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Introduction: High-grade treatment-emergent neuroendocrine prostate cancer (T-NEPC) is a rare subtype of prostate cancer with limited therapeutic options and poor prognosis. Understanding biomarkers that influence the efficacy of immune checkpoint inhibitors (IO) is vital to form a better therapeutic arsenal for these patients. Case Presentation: We describe an impressive response to IO combination immunotherapy with ipilimumab plus nivolumab (Ipi/nivo) in a patient with T-NEPC who had failed standard treatment approaches. The patient was showing signs of a rapid decline in quality of life despite his prostate-specific antigen levels remaining undetectable and had no previous response to standard therapies. The results of the next-generation sequencing DNA analysis demonstrated the presence of intermediary tumor burden, an ATM mutation and a rare SF3B1 (G742D) mutation, and served as rational for IO therapy in this patient. Conclusions: This case highlights the genetic profile of tumor with a rare combination of ATM and SF3B1 mutations that could be further explored as biomarkers for IO therapy in T-NEPC and other tumor types.

Abstract Patients with acute exacerbation of lung fibrosis with usual interstitial pneumonia (EUIP) pattern are at increased risk for ventilator-induced lung injury (VILI) and mortality when exposed to mechanical ventilation (MV). Yet, lack of a mechanical model describing UIP-lung deformation during MV represents a research gap. Aim of this study was to develop a constitutive mathematical model for UIP-lung deformation during lung protective MV based on the stress–strain behavior and the specific elastance of patients with EUIP as compared to that of acute respiratory distress syndrome (ARDS) and healthy lung. Partitioned lung and chest wall mechanics were assessed for patients with EUIP and primary ARDS (1:1 matched based on body mass index and PaO2/FiO2 ratio) during a PEEP trial performed within 24 h from intubation. Patient’s stress–strain curve and the lung specific elastance were computed and compared with those of healthy lungs, derived from literature. Respiratory mechanics were used to fit a novel mathematical model of the lung describing mechanical-inflation-induced lung parenchyma deformation, differentiating the contributions of elastin and collagen, the main components of lung extracellular matrix. Five patients with EUIP and 5 matched with primary ARDS were included and analyzed. Global strain was not different at low PEEP between the groups. Overall specific elastance was significantly higher in EUIP as compared to ARDS (28.9 [22.8–33.2] cmH2O versus 11.4 [10.3–14.6] cmH2O, respectively). Compared to ARDS and healthy lung, the stress/strain curve of EUIP showed a steeper increase, crossing the VILI threshold stress risk for strain values greater than 0.55. The contribution of elastin was prevalent at lower strains, while the contribution of collagen was prevalent at large strains. The stress/strain curve for collagen showed an upward shift passing from ARDS and healthy lungs to EUIP lungs. During MV, patients with EUIP showed different respiratory mechanics, stress–strain curve and specific elastance as compared to ARDS patients and healthy subjects and may experience VILI even when protective MV is applied. According to our mathematical model of lung deformation during mechanical inflation, the elastic response of UIP-lung is peculiar and different from ARDS. Our data suggest that patients with EUIP experience VILI with ventilatory setting that are lung-protective for patients with ARDS.

There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM) and automated insulin delivery systems. These technological advances have radically changed the daily lives of people living with diabetes, improving the quality of life of both children and their families. Despite this, hypoglycemia remains the primary side-effect of insulin therapy. Based on a systematic review of the available scientific evidence, this paper aims to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia. The objective of these recommendations is to unify the behavior of pediatric diabetologists with respect to the timely recognition and prevention of hypoglycemic episodes and the correct treatment of hypoglycemia, especially in patients using CGM or advanced hybrid closed-loop systems. All authors have long experience in the specialty and are members of the Italian Society of Pediatric Endocrinology and Diabetology. The goal of treating hypoglycemia is to raise blood glucose above 70 mg/dL (3.9 mmol/L) and to prevent further decreases. Oral glucose at a dose of 0.3 g/kg (0.1 g/kg for children using “smart pumps” or hybrid closed loop systems in automated mode) is the preferred treatment for the conscious individual with blood glucose

Background: The molecular pathways involved in the onset and progression of idiopathic pulmonary fibrosis (IPF) still need to be fully clarified as some are shared with lung cancer development. HOXB7, a member of the homeobox (Hox) gene family, has been found involved in various cancers. Methods: Immunohistochemical (IHC) analysis was run on lung tissue samples from surgical lung biopsy (SLB) of 19 patients with IPF, retrospectively selected from the IPF database of the University Hospital of Modena. HOXB7 expression was analyzed and compared with that of five patients with no evidence of pulmonary fibrosis as controls. Results: The semi-quantitative analysis of IHC showed that HOXB7 protein expression was higher in IPF patients compared to controls (difference between means = 6.2 ± 2.37, p = 0.0157). Further, HOXB7 expression was higher in IPF patients with a higher extent of fibrosis (50–75%)—measured with high-resolution computer tomography—compared to those with a lower extent (0–25%) (difference between means = 25.74 ± 6.72, p = 0.004). Conclusions: The expression of HOXB7 is higher in the lung of IPF patients compared to controls, and was represented in different cellular compartments within the lung niche. Further investigations are needed to clarify its role in the pathogenesis and progression of IPF.

Abstract Measurement of body core temperature (Tcore) is paramount to determining the thermoregulatory strain of athletes. However, standard measurement procedures of Tcore are not practical for extended use outside the laboratory environment. Therefore, determining the factors that predict Tcore during a self‐paced run is crucial for creating more effective strategies to minimize the heat‐induced impairment of endurance performance and reduce the occurrence of exertional heatstroke. The aim of this study was to identify the factors predicting Tcore values attained at the end of a 10 km time trial (end‐Tcore) under environmental heat stress. Initially, we extracted data obtained from 75 recordings of recreationally trained men and women. Next, we ran hierarchical multiple linear regression analyses to understand the predictive power of the following variables: wet‐bulb globe temperature, average running speed, initial Tcore, body mass, differences between Tcore and skin temperature (Tskin), sweat rate, maximal oxygen uptake, heart rate and change in body mass. Our data indicated that Tcore increased continuously during exercise, attaining 39.6 ± 0.5°C (mean ± SD) after 53.9 ± 7.5 min of treadmill running. This end‐Tcore value was primarily predicted by heart rate, sweat rate, differences between Tcore and Tskin, wet‐bulb globe temperature, initial Tcore, running speed and maximal oxygen uptake, in this order of importance (β power values corresponded to 0.462, −0.395, 0.393, 0.327, 0.277, 0.244 and 0.228, respectively). In conclusion, several factors predict Tcore in athletes subjected to self‐paced running under environmental heat stress. Moreover, considering the conditions investigated, heart rate and sweat rate, two practical (non‐invasive) variables, have the highest predictive power.

Objective: This Italian survey aims to evaluate real-life long-term efficac y and safety of recombinant human growth hormone (rhGH) therapy in children wit h short stature homeobox-containing gene deficiency disorders (SHOX-D) and to id entify potential predictive factors influencing response to rhGH therapy. Design and methods: This is a national retrospective observational study collectin g anamnestic, anthropometric, clinical, instrumental and therapeutic data in children and adolescents with a genetic confirmation of SHOX-D treated on rhG H. Data were collected at the beginning of rhGH therapy (T0), yearly during the first 4 years of rhGH therapy (T1, T2, T3 and T4) and at near-final height (nFH) (T5), when availab le. Results: One hundred and seventeen SHOX-D children started rhGH therapy (initial dose 0.23 ± 0.04 mg/kg/week) at a mean age of 8.67 ± 3.33 years (74% prepubertal), 99 completed the first year of treatment and 46 reached nFH. During rhGH therapy, growth velocity (GV), standard deviation score (SDS) and height (H) SD S improved significantly. Mean H SDS gain from T0 was +1.14 ± 0.58 at T4 and +0.80 ± 0.98 at T5. Both patients carrying mutations involving intragenic SHOX region (group A) a nd ones with regulatory region defects (group B) experienced a similar beneficial therap eutic effect. The multiple regression analysis identified the age at the start of rhGH trea tment (β = −0.31, P = 0.030) and the GV during the first year of rhGH treatment ( β = 0.45, P = 0.008) as main independent predictor factors of height gain. During rhGH thera py, no adverse event of concern was reported. Conclusions: Our data confirm the efficacy and safety of rhGH therapy in SHOX- D children, regardless the wide variety of genotype. Significance Statement: Among children with idiopathic short stature, the prevalence o f SHOX-D is near to 1/1000–2000 (1.1–15%) with a wide phenotypic spectrum. Current guidelines support rhGH therapy in SHOX-D children, but long-te rm data are still few. Our real-life data confirm the efficacy and safety of rhGH therapy in SHOX-D children, regardless of the wide variety of genotypes. Moreover, rhGH the rapy seems to blunt the SHOX-D phenotype. The response to rhGH in the first year of trea tment and the age when rhGH was started significantly impact the height gain.

