Systemic Inflammatory Response Index (SIRI) as a Predictive Marker for Adverse Outcomes in Children with New-Onset Type 1 Diabetes Mellitus.

(1) Background: Although most cases of new-onset type 1 diabetes mellitus (T1DM) are managed without serious events, life-threatening complications do arise in a subset of patients. Our objective was to assess the correlation between elevated SIRI values and adverse events related to the onset of T1DM. (2) Methods: This retrospective study, spanning ten years, included 187 patients with new-onset T1DM divided into three groups based on SIRI tertiles. The primary outcome was the occurrence of acute complications during hospital admission, while the secondary outcome was prolonged Intensive Care Unit (ICU) admission. (3) Results: Patients with high SIRI values were more likely to experience higher disease activity, leading to longer ICU admission times and more frequent complications. Multivariate logistic regression analysis revealed that the SIRI was independently associated with acute complications (p = 0.003) and prolonged ICU length of stay (p = 0.003). Furthermore, receiver operating characteristic analysis demonstrated the SIRI's superior predictive accuracy compared to venous pH (AUC = 0.837 and AUC = 0.811, respectively) and to the individual component cell lineages of the SIRI. (4) Conclusions: These findings emphasize the potential utility of the SIRI as a prognostic marker in identifying patients at increased risk during T1DM hospital admissions.

Exploring Adult Eating Behaviors and Food Neophobia: A National Study in Romania.

Food neophobia involves avoiding new foods due to reluctance, aversion, or disgust. The Food Neophobia Scale (FNS) is the most reliable and common adult food neophobia test. It helps compare food neophobia across cultures by being translated into numerous languages. This study adapted, translated, and validated the FNS for Romania. This translated version was piloted in November 2023 on 59 students in the medical field from two distinct Romanian cities. Between December 2023 and February 2024, 375 adults were surveyed, representing Romania's population within a 90% confidence interval. The average age of responders was 38.07 years, with a standard deviation of 10.75 and a 4:1 female-to-male sex ratio. The Cronbach's alpha test was used to validate the questionnaire. Our study found that the mean FNS value was 31.86; most Romanian respondents (69.20%) were neutral towards trying new foods, with a significant portion being neophobes (18.21%) outnumbering neophiles (12.59%). When compared to international study results, Romanian adults, on average, exhibited a higher percentage of neophobes compared to those in Korea (13%), Hungary (16.8%), Italy (17%), and Brazil (17.5%), but a lower percentage than those in Lebanon (21.5%). The findings indicate that the translated scale can be utilized to assess neophobia among Romanian speakers.

Exploring Chronic Hypocalcemia: Insights into Autoimmune Polyglandular Syndrome Type 1-A Case Study and Literature Review.

Hypocalcemia is a common occurrence in pediatric patients, attributed to various causes and presenting with diverse clinical manifestations. A prompt evaluation is necessary to determine its underlying cause, whether it presents acutely or chronically, and to tailor treatment based on its severity. Among the potential causes of chronic hypocalcemia, primary hypoparathyroidism stands out. The case of a seven-year-old male patient with hypocalcemia reported in this article serves as an illustration, wherein targeted next-generation sequencing revealed a homozygous p.R257X mutation in the AIRE gene, indicative of autoimmune polyendocrine syndrome type 1 (APS-1). It poses challenges due to its multisystemic nature and involvement of specific autoantibodies, often leading to underdiagnosis, owing to its rarity, varied manifestations, and incomplete penetrance. A comprehensive review of the APS-1 literature was conducted to provide insights into the clinical manifestations, genetic spectrum, potential immunological mechanisms, and current medical strategies. Additionally, the recognition of AIRE gene mutations is crucial for facilitating genetic diagnosis, prognosis, and potential treatment strategies for APS-1. The management of such cases involves individualized approaches to treatment, regular monitoring, medication adjustments, and the early identification of associated conditions.

The Interaction between Stress and Inflammatory Bowel Disease in Pediatric and Adult Patients.

