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Background: As the novel SARS-CoV-2 pandemic occurred, no specific treatment was yet available. Inflammatory response secondary to viral infection might be the driver of severe diseases. We report the safety and efficacy (in terms of overall survival and hospital discharge) of the anti-IL6 tocilizumab (TCZ) in subjects with COVID-19.Methods: This retrospective, single-center analysis included all the patients consecutively admitted to our Hospital with severe or critical COVID-19 who started TCZ treatment from March 13th to April 03rd, 2020. A 1:2 matching to patients not treated with TCZ was performed according to age, sex, severity of disease, P/F, Charlson Comorbidity Index and length of time between symptoms onset and hospital admittance. Descriptive statistics and non-parametric tests to compare the groups were applied. Kaplan Meier probability curves and Cox regression models for survival, hospital discharge and orotracheal intubation were used.Results: Seventy-four patients treated with TCZ were matched with 148 matched controls. They were mainly males (81.5%), Caucasian (82.0%) and with a median age of 59 years. The majority (69.8%) showed critical stage COVID-19 disease. TCZ use was associated with a better overall survival (HR 0.499 [95% CI 0.262-0.952], p = 0.035) compared to controls but with a longer hospital stay (HR 1.658 [95% CI 1.088-2.524], p = 0.019) mainly due to biochemical, respiratory and infectious adverse events.Discussion: TCZ use resulted potentially effective on COVID-19 in terms of overall survival. Caution is warranted given the potential occurrence of adverse events.Financial Support: Some of the tocilizumab doses used in the subjects included in this analysis were provided by the "Multicenter study on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia" (EudraCT Number: 2020-001110-38) supported by the Italian National Agency for Drugs (AIFA). No specific funding support was planned for study design, data collection and analysis and manuscript writing of this paper. [ABSTRACT FROM AUTHOR]

The current paper describes the natural history and management of mucopolysaccharidosis VI (MPS VI) in all patients currently diagnosed with the disease in Italy. Nine patients (5.5-14.4 years) were included in the data review in March 2008. Gestational and perinatal data were normal for all patients. Median age at diagnosis was 1.9 years. During the course of the disease, all patients developed coarsened facial features, short stature, heart valve disease, eye problems, musculoskeletal problems, hepatosplenomegaly and neurological abnormalities. All patients received rhASB enzyme replacement therapy (ERT) and showed improvement or stabilisation in clinical manifestations after onset of therapy. The most frequently reported improvements were increased joint mobility and reduced hepatosplenomegaly. No relevant safety issues of ERT were reported. In conclusion, patients in Italy with MPS VI are diagnosed early in life. All patients have access to ERT and appear to benefit from this therapy. [ABSTRACT FROM AUTHOR]

The purpose of this paper is twofold: on the one hand, to confirm the positive results on n-3 PUFA from the overall results Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GlSSI)-Prevenzione trial; on the other, to summarize and describe how the results of an important trial can help generate hypotheses either on mechanisms of action or on differential results in particular subgroups of patients, as well as test the pathophysiological hypotheses that have accompanied in the years the story of the hypothesized mechanisms of action of a drug. GISSI-Prevenzione was conceived as a pragmatic population trial on patients with recent myocardial infarction and it was conducted in the framework of the Italian public health system. In GISSI-Prevenzione, 11,323 patients were enrolled in a clinical trial aimed at testing the effectiveness of n-3 polyunsaturated fatty acids (PUFA) and vitamin E. Patients were invited to follow Mediterranean dietary habits, and were treated with up-to-date preventive pharmacological interventions. Long-term n-3 PUFA at 1 g daily, but not vitamin E at 300 mg daily, was beneficial for death and for combined death, non-fatal myocardial infarction, and stroke. All the benefit, however, was attributable to the decrease in risk for overall (-20%), cardiovascular (-30%), and sudden death (-45%). At variance from the orientation of a scientific scenario largely dominated by the "cholesterol-heart hypothesis", GISSI-Prevenzione results indicate n-3 PUFA (virtually devoid of any cholesterol-lowering effect) as a relevant pharmacological treatment for secondary prevention after myocardial infarction. [ABSTRACT FROM AUTHOR]

Background: Duodenal fistula (DF) after gastrectomy continues to be a life-threatening problem. We performed a retrospective multicenter study analyzing the characteristics of DF after elective gastrectomy for malignant disease.Methods: Three thousand seven hundred eighty-five patients who had undergone gastrectomy with duodenal stump in 11 Italian surgical units were analyzed.Results: Sixty-eight DFs occurred, with a median frequency of 1.6% and a mortality rate of 16%. Complications were mainly septic but fistulas or bleeding of surrounding organs accounted for about 30%. Reoperation was performed in 40% of patients. We observed a correlation between mortality and age (hazard ratio 1.09; 95% CI 1.00-1.20) and serum albumin (hazard ratio 0.90; 95% CI 0.83-0.99). The appearance of further complications was associated with reoperation (P < 0.001) and death (P = 0.054), while the preservation of oral feeding was related to DF healing (P < 0.001).Conclusions: This paper represents the largest series ever published on DF and shows that its features have changed in the last 20 years. DF alone no longer leads to death and some complications observed in the past have disappeared, while new ones are emerging. Nowadays, medical therapy is preferred and surgery is indicated only in cases of abdominal sepsis or bleeding. [ABSTRACT FROM AUTHOR]

