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Abstract 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.

Acute Bacterial Skin and Skin Structure Infections (ABSSSI) are marked by substantial morbidity, frequent need for hospitalization, and long courses of intravenous antibiotic therapy. Herein, we report four cases of pediatric patients admitted for ABSSSI and managed with a combination antibiotic regimen incorporating dalbavancin: a second-generation lipoglycopeptide active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. In our experience, particularly in a setting with a high methicillin-resistance rate, dalbavancin demonstrated safety and efficacy, simplifying ABSSSI management in childhood. Its prolonged half-life enables a single-dose administration regimen, offering potential solutions to numerous challenges encountered in pediatric care, such as extended hospital stays, difficulties in securing and maintaining vascular access, lack of pediatric-specific drug indications, and limited availability of suitable oral formulations.

BackgroundThe treatment of multisystem inflammatory syndrome in children unresponsive to first-line therapies (IVIG and/or steroids) is challenging. The effectiveness of IL-1 receptor antagonist, anakinra, is debated.Patients and methodsWe conducted an anonymous retrospective multicenter study on MIS-C patients treated with anakinra in Italy from January 2020 to February 2021. Our study outcomes included the percentage of patients who required further therapeutic step-up, the percentage of patients who experienced fever resolution within 24 h and a reduction of CRP by half within 48 h, and the percentage of patients who developed Coronary Artery Anomalies (CAA) during follow-up.Results35 cases of MIS-C were treated in 10 hospitals. Of these, 13 patients started anakinra while in the ICU, and 22 patients started anakinra in other wards. 25 patients (71.4%) were treated with corticosteroids at a starting dose 2–30 mg/Kg/day plus IVIG (2 g/Kg), 10 patients (28.6%) received only corticosteroids without IVIG. Anakinra was administered intravenously to all patients in Group A (mean dose 8 mg/Kg/day), and subcutaneously in Group B (mean dose 4 mg/Kg/day). Only two patients required further treatment step-up and no patients developed CAA after receiving anakinra. The most commonly observed side effect was an increase in ALT, occurring in 17.1% of patients.ConclusionsIn this retrospective cohort of severe MIS-C patients treated with anakinra we report favorable clinical outcomes with a low incidence of side effects. The simultaneous use of steroids ± IVIG in these patients hinders definitive conclusions regarding the need of IL-1 inhibition in MIS-C treatment.

BackgroundAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of disorders characterized by necrotizing inflammation of small- and medium-sized blood vessels and the presence of circulating ANCA. Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic ANCA-associated vasculitis, characterized by peripheral eosinophilia, neuropathy, palpable purpuras or petechiae, renal and cardiac involvement, sinusitis, asthma, and transient pulmonary infiltrates. Middle lobe syndrome (MLS) is defined as recurrent or chronic atelectasis of the right middle lobe of the lung, and it is a potential complication of asthma.Case presentationHerein, we describe a case of MLS in a 51-year-old woman, never-smoker, affected by EGPA, presenting exclusively with leukocytosis and elevated concentrations of acute-phase proteins, without any respiratory symptom, cough, or hemoptysis. Chest computed tomography (CT) imaging documented complete atelectasis of the middle lobe, together with complete obstruction of lobar bronchial branch origin. Fiberoptic bronchoscopy (FOB) revealed complete stenosis of the middle lobar bronchus origin, thus confirming the diagnosis of MLS, along with distal left main bronchus stenosis. Bronchoalveolar lavage (BAL) did not detect any infection. Bronchial biopsies included plasma cells, neutrophil infiltrates, only isolated eosinophils, and no granulomas, providing the hypothesis of vasculitic acute involvement less likely. First-line agents directed towards optimizing pulmonary function (mucolytics, bronchodilators, and antibiotic course) were therefore employed. However, the patient did not respond to conservative treatment; hence, endoscopic management of airway obstruction was performed, with chest CT documenting resolution of middle lobe atelectasis.ConclusionTo the best of our knowledge, this is the first detailed description of MLS in EGPA completely resolved through FOB. Identification of MLS in EGPA appears essential as prognosis, longitudinal management, and treatment options may differ from other pulmonary involvement in AAV patients.

Abstract Background US Food and Drug Administration has issued Emergency Use Authorizations for hundreds of serological assays to support Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) diagnosis. The aim of this study is to evaluate, for the first time in children, the performance of three widely utilized SARS-CoV-2 serology commercial assays, Diesse Diagnostics (IgG, IgA, IgM) and Roche Diagnostics, both Roche Nucleocapsid (N) IgG and Roche Spike (S) IgG assays. Methods Sensitivity and 95% confidence intervals (CIs) were estimated for each of the three different serological tests and mixed and direct comparison were performed. Univariate and multivariate Poisson regression models were fitted to calculate incidence rate ratios and 95% CIs as estimate of the effects of age, gender, time on the serology title. A p-value

Abstract Background This study aimed to investigate the trajectory of damage accrual, associated factors, and impact on health-related quality of life (HR-QoL) in a multicenter cohort of patients with Behçet’s syndrome (BS) over 2 years of follow-up. Methods Patients recruited in the BS Overall Damage Index (BODI) validation study were prospectively monitored for 2 years and assessed for damage accrual, defined as an increase ≥1 in the BODI score, and HR-QoL was evaluated by the SF-36 questionnaire. Logistic and multiple linear regression models were built to determine factors associated with damage accrual and impairment in the different SF-36 domains. Results During follow-up, 36 out of 189 (19.0%) patients had an increase ≥1 in the BODI score with a mean (SD) difference of 1.7 (0.8) (p

The Spike protein of SARS-CoV-2 acts as an enterotoxin able to induce chloride secretion and production of reactive oxygen species (ROS), involved in diarrhea pathogenesis. L. rhamnosus GG (LGG) is recommended in pediatric acute gastroenteritis guidelines as a therapy independent of infectious etiology. We tested a postbiotic preparation of LGG (mLGG) in an in vitro model of COVID-associated diarrhea. Caco-2 cell monolayers mounted in Ussing chambers were exposed to Spike protein, and electrical parameters of secretory effect (Isc and TEER) were recorded in the Ussing chambers system. Oxidative stress was analyzed by measuring ROS production (DCFH-DA), GSH levels (DNTB), and lipid peroxidation (TBARS). Experiments were repeated after mLGG pretreatment of cells. The Isc increase induced by Spike was consistent with the secretory diarrhea pattern, which was dependent on oxidative stress defined by a 2-fold increase in ROS production and lipid peroxidation and variation in glutathione levels. mLGG pretreatment significantly reduced the secretory effect (p = 0.002) and oxidative stress, namely ROS (p < 0.001), lipid peroxidation (p < 0.001), and glutathione level changes (p < 0.001). LGG counteracts Spike-induced diarrhea by inhibiting the enterotoxic effect and oxidative stress. The LGG efficacy in the form of a postbiotic depends on metabolites secreted in the medium with antioxidant properties similar to NAC. Because SARS-CoV-2 is an enteric pathogen, the efficacy of LGG independent of etiology in the treatment of acute gastroenteritis is confirmed by our data.

