Thyroid function, sensitivity to thyroid hormones, and metabolic syndrome in euthyroid children and adolescents with Down syndrome.

PURPOSE: Patients with Down Syndrome (DS) showed multiple comorbidities, including thyroid disorders, obesity, and metabolic derangement. Different thyroid hormone (THs) patterns and sensitivity to thyroid hormone indices (STHI) seem to be associated with metabolic disorders. The study's aim was to evaluate the prevalence of metabolic syndrome (MS) in pediatric patients affected by DS, taking into consideration the relationship between the metabolic parameters, THs and STHI. METHODS: We enlisted 50 euthyroid patients with DS (9.03 ± 4.46). Clinical parameters, TSH, FT3, FT4 and the presence of MS were recorded. Indexes of peripheral sensitivity (FT3/FT4 ratio) and central sensitivity (TSH index, TSHI; TSH T4 resistance index, TT4RI; TSH T3 resistance index, TT3RI) were also detected. Thirty healthy subjects were included as a control group. RESULTS: MS was detected in 12% of the subjects with DS. FT3, FT4, and TSH levels were higher in DS than in the control group (p < 0.01); higher levels of FT3/FT4 ratio, TSHI and TT3RI and lower TT4RI values (p < 0.01) were also detected. A significant correlation was detected between FT3 and fasting blood glucose (FBG) (R = 0.46), triglyceride (TG) (r = 0.37), total (r = 0.55) and high density lipoprotein-cholesterol (HDL-C) (r = - 0.38), diastolic blood pressure (DBP) (r = - 0.4); FT3/FT4 ratio and waist circumference (WC) (r = 0.36); TSHI and total (r = 0.30) and HDL cholesterol (r = - 0.31); TT4RI and HDL cholesterol (r = - 0.31); TT3RI and total (r = 0.39) and HDL cholesterol (r = - 032). CONCLUSION: We confirmed a higher MS prevalence in children with DS compared to the control group. A significant association between THs, STHI, and the glucose and lipid metabolism parameters was detected supporting their role in metabolic alterations related to the DS.

Hypertension in a cohort of obese Caucasian children and adolescents and its association with glycometabolic indices: A proposed screening tool.

BACKGROUND AND AIM: Hypertension (HTN) is common among obese children and adolescents and increases their cardiovascular risk later in adulthood. The aim of the study was to evaluate the prevalence of HTN identified by office blood pressure (BP) measurement and ambulatory BP monitoring (ABPM) in a cohort of obese children and adolescents and its association with anthropometric and glycometabolic indices. METHODS AND RESULTS: Seventy consecutive obese Caucasian children and adolescents aged 7-16 years were enrolled. Patients underwent ABPM, echocardiogram and carotid ultrasonography. Sex- and age-adjusted logistic multivariable analysis models were used to assess the association between HOMA-IR, HOMA-ß, QUICKI with HTN at ABPM. Receiver Operation Curve (ROC) analysis with Youden J statistics was used to identify the optimal HOMA-IR, HOMA-ß and QUICKI cut-off to predict HTN at ABPM. Hypertensive office BP was found in 25.7% of obese patients. ABPM diagnosed HTN in 34.9% of patients: 20.6% of obese patients had masked HTN (MHTN), and 12.7% had white coat HTN (WCH). Hypertensive obese patients (according to ABPM) had higher HOMA-IR and HOMA-ß, and a lower QUICKI than normotensive subjects. HOMA-IR, HOMA-ß and QUICKI predicted HTN at ABPM in obese patients in age- and sex-adjusted logistic multivariable models. Optimal cut-offs to predict HTN at ABPM in obese patients were: HOMA-IR ≥ 3.30, HOMA-ß ≥ 226.7 and QUICKI <0.33, with high sensitivity. CONCLUSIONS: A sequential testing strategy applying office BP and glycometabolic indices can identify hypertensive obese pediatric patients with high diagnostic accuracy and potentially reducing costs. This strategy needs validation in an external and larger cohort.

Non-thyroidal illness syndrome and SARS-CoV-2-associated multisystem inflammatory syndrome in children.

