Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6-7 Months of age: A Phase 1/2 Randomized Trial.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. METHODS: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. RESULTS: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. CONCLUSIONS: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.

Assessing the change in the epidemiology of seasonal respiratory viruses with the onset of the COVID-19 pandemic.

Background. Respiratory tract infections are among the most important causes of mortality and morbidity in children worldwide. The COVID-19 pandemic has affected the distribution of seasonal respiratory viruses as in all areas of life. In this study, we have aimed to evaluate the changes in the rates of seasonal respiratory viruses with the onset of the pandemic.Methods. This study included patients who were admitted to the Pediatrics Clinic of Eskisehir Osmangazi University Faculty of Medicine Hospital between December 2018 and February 2022 with respiratory tract infections and in whom pathogens were detected from nasopharyngeal swab samples analysed by multiplex PCR method.Results. A total of 833 respiratory tract pathogens were detected in 684 cases consisting of male (55.3 %), and female (44.7 %), patients with a total mean age of 42 months. Single pathogen was revealed in 550, and multiple pathogens in 134 cases. Intensive care was needed in 14 % of the cases. Most frequently influenza A/B, rhinovirus and respiratory syncytial virus (RSV) were detected during the pre-pandemic period, while rhinovirus, RSV, and adenovirus were observed during the lockdown period. In the post-lockdown period, the incidence rates of rhinovirus, RSV, human bocavirus (HboV) (12 %), influenza virus infections increased, and patients with RSV and bocavirus infections required intensive care hospitalization.Conclusion. It is thought that the COVID-9 pandemic lockdown measures may have an impact on the distribution of seasonal respiratory viruses, especially RSV and influenza. Current, prospective and large case series regarding the mechanism of action and dynamics are needed.

Prebiotics in the management of pediatric gastrointestinal disorders: Position paper of the ESPGHAN special interest group on gut microbiota and modifications.

Prebiotics are substrates that are selectively utilized by host microorganisms conferring a health benefit. Compared to probiotics there are few studies with prebiotics in children. Most studies have been performed using infant formula supplemented with prebiotics, while add-on prebiotic supplementation as prevention or treatment of childhood gastrointestinal disorders has rarely been reported. The aim of this position paper was to summarize evidence and make recommendations for prebiotic supplementation in children with gastrointestinal diseases. Recommendations made are based on publications up to January 1, 2023. Within the scope of the European Society for Paediatric Gastroenterology Hepatology and Nutrition Special Interest Group on Gut Microbiota and Modifications, as in our previous biotic recommendations, at least two randomized controlled clinical trials were required for recommendation. There are some studies showing benefits of prebiotics on selected outcomes; however, we cannot give any positive recommendations for supplementing prebiotics in children with gastrointestinal disorders.

Pneumococcal carriage and serotype distribution in children with nephrotic syndrome.

BACKGROUND: Patients with nephrotic syndrome (NS) are at a higher risk of developing invasive pneumococcal disease (IPD). Pneumococcal carriage studies are helpful tools for detecting potentially infectious serotypes and guiding immunization efforts. Pneumococcal nasopharyngeal colonization is common, and IPD can easily occur in an immunosuppressed state. Limited information is available regarding the frequency of pneumococcal carriage in individuals with NS. The aim of this study was to evaluate pneumococcal carriage and serotype distribution in children with NS. METHODS: Pneumococcal carriage was detected by real-time PCR assays from nasopharyngeal swab samples from 98 children with NS, and 100 healthy controls. Isolates were serotyped by real-time PCR. RESULTS: The pneumococcal carriage rate was 44.9% in children with NS. Regarding the recommendation about pneumococcal immunization in children with NS, the vaccination rate was low. Also, non-PCV13 serotypes have been detected in at least 25% of PCV13-vaccinated children. There is no statistically significant difference in total pneumococcal carriage rate, PCV13 serotype carriage rate, or non-PCV13 serotype carriage rate between children with NS and healthy controls (p > 0.05 for all). CONCLUSIONS: The pneumococcal carriage rate was similar between children with NS and healthy controls. However, because children with NS have an increased risk for IPD, the serotype distribution of children with NS can demonstrate the improved protection offered by new pneumococcal vaccines. Regular monitoring for IPD is crucial for assessing the evolving sero-epidemiology of pneumococcal infections and evaluating the effectiveness of vaccines for children with NS.

