anticoagulation for Patients with Peripheral Artery Disease to Prevent Adverse Vascular Events: A Systematic Review and Meta-Analysis.

The best method of anticoagulation for patients with peripheral artery disease (PAD) is still a topic of interest for physicians. We conducted a meta-analysis to compare the effects of direct oral anticoagulants (DOACs) with those of vitamin-K-antagonist (VKA) anticoagulants in patients with peripheral artery disease. Five databases (Medline (via PubMed), EMBASE, Scopus, Web of Science, and CENTRAL) were searched systematically for studies comparing the effects of the two types of anticoagulants in patients with PAD, with an emphasis on lower-limb outcomes, cardiovascular events, and mortality. In PAD patients with concomitant non-valvular atrial fibrillation (NVAF), the use of DOACs significantly reduced the risk of major adverse limb events (HR = 0.58, 95% CI, 0.39-0.86, p < 0.01), stroke/systemic embolism (HR 0.76; 95% CI 0.61-0.95; p < 0.01), and all-cause mortality (HR 0.78; 95% CI 0.66-0.92; p < 0.01) compared with warfarin, but showed similar risks of MI (HR = 0.81, 95% CI, 0.59-1.11, p = 0.2) and cardiovascular mortality (HR = 0.77, 95% CI, 0.58-1.02, p = 0.07). Rivaroxaban at higher doses significantly increased the risk of major bleeding (HR = 1.16, 95% CI, 1.07-1.25, p < 0.01). We found no significant difference in terms of revascularization (OR = 1.49, 95% CI, 0.79-2.79, p = 0.14) in PAD patients in whom a poor distal runoff was the reason for the anticoagulation. DOACs have lower rates of major limb events, stroke, and mortality than VKAs in PAD patients with atrial fibrillation. Rivaroxaban at higher doses increased the risk of major bleeding compared with other DOAC drugs. More high-quality studies are needed to determine the most appropriate anticoagulation regimen for patients with lower-limb atherosclerosis.

The combination of ulinastatin and somatostatin reduces complication rates in acute pancreatitis: a systematic review and meta-analysis of randomized controlled trials.

Currently, there is no specific pharmaceutical agent for treating acute pancreatitis (AP). Somatostatin and its analogues have been used to prevent the autolysis of the pancreas in AP, however, their effectiveness has not been confirmed. This investigation aimed to examine the efficacy of ulinastatin, a protease inhibitor, combined with somatostatin analogues in the treatment of AP. We conducted a systematic database search in 4 databases to identify randomized controlled trials in which the efficacy of ulinastatin in combination with somatostatin analogue was compared to somatostatin analogue alone in patients with AP. Since the patient populations of analysed papers were slightly different, we used random effect models to pool odds ratios (OR) and mean differences (MD) and the corresponding 95% confidence intervals (CI). A total of 9 articles comprising 1037 patients were included in the meta-analysis. The combination therapy significantly reduced the complication rates for acute respiratory distress syndrome, acute kidney injury, and multiple organ dysfunction. Symptoms were relieved threefold with the combination therapy compared to somatostatin alone, and combination therapy significantly shortened the length of hospital stay. The decrease in mortality was not statistically significant..

Early prediction of acute necrotizing pancreatitis by artificial intelligence: a prospective cohort-analysis of 2387 cases.

Pancreatic necrosis is a consistent prognostic factor in acute pancreatitis (AP). However, the clinical scores currently in use are either too complicated or require data that are unavailable on admission or lack sufficient predictive value. We therefore aimed to develop a tool to aid in necrosis prediction. The XGBoost machine learning algorithm processed data from 2387 patients with AP. The confidence of the model was estimated by a bootstrapping method and interpreted via the 10th and the 90th percentiles of the prediction scores. Shapley Additive exPlanations (SHAP) values were calculated to quantify the contribution of each variable provided. Finally, the model was implemented as an online application using the Streamlit Python-based framework. The XGBoost classifier provided an AUC value of 0.757. Glucose, C-reactive protein, alkaline phosphatase, gender and total white blood cell count have the most impact on prediction based on the SHAP values. The relationship between the size of the training dataset and model performance shows that prediction performance can be improved. This study combines necrosis prediction and artificial intelligence. The predictive potential of this model is comparable to the current clinical scoring systems and has several advantages over them.