The novel coronavirus pneumonia (COVID-19) is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a novel virus of the coronavirus family, SARSCoV-2. A recent PRE-print study has showed a heme attack on the 1-beta chain of hemoglobin by COVID19. Beta-thalassemia results of a default in the hemoglobin beta-chain synthesis. 1,5% global population are heterozygotes for this disease. In this study, by a multiple linear regression, we have analyzed the evolution of COVID-19 infection in three Italian regions (Puglia, Sardinia, Sicilia) with different beta-thalassemic prevalences, in order to search a link. The results have showed that betathalassemic heterozygote population prevalence is correlated to immunity against COVID-19, by a regression. This paper is only for academic discussion, the hypotheses and conclusions needs to be confirmed by further research. [ABSTRACT FROM AUTHOR]

The aim of this multicentric, prospective study was to evaluate the effects of vaginal erbium laser (VEL-SMOOTH®) on sexual function in postmenopausal women suffering from the genitourinary syndrome of menopause (GSM). This study was performed on an outpatient basis without anesthesia or drug use before or after the intervention, using an erbium laser (XS Fotona Smooth®, Fotona, Ljubljana, Slovenia) in 1081 postmenopausal women (age 54.3 ± 3.9 years) treated with up to three laser applications every 30 days. Patients were assessed using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R). No adverse events were recorded during the study. The FSDS-R scores (n = 554), from basal values of 25.5 ± 3.5, were 11.5 ± 3.0, 10.5 ± 3.5 and 11.5 ± 3.5 at the 4-, 12- and 24-week follow-ups, respectively (p < 0.01 vs. corresponding basal values). Individual FSFI domain scores (n = 569) significantly (p < 0.001) increased after VEL-SMOOTH® treatment and remained significantly higher up to the 24th week after the end of treatment. The total scores, from basal values of 15.5 ± 1.5, were 27.5 ± 2.5, 27.6 ± 2.7and 27.0 ± 3.5 at the 4-, 12- and 24-week follow-ups, respectively (p < 0.01 vs. corresponding basal values). Albeit not randomized, this large, prospective study shows that VEL-SMOOTH® treatment may improve sexual function in postmenopausal women suffering from GSM. [ABSTRACT FROM AUTHOR]

Background: Lateral elbow pain (LEP) due to tendinosis is one of the most common musculoskeletal pains of the upper limbs, yet there is no satisfactory treatment. This study was an international, prospective, multi-centre, randomized, controlled, clinical trial to evaluate the efficacy of acupuncture compared to sham laser in the treatment of LEP.Methods: The study used a parallel and stratified design (1:1 allocation using a computer-generated sequence) and was participant-, outcome assessor- and statistician-blinded. Subjects from 18 to 80 years with unilateral chronic LEP (minimum three months) were recruited at four centres in Australia, China, Hong Kong and Italy. The treatment group received manual acupuncture at acupoints LI 10 and LI 11 on the affected side whereas the control group received sham laser acupuncture at the same acupoints. The primary endpoint was disabilities of the arm, shoulder, and hand (DASH) questionnaire score at the three-week post-treatment follow-up visit. Three VAS scales (pain at rest, pain on motion and pain during exertion) were secondary outcomes measures. Ninety-six subjects were allocated to either the treatment group (n = 47) or control group (n = 49) and were all included in the analysis.Results: At the follow-up visit, we found significant differences in DASH score between the two groups (p = .015). The median change to baseline for the treatment group was -11.7 (interval: -50.83 to 23.33), and for the control group -7.50 (interval: -36.67 to 29.10). The estimated effect size was 0.47, indicating a medium effect. Significant differences were also found for secondary outcome measures for VAS of pain. There were no severe adverse events. Our findings suggest that acupuncture has a moderate efficacy in the treatment of LEP.Conclusions: Acupuncture was shown to be efficacious in improving the function of the arm associated with lateral elbow tendinosis. Both the DASH score and the pain VAS on two occasions (at rest and during motion) showed a significant change over time indicating acupuncture as a potential treatment for LEP due to tendinosis. [ABSTRACT FROM AUTHOR]

Background: A new prepared oral viscous budesonide (PVB) has been effective in inducing clinical and histological remission in pediatric eosinophilic esophagitis (EoE).Aims: To evaluate the efficacy of a 12-week maintenance therapy on clinical, endoscopic, and histological remission using half of the dose used in the induction therapy.Methods: We prospectively enrolled pediatric patients with active EoE. After 12 weeks of induction therapy with PVB (< 150 cm: 2 mg/day; ≥ 150 cm: 4 mg/day) patients received a maintenance dose of half of the dose used in the induction therapy (1 mg or 2 mg) for another 12 weeks. A 12-week follow-up was then performed in all patients after the end of therapy. Endoscopy was performed at weeks 0, 12, 24, and 36. Symptoms, endoscopy, and histology scores were also calculated. Serum cortisol was evaluated during the treatment period.Results: We enrolled 20 children (15 males; median age 10 years; range 4-17). After the 12-week induction therapy 18 patients (90%) were in remission, with a significant decrease in the median peak of eosinophil count/HPF as well as a marked reduction in clinical, endoscopic, and histological scores (p < 0.01). At the end of the maintenance therapy (week 24), 17 patients (85%) were still in remission, while there were only 9 at week 36 (45%). No significant changes in cortisol levels were observed during the study period.Conclusions: The 12-week maintenance treatment with the half the dose of PVB was effective in sustaining remission at week 24; however, no reduction in the rate of relapse after suspension of treatment occurred. [ABSTRACT FROM AUTHOR]

