The use of omega-3 fatty acids (omega-3 FA) in the treatment of atopic dermatitis (AD) is an area of ongoing research. Some studies suggest that dietary supplementation with omega-3 FA can help manage symptoms of AD by reducing lesion severity, skin inflammation, dryness and itching, while other show no significant beneficial effect. The aim of this study was to evaluate the effect of omega-3 FA form fish oil in combination with GLA form blackcurrant seed oil in children with AD. This is a longitudinal, prospective, randomized, triple blind, placebo-controlled parallel clinical trial. The study was conducted during the 2-year period from autumn, winter, and spring avoiding the summer when AD usually improves. Children were randomized to receive the active study product (Mega Kid®) containing specific blend of omega-3 and omega-6 fatty acids or placebo. Primary outcomes were change in severity of AD measured using SCORing Atopic Dermatitis (SCORAD) patient oriented SCORAD (PO-SCORAD) and the difference in TCS use. Secondary outcomes were change in itch intensity, sleep quality and Family Dermatology Life Quality Index (FDLQI). Data were analyzed for 52 children (26 in the intervention group and 26 in the placebo group). In children receiving active product intention-to-treat analysis showed that after 4 months of treatment, there was a significant decrease in the SCORAD index (from median 42 to 25, p < 0.001) and use of topical corticosteroids (from median 30 to 10 mg/day, p < 0.001) but also significant improvement in itch, sleep quality and overall quality of life. Omega-3 fatty acids in combination with GLA and vitamin D has a great beneficial effect in treatment of atopic dermatitis in children. Therefore, we can conclude that supplementation with this specific combination could be considered a safe and effective intervention that can significantly reduce the severity of AD in pediatric patients.

Crohn’s disease (CD) is a progressive, multifactorial, immune-mediated disease characterized by chronic inflammation of any part of the gastrointestinal (GI) tract. Pediatric patients present with a more extensive form of the disease, especially in the upper GI tract with various histopathological inflammatory patterns. Our study aims to analyze the endoscopic and histopathological findings in children with diagnosed CD and compare results on the initial and follow-up tests. Our study included 100 children and adolescents with CD, with performed endoscopic and histopathological (HP) procedures. The results of multiple biopsies performed in these 8 years were matched and compared. We found a statistically significant decrease in stool changes, weight loss, and abdominal pain as presenting symptoms, and in the fecal calprotectin levels. On esophagogastroduodenoscopy and ileo-colonoscopy 36.59% and 64.86% patients had specific findings, respectively. Non-caseating granulomas were found on 9% of oesophageal, 18% of gas-tric, and 12% of duodenal biopsies. In the lower GI tract, we have observed a disease progression in the rectum and descending colon between the first and second biopsies. Our study showed that more than a third of patients had specific endoscopic (36.59%) and histopathologic (32%) findings in the upper GI tract, and an additional 23% had HP findings highly suggestive of CD. We demonstrated the importance of regular endoscopic and histopathological assessments of pediatric CD patients.

Purpose: This study aimed to identify the risk factors for acute pancreatitis (AP) and its impact on outcomes in Polish children treated for ALL. Methods: The study group included 2303 children who received intensive chemotherapy for ALL. The group was subdivided into patients with at least one episode of AP and those who did not develop AP following treatment for ALL. Results: The cumulative incidence of AP in the study group was 4.08%. Older age was an independent risk factor for AP development (OR 1.05; 95%CI: 1.006 – 1.098; p=0.03). The overall mortality related to AP was 2.13%. The probabilities of disease-free survival (p-DFS) and event-free survival (p-EFS) were 0.84 vs. 0.86, log-rank: p=0.65 and 0.75 vs. 0.80, log-rank: p=0.12, respectively in both subgroups. A total of 22 out of 94 patients (23.4%) with AP were re-exposed to asparaginase (ASP) during the subsequent phases of the treatment. Only one re-exposed to ASP patient (4.5%) developed a second episode of AP. There were no significant differences in p-DFS and p-EFS between patients re-exposed and not re-exposed to asparaginase (0.78 vs. 0.86, log-rank p=0.27 and 0.63 vs. 0.79, log-rank p=0.09 respectively). Conclusions: The incidence of AP in children with ALL is low and related to the patient’s age. AP development doesn’t seem to impact p-DFS and p-EFS in children with ALL. The recurrence of AP following re-exposure to asparaginase in patients with ALL and a history of AP is low (4.5%). Re-exposure to asparaginase after the first episode of AP doesn’t improve either p-DFS or p-EFS in children with ALL.

The relationship between antitumor response and tumor marker changes was evaluated in patients with advanced hepatocellular carcinoma treated with durvalumab plus tremelimumab (Dur/Tre). Thirty-two patients were enrolled in this retrospective evaluation of treatment outcomes. According to Response Evaluation Criteria for Solid Tumors at 8 weeks, the objective response rate (OR) was 25% and the disease control rate (DC) was 56.3%. Median alpha-fetoprotein (AFP) ratio at 4 weeks was 0.310 in patients who achieved OR at 8 weeks (8W-OR group), significantly lower than the 1.105 in the non-8W-OR group (p=0.0020), but was 1.210 in patients who did not achieve DC at 8 weeks (non-8W-DC group), significantly higher than the 0.470 in the 8W-DC group (p=0.0006). Similarly, median des-γ-carboxy-prothrombin (DCP) ratio at 4 weeks was 0.125 in the 8W-OR group, significantly lower than the 1.225 in the non-8W-OR group (p=0.0001), but was 1.120 in the non-8W-DC group, significantly higher than the 0.480 in the 8W-DC group (p=0.0255). Early changes in tumor markers after Dur/Tre initiation were associated with antitumor response. In particular, changes in AFP and DCP at 4 weeks may offer useful biomarkers for early prediction of both response and progressive disease following Dur/Tre.

Background: Patients with Inflammatory Bowel Disease (IBD) believe that diet is a key factor in the pathogenesis of their disease and in worsening their symptoms; they often follow restrictive diets that can lead to malnutrition, anxiety, and stress. Recent studies have found an association between eating disorders and IBD, particularly anorexia nervosa and ARFID (Avoidant Restrictive Food Intake Disorder). None of these studies report the association with orthorexia nervosa, that is the obsession with healthy and natural foods. Aim: to assess the risk of orthorexia nervosa in patients with IBD. Methods: 158 consecutive subjects were recruited, including 113 patients diagnosed with IBD and 45 controls. The Donini standardized questionnaire ORTO-15 was administered to assess the risk of orthorexia; clinical and demographic data were also collected. Results: patients with IBD have a prevalence of orthorexia of 77%, significantly higher than the 47% observed in the control group. In patients with IBD, the risk of orthorexia is associated with lower BMI and history of previous surgery. Conclusion: Many patients with IBD develop orthorexia nervosa that impacts the patient's psychological and social sphere, exposes them to a high risk of nutritional deficiencies, and affects quality of life. Further high quality studies are warranted to evaluate the clinical impact of orthorexia and its correlation with clinical features and frank eating disorders.

Background/Aim: Stool gluten immunogenic peptides (GIP) determination is now considered a valuable tool for detecting dietary lapses in treated celiac disease (CeD) patients. Our study aims to explore the diagnostic performance of a qualitative lateral flow immunoassay point-of-care test (LFIA/PoCT) compared with a qualitative enzyme-linked immunosorbent assay (ELISA) for detection of stool GIP. Methods: The study is a post hoc analysis of stool samples collected in the real-life conditions from a cohort of gluten-free diet-treated CeD patients. Stool GIP was measured in µg/g of stool using an ELISA kit (iVYLISA GIP S®, Biomedal SL). For the qualitative evaluation of stool GIP, a LFIA/PoCT test (GlutenDetect®; Biomedal S.L) was employed, which reported results as positive or negative. The LFIA/PoCT performance was evaluated against ELISA, considered as the gold standard. GIP concentrations

(1) Background: Cardiorespiratory fitness (CRF) is a prognostic factor regarding long time morbidity and mortality. To assess CRF the well-known gold standard is cardiopulmonary exercise testing (CPET), which is a time consuming and expensive test. Therefore, alternative methods for routine evaluation of CRF are needed for the general population as well as for specific patient groups such as children and young adults with congenital heart disease. The Stair Climbing Test (SCT) is a simple and resource saving test reported in the current literature. This test is used in various settings to assess different health associated risk factors including cardiorespiratory fitness, muscular resilience, therapy effectiveness or pre- and postoperative morbidity and mortality.

The gastrointestinal tract is colonized by trillions of different microorganisms, named the gut microbiota, which is key to degrade undigested food such as dietary fibers. The fermentation of these food components leads to the production of short-chain fatty acids (SCFA) acetate, propionate, and butyrate, which exploit several beneficial roles for the host’s health. Their production and absorption happen in different ways in the human intestine and depend on the type of dietary fiber reaching the gut and the microorganisms involved in the fermentation. The supplementation of SCFAs, mostly butyrate, in treating gastrointestinal, metabolic, cardiovascular, and gut-brain-related diseases has been reported in the medical literature. This review aims to give an overview of the production and absorption dynamics of acetate, propionate, and butyrate in the human gut, with a final focus on the role played by these SCFAs on gastrointestinal and metabolic health and the present therapeutic implications.

Serotonin (5-hydroxytryptamine: 5-HT), a neurotransmitter that regulates mood in the brain and signaling in the gut, has receptors throughout the body that serve various functions. Selective serotonin reuptake inhibitors (SSRIs) are used to treat depression, but their efficacy is uncertain. Depression is often associated with early gastrointestinal symptoms. Gut disorders such as functional dyspepsia (FD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are linked to elevated serotonin levels. In this review, we would like to discuss the approach of using serotonin as a biomarker for gut-brain and body-wide organ communication may lead to the development of preventive and innovative treatments for gut-brain disorders, offering improved visibility and therapeutic monitoring. It could also be used to gauge stress intensity for self-care and mental health improvement.

Background: Endoscopic sphincterotomy (EST) has been employed for the endoscopic treatment of common bile duct stones (CBDSs), and a high success rate of stone removal has been reported. However, EST is associated with the risk of bleeding, perforation, and sphincter of Oddi function disruption. To avoid these risks, endoscopic papillary balloon dilation (EPBD) is an option for CBDS. Sphincter of Oddi function preservation decreases long-term biliary infection and gallstone recurrence. EPBD may have advantages in children who require a long follow-up. However, there have been few reports on pediatric cases, particularly in infants. Methods: From September 2017 to December 2023, we performed EPBD for four pediatric CBDSs. The patients were aged from 5 months to 8 years; including two infants aged 5 and 6 months. Furthermore, we reviewed the stone removal rate and complications of 545 ESTs performed at high-volume centers and 13 EPBD-reported cases in children with CBDSs. Results: CBDSs of all patients who underwent EPBD in our institution were successfully removed. No bleeding or perforation was noted, and pancreatitis was observed in three patients. In an analysis of 545 ESTs in children, the stone removal rate was high, ranging from 83% to 100% (mean, 96%). The incidence of pancreatitis was 0%–9.6% (mean, 4.4%), and the grade of pancreatitis was almost mild. The bleeding frequency was 1.3%–5.4% (mean, 2.7%). According to the grade of bleeding, seven and four cases were mild (64%) and moderate (36%), respectively, Compared with adult cases who underwent EST, the frequency of pancreatitis and bleeding was almost similar in children.; however once bleeding occur, it has a higher risk of leading to blood transfusion in children. Stone removal by EPBD in children was 100% successful. All complications were pancreatitis, and its frequency was 46% (6/13 patients, including five mild cases and one moderate case), which is higher than that of EST and adult cases who underwent EPBD. In most children with pancreatitis, pancreatic enzyme levels returned to normal within 2–3 days following EPBD, and no severe cases caused by EPBD were reported. Conclusions: CBDS removal by EPBD in children has a high success rate with very low risk of bleeding and perforation. Although pancreatitis frequently occurs, most cases are mild. Sphincter of Oddi function preservation by EPBD is expected to prevent long-term stone recurrence and biliary tract infection, and EPBD is considered an effective method for CBDS removal in children.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and encompasses two main subtypes, Crohn’s disease (CD) and ulcerative colitis (UC). IBD is frequently accompanied by extraintestinal manifestations (EIMs), with axial and peripheral spondyloarthritis (SpA) being the most common. Enthesitis, an inflammation of the bone insertions of capsules, ligaments, and tendons, represents an initial lesion in SpA. However, enthesitis remains an underestimated and often obscured EIM. The early detection of subclinical enthesial involvement in IBD patients using ultrasound (US) could provide an opportunity for timely intervention. While previous meta-analyses have reported on the incidence and prevalence of SpA in IBD, specific attention to enthesitis has been lacking. Therefore, this narrative review aims to resume the current knowledge on existing IBD-SpA cohorts, focusing specifically on enthesitis.

To clarify the risk factors for aggravation of esophagogastric varices (EGV) after hepatitis C virus (HCV) eradication with direct-acting antiviral (DAA) therapy, we enrolled 167 consecutive patients with HCV-related compensated cirrhosis who achieved a sustained virological response (SVR) after DAA therapy. During a median of 69 months, EGV was aggravated in 42 (25%) patients despite SVR. The cumulative 1, 3, 5, and 10-year aggravated EGV rates were 7%, 23%, 25%, and 27%, respectively. Multivariate analysis identified platelet count <11.0×10⁴/μL, LSM ≥18.0 kPa, total bile acid ≥33.0 μmol/L, and diameter of left gastric vein (LGV) ≥5.0 mm at HCV eradication as independent risk factors for EGV aggravation post-SVR. In groups that meet all of these risks, the cumulative EGV aggravation rates at 1, 3, and 5 years were 27%, 87%, and 91%, respectively. However, none of the patients who had only one or none of the risk factors experienced EGV aggravation. Platelet count, LSM, total bile acid, and diameter of LGV at HCV eradication were associated with aggravated EGV post-SVR. EGV tends to worsen as two or more of these risk factors increase.

Patients with inflammatory bowel diseases (IBD), including both ulcerative colitis (UC) and Crohn's disease (CD), are at a higher risk of developing colorectal cancer (CRC). However, advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have led to a decrease in the incidence of CRC among IBD patients. Currently, the management of patients with IBD who have a history of or ongoing active malignancy is an unmet need. This involves balancing the risk of cancer recurrence/progression with the potential exacerbation of IBD if the medications are discontinued. The objective of this review is to provide an updated summary of the epidemiology, causes, risk factors, and surveillance approaches for CRC in individuals with IBD, and to offer practical guidance on managing IBD patients with history of previous or active cancer.