Abstract Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs. Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs.

Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease, including multisystem inflammatory syndrome in children (MIS-C) and chilblain-like lesions (CLLs), otherwise known as “COVID toes,” remains unclear. Studying multinational cohorts, we found that, in CLLs, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs after disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19–affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased NET levels when compared with other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.

Abstract Background Acute hematogenous osteomyelitis (AHOM) is an insidious infection of the bone that more frequently affects young males. The etiology, mainly bacterial, is often related to the patient’s age, but it is frequently missed, owing to the low sensitivity of microbiological cultures. Thus, the evaluation of inflammatory biomarkers and imaging usually guide the diagnosis and follow-up of the infection. The antibiotic treatment of uncomplicated AHOM, on the other hand, heavily relies upon the clinician experience, given the current lack of national guidelines for the management of this infection. Methods A systematic review of the studies on the empirical treatment of uncomplicated AHOM in children published in English or Italian between January 1, 2009, and March 31, 2020, indexed on Pubmed or Embase search engines, was carried out. All guidelines and studies reporting on non-bacterial or complicated or post-traumatic osteomyelitis affecting newborns or children older than 18 years or with comorbidities were excluded from the review. All other works were included in this study. Results Out of 4576 articles, 53 were included in the study. Data on different topics was gathered and outlined: bone penetration of antibiotics; choice of intravenous antibiotic therapy according to the isolated or suspected pathogen; choice of oral antibiotic therapy; length of treatment and switch to oral therapy; surgical treatment. Conclusions The therapeutic management of osteomyelitis is still object of controversy. This study reports the first Italian consensus on the management of uncomplicated AHOM in children of pediatric osteomyelitis, based on expert opinions and a vast literature review.

Background and aims: The pathophysiology of SARS-CoV-2-associated diarrhea is unknown. Using an experimental model validated for rotavirus-induced diarrhea, we investigated the effects of SARS-CoV-2 on transepithelial ion fluxes and epithelial integrity of human intestinal cells. The effect of the antidiarrheal agent diosmectite on secretion was also evaluated following its inclusion in COVID-19 management protocols. Methods: We evaluated electrical parameters (intensity of short-circuit current [Isc] and transepithelial electrical resistance [TEER]) in polarized Caco-2 cells and in colonic specimens mounted in Ussing chambers after exposure to heat-inactivated (hi) SARS-CoV-2 and spike protein. Spectrofluorometry was used to measure reactive oxygen species (ROS), a marker of oxidative stress. Experiments were repeated after pretreatment with diosmectite, an antidiarrheal drug used in COVID-19 patients. Results: hiSARS-CoV-2 induced an increase in Isc when added to the mucosal (but not serosal) side of Caco-2 cells. The effect was inhibited in the absence of chloride and calcium and by the mucosal addition of the Ca2+-activated Cl– channel inhibitor A01, suggesting calcium-dependent chloride secretion. Spike protein had a lower, but similar, effect on Isc. The findings were consistent when repeated in human colonic mucosa specimens. Neither hiSARS-CoV-2 nor spike protein affected TEER, indicating epithelial integrity; both increased ROS production. Pretreatment with diosmectite inhibited the secretory effect and significantly reduced ROS of both hiSARS-CoV-2 and spike protein. Conclusions: SARS-CoV-2 induces calcium-dependent chloride secretion and oxidative stress without damaging intestinal epithelial structure. The effects are largely induced by the spike protein and are significantly reduced by diosmectite. SARS-CoV-2 should be added to the list of human enteric pathogens.

