Search

An observational retrospective study was conducted on 180 young competitive athletes. These children were revaluated after a mild/moderate SARS-CoV-2 infection through 3 different kind of protocol aimed at recognizing any cardiorespiratory complications due to the infection. The aim of the present study was to evaluate the results of “return to play” Italian protocols for readmission to competitive sport in the pediatric population. All of the subjects analyzed were readmitted to competitive sports after revaluation. None of the young athletes showed cardiorespiratory compromises at first and/or second level evaluation, confirming that in young population there is low risk of hospitalization and life-threatening complications after a mild/moderate infection. Italian simplified protocol for resuming sport have proved to be a valuable tool for health assessment both in adult and young athletes allowing them to resume their training in safety.

Introduction COVID-19 is generally milder in children than in adults, however severe infection has been described in some patients. Few data are available on use of Remdesivir (RDV) in children, as most clinical trials focused on adult patients. We report a multicenter study to investigate the safety of RDV in children affected by COVID-19. Methods We collected the clinical data of children with COVID-19 treated with RDV between March 2020 and February 2022 in 10 Italian hospitals. Clinical data were compared according to the duration of RDV therapy. Linear and logistic regression models were used to determine the association of significant variables from the bivariate analysis to the duration of RDV therapy. Results A total of 50 patients were included, with a median age of 12.8 years. Many patients had at least one comorbidity (78%), mostly obesity. Symptoms were fever (88%), cough (74%) and dyspnea (68%). Most patients were diagnosed with pneumonia of either viral and/or bacterial etiology. Blood test showed leukopenia in 66% and increased C-reactive protein (CRP) levels in 63% of cases. Thirty-six patients received RDV for 5 days, nine patients up to 10 days. Most children who received RDV longer were admitted to the PICU (67%). Treatment with RDV was well tolerated with rare side effects (Table 1): bradycardia was recorded in 6% of cases, solved in less than 24 hours after discontinuation. A mild elevation of transaminases was observed in 26% of cases, however for the 8%, it was still detected before the RDV administration. Therefore, in these cases, we could not establish if it was caused by COVID-19, RDV o both. Patients who received RDV for more than 5 days waited longer for its administration after pneumonia diagnosis. The presence of comorbidities and the duration of O2 administration significantly correlated with the duration of RDV therapy at the linear regression analysis. Conclusion Our experience indicates that RDV against SARS-CoV-2 is safe and well-tolerated in pediatric populations at high risk of developing severe COVID-19. Our data suggest that delaying RDV therapy after diagnosis of pneumonia may be associated with a longer duration of antiviral therapy, especially in patients with comorbidities.

An observational retrospective study was conducted on 180 young competitive athletes. These children were revaluated after a mild/moderate SARS-CoV-2 infection through 3 different kind of protocol aimed at recognizing any cardiorespiratory complications due to the infection. The aim of the present study was to evaluate the results of "return to play" Italian Protocols for readmission to competitive sport in pediatric population. All of the subjects analyzed were readmitted at competitive sport after revaluation. None of the young athletes showed cardiorespiratory compromises at first and/or second level evaluation, confirming that in young population there is low risk of hospitalization and life threatening complications after a mild/moderate infection. Italian simplified protocol for resuming sport have proved to be a valuable tool for health assessment both in adult and young athletes allowing them to resume their training in safety.

Background Lately, one of the major clinical and public health issues has been represented by Coronavirus disease of 2019 (COVID-19) during pregnancy and the risk of transmission of the infection from mother to child. Debate on perinatal management and postnatal care is still ongoing, principally questioning the option of the joint management of mother and child after birth and the safety of breastfeeding. According to the available reports, neonatal COVID-19 appears to have a horizontal transmission and seems to be paucisymptomatic or asymptomatic, compared to older age groups. The aim of this work is to describe a cluster of neonatal COVID-19 and discuss our experience, with reference to current evidence on postnatal care and perinatal management. Methods This is a retrospective observational case series of five mother-child dyads, who attended the Labor and Delivery Unit of a first-level hospital in Italy, in March 2020. Descriptive statistics for continuous variables consisted of number of observations, mean and the range of the minimum and maximum values. Results Five women and four neonates tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In one case, the mother-child dyad was separated and the neonate remained negative on two consecutive tests. Two positive neonates developed symptoms, with a predominant involvement of the gastrointestinal tract. Blood tests were unremarkable, except for a single patient who developed mild neutropenia. No complications occurred. Conclusions We agree that the decision on whether or not to separate a positive/suspected mother from her child should be made on an individual basis, taking into account the parent’s will, clinical condition, hospital logistics and the local epidemiological situation. In conformity with literature, in our study, affected neonates were asymptomatic or paucisymptomatic. Despite these reassuring findings, a few cases of severe presentation in the neonatal population have been reported. Therefore, we agree on encouraging clinicians to monitor the neonates with a suspected or confirmed infection.

