Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.

Nationwide observational study of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the Czech Republic.

The worldwide outbreak of the novel 2019 coronavirus disease (COVID-19) has led to recognition of a new immunopathological condition: paediatric inflammatory multisystem syndrome (PIMS-TS). The Czech Republic (CZ) suffered from one of the highest incidences of individuals who tested positive during pandemic waves. The aim of this study was to analyse epidemiological, clinical, and laboratory characteristics of all cases of paediatric inflammatory multisystem syndrome (PIMS-TS) in the Czech Republic (CZ) and their predictors of severe course. We performed a retrospective-prospective nationwide observational study based on patients hospitalised with PIMS-TS in CZ between 1 November 2020 and 31 May 2021. The anonymised data of patients were abstracted from medical record review. Using the inclusion criteria according to World Health Organization definition, 207 patients with PIMS-TS were enrolled in this study. The incidence of PIMS-TS out of all SARS-CoV-2-positive children was 0.9:1,000. The estimated delay between the occurrence of PIMS-TS and the COVID-19 pandemic wave was 3 weeks. The significant initial predictors of myocardial dysfunction included mainly cardiovascular signs (hypotension, oedema, oliguria/anuria, and prolonged capillary refill). During follow-up, most patients (98.8%) had normal cardiac function, with no residual findings. No fatal cases were reported.Conclusions: A 3-week interval in combination with incidence of COVID-19 could help increase pre-test probability of PIMS-TS during pandemic waves in the suspected cases. Although the parameters of the models do not allow one to completely divide patients into high and low risk groups, knowing the most important predictors surely could help clinical management.

Two Bonebridge bone conduction hearing implant generations: audiological benefit and quality of hearing in children.

PURPOSE: The study aimed to evaluate audiological benefits, quality of hearing and safety of two Bonebridge generation: BCI601 and BCI602 (MED-EL, Innsbruck, Austria) in children. METHODS: Twelve children were implanted: five BCI601 and seven BCI602 comprising of ten conductive hearing loss, and two single sided deaf SSD subjects. Audiological outcomes tested were sound field audiometry, functional gain, speech recognition threshold (SRT50), speech recognition in noise (SPRINT) and localisation abilities. Subjective measures were Speech, Spatial and Qualities of Hearing Scale (SSQ12). RESULTS: The mean FG with the BCI601 was 25.0 dB and with the BCI602 28.0 dB. The benefit in SRT50 was 23.2 dB and 33.8 dB, respectively. The mean benefit in SPRINT was 15% and 6.7% and the localisation ability improved from 33.3° to 16° and from 26.2° to 17.6°, respectively. The two SSD subjects reported a FG of 17 dB, a benefit in SRT50 of 22.5 and a benefit in SPRINT of 20%. Subjective outcomes improved significantly and even exceeded the values of their age-and sex matched normal hearing peers. One revision was reported: a retroauricular emphysema above the implant occurred 12 months post-OP, it was resolved operatively with the implant still being functional. CONCLUSION: The pediatric cohort reports significant audiological benefit, even exceeding that of the age- and sex matched control. The combination of the high safety and audiological benefit makes the Bonebridge a comfortable and effective option in hearing rehabilitation in children.

MicroRNAs in the development of resistance to antiseizure drugs and their potential as biomarkers in pharmacoresistant epilepsy.

Although many new antiseizure drugs have been developed in the past decade, approximately 30%-40% of patients remain pharmacoresistant. There are no clinical tools or guidelines for predicting therapeutic response in individual patients, leaving them no choice other than to try all antiseizure drugs available as they suffer debilitating seizures with no relief. The discovery of predictive biomarkers and early identification of pharmacoresistant patients is of the highest priority in this group. MicroRNAs (miRNAs), a class of short noncoding RNAs negatively regulating gene expression, have emerged in recent years in epilepsy, following a broader trend of their exploitation as biomarkers of various complex human diseases. We performed a systematic search of the PubMed database for original research articles focused on miRNA expression level profiling in patients with drug-resistant epilepsy or drug-resistant precilinical models and cell cultures. In this review, we summarize 17 publications concerning miRNAs as potential new biomarkers of resistance to antiseizure drugs and their potential role in the development of drug resistance or epilepsy. Although numerous knowledge gaps need to be filled and reviewed, and articles share some study design pitfalls, several miRNAs dysregulated in brain tissue and blood serum were identified independently by more than one paper. These results suggest a unique opportunity for disease monitoring and personalized therapeutic management in the future.

Videolaryngoscopy vs. Direct Laryngoscopy for Elective Airway Management in Paediatric Anaesthesia: A prospective randomised controlled trial.

BACKGROUND: The indirect visualisation of the glottic area with a videolaryngoscope could improve intubation conditions which may possibly lead to a higher success rate of the first intubation attempt. OBJECTIVE: Comparison of videolaryngoscopy and direct laryngoscopy for elective airway management in paediatric patients. DESIGN: Prospective randomised controlled trial. SETTINGS: Operating room. PARTICIPANTS: 535 paediatric patients undergoing elective anaesthesia with tracheal intubation. 501 patients were included in the final analysis. INTERVENTIONS: Patients were randomly allocated to the videolaryngoscopy group (n  = 265) and to the direct laryngoscopy group (n  = 269) for the primary airway management. MAIN OUTCOME MEASURES: The first attempt intubation success rate was assessed as the primary outcome. The secondary outcomes were defined as: the time to successful intubation (time to the first EtCO2 wave), the overall intubation success rate, the number of intubation attempts, the incidence of complications, and the impact of the length of the operator's clinical practice. RESULTS: The study was terminated after the planned interim analysis for futility. There were no significant demographic differences between the two groups. The first attempt intubation success rate was lower in the videolaryngoscopy group; 86.8% (n  = 211) vs. 92.6% (n  = 239), P = 0.046. The mean time to the first EtCO2 wave was longer in the videolaryngoscopy group at 39.0 s ±â€Š36.7 compared to the direct laryngoscopy group, 23.6 s ±â€Š24.7 (P < 0.001). There was no difference in the overall intubation success rate, in the incidence of complications nor significant difference based on the length of the clinical practice of the operator. CONCLUSIONS: The first attempt intubation success rate was lower in the videolaryngoscopy group in comparison to the direct laryngoscopy group. The time needed for successful intubation with videolaryngoscopy was longer compared with direct laryngoscopy. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03747250.

Unvaccinated child tetanus from nasal toy battery.

We present the case report of an unvaccinated Czech child with tetanus. The child had not received any vaccines due to its parent's refusal. The disease originated from the wound in the nose caused by a small flat battery. The typical onset of tetanus followed after two weeks, rapidly progressing to respiratory failure with the need for mechanic ventilation despite intensive treatment. The child spent five weeks in the hospital. Mild long-term sequelae persisted 5 months.

Liver cirrhosis and pregnancy: a case report and review of literature.

Liver cirrhosis is a chronic liver disease in which the liver tissue and the vascular beds are remodeled leading to impaired hepatic function. Portal hypertension and subsequent esophageal varices are a frequent complication of liver cirrhosis and are a cause of mortality in patients with liver cirrhosis. Pregnancy in women with liver cirrhosis is uncommon, the incidence being about 1 in 5 950 pregnancies. Hepatocellular damage and the associated alteration in the metabolism of the sex hormones is thought to be responsible and leads to anovulation. In spite of all these factors, women with cirrhosis can and do become pregnant. Pregnancy is successful in most of the patients with chronic liver disease, but maternal and fetal complication rates are still high for decompensated liver cirrhosis. Portal hypertension associated with pregnancy is a high-risk situation as both pregnancy and portal hypertension share some of the hemodynamic changes. Risks of variceal bleeding and hepatic decompensation increases many fold during pregnancy. Despite the possible complications mentioned above, the maternal-fetal morbidity and mortality rates have been decreased by the current developments in hepatology, prevention of bleeding from varices with drugs and/or endoscopic variceal ligation, improvement in liver transplantation, and an increased experience in these issues. We present a case of a 31-year-old female patient with liver cirrhosis who successfully managed pregnancy and birth without complications after the insertion of transjugular intrahepatic portosystemic shunt (TIPS). Unfortunately, 2 years after delivery, the patient developed lymphoblastic lymphoma and, despite intensive therapy for this disease, the patient died at the age of 40. We did not find any link between liver cirrhosis and lymphoblastic lymphoma.

Diagnostics and therapy of chronic pancreatitis according to UEG guidelines.

