Therapeutic Options for Crigler-Najjar Syndrome: A Scoping Review.

Crigler-Najjar Syndrome (CNS) is a rare genetic disorder caused by mutations in the UGT1A1 gene, leading to impaired bilirubin conjugation and severe unconjugated hyperbilirubinemia. CNS presents in the following forms: CNS type 1 (CNS1), the more severe form with the complete absence of UGT1A1 activity, and CNS type 2 (CNS2), with partial enzyme activity. This narrative review aims to provide a detailed overview of CNS, highlighting its clinical significance and the need for new, more effective treatments. By summarizing current knowledge and discussing future treatments, this article seeks to encourage further research and advancements that can improve outcomes for CNS patients. The literature analysis showed that CNS1 requires aggressive management, including phototherapy and plasmapheresis, but liver transplantation (LT) remains the only definitive cure. The timing of LT is critical, as it must be performed before the onset of irreversible brain damage (kernicterus), making early intervention essential. However, LT poses risks such as graft rejection and lifelong immunosuppression. CNS2 is milder, with patients responding well to phenobarbital and having a lower risk of kernicterus. Recent advancements in gene therapy and autologous hepatocyte transplantation offer promising alternatives to LT. Gene therapy using adeno-associated virus (AAV) vectors has shown potential in preclinical studies, though challenges remain in pediatric applications due to liver growth and pre-existing immunity. Autologous hepatocyte transplantation avoids the risk of rejection but requires further research. These emerging therapies provide hope for more effective and less invasive treatment options, aiming to improve the quality of life for CNS patients and reduce reliance on lifelong interventions.

Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus (RSV) Vaccine in Healthy RSV-Seropositive Children 12-23 Months of Age.

BACKGROUND: Safe and effective respiratory syncytial virus (RSV) vaccines remain elusive. This was a phase I/II trial (NCT02927873) of ChAd155-RSV, an investigational chimpanzee adenovirus-RSV vaccine expressing 3 proteins (fusion, nucleoprotein, and M2-1), administered to 12-23-month-old RSV-seropositive children followed up for 2 years after vaccination. METHODS: Children were randomized to receive 2 doses of ChAd155-RSV or placebo (at a 1:1 ratio) (days 1 and 31). Doses escalated from 0.5 × 1010 (low dose [LD]) to 1.5 × 1010 (medium dose [MD]) to 5 × 1010 (high dose [HD]) viral particles after safety assessment. Study end points included anti-RSV-A neutralizing antibody (Nab) titers through year 1 and safety through year 2. RESULTS: Eighty-two participants were vaccinated, including 11, 14, and 18 in the RSV-LD, RSV-MD, and RSV-HD groups, respectively, and 39 in the placebo groups. Solicited adverse events were similar across groups, except for fever (more frequent with RSV-HD). Most fevers were mild (≤38.5°C). No vaccine-related serious adverse events or RSV-related hospitalizations were reported. There was a dose-dependent increase in RSV-A Nab titers in all groups after dose 1, without further increase after dose 2. RSV-A Nab titers remained higher than prevaccination levels at year 1. CONCLUSIONS: Three ChAd155-RSV dosages were found to be well tolerated. A dose-dependent immune response was observed after dose 1, with no observed booster effect after dose 2. Further investigation of ChAd155-RSV in RSV-seronegative children is warranted. CLINICAL TRIALS REGISTRATION: NCT02927873.

Respiratory syncytial virus (RSV) is among the main causes of bronchiolitis and pneumonia regularly leading to hospitalization in children. A safe and effective vaccine to prevent RSV infection in this age group has not yet been found, despite great efforts over several decades. This study tested a new candidate RSV vaccine, expressing 3 important pieces of the virus, in toddlers who already had a previous RSV infection. The vaccine was generally well tolerated. Vaccination triggered antibodies against RSV that were able to block the virus in laboratory tests and that persisted for 1 year.

Novel mutations in the WFS1 gene are associated with Wolfram syndrome and systemic inflammation.

