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Short-range wireless technologies will enable vehicles to communicate and coordinate their actions, thus improving people's safety and traffic efficiency. Whereas IEEE 802.11p (and related standards) had been the only practical solution for years, in 2016 a new option was introduced with Release of 14 long-term evolution (LTE), which includes new features to enable direct vehicle-to-vehicle (V2V) communications. LTE-V2V promises a more efficient use of the channel compared to IEEE 802.11p, thanks to an improved PHY layer and the use of orthogonal resources at the MAC layer. In LTE-V2V, a key role is played by the resource allocation algorithm and increasing efforts are being made to design new solutions to optimize the spatial reuse. In this context, an important aspect still little studied, is therefore that of identifying references that allow, first, to have a perception of the space in which the resource allocation algorithms move and, second, to verify the performance of new proposals. In this paper, we focus on a highway scenario and identify two algorithms to be used as a minimum and maximum reference in terms of the packet reception probability (PRP). The PRP is derived as a function of various parameters that describe the scenario and settings, from the application to the physical layer. Results, obtained both in a simplified Poisson point process scenario and with realistic traffic traces, show that the PRP varies considerably with different algorithms and that there is room for the improvement of current solutions.

The opinion on the mechanisms underlying the pathogenesis of preeclampsia still divides scientists and clinicians. This common complication of pregnancy has long been viewed as a disorder linked primarily to placental dysfunction, which is caused by abnormal trophoblast invasion, however, evidence from the previous two decades has triggered and supported a major shift in viewing preeclampsia as a condition that is caused by inherent maternal cardiovascular dysfunction, perhaps entirely independent of the placenta. In fact, abnormalities in the arterial and cardiac functions are evident from the early subclinical stages of preeclampsia and even before conception. Moving away from simply observing the peripheral blood pressure changes, studies on the central hemodynamics reveal two different mechanisms of cardiovascular dysfunction thought to be reflective of the early-onset and late-onset phenotypes of preeclampsia. More recent evidence identified that the underlying cardiovascular dysfunction in these phenotypes can be categorized according to the presence of coexisting fetal growth restriction instead of according to the gestational period at onset, the former being far more common at early gestational ages. The purpose of this review is to summarize the hemodynamic research observations for the two phenotypes of preeclampsia. We delineate the physiological hemodynamic changes that occur in normal pregnancy and those that are observed with the pathologic processes associated with preeclampsia. From this, we propose how the two phenotypes of preeclampsia could be managed to mitigate or redress the hemodynamic dysfunction, and we consider the implications for future research based on the current evidence. Maternal hemodynamic modifications throughout pregnancy can be recorded with simple-to-use, noninvasive devices in obstetrical settings, which require only basic training. This review includes a brief overview of the methodologies and techniques used to study hemodynamics and arterial function, specifically the noninvasive techniques that have been utilized in preeclampsia research.

ObjectiveThere is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics.MethodsA multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared.ResultsThe overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs.ConclusionOur study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

Autoimmune systemic diseases (ASD) may show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed to evaluate the seroconversion after the vaccination cycle and at 6-12-month follow-up, as well the safety and efficacy of vaccines in preventing COVID-19. The study included 478 unselected ASD patients (mean age 59 ± 15 years), namely 101 rheumatoid arthritis (RA), 38 systemic lupus erythematosus (SLE), 265 systemic sclerosis (SSc), 61 cryoglobulinemic vasculitis (CV), and a miscellanea of 13 systemic vasculitis. The control group included 502 individuals from the general population (mean age 59 ± 14SD years). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was evaluated by measuring serum IgG-neutralizing antibody (NAb) (SARS-CoV-2 IgG II Quant antibody test kit; Abbott Laboratories, Chicago, IL) on samples obtained within 3 weeks after vaccination cycle. The short-term results of our prospective study revealed significantly lower NAb levels in ASD series compared to controls [286 (53–1203) vs 825 (451–1542) BAU/mL, p < 0.0001], as well as between single ASD subgroups and controls. More interestingly, higher percentage of non-responders to vaccine was recorded in ASD patients compared to controls [13.2% (63/478), vs 2.8% (14/502); p < 0.0001]. Increased prevalence of non-response to vaccine was also observed in different ASD subgroups, in patients with ASD-related interstitial lung disease (p = 0.009), and in those treated with glucocorticoids (p = 0.002), mycophenolate-mofetil (p < 0.0001), or rituximab (p < 0.0001). Comparable percentages of vaccine-related adverse effects were recorded among responder and non-responder ASD patients. Patients with weak/absent seroconversion, believed to be immune to SARS-CoV-2 infection, are at high risk to develop COVID-19. Early determination of serum NAb after vaccination cycle may allow to identify three main groups of ASD patients: responders, subjects with suboptimal response, non-responders. Patients with suboptimal response should be prioritized for a booster-dose of vaccine, while a different type of vaccine could be administered to non-responder individuals.

The impact of reperfusion delay in ST-elevation myocardial infarction (STEMI) is well known. We aimed to describe the specific reasons for delay to primary percutaneous coronary intervention (pPCI), and their impact on mortality after adjusting for confounders, using the first-medical-contact-to-device (FMCTD) time to measure the delay.Between January 2006 and December 2019, 2149 STEMI patients underwent pPCI at our centre. Delayed pPCI was defined as FMCTD 90 min or 120 min in the case of inter-hospital transfer. The causes of delay were classified as system-related (related to the network organization) or patient-related (related to the clinical condition of the patient). Primary outcome was 1-year all-cause mortality.The pPCI was timely in 69.9% of patients, delayed for system-related causes in 16.4% or for patient-related causes in 13.7%. Different patient-related causes induced variable median FMCTD time (from 114 min for technically difficult pPCI to 159 min for ECG and/or symptom resolution). By multivariable Cox-regression models, the main independent risk factors for mortality were delay due to comorbidities [hazard ratio (HR) 2.19 (1.22-3.91)], or hemodynamic instability [HR 2.05 (1.25-3.38)], after adjusting for Global Registry of Acute Coronary Events risk score tertiles and angiographic success. The difference in risk of mortality is maintained over the entire spectrum of time from symptom onset.Different causes of delay had different impacts on mortality, generally more important than the length of the delay. Causes of delay such as hemodynamic instability and comorbidities should prompt specific programs of performance improvement. Timely pPCI maintains prognostic advantages after several hours from symptom onset, mandating prompt reperfusion also in late-presenter patients.

Background Since summer 2014, the National MCH Workforce Development Center has placed students from MCH public health graduate (Centers of Excellence and Catalyst) and undergraduate (MCH Pipeline) programs, all funded by the Maternal and Child Health Bureau, in summer internships with state and territorial Title V agencies. In 2020, due to the COVID-19 pandemic the Title V MCH Internship Program was offered virtually. Participants and Methods This manuscript includes quantitative and qualitative data from 2017 to 2020 generated by both Title V MCH Internship student interns (n = 76) and their preceptors (n = 40) with a focus on a comparison between the 2020 virtual year and the 2017–2019 years. Results Evaluation data from the 2017 to 2020 Title V MCH Internship Program from both students and preceptors revealed the implementation of a robust and successful internship program in which students increased their confidence in a variety of team, mentorship, and leadership skills while gaining direct exposure to the daily work of state Title V agencies. However, students and preceptors identified more challenges during 2020 compared to previous years. Conclusions The COVID-19 Pandemic was both a disruption and a catalyst for change in education. While there were clearly some challenges with the pivot to a virtual Title V MCH Internship Program in summer 2020, students were able to participate in meaningful internship experiences. This success can be attributed to the ability of the internship sponsor to engage in best practices, including extensive planning and provision of ongoing support to the students. Going forward, it is recognized that virtual internships may facilitate access to agencies in distant locales, eliminating issues related to housing and transportation. When both virtual and in-person relationships are available, those responsible for internship programs, including the Title V MCH Internship, will need to weigh these type of benefits against the potential missed opportunities students may have when not able to participate in on-site experiences.

