Tuberculosis disease in immunocompromised children and adolescents: a pTBnet multi-centre case-control study.

BACKGROUND: In high-resource settings the survival of immunocompromised (IC) children has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools and outcome of IC children with TB in Europe. METHODS: Multicentre, matched case-control study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), capturing TB cases <18 years diagnosed 2000-2020. RESULTS: 417 TB cases were included, comprising 139 children with IC (HIV, inborn errors of immunity, drug-induced immunosuppression and other immunocompromising conditions) and 278 non-IC children as controls. Non-respiratory TB was more frequent among cases than controls (32.4% vs. 21.2%; p = 0.013). IC patients had an increased likelihood of presenting with severe disease (57.6% vs. 38.5%; p < 0.001; OR [95% CI]: 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs. 6.0%; p < 0.001) and QuantiFERON-TB Gold assay (30.0% vs. 7.3%; p < 0.001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs. 49.3%; p = 0.083). Although the mortality in IC children was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs. 6.1%; p = 0.004). CONCLUSIONS: IC children with TB disease in Europe have increased rates of non-respiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in IC patients, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.

The Thousand Faces of Invasive Group A Streptococcal Infections: Update on Epidemiology, Symptoms, and Therapy.

Invasive infections caused by Streptococcus pyogfenes (iGAS), commonly known as Group A Streptococcus, represent a significant public health concern due to their potential for rapid progression and life-threatening complications. Epidemiologically, invasive GAS infections exhibit a diverse global distribution, affecting individuals of all ages with varying predisposing factors. The pathogenesis of invasive GAS involves an array of virulence factors that contribute to tissue invasion, immune evasion, and systemic dissemination. In pediatrics, in the last few years, an increase in iGAS infections has been reported worldwide becoming a challenging disease to diagnose and treat promptly. This review highlights the current knowledge on pathogenesis, clinical presentations, and therapeutic approaches for iGAS in children.

Molecular characterization of SARS-CoV-2 Omicron clade and clinical presentation in children.

Since its emergence, SARS-CoV-2 Omicron clade has shown a marked degree of variability and different clinical presentation compared with previous clades. Here we demonstrate that at least four Omicron lineages circulated in children since December 2021, and studied until November 2022: BA.1 (33.6%), BA.2 (40.6%), BA.5 (23.7%) and BQ.1 (2.1%). At least 70% of infections concerned children under 1 year, most of them being infected with BA.2 lineages (n = 201, 75.6%). Looking at SARS-CoV-2 genetic variability, 69 SNPs were found to be significantly associated in pairs, (phi < - 0.3 or > 0.3 and p-value < 0.001). 16 SNPs were involved in 4 distinct clusters (bootstrap > 0.75). One of these clusters (A23040G, A27259C, T23617G, T23620G) was also positively associated with moderate/severe COVID-19 presentation (AOR [95% CI] 2.49 [1.26-4.89] p-value: 0.008) together with comorbidities (AOR [95% CI] 2.67 [1.36-5.24] p-value: 0.004). Overall, these results highlight the extensive SARS-CoV-2 Omicron circulation in children, mostly aged < 1 year, and provide insights on viral diversification even considering low-abundant SNPs, finally suggesting the potential contribution of viral diversification in affecting disease severity.

Use of Remdesivir in children with COVID-19: report of an Italian multicenter study.

BACKGROUND: 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 conducted in 10 Italian Hospitals 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 a duration of RDV therapy more or less than 5 days. Linear regression model was 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: bradycardia was recorded in 6% of cases, solved in less than 24 h 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.

Back to the Future: Intravenous Fosfomycin is Safe and Effective for the Treatment of Complicated Infections in Children.

BACKGROUND: Despite its broad spectrum and excellent safety profile, fosfomycin is still rarely used in pediatrics, with very limited experience from clinicians. METHODS: We retrospectively reviewed the medical records of all children admitted to Bambino Gesù Children's Hospital, IRCCS, Rome, Italy, and treated with fosfomycin for any serious infection. Children with immunodeficiency and oncologic diseases were excluded. Of each, we reported and analyzed demographic and clinical data. RESULTS: The clinical charts of 20 patients were reviewed and analyzed. The mean age was 10.2 years. Most children were males (85%). Most patients treated had an osteo-articular infection (65%). In our sample, 7 patients (35%) had an underlying comorbidity. The causative agent was isolated in 14 cases (70%). All patients were treated with a combination of 2-3 antibiotics, including fosfomycin. The average duration of antibiotic treatment was 18 days. After treatment, 8 patients (40%) experienced a mild adverse reaction, possibly correlated with the administration of fosfomycin. All patients were discharged in good clinical condition. CONCLUSIONS: The present study reports on a sample of pediatric patients with complicated infections where administration of fosfomycin led to eradication of the disease with little or no side effects. Role of the underlying condition and concomitant medication in causing the reaction could not be ruled out. These data suggest that fosfomycin is an effective and safe antibiotic in the pediatric population, particularly for deep-seated infections sustained by multi-drug resistant pathogens.

