Microbiota in Autism Spectrum Disorder: A Systematic Review.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by several core symptoms: restricted interests, communication difficulties, and impaired social interactions. Many ASD children experience gastrointestinal functional disorders, impacting their well-being. Emerging evidence suggests that a gut microbiota imbalance may exacerbate core and gastrointestinal symptoms. Our review assesses the gut microbiota in children with ASD and interventions targeting microbiota modulation. The analysis of forty-four studies (meta-analyses, reviews, original research) reveals insights into the gut microbiota-ASD relationship. While specific microbiota alterations are mixed, some trends emerge. ASD children exhibit increased Firmicutes (36-81%) and Pseudomonadota (78%) and decreased Bacteroidetes (56%). The Bacteroidetes to Firmicutes ratio tends to be lower (56%) compared to children without ASD, which correlates with behavioral and gastrointestinal abnormalities. Probiotics, particularly Lactobacillus, Bifidobacterium, and Streptococcus strains, show promise in alleviating behavioral and gastrointestinal symptoms (66%). Microbiota transfer therapy (MTT) seems to have lasting benefits for the microbiota and symptoms in one longitudinal study. Prebiotics can potentially help with gastrointestinal and behavioral issues, needing further research for conclusive efficacy due to different interventions being used. This review highlights the gut microbiota-ASD interplay, offering potential therapeutic avenues for the gut-brain axis. However, study heterogeneity, small sample sizes, and methodological variations emphasize the need for comprehensive, standardized research. Future investigations may unveil complex mechanisms linking the gut microbiota to ASD, ultimately enhancing the quality of life for affected individuals.

Air pollution might affect the clinical course of COVID-19 in pediatric patients.

Air pollution, to which children are more susceptible than adults, can promote airway inflammation, potentially exaggerating the effects of respiratory viral infection. This study examined the association between the clinical manifestation of COVID-19 in unvaccinated pediatric patients hospitalized in Poland (n = 766) and levels of particulate matter 2.5 (PM2.5) and benzo(a)pyrene (B(a)P) within a week before hospitalization. Children aged ≤ 12 years exposed to mean and max 24 h B(a)P levels > 1 ng/m3 revealed higher odds of cough, dyspnea, fever, and increased concentrations of inflammatory markers (C-reactive protein, interleukin-6, procalcitonin, white blood cell count). In older patients (13-17 years), elevated mean 24 h B(a)P levels increased odds of dyspnea, fever, and diarrhea, and higher concentrations of C-reactive protein and procalcitonin. Exposure to max 24 h PM2.5 levels > 20 µg/m3 was associated with higher odds of cough, increased concentrations of C-reactive protein (group ≤12 years), and increased procalcitonin concentration (groups ≤12 years and 13-17 years). In both age groups, length of stay was extended in patients exposed to elevated levels of max 24 h PM2.5, mean and max 24 h B(a)P. This study suggests that worse air quality, particularly reflected in increased B(a)P levels, might affect the clinical course of COVID-19 in pediatric patients and adds to the disease burden during a pandemic.

Serum proteome assessment in nonalcoholic fatty liver disease in children: a preliminary study.

OBJECTIVES: Nonalcoholic fatty disease (NAFLD) affects 3-10% of the pediatric population, making it the most common chronic liver disease among children. The aim of the study is to identify potential biomarkers enabling the diagnosis of NAFLD and monitoring the course of the disease. METHODS: Proteome analysis was performed in a group of 30 patients (19 boys and 11 girls) in total, of whom 16 children had previously diagnosed NAFLD based on the abdominal ultrasound after excluding other diseases of this organ. RESULTS: A total of 297 proteins have been identified. Thirty-seven proteins (responsible for inflammation, stress response, and regulation of this process) differentiating both experimental groups were identified. Up-regulated proteins included afamin, retinol-binding protein-4, complement components, and hemopexin; while serum protease inhibitors, clusterin, immunoglobulin chains, and vitamin D binding protein were found in the down-regulated group. The correlation between selected proteins and indicators of noninvasive assessment of liver fibrosis (APRI, FIB-4) as well as differences between the serum proteome of patients with normal weight, overweight, and obesity were also assessed. CONCLUSION: The plasma protein profile is significantly altered in nonalcoholic liver disease in children and may prove to be a valuable source of biomarkers to evaluate the extent of liver disease.

