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Background: Respiratory syncytial virus (RSV) infection in children under 5 years have a significant clinical burden, also in primary care settings. This study investigates the epidemiology and burden of RSV in Italian children during the 2019/20 pre-pandemic winter season., Methods: A prospective cohort study was conducted in two Italian regions. Children with Acute Respiratory Infection (ARI) visiting pediatricians were eligible. Nasopharyngeal swabs were collected and analyzed via multiplex PCR for RSV detection. A follow-up questionnaire after 14 days assessed disease burden, encompassing healthcare utilization and illness duration. Statistical analyses, including regression models, explored associations between variables such as RSV subtype and regional variations., Results: Of 293 children with ARI, 41% (119) tested positive for RSV. Median illness duration for RSV-positive cases was 7 days; 6% required hospitalization (median stay: 7 days). Medication was prescribed to 95% (110/116) of RSV cases, with 31% (34/116) receiving antibiotics. RSV subtype B and regional factors predicted increased healthcare utilization. Children with shortness of breath experienced a 36% longer illness duration., Conclusions: This study highlights a significant clinical burden and healthcare utilization associated with RSV in pre-pandemic Italian primary care settings. Identified predictors, including RSV subtype and symptomatology, indicate the need for targeted interventions and resource allocation strategies. RSV epidemiology can guide public health strategies for the implementation of preventive measures., (© 2024. The Author(s).)

Background: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts., Methods: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression., Results: M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2., Conclusions: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification., (Copyright © 2024 by the American Society of Nephrology.)

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., (© 2023. Società Italiana di Pediatria.)

Purpose: Paediatric obesity is a well-known risk factor for metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate the effects of laparoscopic sleeve gastrectomy (LSG) on the levels of total homocysteine (tHcy) and total glutathione (tGSH) plasma levels in children with MAFLD., Material and Methods: Twenty-four children with severe obesity who underwent LSG were included in the study. The metabolic parameters, systemic inflammatory markers, one-carbon metabolism products, ultrasound and histological improvement were evaluated at baseline (T0M) and after 12 months from LSG (T12M)., Results: The patients exhibited a significant amelioration of several metabolic parameters at T12M. A significant reduction of steatosis was observed at ultrasound (from 72.7% of moderate-severe grade to 0% severe steatosis), accompanied by a statistically significant improvement of ballooning, portal and lobular inflammation and fibrosis. A statistically significant decrease of tumour necrosis factor circulating levels was also observed (T0M median = 290.3, IQR = 281.0-317.0 pg/mL; T12M median = 260.4, IQR = 240.0-279.0 pg/mL; p < 0.0001). After 12 months from LSG, a significant increase of mean plasma levels of tHcy(T0M mean = 15.7 ± 4.1 μmol/L; T12M mean = 21.1 ± 9.3 μmol/L; p = 0.0146) was also observed. The increase of tHcy showed no causal link with the improvement of MAFLD-related inflammatory, metabolic and histological pattern., Conclusion: LSG in children with obesity induces an improvement of MAFLD-related metabolic derangement and liver damage, but also a mild hyperhomocysteinemia that should be avoided to prevent cardiovascular risk., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A comprehensive understanding of the microbiome-host relationship in respiratory diseases can be elucidated by exploring the landscape of virome-bacteriome-host metabolome data through unsupervised 'multi-omics' approaches. Here, we describe how the composition and function of airway and gut virome and bacteriome may contribute to pathogen establishment and propagation in airway districts and how the virome-bacteriome communities may react to respiratory diseases. A new systems medicine approach, including the characterization of respiratory and gut microbiome, may be crucial to demonstrate the likelihood and odds of respiratory disease pathophysiology, opening new avenues to the discovery of a chain of causation for key bacteria and viruses in disease severity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: In December 2019, a novel coronavirus named SARS-CoV-2 started circulating in China and this led to a major epidemic in Northern Italy between February and May 2020. Young children (aged <5 years) seem to be less affected by this coronavirus disease (COVID-19) compared to adults, although there is very little information on the circulation of this new virus among children in Italy. We retrospectively tested nasopharyngeal swabs for SARS-CoV-2 in samples collected in young children between November, 2019 and March, 2020 in the context of the RSV ComNet study. Methods: Two networks of primary care pediatricians in Lazio (Central Italy) and Puglia (Southern Italy) collected nasopharyngeal swabs from children, aged <5 years, presenting with symptoms for an acute respiratory infection (ARI). The RSV ComNet study is a multicenter study implemented to estimate the burden of RSV in young children (aged <5 years) in the community. Swabs were sent to a central reference laboratory and tested for 14 respiratory viruses through RT-PCR. All collected samples were retrospectively tested for SARS-CoV-2 using RT-PCR (Istituto Superiore di Sanità protocol). Results: A total of 293 children with ARI were identified in the two participating networks. The highest number of cases were recruited in weeks 51/2019 and 3/2020. The majority of patients (57%) came from the Lazio region. All of the 293 samples tested negative for SARS-Cov2. Rhinovirus was the most frequently detected virus (44%), followed by RSV (41%) and influenza viruses (14%). Conclusions: Our study shows that in Lazio (a region of intermediate SARS-COV-2 incidence) and Puglia (a region of low incidence), the SARS-Cov2 virus did not circulate in a sample of ARI pediatric cases consulting primary care pediatricians between November 2019 and March 2020., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rizzo, Loconsole, Pandolfi, Ciofi Degli Atti, van Summeren, Paget, Russo, Campagna, Croci, Gesualdo, Concato, Linardos, Bartolucci, Ciampini, Muda, Raponi and Chironna.)