Cellular-vehicle-to-everything (C-V2X) is gaining an increasing interest among the technologies under consideration for future connected and automated vehicles, especially for sidelink LTE-V2X Mode 4 and sidelink 5G-V2X Mode 2, where nodes autonomously perform resource allocations and transmissions, without relying on any infrastructure. In these cases, the allocation process has been designed based on the assumption of periodic packet generation constrained to a few possible allocation periods. Nevertheless, even assuming that the awareness messages are continuously exchanged, the packet generation might not always be exactly periodical or might come with a periodicity not constrained to the expected values, as for example with the Cooperative Intelligent Transport Systems (C-ITS) standard defined by the European Telecommunications Standards Institute (ETSI). The non-ideal periodicity of packet generation, if not properly taken into account, can significantly impact the operation and performance of C-V2X when vehicles autonomously select their radio resources. This paper provides an analysis of how a misalignment between packet generation and resource allocation affects the system performance and provides insights into how to design the parameter settings to improve the performance. A case study is provided, focusing on LTE-V2X Mode 4 and the cooperative awareness message (CAM) generation in agreement with the the ETSI specifications. Results show that the performance generally improves if the smallest allocation interval is adopted and if the reservation is maintained even when no packets are ready for transmission. It is also shown how the parameter controlling the maximum latency in LTE-V2X, jointly with the misalignment between the allocation and generation intervals, can further affect the packet reception rate.

Sjögren’s syndrome (SS) is an autoimmune disease that involves the nervous system in about 20% of cases. In 25-92% of patients affected by Sjögren’s syndrome, neurological symptoms may precede the sicca syndrome. A 65-year-old male presented with a seven-month history of episodes of near-syncope, constipation, anhidrosis, disabling fatigue and asthenia. Physical examination was unremarkable, whilst the ECG revealed sinus bradycardia. Laboratory tests showed lymphopenia and normal inflammatory markers. In order to assess a potential autonomic neuropathy, “Deep Breathing Test” (E/I 1.02), “Lying to Standing Test” (R/R’ 0.95), and “Orthostatic Hypotension Tests” (T 120s Systolic reduction >20 mmHg and Diastolic reduction >10 mmHg) were performed, all of which were abnormal. ECG Holter monitoring revealed sinus bradycardia, and right bundle branch block with 24-h blood pressure monitoring revealing a diurnal hypotensive profile. The patient reported a three-month history of worsening dry mouth. On physical examination, the patient had anisocoria in response to light stimulation. Auto-antibody testing was performed to evaluate the presence of any autoimmune disease. The results of these studies included an abnormal elevation of ANA (1:320 speckled pattern), Ro/SS-a (>240U/l), and La/SS-b (162 U/ml) antibodies. The patient was discharged with a diagnosis of “Autonomic Neuropathy Most Likely Due to Primary Sjögren’s Syndrome (SS)” and started the immunotherapy. After one month, he reported a significant improvement in his symptoms with a concomitant normalization of his “Orthostatic Hypotension Tests.” This case underlines the potential for dys-autonomic symptoms to precede the onset of sicca syndrome in patients with Sjogren’s Syndrome.

Purpose No accepted benchmarks for open pancreaticoduodenectomy (PD) exist. The study assessed the time to functional recovery after open PD and how this could be affected by the magnitude of midline incision (MI). Materials and methods Prospective snapshot study during 1 year. Time to functional recovery (TtFR) was assessed for the entire cohort. Further analyses were conducted after excluding patients developing a Clavien-Dindo ≥ 2 morbidity and after stratifying for the relative length of MI. Results The overall median TtFR was 7 days (n = 249), 6 days for uncomplicated patients (n = 124). A short MI (SMI, n = 62) was compared to a long MI (LMI, n = 62) in uncomplicated patients. The choice of a SMI was not affected by technical issues and provided a significantly shorter TtFR (5 vs 6 days, p = 0.002) especially for pain control (4 vs. 5 days, p = 0.048) and oral food intake (5 vs. 6 days, p = 0.001). Conclusion Functional recovery after open PD with MI is achieved within 1 week from surgery in half of the patients. This should be the appropriate benchmark for comparison with minimally invasive PD. Moreover, PD with a SMI is feasible, safe, and associated with a faster recovery.

Background This study was designed to demonstrate the non-inferiority (NI) in overall survival (OS) of suspension of androgen deprivation therapy (ADT) versus maintenance and intermittent versus continuous docetaxel administration in metastatic castration-resistant prostate cancer (mCRPC) patients. Patients and methods mCRPC patients were randomised to first-line docetaxel with maintenance or suspension of ADT. Patients attaining a prostate-specific antigen (PSA) response after four chemotherapy cycles underwent second randomisation to receive continuous or intermittent docetaxel therapy. Six hundred patients were to be randomised to achieve 80% statistical power to demonstrate an NI hazard ratio (HR) of 1.25 of interruption versus maintenance of ADT. Results The trial was prematurely closed when 198 participants were randomised. OS was similar in patients who continued (N = 96) versus those who interrupted (n = 102) ADT during docetaxel therapy (HR 0.98, 95% confidence interval [CI] 0.72–1.33] and those on a continuous (N = 35) versus an intermittent (N = 42) docetaxel schedule (HR 0.86, 95% CI 0.55–1.43). No difference in radiological progression-free survival, PSA response, or toxicity was observed between the study arms. The actual NI hazard margins of OS in Arms A and B patients were 1.33 and 1.43, respectively. Conclusions This trial enrolled one-third of the planned patients; this main weakness dramatically limits the interpretation of the results. ADT discontinuation and switching to an intermittent schedule did not seem to affect docetaxel efficacy. The absence of testosterone recovery in the majority of patients could have been a contributory factor. In men with mCRPC, ADT discontinuation should only be done with regular biochemical and clinical monitoring, with the option of quickly restarting ADT at disease progression.

Early identification of preeclampia in the first trimester of pregnancy represents one of the major challenges of modern fetal medicine. The primary aim of our study was to evaluate the effectiveness of implementation of preeclampsia screening in Tuscany, Italy. The secondary aim was to evaluate pregnancy/neonatal outcome in the positive screening group compared with the negative screening group.Retrospective study including singleton pregnancies undergoing screening for preeclampsia. The screening test was a multiparametric algorithm based on maternal history, biochemical and biophysical parameters (Fetal Medicine Foundation algorithm).The overall performance of the test was calculated, in terms of sensitivity, specificity, positive and negative predictive value and in relation to gestational age at onset (primary aim). Pregnancy and neonatal outcomes were then compared between the positive and negative population at preeclampsia screening test (secondary aim).Of the 5719 patients enrolled, 4797 were included in the analysis. The sensitivity for early onset of preeclampsia (≤34 weeks) was 0.75 (CI:0.41-0.93) and specificity 0.93 (CI:0.92-0.94) for a false positive rate of 7%. The population that tested positive for preeclampsia screening showed a higher incidence of deliveries at lower gestational ages (p 0.001), preeclampsia onset despite prophylaxis with aspirin (p 0.001), emergency caesarean section (p 0.001), low fetal birth weight (p 0.001) and neonatal admission in intensive care unit (p 0.001).Our data confirm the validity of first trimester screening test in identifying a category of patients at greatest risk for preeclampsia even in the presence of a post-test pharmacological prophylaxis.