Safety of Sotrovimab use in children with COVID-19: an Italian experience.

Sotrovimab is a monoclonal antibody approved in adult and adolescents at high risk for COVID-19. Thirty-three children evaluated in five Italian paediatric centres received Sotrovimab infusion and were retrospectively enrolled from December 2021 to April 2022. In more than half of cases (19/33, 57.6%) Sotrovimab was prescribed off-label. Overall, the infusion was well tolerated with no significative differences in those receiving an off-label prescription. All children had a complete recovery. Data on the safety of Sotrovimab should be investigated in a larger paediatric cohort, considering the continuous selection of new SARS CoV-2 variants which may be more or less susceptible to the effects of the Sotrovimab.

Accuracy of Pancreatic Stone Protein for diagnosis of sepsis in children admitted to pediatric intensive care or high-dependency care: a pilot study.

BACKGROUND: Pancreatic Stone Protein (PSP) is one of the most promising diagnostic and prognostic markers. The aim of the study was to assess the accuracy of PSP, compared to C-Reactive Protein (CRP), and Procalcitonin (PCT) for sepsis diagnosis in pediatric patients. Furthermore, we explored the correlation of PSP levels with sepsis severity and organ failure measured with PELOD-2 score. METHODS: Forty pediatric patients were enrolled following admission to pediatric intensive care, high dependency care or pediatric ward. PSP blood levels were measured in Emergency Department (nanofluidic point-of-care immunoassay; abioSCOPE, Abionic SA, Switzerland) on day 1, 2, 3, 5 and 7 from the onset of the clinical signs and symptoms of sepsis or SIRS. Inclusion criteria were: 1) patient age (1 month to 18 years old), 2) signs and symptoms of SIRS, irrespective of association with organ dysfunction. Exclusion criteria were: 1) hemato-oncological diseases and/or immunodeficiencies, 2) pancreatic diseases. RESULTS: Septic patients showed higher PSP levels than those with non-infectious systemic inflammation. The optimal cut-off in diagnosis of sepsis for PSP at day 1 was 167 ng/ml resulted in a sensitivity of 59% (95% IC 36%-79%) and a specificity of 83% (95% IC 58%-96%) with an AUC of 0.636 for PSP in comparison to AUC of 0.722 for PCT and 0.503 for C-RP. ROC analysis for outcome (survival versus no survival) has showed AUC 0.814 for PSP; AUC 0.814 for PCT; AUC of 0.657 for C-RP. CONCLUSIONS: PSP could distinguish sepsis from non-infectious systemic inflammation; however, our results need to be confirmed in larger pediatric population.

Monocyte-to-lymphocyte, neutrophil-to-lymphocyte and neutrophil-to-monocyte plus lymphocyte ratios in children with active tuberculosis: A multicentre study.

AIM: Higher number of monocytes and neutrophils may correlate with active tuberculosis (TB) in children. However, the few paediatric studies available are limited by the small numbers of children with TB disease or infection included. METHODS: We calculated the monocyte-to-lymphocyte-ratio (MLR), neutrophil-to-lymphocyte-ratio (NLR) and neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) in children with active TB, latent TB infection (LTBI), other infectious and non-infectious conditions and healthy children evaluated in two referral centres in Rome. RESULTS: Overall, 649 children were included (41.8% females, mean age of 5.74 years). MLR, NLR and NMLR values were always significantly higher in patients with TB compared with the other groups (p < 0.001). Considering the entire population with the outcome of TB diagnosis, NMLR, with a cut-off of 1.2, had a sensitivity of 63% and a specificity of 76% (AUC: 0.71 [0.64-0.78]); NLR, with a cut-off of 1.5, had a sensitivity of 61% and a specificity of 79% (AUC: 0.72 [0.65-0.79]); MLR, considering a cut-off of 0.2, was less sensitive (56%) but more specific (82%) with a similar AUC (0.72 [0.65-0.79]). CONCLUSION: Our study provides further evidence that MLR, NLR and NMLR can serve as first level diagnostics to support the clinical suspicion of TB in children.