Background: In Italy, the response to coronavirus disease 2019 (COVID-19) pandemic upgraded from social distancing on February 23, 2020, to national lockdown on March 11, 2020. We described how the pandemic affected a tertiary care children hospital with a dedicated COVID-19 regional center., Methods: We analyzed the characteristics of emergency department (ED) visits, urgent hospitalizations and severe acute respiratory syndrome (SARS)-COV-2 reverse transcription-polymerase chain reaction testing, and COVID-19 patients across 3 response phases: before the first Italian case, before national lockdown and during lockdown., Results: ED visits decreased from a daily mean of 239.1 before the first COVID-19 Italian case, to 79.6 during lockdown; urgent hospitalizations decreased from 30.6 to 21.2. As of April 20, 2020, 1970 persons were tested for SARS-CoV-2 reverse transcription-polymerase chain reaction and 2.6% were positive. Positive rates were 1.2% in the ED, 21.1% in the COVID center and 0.5% in other wards. The median age of COVID-19 patients (N = 33) was 6.7 years, 27% had coexisting conditions and 79% were related to family clusters., Conclusions: The pandemic strongly impacted on the use of hospital services, with a 67% reduction in ED visits and a 31% reduction in urgent hospitalizations. Separating the flows of suspected patients from all other patients, and centralization of suspected and confirmed cases in the COVID center enabled to control the risk of nosocomial SARS-CoV-2 transmission. Delay in hospital use for urgent care must be avoided, and clear communication on infection prevention and control must be provided to families. Further studies are needed to assess how the reduction in hospital use affected children healthcare needs during the pandemic.

Background: The expression of human equilibrative nucleoside transporter 1 (hENT1), the major gemcitabine transporter into cells, has been thoroughly investigated as a predictive marker of response to gemcitabine in pancreatic cancer and biliary tract cancers. Since gemcitabine is widely used in the treatment of leiomyosarcoma and angiosarcoma, we investigated the correlation between hENT1 expression and gemcitabine efficacy in these sarcoma subtypes., Methods: We retrospectively identified 71 patients affected by advanced angiosarcoma (26) or leiomyosarcoma (45) treated within five Italian referral centres for sarcoma; among them, 49 patients (15 angiosarcoma, 34 leiomyosarcoma) were treated with gemcitabine. All tumour samples were analysed for hENT1 expression by real-time PCR. Median 2 -ΔCt value was used as the cutoff to dichotomise patients into 'high' expression and 'low' expression groups. Kaplan-Meier analysis was performed to estimate progression-free survival (PFS) and overall survival (OS)., Results: We found a significant association between high hENT1 expression levels and favourable outcome in terms of PFS and OS compared to cases with low hENT1 expression in leiomyosarcoma treated with gemcitabine (PFS: 6.8 vs 3.2 months, P=0.004; OS: 14.9 vs 8.5 months, P=0.007). In addition, hENT1 overexpression correlated with a significant improvement in PFS (9.3 vs 4.5 months; P=0.02) and OS (20.6 vs 10.8 months; P=0.001) in angiosarcoma patients treated with gemcitabine., Conclusions: Our study suggests that higher hENT1 expression are associated to gemcitabine efficacy both in patients with advanced leiomyosarcoma and angiosarcoma.