BackgroundDignity is a basic principle of palliative care and is intrinsic in the daily practice of professionals assisting individuals with incurable diseases. Dignity Therapy (DT) is a short-term intervention aimed at improving the sense of purpose, meaning and self-worth and at reducing the existential distress of patients facing advanced illness. Few studies have examined how DT works in countries of non-Anglo Saxon culture and in different real-life settings. Moreover, most studies do not provide detailed information on how DT is conducted, limiting a reliable assessment of DT protocol application and of its evaluation procedure.The aim of this study was to assess the feasibility and acceptability of a nurse-led DT intervention in advanced cancer patients receiving palliative care.MethodThis is a mixed-method study using before and after evaluation and semistructured interviews. Cancer patients referred to a hospital palliative care unit were recruited and provided with DT. The duration of sessions, and timeframes concerning each step of the study, were recorded, and descriptive statistical analyses were performed.The patients' dignity-related distress and feedback toward the intervention were assessed through the Patient Dignity Inventory and the Dignity Therapy Patient Feedback Questionnaire, respectively. Three nurses were interviewed on their experience in delivering the intervention, and the data were analyzed qualitatively.ResultsA total of 37/50 patients were enrolled (74.0%), of whom 28 (75.7%) completed the assessment. In 76.7% of cases, patients completed the intervention in the time limit scheduled in the study. No statistically significant reduction in the Patient Dignity Inventory scores was observed at the end of the intervention; most patients found DT to be helpful and satisfactory. Building opportunities for personal growth and providing holistic care emerged among the facilitators to DT implementation. Nurses also highlighted too great of a time commitment and a difficult collaboration with ward colleagues among the barriers.ConclusionsOur findings strongly support the acceptability, but only partially support the feasibility, of nurse-led DT in advanced cancer patients in a hospital setting. Further research is needed on how to transfer the potential benefits of DT into clinical practice.Trial registrationRetrospectively registered on ClinicalTrial.govNCT04738305.

Background Several advantages and pitfalls have been related to externalized trans-anastomotic stents (ETS) after pancreaticoduodenectomy. The purpose of this study was to investigate the effect of an ETS effect in a risk-stratified setting. Methods Data from patients at either intermediate- or high-risk for postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy were prospectively analyzed from January 2016 to December 2019. Outcomes included POPF rate, mean complication burden (ACB), and complications related to ETS malfunction. Results A total of 540 patients met the inclusion criteria. Following an intention-to-treat analysis, there was no difference in terms of POPF and the ACB in the intermediate (22 vs.29%, p = 0.148; 0.38 vs.0.24, p = 0.082) and high-risk categories (58 vs.37%, p = 0.103; 0.33 vs.0.33, p = 0.478) comparing PJ to PJ-ETS. Excluding patients experiencing ETS malfunction (n = 45, 22%), ETS was associated with a significantly reduced ACB in the intermediate-risk (0.38 vs.0.26, p = 0.009) and POPF rate in the high-risk category (58 vs.32%, p = 0.033). In patients with ETS malfunction an increased rate of severe morbidity (Clavien-Dindo ≥ III, 33 vs.19%, p = 0.044) was observed as compared to patients with functioning ETS. Conclusion ETS provides crucial advantages for prevention and mitigation of POPF depending on risk setting and its correct functioning. ETS malfunction is not uncommon and increases morbidity. Improving ETS design and fixing technique might lead to better outcomes.

Aims: \ud Iron deficiency (ID) and anaemia are common in heart failure; less is known about changes over time.\ud \ud Methods and results: \ud We investigated prevalence, incidence and resolution of ID and anaemia in 906 patients with chronic heart failure (median age 73 (65–79) years, 70% men, 51% with heart failure with reduced ejection fraction) 1 year apart. ID was defined as serum iron ≤13 µmol/L and anaemia as haemoglobin 13 µmol/L), mortality was higher in those with persistent or incident ID at 1 year [hazard ratio (HR) 1.81 (1.23–2.67), and HR 1.40 (0.91–2.14), respectively] in multivariable models (P = 0.02). Compared to persistent ID, resolution of ID was associated with a lower mortality [HR 0.61 (0.44–0.86); P = 0.004]. Changes in ID defined by FAIR-HF criteria were not similarly associated with mortality. Anaemia was associated with a poor outcome even if it resolved.\ud \ud Conclusions: \ud The prevalence and incidence of ID and anaemia are high in chronic heart failure but so is the rate of resolution. Persistent or incident ID, defined by a serum iron ≤13 µmol/L, is associated with higher mortality and resolution of ID with lower mortality.

BACKGROUND: TB is the leading cause of mortality among people living with HIV (PLHIV), for whom isoniazid preventive therapy (IPT) has a proven mortality benefit. Despite WHO recommendations, countries have been slow in scaling up IPT. This study describes processes, challenges, solutions, outcomes and lessons learned during IPT scale‐up in Kenya.METHODS: We conducted a desk review and analyzed aggregated Ministry of Health (MOH) IPT enrollment data from 2014 to 2018 to determine trends and impact of program activities. We further analyzed IPT completion reports for patients initiated from 2015 to 2017 in 745 MOH sites in Nairobi, Central, Eastern and Western Kenya.RESULTS: IPT was scaled up 75‐fold from 2014 to 2018: the number of PLHIV covered increased from 9,981 to 749,890. The highest percentage increases in the cumulative number of PLHIV on IPT were seen in the quarters following IPT pilot projects in 2014 (49%), national launch in 2015 (54%), and HIV treatment acceleration in 2016 (158%). Among 250,069 patients initiating IPT from 2015 to 2017, 97.5% completed treatment, 0.2% died, 0.8% were lost to follow‐up, 1.0% were not evaluated, and 0.6% discontinued treatment.CONCLUSIONS: IPT can be scaled up rapidly and effectively among PLHIV. Deliberate MOH efforts, strong leadership, service delivery integration, continuous mentorship, stakeholder involvement, and accountability are critical to program success.

Background: Regular physical activity (PA) practice during pregnancy offers health and fitness benefits for both mother and baby. Therefore, healthy pregnant women with no contraindications to exercise should be encouraged to perform PA. Nevertheless, their levels of PA are generally low. The aim of the WELL-DONE! Study is to co-design an adapted physical activity intervention (APAI) for pregnant women to include in childbirth preparation classes (CPCs) evaluating its feasibility and efficacy on quality of life (QoL), PA levels and other outcomes. Methods: A quasi-experimental study was divided in two progressive stages. First, APAI was developed in collaboration with pregnant women and midwives using focus groups; second, APAI’s efficacy was evaluated comparing two groups: the experimental group engaged in the CPCs integrated with 1 h/week of the APAI administered by midwives and the control group participating in the standard CPCs. Pre-post evaluation was carried out in three stages through questionnaires and tests. Data analysis involved the combination of qualitative and quantitative methodologies. Discussion: Findings from the WELL-DONE! Study will help to assess the feasibility, sustainability, and efficacy of incorporating APAI inside CPCs as a new public health strategy oriented to QoL, well-being, and PA level improvements.

