Search

Andrea Casadei-Gardini,1 Francesco Montagnani,2 Chiara Casadei,1 Francesca Arcadipane,3 Kalliopi Andrikou,4 Deborah Aloi,5 Alessandra Anna Prete,6,7 Maria Giulia Zampino,8 Antonella Argentiero,9 Giuseppe Pugliese,4 Stefania Martini,10 Giuseppe Carlo Iorio,10 Mario Scartozzi,11 Massimiliano Mistrangelo,12 Lorenzo Fornaro,13 Paola Cassoni,14 Giorgia Marisi,15 Veronica Dell’Acqua,16 Paola Simona Ravenda,8 Sara Lonardi,6 Nicola Silvestris,7 Berardino De Bari,5 Umberto Ricardi,3 Stefano Cascinu,4 Pierfrancesco Franco91Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; 2Oncology Department, SOC Oncology, ASL (Health Local Authority), Biella, Italy; 3Department of Oncology, Radiation Oncology, AOU Città della Salute e della Scienza, Turin, Italy; 4Department of Hematology and Oncology, University of Modena and Reggio Emilia, Modena, Italy; 5Radiation Oncology Department, Centre Hospitalier Régional Universitaire “Jean Minjoz”, Besançon Cedex, France; 6Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto, IRCCS, Padua, Italy; 7Department of Radiological, Oncological and Pathological Sciences, Policlinico Umberto I University Hospital, Rome, Italy; 8Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy; 9Medical Oncology Unit, Cancer Institute Giovanni Paolo II, Bari, Italy; 10Department of Oncology, Radiation Oncology, University of Turin, Turin, Italy; 11Department of Medical Oncology, University of Cagliari, Cagliari, Italy; 12Department of Surgical Sciences, University of Turin, Turin, Italy; 13Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana University, Pisa, Italy; 14Department of Medical Sciences, Pathology Unit, University of Turin, Turin, Italy; 15Biosciences Laboratory, Istituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) IRCCS, Meldola, Italy; 16Department of Radiotherapy, IRCCS, European Institute of Oncology, Milan, ItalyBackground: In anal cancer, there are no markers nor other laboratory indexes that can predict prognosis and guide clinical practice for patients treated with concurrent chemoradiation. In this study, we retrospectively investigated the influence of immune inflammation indicators on treatment outcome of anal cancer patients undergoing concurrent chemoradiotherapy.Methods: All patients had a histologically proven diagnosis of squamous cell carcinoma of the anal canal/margin treated with chemoradiotherapy according to the Nigro’s regimen. Impact on prognosis of pre-treatment systemic index of inflammation (SII) (platelet x neutrophil/lymphocyte), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were analyzed.Results: A total of 161 consecutive patients were available for the analysis. Response to treatment was the single most important factor for progression-free survival (PFS) and overall survival (OS). At univariate analysis, higher SII level was significantly correlated to lower PFS (p