Mutations in the WFS1 gene, encoding wolframin (WFS1), cause endoplasmic reticulum (ER) stress and are associated with a rare autosomal-recessive disorder known as Wolfram syndrome (WS). WS is clinically characterized by childhood-onset diabetes mellitus, optic atrophy, deafness, diabetes insipidus and neurological signs. We identified two novel WFS1 mutations in a patient with WS, namely, c.316-1G > A (in intron 3) and c.757A > T (in exon 7). Both mutations, located in the N-terminal region of the protein, were predicted to generate a truncated and inactive form of WFS1. We found that although the WFS1 protein was not expressed in peripheral blood mononuclear cells (PBMCs) of the proband, no constitutive ER stress activation could be detected in those cells. In contrast, WS proband's PBMCs produced very high levels of proinflammatory cytokines (i.e. TNF-α, IL-1ß, and IL-6) in the absence of any stimulus. WFS1 silencing in PBMCs from control subjects by means of small RNA interference also induced a pronounced proinflammatory cytokine profile. The same cytokines were also significantly higher in sera from the WS patient as compared to matched healthy controls. Moreover, the chronic inflammatory state was associated with a dominance of proinflammatory T helper 17 (Th17)-type cells over regulatory T (Treg) lymphocytes in the WS PBMCs. The identification of a state of systemic chronic inflammation associated with WFS1 deficiency may pave the way to innovative and personalized therapeutic interventions in WS.

Association of viral load with TRAIL, IP-10, CRP biomarker signature and disease severity in children with respiratory tract infection or fever without source: A prospective, multicentre cohort study.

BACKGROUND: To investigate the association of viral load (VL) with (i) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10, C-reactive protein, and a combinatorial score (BV score), and (ii) clinical severity. STUDY DESIGN: In this prospective, multicentre cohort substudy, children with respiratory tract infection or fever without source were enrolled. VL for influenza virus, rhinovirus, respiratory syncytial virus, and adenovirus was measured from nasopharyngeal swabs. The reference standard diagnosis was established based on expert panel adjudication. RESULTS: Of 1140 recruited patients, 333 had a virus monodetection. VL for the aggregated data set correlated with TRAIL and IP-10 levels, with the length of oxygen therapy, and inversely with the BV score. At a single viral level, only the influenza VL yielded a correlation with TRAIL, IP-10 levels, and the BV score. Children with a viral reference standard diagnosis had significantly higher VL than those with bacterial infection (p = 0.0005). Low TRAIL (incidence rate ratio [IRR] 0.6, 95% confidence interval [CI] 0.39-0.91) and young age (IRR 0.62, 95% CI 0.49-0.79) were associated with a longer hospital stay, while young age (IRR 0.33, 95% CI 0.18-0.61), low TRAIL (IRR 0.25, 95% CI 0.08-0.76), and high VL (IRR 1.16, 95% CI 1.00-1.33) were predictive of longer oxygen therapy. CONCLUSION: These findings indicate that VL correlates with biomarkers and may serve as a complementary tool pertaining to disease severity.

Acute pharyngitis in children and adults: descriptive comparison of current recommendations from national and international guidelines and future perspectives.

