Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) ...signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. TRIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children and in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19 children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Antimicrobial resistance is one of the most relevant threats in public health worldwide. Strategies as antimicrobial stewardship programs, aiming to preserve our antibiotic armamentarium, have been ...implemented since 2007 in adult and paediatric patients. We aim to describe the first experience of a paediatric antimicrobial stewardship program. We conducted a retrospective observational study in a tertiary care children’s hospital. A team composed of a microbiologist, an infectious diseases physician, and a paediatrician led the project. All positive blood and cerebrospinal fluid cultures and other biological samples yielding multi-drug-resistant bacteria were collected and reviewed through a prospective-audit-with-feedback strategy. We recorded patient characteristics and worth monitoring prescribed antibiotics. The antimicrobial stewardship audit could end in intervention (step-up/step-down and broadening/narrowing) or recommendation(s). We then checked out wards staff compliance. The team performed 192 interventions out of 584 reviews, mostly suggesting discontinuation of antibiotics (in 76.0% of cases and 39.7% of running molecules). The antibiotic spectrum was more likely tapered than expanded (
p
< 0.0001), and we ordered more narrow-spectrum antibiotic molecules than local medical staff straightaway did (
p
= 0.0113). Interventions were most likely needed in case of documented infections (
p
< 0.0001) and in surgical patients (
p
= 0.0002). In 85.9% of interventions, ward teams fully agreed with our argument. This study demonstrated an antimicrobial stewardship program to be a suitable method for improving the appropriateness of antimicrobial use in hospitalized children.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Background
Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinical-radiological syndrome that can be related to infectious and non-infectious conditions. The ...most prominent neurological symptoms are disturbance of consciousness, abnormal speech, delirious behavior, seizures, muscle weakness, ophthalmoplegia, facial nerve paralysis and headache. Here we report the case of a child with MERS presenting with the unusual symptom of bilateral transient blindness.
Case presentation
A 4-year-old female patient, with a history of fever, abdominal pain, loss of appetite and cough lasted for a few days, experienced 3 episodes of transient bilateral loss of vision with difficulty in walking. Her physical examination showed absence of focal neurological and meningeal irritation signs, although responsiveness was slightly impaired. The ophthalmologic evaluation, including a fundus oculi examination, was negative.
The electroencephalogram showed slow activity in the temporo-occipital regions, more evident in the right hemisphere. A lumbar puncture was performed and cerebrospinal fluid analysis revealed normal glycorrhachia, cell counts, protein levels and IgG index.
Magnetic resonance imaging of the brain showed a signal alteration in the splenium of the corpus callosum, without contrast enhancement. This finding was suggestive of a reversible cytotoxic lesion. Empiric antiviral treatment with acyclovir and intravenous dexamethasone was initiated. Polymerase chain reaction search for neurotropic viral nucleic acid sequences in the cerebrospinal fluid was negative, while a low number of HHV-6 DNA copies was detected in the blood.
Electroencephalograms were repeated in the following days, showing a progressive normalization of the pattern. The child was discharged without symptoms after 10 days of treatment with oral corticosteroids. After 40 days, brain magnetic resonance imaging showed a complete normalization of the signal alteration in the splenium of the corpus callosum.
Conclusion
Transient blindness was reported as an initial symptom of MERS in a few children. To date, there is no evidence of effective treatment methods. Nonetheless, MERS diagnosis provides pediatricians with valuable prognostic information in order to reassure patients and their families about the good outcome of this disease.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ceftolozane-tazobactam is a novel fifth-generation cephalosporin/β-lactamase inhibitor combination recently approved for treatment of both complicated intra-abdominal and urinary tract infections in ...adults. Considering its potent bactericidal activity against
, it might represent an important option also for treating children with exacerbations of cystic fibrosis due to
when other alternative treatments have been exhausted. We hereby review available data on the use of ceftolozane-tazobactam in children, focusing on cystic fibrosis.
Malnutrition constitutes one of the major public health challenges throughout the developing world. Urban poverty and malnutrition have been on the rise, with an increased rate of morbidity. We ...herein explore the relationship between infections and nutritional status and the related association with hygienic conditions as risk of infection in children residing in the slums of Nairobi.
Case-control study based on a secondary analysis of quantitative data collected from a cluster randomized trial carried out in two slums of Nairobi. The following information about resident children were selected: babies' anthropometric measurements, related life conditions, data on infant-feeding practices, food security, hygiene, immunization coverage and morbidity were collected and updated with structured questionnaires until 12 months of life. Prevalence of malnutrition was calculated, then both bivariate and multivariate analysis were used to explore the relationship between malnutrition and its determinants.