Prisco Piscitelli,1,2 Giovanni Iolascon,3 Alberto Argentiero,2 Giovanna Chitano,2 Cosimo Neglia,2 Gemma Marcucci,1 Manuela Pulimeno,2 Marco Benvenuto,2 Santa Mundi,2 Valentina Marzo,2 Daniela Donato,4 Angelo Baggiani,4 Alberto Migliore,5 Mauro Granata,6 Francesca Gimigliano,3 Raffaele Di Blasio,7 Alessandra Gimigliano,3 Lorenzo Renzulli,7 Maria Luisa Brandi,1 Alessandro Distante,2,4 Raffaele Gimigliano3,71University of Florence, Florence Italy; 2ISBEM Research Centre, Brindisi, Italy; 3Second University of Naples, Naples, Italy; 4University of Pisa, Pisa, Italy; 5Fatebenefratelli St Peter’s Hospital, Rome, Italy; 6St Filippo Neri Hospital, Rome, Italy; 7Casa di Cura Santa Maria del Pozzo, Somma Vesuviana, ItalyObjectives: As osteoporotic fractures are becoming a major health care problem in countries characterized by an increasing number of older adults, in this study we aimed to compare the incidence and costs of hip fragility fractures in Italian elderly people versus those of major cardiovascular diseases (strokes and acute myocardial infarctions [AMI]) occurring in the whole adult population.Methods: We analyzed hospitalization records maintained at the national level by the Italian Ministry of Health for the diagnosis of hip fractures (ICD-9-CM codes 820–821), AMI (code 410), hemorrhagic (codes 430, 431, 432) and ischemic strokes (codes 433–434), and TIA (code 435) between 2001–2005. Cost analyses were based on diagnosis-related groups.Results: The incidence of hip fractures in elderly people has increased (+12.9% between 2001 and 2005), as well as that of AMI (+20.2%) and strokes (hemorrhagic: +9.6%; ischemic: +14.7) occurring in the whole adult population; conversely, hospitalization due to TIA decreased by a rate of 13.6% between 2001 and 2005. In 2005, the hospital costs across the national health care system that were associated with hip fragility fractures in the elderly were comparable to those of strokes (both hemorrhagic and ischemic), which occurred in the whole Italian adult population. Moreover, these costs were higher than those generated by AMI and TIA. Rehabilitation costs following strokes reached about 3 billion Euros in 2005, but rehabilitative costs of hip fractures and AMI were comparable (about 530 million Euros in 2005).Conclusion: The burden of hip fragility fractures in Italy is comparable to that of AMI and strokes.Keywords: hip fractures, strokes, acute myocardial infarction, incidence, hospital costs, rehabilitation costs

BackgroundThe use of Non-Pharmaceutical Interventions (NPIs) during the COVID-19 pandemic is debated. Understanding the consequences these measures may have on vulnerable populations including children and adolescents is important.MethodsThis is a multicenter, quasi-experimental before-after study involving 12 hospitals of the North Italian Emilia-Romagna Region, with NPI implementation as the intervention event. The 3 years preceding NPI implementation (in March 2020) constituted the pre-pandemic phase. The subsequent 2 years were further subdivided into a school closure phase (SC) and a subsequent mitigation measures phase (MM) with milder restrictions. Interrupted Time Series (ITS) regression analysis was used to calculate PED Standardized Incidence Rate Ratios (SIRR) on the diagnostic categories exhibiting the greatest frequency and/or variation.ResultsIn the 60 months of the study there were 765,215 PED visits. Compared to the pre-pandemic rate, overall PED presentations dropped by 58 and 39% during SC and MM, respectively. “Symptoms, signs and Ill-defined conditions,” “Injury and poisoning” and “Diseases of the Respiratory System” accounted for 74% of the reduction. A different pattern was instead seen for “Mental Disorders,” which exhibited the smallest decrease during SC, and is the only category which rose already at the end of SC. ITS analysis confirmed the strong decrease during SC (level change, IRR 0.17, 95%CI 0.12–0.27) and a significant increase in MM (slope change, IRR 1.23, 95%CI 1.13–1.33), with the sharpest decline (−94%) and rise (+36%) observed in the “Diseases of the Respiratory System” category. Mental Disorders showed a significant increasing trend of 1% monthly over the whole study period exceeding pre-pandemic levels at the end of MM. Females and adolescents showed higher increasing rates both in SC and MM.ConclusionNPIs appear to have influenced PED attendance in different ways according to diagnostic categories, mirroring different mechanisms of action. These effects are beneficial in some cases and harmful in others, and establishing a clear balance between pros and cons is a difficult task for public health decision makers. The role of NPIs on PED use appropriateness deserves investigation. The rise in pediatric mental disorders independent of the pandemic makes interventions addressing these issues urgent.