This study aims to provide a comparison of the current recommendations about the management of acute pharyngitis. A literature search was conducted from January 2009 to 2023. Documents reporting recommendations on the management of acute pharyngitis were included, pertinent data were extracted, and a descriptive comparison of the different recommendations was performed. The quality of guidelines was assessed through the AGREE II instrument. Nineteen guidelines were included, and an overall moderate quality was found. Three groups can be distinguished: one group supports the antibiotic treatment of group A ß-hemolytic Streptococcus (GABHS) to prevent acute rheumatic fever (ARF); the second considers acute pharyngitis a self-resolving disease, recommending antibiotics only in selected cases; the third group recognizes a different strategy according to the ARF risk in each patient. An antibiotic course of 10 days is recommended if the prevention of ARF is the primary goal; conversely, some guidelines suggest a course of 5-7 days, assuming the symptomatic cure is the goal of treatment. Penicillin V and amoxicillin are the first-line options. In the case of penicillin allergy, first-generation cephalosporins are a suitable choice. In the case of beta-lactam allergy, clindamycin or macrolides could be considered according to local resistance rates.    Conclusion: Several divergencies in the management of acute pharyngitis were raised among guidelines (GLs) from different countries, both in the diagnostic and therapeutic approach, allowing the distinction of 3 different strategies. Since GABHS pharyngitis could affect the global burden of GABHS disease, it is advisable to define a shared strategy worldwide. It could be interesting to investigate the following issues further: cost-effectiveness analysis of diagnostic strategies in different healthcare systems; local genomic epidemiology of GABHS infection and its complications; the impact of antibiotic treatment of GABHS pharyngitis on its complications and invasive GABHS infections; the role of GABHS vaccines as a prophylactic measure. The related results could aid the development of future recommendations. What is Known: • GABHS disease spectrum ranges from superficial to invasive infections and toxin-mediated diseases. • GABHS accounts for about 25% of sore throat in children and its management is a matter of debate. What is New: • Three strategies can be distinguished among current GLs: antibiotic therapy to prevent ARF, antibiotics only in complicated cases, and a tailored strategy according to the individual ARF risk. • The impact of antibiotic treatment of GABHS pharyngitis on its sequelae still is the main point of divergence; further studies are needed to achieve a global shared strategy.

Vascular Endothelial Growth Factor as Molecular Target for Bronchopulmonary Dysplasia Prevention in Very Low Birth Weight Infants.

Bronchopulmonary dysplasia (BPD) still represents an important burden of neonatal care. The definition of the disease is currently undergoing several revisions, and, to date, BPD is actually defined by its treatment rather than diagnostic or clinic criteria. BPD is associated with many prenatal and postnatal risk factors, such as maternal smoking, chorioamnionitis, intrauterine growth restriction (IUGR), patent ductus arteriosus (PDA), parenteral nutrition, sepsis, and mechanical ventilation. Various experimental models have shown how these factors cause distorted alveolar and vascular growth, as well as alterations in the composition and differentiation of the mesenchymal cells of a newborn's lungs, demonstrating a multifactorial pathogenesis of the disease. In addition, inflammation and oxidative stress are the common denominators of the mechanisms that contribute to BPD development. Vascular endothelial growth factor-A (VEGFA) constitutes the most prominent and best studied candidate for vascular development. Animal models have confirmed the important regulatory roles of epithelial-expressed VEGF in lung development and function. This educational review aims to discuss the inflammatory pathways in BPD onset for preterm newborns, focusing on the role of VEGFA and providing a summary of current and emerging evidence.

Clinical impact and disease evolution of SARS-CoV-2 infection in familial Mediterranean fever.

The innate immune system is critically involved in the pathogenesis of familial Mediterranean fever (FMF), characterized by dysregulated inflammasome activity and recurrent inflammatory attacks: this is the most common among monogenic autoinflammatory diseases, which shares some biochemical pathways with the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. In this short review we explore the overlap in the pathophysiology of FMF and SARS-CoV-2 infection, discussing how to understand better the interaction between the two diseases and optimize management. A poorer outcome of SARS-CoV-2 infection seems not to be present in infected FMF patients in terms of hospitalization time, need for oxygen support, need for intensive care, rate of complications and exitus. Long-term surveillance will confirm the relatively low risk of a worse prognosis observed so far in SARS-CoV-2-infected people with FMF. In these patients COVID-19 vaccines are recommended and their safety profile is expected to be similar to the general population.

Off-label use of combined antiretroviral therapy, analysis of data collected by the Italian Register for HIV-1 infection in paediatrics in a large cohort of children.

BACKGROUND: Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children < 2 years of age and 60% in those aged 2-12 years, due to the lack of adequate paediatric clinical studies on pharmacokinetics, pharmacodynamics and drug safety in children. METHODS: An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. RESULTS: 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13-5.19; p = 0.024). Moreover, children < 2 years of age were at increased risk for receiving off-label HAART with respect to older children (OR: 3.24; 95% CI 1063-7.3; p = 0.001). Even if our safety data regarding off-label regimens where poor, no adverse event was reported. CONCLUSION: The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.

