Exercise intervention improves macrovascular function in metabolic syndrome (MeS) patients, but few studies have evaluated the effect of exercise on microcirculatory dysfunction, which plays a key ...role in the development of MeS and its correlated organ damage. We carried out this intervention study to evaluate the influence of an aerobic and resistance training on skin microvascular reactivity in MeS patients.
Postocclusive reactive hyperemia (PORH) of the forearm skin was evaluated, by laser-Doppler flowmetry, before and after a 12-week program of aerobic and resistance training in 15 MeS patients referring to our Lipid Metabolism Outpatients Clinic, together with anthropometric, fitness and metabolic parameters; 15 matched MeS patients who did not exercise, served as a control group. The exercise training consisted of 2 sessions/week of aerobic and resistant exercise.
Following exercise program, we observed a significant reduction in body weight, fat mass, fasting blood glucose, serum HbA1c and triglycerides, while HDL-cholesterol significantly increased. The exercise-treated group experienced a significant improvement in the area of hyperemia (AH) after PORH, and in all fitness parameters: VO2max, strength on the pulldown lat machine, chest press, leg press and leg extension. A significant correlation emerged between the increase in AH and the reduction in HbA1c and between increase in AH and strength at the chest press, and at the leg extension.
Our study showed that a short-term combined aerobic-resistance training positively affects microvascular reactivity in MeS patients. This improvement is correlated with the reduction of HbA1c and fitness parameters, and particularly with increased muscle strength at the upper and lower limbs.
The phase 3 JAVELIN Renal 101 trial (NCT02684006) demonstrated significantly improved progression-free survival (PFS) with first-line avelumab plus axitinib versus sunitinib in advanced renal cell ...carcinoma (aRCC). We report updated efficacy data from the second interim analysis.
Treatment-naive patients with aRCC were randomized (1 : 1) to receive avelumab (10 mg/kg) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were PFS and overall survival (OS) among patients with programmed death ligand 1–positive (PD-L1+) tumors. Key secondary end points were OS and PFS in the overall population.
Of 886 patients, 442 were randomized to the avelumab plus axitinib arm and 444 to the sunitinib arm; 270 and 290 had PD-L1+ tumors, respectively. After a minimum follow-up of 13 months (data cut-off 28 January 2019), PFS was significantly longer in the avelumab plus axitinib arm than in the sunitinib arm {PD-L1+ population: hazard ratio (HR) 0.62 95% confidence interval (CI) 0.490–0.777}; one-sided P < 0.0001; median 13.8 (95% CI 10.1–20.7) versus 7.0 months (95% CI 5.7–9.6); overall population: HR 0.69 (95% CI 0.574–0.825); one-sided P < 0.0001; median 13.3 (95% CI 11.1–15.3) versus 8.0 months (95% CI 6.7–9.8). OS data were immature PD-L1+ population: HR 0.828 (95% CI 0.596–1.151); one-sided P = 0.1301; overall population: HR 0.796 (95% CI 0.616–1.027); one-sided P = 0.0392.
Among patients with previously untreated aRCC, treatment with avelumab plus axitinib continued to result in a statistically significant improvement in PFS versus sunitinib; OS data were still immature.
NCT02684006.
•Avelumab plus axitinib significantly prolonged progression-free survival versus sunitinib in advanced renal cell carcinoma.•Although overall survival data were immature, results favored the combination over sunitinib across prespecified subgroups.•Adjusting for subsequent use of PD-1/PD-L1 inhibitors in the sunitinib arm predicted a survival benefit for the combination.•Among all randomized patients, avelumab plus axitinib had a longer mean duration of response than sunitinib.•Avelumab plus axitinib prolonged progression-free survival on next-line therapy versus sunitinib.
We report updated data for avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma from the third interim analysis of the phase III JAVELIN Renal 101 trial.
...Progression-free survival (PFS), objective response rate (ORR), and duration of response per investigator assessment (RECIST version 1.1) and overall survival (OS) were evaluated in the overall population and in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups; safety was also assessed.