Phase I clinical trials represent a critical point in drug development because the investigational medicinal product is being tested in humans for the first time. For this reason, it is essential to evaluate and identify the Maximum Tolerated Dose (MTD) and the safety of the new compound. To mitigate the possible risks associated with drug administration and treatment, the European Competent Authority issued various guidelines to provide provisions and harmonize risk management processes. In the UK and Italy, particular attention should be paid to the Medicines & Healthcare Products Regulatory Agency (MHRA) phase I accreditation scheme and the specific rules set by the Italian Drug Authority through the AIFA Determination no. 809/2015. Both reference documents are based on the concept of quality risk management while conducting phase I clinical studies. Moreover, the AIFA determination outlines specific requirements for those sites that want to conduct non-profit phase I clinical trials. Indeed, the document reports peculiar activities to the “Clinical Trial Quality Team”, which is a team that should support the clinical site researchers in designing, starting, performing, and closing non-profit phase I studies. In this paper, we provide a general overview of the main European guidelines concerning the management of risks during phase I trials, focusing on the main peculiarities of the schemes and rules set by the MHRA and AIFA.

Non-Hodgkin’s lymphomas (NHLs) are a heterogeneous group of lymphoproliferative disorders originating from B, T, or NK lymphocytes. They represent approximately 4–5% of new cancer cases and are classified according to the revised WHO system based on cell lineage, morphology, immunophenotype, and genetics. Diagnosis requires adequate biopsy material, though integrated approaches are used for leukemic presentations. Molecular profiling is improving classification and identifying prognostic markers. Indolent NHLs, such as follicular lymphoma and marginal zone lymphoma, typically pursue a non-aggressive clinical course with long survival. Aggressive diffuse large B-cell lymphoma (DLBCL) is the most common subtype. Recent studies have elucidated pathogenic mechanisms like MYC translocations and BCR pathway mutations. “Double hit” lymphomas with MYC and BCL2/BCL6 alterations confer a poor prognosis. Treatment approaches are evolving, with chemoimmunotherapy remaining standard for many indolent cases while intensified regimens and targeted agents show promise for refractory or high-risk aggressive disease. Continued elucidation of the genetic and microenvironmental underpinnings of lymphomagenesis is critical for developing personalized therapeutic strategies.

BackgroundThe use of Non-Pharmaceutical Interventions (NPIs), such as lockdowns, social distancing and school closures, against the COVID-19 epidemic is debated, particularly for the possible negative effects on vulnerable populations, including children and adolescents. This study therefore aimed to quantify the impact of NPIs on the trend of pediatric hospitalizations during 2 years of pandemic compared to the previous 3 years, also considering two pandemic phases according to the type of adopted NPIs.MethodsThis is a multicenter, quasi-experimental before-after study conducted in 12 hospitals of the Emilia-Romagna Region, Northern Italy, with NPI implementation as the intervention event. The 3 years preceding the beginning of NPI implementation (in March 2020) constituted the pre-pandemic phase. The subsequent 2 years were further subdivided into a school closure phase (up to September 2020) and a subsequent mitigation measures phase with less stringent restrictions. School closure was chosen as delimitation as it particularly concerns young people. Interrupted Time Series (ITS) regression analysis was applied to calculate Hospitalization Rate Ratios (HRR) on the diagnostic categories exhibiting the greatest variation. ITS allows the estimation of changes attributable to an intervention, both in terms of immediate (level change) and sustained (slope change) effects, while accounting for pre-intervention secular trends.ResultsOverall, in the 60 months of the study there were 84,368 cases. Compared to the pre-pandemic years, statistically significant 35 and 19% decreases in hospitalizations were observed during school closure and in the following mitigation measures phase, respectively. The greatest reduction was recorded for “Respiratory Diseases,” whereas the “Mental Disorders” category exhibited a significant increase during mitigation measures. ITS analysis confirms a high reduction of level change during school closure for Respiratory Diseases (HRR 0.19, 95%CI 0.08–0.47) and a similar but smaller significant reduction when mitigation measures were enacted. Level change for Mental Disorders significantly decreased during school closure (HRR 0.50, 95%CI 0.30–0.82) but increased during mitigation measures by 28% (HRR 1.28, 95%CI 0.98–1.69).ConclusionOur findings provide information on the impact of COVID-19 NPIs which may inform public health policies in future health crises, plan effective control and preventative interventions and target resources where needed.