First case of convalescent plasma transfusion in a child with COVID-19-associated severe aplastic anemia.

We present the case of a six-year-old girl with severe COVID-19, in whom SARS-CoV-2 was successfully eliminated after convalescent plasma transfusion. Children show a variable clinical course of COVID-19, from asymptomatic to critical. In our patient, we diagnosed COVID-19-associated aplastic anemia with severe pancytopenia. The correlation between SARS-CoV-2 infection with aplastic anemia remains unclear. At the beginning of the disease, we used antiviral drugs and immune modulators as therapy but without any positive results. After providing a transfusion of convalescent plasma, the elimination of SARS-CoV-2 was observed. We did not observe any adverse events of this treatment. The girl still has a diagnosis of aplastic anemia and requires specialist therapy.

Skin lesions caused by Orthopoxvirus in children.

INTRODUCTION: The global eradication of smallpox and abandonment of mandatory smallpox vaccination has led to an increased proportion of the population who are immunologically naïve to infections caused by Orthopoxviruses (OPV). AIM: To present the different courses of OPV infection in children and to highlight the diagnostic difficulties in their differentiation from the other inflammatory processes. MATERIAL AND METHODS: We retrospectively evaluated the medical documentation of 5 children with OPV infection. Clinical diagnosis of OPV infection was based on evaluation of animal contact and skin symptoms, characterised by either a single ulcer or disseminated lesions. In all five cases, blood samples and skin swabs were collected from the lesion(s) to identify specific OPV DNA fragments (Vgf, b9R and D11L genes) using PCR. RESULTS: Two children presented with high fever, a single ulcer on the skin and local lymphadenopathy. The three other patients were in good general health and their skin lesions presented as a disseminated vesicular rash. Using the Vgf gene as the target for PCR, OPV infection was confirmed in material collected from skin lesions of all children and in blood samples of 4 children. The B9R and d11L genes tested positive in the skin material of 2 children and blood samples of 2 children. All analysed patients presented a history of ineffective antibiotic therapy. CONCLUSIONS: In the case of unclear necrotising skin lesions in children, the primary diagnosis always includes bacterial dermatitis. However, if the patient has come into contact with animals, diagnosis of OPV infection should also be considered.

Epstein-Barr virus infection with acute acalculous cholecystitis in previously healthy children.

BACKGROUND: Acute acalculous cholecystitis (AAC), an inflammatory process of the gallbladder (GB) in the absence of gallstones, typically occurs in seriously ill patients. AAC can complicate primary Epstein-Barr virus (EBV) infection, but it is an atypical clinical presentation. AIM: The aim of our study was to analyse AAC occurrence in children with primary symptomatic EBV infection who had been admitted to the hospital. METHODS: We retrospectively evaluated the medical documentation of 181 children with EBV infection who were diagnosed based on the presence of viral capsid antigen IgM antibodies. All EBV-positive patients underwent transabdominal ultrasonography of the liver in the supine and right anterior oblique positions. Fifteen children who presented with AAC symptoms, including abdominal pain and a positive Murphy's sign, were analysed as a subsample and re-evaluated after 2-3 months. RESULTS: The incidence of AAC in children hospitalised with infectious mononucleosis (IM) was estimated at 8.3%. Analysis of the laboratory results confirmed that the C-reactive protein (CRP) concentration was the only parameter which was higher in children who presented with AAC symptoms. The mean number of leucocytes and monocytes and liver enzyme activities were not significantly higher. The radiological findings of AAC were evident: increased GB wall thickness, non-shadowing echogenic sludge and pericholecystic fluid collection. CONCLUSION: AAC during primary EBV infection appears to be a more common pathology than previously suspected. Its relatively mild nature and the lack of laboratory abnormalities mean that ultrasonographic examination is required for diagnosis. This might explain why the prevalence in children is underestimated.