Chronic pancreatitis is one of the diseases whose incidence is slightly increasing long-term. Apparently this is related to our current dietary habits and to the way of life in industrialized societies in general. In recent years, chronic pancreatitis has experienced greater diagnostic accuracy and reliability, although we are still unable to diagnose the early stages of the disease. In diagnostics, sophisticated imaging methods are in the forefront, and less frequent is the use of tests that assess the exocrine function of the gland. Non-invasive therapeutic approaches include dietary measures, including an absolute ban on alcohol. Drug therapy consists of the application of drugs containing pancreatic digestive enzymes and the treatment of pancreatic pain. The administration of capsules containing microparticles containing pancreatic enzymes, protected against inactivation of enzymes in an acidic gastric environment, is effective. In the treatment of pancreatic pain, we use a range of analgesic drugs, but abstinence from alcohol itself leads to a decrease in the frequency of pancreatic pain. Surgical therapy is very effective. Among other treatment methods include also endoscopic therapy. From the point of view of diagnosis and therapy, chronic pancreatitis is one of the conditions requiring a multidisciplinary approach. In this review article, we discuss the possibilities of diagnosis and treatment of chronic pancreatitis according to the current recommendations of UEG (United European Gastroenterology).

Is autoimmune pancreatitis a risk factor for pancreatic adenocarcinoma?

Immunoglobulin G4-related diseases (IgG4-RD) are a group of diseases characterized by high serum levels of immunoglobulin G4 (IgG4), increased lymphocyte and plasma cell with IgG4 positivity in the parenchyma of some organs, and storiform fibrosis. The most frequently affected organ is the pancreas. This is an autoimmune form of pancreatitis, which can be divided into two types: Type 1, which is significantly more common than Type 2, is high in IgG4 in the pancreatic parenchyma and shows a fundamental difference in the noted presence of extrapancreatic disorders. In general, chronic inflammation is a risk factor in the development of carcinomas. Chronic pancreatitis is an accepted risk factor for the development of pancreatic cancer. The question is whether this also applies to autoimmune pancreatitis (AIP), which has some mediators of inflammation in common with sporadic pancreatitis, and what role the presence of IgG4 plays. The vast majority of the work on this topic consists of case reports, yet, even based on our own experience, we would like to say that there is a relationship between the autoimmune form of pancreatitis and pancreatic cancer, which usually occurs in the first two years after diagnosis of AIP. Also significant is the fact that the group of people with AIP, who is a clinical manifestation of IgG4-RD, was found to have an even higher incidence of extrapancreatic cancer than in the pancreas itself. Differentiating AIP from pancreatic cancer can sometimes be problematic since these diseases can both present as focal pancreatic lesions. IgG4 has been considered useful for AIP diagnosis, however, IgG4 levels can be slightly elevated, as in the case with pancreatic adenocarcinoma. IgG4 levels of over twice the upper limit are rare among patients with pancreatic adenocarcinoma. However, cases of simultaneous presentation of pancreatic cancer and AIP have been documented and should not be neglected. AIP is a condition where regular followup is mandatory, including from the perspective of possible cancerogenesis.

Nonalcoholic Fatty Pancreas Disease: Clinical Consequences.

Metabolic syndrome and its components such as obesity, hypertriglyceridemia, type-2 diabetes mellitus (DM-T2), and arterial hypertension are unequivocally serious problems for every society. This is especially true in economically developed countries where the imbalance in lifestyle between caloric intake and caloric output still gets greater and greater. This fact is not only a concern for the adult population but for children as well. However, metabolic syndrome does not only affect society and health in regards to cardiovascular diseases, it significantly concerns gastroenterology where it is classified as nonalcoholic fatty pancreas disease (NAFPD). The data gained from several trials show that the prevalence of NAFDP is 33% (95% CI 24-41%). When it comes to the diagnostic procedures concerning the presence of pancreatic fat, a whole spectrum of suitable methods are recommended. Probably, the most exact method is the use of magnetic resonance imaging. However, for common clinical practice, the abdominal sonographic examination based on the comparison of the pancreatic parenchymatous echogenity versus renal or hepatic echogenity is used. The clinical consequences of pancreatic steatosis and steatopancreatitis are significant. These diseases are connected with DM-T2 and insulin resistance. In recent years, changes of exocrine pancreatic function, particularly its decrease, have also been described. It is known that there is a close correlation between NAFPD and nonalcoholic hepatic steatosis and also with the increased thickness of aortic intima-media. There is also an important relationship between NAFPD and pancreatic carcinoma. Pancreatic steatosis, and especially its NAFPD form, is a serious state which can be treatable by the possible effective management of metabolic syndrome parameters, including obesity.

Regional Incidence of Inflammatory Bowel Disease in a Czech Pediatric Population: 16 Years of Experience (2002-2017).

