The blocking of angiotensin II type 1 receptor and RhoA/Rho kinase activity in hypertensive patients: Effect of olmesartan medoxomil and implication with cardiovascular-renal remodeling

Hypothesis/Introduction: The pathophysiological role of oxidative stress (OxSt) in hypertension and target organ damage is recognized. Angiotensin II (Ang II) induces OxSt via NAD(P)H oxidase activation and production of proinflammatory cytokines/growth factors leading to cardiovascular-renal remodeling. Ang II stimulates the RhoA/Rho kinase (ROCK) pathway, which is deeply involved in the development of cardiovascular-renal remodeling via OxSt induction. Olmesartan, an Ang II type 1 receptor blocker, possesses antioxidant and activating nitric oxide system-related effects, which we have shown in terms of p22 phox reduction, heme oxygenase-1 and calcitonin gene-related peptide increase. This study evaluates in 15 untreated hypertensive patients the effect of olmesartan treatment on p63RhoGEF, key in Ang II-induced ROCK activation, and MYPT-1 phosphorylation, a marker of ROCK activity. Materials and methods: The p63RhoGEF protein level and MYPT-1 phosphorylation (Western blot) were evaluated at baseline, and after three and six months of olmesartan treatment. Results: Olmesartan normalized systolic and diastolic BP ( p < 0.001), reduced p63RhoGEF level: 1.3±0.25 d.u. (baseline) vs 1.0±0.29 (three months), p < 0.0001 vs 1.0±0.22, (six months), p < 0.0001 and MYPT-1 phosphorylation: 1.2 ±0.14 (baseline) vs 0.9±0.19 (three months), p = 0.008, vs 0.8±0.16 (six months), p = 0.001. Conclusions: These data added to our previous results further provide a mechanistic rationale for olmesartan's antioxidant/anti-inflammatory potential translation, in the long term, toward anti-atherosclerotic/anti-remodeling effects reported by clinical trials

Segmentation and Identification of Vertebrae in CT Scans Using CNN, k-Means Clustering and k-NN

The accurate segmentation and identification of vertebrae presents the foundations for spine analysis including fractures, malfunctions and other visual insights. The large-scale vertebrae segmentation challenge (VerSe), organized as a competition at the Medical Image Computing and Computer Assisted Intervention (MICCAI), is aimed at vertebrae segmentation and labeling. In this paper, we propose a framework that addresses the tasks of vertebrae segmentation and identification by exploiting both deep learning and classical machine learning methodologies. The proposed solution comprises two phases: a binary fully automated segmentation of the whole spine, which exploits a 3D convolutional neural network, and a semi-automated procedure that allows locating vertebrae centroids using traditional machine learning algorithms. Unlike other approaches, the proposed method comes with the added advantage of no requirement for single vertebrae-level annotations to be trained. A dataset of 214 CT scans has been extracted from VerSe'20 challenge data, for training, validating and testing the proposed approach. In addition, to evaluate the robustness of the segmentation and labeling algorithms, 12 CT scans from subjects affected by severe, moderate and mild scoliosis have been collected from a local medical clinic. On the designated test set from Verse'20 data, the binary spine segmentation stage allowed to obtain a binary Dice coefficient of 89.17%, whilst the vertebrae identification one reached an average multi-class Dice coefficient of 90.09%. In order to ensure the reproducibility of the algorithms hereby developed, the code has been made publicly available

Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study

Introduction: Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs). Methods: We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents. Over the course of 5 study days, 6925 PICU patients &lt;18 years of age were screened, and 706 with severe sepsis defined either by physician diagnosis or on the basis of 2005 International Pediatric Sepsis Consensus Conference consensus criteria were enrolled. The primary endpoint was agreement of pediatric severe sepsis between physician diagnosis and consensus criteria as measured using Cohen's ?. Secondary endpoints included characteristics and clinical outcomes for patients identified using physician diagnosis versus consensus criteria. Results: Of the 706 patients, 301 (42.6 %) met both definitions. The inter-rater agreement (? ± SE) between physician diagnosis and consensus criteria was 0.57 ± 0.02. Of the 438 patients with a physician's diagnosis of severe sepsis, only 69 % (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria. Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions. After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria. Conclusions: Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly. Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis

Incidence of Healthcare-Associated Infections in a Pediatric Population With an Extracorporeal Ventricular Assist Device