Antibiotic associated diarrhea in outpatient pediatric antibiotic therapy.

BACKGROUND: Antibiotic-associated diarrhea is one of the most frequent side effects of antimicrobial therapy. We assessed the epidemiological data of antibiotic-associated diarrhea in pediatric patients in our region. METHODS: The prospective multi-center study included pediatric patients who were initiated an oral antibiotic course in outpatient clinics and followed in a well-established surveillance system. This follow-up system constituded inclusion of patient by the primary physician, supply of family follow-up charts to the family, passing the demographics and clinical information of patient to the Primary Investigator Centre, and a close telephone follow-up of patients for a period of eight weeks by the Primary Investigator Centre. RESULTS: A result of 758 cases were recruited in the analysis which had a frequency of 10.4% antibiotic-associated diarrhea. Among the cases treated with amoxicillin-clavulanate 10.4%, and cephalosporins 14.4% presented with antibiotic-associated diarrhea. In the analysis of antibiotic-associated diarrhea occurrence according to different geographical regions of Turkey, antibiotic-associated diarrhea episodes differed significantly (p = 0.014), particularly higher in The Eastern Anatolia and Southeastern Anatolia. Though most commonly encountered with cephalosporin use, antibiotic-associated diarrhea is not a frequent side effect. CONCLUSION: This study on pediatric antibiotic-associated diarrhea displayed epidemiological data and the differences geographically in our region.

Intestinal mycobiota composition and changes in children with thalassemia who underwent allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) alters the diversity of the intestinal bacterial microbiota. This study aimed to evaluate human mycobiota composition pre-HSCT and post-HSCT in children with thalassemia. METHOD: Ten children with thalassemia undergoing allogeneic HSCT were enrolled. The stool samples were collected before the transplantation regimen, before the transplant day, and +15, +30 days, and three months after transplantation. Stool samples were also collected from the donor and the patient's caregivers. Gut mycobiota composition was evaluated with metagenomic analysis. RESULTS: Pretransplant mycobiota of children with thalassemia (the predominant genus was Saccharomyces, 64.1%) has been shown to approximate the diverse mycobiota compositions of healthy adult donors but becomes altered (lower diversity) following transplant procedures. Three months after HSCT, phyla Ascomycota and Basidiomycota were 83.4% and 15.6%, respectively. The predominant species were Saccaharomyces_uc and Saccharomyces cerevisiae (phylum Ascomycota); we also observed Malassezia restricta and Malassezia globosa (phylum Basidiomycota) (∼13%). On day 90 after HSCT, we observed 65.3% M. restricta and 18.4% M. globosa predominance at the species level in a four-year-old boy with acute graft-versus-host disease (GVHD) (skin and gut involvement) 19 days after transplantation included. CONCLUSION: The mycobiota composition of children with thalassemia altered after HSCT. We observed Malassezia predominance in a child with GVHD. Further studies in children with GVHD will identify this situation.

Intestinal microbiota composition of children with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome (MIS-C).

Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19. There are studies evaluating the microbiota composition at the time of diagnosis and during the course of COVID-19, especially in adults, while studies in children are limited and no study available in children with multisystem inflammatory syndrome in children (MIS-C). This study was planned to compare intestinal microbiota composition in children diagnosed with MIS-C and acute COVID-19 infection with healthy children. In this prospective multicenter study, 25 children diagnosed with MIS-C, 20 with COVID-19 infection, and 19 healthy children were included. Intestinal microbiota composition was evaluated by 16 s rRNA gene sequencing. We observed changes of diversity, richness, and composition of intestinal microbiota in MIS-C cases compared to COVID-19 cases and in the healthy controls. The Shannon index was higher in the MIS-C group than the healthy controls (p < 0.01). At phylum level, in the MIS-C group, a significantly higher relative abundance of Bacteroidetes and lower abundance of Firmicutes was found compared to the control group. Intestinal microbiota composition changed in MIS-C cases compared to COVID-19 and healthy controls, and Faecalibacterium prausnitzii decreased; Bacteroides uniformis, Bacteroides plebeius, Clostridium ramosum, Eubacterium dolichum, Eggerthella lenta, Bacillus thermoamylovorans, Prevotella tannerae, and Bacteroides coprophilus were dominant in children with MIS-C. At species level, we observed decreased Faecalibacterium prausnitzii, and increased Eubacterium dolichum, Eggerthella lenta, and Bacillus thermoamylovorans in children with MIS-C and increased Bifidobacterium adolescentis and Dorea formicigenerasus in the COVID-19 group. Our study is the first to evaluate the microbiota composition in MIS-C cases. There is a substantial change in the composition of the gut microbiota: (1) reduction of F. prausnitzii in children with MIS-C and COVID-19; (2) an increase of Eggerthella lenta which is related with autoimmunity; and (3) the predominance of E. dolichum is associated with metabolic dysfunctions and obesity in children with MIS-C. CONCLUSIONS:  Alterations of the intestinal microbiota might be part of pathogenesis of predisposing factor for MIS-C. It would be beneficial to conduct more extensive studies on the cause-effect relationship of these changes in microbiota composition and their effects on long-term prognosis. WHAT IS KNOWN: • Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19.  • However, the number of studies on children is limited, and no study on multisystem inflammatory syndrome in children is currently available (MIS-C). WHAT IS NEW: • In individuals with MIS-C, the composition of the gut microbiota changed dramatically. • Decreased Faecalibacterium prausnitzii have been observed, increased Eggerthella lenta, which was previously linked to autoimmunity, and predominance of Eubacterium dolichum which was linked to metabolic dysfunction and obesity.

Clinical and laboratory responses to tigecycline in children.

WHAT IS KNOWN AND OBJECTIVE: The frequency of multidrug-resistant bacterial infections is increasing worldwide. Tigecycline may be an important option for children with life-threatening nosocomial infections due to multidrug-resistant bacteria. However, there are few published data on the use of tigecycline in paediatric patients. By examining the results of tigecycline use in children, we aimed to draw attention to the fact that tigecycline may be an alternative in the treatment of resistant infections in children. METHODS: Paediatric patients treated with tigecycline from 1 January 2010 to 31 October 2018 at Eskisehir Osmangazi University Medical Faculty, which is a tertiary hospital, were analysed retrospectively to assess the efficacy and safety of tigecycline treatment in children. Patients using tigecycline were identified using the pharmacy database. Clinical and laboratory data were obtained from the files. RESULTS AND DISCUSSION: This study included 91 children aged 7 months to 17.5 years; 52 were female (57.1%). At least one predisposing factor was present in 98.9% of the patients. Fifty-one bacteria were isolated from 44 patients. The tigecycline resistance rate was 3.9%. Only 2 of 91 patients experienced one or more side effects of tigecycline. Tigecycline can be used as salvage therapy in resistant infections where options are limited, although definitive conclusions about the efficacy and safety of tigecycline in children cannot be reached. WHAT IS NEW AND CONCLUSION: Tigecycline may be a safe and important option in paediatric nosocomial infections due to resistant bacteria. Resistant bacterial infections have become more common in recent years, its treatment becomes a difficult problem. Tigecycline has a broad-spectrum antibacterial activity including resistant pathogens.

Investigation of the use of multiplex PCR in childhood diarrhea with clinical and epidemiological features.