Background and Aims: Sustained virologic response (SVR) lead to the decrease of portal hypertension, the regression of fibrosis, the improvement of the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in HCV cirrhotic patients treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological and coagulation tests were collected at baseline, EOT and SVR12/24. Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVR. The MELD score decrease at EOT (13.48 ± 4.273; p =0.001), and SVR (9.88 ± 2.774; p = 0.000), compared to baseline (14.92 ± 4.707). Fibroscan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT) there was a trend towards improvement during treatment, changes that were statistically significant for the majority of patients. Factor II low at baseline (75.40 ± 7.506), increases at EOT (87.40 ± 9.587), and later at SVR (99.12 ± 11.695; p = 0.000). FVIII values increased at baseline (175.52 ± 16.414) decrease at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). FvW values decreased during treatment (146.84 ± 9.428 – baseline, 141.32 ± 9.690; p =0.000 – EOT, 126.68 ± 17.960 – SVR). In regards to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the “reset” of the coagulopathy might be due to the improving of the liver function due to viral eradication secondary to AAD therapy.

Furthermore, the nasal congestion typical of rhinitis can contribute to upper airway obstruction and sleep-disordered breathing. A vicious circle is created between asthma and sleep-disordered breathing: uncontrolled asthma and sleep-disordered breathing can worsen each other. In children with genetic obesity, despite alterations in the immune system, fewer allergies are found compared to the general population. The causes of this reduced allergenicity are unclear but probably involve genetic, immunological, and environmental factors. Further studies are needed to understand the mechanisms. The study emphasizes the importance of jointly evaluating and managing allergies, obesity, and sleep-disordered breathing in children, considering their close interconnection.

Background: Helicobacter pylori (H. pylori) is a prevalent bacterial pathogen implicated in various gastroduodenal diseases, including chronic gastritis, peptic ulcer disease, and gastric cancer. The COVID-19 pandemic has significantly influenced antibiotic prescription practices, potentially exacerbating antibiotic resistance in H. pylori. Objective: This study aims to investigate antibiotic prescription during COVID-19 pandemic in Croatia and its possible impact on H. pylori antibiotic resistance, with a focus on Croatia. Methods: A comprehensive literature search was conducted to identify relevant studies from March 2020 to June 2024. The search strategy included terms related to COVID-19, antibiotic prescription, and Croatia. Studies were selected based on predefined eligibility criteria, focusing on observational research addressing antibiotic use during the pandemic. Results: The COVID-19 pandemic leads to significant fluctuations in community antibiotic consumption within the European Union/European Economic Area. In Croatia, antibiotic use in 2022 surpassed 2019 levels, driven by increased consumption of macrolides and other antibiotics. This surge, influenced by early pandemic treatment claims and penicillin shortages, contributed to rising antibiotic resistance in H. pylori. Resistance rates to clarithromycin and levofloxacin were notably high, driven by mutations in the 23S rRNA, gyrA, and gyrB genes. Discussion: The increased antibiotic use during the COVID-19 pandemic has highly likely complicated H. pylori eradication efforts, highlighting the necessity of judicious antibiotic use and robust antimicrobial stewardship. The pandemic underscored the need for new therapeutic strategies, optimized eradication regimens, and advanced diagnostic methods to manage bacterial infections effectively. Conclusions: The COVID-19 pandemic has significantly impacted antibiotic use and resistance patterns, posing new challenges for H. pylori eradication. Addressing these challenges requires a multifaceted approach, including the development of new drugs and advanced diagnostics, coupled with sustained efforts in antimicrobial stewardship to combat emerging resistance threats.

Background: Osteoporosis and bone fractures affect health and quality of life. Since bone disease is multifactorial, identifying risk factors is key in prevention. There are multiple reports on how viral hepatitis especially chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are affecting bone disease, but results vary. Here, we analyzed the potential association between CHB/CHC and osteoporosis or bone fractures in a large outpatient cohort in Germany. Methods: We included 3,136 outpatients with CHB and 15,608 matched non-hepatitis individuals as well as 2,867 outpatients with CHC and 14,335 matched non-hepatitis individuals from the Disease Analyzer Database between 2005 and 2022. The main outcome was the 5-year cumulative incidence of osteoporosis and bone fractures as a function of either CHB or CHC. Results: Within 5 years of the index date, 2.9% vs. 1.6% of patients with and without CHB were diagnosed with osteoporosis (p=0.001) and 1.0% vs. 0.4% were diagnosed with bone fractures (p<0.001). Moreover, 3.3% of CHC patients and 2.2% of individuals without hepatitis were diagnosed with osteoporosis (p=0.002). In Cox-regression analyses, CHB was significantly associated with an increased risk for osteoporosis (HR: 1.76) and fractures (HR:2.43) and CHC with osteoporosis (HR: 1.54). For both CHB and CHC, the association with osteoporosis was restricted to the female subgroup. Conclusion: CHB and CHC are associated with osteoporosis in women. CHB in male patients is associated with a higher risk of fractures. More research is are needed to understand the underlying pathophysiological mechanisms.

Metabolic Associated Steatohepatitis Liver Disease (MASLD) currently impacts a quarter of the global population and its prevalence is expected to increase in the future. As a result, the incidence of hepatocellular carcinoma associated with MASLD is also on the rise. Notably, hepatocellular carcinoma in this group does not always develop alongside liver cirrhosis, often leading to a more advanced stage at diagnosis. The challenge lies in accurately identifying patients who are at a higher risk of hepatocellular carcinoma to tailor screening processes effectively. Additionally, several therapeutic approaches are being explored to prevent hepatocellular carcinoma, although there are yet no universally accepted guidelines

Chronic pancreatitis is a progressive fibroinflammatory disorder with no currently satisfactory treatment. Emerging evidence suggests an association between gut microbial dysbiosis and chronic pancreatitis. Although direct causative evidence is lacking, it is hypothesized that the gut microbiota may play a pivotal role in modulating pancreatic function via the gut-pancreas axis. Thus, modulating the gut microbiota through the administration of probiotics or prebiotics may alleviate pancreatic disorders. In this review, we first propose the potential mechanisms by which specific probiotics or prebiotics may ameliorate chronic pancreatitis, including the alleviation of small intestinal bacterial overgrowth (SIBO), facilitation of short-chain fatty acids (SCFAs) production, activation of the glucagon-like peptide 1 receptors (GLP-1Rs) in the pancreas. Since there are currently no probiotics or prebiotics used for the treatment of chronic pancreatitis, we have discussed research in other disease models that use probiotics or prebiotics to modulate pancreatic endocrine and exocrine functions and prevent pancreatic fibrosis. This provides indirect evidence for their potential application in the treatment of chronic pancreatitis. We anticipate that this research will stimulate further investigation into the gut-pancreas axis and the potential therapeutic value of probiotics and prebiotics in chronic pancreatitis.

Background and aims. Clinically significant delayed bleeding (CSDB) may complicate endoscopic colorectal submucosal dissection (ESD). Methods. We assessed the results of a prospective registry of colorectal ESD. We evaluated the effect of clip closure and PuraStat application for prevention of CSDB. Results. 40 patients with 41 colorectal ESD were included. ESD was successful in 38 lesions (92.7%), 35 with R0 resection (92.1%) and 33 with curative resection (86.8%). CSDB occurred in 3 out 38 lesions (7.9%, 95% CI [1.7 – 21.4%]), exclusively after rectal ESD (3 of 22 rectal lesions vs. 0 of 16 colonic lesions, p = 0.249). Clip closure was more frequently used after colonic ESD (12 of 16 colonic lesions vs. 2 of 22 rectal lesions, p < 0.001) and was not protective for CSDB in univariate analysis, even though no events occurred after clip closure (0 of 14 lesions with clip closure vs. 3 of 27 lesions without, p = 0.283). PuraStat was more frequently applied after ESD for rectal lesions (16 of 22 rectal lesions vs. 2 of 16 colonic le-sions, p < 0.001) and was not protective for CSDB, all three events occurring after PuraStat application (3 of 21 lesions with PuraStat application vs. 0 of 20 lesions without, p = 0.097). Conclusions. CSDB occurred exclusively after rectal ESD, and no predictive factors were identified in uni-variate analysis. Clip closure and PuraStat application were not protective for CSDB.

Severe early childhood caries remains the most common chronic disease affecting children. Its multifactorial etiology has established a controversy about which risk factors were more significant to its development. Therefore our study aimed through meticulous statistical analysis to arrange the “well agreed upon” common risk factors in order of significance, to aid the clinician in tailoring an adequate preventive program for this affected age group. The study reshuffled the risk factors contributing to severe early childhood caries and placed them in the order of their significance as follows: snacking of sugary food several times a day, increased number of siblings to 3 or more, night feeding, child self-employed brushing, mother caries experience, 2 siblings, on demand feeding, once/day sugary food, sharing utensils, 1 Sibling, male gender, father’s education, late first child dental visit, brushing time, mother’s education, no dental visit, decreased brushing frequency & no night brushing.

Lung involvement in rheumatic diseases is a major determinant of patient morbidity and mortality; however, its diagnosis depends on the detection methods used. We compared the incidence of pulmonary involvement in newly diagnosed treatment-naive patients with rheumatic diseases, as assessed by pulmonary function tests (PFTs) and chest high-resolution computed tomography (HRCT). This retrospective study reviewed the symptoms, spirometry results, and HRCT scans of 22 newly diagnosed, treatment-naïve patients and age-matched controls from the University General Hospital “Attikon”, Athens, Greece, between January 2021 and December 2023. Correlations between clinical findings and spirometry parameters were tested. HRCT scans revealed lung abnormalities in all patients, including peribronchial wall thickening (61.5%), ground glass opacities (59.1%), parenchymal bands (54.5%), air-trapping (50%), reticular patterns (45.5%), bronchiectatic changes (40.9%), and parenchymal opacities (31.8%). PFTs, performed in 17/22 (77.3%) patients, revealed definite pathology in 5 patients (restrictive: N=4; obstructive: N=1). No association was found between spirometric indices and clinical parameters. The results indicate a higher prevalence of abnormal chest CT than of PFT abnormalities, suggesting that HRCT is more sensitive in detecting early lung involvement in pediatric patients with rheumatic disease and should be considered in the routine evaluation of these patients.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron and over time the cystic dilatation lead to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts lead to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and haematuria. However, the presentation of ADPKD varies in children from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset of ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide the clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra normal kidney function we explored the glomerular filtration rates dynamics and the renal ultrasound adjusted percentiles. 14 out of 16 patients had kidney percentile over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 ml/min/1.73m2 compared to Schwartz eGFR 126.28 ± 33.07ml/min/1.73m2, p=0.14). Also, when the quadratic equation was employed, not even a patient reached the glomerular hyperfiltration thresholds. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1-year of follow-up (Quadratic ΔeGFR=0.32±5.78ml/min/1.73m2) as opposed to Schwartz formula that can falsely classify children in a hyperfiltration state ΔeGFR=7.51±19.46ml/min/1.73m2), p=0.019.

PARP inhibitors are used in tumor therapy exploiting their inhibitory role in DNA repair. Radiation therapy leads to DNA damage in the affected region comprising both tumor tissue and adjacent normal tissue. In addition, radiotherapy has long-standing effects on DNA integrity. The mechanisms for this are not well understood. We studied normal tissue damage of the lung after application of ionizing radiation (IR) in two well established rat models comprising both external (eIR) and internal (iIR) ionizing radiation. We found a nearly complete (~350-fold) loss of PARP-1 in the irradiated tissue in both models but no change in PARylated protein. This may be explained by the strong decrease in both ARH3 and PARG, both deparylating enzymes. We demonstrate, that of all these proteins are expressed in type II pneumocytes, but also in type I pneumocytes and the bronchiolar epithelium. The data suggest a severe disturbance of PARylation in these cells which may affect their major functions such as maintenance of the integrity of the alveolar wall. It is likely that the application of PARP inhibitors could have cumulative effects in radiation-damaged normal tissue.

This study aimed to introduce a novel machine learning (ML) model designed to predict the need of interventions during endoscopy in patients with upper gastrointestinal bleeding (UGIB). The risk stratification tools in current use, such as the Glasgow Blatchford Score (GBS) and pre-endoscopic Rockall score, have limitations in accurately predicting the need for endoscopic interventions. All patients diagnosed with UGIB from January 2013 to October 2023 who underwent endoscopy were included in the study. Variables extracted included demographics, social history ,clinical history, clinical presentation and symptoms, drug history, management prior to endoscopy, findings during endoscopy, laboratory variables and vitals, and post-endoscopic results. Three machine learning models including Random Forest Classifier (RFC), Gradient Boosting Classifier (GBC), and AdaBoost Classifier were used to evaluate the need for intervention during endoscopy in our study. A total of 1372 patients were included from three major hospitals in Jordan, of whom 242 underwent endoscopic intervention. The GBC outperformed all other models and pre-endoscopic scores in predicting the need for endoscopic intervention with an area under the curve of 0.861. Findings during endoscopy, platelet count, pulse rate and systolic blood pressure during admission were the most contributing features in predicting the need for the need of endoscopic intervention. This study highlights the potential of machine learning models in enhancing decision making for UGIB management.

Lower cutoff levels in screening programs have led to an increase in the proportion of detected cases with transient hypothyroidism, leading to increase of the overall incidence of primary congenital hypothyroidism (CH) in several countries. We have performed retrospective evaluation on the data from 251,008 (96.72%) neonates screened for thyroid-stimulating hormone (TSH) level in dried blood spot specimens taken 48 hours after birth, between 2002 and 2015, using DELFIA method. A TSH value of 15 mIU/L was used as the cutoff point until 2010 and 10 mIU/L thereafter. Primary CH was detected in 127 newborns (1/1976) of which 81.1% had permanent and 18.9% had transient CH. The incidence of primary CH was increased from 1/2489 until to 2010 to 1/1585 thereafter (p=0.131). However, the incidence of permanent CH was slightly increased (p=0.922), while the transient CH incidence had 8-fold increasing after lowering the TSH cutoff level (p<0.001). In cases with permanent CH, we observed lower frequency for thyroid dysgenesis (82.7 vs. 66.7%) and higher frequency for normal in-situ thyroid gland (17.3 vs. 33.3%), for the period with reduced TSH cutoff value. Our findings support the impact of lower TSH cutoff on the increasing incidence of congenital hypothyroidism.