Overall, median OS 95% confidence interval (CI) was not reached 42.2 months-not estimable (NE) with avelumab plus axitinib versus 37.8 months (31.4-NE) with sunitinib hazard ratio (HR) 0.79, 95% CI 0.643-0.969; one-sided P = 0.0116, and median PFS (95% CI) was 13.9 months (11.1-16.6 months) versus 8.5 months (8.2-9.7 months), respectively (HR 0.67, 95% CI 0.568-0.785; one-sided P < 0.0001). In patients with IMDC favorable-, intermediate-, poor-, or intermediate plus poor-risk disease, respectively, HRs (95% CI) for OS with avelumab plus axitinib versus sunitinib were 0.66 (0.356-1.223), 0.84 (0.649-1.084), 0.60 (0.399-0.912), and 0.79 (0.636-0.983), and HRs (95% CIs) for PFS were 0.71 (0.490-1.016), 0.71 (0.578-0.866), 0.45 (0.304-0.678), and 0.66 (0.550-0.787), respectively. ORRs, complete response rates, and durations of response favored avelumab plus axitinib overall and across all risk groups. In the avelumab plus axitinib arm, 81.1% had a grade ≥3 treatment-emergent adverse event (TEAE), and incidences of TEAEs and immune-related AEs were highest <6 months after randomization.
Avelumab plus axitinib continues to show improved efficacy versus sunitinib and a tolerable safety profile overall and across IMDC risk groups. The OS trend favors avelumab plus axitinib versus sunitinib, but data remain immature; follow-up is ongoing.
ClinicalTrials.govNCT02684006; https://clinicaltrials.gov/ct2/show/NCT02684006
•Immunotherapy-based regimens can have varying efficacy benefits in patients with advanced renal cell carcinoma.•Patient outcomes can vary based on IMDC risk.•Follow-up from the JAVELIN Renal 101 trial confirms the efficacy and safety of first-line avelumab + axitinib versus sunitinib.•Avelumab + axitinib had a positive benefit-to-risk ratio versus sunitinib across all IMDC risk groups.•Long-term treatment with avelumab + axitinib did not result in new safety signals, and AEs decreased over time.
Among patients with advanced renal cell carcinoma (RCC), those with sarcomatoid histology (sRCC) have the poorest prognosis. This analysis assessed the efficacy of avelumab plus axitinib versus ...sunitinib in patients with treatment-naive advanced sRCC.
The randomized, open-label, multicenter, phase III JAVELIN Renal 101 trial (NCT02684006) enrolled patients with treatment-naive advanced RCC. Patients were randomized 1 : 1 to receive either avelumab plus axitinib or sunitinib following standard doses and schedules. Assessments in this post hoc analysis of patients with sRCC included efficacy (including progression-free survival) and biomarker analyses.
A total of 108 patients had sarcomatoid histology and were included in this post hoc analysis; 47 patients in the avelumab plus axitinib arm and 61 in the sunitinib arm. Patients in the avelumab plus axitinib arm had improved progression-free survival stratified hazard ratio, 0.57 (95% confidence interval, 0.325-1.003) and a higher objective response rate (46.8% versus 21.3%; complete response in 4.3% versus 0%) versus those in the sunitinib arm. Correlative gene expression analyses of patients with sRCC showed enrichment of gene pathway scores for cancer-associated fibroblasts and regulatory T cells, CD274 and CD8A expression, and tumors with The Cancer Genome Atlas m3 classification.
In this subgroup analysis of JAVELIN Renal 101, patients with sRCC in the avelumab plus axitinib arm had improved efficacy outcomes versus those in the sunitinib arm. Correlative analyses provide insight into this subtype of RCC and suggest that avelumab plus axitinib may increase the chance of overcoming the aggressive features of sRCC.
•Patients with sarcomatoid renal cell carcinoma had improved progression-free survival with avelumab + axitinib versus sunitinib.•The objective response rate was 46.8% for patients in the avelumab + axitinib arm versus 21.3% for those in the sunitinib arm.•Correlative analyses showed enrichment for cancer-associated fibroblasts and regulatory T cells, and CD274 and CD8A expression.•Our findings suggest that avelumab + axitinib may improve the chance of overcoming the aggressive features of this subtype.
COPD frequently coexists with HF with which shares several risk factors. A greater collaboration is required between cardiologists and pulmonologists to better identify and manage concurrent HF and ...COPD. This observational, retrospective study provides new data regarding the management of these patients.
from the Health Search Database which collects information generated by the routine activity of general practitioners, we selected 803 patients suffering from COPD or HF alone or combined analyzing similarities and differences regarding risk factors, diagnostic workup and therapeutic approaches.