OBJECTIVES: Inflammatory bowel disease (IBD) is today a global disease, the incidence of which is growing in the pediatric population. This prospective study aims to decipher IBD incidence and its trend in a pediatric population through 16 years in the South Moravian Region of the Czech Republic. METHODS: We evaluated data concerning 358 pediatric patients with newly diagnosed IBD at University Hospital Brno, which is a gastroenterology center for the entire pediatric population (0-18 years) and cares for all pediatric IBD patients in the South Moravian Region (1,187,667 inhabitants). RESULTS: The study encompassed 3,488,907 children during 16 years. We diagnosed 192 children (53.6%) with Crohn disease (CD), 123 (34.4%) with ulcerative colitis (UC), and 43 (12.0%) with IBD-unclassified (IBD-U). The incidence of IBD increased from 3.8 (CD 2.9, UC 0.9, and IBD-U 0.0) per 100 000/year in 2002 to 14.7 (CD 9.8, UC 4.0, and IBD-U 0.9) per 100,000/year in 2017 (P < 0.001). The overall IBD incidence per 100,000/year was 9.8 (95% confidence interval [CI]: 8.8--10.9). Constituent incidences per 100,000/year were CD 5.2 (95% CI: 4.5--6.0), UC 3.4 (95% CI: 2.8--4.0), and IBD-U 1.2 (95% CI: 0.9--1.6). IBD incidence was projected to reach 18.9 per 100,000/year in 2022. CONCLUSIONS: The overall incidence of pediatric IBD in the Czech Republic is increasing, and especially that of CD, whereas trends in UC and IBD-U appear to be constant. These data highlight the need to identify risk factors involved in the rising incidence of IBD.

Small bowel adenocarcinoma diagnosed by video capsule endoscopy in a patient with celiac disease: a case report and review of literature.

Celiac disease is an immune mediated entheropathy triggered by gluten in genetically predisposed individuals. Patients with celiac disease are at a higher risk of gastrointestinal malignancies. Diagnosis at an advance stage is one of the factors of an unfavorable prognosis of these complications. Our patient is a woman who was diagnosed with celiac disease at 53 years of age. After two years on a gluten-free diet she developed sideropenic anemia. No source of bleeding was found on the esophagogastroduodenoscopy or colonoscopy. Video capsule endoscopy revealed exulcerated bleeding stenosis in the jejunum, in front of which the capsule lodged. There were no signs of infiltration on simultaneous CT enterography. The patient was operated on and the infiltration of the jejunum was resected. The specimen was evaluated by a histopathologist as a moderately differentiated adenocarcinoma. Due to the risk factors, the patient received adjuvant chemotherapy. The knowledge of the malignant complications of celiac disease, their risk factors and the possibilities of modern enteroscopic methods could help in the early diagnosis and improvement of the prognosis of these diseases. Due to a lack of data and an absence of guidelines, treatment of a small bowel adenocarcinoma is based on an expert agreement and guidelines for colon cancer. Surgical treatment is the only potentially curative option. For stage II with risk factors and stage III adjuvant chemotherapy should be considered.

Confocal laser endomicroscopy in the diagnostics of esophageal diseases: a pilot study.

BACKGROUND: Probebased confocal laser endomicroscopy (pCLE) is a novel diagnostic technique for endoscopy which enables a microscopic view at a cellular resolution in realtime. Endoscopic detection of early neoplasia in the distal esophagus is difficult and often these lesions can be missed. The aim of the pilot study was to obtain characteristic pCLE figures in esophageal diseases for following studies, and to evaluate the possible future role of pCLE in the diagnostics of dysplastic Barretts esophagus (BE) or early esophageal adenocarcinoma (EAC). METHODS: A review of the current literature was performed and previously published pCLE images and classifications of esophageal diseases were searched and studied first. In phase two of the pilot study patients with esophageal diseases such as reflux esophagitis, BE and EAC were enrolled and scheduled for upper endoscopy with pCLE. A healthy cohort was also included. RESULTS: From January 2019 to July 2019, a total of 14 patients were enrolled in this prospective pilot study: 3 patients with reflux esophagitis, 4 with BE, 3 with EAC and 4 persons were included in the healthy cohort. The endoscopy with pCLE was performed and characteristic pCLE figures were obtained. The correct diagnoses based on realtime pCLE were evaluated by an endoscopist in 11 of the 14 cases (78.6 %). CONCLUSION: It was possible to obtain typical pCLE images of esophageal diseases during a standard capassisted endoscopic procedure. pCLE seems to be a feasible new technique in BE surveillance and early neoplastic lesion detection. However, more studies and data on larger number of patients are needed.