IntroductionIdiopathic pulmonary fibrosis (IPF) severely affects the lung leading to aberrant deposition of extracellular matrix and parenchymal stiffness with progressive functional derangement. The limited availability of fresh tissues represents one of the major limitations to study the molecular profiling of IPF lung tissue. The primary aim of this study was to explore the proteomic profiling yield of archived formalin-fixed paraffin-embedded (FFPE) specimens of IPF lung tissues.MethodsWe further determined the protein expression according to respiratory functional decline at the time of biopsy. The total proteins isolated from 11 FFPE samples of IPF patients compared to 3 FFPE samples from a non-fibrotic lung defined as controls, were subjected to label-free quantitative proteomic analysis by liquid chromatography-mass spectrometry (LC-MS/MS) and resulted in the detection of about 400 proteins.ResultsAfter the pairwise comparison between controls and IPF, functional enrichment analysis identified differentially expressed proteins that were involved in extracellular matrix signaling pathways, focal adhesion and transforming growth factor β (TGF-β) signaling pathways strongly associated with IPF onset and progression. Five proteins were significantly over- expressed in the lung of IPF patients with either advanced disease stage (Stage II) or impaired pulmonary function (FVC

The aim of this study is to investigate the feasibility of manufacturing thin real-time relative dosimeters for clinical radiotherapy (RT) with potential applications for transmission monitoring in vivo dosimetry and pre-treatment dose verifications. Thin (≈1 μm) layers of a high sensitivity, wide bandgap semiconductor, the inorganic perovskite CsPbCl3, have been grown for the first time by magnetron sputtering on plastic substrates equipped with electrode arrays. Prototype devices have been tested in real-time configuration to evaluate the dose delivered by a 6 MV photon beam from a linear accelerator. Linearity of the charge with the dose has been verified over three order of magnitudes, linearity of the current signal with the dose rate has been also successfully tested in the range 0.5-4.3 Gy/min. The combination of high sensitivity per unit volume and wide bandgap provides high signal-to-noise ratios, up to 70, even at moderate applied voltages. The Schottky diode configuration allows the detector to operate without bias voltage (null bias).The blocking-barrier structure allows to confine the active volume within sub-millimetric sizes, a quite attractive feature in view to increase granularity and achieve the high spatial resolutions required in modern RT techniques. All the above-mentioned features indeed pave the way to a novel generation of flexible, transmission, real time dosimeters for clinical radiotherapy.

IntroductionAdvanced urothelial carcinoma remains aggressive and very hard to cure, while new treatments will pose a challenge for clinicians and healthcare funding policymakers alike. The U-CHANGE Project aimed to redesign the current model of care for advanced urothelial carcinoma patients to identify limitations (“as is” scenario) and recommend future actions (“to be” scenario).MethodsTwenty-three subject-matter experts, divided into three groups, analyzed the two scenarios as part of a multidimensional consensus process, developing statements for specific domains of the disease, and a simplified Delphi methodology was used to establish consensus among the experts.ResultsRecommended actions included increasing awareness of the disease, increased training of healthcare professionals, improvement of screening strategies and care pathways, increased support for patients and caregivers and relevant recommendations from molecular tumor boards when comprehensive genomic profiling has to be provided for appropriate patient selection to ad hoc targeted therapies.DiscussionWhile the innovative new targeted agents have the potential to significantly alter the clinical approach to this highly aggressive disease, the U-CHANGE Project experience shows that the use of these new agents will require a radical shift in the entire model of care, implementing sustainable changes which anticipate the benefits of future treatments, capable of targeting the right patient with the right agent at different stages of the disease.

BackgroundAchondroplasia is a rare genetic disorder caused by a mutation in the FGFR3 gene, leading to skeletal changes and other systemic complications that greatly impact the patient's quality of life. There currently are differences in achondroplasia patients' management among countries and centers within the same country.MethodA group of Italian experts discussed the best practice and the current unmet needs in the management of patients with achondroplasia though a two-round Delphi panel, between September and November 2022. The Delphi survey consisted of 32 questions covering organizational aspects, diagnosis and follow-up, and management of achondroplasia patient, and was shared among 54 experts from 25 different centers in Italy. The consensus was determined on the basis of the percentage of agreement or disagreement to each statement on a 5-point Likert scale.ResultsPediatricians (including specialists in pediatrics, medical genetics, and pediatric endocrinology) orthopedics and medical geneticists were the most represented specialists accounting for 64%, 9% and 9% of participants, respectively. The panel highlighted the need for standardized procedures to identify reference centers, the crucial role of multidisciplinary team, and effective communication among centers (Hub and Spoke model) as the essential organizational features; the importance of genetic counseling, presence of a psychologist, and clear communication during prenatal diagnosis as main points for diagnosis; early intervention by different specialists, personalized care, and promotion of a healthy lifestyle as major points for patient management.ConclusionTo ensure an adequate continuity of care over the whole lifespan of a patient with achondroplasia a shared model for patient management is suggested by Italian specialists.