During the last decade, ventricular assist devices (VADs) have become a precious tool to support children with end-stage heart failure. However, thromboembolic events, bleeding, and infections may have a considerable impact on outcome. We retrospectively analyzed the incidence of healthcare-associated infections (HAIs) in nine patients supported by EXCOR Pediatric (Berlin Heart [BH]) VAD in a pediatric cardiosurgical intensive care unit between January 1, 2009 and March 31, 2011 (27 months). Median age was 8 months (interquartile range [IQR] 6-11), median weight 7.5kg (IQR 4.5-8.5). Seven patients were supported with a left VAD, two with a biventricular VAD (BiVAD). Six patients with a left VAD underwent heart transplant after 89 days (median, IQR 41-143) of support. One patient is still on the waiting list. All patients with BiVAD died after 12 days of assistance due to VAD malfunction. Sixteen HAIs were reported in five out of nine patients (56%). All infected patients were supported by a left VAD. When compared with noninfected patients, they had a longer mechanical support period (median 131 days, IQR 75-164, vs. 25 days, IQR 11-61, P=0.03), a longer intensive care unit stay (median 159 days, IQR 85-188, vs. 48 days, IQR 17-87, P=0.06) and a longer length of hospital stay (median 186 days, IQR 105-222, vs. 64 days, IQR 34-113, P=0.06). Overall, nine mechanical devices were replaced for thromboembolic issues, most of them (67%) in patients with VAD-related infections. Overall, infection rate was 17.6 per 1000 patients days, 1.3 BH endocarditis per 1000 BH days, 4.0 surgical sites infections per 1000 BH days, 12.5 central line-associated blood stream infections per 1000 central venous catheter days, 5 catheter-associated urinary tract infections per 1000 urinary catheter days, and 13.5 ventilator-associated pneumonia cases per 1000 mechanical ventilation days. Overall, VAD-related infections were 5.4 per 1000 BH days. Of the 17 isolated pathogens, 53% were Gram-negative rods, with a prevalence of Pseudomonas aeruginosa (35.3%). Four bacteria were multidrug resistant (25%), three were carbapenem-resistant P. aeruginosa (50% of all isolated pseudomonads), and one was a methicillin-resistant S.aureus. VADs used as a bridge to cardiac transplantation are associated with a large number of HAIs. Patients with infected VADs were admitted for longer time in intensive care and in hospital with increased healthcare costs but with no impact on surviva

The blocking of angiotensin II type 1 receptor and RhoA/Rho kinase activity in hypertensive patients: Effect of olmesartan medoxomil and implication with cardiovascular-renal remodeling

Hypothesis/Introduction: The pathophysiological role of oxidative stress (OxSt) in hypertension and target organ damage is recognized. Angiotensin II (Ang II) induces OxSt via NAD(P)H oxidase activation and production of proinflammatory cytokines/growth factors leading to cardiovascular-renal remodeling. Ang II stimulates the RhoA/Rho kinase (ROCK) pathway, which is deeply involved in the development of cardiovascular-renal remodeling via OxSt induction. Olmesartan, an Ang II type 1 receptor blocker, possesses antioxidant and activating nitric oxide system-related effects, which we have shown in terms of p22 phox reduction, heme oxygenase-1 and calcitonin gene-related peptide increase. This study evaluates in 15 untreated hypertensive patients the effect of olmesartan treatment on p63RhoGEF, key in Ang II-induced ROCK activation, and MYPT-1 phosphorylation, a marker of ROCK activity. Materials and methods: The p63RhoGEF protein level and MYPT-1 phosphorylation (Western blot) were evaluated at baseline, and after three and six months of olmesartan treatment. Results: Olmesartan normalized systolic and diastolic BP ( p < 0.001), reduced p63RhoGEF level: 1.3±0.25 d.u. (baseline) vs 1.0±0.29 (three months), p < 0.0001 vs 1.0±0.22, (six months), p < 0.0001 and MYPT-1 phosphorylation: 1.2 ±0.14 (baseline) vs 0.9±0.19 (three months), p = 0.008, vs 0.8±0.16 (six months), p = 0.001. Conclusions: These data added to our previous results further provide a mechanistic rationale for olmesartan's antioxidant/anti-inflammatory potential translation, in the long term, toward anti-atherosclerotic/anti-remodeling effects reported by clinical trials

Prognostic role of stress/rest myocardial perfusion scintigraphy in patients with cardiac syndrome x.

The prognostic utility of myocardial perfusion scintigraphy (MPS) in patients with angiographically normal coronary arteries has not been evaluated yet. Our aim was to determine the prognostic role of positive MPS in patients with angina, positive exercise test and smooth coronary arteries (syndrome X).info:eu-repo/semantics/publishe

Impact and evolution of right ventricular dysfunction after successful MitraClip implantation in patients with functional mitral regurgitation

Right ventricular dysfunction (RVdysf) is a predictor of poor outcome in patients with heart failure and valvular disease. The aim of this study was to evaluate the evolution and the impact of RVdysf in patients with moderate–severe functional mitral regurgitation (FMR) successfully treated with MitraClip. From October 2008 to July 2014, 60 consecutive high surgical risk FMR patients were evaluated and stratified into two groups: RVdysf group (TAPSE < 16 mm and/or S′TDI < 10 cm/s, 21 patients) and No-RVdysf group (38 patients). The overall mean age of patients was 73 ± 8 (83% male). Ischemic FMR etiology was present in 67%. Mean LVEF was 30 ± 10%. Overall mean time follow-up was 565 ± 310 days. The only significant difference between the two groups was a greater prevalence of stroke, ICD and use of aldosterone antagonist in RVdysf group. Acute procedural success was achieved in 90% of patients. At 6-month echo-matched analysis significant RV function improvement was observed in patients with baseline RVdysf (TAPSE 15 ± 3.0 vs. 19 ± 4.5, p = 0.007, S′TDI 7 ± 1.2 vs. 11 ± 2.8, p < 0.0001, baseline vs. 6-month, respectively). The mean improvement in the 6-min walking test was significant in both groups (120 and 143 m, RVdysf and No-RVdysf groups, respectively). At Kaplan–Meier analysis, the presence of RVdysf did not affect the outcome in terms of freedom from composite efficacy endpoint. This study shows that successful MitraClip implantation in patients with FMR and concomitant right ventricular dysfunction yields significant improvement of RV function at mid-term follow-up. Further data on larger population will be required to confirm our observations