A Multifaced Aspect of Clostridium difficile Infection in Pediatric Patients with Inflammatory Bowel Disease: Case Series and Literature Review.

Children with inflammatory bowel disease (IBD) have an increased susceptibility to Clostridium difficile infection (CDI), with a rising incidence over time. Differentiating between CDI and IBD exacerbation is challenging due to overlapping symptoms. In our cohort of 55 pediatric IBD patients, 6 were diagnosed with CDI. Upon conducting a thorough patient evaluation and subsequent data analysis, an exhaustive review of the existing literature was undertaken. CDI is more prevalent in ulcerative colitis (UC) than Crohn's disease (CD) patients, as seen in our patients and in the existing literature. The management of a pediatric patient with IBD is itself a challenge for a clinician because of the chronic, possibly relapsing course, and substantial long-term morbidity. When CDI is added, it becomes even more demanding, since CDI leads to more severe disease in children with IBD. A multidisciplinary approach and intensive treatment for possible sepsis, anemia, hypoalbuminemia, and hydro-electrolytic and acid-base imbalances are frequently mandatory in patients with CDI and IBD, which leads to a significant health care burden in hospitalized children with IBD. After the infection is treated with antibiotic therapy, important considerations regarding the future treatment for the underlying IBD are also necessary; in most cases, a treatment escalation is required, as also seen in our study group.

Changes in C-Peptide Values in Children with Type 1 Diabetes - a Three-Year Study.

Background: C-peptide is used as an important indicator of residual insulin secretion in patients diagnosed with type 1 diabetes mellitus (T1DM) and treated with insulin. Aim:We have aimed to monitor the serum C-peptide (CP) levels during the first three years after diagnosis of T1DM in a cohort of children admitted to the Diabetes Department of "M. S. Curie" Emergency Clinical Hospital for Children, Bucharest, Romania, and to investigate the factors that could influence the rate of decline in its secretion. Method:We conducted a longitudinal, retrospective cohort study on a group of 215 children and adolescents who met the inclusion criteria and were monitored in our clinic over the course of a long period of time. We analyzed several parameters, including fasting serum CP values at diagnosis and yearly throughout T1DM evolution, the severity of diabetic ketoacidosis (DKA) at onset, HbA1c at diagnosis, family history of T1DM/T2DM, patient gender and presence of concurrent acute infectious disease at diagnosis, with the purpose of evaluating their influence on the preservation of endogenous insulin secretion. Based on serum CP value measured three years after T1DM onset, patients were divided into two groups: group 1, with low insulin residual secretion (CP < 0.6 ng/mL), and group 2, with preserved insulin residual secretion (CP ≥0.6 ng/mL) Results:At the moment of diagnosis, patients in group 1 were younger than those in group 2 (6.03 ± 3.54 years and 9.76 ± 2.75 years, respectively). The proportion of children with diabetic ketoacidosis (DKA) at onset was greater in group 1 (68% of patients) than group 2, in which the majority of subjects (60%) did not have DKA. The C-peptide value at diagnosis was significantly lower (0.55 ± 0.36 ng/mL) among patients in group 1 than those in group 2 (1.11 ± 0.59 ng/mL). In group 1 there was a higher proportion of patients (65%) with acute infectious disease at onset. Family history of T1DM/T2DM was associated with a more rapid decline in CP values. Our data showed no correlation between CP levels monitored for three years and HbA1c at diagnosis and no association with the gender of each patient. Conclusion:Patients with higher CP concentrations at diagnosis maintained increased values (> 0.6 ng/mL) three years after disease onset. Younger children had a faster decline of CP secretion during the first three years following diabetes diagnosis. In patients with severe symptoms (DKA) and associated infectious disease at onset, a risk of rapid CP decline was found.

Bacterial Species and Antibiotic Resistance-A Retrospective Analysis of Bacterial Cultures in a Pediatric Hospital.

Antimicrobial resistance (AMR) has become a major healthcare concern having a rising incidence, especially in pediatric patients who are more susceptible to infections. The aim of our study was to analyze the bacterial species isolated from patients admitted to our tertiary hospital and their AMR profiles. We conducted a retrospective observational study by examining the bacterial cultures collected from pediatric patients admitted to our hospital over a period of one year. We identified the most common bacterial species from 1445 clinical isolates and their AMR patterns using standard microbiological techniques. Our analysis revealed that the most frequently isolated bacterial species were Escherichia coli (23.73%), Staphylococcus aureus (15.64%), Klebsiella species (12.04%), and Pseudomonas species (9.96%). Additionally, these species exhibited varying levels of resistance to commonly used antibiotics. Notably, we observed high rates of resistance among Gram-negative bacteria, including extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species. Among Gram-positive bacteria, we observed a high level of methicillin-resistant Staphylococcus aureus. Our findings highlight the urgent need for effective antibiotic management programs and infection control measures to address the rising incidence of AMR in pediatric hospitals. Further research is needed to identify the mechanisms of resistance in these bacterial species and to develop new strategies for preventing and treating infections caused by antibiotic-resistant bacteria in pediatric patients.

SARS-CoV-2 Positive Serology and Islet Autoantibodies in Newly Diagnosed Pediatric Cases of Type 1 Diabetes Mellitus: A Single-Center Cohort Study.

Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although presenting less severe forms of the disease in children, seems to play a role in the development of other conditions, including type 1 diabetes mellitus (T1DM). After the beginning of the pandemic, an increase in the number of T1DM pediatric patients was observed in several countries, thus leading to many questions about the complex relationship between SARS-CoV-2 infection and T1DM. Our study aimed to highlight possible correlations between SARS-CoV-2 serology and T1DM onset. Therefore, we performed an observational retrospective cohort study that included 158 children diagnosed with T1DM in the period April 2021-April 2022. The presence or absence of SARS-CoV-2 and T1DM-specific antibodies and other laboratory findings were assessed. In the group of patients with positive SARS-CoV-2 serology, a higher percentage had detectable IA-2A antibodies, more children were positive for all three islet autoantibodies determined (GADA, ICA, and IA-2A), and a higher mean HbA1c value was found. No difference existed between the two groups regarding DKA presence and severity. A lower C-peptide level was found in the patients presenting diabetic ketoacidosis (DKA) at T1DM onset. When compared to a group of patients diagnosed before the pandemic, an increased incidence of both DKA and severe DKA, as well as a higher age at diagnosis and higher levels of HbA1c were present in our study group. These findings have important implications for the ongoing monitoring and management of children with T1DM after the COVID-19 pandemic and highlight the need for further research to better understand the complex relationship between SARS-CoV-2 infection and T1DM.

Antibiotic Resistance and Therapeutic Efficacy of Helicobacter pylori Infection in Pediatric Patients-A Tertiary Center Experience.

One of the most widespread bacterial infections worldwide, Helicobacter pylori is thought to affect almost half of the world's population. Due to rising antibiotic resistance, treatment should be tailored according to antibiotic susceptibility testing (AST). This study aims to evaluate Helicobacter pylori antibiotic resistance and its therapeutic efficacy in children. We conducted a prospective, single-center study, that evaluated 68 children referred for upper gastrointestinal endoscopy (UGE) following chronic dyspeptic syndrome. Each patient underwent multiple biopsies to perform bacterial cultures with AST and histopathological examinations for the diagnosis. Patients without antibiotic resistance or negative cultures received a 10-day sequential therapy, while the others had the antibiotic regimen tailored based on AST. Fifty-nine patients with a positive biopsy-based diagnosis (24 males) were finally included. Bacterial cultures with AST were positive for 13 patients (22.03%) and the antibiotic resistance for clarithromycin was 15.38%. Fifty-seven patients were administered sequential therapy with an eradication rate of 94.73%. Clarithromycin-resistant patients were successfully treated with 10-day triple therapy of esomeprazole, amoxicillin, and metronidazole. Although bacterial cultures had a low positivity rate, sequential therapy had a successful eradication rate. Further studies are necessary to better assess Helicobacter pylori antibiotic resistance to provide tailored treatment and identify children that need closer monitoring.

Applicability of the PedsQLTM 4.0 Generic and Fatigue Modules in Romanian Children with Inflammatory Bowel Disease: Pilot Study.