Novel Beta Lactam Antibiotics for the Treatment of Multidrug-Resistant Gram-Negative Infections in Children: A Narrative Review.

Infections due to carbapenem-resistant Enterobacterales (CRE) are increasingly prevalent in children and are associated with poor clinical outcomes, especially in critically ill patients. Novel beta lactam antibiotics, including ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, and cefiderocol, have been released in recent years to face the emerging challenge of multidrug-resistant (MDR) Gram-negative bacteria. Nonetheless, several novel agents lack pediatric indications approved by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA), leading to uncertain pediatric-specific treatment strategies and uncertain dosing regimens in the pediatric population. In this narrative review we have summarized the available clinical and pharmacological data, current limitations and future prospects of novel beta lactam antibiotics in the pediatric population.

Pediatric COVID-TB: A Clinical Perspective Based on the Analysis of Three Cases.

Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are currently two major causes of death among infectious diseases. Active tuberculosis and a history of tuberculosis appear to be associated with an increased risk of COVID-19. This coinfection, named COVID-TB, was never described in previously healthy children. We report three cases of pediatric COVID-TB. We describe three girls affected by tuberculosis, who tested positive for SARS-CoV-2. The first patient is a 5-year-old girl who was hospitalized for recurrent TB lymphadenopathy. As she never had any complications related to the concomitant infection with SARS-CoV-2, she received TB treatment. The second case is a 13-year-old patient with a history of pulmonary and splenic tuberculosis. She was admitted to the hospital due to deteriorating respiratory dynamics. She was already undergoing treatment for TB, but in the absence of improvement, she also required treatment for COVID-19. Slowly, the general condition improved until discharge. The last patient, a 10-year-old girl, was hospitalized for supraclavicular swelling. The investigations showed disseminated TB characterized by lung and bone involvement without COVID-19-related complications. She was treated with antitubercular and supportive therapy. Based on the data obtained from the adult population and our small experience, a pediatric patient with COVID-TB infection should be considered potentially at risk of worse clinical outcomes; for this reason, we suggest close observation, careful clinical management, and consideration of targeted anti-SARS-CoV-2 therapies.

The Prevalence of Carbapenemase-Producing Microorganisms and Use of Novel Cephalosporins for the Treatment of Severe Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria in a Pediatric Cardiac Intensive Care Unit.

BACKGROUND: The spread of carbapenem-resistant organisms (CROs) is an increasingly serious threat globally, especially in vulnerable populations, such as intensive care unit (ICU) patients. Currently, the antibiotic options for CROs are very limited, particularly in pediatric settings. We describe a cohort of pediatric patients affected by CRO infections, highlighting the important changes in carbapenemase production in recent years and comparing the treatment with novel cephalosporins (N-CEFs) to Colistin-based regimens (COLI). METHODS: All patients admitted to the cardiac ICU of the Bambino Gesù Children's Hospital in Rome during the 2016-2022 period with an invasive infection caused by a CRO were enrolled. RESULTS: The data were collected from 42 patients. The most frequently detected pathogens were Pseudomonas aeruginosa (64%), Klebsiella pneumoniae (14%) and Enterobacter spp. (14%). Thirty-three percent of the isolated microorganisms were carbapenemase producers, with a majority of VIM (71%), followed by KPC (22%) and OXA-48 (7%). A total of 67% of patients in the N-CEF group and 29% of patients in the comparative group achieved clinical remission (p = 0.04). CONCLUSION: The increase over the years of MBL-producing pathogens in our hospital is challenging in terms of therapeutic options. According to the present study, N-CEFs are a safe and effective option in pediatric patients affected by CRO infections.

Aggregatibacter actinomycetemcomitans infection in a 15-year-old boy with pulmonary empyema: a case report and review of literature.

