Congenital Hyperinsulinism Caused by Mutations in ABCC8 Gene Associated with Early-Onset Neonatal Hypoglycemia: Genetic Heterogeneity Correlated with Phenotypic Variability.

Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset HH caused by ABCC8 gene mutations. In the first patient, who presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330-1)del] that correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of the focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) positron emission tomography/computed tomography (PET/CT) was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

Insights into the Management of Chronic Hepatitis in Children-From Oxidative Stress to Antioxidant Therapy.

Recent research has generated awareness of the existence of various pathophysiological pathways that contribute to the development of chronic diseases; thus, pro-oxidative factors have been accepted as significant contributors to the emergence of a wide range of diseases, from inflammatory to malignant. Redox homeostasis is especially crucial in liver pathology, as disturbances at this level have been linked to a variety of chronic diseases. Hepatitis is an umbrella term used to describe liver inflammation, which is the foundation of this disease regardless of its cause. Chronic hepatitis produces both oxidative stress generated by hepatocyte inflammation and viral inoculation. The majority of hepatitis in children is caused by a virus, and current studies reveal that 60-80% of cases become chronic, with many young patients still at risk of advancing liver damage. This review intends to emphasize the relevance of understanding these pathological redox pathways, as well as the need to update therapeutic strategies in chronic liver pathology, considering the beneficial effects of antioxidants.

SARS-CoV-2 Seroprevalence in Children under 5 Years Old-A Regional Seroepidemiological Study.

Background and Objectives: The aim of this research was to assess the spread of SARS-CoV-2 infection; the study was motivated by parental hesitancy regarding child vaccination, and the potential passive immunity of infants acquired through breastfeeding from mothers vaccinated against COVID-19 or infected with SARS-CoV-2. Materials and Methods: We quantified the anti-SARS-CoV-2 immunoglobulin G (IgG) titer in the serum of 743 children under 5 years old, hospitalized between 1 August 2022, and 15 September 2023. Results: Among the participants, 52.76% had an anti-SARS-CoV-2 IgG titer that exceeded the reactivity threshold of the kit used, with an average of 1558.01 U/mL across the entire group. By age-specific categories, SARS-CoV-2 antibody prevalence was 43.04% for 0-12 months, 42.22% for 12-24 months, 61.67% for 24-36 months, 65.17% for 36-48 months, and 68.55% for 48-59 months. Gender analysis revealed 55.32% male participants, with a 52.07% seropositivity rate. Notably, IgG titer correlated positively with the child's age. Gender, admission diagnosis, and emergency department presentation were not variation factors of the IgG titer. Conclusions: The majority of children in the study group demonstrated IgG against SARS-CoV-2, and this rate increased with the child's age. Also, the IgG titer increased with the child's age.

The Overlap of Kidney Failure in Extrapulmonary Sarcoidosis in Children-Case Report and Review of Literature.

Sarcoidosis is a non-necrotizing granulomatous inflammatory multisystemic disorder of unknown etiology. In children, as in adults, it can involve a few or all organ systems to a varying extent and degree, entailing multisystemic manifestations. Kidney involvement in pediatric-onset adult-type sarcoidosis is rare, with a wide range of renal manifestations, most of them related to calcium metabolism. Children with renal sarcoidosis tend to be more symptomatic than adults, although male patients have a higher prevalence. We present the case of a 10-year-old boy who presented with advanced renal failure with nephrocalcinosis and important hepatosplenomegaly. The diagnosis was established by histopathological examination, with consequent cortisone therapy and hemodialysis. This review emphasizes that sarcoidosis should be considered in the differential diagnosis of pediatric patients with acute kidney insufficiency or chronic kidney disease of an unknown etiology. As far as we know, this is the first study regarding extrapulmonary sarcoidosis in children from Romania.

