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Background The World Health Organization stated an average of 60 min of Moderate to Vigorous Physical Activity (MVPA) that children should accumulate every day. Nevertheless physical inactivity is growing and, due to restrictions imposed during pandemic, PA levels of children might be more negatively affected. The study aimed to analyse the impact of COVID-19 on the PA of an Italian sample of primary school children by comparing it before and during COVID-19 considering gender differences. Methods A pre-post analysis (October 2019–January 2021) was conducted using a randomized sample (N = 77) from the I-MOVE study settled in an Italian primary school. Both objective (Actigraph accelerometers) and self-reported (PAQ-c questionnaires) assessments of PA were performed. Changes were compared using T-Student and Chi-Square test. Gender differences were calculated using Anova. Results Weekly and daily minutes time spent in MVPA significantly decreased respectively by − 30.59 ± 120.87 and − 15.32 ± 16.21 from before to during pandemic while the weekly time spent in sedentary behaviour increased (+ 1196.01 ± 381.49). PAQ-c scores followed the same negative trend (− 0.87 ± 0.72). Boys seem to have suffered more than girls from the imposed restrictions. Conclusion These findings outline the need for strategies to promote PA and reduce sedentary behaviours in children to prevent COVID-19 restriction long-term effects.

OBJECTIVES We aim to describe the use of continuous infusion of neuromuscular blocking agents in mechanically ventilated critically ill children and to test its association with in-hospital mortality. DESIGN Multicenter, registry-based, observational, two-cohort-comparison retrospective study using prospectively collected data from a web-based national registry. SETTING Seventeen PICUs in Italy. PATIENTS We included children less than 18 years who received mechanical ventilation and a neuromuscular blocking agent infusion from January 2010 to October 2017. A propensity score-weighted Cox regression analysis was used to assess the relationship between the use of neuromuscular blocking agents and in-hospital mortality. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Of the 23,227 patients admitted to the PICUs during the study period, 3,823 patients were included. Patients who received a continuous infusion of neuromuscular blocking agent were more likely to be younger (p < 0.001), ex-premature (p < 0.001), and presenting with less chronic respiratory insufficiency requiring home mechanical ventilation (p < 0.001). Reasons for mechanical ventilation significantly differed between patients who received a continuous infusion of neuromuscular blocking agent and patients who did not receive a continuous infusion of neuromuscular blocking agent, with a higher frequency of respiratory and cardiac diagnosis among patients who received neuromuscular blocking agents compared with other diagnoses (all p < 0.001). The covariates were well balanced in the propensity-weighted cohort. The mortality rate significantly differed among the two cohorts (patients who received a continuous infusion of neuromuscular blocking agent 21% vs patients who did not receive a continuous infusion of neuromuscular blocking agent 11%; p < 0.001 by weighted logistic regression). Patients who received a continuous infusion of neuromuscular blocking agent experienced longer mechanical ventilation and PICU stay (both p < 0.001 by weighted logistic regression). A weighted Cox regression analysis found the use of neuromuscular blocking agents to be a significant predictor of in-hospital mortality both in the unadjusted analysis (hazard ratio, 1.7; 95% CI, 1.3-2.2) and in the adjusted one (hazard ratio, 1.6; 95% CI, 1.2-2.1). CONCLUSIONS Thirteen percent of mechanically ventilated children in PICUs received neuromuscular blocking agents. When adjusting for selection bias with a propensity score approach, the use of neuromuscular blocking agent was found to be a significant predictor of in-hospital mortality.

Left-ventricular-assist-device (LVAD) implantation in patients with antiphospholipid-syndrome (APS) is considered a high-risk procedure and its indication still represents an open challenge. Herein, we report a 63-year-old man with APS and end-stage heart failure, for whom a HeartMate3-LVAD and a continuous rheologic profile monitoring with a multiparametric assessment resulted the optimal therapeutic strategy.

Introduction: Bullous pemphigoid (BP) is an autoimmune disease that typically presents with blisters, but sometimes early lesions may be eczematous, maculopapular, or urticarial. The aim of the present study was to highlight possible differences between typical bullous and non-bullous pemphigoid (NBP) and compare results with the literature. Material & methods: Patients receiving a diagnosis of BP between January 2000 and December 2019 were analyzed. Patients who developed a blister after 3 months from the onset of pruritus were considered as NBP. Demographic features, clinical findings at diagnosis and at 2-year follow-up, histological features, auto-antibodies titers, comorbidities and their treatment were retrieved. Categorical variables were evaluated for normal distribution using a histogram and a Q-Q plot. The χ2 and Fisher’s exact tests were used to compare categorical variables between the groups. Continuous variables were compared between the groups using analysis of variance and the independent-samples t test. For multivariate analysis, logistic regression was performed. Results: A total of 532 patients received a diagnosis of BP. A total of 122 patients were enrolled in the study; 63 were females, and the mean age at the diagnosis was 77.2 years (±11.9 SD). 98 were affected by BP and 24 were categorized as NBP. Mean time to diagnosis was 2.9 months (±5.8 SD) for BP and 30.4 months (±59.8 SD) for NBP (p = 0.0001). Skin manifestations in NBP patients were, in order of frequency: urticarial, papular or nodular, eczematous, and excoriations. Pruritus intensity was high but similar in the two groups (Numerical Rating Scale – NRS, 9.3 vs. 8.9). Seven out of 24 NBP patients (29%) never developed blisters; the other patients developed blisters after a mean follow-up time of 24.9 months (±54.9 SD). NBP patients had a more frequent history of myocardial infarction than BP patients (37.5 vs. 10.2%; p < 0.003). More NBP patients were taking diuretics than BP patients (66.7 vs. 49%; p = 0.03). NBP patients had a worse response to pruritus compared to BP patients at 2 years (NRS 3.7 vs. 11; p 0.001). Conclusions: NBP patients have a delayed diagnosis and may be at an increased risk of cardiovascular disease, especially myocardial infarction. Severely and persistently itchy skin disorders in aged patients should be investigated for BP diagnosis.

Continuous flow left ventricular assist devices (LVADs) have become a valuable therapy for end-stage heart failure. In vitro research highlighted a role of outflow cannula position on the pattern of blood flow in the aorta. However, the clinical effects of the alterations of flow remain unclear. We investigate short- and long-term outcomes of patients implanted with Jarvik 2000 LVAD, according to the ascending (Group 1) versus descending (Group 2) outflow graft connection to the aorta in a multicenter study. From May 2008 to October 2014, 140 consecutive end-stage heart failure patients underwent Jarvik 2000 LVAD implantation in 17 Italian centers. According with a preliminary multivariate analysis, we selected the 90 patients implanted in the four high-volume centers to avoid bias (Group 1 n = 39, Group 2 n = 51). Among the groups, no differences were recorded in the hospital mortality and the main complications occurring after LVAD implantation were similar. In multivariable analysis, the ascending aorta outflow cannula position and higher creatinine at discharge were significant predictors for long-term survival. Postimplant hemolysis was more pronounced in descending aorta outflow graft anastomosis. Outflow graft anastomosis to the ascending aorta is associated with better long-term survival, independent of age and perfusion techniques, reflecting the previous in vitro results.

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Objective To identify the epidemiological profile and prognostic factors of open globe injuries that require emergency surgical treatment. Design Retrospective cohort study. Subjects Patients with OGI who underwent publicly funded emergency surgical treatment in the Federal District from 2014 to 2018. Methods Data were collected by reviewing electronic medical records through a questionnaire and tabulated. The statistical analysis was performed in SPSS Statistics 26.0.0.0 (p ≤ 0.05). Results A total of 359 records were included, corresponding to 336 eyes of 334 patients (294 males and 40 females). The average age was 32.7 years. The affected eye was the right eye in 165 cases, the left eye in 166 cases, and both eyes in 3 cases. The average time between injury and hospitalization was 75.7 h, and the time between injury and surgery averaged 173.7 h. The injury types were as follows: 197 penetrating; 109 rupture; 19 IOFB; 11 perforating. The injuries were in the following zones: 181 zone I; 82 zone II; 70 zone III. The OTS grades were as follows: 57 were classified as grade 1; 101 were grade 2; 142 were grade 3; 28 were grade 4; and 8 were 5. The most commonly performed surgeries were corneal suture, corneoscleral suture, and evisceration. The most common clinical features were traumatic cataract, herniated iris and hyphema. The following were risk factors for poor prognosis: zone III, time between trauma and surgery > 72 h, rupture injury, retinal detachment, disorganization of the eyeball, endophthalmitis, uveal prolapse, OTS classification 1 or 2, and low initial visual acuity. The following factors predicted a good prognosis: initial VA > 1/200, penetrating injury, OTS 4 and zone II. Conclusions The high frequency of many of these factors may explain the high rate of severe visual loss found. Injury localization in zone II was identified as a previously unrecognized protective factor against severe visual loss.