Statistical analyses have evidenced significant differences regarding exposure to cigarette smoke and the prevalence of diabetes and hypertension in the three groups of patients. As regard to the diagnostic workup, it has been found that the 63,9% of COPD patients and the 57,1% of COPD + HF patients performed a spirometry vs the 95,4% of HF patients and the 95,2% of COPD + HF patients that performed an ECG.
Regarding the pharmacologic treatment, the 47% of COPD patients was treated with an ICS/LABA association and the 22% with ICS/LABA + LAMA. In the COPD + HF group, 47% of patients were treated with ICS/LABA association, while 32% of these patients were treated with ICS/LABA + LAMA. The pharmacologic treatment most prescribed in HF was β-blockers (68%), diuretics (92.8%), antiplatelet therapy (55.6%) and ACE inhibitors (38.1%). In the COPD + HF group, β-blockers (40.1%), diuretics (89.8%), antiplatelet therapy (57.1%) and ACE inhibitors (44.9%) were prescribed.
this study has evidenced a disparity in performing instrumental diagnosis between COPD and HF groups that persists when both conditions coexist. Moreover, the pharmacological treatment of the two conditions shows a consistent under treatment with bronchodilators in COPD patients and with β-blockers in HF patients.
•COPD and HF are highly incident in the general population.•Their coexistence lead to prognosis worsening and to high mortality.•General practitioners manage differently COPD and HF during diagnostic workup.•Therapy is characterized by:1)under treatment of COPD patients with bronchodilators.•2) Under treatment of COPD-HF patients with bronchodilators and β-blockers.
Abstract
Aims
A previous randomized study demonstrated that the subcutaneous implantable cardioverter defibrillator (S-ICD) was noninferior to transvenous ICD with respect to device-related ...complications and inappropriate shocks. However, that was performed prior to the widespread adoption of pulse generator implantation in the intermuscular (IM) space instead of the traditional subcutaneous (SC) pocket. The aim of this analysis was to compare survival from device-related complications and inappropriate shocks between patients who underwent S-ICD implantation with the generator positioned in an IM position in comparison with an SC pocket.
Methods and results
We analysed 1577 consecutive patients who had undergone S-ICD implantation from 2013 to 2021 and were followed up until December 2021. Subcutaneous patients (n = 290) were propensity matched with patients of the IM group (n = 290), and their outcomes were compared. : During a median follow-up of 28 months, device-related complications were reported in 28 (4.8%) patients and inappropriate shocks were reported in 37 (6.4%) patients. The risk of complication was lower in the matched IM group than in the SC group hazard ratio 0.41, 95% confidence interval (CI) 0.17–0.99, P = 0.041, as well as the composite of complications and inappropriate shocks (hazard ratio 0.50, 95% CI 0.30–0.86, P = 0.013). The risk of appropriate shocks was similar between groups (hazard ratio 0.90, 95% CI 0.50–1.61, P = 0.721). There was no significant interaction between generator positioning and variables such as gender, age, body mass index, and ejection fraction.
Conclusion
Our data showed the superiority of the IM S-ICD generator positioning in reducing device-related complications and inappropriate shocks.
Clinical trial registration
Clinical Trial Registration: ClinicalTrials.gov; NCT02275637.
Graphical Abstract
Graphical Abstract
Abstract
An accelerator-driven 14 MeV neutron source of new concept, denominated SORGENTINA-RF, will be installed in ENEA Brasimone Research Centre, to test the feasibility of producing radionuclides ...of medical relevance using fusion neutrons. The main goal of the facility is generating 99Mo as precursor of 99mTc, a radionuclide widely used in nuclear medicine diagnostic procedures, using the 14 MeV fusion neutrons produced by the plant. This work describes the study performed for the design of a proper shielding structure that aims at fulfilling the requirement of 0.01 mSv/h dose rate limit on the external surface of the shielding during beam-on operations. The proposed shielding consists of a layered structure composed of 2 m standard concrete and 1 m baritic concrete. The design is still in the preliminary phase to assess the feasibility and the economic issues as well as structural impact of the shielding structure.
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