Abstract Background Where population coverage is limited, the exclusive use of Cancer Registries might limit ascertainment of incident cancer cases. We explored the potentials of Nationwide hospital discharge records (NHDRs) to capture incident breast cancer cases in Italy. Methods We analyzed NHDRs for mastectomies and quadrantectomies performed between 2001 and 2008. The average annual percentage change (AAPC) and related 95% Confidence Interval (CI) in the actual number of mastectomies and quadrantectomies performed during the study period were computed for the full sample and for subgroups defined by age, surgical procedure, macro-area and singular Region. Re-admissions of the same patients were separately presented. Results The overall number of mastectomies decreased, with an AAPC of −2.1% (−2.3 -1.8). This result was largely driven by the values observed for women in the 45 to 64 and 65 to 74 age subgroups (−3.0%, -3.4 -3.6 and −3.3%, -3.8 -2.8, respectively). We observed no significant reduction in mastectomies for women in the remaining age groups. Quadrantectomies showed an overall +4.7 AAPC (95%CI:4.5–4.9), with no substantial differences by age. Analyses by geographical area showed a remarkable decrease in mastectomies, with inter-regional discrepancies possibly depending upon variability in mammography screening coverage and adherence. Quadrantectomies significantly increased, with Southern Regions presenting the highest average rates. Data on repeat admissions within a year revealed a total number of 46,610 major breast surgeries between 2001 and 2008, with an overall +3.2% AAPC (95%CI:2.8-3.6). Conclusions In Italy, NHDRs might represent a valuable supplemental data source to integrate Cancer Registries in cancer surveillance.

Hepatitis E virus (HEV) infection is typically a self-limiting, acute illness that spreads through the gastrointestinal tract but replicates in the liver. However, chronic infections are possible in immunocompromised individuals. The HEV virion has two shapes: exosome-like membrane-associated quasi-enveloped virions (eHEV) found in circulating blood or in the supernatant of infected cell cultures and non-enveloped virions (“naked”) found in infected hosts’ feces and bile to mediate inter-host transmission. Although HEV is mainly spread via enteric routes, it is unclear how it penetrates the gut wall to reach the portal bloodstream. Both virion types are infectious, but they infect cells in different ways. To develop personalized treatment/prevention strategies and reduce HEV impact on public health, it is necessary to decipher the entry mechanism for both virion types using robust cell culture and animal models. The contemporary knowledge of the cell entry mechanism for these two HEV virions as possible therapeutic target candidates is summarized in this narrative review.

IntroductionThe aim of our single-center case–control study is to evaluate whether minipuberty occurs in patients with hypoxic ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). We intend to conduct this evaluation by confronting the values of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and the values of testosterone in males and estradiol in females between newborns with HIE and in subsequent TH and healthy controls.MethodsWe enrolled 40 patients (age: 56–179 days; 23 males), of whom 20 met the inclusion criteria for the case group and who underwent TH. A blood sample was taken from each patient at approximately 10 weeks of age to evaluate FSH and LH from the serum samples of all patients and to evaluate 17-beta estradiol (E2) and testosterone levels, respectively, from the serum samples of female and male patients.ResultsIt was found that minipuberty occurred in the case group patients, with no significant differences reported from the control group and with hormonal serum levels comparable to healthy infants of the control group (FSH 4.14 mUI/ml ± 5.81 SD vs. 3.45 mUI/ml ± 3.48 SD; LH 1.41 mUI/ml ±1.29 SD vs. 2.04 mUI/ml ±1.76 SD; testosterone in males 0.79 ng/ml ± 0.43 SD vs. 0.56 ng/ml ± 0.43 SD; 17-beta estradiol in females 28.90 pg/ml ± 16.71 SD vs. 23.66 pg/ml ± 21.29 SD).DiscussionThe results of the present study may pave the way for further research and the evaluation of more possible advantages of TH.