Aim: We performed a multicenter retrospective cohort study of eribulin mesylate (EM) use in Italy, to describe the current practice for metastatic breast cancer patients (ESEMPiO) in the real-world.Patients& Methods: Baseline characteristics, treatment administration and safety were summarized using descriptive statistics.Results: No safety concerns were raised in the population enrolled in the ESEMPiO database and treated in a real-life practice. Median progression-free survival and overall survival were 3.2 and 10.1 months, respectively. EM activity was similar between breast cancer subtypes.Conclusion: In metastatic breast cancer patients treated with EM in 'real-world' setting, the clinician-registered outcomes were comparable to those reported in pivotal trials. Furthermore, EM maintained clinical activity and a tolerable safety profile. [ABSTRACT FROM AUTHOR]

Aim: This multicenter field-practice study evaluates outcomes of long-term sorafenib in hepatocellular carcinoma (HCC) patients.Methods: Consecutive HCC patients on sorafenib were enrolled. We evaluated those receiving sorafenib for ≥12 months.Results: Out of 800 patients on sorafenib, 81 (10%) received long-term treatment. Median duration of treatment was 22.7 months (range: 12.3-92.6). Only 21 (26%) reported grade 3/4 adverse events. Complete response was reported in 11 patients (14%). Median overall survival was 34.8 months (95% CI: 29.9-44.3). Only baseline Child-Pugh class was associated with survival.Conclusion: Sorafenib could result in long-term control of HCC in a relevant proportion of patients. Given the availability of regorafenib in the second-line setting, an earlier introduction of systemic therapy may be considered according to clinical indications. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the results of isolated left subclavian artery (LSA) revascularization during thoracic endovascular aortic repair (TEVAR) using carotid-subclavian bypass (CSbp) or chimney grafts (CGs).Methods: A retrospective multicenter, observational study identified 73 patients (mean age 68±13 years, range 22-87; 56 men) with acute or chronic thoracic aortic lesions who underwent TEVAR with isolated LSA revascularization using either CSbp (n=42) or CGs (n=31) from January 2010 and February 2017. Primary endpoints were TEVAR-related mortality, postoperative stroke, freedom from type Ia endoleak, and LSA patency.Results: Primary technical success was achieved in all cases. Early TEVAR-related mortality was 4.2% (CSbp 2% vs CG 6%, p=0.571). Two (3%) patients had major ischemic strokes (one in each group). Mean follow-up was 24±21 months (range 1-72; median 15). Estimated freedom from TEVAR-related mortality was 93%±3% (95% CI 84.3% to 97.0%) at 12 and 36 months, with no significant difference between CSbp and CG (p=0.258). Aortic reintervention did not differ between the groups (CSbp 5% vs CG 6%, p=0.356); nor did freedom from type Ia endoleak (CSbp 98% vs CG 87%, p=0.134). Gutter-related endoleaks occurred in 4 (13%) CG patients, but none of the patients experienced sac enlargement or the need for reintervention and none died. Primary patency of the LSA was 100% for the entire group during the observation period.Conclusion: In our experience, LSA revascularization proved most satisfactory and equally effective with both the CSbp and CG techniques, without discernible differences at midterm follow-up. [ABSTRACT FROM AUTHOR]

Background: Two phase III trials have demonstrated the clinical and radiological efficacy of delayed-release dimethyl fumarate (DMF) in relapsing-remitting multiple sclerosis (RRMS). However, data on its safety and effectiveness in real-world practice are still limited.Objectives: The aim of our study was to explore the safety and tolerability profile of DMF in RRMS. We also tried to identify individual variables associated with better clinical and radiological outcomes.Methods: We collected the clinical and magnetic resonance imaging (MRI) data of patients with RRMS who started DMF between 2012 and 2017 in seven MS clinics in central Italy. We first evaluated DMF discontinuation rates and the incidence of adverse events and side effects. We then assessed the annualized relapse rate (ARR), the number of patients with clinical relapses or disability worsening and the presence of radiological activity. Third, we investigated which baseline variables were associated with clinical and radiological outcomes.Results: We collected data for 1089 patients with a mean on-treatment follow-up of 17 ± 8 months; 331 (30.4%) of these patients were treatment naïve. In total, 210 (19.5%) patients discontinued DMF mainly because of poor tolerability (n = 103) and disease activity (n = 63), and 166 (16.5%) patients presented with lymphopenia. The ARR reduced from 0.55 to 0.13. Mean change in Expanded Disability Status Scale (EDSS) score was 0.08 ± 0.44 per year. The occurrence of clinical and/or radiological activity during follow-up was associated with younger age [hazard ratio (HR) 0.97; p < 0.001], higher EDSS score (HR 1.18; p < 0.001), greater number of Gd-enhancing lesions at baseline scan (HR 1.14; p = 0.003) and prior exposure to MS treatments (HR 1.43; p = 0.02).Conclusion: This post-marketing data confirms the short-term safety, tolerability and effectiveness of DMF, supporting its use as an early treatment in MS. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the efficacy of a combined nutraceutical supplement on symptoms and early metabolic alterations during the menopausal transition. This pilot randomized study was conducted at the service for menopause disorders of the Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.Methods: Ninety women in menopausal transition who attended our service with menopausal symptoms were enrolled in the study. Sixty patients, randomly assigned to the treatment group, were prescribed one daily tablet of a combined nutraceutical compound with phytoestrogen substances, vitamins, micronutrients and passion flower herbal medicine for 6 months. Thirty patients did not receive any treatment and comprised the control group. The intensity of perimenopausal symptoms was assessed by the modified Kuppermann Index (KI) at enrollment and at 3 and 6 months of treatment. At baseline and at the end of the study, patients underwent a clinical evaluation, a pelvic ultrasound and analysis of blood samples.Results: In the nutraceutical supplemented group, a significant reduction in menopausal symptoms was demonstrated according to the KI after 3 and 6 months of supplementation (p < 0.01). The within-group analysis of different KI parameters in the treated group showed a significant improvement in hot flushes (p < 0.001), insomnia (p < 0.01), fatigue (p < 0.01) and irritability (p < 0.01). Metabolic parameters did not change significantly in the nutraceutical supplemented group. In the control group, total cholesterol level showed a significant increase (p < 0.05).Conclusions: Combined nutraceutical supplementation provides an effective and safe solution for early symptoms occurring during menopausal transition. [ABSTRACT FROM AUTHOR]

