Head-to-head comparison of influenza vaccines in children: a systematic review and meta-analysis.

Although vaccination is considered the most effective weapon against influenza, coverage rates, national vaccination policies, and funding vary largely around the globe. Despite their huge potential for achieving herd immunity, child-focused national vaccination strategies that favor pain-free nasal vaccines are uncommon. CENTRAL, Embase, and MEDLINE were last searched on November 13, 2023. Active-controlled randomized controlled trials comparing the live-attenuated intranasal vaccine with the inactivated intramuscular influenza vaccine in children were included. Event rates of laboratory-confirmed influenza virus infection, all-cause mortality, hospitalization, serious adverse events, adverse events, and financial outcomes were extracted based on the PRISMA 2020 Guideline. PROSPERO: CRD42021285412. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the random-effects model when at least three comparable outcomes were available. We found no significant difference between quadrivalent live-attenuated intranasal and trivalent inactivated intramuscular (OR = 1.48; 95% CI 0.49-4.45) or between trivalent live-attenuated intranasal and inactivated intramuscular vaccines (OR = 0.77, CI = 0.44-1.34) regarding their efficacy. However, the subgroup analysis of large, multi-center trials indicated that the trivalent live attenuated intranasal influenza vaccine was superior to the trivalent inactivated intramuscular influenza vaccine (12,154 people, OR = 0.50, CI = 0.28-0.88). Only 23 "vaccine-related serious adverse events" were recorded among 17 833 individuals, with no significant difference between methods. The widespread initiation of pediatric national flu vaccination programs prioritizing the live-attenuated intranasal influenza vaccine would be beneficial. Multi-continent, high-quality studies that include children younger than two years old and those living in subtropical and tropical regions are needed to further enhance our understanding.

Antibiotic-Impregnated Ventriculoperitoneal Shunts Decrease Bacterial Shunt Infection: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Antibiotic-impregnated shunts seem to be beneficial in preventing bacterial infections and decreasing mortality by effectively inhibiting microbial growth in the shunt system and reducing the risk of shunt-associated infections. This study aimed to evaluate the efficacy of antibiotic-impregnated shunt catheters (AISC) in reducing the incidence of bacterial shunt infection in patients with hydrocephalus. METHODS: The protocol was registered on PROSPERO. A meta-analysis was conducted by searching 3 databases (PubMed, Scopus, CENTRAL) for relevant randomized controlled trials and observational studies. We included all studies published until November 2022 in any language. The primary outcome was the rate of bacterial infections, whereas the rate of shunt failure was our secondary endpoint. Odds ratios (OR) with 95% CI were calculated using a random-effects model. RESULTS: A total of 27 articles with 27 266 shunt operations were included in this study. The results indicated that using AISC is significantly associated with reduction in infections (OR = 0.42; 95% CI: 0.33-0.54). Regarding shunt failure, there was a tendency in favor of AISC use (OR = 0.73; 95% CI: 0.51-1.06). CONCLUSION: Our study provided evidence that AISC is significantly associated with the reduction in the rate of bacterial ventriculoperitoneal-shunt infection. In addition, there was a tendency toward AISC to decrease shunt failure compared with the standard shunt.

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.

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.

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.

Association of tumor location with anxiety and depression in childhood brain cancer survivors: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the association between the location (supratentorial or infratentorial) of brain tumors and the development of depression and anxiety in childhood cancer survivors. Understanding the risk factors for the development of depression and anxiety disordersin these patients is crucial for early diagnosis and successful treatment. METHODS: The meta-analysis included articles that listed patients diagnosed with an intracranial tumor before the age of 18 years, provided the location of the tumor, had exact data on the prevalence of anxiety and depression, or measured these disorders using different assessment tools. The search was conducted in five different databases (MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library). Risk of bias was assessed using QUIPS-2. Outcome measures used were prevalences and standardized means. RESULTS: The analysis included 42 eligible articles with a total number of 1071 patients. Relevant articles were cohort studies, cross-sectional studies, and case series. Based on the available data infratentorial brain tumor survivors had significantly higher scores on various assessment tools measuring anxiety (MRAW (raw mean scores): 36.24 [CI (confidence interval): 28.81-43.67]; versus MRAW: 23.21 (CI 0.91-45.51); p = 0.02, and depression (MRAW: 27.57 (CI 14.35-40.78) versus MRAW: 13.84 (CI 11.43-16.26); p < 0.01. CONCLUSION: Childhood infratentorial cancer survivors have more impairments in terms of depression and anxiety; these children and adults should be monitored more frequently and may require closer follow-up on their mental health. The main limitation of our study originates from the lack of data on follow-up times used by different studies.

Neonatal Screening for Cystic Fibrosis in Hungary-First-Year Experiences.