Modernity unfolds through the unrelenting exploitation, appropriation, and dispossession of human and natural substance; through the radical devaluation of nature, both human and extra-human; on hierarchy, racism, patriarchy, all in service to capitalist accumulation. A grasp of what lies at the base of one of the most important world-historical mechanisms of power formation and systemic reproduction that has hitherto kept the capitalist world-system/ecology going, hegemony, can be relevant for the formulation of new strategies of contention and practices of anti-systemic movements against this perverse mode of life organization. Such a grasp, thus, can be regarded as part of the anti-systemic program towards a more just society and ecologically-devoted humanity. Understanding how a hegemon can form and produce power can be conducive to the comprehension of how to jam or confront such a world-systemic mechanism, which is pivotal for the unabated expansion and reproduction of capitalism. This investigation endeavors to shed some light on this agency of world-historical power and systemic re/production. More to the point, it will posit a methodological way of reading and understanding the inner source and morphology of the hegemonic power. This paper, however, represents the spadework for further research. As we shall see, the complexity of the argument imposed a provisional “ecological expurgation”. As a consequence, nature will be silenced in Part I. The reasons for such a painful expurgation will be clear once we delve into the articulation of analysis and narrative. Such methodological and conceptual weakness is to be overcome through further research in Part II. It shall posit a complete hegemon’s perspective, namely, a world-ecological perspective on the hegemonic power. Part I, hence, will explore part of the material relational complexity that spawns hegemony in reality. On the present groundwork indeed, an understanding of the hegemonic power through post-Cartesian, that is, a world-ecological lens, could be unfolded to the fullest, both methodologically and historically. Provisional and fictional separation calls for permanent and lifelike reconstitution —which is the final aim of the research—. Part I will not engage in a traditional analysis of hegemony as a projection of power towards and onto world space. By contrast, it will deal with how a hegemon succeeds in projecting such power; that is, how the hegemon manages to internally generate power enough to make masses and states throughout the world captive and legible to the hegemon’s project of world leadership and historical development. What is seldom acknowledged is that a hegemon, before projecting power outward, must develop an internal formula. Hence, through this (provisional) methodological frame it will be argued that it is not simply an overt power that defines a hegemon, but its infra-structural power. More to the point, in Part I will posit the hegemon as a regime of power accumulation wherein state, capital and society work hand in glove with a particular degree of coherence developed within the established, or legal, boundaries of its territorial sovereignty. The internal organization of power that originates from this “coherent work” breeds hegemony, that is, the capacity to project power towards and onto world space. Part I purports to provide a way to explain analytically the hegemon’s organization, control, and logistics in order to understand sociospatial capacity for infrastructural power — a mode for investigating the tangled whole of powers, relations and networks that makes and permeates the fabric of the hegemon itself -. I would here hint at the world-ecological reading of the hegemon. In short: the world-ecological perspective of the Hegemon thinks of hegemonic power not solely as infra-structural power but as infra-relational power —meaning the capacity to historically design first, and then organize the project of power, science and nature by activating operations to harness the relational forces between humans and nature (as well as within both and their own inextricable intertwining) in service of capitalist power—. The hegemon is thus an organization of human-and-extra-human space that extensively and intensively re/produces, organizes, mobilizes and maximizes human-and-extra-human wealth, knowledge and interaction better than any other organization in the modern world-ecology. In short: before projecting power outward, the hegemon must develop a socioecological formula. Thus, from a complete hegemon’s perspective, hegemony is firstly an inner actual world-ecological design of the world. This is the idea behind the methodological and historical investigation of world-ecology to be carried out. Part I maintains that hegemonic power is the product of a trialectic unity of state, capital and society in which multiple overlapping and intersecting spatial networks of power, and the attendant immanent relations, are viewed as constitutive of the working totality. A hegemon deploys the most coherent – efficient and effective – design and operationalization of infrastructural power. Complementary then, hegemonic infrastructural power is to be also seen as the specifically-organic product and conflation of extensive and intensive power – firstly, within its own legal space and borders. The hegemon is a regime of power accumulation that extensively and intensively re/produces, organizes, mobilizes, and maximizes wealth, knowledge and interaction better than any other organization in the modern world-system. Hence, compared to any other jurisdiction that vies with it, a hegemonic regime manages to generate and combine the highest organizational cooperation (put simply: cooperation among the largest number of people with and through the most expansive management of resources – extensive power) with the greatest organizational command (put simply: the highest level of commitment from participants and utilization of resources – intensive power). The investigation of networks and relations, (bundled by) extensive and intensive power, is, in short, the method being argued for. As a whole, this will allow us to see the socio-spatial dynamic of infrastructural power production and to account for (the coherence of) the hegemon’s structure – the hegemony’s source. Finally, this is to prepare the ground, on the one hand, for the factual analysis of the hegemons’ historical development, since it purports to provide a useful framework to investigate the hegemons’ historical organization as well as the manifold web of power relations contained within it. On the other, it provides, as a whole, the springboard through which to unfold the world-ecological perspective on the hegemon, both methodologically and historically.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the implementation of restrictive measures led to a dramatic reduction in respiratory syncytial virus (RSV) occurrence together with rare and mild bronchiolitis induced by SARS-CoV-2. We described the respiratory picture of SARS-CoV-2 infection and evaluated the frequency and the severity of SARS-CoV-2 bronchiolitis comparing it with other respiratory viral infections in children less than two years of age. The severity of respiratory involvement was evaluated based on the need for oxygen therapy, intravenous hydration, and the length of hospital stay. A total of 138 children hospitalized for respiratory symptoms were enrolled: 60 with SARS-CoV-2 and 78 with RSV. In the group of SARS-CoV-2-infected children, 13/60 (21%) received a diagnosis of co-infection. Among the enrolled children, 87/138 (63%) received a diagnosis of bronchiolitis. The comparative evaluation showed a higher risk of the need for oxygen therapy and intravenous hydration in children with RSV infection and co-infection compared to children with SARS-CoV-2 infection. In the children with a diagnosis of bronchiolitis, no differences in the main outcomes among the groups were observed. Although children with SARS-CoV-2 infection have less severe respiratory effects than adults, the pediatrician should pay attention to bronchiolitis due to SARS-CoV-2, which could have a severe clinical course in younger children.

Antimicrobial resistance (AMR) represents a major issue in healthcare being correlated to global inappropriate use of antibiotics. The aim of this study was to compare the data on hospital antibiotic consumption in 2020–2021 with those related to 2019 in order to evaluate the impact of the COVID-19 pandemic on antibiotic prescriptions and appropriate use at national level and in the different geographical areas. To estimate the consumption of antibiotics, two indicators were calculated: “number of DDD per 1000 inhabitants per day” and “number of DDD per 100 hospitalisation days”. Consumption data on antibiotics dispensed in public health facilities were based on the Italian “traceability of medicines” information flow. Data on hospitalisation days were extracted from the Italian “hospital discharge form” flow. Pearson correlation analysis was performed between the number of patients hospitalised for COVID-19 and the consumption of antibiotics in public healthcare facilities. During 2020, about 1.7 DDD/1000 inhabitants per day (12.3% of the overall consumption of reimbursed antibiotics) were dispensed exclusively in Italian hospitals (+0.8% compared to 2019). Considering the number of DDD per 100 hospitalisation days, consumption increased by 19.3% in 2020 compared to 2019. Comparing the first semester of 2020 and 2019, a decrease of DDD/1000 inhabitants per day was observed (−1.6%) at national level, with opposite trends in the different geographical areas; an increase in the use of azithromycin and carbapenems was also observed, with a stable consumption of third-generation cephalosporins. The use of antibiotics in the second semester of 2020 compared to the same period of 2019 showed a clear reduction at national level (−8.5%), appreciable to a similar extent in all geographic areas. In the first semester of 2021 compared to the same period of 2020, there was a huge reduction (−31.4%) in consumption at national level. However, the variations were heterogeneous between different geographical areas. To our knowledge, this study represents the most comprehensive analysis performed on antibiotic consumption data in hospital settings in Italy during the COVID-19 pandemic to date. Despite international and national guideline recommendations, a substantial overall increase in antibiotic prescriptions was observed during the COVID-19 pandemic, with variability in terms of geographical distribution and prescription strategies. These findings may be related to the dichotomy between perceived and real significance of guidelines, expert panels, or consensus. Therefore, new approaches or strategies to antimicrobial stewardship should be proposed.

Abstract Background In comparison with adults, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection in children has a milder course. The management of children with suspected or confirmed coronavirus disease (COVID-19) needs to be appropriately targeted. Methods We designed a hub-and-spoke system to provide healthcare indications based on the use of telemedicine and stringent admission criteria, coordinate local stakeholders and disseminate information. Result Between March 24th and September 24th 2020, the Hub Centre managed a total of 208 children (52% males, median age, 5.2, IQR 2–9.6 years) with suspected or confirmed COVID-19. Among them, 174 were managed in cooperation with family pediatricians and 34 with hospital-based physicians. One hundred-four (50%) received a final diagnosis of SARS-CoV-2 infection. Application of stringent criteria for hospital admission based on clinical conditions, risk factors and respect of biocontainment measures, allowed to manage the majority of cases (74, 71.1%) through telemedicine. Thirty children (28%) were hospitalized (median length 10 days, IQR 5–19 days), mainly due to the presence of persistent fever, mild respiratory distress or co-infection occurring in infant or children with underlying conditions. However, the reasons for admission slightly changed over time. Conclusion An hub-and-spoke system is effective in coordinate territorial health-care structures involved in management paediatric COVID-19 cases through telemedicine and the definition of stringent hospital admission criteria. The management of children with COVID-19 should be based on clinical conditions, assessed on a case-by-case critical evaluation, as well as on isolation measures, but may vary according to local epidemiological changes.

