Immunohistochemical Detection of the Presence of Vitamin D Receptor in Childhood Solid Tumors

SIMPLE SUMMARY: Childhood cancer cannot generally be prevented or identified through screening. The disease is often diagnosed at advanced stages, and this obviously affects patient outcomes negatively. There is an urgent need for the identification of prognostic and therapeutic biomarkers. In this study, lower vitamin D receptor (VDR) expression was associated with a worse prognosis in various childhood cancer patients (significant correlation, p = 0.0061). The identification of VDR status in various childhood cancers has highlighted potential patient populations that could benefit from the newly identified biomarker. Knowledge of the VDR status in childhood solid tumors provides clinicians with a valuable biomarker and based on this, additional therapy (vitamin D and analogs) to use alongside conventional first-line oncotherapy. ABSTRACT: Background: Our previous work has shown a correlation between lower vitamin D levels in children with cancer and adverse prognosis. It suggests that supplying vitamin D is reasonable. VDR expression in childhood solid tumors has been linked to tumor characteristics and patient survival in only a few studies. Methods: For this study, 177 children with solid tumors were selected whose biopsies and tumor tissue formalin-fixed, paraffin-embedded tissue blocks were available for immunohistochemical analysis at Semmelweis University, Budapest (Hungary). Results: We found that non-significant VDR expression was associated with a significantly less favorable prognosis (p = 0.0061) in the examined childhood solid tumors. There was a clinically significant association; non-significant VDR expression had more than 14-fold odds of an unfavorable prognosis (OR = 14.74). The rate of VDR expression differed significantly between tumor types (p < 0.0001). Conclusion: In conclusion, VDR expression measured by IHC staining is inversely associated with aggressive characteristics in different childhood cancers. The downregulation of VDR expression in more aggressive childhood cancers suggests that functional vitamin D activity may slow or block cancer progression

Increased Prevalence of Celiac Disease in Patients with Cystic Fibrosis: A Systematic Review and Meta-Analysis

Objectives: Immune regulation seems to be altered in cystic fibrosis (CF), thus potentially predisposing patients to developing autoimmune diseases (AID). In this meta-analysis, we aimed to evaluate the prevalence of celiac disease (CeD) among CF patients as by far the most commonly reported autoimmune disease in this population and, secondly, to review the observations on other, less frequently studied autoimmune diseases. Methods: We conducted a systematic literature search for studies that discussed AIDs among CF patients. Following standard selection and data collection, we calculated pooled raw prevalence with 95% confidence intervals (CI) for biopsy-verified CeD and seropositivity. Results: Out of the 21 eligible studies, 15 reported on CeD. Pooled prevalence of biopsy-verified CeD was 1.8% (CI 1.1–2.7%) according to a homogeneous dataset from six prospective, consecutive screening studies, while it proved to be 2.3% (CI 1.1–4.7%) according to a heterogeneous dataset from the other studies. Tissue transglutaminase IgA positivity was detected in 4.5% of CF cases (CI 2.8–6.9%), while tissue transglutaminase IgA–endomysial antibody IgA double positivity was found in 2.4% of them (CI 1.5–3.9%). Findings on other AIDs were strongly limited. Conclusions: The pooled prevalence of CeD in CF seemed to be more than twice as high compared to the global prevalence; therefore, routine screening of CeD could be considered in CF

Detailed characteristics of post-discharge mortality in acute pancreatitis

The in-hospital survival of patients suffering from acute pancreatitis (AP) is 95-98%. 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.2,613, well-characterized patients from twenty-five centers were collected 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.After an AP episode patients have an approximately three-fold higher incidence rate of mortality than the general population (0.0404vs.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, while cancer-related cachexia and non-AP-related infection were the key causes in the later phase.Almost as many patients in our cohort die 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

Hypoalbuminemia affects one third of acute pancreatitis patients and is independently associated with severity and mortality