Duchenne muscular dystrophy (DMD) is the most prevalent progressive muscular dystrophy, and the guidelines recommend the regular assessment of respiratory muscle function. This study aimed to assess the relationship between maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP) and sniff nasal inspiratory pressure (SNIP) measurements and upright-supine spirometry parameters in children with DMD, predictability of upright-supine spirometry in terms of diaphragm involvement, and impact of nutrition on muscle strength. This prospective cross-sectional study examined patients with DMD by comparing upright and supine FVC, MIP, MEP, and SNIP measurements. Forty-four patients were included in the study. The mean patient age was 10.8±2.9 years. Twenty-five patients were ambulatory. A significant decrease in FVC, FEV1, and FEF25-75 values was detected in the supine position in both ambulatory and nonambulatory patients (p&lt;0.05). All patients had low MIP, MEP, and SNIP measurements (less than 60 cm H2O). MIP, MEP, and SNIP values were significantly lower in patients with malnutrition than in those without (p&lt;0.05). To accurately assess respiratory muscle strength, supine FVC should be combined with upright FVC, MIP, MEP, and SNIP measurements. It is crucial to regularly screen patients for malnutrition, as this can significantly affect respiratory muscle function during pulmonology follow-up.

Steroidogenic factor 1 (SF-1) is a nuclear receptor that regulates steroidogenesis and reproductive development. NR5A1/SF-1 variants are associated with a broad spectrum of phenotypes across individuals with disorders of sex development (DSD). Oligogenic inheritance has been suggested as an explanation. However, testing the impact of specific gene variants involved in a network remains difficult. To confirm the hypothesis that NR5A1/SF-1-related DSD follow an oligogenic mode of inheritance, we investigated a constellation of gene variants identified in a 46,XY severely undervirilized individual. Candidate genes were revealed by whole exome sequencing, and pathogenicity was predicted by different in silico tools. We found variants in NR1H2 and INHA associated with steroidogenesis, sex development, and reproduction. Functional testing was conducted in cell models. Novel SF-1 and NR1H2 binding sites in the AR and INHA gene promoters were found. Transactivation studies showed that wild-type NR5A1/SF-1 regulates INHA and AR gene expression, while the NR5A1/SF-1 variant had decreased transcriptional ac-tivity. NR1H2 was found to regulate AR gene transcription; however, the NR1H2 variant showed normal activity. This study expands the NR5A1/SF-1 network of interacting partners while strengthening the hypothesis that the broad phenotype observed in 46,XY DSD individuals may be caused by oligogenic pathogenicity.

Background: Pediatric forearm fractures represent a substantial proportion of childhood injuries, requiring effective and minimally invasive treatments. Our study investigated the mid-term outcomes of biodegradable poly-L-lactide-co-glycolide (PLGA) intramedullary implants in managing diaphyseal forearm fractures in children. Methods: A follow-up cohort study was conducted with 38 patients treated with PLGA implants. Control examinations were performed one year post-operation, assessing bone healing through radiographic evaluations and functional outcomes using injured and uninjured limb range of motion (ROM) comparisons. Scarring was evaluated employing the Vancouver Scar Scale (VSS), and satisfaction via a questionnaire. Results: Children were predominantly female (76.4%), with a mean age of 9.71 (SD: 2.69) years. Effective fracture stabilization and bone healing were found in all patients, with a minor reduction (mean difference of -1.5°, p = 0.282) in elbow flexion on the operated side (139.3°) compared to the intact (140.8°). Elbow extension presented negligible average changes (0.2°, p= 0.098). Forearm movements were slightly reduced on the operated side (mean pronation: 80.8° vs. 83.7°, p= 0.166; average supination: 83.5° vs. 85.7°, p= 0.141). Wrist palmar flexion and dorsiflexion showed no significant differences. VSS ratings indicated minimal scarring (mean guardian and doctor scores were 1.13 and 0.55, respectively, p= 0.020), and all patients reported satisfaction with the treatment outcomes. Conclusion: Biodegradable implants are effective for pediatric forearm fractures, providing stable bone healing while preserving functional ROM with minimal scarring and high patient satisfaction. PLGA proved to be a viable alternative to traditional metal implants, eliminating secondary removal surgeries.

In pediatric burn care, achieving swift healing with minimal complications remains paramount. This investigation assesses polyhexamethylene biguanide (PHMB)'s role in managing superficial partial-thickness burns in children, focusing on the effects of various patient-specific factors on recovery. Through a retrospective analysis of 27 pediatric cases treated with PHMB, we explored the impact of age, burn size, dressing frequency, treatment delay, cold therapy application, and analgesic usage on the duration until reepithelialization. Notably, the majority of patients benefited from early cold therapy, yet only 1 in 3 patients received analgesics. The study reveals a mean healing time of 8.78 days, with the extent of the burn showing a strong correlation to recovery speed. Most treatments were managed outpatient, evidenced by a negligible average hospital stay. Impressively, the intervention recorded no complications. Our findings endorse PHMB as a promising treatment for second-degree burns in young patients, offering healing efficiency on par with or surpassing traditional methods, without increasing complication risks. This investigation underscores the necessity for continued exploration into the optimal application of prehospital interventions and the comprehensive benefits of PHMB in pediatric burn management, advocating for future research aimed at assessing long-term outcomes, including scar quality and patient satisfaction.

Delayed Gastric Conduit Emptying (DGCE) occurs in 15-39% of patients who underwent esophagectomy. Intra-Pyloric Injection of Botulinum Toxin (IPBT), Pneumatic Balloon Dilation (PBD), and the same session combination (BTPD), represent the main endoscopic procedures, but comparative data are currently unavailable. We retrospectively analyzed prospectively collected data on all consecutive patients with DGCE treated endoscopically with IPBT, PBD, or BTPD. ISDE Diagnostic Criteria were used for DGCE diagnosis and classification. Gastric Outlet Obstruction Score was used for clinical staging. All patients undergoing IPBT received 100 UI of toxin, while those undergoing PBD were dilated up to 20mm. Clinical success (CS) was defined as the resolution of symptoms/resumption of feeding at discharge or expanding dietary intake at any rate. Recurrence was defined as symptom relapse after more than 15 days of well-being requiring endoscopic/surgical intervention. 64 patients (81.2% male, 90.6% Ivor-Lewis esophagectomy, 77.4% adenocarcinoma), median age 62 years (IQR 55-70), were enrolled: 18 (28.1%) in the IPBT group, 24 (37.5%) in the PBD group and 22 (34.4%) in the BTPD group. No statistically significant differences were found in the baseline characteristics, surgical techniques, and median follow-up among the three groups. BTPD showed a higher CS rate (100%) compared to the PD and BTPD groups (p=0.02) and Kaplan-Meier analysis with log-rank test revealed that the BTPD group was associated both with a significatively shorter mean time to refeed of 1.16 days (95% CI 0.8-1.5; p=0.001) and a shorter median time to discharge of 1 day (95% CI 1-3; p=0.0001). Endoscopic management of DGCE remains challenging. Waiting for further strong evidence, BTPD can offer patients a higher clinical efficacy rate and a shorter time to refeed and be discharged.

Proton-pump inhibitors (PPIs) are the most administered first-line treatment for eosinophilic esophagitis (EoE). However, only around half of EoE patients respond histologically to PPI at double dosage. In addition, 70% of responders maintain EoE in remission after tapering the PPI dose. In order to avoid endoscopy with biopsies − the only accurate method of assessing PPI response − efforts have been made to identify PPI responder patients. Clinical or endoscopic features and biomarkers evaluated so far however, have not proved good enough in predicting PPI response. Although new approaches based on omics technologies have uncovered promising biomarkers, the specialized and complex procedures required are difficult to implement in clinical settings. Alternatively, PPI pharmacogenetics based on identifying variations in CYP2C19 and STAT6 genes have shown promising results in EoE, and could easily be performed in most laboratories. Other genetic variations have also been associated with PPI response and may explain those cases not related to CYP2C19 or STAT6. Here, we give an overview of PPI treatment in EoE and evidence of how genetic variations in CYP2C19 and other genes could affect PPI effectiveness, and also discuss studies evaluating the role of pharmacogenetics in predicting PPI response in patients with EoE.

Background: Infantile tibia vara (ITV) is a rare proximal tibia deformity in infancy, leading to progressive knee varus. High tibial osteotomy is commonly practiced but has high recurrence rates. This study analyzed factors affecting treatment failure and recurrence in children undergoing opening-wedge high tibial osteotomy (OWHTO) for ITV. Methods: We retrospectively studied children with ITV who had OWHTO with press-fit cancellous bone allograft between 2000 and 2020, with ≥2-year follow-up. Outcomes included recurrence (knee varus with tibiofemoral angle >10°), complications, and reintervention. Results: We analyzed 39 knees in 29 patients (mean age: 4.8 ± 1.9 years; median follow-up: 7.4 years). Recurrence occurred in 22 cases (56%). Age at surgery significantly influenced recurrence, with rates of 16% before age 5 versus 95% later (hazard ratio: 12.0, p = 0.001). Langenskiöld stage also affected recurrence (β-coefficient: 2.7, 95% C.I. 1.0–4.5, p = 0.002; pseudo-R-squared: 0.50, p = 0.001), with recurrence in all stage III IV or higher cases. Conclusions: Early diagnosis and treatment before age 45, ideally with Langenskiöld stage III or lower, are crucial for stable correction with OWHTO alone. Late, high-grade ITV may require combined, acute or gradual, and/or staged correction. Further evidence is needed for optimal management.

BACKGROUND: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is essential technique for sampling solid pancreatic lesions. However, the optimal needle type for achieving high histological diagnostic capability remains unclear. This study compares the histological diagnostic capabilities of the 19G FNA needle and the 22G FNB needle for solid pancreatic lesions. METHODS: This single-center, retrospective study was conducted in patients who underwent EUS-TA for solid pancreatic lesions. Patients were allocated to either Group A, utilizing the 19G FNA needle, or Group B, utilizing the 22G FNB needle. The primary outcome was the diagnostic accuracy based on histology alone. RESULTS: 143 patients were analyzed, with 61 in Group A and 82 in Group B. Diagnostic accuracy was significantly higher in Group B for both histology alone (85.4% vs. 68.9%, p=0.02) and overall diagnostic accuracy (85.4% vs. 73.8%, p=0.02). Logistic regression analysis revealed that lesion size ≥25 mm was an independent factor contributing to higher diagnostic accuracy (OR 3.32, 95% CI 1.28-8.64, p=0.01). Subgroup analysis showed that diagnostic accuracy for 15–25 mm lesions was significantly higher in Group B (90.0% vs. 63.2%, p=0.02). Additionally, trans-gastric punctures had higher accuracy in Group B (94.7% vs. 73.5%, p=0.01). CONCLUSIONS: Our study showed the overall superiority of the 22G FNB needle for EUS-TA of solid pancreatic lesions. However, 19G FNA needle remains a valuable option under specific conditions.

Evaluation of biliary strictures remains a challenge due to the low sensitivity of standard diagnostic work up, but the introduction of direct single-operator cholangioscopy (DSOC) changed this paradigm. Aim of our study was to evaluate diagnostic performance of DSOC and DSOC-targeted biopsies, intraductal ultrasound (IDUS) and brush cytology in patients with indeterminate biliary stricture (IBS). We evaluated patients who underwent advanced diagnostic work up for IBS in our endoscopy unit from ‘01/2018 to ‘12/2022; all patients had at least one previous attempt to characterize the biliary stricture. Final diagnosis was based on surgical pathology and/or clinical and radiological follow-up of at least 12 months. A total of 57 patients with a mean age of 67.2 ± 10.0 years were included, with a mean follow up of 18.2 ± 18.1 months. IBS were mostly located in the distal common bile duct (45.6%) and final diagnosis was consistent with malignancy in 35 patients (61.4%). DSOC and IDUS showed a significantly higher accuracy (89.5% and 82.7% respectively) compared to standard cytology (61.5%, p <0.05). In our experience, DSOC visualization and IDUS both demonstrated an optimal diagnostic yield in the differentiation of IBS, with an acceptable safety profile both quantitatively and qualitatively.

GCTs are developmental tumors and likely to reflect ontogenetic and teratogenetic determinants. The objective was to identify syndromes with or without congenital anomalies and non-syndromic defects as potential risk factors. Patients with extracranial GCTs (eGCTs) registered in MAKEI 96/MAHO 98 between 1996 and 2017 were used. According to Teilum's holistic concept malignant and benign teratomas were registered. We used a case control study design with Orphanet as a reference group for syndromic defects and the Mainz birth registry (EUROCAT) for congenital anomalies at birth. Co-occurring genetic syndromes and/or congenital anomalies were assessed accordingly. Odds ratios and 95% confidence intervals were calculated and p-values for Fisher’s exact test with Bonferroni correction if needed. A strong association was confirmed for Swyer (OR 338.6, 95% CI 43.7-2623.6) and Currarino syndrome (OR 34.2, 95% CI 13.2-88.6). We additionally found 17 isolated cases of eGCT with a wide range of syndromes, however not significantly associated following Bonferroni correction. All these cases pertained to girls. Regarding non-syndromic defects, no association with eGCTs could be identified. In our study we confirmed a strong association for Swyer and Currarino syndromes with additional congenital anomalies.

Hereditary hemochromatosis (HH) is the main genetic cause of iron overload and is regarded as metal-related human toxicosis. HH may result from HFE and non-HFE gene mutations causing hepcidin deficiency or hepcidin resistance. The disorder has a high biochemical penetrance, but a low clinical prevalence. Unfortunately, the majority of patients with HH remain undiagnosed at their disease-curable stage. The main aim of HH therapy is to prevent iron overload in the early-phase disease and elimination of excess iron from the body by phlebotomy in its late stage. Raising global awareness of HH among health professionals, their training to pay attention to early HH signs and symptoms, and strict patient monitoring are critical management strategies for preventing treatment delays, upgrading its efficacy, and improving patient prognosis.

We analyzed data of pediatric invasive fungal diseases of the central nervous system (CNS-IFDs) reported by five of total eight Pediatric Hematology-Oncology Departments in Greece for 15 years (2007-2022). A total of twelve patients (11 boys, median age: 9.5yrs range: 2-16) were reported suffering from CNS-IFDs. Underlying malignancy was acute lymphoblastic leukemia in 9/12, and acute myeloid leukemia, Ewing sarcoma and rhabdomyosarcoma in one each. Eleven patients presented with CNS-related symptoms (i.e seizures, headache, cerebral palsy, ataxia, hallucination, seizures, blurred vision, amaurosis). All patients had pathological MRI findings. Multifocal fungal disease was observed in 6/12 patients. Nine proven and three probable CNS-IFD cases were diagnosed. Causative pathogens in proven cases were Aspergillus spp. and Candida albicans (n=2 each), Mucor spp., Rhizopus arrhizus, Absidia spp., Fusarium oxysporum and Cryptococcus neoformans (n=1 each). Causative pathogens in probable cases were Aspergillus spp. (n=2) and Candida spp. (n=1). All patients received appropriate antifungal therapy (median duration: 69.5 days, range 19-364). Two patients underwent additional surgical treatment. Six patients admitted to ICU due to complications. Three patients (25%) died, two due to IFD and one due to underlying disease. Early recognition and prompt intervention of CNS-IFDs may rescue the patients and improve overall survival.