Background With the gradual resumption of sports activities after the lock-down period for coronavirus pandemic, a new problem is emerging: Allow all athletes to be able to return to compete after SARS-CoV-2 infection in total safety. Several protocols have been proposed for healed athletes but all of them have been formulated for the adult population. The aim of the present study is to evaluate the adequacy of Italian practical recommendations for return-to-paly, in order to exclude cardiorespiratory complications due to COVID-19 in children and adolescents. Methods Between April 2020 and January 2021 the Italian Sports Medical Federation formulated cardiorespiratory protocols to be applied to athletes recovered from SARS-CoV-2 infection. The protocols take into account the severity of the infection. Protocols include lung function tests, cardiopulmonary exercise test, echocardiographic evaluation, blood chemistry tests. Results From September 2020 to February 2021, 45 children and adolescents (aged from 9 to 18 years; male = 26) with previous SARS-CoV-2 infection were evaluated according to the protocols in force for adult. 55.5% of the subjects (N = 25) reported an asymptomatic infection; 44.5% reported a mild symptomatic infection. Results of lung function test have exceeded the limit of 80% of the theoretical value in all patients. The cardiorespiratory capacity of all patients was within normal limits (average value of maximal oxigen uptake 41 ml/kg/min). No arrhythmic events or reduction in the ejection fraction were highlighted. Conclusion The data obtained showed that, in the pediatric population, mild coronavirus infection does not cause cardiorespiratory complications in the short and medium term. Return to play after Coronavirus infection seems to be safe but it will be necessary to continue with the data analysis in order to modulate and optimize the protocols especially in the pediatric field.

Cutaneous leishmaniasis (CL) is the most frequent form of leishmaniasis. The auricle is an extremely rare site for CL in the Old World. Auricular CL may be mistaken for other entities, such as relapsing polychondritis (RP). Here we report a pediatric case of Old World auricular CL mimicking RP in a child successfully treated with intralesional liposomal amphotericin B.

BackgroundSARS-CoV-2 infection in children is often non severe and in the majority of cases does not require long term hospitalization, nevertheless it is burdened with social issues and managing difficulties. To our knowledge there is no literature on telephonic follow up in pediatric patients with positive PCR for SARS-CoV-2 on rhino-pharyngeal swab after discharge. The aim of the study is to describe our experience in a telephonic follow up which can allow early and safe discharge from hospital while keeping the patients under close clinical monitoring.Materials and Methods65 children were admitted for SARS-CoV-2 infection at Bambino Gesù Pediatric Hospital COVID Center from 16th March to 3rd July. We monitored through a telephonic follow-up, using a specific survey, the patients discharged still presenting a positive PCR for SARS-CoV-2. We checked if any symptoms occurred at home until recovery, defined as two consecutive negative PCR for SARS-CoV-2 on rhino-pharyngeal swabs.ResultsDuring the follow up 7 patients had mild and self-limited symptoms related to SARS-CoV-2 infection, while 2 patients were re-hospitalized. 1 patient had Multisystem Inflammatory Syndrome in Children (MIS-C), the other patient had an increase in troponin and D-dimers. We also monitored the average time of viral shedding, resulting in a median duration of 28 days.ConclusionOur experience describes the daily telephonic follow up as safe in pediatric patients discharged with positive PCR. As a matter of fact it could avoid long term hospitalization and allow to promptly re-hospitalize children with major complications such as MIS-C.