Lessons Learned Background The objectives of this study were to compare the safety profiles of sodium levofolinate (Na-Lev) and calcium levofolinate (Ca-Lev) in combination with 5-fluorouracil (5-FU) in the FOLFIRI regimen and to measure the organizational impact of the introduction of Na-Lev on drug production and administration. Methods The study opened in November 2015 and closed in August 2019. Patients with gastrointestinal cancers who were candidates for treatment with the FOLFIRI regimen were included in this nonrandomized study. Age ≥18 years, life expectancy Results Sixty patients were enrolled, 30 in each arm. Patient characteristics were balanced. Grade (G)1–2 adverse events occurred in 18 (60.0%) and 19 (63.4%) patients of Na-Lev and Ca-Lev cohorts, respectively, whereas G3–4 adverse events occurred in 12 (40.0%) and 11 (36.6%) patients, respectively. The use of Na-Lev enabled us to save approximately 13 minutes for drug preparation and 2 hours for treatment administration, per patient per cycle. Conclusion Na-Lev showed a reassuring toxicity profile and a favorable impact on drug preparation and administration.

Resumo Objetivos Avaliar a força muscular dos rotadores medial (RM) e lateral (RL) do ombro após cirurgia de Bristow/Latarjet. Métodos Estudo transversal com 18 pacientes (36 ombros). A avaliação isocinética foi realizada por meio do dinamômetro Biodex 3 System Pro (Biodex Medical System, Inc., Shirley, NY, EUA). A escala de avaliação dos resultados do ombro do esportista (EROE) e a escala visual analógica (EVA) da dor foram aplicadas. Resultados Os valores do pico de torque e o trabalho máximo no modo concêntrico e excêntrico no ombro não-operado foram maiores que no lado operado, tanto para o RM e como para o RL (p Conclusões Houve diminuição da força do RM e do RL no ombro operado em relação ao ombro saudável; porém, o equilíbrio convencional e funcional foi mantido.

The Italian Society of Diabetology and the Italian Association of Clinical Diabetologists are developing new guidelines for drug treatment of type 2 diabetes. The effects of anti-hyperglycaemic drugs on all-cause mortality and major adverse cardiovascular events (MACEs) were included among the critical clinical outcomes. We have therefore carried out an updated meta-analysis on the effects of metformin on these outcomes.A MEDLINE and EMBASE search was performed to identify all randomized controlled trials (RCTs) with duration ≥52 weeks (published up to August 2020), in which metformin was compared with either placebo/no therapy or active comparators. MACEs (restricted for RCT reporting MACEs within their study endpoints) and all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified endpoints) were considered as the primary endpoints. Mantel-Haenszel odds ratio (MH-OR) with 95% confidence interval was calculated for all endpoints considered. Metformin was associated with a nonsignificant reduction of all-cause mortality (n = 13 RCTs; MH-OR 0.80 [95% CI 0.60, 1.07]). However, this association became statistically significant after excluding RCTs comparing metformin with sulfonylureas, SGLT-2 inhibitors or GLP-1 analogues (MH-OR 0.71 [0.51, 0.99]). Metformin was associated with a lower risk of MACEs compared with comparator treatments (n = 2 RCTs; MH-OR 0.52 [0.37, 0.73]), p 0.001. Similar results were obtained in a post-hoc analysis including all RCTs fulfilling criteria for inclusion in the analysis (MH-OR: 0.57 [0.42, 0.76]).This updated meta-analysis suggests that metfomin is significantly associated with lower risk of MACEs and tendentially lower all-cause mortality compared to placebo or other anti-hyperglycaemic drugs.

This study aims to contribute to the long-standing debate on technology-push versus demand-pull mechanisms to support the creation and diffusion of innovations. We argue that in addition to the traditional push–pull dichotomy, technological change drivers must be differentiated by whether they are exogenous or endogenous to the economic system and must be assessed against their contribution to both the creation and the diffusion of innovation. We apply this perspective to study innovation in the renewable energy (RE) industry in 15 European Union countries. We find that public R&D investments, public policies, and per capita income positively affect either innovation creation or diffusion. However, impacts differ depending on the innovation dimension considered. Economic growth is relatively ineffective at stimulating innovation creation. In contrast, it is a strong driver of RE diffusion with a nonlinear, U-shaped impact that has both a direct cause and an indirect cause. Our findings highlight the importance of deploying diverse policy instruments simultaneously to enhance the effectiveness of clean energy policies.

Objective: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography. Method: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (

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.

Objective To assess the performance of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses diagnosed with isolated corpus callosal (CC) anomaly on multiplanar ultrasound evaluation of the fetal brain (neurosonography). Methods This was a multicenter, retrospective cohort study involving 14 fetal medicine centers in Italy, UK, Portugal, Canada, Austria and Spain. Inclusion criteria were fetuses with an apparently isolated CC anomaly, defined as an anomaly of the CC and no other additional central nervous system (CNS) or extra-CNS abnormality detected on expert ultrasound, including multiplanar neurosonography; normal karyotype; maternal age >= 18 years; and gestational age at diagnosis >= 18 weeks. The primary outcome was the rate of additional CNS abnormalities detected exclusively on fetal MRI within 2 weeks following neurosonography. The secondary outcomes were the rate of additional abnormalities according to the type of CC abnormality (complete (cACC) or partial (pACC) agenesis of the CC) and the rate of additional anomalies detected only on postnatal imaging or at postmortem examination. Results A total of 269 fetuses with a sonographic prenatal diagnosis of apparently isolated CC anomalies (207 with cACC and 62 with pACC) were included in the analysis. Additional structural anomalies of the CNS were detected exclusively on prenatal MRI in 11.2% (30/269) of cases, with malformations of cortical development representing the most common type of anomaly. When stratifying the analysis according to the type of CC anomaly, the rate of associated anomalies detected exclusively on MRI was 11.6% (24/207) in cACC cases and 9.7% (6/62) in pACC cases. On multivariate logistic regression analysis, only maternal body mass index was associated independently with the likelihood of detecting associated anomalies on MRI (odds ratio, 1.07 (95% CI, 1.01-1.14); P = 0.03). Associated anomalies were detected exclusively after delivery and were missed on both types of prenatal imaging in 3.9% (8/205) of fetuses with prenatal diagnosis of isolated anomaly of the CC. Conclusion In fetuses with isolated anomaly of the CC diagnosed on antenatal neurosonography, MRI can identify a small proportion of additional anomalies, mainly malformations of cortical development, which are not detected on ultrasound. (c) 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Background: The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations. Objective: This study aims to investigate the prevalence of symptomatic Covid-19 and its correlations with both organ involvement and ongoing treatments in a large series of Italian ASD patients during the first wave of pandemic. Methods: Our multicenter telephone 6-week survey included 3,029 unselected ASD patients enrolled at 36 tertiary referral centers of northern, central, and southern Italian macro-areas with different diffusion of the pandemic. Symptomatic SARS-CoV-2 infection was classified as definite Covid-19 (presence of symptoms plus positive oral/nasopharyngeal swabs) or highly suspected Covid-19 (highly suggestive symptoms, in the absence of a swab testing). Results: A significantly higher prevalence of definite plus highly suspected Covid-19 compared to the Italian general population was detected in the whole ASD series (p=.000), as well as in patients from the three macro-areas (p=.000 in all). Statistically higher prevalence of Covid-19 was also found in connective tissue diseases compared to chronic arthritis subgroup (p=.000) and in ASD patients with pre-existing interstitial lung involvement (p=.000). Patients treated with either conventional disease-modifying anti-rheumatic drugs (DMARDs) and/or biological DMARDs showed a significantly lower prevalence of Covid-19 (p=.000 in both). Finally, scleroderma patients undergoing low-dose aspirin showed a significantly lower rate of Covid-19 compared to those without (p=0.003). Conclusion: The higher prevalence of Covid-19 in ASD patients, along with the significant correlations with important clinical features and therapeutic regimens, suggests the need to develop targeted prevention/management strategies during the current pandemic wave.