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren’s syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

BackgroundAdministration of Lacticaseibacillus rhamnosus GG (LGG) to children with gastroenteritis is recommended by universal guidelines. Rotavirus (RV) causes diarrhea through combined cytotoxic and enterotoxic effects. Aim of this study was to evaluate the mechanisms of efficacy of LGG in an in-vitro model of RV diarrhea in its viable form (LGG) and conditioned medium (mLGG).MethodsIon secretion corresponding to the NSP4 enterotoxic effect, was evaluated by short circuit current (Isc) and the cytotoxic effect by transepithelial electrical resistance (TEER) in Ussing chambers, upon exposure to RV in Caco-2 enterocyte monolayers treated or not with living probiotic or its culture supernatant. Mechanisms of enterotoxic and cytotoxic damage were evaluated including oxidative stress measured by reactive oxygen species, apoptosis evaluated by DAPI and nuclear staining, NFkβ immunofluorescence.ResultsRV induced Isc increase and TEER decrease, respectively indicating ion secretion and epithelial damage, the two established pathways of diarrhea. Both probiotic preparations reduced both diarrheal effects, but their potency was different. Live LGG was equally effective on both enterotoxic and cytotoxic effect whereas mLGG was highly effective on ion secretion and showed minimal protective effects on cytoskeleton, apoptosis and NFkβ.ConclusionsLGG counteracts RV-induced diarrhea by inhibiting both cytotoxic and enterotoxic pathogenic mechanisms. Namely, LGG inhibits chloride secretion by specific moieties secreted in the medium with a direct pharmacologic-like action. This is considered a postbiotic effect. Subsequently, live bacteria exert a probiotic effect protecting the enterocyte structure.

Four-wire measurements have been introduced by Lord Kelvin in 1861 and have since become the standard technique for characterizing small resistances and impedances. However, high-density 4-wire measurements are generally complex, time-consuming, and inefficient because of constraints on interconnects, pads, external wires, and mechanical contacts, thus reducing reproducibility, statistical significance, and throughput. Here, we introduce, systematically design, analyze, and experimentally validate zero interconnect networks interfaced to external instrumentation by couples of twin wire. 3D-printed holders with magnets, interconnects, nonadhesive layers, and spacers can effortlessly establish excellent electrical connections with tunable or minimum contact forces and enable accurate measurements even for delicate devices, such as thin metals on soft polymers. As an example, we measured all the resistances of a twin-wire 29-resistor network made of silver-nanoparticle ink printed on polyimide, paper, or photo paper, including during sintering or temperature calibration, resulting in an unprecedentedly easy and accurate characterization of both resistivity and its temperature coefficient. The theoretical framework and experimental strategies reported here represent a breakthrough toward zero interconnect, simple, and efficient high-density 4-wire characterizations, can be generalized to other 4-wire measurements (impedances, sensors) and can open the way to more statistically meaningful and reproducible analyses of materials, high-throughput measurements, and minimally invasive characterizations of biomaterials.

Abstract A statement of consensus was formulated after reviewing available literature on pediatric treatment strategies for COVID-19 by the Steering and Scientific Committee of the Italian Society of Infectious Pediatric Diseases in connection with the Italian Society of Paediatrics.

Abstract During the last decade several paediatric studies have been published with different possible indications for probiotics, leading to a global increase of probiotics’ market. Nevertheless, different study designs, multiple single/combined strains and small sample size still leave many uncertainties regarding their efficacy. In addition, different regulatory and quality control issues make still very difficult the interpretation of the clinical data. The objective of this review is to critically summarise the current evidence on probiotics’ efficacy and safety on a different number of pathologies, including necrotizing enterocolitis, acute infectious diarrhoea, allergic diseases and functional gastrointestinal disorders in order to guide paediatric healthcare professionals on using evidence-based probiotics’ strains. To identify relevant data, literature searches were performed including Medline-PubMed, the Cochrane Library and EMBASE databases. Considering probiotics strain-specific effects, the main focus was on individual probiotic strains and not on probiotics in general.

Abstract Background Ascites can develop as a consequence of a number of diseases in childhood. Despite chronic liver disease is the most common cause, several conditions can lead to ascites also in the absence of liver dysfunction. As non-cirrhotic ascites shows a high degree of overlapping sign and symptoms it is still a challenge for physicians. Case presentation A 8-year-old Caucasian girl was referred for fever, vomit and diarrhea occurred over the past few weeks. Physical examination showed timpanitic distension of the abdomen with marked tenderness and increased abdominal wall rigidity. Abdominal imaging showed diffuse ascites and thickened omentum and bowel wall. Blood tests showed increased C- reactive protein levels and decreased lymphocyte count. Specific treatment for inflammatory bowel disease was started. Persisting of ascites required additional investigations. Positive tuberculin skin test and Interferon Gamma release assay (IGRA) as well as increased Ca125 serum concentrations were found. Computed tomography scan showed mediastinal and mesenteric adenopathies and diffuse smooth thickening of the omentum with significant enhancement (omental cake-like). Ascitic fluid analysis revealed high leucocytes and protein levels. Presumptive diagnosis of peritoneal tuberculosis (PTB) was made. Antituberculous treatment resulted in the resolution of ascites and normalization of lymphocyte count and Ca125 serum concentrations. Conclusions PTB is still possible in low-prevalence countries. As it is a great mimicker of other abdominal pathology whose treatment might worsen tuberculosis progression, clinical suspicion and adequate screening are required to avoid unnecessary interventions and delayed treatment. Ca125 is a non-specific marker of peritoneal inflammation but it might be helpful in monitoring the treatment response.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pathogen with enteric tropism. We compared the clinical, biochemical and radiological features of children hospitalized for acute SARS-CoV-2 infection, classified in two groups based on the presence of diarrhea. Logistic regression analyses were used to investigate the variables associated with diarrhea. Overall, 407 children were included in the study (226 males, 55.5%, mean age 3.9 ± 5.0 years), of whom 77 (18.9%) presented with diarrhea, which was mild in most cases. Diarrhea prevalence was higher during the Alpha (23.6%) and Delta waves (21.9%), and in children aged 5–11 y (23.8%). Other gastrointestinal symptoms were most commonly reported in children with diarrhea (p < 0.05). Children with diarrhea showed an increased systemic inflammatory state (higher C-reactive protein, procalcitonin and ferritin levels, p < 0.005), higher local inflammation as judged by mesenteric fat hyperechogenicity (adjusted Odds Ratio 3.31, 95%CI 1.13–9.70) and a lower chance of previous immunosuppressive state (adjusted Odds Ratio 0.19, 95%CI 0.05–0.70). Diarrhea is a frequent feature of pediatric COVID-19 and is associated with increased systemic inflammation, which is related to the local mesenteric fat inflammatory response, confirming the implication of the gut not only in multisystem inflammatory syndrome but also in the acute phase of the infection.