Background SARS-CoV-2 infection in children is often non severe and in the majority of cases does not require long term hospitalization, nevertheless it is burdened with social issues and managing difficulties. To our knowledge there is no literature on telephonic follow up in pediatric patients with positive PCR for SARS-CoV-2 on rhino-pharyngeal swab after discharge. The aim of the study is to describe our experience in a telephonic follow up which can allow early and safe discharge from hospital while keeping the patients under close clinical monitoring. Materials and methods Sixty-five children were admitted for SARS-CoV-2 infection at Bambino Gesù Pediatric Hospital COVID Center from 16th March to 3rd July. We monitored through a telephonic follow-up, using a specific survey, the patients discharged still presenting a positive PCR for SARS-CoV-2. We checked if any symptoms occurred at home until recovery, defined as two consecutive negative PCR for SARS-CoV-2 on rhino-pharyngeal swabs. Results During the follow up 7 patients had mild and self-limited symptoms related to SARS-CoV-2 infection, while 2 patients were re-hospitalized. One patient had Multisystem Inflammatory Syndrome in Children (MIS-C), the other patient had an increase in troponin and D-dimers. We also monitored the average time of viral shedding, resulting in a median duration of 28 days. Conclusion Our experience describes the daily telephonic follow up as safe in pediatric patients discharged with positive PCR. As a matter of fact it could avoid long term hospitalization and allow to promptly re-hospitalize children with major complications such as MIS-C.

BackgroundIn early January 2020, a novel type of Coronavirus was identified in a patient affected by pneumonia of unknown origin. The virus will be named SARS-CoV-2 and the disease COVID-19 a month later by the International Committee on Virus Taxonomy.Italy is one of the first countries in the world affected by the COVID-19 pandemic, with 1.2% of all patients represented by children. Although the infection in children is often non severe and in the majority of cases does not require long term hospitalization, it is burdened with social issues and managing difficulties.To our knowledge there is no literature on telephonic follow up in pediatric patients with positive rhino-pharyngeal swab for SARS-CoV-2 after discharge.Materials and MethodsWe monitored through a telephonic follow-up, using a specific survey, 19 children aged between 8 months and 15 years, hospitalized in the “Ospedale Pediatrico Bambino Gesù” COVID Center with positive rhino-pharyngeal swab at discharge. We checked if any symptoms occurred at home until recovery, defined as two consecutive negative rhino-pharyngeal swabs.ResultsDuring the follow up 7 patients had mild and self-limited symptoms related to SARS-CoV-2 infection, while 2 patients were re-hospitalized, 1 patient had Multisystem Inflammatory Syndrome in Children (MIS-C), the other patient had an increase in troponin a D-dimers.We didn’t miss any patient during the follow up.ConclusionWe demonstrated that daily telephonic follow up is safe in pediatric patients discharged with positive swab, it allows to avoid long term hospitalization and to promptly re-hospitalize children with major complication such as MIS-C.

Background:In severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) critically ill adults, hyperinflammation plays a key role in disease progression. The clinical manifestations of SARS-CoV-2 infection among children are much less severe compared with adult patients and usually associated with a good prognosis. However, hyperinflammation in SARS-CoV-2-infected pediatric patients has been described as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 or as Kawasaki-like disease but is still little known, and optimal management has to be defined. The World Health Organization (WHO) on the 15th of May 2020 has developed a preliminary case definition for multisystem inflammatory disorder in children and adolescents with coronavirus disease 2019 (COVID-19) and stated for an urgent need to collect data on this condition. Here, we report two adolescent patients affected by COVID-19 presenting with multisystem inflammatory disorder, 3–4 weeks after the first symptoms of SARS-CoV-2 infection, treated with the interleukin-1 receptor antagonist anakinra and glucocorticoids with good clinical response.Cases:We report two patients chronically ill appearing, with high fever, severe gastrointestinal involvement, and increased biomarkers of inflammation onset 3–4 weeks after paucisymptomatic SARS-CoV-2 infection. They had no lung involvement, but abdominal ultrasound and CT scan showed thickening of the bowel wall. SARS-CoV-2 PCR was positive on ileum biopsy in both patients, whereas it was negative on other common sampled sites. They have been admitted to the pediatric intensive care unit and have been treated with a combination of anakinra 6–8 mg/kg/day i.v. and a standard dose of methylprednisolone 2 mg/kg/day in addition to lopinavir/ritonavir 400 mg q12h and low molecular weight heparin 100 UI/kg q12h with good clinical response.

Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one ( Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. Funding ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.

We evaluated severe acute respiratory syndrome coronavirus 2 RNA clearance in 22 children. The estimation of positivity at day 14 was 52% for nasopharyngeal swab and 31% for stool samples. These data underline the significance of nasopharyngeal and stoolsample for detecting infected children. Additional studies are needed for transmissibility.