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We investigate the relationship between maternal cardiovascular (CV) function and fetal Doppler changes in healthy pregnancies and those with pre-eclampsia (PE), small for gestational age (SGA) or fetal growth restriction (FGR). This was a three-centre prospective study, where CV assessment was performed using inert gas rebreathing, continuous Doppler or impedance cardiography. Maternal cardiac output (CO) and peripheral vascular resistance (PVR) were analysed in relation to the uterine artery, umbilical artery (UA) and middle cerebral artery (MCA) pulsatility indices (PI, expressed as z-scores by gestational week) using polynomial regression analyses, and in relation to the presence of absent/reversed end diastolic (ARED) flow in the UA. We included 81 healthy controls, 47 women with PE, 65 with SGA/FGR and 40 with PE + SGA/FGR. Maternal CO was inversely related to fetal UA PI and positively related to MCA PI, the opposite was observed for PVR, which was also positively associated with increased uterine artery impedance. CO was lower (z-score 97, p = 0.02) and PVR higher (z-score 2.88, p = 0.02) with UA ARED flow. We report that maternal CV dysfunction is associated with fetal vascular changes, namely raised impedance in the fetal-placental circulation and low impedance in the fetal cerebral vessels. These findings are most evident with critical UA Doppler changes and represent a potential mechanism for therapeutic intervention.

Background: Considering the growing genitourinary (GU) cancer population undergoing systemic treatment with immune checkpoint inhibitors (ICIs) in the context of the COVID-19 pandemic, we planned a clinical audit in 24 Italian institutions treating GU malignancies. Objective: The primary objective was investigating the clinical impact of COVID-19 in GU cancer patients undergoing ICI-based therapy during the first outbreak of SARS-CoV-2 contagion in Italy. Design, setting, and participants: The included centers were 24 Oncology Departments. Two online forms were completed by the responsible Oncology Consultants, respectively, for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC) patients receiving at least one administration of ICIs between 31 January 2020 and 30 June 2020. Results and limitation: In total, 287 mRCC patients and 130 mUC patients were included. The COVID-19 incidence was, respectively, 3.5%, with mortality 1%, in mRCC patients and 7.7%, with mortality 3.1%, in mUC patients. In both groups, 40% of patients developing COVID-19 permanently discontinued anticancer treatment. The pre-test SARS-CoV-2 probability in the subgroup of patients who underwent nasal/pharyngeal swab ranged from 14% in mRCC to 26% in mUC. The main limitation of the work was its nature of audit: data were not recorded at the single-patient level. Conclusion: GU cancer patients undergoing active treatment with ICIs have meaningful risk factors for developing severe events from COVID-19 and permanent discontinuation of therapy after the infection. Treatment delays due to organizational issues during the pandemic were unlikely to affect the treatment outcome in this population.

Background The COVID-19 outbreak has forcibly overshadowed the physical well-being of children and adolescents, of which we will see the consequences in near future. The programs to contain the spread of Sars-CoV-2 resulted in prolonged lockdown periods, discontinuity of educational services and a possible decrease in physical activities (PA) among the youngest. In the local reality of the Metropolitan City of Bologna children and adolescents underwent a radical change in habits and lifestyle, overall predisposing sedentariness and unhealthy behaviors. Our project, “Come te la passi?”, aims to acknowledge lifestyle variations (concerning diet, PA, sleep behavior/quality) to design, in second-phase interventions, individualized school-based educational programs. Methods This ongoing study is being conducted using an on-line anonymous questionnaire targeting parents/guardian of children and adolescents aged 6-17 recruited from 26th to 28th of April in Bologna, a city in Northern Italy. Results Preliminary data suggested that among adolescents (n = 124) 91.2% used to do PA 2 or more times a week before lockdown, while during lockdown this percentage decreased, reaching 41.1%. In children (n = 38) we observed an even more pronounced difference, with PA decreasing from 89.5% to 26.3%. In children 29% of the participants also reported a weight gain, while 65.8% did not report any variation and only 5.2% reported a weight loss. For the majority of both children's and adolescents' parents (n = 162), the strategies to address the reduction in PA were predominantly having school time dedicated only to PA (53.1%) and being more educated about simple physical exercises (14.5%). Conclusions Our preliminary findings suggest that the current pandemic had a strong impact on the well-being of children and adolescents; “Come te la passi?” second-phase interventions could be crucial in addressing the youngest' needs, to educate and promote healthier lifestyles through school-based programs. Key messages Children’s and adolescents’ lifestyle behaviors were strongly affected by the current pandemic, with physical activity frequency more than halved. “Come te la passi?” objectives are to frame the major critical issues detected and to shape educational school programs based on identified needs.

The process of bone loss occurs silently and progressively with age, often appearing as osteopenia or osteoporosis or related fractures. Given the rapid raise in disease burden and socio-economic costs of these conditions worldwide, drug therapy combined with physical activity can be a useful strategy and bone biomarkers, can represent a useful evaluation tool to assess their effects. The objective of this systematic review, conducted according to PRISMA statement, was to investigate the effects of physical activity interventions combined with drug treatments on bone biomarkers in people with osteopenia and osteoporosis. Through PubMed, Cochrane, Cinahl, Embase, Trip, a comprehensive literature search was performed. Each study’s quality was assessed according to the Cochrane risk-of-bias tool. Out of 582 identified articles, 50 full texts were screened. Only one matched the eligibility criteria. The study, scored as high quality, showed, in both experimental and control groups, an increase of CTX and P1NP bone biomarkers, without statistically significant differences. Based on available evidence, no exhaustive conclusion can be drawn. However, this systematic review critically analyses the literature, highlighting the knowledge gap on combined treatments efficacy assessed by bone biomarkers. Moreover, an outlook is provided for the planning of future studies.

The purpose of the study was to investigate the magnitude of bilateral deficit (BLD) in trained males and examine its relationship with functional performance and recent resistance training history. Ten physically active males (age: 23.02±1.27 years) self-reported the number of unilateral and bilateral exercises within their structured resistance training schedule. During two visits to the laboratory, participants performed unilateral and bilateral squat jumps (SJ) and isometric leg extensions (ILE) for the quantification of BLD. Participants also performed bilateral countermovement jumps (CMJ) and a change of direction (COD) test to quantify functional performance. The performance outcomes and information regarding training history were then correlated with the bilateral index (BLI) metric. The key findings were that: (a) a lower BLD in SJ peak power related to a greater CMJ peak force (r=.728; p=.02) and peak power (r=.750; p=.01), (b) the BLI in the ILE was unrelated to performance outcomes, and (c) BLI was unrelated to the mean number of bilateral and unilateral exercises in the structured resistance training programme of participants. In conclusion, lower levels of BLD may be advantageous for bilateral tests of functional performance (i.e. jumps) however there is a need to consider the mechanical similarity between the performance and BLD measure. Finally, the balance of unilateral and bilateral exercises in an individual’s recent resistance training history is not sensitive to the BLI measured during dynamic or isometric assessments.