Introduction. Intra-abdominal cystic formations represent heterogeneous pathologies with varied localization and clinical manifestation. The first challenge of a giant intra-abdominal cystic lesion is identifying the organ of origin. The clinical presentation of intra-abdominal cystic lesions varies from acute manifestations to non-specific symptoms or accidental discovery. Case presentation: A 2-year-old girl presents to the emergency unit with a fever of 38.5 Celsius, loss of appetite, and apathy. The investigations showed a gigantic intra-abdominal mass whose organ belonging could not be specified. Postoperatively, a giant mesenteric lymphangioma was evident, which was completely excised. Discussions Giant cystic formations modify the anatomical reports and become space-replacing formations, and the starting point is even more challenging to assess preoperatively. Nevertheless, the careful evaluation of the characteristics of the formation, the effect on the adjacent organs, the age of the patient, and the clinical picture can provide elements of differential diagnosis.

The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. We aimed to compare the opinions of expert groups from the Middle East (n=14) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n=13). These Expert groups voted on statements developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Overall, there was consensus amongst both groups of experts. Most experts agreed that symptoms of crying, irritability and colic, as single manifestations, do not suggest CMA. They agreed that amino-acid-based formula (AAF) should be reserved for severe cases (e.g. malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no consensus on the statement that a cow’s milk-based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role of hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle East region. All ESPGHAN experts agreed that there was no added value of probiotics, prebiotics, and synbiotics to the efficacy of elimination diets, whereas 3/14 of the Middle East group thought there was sufficient evidence. Therefore, there is not a consensus on the optimal diagnostic and therapeutic elimination diet for CMA, but the first-choice elimination diet and the stepwise management approach reveal some differences.

Aim: To evaluate the panmacular subthreshold micropulse laser treatment results among patients with central serous chorioretinopathy (CSC) and their correlation with functional and morphological parameters. Material and methods: The examined group included 10 non-treated and 41 treated patients with acute, recurrent, and chronic CSC (13 F, 38 M, mean age 44.11±6.5) and 14 healthy controls (6 F, 8 M, mean age 45±9.3). The BCVA examination, ophthalmoscopy, microp-erimetry, angio-OCT and OCT were performed. The medical history regarding chronic general disorders and known risk factors were recorded. Results: Complete resorption of SRF was obtained in 100% aCSC, 86.66% cCSC, and 63.63% r CSC. BCVA and RetSens significantly improved most of the patients treated in aCSC. The lowest BCVA and RetSens, but the largest pachyvessel and disease duration, were found in rCSC. A strong negative correlation between final BCVA and disease duration was found. No patient demonstrated laser lesions following treatment. Conclusions: The panmacular MPLT therapy leads to long-term enhancement of functional and morphological parameters in all CSC patients. The acute CSC patients showed the most significant improvement. The procedure is safe and could be considered a preferred treatment option for all active CSC cases. Timely treatment is crucial for beneficial outcomes.

The causes of pediatric cancers often remain unknown; however, due to the development of medicine and technology, genetic disorders may play a crucial role in the genesis of neoplasms. Over time, the number of cancer predisposition syndromes (CPS) and awareness of them are increasing, providing the possibility of cancer prevention and early detection. In this study, we presented data concerning the number and type of oncological cases and their correlation with CPS occurrence in a cohort of Central and Eastern European pediatric population. The data were collected between 2000 and 2019 at the Karol Jonscher Clinical Hospital of Poznan University of Medical Sciences, resulting in a cohort of 2,190 cases in total, of which 193 children (8.81%) were confirmed to have CPS. CPS occurred most frequently in infancy (22.90% of all children suffering from any diagnosed cancer during the first year of life, p &lt; 0.0001), accounting for more than a quarter of all CPS cases in our cohort. CPS were least likely to be observed in patients aged 14 and 15 years (2.17% and 2.44% of children diagnosed with any of the listed cancers at the exact age, respectively, p &lt; 0.05). Among CPS, the most common were neurofibromatosis type I (NF1), Li-Fraumeni syndrome (LFS), and Down syndrome (DS). To conclude, it is important to emphasize the need for personalized treatment for each patient affected by both CPS and subsequent cancer in order to reduce the toxicity of therapy and improve quality of life by reducing the risk of side effect.

Background: By 2025, road traffic injuries are projected to rank third in the global burden of disease, posing a significant challenge that affects health, social well-being, and economic aspects. According to data from the Romanian Police National Statistics Center, there has been an average of 342 traffic accidents per year involving pediatric patients over the past 10 years. Materials and Methods: A retrospective research study was conducted, encompassing 358 cases of road traffic accidents identified for the study. Data collection was conducted at "St. Mary’s" Emergency Hospital for Children in Iasi, Romania, from January 2015 to December 2022. To facilitate statistical analyses, participants were categorized into three specific age groups, correlating between the anatomical region affected and different types of accidents was examined, and the classification of injury types was determined based on the characteristics of the harm inflicted. Results: An oscillating trend is observed from 2015 to 2020, with its lowest value recorded in 2017 at around 6.8% and its peak in 2019 at 20.1%. Notably, post-pandemic (Covid-19), the cases underwent a substantial decline of approximately 50%. At least 78.7% of those who did not undergo orthopedic reduction required surgery, whereas among those who underwent orthopedic reduction, only 23.4% needed surgery. Regarding the frequency of complications 7,9% of the total cases experienced complications. Conclusion: The increased frequency of pediatric traffic accidents is attributed to the extensive services provided by "St. Mary’s" Emergency Hospital for Children, Iasi, to a significant number of patients from both rural and urban areas across the seven counties of the Moldova, Romania.

Background:Fontan completion is the last stage of univentricular repair, which drains the inferior vena cava against gravity to a higher-pressure pulmonary arterial circulation. The passivity and anti-gravity nature of this circulation render a failing Fontan, not an uncommon encounter, twenty years ago, Rodefeld and colleagues, decided to explore the feasibility of vascular pumps to support the passive nature of Fontan circulation, and since then, trials are still ongoing, and we aimed through this review to wrap up the results of these trials. Methods:A literature review has been conducted, to identify any in vivo or in vitro trial of a Fontan assist device. Several outcome parameters determined whether the trial will be included or not in this review, including, the flow rate of a pump if applicable, the number of compressions per minute if a compression device has been used, the resultant flow rate, the inferior and superior vena cava pressures, associated with each setting of the respective device, and any evidence of hemolysis or clotting within the circuit. Results:A total of ten trials have been included, with 23 different settings. Three designs have been identified, out of which two fall within the pump design, namely the connecting chamber and the intravascular pump designs; only one trial explored the possible use of a compression device. The commonest design encountered in in-vivo trials was the intravascular pump (67%). No reports of significant hemolysis or thrombosis were found. An increasing flow rate beyond 5L/min was associated with a negative outcome in the connecting chamber design, increasing upstream pressure in the SVC, while intravascular pumps did not display this limitation. Conclusion:Univentricular heart patients are a relatively small population, with very extensive needs, despite twenty years of trials, no study has yet concluded the optimal design or settings for a Fontan assist device. In this review, we identified that the intravascular pump remains the most practical design, due to its easy mode of insertion, and that it is not faced with the limitation or risk of increasing upstream resistance. There is still a long way to conclude its use as other designs such as compression devices have not yet been fully studied.

Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the formidable challenges and facilitating factors essential for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.

(1) Background: Impaired colonic motility is common in patients with ulcerative colitis. The patients often complain the symptoms related to colonic motility dysfunction such as loose stools or diarrhea and these symptoms make therapy more challenging; (2) Methods: This study aimed to examine the movement of the colon in mice with ulcerative colitis and determine if the glial-derived neurotrophic factor (GDNF) may enhance aberrant colonic motility through Connexin 43 (Cx43).A model of ulcerative colitis was created using 32 male C57BL/6 mice. Colonic transit time was measured in all mice, and colon tissues were examined using hematoxylin-eosin staining (HE) and transmission electron microscopy (TEM). The levels of GDNF and Cx43 were determined via immunohistochemistry, immunofluorescence, and RT-PCR techniques. The levels of C-reactive protein (CRP),TNF-α, IL-1β, and IL-6 were quantified using the enzyme-linked immunosorbent assay (ELISA); (3) Results: 1) The UC models were effectively established by administering dextran sodium sulfate (DSS) water. Mice with ulcerative colitis exhibited a delay in colonic transit time. 2) GDNF can improve the delayed movement of the colon in mice with UC by activating the Cx43 protein; (4) Conclusions: GDNF can ameliorate impaired colonic motility in mice with ulcerative colitis, and its mechanism is related to the activity of Cx43. GDNF could potentially be utilized as a therapeutic option for addressing aberrant colonic motility in patients.

Injury to the peritoneum during surgery is followed by a healing process that frequently results in the attachment of adjacent organs by a fibrous mass, referred to commonly as adhesions. Because injuries to the peritoneum during surgery are inevitable, one must understand the mechanisms of adhesion formation to prevent its occurrence. This requires a thorough understanding of the molecular sequence that results in the attachment of injured peritoneum and the development of fibrous tissue. Recent data show that fibroblasts from the injured peritoneum may play a critical role in forming adhesion tissues. Therefore, identifying changes in gene expression patterns in the peritoneal fibroblasts during the process may provide clues to the mechanisms by which adhesion develops. This review presents many papers discussing genes implied in peritoneal adhesion.

Objectives: This study aimed to compare the similarities and differences between the Kawasaki disease (KD) during the SARS-CoV-2 pandemic and multisystem inflammatory syndrome in children (MIS-C). Methods: The medical records of patients diagnosed with KD and MIS-C at a single center between July 2020 and November 2021 were retrospectively reviewed. Results: The study included 39 MIS-C patients (84.6% male) with a median age of 138 months and 17 KD patients (58.8% male) with a median age of 36 months. Compared with the KD patients, MIS-C patients were older (p<0.001), had longer hospital stays (p=0.023), elevated neutrophil count (p<0.001), C-reactive protein (p<0.001), procalcitonin (p<0.001), interleukin-6 (p<0.014), ferritin (p<0.001), fibrinogen (p<0.001), troponin I (p=0.001), NT-proBNP (p<0.001), and, D-dimer levels (p<0.001). They had more hypotension (p=0.024), decreased left ventricular function (p=0.023), and a greater need for corticosteroids (p<0.001), enoxaparin (p=0.045), and therapeutic plasma exchange (p<0.001). Patients with KD displayed a higher frequency of rash (p<0.001), oral mucosal changes (p<0.001), conjunctival injection (p<0.001), extremity changes (p<0.001), and cervical lymphadenopathy (p<0.001). They had a longer duration of fever (p<0.001), elevated white blood cell count (p<0.001), platelet count (p<0.001), and alanine aminotransferase level (p<0.001). The two groups were similar in terms of hemoglobin levels, erythrocyte sedimentation rate, albumin levels, or the frequency of coronary dilation/aneurysm, myocarditis, pericarditis, invasive mechanical ventilatory support, and intravenous immunoglobulin treatment. Conclusions: Older patient age, a greater presence of gastrointestinal and cardiac findings associated with hypotension, increased NT-proBNP levels, decreased left ventricular function, the use of various treatment modalities, and longer hospital stays suggest MIS-C, whereas a longer duration of fever and classical clinical features of KD favor KD.

This six-year multicentre study investigated acute intentional poisoning with substances of abuse in adolescents to identify changes and patterns in substance use. Data from 568 adolescents were collected from three paediatric poison centres in Romania between January 2017 and December 2022. The study analysed the epidemiological and sociodemographic characteristics of the adolescents, including age, gender, place of residence, history of substance abuse, psychiatric history, and history of institutionalized care. The findings revealed that cannabis and new psychoactive sub-stances (NPSs) are the most commonly implicated substances, each with distinct profiles among adolescents. Cannabis was involved in 45.6% of cases, with a significant association with urban residency. NPSs were identified as the second most prevalent substance, accounting for 38.9% of cases. These were more prevalent in rural areas and among patients with psychiatric disorders. Cannabis and NPSs were also the most commonly implicated substances in acute intentional poisoning cases with substances of abuse. These substances have distinct profiles among adolescents, including age, gender, residency area, history of substance abuse, psychiatric history, and institutional care. These findings underscore the necessity of targeted public health interventions and integrated care approaches to address substance use and related mental health issues in adolescents.

Anastomotic insufficiencies are severe complications of abdominal surgery, often leading to pro-longed hospitalization, serious tissue inflammation, even sepsis and the need for recurrent sur-gery. Current non-surgical treatments such as self-expanding metal stents (SEMS) and endoscopic vacuum therapy (EVT) have limitations, including stent migration or perforation. This review evaluates the effectiveness of the VacStent GITM, a novel medical device combining SEMS and negative-pressure wound therapy in treating gastrointestinal leaks. Data were gathered from four prospective studies and compared with existing treatments. Studies on the VacStent GITM applica-tion demonstrate technical success and competitive closure rates in upper gastrointestinal leaks, with minimal complications reported. Comparative analyses with SEMS and EVT reveal prom-ising and most importantly equally good outcomes while maintaining the possibility for sus-tained enteral nutrition and reducing stent migration risk. The VacStent GITM presents a promis-ing alternative to current non-surgical treatments. Ongoing research aims to validate its efficacy in lower gastrointestinal leaks and establish its role in leak management comprehensively. Fur-ther investigation is necessary to confirm these findings and optimize treatment protocols. Future usages of the VacStent GITM in colonic anastomotic insufficiencies promise an effective approach and might be able to lower the rates of necessary implementations of a stoma.