Higher expression of inhibitory CD158b and CD158e NK cell receptor and age predicts treatment response in children with chronic hepatitis C.

Treatment with pegylated interferon-α and ribavirin (PEG-IFN/RBV) is the only choice for chronic hepatitis C (CHC) in children. Natural killer (NK) cells were described to play a vital role in CHC. The aim of this study was to analyze the expression of peripheral blood NK cell receptors in their relation to PEG-IFN/RBV treatment response. Study included 26 children with CHC-13 boys, age range 13.42 ± 3.28 years. Blood for biochemical, virological and cytometric testing was taken for evaluation prior to the antiviral treatment. NK cell receptors were detected by flow cytometry and the results were presented as proportion of cells and mean fluorescence intensity (MFI). Therapy consisted of PEG-IFNα-2b (60 µg/m2 s.c 1×/week) and RBV (15 mg/kg p.o. daily). Treatment duration was response-related and varied from 12 to 72 weeks. Rapid virological response (RVR) was evaluated in the 4th week and sustained virological response (SVR) 6 months after completion of the therapy. RVR children were younger (11.67 ± 3.74 vs 15.35 ± 2.42; p = 0.001) and displayed higher CD158b (3.58 ± 0.16 vs 3.45 ± 0.13; p = 0.038) and CD158e expression (4.33 ± 0.21 vs 4.03 ± 0.16; p = 0.039). Density of CD158b (logMFI = 3.68 ± 0.22 vs 3.36 ± 0.16; p = 0.036) and CD158e expression was significantly higher (4.37 ± 0.14 vs 4.12 ± 0.21; p = 0.046) and NKG2D expression significantly lower (97.50 ± 3.46 vs 94.92 ± 5.93; p = 0.049) in SVR children. SVR children were also significantly younger (12.40 ± 3.66 vs 15.13 ± 2.83; p = 0.003). Significance of the age of patients, and expression of CD158b and CD158e were confirmed in univariate and multivariate analysis. Age of patients is negatively related to RVR and SVR. NK cell phenotype with higher expression density of CD158b and CD158e receptor was a positive predictor of SVR.

Expression of Natural Killer Cell Inhibitory Receptors is Associated with Significant Liver Injury in Chronic Hepatitis C in Children.

INTRODUCTION AND AIM: Natural Killer (NK) cells play an important role in innate immune response to viral infections and their high proportion is situated in the liver. The aim of this study was to analyze possible relation between the expression of NK cell receptors and varied intensity of liver lesions in chronic hepatitis C (CHC) in children. MATERIAL AND METHODS: Study included 105 children with CHC - 54 boys and 51 girls, age 13.62 ± 3.48 years. Blood specimens were taken at the day of the liver biopsy. Histological evaluation was performed according to METAVIR scoring system. Circulating NK cells were evaluated by flow cytometry. The results were shown as a proportion of cells expressing evaluated receptor and its' mean fluorescent intensity (MFI). RESULTS: In 58 children with CHC (55.2%) significant liver fibrosis was observed ( ≥F2). Higher proportion of cells expressing CD158e inhibitory receptors was observed in the group of children with ALT > 2UNL (21.11 ± 14.60 vs. 12.22 ± 8.99%; p = 0.037). While higher proportion of cells expressing inhibitory CD158b receptor was observed in children with significant fibrosis (F ≥ 2) compared to minimal fibrosis (F < 2) - (34.14 ± 12.44 vs. 27.48 ± 8.71%; p = 0.049). Children with advanced fibrosis (F ≥ 3) had higher MFI of NK cell CD 158b receptor than children with fibrosis scored F < 3 - (5344.20 ± 3407.49 vs. 2979.67 ± 1190.64; p = 0.049). Proportion of NK cells expressing CD158b was found a predictor of significant fibrosis in univariate analysis - [OR 1.065; 95%CI (1.07-1.15); p = 0.046]. CONCLUSIONS: Higher proportion of NK cells expressing inhibitory CD158b and CD158e receptors is associated with significant liver injury.