BackgroundThe prevalence of diseases other than TB detected during chest X-ray (CXR) screening is unknown in sub-Saharan Africa. This represents a missed opportunity for identification and treatment of potentially significant disease. Our aim was to describe and quantify non-TB abnormalities identified by TB-focused CXR screening during the 2016 Kenya National TB Prevalence Survey.MethodsWe reviewed a random sample of 1140 adult (≥15 years) CXRs classified as ‘abnormal, suggestive of TB’ or ‘abnormal other’ during field interpretation from the TB prevalence survey. Each image was read (blinded to field classification and study radiologist read) by two expert radiologists, with images classified into one of four major anatomical categories and primary radiological findings. A third reader resolved discrepancies. Prevalence and 95% CIs of abnormalities diagnosis were estimated.FindingsCardiomegaly was the most common non-TB abnormality at 259 out of 1123 (23.1%, 95% CI 20.6% to 25.6%), while cardiomegaly with features of cardiac failure occurred in 17 out of 1123 (1.5%, 95% CI 0.9% to 2.4%). We also identified chronic pulmonary pathology including suspected COPD in 3.2% (95% CI 2.3% to 4.4%) and non-specific patterns in 4.6% (95% CI 3.5% to 6.0%). Prevalence of active-TB and severe post-TB lung changes was 3.6% (95% CI 2.6% to 4.8%) and 1.4% (95% CI 0.8% to 2.3%), respectively.InterpretationBased on radiological findings, we identified a wide variety of non-TB abnormalities during population-based TB screening. TB prevalence surveys and active case finding activities using mass CXR offer an opportunity to integrate disease screening efforts.FundingNational Institute for Health Research (IMPALA-grant reference 16/136/35).

The pandemic stressed the key role of sustainable consumption and production patterns and highlighted the role of local systems as key actors of a recovery aiming at enhanced resilience to endogenous and exogenous shocks. Although the Recovery Plan marked a radical shift in the attitude of the EU towards crisis management and allowed for an unprecedented joint financial effort, it might not be enough for tackling the challenges ahead. In this paper we suggest that two instruments should be further explored for this purpose: the Euratom Treaty and the European Stability Mechanism.

Background Immunotherapy has brought clinical benefits to patients with metastatic renal cell cancer (mRCC). Most patients tolerate immunotherapy but serious immune-related adverse events (irAEs) have been reported. Some studies indicate a correlation between irAEs and clinical response in other cancer types (eg, lung cancer and melanoma). For patients with mRCC, the impact of irAE on clinical outcome is unknown. Patients and Methods A retrospective review of 167 patients with mRCC treated with nivolumab as standard of care between March 2017 and January 2018 in 16 Italian centers was performed. irAEs were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Results Any grade and grade 3/4 irAEs occurred in 46% and 8.9% of patients, respectively. The median time to appearance of irAEs was 10 weeks; 38.8% of patients required steroid treatment. The most common irAEs were cutaneous (33.7%) and gastrointestinal (23.3%). The median overall survival and progression-free survival were 20.13 and 7.86 months, respectively. Patients with irAEs showed a greater overall survival (hazard ratio, 0.38; 95% confidence interval [CI], 0.23-0.63) and progression-free survival (hazard ratio, 0.44; 95% CI, 0.29-0.66) benefit as well as better overall response rate (27.3% vs. 13.7%; odds ratio, 2.36; 95% CI, 1.03-5.44) and disease control rate (68.8% vs. 48%; odds ratio, 2.4; 95% CI, 1.23-4.67) if compared with those without irAEs. No correlation was found between steroid use and clinical outcomes. Conclusions Our analysis revealed that the appearance of irAEs was associated with better outcomes in patients treated with nivolumab. This data may be limited by sample size and the retrospective nature of the study.

The Middle Ages have been traditionally considered a crisis period due to the demographic decrease and economic deterioration occurred in Western Europe. Nevertheless, the historical reconsideration has been focused not only on decline and decay, but also on resilience and recovery which characterized the Europe of the fourteenth and fifteenth centuries. So, today the main open question is as follows: how can we explain the diverse attitude (namely recovery versus decline) and the reasons why some settlements were more (or less) resilient than others? To provide a contribution to this issue, we focused on two medieval villages which are located very close to each other (in the Basilicata Region Southern Italy) and selected because they are characterized by diverse vicissitudes: Irsi abandoned in the fourteenth century and Montepeloso (still "existing" and renamed Irsina) where the population of Irsi moved to. To improve our current knowledge on Irsi, we reused and integrated multiscale LiDAR datasets in order to cope with the lack of documentary source. The use of LiDAR data enabled (i) the reconstruction of the potential urban fabric of Irsi, along with its temporal development and the transformation of the surrounding landscape, and (ii) the definition of a hypothesis about the causes of its desertification based on the inter-site analysis between Irsi and Montepeloso. The main results from the LiDAR-based analysis were as follows: (i) the diachronic reconstruction of the building phases of the village and (ii) the identification of a significant indicator obtained as the ratio between the amount of cultivatable land (close to the settlement area) and the population to characterize the resilience behavior in hilly landscape. This approach has been also successfully applied to another similar case study. Outputs from our analyses pointed out that LiDAR data can fruitfully improve medieval archaeological investigations and facilitate knowledge improvement from intra to- inter-site scale analyses and from local up to a landscape perspective.

Neoadjuvant chemotherapy has become a powerful tool to convert borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) into a resectable scenario. However, data analyzing the optimal type of therapy are scarce. In the present multicenter retrospective study, we evaluated the influence of FOLFIRINOX (FFX) and gemcitabine (GEM)-based neoadjuvant therapy on patient prognosis.Data on 239 patients from 7 centers across Europe was gathered using an online database. Patients having received their first cycle of chemotherapy for BRPC/LAPC before 06/2017, with a minimum follow-up of 12 months, were included in the intention-to-treat analysis.Patients treated with neoadjuvant FFX (n = 135) or gemcitabine + nab-paclitaxel (GNP) (n = 38) had significantly improved radiological response according to RECIST criteria as compared to single-agent GEM (n = 16), with a partial/complete response of 59.3%, 55.3% and 6.25% respectively (p = 0.001). Treatment with FFX (n = 135) and GNP (n = 38) resulted in higher resection rates compared to GEM (73.3%, 81.6% and 43.8%; p = 0.01 and p = 0.005). Regardless of regimen, patients who were resected had significantly prolonged overall survival compared to non-resected patients (p 0.01). Complete pathological responses (ypT0 ypN0) were predominantly observed with FFX (p = 0.01). Adjuvant GNP in addition to successful neoadjuvant therapy and surgery resulted in a trend towards improved median survival as compared to postoperative observation (47.0 vs. 30.1 months, p = 0.06).Representing one of the largest studies published so far, our results reveal that patients with BRPC/LAPC should be offered either FFX or GNP to improve chances of resection and with this also survival.

The West European kinematic evolution results from the opening of the West Neotethys and the Atlantic oceans since the late Paleozoic and the Mesozoic. Geological evidence shows that the Iberian domain well preserved the propagation of these two rift systems and is therefore key to significantly advance our understanding of the regional plate reconstructions. The Late Permian-Triassic tectonic evolution of Iberian rift basins shows that they have accommodated significant extension, but this tectonic stage is often neglected in most plate kinematic models, leading to the overestimation of the movements between Iberia and Europe during the subsequent Mesozoic (Early Cretaceous) rift phase. By compiling existing seismic profiles and geological constraints along the North Atlantic margins, including well data over Iberia, as well as recently published kinematic and paleogeographic reconstructions we propose a coherent kinematics model of Iberia that considers both the Neotethyan and Atlantic evolutions. Our model shows that the Europe-Iberia plate boundary was a domain of distributed and oblique extension made of two rift systems, in the Pyrenees and in the Iberian intra-continental basins. It differs from standard models that consider left-lateral strike-slip movement localized only in the northern Pyrenees in introducing a significant strike-slip movement south of Ebro accounting for Late Permian-Triassic extension and by emphasizing the need for an Ebro microcontinent. At a larger scale it emphasizes the role played by the late Permian-Triassic rift and magmatism, as well as strike-slip faulting in the evolution of the western Neotethyan Ocean and their control on localization of the Atlantic rift.