Introduction: Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent episodes of upper airway obstruction and involves intermittent hypoxia and sleep fragmentation, with potentially serious consequences for affected patients. (1–3). Although nocturnal polysomnography is the gold standard, it is an exam that is not readily available and is very expensive. (4). Hence, the need to find new diagnostic methods. Considering that the causes of OSAS can be divided into anatomical-structural ones, related to craniofacial anomalies, it has been hypothesized that anthropometric measurements taken by new 3D stereophotogrammetric systems could be useful as a diagnostic tool in pediatric patients with OSAS (5) (6). The primary objective of the study is, therefore, to evaluate the correlation between mandibular length measured between menton and gonion, obtained through 3D stereophotogrammetry using the "Face Scanner maxi 6", and the severity of OSAS (AHI classification), defined by the score of the Sleep Clinical Record (SCR) questionnaire in a group of pediatric patients with suspected obstructive sleep disorders. The secondary objective concerns the identification of possible correlations between other mandibular parameters estimated by 3D stereophotogrammetry and the severity of OSAS, defined by the McGill Oximetry Score (MOS), and the association between MOS and SCR to determine the AHI level. Materials and methods: The study considered patients who were prescribed a pulseoximetry exam due to suspected obstructive sleep disorders. All participating patients underwent a specialized orthodontic examination, which included completing the SCR questionnaire and taking facial photographs using a 3D stereophotogrammetric system. The SCR questionnaire considers 11 dental, nasal, oropharyngeal, and facial phenotype parameters to determine a final score from 0 to 18, indicating the risk of obstructive sleep apnea syndrome. The acquired stereophotogrammetric images were processed using dedicated software to obtain a three-dimensional model representing the patient's facial phenotype. Subsequently, anatomical landmarks and relevant anthropometric measurements were identified on the model, and it was assessed whether one or more of these showed concordance criteria with the parameters derived from SCR and MOS. The anthropometric evaluation was performed by expert operators, taking into account mandibular variables. Results: Fifteen patients were analyzed, with 2 excluded due to alterations in the stereophotogrammetric images caused by poor patient cooperation during the acquisition of the photographs. Spearman's correlation analysis was performed to investigate the relationship between anthropometric measurements, obtained by 3D stereophotogrammetry, and OSAS severity, by means of SCR, MOS, and SCR+MOS. A significant and negative correlation was observed between right mandibular length (gonion-menton) and MOS (ρ=−0.586, p=0.036). Conclusions: The result obtained has important implications for the field of study and suggests that future attention should focus more on the mandibular length variable as a determining factor for OSAS. However, the sample examined was relatively small, which might obscure the correlation with contralateral mandibular length and potential correlations with other mandibular/facial parameters. Additionally, the small sample size prevented stratification by sex and age. The study thus provides an important contribution to understanding the relationships between 3D stereophotogrammetry and pediatric OSAS but also highlights the need for further research that could potentially influence future developments in diagnosing OSAS in children.

Malignant lymphoma is an unusual form of gallbladder neoplasm. Almost all of these tumors are diffuse large B-cell lymphomas or mucosa-associated lymphoid tissue-type lymphomas. Herein, we report a rare case of a gallbladder Burkitt’s lymphoma (BL) in a child living with HIV. As far as we are concerned, this is the secondfirst report in the pediatric population and the first one in an individual living with HIV. The patient (a five-year-old black female child) attended the Federal Hospital of Lagoa, Rio de Janeiro, Brazil, underwent cholecystectomy and the postoperative pathological analysis of the gallbladder revealed a diagnosis of BL (EBV-positive). Also, HIV serology was performed and returned positive. She was transferred to the Martagão Gesteira Institute of Pediatrics and Childcare for oncological treatment, dying from sepsis and disease progression about 18 months later. Patient did not undergo ART/cART. Previous cases of gallbladder BL were herein described and analyzed to characterize the clinicopathological features and possible similarities. BL can occur in the gallbladder both in the context of HIV infection and in the pediatric population. Biopsy is mandatory in cases with suggestive findings of lymphoma, and an early diagnosis can change the course of the disease. Furthermore, the case highlights the importance of an early initiation of ART/cART in people living with HIV (PLWH).

Background: Bronchopulmonary dysplasia (BPD) is the most common respiratory disease in pre-term and is still associated with increased mortality and morbidity. The great interest lies in iden-tifying early biomarkers that can predict the development of BPD. Objectives: This pilot study explores the potential of e-nose for early identification of BPD risk in premature infants by analyzing volatile organic compounds (VOCs) in the exhaled breath con-densate (EBC). Materials and Methods: Fourteen mechanically ventilated very preterm infants were included in the study. Clinical parameters and EBC were collected within the first 24 hours of life. The dis-criminative ability of breath-prints between preterms who did and did not develop BPD was in-vestigated by pattern recognition, machine learning algorithm, and standard statistical methods. Results: We found that e-nose probes can significantly predict the outcome of “no-BPD” vs “BPD”. Specifically, a subset of probes (S18, S24, S14, and S6) were found to be significantly predictive, with an AUC of 0.87, 0.89, 0.82, 0.8 and p=0.019, 0.009, 0.043, 0.047, respectively. Conclusion: The E-nose is an easy-to-use, handheld, non-invasive electronic device that quickly samples breath. Our preliminary study has shown that it has the potential for early prediction of BPD in preterms.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and the third leading cause of cancer-related death worldwide. Liver transplantation (LT) is the best therapy for most patients with non-metastatic HCC. In recent years, the management of patients with HCC has changed considerably, thanks to the improvement of molecular biology knowledge and the introduction of immunotherapy. To date, systemic therapy is authorized in the Western world only in patients with advanced HCC. However, this therapy could lead not only to stabilize the tumour disease or improve survival but could display excellent response and lead to downstaging of the tumor that finally permits liver transplantation. There are increasing reports of patients that have performed liver transplantation after pretreatment with immune checkpoint inhibitors (ICIs). However, due to the intrinsic mechanism of ICIs to stimulate the immune response against tumors, they could also cause graft rejection. This review aims to evaluate the readiness and outcomes of liver transplantation in patients with advanced HCC who have previously undergone treatment with ICIs. It seeks to identify the challenges, risks, and benefits associated with this conversion therapy. The integration of ICIs into the treatment paradigm for advanced HCC necessitates a nuanced approach to liver transplantation. While early evidence supports the feasibility of LT following ICI therapy, there is an urgent need for standardized guidelines and more extensive longitudinal studies to optimize patient selection, timing, and post-transplant management.

Background: Patients with mutations in the monocarboxylate transporter 8 (MCT8) suffer from Allan-Herndon-Dudley syndrome (AHDS), characterized by developmental delay and a highly disabling movement disorder. Despite the potential of thyroid hormone derivatives to overcome the transporter defect, current trials did not achieve patient-oriented therapeutic goals. Objectives: Since most neurological symptoms are related to the dopaminergic system, we investigated the role of dopamine and its metabolites in MCT8 deficiency with regard to pathophysiology and potential therapeutic strategies in an observational cohort study. Methods: We present longitudinal data from the DEEPTYPE registry of ten patients with video-documentation, standardized phenotyping, cerebrospinal fluid analysis, treatment response to levodopa/carbidopa supplementation, and neuroimaging data. To establish a cell-based model for pathophysiological studies, we differentiated healthy human induced pluripotent stem cells (hiPSCs) into dopaminergic neurons. Results: Children presented with signs of parkinsonism in childhood, including hypokinesia, hypomimia, inability to sit or stand, rigidity, dystonia, and autonomic dysfunction along the classification of Leuzzi and colleagues. Cerebrospinal fluid homovanillic acid concentrations were decreased (n=11), suggesting isolated dopamine pathway impairment. Six out of seven patients responded favorably to levodopa/carbidopa supplementation and we did not see any adverse drug reactions. Our cell-based studies showed that hiPSC-derived dopaminergic neurons expressed MCT8 and produced quantifiable levels of biogenic amines. Conclusions: Parkinsonism is part of AHDS's clinical presentation and may be amenable to treatment. The precise impact of MCT8 deficiency on the dopamine metabolism needs to be further elucidated, e.g. by using patient iPSC-derived dopaminergic neurons in future studies.

Abstract: Background: The optimal strategy for the microelimination of HCV within community settings remains ambiguous. We evaluated the percentage of participants who achieved linkage to care (LTC) following the conclusion of the screening campaign, and examined the diverse factors influencing LTC among these individuals. The effectiveness of recall intervention for the non-LTC population and its barriers were analyzed. Methods: We initiated an HCV patients recall program to identify the HCV participants who might not be treated after the HCV screening campaign. A program staff recalled HCV participants who lost to follow-up through the telephone from March 2019 to June 2019. They were informed of HCV treatment's importance, efficacy, availability, and safety. Result: Among 185 HCV-infected participants, 109 (58.9%) HCV-infected participants had obtained LTC. Compared with those who had LTC, those without LTC were older, lower education levels, were less aware of their HCV infection, less frequently lived in urban areas, and had less health insurance. At the end of the recall program, 125 (67.6 %) persons had liked to care. The proportion of LTC increased by 8.7 %. 119 persons had an HCV RNA test, and 82 (68.9%) had viremia. Of 82 patients with viremia, 78 (95.1%) received antiviral therapy. 76 (97.4 %) of them achieved a sustained virological response. Conclusion: After a community screening campaign, 59 % of participants with anti-HCV positive had LTC. The recall program can increase by 9 %. However, there were still 32% of HCV participants who couldn't be linked to care. Outreach care for non-LTC patients is a way worth trying to achieve micro-elimination of HCV in the rural community.

Pediatric psychology action in the pediatric clinical-surgical high complexity unit has become increasingly necessary. It allows for the possibility of integrating complex pediatric clinical-surgical operations by reducing painful effects on the emotional world of children and adolescents. The pediatric psychologist in a pediatric unit continuously oversees children and adolescents (C/A) throughout the entire therapeutic process, extending activity to parents and healthcare personnel. In ill children and adolescents, physical pain and psychological suffering follow, with minimal temporary variations, the same clinical path with continuous changes which put a strain on the ability of children, adolescents, parents and healthcare staff to cope with stress.

Background/Objectives: Obstructive Sleep Apnoea Syndrome (OSA) in children disrupts standard breathing patterns and sleep architecture, potentially leading to severe consequences. Early identification and intervention for OSA are crucial to prevent these issues. This study explored the relationships between waiting times for polysomnography (PSG), clinical history, age at the time of PSG, and PSG outcomes in children; Methods: Two hundred and fourteen children were prospectively enrolled. Data were extracted from medical records on the age at referral for PSG and at the time of its execution, the waiting time for PSG, diagnosis (primary snoring, mild, moderate, and severe OSA), history of snoring and apnoea, medications taken, surgical interventions, passive smoke exposure, and allergies. The records also included the Pediatric Sleep Questionnaire (PSQ); Results: The mean age at referral for PSG was 5.2 (2.8) years, the waiting time for PSG was 5.2 (5.0) months, and the age at the time of PSG was 5.6 (2.8) years. Children with a shorter history of OSA (≤12 months) underwent PSG at an earlier age (4.9 (2.7) years) compared to those with a more extended history (6.0 (2.7) years; p=0.006). A younger age at referral for PSG was associated with a lower PSQ score (r=0.167; p=0.015), a shorter history of apnoea (r=0.216; p=0.003) and snoring (r=0.187; p=0.023), but also with greater OSA severity, expressed as oxygen desaturation index (r=-0.152; p=0.026). In the correlation analysis, the waiting time for PSG, adjusted for age at referral, was longer in children with a prolonged history of apnoea (r=0.195; p=0.023) and snoring (r=0.259; p=0.002) but with a lower PSQ score (r=-0.172; p=0.045); Conclusions: Some children receive delayed treatment, increasing the risk of long-term complications. In evaluating children with suspected OSA, the duration of symptoms and the PSQ score at referral emerge as crucial factors that should be considered to optimise prioritisation for PSG access.

Background/Objectives: Endometriosis represents substantial direct and indirect healthcare costs impacted by absent accurate, non-invasive uniformly diagnostic tools. We endeavored to demonstrate gastrointestinal myoelectrical activity (GIMA) biomarkers unique to endometriosis allow noninvasive, uniformly accurate diagnosis or exclusion of endometriosis. Methods: Prospective open-label comparative study of 154 patients, age &gt;18, with or without diagnosed endometriosis. Population included 62 non-endometriosis controls (Cohort 1), 43 subjects with surgically histologically-confirmed endometriosis (Cohort 2), and 49 subjects with abdominal pain and negative imaging (Cohort 3). Electroviscerography (EVG) recorded GIMA biomarkers from three abdominal electrodes before and 30-minutes post water-load protocol. Cohort 2 had postoperative EVG and Cohort 3 had preoperative EVG. Calculated specificity, sensitivity, NPV, PPV and predictive probability or C-Statistic used univariate, multivariate, linear and logistical regression analyses of the area under the curve (AUC) at all frequency and time points, including age and pain covariants. Results: Non-endometriosis cohort differed significantly from endometriosis cohorts (p&lt;0.001) for median (IQR), and AUC percent frequency distribution of power at baseline, 10-minute, 20-minute, and 30-minute post water-load at all frequency ranges 15-20cpm, 30-40cpm and 40-50cpm. Endometriosis cohorts were statistically similar (p&gt;0.05). GIMA biomarker threshold scoring demonstrated 95%/91% sensitivity and PPV, 96%/95% specificity and NPV and C-statistic of &gt;99%/98% respectively for age subsets. GIMA biomarkers in Cohort 3 predicted 47/49 subjects positive and 2/49 negative for endometriosis, confirmed surgically. Hormonal therapy, surgical stage, nor pain score affected diagnostic accuracy. Conclusions: Non-invasive electroviscerography with GIMA biomarker detection distinguished participants with and without endometriosis based upon endometriosis specific GIMA biomarkers threshold scoring.

Artificial Intelligence (AI) and Machine Learning (ML) approaches that could learn from large data sources have been identified as useful tools to support clinicians in their decisional process; AI and ML implementations have had a rapid acceleration during the recent COVID-19 pandemic. However, many ML classifiers are “black box” to the final user, since their underlying reasoning process is often obscure. Additionally, the performance of such models suffer from poor generalization ability in presence of dataset shift. Here, we present a comparison between an explainable-by-design (“white box”) model (Bayesian Network (BN)) versus a black-box model (Random Forest), both studied with the aim to support clinicians of Policlinico San Matteo University Hospital in Pavia (Italy) during the triage of COVID-19 patients. Our aim is to evaluate whether the BN predictive performances are comparable with those of a widely used but less explainable ML model such as Random Forest and to test the generalization ability of the ML models across different waves of the pandemic.