The Role of Urinary NGAL in the Management of Primary Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is the most frequent congenital urinary tract malformation and an important risk factor for urinary tract infections (UTIs). Up to 50% of children with VUR may develop reflux nephropathy (RN), and the diagnosis and monitoring of renal scars are invasive and costly procedures, so it is paramount to find a non-invasive and accurate method to predict the risk of renal damage. Neutrophil gelatinase-associated lipocalin (NGAL) has already proven to be a good predictive biomarker in acute kidney injuries, but there are few studies that have investigated the role of NGAL in primary VUR in children. Our aim is to review the predictive value of urine NGAL (uNGAL) as a non-invasive biomarker of RN in children with primary VUR, as well as its ability to predict the evolution of chronic kidney disease (CKD). Based on our analysis of the available original studies, uNGAL can be an accurate and reliable biomarker of RN and its progression to CKD. Some studies suggested a good correlation between VUR severity and uNGAL levels, but other studies found no significant correlation. The relationship between VUR severity and uNGAL levels is likely complex and influenced by factors such as UTIs, the timing of the urine sample collection, and the age and overall health of the patient.

Unraveling chronic kidney disease in children: a surprising manifestation of celiac disease.

Celiac disease, firstly described in children, is a type of T-cell enteropathy that occurs in individuals genetically predisposed to gluten exposure. The estimated global prevalence of celiac disease is continuously increasing. Although, traditionally, celiac disease was diagnosed in children with failure to thrive and digestive issues, it is now recognized that may present with a wide range of symptoms beyond gastrointestinal ones. Celiac disease continues to pose significant challenges due to the continuous advancement of knowledge in understanding its pathophysiology, diagnosing the condition, managing its effects, and exploring potential therapeutic approaches. The prevalence of celiac disease is increased among individuals with chronic kidney disease, also. The most frequent associations are with diabetic nephropathy, IgA nephropathy and urolithiasis. A gut-kidney axis has been recognized to play a significant role in chronic kidney diseases. This literature review aims to review the chronic renal pathology associated with celiac disease, with emphasis on childhood.

Lung microbiome: new insights into bronchiectasis' outcome.

The present treatments for bronchiectasis, which is defined by pathological dilatation of the airways, are confined to symptom relief and minimizing exacerbations. The condition is becoming more common worldwide. Since the disease's pathophysiology is not entirely well understood, developing novel treatments is critically important. The interplay of chronic infection, inflammation, and compromised mucociliary clearance, which results in structural alterations and the emergence of new infection, is most likely responsible for the progression of bronchiectasis. Other than treating bronchiectasis caused by cystic fibrosis, there are no approved treatments. Understanding the involvement of the microbiome in this disease is crucial, the microbiome is defined as the collective genetic material of all bacteria in an environment. In clinical practice, bacteria in the lungs have been studied using cultures; however, in recent years, researchers use next-generation sequencing methods, such as 16S rRNA sequencing. Although the microbiome in bronchiectasis has not been entirely investigated, what is known about it suggests that Haemophilus, Pseudomonas and Streptococcus dominate the lung bacterial ecosystems, they present significant intraindividual stability and interindividual heterogeneity. Pseudomonas and Haemophilus-dominated microbiomes have been linked to more severe diseases and frequent exacerbations, however additional research is required to fully comprehend the role of microbiome in the evolution of bronchiectasis. This review discusses recent findings on the lung microbiota and its association with bronchiectasis.

Morphological Aspects of the Aberrant Right Subclavian Artery-A Systematic Review of the Literature.

BACKGROUND: The aberrant origin of the right subclavian artery (ARSA), also known as the lusoria artery, is a congenital malformation with an incidence of 0.5-4.4%. Most cases are incidental due to minimal clinical manifestations. Computer tomography (CT) is important in diagnosing and evaluating these patients. MATERIALS AND METHODS: We conduct a computerized search in two databases, PubMed and EMBASE, for articles published between 1 January 2022 and 31 December 2023, PROSPERO code: CRD42024511791. Eligible for inclusion were case reports and case series that presented the aberrant origin of the right subclavian artery. The main outcome was the highlighting of the morphological types of ARSA. In this context, we proposed a new classification system of this anomaly. The secondary outcome was the evaluation of the demographic distribution of the lusoria artery. RESULTS: Our search identified 47 articles describing 51 patients with ARSA. The typical course for ARSA is retroesophageal, being registered in 49 out of 51 patients. This malformation is frequently associated with Kommerell diverticulum (15 out of 51), troncus bicaroticus (7 out of 51), and aberrant origins of the right vertebral artery (7 out of 51). We observed a higher incidence of the condition among women (32 out of 51) compared to men (19 out of 51). From a demographic point of view, ARSA is more frequent in the "44 to 57 years" and "58 to 71 years" age ranges. CONCLUSIONS: ARSA is a congenital malformation resulting from a defect in the development of the aortic arches. The imaging studies such as computer tomography play a defined diagnostic role.