Multiple gene-to-gene interactions in children with sepsis: a combination of five gene variants predicts outcome of life-threatening sepsis.

INTRODUCTION: The aim of the study was to identify the dependency structure of genetic variants that can influence the outcome for paediatric patients with sepsis. METHODS: We evaluated the role of single nucleotide polymorphisms for five genes: bactericidal permeability increasing protein (BPI; rs5743507), lipopolysaccharide-binding protein (LBP; rs2232618), toll-like receptor 4 (TLR4; rs4986790), heat shock protein 70 (HSP 70; rs2227956), and interleukin 6 (IL-6; rs1800795) in 598 children aged 0 to 19 years that were admitted to a paediatric intensive care unit with fever, systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, or multiple organ dysfunction syndrome. A control group of 529 healthy individuals was included. Multi-way contingency tables were constructed and statistically evaluated using log-linear models. Typical gene combinations were found for both study groups. RESULTS: Detailed analyses of the five studied gene profiles revealed significant differences in sepsis survival. Stratification into high-risk, intermediate-risk, and low-risk groups of paediatric patients can predict the severity of sepsis. CONCLUSIONS: Analysis of single nucleotide polymorphisms for five genes can be used as a predictor of sepsis outcome in children.

[Dynamics of interleukin 6 levels in the patients with cardiogenic and septic shock and in a control group of patients with uncomplicated AMI]. / Dynamika hladiny interleukinu 6 u pacientu v septickém a kardiogenním soku a u pacientu s akutním infarktem myokardu s elevacemi ST.

INTRODUCTION: Cardiogenic shock (CS) is the leading cause of mortality in patients with acute myocardial infarction (AMI). Inflammatory response seems to be common response in patients with AMI, especially those with CS. We have therefore conducted a study to determine diagnostic and prognostic utility of interleukin 6 (IL6) levels in the cohort of patients with cardiogenic and septic shock (SS) and in a control group of patients with uncomplicated AMI. METHODS: In this prospective study 71 patients fulfilled the inclusion criteria: 30 patients with cardiogenic shock, 21 patients with septic shock and 20 patients with ST elevation myocardial infarction (STEMI). Plasma levels of IL6 were measured at 8 time points. The main endpoint was 3 month mortality. RESULTS: We have shown that the highest IL6 levels during the first week were recorded in patients with septic shock with peak value at admission. The maximum level of IL6 was detected between 12 to 24 hours after the onset of MI among patients with cardiogenic shock. According to Receiver operating characteristic (ROC) statistics levels of IL6 > 357 pg/ml at admission (AUC 0.730, p = 0.031) were typical for patients with CS in comparison with control group of STEMI patients. Values of IL6 > 1 237 pg/ml at admission and > 1 071 pg/ml at 24 hours (after admission?) were typical for thouse in septic shock in comparison with CS patients. We found only a non-significant trend of IL6 for the prediction of mortality in the cohort of CS patients for levels 1 854 pg/ml (AUC 0.769, p = 0.066) sampled 12 hours after admission. There was no association of plasma levels of IL6 with mortality in septic shock patients. CONCLUSIONS: Patients with cardiogenic shock demonstrated more pronounced cytokine response as evidenced by increased levels of IL6 compared to patients with uncomplicated STEMI. Levels of IL6 peaked in SS patients at admission, in CS patients 12-24 hours after admission. In daily clinical practice routine measurement of IL6 levels for prediction of prognosis both in cardiogenic and septic shock are of little value mainly due to significant interindividual variability of IL6 values.

Hydrocolpos causing bowel obstruction in a preterm newborn: a case report.