Background: Inflammatory bowel diseases (IBDs) have seen an exponential increase in incidence, particularly among pediatric patients. Psychological stress is a significant risk factor influencing the disease course. This review assesses the interaction between stress and disease progression, focusing on articles that quantified inflammatory markers in IBD patients exposed to varying degrees of psychological stress. Methods: A systematic narrative literature review was conducted, focusing on the interaction between IBD and stress among adult and pediatric patients, as well as animal subjects. The research involved searching PubMed, Scopus, Medline, and Cochrane Library databases from 2000 to December 2023. Results: The interplay between the intestinal immunity response, the nervous system, and psychological disorders, known as the gut-brain axis, plays a major role in IBD pathophysiology. Various types of stressors alter gut mucosal integrity through different pathways, increasing gut mucosa permeability and promoting bacterial translocation. A denser microbial load in the gut wall emphasizes cytokine production, worsening the disease course. The risk of developing depression and anxiety is higher in IBD patients compared with the general population, and stress is a significant trigger for inducing acute flares of the disease. Conclusions: Further large studies should be conducted to assess the relationship between stressors, psychological disorders, and their impact on the course of IBD. Clinicians involved in the medical care of IBD patients should aim to implement stress reduction practices in addition to pharmacological therapies.

Factors Impacting the Reduction in Neophobia Prevalence in Phenylketonuria Patients.

Food neophobia (FN), the fear of sampling new foods, can have a significant impact on children's eating habits. Children with phenylketonuria (PKU), a hereditary condition that inhibits the body's capacity to metabolize phenylalanine, should take this attitude with caution. Patients with PKU must follow a rigorous phenylalanine (Phe)-restricted diet to avoid brain malfunction that can include intellectual disability, seizures, and behavioral difficulties. The novelty of our work stems from the fact that we explored the origins of this incorrect intake pattern, which exacerbates PKU patients' already fragile health. We conducted a cross-sectional study on 34 previously diagnosed phenylketonuria patients and a control group ranging in age from 7 months to 40 years, with a sex ratio of M/F 2:1. The Food Neophobia Scale (FNS) was used to determine neophobia. We used JASP (version 0.18.1) statistical analysis to examine the relationship between neophobia and PKU condition, age and nutritional status at the time of study, diet compliance, parental educational level, period from birth to PKU diagnosis, and environmental (rural/urban) provenience of PKU patients. According to the data, 61.76% of patients with PKU were neophobic, as were 70.57% of the control group. Food neophobia was associated with PKU patients' present age, the period from birth to PKU diagnosis, and parental educational level.

Examining the Relationship between Systemic Immune-Inflammation Index and Disease Severity in Juvenile Idiopathic Arthritis.

Juvenile Idiopathic Arthritis (JIA), the leading childhood rheumatic condition, has a chronic course in which persistent disease activity leads to long-term consequences. In the era of biologic therapy and tailored treatment, precise disease activity assessment and aggressive intervention for high disease activity are crucial for improved outcomes. As inflammation is a fundamental aspect of JIA, evaluating it reflects disease severity. Recently, there has been growing interest in investigating cellular immune inflammation indices such as the neutrophil-to-lymphocyte ratio (NLR) and systemic immune inflammation index (SII) as measures of disease severity. The aim of this retrospective study was to explore the potential of the SII in reflecting both inflammation and disease severity in children with JIA. The study comprised 74 JIA patients and 50 healthy controls. The results reveal a notable increase in median SII values corresponding to disease severity, exhibiting strong correlations with traditional inflammatory markers, including CRP and ESR (ρ = 0.714, ρ = 0.661), as well as the JADAS10 score (ρ = 0.690). Multiple regression analysis revealed the SII to be independently associated with JADAS10. Furthermore, the SII accurately distinguished patients with high disease activity from other severity groups (AUC = 0.827, sensitivity 81.5%, specificity 66%). These findings suggest that integrating the SII as an additional measure holds potential for assessing disease activity in JIA.

Correlation between Neutrophil-to-Lymphocyte Ratio and Cerebral Edema in Children with Severe Diabetic Ketoacidosis.