46, XY disorders (or differences) of sex development (DSD) are a group of clinical conditions with variable genetic background; correct diagnosis is often difficult, but it permits to optimize the management. The aim of this study is to identify clinical and genetics features of a group of women with 46, XY DSD to define some issues characterizing people with 46, XY DSD in Italy. Retrospective analysis of girls and women with 46, XY DSD and female phenotype evaluated between year 2000 and 2016, performed by anonymised database, focusing on the clinical features and management, including presentation, first diagnostic suspect, gonadal surgery and molecular diagnostic delay. A total of 84 records were collected (mean age at clinical presentation: 9.1 ± 7.9 years; mean age at definitive diagnosis: 20.1 ± 15.0 years). Complete androgen insensitivity syndrome was the most common diagnosis (60%). Only 12 patients (14.3%) did not receive a molecular diagnosis. Early misdiagnoses frequently occurred; diagnostic delay was 10.2 ± 11.2 years, being reduced in patients presenting from 2007 to 2016. The discordance between genotypic and phenotypic sex during pregnancy or at birth determined early reason for referral in a considerable percentage (4.9%). Misdiagnosis and long diagnostic delays are present in females with 46, XY DSD in Italy, but the new genetic techniques permit faster right diagnoses in the last years. The centralization in dedicated third level units permits to reduce the number of patients without a molecular diagnosis, allowing better clinical management and appropriate genetic counselling.

Purpose Calcium levofolinate (CaLev) for intravenous administration is commercially available as a powder that must be reconstituted for injection or reconstituted and then diluted before administration. The lack of stability data on CaLev solutions renders necessary extemporaneous manual preparation, preventing the use of automated/semi-automated systems, with a consequent loss in terms of quality and safety. Methods The present work assessed the chemical–physical and microbiological stability of CaLev prepared in sodium chloride 0.9%, glucose 5% and water for injections and stored in polyolefin/polyamide bags and polypropylene syringes at 2–8°C protected from light. For this purpose, we developed and validated a new rapid High Performance Liquid Chromatography with Ultra Violet Diode-Array Detection (HPLC-UV-DAD) method. Results The samples tested were stable for 14 days, retaining >95% of their initial concentration and showing no change in colour, turbidity or pH. Microbiological tests performed on the samples were negative. Conclusions Our results confirmed the analytical stability of CaLev in NaCl 0.9%, glucose 5% and water for injection at concentrations used in clinical practice at our institute. This enables our centralized laboratory to organize the preparation of this drug in advance and the use of robots rather than manual preparation reduces the workload and the risk of preparation errors.

Connectivity and automation are increasingly getting importance in the automotive industry, which is observing a radical change from vehicles driven by humans to fully automated and remotely controlled ones. The test and validation of all the related devices and applications is thus becoming a crucial aspect; this is raising the interest on hardware-in-the-loop (HiL) platforms which reduce the need for complicated field trials, thus limiting the costs and delay added to the process. With reference to the test and validation of vehicle-to-everything (V2X) communications aspects, and assuming either sidelink LTE/5GV2X or IEEE 802.11p/bd technologies, in this work we focus on the real-time HiL simulation of the information exchanged by one vehicle under test and the surrounding, simulated, objects. Such exchange must be reproduced in a time-efficient manner, with elaborations done fast enough to allow testing the applications in real-time. More precisely, we discuss the simulation of nonideal positioning and channel propagation taking into account current impairments. We also provide details on optimization solutions that allowed us to trade-off minor loss in accuracy with a significant reduction of the computation time burden, reaching up to more than one order of magnitude speed increase in our experiments., The 2021 IEEE 93rd Vehicular Technology Conference: VTC2021-Spring

Background: Health-related quality of life (HRQoL) in childhood is a multidimensional construct with many sub dimensions of subjective experience, including physical activity (PA), psychological well-being, social interaction, and school performance, that represents a fundamental health outcome to assess a child’s physical and psycho-social functioning. Our study aims to explore the potential predictors of children’s health-related quality of life, using a convenience sample from the Imola Active Break Study (I-MOVE), considering demographic, anthropometric measures, PA level measured by Actigraph accelerometers, parent-reported/self-reported HRQoL, and body image. Methods: A cross-sectional analysis was conducted among 151 primary school children in Italy. HRQoL was assessed using the Italian version 4.0 of the Paediatric Quality of Life (PedsQL) questionnaire. Results: Children who spent more time partaking in moderate PA were associated with a higher total PedsQL score (p &lt, 0.03). Mother’s body mass index (BMI) was the only variable statistically significant associated with the physical health domain of PedsQL. Parent’s proxy-report perception concerning children’s psychosocial health was statistically relevant. The children’s gender, age, and BMI had no association with any of the HRQoL outcomes. Discussion: Parent proxy-report psychosocial health and mother’s BMI should be considered as predictors of HRQoL for the psychosocial and physical domain. PA should be implemented in order to improve the HRQoL of primary school children.

Objectives: Cardiac autonomic neuropathy is among the known cardiovascular complications of systemic sclerosis and may affect the whole prognosis of the disease. The aim of our study was to assess cardiac autonomic neuropathy prevalence in our cohort of systemic sclerosis patients and compare its main features with clinical and epidemiological data, particularly with the severity of microvascular damage, as detected by nailfold videocapillaroscopy. Methods: Twenty-six patients with definite systemic sclerosis were consecutively enrolled at our outpatient rheumatology clinic. All patients underwent physical examination, nailfold videocapillaroscopy, and autonomic neuropathy diagnostic tests (orthostatic hypotension test, deep breathing test, lying-to-standing, and Valsalva maneuvers). Results: Cardiac autonomic neuropathy prevalence was 50% (13 cases). On univariate analysis, cardiac autonomic neuropathy was shown to be significantly associated with an active pattern on nailfold videocapillaroscopy (odds ratio 5.86, 95% confidence interval 1.59–9.24; p = 0.032), whereas anti-Scl-70 positivity (odds ratio, 0.24; 95% confidence interval, 0.03–2.12; p = 0.049) and C-reactive protein (odds ratio, 19.32; 95% confidence interval, 1.79–56.71; p = 0.036) reached only a borderline statistical association. The time-dependent Cox multivariate regression model showed cardiac autonomic neuropathy development to be independently associated with an active pattern on nailfold videocapillaroscopy (odds ratio, 7.19; 95% confidence interval, 1.87–8.96; p = 0.042) and anti-Scl-70 positivity (odds ratio, 5.92; 95% confidence interval, 1.06–18.43; p = 0.048). Conclusions: Severe microvascular damage, as detected by nailfold videocapillaroscopy, may suggest the coexistence of autonomic dysfunction and should be considered as a red flag for the identification of patients particularly at risk of cardiac morbidity and mortality.