BACKGROUND: Aggregatibacter actinomycetemcomitans (Aa), previously known as Actinobacillus actinomycetemcomitans, is a slow-growing Gram-negative coccobacillus, member of the HACEK group of bacteria colonizing oral flora. Besides causing infectious diseases in the oral cavity such as dental caries and periodontitis, it is responsible for severe extra-oral infections secondary to hematogenous spread or aspiration, such as endocarditis, soft tissue abscesses and osteomyelitis. The diagnosis depends on prolonged bacterial culture of biological material obtained through biopsy. Aa is susceptible to most antibiotics but complete eradication often requires a long term treatment. CASE PRESENTATION: We report the case of a 15-year-old previously healthy boy diagnosed with both pulmonary empyema and subphrenic chest wall abscess caused by Aa. He was admitted to our Pediatric Emergency department for evaluation of a right mass associated with marked asthenia and dry cough. After radiological findings etiological diagnosis was made by culture of fluid drainage of pleural empyema. He started empirical antibiotic therapy with intravenous piperacillin/tazobactam, whose sensibility was confirmed by the antibiogram, then, for occurrance of hepatopathy it was switched to ciprofloxacin: the patient almost completely recovered after 6-month therapy. CONCLUSIONS: Extra-oral infections caused by Aa are extremely rare, especially in children, and not well described yet. To our knowledge, there is only another similar case described in literature. However, the case described in our manuscript represents the only one presenting with pulmonary empyema without involvement of lung parenchyma in children. We also conducted a brief review of published cases of Aa infection in the pediatric population. This case report reminds us the importance of an accurate inspection of the oral cavity during the examination of pediatric patients.

Abdominal Tuberculosis in Children: A Case Series of Five Patients.

Tuberculosis remains (TB) to be one of the most common causes of child morbidity and mortality. Abdominal TB is not frequently diagnosed and, although its incidence is not definitively established, there are data that seem to indicate that it accounts for approximately 1-3% of all pediatric TB cases and for no more than 10% of those with extrapulmonary manifestations. It seems, however, that abdominal TB is significantly more common than usually thought as signs and symptoms are non-specific and may mimic other diseases. The delayed or wrong diagnosis of pediatric abdominal TB can have dramatic consequences as they can lead to untreated TB with miliary dissemination, unnecessary surgery, or dangerous drug therapies. This report describes five cases of abdominal TB diagnosed among 216 pediatric patients admitted for TB in Italy from 2011 to 2021. Our cases evidence that abdominal TB is a complex and potentially very severe disease that, when not appropriately diagnosed, may be associated with severe complications and prolonged anti-TB therapy. Discussion among specialists is crucial to achieve an early diagnosis and to promptly start the anti-TB treatment. Further studies are needed to clarify the appropriate duration of therapy as well as management of MDR abdominal TB cases.

Performance of QuantiFERON-TB Gold Plus assays in paediatric tuberculosis: a multicentre PTBNET study.

RATIONALE: In 2016, a new interferon-gamma release assay (IGRA) was introduced, QuantiFERON-TB Gold Plus (QFT-Plus), claimed to have improved sensitivity in active tuberculosis (TB). OBJECTIVES: This study aimed to determine the performance of QFT-Plus, compared with previous generation IGRAs and the tuberculin skin test (TST), in children with TB in Europe. METHODS: Multicentre, ambispective cohort study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), a dedicated paediatric TB research network comprising >300 members, capturing TB cases <18 years-of-age diagnosed between January 2009 and December 2019. MEASUREMENTS AND MAIN RESULTS: 1001 TB cases from 16 countries were included (mean age (IQR) 5.6 (2.4-12.1) years). QFT-Plus was performed in 358, QFT Gold in-Tube (QFT-GIT) in 600, T-SPOT.TB in 58 and TST in 636 cases. The overall test sensitivities were: QFT-Plus 83.8% (95% CI 80.2% to 87.8%), QFT-GIT 85.5% (95% CI 82.7% to 88.3%), T-SPOT.TB 77.6% (95% CI 66.9% to 88.3%) and TST (cut-off ≥10 mm) 83.3% (95% CI 83.3% to 86.2%). There was a trend for tests to have lower sensitivity in patients with miliary and/or central nervous system (CNS) TB (73.1%, 70.9%, 63.6% and 43.5%, respectively), and in immunocompromised patients (75.0%, 59.6%, 45.5% and 59.1%, respectively). CONCLUSIONS: The results indicate that the latest generation IGRA assay, QFT-Plus, does not perform better than previous generation IGRAs or the TST in children with TB disease. Overall, tests performed worse in CNS and miliary TB, and in immunocompromised children. None of the tests evaluated had sufficiently high sensitivity to be used as a rule-out test in children with suspected TB.

Severe viral respiratory infections in the pre-COVID era: A 5-year experience in two pediatric intensive care units in Italy.