Background: The school gives access to children, regardless of age, ethnicity, gender and socio-economic class and can be identified as the key environment in which to promote children&rsquo, s physical activity (PA). The guidelines of the European Union recommend accumulating at least 10-min bouts of PA to reach the daily 60 min. Active breaks (ABs) led by teachers inside the classroom represent a good strategy to promote PA. The aim of this pilot and feasibility study was to evaluate the feasibility and effectiveness in terms of PA level of an AB programme in children aged 8&minus, 9 years attending primary school. Methods: A pre-post quasi-experimental pilot and feasibility study was performed in two primary school classes, one of which was assigned to a 14-week AB intervention (AB group) and the other to the control group (CG). At baseline and at follow-up, children were monitored for sedentary and motor activity during an entire week using ActiGraph Accelerometer (ActiLife6 wGT3X-BT). The satisfaction of children and teachers was assessed by self-administered questionnaires. Results: In the pre-post comparison, AB group (n = 16) showed a reduction in the minutes spent in weekly sedentary activity (-168.7 min, p &gt, 0.05), an increase in the number of step counts (+ 14,026.9, p &lt, 0.05) and in time spent in moderate to vigorous PA (MVPA): weekly MVPA: + 64.4 min, daily MVPA: + 8.05 min, percentage of MVPA: + 0.70%. On the contrary, CG showed a worsening in all variables. ANCOVA analysis, after adjusting for baseline values, showed significant differences between the AB group and CG for time spent in MVPA, percentage of MVPA and step counts. The satisfaction of children and teachers was good. Teachers were able to adapt the AB protocol to the needs of the school curriculum, thus confirming the feasibility of the AB programme. Conclusions: This pilot and feasibility study showed the feasibility and effectiveness of the AB protocol and represented the basis for a future controlled trial.

Accumulating evidence supports the view that the medial part of the posterior parietal cortex (mPPC) is involved in the planning of reaching, but while plenty of studies investigated reaching performed toward different directions, only a few studied different depths. Here, we investigated the causal role of mPPC (putatively, human area V6A–hV6A) in encoding depth and direction of reaching. Specifically, we applied single-pulse transcranial magnetic stimulation (TMS) over the left hV6A at different time points while 15 participants were planning immediate, visually guided reaching by using different eye-hand configurations. We found that TMS delivered over hV6A 200 ms after the Go signal affected the encoding of the depth of reaching by decreasing the accuracy of movements toward targets located farther with respect to the gazed position, but only when they were also far from the body. The effectiveness of both retinotopic (farther with respect to the gaze) and spatial position (far from the body) is in agreement with the presence in the monkey V6A of neurons employing either retinotopic, spatial, or mixed reference frames during reach plan. This work provides the first causal evidence of the critical role of hV6A in the planning of visually guided reaching movements in depth.

Left ventricular assist device implantation is an established treatment for patients with end-stage heart failure. The HeartMate 3 (Abbott Laboratories, Abbott Park, IL) is a continuous-flow centrifugal pump, recently introduced in the clinic, that has shown greater hemocompatibility compared with similar devices of previous generations. Nevertheless, anticoagulation is still required after HeartMate 3 implant to avoid pump dysfunction. Hereafter, we describe the case of a patient candidate to left ventricular assist device implantation for end-stage heart failure presenting a concomitant cerebrovascular lesion, accidentally found during preoperative assessment, that would have contraindicated the procedure (for the prohibitive risk of cerebral hemorrhage), unless a step by step problem-solving approach was adopted.

Immunotherapy (IO) is effective in metastatic Non Small Cell Lung Cancer (NSCLC). Gut microbiota has an impact on immunity and its imbalance due to antibiotics may impair the efficacy of IO. We investigated this topic in a case series of NSCLC patients treated with IO.Data about all metastatic NSCLC patients treated with IO between 04/2013 and 01/2018 were collected. Patients were stratified according to antibiotic use during the Early IO Period (EIOP), and according to the Antibiotic-Immunotherapy Exposure Ratio (AIER) defined as "days of antibiotic/days of IO" during the Whole IO Period (WIOP). Survival was estimated using the Kaplan-Meier method. Log-rank test was used to compare the curves. Multivariate analyses were performed with the Cox model.We analyzed 157 patients. Forty-six patients received antibiotics during the WIOP, 27 patients during the EIOP. No differences in either Progression-Free Survival (PFS) or Overall Survival (OS) were observed according to antibiotic use during the EIOP (p = 0.1772 and p = 0.2492, respectively). Considering the WIOP, median AIER was 4.2%. The patients with a higher AIER had worse PFS (p 0.0001) and OS (p = 0.0004) than the others. Results were significant also after correction for the IO line (p = 0.0018 for PFS) and performance status (p 0.0001 for PFS, p = 0.0052 for OS).Although no difference in outcome were observed with antibiotic use in the EIOP, a detrimental effect became evident for patients with a higher AIER in the WIOP. If its relevance is confirmed, AIER may become an innovative variable for estimating the impact of antibiotics on IO efficacy.

BACKGROUND High-fiber diets (HFDs) are recommended in the diet of persons with diabetes, yet such diets can impair macronutrient digestion and/or absorption, modify insulin sensitivity, and reset metabolism. OBJECTIVES We studied the effects of a HFD on the kinetics of whole-body protein, a macronutrient that could be affected by dietary fiber, in type 1 diabetes mellitus (T1DM), under both basal-low insulinemic and hyperinsulinemic conditions. METHODS Eight men with T1DM (body mass index range: 21.8-27.8 kg/m2) were studied twice - before and after the addition of guar gum (∼15 g/d) to their usual diet for ∼4 mo. Whole-body protein degradation (i.e., the rate of appearance [Ra] of endogenous leucine), leucine disposal to protein synthesis (PS), deamination, and reamination, were determined before and after the HFD, both in the postabsorptive state and following a euglycemic, hyperinsulinemic, hyperaminoacidemic clamp, using isotope dilution methods. RESULTS After the HFD, mean values (± SEs) for postabsorptive leucine Ra decreased by ∼20%: from 2.52 (0.15) to 2.03 (0.16) μmol x kg-1 x min-1, P

OBJECTIVE This study aimed to assess the effects of sperm DNA fragmentation in parents belonging to different age groups. The couples included in the study comprised normozoospermic men and infertile women undergoing conventional IVF. METHODS The results obtained from 163 conventional IVF cycles were analyzed retrospectively. The couples enrolled in the study included women aged between 30 and 37 years. Sperm DNA fragmentation was studied using the TUNEL assay. The patients were split into four groups based on male age and sperm DNA fragmentation, as follows: Group 1: ≤39 years and TUNEL assay ≤20%; Group 2: ≤39 years and TUNEL assay >20%; Group 3: ≥40 years and TUNEL assay ≤20%; and Group 4: ≥40 years and TUNEL assay >20%. RESULTS No significant differences were found in semen parameters or fertilization rates between groups. Groups with

Background The aim of this multicenter retrospective study was to compare early and midterm clinical and hemodynamic results of aortic valve replacement with rapid-deployment bioprostheses performed through conventional full-sternotomy vs mini-sternotomy. Methods Data from the Italian multicenter registry of aortic valve replacement with rapid-deployment bioprostheses (INTU-ITA registry) were analyzed. Patients were divided into 2 groups: full sternotomy (FS) and ministernotomy (MS). Primary endpoint was the comparison of early and midterm mortality. Secondary endpoints were: comparison of intraoperative variables, complications, and hemodynamic performance. A propensity score weighting approach was used for data analysis. Results A total of 1057 patients were analyzed: 435 (41.2%) and 622 (58.8%) in group FS and MS, respectively. Thirty-day mortality was 1.6% and 0.6% in FS and MS groups, respectively (P = .074). cardiopulmonary bypass time was 78.5 minutes and 83 minutes in FS and MS groups, respectively (P = .414). In the overall cohort, the incidence of intraoperative complications and of device success was 3.8% (40 patients) and 95.9% (1014 patients), respectively, with no significant differences between groups. Survival at 1, 3, and 5 years was 94.1%, 98.1%, 88.5% and 91.8%, 85.2%, and 84.8% in FS and MS groups, respectively (P = .412). The 2 groups showed similar postoperative gradients (median mean gradient, FS: 10.0 mm Hg, MS: 11.0 mm Hg; P = .170) and also similar incidence of patient–prosthesis mismatch (FS: 7%, MS: 6.4%, P = .647). Conclusions According to our data, rapid-deployment bioprostheses allow the performance of minimally invasive aortic valve replacement with similar surgical times and similar clinical and hemodynamic outcomes to conventional surgery and should be considered the first choice in these procedures.