Overuse and misuse of antibiotics have strongly accelerated the progressive increase in bacterial antimicrobial resistance (AMR). The evidence that antimicrobial selective pressure was greater the longer the antibiotic therapy was continued has led some experts to reconsider duration of antibiotic therapy testing the use of short-term drug administration. If as effective as long-term therapy, short-term therapy could have been an easy measure to limit AMR emergence. In the present narrative review, whether present knowledge on short-term therapy of acute streptococcal pharyngitis (ASF), acute otitis media (AOM) and mild to moderate community-acquired pneumonia (CAP) allows systematic use of short-term therapy in infants and children with these diseases is discussed. Literature analysis showed that reducing the duration of antibiotic therapy for some of the most common pediatric respiratory infections could be a valid measure to contain the antibiotic abuse and the consequent impact on the emergence of AMR. Several data seem to indicate that this type of intervention is possible, as short-term therapy has been found as effective as the traditionally recommended long-term therapy in some cases of ASF, AOM and mild to moderate CAP. However, further studies are needed to better characterize infants and children who can have benefit with short-term antibiotic therapy in common bacterial respiratory infections.

Malnutrition is a common condition in cancer patients which is usually associated with functional limitations, as well as increased morbidity and mortality. Based on the support of the young sections of Italian Association of Medical Oncology (AIOM), Italian Association of Radiotherapy and Clinical Oncology (AIRO) and Italian Society of Surgical Oncology (SICO) merged into the NutriOnc Research Group, we performed a multidisciplinary national survey with the aim to define the awareness of nutritional issues among healthcare professionals delivering anticancer care. The questionnaire was organized in four sections, as follows: Knowledge and practices regarding Nutritional Management of cancer patients; Timing of screening and assessment of Nutritional Status; Nutritional Treatment and prescription criteria; Immunonutrition and educational topics. The modules focused on esophagogastric, hepato-bilio-pancreatic and colorectal malignancies. Overall, 215 physicians completed the survey. As regards the management of Nutritional Status of cancer patients, many responders adopted the ERAS program (49.3%), while a consistent number of professionals did not follow a specific validated nutritional care protocol (41.8%), mainly due to lack of educational courses (14.5%) and financial support (15.3%). Nearly all the included institutions had a multidisciplinary team (92%) to finalize the treatment decision-making. Cancer patients routinely underwent nutritional screening according to 57.2% of interviewed physicians. The timing of nutritional assessment was at diagnosis (37.8%), before surgery (25.9%), after surgery (16.7%), before radiochemotherapy (13.5%) and after radiochemotherapy (7%). Most of the responders reported that nutritional status was assessed throughout the duration of cancer treatments (55.6%). An important gap between current delivery and need of nutritional assessment persists. The development of specific and defined care protocols and the adherence to these tools may be the key to improving nutritional support management in clinical practice.

Multiple myeloma (MM) is a cancerous condition characterized by the proliferation of plasma cells within the hematopoietic marrow, resulting in multiple osteolytic lesions. MM patients typically experience bone pain, kidney damage, fatigue due to anemia, and infections. Historically, MM was an incurable disease with a life expectancy of around three years after diagnosis. However, over the past two decades, the development of novel therapeutics has significantly improved patient outcomes, including response to treatment, remission duration, quality of life, and overall survival. These advancements include thalidomide and its derivatives, lenalidomide and pomalidomide, which exhibit diverse mechanisms of action against the plasma cell clone. Additionally, proteasome inhibitors such as bortezomib, ixazomib, and carfilzomib disrupt protein degradation, proving specifically toxic to cancerous plasma cells. Recent advancements also involve monoclonal antibodies targeting surface antigens, such as elotuzumab (anti-CS1) and daratumumab (anti-CD38), bispecific t-cell engagers such as teclistamab (anti-BCMA/CD3) and Chimeric antigen receptor T (CAR-T)-based strategies, with a growing focus on drugs that exhibit increasingly targeted action against neoplastic plasma cells and relevant effects on the tumor microenvironment.