Diabetic ketoacidosis (DKA), a common onset modality of type 1 diabetes mellitus (T1DM), can lead, in rare instances, to the development of cerebral edema, which is the leading cause of mortality in T1DM. Aside from the identification of several demographic and clinical risk factors for cerebral edema, attention has also been drawn to the possible link between systemic inflammation and neuroinflammation. This single-center retrospective study of 98 children with severe DKA aimed to investigate the possible relationship between neutrophil-to-lymphocyte ratio NLR) levels and the presence of cerebral edema. Patients were classified into three groups: alert (n = 28), subclinical cerebral edema (n = 59), and overt cerebral edema (n = 11). Lower blood pH and elevated NLR and blood urea were correlated with the presence of cerebral edema (p < 0.001). After a multivariable risk adjustment for possible confounding factors, such as age, pH, corrected sodium, and BUN, the NLR remained positively associated with cerebral edema (p = 0.045). As such, NLR may be an additional instrument to help practitioners target patients with a higher risk of severe cerebral edema. These patients would benefit from more rigorous neurologic surveillance, enabling the prompt identification of early signs of cerebral edema.

Chronic Diarrhea Caused by Vasoactive Intestinal Peptide-Secreting Tumor.

VIPomas are a type of neuroendocrine tumor that independently produces vasoactive intestinal peptide (VIP). VIPomas causing watery diarrhea, hypokalemia, and achlorhydria (WDHA) syndrome are not frequently observed in adult patients without pancreatic ailments. However, in children, the occurrence of a VIPoma originating in the pancreas is exceedingly uncommon. Instead, WDHA syndrome is more commonly associated with neurogenic tumors that secrete VIP, often located in the retroperitoneum or mediastinum. Among infants, chronic diarrhea is a prevalent issue that often necessitates the attention of pediatric gastroenterologists. The underlying causes are diverse, and delays in arriving at a definitive diagnosis can give rise to complications affecting the overall well-being of the child. The authors present the case of an infant with chronic watery diarrhea, subocclusion manifestations, mild hypokalemia, and metabolic hyperchloremic acidosis secondary to a VIPoma in the retroperitoneum that was diagnosed via abdominal ultrasound and tomography. The laboratory results revealed lowered potassium levels and an excessive secretion of VIP. Following the surgical removal of the tumor, the diarrhea resolved, and both electrolyte levels and the imbalanced hormone levels returned to normal. Immunohistochemical examination confirmed the diagnosis of ganglioneuroblastoma, with N-MYC negative on molecular biology tests. We present the clinical and histo-genetic aspects of this rare clinical entity, with a literature review.

The Role of Intestinal Microbiota in Celiac Disease and Further Therapeutic Perspectives.

Celiac disease (CD) is an immune-mediated enteropathy caused by exposure to gluten and related prolamins in genetically susceptible individuals. It is a complex genetic disorder with multiple contributing genes. Linkage studies have identified several genomic regions that probably contain CD susceptibility genes. The most important genetic factors are HLA-DQ2 and DQ8. Several known environmental triggers promote the onset of CD at any age after gluten introduction in individuals with a genetic background, such as viral infections and intestinal dysbiosis. Recent publications have described the interference of the intestinal microbiome in gluten metabolism, modulation of local immune reactions, and in maintaining normal gut permeability. These results have promoted further lines of research on the benefit of probiotic administration to prevent disease onset or alleviate clinical symptoms along with a gluten-free diet (GFD). The relationship between gut microbiome changes and the onset of CD is incompletely understood, still being the subject of current research. This narrative review analyzes the interplay between environmental factors, intestinal microbiome alterations, and the course of CD. Furthermore, this review sets out to discuss if modulation of intestinal microflora with pre- and probiotics along with a GFD could represent a reliable therapeutic target for celiac patients.

The Neutrophil-to-Lymphocyte Ratio (NLR) Can Predict Sepsis's Presence and Severity in Malnourished Infants-A Single Center Experience.

Sepsis represents one of the leading causes of death in newborns and infants, and prompt diagnosis is essential for achieving favorable outcomes. Regarding malnourished children with concurrent infection, most studies have focused, besides blood culture, on C-reactive protein and procalcitonin. Because malnutrition has a deleterious effect on cellular immune competence, the present study characterized the acute-phase response, including hematological indices, in response to sepsis. Among the examined laboratory biomarkers, procalcitonin and neutrophil-to-lymphocyte ratio were the most accurate discriminators between sepsis patients and those with bacterial infection. Moreover, these two parameters showed a gradual increase between sepsis, severe sepsis, and septic shock patients (p < 0.001). Subgroup analysis of the sepsis group revealed positive correlations of NLR with prolonged ICU stay (<0.001), acute organ dysfunction (0.038), mechanical ventilation (<0.001), and fatality (<0.001). In summary, our results suggest that the neutrophil-to-lymphocyte ratio can be used as an auxiliary diagnostic index in discriminating the presence and severity of bacterial sepsis in malnourished infants.