Background: Chronic vascular wounds have a significant economic and social impact on our society calling for allocation of a great deal of attention and resources. Efforts should be oriented toward the achievement of the most effective and efficient clinical management. The Angiology Unit at the University Hospital of Padova, Italy, developed a performance improvement project to enhance the quality of practice for vascular ulcers.Methods: The project consisted in a multistep process comprising a critical revision of the previous clinical process management, staff education, tightening connections between operators and services, and creation of a position for a wound care nurse. The previous standard of practice was modified according to the results of revision and the current evidence-based practice.Results: The new standard of practice reached its full application in September 2015. The number of patients treated and the number of visits in 2015 remained almost unvaried from 2014. However, the total annual expenditure for treating vascular ulcers was reduced by ~60% from the previous year.Conclusion: Standardization of guidelines and practice is effective in creating an efficient clinical management and in reducing the economic burden of vascular ulcers. [ABSTRACT FROM AUTHOR]

Aim: The aim of this multicentre, observational, transversal study was to evaluate pacemaker (PM) choice and setting in a large number of patients, in order to understand their relationship with the patients' clinical characteristics.Methods and Results: The study enrolled a total of 1858 patients (71 ± 14 years, 54% male), consecutively evaluated during scheduled PM follow-up visits in 7 Italian cardiac arrhythmia centres. To evaluate the appropriateness of PM choice in relation to the patients' clinical characteristics, we analysed their rhythm disorders at the time of device implantation and the characteristics of the devices implanted. To evaluate the appropriateness of device setting, current rhythm disorders and device setting at the time of enrolment were analysed. In the overall study population, 64.3% of the patients received a PM with all of the features required for their rhythm disorder [80.8% in persistent atrioventricular (AV) block, 76.5% in atrial fibrillation needing pacing, 71.0% in sinus node disease, 58.7% in non-persistent atrioventricular block (AVB), 52.7% in neuro-mediated syncope]. The most frequent cause of inappropriate PM choice was the lack of an algorithm to promote intrinsic AV conduction in non-persistent AVB patients (38.1%). In 76.2% of the patients with an appropriate PM (n = 1301), the PM was optimally set for their rhythm disorder.Conclusions: In the present 'real-world' registry, a large number of patients (35.7%) did not receive an optimal PM for their rhythm disorders. Moreover, one-fourth of appropriate PMs were not programmed according to the patients' clinical characteristics. [ABSTRACT FROM AUTHOR]

Objectives: Most elderly patients affected by reflex vasodepressor syncope take one or more hypotensive drugs. The role of these drugs in causing syncope has not yet been established. We hypothesised that recurrence of syncope and presyncope can be reduced by discontinuing/reducing vasoactive therapy without increasing the risk of cardiovascular and neurological events.Methods: This randomised, parallel, prospective, trial was conducted from January 2014 to March 2016 in four general hospitals. Of 328 initially screened participants, 58 patients (mean (SD) age 74±11 years) affected by vasodepressor reflex syncope, which was reproduced by tilt testing (n=54) or carotid sinus massage (n=4), were randomised to stop/reduce vasoactive therapy or to continue it. Primary end point was recurrence of syncope, presyncope or adverse events (defined as stroke, cerebral transient ischaemic attacks, worsening heart failure, myocardial infarction).Results: Of 58 patients who were randomised, 55 completed the trial. After 1 month, systolic blood pressure was significantly higher in the 'stop/reduce' group than in the 'continue' group, in both supine (141±13 mm Hg vs 128±14 mm Hg; p=0.004) and standing (133±13 mm Hg vs 122±15 mm Hg; p=0.02) positions. During a mean follow-up of 13±7 months, the primary combined end point occurred in seven 'stop/reduce' patients (23%): three had syncope, three had presyncope and one had heart failure. Conversely, it occurred in 13 'continue' patients (54%): 10 had syncope, 2 had presyncope and 1 had cerebral transient ischaemic attack. The log-rank p value was 0.02 and the HR was 0.37 (95% CI 0.15 to 0.91).Conclusions: Recurrence of syncope and presyncope can be reduced by discontinuing/reducing vasoactive therapy in most elderly patients affected by reflex vasodepressor syncope.Trial Registration Number: NCT01509534; EudraCT2013-004364-63; Results. [ABSTRACT FROM AUTHOR]