Aim Patient education is an essential component of the treatment of type 2 diabetes mellitus (T2DM). The present meta-analysis was aimed at verifying the efficacy of group-based versus individual education for self-management in patients with T2DM. Methods A Medline and Embase search up to January 1st, 2021, was performed, including Randomized Controlled Trials (RCT) with duration>6 months, enrolling patients with T2DM and comparing individual-based with group-based educational programs. The primary outcome was endpoint HbA1c; secondary endpoints were lipid profile, body weight, blood pressure, patients’ adherence/knowledge, and quality of life. The weighed difference in means (WMD) and Mantel-Haenzel Odds Ratio (MH-OR), with 95% Confidence Interval (CI), were calculated. Results We retrieved 14 RCT. No significant between-group difference in HbA1c (WMD -0.39[-0.89;0.09] mmol/mol, p=0.11) was observed. At metaregression analyses, longer trial duration, higher baseline mean age and duration of diabetes, and lower baseline HbA1c were correlated with greater efficacy of group-based programs in reducing HbA1c. When analyzed separately, trials excluding insulin-treated patients showed a significant reduction of HbA1c in favor of group education. Conclusions In patients with T2DM, group education has similar efficacy as individual education on glucose control. Group programs are associated with an improved quality of life and patients’ knowledge. PROSPERO and OSF registration ID243149.

The paper describes the creation of a manually validated dataset of Italian multiword expressions, building on candidates automatically extracted from corpora of written Italian. The main features of the resource, such as POS-pattern and lemma distribution, are also discussed, together with possible applications.

Objectives: To assess the role of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses presenting with mild or moderate isolated ventriculomegaly (VM) undergoing multiplanar ultrasound evaluation of the fetal brain. Methods: This was a multicenter, retrospective, cohort study involving 15 referral fetal medicine centers in Italy, the UK and Spain. Inclusion criteria were fetuses affected by isolated mild (ventricular atrial diameter, 10.0–11.9 mm) or moderate (ventricular atrial diameter, 12.0–14.9 mm) VM on ultrasound, defined as VM with normal karyotype and no other additional central nervous system (CNS) or extra-CNS anomalies on ultrasound, undergoing detailed assessment of the fetal brain using a multiplanar approach as suggested by the International Society of Ultrasound in Obstetrics and Gynecology guidelines for the fetal neurosonogram, followed by fetal MRI. The primary outcome of the study was to report the incidence of additional CNS anomalies detected exclusively on prenatal MRI and missed on ultrasound, while the secondary aim was to estimate the incidence of additional anomalies detected exclusively after birth and missed on prenatal imaging (ultrasound and MRI). Subgroup analysis according to gestational age at MRI (< 24 vs ≥ 24 weeks), laterality of VM (unilateral vs bilateral) and severity of dilatation (mild vs moderate VM) were also performed. Results: Five hundred and fifty-six fetuses with a prenatal diagnosis of isolated mild or moderate VM on ultrasound were included in the analysis. Additional structural anomalies were detected on prenatal MRI and missed on ultrasound in 5.4% (95% CI, 3.8–7.6%) of cases. When considering the type of anomaly, supratentorial intracranial hemorrhage was detected on MRI in 26.7% of fetuses, while polymicrogyria and lissencephaly were detected in 20.0% and 13.3% of cases, respectively. Hypoplasia of the corpus callosum was detected on MRI in 6.7% of cases, while dysgenesis was detected in 3.3%. Fetuses with an associated anomaly detected only on MRI were more likely to have moderate than mild VM (60.0% vs 17.7%; P < 0.001), while there was no significant difference in the proportion of cases with bilateral VM between the two groups (P = 0.2). Logistic regression analysis showed that lower maternal body mass index (adjusted odds ratio (aOR), 0.85 (95% CI, 0.7–0.99); P = 0.030), the presence of moderate VM (aOR, 5.8 (95% CI, 2.6–13.4); P < 0.001) and gestational age at MRI ≥ 24 weeks (aOR, 4.1 (95% CI, 1.1–15.3); P = 0.038) were associated independently with the probability of detecting an associated anomaly on MRI. Associated anomalies were detected exclusively at birth and missed on prenatal imaging in 3.8% of cases. Conclusions: The incidence of an associated fetal anomaly missed on ultrasound and detected only on fetal MRI in fetuses with isolated mild or moderate VM undergoing neurosonography is lower than that reported previously. The large majority of these anomalies are difficult to detect on ultrasound. The findings from this study support the practice of MRI assessment in every fetus with a prenatal diagnosis of VM, although parents can be reassured of the low risk of an associated anomaly when VM is isolated on neurosonography. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Contains fulltext : 231528.pdf (Publisher’s version ) (Closed access) BACKGROUND: TNF receptor-associated periodic syndrome (TRAPS) is a rare autoinflammatory disease caused by dominant mutation of the TNF super family receptor 1A (TNFRSF1A) gene. Data regarding long-term treatment outcomes are lacking. OBJECTIVE: To assess correlations of genotype-phenotypes in patients with TRAPS, as defined by the International Study Group for Systemic Autoinflammatory Diseases (INSAID) classification and Eurofever criteria, with treatment responses. METHODS: Data from 226 patients with variants of the TNFRSF1A gene and enrolled in the Eurofever registry were classified according to the INSAID classification in groups A (pathogenic or likely pathogenic variants), B (variants of uncertain significance or not classified variants), and C (benign or likely benign variants) and screened for Eurofever criteria. RESULTS: In group A (127 of 226 patients, 56%), all fulfilled Eurofever criteria and 20 of 127 patients (16%) developed AA amyloidosis. In group B (78 of 226 patients, 35%), 40 of 78 patients (51%) did not fulfill Eurofever criteria, displaying a lower incidence of abdominal pain (P < .02) and higher efficacy rate of on-demand nonsteroidal anti-inflammatory drugs (P 85% complete response). No patients on anti-IL-1 treatments developed AA amyloidosis, and 7 women with a history of failure to conceive had successful pregnancies. CONCLUSION: Anti-IL-1 drugs are the best maintenance treatment in patients with TRAPS. The diagnosis of TRAPS should be considered very carefully in patients of group B not fulfilling Eurofever criteria and group C, and colchicine may be preferable as the first maintenance treatment.

Background: The retrospective studies that have so far described the outcomes of the sequential use of life-prolonging agents (LPAs) did not include metastatic castration-resistant prostate cancer (mCRPC) patients who received radium-223 (223Ra) as part of their treatment. Consequently, it is not known whether including 223Ra in the therapeutic sequence has an impact on cumulative survival. The aim of this study was to evaluate this impact by comparing the cumulative overall survival (OS) in two series of mCRPC patients sequentially treated with two or three LPAs after first-line docetaxel (DOC), including 223Ra and not. Materials and Methods: The authors retrospectively reviewed the records of mCRPC patients with bone involvement alone who received two or three LPAs (including 223Ra) after first-line DOC. The control group was a contemporary series of mCRPC patients with bone involvement alone treated with sequences of two or three LPAs other than 223Ra after first-line DOC. Results: Median cumulative OS was 40.6 months in the 223Ra group of 78 patients and 36.2 months in the non-223Ra group of 186 patients (p = 0.08). OS outcomes were significantly influenced by the number of treatment lines, and baseline Eastern Cooperative Oncology Group performance status (PS) and prostate-specific antigen levels. Conclusions: To the best of the authors' knowledge, this is the first study designed to evaluate the impact of introducing 223Ra in the treatment sequences for mCRPC patients, and the results show that its use does not negatively affect cumulative OS.