Phenotype of Idiopathic Infantile Hypercalcemia Associated with the Heterozygous Pathogenic Variant of SLC34A1 and CYP24A1.

Idiopathic infantile hypercalcemia (IIH) is a rare genetic disease, also called hypersensitivity to vitamin D3. The molecular heterogeneity allows for the differentiation between the two forms; IIH type 1 caused by CYP24A1 genetic variants and IIH type 2 associated with SLC34A1 mutations. The affected individuals express a variety of symptoms: hypercalcemia, hypercalciuria, suppressed intact parathormone levels (PTH), nephrocalcinosis, elevated levels of serum 1,25 (OH)2-vitamin D3 or inappropriately normal levels, and kidney phosphate wasting. The present paper describes three cases of IIH with heterozygous mutations in SLC34A1 and CYP24A1 genes, respectively. The genetic diagnosis is of paramount importance for proper treatment and the prediction of long-term outcomes.

Central precocious puberty in Prader-Willi syndrome: a narrative review.

Prader-Willi syndrome (PWS, OMIM176270) is a rare genetic disorder with recognizable dysmorphic features and multisystemic consequences such as endocrine, neurocognitive and metabolic ones. Although most patients with Prader-Willi syndrome exhibit hypogonadotropic hypogonadism, there is variability regarding sexual maturation, with precocious puberty occurring in rare cases. Our aim is to elaborate a thorough review of Prader-Willi patients with central precocious puberty, in order to raise awareness of such cases and to enhance our knowledge regarding the diagnosis and prompt treatment of this particular PWS patients.

Assessing the Relationship between Systemic Immune-Inflammation Index and Metabolic Syndrome in Children with Obesity.

Childhood obesity represents a worldwide concern as many countries have reported an increase in its incidence, with possible cardiovascular long-term implications. The mechanism that links cardiovascular disease to obesity is related to low-grade inflammation. We designed this study to investigate the diagnostic utility of inflammatory indices (NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; SII, systemic immune-inflammation index; SIRI, systemic inflammation response index) in obese children with metabolic syndrome (MetS) and their relationship with cardiometabolic risk biomarkers, such as the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), triglyceride-to-high-density lipoprotein cholesterol (TG:HDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C). A total of 191 obese children from one large Romanian reference center was included in the study. Patients were classified in two groups according to the presence (MetS group) or absence (non-MetS group) of metabolic syndrome. According to our results, the SII index proved to have diagnostic value in distinguishing MetS patients among children with obesity (AUC = 0.843, a sensitivity of 0.83, and a specificity of 0.63). Furthermore, the SII was positively associated with cardiometabolic risk biomarkers (HOMA-IR, p < 0.001; TG:HDL-C, p = 0.002; non-HDL-C, p = 0.021), highlighting its possible role as an additional measure of cardiometabolic instability in obese children.

Selenium status in term neonates, according to birth weight and gestational age, in relation to maternal hypertensive pathology.