The role of vitamin D in pediatric systemic lupus erythematosus - a double pawn in the immune and microbial balance.

Having increased popularity during the Covid-19 pandemic, vitamin D3 is currently impressing thanks to the numerous researches aimed at its interactions with the body's homeostasis. At the same time, there is a peak in terms of recommendations for supplementation with it. Some of the studies focus on the link between autoimmune diseases and nutritional deficiencies, especially vitamin D3. Since the specialized literature aimed at children (patients between 0-18 years old) is far from equal to the informational diversity of the adult-centered branch, this review aims to bring up to date the relationship between the microbial and nutritional balance and the activity of pediatric systemic lupus erythematosus (pSLE). The desired practical purpose resides in a better understanding and an adequate, individualized management of the affected persons to reduce morbidity. The center of the summary is to establish the impact of hypovitaminosis D in the development and evolution of pediatric lupus erythematosus. We will address aspects related to the two entities of the impact played by vitamin D3 in the pathophysiological cascade of lupus, but also the risk of toxicity and its effects when the deficiency is over supplemented (hypervitaminosis D). We will debate the relationship of hypovitaminosis D with the modulation of immune function, the potentiation of inflammatory processes, the increase of oxidative stress, the perfusion of cognitive brain areas, the seasonal incidence of SLE and its severity. Finally, we review current knowledge, post-pandemic, regarding the hypovitaminosis D - pSLE relationship.

Celiac disease - a pluripathological model in pediatric practice.

Being defined as an autoimmune, chronic pathology, frequently encountered in any age group, but especially in pediatrics, celiac disease (also called gluten enteropathy), is gaining more and more ground in terms of diagnosis, but also interest in research. The data from the literature of the last decades attest the chameleonic way of its presentation, there may be both classic onset symptoms and atypical symptoms. Given the impact played by celiac disease, especially in the optimal growth and development of children, the current narrative review aims to highlight the atypical presentation methods, intended to guide the clinician towards the inclusion of the pathology in the differential diagnosis scheme. To these we add the summary presentation of the general data and therapeutic lines regarding the underlying condition and the existing comorbidities. In order to place the related information up to date, we performed a literature review of the recent articles published in international databases. We bring forward the current theories and approaches regarding both classic celiac disease and its atypical manifestations. Among these we note mainly constitutional, skin or mucous, bone, neuro-psychic, renal, reproductive injuries, but also disorders of biological constants and association with multiple autoimmunities. Knowing and correlating them with celiac disease is the key to optimal management of patients, thus reducing the subsequent burden of the disease.

Cardiac and Renal Fibrosis, the Silent Killer in the Cardiovascular Continuum: An Up-to-Date.

Cardiovascular disease (CVD) and chronic kidney disease (CKD) often coexist and have a major impact on patient prognosis. Organ fibrosis plays a significant role in the pathogenesis of cardio-renal syndrome (CRS), explaining the high incidence of heart failure and sudden cardiac death in these patients. Various mediators and mechanisms have been proposed as contributors to the alteration of fibroblasts and collagen turnover, varying from hemodynamic changes to the activation of the renin-angiotensin system, involvement of FGF 23, and Klotho protein or collagen deposition. A better understanding of all the mechanisms involved has prompted the search for alternative therapeutic targets, such as novel inhibitors of the renin-angiotensin-aldosterone system (RAAS), serelaxin, and neutralizing interleukin-11 (IL-11) antibodies. This review focuses on the molecular mechanisms of cardiac and renal fibrosis in the CKD and heart failure (HF) population and highlights the therapeutic alternatives designed to target the responsible pathways.