PURPOSE: COVID-19 disease may result in a severe multisystem inflammatory syndrome in children (MIS-C), which in turn may alter thyroid function (TF). We assessed TF in MIS-C, evaluating its impact on disease severity. METHODS: We retrospectively considered children admitted with MIS-C to a single pediatric hospital in Milan (November 2019-January 2021). Non-thyroidal illness syndrome (NTIS) was defined as any abnormality in TF tests (FT3, FT4, TSH) in the presence of critical illness and absence of a pre-existing hormonal abnormality. We devised a disease severity score by combining severity scores for each organ involved. Glucose and lipid profiles were also considered. A principal component analysis (PCA) was performed, to characterize the mutual association patterns between TF and disease severity. RESULTS: Of 26 (19 M/7F) patients, median age 10.7 (IQR 5.8-13.3) years, 23 (88.4%) presented with NTIS. A low FT3 level was noted in 15/23 (65.3%), while the other subjects had varying combinations of hormone abnormalities (8/23, 34.7%). Mutually correlated variables related to organ damage and inflammation were represented in the first dimension (PC1) of the PCA. FT3, FT4 and total cholesterol were positively correlated and characterized the second axis (PC2). The third axis (PC3) was characterized by the association of triglycerides, TyG index and HDL cholesterol. TF appeared to be related to lipemic and peripheral insulin resistance profiles. A possible association between catabolic components and severity score was also noted. CONCLUSIONS: A low FT3 level is common among MIS-C. TF may be useful to define the impact of MIS-C on children's health and help delineate long term follow-up management and prognosis.

Neurological manifestations of Kawasaki disease and multisystem inflammatory syndrome in children associated with COVID-19: A comparison of two different clinical entities.

Kawasaki disease (KD) is one of the most frequent idiopathic vasculitis in children, affecting medium- and small-sized vessels. Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 has recently emerged as a new systemic hyperinflammatory condition affecting children some weeks after an acute COVID-19 infection. KD and MIS-C share different aspects and differ in many others: patients affected by MIS-C are usually older, with prominent gastrointestinal manifestations, diffuse adenopathy, extensive conjunctivitis, myocardial damage, leukopenia, and thrombocytopenia at the laboratory exams. Both conditions can present neurological complications. The aim of this manuscript is to provide a narrative review of neurological involvement in KD and MIS-C. A comprehensive review literature has been performed, and the main clinical features have been analyzed, contributing to neurological differential diagnosis.

New perspective for pain control in neonates: a comparative effectiveness research.

OBJECTIVE: To compare sucrose 24% oral gel formulation to liquid formula and breastfeeding during a heel prick in neonates. STUDY DESIGN: In this comparative effectiveness research 195 neonates >36 weeks' gestation were randomised to three groups, receiving during heel stick: (i) breastfeeding, (ii) sucrose 24% liquid with non-nutritive sucking and (iii) sucrose 24% gel with non-nutritive sucking. The pain was assessed through the Neonatal Infant Pain Scale. RESULTS: All the methods analysed has shown to be effective in reducing pain. There was an increase in odds of pain following liquid sucrose compared to breastfeeding (OR = 1.60; 95% CI: 0.82-3.3; p = 0.17). A reduction of odds of pain was showed comparing sucrose to breastfeeding (OR = 0.78; 0.38-1.6; 0.48), and comparing sucrose gel to liquid formula (OR = 0.48; 0.23-0.96; p = 0.04). CONCLUSION: Sucrose 24% gel with non-nutritive sucking seems to be a valid alternative when breastfeeding is not possible. Further research is needed.

Anti-inflammatory effects of diet and caloric restriction in metabolic syndrome.

BACKGROUND: Weight loss in patients with metabolic syndrome has positive effects on cardiovascular and type 2 diabetes risks, but its effects on peripheral cytokines and lipid profiles in patients are still unclear. AIM: To determine the effects of diet-induced weight loss on metabolic parameters, lipids and cytokine profiles. METHODS: Eighteen adult males with metabolic syndrome (defined according to IDF 2009) and Body Mass Index (BMI) between 25 and 35 kg/m2 were subjected to a balanced hypocaloric diet for 6 months to reach at least a 5% body weight loss. RESULTS: After weight loss, a significant improvement in BMI, waist circumference, insulin, fasting blood glucose and HOMA-IR (homeostasis model assessment of insulin resistance) was observed. The analysis of LDL (low-density lipoprotein cholesterol) and HDL (high-density lipoprotein cholesterol) lipoproteins showed a change in their composition with a massive transfer of triacylglycerols from HDL to LDL. This was associated with a significant reduction in peripheral pro-inflammatory cytokines such as IL-6, TNF-α, IL-8 and MIP-1ß, leading to an overall decreased inflammatory score. An interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of CETP (cholesteryl ester transfer protein), an enzyme with a key role in lipid change. CONCLUSION: Weight loss through caloric restriction is associated with an improvement in peripheral lipid and cytokine profiles that may play a major role in improving cardiovascular risk.