The aim of this study is to evaluate the strategy of the cystic fibrosis newborn screening (CFNBS) programme in Hungary based on the results of the first year of screening. A combined immunoreactive trypsinogen (IRT) and pancreatitis-associated protein (PAP) CFNBS protocol (IRT/IRT×PAP/IRT) was applied with an IRT-dependent safety net (SN). Out of 88,400 newborns, 256 were tested screen-positive. Fourteen cystic fibrosis (CF) and two cystic fibrosis-positive inconclusive diagnosis (CFSPID) cases were confirmed from the screen-positive cases, and two false-negative cases were diagnosed later. Based on the obtained results, a sensitivity of 88% and a positive predictive value (PPV) of 5.9% were calculated. Following the recognition of false-negative cases, the calculation method of the age-dependent cut-off was changed. In purely biochemical CFNBS protocols, a small protocol change, even after a short period, can have a significant positive impact on the performance. CFNBS should be monitored continuously in order to fine-tune the screening strategy and define the best local practices.

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.

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.

Lactated Ringer's Solution Reduces Severity, Mortality, Systemic and Local Complications in Acute Pancreatitis: A Systematic Review and Meta-Analysis.

Fluid therapy is the cornerstone of early supportive therapy in acute pancreatitis (AP). Regrettably, the type of fluid is still debated among clinicians, despite recent evidence from randomized controlled trials (RCTs). We aimed to incorporate all evidence from RCTs comparing lactated Ringer's solution (LR) with normal saline (NS) in adult and pediatric AP patients, with particular emphasis on clinically relevant outcomes. We evaluated RCTs comparing intravenous fluid resuscitation with LR to NS in adult or pediatric AP patients according to a prospectively registered protocol (CRD42021224542). Moderate-to-severe AP (MSAP), mortality, length of hospitalization (LoH), need for intensive care, the incidence of systemic (organ failure, OF) and local complications (in total), necrosis and pseudocyst formation were analyzed separately. Risk ratio (RR) and median difference (MD) were calculated with 95% confidence intervals (CI) using a random effect model. Risk of bias and quality of evidence were assessed. Altogether, 8 eligible RCTs were found, including 557 patients (LR: 278; NS: 279). LR reduced the risk of MSAP by 31% (RR: 0.59, 95% CI: 0.36-0.97, high quality) and the risk of death by 62% (RR: 0.48; 95% CI: 0.24-0.98, very low quality). LR was associated with a significantly lower risk of need for intensive care (RR: 0.50, 95% CI: 0.33-0.77), OF (RR: 0.78, 95% CI: 0.61-0.99) and local complications (RR: 0.64, 95% CI: 0.46-0.89). No significant risk reduction was observed for LoH (MD: -0.57 days, CI: -1.33-0.19), necrosis, pseudocyst and inflammatory parameters by LR compared to NS. LR reduces severity, mortality, need of intensive care and systemic and local complications in AP.

Safety Analysis of Preoperative Anti-TNF-α Therapy in Pediatric IBD After Intestinal Resection: A Systematic Review and Meta-analysis.

BACKGROUND: Biological agents have transformed the management of inflammatory bowel disease (IBD). However, intestinal resection is still unavoidable in complicated IBD. It is still under debate whether antitumor necrosis factor (TNF)-α is related to higher postoperative complications in children with IBD. Therefore, we aimed to analyze data on preoperative anti-TNF-α and postoperative complications in pediatric IBD. METHODS: We conducted a systematic literature search in 4 databases for studies that compared the incidence of postoperative complications between children with IBD who received anti-TNF-α treatment within 12 weeks prior to intestinal resection and who did not receive anti-TNF-α before the operation. To analyze this question, pooled odds ratios (ORs) were calculated with 95% confidence intervals (CIs). Odds ratios higher than 1 mean higher complication rate among children treated with preoperative anti-TNF-α, whereas an OR lower than 1 means lower complication rate. The I² value was calculated to measure the strength of the between-study heterogeneity, where a smaller percentage means the lower heterogeneity. RESULTS: We found 8 eligible articles with 526 pediatric patients with IBD. The primary outcome was the overall complication. The pooled OR of overall complications was 1.38 (95% CI, 0.10-18.76; P = .65; I2 = 34%) in contrast, the OR of infectious and noninfectious complications were 0.59 (95% CI, 0.21-1.69; P = .16; I2 = 0%) and 0.48 (95% CI, 0.18-1.25; p = .09; I2 = 0%), although both showed a nonsignificant result. CONCLUSION: There is no significant association between preoperative anti-TNF-α therapy and postoperative complications in children with IBD after intestinal resection. However, the evidence is low due to the low number of studies investigating this question.

Inflammatory bowel disease does not alter the clinical features and the management of acute pancreatitis: A prospective, multicentre, exact-matched cohort analysis.