Peripheral Saturation and Perfusion Index on the First Day of Life Play a Role in Early Discharge of Healthy Term Newborns.

Introduction: Pulse oximetry screening is a safe, feasible test, effective in identifying congenital heart diseases in otherwise well-appearing newborns. Uncertainties still persist on the most effective algorithm to be used and the timing of screening. The aim of this study was to evaluate the role of the pulse oximetry screening associated with the peripheral perfusion index performed in the first 24 hours of life for the early detection of congenital heart diseases and noncongenital heart diseases in the newborns. Materials and Methods: A prospective observational cohort study was conducted. The enrollment criteria were as follows: term newborns with an APGAR score >8 at 5 minutes. The exclusion criteria were as follows: clinical signs of prenatal/perinatal asphyxia or known congenital malformations. Four parameters of pulse oximetry screening were utilized: saturation less than 90% (screening 1), saturation of less than 95% in one or both limbs (screening 2), difference of more than 3% between the limbs (screening 3), and preductal peripheral perfusion index or postductal peripheral perfusion index below 0.70 (screening 4). The likelihood ratio, sensibility, specificity, and positive and negative predictive values for identification of congenital heart diseases or noncongenital heart diseases (suspicion of perinatal infection and any respiratory diseases) were evaluated. Results: The best predictive results for minor congenital heart disease were obtained combining screening 3 and screening 4 (χ 2 (1) = 15,279; p < 0.05; OR = 57,900 (9,465-354,180)). Screening 2, screening 3, and screening 4 were predictive for noncongenital heart diseases (χ 2 (1) = 11,550; p < 0.05; OR = 65,744 (10,413-415,097)). Combined screenings 2-4 were predictive for both congenital heart disease and noncongenital heart disease (χ 2 (1) = 22,155; p < 0.05; OR = 117,685 (12,972-1067,648)). Conclusions: Combining peripheral saturation with the peripheral perfusion index in the first 24 hours of life shows a predictive role in the detection of minor congenital heart diseases and neonatal clinical conditions whose care needs attention.

Impact of CFTR Modulators on the Impaired Function of Phagocytes in Cystic Fibrosis Lung Disease.

Cystic fibrosis (CF), the most common genetically inherited disease in Caucasian populations, is a multi-systemic life-threatening autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In 2012, the arrival of CFTR modulators (potentiators, correctors, amplifiers, stabilizers, and read-through agents) revolutionized the therapeutic approach to CF. In this review, we examined the physiopathological mechanism of chronic dysregulated innate immune response in the lungs of CF patients with pulmonary involvement with particular reference to phagocytes, critically analyzing the role of CFTR modulators in influencing and eventually restoring their function. Our literature review highlighted that the role of CFTR in the lungs is crucial not only for the epithelial function but also for host defense, with particular reference to phagocytes. In macrophages and neutrophils, the CFTR dysfunction compromises both the intricate process of phagocytosis and the mechanisms of initiation and control of inflammation which then reverberates on the epithelial environment already burdened by the chronic colonization of pathogens leading to irreversible tissue damage. In this context, investigating the impact of CFTR modulators on phagocytic functions is therefore crucial not only for explaining the underlying mechanisms of pleiotropic effects of these molecules but also to better understand the physiopathological basis of this disease, still partly unexplored, and to develop new complementary or alternative therapeutic approaches.

Pediatric Multisystem Syndrome Associated with SARS-CoV-2 (MIS-C): The Interplay of Oxidative Stress and Inflammation.

Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (MIS-C) is characterized by persistent fever and evidence of single or multiorgan dysfunction, and laboratory evidence of inflammation, elevated neutrophils, reduced lymphocytes, and low albumin. The pathophysiological mechanisms of MIS-C are still unknown. Proinflammatory mediators, including reactive oxygen species and decreased antioxidant enzymes, seems to play a central role. Virus entry activates NOXs and inhibits Nrf-2 antioxidant response inducing free radicals. The biological functions of nonphagocytic NOXs are still under study and appear to include: defense of epithelia, intracellular signaling mechanisms for growth regulation and cell differentiation, and post-translational modifications of proteins. This educational review has the aim of analyzing the newest evidence on the role of oxidative stress (OS) in MIS-C. Only by relating inflammatory mediators to OS evaluation in children following SARS-CoV-2 infection will it be possible to achieve a better understanding of these mechanisms and to reduce long-term morbidity. The link between inflammation and OS is key to developing effective prevention strategies with antioxidants to protect children.