BackgroundAlbuminuria develops in ~40% of subjects with Type 2 Diabetes Mellitus (T2DM), and is often associated with malnutrition, severe comorbidities and decreased life expectancy. The association between albuminuria and altered whole body protein turnover in T2DM is currently unknown.ObjectiveTo assess whole body protein degradation and synthesis in type 2 diabetes with and without albuminuria.MethodsFourteen T2DM male subjects, with either increased [AER+] or normal [AER-] urinary albumin excretion rate, and eleven age-matched male healthy controls, were infused with phenylalanine [Phe] and tyrosine [Tyr] tracers. Post-absorptive rates of appearance (Ra) of Phe (= protein degradation) and Tyr, Phe hydroxylation to Tyr (Hy) (catabolic pathway), and Phe disposal to protein synthesis [PS], were determined.ResultsPhe and Tyr Ra were not different among the groups. However, in T2DM [AER+], the fraction of Phe disposal to hydroxylation was ~50% and ~25% greater than that of both controls and T2DM [AER-] (pConclusionsOn the basis of the kinetics of the essential amino acid phenylalanine, T2DM subjects with increased AER exhibit a catabolic pattern of whole body protein turnover.

Purpose: To evaluate if jugular vein flow restoration in various venographic defects indicative of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS) patients can have positive effects on cerebral lesions identified using magnetic resonance imaging (MRI). Materials and Methods: The Brave Dreams trial ( ClinicalTrials.gov identifier NCT01371760) was a multicenter, randomized, parallel group, double-blind, sham-controlled trial to assess the efficacy of jugular venoplasty in MS patients with CCSVI. Between August 2012 and March 2016, 130 patients (mean age 39.9±10.6 years; 81 women) with relapsing/remitting (n=115) or secondary/progressive (n=15) MS were randomized 2:1 to venography plus angioplasty (n=86) or venography (sham; n=44). Patients and study personnel (except the interventionist) were masked to treatment assignment. MRI data acquired at 6 and 12 months after randomization were compared to the preoperative scan for new and/or >30% enlargement of T2 lesions plus new gadolinium enhancement of pre-existing lesions. The relative risks (RR) with 95% confidence interval (CI) were estimated and compared. In a post hoc assessment, venograms of patients who underwent venous angioplasty were graded as “favorable” (n=38) or “unfavorable” (n=30) for dilation according to the Giaquinta grading system by 4 investigators blinded to outcomes. These subgroups were also compared. Results: Of the 130 patients enrolled, 125 (96%) completed the 12-month MRI follow-up. Analysis showed that the likelihood of being free of new cerebral lesions at 1 year was significantly higher after venoplasty compared to the sham group (RR 1.42, 95% CI 1.00 to 2.01, p=0.032). Patients with favorable venograms had a significantly higher probability of being free of new cerebral lesions than patients with unfavorable venograms (RR 1.82, 95% CI 1.17 to 2.83, p=0.005) or patients in the sham arm (RR 1.66, 95% CI 1.16 to 2.37, p=0.005). Conclusion: Expanded analysis of the Brave Dreams data that included secondary/progressive MS patients in addition to the relapsing/remitting patients analyzed previously showed that venoplasty decreases new cerebral lesions at 1 year. Post hoc analysis confirmed the efficacy of the Giaquinta grading system in selecting patients appropriate for venoplasty who were more likely to be free from accumulation of new cerebral lesions at MRI.

Background: During the COVID-19 pandemic, the scarcity of resources has necessitated triage of critical care for patients with the disease. In patients aged 65 years and older, triage decisions are regularly based on degree of frailty measured by the Clinical Frailty Scale (CFS). However, the CFS could also be useful in patients younger than 65 years. We aimed to examine the association between CFS score and hospital mortality and between CFS score and admission to intensive care in adult patients of all ages with COVID-19 across Europe. Methods: This analysis was part of the COVID Medication (COMET) study, an international, multicentre, retrospective observational cohort study in 63 hospitals in 11 countries in Europe. Eligible patients were aged 18 years and older, had been admitted to hospital, and either tested positive by PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or were judged to have a high clinical likelihood of having SARS-CoV-2 infection by the local COVID-19 expert team. CFS was used to assess level of frailty: fit (CFS 1–3), mildly frail (CFS 4–5), or frail (CFS 6–9). The primary outcome was hospital mortality. The secondary outcome was admission to intensive care. Data were analysed using a multivariable binary logistic regression model adjusted for covariates (age, sex, number of drugs prescribed, and type of drug class as a proxy for comorbidities). Findings: Between March 30 and July 15, 2020, 2434 patients (median age 68 years [IQR 55–77]; 1480 [61%] men, 954 [30%] women) had CFS scores available and were included in the analyses. In the total sample and in patients aged 65 years and older, frail patients and mildly frail patients had a significantly higher risk of hospital mortality than fit patients (total sample: CFS 6–9 vs CFS 1–3 odds ratio [OR] 2·71 [95% CI 2·04–3·60], p4–5 vs CFS 1–3 OR 1·54 [1·16–2·06], p=0·0030; age ≥65 years: CFS 6–9 vs CFS 1–3 OR 2·90 [2·12–3·97], p4–5 vs CFS 1–3 OR 1·64 [1·20–2·25], p=0·0020). In patients younger than 65 years, an increased hospital mortality risk was only observed in frail patients (CFS 6–9 vs CFS 1–3 OR 2·22 [1·08–4·57], p=0·030; CFS 4–5 vs CFS 1–3 OR 1·08 [0·48–2·39], p=0·86). Frail patients had a higher incidence of admission to intensive care than fit patients (CFS 6–9 vs CFS 1–3 OR 1·54 [1·21–1·97], p=0·0010), whereas mildly frail patients had a lower incidence than fit patients (CFS 4–5 vs CFS 1–3 OR 0·71 [0·55–0·92], p=0·0090). Among patients younger than 65 years, frail patients had an increased incidence of admission to intensive care (CFS 6–9 vs CFS 1–3 OR 2·96 [1·98–4·43], p4–5 vs CFS 1–3 OR 0·93 [0·63–1·38], p=0·72). Among patients aged 65 years and older, frail patients had no significant difference in the incidence of admission to intensive care compared with fit patients (CFS 6–9 vs CFS 1–3 OR 1·27 [0·92–1·75], p=0·14), whereas mildly frail patients had a lower incidence than fit patients (CFS 4–5 vs CFS 1–3 OR 0·66 [0·47–0·93], p=0·018). Interpretation: The results of this study suggest that CFS score is a suitable risk marker for hospital mortality in adult patients with COVID-19. However, treatment decisions based on the CFS in patients younger than 65 years should be made with caution. Funding: LOEY Foundation.

Background: High concentrations of ivermectin demonstrated antiviral activity against SARS-CoV-2 in vitro. Aim of this study was to assess safety and efficacy of high-dose ivermectin in reducing viral load in individuals with initial SARS-CoV-2 infection. Methods: Randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial performed in outpatients in Italy. Participants: adults recently diagnosed with asymptomatic/oligosymptomatic SARS-CoV-2 infection, providing informed consent. Exclusion criteria: pregnant or lactating women; CNS diseases; participants under dialysis; severe medical condition with prognosis < 6 months; warfarin treatment; antiviral/chloroquine phosphate/hydroxychloroquine treatment. Participants were assigned according to a randomized permuted block procedure to one of the following arms with allocation ratio 1:1:1: placebo (arm A); single dose ivermectin 600 μg/kg plus placebo for 5 days (arm B); single dose ivermectin 1200 μg/kg for 5 days (arm C). The pharmacist prepared the treatment according to the randomization list and on the basis of the participant’s weight. Primary outcomes: serious adverse drug reactions (SADR) and change of viral load at Day 7. The protocol was registered with ClinicalTrials.gov , NCT04438850. Findings. From 31th July, 2020 to 26th May, 2021, 32 participants were randomized to arm A, 29 to arm B and 32 to arm C. The recruitment was stopped on 10th June, because of a dramatic drop of cases. Eighty-nine participants were included in the safety analysis set, the change in viral load was calculated on 87 participants. No SADR were registered. The mean log10 viral load reduction was 2.9 in arm C (SD 1.6), 2.5 (2.2) in arm B and 2.0 (2.1) in arm A, with no significant differences (p=0.099 and 0.122 for C versus A and B versus A, respectively). Interpretation: High- dose ivermectin demonstrated safe, but did not prove efficacy to reduce viral load. Trial Registration: The protocol was registered with ClinicalTrials.gov , NCT04438850. Funding: The trial was partly funded by the Italian Ministry of Health. Declaration of Interest: None to declare. Ethical Approval: This study was approved by the national Ethics Committee of INMI – Spallanzani in Rome that is competent for all COVID-19 trials in Italy (resolution 139/2020 of 28th May, 2020), and by the Italian drug agency AIFA (resolution 136BIS/2020 of 18th May, 2020).