OBJECTIVE AND AIMS: Acute pancreatitis in inflammatory bowel disease occurs mainly as an extraintestinal manifestation or a side effect of medications. We aimed to investigate the prognostic factors and severity indicators of acute pancreatitis and the treatment of patients with both diseases. DESIGN: We performed a matched case-control registry analysis of a multicentre, prospective, international acute pancreatitis registry. Patients with both diseases were matched to patients with acute pancreatitis only in a 1:3 ratio by age and gender. Subgroup analyses were also carried out based on disease type, activity, and treatment of inflammatory bowel disease. RESULTS: No difference in prognostic factors (laboratory parameters, bedside index of severity in acute pancreatitis, imaging results) and outcomes of acute pancreatitis (length of hospitalization, severity, and local or systemic complications) were detected between groups. Significantly lower analgesic use was observed in the inflammatory bowel disease population. Antibiotic use during acute pancreatitis was significantly more common in the immunosuppressed group than in the non-immunosuppressed group (p = 0.017). However, none of the prognostic parameters or the severity indicators showed a significant difference between any subgroup of patients with inflammatory bowel disease. CONCLUSION: No significant differences in the prognosis and severity of acute pancreatitis could be detected between patients with both diseases and with pancreatitis only. The need for different acute pancreatitis management is not justified in the coexistence of inflammatory bowel disease, and antibiotic overuse should be avoided.

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.

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.

Hungarian Linguistic, Cross-Cultural, and Age Adaptation of the Patient Satisfaction with Health Care in Inflammatory Bowel Disease Questionnaire (CACHE) and the Medication Adherence Report Scale (MARS).

BACKGROUND: The TRANS-IBD study examines the superiority of joint transition visits, with drug adherence and patient satisfaction among the outcome measures. Our aim was a cross-cultural, age- and disease-specific adaptation of the 'Medication Adherence Rating Scale' (MARS) and 'Patient satisfaction with health care in inflammatory bowel disease questionnaire' (CACHE) questionnaires in patients with inflammatory bowel disease (IBD). METHODS: Linguistic and cultural adaptation using test and re-test procedures were performed. Internal consistency with Cronbach's α coefficients, confirmatory factor analyses with root Mean Square Error of Approximation (RMSEA), Comparative Fit Index (CFI), and Tucker-Lewis Index (TLI) were determined. RESULTS: A total of 122 adolescents and 164 adults completed the questionnaires (47.5% male, mean age 17 ± 1; and 29.3% male, mean age 38 ± 11, respectively). In the MARS questionnaire, Cronbach's α scores were found good in adolescents (0.864) and acceptable in adults (0.790), while in the CACHE questionnaire, scores were rated as excellent in both populations (0.906 and 0.945, respectively). The test-retest reliabilities were satisfactory in both groups (MARS questionnaire: r = 0.814 and r = 0.780, CACHE questionnaire: r = 0.892 and r = 0.898, respectively). RMSEA showed poor fit values in the MARS questionnaire and reasonable fit values in the CAHCE questionnaire, CFI and TLI had statistically acceptable results. CONCLUSION: Age-and disease-specific Hungarian versions of the questionnaires were developed, which are appropriate tools for TRANS-IBD RCT and daily IBD care.

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.

Loss-of-function variant in chymotrypsin like elastase 3B (CELA3B) is associated with non-alcoholic chronic pancreatitis.

BACKGROUND: Genetic alterations in digestive enzymes have been associated with chronic pancreatitis (CP). Recently, chymotrypsin like elastase 3B (CELA3B) emerged as a novel risk gene. Thus, we evaluated CELA3B in two European cohorts with CP. METHODS: We analyzed all 8 CELA3B exons in 550 German non-alcoholic CP (NACP) patients and in 241 German controls by targeted DNA sequencing. In addition, we analyzed exons 6 and 7 by Sanger sequencing and the c.129+1G>A variant by melting curve analysis in 1078 further German controls. As replication cohort, we investigated up to 243 non-German European NACP patients and up to 1665 controls originating from Poland, Hungary, and Sweden. We assessed the cellular secretion and the elastase activity of recombinant CELA3B variants. RESULTS: In the German discovery cohort, we detected a splice-site variant in intron 2, c.129+1G>A, in 9/550 (1.64%) CP patients and in 5/1319 (0.38%) controls (P=0.007, OR=4.4, 95% CI=1.5-13.0). In the European replication cohort, this variant was also enriched in patients (9/178 [5.06%]) versus controls (13/1247 [1.04%]) (P=0.001, OR=5.1, 95% CI=2.1-12.0). We did not find the two previously reported codon 90 variants, p.R90C and p.R90L. CONCLUSIONS: Our data indicate that CELA3B is a susceptibility gene for CP. In contrast to previous reports suggesting that increased CELA3B activity is associated with CP risk, the splice-site variant identified here is predicted to cause diminished CELA3B expression. How reduced CELA3B function predisposes to pancreatitis remains to be elucidated.

EASY-APP: An artificial intelligence model and application for early and easy prediction of severity in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed. METHODS: The early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit-learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross-validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross-validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP). RESULTS: The prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy-to-use web application in the Streamlit Python-based framework (http://easy-app.org/). CONCLUSIONS: The EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model.