Transient lesion in the splenium of the corpus callosum due to rotavirus infection.

Transient signal changes in magnetic resonance imaging (MRI) of the splenium of the corpus callosum (SCC) can result from many different reasons, including encephalitis and encephalopathy caused by infection, seizures, metabolic disorders and asphyxia. We report a case of a 6-year-old Polish girl with rotavirus infection demonstrating a reversible SCC lesion on diffusion-weighted MRI images. She presented six episodes of generalized tonic seizures with mild acute gastroenteritis. Stool test for rotavirus antigen was positive. At the time of admission imaging showed the hyperintense region in T2-weighted and fluid-attenuated inversion-recovery MRI, a well-defined lesion in the splenium of the corpus callosum with restricted diffusion in diffusion-weighted MRI and no enhancement in post contrast T1-weighted imaging. Her first EEG showed slow brain activity in the posterior occipitotemporal portion, consisting mainly of theta waves with a frequency of 4.5-5.5 Hz and amplitude of 40 uV. The lesion had completely disappeared on follow-up MRI 10 days later. The patient recovered fully without any sequelae.

Pulmonary presentation of Toxocara sp. infection in children.

INTRODUCTION: The aim of this study was to investigate the associations between radiological findings, blood eosinophilia, hyperimmunoglobulinemia E and G and Toxocara seropositivity in Polish children with newly diagnosed pulmonary infiltration. MATERIAL AND METHODS: We retrospectively analyzed the documentation of 119 patients, aged 1 to 18 years (mean age: 7.21 ± 4.82), who were seropositive in Toxocara sp. antibodies. In all cases, peripheral blood eosinophils and leukocyte counts, serum total IgE, IgG levels and specific IgG antibodies against excretory and secretory Toxocara sp. antigens were measured at the first presentation. After the confirmation of seropositivity, all children had a routine radiological examination. RESULTS: In the documentation of 23 children (mean age 3.58 ± 2.63 years) we found abnormalities in the radiological examination of their lungs. Fifteen children who had abnormalities in radiological findings presented clinical respiratory complaints such as chronic cough, wheezing, asthma and haemoptysis. Eight children were asymptomatic. The analysis of peripheral eosinophils and leukocyte number, the level of IgE and specific anti-Toxocara IgG presented significantly higher values in children with radiological lesions than in children who had correct radiology. The concentrations of total IgG and gamma globulins were not significantly different. In 10 patients CT showed irregular round nodules with and without halo ranging from 1 to 13 mm. The number of nodules varied from a single lesion to multiple, disseminated ones. All nodules were located in peripheral areas of the lungs. None of them were found in the central areas. In 13 patients, CT images showed ground-glass opacities with ill-defined margins. None of the CT images presented lymphadenopathy and pleural effusion. CONCLUSION: The pulmonary lesions in small children with high eosinophilia and hyperimmunoglobulinemia E could be related to toxocariasis and for this reason they are eligible to undergo therapy with prolonged observation for several months, rather than start invasive malignancy investigations.

Cat-scratch disease: a wide spectrum of clinical pictures.

The aim of this review is to present an emerging zoonotic disease caused by Bartonella henselae. The wide spectrum of diseases connected with these bacteria varies from asymptomatic cases, to skin inflammation, fever of unknown origin, lymphadenopathy, eye disorders, encephalitis and endocarditis. The reservoirs of B. henselae are domestic animals like cats, guinea pigs, rabbits and occasionally dogs. Diagnosis is most often based on a history of exposure to cats and a serologic test with high titres of the immunoglobulin G antibody to B. henselae. Most cases of cat-scratch disease are self-limited and do not require antibiotic treatment. If an antibiotic is chosen, however, azithromycin has been shown to speed recovery.

Anti-SARS-CoV-2 Antibodies Level and COVID-19 Vaccine Boosters among Healthcare Workers with the Highest SARS-CoV-2 Infection Risk-Follow Up Study.