The first cases of Coronavirus disease-2019 (COVID-19) were reported on 21 February in the small town of Vo&rsquo, near Padua in the Veneto region of Italy. This event led to 19,286 infected people in the region by 30 June 2020 (39.30 cases/10,000 inhabitants). Meanwhile, Rovigo Local Health Unit n. 5 (ULSS 5), bordering areas with high epidemic rates and having one of the world&rsquo, s oldest populations, registered the lowest infection rates in the region (19.03 cases/10,000 inhabitants). The aim of this study was to describe timing and event management by ULSS 5 in preventing the propagation of infection within the timeframe spanning from 21 February to 30 June. Our analysis considered age, genetic clusters, sex, orography, the population density, pollution, and economic activities linked to the pandemic, according to the literature. The ULSS 5 Health Director General&rsquo, s quick decision-making in the realm of public health, territorial assistance, and retirement homes were key to taking the right actions at the right time. Indeed, the number of isolated cases in the Veneto region was the highest among all the Italian regions at the beginning of the epidemic. Moreover, the implementation of molecular diagnostic tools, which were initially absent, enabled health care experts to make quick diagnoses. Quick decision-making, timely actions, and encouraging results were achieved thanks to a solid chain of command, despite a somewhat unclear legislative environment. In conclusion, we believe that the containment of the epidemic depends on the time factor, coupled with a strong sense of awareness and discretion in the Health Director General&rsquo, s decision-making. Moreover, real-time communication with operating units and institutions goes hand in hand with the common goal of protecting public health.

ObjectivesAcquiring central venous pressure (CVP), an important clinical parameter, requires an invasive procedure, which poses risk to patients. The aim of the study was to develop a non-invasive methodology for determining mean-CVP from ultrasound assessment of the jugular venous pulse.MethodsIn thirty-four adult patients (age = 60 ± 12 years; 10 males), CVP was measured using a central venous catheter, with internal jugular vein (IJV) cross-sectional area (CSA) variation along the cardiac beat acquired using ultrasound. The resultant CVP and IJV-CSA signals were synchronized with electrocardiogram (ECG) signals acquired from the patients. Autocorrelation signals were derived from the IJV-CSA signals using algorithms in R (open-source statistical software). The correlation r-values for successive lag intervals were extracted and used to build a linear regression model in which mean-CVP was the response variable and the lagging autocorrelation r-values and mean IJV-CSA, were the predictor variables. The optimum model was identified using the minimum AIC value and validated using 10-fold cross-validation.ResultsWhile the CVP and IJV-CSA signals were poorly correlated (mean r = -0.018, SD = 0.357) due to the IJV-CSA signal lagging behind the CVP signal, their autocorrelation counterparts were highly positively correlated (mean r = 0.725, SD = 0.215). Using the lagging autocorrelation r-values as predictors, mean-CVP was predicted with reasonable accuracy (r2 = 0.612), with a mean-absolute-error of 1.455 cmH2O, which rose to 2.436 cmH2O when cross-validation was performed.ConclusionsMean-CVP can be estimated non-invasively by using the lagged autocorrelation r-values of the IJV-CSA signal. This new methodology may have considerable potential as a clinical monitoring and diagnostic tool.

Background This single-center retrospective study assessed the variation of left ventricular ejection fraction (LVEF) after transapical transcatheter aortic valve implantation and its effect on survival. We also evaluated the effect of sheath diameter on LVEF. Methods We analyzed data of all consecutive patients who underwent transapical transcatheter aortic valve implantation with the Sapien (Edwards Lifesciences, Irvine, CA) device (and its evolutions) between 2009 and 2015. We analyzed the difference between preoperative LVEF and LVEF at discharge (ΔEF = LVEFpost-op – LVEFpre-op) and considered its interquartile range (±5%) as the cutoff. Patients were divided in three groups: (1) improved LVEF (ΔEF ≥ +5%); (2) unchanged LVEF (ΔEF –5% to +5%), and (3) worsened LVEF (ΔEF ≤ –5%). Survival was evaluated with Kaplan-Meier analysis, and logistic regression multivariable analysis was used to determine independent predictors of LVEF improvement. Results Data of 122 patients were analyzed. Patients in the three groups were distributed as follows: (group 1) 27 patients (22.1%), (group 2) 69 (56.6%), and (group 3) 26 (21.3%). The mean ΔEF was 12.7% ± 4.7% in group 1 and –10.8% ± 3.9% in group 3. The ΔEF was more likely to improve in patients with preoperative LVEF of less than 0.35 ( p = 0.014). There were no significant differences in survival ( p = 0.41), rehospitalization ( p = 0.472), and New York Heart Association Functional Classification ( p = 0.307) among the groups. The use of the smallest available sheath (18F) was not associated with a significant change of ΔEF. Conclusions LVEF worsened in a small number of patients after transapical transcatheter aortic valve implantation, but this change was not associated with worse postoperative outcomes. Patients with a low LVEF showed better improvement. The progressive reduction of sheath diameter does not have a significant effect on LVEF changes.

Background. Sepsis is the major cause of mortality from any infectious disease worldwide. Sepsis may be the result of a healthcare associated infection (HAI): the most frequent adverse events during care delivery especially in Intensive Care Units (ICUs). The main aim of the present study was to describe the epidemiology of ICU-acquired sepsis and related outcomes among patients enrolled in the framework of the Italian Nosocomial Infections Surveillance in ICUs - SPIN-UTI project. Study design. Prospective multicenter study. Methods. The SPIN-UTI network adopted the European protocols for patient-based HAI surveillance. Results. During the five editions of the SPIN-UTI project, from 2008 to 2017, 47.0% of HAIs has led to sepsis in 832 patients. Overall, 57.0% episodes were classified as sepsis, 20.5% as severe sepsis and 22.5% as septic shock. The most common isolated microorganisms from sepsis episodes were Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. The case fatality rate increased with the severity of sepsis and the mean length of ICU-stay was significantly higher in patients with ICU-acquired sepsis than in patients without. Conclusions. Our study provides evidence that ICU-acquired sepsis occurs frequently in Italian ICU patients and is associated with a high case fatality rate and increased length of stay. However, in order to explain these findings further analyses are needed in this population of ICU patients.

Background: Although optimization of immunosuppressive schemes in renal transplantation have minimized acute posttransplant complications, long-term outcomes are still not optimal and most of the chronic graft damage is drug-related. Therefore, to define the best long-term maintenance immunosuppressive regimen is of major importance in renal transplantation. To assess this objective, we undertook a large, multicenter cohort study in Italy. Methods: We retrospectively analyzed data of 5635 patients (enrolled from 1983 to 2012) and we assessed the impact of 3 major immunosuppressive regimens (calcineurin inhibitors+antimetabolites+corticosteroids [CNI+ANT+CS] vs CNI+mammalian target-of-rapamycin (mTOR) inhibitors+CS [CNI+mTOR-I+CS] vs CNI+CS) on long-term clinical outcomes by employing several statistical algorithms. Results: The overall difference in the incidence of outcome over time was not statistically different within the first 5 years of follow-up (P =.13); however, it became significant at 10 years and 20 years (P

BACKGROUND High prevalence of valve absence was found in the internal jugular vein (IJV) of healthy volunteers by means of M-mode high-resolution Echo Colour Doppler (ECD). However, the prevalence of valve in neurovascular disorders linked to Chronic Cerebrospinal Venous Insufficiency (CCSVI) is still unknown. METHODS A cohort of 83 Healthy Controls (HC), 71 Multiple Sclerosis (MS), 99 Inner Ear Disorders (IED) underwent ECD investigation of the IJV valve, including M-mode evaluation and related hemodynamics. The primary outcome measure was characterization of valve presence, morphology and motility, whereas the secondary outcome was the rate of flow alteration. RESULTS Bilateral valve presence was found in 38% of HC, 58% of MS and 25% of IED, whereas, bilateral valve absence was recorded in 16% of HC, 10% of MS and 31% of IED (p

Background: Insulin and age affect leucine (and protein) kinetics in vivo. However, to our knowledge, leucine transamination and the effects of insulin have not been studied in participants of different ages.Objective: The aims of the study were to measure whole-body leucine deamination to α-ketoisocaproate (KIC) and KIC reamination to leucine in middle-aged and younger healthy adults, both in the postabsorptive state and after hyperinsulinemia.Methods: Younger (mean ± SE age: 26 ± 2 y) and middle-aged (54 ± 3 y) healthy men and women were enrolled. Isotope dilution methods with 2 independent leucine and KIC tracers, a dual isotope model and the euglycemic, hyperinsulinemic clamp technique, were used.Results: Leucine deamination [expressed as μmol/(kg × min)] was consistently greater than KIC reamination. In middle-aged adults, postabsorptive leucine deamination (0.77 ± 0.05), reamination (0.49 ± 0.04), and net deamination (0.28 ± 0.04) were ∼30% lower than in the younger group (deamination: 1.12 ± 0.07; reamination: 0.70 ± 0.09; net deamination: 0.42 ± 0.04) (P < 0.002, P < 0.05, and P < 0.015, respectively). After the hyperinsulinemic clamp, plasma leucine and KIC concentrations were reduced by ∼50% in both groups. Deamination and reamination also were suppressed by ∼40-50% in both groups (P < 0.001); however, they remained lower [-35% (P = 0.02) and -25% (P = 0.036), respectively] in the middle-aged than in the younger participants. The leucine rate of appearance and its suppression by insulin were similar in the middle-aged and in the younger subjects. By using both the basal and the clamp data, deamination was directly correlated with the plasma leucine concentration (r = 0.61, P < 0.0025) and reamination to that of plasma KIC (r = 0.79, P < 0.00002). Expressing the data relative to lean body mass did not substantially alter the results.Conclusions: Leucine deamination and reamination are lower in middle-aged than in younger adults, both in the postabsorptive and in the insulin-stimulated state. In middle age, a decreased net leucine transamination may represent a mechanism to spare this essential amino acid.