BackgroundDespite bariatric surgery showing significant weight loss trajectories for many patients, a substantial proportion regain weight after the first year following surgery. The addition of telemedicine to standard care could support patients with engaging in a more active lifestyle and thus improve clinical outcomes. ObjectiveOur aim was to evaluate a telemedicine intervention program dedicated to the promotion of physical activity including digital devices, teleconsultation, and telemonitoring the first 6 months following bariatric surgery. MethodsThis study employed a mixed methods design based on an open-label randomized controlled trial. Patients were included during the first week after bariatric surgery; then, they were randomized into 2 intervention groups: The TelePhys group received a monthly telemedicine consultation focusing on physical activity coaching, while the TeleDiet group received a monthly telemedicine consultation involving diet coaching. Data were collected using a watch pedometer and body weight scale, both of which were connected wirelessly. The primary outcome was the difference between the 2 groups in the mean numbers of steps at the first and sixth postoperative months. Weight change was also evaluated, and focus groups and interviews were conducted to enrich the results and capture perceptions of the telemedicine provided. ResultsAmong the 90 patients (mean age 40.6, SD 10.4 years; 73/90, 81% women; 62/90, 69% gastric bypass), 70 completed the study until the sixth month (n=38 TelePhys; n=32 TeleDiet), and 18 participants agreed to be interviewed (n=8 Telephys; n=10 TeleDiet). An increase in the mean number of steps between the first and sixth months was found in both groups, but this change was significant only in the TeleDiet group (P=.01). No difference was found when comparing both intervention groups. Interviewed participants reported having appreciated the teleconsultations, as the individualized tailored counseling helped them to make better choices about behaviors that could increase their likelihood of a daily life in better health. Weight loss followed by social factors (such as social support) were identified as the main facilitators to physical activity. Family responsibilities, professional constraints as well as poor urban policies promoting physical activity, and lack of accessibility to sport infrastructure were their major barriers to postoperative lifestyle adherence. ConclusionsOur study did not show any difference in mobility recovery after bariatric surgery related to a telemedicine intervention dedicated to physical activity. The early postoperative timing for our intervention may explain the null findings. eHealth interventions aiming to change behaviors and carried out by clinicians require support from structured public health policies that tackle patients’ obesogenic environment in order to be efficient in their struggle against sedentary lifestyle–related pathologies. Further research will need to focus on long-term interventions. Trial RegistrationClinicalTrials.gov NCT02716480, https://clinicaltrials.gov/ct2/show/NCT02716480

Introduction: This paper deals with the class of versatile semiconducting materials called perovskites, which have been deposited for the first time on flexible substrates and then tested for radiation detection monitoring applications.Methods: Lead halide inorganic perovskite, CsPbCl3, 0.4–1 μm-thick films have been grown on plastic flexible substrates equipped with interdigitated electrodes (IDEs) by magnetron sputtering at room temperature.Results: First measurements in realtime configuration are reported for a 1–µm thick prototype under proton beams with energy in the range 100–228 MeV and 1–10 nA extraction currents, of interest for protontherapy applications.Discussion: Experimental results evidence good performances of our sample as a real-time monitoring device. Current stability under UV and proton beam exposure has been tested in the range 0.1–120 s, as well as reproducibility under multiple exposures. The measured current signal proved to be linearly dependent on the extraction currents at a given proton energy. Linearity of the current signal of the device with proton fluxes was also proved within two order of magnitude range, about 107–109 p/s. These promising results, when coupled with easyness of fabrication, low processing costs and high versatility of electrode configurations, all features characterizing the manufacturing process, put into evidence lead halide perovskites as promising candidates for real-time radiation detection in protontherapy.