INTRODUCTION: Acute gastroenteritis is one of the most common causes of hospital admission in children. Treatment regimens differ depending on the pathogen. In our study, we aimed to evaluate the epidemiological and clinical features of pediatric patients whose gastrointestinal agents were detected by multiplex PCR. MATERIALS AND METHODS: The study included 131 pediatric patients who were followed up at Eskisehir Osmangazi University, Pediatric Department between January 2018 and December 2021.Gastrointestinal pathogens were detected in stool samples by multiplex PCR. The epidemiological and clinical features were reviewed retrospectively. RESULTS: A total of 203 gastrointestinal pathogens were detected from the stool samples of 131 cases. Of these cases, 56% were male and 44% were female. The mean age was 66 (2-204) months. The most common symptoms were diarrhea, fever, vomiting and abdominal pain. The pathogen detection rate was 69% by multiplex PCR. A single pathogen was detected in 85 (65%) cases and multiple pathogens were detected in 46 (35%) cases. The most common pathogens were enteropathogenic Escherichia coli (EPEC, 23%), Clostridium difficile (21%), norovirus (17%), rotavirus (15%), salmonella (12%) and enterotoxigenic E. coli (ETEC, 11%). Stool culture was positive in 16 (12%) cases and microscopic examination positive in 17 (13%) cases. Probiotic treatment was given to 119 (92%) cases and antimicrobial treatment (metroinidazole, ceftriaxone, azithromycin and oral vancomycin) to 34 (26%) cases. Of the cases, 56 (42%) had chronic disease, 40 (30%) had a history of previous antibiotic use and 17 (13%) had a history of hospitalization in the intensive care unit. CONCLUSION: The sensitivity of the multiplex PCR in the detection of acute gastroenteritis agents is higher than stool microscopy, stool culture and stool antigen tests. However, due to the inability to distinguish between colonization, carrier state and pathogenicity, it should be evaluated together with other diagnostic tests and clinical findings in order to determine whether the determined agent is pathogenic or not and in the regulation of antimicrobial therapy.

Intestinal microbiota composition of patients with Behçet's disease: differences between eye, mucocutaneous and vascular involvement. The Rheuma-BIOTA study.

OBJECTIVES: Changes in microbiota composition affect the aetiology and patho-genesis of chronic diseases, including Behçet's disease (BD). However, no studies have analysed the potential gut microbiota changes among different clinical forms of BD. This study evaluated the intestinal microbiota composition of patients with BD and healthy controls and also compared differences between patients with BD with respect to eye, mucocutaneous, and vascular involvement. METHODS: In this prospective cohort study, 27 patients diagnosed with BD according to the International Study Group criteria and 10 age- and sex-matched healthy controls were included. Detailed intestinal microbiota analysis was performed. RESULTS: There were no differences between the BD group and the control group in terms of alpha and beta microbial diversity and abundance indices (p>0.05). Actinomyces, Libanicoccus, Collinsella, Eggerthella, Enetrohabdus, Catenibacterium, and Enterobacter were significantly higher in the BD group than in the control group. In addition, Bacteroides, Cricetibacter, Alistipes, Lachnospira, Dielma, Akkermansia, Sutterella, Anaerofilum, Ruminococcease-UCG007, Acetanaerobacterium, and Copropaacter were lower in the BD group than in the control group. When we compared three different system involvement (eye, mucocutaneous, and vascular), the linear discriminant analysis effective size revealed a difference for the following genera: Lachnospiraceae NK4A136 in the uveitis group; Dialister, Intestinomonas, and Marvinbryantia in the mucocutaneous group; and Gemella in the vascular group. CONCLUSIONS: The composition of intestinal microbiota was significantly different in patients with BD compared with healthy adults. Ours is the first study to show differences in microbiota composition in isolated mucocutaneous, eye, and vascular involvement. These findings should be evaluated in a larger series.

[Meningitis Due to Streptococcus pneumoniae Serotype 24B in a Patient with Cochlear Implant Previously Vaccinated with the Pneumococcal Vaccine]. / Pnömokok Asili Koklear Implantli Hastada Streptococcus pneumoniae Serotip 24B'ye Bagli Menenjit.