Background: Over the past few decades, there has been much debate and research into the link between alcohol consumption and the development and progression of pancreatic ductal adenocarcinoma (PDAC). Objectives: To contribute to the ongoing discussion and gain further insights into this topic, our study analysed the gene expression differences in PDAC patients based on their alcohol consumption history. Methods: To this end, we interrogated a large publicly available dataset. We next validated our findings in vitro. Results: Our findings revealed that patients with a history of alcohol consumption showed significant enrichment in the TGFβ-pathway: a signaling pathway implicated in cancer development and tumor progression. Specifically, our bioinformatic dissection of gene expression differences in 171 patients with PDAC showed that those who had consumed alcohol had higher levels of TGFβ-related genes. Moreover, we validated the role of the TGFβ pathway as one of the molecular drivers in producing massive stroma, a hallmark feature of PDAC, in patients with a history of alcohol consumption. This suggests that inhibition of the TGFβ pathway could serve as a novel therapeutic target for PDAC patients with a history of alcohol consumption and lead to increased sensitivity to chemotherapy. Our study provides valuable insights into the molecular mechanisms underlying the link between alcohol consumption and PDAC progression. Conclusions: Our findings highlight the potential significance of the TGFβ pathway as a therapeutic target. The development of TGFβ-inhibitors may pave the way for developing more effective treatment strategies for PDAC patients with a history of alcohol consumption.

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a complex tumor microenvironment (TME) that promotes cancer progression. The tumor stroma is characterized by cancer-associated fibroblasts (CAFs) that secrete factors stimulating tumor growth, invasion, and immunosuppression. Macrophages tend to polarize toward a pro-tumor phenotype. Various other components, including endothelial cells, pericytes, and neural cells, likely contribute to the complexity of the PDAC TME. Epidemiological investigations have highlighted obesity as a risk factor for pancreatic cancer, suggesting that adipocytes may also play a significant role. This manuscript offers an overview of the main actors in TME, as well as dysregulated signaling pathways and gene mutations. It underlines how strategies modulating the TME hold promise for improving outcomes. Lastly, it describes how integrating multi-omic approaches may represent a future trajectory to explore novel therapeutic possibilities. Pancreatic ductal adenocarcinoma (PDAC) presents significant oncological challenges due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) plays a critical role in progression and treatment resistance. Non-neoplastic cells, such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), contribute to tumor growth, angiogenesis, and immune evasion. Although immune cells infiltrate TME, tumor cells evade immune responses by secreting chemokines and expressing immune checkpoint inhibitors (ICIs). Vascular components, like endothelial cells and pericytes, stimulate angiogenesis to support tumor growth, while adipocytes secrete factors that promote cell growth, invasion, and treatment resistance. Additionally, perineural invasion, a characteristic feature of PDAC, contributes to local recurrence and poor prognosis. Moreover, key signaling pathways including Kirsten rat sarcoma viral oncogene (KRAS), transforming growth factor beta (TGF-β), Notch, hypoxia-inducible factor (HIF), and Wnt/β-catenin drive tumor progression and resistance. Targeting the TME is crucial for developing effective therapies, including strategies like inhibiting CAFs, modulating immune response, disrupting angiogenesis, and blocking neural cell interactions. A recent multi-omic approach has identified signature genes associated with anoikis resistance, which could serve as prognostic biomarkers and targets for personalized therapy. [ABSTRACT FROM AUTHOR]