The study involved a total of 1119 babies registered at birth (51.28% male and 48.03% female infants). Overall the prevalence of malnutrition was high, with 26.3% of the children being stunted, 6.3% wasted and 13.16% underweight. Prevalence of wasting was higher in the first months of life, while in older children more case of stunting and underweight were captured. Wasted infants were significantly associated with common childhood illnesses: with cough and rapid breathing as well as with diarrhea (p-value< 0.05). Stunting was associated with hygienic conditions (p-value< 0.05 in households that did not perform any water treatment and for children that had a toilet within the house compound), immunization program and low-birth-weight. Moreover, regression analysis showed that significant determinants of stunting were sex and feeding practices. Underweight was significantly associated with socio-demographic factors.
In the specific environment where the study was conducted acute malnutrition is correlated with acute infections, while chronic malnutrition is more influenced by WASH conditions. Therefore, our findings suggest that one cannot separate infection and its risk factors as determinants of the whole malnutrition burden.
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The natural history of vertically acquired HCV infection is ill defined. The aim of this study was to outline the natural course of vertical HCV infection in a cohort of untreated children, including ...rate of spontaneous viral clearance, frequency and features of HCV-related autoimmune disorders. Children with vertical HCV infection were prospectively followed from the first month of life with regular clinical and laboratory assessments. Statistical analysis was performed using Prism 5.0. Forty-five children (median age 12 years, interquartile range 6.9–15.5) were studied. Genotype 1 was predominant (53.3 %). Spontaneous viral clearance was achieved by 12 patients (26.7 %) and associated with genotype 3. Alanine-amino-transferase levels were increased in most children in the first 2 years of life with higher values in those who later cleared the infection. All children were asymptomatic for liver disease. Transient elastography (32 patients) showed mild or moderate fibrosis in nine and two cases, respectively. Non-organ-specific autoantibodies were detected in 24 children (53.3 %) independently of viremia; of these, one developed type-1 diabetes. Cryoglobulinemia was associated with genotype 1 infection and found in 15 subjects (33.3 %): two had low C4 levels and persistent proteinuria.
Conclusions
: Vertically acquired HCV infection may result in spontaneous clearance in up to 27 % of children. Resolution of infection is higher with genotype 3, usually occurs in preschool age and persists over time. Chronic infection is generally asymptomatic, although hepatomegaly and mild fibrosis may develop. Autoantibodies and cryoglobulins are frequent, whereas the associated clinical manifestations are rare.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Sepsis is the major cause of morbidity and mortality in children, especially in immunocompromised patients, and a rapid identification of causative pathogen is strongly related with a better outcome. ...This prospective study analyzes the role of a multiplex real-time polymerase chain reaction in sepsis' etiological diagnosis. Magicplex(TM) Sepsis Real-Time tests were performed in tertiary Regina Margherita Children's Hospital (Turin, Italy), and the medical records of children who underwent a Magicplex test were prospectively evaluated. Results of the Magicplex test were compared with those of blood culture collected at a close time point. One hundred fifty Magicplex tests were collected from 89 patients (54 males and 35 females, age interquartile range: 2.6-12.1 years). Etiological definition was achieved in 60 bloodstream infection cases (40 %). In 32 episodes, Magicplex test alone gave a positive result, and blood culture alone permitted the etiological diagnosis in 5 septic episodes. Magicplex test allowed a 143 % increase in the diagnostic value of blood cultures.
These results suggest that molecular biology can be useful for rapid pathogen's identification also in children.
• Sepsis represents a major cause of morbidity and mortality in children. • Sepsis outcome is strongly related to rapid microbiological identification and prompt initiation of an appropriate chemotherapy. What is New: • This manuscript is the first that describes the use of Magicplex (TM) Sepsis Real-Time test in children. • The results suggest that molecular biology can be useful for rapid pathogen's identification also in children.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
9.
Lung Ultrasound in Children With COVID-19 Denina, Marco; Scolfaro, Carlo; Silvestro, Erika ...
Pediatrics (Evanston),
07/2020, Volume:
146, Issue:
1
Journal Article
Sepsis related coagulopathy ranges from mild laboratory alterations up to severe disseminated intravascular coagulation (DIC). There is evidence that DIC is involved in the pathogenesis of ...microvascular dysfunction contributing to organ failure. Additionally, the systemic activation of coagulation, by consuming platelets and coagulation factors, may cause bleeding. Thrombin generation via the tissue factor/factor VIIa route, contemporary depression of antithrombin and protein C anticoagulant systems, as well as impaired fibrin degradation, due to high circulating levels of PAI-1, contribute to enhanced intravascular fibrin deposition. This deranged coagulopathy is an independent predictor of clinical outcome in patients with severe sepsis. Innovative supportive strategies aiming at the inhibition of coagulation activation should comprise inhibition of tissue factor-mediated activation or restoration of physiological anticoagulant pathways, as the administration of recombinant human activated protein C or concentrate. In spite of some promising initial studies, additional trials are needed to define their clinical effectiveness in adults and children with severe sepsis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK