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Previous studies have shown discrepancies among countries in terms of treatment indications and patients' management due to different health care policies. Penile prosthesis implantation (PPI) is a highly effective treatment for erectile dysfunction (ED), which may have different accessibility according to the type of health system. We compared clinical characteristics of patients included in two national registries on PPI to investigate the influence of different health care systems on treatment indication and accessibility. The multicenter Italian Nationwide Systematic Inventarization of Surgical Treatment for ED (INSIST-ED) Registry and the multicenter Prospective Registry of Outcomes with Penile Prosthesis for Erectile Restoration (PROPPER), respectively for Italy and North America were considered. Clinical characteristics of patients included in both registries were compared using Wilcoxon Rank Sum test and the Pearson's Chi square test. Patients submitted to PPI in Italy are significantly younger (age: 61.2 vs. 63.8 years; p ≤ 0.001) compared with North America. The majority of patients are treated for post-radical prostatectomy ED in both registries (Italy: 31%; North America: 27%), although diabetes and cardiovascular diseases are more frequent reasons for PPI in the PROPPER registry (p ≤ 0.001), reflecting differences in disease prevalence among countries. In North America a non-hydraulic implant is considered only in 1% of cases as compared with 3% in Italy (p ≤ 0.001). In terms of postoperative management, a compressive surgical dressing (98% vs. 24%; p ≤ 0.001) is a more common strategy in North America. Finally, in Italy most surgeries are performed in a public hospital (82%), while the private setting (70.8%) is more common in North America (p ≤ 0.001). These findings suggest differences in health care systems between Italy and North America. A system like the American one would guarantee easier access to PPI in countries where the National Health System is mainly based on reimbursement to public hospital settings and where patients choosing private settings have to pay by themselves.

Behavioral interventions have shown promising neuroprotective effects, but the cascade of molecular, brain and behavioral changes involved in these benefits remains poorly understood. Projecte Moviment is a 12-week (5 days per week-45 min per day) multi-domain, single-blind, proof-of-concept randomized controlled trial examining the cognitive effect and underlying mechanisms of an aerobic exercise (AE), computerized cognitive training (CCT) and a combined (COMB) groups compared to a waitlist control group. Adherence was > 80% for 82/109 participants recruited (62% female; age = 58.38 ± 5.47). In this study we report intervention-related changes in plasma biomarkers (BDNF, TNF-a, HGF, ICAM-1, SDF1-a) and structural-MRI (brain volume) and how they related to changes in physical activity and individual variables (age and sex) and their potential role as mediators in the cognitive changes. Our results show that although there were no significant changes in molecular biomarker concentrations in any intervention group, changes in ICAM-1 and SDF1-a were negatively associated with changes in physical activity outcomes in AE and COMB groups. Brain volume changes were found in the CCT showing a significant increase in precuneus volume. Sex moderated the brain volume change in the AE and COMB groups, suggesting that men may benefit more than women. Changes in molecular biomarkers and brain volumes did not significantly mediate the cognitive-related benefits found previously for any group. This study shows crucial initial molecular and brain volume changes related to lifestyle interventions at early stages and highlights the value of examining activity parameters, individual difference characteristics and using a multi-level analysis approach to address these questions.

Apolipoprotein E (APOE) has an important role in the multiple trajectories of cognitive aging. However, environmental variables and other genes mediate the impact of APOE on cognition. Our main objective was to analyze the effect of APOE genotype on cognition and its interactions and relationships with sex, age, lipid profile, C-reactive protein, and Brain-derived neurotrophic factor (BDNF) genotype in a sample of 648 healthy participants over 50 years of age with a comprehensive neuropsychological assessment. Our results showed that APOE epsilon 2 carriers performed better in the Verbal Memory (p = .002) and Fluency Domains (p = .001). When we studied the effect of sex, we observed that the beneficial effect of APOE epsilon 2 on the normalized values of these cognitive domains occurred only in females (beta = 0.735; 95% confidence interval, 0.396-1.074; p = 3.167-10(-5) and beta = 0.568; 95% confidence interval, 0.276-0.861; p = 1.853.10(-4), respectively). Similarly, the sex-specific effects of APOE epsilon 2 were further observed on lipidic and inflammation biomarkers. In the whole sample, APOE epsilon 2 carriers showed significantly lower levels of total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein. These differences were found only among females. Furthermore, total cholesterol and low-density lipoprotein cholesterol mediated the protective effect of APOE epsilon 2 on cognition in the whole sample and total cholesterol in females, providing candidate physiological mechanisms for the observed genetic effects. Our results show that the neuroprotective role of APOE epsilon 2 in cognition varies with sex and that the lipidic profile partially mediates this protection. Age-related cognitive and functional decline is a continuous biological process with different cognitive trajectories (1). Complex interactions between heritability, environmental influence, and cognitive functions in aging have been highlighted (2). In particular, genetic differences explain around 15%-25% of the variance in life expectancy (3). Therefore, the identification of susceptibility genes and their biological effects on cognitive aging is required to establish interindividual differences in this process and promote early personalized interventions to delay cognitive decline and minimize the financial burden of aging in the health care system.

PURPOSE: The benefits from physical activity (PA) and cardiorespiratory fitness (CRF) on normal age-related cognitive decline might be sex dependent. Our aim was to explore the relationship between different types of PA, CRF, and cognition and to identify the mediating effects of CRF in the association between PA and cognition in women and men. METHODS: We recruited 115 healthy adults 50-70 yr of age. We obtained demographic, cognitive, and PA status data based on the Projecte Moviment protocol. We calculated cognitive domains by grouping z-sample scores. We obtained self-reported total energy expenditure during the last month and grouped it into sportive PA (S-PA) and nonsportive PA (NS-PA). CRF was estimated using the Rockport 1-Mile Walk Test. We applied regression models and mediation analyses in a final sample of 104 individuals (65 women and 39 men). RESULTS: In the total sample, CRF was positively associated with executive function, verbal memory, and attention-speed. S-PA was positively related to executive function and attention-speed, whereas NS-PA was unrelated to cognitive domains. Greater amounts of S-PA were associated with executive function and attention-speed for both women and men. Higher CRF was associated with executive function, memory, language, and attention-speed only in men. Mediation analyses showed that CRF was a significant mediator of the positive effects of S-PA on executive function and attention-speed in men but not in women. CONCLUSIONS: Both women and men show cognitive benefits from greater S-PA, but not from NS-PA. However, there were sex differences in the mediating effects of CRF in this relationship, showing that CRF was mediating these benefits only in men.

Objective: To investigate the prevalence and risks factors associated wit h the presence of liver fibrosis in subjects with nonalcoholic fatty liver disease (NAFLD) with and without type 2 diabetes mellitus (T2D). Design and methods: This study was part of a population-based study conducted in t he Barcelona metropolitan area among subjects aged 18-75 years old. Secondary causes of steato sis were excluded. Moderate-to-advanced liver fibrosis was defined as a liver stiffness measurement (LSM) = 8.0 kPa assessed by transient elastography. Results: Among 930 subjects with NAFLD, the prevalence of moderate-to-a dvanced liver fibrosis was higher in subjects with T2D compared those without (30.8% vs 8.7%). By multivariab le analysis, one of the main factors independently associated with increased LSM in subjects with NAFLD was athero genic dyslipidemia but only in those with T2D. The percentage of subjects with LSM = 8.0 kPa was higher in subjects with T2D and atherogenic dyslip idemia than in those with T2D without atherogenic dyslipidemia both for the cut-off p oint of LSM =8.0 kPa (45% vs 24% P = 0.002) and =13 kPa (13% vs 4% P = 0.020). No differences were observed in the prevalence of LSM =8.0 kPa regarding glycemic control among NAFLD-diabetic subjects. Conclusions: Factors associated with moderate-to-advanced liver fibrosis in NAFLD are different in subjects with and without T2D. Atherogenic dyslipidemia was associated with the p resence of moderate-to-advanced liver fibrosis in T2D with NAFLD but not in non-diabetic subjects. These findings high light the need for an active search for liver fibrosis in subjects with T2D NAFLD and atherogenic dyslipidemia. © 2021 European Society of Endocrinology.

Apolipoprotein E (APOE) has an important role in the multiple trajectories of cognitive aging. However, environmental variables and other genes mediate the impact of APOE on cognition. Our main objective was to analyze the effect of APOE genotype on cognition and its interactions and relationships with sex, age, lipid profile, C-reactive protein, and Brain-derived neurotrophic factor (BDNF) genotype in a sample of 648 healthy participants over 50 years of age with a comprehensive neuropsychological assessment. Our results showed that APOE e2 carriers performed better in the Verbal Memory (p = .002) and Fluency Domains (p = .001). When we studied the effect of sex, we observed that the beneficial effect of APOE e2 on the normalized values of these cognitive domains occurred only in females (ß = 0.735; 95% confidence interval, 0.396-1.074; p = 3.167·10-5 and ß = 0.568; 95% confidence interval, 0.276-0.861; p = 1.853·10-4, respectively). Similarly, the sex-specific effects of APOE e2 were further observed on lipidic and inflammation biomarkers. In the whole sample, APOE e2 carriers showed significantly lower levels of total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein. These differences were found only among females. Furthermore, total cholesterol and low-density lipoprotein cholesterol mediated the protective effect of APOE e2 on cognition in the whole sample and total cholesterol in females, providing candidate physiological mechanisms for the observed genetic effects. Our results show that the neuroprotective role of APOE e2 in cognition varies with sex and that the lipidic profile partially mediates this protection. Age-related cognitive and functional decline is a continuous biological process with different cognitive trajectories (1). Complex interactions between heritability, environmental influence, and cognitive functions in aging have been highlighted (2). In particular, genetic differences explain around 15%-25% of the variance in life expectancy (3). Therefore, the identification of susceptibility genes and their biological effects on cognitive aging is required to establish interindividual differences in this process and promote early personalized interventions to delay cognitive decline and minimize the financial burden of aging in the health care system.

Background: Lung ultrasound (LUS) is useful for diagnosing pulmonary congestion, but its value in primary care remains unclear. We investigated whether LUS improved diagnostic accuracy in outpatients with heart failure (HF) suspicion. Methods and results: LUS was performed on 2 anterior (A), 2 lateral (L), and 2 posterior (P) areas per hemithorax. An area was positive when >= 3 B-lines were observed. Two diagnostic criteria were used: for LUS-C1, 2 positive areas of 4 (A-L) on each hemithorax; and for LUS-C2, 2 positive areas of 6 (A-L-P) on each hemithorax. A cardiologist blinded to LUS validated HF diagnosis. 162 patients were included (age 75.6 +/- 9.4 years, 70.4% women). Both LUS criteria, alone and combined with other HF diagnostic criteria, were accurate for identifying HF. LUS-C2 outperformed LUS-C1, showing remarkable specificity (0.99) and positive predictive value (0.92). LUS-C2, together with Framingham criteria, N-terminal pro-B-type natriuretic peptide, and electrocardiogram, added diagnostic value (area under the receiver operating characteristic curves 0.90 with LUS-C2 vs 0.84 without; P =.006). In the absence of N-terminal pro-B-type natriuretic peptide, LUS-C2 significantly reclassified one-third of patients above Framingham criteria and electrocardiogram (net reclassification improvement 0.65, 95% confidence interval 0.04-1.1). Conclusions: LUS was accurate enough to rule-in HF in a primary care setting. The accuracy of diagnostic workup for HF in primary care is enhanced by incorporating LUS, irrespective NT-proBNP availability.

Objective: Local infections still represent the most fearsome complication of penile prosthesis implantation (PPI). Aim of this study was to analyze differences in perioperative management strategies applied for PPI in a national-based registry. Materials and Methods: Data were analysed from a national multi-institutional database of PPI including patients treated from 2014 to 2017 in Italy (INSIST-ED). All data have been prospectively recorded by 45 surgeons on a dedicated website (www.registro.andrologiaitaliana.it) and critically revised by a single datamanager. The application of perioperative management strategies to avoid local infection as suggested by the ISSM guidelines (namely, double-agent preoperative antibiotic therapy, use of double gloves and application of the “no-touch” technique) were analysed. Results: Complete data were available for 402 patients. Overall, one-shot preoperative antibiotic therapy (1h before surgery), with a double agent covering Gram+ and Gram- bacteria, was used in 69% (279) of cases. Among them, the combination of Aminoglycosides + Glycopeptides emerged as the most frequently used therapy [167 (59.8%)]. A total of 123 (31%) patients received a single drug as preoperative antibiotic prophylaxis; of them, 30.1% (37) had already received an antibiotic therapy course within 1 and 7 days before surgery. During the procedure, the application of the “no-touch” technique and the use of double gloves were reported in 13% (52) and 29% (115) of the cases, respectively. A surgical drain was placed in 44% (176) of the cases. Overall, the ISSM recommendations to reduce the risk of local infections, were thoroughly followed in only 4% (16) of the cases. Conclusions: Perioperative management strategies to prevent surgical infection in PPI emerged to be highly heterogeneous. Physicians should be aware of the importance to properly follow the available recommendations in order to reduce the risk of infections in penile prosthesis surgery

Background: Right bundle branch block (RBBB) is among the most common electrocardiographic abnormalities. Objectives: To establish the prevalence and incidence of RBBB in the general population without cardiovascular events (CVE) and whether RBBB increases cardiovascular morbidity and mortality compared with patients with a normal electrocardiogram (ECG). Methods: A historical study of two cohorts including 2981 patients from 29 primary health centres without baseline CVE. Cox (for CVE) and logistic (for cardiovascular factors) regression was used to assess their association with RBBB. Results: Of the patients (58% women; mean age 65.9), 92.2% had a normal ECG, 4.6% incomplete RBBB (iRBBB) and 3.2% complete RBBB (cRBBB). Mean follow-up was five years. Factors associated with appearance of cRBBB were male sex (HR = 3.8; 95%CI: 2.4-6.1) and age (HR = 1.05 per year; 95%CI: 1.03-1.08). In a univariate analysis, cRBBB was associated with an increase in all-cause mortality but only bifascicular block (BFB) was significant after adjusting for confounders. cRBBB tended to increase CVE but the results were not statistically significant. Presence of iRBBB was not associated with adverse outcomes. Patients with iRBBB who progressed to cRBBB showed a higher incidence of heart failure and chronic kidney disease. Conclusion: In this general population cohort with no CV disease, 8% had RBBB, with a higher prevalence among men and elderly patients. Although all-cause mortality and CVE tended to increase in the presence of cRBBB, only BFB showed a statistically significant association with cRBBB. Patients with iRBBB who progressed to cRBBB had a higher incidence of CVE. We detected no effect of iRBBB on morbidity and mortality.