Background/Objectives: Multisystem Inflammatory Syndrome in children (MIS-C) is a rare but severe post-infectious complication of COVID-19, that often requires admission to the Pediatric Intensive Care Unit (PICU). The present study aimed to compare the demographic, clinical and laboratory characteristics between children diagnosed with MIS-C who were admitted to the PICU or did not require PICU admission. Methods: Children diagnosed with MIS-C from September 2020 to April 2023 were included in this case-control study. Patient’s demographic, clinical and laboratory data, were collected from medical records. Results: Fifty children with MIS-C were included in the study [median (IQR) age: 7.5 (4.3, 11.4) years, 28/50 (56%) males]. Twenty-two (22/50, 44%) children required admission to the PICU. In the multivariate regression analysis, hepatic (OR:12.89, 95%CI: 1.35-123.41, p-value=0.03) and cardiological involvement (OR:34.55, 95%CI: 2.2-541.91, p-value=0.01) were significantly associated with hospitalization at the PICU. Regarding the laboratory and imaging parameters during the first 48 hours from admission, D-dimer levels higher than 4μg/mL and decreased Left Ventricular Ejection Fraction were associated with an increased risk of PICU admission (OR:7.95, 95%CI:1.48-42.78, p-value=0.02 and OR=1.28, 95%CI:1.07-1.53, p-value=0.01). Children who were admitted to the PICU were more likely to develop complications during their hospitalization (10/22, 45.5% vs. 3/28, 10.7%, p-value=0.005) and were hospitalized for more days, than children in the pediatric wards (median length of stay (IQR): 20 (15,28) days vs. 8.5 (6, 14) days, p-value&lt;0.001). Conclusions: In the present study, cardiovascular, hepatic involvement and increased D-dimer levels in children with MIS-C were associated with admission to the PICU.

Background: The two-stage technique combining the Endoscopic Retrograde CholangioPancreatography (ERCP) with common bile duct (CBD) clearance carried out before the laparoscopic cholecystectomy represents the most common approach for CBD stones. Over time, different techniques have been proposed to manage cholecysto- choledocholithiasis (CCL) advantageously in one stage. Among these, the laparoendoscopic rendez-vous (LERV) addresses the CCL issue with a laparoscopic cholecystectomy with insertion of a guide wire performed at initial stage of the procedure, followed by the clearance of the bile duct carried out by the endoscopists. The goal of this study was to evaluate the efficacy and safeness of LERV procedure recording results and complications, also making a comparison between our results and current literature. Methods: We reviewed our experience of all consecutive patients with cholecysto-choledocholithiasis managed with LERV between January 2018 and December 2023. LERV success rate, operative time, length of hospital stay, stone recurrence, incidence of endoscopic and surgical complications were analysed. Results: A total of 120 patients underwent LERV in our facilities. We reported a 97% LERV success rate, 1.6% conversion-to-open rate, a median intraoperative time of 122 (range 95-220) min. The median hospital stay was 4 (range 2-38) days. An overall morbidity of 15% was reported (18/120): 15 Clavien-Dindo type 1/2, 2 type 3a and one type 3b. In two cases a re-operation during the hospital stay was necessary. At a median follow-up of 14 months (3-59) five patients experienced stone recurrence requiring redo-ERCP in two cases. Conclusion: LERV offers the significant advantage of a single stage procedure and hospitalisation along with a lower risk of post-ERCP pancreatitis, failed CBD cannulation and complications. Our experience confirms safety and effectiveness of the technique for CCL management.

Patients with hematologic malignancies or non-malignant diseases may undergo allogeneic hematopoietic cell transplantation (HCT), which represents a potential curative treatment. However, they are still at risk of life-threatening complications, such as relapse, acute graft-versus-host disease (GvHD), and opportunistic infections. These complications are more likely if T cell reconstitution is delayed during the initial 3-4 months after HCT. Therefore, it is of clinical importance to advance early peripheral T cell expansion.The thymus is the cradle of T cell production, but it is extremely sensitive to conditioning drugs used in HCT. As a result, egress of T cells from the thymus is abrogated during the first 3-6 months after HCT. Instead, early T cell reconstitution depends on peripheral expansion of engrafted donor T cells. However, besides its established function to produce T cells, the thymus also produces thymic peptides with hormone-like activity. These molecules play an essential part in the development and nature of immune responses, and may have a role in modulating T cell expansion and function after HCT. In this review, we investigate the role of thymic peptides in shaping the dynamics of immune reconstitution early after HCT. Furthermore, we summarize current reports on clinical application of thymic peptides post-HCT and discuss their potential use in improving patient outcomes.

Background: Pediatric obesity treatment is based on high-intensity lifestyle counseling. However, high dropout rates and low effectiveness have been reported even in specialized centers. Mobile health technologies have been used in research settings to overcome these limits with contrasting results. This study aims to evaluate the effectiveness of a six-month intervention with a mobile app for the treatment of pediatric obesity at 6 and 12 months of follow-up. Methods: Patients were randomly assigned to standard care or standard care plus mobile app (2:1). The mobile app delivered high-intensity lifestyle counseling for diet and physical activity. Results: Seventy-five subjects were prospectively enrolled. At six months of follow-up, the m-app group showed significantly lower dropout rates compared to standard care(p=0.01). The risk of dropout was significantly higher in controls compared to the intervention group (OR 3.86,95%C.I. 1.39-10.42,p=0.01). After one year of follow-up, we observed lower albeit non statistically significant dropout rates in the m-app compared to the standard care group(p=0.24). No differences were observed in terms of z-score BMI and percentage of BMI reduction between the two groups. Conclusion: our findings suggest that mobile app might help in the clinical management of children and adolescents with obesity in terms of dropout reduction.

Depressive disorder in childhood and adolescence is a highly prevalent mood disorder that tends to recur throughout life. Untreated mood disorders can adversely impact a patient's quality of life and cause socioeconomic loss. Thus, an accurate diagnosis and appropriate treatment is crucial. However, until now, diagnoses and treatments are conducted according to clinical symptoms. Objective and biological validation are lacking. This may result in a poor outcome for patients with depressive disorder. Research has been conducted to identify the biomarkers that are related to depressive disorder. Cumulative evidence has revealed that certain immunologic biomarkers in-cluding brain-derived neurotrophic factor (BDNF) and cytokines, gastrointestinal biomarkers, hormones, oxidative stress, and certain hypothalamus-pituitary axis biomarkers are associated with depressive disorder. This article reviews the biomarkers related to the diagnosis and treatment of pediatric depressive disorders. To date, clinical biomarker tests are not yet available for diagnosis or for the prediction of treatment prognosis. However, cytokines such as Interleukin-2, interfer-on-gamma, tumor necrosis factor-alpha, and BDNF have shown significant results in previous studies of pediatric depressive disorder. These biomarkers have the potential to be used for diagnosis, prognostic assessment, and group screening for those at high risk.

The ultimate goal of our review is to draw clinician’s attention, especially of those who are managing pediatric patients with permanent, long-standing, ventriculoperitoneal or, less commonly, ventriculo-atrial shunts. This specific subgroup of patients may eventually suffer from severe, intractable headaches which may negatively impair their quality of daily living. In the absence of any other clinical condition that could be attributed as the cause of the headache, shunt overdrainage should not be overlooked but, on the contrary, should be seriously taken into consideration in the therapeutic armamentarium of such cases, that are difficult to be handled.

Critical aortic valve stenosis (CAVS) is a life-threatening cardiac disease of the newborn requiring urgent treatment. First-line therapy is still controversial. The aim of our study was (1) to analyze retrospectively the patients of our institution who underwent balloon aortic valvuloplasty (BAV) due to CAVS, and (2) to describe techniques for improved feasibility of the intervention using microcatheters and retrieval loops. Twelve patients underwent 23 BAVs: 1 BAV was performed in 3 patients, 2 BAVs in 7 patients, and 3 BAVs in 2 patients. Trans-valvular pressure gradient (Δp) and left ventricular shortening fraction (LVSF) improved significantly in the first two interventions; first BAV: Δp from 73.7 ±34.5 mmHg to 39.8 ±11.9 mmHg (p=0.003) and LVSF from 22.3 ± 13.5 % to 31.6 ±10.2 % (p=0.001); second BAV: Δp from 73.2 ±33.3 mmHg to 35.0 ± 20.2 mmHg (p&lt;0.001) and LVSF from 26.7 ±9.6 % to 33.3 ±7.4 % (p=0.004). Cardiac surgery during the neonatal period was avoided for all children; median time to valve surgery was 5.75 years. Few complications occurred: mild to moderate aortic regurgitation, one remediable air embolism, and one intimal injury of the ascending aorta. We conclude that BAV is a successful primary treatment for CAVS resulting in left ventricular relief, stabilization of the neonate, and a time gain until cardiac surgery.

High-flow oscillatory ventilation (HFOV) is a common rescue treatment in infants and children with respiratory failure. This type of ventilation is an effective technique in numerous diseases that affect a child in the postnatal period, such as ARDS, meconium aspiration syndrome (MIS), postnatal pulmonary bleeding and idiopathic pulmonary hypertension (IPH). Although this ventilation technique is commonly recognized as a valuable therapeutic option in the general pediatric population, this is not the same for children with congenital cardiovascular diseases. The key mechanism of oscillatory ventilation is continuous positive pressure administered within the airways via a small tidal volume at high frequency. Tidal volumes are between 1 and 3 ml/kg delivered at 5 – 15 Hz equivalent to 300 – 900 breaths per minute. Few older studies conducted on humans and animals highlight that HFOV may be dangerous for congenital heart patients. According to these evidences, hemodynamic parameters such as blood pressure, wedge pressure, central venous pressure, heart rate and inotrope level can be dangerously changed for patients with congenital heart disease, therefore oscillatory ventilation should be avoided. Numerous retrospective studies have pointed out how oscillatory ventilation constitutes a valid therapeutic option in children with congenital heart disease. Recently, new evidences have highlighted how hemodynamic parameters are modified in a non-significant way by this type of ventilation, remaining beneficial as in the normal pediatric population. This narrative review aims to describe the mechanisms of oscillatory ventilation and collect all the available evidences to support its use in pediatric patients with congenital heart problems.

Iron metabolism plays a crucial role in the management of hemoglobinopathies, particularly in conditions such as β-thalassemia and sickle cell anemia (SCA). This paper describes the mechanisms of iron overload in patients with transfusion-dependent thalassemia (TDT), non-transfusion-dependent thalassemia (NTDT), and SCA, highlighting the distinct paths leading to iron accumulation in each condition. The primary focus of this review article is on the role of genetic modifiers influencing iron metabolism and the variability in iron overload presentation among patients. Genetic mutations in genes such as HFE, HAMP, TFR2, SLC40A1, and others significantly impact iron regulation. These modifiers can exacerbate or ameliorate iron overload, and understanding these genetic factors is important for explaining the diverse disease severity and differences in the mechanism and clinical presentation of iron overload in these patients. The ongoing INHERENT study aims to further elucidate the influence of these genetic modifiers through a comprehensive genome-wide association study, potentially leading to novel therapeutic interventions for managing iron homeostasis in hemoglobinopathy patients.

Recent years have been abundant in research concerning human microbiome and its impact on the host’s health. Studies have shown, that not only the commensal bacteria itself, but also postbiotics, understood as unalived microorganisms, possibly with the presence of their components, may have themselves effect on various elements of human physiology. In this article we take a closer look on the specific ways in which postbiotics can alter immune response in allergic asthma, which is one of the most prevalent allergic diseases in today’s world being a serious subject of concern. Through altering patients’ immune response, not only to allergens but also to pathogens, postbiotics could have a significant role in lowering the number of asthma exacerbations. We suggest that more profound research should be undertaken in order to launch postbiotics into clinical standards of asthma treatment, given greatly promising findings in the field of their immunomodulating potential.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the results of traditional immunosuppressive therapy are disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients would eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and there is increasing evidence that gut microbiota and bile acids play an important role in cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Understanding the gut microbiota-bile acid network and corresponding immune functions in PBC provides a new perspective for its treatment strategies. Therefore, we summarize the latest advancements in research of gut microbiota and bile acids in PBC and, for the first time, explore the potential of immune factors related to them as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

Background: Systemic-to pulmonary collaterals (SPC) are common in congenital heart disease (CHD). Particularly in single ventricle anatomy and Fontan circulation, SPC can both complicate the postoperative course and lead to clinical deterioration in the long term. Treatment of SPC is controversial. The aim of our study was (1) to analyze retrospectively patients who underwent SPC embolization using Concerto™ Helix nylon-fibred microcoils (CHM) and (2) to describe the interventional technique. Methods: In this a single-center retrospective observational cohort study, we analyzed clinical and imaging data of all patients who underwent transcatheter embolization of SPC using CHM from January 2016 to December 2023. Results: In 38 consecutive patients (65.8 % male, median age 41 months, range 2 – 490), a total number of 141 CHM had been implanted into 64 SPC in 49 procedures. The majority were arterial SPC (n = 59/64) originating from the thoracic aorta or its branches; 5/64 were veno-venous SPC. Primary closure succeeded in all procedures. The CHM diameters ranged from 3 to 8 mm, with 5 mm being the most commonly used diameter. The mean coil / SPC ratio was 2.6 (range 1.3 – 5.3). CHM implantation was performed via 4 French sheaths. Both detachment and stable positioning was simple and safe. Neither non-target embolization nor coil migration occurred. One complication occurred with a minor vascular injury without clinical relevance. Conclusion: CHM are easy to use and appropriate for SPC embolization in all age groups, including infants, with a low complication rate. The coils are particularly suitable for closure of collaterals with small diameter or tortuous course.

Introduction: Subtalar Arthroereisis (STA) is a surgical intervention for pediatric flexible flatfoot (PFF), primarily targeting hindfoot alignment by limiting excessive subtalar eversion. However, its effects on forefoot parameters remain underexplored. This study aims to investigate radiological changes following STA in pediatric patients. Materials and Methods: A retrospective analysis was conducted on consecutive patients treated with STA for PFF. First ray-related angles, including Hallux Valgus Angle (HVA) and Inter-Metatarsal Angle (IMA), alongside hindfoot radiological parameters such as Meary, Calcaneal Pitch, and Costa Bartani angles, were assessed. Subgroup analysis by gender was performed, and correlations between demographic and pre-operative radiological parameters were examined. Results: Forty-one patients (81 feet) with a mean age of 11.6 years were included, with a mean follow-up duration of 6.4 months. No significant differences were observed in first ray-related an-gles pre- and post-operatively, with mean IMA changing from 7.97° to 7.18° and mean HV angles from 9.51° to 8.66°. Noteworthy improvements were seen in flat foot angles, including Meary, Calcaneal Pitch, and Costa Bartani angles, postoperatively. Age subgroup analysis revealed similar trends in IMA and HVA changes between Group A (operated before peak growth) and Group B (operated later). Higher preoperative angles tended to improve, while lower preoperative IMA and HVA tended to worsen postoperatively, all remaining within normal ranges. Conclusion: STA showed positive radiological outcomes for PFF treatment, while negligible changes in first ray-related angles were observed. Age subgroup analysis indicated similar trends regardless of operation timing. Higher preoperative angles tended to improve, while lower preoperative angles tended to worsen postoperatively, despite all falling within non-pathological ranges. Further re-search is warranted to confirm this correlation.

