Possible predicative role of electrical risk score on transcatheter aortic valve replacement outcomes in older patients. preliminary data

Background:Transcatheter aortic valve replacement (TAVR) is an effective procedure capable to change the natural history of the degenerative aortic valve stenosis. Despite the TAVR, the patients with advanced valve disease and severe myocardial damage (low flow, gradient and ejection fraction)show high mortality level. Aim of this study was toevaluate the predicative power of a noninvasive and inexpensive test obtained by means of a simple standard 12-leads electrocardiogram,known as the Electrical Risk Score (ERS). Methods: ERS was composed by seven simple ECG markers: heart rate (>75 bpm); QRS duration (>110 ms), left ventricular hypertrophy (Sokolow-Lyon criteria), delayed QRS transition zone (≥ V4), frontal QRS-T angle (>90°), long QTBazett (>450 ms for men and >460 in women) or JTBazett(330 ms for men and > 340 ms for women);long T peak to T end interval (Tp-e)( >89 ms). An ERS ≥ 4was considered high risk for all-cause or cardiovascular mortality.We calculated retrospectively the pre-procedure ERS in 40 TAVR patients after one year of follow-up. Results: In the follow up the all-cause and cardiovascular mortality were respectively 25% and 15%.None of survivors reported ERS ≥ 4,moreover, the ERS was the strongest predictor of all-cause (odd ratio 3.73, 95% CI: 1.44-9.66, p<0.05) or cardiovascular (odd ratio 3.95, 95% CI: 1.09-14.27, p<0.05) mortality.ROC curves showed that ERS had the widest significant sensitivity-specificity area under the curve (auc) predicting all-cause (auc: 0.855, p<0.05) or cardiovascular mortality (auc: 0.908, p<0.05). Conclusions:In this pivotal study, ERS resulted an useful tool to stratify the risk of mortality in one-year follow-up TAVR patients. Obviously, it is necessary to confirm these data in large prospective studies

S-Adenosyl-L-Methionine Augmentation in Patients with Stage II Treatment-Resistant Major Depressive Disorder: An Open Label, Fixed Dose, Single-Blind Study

We investigated the efficacy of S-Adenosyl-L-Methionine (SAMe) augmentation in patients with treatment-resistant depressive disorder (TRD). Thirty-three outpatients with major depressive episode who failed to respond to at least 8 weeks of treatment with two adequate and stable doses of antidepressants were treated openly with fixed dose of SAMe (800 mg) for 8 weeks, added to existing medication. The primary outcome measure was the change from baseline in total score on Hamilton Rating Scale for Depression (HAM-D). The Clinical Global Impression of Improvement (CGI-I) was rated at the endpoint. Patients with a reduction of 50% or more on HAM-D total score and a CGI-I score of 1 or 2 at endpoint were considered responders; remission was defined as a HAM-D score ≤7. Secondary outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS) and the Sheehan Disability Scale (SDS). At 8 weeks, a significant decrease in HAM-D score was observed with response achieved by 60% of the patients and remission by 36%. Also a statistically significant reduction in SHAPS and SDS was observed. Our findings indicate that SAMe augmentation may be effective and well tolerated in stage II TRD. However, limitations of the present study must be considered and further placebo-controlled trials are needed

Implementing an evidence-based computerized decision support system linked to electronic health records to improve care for cancer patients: the ONCO-CODES study protocol for a randomized controlled trial.

BACKGROUND: Computerized decision support systems (CDSSs) are computer programs that provide doctors with person-specific, actionable recommendations, or management options that are intelligently filtered or presented at appropriate times to enhance health care. CDSSs might be integrated with patient electronic health records (EHRs) and evidence-based knowledge. METHODS/DESIGN: The Computerized DEcision Support in ONCOlogy (ONCO-CODES) trial is a pragmatic, parallel group, randomized controlled study with 1:1 allocation ratio. The trial is designed to evaluate the effectiveness on clinical practice and quality of care of a multi-specialty collection of patient-specific reminders generated by a CDSS in the IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) hospital. We hypothesize that the intervention can increase clinician adherence to guidelines and, eventually, improve the quality of care offered to cancer patients. The primary outcome is the rate at which the issues reported by the reminders are resolved, aggregating specialty and primary care reminders. We will include all the patients admitted to hospital services. All analyses will follow the intention-to-treat principle. DISCUSSION: The results of our study will contribute to the current understanding of the effectiveness of CDSSs in cancer hospitals, thereby informing healthcare policy about the potential role of CDSS use. Furthermore, the study will inform whether CDSS may facilitate the integration of primary care in cancer settings, known to be usually limited. The increasing use of and familiarity with advanced technology among new generations of physicians may support integrated approaches to be tested in pragmatic studies determining the optimal interface between primary and oncology care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02645357

Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer

The nuclease MRE11A is often included in genetic test panels for hereditary breast and ovarian cancer (HBOC) due to its BRCA1-related molecular function in the DNA repair pathway. However, whether MRE11A is a true predisposition gene for HBOC is still questionable. We determined to investigate this notion by dissecting the molecular genetics of the c.1516G > T;p.E506* truncating MRE11A variant, that we pinpointed in two unrelated French-Canadian (FC) HBOC patients. We performed a case-control study for the variant in ~ 2500 breast, ovarian, and endometrial cancer patients from the founder FC population of Quebec. Furthermore, we looked for the presence of second somatic alterations in the MRE11A gene in the tumors of the carriers. In summary, these investigations suggested that the identified variant is not associated with an increased risk of developing breast or ovarian cancer. We finally performed a systematic review for all the previously reported MRE11A variants in breast and ovarian cancer. We found that MRE11A germline variants annotated as pathogenic on ClinVar often lacked evidence for such classification, hence misleading the clinical management for affected patients. In summary, our report suggests the lack of clinical utility of MRE11A testing in HBOC, at least in the White/Caucasian populations

Hyperactive HRAS dysregulates energetic metabolism in fibroblasts from patients with Costello syndrome via enhanced production of reactive oxidizing species

Germline-activating mutations in HRAS cause Costello syndrome (CS), a cancer prone multisystem disorder characterized by reduced postnatal growth. In CS, poor weight gain and growth are not caused by low caloric intake. Here, we show that constitutive plasma membrane translocation and activation of the GLUT4 glucose transporter, via reactive oxygen species-dependent AMP-activated protein kinase α and p38 hyperactivation, occurs in primary fibroblasts of CS patients, resulting in accelerated glycolysis and increased fatty acid synthesis and storage as lipid droplets. An accelerated autophagic flux was also identified as contributing to the increased energetic expenditure in CS. Concomitant inhibition of p38 and PI3K signaling by wortmannin was able to rescue both the dysregulated glucose intake and accelerated autophagic flux. Our findings provide a mechanistic link between upregulated HRAS function, defective growth and increased resting energetic expenditure in CS, and document that targeting p38 and PI3K signaling is able to revert this metabolic dysfunction.n

How the First Year of the COVID-19 Pandemic Impacted Patients’ Hospital Admission and Care in the Vascular Surgery Divisions of the Southern Regions of the Italian Peninsula

Background: To investigate the effects of the COVID-19 lockdowns on the vasculopathic population. Methods: The Divisions of Vascular Surgery of the southern Italian peninsula joined this multicenter retrospective study. Each received a 13-point questionnaire investigating the hospitalization rate of vascular patients in the first 11 months of the COVID-19 pandemic and in the preceding 11 months. Results: 27 out of 29 Centers were enrolled. April-December 2020 (7092 patients) vs. 2019 (9161 patients): post-EVAR surveillance, hospitalization for Rutherford category 3 peripheral arterial disease, and asymptomatic carotid stenosis revascularization significantly decreased (1484 (16.2%) vs. 1014 (14.3%), p = 0.0009; 1401 (15.29%) vs. 959 (13.52%), p = 0.0006; and 1558 (17.01%) vs. 934 (13.17%), p &lt; 0.0001, respectively), while admissions for revascularization or major amputations for chronic limb-threatening ischemia and urgent revascularization for symptomatic carotid stenosis significantly increased (1204 (16.98%) vs. 1245 (13.59%), p &lt; 0.0001; 355 (5.01%) vs. 358 (3.91%), p = 0.0007; and 153 (2.16%) vs. 140 (1.53%), p = 0.0009, respectively). Conclusions: The suspension of elective procedures during the COVID-19 pandemic caused a significant reduction in post-EVAR surveillance, and in the hospitalization of asymptomatic carotid stenosis revascularization and Rutherford 3 peripheral arterial disease. Consequentially, we observed a significant increase in admissions for urgent revascularization for symptomatic carotid stenosis, as well as for revascularization or major amputations for chronic limb-threatening ischemia

Making use of comparable health data to improve quality of care and outcomes in diabetes : The EUBIROD review of diabetes registries and data sources in Europe

Background: Registries and data sources contain information that can be used on an ongoing basis to improve quality of care and outcomes of people with diabetes. As a specific task of the EU Bridge Health project, we carried out a survey of diabetes-related data sources in Europe. Objectives: We aimed to report on the organization of different sources of diabetes information, including their governance, information infrastructure and dissemination strategies for quality control, service planning, public health, policy and research. Methods: Survey using a structured questionnaire to collect targeted data from a network of collaborating institutions managing registries and data sources in 17 countries in the year 2017. Results: The 18 data sources participating in the study were most frequently academic centres (44.4%), national (72.2%), targeting all types of diabetes (61.1%) covering no more than 10% of the target population (44.4%). Although population-based in over a quarter of cases (27.8%), sources relied predominantly on provider-based datasets (38.5%), fewer using administrative data (16.6%). Data collection was continuous in the majority of cases (61.1%), but 50% could not perform data linkage. Public reports were more frequent (72.2%) as well as quality reports (77.8%), but one third did not provide feedback to policy and only half published ten or more peer reviewed papers during the last 5 years. Conclusions: The heterogeneous implementation of diabetes registries and data sources hampers the comparability of quality and outcomes across Europe. Best practices exist but need to be shared more effectively to accelerate progress and deliver equitable results for people with diabetes.publishedVersionPeer reviewe

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio