The EFFect of dietary fat content on the recurrence of pancreaTitis (EFFORT): Protocol of a multicenter randomized controlled trial.

BACKGROUND: Around 20% of patients with acute pancreatitis (AP) will develop acute recurrent pancreatitis (ARP) and 10% will progress to chronic pancreatitis. While interventions to avoid recurrences exist for the two most common causes - abstinence for alcoholic and cholecystectomy for biliary pancreatitis - the are no known preventive measures in idiopathic ARP. Though it is not included in any of the guidelines, a low-fat diet is often recommended. Our aim is to test dietary fat reduction's effect on AP recurrence in a randomized controlled setting, in order to provide high-quality evidence for the validity of such an intervention. METHODS, DESIGN: Participants with at least 2 episodes of AP in the preceding 2 years of which the last episode was idiopathic will be randomized to one of two diets with different fat contents: a 'reduced fat diet' (15% fat, 65% carbohydrate, 20% protein) and a 'standard healthy diet' (30% fat, 50% carbohydrate, 20% protein; based on WHO recommendations). Participants will be followed-up for 2 years (visits will be scheduled for months 3, 6, 12, 18 and 24) during which they will receive a repeated session of nutritional guidance, complete food frequency questionnaires and data on relapse, mortality, BMI, cardiovascular parameters and serum lipid values will be collected. DISCUSSION: This study will determine the effect of modifying the dietary fat content on AP recurrence, mortality, serum lipids and weight loss in idiopathic cases.

Glucose levels show independent and dose-dependent association with worsening acute pancreatitis outcomes: Post-hoc analysis of a prospective, international cohort of 2250 acute pancreatitis cases.

BACKGROUND: Metabolic risk factors, such as obesity, hypertension, and hyperlipidemia are independent risk factors for the development of various complications in acute pancreatitis (AP). Hypertriglyceridemia dose-dependently elicits pancreatotoxicity and worsens the outcomes of AP. The role of hyperglycemia, as a toxic metabolic factor in the clinical course of AP, has not been examined yet. METHODS: We analyzed a prospective, international cohort of 2250 AP patients, examining associations between (1) glycosylated hemoglobin (HbA1c), (2) on-admission glucose, (3) peak in-hospital glucose and clinically important outcomes (mortality, severity, complications, length of hospitalization (LOH), maximal C-reactive protein (CRP)). We conducted a binary logistic regression accounting for age, gender, etiology, diabetes, and our examined variables. Receiver Operating Characteristic Curve (ROC) was applied to detect the diagnostic accuracy of the three variables. RESULTS: Both on-admission and peak serum glucose are independently associated with AP severity and mortality, accounting for age, gender, known diabetes and AP etiology. They show a dose-dependent association with severity (p < 0.001 in both), mortality (p < 0.001), LOH (p < 0.001), maximal CRP (p < 0.001), systemic (p < 0.001) and local complications (p < 0.001). Patients with peak glucose >7 mmol/l had a 15 times higher odds for severe AP and a five times higher odds for mortality. We found a trend of increasing HbA1c with increasing LOH (p < 0.001), severity and local complications. CONCLUSIONS: On-admission and peak in-hospital glucose are independently and dose-dependently associated with increasing AP severity and mortality. In-hospital laboratory control of glucose and adequate treatment of hyperglycemia are crucial in the management of AP.

Early occurrence of pseudocysts in acute pancreatitis - A multicenter international cohort analysis of 2275 cases.

BACKGROUND: Pseudocysts being the most frequent local complications of acute pancreatitis (AP) have substantial effect on the disease course, hospitalization and quality of life of the patient. Our study aimed to understand the effects of pre-existing (OLD-P) and newly developed (NEW-P) pseudocysts on AP. METHODS: Data were extracted from the Acute Pancreatitis Registry organized by the Hungarian Pancreatic Study Group (HPSG). 2275 of 2461 patients had uploaded information concerning pancreatic morphology assessed by imaging technique. Patients were divided into "no pseudocyst" (NO-P) group, "old pseudocyst" (OLD-P) group, or "newly developed pseudocyst" (NEW-P) groups. RESULTS: The median time of new pseudocyst development was nine days from hospital admission and eleven days from the beginning of the abdominal pain. More NEW-P cases were severe (15.9% vs 4.7% in the NO-P group p < 0.001), with longer length of hospitalization (LoH) (median: 14 days versus 8 days, p < 0.001), and were associated with several changed laboratory parameters. OLD-P was associated with male gender (72.2% vs. 56.1%, p = 0.0014), alcoholic etiology (35.2% vs. 19.8% in the NO-P group), longer hospitalization (median: 10 days, p < 0.001), a previous episode of AP (p < 0.001), pre-existing diagnosis of chronic pancreatitis (CP) (p < 0.001), current smoking (p < 0.001), and increased alcohol consumption (unit/week) (p = 0.014). CONCLUSION: Most of the new pseudocysts develop within two weeks. Newly developing pseudocysts are associated with a more severe disease course and increased length of hospitalization. Pre-existing pseudocysts are associated with higher alcohol consumption and smoking. Because CP is more frequently associated with a pre-existing pseudocyst, these patients need closer attention after AP.

Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID-19: a systematic review and meta-analysis.

Despite the growing knowledge of the clinicopathological features of COVID-19, the correlation between early changes in the laboratory parameters and the clinical outcomes of patients is not entirely understood. In this study, we aimed to assess the prognostic value of early laboratory parameters in COVID-19. We conducted a systematic review and meta-analysis based on the available literature in five databases. The last search was on July 26, 2020, with key terms related to COVID-19. Eligible studies contained original data of at least ten infected patients and reported on baseline laboratory parameters of patients. We calculated weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) with 95% confidence intervals. 93 and 78 studies were included in quantitative and qualitative syntheses, respectively. Higher baseline total white blood cell count (WBC), C-reactive protein (CRP), lactate-dehydrogenase (LDH), creatine kinase (CK), D-dimer and lower absolute lymphocyte count (ALC) (WMDALC = - 0.35 × 109/L [CI - 0.43, - 0.27], p < 0.001, I2 = 94.2%; < 0.8 × 109/L, ORALC = 3.74 [CI 1.77, 7.92], p = 0.001, I2 = 65.5%) were all associated with higher mortality rate. On admission WBC, ALC, D-dimer, CRP, LDH, and CK changes could serve as alarming prognostic factors. The correct interpretation of laboratory abnormalities can guide therapeutic decisions, especially in early identification of potentially critical cases. This meta-analysis should help to allocate resources and save lives by enabling timely intervention.

Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis - An international cohort study.

BACKGROUND: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP. METHODS: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018. RESULTS: Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality. CONCLUSIONS: Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP.

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.

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

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

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

Invalidity of Tokyo guidelines in acute biliary pancreatitis: A multicenter cohort analysis of 944 pancreatitis cases.

BACKGROUND: There is a noteworthy overlap between the clinical picture of biliary acute pancreatitis (AP) and the 2018 Tokyo guidelines currently used for the diagnosis of cholangitis (AC) and cholecystitis (CC). This can lead to significant antibiotic and endoscopic retrograde cholangiopancreatography (ERCP) overuse. OBJECTIVES: We aimed to assess the on-admission prevalence of AC/CC according to the 2018 Tokyo guidelines (TG18) in a cohort of biliary AP patients, and its association with antibiotic use, ERCP and clinically relevant endpoints. METHODS: We conducted a secondary analysis of the Hungarian Pancreatic Study Group's prospective multicenter registry of 2195 AP cases. We grouped and compared biliary cases (n = 944) based on the on-admission fulfillment of definite AC/CC according to TG18. Aside from antibiotic use, we evaluated mortality, AC/CC/AP severity, ERCP performance and length of hospitalization. We also conducted a literature review discussing each criteria of the TG18 in the context of AP. RESULTS: 27.8% of biliary AP cases fulfilled TG18 for both AC and CC, 22.5% for CC only and 20.8% for AC only. Antibiotic use was high (77.4%). About 2/3 of the AC/CC cases were mild, around 10% severe. Mortality was below 1% in mild and moderate AC/CC patients, but considerably higher in severe cases (12.8% and 21.2% in AC and CC). ERCP was performed in 89.3% of AC cases, common bile duct stones were found in 41.1%. CONCLUSION: Around 70% of biliary AP patients fulfilled the TG18 for AC/CC, associated with a high rate of antibiotic use. Mortality in presumed mild or moderate AC/CC is low. Each of the laboratory and clinical criteria are commonly fulfilled in biliary AP, single imaging findings are also unspecific-AP specific diagnostic criteria are needed, as the prevalence of AC/CC are likely greatly overestimated. Randomized trials testing antibiotic use are also warranted.

Risk factors for diabetes mellitus after acute pancreatitis: a systematic review and meta-analysis.

Introduction: Within 5 years of having acute pancreatitis (AP), approximately 20% of patients develop diabetes mellitus (DM), which later increases to approximately 40%. Some studies suggest that the prevalence of prediabetes (PD) and/or DM can grow as high as 59% over time. However, information on risk factors is limited. We aimed to identify risk factors for developing PD or DM following AP. Methods: We systematically searched three databases up to 4 September 2023 extracting direct, within-study comparisons of risk factors on the rate of new-onset PD and DM in AP patients. When PD and DM event rates could not be separated, we reported results for this composite outcome as PD/DM. Meta-analysis was performed using the random-effects model to calculate pooled odds ratios (OR) with 95% confidence intervals (CI). Results: Of the 61 studies identified, 50 were included in the meta-analysis, covering 76,797 participants. The studies reported on 79 risk factors, and meta-analysis was feasible for 34 risk factor and outcome pairs. The odds of developing PD/DM was significantly higher after severe and moderately severe AP (OR: 4.32; CI: 1.76-10.60) than mild AP. Hypertriglyceridemic AP etiology (OR: 3.27; CI: 0.17-63.91) and pancreatic necrosis (OR: 5.53; CI: 1.59-19.21) were associated with a higher risk of developing PD/DM. Alcoholic AP etiology (OR: 1.82; CI: 1.09-3.04), organ failure (OR: 3.19; CI: 0.55-18.64), recurrent AP (OR: 1.89; CI: 0.95-3.77), obesity (OR: 1.85; CI: 1.43-2.38), chronic kidney disease (OR: 2.10; CI: 1.85-2.38), liver cirrhosis (OR: 2.48; CI: 0.18-34.25), and dyslipidemia (OR: 1.82; CI: 0.68-4.84) were associated with a higher risk of developing DM. Discussion: Severe and moderately severe AP, alcoholic and hypertriglyceridemic etiologies, pancreatic necrosis, organ failure, recurrent acute pancreatitis and comorbidities of obesity, chronic kidney disease liver disease, and dyslipidemia are associated with a higher risk of developing PD or DM. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021281983.

Admission risk factors and predictors of moderate or severe pediatric acute pancreatitis: A systematic review and meta-analysis.

Introduction: Pediatric acute pancreatitis (PAP) has an increasing incidence and is now estimated to be almost as common as in adults. Up to 30% of patients with PAP will develop moderate or severe disease course (M/SPAP), characterized by organ failure, local or systemic complications. There is still no consensus regarding on-admission severity prediction in these patients. Our aim was to conduct a systematic review and meta-analysis of available predictive score systems and parameters, and differences between on-admission parameters in mild and M/SPAP. Methods: We conducted a systematic search on the 14th February, 2022 in MEDLINE, Embase and CENTRAL. We performed random-effects meta-analysis of on-admission differences between mild and M/SPAP in laboratory parameters, etiology, demographic factors, etc. calculating risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI) and created forest plots. For the meta-analysis of predictive score systems, we generated hierarchical summary receiver operating characteristic curves using a bivariate model. Chi-squared tests were performed and I2 values calculated to assess statistical heterogeneity. Results: We included 44 studies - mostly retrospective cohorts - in our review. Among predictive score systems examined by at least 5 studies, the modified Glasgow scale had the highest specificity (91.5% for values ≥3), and the Pediatric Acute Pancreatitis Severity score the highest sensitivity (63.1% for values ≥3). The performance of other proposed score systems and values were summarized. Traumatic (RR: 1.70 95% CI: 1.09-2.67) and drug-induced (RR: 1.33 95% CI: 0.98-1.87) etiologies were associated with a higher rate of M/SPAP, while anatomical (RR: 0.6195% CI: 0.38-0.96) and biliary (RR: 0.72 95% CI: 0.53-0.99) PAP tended to be less severe. Discussion: Many predictive score systems were proposed to assess the possibility of M/SPAP course. The most commonly used ones exhibit good specificity, but subpar sensitivity. Our systematic review provides a rigorous overview of predictive options assessed thus far, that can serve as a basis for future improvement of scores via the addition of parameters with a better observed sensitivity: e.g., lipase exceeding 7-times the upper threshold, hemoglobin, etc. The addition of etiological factors is another possibility, as they can herald a more severe disease course. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=307271, PROSPERO, identifier: CRD42022307271.

Exosomes as prognostic biomarkers in pancreatic ductal adenocarcinoma-a systematic review and meta-analysis.

Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this highly lethal malignancy. We performed a systematic review and meta-analysis on the prognostic value of exosomal biomarkers in pancreatic ductal adenocarcinoma (PDAC). MEDLINE, Embase, Scopus, Web of Science, and CENTRAL were systematically searched on the 18th of January, 2021 for studies reporting on the differences in overall (OS) and progression-free survival (PFS) in PDAC patients with positive vs negative exosomal biomarkers isolated from blood. The random-effects model estimated pooled multivariate-adjusted (AHR) and univariate hazard ratios (UHRs) with 95% confidence intervals (CIs). Eleven studies comprising 634 patients were eligible for meta-analysis. Detection of positive exosomal biomarkers indicated increased risk of mortality (UHR = 2.81, CI:1.31-6,00, I2 = 88.7%, P < 0.001), and progression (UHR = 3.33, CI: 2.33-4.77, I2 = 0, P = 0.879) across various disease stages. Positive exosomal biomarkers identified preoperatively revealed a higher risk of mortality in resectable stages (UHR = 5.55, CI: 3.24-9.49, I2 = 0, P = 0.898). The risk of mortality in unresectable stages was not significantly increased with positive exosomal biomarkers (UHR = 2.51, CI: 0.55-11.43, I2 = 90.3%, P < 0.001). Detectable exosomal micro ribonucleic acids were associated with a decreased OS (UHR = 4.08, CI: 2.16-7.69, I2 = 46.9%, P = 0.152) across various stages. Our results reflect the potential of exosomal biomarkers for prognosis evaluation in PDAC. The associated heterogeneity reflects the variability of study methods and need for their uniformization before transition to clinical use.

The risk of postoperative respiratory complications following adenotonsillar surgery in children with or without obstructive sleep apnea: A systematic review and meta-analysis.

OBJECTIVES: Obstructive sleep apnea (OSA) appears in 2%-5% of children, with first-line treatment being adenotonsillar (AT) surgery. Our aim was to examine the risk of postoperative respiratory complications (PoRCs) in non-OSA and the different OSA severity (mild, moderate, severe) groups. STUDY DESIGN: We conducted a systematic review and meta-analysis of studies comparing PoRCs following AT surgery in children with and without OSA. METHODS: Nineteen observational studies were identified with the same search key used in MEDLINE, Embase, and CENTRAL. The connection between PoRCs, the presence and severity of OSA, and additional comorbidities were examined. Odds ratios (OR) were calculated with 95% confidence intervals (CI). RESULTS: We found that PoRCs appeared more frequently in moderate (p = 0.048, OR: 1.79, CI [1.004, 3.194]) and severe OSA (p = 0.002, OR: 4.06, CI [1.68, 9.81]) compared to non-OSA patients. No significant difference was detected in the appearance of major complications (p = 0.200, OR: 2.14, CI [0.67, 6.86]) comparing OSA and non-OSA populations. No significant difference was observed in comorbidities (p = 0.669, OR: 1.29, CI [0.40, 4.14]) or in the distribution of PoRCs (p = 0.904, OR: 0.94, CI [0.36, 2.45]) between the two groups. CONCLUSION: Uniform guidelines and a revision of postoperative monitoring are called for as children with moderate and severe OSA are more likely to develop PoRCs following AT surgery based on our results, but no significant difference was found in mild OSA. Furthermore, the presence of OSA alone is not associated with an increased risk of developing major complications.

Pancreatic family history does not predict disease progression but connotes alcohol consumption in adolescents and young adults with acute pancreatitis: Analysis of an international cohort of 2,335 patients.