Background: Pregnancy represents a state of increased oxidative stress and antioxidants, in which selenium (Se) plays a pivotal role, contribute to maintain the oxidative balance. If antioxidant defenses are depleted, placental function is disrupted, resulting in pregnancy complications, including pregnancy-induced hypertension (PIH). Little is known about fetal selenium status in concomitant relation to maternal PIH, gestational age (GA) and birthweight (BW). Methods: We examined over a 3-year period the serum (SeS) and urine selenium (SeU) status in term neonates from normotensive (nonPIH) and hypertensive (PIH) mothers as clinical markers of oxidative stress. In this retrospective observational study, 72 neonates with maternal PIH were matched for GA and BW to 72 neonates of normotensive mothers. Four groups were obtained, based on maternal PIH and BW relative to GA (appropriate-for-gestational-age-AGA, small-for-gestational-age-SGA): nonPIH-AGA (control group), nonPIH-SGA, PIH-AGA, and PIH-SGA. Results: The results showed significant differences (p < 0.001) in selenium levels among the study groups: SeS - 44.85 ± 7.56 µg/L in nonPIH-AGA, 39.62 ± 11.42 µg/L in nonPIH-SGA, 40.01 ± 10.07 µg/L in PIH-AGA, and 25.39 ± 8.99 µg/L in PIH-SGA; SeU - 27.98 ± 7.99 µg/L in nonPIH-AGA, 22.85 ± 9.48 µg/L in nonPIH-SGA, 23.44 ± 6.73 µg/L in PIH-AGA, and 13.05 ± 5.86 µg/L in PIH-SGA. Selenium depletion was more common in neonates born from hypertensive mothers and those born small for gestational age. Though moderate in intensity, selenium levels were positively correlated with BW (0.319 for SeS, 0.397 for SeU) and negatively correlated with maternal systolic blood pressure (-0.313 for SeS, -0.324 for SeU). The main independent effects on SeS and SeU of each maternal blood pressure and birth weight turned out statistically significant. In interaction, a more pronounced effect was reached in PIH-SGA neonates. Conclusion: Selenium status seemed to reflect the negative impact that PIH exerts in neonates during intrauterine development. Clinical markers of selenium status could thus be of great value for tracking responses of individuals to selenium supplementation as part of health improvement and harm mitigation approaches.

Evaluating the Diagnostic Performance of Systemic Immune-Inflammation Index in Childhood Inflammatory Arthritis: A Focus on Differentiating Juvenile Idiopathic Arthritis from Reactive Arthritis.

In pediatric care, the range of potential diagnoses for arthritis can be relatively extensive, primarily involving infectious and inflammatory causes and, to a lesser extent, oncological conditions. Specifically, when addressing inflammatory causes, differentiating between Juvenile Idiopathic Arthritis (JIA) and Reactive Arthritis (ReA) can prove to be challenging during the first weeks, owing to the lack of specific antibodies in several JIA subtypes. This single-center retrospective study of 108 children with arthritis aimed to evaluate in greater detail the complete blood count (CBC) profiles of children with JIA and ReA in greater detail. The most significant differences were noted in terms of the Systemic Immune-Inflammation Index (SII), with higher values in the JIA group. Moreover, within the JIA group, SII displayed a significant positive correlation with conventional inflammatory biomarkers, specifically C-reactive protein (ρ = 0.579) and Erythrocyte Sedimentation Rate (ρ = 0.430). It was the only independent factor associated with the presence of JIA after adjusting for age (p = 0.030). Also, even with the moderate diagnostic value, the discriminating capacity of SII was superior to those of each of its component CBC parameters according to receiver operating characteristic (ROC) analysis. In summary, this study identified elevated SII values in the JIA group compared to the ReA group, indicating the potential utility of SII as an adjuvant discriminatory marker between these two arthritis forms.

Extreme Birth Weight and Metabolic Syndrome in Children.

Small and large birth weights (BWs) for gestational age (GA) represent extremes, but the correlation between extreme BW and metabolic syndrome (MetS) has not been fully elucidated. In this study, we examined this correlation in obese children based on changes in their metabolic profile from childhood to adolescence. A retrospective observational study was performed on 535 obese patients aged 0-18 years in the Clinical and Emergency Hospital for Children "Louis Turcanu" in Timisoara, Romania, based on clinical and biological data from January 2015 to December 2019. We emphasized the links between extreme BW and obesity, extreme BW and cardiometabolic risk, obesity and cardiometabolic risk, and extreme BW, obesity and MetS. Children born large for gestational age (LGA) predominated over those born small for gestational age (SGA). Our findings showed that BW has an independent effect on triglycerides and insulin resistance, whereas obesity had a direct influence on hypertension, impaired glucose metabolism and hypertriglyceridemia. The influences of BW and obesity on the development of MetS and its components are difficult to separate; therefore, large prospective studies in normal-weight patients are needed.

Neutrophil-to-Lymphocyte Ratio Adds Valuable Information Regarding the Presence of DKA in Children with New-Onset T1DM.