Congenital cytomegalovirus (CMV) infection is one of the main causes of deafness in childhood. It frequently causes serious long-term neurological sequelae. In children who are asymptomatic at birth, tests to accurately predict these sequelae are still unavailable.We describe different brain MRI patterns of congenital CMV infection correlated with clinical data and propose a new MRI severity score to early predict long-term neurological sequelae.We explored clinical records and neuroimaging data of 224 neonates and children with congenital Cytomegalovirus infection, 180 of them did not meet inclusion criteria. Forty-four babies met inclusion criteria and were enrolled in the study. We retrospectively collected clinical data concerning hospitalization, 2 years outpatient follow-up and brain MRI findings of those 44 children, symptomatic and asymptomatic at birth. Clinical data were then correlated with children's brain MRI examinations. We defined neurological and sensorial impairment (hearing or visual) as "adverse neurological outcomes". Brain MRI score was constructed assigning different values to white matter and ventricular dilation.In 44 children enrolled in the study we found that 28/35 (80%) with abnormal and 2/9 (22,2%) with normal MRI examination developed adverse neurological outcomes (OR = 3.6) (95% IC 1.0-12.0). Infants who were symptomatic at birth showed a probability of MRI brain lesions 3.2 times higher than those who were asymptomatic. Ten out of 17 (59%) children who were asymptomatic at birth showed MRI-WM alterations or ventriculomegaly.Brain MRI abnormalities, such as WM alterations and ventriculomegaly, expressed as MRI score higher than 2 are associated with an increased probability of long-term adverse neurological outcome in congenitally CMV infected infants, symptomatic and asymptomatic at birth.

BackgroundThe early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad-spectrum antibiotic is superior to standard of care regimens (SOC) in empiric treatment of LOS and aimed to compare meropenem to SOC in infants aged Methods and findingsNeoMero-1 was a randomized, open-label, phase III superiority trial conducted in 18 neonatal units in 6 countries. Infants with post-menstrual age (PMA) of ≤44 weeks with positive blood culture and one, or those with negative culture and at least with two predefined clinical and laboratory signs suggestive of LOS, or those with PMA >44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or one of the two SOC regimens (ampicillin+gentamicin or cefotaxime+gentamicin) chosen by each site prior to the start of the study for 8-14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and Day 28 for meropenem-resistant Gram-negative organisms (CRGNO). The primary analysis was performed in all randomised patients and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors. From September 3, 2012 to November 30th 2014, total of 136 patients (instead of planned 275) in each arm were randomized; 140 (52%) were culture positive. Successful outcome at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p = 0.087). The respective numbers in patients with positive cultures were 17/63 (27%) vs. 10/77 (13%) (p = 0.022). The main reason of failure was modification of allocated therapy. Treatment emergent adverse events occurred in 72% and serious adverse events in 17% of patients, the Day 28 mortality was 6%. Cumulative acquisition of CRGNO by Day 28 occurred in 4% of patients in the meropenem and 12% in the SOC arm (p = 0.052).ConclusionsWithin this study population, we found no evidence that meropenem was superior to SOC in terms of success at TOC, short term hearing disturbances, safety or mortality were similar in both treatment arms but the study was underpowered to detect the planned effect. Meropenem treatment did not select for colonization with CRGNOs. We suggest that meropenem as broad-spectrum antibiotic should be reserved for neonates who are more likely to have Gram-negative LOS, especially in NICUs where microorganisms producing extended spectrum- and AmpC type beta-lactamases are circulating.

Haemophilia A is a rare X-linked recessive bleeding disorder caused by deficiency or functional defects in coagulation factor VIII (FVIII). Here, we report two cases of challenging diagnosis of haemophilia A because of unusual presentation. The first case is a 10-month-old female, admitted to our hospital because a neck mass appeared within the previous 24 h, who had a past medical history consistent with recurrent spontaneous haematomas but no family history of bleeding disorders. Despite several radiological evaluations, only the histology of the mass defined the presence of a haematoma. Chromosomal analysis revealed a normal female karyotype and a de-novo mutation into the FVIII intron 22 associated with a skewed X chromosome inactivation. The second case is a male neonate with a history of seizures who underwent brain MRI that showed a suspicious vascular malformation on the quadrigeminal cistern, causing cerebellum compression and hydrocephalus. The clinical conditions of the child progressively worsened and blood tests revealed a severe deficit of FVIII levels. The radiological images were re-evaluated; vascular anomalies were excluded and the diagnosis of haematoma was made. Family history was negative for coagulation disorders. Molecular studies revealed a rearrangement of the FVIII gene involving intron 22. The haemophilia A diagnosis can be challenging. Lack of family history, difficulties in detecting haematomas by imaging techniques, female sex and neonatal age represent misleading factors that can delay the diagnosis.