Background: Currently, the novel coronavirus (SARS-CoV-2) causes an acute respiratory illness named COVID-19 and is a controversial risk factor for hearing loss (HL). Herein, we aim to describe the associated symptoms and to evaluate hearing function in the COVID-19 pediatric population. Methods: A retrospective cross-sectional observational study was carried out on 37 children who contracted COVID-19 infection with no previous audio-vestibular disorders. Clinical data on the infections were collected, and an audiological assessment of all affected children was performed by using different diagnostic protocols according to their age. Results: Fever, upper respiratory and gastrointestinal manifestations were common presentations of infection. Audiological function was normal in 30 (81.08%) children, while 7 children showed an increased hearing threshold: 6 (16.21%) had transient conductive hearing loss (CHL) due to middle ear effusion and normalized at the follow-up and 1 had sensorineural hearing loss (SNHL). A single child was affected by bilateral SNHL (2.7%); however, he underwent a complete audiological work-up leading to a diagnosis of genetic HL due to a MYO6 gene mutation which is causative of progressive or late onset SNHL. Conclusions: HL needs to be considered among the manifestations of COVID-19 in children, nevertheless, we found cases of transient CHL. The onset of HL during or following COVID-19 infection does not eliminate the indication for maintaining audiological surveillance and audiological work-ups, including genetic diagnosis, to avoid the risk of mistaking other causes of HL.

Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature. Methods: Subjects under 90 days of age admitted to 35 Italian institutions for COVID-19 were included. The severity of COVID-19 was scored as mild/moderate or severe/critical following the classification reported in the literature by Venturini, Dong, Kanburoglu, and Gale. To assess the diagnostic accuracy of each classification system, we stratified all enrolled patients developing a posteriori severity score based on clinical presentation and outcomes and then compared all different scores analyzed. Results: We included 216 infants below 90 days of age. The most common symptom was fever, followed by coryza, poor feeding, cough, and gastrointestinal manifestations. According to Venturini, Dong, Kanburoglu, and Gale’s severity scores, 18%, 6%, 4.2%, and 29.6% of infants presented with severe/critical disease, respectively. A correlation analysis between these four scores and the a posteriori severity score assigned to all enrolled subjects was performed, and a crescent strength of correlation from Gale (R = 0.355, p < 0.001) to Venturini (R = 0.425, p < 0.001), Dong (R = 0.734, p < 0.001), and Kanburoglu (R = 0.859, p < 0.001) was observed. Conclusions: The percentage of infants with severe COVID-19 varies widely according to the score systems. A unique clinical score should be designed for neonates and infants with COVID-19.

Cu nanoparticles were produced by using solid-state dewetting (dry) of a 1.3 nm Cu layer or laser ablation of a Cu solid target (wet) in acetone and methanol. The morphology and chemical composition of the nanoparticles were investigated as a function of the synthesis methods and their key parameters of the annealing temperature (200–500 °C) and the liquid environment during the ablation. Cu nanoparticles were then embedded in transparent conductive oxide (TCO) films as aluminum-doped zinc oxide (AZO) or zirconium-doped indium oxide (IZrO); the TCObott/Cu nanoparticle/TCOtop structures were synthesized with all combinations of AZO and IZrO as the top and bottom layers. The goal was to achieve a plasmonic and conductive structure for photovoltaic applications via a comparison of the involved methods and all fabricated structures. In particular, solid-state dewetting produced faceted or spherical (depending on the annealing temperature) nanoparticles with an average size below 150 nm while laser ablation produced spherical nanoparticles below 250 nm. Dry and wet plasmonic conductive structures as a function of the TCOs employed and the temperature of annealing could reach a sheet resistance of 86 Ω/sq. The energy band-gap Egap, absorbance, transmittance, and reflectance of the plasmonic conductive structures were investigated in the UV–vis–NIR range. They showed a dependence on the sequence of the top and bottom TCO, with best transmittances of 89.4% for the dry plasmonic conductive structure and 84.7% for the wet plasmonic conductive structure. The latter showed a higher diffused transmittance of between 10–20% in the visible range.

Introduction: The transmission rates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from children to adults are unclear due to a lack of controlled conditions.Materials and Methods: We investigated the occurrence of SARS-CoV-2 transmission among 12 discordant child-parent pairs in our ward. In each hospital isolation room, caregivers and children lived in close contact during the entire hospitalization period.Results: A total of 136 swab-positive children (mean age, 3.6 ± 4.9 median age, 1; IQR 0–6.2, range 0.1–17) attended by their caregivers were hospitalized. Of those, 12/136 (8.8%, mean age, 6.1 ± 5.3 median age, 4.5) were attended by caregivers who were swab and serology negative at admission despite previous close contact with positive children at home. Three children were completely dependent on their mothers, one of whom was being breastfed. The mean duration of overall exposure to the index case was 20.5 ± 8.2 days.Conclusion: None of the infected children transmitted SARS-CoV-2 infection to their caregivers, raising the hypothesis of a cluster of resistant mothers or of limited transmission from children to adults despite prolonged exposure and close contact. These data might provide reassurance regarding school openings and offer the chance of investigating SARS-CoV-2 variants in the future under the same quasi-experimental conditions.

Despite the implementation of widespread vaccination programs, the European Health Systems continue to experience care challenges attributable to organizational and structural issues. This study aimed to review the available data on aspects within the organizational and structural domains that might impact vaccination coverage. We searched a comprehensive range of databases from 1 January 2007 to 6 July 2021 for studies that reported quantitative or qualitative research on interventions to raise childhood vaccine coverage. Outcome assessments comprised organizational and structural factors that contribute to vaccine concern among pediatric parents, as well as data reported influencing the willingness to vaccinate. To analyze the risk of bias, the Ottawa, JBI’s (Joanna Briggs Institute) critical appraisal tool, and Amstar quality assessment were used accordingly. The inclusion criteria were met by 205 studies across 21 articles. The majority of the studies were conducted in the United Kingdom (6), the European Union (3), and Italy (3). A range of interventions studied in primary healthcare settings has been revealed to improve vaccination coverage rates including parental engagement and personalization, mandatory vaccination policies, program redesign, supply chain design, administering multiple/combination vaccines, improved vaccination timing and intervals, parental education and reminders, surveillance tools and Supplemental Immunisation Activity (SIA), and information model.

The transport of particulate by wind constitutes a relevant phenomenon in environmental sciences and civil engineering, because erosion, transport and deposition of particulate can cause serious problems to human infrastructures. From a mathematical point of view, modeling procedure for this phenomenon requires handling the interaction between different constituents, the transfer of a constituent from the air to the ground and viceversa, and consequently the ground-surface interaction and evolution. Several approaches have been proposed in the literature, according to the specific particulate or application. We here review these contributions focusing in particular on the behavior of sand and snow, which almost share the same mathematical modeling issues, and point out existing links and analogies with wind driven rain. The final aim is then to classify and analyze the different mathematical and computational models in order to facilitate a comparison among them. A first classification of the proposed models can be done distinguishing whether the dispersed phase is treated using a continuous or a particle-based approach, a second one on the basis of the type of equations solved to obtain particulate density and velocity, a third one on the basis of the interaction model between the suspended particles and the transporting fluid.

A surgical site infection (SSI) is an infection that occurs in the incision created by an invasive surgical procedure. Although most infections are treatable with antibiotics, SSIs remain a significant cause of morbidity and mortality after surgery and have a significant economic impact on health systems. Preventive measures are essential to decrease the incidence of SSIs and antibiotic abuse, but data in the literature regarding risk factors for SSIs in the pediatric age group are scarce, and current guidelines for the prevention of the risk of developing SSIs are mainly focused on the adult population. This document describes the current knowledge on risk factors for SSIs in neonates and children undergoing surgery and has the purpose of providing guidance to health care professionals for the prevention of SSIs in this population. Our aim is to consider the possible non-pharmacological measures that can be adopted to prevent SSIs. To our knowledge, this is the first study to provide recommendations based on a careful review of the available scientific evidence for the non-pharmacological prevention of SSIs in neonates and children. The specific scenarios developed are intended to guide the healthcare professional in practice to ensure standardized management of the neonatal and pediatric patients, decrease the incidence of SSIs and reduce antibiotic abuse.

Ocular surgery encompasses a wide range of procedures, including surgery of the tear ducts, eyelid, cornea and conjunctiva, lens, ocular muscle, and vitreoretinal and iris surgery. Operations are also performed for the removal of tumors, repairs of ocular trauma and, finally, corneal transplantation. Antibiotic prophylaxis for the prevention of surgical site infections (SSIs) in ocular surgery is a complex field in which shared lines of action are absent. In light of the scarcity of shared evidence in the use of ocular antimicrobial prophylaxis for the pediatric population, this consensus document aims to provide clinicians with a series of recommendations on antimicrobial prophylaxis for patients of neonatal and pediatric age undergoing eye surgery. The following scenarios are considered: (1) intraocular surgery; (2) extraocular surgery; (3) ocular trauma; (4) ocular neoplasm; (5) ocular surface transplantations; (6) corneal grafts. 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 regarding clinical actions in the peri-operative environment in eye surgery. The application of uniform and shared protocols aims to improve surgical practice, through the standardization of procedures, with a consequent reduction of SSIs, also limiting the phenomenon of antimicrobial resistance.

Surgical site infections (SSIs) represent a potential complication of surgical procedures, with a significant impact on mortality, morbidity, and healthcare costs. Patients undergoing cardiac surgery and thoracic surgery are often considered patients at high risk of developing SSIs. This consensus document aims to provide information on the management of peri-operative antibiotic prophylaxis for the pediatric and neonatal population undergoing cardiac and non-cardiac thoracic surgery. The following scenarios were considered: (1) cardiac surgery for the correction of congenital heart disease and/or valve surgery; (2) cardiac catheterization without the placement of prosthetic material; (3) cardiac catheterization with the placement of prosthetic material; (4) implantable cardiac defibrillator or epicardial pacemaker placement; (5) patients undergoing ExtraCorporal Membrane Oxygenation; (6) cardiac tumors and heart transplantation; (7) non-cardiac thoracic surgery with thoracotomy; (8) non-cardiac thoracic surgery using video-assisted thoracoscopy; (9) elective chest drain placement in the pediatric patient; (10) elective chest drain placement in the newborn; (11) thoracic drain placement in the trauma setting. This consensus provides clear and shared indications, representing the most complete and up-to-date collection of practice recommendations in pediatric cardiac and thoracic surgery, in order to guide physicians in the management of the patient, standardizing approaches and avoiding the abuse and misuse of antibiotics.

For many years, it was clearly shown that surgical procedures might be associated with surgical site infection (SSI). Many scientific institutions prepared guidelines to use in surgery to reduce abuse and misuse of antibiotics. However, in the general guidelines for surgical antibiotic prophylaxis, plastic surgical procedures are not addressed or are only marginally discussed, and children were almost systematically excluded. The main aim of this Consensus document is to provide clinicians with recommendations on antimicrobial prophylaxis for pediatric patients undergoing plastic surgery. The following scenarios were considered: clean plastic surgery in elective procedures with an exclusive skin and subcutis involvement; clean-contaminated/contaminated plastic surgery in elective procedures with an exclusive skin and subcutis involvement; elective plastic surgery with use of local flaps; elective plastic surgery with the use of grafts; prolonged elective plastic surgery; acute burns; clean contused lacerated wounds without bone exposure; high-risk contused lacerated wounds or with bone exposure; contused lacerated wound involving the oral mucosa; plastic surgery following human bite; plastic surgery following animal bite; plastic surgery with tissue expander insertion. Our Consensus document shows that antimicrobial perioperative prophylaxis in pediatric patients undergoing plastic surgery is recommended in selected cases. While waiting the results of further pediatric studies, the application of uniform and shared protocols in these procedures will improve surgical practice, with a reduction in SSIs and consequent rationalization of resources and costs, as well as limiting the phenomenon of antimicrobial resistance.

Background: Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear and optimal treatment is debated. The objective of our study was to investigate epidemiological, clinical and therapeutic characteristics of pediatric SARS-CoV-2 infection, focusing on risk factors for complicated and critical disease.Methods: The present multicenter Italian study was promoted by the Italian Society of Pediatric Infectious Diseases, involving both pediatric hospitals and general pediatricians/family doctors. All subjects under 18 years of age with documented SARS-CoV-2 infection and referred to the coordinating center were enrolled from March 2020.Results: As of 15 September 2020, 759 children were enrolled (median age 7.2 years, IQR 1.4; 12.4). Among the 688 symptomatic children, fever was the most common symptom (81.9%). Barely 47% of children were hospitalized for COVID-19. Age was inversely related to hospital admission (p < 0.01) and linearly to length of stay (p = 0.014). One hundred forty-nine children (19.6%) developed complications. Comorbidities were risk factors for complications (p < 0.001). Viral coinfections, underlying clinical conditions, age 5–9 years and lymphopenia were statistically related to ICU admission (p < 0.05).Conclusions: Complications of COVID-19 in children are related to comorbidities and increase with age. Viral co-infections are additional risk factors for disease progression and multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) for ICU admission.