Context Homocysteine is an independent cardiovascular risk factor and is elevated in essential hypertension. Insulin stimulates homocysteine catabolism in healthy individuals. However, the mechanisms of hyperhomocysteinemia and its relationship with insulin resistance in essential hypertension are unknown. Objective To investigate whole body methionine and homocysteine kinetics and the effects of insulin in essential hypertension. Design and Setting Eight hypertensive male subjects and six male normotensive controls were infused with l-[methyl-2H3,1-13C]methionine for 6 hours. In the last 3 hours a euglycemic, hyperinsulinemic clamp was performed. Steady-state methionine and homocysteine kinetics were determined in postabsorptive and hyperinsulinemic conditions. Results Postabsorptive hypertensive subjects had elevated homocysteine concentrations (+30%, P = 0.035) and slightly (by 15% to 20%) but insignificantly lower methionine rates of appearance (Ras) (P = 0.07 to P = 0.05) and utilization for protein synthesis (P = 0.06) than postabsorptive normotensive controls. Hyperinsulinemia suppressed methionine Ra and protein synthesis, whereas it increased homocysteine trans-sulfuration, clearance, and methionine transmethylation (the latter only in the normotensive subjects). However, in the hypertensive subjects trans-sulfuration was significantly lower (P < 0.05) and increased ~50% less [by +1.59 ± 0.34 vs +3.45 ± 0.52 µmol/kg lean body mass (LBM) per hour, P < 0.005] than in normotensive controls. Homocysteine clearance through trans-sulfuration was ~50% lower in hypertensive than in normotensive subjects (P < 0.005). In the hypertensive subjects, insulin-mediated glucose disposal was ~45% lower (460 ± 44 vs 792 ± 67 mg/kg LBM per hour, P < 0.0005) than in normotensive controls and was positively correlated with the increase of trans-sulfuration (P < 0.0015). Conclusions In subjects with essential hypertension, hyperhomocysteinemia is associated with decreased homocysteine trans-sulfuration and probably represents a feature of insulin resistance.

Background The elongation of the styloid process is historically associated with two variants of the Eagle syndrome. The classic one, mainly characterized by pain and dysphagia, and the carotid variant characterized by pain and sometimes by cerebral ischemia. We observed a further variant characterized by a styloid elongation coursing adjacent to the transverse process of C1, causing significant compression of the internal jugular vein. Methods We reviewed all the cases of Eagle syndrome, including the jugular variant, admitted in our Hospital in the last six years. We compared symptomatology, associated comorbidities and imaging. Data were statistically analyzed. Results Overall 23 patients were admitted to the Hospital for symptomatic elongation of the styloid process, 11 male and 12 females. The jugular variant of the Eagle syndrome is clinically delineated by significant differences, as compared to the classic variant and carotid variants. Headache was the more prominent symptom (p p Conclusions The elongation of the styloid process may have different paths which creates compression on the surrounding anatomical structures. There may be a possible association of jugular impingement by an elongated styloid process with symptoms. Trial registration Protocol n°45–2013.

The aim of this retrospective multicenter study was to compare early clinical and hemodynamic outcomes of Perceval-S sutureless (Livanova, London, United Kingdom) and Intuity rapid-deployment (Edwards Lifesciences, Irvine, Calif) bioprostheses.Data from patients who underwent isolated or combined aortic valve replacement with Perceval-S and with Intuity bioprostheses at 18 cardiac surgical institutions were analyzed. Propensity matching was performed to identify similar patient cohorts.We included 911 patients from March 2011 until May 2017. Perceval-S and Intuity valves were implanted in 349 (38.3%) and in 562 (61.7%) patients, respectively. Propensity score identified 117 matched pairs. In the matched cohort, device success was 99.1% and 100% in Perceval-S and Intuity group, respectively (P = 1.000). Thirty-day Valve Academic Research Consortium mortality occurred in 2 (1.7%) and 4 (3.4%) patients in the Perceval-S and in Intuity group, respectively (P = .6834). The rate of postoperative new permanent pacemaker implantation was 6% (7 patients) and 6.8% (8 patients) in the Perceval-S and in Intuity group, respectively (P = .7896). Perceval-S valve implantation requires significantly shorter aortic crossclamp and cardiopulmonary bypass times than Intuity valve implantation (aortic crossclamp time for isolated, 52 ± 14 minutes vs 62 ± 24 minutes; P .0001). Peak transaortic gradients were 22.4 ± 8.1 mm Hg and 19.6 ± 6.7 mm Hg (P = .0144), whereas mean gradients were 11.8 ± 4.7 mm Hg and 10.5 ± 3.9 mm Hg (P = .0388) in the Perceval-S and Intuity groups, respectively.Sutureless Perceval-S and rapid-deployment Intuity bioprostheses provide good and similar early clinical and hemodynamic outcomes. Perceval-S valve implantation requires shorter crossclamp and cardiopulmonary bypass times, whereas Intuity valve implantation provides lower transaortic peak and mean gradients.

We propose STIMA, a short test for ideo-motor apraxia, allowing us to quantify the apraxic deficit according to action meaning and affected body segment. STIMA is based on a neurocognitive model holding that there are two processes involved in action imitation (i.e., a semantic route for recognizing and imitating known gestures, and a direct route for reproducing new gestures). The test allows to identify which imitative process has been selectively impaired by brain damage (direct vs. semantic route) and possible deficits depending on the body segment involved (hand/limb vs. hand/fingers). N = 111 healthy participants were administered with an imitation task in two separated blocks of known and new gestures. In each block, half of the gestures were performed mainly with the proximal part of the upper limb and the remaining half with the distal one. It resulted in 18 known gestures (nine proximal and nine distal) and 18 new gestures (nine proximal and nine distal) for a total of 36. Each gesture was presented up to a maximum of two times. Detailed criteria are used to assign the final imitation score. Cut offs, equivalent scores and main percentile scores were computed for each subscale. Participants imitated better known than new gestures, and proximal better than distal gestures. Age influenced performance on all subscales, while education only affected one subscale. STIMA is easy and quick to administer, and compared to previous tests, it offers important information for planning adequate rehabilitation programs based on the functional locus of the deficit.

To analyze the effects of anthropometric measures change on quality of life (QoL) in elderly, using measured anthropometric data on body mass index (BMI) and waist circumference (WC). Population-based cohort study investigating a sample of elderly (≥60) assessed in 2009 (n = 1705) and followed up in 2013 (n = 1197). QoL was evaluated in 2013 using the CASP-19. Variables evaluated as exposure including BMI and WC in 2009 (both standardized), categories of anthropometric measures change from 2009 to 2013 (excess weight = BMI ≥ 25.0 kg/m2; large WC = top quartile), and the absolute BMI and WC change in same period. Multivariate linear regressions adjusted for possible confounding factors and mediators were used. Both BMI and WC at baseline were associated with lower QoL scores, even after adjustment for confounding variables (β BMI = −0.9; 95 % CI −1.5; −0.3 and β WC = −1.0; 95 % CI −1.7; −0.4). Additionally, QoL scores were lower among elderly with excess weight (β = −1.4; 95 % CI −2.9; 0.0) or large WC (β = −3.3; 95 % CI −5.2; −1.4) in both waves than among those whose BMI and WC were always normal, but changes in anthropometric measures did not affect QoL. The presence of chronic diseases was a partial mediator of these associations, especially for effects of BMI change. Anthropometric measures change treated as a continuous variable was not associated with QoL. Having excess weight and large WC in both waves was associated with lower QoL scores in elderly, but changing the anthropometric measures did not affect this outcome. Maintaining weight and WC within normal limits during aging can help to preserve QoL.