Vaginal delivery in SARS-CoV-2-infected pregnant women in Northern Italy: a retrospective analysis.

OBJECTIVE: To report mode of delivery and immediate neonatal outcome in women infected with COVID-19. DESIGN: Retrospective study. SETTING: Twelve hospitals in northern Italy. PARTICIPANTS: Pregnant women with COVID-19-confirmed infection who delivered. EXPOSURE: COVID 19 infection in pregnancy. METHODS: SARS-CoV-2-infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co-morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. MAIN OUTCOME AND MEASURES: Data on mode of delivery and neonatal outcome. RESULTS: In all, 42 women with COVID-19 delivered at the participating centres; 24 (57.1%, 95% CI 41.0-72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7-59.0) cases: in eight cases the indication was unrelated to COVID-19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8-61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3-61.6) required oxygen support and 4/19 (21.1%, 95% CI 6.1-45.6) were admitted to a critical care unit. Two women with COVID-19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS-Cov-2 infection. In one case, a newborn had a positive test after a vaginal operative delivery. CONCLUSIONS: Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn. TWEETABLE ABSTRACT: This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn.

Exacerbations and Pseudomonas aeruginosa colonization are associated with altered lung structure and function in primary ciliary dyskinesia.

BACKGROUND: Recurrent bacterial infections of the respiratory tract are one of the major clinical features of the primary ciliary dyskinesia (PCD), a rare genetic disease due to malfunctioning of motile cilia. Chronic infections and persistent inflammation of the respiratory system result in progressive lung disease. Aim of the study was to highlight the main factors associated with clinical, functional and anatomical deterioration in PCD patients. METHODS: We retrospectively analyzed data from 58 patients with PCD, 37 adults and 21 children. The demographic and clinical data, forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC), sputum microbiology and imaging results (chest CT scores-modified Bhalla) were recorded. Patients were stratified according to the number of exacerbations (< 2/year vs ≥ 2/year) and chronic Pseudomonas aeruginosa (PA) colonization. The possible correlations between lung function and chest CT scores were assessed; we also evaluated the correlation between these parameters and the severity scores for bronchiectasis (BSI, FACED and e-FACED). RESULTS: Chest CT scores showed a significant correlation with FEV1 (p = 0.0002), age (p <  0.0001), BMI (p = 0.0002) and number of lung lobes involved (p <  0.0001). PA colonization had an overall prevalence of 32.6%: no significant difference in FEV1 between PA colonized and non-colonized patients was found (p = 0.70), while chest CT score was significantly worse in chronic PA colonized patients (p = 0.009). Patients with a high number of exacerbation (≥ 2/year) were older (p = 0.01), had lower FEV1 (p = 0.03), greater number of lobes involved (p < 0.001) and worse CT score than patients with low number of exacerbations (p = 0.001); they also had higher prevalence of PA chronic bronchial infection (33.3% versus 13.6%, p = 0.10). Multivariable linear regression analyses adjusted for gender, age and BMI showed positive associations between PA colonization and number of exacerbations with severity of disease (number of lobes involved, CT score, BSI, FACED, and e-FACED). CONCLUSIONS: In our PCD population the number of exacerbations (≥ 2/year) and PA colonization were the two most relevant factors associated with severity of disease.

Response to: Bias in the use of a SSClow/CCR3pos gate to capture basophils in chronic urticaria?

A response to Chirumbolo S, Bjørklund G, and Vella A, Bias in the use of a SSClow/CCR3pos gate to capture basophils in chronic urticaria? Immunobiology, 224(3), 2019, 353-354.

Effects and safety of delayed versus early umbilical cord clamping in newborns of HIV-infected mothers.