Background: Recent data have highlighted a higher rate of neurological injuries in minimal invasive mitral valve surgery (MIMVS) compared with the standard sternotomy approach; therefore, the role of specific clamping techniques and perfusion strategies on the occurrence of this complication is a matter of discussion in the medical literature. The purpose of this trial is to prospectively evaluate major, minor and silent neurological events in patients undergoing right mini-thoracotomy mitral valve surgery using retrograde perfusion and an endoaortic clamp or a transthoracic clamp.Methods/design: A prospective, blinded, randomized controlled study on the rate of neurological embolizations during MIMVS started at the University of Turin in June 2014. Major, minor and silent neurological events are being investigated through standard neurological evaluation and magnetic resonance imaging assessment. The magnetic resonance imaging protocol includes conventional sequences for the morphological and quantitative assessment and nonconventional sequences for the white matter microstructural evaluation. Imaging studies are performed before surgery as baseline assessment and on the third postoperative day and, in patients who develop postoperative ischemic lesions, after 6 months.Discussion: Despite recent concerns raised about the endoaortic setting with retrograde perfusion, we expect to show equivalence in terms of neurological events of this technique compared with the transthoracic clamp in a selected cohort of patients. With the first results expected in December 2016 the findings would be of help in confirming the efficacy and safety of MIMVS.Trial Registration: ClinicalTrials.gov, Identifier: NCT02818166 . Registered on 8 February 2016 - trial retrospectively registered. [ABSTRACT FROM AUTHOR]

Aims: A long-detection interval (LDI) (30/40 intervals) has been proved to be superior to a standard-detection interval (SDI) (18/24 intervals) in terms of reducing unnecessary implantable cardioverter defibrillator (ICD) therapies. To better evaluate the different impact of LDI and anti-tachycardia pacing (ATP) on reducing painful shocks, we assessed all treated episodes in the ADVANCE III trial.Methods and Results: A total of 452 fast (200 ms < cycle length ≤ 320 ms) arrhythmic episodes were recorded: 284 in 138 patients in the SDI arm and 168 in 82 patients in the LDI arm (106/452 inappropriate detections). A total of 346 fast ventricular tachycardias (FVT) were detected in 169 patients: 208 in 105 patients with SDI and 138 in 64 patients with LDI. Setting LDI determined a significant reduction in appropriate but unnecessary therapies [208 in SDI vs. 138 in LDI; incidence rate ratio (IRR): 0.61 (95% CI 0.45-0.83), P = 0.002]. Anti-tachycardia pacing determined another 52% reduction in unnecessary shocks [208 in SDI with hypothetical shock-only programming vs. 66 in LDI with ATP; IRR: 0.37 (95% CI 0.25-0.53, P < 0.001)]. The efficacy of ATP in terminating FVT was 63% in SDI and 52% in LDI (P = 0.022). No difference in the safety profile (acceleration/degeneration and death/cardiovascular hospitalizations) was observed between the two groups.Conclusion: The combination of LDI and ATP during charging is extremely effective and significantly reduces appropriate but unnecessary therapies. The use of LDI alone yielded a 39% reduction in appropriate but unnecessary therapies; ATP on top of LDI determined another 52% reduction in unnecessary shocks. The strategy of associating ATP and LDI could be considered in the majority of ICD recipients. [ABSTRACT FROM AUTHOR]

Aims: Atrial fibrillation (AF) affects ∼2% of the total population. In order to prevent AF recurrences, many anti-arrhythmic drugs are currently available, but most of them are burdened by serious side effects and suboptimal efficacy. The aim of the present study was to test efficacy and safety of a combination of flecainide and metoprolol in preventing AF clinical recurrences.Methods and Results: This study is a monocentric, prospective, randomized, open-blinded trial on 173 patients with a recent episode of paroxysmal or persistent AF. Patients were randomized into group A (flecainide + metoprolol; n = 80), group B (flecainide only; n = 72), or group C (metoprolol only; n = 21). Main exclusion criteria were recent acute coronary syndrome, heart failure New York Heart Association class III-IV, left ventricular ejection fraction <0.40, atrioventricular conduction disorders, and severe bradycardia. Primary endpoint was symptomatic recurrence over 1-year follow-up. Secondary endpoint was quality of life (QoL) over 1-year follow-up, as assessed by the SF-36 and Atrial Fibrillation Severity Scale questionnaires. Combination therapy with flecainide and metoprolol significantly reduced recurrences at 1-year follow-up when compared with flecainide alone in the whole population (66.7 vs. 46.8%; P < 0.001) and in patients with persistent AF (71.1 vs. 43.6%; P = 0.025) while adding beta-blocker therapy to paroxysmal AF showed no benefit over IC anti-arrhythmic drug-only. Patients randomized to combination therapy experienced a significant improvement of QoL when compared with those assigned to a flecainide-only regimen irrespective of AF type.Conclusion: Flecainide-metoprolol combination therapy improves effectiveness of rhythm control in persistent symptomatic AF and increases tolerability, with a concomitant reduction of side effects and a better compliance. [ABSTRACT FROM AUTHOR]