Background: L-type calcium channels (LTCCs) play important roles in regulating cardiomyocyte physiology, which is governed by appropriate LTCC trafficking to and density at the cell surface. Factors influencing the expression, half-life, subcellular trafficking, and gating of LTCCs are therefore critically involved in conditions of cardiac physiology and disease. Methods: Yeast 2-hybrid screenings, biochemical and molecular evaluations, protein interaction assays, fluorescence microscopy, structural molecular modeling, and functional studies were used to investigate the molecular mechanisms through which the LTCC Ca v β2 chaperone regulates channel density at the plasma membrane. Results: On the basis of our previous results, we found a direct linear correlation between the total amount of the LTCC pore-forming Ca v α1.2 and the Akt-dependent phosphorylation status of Ca v β2 both in a mouse model of diabetic cardiac disease and in 6 diabetic and 7 nondiabetic cardiomyopathy patients with aortic stenosis undergoing aortic valve replacement. Mechanistically, we demonstrate that a conformational change in Ca v β2 triggered by Akt phosphorylation increases LTCC density at the cardiac plasma membrane, and thus the inward calcium current, through a complex pathway involving reduction of Ca v α1.2 retrograde trafficking and protein degradation through the prevention of dynamin-mediated LTCC endocytosis; promotion of Ca v α1.2 anterograde trafficking by blocking Kir/Gem-dependent sequestration of Ca v β2, thus facilitating the chaperoning of Ca v α1.2; and promotion of Ca v α1.2 transcription by the prevention of Kir/Gem-mediated shuttling of Ca v β2 to the nucleus, where it limits the transcription of Ca v α1.2 through recruitment of the heterochromatin protein 1γ epigenetic repressor to the Cacna1c promoter. On the basis of this mechanism, we developed a novel mimetic peptide that, through targeting of Ca v β2, corrects LTCC life-cycle alterations, facilitating the proper function of cardiac cells. Delivery of mimetic peptide into a mouse model of diabetic cardiac disease associated with LTCC abnormalities restored impaired calcium balance and recovered cardiac function. Conclusions: We have uncovered novel mechanisms modulating LTCC trafficking and life cycle and provide proof of concept for the use of Ca v β2 mimetic peptide as a novel therapeutic tool for the improvement of cardiac conditions correlated with alterations in LTCC levels and function.

In major depressive disorder (MDD) patients, life stress events represent a risk factor for a severe, early-onset, treatment-resistant and chronic endophenotype. Treatment-resistant depression (TRD) patients who have experienced traumatic events could benefit from evidence-based trauma-focused psychotherapies. Because this topic has never been investigated, the aim of this pilot trial was to evaluate whether trauma-focused cognitive-behavioural therapy (TF-CBT) and/or eye movement desensitization and reprocessing (EMDR) can help achieve depressive symptom remission in TRD patients. We carried out a single-blind randomized controlled trial with TRD patients and we compared EMDR (N = 12) with TF-CBT (N = 10). Patients received 3 individual sessions per week over a period of 8 weeks. The symptomatological assessments were performed at 4 timepoints: baseline (T0), 4 (T4), 8 (T8) and 12 (T12) weeks. After 24 weeks, a clinical interview was carried out by phone. All TRD patients showed a significant improvement in depressive symptomatology; however, post hoc comparisons showed a significant difference between the two treatment groups, with lower depressive symptom scores in the EMDR than in the TF-CBT group at the follow-up (T12). This effect was partly maintained at 24 weeks. This pilot study suggests that evidence-based trauma-focused psychotherapies, particularly EMDR, can represent effective interventions to treat TRD patients.

Coercive treatments are often regarded as an inevitable and yet highly debated feature of psychiatric care. Perceived coercion is often reported by patients involuntarily committed as well as their voluntary counterparts. The Admission Experience Survey (AES) is a reliable tool for measuring perceived coercion in mental hospital admission. We developed the Italian AES (I-AES) through translation back-translation and administered it to 156 acutely hospitalized patients (48% women, 69% voluntarily committed) in two university hospitals in Rome (Policlinico Umberto I, Sant'Andrea Hospital). A principal component analysis (PCA) with equamax rotation was conducted. The I-AES showed good internal consistency (Cronbach's alpha = 0.90); Guttmann split-half reliability coefficient was 0.90. AES total score significantly differed between voluntary and involuntary committed patients (5.08 ± 4.1 vs. 8.1 ± 4.9, p .05). PCA disclosed a three-factor solution explaining 59.3 of the variance. Some discrepancies were found between the factor structure of the I-AES and the original version. I-AES total score was positively associated with numbers of previous involuntarily hospitalization (r = 0.20, p .05) and psychiatric symptoms' severity (r = 0.22, p .02). I-AES and its proposed new factor structure proved to be reliable to assess perceived coercion in mental hospital admission. Consequently, it may represent a helpful instrument for the study and reduction of patients' levels of perceived coercion.

Because the internal jugular vein (IJV) valve is the only protective valve between the brain and heart, recent studies have focused on the dynamic behaviour of the valve and its importance in regulating the cerebral blood outflow pathway. However, the mechanism underlying valve opening and closure, as well as the normal opening time, has not been investigated before. The aim of the study described here was to investigate IJV physiology in healthy young adults by means of ultrasound imaging. Twenty-four normal young adults (16 male, 8 female, 21.79 ± 0.79 y of age) were enrolled in this study. Each participant underwent IJV B- and M-mode ultrasound scans of the neck veins in supine position. Data on IJV leaflet movement and IJV blood velocity were extracted from images with the associated electrocardiogram traces to analyze the opening and closure cycles of IJV leaflets. The normal opening time calculated in this study includes 70% of the dynamic valve cycle. The normal opening time of the IJV valve could be a new physiologic metric and serves as a premise for further studies in the field of cerebral venous return.

OBJECTIVES Our goal was to evaluate the results of our 20-year experience with minimally invasive surgical approaches for closing ostium secundum atrial septal defects, focusing on clinical results, patient satisfaction and cost-effectiveness. METHODS We included 538 patients who underwent surgical ostium secundum atrial septal defects closure with minimally invasive approaches. RESULTS The minimally invasive approaches included right anterior minithoracotomy (n = 335, 62%), midline lower ministernotomy (135, 25%) and right lateral minithoracotomy (n = 68, 13%). Central cannulation was used in 374 patients (69%), whereas, more recently, a remote cardiopulmonary bypass with peripheral cannulation was used in 164 selected patients (31%). Median intensive care unit and postoperative hospitalization stays were 1 day [interquartile range (IQR) 1-1 day] and 5 days (IQR 5-6 days), respectively. Thirty-one patients had postoperative complications (5.8%); postcardiotomy syndrome was the most frequent complication (n = 20/538, 3.7%). Decreases in the length of postoperative hospitalization (P

Organ transplant recipients (OTRs) have a 100‐fold increased risk of cutaneous squamous cell carcinoma (cSCC). We prospectively evaluated the association between β genus human papillomaviruses (βPV) and keratinocyte carcinoma in OTRs. Two OTR cohorts without cSCC were assembled: cohort 1 was transplanted in 2003‐2006 (n = 274) and cohort 2 was transplanted in 1986‐2002 (n = 352). Participants were followed until death or cessation of follow‐up in 2016. βPV infection was assessed in eyebrow hair by using polymerase chain reaction–based methods. βPV IgG seroresponses were determined with multiplex serology. A competing risk model with delayed entry was used to estimate cumulative incidence of histologically proven cSCC and the effect of βPV by using a multivariable Cox regression model. Results are reported as adjusted hazard ratios (HRs). OTRs with 5 or more different βPV types in eyebrow hair had 1.7 times the risk of cSCC vs OTRs with 0 to 4 different types (HR 1.7, 95% confidence interval 1.1‐2.6). A similar risk was seen with high βPV loads (HR 1.8, 95% confidence interval 1.2‐2.8). No significant associations were seen between serum antibodies and cSCC or between βPV and basal cell carcinoma. The diversity and load of βPV types in eyebrow hair are associated with cSCC risk in OTRs, providing evidence that βPV is associated with cSCC carcinogenesis and may present a target for future preventive strategies., In two cohorts of organ transplant recipients, those with five and more different beta‐genus human papillomavirus types and high virus loads in eyebrow hairs subsequently develop significantly more cutaneous squamous cell carcinomas than others, suggesting that these virus types may increase the risk of cutaneous squamous cell carcinoma in these patients.