OBJECTIVE: To investigate the effect of a 2 minutes-delayed cord clamp (DCC) versus early cord clamp (ECC) on neonate haemoglobin concentration 24 hours and 1 month after birth, and assess the safety of DCC concerning the risk of HIV infection. DESIGN: Sixty-four mother-infant peers were enrolled. All mothers were on stable ARV therapy. Viral load, CD4+ count and blood haemoglobin (Hb) concentrations 24 hours before delivery were collected from all mothers and their infants. METHODS: All patients were enrolled at the Department of Paediatrics, AO FBF Sacco Hospital in Milan, and were followed until 18 months after birth. Women with haematological diseases and obstetrical complications were excluded. All of 64 mother and infants couples (32 ECC group and 32 DCC group) completed the study. ECC and DCC are defined as application of umbilical clamp within 30 seconds and 120 seconds after birth, respectively. RESULTS: Mean birth weight was significantly higher in the DCC compared with ECC group. Mean Hb levels at birth were significantly higher in DCC than in ECC group (p = .05): this difference persisted at 1 month of life. All newborns showed negative viral load. CONCLUSIONS: DCC 2 minutes after birth is proven to be a safe procedure, particularly beneficial in newborns from HIV mothers. The risk of anemia is significantly decreased at 24 hours after birth and persists at age of 1 month without any increased risk of neonatal jaundice or polycitemia.

Indications and complications of inpatient parenteral nutrition prescribed to children in a large tertiary referral hospital.

BACKGROUND: Parenteral Nutrition (PN) is prescribed to children with intestinal failure. Although life saving, complications are common. Recommendations for indications and constituents of PN are made in the 2005 guidelines by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). The aim of this study was to establish if the indications for prescribing PN in a tertiary children's hospital were appropriate, and to identify complications encountered. Data were compared to those published by the National Confidential Enquiry into patient outcome and death (NCEPOD) carried out in the United Kingdom in 2010. METHODS: Children and newborns receiving inpatient PN over a 6 months period were entered into the study and data was collected prospectively. The appropriate indications for the use of PN were based on the ESPGHAN guidelines. Recorded complications were divided into metabolic, central venous catheter (CVC) related, hepatobiliary and nutritional. RESULTS: A total of 303 children (67 newborns) were entered into the study. The main indications for the start of PN were critical illness (66/303), surgery (63/303) and bone marrow transplantation (28/303). The ESPGHAN recommendations were followed in 91.7% (278/303) of cases (95.5% of newborns, 90.7% of children). PN was considered inappropriate in 12/303 patients and equivocal in 13. The mean PN duration was 18 days (1-160) and the incidence of complications correlated to the length of PN prescribed. Metabolic, hepatobiliary and CVC related complications affected 74.6, 24.4, 16.4% of newborns and 76.7, 37.7 and 24.6% of children respectively. In relation to the appropriate indications for the start of PN our results mirrored those reported by the NCEPOD audit (92.4% of newborns and 88.6% children). However, the incidence of metabolic disturbances was higher in our cohort (74.6% vs 30.4% in children, 76.7% vs 14.3% in newborns) but CVC related complications lower amongst our newborns (16,4% vs 25%). CONCLUSIONS: Although the indications for inpatient PN in children is mostly justified, there is still a proportion who is receiving PN unnecessarily. PN related complications remain common. There is a need for better education amongst health professionals prescribing PN and access to nutritional support teams to reduce unwanted side effects.

Could seasonal allergy be a risk factor for acute rhinosinusitis in children?

OBJECTIVE: To evaluate the incidence of acute rhinosinusitis in children with grass pollen induced rhinitis during the period of grass pollinosis. METHODS: Children with nasal symptoms from grass pollen induced rhinitis but without rhinosinusitis symptoms were selected. Their parents were asked to complete a diary during pollen exposure to report nasal symptoms and drugs used daily. When rhinosinusitis was suspected, the confirmatory diagnosis of acute rhinosinusitis was made by fibro-endoscopy. Children without inhalant allergy served as controls. RESULTS: Seventeen out of 242 children (7.0 per cent) had a diagnosis of acute rhinosinusitis, confirmed by fibro-endoscopy, during grass pollination, compared to 3 out of 65 (4.6 per cent) in the control group (p = 0.49). Among allergic children, those with acute rhinosinusitis had symptoms for a greater number of days and/or a higher symptoms score than children without acute rhinosinusitis. CONCLUSION: Children with grass pollen induced rhinitis during exposure to pollen have an incidence of endoscopically confirmed acute rhinosinusitis comparable to non-allergic children. This suggests that grass pollen induced rhinitis is a negligible risk factor for acute rhinosinusitis.

WNT10A gene is the second molecular candidate in a cohort of young Italian subjects with ectodermal derivative impairment (EDI).