Aims: To assess the results and impact of lesion set and surgical technique on long-term success of surgical ablation during mitral surgery.Methods and Results: The patient population consisted of 685 subjects with persistent and long-standing persistent atrial fibrillation (AF) undergoing cardiac surgery for mitral valve disease as the primary indication and concomitant ablation between January 2003 and January 2012 at three institutions. One hundred and sixty-six underwent unipolar (24.2%), 371 (54.2%) bipolar, and 148 (21.6%) had combined ablation. Median follow-up was 58.4 months (interquartile range 43.3-67.9). To appropriately account for death, a competing risk model was employed to identify predictors of cumulative incidence of recurrent AF among lesion set and surgical techniques. Eight-year freedom from recurrent arrhythmia without antiarrhythmic drugs was 0.60 ± 0.02. Success rate was higher using bipolar radiofrequency (RF) (P < 0.001), after performing mitral isthmus line (P = 0.003) and following the biatrial technique (P < 0.001). Competing risk regression revealed that use of unipolar RF [sub-hazard ratio (SHR) 2.41 (1.52-3.43), P < 0.001], combined unipolar/bipolar ablation [SHR 1.93 (0.89-2.57), P = 0.003] and the absence of right atrial ablation [SHR 2.79 (1.27-3.48), P < 0.001] were predictors of cumulative incidence of long-term recurrence.Conclusions: Our experience suggests that the use of bipolar clamp improves long-term results in surgical treatment of AF and that right-sided ablation should be routinely added. Randomized studies are necessary to confirm our findings. [ABSTRACT FROM AUTHOR]

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Background: The advent of Internet and World Wide Web has created new perspectives toward interaction between patients and healthcare professionals. Telemonitoring patients with rheumatoid arthritis (RA) is an emerging concept to guide the collaborative management treatment and improve outcomes in patients. The objective of this study was to investigate whether an intensive treatment strategy, according to a telemonitoring protocol, is more effective than conventional management strategy in reaching remission and comprehensive disease control (CDC) after 1 year in early rheumatoid arthritis (ERA) patients.Methods: Forty-four ERA patients were randomly allocated into two groups: the telemonitoring intensive strategy (TIS) group (group 1) or the conventional strategy (CS) group (group 2). Three patients refused to participate. In group 1 (n = 21), a remote monitoring system of disease activity, in combination with protocolised treatment adjustments aiming for remission was applied. In group 2 (n = 20), patients were treated according to daily clinical practice, with regular evaluation of disease activity, but without protocolised treatment adjustments. A telemedical care called "REmote TElemonitoring for MAnaging Rheumatologic Condition and HEaltcare programmes" (RETE-MARCHE), was developed to perform the remote monitoring.Results: A higher percentage of patients in the TIS group achieved CDAI remission vs patients in the CS group (38.1 % vs 25 % at year 1, p <0.01). Time to achieve remission was significantly shorter in the group 1 than in the group 2, with a median of 20 weeks vs a median over 36-weeks (p <0.001). Concordantly, the patients in group 1 showed a greater improvement (p <0.001), compared with group 2 in terms of functional impairment (71.4 % vs 35 %) and radiological damage progression (23.8 % vs 10 %), resulting in a greater rate of CDC (19.4 % vs 5 %).Conclusions: According to our results, an intensive treatment strategy by telemonitoring leads to more effective disease remission and more rapid CDC than treatment according to conventional management strategy in ERA.Trial Registration: Trial Registration Number: ISRCTN13142685 Date of registration: March, 17(th) 2016. [ABSTRACT FROM AUTHOR]

Most patients with advanced or metastatic cancer experience pain and despite several guidelines, undertreatment is well documented. A multicenter, open-label, prospective, non-randomised study was launched in Italy in 2006 to evaluate the epidemiology, patterns and quality of pain care of cancer patients. To assess the adequacy of analgesic care, we used a standardised measure, the pain management index (PMI), that compares the most potent analgesic prescribed for a patient with the reported level of the worst pain of that patient together with a selected list of clinical indicators. A total of 110 centres recruited 1801 valid cases. 61% of cases were received a WHO-level III opioid; 25.3% were classified as potentially undertreated, with wide variation (9.8-55.3%) according to the variables describing patients, centres and pattern of care. After adjustment with a multivariable logistic regression model, type of recruiting centre, receiving adjuvant therapy or not and type of patient recruited (new or already on follow-up) had a significant association with undertreatment. Non-compliance with the predefined set of clinical indicators was generally high, ranging from 41 to 76%. Despite intrinsic limitations of the PMI that may be considered as an indicator of the poor quality of cancer pain care, results suggest that the recourse to WHO third-level drugs still seems delayed in a substantial percentage of patients. This delay is probably related to several factors affecting practice in participating centres and suggests that the quality of cancer pain management in Italy deserves specific attention and interventions aimed at improving patients' outcomes. [ABSTRACT FROM AUTHOR]