Sudden neck swelling with rash as late manifestation of COVID-19: a case report.

BACKGROUND: Although there are reports of otolaryngological symptoms and manifestations of CoronaVirus Disease 19 (COVID-19), there have been no documented cases of sudden neck swelling with rash in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection described in literature. CASE PRESENTATION: We report a case of a sudden neck swelling and rash likely due to late SARS-CoV-2 in a 64-year-old woman. The patient reported COVID-19 symptoms over the previous three weeks. Computed Tomography (CT) revealed a diffuse soft-tissue swelling and edema of subcutaneous tissue, hypodermis, and muscular and deep fascial planes. All the differential diagnoses were ruled out. Both the anamnestic history of the patient's husband who had died of COVID-19 with and the collateral findings of pneumonia and esophageal wall edema suggested the association with COVID-19. This was confirmed by nasopharyngeal swab polymerase chain reaction. The patient was treated with lopinavir/ritonavir, hydroxychloroquine and piperacillin/tazobactam for 7 days. The neck swelling resolved in less than 24 h, while the erythema was still present up to two days later. The patient was discharged after seven days in good clinical condition and with a negative swab. CONCLUSION: Sudden neck swelling with rash may be a coincidental presentation, but, in the pandemic context, it is most likely a direct or indirect complication of COVID-19.

COVID-19 in Children: Update on Diagnosis and Management.

In December 2019, a new infectious disease called coronavirus disease 2019 (COVID-19) attributed to the new virus named severe scute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected. The gold standard for the diagnosis of SARS-CoV-2 infection is the viral identification in nasopharyngeal swab by real-time polymerase chain reaction. Few data on the role of imaging are available in the pediatric population. Similarly, considering that symptomatic therapy is adequate in most of the pediatric patients with COVID-19, few pediatric pharmacological studies are available. The main aim of this review is to describe and discuss the scientific literature on various imaging approaches and therapeutic management in children and adolescents affected by COVID-19. Clinical manifestations of COVID-19 are less severe in children than in adults and as a consequence the radiologic findings are less marked. If imaging is needed, chest radiography is the first imaging modality of choice in the presence of moderate-to-severe symptoms. Regarding therapy, acetaminophen or ibuprofen are appropriate for the vast majority of pediatric patients. Other drugs should be prescribed following an appropriate individualized approach. Due to the characteristics of COVID-19 in pediatric age, the importance of strengthening the network between hospital and territorial pediatrics for an appropriate diagnosis and therapeutic management represents a priority.

Immunity to measles in Italian children and adolescents: a persistent problem in view of measles elimination.

BACKGROUND: Despite efforts to increase coverage by two doses of measles vaccine in Italy, measles continues to circulate, with over 13 000 cases of disease since 2013. This study aimed to evaluate immunity to measles in Italian children and adolescents. METHODS: A total of 378 serum samples from subjects aged 9 months-18 years were collected in Northern, Central and Southern regions of Italy between 2012 and 2016. Specific IgG antibodies against measles were measured by a commercial ELISA kit. RESULTS: The frequency of IgG-positive samples ranged from 10.5% in infants under 1 year to 98.3% in children aged 6-7 years. The frequency of IgG was 72.2% in subjects aged 1-2 years, 85.6% in those aged 3-5 years and 88.3 and 86.8% in those aged 8-10 and 11-18 years, respectively. In Northern Italy, IgG prevalence was consistent with data on vaccination coverage, whereas some differences were observed in samples from subjects aged more than 8 years in Central and Southern Italy. CONCLUSIONS: Our findings confirm that a large proportion of children and adolescents in Italy are still susceptible to measles. While data on first- and second-dose measles vaccination are essential, they are not sufficient to identify susceptible population cohorts to be targeted by vaccination.

