Loss of p53 activates thyroid hormone via type 2 deiodinase and enhances DNA damage

: The Thyroid Hormone (TH) activating enzyme, type 2 Deiodinase (D2), is functionally required to elevate the TH concentration during cancer progression to advanced stages. However, the mechanisms regulating D2 expression in cancer still remain poorly understood. Here, we show that the cell stress sensor and tumor suppressor p53 silences D2 expression, thereby lowering the intracellular THs availability. Conversely, even partial loss of p53 elevates D2/TH resulting in stimulation and increased fitness of tumor cells by boosting a significant transcriptional program leading to modulation of genes involved in DNA damage and repair and redox signaling. In vivo genetic deletion of D2 significantly reduces cancer progression and suggests that targeting THs may represent a general tool reducing invasiveness in p53-mutated neoplasms

Inter-society consensus for the use of inhaled corticosteroids in infants, children and adolescents with airway diseases

Background: In 2019, a multidisciplinary panel of experts from eight Italian scientific paediatric societies developed a consensus document for the use of inhaled corticosteroids in the management and prevention of the most common paediatric airways disorders. The aim is to provide healthcare providers with a multidisciplinary document including indications useful in the clinical practice. The consensus document was intended to be addressed to paediatricians who work in the Paediatric Divisions, the Primary Care Services and the Emergency Departments, as well as to Residents or PhD students, paediatric nurses and specialists or consultants in paediatric pulmonology, allergy, infectious diseases, and ear, nose, and throat medicine. Methods: Clinical questions identifying Population, Intervention(s), Comparison and Outcome(s) were addressed by methodologists and a general agreement on the topics and the strength of the recommendations (according to the GRADE system) was obtained following the Delphi method. The literature selection included secondary sources such as evidence-based guidelines and systematic reviews and was integrated with primary studies subsequently published. Results: The expert panel provided a number of recommendations on the use of inhaled corticosteroids in preschool wheezing, bronchial asthma, allergic and non-allergic rhinitis, acute and chronic rhinosinusitis, adenoid hypertrophy, laryngitis and laryngospasm. Conclusions: We provided a multidisciplinary update on the current recommendations for the management and prevention of the most common paediatric airways disorders requiring inhaled corticosteroids, in order to share useful indications, identify gaps in knowledge and drive future research

Effective treatment of late-onset noninfectious pulmonary complication with ruxolitinib in an 8-year-old boy

Ruxolitinib could be considered as an option in the treatment of LONIPCs in children when other treatments are ineffective. Spirometry is a valuable tool for both diagnosis and follow-up of LONIPCs in children

Atypical periprosthetic femoral fractures of the hip: characterisation of three cases

Introduction: Long-term use of bisphosphonates (BPs) has been associated with a specific type of tensile side femoral stress fracture known as Atypical Femoral Fracture (AFF). Theoretically periprosthetic femoral fractures (PFF) should be excluded from the diagnosis of AFF. However, emerging evidence correlates prolonged BPs use with the occurrence of a type of PFF with an atypical pattern (atypical PFF, APFF). The aim of the present study is to report 3 cases of APFF treated at a single centre. Methods: Clinical and radiographic records of PFF that occurred between January 2016 and August 2018 were retrospectively reviewed. All patients meeting the American Society for Bone and Mineral Research (ASBMR) criteria for definition of PFF were included. Management strategies for APFF and patient outcomes, including fracture healing and hip function (assessed by the Oxford Hip Score [OHS]) were collected. Results: 3 patients in the study period were identified as APFF (1 incomplete, 2 complete). All patients were females with a mean age of 83.3 years. All patients were treated with lateral plating. The application of a contralateral strut allograft resulted in fracture healing in cases of complete fractures. Mean OHS at final follow-up was 34.3. Conclusions: Despite occurring around a hip stem like PFF, APFF had peculiar clinical and radiographic features, making them more similar to AFF. Therefore, the orthopaedic surgeon should also consider the natural history and healing problems associated with AFF prior in order to choose the most appropriate management for APFF

Atypical periprosthetic femoral fractures of the hip: characterisation of three cases

Introduction:Long-term use of bisphosphonates (BPs) has been associated with a specific type of tensile side femoral stress fracture known as Atypical Femoral Fracture (AFF). Theoretically periprosthetic femoral fractures (PFF) should be excluded from the diagnosis of AFF. However, emerging evidence correlates prolonged BPs use with the occurrence of a type of PFF with an atypical pattern (atypical PFF, APFF). The aim of the present study is to report 3 cases of APFF treated at a single centre.Methods:Clinical and radiographic records of PFF that occurred between January 2016 and August 2018 were retrospectively reviewed. All patients meeting the American Society for Bone and Mineral Research (ASBMR) criteria for definition of PFF were included. Management strategies for APFF and patient outcomes, including fracture healing and hip function (assessed by the Oxford Hip Score [OHS]) were collected.Results:3 patients in the study period were identified as APFF (1 incomplete, 2 complete). All patients were females with a mean age of 83.3 years. All patients were treated with lateral plating. The application of a contralateral strut allograft resulted in fracture healing in cases of complete fractures. Mean OHS at final follow-up was 34.3.Conclusions:Despite occurring around a hip stem like PFF, APFF had peculiar clinical and radiographic features, making them more similar to AFF. Therefore, the orthopaedic surgeon should also consider the natural history and healing problems associated with AFF prior in order to choose the most appropriate management for APFF.</jats:sec