Ectodermal dysplasias are a group of genetic disorders defined by ectodermal derivative impairment (EDI). To test the impact of the Wnt/beta-catenin pathway in the genetic screening of EDI, we performed a molecular gene study of WNT10A in 60 subjects from a population of 133 young Italian patients referred for the impairment of at least one major ectodermal-derived structure and who had a previous negative molecular screen for ectodysplasin signaling pathway genes ED1, EDAR, and EDARADD. Fourteen WNT10A mutations were identified in 33 subjects (24.8%), 11 of which were novel variants. The phenotype was evaluated through a detailed clinical examination of the major and minor ectodermal-derived structures. This study is the first to show that, after ED1, WNT10A is the second molecular candidate for EDI in a large Italian Caucasian population. The study confirmed that Phe228Ile is the most frequent WNT10A variant in Caucasian populations, and that WNT10A mutations are associated with large variability in EDI.

Combined use of a wristband and a smartphone to reduce body weight in obese children: randomized controlled trial.

BACKGROUND: Technological instruments may help control paediatric obesity. OBJECTIVE: We tested whether a personalized programme based on the energy expenditure obtained from a wristband (WB) and the energy intake obtained from a smartphone application (APP) is superior to a standard approach at promoting weight loss. METHODS: We performed a randomized controlled trial in obese children aged 10-17 years. The experimental (EXP) and control (CTR) groups were given a low-energy diet and a prescription for physical activity. The EXP group was equipped with a WB and an APP and given personalized feedback every 7 days. The main outcome was weight loss at 3 months. RESULTS: The mean (standard deviation) z-score of body mass index at the enrollment was 2.20 (0.47) in the EXP (n = 16 out of 23) and 2.09 (0.34) in the CTR group (n = 14 out of 20) of children who completed the trial. The mean (95%CI) difference in weight loss at 3 months was 0.07 kg (95%CI: 2.81 to 2.96) for EXP vs. the CTR. CONCLUSION: A personalized lifestyle programme based on a WB and an APP was not superior to a standard lifestyle programme at promoting weight loss in obese children.

Cranial ultrasound is a reliable first step imaging in children with suspected craniosynostosis.

PURPOSE: Skull radiography (SR) and Computed Tomography (CT) are still proposed as the first-line imaging choice for the diagnosis of craniosynostosis (CS) in children with abnormal head shape, but both techniques expose infants to ionizing radiation. Several studies shown that ultrasound may play an important role in the diagnosis of craniosynostosis. The aim of our study is to assess the diagnostic accuracy of cranial ultrasound scan (CUS) and confirm if it is a reliable first step imaging evaluation for the diagnosis of craniosynostosis in newborn. METHOD: A cohort of 196 infants (122/74 males/females), with a mean age of 4 months, clinically suspected to have abnormal closure of cranial sutures, were firstly examined by CUS and then referred to neuroradiologists to perform volumetric CT scan if the suspicion of stenosis was ecographically confirmed; otherwise, a routine follow-up and physical treatment was performed, to observe the evolution of the head shape. RESULTS: Of the 196 children studied by CUS, only two had inconclusive studies due to age limitation (>12 months). Thirty children were diagnosed with cranial synostosis at CUS and verified by CT; all the CUS results were confirmed, except two cases, that were revealed as false positives in the starting phase of the study. Twelve patients with very prominent head deformity and negative CUS underwent CT, which confirmed the CUS results in all of them; one case of closure of both temporal sutures, not studied by CUS, was documented by CT. All the 148 children with poor clinical suspicion and negative CUS underwent just a prolonged clinical follow-up. In all of them, a progressive normalization of head shape was observed, and the craniosynostosis was excluded on a clinical base. CONCLUSIONS: CUS is a highly specific and sensitive imaging technique. In referral centers, expert hands can use it as a reliable first-step screening for infants younger than 1 year, suspected to have a craniosynostosis, thus avoiding unnecessary exposure to ionizing radiation. The "golden age" to obtain the best CUS results is under 6 months of life. Because the method is operator-dependent and there is a learning curve, a case centralization is advisable.

Dysphagia screening in subacute care settings using the Italian version of the Royal Brisbane and Women's Hospital (I-RBWH) dysphagia screening tool.