Despite remarkable progress in diagnosis and understanding the pathogenesis of rare diseases, their management still remains very difficult and reserved especially for specialized medical center. Skin disorders [(systemic phacomatosis pigmentovascularis (PPV) and persistent lymphadenopathy (Kikuchi-Fujimoto disease (KFD)] are two rare conditions in the pediatric age. We describe an 11-year-old boy with congenital phacomatosis pigmentovascularis suffering from fever, nocturnal perspiration, fatigue, poor appetite and right cervical lymphadenopathy. The predominance of systemic symptoms prompted an extensive investigation. The diagnosis of PPV was confirmed by physical examination and MRI, and diagnosis of KFD was made after direct histological examination of a lymph node biopsy. Seeing the low prevalence of these two diseases, it becomes important that a prompt and correct diagnosis is required to minimize unnecessary investigation and the inappropriate instigation of potentially harmful treatments as well as providing reassurance to the child, parents and doctors involved.

Accurate and timely diagnosis of community-acquired bacterial versus viral infections in children with systemic inflammatory response syndrome (SIRS) remains challenging both for clinician and laboratory. In the quest of new biochemical markers to distinguish bacterial from viral infection, we have explored the possible role of the soluble secreted form of ST2 (sST2).This explorative prospective cohort study included children with SIRS who were suspected of having community-acquired infections. Plasma samples for sST2 measurement were obtained from 64 hospitalized children, 41 of whom had SIRS of bacterial etiology and 23 SIRS of viral etiology, and from 20 healthy, age- and sex-matched control children. sST2 measurement was carried out by enzyme-linked immunosorbent assay in parallel with standard measurements of procalcitonin (PCT) and C reactive protein (CRP).Our findings demonstrate that children with SIRS associated with bacterial infection present significantly increased levels of sST2, when compared with patients with SIRS of viral etiology and healthy children. More important, receiver operating characteristic curve analysis indicated that sST2 has a significant diagnostic performance with respect to early identification of SIRS of bacterial etiology, which was similar to that of PCT and greater than that of CRP. Finally, the combination of sST2 plus PCT and/or CRP, and PCT plus CRP increased their sensitivity and negative predictive value compared with sST2, PCT and CRP alone.In conclusion, sST2 level may prove useful in predicting bacterial etiology in children with SIRS.

Background: Neutropenia is not uncommon in childhood. The aim of our study was to analyze the underlying causes of neutropenia and to evaluate its clinical significance in a series of children referred to our center. Methods: One hundred and four consecutive children with neutropenia were enrolled in this study. Clinical and laboratory features were analyzed. Results: The majority of patients (63.5%) showed chronic neutropenia. Among all chronic forms, the most frequent was chronic idiopathic neutropenia (CIN), followed by autoimmune neutropenia (AIN). Congenital neutropenia was identified in 6 patients. Acute neutropenia was mainly due to infections.Overall, at the time of first detection, neutropenia was more frequently severe or moderate. One-third of our patients who presented with severe neutropenia were ultimately diagnosed with a postinfectious acute form. Conversely, nearly half patients with CIN, AIN, or congenital neutropenia showed moderate/mild neutropenia at onset.Among patients with AIN and CIN, nearly half recovered between 7 months and 46 months and approximately one-fourth experienced infectious episodes during follow-up. No significant difference was noticed in terms of mean ANC between patients with and without remission, neither between patients with and without infections. Conclusions: Our study confirms the great etiological heterogeneity of neutropenia in children. We could not demonstrate a correlation between ANC level at onset and the underlying disorder, nor a correlation between mean ANC and duration of neutropenia or infectious episodes during follow-up. Neutropenia remains a disease of concern to pediatricians, requiring several laboratory investigations, prolonged follow-up, and, in few cases, advanced molecular methods.

Hypertension and reduced HRV are frequent in heart-transplanted recipients. We studied 26 young recipients to investigate the relationship between BP and HRV during simultaneous 24-h monitoring. Presence of CAV was considered. All HRV measures were significantly lower than normal values. Significant correlations were found between mean daytime systolic BP and the rMSSD (p = 0.04), and mean daytime DBP and SDANN for all 5-min segments (p = 0.03) and between rMSSD and mean nighttime DBP (p = 0.03). Four patients were hypertensive during daytime, seven had a reduced nocturnal fall and two had a nocturnal rise in BP. Eight patients showed severe CAV grade (grade IV) on the Stanford scale, 13 moderate (grade III) and five mild (grade I-II). After a follow-up time of 30 months, four of the 13 patients (30%) with CAV grade III showed an increase to grade IV and all showed abnormalities of both HRV and ABPM patterns. The relationship between HRV abnormalities and arterial hypertension and CAV should be further explored.