Streptococcus pneumoniae is a major cause of bacterial meningitis in children. It can progress and carries a serious risk of mortality and morbidity despite effective treatment. Cochlear implantation is a fairly successful procedure for restoring hearing in cases of sensorineural hearing loss. Moreover, patients with cochlear implants are at increased risk of contracting pneumococcal meningitis compared to the general population. The development of meningitis is associated with pathogens in the middle ear that contaminate the cerebrospinal fluid (CSF), as a result of congenital anomalies in the cochlea, and the cochlear implant. A 4-year-old girl presented to our clinic with fever, vomiting, and weakness. A physical examination showed an axillary temperature of 38.3°C, heart rate of 134/min, respiration rate of 50 breaths/minute, and arterial blood pressure of 120/88 mmHg. The patient also had a neck stiffness and her Kernig and Brudzinski signs were positive. It was discovered that the patient had undergone cochlear implantation approximately five months prior due to bilateral congenital sensorineural hearing loss. She had also received the Haemophilus influenzae type b and PCV-13 vaccines in line with the national immunization calendar. Her laboratory findings showed a leukocyte count of 21.900/mm3 (neutrophils 90% and lymphocytes 10%) and her procalcitonin level was 1.22 ng/ml. An uncountable number of neutrophils was identified in her cerebrospinal fluid, which led to the initial diagnosis of meningitis. There was also 1 mg/dl of glucose (blood glucose, 102 mg/dl) and 706 mg/dl of protein in her cerebrospinal fluid. Empirically, vancomycin (60 mg/kg/day) and ceftriaxone (100 mg/kg/day) were started. Following 5 days of antibiotic treatment, penicillin-susceptible S.pneumoniae was yielded in her CSF culture and identified as serotype 24B. S.pneumoniae with the same antibiotic sensitivity was also identified in her blood culture. Since rhinorrhea was observed on day 16 of hospitalization, she underwent an operation to repair the fistula tract. A computerized tomography cranial scan was performed after the development of acute mental fog at postoperative day 3 and showed brain edema and a thrombus in the right middle cerebral artery. The patient died on day 42 of hospitalization due to multiple organ failure. To our knowledge, this is the first case of meningitis reported in our country associated with S.pneumoniae serotype 24B in a patient with a cochlear implant. While there has been a decrease in the prevalence of invasive pneumococcal disease with routine administration of the pneumococcal conjugate vaccine, a relative increase has been observed in its non-vaccine serotypes. This is relevant not only to patients with more risk factors, such as a cochlear implant, but also those who are at lower risk for pneumococcal infection.

Economic evaluation of micafungin versus liposomal amphotericin B (LAmB) for treating patients with candidaemia and invasive candidiasis (IC) in Turkey.

Micafungin was reported to be non-inferior to liposomal amphotericin B (LAmB) in treating patients with candidaemia and invasive candidiasis (IC). The current study aimed to evaluate the economic impact of using micafungin versus LAmB for treatment of candidaemia and IC in Turkey. A decision analytic model, which depicted economic consequences upon administration of micafungin or LAmB for treating patients with candidaemia and IC in the Turkish hospitals, was constructed. Patients were switched to an alternative antifungal agent if initial treatment failed due to mycological persistence. All patients were followed up until treatment success or death. Outcome probabilities were obtained from published literature and cost inputs were derived from the latest Turkish resources. Expert panels were used to estimate data that were not available in the literature. Cost per patient treated for each intervention was then calculated. Sensitivity analyses including Monte Carlo simulation were performed. For treatment of candidaemia and IC, micafungin (€4809) was associated with higher total cost than LAmB (€4467), with an additional cost of €341 per treated patient. Cost of initial antifungal treatment was the major cost driver for both comparators. The model outcome was robust over a wide variation in input variables except for drug acquisition cost and duration of initial antifungal treatment with micafungin or LAmB. LAmB is cost-saving relative to micafungin for the treatment of candidaemia and IC from the Turkish hospital perspective, with variation in drug acquisition cost of the critical factor affecting the model outcome.

Comparison of Methods Used for the Diagnosis of Epstein-Barr Virus Infections in Children.

The accurate diagnosis of Epstein-Barr virus (EBV) infections is important, as many other infectious agents or diseases can cause similar symptoms. In this study, sera of pediatric patients who were suspected to have an EBV infection, were sent to Eskisehir Osmangazi University Faculty of Medicine, Department of Clinical Microbiology, and investigated by IFA, ELISA, immunoblotting and Real-time PCR. The performances of these tests were compared with IFA. The rates of agreement between ELISA and IFA were found as 100% for seronegative, 100% for acute primary infection, 22.2% for late primary infection, 92.1% for past infection. The rates of agreement between immunoblotting and IFA were found as 80.8% for seronegative, 68.8% for acute primary infection, 55.6% for late primary infection, 86.6% for past infection. The sensitivity of immunoblotting for anti-VCA IgM was identical with ELISA, and higher for anti-VCA IgG, anti-EBNA IgG, anti-EA antibodies, while the specificity of immunoblotting for these antibodies were found to be lower. The sensitivity and specificity of Real-time PCR for detection of viremia in acute primary infection were found as 56.25% (9/16) and 97.89% (139/142), respectively. The diagnostic methods should be chosen by evaluating the demographic characteristics of patients and laboratory conditions together.