Abstract Background It is well known that benign tracheal stenosis represents an obstacle to open surgery, and that its treatment could be challenging. Two endoscopic techniques have so far been adopted to restore tracheal patency: balloon dilatation (BA) through laryngoscopy, and tracheal stenting (ST) with rigid bronchoscopy. The main objective of this study was to compare the efficacy of BA and ST to treat benign tracheal stenosis not eligible for surgery. We also compared the rate of adverse events in the two treatment groups. Methods A retrospective, observational cohort study was carried out at the University Hospital of Modena (Italy) from November 2012 to November 2017 in two separate departments. Patients were considered to be “stabilized” (primary outcome) if they did not report significant respiratory symptoms, or restenosis in the long‐term (2 years) following the endoscopic procedure. Results Sixty‐six patients were included in the study (33 in the BA and 33 in the ST group, respectively). Unadjusted Kaplan–Meier estimates showed a greater therapeutic effect of ST compared to BA at 2 years (hazard ratio = 3.9 95%CI [1.5–9.8], p = .01). After adjusting for confounders, stratified analyses showed that this effect was significant in patients with complex stenosis, idiopathic etiology, and degree of stenosis >70%. Compared with BA, ST showed a higher rate of adverse events (p = .01). Conclusions Compared to BA, ST seems to be more effective in achieving stabilization of tracheal patency in complex benign tracheal stenosis, although burdened with a significantly higher number of adverse effects. These findings warrant future prospective study for confirmation. Level of evidence: 3.

Abstract Background Excessive inspiratory effort could translate into self-inflicted lung injury, thus worsening clinical outcomes of spontaneously breathing patients with acute respiratory failure (ARF). Although esophageal manometry is a reliable method to estimate the magnitude of inspiratory effort, procedural issues significantly limit its use in daily clinical practice. The aim of this study is to describe the correlation between esophageal pressure swings (ΔP es) and nasal (ΔP nos) as a potential measure of inspiratory effort in spontaneously breathing patients with de novo ARF. Methods From January 1, 2021, to September 1, 2021, 61 consecutive patients with ARF (83.6% related to COVID-19) admitted to the Respiratory Intensive Care Unit (RICU) of the University Hospital of Modena (Italy) and candidate to escalation of non-invasive respiratory support (NRS) were enrolled. Clinical features and tidal changes in esophageal and nasal pressure were recorded on admission and 24 h after starting NRS. Correlation between ΔP es and ΔP nos served as primary outcome. The effect of ΔP nos measurements on respiratory rate and ΔP es was also assessed. Results ΔP es and ΔP nos were strongly correlated at admission (R 2 = 0.88, p

Objectives This study aims to evaluate oncological outcomes in women affected by locally advanced cervical cancer (LACC) treated by neoadjuvant chemotherapy before radical surgery (NACT + RS) or concurrent chemo-radiotherapy (CCRT). Methods This was a multicenter retrospective analysis of data related to women with LACC (FIGO stage IB2-IVA), who were treated by NACT + RS or CCRT between November 2006 and January 2018. The first endpoints were the evaluation of disease-free survival (DFS) and overall survival (OS); univariate and multivariate analyses were performed for identifying the prognostic factors independently associated with these oncological outcomes. Results Overall, 106 women were included in the analysis; 55 of them (51.9%) underwent NACT + RS and 51 (48.1%) CCRT, respectively. Patients in the NACT + RS group had a significant better five-year DFS and five-year OS than those in the CCRT group (77.4% vs. 33.4%, p

Abstract Gas-Coupled Laser Acoustic Detection (GCLAD) is an ultrasonic, non-contact detection technique that has been recently proven to be applicable to the inspection of mechanical components. GCLAD response raises as the intersection length between the probe laser beam and the acoustic wavefront propagating in the air increases; such feature differentiates the GCLAD device from other optical detection instruments, making it a line detection system rather than a point detector. During the inspection of structures mainly extending in two dimensions, the capability to evidence presence of defects in whichever point over a line would enable moving the emitter and the detector along a single direction: this translates in the possibility to decrease the overall required time for interrogation of components compared to point detectors, as well as generating simpler automated monitoring layouts. Based on this assumption, the present study highlights the possibility of employing the GCLAD device as a line inspection tool. To this end, preliminary concepts are provided allowing maximization of the GCLAD response for the non-destructive testing of components which predominantly extend in two dimensions. Afterwards, the GCLAD device is employed in pulse-echo mode for the detection of artificial defects machined on a 12 mm-thick steel plate: the GCLAD probe laser beam is inclined to be perpendicular to the propagation direction of the airborne ultrasound, generated by surface acoustic waves (SAWs) in the solid which are first reflected by the defect flanks and subsequently refracted in the air. Numerical results are provided highlighting the SAW reflection patterns, originated by 3 mm deep surface and subsurface defects, that the GCLAD should interpret. The subsequent experimental campaign highlights that the GCLAD device can identify echoes associated with surface and subsurface defects, located in eight different positions on the plate. B-scan of the component ultimately demonstrates the GCLAD performance in accomplishing the inspection task.