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated idiopathic GHD, with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. Analysis included 260 patients (173 boys, 87 girls) with isolated idiopathic GHD who completed rhGH therapy and have reassessed GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with assessment of GH therapy effectiveness. Incidence of transient GHD, even with respect to pediatric criteria was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in patients with normal IGF-1 before treatment, suggesting that diagnosis of GHD may be false positive. Further efforts should be made to avoid overdiagnosis GHD and overtreatment of the patients.

Background and Aims: Obesity is a pervasive health issue in children. It affects multiple systems in the body including the gastrointestinal tract. Research on obesity-related gastrointestinal diseases has focused mostly on hepatobiliary disorders. However, non-hepatic gastrointestinal diseases such as gastroesophageal reflux, constipation, and functional abdominal pain, though common and debilitating, have not been highlighted in the context of obesity. These entities can downgrade the already compromised lifestyle of obese children. Some of these disorders are more difficult to treat in these children compared to their peers with normal body mass index. Method: We reviewed the available literature on the association between obesity and these three common gastrointestinal disorders. Results: - There appears to be a strong correlation between childhood obesity and constipation and gastroesophageal reflux, and a probable correlation with functional abdominal pain. Conclusion: We suggest that given the available literature, weight management should be an integral part of the management of gastroesophageal reflux, constipation, and functional abdominal pain in obese children. This gains relevance especially because of the recent availability of medications for the treatment of obesity in children.

Ambiguity exists over treatment and surveillance strategies after endoscopic submucosal dissec-tion (ESD) for esophageal squamous cell neoplasia (ESCN) with unfavorable histologic features. This study investigated the long-term outcomes of ESD in high-risk ESCN patients. We retro-spectively included early ESCN patients treated with ESD at two medical centers in Taiwan be-tween August 2010 and December 2023. Demographic, endoscopic, and pathological data were collected. Among 146 patients (mean age 59.17 years) with 183 lesions, 73 (50%) had a history of head and neck cancer (HNC). En bloc and R0 resection were achieved in 100% and 95.6% of the lesions, respectively. The 5-year overall survival (OS), disease-specific survival (DSS) and local recurrence rates were 42.7%, 94.7% and 11%. R0 resection was significantly associated with re-currence in univariate analysis (adjusted OR: 0.23, 95% CI: 0.05-0.99, P=0.05). Alcohol abstinence was independently associated with lower recurrence (adjusted OR: 0.20, 95% CI: 0.08-0.48, P

Introduction Blunt carotid injuries (BCI) in pediatric trauma are quite rare. Due to the low number of cases, only a few reports and studies have been conducted on this topic. This review will discuss how frequent BCI/ BCVI on pediatric patients after blunt trauma is, what routine diagnostics look like, if a CT/ CTA scan on pediatric patients after blunt trauma is always necessary and if there are any negative health effects? Methods This literature review includes reviews, systematic reviews, case reports and original studies in english language between 1999 and 2020 that have dealt with pediatric blunt trauma and the diagnostics of BCI and BCVI. Furthermore, publications on the risk of radiation exposure on children were included in the study. For literature research, Medline (PubMed) and the Cochrane library were used. Results Pediatric BCI/ BCVI, shows an overall incidence between 0.03 – 0.5% of confirmed BCI/ BCVI cases due to pediatric blunt trauma. 1.1 – 3.5% of pediatric blunt trauma patients underwent CTA to detect BCI. Only 0.17 – 1.2% of all CTA scans shows a positive diagnosis for BCI. In children, the median volume CT dose index on a non-contrast head CT is 33 milligray, a computed tomography angiography needs at least 138 mGy. A cumulative doses of about 50 mGy almost triples the risk of leukemia, and doses of about 60 mGy triples the risk of brain cancer. Discussion Knowing that a BCI could have extensive neurologic consequences for children, it is necessary to evaluate routine pediatric diagnostics after blunt trauma. Computed tomography scans (CT) and computed tomography angiography (CTA) are mostly used in routine BCI diagnostics. However, since radiation exposure in children should be as low as reasonably achievable, it should be asked if other diagnostic methods could be used to identify risk groups. Trauma guidelines and clinical scores like the McGovern score are reflect established BCI screening options, as well as using duplex ultrasound.

The clinical features of increasing muscle weakening are shared by a diverse set of illnesses known as muscular dystrophies. In early childhood, males with Duchenne muscular dystrophy (DMD) exhibit proximal muscle weakening and calf enlargement, making it the most frequent X-linked disease of muscular dystrophy in children. Development of motor skills is typically delayed, and wheelchair confinement eventually leads to early death from heart or lung problems. In terms of function, ambulation, quality of life, and life expectancy, treatment approaches like corticosteroid therapy and intermittent positive pressure breathing have improved. This is a case report of a 6-year-old kid who had early ambulatory stage Duchenne Muscular Dystrophy and complained to the neuro-physiotherapy department about frequent falls, walking difficulties, and dyspnea when walking. Other grievances included being unable to get off the ground and having trouble ascending stairs. He had physiotherapy and dynamic neuromuscular stabilization for his complaints. The main goals of treatment were educating the family, respiratory training, preventing ankle plantar flexors, maintaining strength, balance and gait training.

This research ventures into the critical public health challenge of childhood obesity by exploring the dynamic interplay between psychological well-being and Body Mass Index (BMI) throughout various developmental stages of childhood. It delves into how emotional regulation, attachment dynamics, and social relationships correlate with obesity from early childhood to adolescence. Highlighting key findings, such as the negative correlation between psychological resilience and higher BMI in young children, the impact of social relationships on obesity risk during pre-adolescence, and the link between adaptive emotional strategies and higher BMI in adolescents, this study brings to the fore the nuanced relationship between psychological factors and obesity. Utilizing the interdisciplinary process of bioinformatics, this research synergizes psychometric and biomedical data to unearth psychological markers critical for crafting targeted, age-appropriate interventions. This study advocates for a holistic healthcare approach, emphasizing the integration of psychological support within obesity prevention and management strategies, thereby underscoring the indispensable role of psychological factors in the fight against childhood obesity. The application of bioinformatics methods to analyze complex datasets demonstrates how collaboration across medical specialties can enrich our understanding and response to childhood obesity, contributing significantly to the development of comprehensive, bioinformatics-enhanced healthcare solutions.

The field of epigenetics, which explores how heritable traits or stable alterations of cell functions occur without changes to the DNA sequence and how environmental factors affect gene expression, is rapidly advancing. Epigenetics plays a critical role in memory formation, learning, and cognitive functioning, effectively bridging genetics with environmental influence. Maternal behavior in rats, for instance, can modify the stress response of their offspring through epigenetic mechanisms such as histone acetylation and DNA methylation. Understanding neurodegenerative diseases like Parkinson's disease (PD) depends on comprehending the mechanisms of epigenetic regulation. Epigenetic modifications, which alter proteins and DNA structure without changing the DNA sequence, can activate or suppress gene expression, assisting organisms in adapting to environmental changes. These modifications may influence genes involved in inflammation, synaptic plasticity, and neuroprotection, potentially contributing to cognitive deficits in PD patients. MicroRNAs (miRNAs), histone modifications, and DNA methylation are the epigenetic mechanisms that significantly influence cell differentiation and maintain normal cellular activity. Understanding the intricate molecular processes of epigenetics could lead to more targeted and effective therapies. Despite numerous findings on how epigenetics affects cognitive alterations in PD patients, only some studies coordinate and integrate these results. Here, we summarize recent findings on how epigenetic changes impact gene expression linked to cognitive impairments in PD.

: Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and disruption of gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

AI-driven tools can identify nursing students' strengths and weaknesses, thus enabling the development of customized learning plans that target specific areas for improvement. This targeted approach can enhance knowledge retention and skill development, resulting in better prepared healthcare professionals. Nursing students are required to overcome their own psychological stress during their internship in order to understand sick children’s emotional reactions, as well as to be able to interact and communicate with such children. The application of AI picture-based teaching e-books helps nursing students to understand how to use therapeutic games to improve communication with sick children. A comparison of the differences between nursing teachers’ self-efficacy scores and nursing students’ application of AI picture-based teaching e-books (experimental group) and narrative handouts (control group) was achieved via therapeutic games to deal with sick children’s fear of medical examinations and treatments. In addition, a comparison was also conducted on the differences between the impact of the self-efficacy of the experimental group and that of the control group in dealing with sick children’s behavioral responses with respect to fears of medical examinations and treatments. This study is a quasi-experimental study, in which the self-efficacy scores of 30 nursing students were collected and analyzed in both the experimental group and the control group before and after intervention in dealing with sick children’s behavioral responses to fears of medical examinations and treatments. It was found that the self-efficacy score of the experimental group was higher than that of the control group (β coefficient is 0.356) when assessing the self-efficacy scores and behavior of the experimental and control groups in dealing with sick children’s fears of medical examinations and treatments through one-way analysis of covariance (one-way ANCOVA), moreover, a statistically significant difference (p < 0.05) was observed. The experimental group’s score of behavioral responses to the fears of sick children to examinations and treatments was lower than that of the control group (β coefficient was -1.540), wherein a statistically significant difference (p < 0.05) was shown. The self-efficacy of the experimental group in dealing with sick children’s fears of medical examinations and treatments had a statistically significant impact on the sick children’s behavioral responses to the fear of medical examinations and treatments (p < 0.05). In addition, the higher the self-efficacy scores of the experimental group in dealing with sick children’s fear of medical examinations and treatments, the lower the sick children’s behavioral responses to fears of medical examinations and treatments (the β coefficient was -0.914), the control group’s self-efficacy scores in dealing with sick children’s fears of medical examinations and treatments did not have a statistically significant impact on the sick children’s behavioral responses to fears of medical examinations and treatments (p > 0.05). This study proves that the application of AI picture-based teaching e-books by nursing teachers is more effective than narrative handouts in improving nursing students’ self-efficacy when using therapeutic games to deal with, as well as reduce, sick children’s fears of medical examinations and treatments.

Colorectal cancer (CRC) is characterized by a pro-inflammatory microenvironment and features high energy supply molecules that assure tumor growth. A still underestimated macromolecule is the Inorganic Polyphosphate (iPolyP), a high-energy linear polymer that is ubiquitous in all forms of life. Made up of hundreds of repeated orthophosphate units, iPolyP is essential for a wide variety of functions in mammalian cells, including the regulation of proliferative signaling pathways. Some evidence has suggested its involvement in carcinogenesis, although more studies need to be pursued. In this study, we tested the role of iPolyP on CRC proliferation, using in-vitro and ex-vivo approaches, in order to evaluate its effect on tumor growth. We found that iPolyP is significantly increased in tumor tissues compared to the corresponding peritumoral counterparts. In addition, iPolyP signaling occurs through the TRPM8 receptor, promoting CRC cell proliferation. Pharmacological inhibition of TRPM8 or RNA interference experiments showed that the involvement of TRPM8 is essential, greater than that of the other two known iPolyP receptors, P2Y1 and RAGE. The presence of iPolyP drives cancer cells towards the mitotic phase of the cell cycle by enhancing the expression of ccnb1, which encodes for the Cyclin B protein. In-vitro 2D and 3D data reflected the ex-vivo results, obtained by the generation of CRC-derived organoids, which increased in size. These results indicate that iPolyP may be considered a novel and unexpected early biomarker supporting colorectal cancer cell proliferation.

Background: The increasing prevalence of severe obesity among children and adolescents poses a significant challenge for pediatricians and general practitioners. This study aimed to investigate the relationships between biochemical results, anthropometry, blood pressure measurements and bioimpedance analysis (BIA)-derived parameters, to identify potential cardiometabolic complications associated with severe obesity. Methods: The study included 347 children (162 boys, 185 girls) aged 0-19 years, meeting criteria for severe obesity based on BMI thresholds for different age groups. Patients were recruited in four pediatric endocrinology centers in Poland (Zabrze, Cracow, Rzeszow, Szczecin). Each participant underwent anthropometric measurements, pubertal stage assessment, blood pressure measurement, biochemical and hormonal tests and BIA. Results: BMI showed significant associations with fat mass percentage (FM%) and waist-to-height ratio (WHtR), but not waist-to-hip ratio (WHR). The relationship between BMI and FM% was stronger in girls and prepubertal children. Metabolic syndrome (MetS) Z-score showed a strong positive correlation with BMI in pubertal children. Negative correlation between HDL and triglycerides was observed only in boys. Prepubertal children exhibited more significant correlations despite a smaller sample size and shorter duration of obesity. Conclusions: Considering multiple parameters beyond BMI alone provides a better understanding of cardiometabolic risks associated with severe obesity in children. MetS Z-score was not a reliable indicator of increased cardiometabolic risk in younger children. Early-onset severe obesity was associated with a higher risk of metabolic complications. Early intervention is crucial to mitigate metabolic complications in this population.

The potential adverse effects of coronavirus disease 2019 (COVID-19) vaccinations raise public concerns. Data from Taiwan’s Vaccine Injury Compensation Program (VICP) can provide valuable insights. This study analyzed preliminary application data for COVID-19 vaccine compensation in Taiwan’s VICP, focusing on applicants receiving vaccines between March 2021 and June 2022. Among the 2941 adverse events, 113 cases (3.8%) were deemed causally associated with vaccination, 313 (10.6%) were indeterminate, and 2515 (85.5%) had no causal association. Nearly half (47.6%) of applicants were over 60 years old, and 76.6% had a history of preexisting chronic dis-eases. Among the 426 vaccine-associated or indeterminate cases, the most common causes were hematological diseases and thrombosis. There were 920 mortality cases reported, and 97.4% were unassociated with vaccination. Only five deaths were judged to be associated with the COVID-19 vaccination, all involving the adenovirus vector vaccine and thrombosis with thrombocytopenia syndrome. In conclusion, most compensation applications were not causally linked to vaccination. Compared to other countries, the number of applications in Taiwan’s VICP is relatively high. These findings may indicate a need to adjust the application requirements for compensation in Taiwan’s program.