Exploring the Microbial Landscape: Gut Dysbiosis and Therapeutic Strategies in Pancreatitis-A Narrative Review.

The gut microbiota is emerging as an important contributor to the homeostasis of the human body through its involvement in nutrition and metabolism, protection against pathogens, and the development and modulation of the immune system. It has therefore become an important research topic in recent decades. Although the association between intestinal dysbiosis and numerous digestive pathologies has been thoroughly researched, its involvement in pancreatic diseases constitutes a novelty in the specialized literature. In recent years, growing evidence has pointed to the critical involvement of the pancreas in regulating the intestinal microbiota, as well as the impact of the intestinal microbiota on pancreatic physiology, which implies the existence of a bidirectional connection known as the "gut-pancreas axis". It is theorized that any change at either of these levels triggers a response in the other component, hence leading to the evolution of pancreatitis. However, there are not enough data to determine whether gut dysbiosis is an underlying cause or a result of pancreatitis; therefore, more research is needed in this area. The purpose of this narrative review is to highlight the role of gut dysbiosis in the pathogenesis of acute and chronic pancreatitis, its evolution, and the prospect of employing the microbiota as a therapeutic intervention for pancreatitis.

An Innovative Non-Invasive Method for Early Detection and Monitoring of Acute Compartment Syndrome.

Background: Acute compartment syndrome is a major surgical emergency with complex pathophysiology and a highly unpredictable pattern of evolution. We hypothesized that the onset of acute compartment syndrome of the leg or forearm is associated with variations in the surface temperature of the distal segment (foot or hand) with a distinct pattern, which acts as an early warning sign. Materials and Methods: We developed a monitoring device that consists of two thermic sensors attached to a modular limb splint, which continuously measure the temperature difference between the proximal and distal regions of the limb (i.e., arm-hand, thigh-foot). Firstly, we investigated both the arm-hand and thigh-foot temperature gradients of hospitalized patients' healthy limbs (43 patients, 56 upper limbs, 64 lower limbs) in order to establish a baseline. Secondly, we examined the correlation between the thermic gradients and intracompartmental pressure values in compartment syndrome limbs (20 patients, 6 upper limbs, 14 lower limbs). Results: For the control group, the mean values for the normal limb thermic gradients were -0.17 °C for the upper limbs. and 0.03 °C for the lower limbs. In the impending compartment syndrome group (defined by intracompartmental pressure values), the mean index was -0.38 °C. In the fully developed compartment syndrome group, the mean value was 4.11 °C. Discussions: Analysis was performed using the ANOVA one-way statistical method. This showed significant differences between the compartment syndrome group and the impending and control groups. A decreasing trend in the thermic gradient in patients with impending compartment syndrome compared with the control group was noted. Conclusions: The thermic gradient of limbs presenting signs of impending compartment syndrome decreases as a result of the increased temperature of the distal segment. This pattern can be used as an early diagnostic method for acute compartment syndrome. This technique is non-invasive and bears no risk to the patient, allowing facile continuous monitoring during immobilization.

Cystic fibrosis management in pediatric population-from clinical features to personalized therapy.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). In 1949, it's been identified as a monogenic disease and was thought to primarily affect individuals of Northern European descent. It was the most prevalent autosomal recessive disease that shortens life. With the availability of multiple testing methodologies nowadays, there is a chance to create novel and enhanced treatment options. Even in the absence of a high sweat chloride test (SCT) result, the discovery of two causal mutations is diagnostic for cystic fibrosis (CF). For a CF diagnosis, however, at least two positive E sweat chloride tests are still required. In order to achieve early and active intervention to manage cystic fibrosis (CF) and its comorbidities, treatment regimens for pediatric patients should be evaluated, improved, and closely monitored. New developments in the treatment of cystic fibrosis (CF) have led to the development of medications derived from molecules that target the pathogenetic pathway of the illness. These options are very efficient and allow pediatric patients to receive individualized care. However, in order to better direct patient care and enhance patient outcomes, it is crucial to research uncommon CF mutations, which can provide crucial information about the prognosis of the disease and the relationships between genotype and phenotype. To ensure the success of creating novel, safer, and more efficient treatment approaches, a deeper understanding of the pathogeny of the illness is required. In the age of customized medicine, genetic research will be essential to improving patient care and quality of life for those with uncommon mutations.