The Pediatric Quality of Life (PedsQL) Inventory is a tool used to measure Health Related Quality of Life (HRQoL) in children aged 2 to 18 years. The aim of the present study was to investigate the feasibility and reliability of the Romanian version of two PedsQL modules, the Generic Core and the Multidimensional Fatigue Scales, in children with inflammatory bowel disease (IBD). Children diagnosed with IBD in our clinic and their parents completed a total of 26 Romanian version PedsQL forms, while a control group of healthy children and their caregiver filled in 86 identical online forms. We compared total and dimensional scores between controls and subjects, along with age, sex, and active versus inactive disease differences. The results indicated that the PedsQL total and summary scores differentiated between subjects and controls, with lower HRQoL and higher levels of fatigue being reported in children with chronic IBD. The Romanian version of the PedsQL was found to be feasible and reliable, with good internal consistency higher than 0.70 and minimum missing responses. However, the limited number of participants meant that clinical activity severity indices correlated poorly with fatigue and generic scores. Further validation of these models requires larger, multi-centric studies.

Hymenolepis diminuta Infection in a Romanian Child from an Urban Area.

Hymenolepis diminuta is primarily a rodent parasite that is ubiquitously distributed worldwide, but with only a few cases described as human infections. We report a case of Hymenolepis diminuta infection in a 15-month-old child, living in an urban setting, with no previous medical history. The patient presented with two episodes of seizures, and complaints of abdominal pain, vomiting, and diarrhea, with no apparent history of rodent contact. Furthermore, the patient's gastrointestinal symptoms were linked to the emission of suspected tapeworm proglottids in the feces. After excluding other possible etiologies, a diagnosis of Hymenolepis diminuta infection was made, based on the examination of characteristic eggs in a concentrated stool specimen. The infant was successfully treated with praziquantel and fully recovered. After two weeks, the stool sample was free of Hymenolepis diminuta eggs. The clinical follow-up over the next 3 years was normal. Hymenolepis diminuta is rarely found in humans, and, when present, the infection is frequently asymptomatic. Abdominal pain, irritability, itching, eosinophilia, and seizures have also been reported. In this paper, we report, for the first time in the literature, an infection with Hymenolepis diminuta in a Romanian infant who had atypical neurological presentation, with full recovery, without subsequent neurological sequelae.

Advanced Bioinformatics Tools in the Pharmacokinetic Profiles of Natural and Synthetic Compounds with Anti-Diabetic Activity.

Diabetes represents a major health problem, involving a severe imbalance of blood sugar levels, which can disturb the nerves, eyes, kidneys, and other organs. Diabes management involves several synthetic drugs focused on improving insulin sensitivity, increasing insulin production, and decreasing blood glucose levels, but with unclear molecular mechanisms and severe side effects. Natural chemicals extracted from several plants such as Gymnema sylvestre, Momordica charantia or Ophiopogon planiscapus Niger have aroused great interest for their anti-diabetes activity, but also their hypolipidemic and anti-obesity activity. Here, we focused on the anti-diabetic activity of a few natural and synthetic compounds, in correlation with their pharmacokinetic/pharmacodynamic profiles, especially with their blood-brain barrier (BBB) permeability. We reviewed studies that used bioinformatics methods such as predicted BBB, molecular docking, molecular dynamics and quantitative structure-activity relationship (QSAR) to elucidate the proper action mechanisms of antidiabetic compounds. Currently, it is evident that BBB damage plays a significant role in diabetes disorders, but the molecular mechanisms are not clear. Here, we presented the efficacy of natural (gymnemic acids, quercetin, resveratrol) and synthetic (TAK-242, propofol, or APX3330) compounds in reducing diabetes symptoms and improving BBB dysfunctions. Bioinformatics tools can be helpful in the quest for chemical compounds with effective anti-diabetic activity that can enhance the druggability of molecular targets and provide a deeper understanding of diabetes mechanisms.

Ketoacidosis Onset of Diabetes on a Patient with Normal C-Peptide Value.