In-Hospital Patient Education Markedly Reduces Alcohol Consumption after Alcohol-Induced Acute Pancreatitis.

Although excessive alcohol consumption is by far the most frequent cause of recurrent acute pancreatitis (AP) cases, specific therapy is still not well established to prevent recurrence. Generally, psychological therapy (e.g., brief intervention (BI)) is the cornerstone of cessation programs; however, it is not yet widely used in everyday practice. We conducted a post-hoc analysis of a prospectively collected database. Patients suffering from alcohol-induced AP between 2016 and 2021 received 30 min BI by a physician. Patient-reported alcohol consumption, serum gamma-glutamyl-transferase (GGT) level, and mean corpuscular volume (MCV) of red blood cells were collected on admission and at the 1-month follow-up visit to monitor patients' drinking habits. Ninety-nine patients with alcohol-induced AP were enrolled in the study (mean age: 50 ± 11, 89% male). A significant decrease was detected both in mean GGT value (294 ± 251 U/L vs. 103 ± 113 U/L, p < 0.001) and in MCV level (93.7 ± 5.3 U/L vs. 92.1 ± 5.1 U/L, p < 0.001) in patients with elevated on-admission GGT levels. Notably, 79% of the patients (78/99) reported alcohol abstinence at the 1-month control visit. Brief intervention is an effective tool to reduce alcohol consumption and to prevent recurrent AP. Longitudinal randomized clinical studies are needed to identify the adequate structure and frequency of BIs in alcohol-induced AP.

Association of Body Mass Index With Clinical Outcomes in Patients With Cystic Fibrosis: A Systematic Review and Meta-analysis.

IMPORTANCE: The prevalence of overweight (body mass index [BMI] = 25-29.9 [calculated as weight in kilograms divided by height in meters squared]) and obesity (BMI ≥30) is increasing among patients with cystic fibrosis (CF). However, it is unclear whether there is a benefit associated with increasing weight compared with the reference range (ie, normal) in CF. OBJECTIVE: To evaluate the association of altered BMI or body composition and clinical outcomes in patients with CF. DATA SOURCES: For this systematic review and meta-analysis, the literature search was conducted November 2, 2020, of 3 databases: MEDLINE (via PubMed), Embase, and Cochrane Central Register of Controlled Trials. STUDY SELECTION: Patients older than 2 years diagnosed with CF with altered body composition or BMI were compared with patients having the measured parameters within the reference ranges. Records were selected by title, abstract, and full text; disagreements were resolved by consensus. Cohort studies and conference abstracts were eligible; articles with no original data and case reports were excluded. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted data, which were validated by a third author. Studies containing insufficient poolable numerical data were included in the qualitative analysis. A random-effects model was applied in all analyses. MAIN OUTCOMES AND MEASURES: Pulmonary function, exocrine pancreatic insufficiency (PI), and CF-related diabetes (CFRD) were investigated as primary outcomes. Odds ratios (ORs) or weighted mean differences (WMDs) with 95% CIs were calculated. The hypothesis was formulated before data collection. RESULTS: Of 10 524 records identified, 61 met the selection criteria and were included in the qualitative analysis. Of these, 17 studies were included in the quantitative synthesis. Altogether, 9114 patients were included in the systematic review and meta-analysis. Overweight (WMD, -8.36%; 95% CI, -12.74% to -3.97%) and obesity (WMD, -12.06%; 95% CI, -23.91% to -0.22%) were associated with higher forced expiratory volume in the first second of expiration compared with normal weight. The odds for CFRD and PI were more likely in patients of normal weight (OR, 1.49; 95% CI, 1.10 to 2.00) than in those who were overweight (OR, 4.40; 95% CI, 3.00 to 6.45). High heterogeneity was shown in the analysis of pulmonary function (I2 = 46.7%-85.9%). CONCLUSIONS AND RELEVANCE: The findings of this systematic review and meta-analysis suggest that the currently recommended target BMI in patients with CF should be reconsidered. Studies with long-term follow-up are necessary to assess the possible adverse effects of higher BMI or higher fat mass in patients with CF.

Heat therapy shows benefit in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

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

It Is High Time for Personalized Dietary Counseling in Celiac Disease: A Systematic Review and Meta-Analysis on Body Composition.

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