Inhaled corticosteroids use in childhood respiratory diseases: an italian survey on pediatricians’ prescription habits

Abstract Background A national consensus document on inhaled corticosteroids (ICS) use in childhood, produced by the main Italian pediatric scientific societies, has been recently released. The aim of this study was to gather information on the current pediatricians’ ICS prescription habits in Italy for the management of the most common pediatric respiratory diseases, namely allergic rhinitis (AR), asthma, preschool wheezing and laryngitis. Methods From the 1st October 2018 to the 31st January 2019 a link to an online questionnaire was sent monthly through a newsletter to the members of the Italian Society of Pediatrics. The questionnaire included 18 items on ICS use in the most common pediatric respiratory diseases. Data collection and reporting was based on STROBE Statement Checklist for cross-sectional studies. Results One thousand-two questionnaires were returned from primary care pediatricians (39.1%), hospital pediatricians (38.7%), private practicers (16.4%), university pediatricians (3.1%) and Pediatrics residents (2.7%). We found a good adherence to the international guidelines on AR, with prevalent use of oral antihistamine (60.6%) in the secretive phenotype and nasal ICS in the obstructive phenotype (64.8%). In asthma exacerbations ICS are not used in 53.4% of cases, but they are used at high dose in 27.9% and at low dose in 18.7% of cases. In intermittent asthma, ICS are not chosen as a daily controller therapy in 54.1% of cases, while they are chosen as a low dose daily therapy in 44.5% of cases (high dose in 1.4%). In children with persistent asthma, ICS are chosen as a daily low dose therapy in 67.4% of cases and as a daily high dose therapy in 31%. In the management of preschool wheezing, when a long-term treatment is needed, ICS are chosen both alone and in association with antileukotrienes in 71.4% of cases. Children affected by recurrent asthma exacerbations and wheezing are closely followed up, in particular by their primary care pediatricians. The preference for certain molecules in the treatment of different respiratory diseases also emerged. Conclusions Pediatricians’ ICS prescription habits in Italy should be improved, especially in the management of asthma. Future surveys on a more numerous sample will be useful to analyze differences in prescription habits on the basis of pediatricians’ work settings and geographical distribution. </jats:sec

Inhaled corticosteroids use in childhood respiratory diseases: an italian survey on pediatricians' prescription habits

BACKGROUND: A national consensus document on inhaled corticosteroids (ICS) use in childhood, produced by the main Italian pediatric scientific societies, has been recently released. The aim of this study was to gather information on the current pediatricians' ICS prescription habits in Italy for the management of the most common pediatric respiratory diseases, namely allergic rhinitis (AR), asthma, preschool wheezing and laryngitis.METHODS: From the 1st October 2018 to the 31st January 2019 a link to an online questionnaire was sent monthly through a newsletter to the members of the Italian Society of Pediatrics. The questionnaire included 18 items on ICS use in the most common pediatric respiratory diseases. Data collection and reporting was based on STROBE Statement Checklist for cross-sectional studies.RESULTS: One thousand-two questionnaires were returned from primary care pediatricians (39.1%), hospital pediatricians (38.7%), private practicers (16.4%), university pediatricians (3.1%) and Pediatrics residents (2.7%). We found a good adherence to the international guidelines on AR, with prevalent use of oral antihistamine (60.6%) in the secretive phenotype and nasal ICS in the obstructive phenotype (64.8%). In asthma exacerbations ICS are not used in 53.4% of cases, but they are used at high dose in 27.9% and at low dose in 18.7% of cases. In intermittent asthma, ICS are not chosen as a daily controller therapy in 54.1% of cases, while they are chosen as a low dose daily therapy in 44.5% of cases (high dose in 1.4%). In children with persistent asthma, ICS are chosen as a daily low dose therapy in 67.4% of cases and as a daily high dose therapy in 31%. In the management of preschool wheezing, when a long-term treatment is needed, ICS are chosen both alone and in association with antileukotrienes in 71.4% of cases. Children affected by recurrent asthma exacerbations and wheezing are closely followed up, in particular by their primary care pediatricians. The preference for certain molecules in the treatment of different respiratory diseases also emerged.CONCLUSIONS: Pediatricians' ICS prescription habits in Italy should be improved, especially in the management of asthma. Future surveys on a more numerous sample will be useful to analyze differences in prescription habits on the basis of pediatricians' work settings and geographical distribution