Primary CNS tumors are the leading cause of cancer-related death in pediatrics. It is essential to understand treatment trends to interpret national survival data. In Canada, children with CNS tumors are treated at one of 16 tertiary care centers. We surveyed pediatric neuro-oncologists to create a national standard of practice to be used in the absence of a clinical trial for seven of the most prevalent brain tumors in children. This allowed description of practice across the country, along with a consensus. This had a multitude of benefits, including understanding practice patterns, allowing for a basis to compare in future research and informing Health Canada of the current management of patients. This also allows all children in Canada to receive equivalent care, regardless of location.

Surgical site infections (SSIs), which are a potential complications in surgical procedures, are associated with prolonged hospital stays and increased postoperative mortality rates, and they also have a significant economic impact on health systems. Data in literature regarding risk factors for SSIs in pediatric age are scarce, with consequent difficulties in the management of SSI prophylaxis and with antibiotic prescribing attitudes in the various surgical procedures that often tend to follow individual opinions. The lack of pediatric studies is even more evident when we consider surgeries performed in subjects with underlying conditions that may pose an increased risk of complications. In order to respond to this shortcoming, we developed a consensus document to define optimal surgical antimicrobial prophylaxis (SAP) in neonates and children with specific high-risk conditions. These included the following: (1) colonization by methicillin-resistant Staphylococcus aureus (MRSA) and by multidrug resistant (MDR) bacteria other than MRSA; (2) allergy to first-line antibiotics; (3) immunosuppression; (4) splenectomy; (5) comorbidity; (6) ongoing antibiotic therapy or prophylaxis; (7) coexisting infection at another site; (8) previous surgery in the last month; and (9) presurgery hospitalization lasting more than 2 weeks. This work, made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies, represents, in our opinion, the most up-to-date and comprehensive collection of recommendations relating to behaviors to be undertaken in a perioperative site in the presence of specific categories of patients at high-risk of complications during surgery. The application of uniform and shared protocols in these high-risk categories will improve surgical practice with a reduction in SSIs and consequent rationalization of resources and costs, as well as being able to limit the phenomenon of antimicrobial resistance.

Surgical site infections (SSIs), i.e., surgery-related infections that occur within 30 days after surgery without an implant and within one year if an implant is placed, complicate surgical procedures in up to 10% of cases, but an underestimation of the data is possible since about 50% of SSIs occur after the hospital discharge. Gastrointestinal surgical procedures are among the surgical procedures with the highest risk of SSIs, especially when colon surgery is considered. Data that were collected from children seem to indicate that the risk of SSIs can be higher than in adults. This consensus document describes the use of preoperative antibiotic prophylaxis in neonates and children that are undergoing abdominal surgery and has the purpose of providing guidance to healthcare professionals who take care of children to avoid unnecessary and dangerous use of antibiotics in these patients. The following surgical procedures were analyzed: (1) gastrointestinal endoscopy; (2) abdominal surgery with a laparoscopic or laparotomy approach; (3) small bowel surgery; (4) appendectomy; (5) abdominal wall defect correction interventions; (6) ileo-colic perforation; (7) colorectal procedures; (8) biliary tract procedures; and (9) surgery on the liver or pancreas. Thanks to the multidisciplinary contribution of experts belonging to the most important Italian scientific societies that take care of neonates and children, this document presents an invaluable reference tool for perioperative antibiotic prophylaxis in the paediatric and neonatal populations.

Limited data on the coagulation profile in children affected by the SARS-CoV-2 infection are available. We aimed to evaluate the role of d-dimers as predictors of poor outcomes in a pediatric population affected by the SARS-CoV-2 infection or multisystem inflammatory syndrome (MIS-C). We performed a retrospective cross-sectional multicenter study. Data from four different centers were collected. Laboratory tests, when performed, were collected at the time of diagnosis, and 24, 48, 72, 96, 120 and beyond 120 h from diagnosis; blood counts with formula, an international normalized ratio (INR), activated partial thromboplastin time (aPTT), D-dimers and fibrinogen values were collected. Data regarding clinical history, management and outcome of the patients were also collected. Three hundred sixteen patients with a median age of 3.93 years (IQR 0.62–10.7) diagnosed with COVID-19 or MIS-C were enrolled. Fifty-eight patients (18.3%) showed a severe clinical outcome, 13 (4.1%) developed sequelae and 3 (0.9%) died. The univariate analysis showed that age, high D-dimer values, hyperfibrinogenemia, INR and aPTT elongation, and low platelet count were associated with an increased risk of pediatric intensive care unit (PICU) admission (p < 0.01). Three multivariate logistic regressions showed that a d-dimer level increase was associated with a higher risk of PICU admission. This study shows that D-dimer values play an important role in predicting the more severe spectrum of the SARS-CoV-2 infection, and was higher also in those that developed sequelae, including long COVID-19.

Surgical site infections (SSIs) represent a potential complication in any type of surgery and can occur up to one year after the procedure in the case of implant placement. In the field of orthopedic and hand surgery, the rate of SSIs is a relevant issue, considering the need for the placement of synthesis devices and the type of some interventions (e.g., exposed fractures). This work aims to provide guidance on the management of peri-operative antibiotic prophylaxis for the pediatric and neonatal population undergoing orthopedic and hand surgery in order to standardize the management of patients and to reduce, on the one hand, the risk of SSI and, on the other, the development of antimicrobial resistance. The following scenarios were considered: (1) bloodless fracture reduction; (2) reduction of unexposed fracture and grade I and II exposed fracture; (3) reduction of grade III exposed fracture or traumatic amputation; (4) cruel fracture reduction with percutaneous synthesis; (5) non-traumatic amputation; (6) emergency intact skin trauma surgery and elective surgery without synthetic media placement; (7) elective orthopedic surgery with prosthetic and/or synthetic media placement and spinal surgery; (8) clean elective hand surgery with and without bone involvement, without use of synthetic means; (9) surgery of the hand on an elective basis with bone involvement and/or with use of synthetic means. This manuscript 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 regarding the behavior to be adopted in the peri-operative setting in neonatal and pediatric orthopedic and hand surgery. The specific scenarios developed are aimed at guiding the healthcare professional in practice to ensure the better and standardized management of neonatal and pediatric patients, together with an easy consultation.