The aim of this study is to evaluate whether cerebral inflow and outflow abnormalities, assessed by the means of a validated ultrasound model, could be associated with Sudden Sensorineural Hearing Loss (SSNHL). According to Clark, a total of 42 patients affected by severe SSNHL and 19 healthy volunteers matched by gender without any history of sudden hearing impairment have been included in this study. Patients and controls underwent EchocolorDoppler assessment of brain hemodynamics. All subjects affected by SSNHL were also assessed with Auditory Brainstem Responses (ABR) and Magnetic Resonance Imaging (MRI) in order to exclude retrocochlear pathology. The head inflow through the common carotid artery was practically equivalent between groups, but at the level of the carotid bifurcation, the external carotid artery showed a highly significant flow rate in SSNHL 5.4±2 vs 3.9±1.1 ml/s in controls (p=0.01). The brain inflow was similar between patients and controls, but interestingly the flow rate of the vertebral artery was significantly reduced in SSNHL 1.6±0.8 vs 2.8±0.9 ml/s (p=0.01). The brain outflow was found significantly restricted at the level of the jugular outlet 6.6±6 vs 9.9±6 ml/s (p=0.002); consequently, the collateral flow index was significantly increased in SSNHL (p=0.001). The present study shows a discrepant distribution of the brain inflow which seems to penalize the posterior segments of the Willis polygon in patients affected by severe SSNHL. In addition, our study confirms the presence of chronic cerebrospinal venous insufficiency in SSNHL with significant activation of venous collateral circulation.

Although limited by severe side effects and development of resistance, platinum-based therapies still represent the most common first-line treatment for non-small cell lung cancer (NSCLC). However, a crucial need in the clinical management of NSCLC is represented by the identification of cases sensitive to DNA damage response (DDR)-targeting drugs, such as cisplatin or PARP inhibitors. Here, we provide a molecular rationale for the stratification of NSCLC patients potentially benefitting from platinum compounds based on the expression levels of RANBP9, a recently identified player of the cellular DDR. RANBP9 was found overexpressed by immunohistochemistry (IHC) in NSCLC compared to normal adjacent tissues (NATs) (n = 147). Moreover, a retrospective analysis of 132 platinum-treated patients from the multi-centric TAILOR trial showed that RANBP9 overexpression levels are associated with clinical response to platinum compounds [Progression Free Survival Hazard Ratio ((RANBP9 high vs low)) 1.73, 95% CI 1.15–2.59, p = 0.0084; Overall Survival HR ((RANBP9 high vs low)) 1.99, 95% CI 1.27–3.11, p = 0.003]. Accordingly, RANBP9 KO cells showed higher sensitivity to cisplatin in comparison with WT controls both in vitro and in vivo models. NSCLC RANBP9 KO cells were also more sensitive than control cells to the PARP inhibitor olaparib alone and in combination with cisplatin, due to defective ATM-dependent and hyper-activated PARP-dependent DDR. The current investigation paves the way to prospective studies to assess the clinical value of RANBP9 protein levels as prognostic and predictive biomarker of response to DDR-targeting drugs, leading to the development of new tools for the management of NSCLC patients.

Some clinical conditions, including dementia, compromise cognitive functions involved in decision-making processes, with repercussions on the ability to subscribe a will. Because of the increasing number of aged people with cognitive impairment there is an acute and growing need for decision-making capacity evidence-based assessment. Our study investigates the relationship between writing abilities and cognitive integrity to see if it is possible to make inferences on decision-making capacity through handwriting analysis. We also investigated the relationship between signature ability and cognitive integrity. Thirty-six participants with diagnosis of MCI and 38 participants with diagnosis of initial dementia were recruited. For each subject we collected two samples of signature—an actual and a previous one—and an extract of spontaneous writing. Furthermore, we administered a neuropsychological battery to investigate cognitive functions involved in decision-making. We found significant correlations between spontaneous writing indexes and neuropsychological test results. Nonetheless, the index of signature deterioration does not correlate with the level of cognitive decline. Our results suggest that a careful analysis of spontaneous writing can be useful to make inferences on decision-making capacity, whereas great caution should be taken in attributing validity to handwritten signature of subjects with MCI or dementia. The analysis of spontaneous writing can be a reliable aid in cases of retrospective evaluation of cognitive integrity. On the other side, the ability to sign is not an index of cognitive integrity.

Concerns still exist regarding long-term results and freedom from valve-related adverse events in transcatheter aortic valve implantation (TAVI). The aim of this single-center retrospective study was to assess intermediate-term (up to 5-year) clinical and hemodynamic outcomes in patients undergoing TAVI.From 2007 through 2013, 338 consecutive patients underwent TAVI at our institution. Preoperative variables were defined according to the European System for Cardiac Operative Risk Evaluation (EuroSCORE) definitions, and outcomes were reported according to the Valve Academic Research Consortium (VARC)-2 definitions. Multivariate logistic regression analysis was performed to identify independent predictors of mortality at follow-up.transfemoral (TF) and transapical (TA) TAVI were performed in 233 (69%) and 105 (31%) patients, respectively. All-cause 30-day mortality was 4.4%, with no differences between TA and TF procedures. Thirty-day cardiovascular death, stroke, and myocardial infarction were not different between groups. The acute kidney injury (AKI) rate was higher in the TA group (30.5% versus 11.2%; p0.001). Access-related complications were more frequent in the TF group (36.1% versus 11.4%; p0.001). Mean follow-up was 22.3 ± 17.8 months (range, 1-74 months). Overall survival rates at 1, 3, and 5 years were 85.5% ± 2.1%, 69.9% ± 3.2%, and 61% ± 4.3%, respectively. Independent predictors of all-cause mortality at follow-up were previous myocardial infarction (odds ratio [OR], 2.7), any grade of paravalvular leak (PVL) (OR, 2.5), and AKI (OR, 3.1). Mean gradient and effective orifice area at follow-up were 10.7 ± 12.0 mm Hg and 1.1 ± 0.9 cm(2)/m(2), respectively.Our data show that TAVI has good early and intermediate-term clinical and hemodynamic outcomes in high-risk or inoperable patients with severe symptomatic aortic valve stenosis. PVL of any grade has a significant impact on survival.

CK2 is a multifunctional, pleiotropic protein kinase involved in the regulation of cell proliferation and survival. Since fibroblasts from Type 1 Diabetes patients (T1DM) with Nephropathy exhibit increased proliferation, we studied cell viability, basal CK2 expression and activity, and response to specific CK2 inhibitors TBB (4,5,6,7-tetrabenzotriazole) and CX4945, in fibroblasts from T1DM patients either with (T1DM+) or without (T1DM-) Nephropathy, and from healthy controls (N). We tested expression and phosphorylation of CK2-specific molecular targets. In untreated fibroblasts from T1DM+, the cell viability was higher than in both N and T1DM-. CK2 inhibitors significantly reduced cell viability in all groups, but more promptly and with a larger effect in T1DM+. Differences in CK2-dependent phosphorylation sites were detected. In conclusion, our results unveil a higher dependence of T1DM+ cells on CK2 for their survival, despite a similar expression and a lower activity of this kinase compared with those of normal cells.

The purpose of the work described here was to investigate the feasibility of assessing the jugular venous pulse (JVP) using ultrasound (US) equipment. Three young healthy subjects underwent a B-mode US scan of the internal jugular vein (IJV) to acquire a sonogram sequence in the transverse plane. On each acquired sonogram, the IJV contour was manually traced, and both the cross-sectional area (CSA) and the perimeter were measured. The CSA data set represents the US jugular diagram (USJD). The arterial distension waveform of the subjects was compared with its USJD. The correlation between the CSA and the perimeter was assessed during the cardiac cycle to verify IJV distension. For each subject, a short sonogram sequence of a few seconds was recorded, and the USJD obtained exhibited periodic behavior. Furthermore, for all subjects, the CSA was found to be correlated with the perimeter (Pearson coefficient, R > 0.9), indicating that the IJV in supine position is distended. We compared 390 manually traced contours of the IJV cross-sectional area with corresponding values semi-automatically calculated by an algorithm developed in-house. For all subjects, the sensitivity, specificity and accuracy were around 95%, 85% and 90% respectively. We found that a diagram reflecting the JVP can be obtained by analyzing a B-mode sonogram sequence of the IJV; such a diagram can result in a new methodology to assess the IJV functionality.

The present study investigates whether sport activities involving children with a disability can reduce negative attitudes towards disability in children without disability. We compared the effect of being schoolmate or member of the same football team whereby a child with disability was member of the class/team or not. This lead to four groups that were assessed both at the beginning and at the end of the school year. Two measures were collected: an ad-hoc questionnaire and an Implicit Association Test. The two assessments were designed to measure explicit and implicit attitudes towards children with disabilities. Results suggested that sport activities over one school year reduced more (p < .001) the implicit negative attitude towards disability (Mean = -.17, sd = .10) than the contact with the classmate in the school context (Mean = -.03, sd = .14), possibly due to their team building characteristic.