BACKGROUND: Imperforate hymen is the most common congenital defect of the female urogenital tract. The spectrum of clinical manifestations is broad, ranging from mild cases undiagnosed until adolescence to severe cases of giant intraabdominal masses. The most common complication of hydrocolpos is bladder compression, resulting in obstructive uropathy and hydronephrosis. CASE PRESENTATION: We present here the case of a preterm neonate who was admitted to the surgical neonatal intensive care unit for bowel obstruction. The baby did not appear septic or unwell, a small amount of meconium passed frequently, and no bilious gastric residuals occurred. Based on these findings, acute abdominal obstruction was doubtful, and the surgeon chose a conservative (watch and wait) approach. Subsequently, we performed abdominal ultrasound and magnetic resonance imaging based on unclear information about a suspicious abdominal mass raised by the gynecologist shortly before the emergency C-section. The final diagnosis was congenital hydrocolpos due to imperforate hymen. The pediatric gynecologist indicated an incision of the imperforate hymen under general anesthesia. The incision resolved abdominal distention as well as the bowel obstruction. CONCLUSION: The presentation of hydrocolpos was not typical (no bulging in the vaginal introitus) in our case, and clinical symptoms implied acute bowel obstruction shortly after birth. The surgeon chose a conservative (watch and wait) approach as the baby did not appear unwell on the second day of life. Fortunately, diagnostic laparotomy was not required as the next step in bowel obstruction management. All clinical symptoms resolved after a minor surgical procedure.

A Tagging Polymorphism in Fat Mass and Obesity-Associated (FTO) Gene Is Associated with Sepsis Status in Children.

INTRODUCTION: Sepsis is one of the most common causes of death in patients admitted to intensive care units (ICUs). The development of sepsis is significantly influenced by genetic predisposition. In this study, we highlight a potential association between a variant of the fat mass and obesity-associated (FTO) gene and risk of sepsis in children and adolescents. METHODS: We investigated a first-intron tagging FTO polymorphism (rs17817449) by comparing a severe condition (SC) group, comprising 598 paediatric patients (ages 0-19 years) admitted to an ICU with fever, systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, or multiple organ dysfunction syndrome (MODS), with a control group consisting of 616 healthy young adults. RESULTS: We observed a lower prevalence (p < 0.01; OR = 0.59, 95% CI = 0.39-0.87) of the FTO TT genotype in febrile and SIRS patients compared to patients with severe illness. There was a borderline trend towards a lower prevalence of the FTO TT genotype in the control group compared to the SC group (p < 0.09, OR = 0.81, 95% CI = 0.62-1.06). CONCLUSIONS: Our findings suggest that rs17817449, a common FTO polymorphism, may be a predictor of sepsis in paediatric patients, and that higher body weight is protective against this clinical complication.

Role of the microbiome in pathophysiology of necrotising enterocolitis in preterm neonates.

Although necrotising enterocolitis (NEC) is a serious, life-threatening disease, improved neonatal care is increasing the number of survivors with NEC among extremely preterm neonates. Therapy is nevertheless mostly symptomatic and the mortality rate remains high, especially among neonates requiring surgery. Therefore, it is important to focus on preventing the disease and modifiable risk factors. NEC's pathophysiology is multifaceted, with key factors being immaturity of the immune and barrier protective mechanisms of the premature gut and exaggerated proinflammatory reaction to insults like gut hypoxia, enteral nutrition or microbial dysbiosis. The role of the intestinal microbiome in the pathophysiology of NEC has been a subject of research for many years, but to date no specific pathogen or type of dysbiosis has been connected with NEC development. This review assesses current knowledge as to the role of the intestinal microbiota in the pathophysiology of NEC and the possibilities for positively influencing it.

Multivariate linear mixture models for the prediction of febrile seizure risk and recurrence: a prospective case-control study.

Our goal was to identify highly accurate empirical models for the prediction of the risk of febrile seizure (FS) and FS recurrence. In a prospective, three-arm, case-control study, we enrolled 162 children (age 25.8 ± 17.1 months old, 71 females). Participants formed one case group (patients with FS) and two control groups (febrile patients without seizures and healthy controls). The impact of blood iron status, peak body temperature, and participants' demographics on FS risk and recurrence was investigated with univariate and multivariate statistics. Serum iron concentration, iron saturation, and unsaturated iron-binding capacity differed between the three investigated groups (pFWE < 0.05). These serum analytes were key variables in the design of novel multivariate linear mixture models. The models classified FS risk with higher accuracy than univariate approaches. The designed bi-linear classifier achieved a sensitivity/specificity of 82%/89% and was closest to the gold-standard classifier. A multivariate model assessing FS recurrence provided a difference (pFWE < 0.05) with a separating sensitivity/specificity of 72%/69%. Iron deficiency, height percentile, and age were significant FS risk factors. In addition, height percentile and hemoglobin concentration were linked to FS recurrence. Novel multivariate models utilizing blood iron status and demographic variables predicted FS risk and recurrence among infants and young children with fever.