Oral candidiasis is a common problem among immunocompetent patients. The frequent resistance of Candida strains to popular antimycotics makes it necessary to look for alternative methods of treatment. The authors conducted a systematic review following the PRISMA 2020 guidelines. The objective of this review was to determine whether curcumin-mediated aPDT and blue light could be considered as an alternative treatment for oral candidiasis. PubMed, Google Scholar and Cochrane Library databases were searched using a combination of the following keywords: (Candida OR candidiasis oral OR candidosis oral OR denture stomatitis) AND (curcumin OR photodynamic therapy OR aPDT OR photodynamic antimicrobial chemotherapy OR PACT OR photodynamic inactivation OR PDI). The review included in vitro laboratory studies with Candida spp., in vivo animal studies, and randomized control trials (RCTs) involving patients with oral candidiasis or prosthetic stomatitis, published only in English. The method of elimination of Candida species in the studies was curcumin-mediated aPDT. 757 studies were identified. Following the analysis of the titles and abstracts of the studies, only 42 studies were selected for in-depth screening, after which 26 were included in this study. All studies evaluated the antifungal efficacy of curcumin-mediated aPDT against C. albicans and non-albicans Candida. In studies conducted with planktonic cells solutions, seven studies demonstrated complete elimination of Candida spp. cells. The remaining studies demonstrated only partial elimination. In all cases, experiments on single-species yeast biofilms demonstrated partial, statistically significant inhibition of cell growth and reduction of biofilm mass. In vivo, curcumin-mediated aPDT has shown good antifungal activity against oral candidiasis also in an animal model. However, its clinical efficacy as a potent therapeutic strategy for oral candidiasis requires further RCTs.

Background: Pediatric patients with polyuria polydipsia syndrome (PPS) represent a diagnostic challenge for clinicians because of the technical difficulties in performing the gold standard water deprivation test (WDT). Copeptin, a stable biomarker representing the C-terminal portion of the polypeptide chain of antidiuretic hormone, proves to be a more reliable diagnostic tool. Objective: To assess the diagnostic accuracy of copeptin baseline dosing, arginine/saline copeptin stimulation tests, and WDT. Establishing the diagnostic utility of copeptin in pediatrics, for differentiating central and nephrogenic diabetes insipidus, and primary polydipsia. Methods: comparative and non-comparative primary studies, relating to children, were included and searched for in PubMed, Cochrane Library, WOS, ScienceDirect, Scopus, Google Scholar, up to August 2024. QUADAS-2 tool was used to assess risk of bias and applicability. Meta-analyses used fixed effect models due to low heterogeneity and the HSROC model. Results: 11 studies included, with an overall Low bias, no significant applicability concerns. The mean pooled sensitivity = 0.98 (95% CI: 0.936–1.025), pooled specificity=0.947 (95% CI: 0.920–0.973), and AUC=0.972 (95% CI: 0.952–0.992), indicating excellent diagnostic accuracy. Conclusion: Stimulation methods for copeptin dosing represent effective and less invasive diagnostic test for children with PPS, and future development of standard copeptin testing protocols are needed.

Objective: The causes of vertigo and dizziness in children are diverse and require attention from various specialists. Numerous authors have reported that the commonest type of vertigo in children is migraine-associated vertigo (vestibular migraine and benign paroxysmal vertigo of childhood - BPV). We aimed to check whether this could be applied to our group of patients. Materials and methods: A retrospective case series of 257 consecutive pediatric vertigo and diz-ziness patients referred to the tertiary pediatric ENT clinic from 2015 to 2020. Patients received a complete audiovestibular workup and were referred to pediatric neurologists and other special-ists depending on the signs and symptoms. Results: Of 257 children aged 1-17 years, almost one fifth of them, 49/257 (19.1 %) had a central type of vertigo, 20/257 of them (7.8%) had benign paroxysmal vertigo of childhood and 4/257 (1.6%) had a migrainous type of vertigo. Most of the children, 112/257 (43.6%), remained unclas-sified, without a final diagnosis. Conclusion: Due to the numerous possible causes, a child presenting with dizziness and vertigo requires a multidisciplinary approach. In the majority of cases, vertigo spells are self-limiting. They stop spontaneously and sometimes remain clinically undiagnosed. The most prevalent reasons for pediatric vertigo may be temporary hemodynamic (vaso-vagal) and psychological imbalance.

Thalassemia syndromes are common monogenic disorders that represent a significant global health issue. No systematic epidemiological and molecular investigations on thalassemias in Croatian population have been reported to date. This prospective study included 70 children with a presumptive diagnosis of thalassemia, and their 42 first-degree relatives. Molecular characterization was performed using direct sequencing and gap-PCR methods. We identified 46 (30 children and 16 first-degree relatives) β-thalassemia heterozygous carriers from 24 unrelated families, carrying eight different mutations and one hemoglobin variant. Five variants account for approximately 85% of all affected β-globin alleles: Hb Lepore-Boston-Washington (32,6%), HBB: c.93-21G&gt;A (19,6%), HBB:c.315+1G&gt;A (13,1%), HBB:c.92+1G&gt;A (10,9%), and HBB:c.92+6T&gt;C variant (8,7%). A need for more detailed genetic profiling of β-thalassemia carriers is emphasized since genetic modifiers can significantly impact their phenotype. Our study provides important new insights into the relevance of β-thalassemia heterozygosity in the pediatric clinical practice.

Background: Molecular genetic events are among the numerous factors affecting the clinical course of papillary thyroid carcinoma (PTC). Recent studies have demonstrated that aberrant expression of miRNA, as well as different thyroid-related genes, correlate with the aggressive clinical course of PTC and unfavorable treatment outcome, which opens up new avenues for using them in personalization of the treatment strategy for patients with PTC. In the present work, our goal was to assess the applicability of molecular markers in preoperative diagnosis of aggressive variants of papillary thyroid cancer. Methods: The molecular genetic profile (expression levels of 34 different markers and BRAF mutation) was studied for 108 cytology specimens collected by fine-needle aspiration biopsy in patients with PTC having different clinical manifestations. Results: Statistically significant differences with adjustment for multiple comparisons (p &lt; 0.0015) for clinically aggressive variants of PTC were obtained for four markers: miRNA-146b, miRNA-221, FN1, and CDKN2A. Weak statistical correlation (0.0015&lt; р&lt;0.05) was observed for miRNA-31, -375, -551b, -148b, -125b, mtDNA, CITED1, TPO, HMGA2, CLU, NIS, SERPINA1, TFF3, and TMPRSS4. Conclusions: The recurrence risk of papillary thyroid carcinoma can be preoperatively predicted using miRNA-221, the fibronectin and cyclin-dependent kinase inhibitor 2A genes.

Elizabethkingia anophelis is an opportunistic pathogen causing lifethreatening infections in humans, particularly in immunocompromised patients, neonates and elderly. Infections caused by this species are exceptionally challenging to treat due to its multiresistance to antimicrobials. We report a case of central line-associated bloodstream infection by E. anophelis in a 2.5-year-old girl with acute lymphoblastic leukemia successfully treated with a combination of piperacillin/tazobactam and amikacin. The literature was also reviewed on paediatric infections caused by E. anophelis. Accurate identification with MALDI-TOF, or using molecular techniques, is crucial because of varying susceptibilities among species. Early, accurate diagnosis and prompt effective treatment optimize outcomes.

Background: Magnetic Resonance Imaging (MRI) is essential in pediatric diagnostics; however, the need for effective sedation due to children’s inability to remain still presents a challenge. Oral Chloral Hydrate (OCH) is commonly used for its efficacy and safety, but there is a lack of detailed exploration of the median induction time, the period from administration to effective sedation. This study aimed to evaluate the efficacy of OCH and identify the determinants of the median induction time for pediatric MRI procedural sedation.Methods: This retrospective study evaluated oral chloral hydrate (50-100 mg/kg) for pediatric MRI sedation using records from the Imam Abdulrahman Bin Faisal Hospital (2018-2022). Pediatric patients (1–8 years) were assessed for sedation efficacy, with exclusion criteria for allergies or incomplete data. Time-to-event analysis (Kaplan–Meier and Cox regression) was used to identify factors influencing sedation induction time. The data included age, weight, dose, and outcomes. The analysis highlighted the key predictors of sedation success and optimized procedural sedation protocols.Results: The study included 183 pediatric patients with a median age of 30 months and a median chloral hydrate dose of 66 mg. Sedation success was 85.79%, with younger age and shorter induction times being significantly associated with success (p<0.001). Kaplan-Meier analysis showed no significant difference in induction times between the neurological and non-neurological groups (p=0.64). Cox regression identified longer MRI duration and multiple doses as significant factors influencing the timing of sedation (p=0.050, p=0.008). Bootstrap analysis confirmed a robust median induction time of 30 minutes.Conclusions: Oral chloral hydrate achieved 85.79% success in pediatric MRI sedation, with younger and lighter patients having better outcomes. The median sleep induction time was 30 minutes, and extending sedation to 60 minutes further improved the success rate.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Newborn screening using biochemical tests is a widespread practice. However, the recent availability of genetic sequencing has enabled the rapid screening of many monogenic disorders. The purpose of our study was to assess the outcomes of whole exome sequencing (WES) and whole genome sequencing (WGS) as the primary newborn screening test. This cohort study enrolled 26 symptomatic neonates and infants exhibiting a spectrum of neurological symptoms and issues. Genome sequencing (GS) identified relevant diagnostic variants in 9 patients (point mutations, CNVs and one case of aneuploidy), suggesting that using GS as the primary newborn screening test in a general newborn population enhances traditional screening's detection capabilities. This evidence-based finding may support considering GS as a critical method for first-tier screening.

Background: Lower limb length discrepancy (LLD) in children and adolescents, often due to congenital or acquired conditions, is treated to achieve limb equality and alignment, optimizing function and minimizing cosmetic concerns for an active adulthood. This study evaluated the Health-Related Quality of Life (HRQoL) and physical functioning of adults who underwent unilateral limb lengthening with circular external fixators (EFs) in childhood. Methods: Fifty patients treated at a median age of 14.9 years completed the Short Form 36 (SF-36) and Stanmore Limb Reconstruction Score (SLRS) questionnaires in adulthood, with a median follow-up of 8.9 years. Results: Among the 50 patients, 38 underwent a single limb lengthening (21 tibia, 12 femur, 5 both), while 12 required multiple cycles. The median residual LLD was 0.4 cm, with 12 patients (24%) having over 2 cm. Complications occurred in 67% of procedures, mainly due to prolonged healing. Physical and mental health scores were significantly lower than normative data. The mean Physical Component Summary was 52.2 ± 7.2 (p = 0.20). The mean Mental Component Summary was 43.9 ± 8.6 (p = 0.001), notably lower in congenital LLD cases. Many SLRS items (Pain, Social, Physical Function, Work, and Emotions) strongly correlated with SF-36 items. Conclusions: The study highlights the challenges in treating LLD, emphasizing the significant mental health impact, especially in congenital cases, and the necessity for comprehensive long-term care strategies. These findings suggest that future therapeutic strategies should focus on both physical and psychological outcomes to improve overall recovery in LLD treatment.

Introduction: Management of hypoxic-ischemic encephalopathy (HIE) has been the subject of international recommendations. However, some aspects remain within the realm of service practices and appear to vary greatly from one center to another. Objectives: To achieve a multidisciplinary consensus in France regarding management of HIE newborns that are not covered by international and national guidelines. Methods: This is a prospective, multicenter study using the Delphi method from April 21, 2021, to July 15, 2021. Perinatal professionals were contacted through professional societies. Participants received a questionnaire in three successive rounds. Each proposal was rated using a Likert scale from 1 (completely disagree) to 8 (completely agree). An item was considered consensual if at least 70% of responses were in agreement or disagreement. Results: 58 french neonatal professionals participated. A consensus was reached in the first round concerning the use of passive hypothermia in maternity ward, with 84% agreement and to define the target temperature between 35.0°C and 35.5°C at the third round. Regarding hypoglycemia in the delivery room, 79.2% agreed in the first round to correct blood glucose levels below a threshold of <2.2 mmol/l. Parenteral route was the preferred correction method for 91.4% of respondents, while enteral route via nasogastric tube did not reach consensus. Conclusion: This study highlights the variability in definitions and practices among professionals in the management of HIE. Consensus was found regarding certain care practices performed without formal guidelines. The work to harmonize definitions and practices for the management of HIE likely needs to continue.

Objective: This prospective study aimed to compare the efficacy of caudal block (CB) and inguinal block (IB) for providing additional analgesia during unilateral orchidopexy. Methods: Seventy-two boys aged &lt;48 months, classified as ASA I/II, were assigned into CB (n=37) and IB (n=34) groups. Outcome measures included intra- and postoperative analgesic requirements, pain scores, and administration duration. Additional intraoperative analgesia was administered for a 10% increase in heart rate, while postoperative pain was assessed using the Children's and Infants Postoperative Pain Scale (CHIPPS), with scores &gt;4 prompting supplementary analgesia. Monitoring extended for 24 hours post-surgery. Results: CB significantly reduced the need for intraoperative (p&lt;0.001) and early postoperative (p=0.008) analgesia compared to IB. Although the CB group exhibited a slightly higher but non-significant analgesic requirement on the ward. No clinically relevant side effects were observed in either group. Conclusion: Both CB and IB are effective and safe methods for providing regional analgesia during orchidopexy. CB demonstrated superior efficacy intraoperatively and in the early postoperative period, while IB may offer advantages in the later recovery phase. However, additional analgesia is often required for orchidopexy, particularly in outpatient settings.

Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder characterized by difficulty maintaining attention, impulsivity and hyperactivity. Although the cause of this disorder is still unclear, recent studies state that heredity is important in the development of ADHD. This is linked to a few comorbidities: depression, criminal behavior and anxiety. Although genetic factors play a major role in the pathogenesis of ADHD, there are also non-genetic factors, one of which would be oxidative stress (OS) that are associated with ADHD. OS is implicated in the pathogenesis of ADHD, through lower levels of antioxidant enzymes such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), as well as a lower total antioxidant status (TOS) compared to control groups. Moreover, there is a close bidirectional connection between the nervous system and the intestinal microbiota, and the communication between the two systems is carried out through the gut-brain axis (GBA). A thorough review of diet, OS implications, mechanism of action, pharmacokinetics, and drug-drug interactions are reviewed here, with a special focus on treatment in adults with comorbid conditions.

IgE-mediated wheat allergy is a gluten-related disorder. Wheat is one of the five most common food allergens in children. However, the natural history of IgE-mediated wheat allergy has seldom been described in the research literature. This study presents the current state of knowledge about the IgE-mediated wheat allergy in children.

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, the review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.