GD2 expression in breast cancer.

Breast cancer (BC) is a heterogeneous disease, including different subtypes having diverse incidence, drug-sensitivity and survival rates. In particular, claudin-low and basal-like BC have mesenchymal features with a dismal prognosis. Disialoganglioside GD2 is a typical neuroectodermal antigen expressed in a variety of cancers. Despite its potential relevance in cancer diagnostics and therapeutics, the presence and role of GD2 require further investigation, especially in BC. Therefore, we evaluated GD2 expression in a cohort of BC patients and its correlation with clinical-pathological features.Sixty-three patients with BC who underwent surgery without prior chemo- and/or radiotherapy between 2001 and 2014 were considered. Cancer specimens were analyzed by immunohistochemistry and GD2-staining was expressed according to the percentage of positive cells and by a semi-quantitative scoring system.Patient characteristics were heterogeneous by age at diagnosis, histotype, grading, tumor size, Ki-67 and receptor-status. GD2 staining revealed positive cancer cells in 59% of patients. Among them, 26 cases (41%) were labeled with score 1+ and 11 (18%) with score 2+. Notably, the majority of metaplastic carcinoma specimens stained positive for GD2. The univariate regression logistic analysis revealed a significant association of GD2 with triple-receptor negative phenotype and older age (> 78) at diagnosis.We demonstrate for the first time that GD2 is highly prevalent in a cohort of BC patients clustering on very aggressive BC subtypes, such as triple-negative and metaplastic variants

Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

Background: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths

Metapneumovirus Infections and Respiratory Complications

Acute respiratory tract infections (ARTIs) are the most common illnesses experienced by people of all ages worldwide. In 2001, a new respiratory pathogen called human metapneumovirus (hMPV) was identified in respiratory secretions. hMPV is an RNA virus of the Paramyxoviridae family, and it has been isolated on every continent and from individuals of all ages. hMPV causes 7 to 19% of all cases of ARTIs in both hospitalized and outpatient children, and the rate of detection in adults is approximately 3%. Symptoms of hMPV infection range from a mild cold to a severe disease requiring a ventilator and cardiovascular support. The main risk factors for severe disease upon hMPV infection are the presence of a high viral load, coinfection with other agents (especially human respiratory syncytial virus), being between 0 and 5 months old or older than 65 years, and immunodeficiency. Currently, available treatments for hMPV infections are only supportive, and antiviral drugs are employed in cases of severe disease as a last resort. Ribavirin and immunoglobulins have been used in some patients, but the real efficacy of these treatments is unclear. At present, the direction of research on therapy for hMPV infection is toward the development of new approaches, and a variety of vaccination strategies are being explored and tested in animal models. However, further studies are required to define the best treatment and prevention strategies

Vaccine administration in children with chronic kidney disease

Pediatric patients with severe chronic kidney disease (CKD) on conservative treatment, on dialysis, and those with renal transplantation are at a higher risk for infectious diseases as the result of impaired immune responses against infectious agents. Infections in these patients can have drastic consequences for disease morbidity and mortality. Immunization is a crucial preventive strategy for disease management in this pediatric population. However, vaccination coverage among children with CKD remains low due to safety concerns and doubts about vaccine immunogenicity and efficacy. In this study, we reviewed why children with CKD are at higher risk of infections, the importance of vaccinations among these children, barriers to vaccinations, and recommend the best vaccination schedules. Overall, vaccines have acceptable immunogenicity, efficacy, and safety profiles in children with CKD. However, in some cases, the protective antibody levels induced by vaccines and the benefits and risks of booster vaccine doses must be individually managed. Furthermore, close contacts and household members of these children should complete age-appropriate vaccination schedules to increase the child's indirect protection

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) : clues and pitfalls in the pediatric background

The development and increasing diffusion of new vaccinations and global immunization protocols have aroused burning debates about safety of adjuvants and their immunogenicity-enhancing effect in vaccines. Shoenfeld and Agmon-Levin have grouped under the term “autoimmune/inflammatory syndrome induced by adjuvants” (ASIA) a complex of variable signs and symptoms that may occur after a previous exposure to different adjuvants and also external environmental triggers, even eliciting specific overt immune-mediated disorders. This entity subsumes five medical conditions: post-vaccination phenomena, gulf war syndrome, macrophagic myofasciitis syndrome, siliconosis, and sick building syndrome, but the relevance and magnitude of the syndrome in the pediatric age is fundamentally limited to post-vaccination autoimmune or inflammatory disorders. The occurrence of vaccine-triggered phenomena represents a diagnostic challenge for clinicians and a research conundrum for many investigators. In this paper, we will analyze the general features of ASIA and focus on specific post-vaccination events in relation with the pediatric background. In the presence of a favorable genetic background, many autoimmune/inflammatory responses can be triggered by adjuvants and external factors, showing how the man himself might breach immune tolerance and drive many pathogenetic aspects of human diseases. Nonetheless, the elective application of ASIA diagnostic criteria to the pediatric population requires further assessment and evaluations. Additional studies are needed to help clarify connections between innate or adaptive immunity and pathological and/or protective autoantibodies mostly in the pediatric age, as children and adolescents are mainly involved in the immunization agendas related to vaccine-preventable diseases