Background Granulicatella spp. is a fastidious bacteria responsible for bacteremia and endocarditis which are fatal in about 20% of the cases. These severe infections are uncommon in children under 17 years of age and have proven extremely difficult to treat. Cases presentation We report a brief review of the literature and two cases of NVS bacteremia by Granulicatella complicated by infective endocarditis (IE). The first one is that of a 7-year-old Caucasian female with Shone syndrome and IE involving the pulmonary valve homograft, confirmed by echocardiography. The second case is that of a 5-year-old Caucasian male. In this patient echocardiogram was negative for signs of IE; however, a “possible” IE was suspected on the basis of a cardiac catheterization 3 weeks before the onset of fever. Since in both our patients clinical failure of first line antibiotic treatment was observed, we used a combination of meropenem with another anti-streptococcal drug with excellent results. Conclusion In Granulicatella bacteremia in the pediatric population, combination antimicrobial therapy including meropenem should be considered as a second line treatment in non-responding patients.

Polymicrobial sepsis induces the suppression of macrophage function as determined by a reduction of pro-inflammatory cytokine production upon re-exposure to lipopolysaccharide (LPS) in vitro. Here, we examined whether macrophages were refractory to only LPS or if they were unable to respond to other stimuli such as CD40 ligand (CD40L). Monocytic cells exposed in vitro to LPS showed a dose-dependent reduction of their ability to produce interleukin-12 and tumour necrosis factor-alpha upon subsequent CD40L stimulation, as compared to cells stimulated with CD40L alone. Similarly, LPS interfered with the up-regulation of CD40, CD80 and CD86 induced by CD40L in monocytic cells. The effect of LPS on the response of monocytes to CD40L was similar whether these cells were directly exposed to LPS or cocultured with LPS-pretreated cells, indicating that soluble factors released by LPS stimulation could mediate tolerance to CD40L. We also show that the functional alterations induced by LPS in monocytes can be reversed by indomethacin, thus suggesting a role for inducible cyclooxygenase in mediating the LPS-induced hyporesponsive state of monocytes to CD40L. In conclusion, we propose that in vitro CD40L tolerance may be an appropriate model of monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies.

Summary CD4+CD25+ T regulatory cells may play a role in the different clinical presentations of chronic hepatitis C virus (HCV) infection by suppressing CD4+ T cell responses. Peripheral CD4+CD25+ T cells from chronic HCV carriers with normal and abnormal alanine aminotransferase (ALT) were analysed for specificity and effect on HCV-specific CD4+ T cell reactivity by flow cytometry for intracellular cytokine production and proliferation assay. HCV-specific CD4+CD25+high T cells consistently produced transforming growth factor (TGF)-β but only limited amounts of interleukin (IL)-10 and no IL-2 and interferon (IFN)-γ. The HCV-specific TGF-β response by CD4+CD25+high T cells was significantly greater in patients with normal ALT compared to patients with elevated ALT. In addition, a significant inverse correlation was found between the HCV-specific TGF-β response by CD4+CD25+high T cells and liver inflammation. In peripheral blood mononuclear cells (PBMC), both HCV antigen-induced IFN-γ production and proliferation of CD4+ T cells were greater in patients with elevated ALT compared with patients with normal ALT. Depletion of CD4+CD25+ cells from PBMC resulted in an increase of both IFN-γ production and proliferation of HCV-specific CD4+ T cells that was significantly greater in patients with normal ALT levels compared with patients with elevated ALT. In addition, CD4+CD25+ T cells from patients with normal ALT levels proved to be significantly more potent to suppress CD4+ T cell reactivity with respect to those from patients with elevated ALT. In conclusion, these data support the hypothesis that CD4+CD25+ cells may play a role in controlling chronic inflammatory response and hepatic damage in chronic HCV carriers.

Acinetobacter baumannii is a Gram-negative coccobacillus causing serious nosocomial infections. The recent emergence of strains of bacteria, which are resistant to common antibiotics, has made the treatment of these infections increasingly complex. We report the case of a young patient affected by AIDS, who suffered brain toxoplasmosis and sepsis due to multidrug-resistant A baumannii. This bacterial infection was successfully treated with colistin and tigecycline. In addition, we review recent literature on this topic, from the year 2000 to date.