During the COVID-19 pandemic, several vaccines were developed to limit the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, due to SARS-CoV-2 mutations and uneven vaccination coverage among populations, a series of COVID-19 waves have been caused by different variants of concern (VOCs). Despite the updated vaccine formulations for the new VOC, the benefits of additional COVID-19 vaccine doses have raised many doubts, even among high-risk groups such as healthcare workers (HCWs). We examined the factors underlying hesitancy to receive COVID-19 booster vaccine doses and analysed the anti-SARS-CoV-2 IgG antibody response after booster vaccination among HCWs. Our study found that 42% of the HCWs were hesitant about the second booster dose, while 7% reported no intent to get vaccinated with any additional doses. As reasons for not vaccinating, participants most frequently highlighted lack of time, negative experiences with previous vaccinations, and immunity conferred by past infections. In addition, we found the lowest post-vaccination antibody titres among HCWs who did not receive any vaccine booster dose and the highest among HCWs vaccinated with two booster doses.

The Impact of Acute EBV Infection on Changes in the Serum Proteome in Children-A Pilot Study.

This study investigates the impact of Epstein-Barr virus (EBV) infection on children's proteomes across different phases of the disease, utilising seventy-nine blood samples categorised into three groups: EBV-naive patients, acute infectious mononucleosis (IM) cases, and convalescents followed up for 12 months post-IM. The aim is to identify proteins influenced by EBV infection, shedding light on the chronic processes triggered by the virus. The results reveal thirty-nine proteins distinguishing between naive patients and those with IM, including actin, lumican, peroxiredoxin-2, fibulin-1, gelsolin, and alpha-2-macroglobulin, which are involved in immune responses, cell adhesion, and inflammation. Elevated oxidative stress markers like peroxiredoxin-2 in IM patients suggest potential links to EBV's induction of reactive oxygen species. Increased levels of apolipoproteins A-I, A-IV, C-IV, and M during IM imply associations with viral infection, while complement system proteins (C1q, C1r, and C8 gamma chain) are also elevated, reflecting their role in the immune response and viral clearance. This study's focus on children provides unique insights into EBV's impact on young populations, emphasising proteomics' role in uncovering protein associations and understanding the virus's long-term consequences. However, specific relationships between identified proteins and EBV infection require further investigation.

Neuroborreliosis and Post-Treatment Lyme Disease Syndrome: Focus on Children.

Neuroborreliosis is a form of Lyme Borreliosis (LB) that affects various structures of the central and peripheral nervous system. Although most cases of LB can be cured with a course of antibiotics, some children can present prolonged symptoms, which may constitute post-treatment Lyme disease syndrome (PTLDS). The aim of our analysis was the long-term observation of children with NB and the determination of their risk of PTLDS. The clinical observation was supplemented by a laboratory study based on the assessment of the dynamics of anti-VlsE (variable major protein-like sequence, expressed) IgG antibodies in children with NB after antibiotic therapy. The prospective survey based on 40 children presented 1-2 forms of NB. The control group consisted of 36 patients with analogical symptoms for whom LB was excluded. Our long-term observation showed a low risk of developing long-term complications in children who received antibiotic therapy in accordance with the recommendations. The concentration of anti-VlsE IgG demonstrates a statistical significance for differences between the control and the study groups for each measurement period. Higher values of anti-VlsE IgG were observed in the study group, and the concentration decreased from the first measurement period to the next. The article emphasizes the importance of the long-term follow-up of children with neuroborreliosis.

The Coexistence of Antibodies to Neuronal Cell and Synaptic Receptor Proteins, Gangliosides and Selected Neurotropic Pathogens in Neurologic Disorders in Children.