Diabetic ketoacidosis (DKA) is an acute life-threatening complication occurring mainly at the onset of type 1 diabetes mellitus. The neutrophil-to-lymphocyte ratio (NLR), a marker for systemic inflammation, has recently generated increasing interest in many chronic diseases. The aim of this cross-sectional study was to determine the value of the neutrophil-to-lymphocyte ratio (NLR) in association with DKA severity across these cases. A total of 155 children with new-onset type 1 DM from one large center were included in the study. Total and differential leukocyte counts were measured upon admission and calculation of the NLR was performed. Patients were classified into four groups: without DKA, mild, moderate, and severe DKA at disease onset. Total WBCs, neutrophils, and monocytes increased with DKA severity (p-value < 0.005), while eosinophiles displayed an inverse relationship (p-value < 0.001). Median NLR scores increased from those without ketoacidosis (1.11) to mild (1.58), moderate (3.71), and severe (5.77) ketoacidosis groups. The statistical threshold value of the NLR in predicting DKA was 1.84, with a sensitivity of 80.2% and a specificity of 80%. Study findings indicate that a higher NLR score adds valuable information regarding the presence of DKA in children with new-onset T1DM.

Current Paradigm of Hepatitis E Virus Among Pediatric and Adult Patients.

Hepatitis E virus (HEV) infection is a polymorphic condition, present throughout the world and involving children and adults. Multiple studies over the last decade have contributed to a better understanding of the natural evolution of this infection in various population groups, several reservoirs and transmission routes being identified. To date, acute or chronic HEV-induced hepatitis has in some cases remained underdiagnosed due to the lower accuracy of serological tests and due to the evolutionary possibility with extrahepatic manifestations. Implementation of diagnostic tests based on nucleic acid analysis has increased the detection rate of this disease. The epidemiological and clinical features of HEV hepatitis differ depending on the geographical areas studied. HEV infection is usually a self-limiting condition in immunocompetent patients, but in certain categories of vulnerable patients it can induce a sudden evolution toward acute liver failure (pregnant women) or chronicity (immunosuppressed patients, post-transplant, hematological, or malignant diseases). In acute HEV infections in most cases supportive treatment is sufficient. In patients who develop chronic hepatitis with HEV, dose reduction of immunosuppressive medication should be the first therapeutic step, especially in patients with transplant. In case of unfavorable response, the initiation of antiviral therapy is recommended. In this review, the authors summarized the essential published data related to the epidemiological, clinical, paraclinical, and therapeutic aspects of HEV infection in adult and pediatric patients.

Could the burden of pancreatic cancer originate in childhood?

The presence of pancreatic cancer during childhood is extremely rare, and physicians may be tempted to overlook this diagnosis based on age criteria. However, there are primary malignant pancreatic tumors encountered in pediatric patients, such as pancreatoblastoma, and tumors considered benign in general but may present a malignant potential, such as the solid pseudo-papillary tumor, insulinoma, gastrinoma, and vasoactive intestinal peptide secreting tumor. Their early diagnosis and management are of paramount importance since the survival rates tend to differ for various types of these conditions. Many pediatric cancers may present pancreatic metastases, such as renal cell carcinoma, which may evolve with pancreatic metastatic disease even after two or more decades. Several childhood diseases may create a predisposition for the development of pancreatic cancer during adulthood; hence, there is a need for extensive screening strategies and complex programs to facilitate the transition from pediatric to adult healthcare. Nevertheless, genetic studies highlight the fact the specific gene mutations and family aggregations may be correlated with a special predisposition towards pancreatic cancer. This review aims to report the main pancreatic cancers diagnosed during childhood, the most important childhood diseases predisposing to the development of pancreatic malignancies, and the gene mutations associates with pancreatic malignant tumors.

The Relationship Between Dietary Choices and Health and Premature Vascular Ageing.

The paper aims to review the available data about the main mechanisms enabling improvement or accelerating vascular ageing due to food choices, considering recent experimental and clinical data, and emphasising potential implications for clinical practice and therapy. The main food choices which will be discussed are diets rich in fruits and vegetables, the Mediterranean diet, polyunsaturated fatty acids, cocoa, caffeine, tea, meat, dairy products, sodium, and potassium intake.