Abstract In a large number of cancer types, treatment selection depends on the presence of specific tumor biomarkers. Due to the dynamic nature of cancer, very often these predictive biomarkers are not uniformly present in all cancer cells. Tumor heterogeneity represents indeed one of the main causes of therapeutic failure, and its decoding remains a major ongoing challenge in the field. Liquid biopsy is the sampling and analysis of non-solid biological tissue often through rapid and non-invasive methods, which allows the assessment in real-time of the evolving landscape of cancer. Samples can be obtained from blood and most other bodily fluids. A blood-based liquid biopsy can capture circulating tumor cells and leukocytes, as well as circulating tumor-derived nucleic acids. In this review, we discuss the current and possibly future applications of blood-based liquid biopsy in oncology, its advantages and its limitations in clinical practice. We specifically focused on its role as a tool to capture tumor heterogeneity in metastatic cancer patients.

This study was planned to evaluate whether a 3-month treatment with Lactobacillus rhamnosus GG (LGG) can modify immune system functions in children and adolescents with type 1 diabetes (T1D), leading to an increased immune response to an injectable quadrivalent inactivated influenza vaccine (QIV). A total of 87 pediatric patients with T1D were screened, although 34 patients in the Probiotic group and 30 in the Control group accepted to be vaccinated with QIV and completed the study. Vaccine immunogenicity and safety and the inflammatory cytokine response were studied. Results showed that QIV was immunogenic and safe in T1D pediatric patients and pre-administration of LGG for three months did not substantially modify the QIV humoral immunity. The combination of QIV and LGG reduced inflammatory responses (i.e., IFN-γ, IL17A, IL-17F, IL-6, and TNF-α) from activated PBMCs of pediatric patients with T1D, without dampening the production of seroprotective antibodies. In conclusion, QIV is associated with an adequate immunogenicity in children and adolescents with T1D in presence of a good safety profile. Although a systematic administration of LGG did not result in an improvement of humoral responses to an influenza vaccine, the probiotic did induce important anti-inflammatory effects.

Although vaccines are the safest and the most effective measure to prevent disease, disability, and death from various pediatric infectious diseases, parental vaccine hesitancy is a common and increasing phenomenon worldwide. To contribute to improving our knowledge on parental willingness and hesitancy toward COVID-19 vaccine administration in children aged 5–11 years, an anonymous online questionnaire was disseminated in Italy after the COVID-19 vaccine’s authorization for this age group. An online survey was conducted using the Crowd Signal platform from 15 December 2021 to 15 January 2022 in Italy among parents of children 5–11 years old. A total of 3433 questionnaires were analyzed. Overall, a “Favorable” position was observed in 1459 (42.5%) parents, a “Doubtful” one in 1223 (35.6%) and a “Hesitant/Reluctant” one in 751 (21.9%). The univariate multinomial logistic regression analysis and the multivariate multinomial logistic regression analysis showed that the Hesitant/Reluctant parents were younger than 40 years of age, mostly female, with a secondary or middle school degree, an annual income below EUR 28,000, more than one child in the age range from 5 to 11 years, an underestimated consideration of the severity of COVID-19’s effects, and concern regarding the COVID-19 vaccines in general. These results show that in Italy, most parents of children aged 5 to 11 were doubtful or hesitant/reluctant to vaccinate their children against the COVID-19 virus. Poor trust in health institutions as well as poor consideration of the epidemiological and clinical relevance of COVID-19 in children seem to have played the biggest roles in forming these attitudes. Moreover, the negative attitude of several parents who previously agreed to immunize their children against other childhood illnesses according to the official national pediatric immunization schedule clearly indicates that only the COVID-19 vaccine was put in doubt or rejected. All these findings lead us to conclude that to improve COVID-19 vaccination coverage in children aged 5 to 11, health authorities should increase parental education on the true clinical relevance of COVID-19 and on the importance of its prevention to hinder the evolution of the pandemic in pediatric subjects and the emergence of new variants, and its relative weight in influencing the efficacy of vaccines.