Abstract Background The main clinical consequences of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection are pneumonia and respiratory failure even requiring mechanical ventilation. In this context, the lung parenchyma is highly prone to ventilator-related injury, with pneumothorax and persistent air leak as the most serious adverse events. So far, endobronchial valve (EBV) positioning has proved efficacious in treating air leaks with a high success rate. Case presentation We report, for the first time, two cases of patients affected by SARS-CoV-2-related pneumonia complicated with bacterial super-infection, experiencing pneumothorax and persistent air leaks after invasive mechanical ventilation. Despite the severity of respiratory failure both patients underwent rigid interventional bronchoscopy and were successfully treated through EBV positioning. Conclusions Persistent air leaks may result from lung tissue damage due to a complex interaction between inflammation and ventilator-related injury (VILI), especially in the advanced stages of ARDS. EBV positioning seems to be a feasible and effective minimally invasive therapeutic option for treating this subset of patients.

BackgroundGonadotropin-releasing hormone analogs (GnRHas) are effective in increasing the final height of children with idiopathic central precocious puberty (ICPP). However, in previous years, some transient metabolic complications have been described during this treatment, for which there are no long-term outcome data. Our study aimed to evaluate the efficacy of GnRHas and clarify if body mass index (BMI) at diagnosis of ICPP could influence long-term outcomes.MethodsThis was an observational, retrospective study that recruited a cohort of girls with ICPP. Data for anthropometric measures, fasting lipid profile, and glucose metabolism were collected at baseline [when GnRHas treatment started (T1)], at the end of the treatment (T2), and near-final height (nFH) or final height (FH) (T3). Predicted adult height (PAH) was calculated at T1 following Bayley and Pinneau’s method. Analysis was carried out using BMI standard deviation score (SDS) categories at T1 (group A, normal weight, vs. group B, overweight/obese).ResultsFifty-seven girls with ICPP who were treated with GnRHas were enrolled in the study (group A vs. group B: 33 vs. 24 patients, aged 7.86 ± 0.81 vs. 7.06 ± 1.61 years, respectively; p < 0.05). In the study population, nFH/FH was in line with the target height (TH) (p = 0.54), with a mean absolute height gain of 11.82 ± 5.35 cm compared with PAH. Even if the length of therapy was shorter (group A vs. group B: 1.84 ± 2.15 vs. 2.10 ± 0.81 years, respectively; p < 0.05) and the age at menarche was younger (group A vs. group B: 10.56 ± 1.01 vs. 11.44 ± 0.85 years, respectively; p < 0.05) in group B than in group A, the nFH/FH gain was still comparable between the two groups (p = 0.95). At nFH/FH, BMI SDS was still greater in group B than in group A (p = 0.012), despite the fact that BMI SDS significantly increased in group A only (p < 0.05). Glucose metabolism got worst during GnRHa with a complete restoring after it, independently from pre-treatment BMI. The ratio of low-density to high-density lipoprotein cholesterol transiently deteriorated during treatment with GnRHas in group A only (p = 0.030).ConclusionsOur results confirm the effectiveness of treatment with GnRHas on growth and do not support the concern that being overweight and obese can impair the long-term outcomes of GnRHas therapy. However, the observed transient impairment of metabolic parameters during treatment suggests that clinicians should encourage ICPP girls treated with GnRHas to have a healthy lifestyle, regardless of their pretreatment BMI.

Primary tracheal tumors are rare, constituting approximately 0.1–0.4% of malignant diseases. Squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC) account for about two-thirds of these tumors. Despite most primary tracheal cancers being eligible for surgery and/or radiotherapy, unresectable, recurrent and metastatic tumors may require systemic treatments. Unfortunately, the poor response to available chemotherapy as well as the lack of other real therapeutic alternatives affects the quality of life and outcome of patients suffering from more advanced disease. In this condition, target therapy against driver mutations could constitute an alternative to chemotherapy, and may help in disease control. The past two decades have seen extraordinary progress in developing novel target treatment options, shifting the treatment paradigm for several cancers such as lung cancer. The improvement of knowledge regarding the genetic and biological alterations, of major primary tracheal tumors, has opened up new treatment perspectives, suggesting the possible role of biological targeted therapies for the treatment of these rare tumors. The purpose of this review is to outline the state of knowledge regarding the molecular biology, and the preliminary data on target treatments of the main primary tracheal tumors, focusing on salivary-gland-derived cancers and squamous cell carcinoma.