Background: In the cetuximab after progression in KRAS wild-type colorectal cancer patients (CAPRI) trial patients with metastatic colorectal cancer (mCRC) received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) and cetuximab in first line followed by 5-Fluorouracil, folinic acid, oxaliplatin (FOLFOX) with or without cetuximab until progression. Limited data are available on the efficacy and safety of anti-epidermal growth factor receptor (anti-EGFR) agents on elderly patients with mCRC. In the current study we evaluated the efficacy and safety of FOLFIRI plus cetuximab in age-defined subgroups., Methods: A post-hoc analysis was performed in CAPRI trial patients; outcomes (progression-free survival (PFS), overall response rate (ORR), safety) were analysed by age-groups and stratified according to molecular characterisation. 3 age cut-offs were used to define the elderly population (≥65; ≥70 and ≥75 years)., Results: 340 patients with mCRC were treated in first line with FOLFIRI plus cetuximab. Among those, 154 patients were >65 years, 86 >70 years and 35 >75 years. Next-generation sequencing (NGS) was performed in 182 patients. Among them, 87 patients were >65 years, 46 >70 and 17 >75. 104 of 182 patients were wild type (WT) for KRAS, NRAS, BRAF, PIK3CA genes. In the quadruple WT group, 51 patients were ≥65 years; 29 were ≥70; 9 were ≥75. Median PFS was similar within the age-subgroups in the intention-to-treat population, NGS cohort and quadruple WT patients, respectively. Likewise, ORR was not significantly different among age-subgroups in the 3 populations. Safety profile was acceptable and similarly reported among all age-groups, with the exception of grade ≥3 diarrhoea (55% vs 25%, p=0.04) and neutropaenia (75% vs 37%, p=0.03) in patients ≥75 years and grade ≥3 fatigue (31% vs 20%, p=0.01) in patients <75 years., Conclusions: Tolerability of cetuximab plus FOLFIRI was acceptable in elderly patients. Similar ORR and PFS were observed according to age-groups. No differences in adverse events were reported among the defined subgroups with the exception of higher incidence of grade ≥3 diarrhoea and neutropaenia in patients ≥75 years and grade ≥3 fatigue in patients <75 years., Trial Registration Number: 2009-014041-81., Competing Interests: Competing interests: None declared.

Objectives: R1 resection rate after pancreaticoduodenectomy (PD) for cancer is highly variable. The aim of this study was to verify if a standardized histopathological work-up of the specimen affects the rate of R1 resection after PD for cancer., Methods: Two groups of specimens were managed with (standardized method [SM] group) or without (non-standardized method [NSM] group) a SM of histopathological work-up. Each group included 50 cases of PD for periampullary cancer. Differences in terms of R1 resection rate between the 2 groups were evaluated. Correlation between R1 status and local recurrence was also evaluated., Results: The cohort of 100 patients consisted of 66 pancreatic ductal adenocarcinoma, 15 cholangiocarcinoma, and 19 ampullary cancer. The R1 resection rate resulted statistically higher in the SM group (66% vs 10%). Local recurrence was more frequently related to R1 resection in the SM group (34.3% of cases) than in NSM group (20% of cases)., Conclusions: The use of the SM of pathological evaluation of the specimen after PD for cancer determines a significant increase of R1 resection. This remarkable difference seems to be due to the different definition of minimum clearance. The SM seems to better discriminate patients in terms of risk of local recurrence.

Objective: To evaluate the effects of VEGF, BMP-7, Matrigel(TM), hyaluronic acid, in vitro cultured chondrocytes and trephination to promote and enhance the healing process of avascular meniscal tears in an animal model., Methods: A longitudinal tear was produced in the inner avascular part of the meniscus of 24 sheeps. Each tear was treated with trephination technique and suture. The animals were divided into 6 groups to receive a different treatment: control (I); VEGF, BMP-7, Matrigel(TM), hyaluronic acid, in vitro cultured chondrocytes. At 8 weeks from surgery, meniscal samples were explanted and analyzed by histology, immunohistochemistry, and histomorphometry., Results: At the histological examination, Group IV and VI showed a partial closure of the meniscal lesion, whereas Group I, II, III, and V did not show any evidence of healing. In the group IV, the healed tissue represented the 22.95% of the lesion area. In the group VI, the healed tissue represented the 43.75% of the lesion area., Conclusions: Autologous chondrocytes and BMP-7 associated with trephination and suture techniques enhanced healing process of meniscal tears in the avascular inner third of the meniscus in ovine model.