Various primarily non-autoimmune neurological disorders occur synchronously with autoantibodies against tissues in the nervous system. We aimed to assess serum and cerebrospinal fluid (CSF) autoantibodies in children with neurologic disorders. To find new diagnostic tools, we compared the laboratory and clinical findings between the distinguished groups. Retrospectively, 508 patients were divided into six subgroups: neuroinfections, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, neurologic autoimmune and demyelinating diseases, epilepsy, pervasive developmental disorders and other patients. We analysed serum anti-aquaporin-4, antiganglioside, neuronal antinuclear and cytoplasmic antibodies, as well as antibodies against surface neuronal and synaptic antigens in the CSF and serum. We involved available demographic and clinical data. Autoantibodies appeared in 165 (32.3%) children, with 24 showing multiple types of them. The most common were anti-neuroendothelium (anti-NET), anti-N-Methyl-D-Aspartate receptor (anti-NMDAr), anti-glial fibrillary acidic protein and anti-myelin antibodies bothering 46/463 (9.9%), 32/343 (9.4%), 27/463 (5.8%) and 27/463 (5.8%), respectively. Anti-NET and anti-NMDAr antibodies appeared more frequently in children with autoimmunity (p = 0.017; p < 0.001, respectively), increasing the autoimmune disease risk (OR = 2.18, 95% CI 1.13-13.97; OR = 3.91, 95% CI 1.86-8.22, respectively). Similar pathomechanisms appeared in diseases of different aetiology with clinical spectrums mimicking each other, so we proposed the model helping to diagnose autoimmune disease. We proved the influence of age, living place and medical history on the final diagnosis.

Clinical Course and Severity of COVID-19 in 940 Infants with and without Comorbidities Hospitalized in 2020 and 2021: The Results of the National Multicenter Database SARSTer-PED.

This study aimed to analyze the differences in severity and clinical characteristics of COVID-19 in infants hospitalized in Poland in 2021, when the dominance of variants of concern (VOCs) alpha and delta was reported, compared to 2020, when original (wild) SARS-CoV-2 was dominant (III-IV vs. I-II waves of the pandemic, respectively). In addition, the influence of the presence of comorbidities on the clinical course of COVID-19 in infants was studied. This multicenter study, based on the pediatric part of the national SARSTer database (SARSTer-PED), included 940 infants with COVID-19 diagnosed between March 1, 2020, and December 31, 2021, from 13 Polish inpatient centers. An electronic questionnaire, which addressed epidemiological and clinical data, was used. The number of hospitalized infants was significantly higher in 2021 than in 2020 (651 vs. 289, respectively). The analysis showed similar lengths of infant hospitalization in 2020 and 2021, but significantly more children were hospitalized for more than 7 days in 2020 (p < 0.009). In both analyzed periods, the most common route of infection for infants was household contact. There was an increase in the percentage of comorbidities, especially prematurity, in children hospitalized in 2021 compared to 2020. Among the clinical manifestations, fever was predominant among children hospitalized in 2021 and 2020. Cough, runny nose, and loss of appetite were significantly more frequently observed in 2021 (p < 0.0001). Severe and critical conditions were significantly more common among children with comorbidities. More infants were hospitalized during the period of VOCs dominance, especially the delta variant, compared to the period of wild strain dominance, even though indications for hospitalization did not include asymptomatic patients during that period. The course of COVID-19 was mostly mild, characterized mainly by fever and respiratory symptoms. Comorbidities, particularly from the cardiovascular system and prematurity, were associated with a more severe course of the disease in infants.

The Influence of SARS-CoV-2 Variants B.1.1.7 and B.1.617.2 on a Different Clinical Course and Severity of COVID-19 in Children Hospitalized in 2021 Compared With 2020.