The exceptional optoelectronic properties and high radiation resistance of epitaxial silicon carbide make this material attractive for high-energy beam dosimetry and radiation monitoring, especially when strict requirements such as high signal-to-noise ratios, high time and spatial resolutions and low detectivity levels are required. A 4H-SiC Schottky diode has been characterized as a proton-flux-monitoring detector and dosimeter under proton beams for proton therapy. The diode was composed of an epitaxial film grown on 4H-SiC n+-type substrate equipped with a gold Schottky contact. The diode was embedded in a tissue-equivalent epoxy resin and then characterized in terms of capacitance vs. voltage (C-V) and current vs. voltage (I-V) characteristics in the dark in the range of 0–40 V. The dark currents at room temperature are in the order of 1 pA, while the doping and active thicknesses extracted from the C-V are 2.5 × 1015 cm−3 and 2–4 μm, respectively. Proton beam tests have been carried out at the Proton Therapy Center of the Trento Institute for Fundamental Physics and Applications (TIFPA-INFN). They have been carried out with energies and extraction currents of 83–220 MeV and 1–10 nA, respectively, as typical for proton therapy applications, corresponding to dose rates in the range of 5 mGy/s to 2.7 Gy/s. The I-V characteristics measured under proton beam irradiation at the lowest dose rate showed a typical diode photocurrent response and a signal-to-noise ratio well above 10. Investigations with null bias evidenced a very good performance in terms of the diode’s sensitivity, fast rise and decay times and response stability. The diode’s sensitivity was in agreement with the expected theoretical values, and its response was linear throughout the whole investigated dose rate range.

Halide perovskites are a novel class of semiconductors that have attracted great interest in recent decades due to their peculiar properties of interest for optoelectronics. In fact, their use ranges from the field of sensors and light emitters to ionizing radiation detectors. Since 2015, ionizing radiation detectors exploiting perovskite films as active media have been developed. Recently, it has also been demonstrated that such devices can be suitable for medical and diagnostic applications. This review collects most of the recent and innovative publications regarding solid-state devices for the detection of X-rays, neutrons, and protons based on perovskite thin and thick films in order to show that this type of material can be used to design a new generation of devices and sensors. Thin and thick films of halide perovskites are indeed excellent candidates for low-cost and large-area device applications, where the film morphology allows the implementation on flexible devices, which is a cutting-edge topic in the sensor sector.

Pathology registers can be a useful tool to overcome obstacles in the identification and management of familial hypercholesterolemia since childhood. In 2018, the LIPIGEN pediatric group was constituted within the Italian LIPIGEN study to focus on FH subjects under 18 years. This work aimed at discussing its recent progress and early outcomes. Demographic, biochemical, and genetic baseline characteristics were collected, with an in-depth analysis of the genetic defects. The analysis was carried out on 1,602 children and adolescents (mean age at baseline 9.9 ± 4.0 years), and almost the whole cohort underwent the genetic test (93.3%). Overall, the untreated mean value of LDL-C was 220.0 ± 97.2 mg/dl, with an increasing gradient from subjects with a negative (N = 317; mean untreated LDL-C = 159.9 ± 47.7 mg/dl), inconclusive (N = 125; mean untreated LDL-C = 166.4 ± 56.5 mg/dl), or positive (N = 1,053; mean untreated LDL-C = 246.5 ± 102.1 mg/dl) genetic diagnosis of FH. In the latter group, the LDL-C values presented a great variability based on the number and the biological impact of involved causative variants. The LIPIGEN pediatric group represents one of the largest cohorts of children with FH, allowing the deepening of the characterization of their baseline and genetic features, providing the basis for further longitudinal investigations for complete details.