Background: In pediatric acute pancreatitis (AP), a family history of pancreatic diseases is prognostic for earlier onset of recurrent AP (ARP) and chronic pancreatitis (CP). No evidence supports the same association in adult-onset pancreatitis. Age-specific reasons for familial aggregation are also unclear. We aimed to examine the prognostic role of pancreatic family history for ARP/CP and observe possible underlying mechanisms. Methods: We conducted a secondary analysis of the Hungarian Pancreatic Study Group's (HPSG) multicenter, international, prospective registry of patients with AP, both children and adults. We compared the positive family history and the negative family history of pancreatic diseases, in different age groups, and analyzed trends of accompanying factors. Chi-square and Fisher exact tests were used. Results: We found a higher rate of ARP/CP in the positive pancreatic family history group (33.7 vs. 25.9%, p = 0.018), peaking at 6-17 years. Idiopathic AP peaked in childhood in the positive family history group (75% 0-5 years) and was consistently 20-35% in the negative group. A higher rate of alcohol consumption/smoking was found in the positive groups at 12-17 years (62.5 vs. 15.8%, p = 0.013) and 18-29 years (90.9 vs. 58.1%, p = 0.049). The prevalence of diabetes and hyperlipidemia steadily rose with age in both groups. Conclusion: Positive family history most likely signifies genetic background in early childhood. During adolescence and early adulthood, alcohol consumption and smoking emerge-clinicians should be aware and turn to intervention in such cases. Contrary to current viewpoints, positive pancreatic family history is not a prognostic factor for ARP and CP in adults, so it should not be regarded that way.

Recurrent acute pancreatitis prevention by the elimination of alcohol and cigarette smoking (REAPPEAR): protocol of a randomised controlled trial and a cohort study.

BACKGROUND/OBJECTIVES: Acute recurrent pancreatitis (ARP) due to alcohol and/or tobacco abuse is a preventable disease which lowers quality of life and can lead to chronic pancreatitis. The REAPPEAR study aims to investigate whether a combined patient education and cessation programme for smoking and alcohol prevents ARP. METHODS AND ANALYSIS: The REAPPEAR study consists of an international multicentre randomised controlled trial (REAPPEAR-T) testing the efficacy of a cessation programme on alcohol and smoking and a prospective cohort study (REAPPEAR-C) assessing the effects of change in alcohol consumption and smoking (irrespective of intervention). Daily smoker patients hospitalised with alcohol-induced acute pancreatitis (AP) will be enrolled. All patients will receive a standard intervention priorly to encourage alcohol and smoking cessation. Participants will be subjected to laboratory testing, measurement of blood pressure and body mass index and will provide blood, hair and urine samples for later biomarker analysis. Addiction, motivation to change, socioeconomic status and quality of life will be evaluated with questionnaires. In the trial, patients will be randomised either to the cessation programme with 3-monthly visits or to the control group with annual visits. Participants of the cessation programme will receive a brief intervention at every visit with direct feedback on their alcohol consumption based on laboratory results. The primary endpoint will be the composite of 2-year all-cause recurrence rate of AP and/or 2-year all-cause mortality. The cost-effectiveness of the cessation programme will be evaluated. An estimated 182 participants will be enrolled per group to the REAPPEAR-T with further enrolment to the cohort. ETHICS AND DISSEMINATION: The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (40394-10/2020/EÜIG), all local ethical approvals are in place. Results will be disseminated at conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04647097.

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

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

Vitamin D supplementation in patients with cystic fibrosis: A systematic review and meta-analysis.

Despite routine supplementation, vitamin D insufficiency is often seen in cystic fibrosis (CF) patients on account of pancreatic insufficiency. Vitamin D is a crucial component of bone health and affects nearly all cells of the immune system. However, clinical benefits or harms associated with supplementation are poorly documented. In this systematic review, we included randomized controlled trials (RCTs) that compared vitamin D supplementation with placebo (i.e. 'non-increased dose') in CF patients. Analysing the 8 included RCTs, the intervention group had significantly higher serum 25-hydroxyvitamin D (se25OHD) levels, but there were no significant differences found in the quantitative synthesis of clinical outcomes, including bone disease-, respiratory status- and immunological status-related outcomes. Based on our current results, while a higher vitamin D dose elevates se25OHD, it does not seem to influence clinical outcomes. Future RCTs should include outcomes of past studies and apply longer follow-up periods to document long-term patient-important outcomes.

Screening Methods for Diagnosing Cystic Fibrosis-Related Diabetes: A Network Meta-Analysis of Diagnostic Accuracy Studies.