By retrospectively collecting data from nine Italian centres of pediatric endocrinology, we assessed the different management and final outcome of children with short stature and idiopathic delayed puberty. Data were obtained in 77 patients (54 males, 23 females) diagnosed and followed-up in the various centres during the last 15 years. Inclusion criteria were short stature at initial observation and idiopathic delayed puberty diagnosed during follow-up. At first observation, age was 13.8 ± 1.0 years and height standard deviation score (SDS) was –2.6 ± 0.6 in males. In females age was 13.1 ± 0.9 years and height SDS –2.6 ± 0.4. Local diagnostic and therapeutic protocols included testing for growth-hormone deficiency (six centres) and treatment in case of deficiency or, in the remaining centres, testosterone or no treatment in males, and no treatment in females. At diagnosis, both in males and in females, the auxological features (height SDS, target height SDS and bone age delay) were similar in the patients treated with growth hormone, testosterone or not treated. Overall 32 patients received growth hormone (25 males, 7 females), 33 no treatment (17 males, 16 females) and 12 testosterone. There was no difference in the adult height of males and females in the different treatment groups. In males there were no differences between adult and target height SDSs (growth hormone-treated 0.31 ± 0.79, untreated 0.10 ± 0.82, testosterone-treated 0.05 ± 0.95), between adult and initial height SDSs (growth hormone-treated 1.70 ± 0.93, untreated 1.55 ± 0.92, testosterone-treated 1.53 ± 1.43) and percentage of subjects with adult height above target height. In females, there were no differences between adult and target height SDSs (growth hormone-treated –0.49 ± 1.13; untreated 0.10 ± 0.97) and between adult and initial height SDSs (growth hormone-treated 1.76 ± 0.92; untreated 1.77 ± 0.98), whereas a significantly higher percentage of patients remained below target height in the growth hormone-treated group (6/7, 85.7% vs 5/11, 31.3%) ( P = 0.02). In conclusion, the diagnostic and therapeutic management of the patients with short stature and delayed puberty is different among Italian pediatric endocrinologists. Our data do not support the usefulness of growth-hormone therapy in improving adult height in subjects with short stature and delayed puberty, particularly in the female sex. [ABSTRACT FROM AUTHOR]

This observational prospective multicentre study aims to describe a hospital-based database collecting information about clinical features, management and follow-up of stroke patients. In 18 neurological departments (mostly first-referral) in Piedmont and the Aosta Valley, Italy, between May and July 1999, 604 consecutive patients (97 TIA, 443 ischaemic, and 64 haemorrhagic stroke) were studied. Ischaemic stroke aetiologies were as follows: large-artery atherosclerosis (148), small-artery occlusion (133), cardioembolism (76), other causes (13) and undetermined (73). According to Bamford's classification, 164 were PACI, 126 LACI, 87 TACI and 66 POCI. The diagnostic workup and management of patients is described; only 4% of patients did not receive a CT scan. Four hundred and three patients were discharged to their home, 78 to a rehabilitation unit, 44 to long-term institutional care, 20 to other wards and 59 died while in hospital. After six months, 10 patients were lost to follow-up, 499 were alive and 95 had died. The SINPAC database allows for evaluation of current practice of care in a first-referral stroke population. [ABSTRACT FROM AUTHOR]

We investigated the clinical and economic impact of sirolimus-eluting coronary stents (SES) at a nationwide level as to advice about the feasible reimbursement policy for the Italian Health Care System (SSN). A decision model compared bare metal stents (BMS) and SES in terms of costs and repeat coronary revascularizations incurred in 12 months following the first revascularization. The model was compiled for eight subgroups of patients. Rates of events were derived from randomized trials and an 1,809-patient survey. National charges were used to evaluate resources consumption. Compared with BMS, the number of averted revascularizations with SES is 0.16 per patient. SES also save Euro 1,371 per patient. Total savings to SSN are proportional to the rate of SES adoption by Italian hospitals: assuming a complete replacement of BMS with SES, the model estimates that 7,095 revascularizations would be averted and more than Euro 60 million saved by the SSN in 1 year. To stimulate SES adoption a SES-specific DRG might by introduced with a reimbursement value 23% higher than the current charge. SES is thus a cost-saving strategy in the perspective of the SSN that could therefore support the introduction of the new technology by reimbursing about 80% of its current incremental acquisition cost. [ABSTRACT FROM AUTHOR]

