In this randomized trial, patients with type 2 diabetes and atherosclerotic cardiovascular disease received 5 mg or 15 mg of ertugliflozin or placebo once daily. At a mean of 3.5 years, ertugliflozin ...(pooled data from the two doses) was noninferior to placebo with respect to the composite outcome of cardiovascular death, myocardial infarction, or stroke.
Background/Aims: Sleep disturbances are common in the elderly and in persons with cognitive decline. The aim of this study was to describe frequency and characteristics of insomnia, excessive daytime ...sleepiness, sleep-disordered breathing, REM behavior disorder and restless legs syndrome in a large cohort of persons with mild cognitive impairment or dementia. Methods: 431 consecutive patients were enrolled in 10 Italian neurological centers: 204 had Alzheimer’s disease, 138 mild cognitive impairment, 43 vascular dementia, 25 frontotemporal dementia and 21 Lewy body dementia or Parkinson’s disease dementia. Sleep disorders were investigated with a battery of standardized questions and questionnaires. Results: Over 60% of persons had one or more sleep disturbances almost invariably associated one to another without any evident and specific pattern of co-occurrence. Persons with Alzheimer’s disease and those with mild cognitive impairment had the same frequency of any sleep disorder. Sleep-disordered breathing was more frequent in vascular dementia. REM behavior disorder was more represented in Lewy body or Parkinson’s disease dementia. Conclusion: A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of persons with cognitive decline. Instrumental supports should be used only in selected patients.
Abstract Objective To develop an updated laparoscopy-based model to predict incomplete cytoreduction (RT > 0) in advanced epithelial ovarian cancer (AEOC), after the introduction of upper abdominal ...surgery (UAS). Patients and methods The presence of omental cake, peritoneal extensive carcinomatosis, diaphragmatic confluent carcinomatosis, bowel infiltration, stomach and/or spleen and/or lesser omentum infiltration, and superficial liver metastases was evaluated by staging laparoscopy (S-LPS) in a consecutive series of 234 women with newly diagnosed AEOC, receiving laparotomic PDS after S-LPS. Parameters showing a specificity ≥ 75%, PPV ≥ 50%, and NPV ≥ 50% received 1 point score, with an additional one point in the presence of an accuracy of ≥ 60% in predicting incomplete cytoreduction. The overall discriminating performance of the LPS-PI was finally estimated by ROC curve analysis. Results No-gross residual disease at PDS was achieved in 135 cases (57.5%). Among them, UAS was required in 72 cases (53.3%) for a total of 112 procedures, and around 25% of these patients received bowel resection, excluding recto-sigmoid resection. We observed a very high overall agreement between S-LPS and laparotomic findings, which ranged from 74.7% for omental cake to 94.8% for stomach infiltration. At a LPS-PIV ≥ 10 the chance of achieving complete PDS was 0, and the risk of unnecessary laparotomy was 33.2%. Discriminating performance of LPS-PI was very high (AUC = 0.885). Conclusions S-LPS is confirmed as an accurate tool in the prediction of complete PDS in women with AEOC. The updated LPS-PI showed improved discriminating performance, with a lower rate of inappropriate laparotomic explorations at the established cut-off value of 10.
RATIONALE:Hyperglycemia -induced reactive oxygen species are key mediators of cardiac dysfunction. JunD (Jund proto-oncogene subunit), a member of the AP-1 (activator protein-1) family of ...transcription factors, is emerging as a major gatekeeper against oxidative stress. However, its contribution to redox state and inflammation in the diabetic heart remains to be elucidated.
OBJECTIVE:The present study investigates the role of JunD in hyperglycemia-induced and reactive oxygen species–driven myocardial dysfunction.