Do Antimicrobial Resistance Patterns Matter? An Algorithm for the Treatment of Patients With Impetigo.

BACKGROUND: Impetigo, a highly contagious bacterial skin infection commonly occurring in young children, but adults may also be affected. The superficial skin infection is mainly caused by Staphylococcus aureus (S. aureus) and less frequently by Streptococcus pyogenes (S. pyogenes). Antimicrobial resistance has become a worldwide concern and needs to be addressed when selecting treatment for impetigo patients. An evidence-based impetigo treatment algorithm was developed to address the treatment of impetigo for pediatric and adult populations. METHODS: An international panel of pediatric dermatologists, dermatologists, pediatricians, and pediatric infectious disease specialists employed a modified Delphi technique to develop the impetigo treatment algorithm. Treatment recommendations were evidence-based, taking into account antimicrobial stewardship and the increasing resistance to oral and topical antibiotics. RESULTS: The algorithm includes education and prevention of impetigo, diagnosis and classification, treatment measures, and follow-up and distinguishes between localized and widespread or epidemic outbreaks of impetigo. The panel adopted the definition of localized impetigo of fewer than ten lesions and smaller than 36 cm2 area affected in patients of two months and up with no compromised immune status. Resistance to oral and topical antibiotics prescribed for the treatment of impetigo such as mupirocin, retapamulin, fusidic acid, have been widely reported. CONCLUSIONS: When prescribing antibiotics, it is essential to know the local trends in antibiotic resistance. Ozenoxacin cream 1% is highly effective against S. pyogenes and S. aureus, including methycyllin-susceptible and resistant strains (MRSA), and may be a suitable option for localized impetigo.J Drugs Dermatol. 2021;20(2):134-142. doi:10.36849/JDD.5475 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Management of Congenital Diaphragmatic Hernia (CDH): Role of Molecular Genetics.

Congenital diaphragmatic hernia (CDH) is a relatively common major life-threatening birth defect that results in significant mortality and morbidity depending primarily on lung hypoplasia, persistent pulmonary hypertension, and cardiac dysfunction. Despite its clinical relevance, CDH multifactorial etiology is still not completely understood. We reviewed current knowledge on normal diaphragm development and summarized genetic mutations and related pathways as well as cellular mechanisms involved in CDH. Our literature analysis showed that the discovery of harmful de novo variants in the fetus could constitute an important tool for the medical team during pregnancy, counselling, and childbirth. A better insight into the mechanisms regulating diaphragm development and genetic causes leading to CDH appeared essential to the development of new therapeutic strategies and evidence-based genetic counselling to parents. Integrated sequencing, development, and bioinformatics strategies could direct future functional studies on CDH; could be applied to cohorts and consortia for CDH and other birth defects; and could pave the way for potential therapies by providing molecular targets for drug discovery.

Epidemic and pandemic viral infections: impact on tuberculosis and the lung: A consensus by the World Association for Infectious Diseases and Immunological Disorders (WAidid), Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycobacterial Infections (ESGMYC).

Major epidemics, including some that qualify as pandemics, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), HIV, influenza A (H1N1)pdm/09 and most recently COVID-19, affect the lung. Tuberculosis (TB) remains the top infectious disease killer, but apart from syndemic TB/HIV little is known regarding the interaction of viral epidemics and pandemics with TB. The aim of this consensus-based document is to describe the effects of viral infections resulting in epidemics and pandemics that affect the lung (MERS, SARS, HIV, influenza A (H1N1)pdm/09 and COVID-19) and their interactions with TB. A search of the scientific literature was performed. A writing committee of international experts including the European Centre for Disease Prevention and Control Public Health Emergency (ECDC PHE) team, the World Association for Infectious Diseases and Immunological Disorders (WAidid), the Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycobacterial Infections (ESGMYC) was established. Consensus was achieved after multiple rounds of revisions between the writing committee and a larger expert group. A Delphi process involving the core group of authors (excluding the ECDC PHE team) identified the areas requiring review/consensus, followed by a second round to refine the definitive consensus elements. The epidemiology and immunology of these viral infections and their interactions with TB are discussed with implications for diagnosis, treatment and prevention of airborne infections (infection control, viral containment and workplace safety). This consensus document represents a rapid and comprehensive summary on what is known on the topic.