Background: Early implantation may preserve the alveolar anatomy, and the placement of a fixture in a fresh extraction socket helps to maintain the bony crest. Although a number of clinical studies exist, no histological reports show the outcome of implantation in fresh extraction sockets without the use of membranes in humans compared to implants placed in mature bone. Methods: Forty-eight healthy patients, receiving at least 4 fixtures in each of 2 symmetrical quadrants, underwent placement of 1 experimental fixture placed in a fresh extraction socket (TI) and 1 contralateral fixture in mature bone (CI). TI were placed after atraumatical tooth extraction, with a surgical site at the apex of the socket and a tight contact between the fixture and the socket's walls, but without the use of filling materials or membranes. The flap was coronally repositioned to obtain primary wound closure. Immediately after surgical intervention, a standardized periapical radiograph was taken. Second-stage surgery was done after 6 months. Six months after the second surgery, a second standardized periapical radiograph was taken and clinical parameters (bleeding and plaque index) recorded. Marginal bone loss (MBL) from the time of implant placement to the time of fixture removal was calculated by comparing periapical radiographs. TI and CI were then removed by a hollow drill to obtain histological specimens. Non-demineralized sections were stained by acid fuchsin and toluidine blue, and by von Kossa to evaluate the degree of bone mineralization. The percentage of direct implant-bone contact (DBC) was calculated by a computerized microscopic digitizer. Results: No significant differences in the clinical and radiographic parameters were observed between the 2 experimental categories. There was no statistically significant difference between TI and CI for DBC either in the maxilla or in the mandible. No connective or fibrous tissues were present around TI or CI. Bone resorption was not present in any of the histological sections. Conclusions: The present study shows that when a screw-type dental implant is placed without the use of barrier membranes or other regenerative materials into a fresh extraction socket with a bone-to-implant gap of 2 mm or less, the clinical outcome and degree of osteointegration does not differ from implants placed in healed, mature bone. [ABSTRACT FROM AUTHOR]

Background: Pharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still lacking. We have identified IFNβ-1a as the most promising drug to be repurposed for COVID-19. The rationale relies on the evidence of IFNβ anti-viral activity in vitro against SARS-CoV-2 and animal models resembling SARS-CoV-2 infection and on a recent clinical trial where IFNβ was indicated as the key component of a successful therapeutic combination.Methods: This is a randomized, controlled, open-label, monocentric, phase II trial (INTERCOP trial). One hundred twenty-six patients with positive swab detection of SARS-CoV-2, radiological signs of pneumonia, and mild-to-moderate disease will be randomized 2:1 to IFNβ-1a in addition to standard of care vs standard of care alone. No other anti-viral drugs will be used as part of the regimens, both in the control and the intervention arms. IFNβ-1a will be administered subcutaneously at the dose of 44 mcg (equivalent to 12 million international units) three times per week, at least 48 h apart, for a total of 2 weeks. The primary outcome is the time to negative conversion of SARS-CoV-2 nasopharyngeal swabs. Secondary outcomes include improvement or worsening in a clinical severity score measured on a 7-point ordinal scale (including transfer to intensive care unit and death), oxygen- and ventilator-free days, mortality, changes in pulmonary computed tomography severity score, hospital stay duration, reduction of viral load measured on nasopharyngeal swabs, number of serious adverse events, and changes in biochemical markers of organ dysfunction. Exploratory outcomes include blood cell counts, cytokine and inflammatory profile, peripheral mRNA expression profiles of interferon-stimulated genes, and antibodies to SARS-CoV-2 and to IFNβ-1a. INTERCOP is the first study to specifically investigate the clinical benefits of IFNβ-1a in COVID-19 patients.Discussion: Potential implications of this trial are multifaceted: should the primary outcome be fulfilled and the treatment be safe, one may envisage that IFNβ-1a be used to reduce the infectivity of patients with mild-to moderate disease. In case IFNβ-1a reduced the duration of hospital stay and/or ameliorated the clinical status, it may become a cornerstone of COVID-19 treatment.Trial Registration: EudraCT 2020-002458-25. Registered on May 11, 2020 ClinicalTrials.gov Identifier: NCT04449380. [ABSTRACT FROM AUTHOR]

Background: Monovalent varicella vaccines have been available in the Veneto Region of Italy since 2004. In 2006, a single vaccine dose was added to the immunisation calendar for children aged 14 months. ProQuad®, a quadrivalent measles-mumps-rubella-varicella vaccine, was introduced in May 2007 and used, among other varicella vaccines, until October 2008. This study aimed to evaluate the effectiveness of a single dose of ProQuad, and the population impact of a vaccination program (VP) against varicella of any severity in children who received a first dose of ProQuad at 14 months of age in the Veneto Region, METHODS: All children born in 2006/2007, i.e., eligible for varicella vaccination after ProQuad was introduced, were retrospectively followed through individual-level data linkage between the Pedianet database (varicella cases) and the Regional Immunization Database (vaccination status). The direct effectiveness of ProQuad was estimated as the incidence rate of varicella in ProQuad-vaccinated children aged < 6 years compared to children with no varicella vaccination from the same birth cohort. The impact of the VP on varicella was measured by comparing children eligible for the VP to an unvaccinated historical cohort from 1997/1998. The vaccine impact measures were: total effect (the combined effect of ProQuad vaccination and being covered by the Veneto VP); indirect effect (the effect of the VP on unvaccinated individuals); and overall effect (the effect of the VP on varicella in the entire population of the Veneto Region, regardless of their vaccination status).Results: The adjusted direct effectiveness of ProQuad was 94%. The vaccine impact measures total, indirect, and overall effect were 97%, 43%, and 90%, respectively.Conclusions: These are the first results on the effectiveness and impact of ProQuad against varicella; data confirmed its high effectiveness, based on immunological correlates for protection. Direct effectiveness is our only ProQuad-specific measure; all impact measures refer at least partially to the VP and should be interpreted in the context of high vaccine coverage and the use of various varicella vaccines in this region. The Veneto Region offered a unique opportunity for this study due to an individual data linkage between Pedianet and the Regional Immunization database. [ABSTRACT FROM AUTHOR]