METHODS AND RESULTS:JunD mRNA and protein expression were reduced in the myocardium of mice with streptozotocin-induced diabetes mellitus as compared to controls. JunD downregulation was associated with oxidative stress and left ventricular dysfunction assessed by electron spin resonance spectroscopy as well as conventional and 2-dimensional speckle-tracking echocardiography. Furthermore, myocardial expression of free radical scavenger superoxide dismutase 1 and aldehyde dehydrogenase 2 was reduced, whereas the NOX2 (NADPH nicotinamide adenine dinucleotide phosphatase oxidase subunit 2) and NOX4 (NADPH nicotinamide adenine dinucleotide phosphatase oxidase subunit 4) were upregulated. The redox changes were associated with increased NF-κB (nuclear factor kappa B) binding activity and expression of inflammatory mediators. Interestingly, mice with cardiac-specific overexpression of JunD via the α MHC (α- myosin heavy chain) promoter (α MHC JunD) were protected against hyperglycemia-induced cardiac dysfunction. We also showed that JunD was epigenetically regulated by promoter hypermethylation, post-translational modification of histone marks, and translational repression by miRNA (microRNA)-673/menin. Reduced JunD mRNA and protein expression were confirmed in left ventricular specimens obtained from patients with type 2 diabetes mellitus as compared to nondiabetic subjects.
CONCLUSIONS:Here, we show that a complex epigenetic machinery involving DNA methylation, histone modifications, and microRNAs mediates hyperglycemia-induced JunD downregulation and myocardial dysfunction in experimental and human diabetes mellitus. Our results pave the way for tissue-specific therapeutic modulation of JunD to prevent diabetic cardiomyopathy.
Purpose
Chemoradiation (CT/RT) followed by radical surgery (RS) may play a role in locally advanced cervical cancer (LACC) patients with suboptimal response to CT/RT or in low-income countries with ...limited access to radiotherapy. Our aim is to evaluate oncological and surgical outcomes of minimally invasive radical surgery (MI-RS) compared with open radical surgery (O-RS).
Patients and Methods
Data for stage IB2–IVA cervical cancer patients managed by CT/RT and RS were retrospectively analyzed.
Results
Beginning with 686 patients, propensity score matching resulted in 462 cases (231 per group), balanced for FIGO stage, lymph node status, histotype, tumor grade, and clinical response to CT/RT. The 5-year disease-free survival (DFS) was 73.7% in the O-RS patients and 73.0% in the MI-RS patients (HR 1.034, 95% CI 0.708–1.512,
p
= 0.861). The 5-year locoregional recurrence rate was 12.5% (O-RS) versus 15.2% (MI-RS) (HR 1.174, 95% CI 0.656–2.104,
p
= 0.588). The 5-year disease-specific survival (DSS) was 80.4% in O-RS patients and 85.3% in the MI-RS group (HR 0.731, 95% CI 0.438–1.220,
p
= 0.228). Estimated blood loss was lower in the MI-RS group (
p
< 0.001), as was length of hospital stay (
p
< 0.001). Early postoperative complications occurred in 77 patients (33.3%) in the O-RS group versus 88 patients (38.1%) in the MI-RS group (
p
= 0.331). Fifty-six (24.2%) patients experienced late postoperative complications in the O-RS group, versus 61 patients (26.4%) in the MI-RS group (
p
= 0.668).
Conclusion
MI-RS and O-RS are associated with similar rates of recurrence and death in LACC patients managed by surgery after CT/RT. No difference in early or late complications was reported.
During the last decades, the clinical and research interest in atherosclerosis has been mostly focused on coronary arteries. After the publications of the European Society Guidelines and AHA/ACC ...Guidelines on Peripheral artery diseases, and of the Registry REduction in Atherothrombosis for Continued Health Registry, there has been an increased interest in atherosclerosis of the lower extremity arteries and its presence in multifocal disease. However, awareness in the general population and the medical community of non-coronary artery diseases, and of its major prognostic implications remain relatively low. The aim of this general review stemming out of an ESC Working Group on Peripheral Circulation meeting in 2011 is to enhance awareness of this complex disease highlighting the importance of the involvement of atherosclerosis at different levels with respect to clinical presentation, diagnosis, and co-existence of the disease in the distinct arterial territories. We also emphasize the need of an interdisciplinary approach to face the broad and complex spectrum of multifocal disease, and try to propose a series of tentative recommendations and measures to be implemented in non-coronary atherosclerosis.