Therapeutic perspectives in food allergy.

BACKGROUND: In the last twenty years, several studies have been conducted in the search for new therapeutic strategies in patients with food allergy; in particular, after the failure of injection immunotherapy, three different routes of administration, oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT), have been tested. The aim of this manuscript is to review OIT, SLIT, and EPIT clinical trials on food allergies and to suggest advantages and limits of the different routes of immunotherapy administration. MAIN BODY: Of the three different routes of immunotherapy used in the treatment of food allergy, OIT is, at present, the only one actually able to induce an increase in tolerance in the majority of patients. However, its use is affected by serious secondary effects, such as major abdominal symptoms and anaphylaxis. The combination with omalizumab reduces the percentage of serious side effects. There are not many studies with SLIT for food allergy, but they have nevertheless shown that it is possible to obtain an increase in tolerance; however, this increase is modest in comparison with that obtained by OIT. EPIT, performed through the diffusion of allergens on intact skin, is the most recent form of immunotherapy. Although there are many works on EPIT carried out in laboratory animals, only few clinical studies have been published in humans. EPIT, unlike OIT and SLIT, is not responsible for systemic secondary effects such as anaphylaxis and eosinophilic oesophagitis but only for local and mild effects in areas where the devices are applied. Moreover, EPIT is characterized by high patient adherence. CONCLUSION: OIT seems to have a prevalent application in patients who do not report previous symptoms of systemic or gastroenteric anaphylaxis, while SLIT and EPIT, in particular, could be more preferentially used in patients with a risk of anaphylaxis.

To mask or not to mask children to overcome COVID-19.

It has been reported that asymptomatic people can transmit the new coronavirus disease 2019 (COVID-19) and become important sources of COVID-19. To reduce the role of asymptomatic or poorly symptomatic people in COVID-19, universal use of face masks in addition to hand hygiene and safety distance seems extremely useful. Consequently, preparing the healthy child to use face masks is strongly needed. To obtain maximal compliance, reasons for mask wearing without attempts of removing must be clearly explained. Moreover, child's will must not be forced.Conclusion: On the basis of clinical findings, we think that the universal use of facial masks seems necessary when people have to go out in their everyday lives. In addition to the availability of masks of different sizes capable of adapting perfectly to the face, it is necessary that the use of masks in children is preceded by a strong parental work and school lessons on this issue and other hygiene topics with the main aim to obtain child cooperation. What is Known: • Asymptomatic people can transmit and become important sources of COVID-19. • Asymptomatic cases are common also in pediatrics. What is New: • Universal use of face masks for success against COVID-19 seems necessary also in pediatric age when people have to go out in their everyday lives. • In addition to the availability of masks of different sizes capable of adapting perfectly to the face, it is necessary that the use of masks in children is preceded by a strong parental work and school lessons with the main aim to obtain child cooperation.

Updated incidence and costs of hip fractures in elderly Italian population.

PURPOSE: We aimed at updating our previous researches about the burden of hip fractures in elderly Italian population. METHODS: We analyzed national hospitalizations records from 2000 to 2014 to compute age- and sex-specific standardized rates. RESULTS: 1,335,375 hospitalizations were recorded in people ≥ 65 (1,031,816 women: 77.27% and 303,559 men: 22.73%) over 15 years, passing from 73,493 in year 2000 to 94,525 in 2014, with an overall increase of 28.62% over the 15-year period (females: + 25.1%; males: + 41.2%). About 84.9% of total hip fractures were suffered by patients aged ≥ 75 years old. Direct hospitalization costs and rehabilitation costs increased from 343 to 457 million Euros and from 392 to 504 million Euros from year 2000 to 2014, respectively. Overall costs of hip fractures raised from 735 to 961 million Euros (+ 30.74% from 2000 to 2014). CONCLUSION: The number of hip fractures and related hospitalizations costs in Italian elderly population is still increasing due to the absolute number of fractures occurring in people ≥ 65 years old and particularly over 75 years old.