Aim/HypothesisTo compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019.MethodsForty-seven pediatric diabetes centers caring for >90% of young people with diabetes in Italy recruited 4,237 newly diagnosed children with type 1 diabetes between 2017 and 2020 in a longitudinal study. Four subperiods in 2020 were defined based on government-imposed containment measures for COVID-19, and the frequencies of DKA and severe DKA compared with the same periods in 2017-2019.ResultsOverall, the frequency of DKA increased from 35.7% (95%CI, 33.5-36.9) in 2017-2019 to 39.6% (95%CI, 36.7-42.4) in 2020 (p=0.008), while the frequency of severe DKA increased from 10.4% in 2017-2019 (95%CI, 9.4-11.5) to 14.2% in 2020 (95%CI, 12.3-16.4, p

Abstract Open-water diving in a polar environment is a psychophysiological challenge to the human organism. We evaluated the effect of short-term diving (i.e., 10 min) in Antarctic waters on autonomic cardiac control, thyroid hormone concentration, body temperatures, mood, and neuropsychological responses (working memory and sleepiness). Data collection was carried out at baseline, before, and after diving in four individuals divided into the supporting (n=2) and diving (n=2) groups. In the latter group, autonomic cardiac control (by measuring heart rate variability) was also assessed during diving. Diving decreased thyroid-stimulating hormone (effect size = 1.6) and thyroxine (effect size = 2.1) concentrations; these responses were not observed for the supporting group. Diving also reduced both the parasympathetic (effect size = 2.6) and sympathetic activities to the heart (ES > 3.0). Besides, diving reduced auricular (effect size > 3.0), skin [i.e., hand (effect size = 1.2) and face (effect size = 1.5)] temperatures compared to pre-dive and reduced sleepiness state (effect size = 1.3) compared to basal, without changing performance in the working memory test. In conclusion, short-term diving in icy waters affects the hypothalamic-pituitary-thyroid axis, modulates autonomic cardiac control, and reduces body temperature, which seems to decrease sleepiness.

The response of resistive In2O3−x sensing devices was investigated as a function of the NO2 concentration in different operative conditions. Sensing layers are 150 nm thick films manufactured by oxygen-free room temperature magnetron sputtering deposition. This technique allows for a facile and fast manufacturing process, at same time providing advantages in terms of gas sensing performances. The oxygen deficiency during growth provides high densities of oxygen vacancies, both on the surface, where they are favoring NO2 absorption reactions, and in the bulk, where they act as donors. This n-type doping allows for conveniently lowering the thin film resistivity, thus avoiding the sophisticated electronic readout required in the case of very high resistance sensing layers. The semiconductor layer was characterized in terms of morphology, composition and electronic properties. The sensor baseline resistance is in the order of kilohms and exhibits remarkable performances with respect to gas sensitivity. The sensor response to NO2 was studied experimentally both in oxygen-rich and oxygen-free atmospheres for different NO2 concentrations and working temperatures. Experimental tests revealed a response of 32%/ppm at 10 ppm NO2 and response times of approximately 2 min at an optimal working temperature of 200 °C. The obtained performance is in line with the requirements of a realistic application scenario, such as in plant condition monitoring.

BackgroundThe role of excessive inspiratory effort in promoting alveolar and pleural rupture resulting in air leak (AL) in patients with SARS-CoV-2 induced acute respiratory failure (ARF) while on spontaneous breathing is undetermined.MethodsAmong all patients with COVID-19 related ARF admitted to a respiratory intensive care unit (RICU) and receiving non-invasive respiratory support, those developing an AL were and matched 1:1 [by means of PaO2/FiO2 ratio, age, body mass index-BMI and subsequent organ failure assessment (SOFA)] with a comparable population who did not (NAL group). Esophageal pressure (ΔPes) and dynamic transpulmonary pressure (ΔPL) swings were compared between groups. Risk factors affecting AL onset were evaluated. The composite outcome of ventilator-free-days (VFD) at day 28 (including ETI, mortality, tracheostomy) was compared between groups.ResultsAir leak and NAL groups (n = 28) showed similar ΔPes, whereas AL had higher ΔPL (20 [16–21] and 17 [11–20], p = 0.01, respectively). Higher ΔPL (OR = 1.5 95%CI[1–1.8], p = 0.01), positive end-expiratory pressure (OR = 2.4 95%CI[1.2–5.9], p = 0.04) and pressure support (OR = 1.8 95%CI[1.1–3.5], p = 0.03), D-dimer on admission (OR = 2.1 95%CI[1.3–9.8], p = 0.03), and features suggestive of consolidation on computed tomography scan (OR = 3.8 95%CI[1.1–15], p = 0.04) were all significantly associated with AL. A lower VFD score resulted in a higher risk (HR = 3.7 95%CI [1.2–11.3], p = 0.01) in the AL group compared with NAL. RICU stay and 90-day mortality were also higher in the AL group compared with NAL.ConclusionIn spontaneously breathing patients with COVID-19 related ARF, higher levels of ΔPL, blood D-dimer, NIV delivery pressures and a consolidative lung pattern were associated with AL onset.