Traditional farming, where livestock is seasonally managed as free ranging and the use of drugs is reduced or absent, may prove beneficial to biodiversity by fostering the occurrence of spatial ...heterogeneity, and increasing the availability of trophic resources to wildlife. Previous work indicates that the presence of cattle in lowlands leads to an increase in bat foraging activity, yet no study has addressed this topic in mountainous regions, where free-ranging livestock is still common. Here we explore the relationships between landscape structure, farming and bat activity in a mountainous agricultural area, hypothesizing that bat activity will increase in response to the presence of livestock and landscape structure and heterogeneity. We found that traditional cattle farming may have a role in influencing bat activity in mountainous agroecosystems, yet its effects are evident for a limited number of species. Three pipistrelle species favoured foraging in areas subjected to cattle farming by hunting more often over cattle or fresh dung than at control sites. Free-ranging cattle thus provide profitable foraging opportunities for bats in mountainous landscapes, which remarks the importance of traditional farming activities in sustaining biodiversity. Cattle might also benefit from bat foraging activity if this leads to suppression of blood-sucking pests.
Primary prevention studies have confirmed that high-density lipoprotein cholesterol (HDL-C) levels are strongly associated with reduced cardiovascular events. However, recent evidence suggests that ...HDL-C functionality may be impaired under certain conditions. In the present study, we hypothesize that HDL-C may lose their protective role in the secondary prevention of coronary artery disease (CAD).
A consecutive series of 1548 patients undergoing isolated first-time elective CABG at one institution between 2004 and 2009 was studied. According to the ATPIII criteria, pre-operative HDL-C values were used to identify patients with high (Group A) vs. low HDL-C (Group B). To eliminate biased estimates, a propensity score model was built and two cohorts of 1:1 optimally matched patients were obtained. Cumulative survival and major adverse cardiovascular events (MACE) were analysed by means of Kaplan-Meier method. Cox proportional-hazards regression models were used to identify independent predictors of MACE and death. Propensity matching identified two cohorts of 502 patients each. At a median follow-up time of 32 months, there were 44 out of 502 (8.8%) deaths in Group A and 36 out of 502 deaths in Group B (7.2%, HR 1.19; P = 0.42). MACE occurred in 165 out of 502 (32.9%) in Group A and 120 out of 502 (23.9%) in Group B (P = 0.04). Regression analysis showed that pre-operative HDL-C levels were not associated with reduced but rather increased MACE occurrence during follow-up (HR 1.43, P = 0.11).
Higher HDL-C levels are not associated with reduced risk of vascular events in CAD patients undergoing CABG. Our findings may support efforts to improve HDL-C functionality instead of increasing their levels.
Purpose
Uterine carcinosarcomas (UCSs) are aggressive biphasic malignancies, with a carcinomatous/epithelial component and a sarcomatous/mesenchymal counterpart. The aim of this study was to evaluate ...the impact of the sarcomatous component (homologous vs heterologous) on the overall survival (OS) and progression-free survival (PFS).
Methods
This is a multicenter observational retrospective study conducted in patients with stage I and II UCSs.
Results
Ninety-five women with histological diagnosis of early-stage UCSs were retrieved: 60 (63.2%) had tumors with homologous sarcomatous components, and 35 (36.8%) with heterologous. At univariate analysis, a stromal invasion ≥ 50%, the presence of clear cell, serous or undifferentiated carcinomatous component, the heterologous sarcomatous component and FIGO stage IB and II were shown to be variables with a statistically significant negative impact on PFS. Similarly, a depth of invasion ≥ 50%, the heterologous sarcomatous component and FIGO stage IB and II were statistically negative prognostic factors also concerning OS. At multivariate analysis, only the heterologous sarcomatous component was confirmed to be a statistically significant negative prognostic factor both on PFS (HR 2.362, 95% CI 1.207–4.623,
p
value = 0.012) and on OS (HR 1.950, 95% CI 1.032–3.684,
p
= 0.040).
Conclusion
Carcinomatous and sarcomatous components both played a role in tumor progression and patients’ survival. However, only the sarcomatous component retained a statistical significance at the multivariable model suggesting its preeminent prognostic role in early-stage UCSs.
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