Background:Diabetic ketoacidosis is an acute major life-threatening complication of diabetes, characterized by hyperglycemia, ketoacidosis and ketonuria, which can be life threatening if it is not promptly recognized and treated. This occurs mainly in patients with type 1 diabetes, but stressors like trauma and infection can increase the risk of ketoacidosis in other forms of diabetes such as type 2 diabetes. Type 2 diabetes mellitus is a complex metabolic disorder of heterogeneous etiology with behavioral, social, and environmental risk factors that unmask the effects of genetic susceptibility. Recent studies indicate an increasing prevalence of type 2 diabetes mellitus in children and adolescents around the world in all ethnicities. C-peptide is a useful and widely used method of assessing pancreatic beta cell function given his structure: part of proinsulin which is cleaved prior to co-secretion with insulin from pancreatic beta cells. This is used as a tool in the differentiation of type 1 diabetes from type 2 but also other types of diabetes. We present a 12-year-old previously healthy male who was hospitalized in our clinic for polydipsia, polyuria, weight loss and emesis, with symptom onset 10 days prior to admission. On the admission day, he presented to the emergency room for progressively increasing somnolence, apathy, decreased muscle tone and urinary incontinence. Physical examination was significant for grade I obesity [height 168 cm and weight 90 kg, yielding a body index mass (BMI) of 31.78 kg/m2, percentile >97%], lethargy, slurred speech, high blood pressure (145/90 mmHg), tachycardia (145 beats per minute) and acanthosis nigricans. Considering his physical examination, laboratory tests and clinical evolution, he was diagnosed with type 2 diabetes mellitus complicated with hyperosmolar hyperglycemic state and diabetic ketoacidosis. Diabetic ketoacidosis should be considered in the differential diagnosis of metabolic decompensation in all types of diabetes. Although type 2 diabetes mellitus seems to be still rare in childhood and adolescence, prevention and treatment of type 2 diabetes mellitus should become public awareness and public health intervention programs. The particularity of this case was the unusual onset of diabetes mellitus type 2 in a male child with metabolic syndrome.

3D-ALMOND-QSAR Models to Predict the Antidepressant Effect of Some Natural Compounds.

The current treatment of depression involves antidepressant synthetic drugs that have a variety of side effects. In searching for alternatives, natural compounds could represent a solution, as many studies reported that such compounds modulate the nervous system and exhibit antidepressant effects. We used bioinformatics methods to predict the antidepressant effect of ten natural compounds with neuroleptic activity, reported in the literature. For all compounds we computed their drug-likeness, absorption, distribution, metabolism, excretion (ADME), and toxicity profiles. Their antidepressant and neuroleptic activities were predicted by 3D-ALMOND-QSAR models built by considering three important targets, namely serotonin transporter (SERT), 5-hydroxytryptamine receptor 1A (5-HT1A), and dopamine D2 receptor. For our QSAR models we have used the following molecular descriptors: hydrophobicity, electrostatic, and hydrogen bond donor/acceptor. Our results showed that all compounds present drug-likeness features as well as promising ADME features and no toxicity. Most compounds appear to modulate SERT, and fewer appear as ligands for 5-HT1A and D2 receptors. From our prediction, linalyl acetate appears as the only ligand for all three targets, neryl acetate appears as a ligand for SERT and D2 receptors, while 1,8-cineole appears as a ligand for 5-HT1A and D2 receptors.

The Impact of SARS-CoV-2 Pandemic on the New Cases of T1DM in Children. A Single-Centre Cohort Study.

Type 1 diabetes mellitus (T1DM) represents one of the most frequent chronic illnesses affecting children. The early diagnosis of this disease is crucial, as it plays a key role in preventing the development of a life-threatening acute complication: diabetic ketoacidosis. The etiopathogenetic role of viral infections has long been suggested and emerging data are pointing towards a complex bidirectional relationship between diabetes and COVID-19. The aim of this study is to assess the impact of the COVID-19 pandemic on the incidence and severity of new T1DM cases in children in Romania. We analyzed the differences between a group of 312 patients diagnosed with T1DM in the period 2003-2019 and a group of 147 children diagnosed during the pandemic. The data were investigated using statistical analysis of a series of relevant variables. The total number of newly diagnosed T1DM increased by 30.08% in the period March 2020-February 2021 compared to the previous years. The patients in the pandemic group had a higher mean age at the onset of T1DM, were less frequently living in an urban area, and presented a higher mean value of HbA1c. Diabetic ketoacidosis at the onset of T1DM was 67.40% more frequent, and a higher percentage of these patients presented with a severe form. The duration of T1DM symptoms did not differ significantly between the two groups. A number of 8 patients associated SARS-CoV-2 infection at the time of T1DM diagnosis.