BACKGROUND: Cystic fibrosis-related diabetes (CFRD) has become more common due to higher life expectancy with cystic fibrosis. Early recognition and prompt treatment of CFRD leads to improved outcomes. METHODS: We performed a network meta-analysis (NMA) in order to identify the most valuable diagnostic metrics for diagnosing CFRD out of available screening tools (index test), using the oral glucose tolerance test as a reference standard. Pooled sensitivity (Se), specificity (Sp), and superiority indices were calculated and used to rank the index tests. RESULTS: A total of 31 articles with 25 index tests were eligible for inclusion. Two-day, continuous glucose monitoring (CGM) ranked the highest (Se: 86% Sp: 76%), followed by glucose measurement from blood capillary samples (Se: 70%, Sp: 82%) and three-day CGM (Se: 96%, Sp: 56%). When we compared the CGM of different durations, two-day CGM performed best (Se: 88%, Sp: 80%), followed by three-day (Se: 96%, Sp: 59%) and six-day CGM (Se: 66%, Sp: 79%). CONCLUSIONS: Considering its overall performance ranking, as well as the high sensitivity, two-day CGM appears to be a promising screening test for CFRD.

Insufficient etiological workup of COVID-19-associated acute pancreatitis: A systematic review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, mostly causing respiratory symptoms, is also known to affect the gastrointestinal tract. Several case reports hypothesize that SARS-CoV-2 could be an etiological factor in acute pancreatitis (AP). AIM: To assess all the available evidence in the literature relating to coronavirus disease 2019 (COVID-19) and AP. METHODS: We performed a systematic review of the available literature on the topic. The systematic search was conducted on 15 May 2020 on MEDLINE, EMBASE, CENTRAL, Web of Science and Scopus with a search key using the terms "amylase," "lipase," "pancr*," "COVID-19" and synonyms. Due to the low quality and poor comparability of the studies, a meta-analysis was not performed. RESULTS: Six case reports and two retrospective cohorts were included, containing data on eleven COVID-19 patients with AP. Five patients had AP according to the Atlanta classification. Other publications did not provide sufficient information on the diagnostic criteria. Most cases were considered SARS-CoV-2-induced, while several established etiological factors were not investigated. We were able to identify other possible causes in most of them. CONCLUSION: We strongly highlight the need for adherence to the guidelines during a diagnostic and etiological workup, which could alter therapy.

Personalised health education against health damage of COVID-19 epidemic in the elderly Hungarian population (PROACTIVE-19): protocol of an adaptive randomised controlled clinical trial.

BACKGROUND: Early reports indicate that COVID-19 may require intensive care unit (ICU) admission in 5-26% and overall mortality can rise to 11% of the recognised cases, particularly affecting the elderly. There is a lack of evidence-based targeted pharmacological therapy for its prevention and treatment. We aim to compare the effects of a World Health Organization recommendation-based education and a personalised complex preventive lifestyle intervention package (based on the same WHO recommendation) on the outcomes of the COVID-19. METHODS: PROACTIVE-19 is a pragmatic, randomised controlled clinical trial with adaptive "sample size re-estimation" design. Hungarian population over the age of 60 years without confirmed COVID-19 will be approached to participate in a telephone health assessment and lifestyle counselling voluntarily. Volunteers will be randomised into two groups: (A) general health education and (B) personalised health education. Participants will go through questioning and recommendation in 5 fields: (1) mental health, (2) smoking habits, (3) physical activity, (4) dietary habits, and (5) alcohol consumption. Both groups A and B will receive the same line of questioning to assess habits concerning these topics. Assessment will be done weekly during the first month, every second week in the second month, then monthly. The composite primary endpoint will include the rate of ICU admission, hospital admission (longer than 48 h), and mortality in COVID-19-positive cases. The estimated sample size is 3788 subjects per study arm. The planned duration of the follow-up is a minimum of 1 year. DISCUSSION: These interventions may boost the body's cardiovascular and pulmonary reserve capacities, leading to improved resistance against the damage caused by COVID-19. Consequently, lifestyle changes can reduce the incidence of life-threatening conditions and attenuate the detrimental effects of the pandemic seriously affecting the older population. TRIAL REGISTRATION: The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (IV/2428- 2 /2020/EKU) and has been registered at clinicaltrials.gov ( NCT04321928 ) on 25 March 2020.