BACKGROUND: Viral respiratory infections are one of the main causes of hospitalization in children. Even if mortality rate is low, 2% to 3% of the hospitalized children need mechanical ventilation. Risk factors for admission to the pediatric intensive care unit (PICU) are well known, while few studies have described risk factors for invasive ventilator support and prolonged hospitalization. METHODS: A retrospective study including all patients aged between 2 and 18 months with a confirmed viral respiratory infection, requiring admission to PICU from September to March between 2015 and 2019, was conducted at Bambino Gesù Children's Hospital in Rome, Italy. RESULTS: One hundred ninety patients were enrolled, with a median age of 2.7 months; 32.1% had at least one comorbidity, mainly prematurity. The most frequent isolated viruses were RSV-B, rhinovirus, and RSV-A; 38.4% needed mechanical ventilation. This subgroup of patients had lower median birth weight compared with patients not requiring mechanical ventilation (2800 g vs. 3180 g, p = 0.02); moreover, comorbidities were present in 43.8% of intubated patients and in 24.8% of patients treated with non-invasive ventilation (p = 0.006). Viral coinfection did not result to be a risk factor for mechanical support, while virus-bacteria coinfection was significantly associated with mechanical ventilation (p < 0.001). Similar risk factors were identified for prolonged hospitalization. CONCLUSIONS: Early identification of patients who could have a sudden respiratory deterioration and need of mechanical ventilation is crucial to reduce complications due to orotracheal intubation and prolonged hospitalization in PICU. Further studies are needed to define high-risk group of patients and to design targeted interventions.

The Use of Cefiderocol as Salvage Therapy in an Infant Receiving ECMO and Continuous Renal Replacement Therapy.

BACKGROUND: Infections caused by antimicrobial-resistant (AMR) pathogens are increasing worldwide, representing a serious global public health issue with high morbidity and mortality rates The treatment of Pseudomonas aeruginosa (PA) infections has become a significant challenge due to its ability to develop resistance to many of the currently available antibiotics, especially in intensive care unit (ICU) settings. Among the very few therapeutic lines available against extensively drug-resistant (XDR)-PA and/or with difficult-to-treat resistance (DTR)-PA, cefiderocol is an injectable siderophore cephalosporin not licensed for use in pediatric patients. There are only a few case reports and two ongoing trials describing the administration of this cephalosporin in infants. CASE PRESENTATION: This report describes the case of a critically ill 8-month-old girl affected by ventilator-associated pneumonia (VAP) infection complicated by bloodstream infection (BSI) sustained by VIM-producing PA. She was treated with cefiderocol as a salvage therapy during ECMO and CRRT support. CONCLUSIONS: In healthcare settings, treating multidrug-resistant, Gram-negative bacteria poses a serious challenge, especially in pediatric patients. Our findings suggest that cefiderocol can be considered as an off-label rescue therapy in selected pediatric cases.

Clinical report and predictors of sequelae of 319 cases of pediatric bacterial osteomyelitis.

Pediatric osteomyelitis is an insidious disease that can lead to permanent sequelae, the management of which still relies on lengthy intravenous antibiotic therapy. The purpose of this study is to report and describe the clinical course and outcome of pediatric bacterial osteomyelitis in our experience. We reported the clinical, diagnostic, and treatment characteristics of all cases of osteomyelitis in children younger than 18 years of age who were hospitalized between January 2010 and December 2021 at the Bambino Gesù Children's Hospital in Rome, Italy, we compared patients with and without complications at follow-up, to identify any predictive factor for sequelae. The study sample included 319 cases of pediatric bacterial osteomyelitis. The median age was 7.77 years. Males (60.8%) were more affected than females. The most affected bones were the femur, tibia, and spine. Etiology was identified in 40.1% of cases, with S.aureus as the most common causative agent. Sequelae were reported in 43 cases (13.5%). The main predictors of sequelae were sepsis on admission and hypergammaglobulinemia. Our results show that a severe presentation with sepsis and hypergammaglobulinemia on admission may be associated with a higher frequency of late sequelae. Early recognition and aggressive treatment of this subgroup of patients may lead to a reduction in complications.

Case report: Microcirculatory leukocytes in a pediatric patient with severe SARS-CoV-2 pneumonia. Findings of leukocytes trafficking beyond the lungs.