Objective: Clinical and psychological HIV-related problems peak during adolescence, which coincides with transition of children and adolescents infected from mothers from pediatric to adult reference centers for HIV infection. Transition often is done without specific programs. We wanted to explore transition as an opportunity to increase the efficacy of care and the psychological well-being through a specific program.Methods: Thirteen vertically infected patients aged 13–20 years were followed up for 24 months by pediatricians, infectious disease specialists, a psychologist, and a nurse. Interventions consisted in joint clinic, simplification of therapy, patient group discussions, HIV infection explanations, and psychological support, lasting 12 months. Efficacy was measured by viro-immunological outcomes and adherence to therapy and psychological tests. Clinical, viro-immunological, and psychological evaluations were performed at 0 (T0) and 12 months (T12) and 6 months after transition to an adult center (T18). Psychological outcomes were assessed using standardized questionnaires for quality of life and self-esteem.Results: In 11/13 participants, pills administrations/day were significantly reduced. Patients with undetectable viral load and CD4+ >25% increased from 61 to 77% and from 61 to 74%, respectively. Six months after transition, all patients exhibited an undetectable viral load. Adolescents' awareness of the severity of the disease and the risk of sexual transmission was generally poor. Patients classified with “severe” psychological distress according to the quality of life index decreased from 38 to 15% and well-being increased. Similar results were observed 6 months after the transition to adult care. No effect was observed on self-esteem index.Conclusions: Specific protocols for transition should be developed to optimize resilience and psychological well-being, including routine psychological support for adolescents with HIV infection transiting from pediatric to adult centers for HIV infection.

Abstract Background Treatment of HIV infection in adolescents is challenging due to long duration of therapy and poor adherence. Recently, the integrase strand transfer inhibitor dolutegravir (DTG) has been approved for the use in adolescents with HIV, but evidence in clinical practice is very limited. Methods We describe six cases of HIV-infected children/adolescents successfully treated with DTG-based regimen. Data relative to children/adolescents managed at the Referral Center for Pediatric HIV/AIDS of the University of Naples were reviewed. Patients were tested before introduction of DTG, after 1 month and every 3 months in the first 2 years to assess virologic and immunological response, tolerance and development of side effects. Families were asked to report any suspected adverse events. Results Six patients (2 male, median age 17 years, range 12–18) were started on DTG-based anti-retroviral regimen due to low adherence to anti-retroviral treatment (ART), multiple drug resistance mutations, or development of ART-related side effects. Within 4–8 weeks after DTG treatment onset, a complete viral suppression and a concomitant increase of CD4+ cell count was observed. Four patients showed a persistent suppression after 2 years of follow-up, and 2 patients at about 1 year. One month after the introduction of DTG, the patient enrolled because of severe dyslipidaemia and hyper-transaminasemia showed a complete normalization of laboratory values. During follow-up (median 24 months, range 9–24) no adverse events were reported and most patients demonstrated a good adherence to treatment. Conclusions DTG-based treatments demonstrated efficacy and good safety profile in adolescents. All patients demonstrated a rapid virologic and immunological response within 4–8 weeks, with good adherence and absence of side effects.

Thanks to the advances in antiretroviral therapies (ART) and early diagnosis, pediatric HIV has turned into a chronic infection that requires the collaboration of all pediatric subspecialists for holistic patient management. Gastrointestinal complaints are a frequent reason for seeking access to medical care in all pediatric patients worldwide. Intestinal involvement is present in virtually all children with HIV infections. In high-prevalence settings, up to 25% of children accessing the hospital for diarrhea are diagnosed with HIV. More than half of patients with advanced disease present with gastrointestinal symptoms, from mild infectious diarrhea to severe gastrointestinal impairment, malabsorption and failure to thrive. Gastrointestinal disorders do not spare children on ART, particularly in the initial months of therapy. ART-associated pancreatitis and hepatitis are rare but potentially severe adverse events, whereas lower abdominal symptoms have been reported in more than a third of patients. The latter are usually mild and transient, but may limit ART adherence; a correct framing of the problem is necessary to minimize therapy switches while optimizing the quality of life of children on ART. This review aims to provide state-of-the-art guidance for the initial approach to gastrointestinal diseases in children living with HIV.

Introducción: Las reintervenciones en las arterias coronarias siempre representan un gran desafío para todo el equipo quirúrgico. Muy a menudo, el único injerto permeable es la arteria mamaria interna izquierda conectada a la arteria descendente anterior, y es el que mantiene vivo al paciente. En estas condiciones, la re-esternotomía puede originar un episodio catastrófico. Por esta razón, muchos abordajes alternativos han sido propuestos para minimizar este riesgo y mejorar los resultados operatorios. No solo se debe considerar el abordaje, sino también un conjunto de medidas preventivas que representan una estrategia especial que ameritan estos pacientes, generalmente de edad avanzada con patologías asociadas, que comprometen tanto el acto quirúrgico como el curso postoperatorio. Material y métodos: Presentamos nuestra experiencia desde 2003 hasta 2015 de 95 pacientes sometidos a reintervención coronaria evitando la re-esternotomía en todos ellos mediante abordaje por toracotomía izquierda, toracotomía derecha o subxifoideo, con uso de balón intraaórtico profiláctico, máquina de autotransfusión, cirugía sin circulación extracorpórea, no manipulación de la aorta y mínima manipulación del corazón. Resultados: La mortalidad operatoria fue de solo el 1,05%, permitiendo la recuperación rápida y el egreso precoz de la mayoría de los pacientes.

Childhood tuberculosis (TB) indicates a recent infection, particularly in children aged

An amendment to this paper has been published and can be accessed via the original article.

Abstract The Glenn operation involving anastomosis of the superior vena cava to the pulmonary artery has been performed for palliative operations of many cyanotic congenital heart diseases in addition to the single ventricle since the 1960s. The classic procedure is done via median sternotomy and cardiopulmonary bypass. The benefits of this procedure without the use of cardiopulmonary bypass remain mixed within reported series. Cases using this approach and off-pump technique together in Latin-America have not yet been reported in the scientific literature.

Objective: To assess the impact of Clostridium difficile infection (CDI) on hospital resources and costs in Spain and Italy. Methods: CDI data were collected from institutions in Spain and Italy. Each patient was matched with two randomly selected uninfected controls in the same institution. Patient outcomes were assessed for the first and second episodes of CDI and for patients aged ≤65 and >65 years. The impact of CDI on hospital length of stay (LOS) was used to calculate CDI-attributable costs. A multivariate analysis using duration of stay as the continuous outcome variable assessed the independent effect of CDI on hospital costs and LOS. Results: LOS attributable to CDI ranged from 7.6–19.0 days in adults and was 5.0 days in children; the increases were greater in adults in Italy than in Spain. Attributable costs per adult patient ranged from €4396 in Madrid to €14 023 in Rome, with the majority of the cost being due to hospitalization. For children, the total attributable cost was €3545/patient. Conclusions: These data show that the burden of CDI is considerable in Spain and Italy. Treatments that can reduce LOS, disease severity, and recurrence rates, as well as effective infection control measures to prevent transmission, have the potential to reduce the burden of CDI.

A case of visceral disseminated infection by Mycobacterium sherrisii in an African HIV-infected adolescent with multiple abdominal abscesses is reported. Despite multiple drug resistance to first-line antibiotics in vitro, long-term treatment with clarithromycin, moxifloxacin, and clindamycin, together with appropriate antiretroviral treatment, resulted in clinical and radiological cure after 19 months of therapy and follow-up.