Cost-effectiveness analysis of anidulafungin vs fluconazole for the treatment of invasive candidiasis (IC) in Turkey.

Anidulafungin has been shown to be non-inferior to, and possibly more efficacious, than fluconazole in treating patients with invasive candidiasis (IC). This study aimed to determine the cost-effectiveness of anidulafungin vs fluconazole for treatment of IC in the Turkish setting. A decision analytic model was constructed to depict downstream economic consequences of using anidulafungin or fluconazole for treatment of IC in the Turkish hospitals. Transition probabilities (ie treatment success, observed or indeterminate treatment failures) were obtained from a published randomised clinical trial. Cost inputs were from the latest Turkish resources. Data not available in the literature were estimated by expert panels. Sensitivity analyses were performed to assess the robustness of the model outcome. While anidulafungin [TL 17 171 (USD 4589)] incurred a higher total cost than fluconazole [TL 8233 (USD 2200) per treated patient, treatment with anidulafungin was estimated to save an additional 0.58 life-years, with an incremental cost-effectiveness ratio of TL 15 410 (USD 4118) per life-years saved. Drug acquisition cost and hospitalisation were the main cost drivers for anidulafungin and fluconazole arms respectively. The model findings were robust over a wide range of input variables except for anidulafungin drug cost. Anidulafungin appears to be a cost-effective therapy in treating IC from the Turkish hospital perspective.

Evaluation of cardiac autonomic function using heart rate variability in children with acute carbon monoxide poisoning.

Introduction Carbon monoxide poisoning may cause myocardial toxicity and cardiac autonomic dysfunction, which may contribute to the development of life-threatening arrhythmias. We investigated the potential association between acute carbon monoxide exposure and cardiac autonomic function measured by heart rate variability. METHOD: The present study included 40 children aged 1-17 years who were admitted to the Pediatric Intensive Care Unit with acute carbon monoxide poisoning and 40 healthy age- and sex-matched controls. Carboxyhaemoglobin and cardiac enzymes were measured at admission. Electrocardiography was performed on admission and discharge, and 24-hour Holter electrocardiography was digitally recorded. Heart rate variability was analysed at both time points - 24-hour recordings - and frequency domains - from the first 5 minutes of intensive care unit admission. RESULTS: Time domain and frequency indices such as high-frequency spectral power and low-frequency spectral power were similar between patient and control groups (p>0.05). The ratio of low-frequency spectral power to high-frequency spectral power was significantly lower in the carbon monoxide poisoning group (p<0.001) and was negatively correlated with carboxyhaemoglobin levels (r=-0.351, p<0.05). The mean heart rate, QT dispersion, corrected QT dispersion, and P dispersion values were higher in the carbon monoxide poisoning group (p<0.05) on admission. The QT dispersion and corrected QT dispersion remained longer in the carbon monoxide poisoning group compared with controls on discharge (p<0.05). CONCLUSION: The frequency domain indices, especially the ratio of low-frequency spectral power to high-frequency spectral power, are useful for the evaluation of the cardiac autonomic function. The decreased low-frequency spectral power-to-high-frequency spectral power ratio reflects a balance of the autonomic nervous system, which shifted to parasympathetic components.

Lactobacillus reuteri DSM 17938 effectively reduces the duration of acute diarrhoea in hospitalised children.