BACKGROUND: This study aimed to analyze the differences in the epidemiologic and clinical characteristics of coronavirus disease 2019 (COVID-19) in children hospitalized in 2021, when the severe acute respiratory syndrome coronavirus 2 variants B.1.1.7 (alpha) and B.1.617.2 (delta) dominated, compared with 2020. METHODS: In this multicenter study based on the pediatric part of the national SARSTer register (SARSTer-PED), we included 2771 children (0-18 years) with COVID-19 diagnosed between March 1, 2020, and December 31, 2021, from 14 Polish inpatient centers. An electronic questionnaire, which addressed epidemiologic and clinical data, was used. RESULTS: Children hospitalized in 2021 were younger compared with those reported in 2020 (mean 4.1 vs. 6.8 years, P = 0 .01). Underlying comorbidities were reported in 22% of the patients. The clinical course was usually mild (70%). A significant difference in the clinical course assessment between 2020 and 2021 was found, with more asymptomatic patients in 2020 and more severely ill children in 2021. In total, 5% of patients were severely or critically ill, including <3% of the participants in 2020 and 7% in 2021. The calculated mortality rate was 0.1% in general and 0.2% in 2021. CONCLUSION: Infections with severe acute respiratory syndrome coronavirus 2 variants alpha and delta lead to a more severe course of COVID-19 with more pronounced clinical presentation and higher fatality rates than infection with an original strain. Most of the children requiring hospitalization due to COVID-19 do not have underlying comorbidities.

Treatment of chronic hepatitis C in children with pegylated interferon α2a and ribavirin--a multi-center study.

Pegylated interferon α and ribavirin in treatment of chronic hepatitis C in children is used rarely. The aim of the study was to find prognostic factors for sustained virological response and to analyze the safety of pegylated interferon α2a and ribavirin in children with chronic hepatitis C. The study covered a group of 44 children, mean age 14 years, with diagnosed chronic hepatitis C. Clinical, biochemical and virological parameters, as well as side effects were evaluated. Combined treatment allowed to obtain sustained virological response in a total of 77.5% of the treated children. Lower viral load and lower fibrosis grade contributed to sustained virological response. The response was not gender-related. The best response is obtained in children whose treatment was started after they attained the age of 10 years. Therapy with pegylated interferon α2a and ribavirin is well tolerated by pediatric patients.

The History of the Intestinal Microbiota and the Gut-Brain Axis.

The gut-brain axis and the intestinal microbiota have been an area of an intensive research in the last few years. However, it is not a completely novel area of interest for physicians and scientists. From the earliest centuries, both professionals and patients turned their attention to the gastrointestinal system in order to find the root of physical and mental disturbances. The approach to the gut-brain axis and the therapeutic methods have changed alongside the development of different medical approaches to health and illness. They often reflected the social changes. The authors of this article aim to provide a brief history of the gut-brain axis and the intestinal microbiota in order to demonstrate how important the study of these systems is for both scientists and medical professionals, as well as for the general public. We analysed the publications accessible through PubMed regarding the microbiota and gut-brain axis history. If available, we accessed the original historical sources. We conclude that although the history of this science might be long, there are still many areas that need to be researched, analysed, and understood in future projects. The interest in the subject is not diminishing, but rather it has increased throughout the years.

Inflammatory Markers Combined With Metalloproteinase-9, Neopterin, and S100B Concentrations May Indicate the Pathogenesis of Central Nervous System Diseases in Children.

The identification of central nervous system inflammation etiology leads to adjusted therapy. We analyzed the potential inflammatory and neuro-axonal damage markers in children. Our target was to correlate the findings with a disease's course or a sequalae risk and assess their clinical usefulness. The study included 96 children with symptoms of central nervous system inflammation who underwent diagnostics. The research group involved 24 children with autoimmune disorders and 31 with neuroinfection. The control group included patients with both etiologies excluded. We analyzed the results of routine laboratory tests together with chosen serum (neopterin, interleukin [IL]-1ß, IL-6) and CSF (metalloproteinase [MMP]-9, S100B protein) markers. In the whole cohort, CSF MMP-9 correlated with CSF cytosis and serum IL-6 and CRP. In the undivided neuroinflammatory group, CSF S100B correlated with serum IL-6 and IgM concentrations. CSF cytosis was associated with CSF MMP-9 and serum neopterin levels. Among the infective patients, IL-6 was linked with increased CSF MMP-9. We conclude that astroglial protein S100B, neopterin, and cytokine concentrations may enable predicting long-term consequences, whereas CSF MMP-9 concentration may reflect the actual central nervous system injury regardless of etiology.