The incidence and medical costs of acute pancreatitis (AP) are on the rise, and severe cases still have a 30% mortality rate. We aimed to evaluate hypoalbuminemia as a risk factor and the prognostic value of human serum albumin in AP. Data from 2461 patients were extracted from the international, prospective, multicentre AP registry operated by the Hungarian Pancreatic Study Group. Data from patients with albumin measurement in the first 48 h (n = 1149) and anytime during hospitalization (n = 1272) were analysed. Multivariate binary logistic regression and Receiver Operator Characteristic curve analysis were used. The prevalence of hypoalbuminemia (< 35 g/L) was 19% on admission and 35.7% during hospitalization. Hypoalbuminemia dose-dependently increased the risk of severity, mortality, local complications and organ failure and is associated with longer hospital stay. The predictive value of hypoalbuminemia on admission was poor for severity and mortality. Severe hypoalbuminemia (< 25 g/L) represented an independent risk factor for severity (OR 48.761; CI 25.276-98.908) and mortality (OR 16.83; CI 8.32-35.13). Albumin loss during AP was strongly associated with severity (p < 0.001) and mortality (p = 0.002). Hypoalbuminemia represents an independent risk factor for severity and mortality in AP, and it shows a dose-dependent relationship with local complications, organ failure and length of stay.Peer reviewe

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

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.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.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.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%.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

Increased Prevalence of Celiac Disease in Patients with Cystic Fibrosis: A Systematic Review and Meta-Analysis

Objectives: Immune regulation seems to be altered in cystic fibrosis (CF), thus potentially predisposing patients to developing autoimmune diseases (AID). In this meta-analysis, we aimed to evaluate the prevalence of celiac disease (CeD) among CF patients as by far the most commonly reported autoimmune disease in this population and, secondly, to review the observations on other, less frequently studied autoimmune diseases. Methods: We conducted a systematic literature search for studies that discussed AIDs among CF patients. Following standard selection and data collection, we calculated pooled raw prevalence with 95% confidence intervals (CI) for biopsy-verified CeD and seropositivity. Results: Out of the 21 eligible studies, 15 reported on CeD. Pooled prevalence of biopsy-verified CeD was 1.8% (CI 1.1–2.7%) according to a homogeneous dataset from six prospective, consecutive screening studies, while it proved to be 2.3% (CI 1.1–4.7%) according to a heterogeneous dataset from the other studies. Tissue transglutaminase IgA positivity was detected in 4.5% of CF cases (CI 2.8–6.9%), while tissue transglutaminase IgA–endomysial antibody IgA double positivity was found in 2.4% of them (CI 1.5–3.9%). Findings on other AIDs were strongly limited. Conclusions: The pooled prevalence of CeD in CF seemed to be more than twice as high compared to the global prevalence; therefore, routine screening of CeD could be considered in CF

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

Cardiovascular risk factors in coeliac disease (ARCTIC): a protocol of multicentre series of studies

Introduction There is only limited and controversial information available on the cardiovascular (CV) risk in coeliac disease (CD). In this study, we plan to investigate the body composition and CV risk-related metabolic parameters at the diagnosis of CD and on a gluten-free diet in a Hungarian cohort of patients with CD.Methods and analysis This study consists of two case–control studies and a prospective cohort study, involving newly diagnosed and treated patients with CD with age and sex-matched non-CD control subjects with an allocation ratio of 1:1. CD-related symptoms, quality of life, quality of the diet and CV risk will be assessed with questionnaires. Our primary outcomes are body composition parameters, which will be estimated with InBody 770 device. Secondary outcomes are CV-risk related metabolic parameters (eg, serum lipids, haemoglobin A1c, homeostatic model assessment index, liver enzymes, homocysteine, interleukin 6, galectin-3) and enteral hormones (leptin, ghrelin, adiponectin) measured from venous blood samples for all participants. Fatty liver disease will be assessed by transabdominal ultrasonography. In statistical analysis, descriptive and comparative statistics will be performed. With this study, we aim to draw attention to the often neglected metabolic and CV aspect of the management of CD. Findings may help to identify parameters to be optimised and reassessed during follow-up in patients with CD.Ethics and dissemination The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (27521-5/2022/EÜIG). Findings will be disseminated at research conferences and in peer-reviewed journals.Trial registration number NCT05530070