AIM: Guidelines consider certain probiotics useful in the management of acute gastroenteritis. This study evaluated the use of Lactobacillus (L) reuteri DSM 17938. METHODS: A multicentre, randomised, single-blind clinical trial was performed in hospitalised children with acute gastroenteritis lasting 12-72 h. Children received conventional therapy with, or without, 1 × 10(8) CFU of L. reuteri DSM 17938 for 5 days. The primary endpoint was the duration of diarrhoea and secondary outcomes were days of hospitalisation and the percentage of children with diarrhoea after each day of treatment. RESULTS: We compared 64 children receiving L. reuteri with 63 controls. Lactobacillus reuteri reduced the duration of diarrhoea after 24 h (p < 0.001) and more diarrhoea-free children were seen in the L. reuteri than control group after 24 and 48 h (50% versus 5%, p < 0.001) and 72 h (69% versus 11%, p < 0.001). Lactobacillus reuteri reduced mean hospital stays (4.31 ± 1.3 days versus 5.46 ± 1.77 days, p < 0.001). Prolonged diarrhoea occurred in 17% of the controls, but none of the L. reuteri group. No adverse effects were reported. CONCLUSION: Lactobacillus reuteri effectively reduced the duration of acute diarrhoea and hospital stays in children hospitalised with acute gastroenteritis. Outpatient data are now required.

Intestinal microbiota composition of children with glycogen storage Type I patients.

AIM: Dietary therapy of glycogen storage disease I (GSD I) is based on frequent feeding, with a high intake of complex carbohydrates (supplied by uncooked cornstarch), restriction of sugars, and a lower amount of lipids. There is limited information about the dietary regimen in patients with GSD, which might affect the intestinal luminal pH and microbiota composition. The aim of this study to investigate the intestinal microbiota composition in patients with GSD receiving diet treatment. METHOD: Twelve patients who were followed up with GSD I after the diagnosis receiving diet therapy and 11 healthy children have been enrolled. Intestinal microbiota composition was evaluated by 16 s rRNA gene sequencing. RESULTS: A significant difference was found for beta-diversity between the GSD group and controls. A significantly lower abundance of Firmicutes and higher abundance of Actinobacteria was found in GSD group compared to the controls. Akkermansia, Pseudoalteromonas, Uruburella, and Castellaniella were dominant in the GSD patients at the genus level, while Faecalibacterium, Bacterioides, Gemmiger, Parabacteroides in the control group. At species level, Faecalibacterium prausnitzii decreased, and Akkermansia muciniphila were dominant in children with GSD. DISCUSSION: There is a substantial change in the composition of the gut microbiota, reduction of F. prausnitzii and an increase of A. muciniphila in children with GSD receiving consumption of uncooked cornstarch. Alterations of the intestinal microbiota might be related with the disease itself or dietary restrictions in patients with GSD, however, in certain condition, dysbiosis can negatively affect the course and make it difficult to control the disease.

Composition of Microbiota in Transient and Mature Human Milk: Significant Changes in Large for Gestational Age Group.

The composition of the human milk (HM) microbiota and, consequently, the microorganisms that are passed on to the infant through breastfeeding, can be influenced by various factors such as the mother's health and diet, gestational age, delivery mode, lactation stage, method of infant feeding, and geographical location. The aim of the Human Milk-Gest Study was to compare the microbiota of transient (postpartum 7-15 days) and mature HM (postpartum 45-90 days) of 44 mothers, and to investigate any potential changes associated with preterm birth, mode of delivery, and birth weight in relation to gestational age. The data were classified into five study groups: normal spontaneous delivery-term (NS-T) newborns, cesarean delivery-term (CS-T) newborns, preterm (PT) newborns (with a gestational age of less than 37 weeks), small for gestational age (SGA) newborns, and large for gestational age (LGA) newborns. An analysis of differential abundance was conducted using ANCOM-BC to compare the microbial genera between transient and mature HM samples as well as between other study groups. A significant difference was detected between HM samples at different sampling times and between the study groups (p < 0.01). In transient HM samples, Ralstonia, Burkholderiaceae_uc, and Pelomonas were significantly dominant in the LGA group compared to the NS-T, CS-T, PT, and SGA groups. In mature HM samples, Burkholderiaceae_uc, Ralstonia, Pelomonas, and Klebsiella were significantly dominant in the LGA group compared to the NS-T, CS-T, and PT groups, while Ralstonia, Burkholderiaceae_uc, and Pelomonas were significantly dominant in the LGA group compared to the SGA group. Differences were also detected between the transient and mature HM samples in the CS-T, PT, SGA, and LGA groups, but no differences occurred in the NS-T groups. In conclusion, we showed that Ralstonia, Burkholderiaceae_uc, and Pelomonas were significantly dominant in the LGA group in transient HM and continued in mature HM. The body mass index (BMI) of the mothers in the LGA group was not >30 at conception, however, the maternal BMI at birth and maternal weight gain during pregnancy were higher than in the other groups. The nutritional composition of HM is specifically designed to meet infant nutritional requirements during early life. Evaluating the effects of HM microbiota on infant microbiota composition and short- and long-term health effects in larger studies would be useful.