The large majority of the available dysphagia screening tools has been developed for the stroke population. Only few screening tools are suitable for heterogeneous groups of patients admitted to a subacute care unit. The Royal Brisbane and Women's Hospital (RBWH) dysphagia screening tool is a nurse-administered, evidence-based swallow screening tool for generic acute hospital use that demonstrates excellent sensitivity and specificity. No Italian version of this tool is available to date. The aim of this study was to determine the reliability and screening accuracy of the Italian version of the RBWH (I-RBWH) dysphagia screening tool. A total of 105 patients consecutively admitted to a subacute care unit were enrolled. Using the I-RBWH tool, each patient was evaluated twice by trained nurses and once by a speech and language pathologist (SLP) blind to nurses' scores. The SLP also performed standardised clinical assessment of swallowing using the Mann assessment of swallowing ability (MASA). During the first and the second administration of the I-RBWH by nurses, 28 and 27 patients, respectively, were considered at risk of dysphagia, and 27 were considered at risk after SLP assessment. Intra- and inter-rater reliability was satisfactory. Comparison between nurse I-RBWH scores and MASA examination demonstrated a sensitivity and specificity of the I-RBWH dysphagia screening tool up to 93% and 96%, respectively; the positive and negative predictive values were 90% and 97%, respectively. Thus, the current findings support the reliability and accuracy of the I-RBWH tool for dysphagia screening of patients in subacute settings. Its application in clinical practice is recommended.

Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence.

In 2014, the Food and Drug Administration approved a new human papillomavirus 9-valent vaccine (9vHPV), targeting nine HPV types: HPV types 6, 11, 16, and 18, which are also targeted by the quadrivalent HPV vaccine (qHPV), plus five additional high cancer risk HPV types (HPV types 31, 33, 45, 52, and 58). The aim of the current study was to systematically retrieve, qualitatively and quantitatively pool, as well as critically appraise all available evidence on 9vHPV from randomized controlled trials (RCTs). We conducted a systematic review of the literature on 9vHPV efficacy, immunogenicity and safety, as well as a systematic search of registered, completed, and ongoing RCTs. We retrieved and screened 227 records for eligibility. A total of 10 publications reported on RCTs' results on 9vHPV and were included in the review. Sixteen RCTs on 9vHPV have been registered on RCT registries. There is evidence that 9vHPV generated a response to HPV types 6, 11, 16 and 18 that was non-inferior to qHPV. Vaccine efficacy against five additional HPV type-related diseases was directly assessed on females aged 16-26 years (risk reduction against high-grade cervical, vulvar or vaginal disease = 96·7%, 95% CI 80·9%-99·8%). Bridging efficacy was demonstrated for males and females aged 9-15 years and males aged 16-26 years (the lower bound of the 95% CIs of both the geometric mean titer ratio and difference in seroconversion rates meeting the criteria for non-inferiority for all HPV types). Overall, 9vHPV has been proved to be safe and well tolerated. Other RCTs addressed: 9vHPV co-administration with other vaccines, 9vHPV administration in subjects that previously received qHPV and 9vHPV efficacy in regimens containing fewer than three doses. The inclusion of additional HPV types in 9vHPV offers great potential to expand protection against HPV infection. However, the impact of 9vHPV on reducing the global burden of HPV-related disease will greatly depend on vaccine uptake, coverage, availability, and affordability.

Oral manifestations of gastrointestinal diseases in children. Part 3: Ulcerative colitis and gastro-oesophageal reflux disease.

BACKGROUND: Alterations of the oral cavity are common in children: 22% of children aged less than 4 years and 44% of those aged more than 12 develop dental erosion, 9-95% of children in Europe and in North America develop gingivitis, with adolescents showing a prevalence of more than 60% [Italian Ministry of Health, Guidelines 2013]. Alterations within the oral cavity can be the first sign of systemic diseases and may thus allow for an early diagnosis and treatment. In particular, being the oral cavity a part of the gastrointestinal system, oral alterations can be an expression of a gastrointestinal disease. Pyostomatitis vegetans can be a sign of ulcerative colitis. Dental erosion with enamel loss in facial, occlusal, and lingual surfaces, and an increased risk of dental caries have been reported in children and adolescents with gastro-oesophageal reflux with varying prevalence. A prompt recognition of systemic diseases through a careful examination of the oral cavity could allow proper investigations and management in a timely fashion.

Oral manifestations of gastrointestinal diseases in children. Part 2: Crohn's disease.

Alterations within the oral cavity can be the first sign of systemic diseases and may thus allow for an early diagnosis and treatment. In particular, being the oral cavity a part of the gastrointestinal system, oral alterations can be an expression of a gastrointestinal disease. Diffuse mucosal swelling, cobblestone mucosa, localised mucogingivitis, deep linear ulceration, fibrous tissue tags, polyps, nodules, pyostomatitis vegetans, and aphthous-like ulcers have been described in Crohn's disease. A prompt recognition of systemic diseases through a careful examination of the oral cavity allows for proper investigations and timely treatment.