Vitamin D and Its Association with H. pylori Prevalence and Eradication: A Comprehensive Review.

Taking into account previous data that sustain a relationship between vitamin D deficiency and higher H. pylori infection positivity rates, this review aims to assess the influence of vitamin D deficiency and/or insufficiency upon the prevalence of H. pylori infection and its eradication success. Three major databases were searched for articles that analyzed a relationship between vitamin D status and H. pylori infection. The literature search retrieved a total of 37 reports, after the article selection process. Hypovitaminosis D emerged as a potential risk factor for H. pylori infection, given the higher prevalence of vitamin D deficiency and/or insufficiency among H. pylori-positive subjects. Furthermore, the same type of micronutrient deficiency has been directly linked to H. pylori eradication failure. An inverse linear relationship between vitamin D status and gastric cancer risk exists, but the additional involvement of H. pylori in this correlation is still in question. The potential benefit of oral supplements in enhancing the success of classical therapeutic regimens of H. pylori still requires future research. Future population-based studies from larger geographical areas are warranted to address this subject in more depth.

SARS-CoV-2 Possible Etiology of Cerebral Venous Thrombosis in a Teenager: Case Report and Review of Literature.

Cerebral venous thrombosis in pediatric patient has a varied etiology. The authors present the case of a teenager who, since the debut of SARS-CoV-2 infection, has accused intermittent right side hemicrania, which has become persistent in association with nausea and vomiting since the 5th day of quarantine. She was hospitalized in the 9th day since the debut. Neuroimaging revealed extended venous cerebral thrombosis affecting the right sigmoid sinus, the transverse sinus bilaterally, the confluence of the transverse sinuses and the right internal jugular vein. The evolution was favorable under anticoagulant and symptomatic treatment. Laboratory tests excluded other etiological causes for the cerebral venous thrombosis, thus the authors consider that cerebral thrombosis is a possible complication of SARS-CoV-2 infection in teenagers.

Pediatric Gastroenterology Research.

For several decades, before the 19th century, pediatric pathology was considered to be an annex of adult pathology and treated as a secondary matter in medical practice [...].

Palm-Plant Pain, Sign of a Severe Systemic Disease? Case Report and Review of Literature.

Fabry disease is an X-linked lysosomal storage disease, second in prevalence after Gaucher disease. The onset of symptoms occurs in childhood or adolescence with palmo-plantar burning pains, hypo hidrosis, angiokeratomas, and corneal deposits. In the absence of diagnosis and treatment, the disease will progress to the late phase, characterized by progressive cardiac, cerebral and renal damage, and possible death. We present the case of an 11-year-old male boy who was transferred to the Pediatric Nephrology Department for palmo-plantar burning pain and end stage renal disease. Following the evaluations for the etiology of end stage renal disease we excluded the vasculitis, the neurologic diseases, extrapulmonary tuberculosis. Because of suggestive aspect at CT scan and lack of etiologic diagnosis of renal insufficiency we performed lymph node and kidney biopsy, with a surprising result for storage disease. The specific investigation confirmed the diagnosis.

Pediatric Systemic Lupus Erythematous in COVID-19 Era.

Pediatric systemic lupus erythematosus is a chronic autoimmune disorder with a highly variable course and prognosis. It results in functional abnormalities in the immune system due to intrinsic factors and the use of immunosuppressive therapies associated with underlying comorbidities seem to increase the risk of severe COVID-19 and poor outcomes of the disease in pediatric systemic lupus erythematosus (SLE) patients. The aim of this review is to obtain a better understanding of the existing link between this new viral infection and pediatric lupus. We have analyzed the characteristics of newly diagnosed cases of pediatric SLE following COVID-19 which have been reported in the literature and which describe the impact that COVID-19 has on patients already suffering with pediatric SLE.