A spectrum of inflammation and demyelinization in acute disseminated encephalomyelitis (ADEM) of children

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that involves multifocal areas of the white matter, rarely the gray matter and spinal cord, mainly affecting children and mostly occurring 1-2. weeks after infections or more rarely after vaccinations. Though a specific etiologic agent is not constantly identified, to evaluate carefully patient's clinical history and obtain adequate samples for the search of a potential ADEM causal agent is crucial. In the case of a prompt diagnosis and adequate treatment, most children with ADEM have a favorable outcome with full recovery, but in the case of diagnostic delays or inappropriate treatment some patients might display neurological sequelae and persistent deficits or even show an evolution to multiple sclerosis. The suspicion of ADEM rises on a clinical basis and derives from systemic and neurologic signs combined with magnetic resonance imaging of the central nervous system. Other advanced imaging techniques may help an appropriate differential diagnosis and definition of exact disease extension. Although there is no standardized protocol or management for ADEM, corticosteroids, intravenous immunoglobulin, and plasmapheresis have been successfully used. There is no marker that permits to identify the subset of children with worse prognosis and future studies should try to detect any biological clue for prevision of neurologic damage as well as should optimize treatment strategies using an approach based on the effective risk of negative evolution

Influenza immunization in hemodialyzed or kidney transplanted adolescents and young adults

Aim: To clarify the immunogenicity and safety of influenza vaccine in patients with end-stage kidney disease (ESKD) on dialysis or who have received a kidney transplant. Methods: Sixty adolescents and young adults with ESKD (25 on hemodialysis and 35 kidney transplant recipients) were randomized 1:1 to receive a traditional trivalent split virion vaccine (TIIV) or a virosome-adjuvanted trivalent inactivated influenza vaccine (VATIIV). The immunogenicity and safety of the two vaccines was evaluated and compared with the findings observed in 30 healthy subjects of similar age and gender distribution who received TIIV. Results: The results indicate that the immune response of the patients to TIIV and VATIIV were similar. The administered vaccines were safe and well tolerated, and no advantage was found with the use of VATIIV. Conclusion: Given the potential clinical relevance of influenza in patients with ESKD, these findings support the official recommendation that they should receive annual influenza vaccinations. © Informa UK, Ltd

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA): clues and pitfalls in the pediatric background

The development and increasing diffusion of new vaccinations and global immunization protocols have aroused burning debates about safety of adjuvants and their immunogenicity-enhancing effect in vaccines. Shoenfeld and Agmon-Levin have grouped under the term “autoimmune/inflammatory syndrome induced by adjuvants” (ASIA) a complex of variable signs and symptoms that may occur after a previous exposure to different adjuvants and also external environmental triggers, even eliciting specific overt immune-mediated disorders. This entity subsumes five medical conditions: post-vaccination phenomena, gulf war syndrome, macrophagic myofasciitis syndrome, siliconosis, and sick building syndrome, but the relevance and magnitude of the syndrome in the pediatric age is fundamentally limited to post-vaccination autoimmune or inflammatory disorders. The occurrence of vaccine-triggered phenomena represents a diagnostic challenge for clinicians and a research conundrum for many investigators. In this paper, we will analyze the general features of ASIA and focus on specific post-vaccination events in relation with the pediatric background. In the presence of a favorable genetic background, many autoimmune/inflammatory responses can be triggered by adjuvants and external factors, showing how the man himself might breach immune tolerance and drive many pathogenetic aspects of human diseases. Nonetheless, the elective application of ASIA diagnostic criteria to the pediatric population requires further assessment and evaluations. Additional studies are needed to help clarify connections between innate or adaptive immunity and pathological and/or protective autoantibodies mostly in the pediatric age, as children and adolescents are mainly involved in the immunization agendas related to vaccine-preventable diseases