The Diverse Spectrum of Invasive Meningococcal Disease in Pediatric and Adolescent Patients: Narrative Review of Cases and Case Series.

INTRODUCTION: Invasive meningococcal disease (IMD) is a potentially life-threatening disease caused by Neisseria meningitidis infection. We reviewed case reports of IMD from newborns, infants, children, and adolescents, and described the real-life clinical presentations, diagnoses, treatment paradigms, and clinical outcomes. METHODS: PubMed and Embase were searched for IMD case reports on patients aged ≤ 19 years published from January 2011 to March 2023 (search terms "Neisseria meningitidis" or "invasive meningococcal disease", and "infant", "children", "paediatric", pediatric", or "adolescent"). RESULTS: We identified 97 publications reporting 184 cases of IMD, including 25 cases with a fatal outcome. Most cases were in adolescents aged 13-19 years (34.2%), followed by children aged 1-5 years (27.6%), children aged 6-12 years (17.1%), infants aged 1-12 months (17.1%), and neonates (3.9%). The most common disease-causing serogroups were W (40.2%), B (31.7%), and C (10.4%). Serogroup W was the most common serogroup in adolescents (17.2%), and serogroup B was the most common in the other age groups, including children aged 1-5 years (11.5%). The most common clinical presentations were meningitis (46.6%) and sepsis (36.8%). CONCLUSIONS: IMD continues to pose a threat to the health of children and adolescents. While this review was limited to case reports and is not reflective of global epidemiology, adolescents represented the largest group with IMD. Additionally, nearly half of the patients who died were adolescents, emphasizing the importance of monitoring and vaccination in this age group. Different infecting serogroups were predominant in different age groups, highlighting the usefulness of multivalent vaccines to provide the broadest possible protection against IMD. Overall, this review provides useful insights into real-life clinical presentations, treatment paradigms, diagnoses, and clinical outcomes to help clinicians diagnose, treat, and, ultimately, protect patients from this devastating disease.

Invasive meningococcal disease in older adults: current perspectives and call for action.

PURPOSE: Invasive meningococcal disease (IMD) is a devastating condition. While most attention is directed towards disease in children and adolescents, IMD poses an important cause of morbidity and mortality in adults ≥60 years. While immunization is a critical component of healthy ageing strategies, meningococcal immunization is not routinely offered to older adults. The aim of this review was to summarize clinical and epidemiological aspects of IMD and available immunization strategies, with a particular focus on disease in older individuals, to emphasize the importance of this rather neglected area. METHODS: An expert working group was established to evaluate clinical and epidemiological data to raise awareness of IMD in older individuals, and develop suggestions to improve the existing burden. RESULTS: Routine child and adolescent meningococcal immunization has substantially reduced IMD in these targeted populations. Consequently, prevalence and proportion of IMD among those ≥60 years, mostly unvaccinated, is increasing in developed countries (accounting for up to 25% of cases). IMD-related mortality is highest in this age-group, with substantial sequelae in survivors. IMD due to serogroups W and Y is more prevalent among older adults, often with atypical clinical features (pneumonia, gastrointestinal presentations) which may delay timely treatment. CONCLUSIONS: IMD in older adults remains overlooked and greater awareness is required at clinical and societal levels. We encourage clinicians and immunization policy makers to reconsider IMD, with a call for action to remedy existing inequity in older adult access to protective meningococcal immunization.