Background: SARS-CoV-2 can lead to excessive coagulation and thrombo-inflammation with deposition of microthrombi and microvascular dysfunction. Several studies in human and animal models have already evidenced biomarkers of endothelial injury during SARS-CoV-2 infection. Real-time observation of sublingual microcirculation using an handheld vital microscopy with an Incident Dark Field (IDF) technique could represent a non-invasive way to assess early signs of microvascular dysfunction and endothelial inflammation in patients with severe COVID-19 infection. Clinical case: We report for the first time in a pediatric patient with severe SARS-CoV-2 pneumonia findings about microcirculatory leukocytes in the sublingual microcirculation of a 7 month-old patient admitted to our PICU using handheld vital microscopy with IDF technique. Results: Sublingual microcirculation analysis revealed the presence of microcirculatory alterations and an extensive presence of leukocytes in the patient's sublingual microcirculation. It's significant to underline how the patient didn't show a contextual significant increase in inflammatory biomarkers or other clinical signs related to an inflammatory response, beyond the presence of severe hypoxic respiratory failure. Conclusion: Leukocyte activation in multiple organs can occur at the endothelial lining of the microvasculature where a surge of pro-inflammatory mediators can result in accumulation of activated leukocytes and degradation of the endothelium. The introduction of a method to assess in a non-invasive, real-time manner the extent of inflammation in a patient with COVID19 could lead to potential clinical and therapeutic implications. However, more studies are required to prove that studying leukocytes microcirculation using sublingual microcirculation analysis could be useful as a bedside point of care monitor to predict the presence of systemic inflammation associated with the impact of COVID-19, leading in a late phase of severe SARS-CoV-2 infection to a microvascular dysfunction and micro-thrombosis.

Secondary cytomegalovirus infections: How much do we still not know? Comparison of children with symptomatic congenital cytomegalovirus born to mothers with primary and secondary infection.

Congenital cytomegalovirus (cCMV) infection can follow primary and secondary maternal infection. Growing evidence indicate that secondary maternal infections contribute to a much greater proportion of symptomatic cCMV than was previously thought. We performed a monocentric retrospective study of babies with cCMV evaluated from August 2004 to February 2021; we compared data of symptomatic children born to mothers with primary or secondary infection, both at birth and during follow up. Among the 145 babies with available data about maternal infection, 53 were classified as having symptomatic cCMV and were included in the study: 40 babies were born to mothers with primary infection and 13 babies were born to mothers with secondary infection. Analyzing data at birth, we found no statistical differences in the rate of clinical findings in the two groups, except for unilateral sensorineural hearing loss (SNHL) which was significantly more frequent in patients born to mother with secondary infection than in those born to mother with primary infection (46.2 vs. 17.5%, P = 0.037). During follow up, we found a higher rate of many sequelae (tetraparesis, epilepsy, motor and speech delay, and unilateral SNHL) in the group of children born to mothers with secondary infection, with a statistical difference for tetraparesis and unilateral SNHL. Otherwise, only children born to mothers with primary infection presented bilateral SNHL both at birth and follow up. Our data suggest that the risk of symptomatic cCMV and long-term sequelae is similar in children born to mother with primary and secondary CMV infection; it is important to pay appropriate attention to seropositive mothers in order to prevent reinfection and to detect and possibly treat infected babies.

Surgical Antimicrobial Prophylaxis in Neonates and Children Undergoing Neurosurgery: A RAND/UCLA Appropriateness Method Consensus Study.

Pediatric neurosurgery is a highly specialized branch of surgery in which surgical site infections (SSIs) are potentially serious complications that can also adversely affect a good surgical outcome, compromising functional recovery and, in some cases, even putting the patient's life at risk. The main aim of this consensus document is to provide clinicians with a series of recommendations on antimicrobial prophylaxis for neonates and children undergoing neurosurgery. The following scenarios were considered: (1) craniotomy or cranial/cranio-facial approach to craniosynostosis; (2) neurosurgery with a trans-nasal-trans-sphenoidal approach; (3) non-penetrating head injuries; (4) penetrating head fracture; (5) spinal surgery (extradural and intradural); (6) shunt surgery or neuroendoscopy; (7) neuroendovascular procedures. Patients undergoing neurosurgery often undergo peri-operative antibiotic prophylaxis, with different schedules, not always supported by scientific evidence. This consensus provides clear and shared indications, based on the most updated literature. This work has been made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies, and represents, in our opinion, the most complete and up-to-date collection of recommendations on the behavior to be held in the peri-operative setting in this type of intervention, in order to guide physicians in the management of the patient, standardize approaches and avoid abuse and misuse of antibiotics.