There is evidence suggesting that viewing hands triggers automatic access to the Body Structural Description, a visual-spatial representation of human body parts configuration. Hands, however, have a special representational status within the brain because of their significance for action and cognition. We tested whether feet, less important in gestural and object-directed action, would similarly show automatic access to the Body Structural Description. Positive evidence of that would be finding a Sidedness effect (Ottoboni et al. J Exp Psychol Hum Percept Perform 31:778–789, 2005), a Simon-like paradigm previously used to study automatic hand recognition. This effect demonstrates that processing hands generates spatial codes corresponding to the side of the body on which the hand would be located within the Body Structural Description map. Feet were shown with toes pointing upwards (Experiment 1), without any connection to the ankle and the leg (Experiment 2) and with toes pointing downwards (Experiment 3). Results revealed a Sidedness effect in both Experiments 1 and 3: spatial compatibility occurred according to the side of the body that each foot would assume within the Body Structural Description. In Experiment 2, as already found in stimuli similarly featured, no effect emerged, due to the lack of the necessary anatomical links connecting the foot to a body. Results suggest that body parts with variable degrees of significance for action and cognition can access automatically the Body Structural Description hence reinforcing the hypothesis of its pure visuo-spatial nature.

Preclinical and observational reports indicate that adipose tissue (AT) is a safe and promising tool to treat non-healing venous leg ulcers (VLUs).From an initial cohort of 38 patients, 16 patients affected by non-healing VLUs were randomly allocated to the experimental arm (5 men and 3 women) and control arm (5 men and 3 women). In the experimental arm, wounds were treated by debridement, centrifuged adipose tissue (CAT), advanced dressings and compression. No experimental treatment (CAT) was administered to the control arm. We investigated the functional and the immunophenotypical features of the harvested CAT-derived stem cells. The primary outcome measures were healing time and safety of the cell treatment. Secondary outcomes were pain evaluated by numeric rating scale (NRS), complete wound healing at 24 weeks by Margolis Index and wound-healing process expressed in square centimeters per week. The various immunophenotypic and functional characteristics of CAT-derived stem cells were then correlated with the clinical outcomes.No major adverse events were recorded. The healing time was significantly faster by applying CAT, 17.5 ± 7.0 weeks versus 24.5 ± 4.9 weeks recorded in the control arm (P0.036). NRS dropped after the first week to 2.7 ± 2.0 in the experimental arm versus 6.6 ± 3.0 in the control group (P0.01). The rate of healing at the 24th week was not significantly different between arms. Interestingly, we found a strong reverse correlation between the percent of CD34CAT is safe and may accelerate healing time in VLUs as well as reduce wound pain. The percentage of CD34

Primary cutaneous lymphomas (PCLs) are a rare group of extranodal non-Hodgkin lymphomas, and epidemiological data in Mediterranean countries are scarce.To investigate the incidence and characteristics of PCL in a single tertiary referral centre in Italy.A total of 141 PCL patients, seen over a 10-year follow-up period, were investigated.Incidence rate of PCL was 0.8 cases/100,000 person years. T-cell lymphoma represented 78.7% of all cases, the majority being early mycosis fungoides (MF) (64%; median age: 66 years), followed by lymphomatoid papulosis (LyP) (19%; median: age 48 years), and others (median age: 72 years), including eight cases of anaplastic large CD30+ T-cell lymphoma, four CD4+ small-medium pleomorphic T-cell lymphoproliferative disorder, four Sézary syndrome, one subcutaneous panniculitis-like T-cell lymphoma, one extranodal NK/T-cell lymphoma nasal-type, and one angioimmunoblastic T-cell lymphoma. B-cell lymphoma accounted for 21.3% of PCL, with 20 cases of cutaneous follicular centre B-cell (median age: 63 years), four primary cutaneous marginal zone, three primary cutaneous diffuse large B-cell, and three leg-type lymphoma. Complete remission within the first year after diagnosis occurred in 70.4% of MF, 61.9% of LyP, 78.9% of other T-cell lymphoma, and 93.1% of B-cell lymphoma cases. Based on a Cox proportional hazard regression model, age, gender, stage, and lactate dehydrogenase and β2-microglobulin blood levels did not predict clinical remission of MF or LyP.The incidence and characteristics of PCL in Italy are similar to those in other European countries. PCLs may be diagnosed at very early stages with good prognosis.

We aimed to evaluate the effects of intermittent pneumatic compression (IPC) in patients at low mobility with leg edema.A pilot, two-arm, randomized controlled clinical trial was performed. Fifty patients (age, 58.4 ± 9 years; male, 14), randomly allocated to a group (IPC) undergoing 1 month (n = 29) of an in-home cycle of IPC and to a control (C) group (n = 21), were studied. Leg edema was evaluated by measuring subcutaneous thickness (high-resolution ultrasound) and circumferences (metric tape), both assessed at different levels of the lower limbs, and volume (water plethysmography). Ankle range of motion (ROM, goniometer), quality of life (QoL) by the 36-Item Short Form Health Survey, and a pool of plasma inflammatory markers were also evaluated.Edema significantly decreased in the IPC group (for all outcome measures, P .0001), whereas it significantly increased in the C group (P .0001). Ankle ROM was significantly enhanced in the IPC group (dorsiflexion, P .0001; plantar flexion, P = .002) and remained stable in the C group. QoL showed an improvement in the IPC group, particularly significant for the general health subscale (P = .004), whereas no changes were highlighted in the C group. The two groups exhibited different trends and variations for some plasma inflammatory markers, mainly for granulocyte colony-stimulating factor.In a sample of patients at reduced mobility with leg edema, IPC treatment was effective in reducing the edema, improving the ankle ROM, and determining a positive impact on QoL together with a slight modulation of some plasma inflammatory markers.

Objective An educational program was conducted among school-aged children to improve their knowledge about iodine prophylaxis, their iodine status, and their dietary habits. Methods At the baseline (T0) and after 6 mo (T1), participants (970 at T0 and 949 at T1) answered questionnaires testing their knowledge about iodine prophylaxis and their eating habits. Urine samples were collected from a randomly selected subgroup of participants (313 at T0 and 312 at T1). Results From T0 to T1 there was a significant improvement in respondents' knowledge about iodine prophylaxis (from 44% to 70%), iodized salt consumption (from 78% to 84%), and median urine iodine concentrations (from 70 µg/L to 91 µg/L). Milk and iodized salt intakes were associated with a better iodine status per se, and more so when used simultaneously. Girls drank milk less often than boys did (daily in 52% and 59% of cases, respectively). Children of foreign origin ate sodium-rich food more often than Italians did. Conclusion Educational intervention improved the children's knowledge about iodine prophylaxis and use of iodized salt. Consuming salt in addition to milk improves iodine status. Children of foreign origin have different eating habits.

Background Rapid deployment bioprostheses (RDBs) have been recently introduced into clinical practice for the treatment of severe aortic valve stenosis. The aim of this retrospective multicenter study was to assess early and mid-term clinical and hemodynamic outcomes of patients undergoing RDB implantation. Methods Data from a national registry that included patients who underwent isolated or combined aortic valve replacement with RDB in Italy were analyzed. Definitions of the European System for Cardiac Operative Risk Evaluation were used for preoperative variables and updated definitions from the Valve Academic Research Consortium were used for postoperative outcomes assessment. Univariable and multivariable analyses were performed to identify independent predictors of mortality. Follow-up was performed with clinical and echocardiographic examinations at each study site and, if this was not possible, through telephonic interviews. The Kaplan-Meier method was used for survival analysis. Results A total of 902 patients (December 2012 through November 2017) from 20 national centers were included in the registry. Device success was 95.9%, and 30-day all-cause mortality was 2.8%. Postoperative pacemaker implantation was needed in 63 patients (6.9%). At discharge, peak and mean transaortic gradients were 19 ± 7 mm Hg and 11 ± 4 mm Hg, respectively. Mild and moderate aortic regurgitation were found in 71 patients (8.2%) and in 10 patients (1.2%), respectively. Median follow-up time was 357 days (interquartile range: 103 to 638 days). Survival at 4 years was 86% ± 1%. Preoperative conduction disturbances and history of previous myocardial infarction were independently associated with mortality. Conclusions Aortic RDBs provide good early and mid-term clinical and hemodynamic outcomes. These devices may be considered as a reasonable alternative to conventional bioprostheses, especially in minimally invasive and combined operations.

ObjectivesThe present study investigated the cardioprotective role of urocortin (Ucn) and its relationship with protein kinase C (PKC)ε and PKCδ in patients with (DMPs) and without (NDMPs) diabetes mellitus after on-pump cardiac surgery (OPCS). The molecular mechanisms responsible for the reported worse outcomes of DMP after OPCS remain unknown.MethodsTwo sequential biopsy specimens were obtained from the right atrium of 27 DMPs and 22 NDMPs before and after cardiopulmonary bypass.ResultsPostcardioplegic induction of Ucn in NDMPs (P