Area strain from 3D speckle-tracking echocardiography as an independent predictor of early symptoms or ventricular dysfunction in asymptomatic severe mitral regurgitation with preserved ejection fraction

The indication for surgery in asymptomatic severe mitral regurgitation (SMR) with preserved left ventricular ejection fraction (LVEF) is controversial. We sought to study 3D myocardial mechanics in this population and test 3D-speckle tracking (3DST) parameters as possible predictors of events. 45 asymptomatic patients with SMR and LVEF >60?% and 20 control individuals without cardiac disease underwent 3DST echocardiography. MR group additionally underwent further clinical monitoring. Dyspnea, LVEF under 60?%, or admissions for heart failure were considered as events. When compared with control group, MR group showed lower percentage of global 3D strain, (35.4?±?9.1 vs. 43.9?±?10.6; p?=?0.003), lower radial strain, lower area change rate and higher end-diastolic volume. In a follow-up time of 23.2?±?14.5 months we found 15 events (33.3?%). When comparing the remaining patients with this new-onset HF group we found significant differences in longitudinal strain (?17.9?±?3.3 vs. ?15.8?±?2.1; p?=?0.036), area strain (AS) (?48.6?±?4.6 vs. ?43.7?±?6.2; p?=?0.006), circumferential strain (?35.8?±?4.7 vs. ?31.8?±?6.1; p?=?0.034), 3D LVEF (67.1?±?4.6 vs. 63.0?±?7.4; p?=?0.034) and E/E′ index (13.5?±?3.9 vs. 19.3?±?9.5; p?=?0.006). In multivariate Cox regression AS alone was the only independent predictor. A cutoff value of AS greater than ?41.6?% reached a hazard ratio of 4.41 (p?=?0.004) for prediction of events. In asymptomatic patients with SMR and preserved ejection fraction, 3DST derived AS is a promising tool for predicting the development of heart failure. This finding may be useful for guiding the selection of patients for early mitral valve repair/replacement surgery even if they are asymptomatic.     

Three-dimensional power Doppler vascular network assessment of adnexal masses: intraobserver and interobserver agreement analysis.

OBJECTIVE: The purpose of this study was to assess intraobserver and interobserver agreement for tumor vascular network evaluation as assessed by 3-dimensional (3D) power Doppler sonography for discriminating benign from malignant adnexal masses. METHODS: Stored 3D power Doppler angiographic volume data from 39 women with a diagnosis of a vascularized adnexal mass who were evaluated and treated at our institution were retrieved from our database for analysis. Two different examiners (observer A, with 6 years of experience in 3D sonography; and observer B, with 1 year of experience) reviewed 3D sonograms blinded to each other. Three-dimensional vascular network reconstruction was done with surface rendering in the color mode. Malignancy was considered in the presence of at least 2 of the following: irregular branching, vessel caliber changes, microaneurysms, and vascular lakes. A definitive histologic diagnosis was obtained in all cases. Intraobserver and interobserver agreement rates were estimated by calculating the kappa index. RESULTS: Twenty (51%) tumors were malignant, and 19 (49%) were benign. Intraobserver agreement was good for observer A (kappa = 0.69) and moderate for observer B (kappa = 0.54). Interobserver agreement was moderate (kappa = 0.49). CONCLUSIONS: We found intraobserver and interobserver agreement to be moderate for 3D power Doppler assessment of the vascular network in adnexal masses.     

Cyclodextrin Protects Podocytes in Diabetic Kidney Disease

Diabetic kidney disease (DKD) remains the most common cause of end-stage kidney disease despite multifactorial intervention. We demonstrated that increased cholesterol in association with downregulation of ATP-binding cassette transporter ABCA1 occurs in normal human podocytes exposed to the sera of patients with type 1 diabetes and albuminuria (DKD⁺) when compared with diabetic patients with normoalbuminuria (DKD⁻) and similar duration of diabetes and lipid profile. Glomerular downregulation of ABCA1 was confirmed in biopsies from patients with early DKD (n = 70) when compared with normal living donors (n = 32). Induction of cholesterol efflux with cyclodextrin (CD) but not inhibition of cholesterol synthesis with simvastatin prevented podocyte injury observed in vitro after exposure to patient sera. Subcutaneous administration of CD to diabetic BTBR (black and tan, brachiuric) ob/ob mice was safe and reduced albuminuria, mesangial expansion, kidney weight, and cortical cholesterol content. This was followed by an improvement of fasting insulin, blood glucose, body weight, and glucose tolerance in vivo and improved glucose-stimulated insulin release in human islets in vitro. Our data suggest that impaired reverse cholesterol transport characterizes clinical and experimental DKD and negatively influences podocyte function. Treatment with CD is safe and effective in preserving podocyte function in vitro and in vivo and may improve the metabolic control of diabetes.Diabetic kidney disease (DKD) is responsible for nearly half of the incidents of end-stage kidney disease in the U.S. (1), yet our current understanding of the pathophysiological processes responsible for DKD has led to limited improvements in patient outcomes. Multifactorial intervention reduces the rate of progression of DKD but does not prevent end-stage kidney disease in type 1 (T1D) or type 2 diabetes (T2D) (2,3). A key factor for this translation gap is the current lack of adequate mechanistic insight into DKD in humans.The kidney glomerulus is a highly specialized structure that ensures the selective ultrafiltration of plasma so that essential proteins are retained in the blood (4). Podocytes are glomerular epithelial cells that contribute to the glomerular filtration barrier through a tight regulation of actin cytoskeleton remodeling (4). Currently, the diagnosis of DKD relies on the detection of microalbuminuria (5). However, a growing body of evidence suggests that key histological lesions precede the development of albuminuria (6,7); among them, decreased podocyte number (podocytopenia) has been described as an independent predictor of DKD progression (8–12). Although we have previously shown that podocyte insulin resistance and susceptibility to apoptosis is already present at the time of onset of microalbuminuria in experimental models of DKD, the cause of podocyte injury in early DKD remains unknown (13).We used a previously established cell-based assay in which differentiated human podocytes are exposed to 4% patient sera for 24 h (14) to identify new pathways and targets in DKD. Podocytes exposed to the sera of patients with DKD showed increased cholesterol accumulation in association with downregulation of ATP-binding cassette transporter 1 (ABCA1) expression that was independent of circulating cholesterol.ABCA1 is a major regulator of cellular cholesterol homeostasis by mediating efflux to lipid-poor apolipoprotein acceptors in the bloodstream (15). ABCA1 genetic variants are strongly associated with the risk of coronary artery disease (16). Furthermore, the capacity of patient sera to induce ABCA1-mediated cholesterol efflux in macrophages is impaired in patients with T2D and incipient or overt nephropathy (17). Excessive cholesterol accumulation has been described in glomeruli of rodent models of T1D and T2D (18–20) and may contribute to DKD development and progression. Finally, inactivating mutations of ABCA1 result in Tangier disease, which causes premature atherosclerosis and proteinuria (21).Although interventions that increase ABCA1 expression (such as liver X receptor agonists) may be beneficial in DKD, they have a relatively high incidence of adverse events (22) as well as intrinsic lipogenic effects (23). We used β-cyclodextrins, cyclic oligosaccharides consisting of seven β(1-4)-glucopyranose rings, to remove cholesterol from differentiated human podocytes in vitro and from diabetic animals in vivo. The exact mechanism by which cyclodextrins (CDs) remove cholesterol from cells is not completely understood, but the formation of cholesterol/CD inclusion complexes at the membrane surface plays an important role in this process (24).We hypothesized that 2-hydroxypropyl-β-cyclodextrin, which was recently approved by the U.S. Food and Drug Administration (FDA) for the cure of Niemann-Pick disorder (25,26), would be an effective way to sequester cholesterol and to protect podocytes from cholesterol-dependent damage in DKD in vivo and in vitro.     

Conversion of atrial fibrillation to sinus rhythm during treatment with intravenous esmolol or diltiazem: a prospective, randomized comparison

Prior studies have suggested that intravenous diltiazem reduces the probability of spontaneous conversion of atrial fibrillation (AF) to sinus rhythm in the electrophysiology laboratory and in patients with postoperative AF. Whether diltiazem exerts the same effect in patients presenting to the emergency department (ED) with spontaneous AF is unclear. Fifty patients presenting to the ED with new-onset or paroxysmal AF and a rapid ventricular rate (>100 beats per minute) were randomly assigned to receive intravenous diltiazem or esmolol during the first 24 hours of presentation. Conversion to sinus rhythm occurred in 10 patients (42%) in the diltiazem group compared with 10 patients (39%) in the esmolol group (P = 1.0). Diltiazem does not decrease the likelihood of spontaneous conversion of AF to sinus rhythm in the ED setting.     

Expert Consensus on the Management of Patients with Postmenopausal Osteoporosis in the Spanish Healthcare System

Introduction

The management of postmenopausal osteoporosis (PMO) in routine clinical practice differs considerably from guideline recommendations. The objective of our study was to reach a consensus on the management of PMO, considering prevention, diagnosis, treatment and follow-up, according to expert opinion in Spain.

Methods

A two-round Delphi technique was conducted, including 38 experts. The questionnaire contained 35 sections, each one including 1–10 questions (n = 308) based on a literature review and contributions from the scientific steering committee. Each question was scored by experts from the current (1 = no occurrence, 9 = occurrence in all cases), wish (1 = total rejection; 9 = wish) and prediction (1 = no occurrence at all; 9 = occurs with maximum probability) perspectives. Consensus (wish and prediction perspectives) was considered when ≥75% of experts scored 7–9 (agreement) or 1–3 (disagreement).

Results

Overall, consensus was achieved on 75% of questions. While protocols of clinical management and consultation/referral should be followed, their implementation is unlikely. Furthermore, the medical specialties currently involved in PMO management are poorly defined. PMO patients without fracture should be managed (prevention, diagnosis, treatment and follow-up) in both primary care and rheumatology settings; however, experts predicted that only treatment and follow-up will be assumed by these specialties. A multidisciplinary team should be involved in patients with fracture. No assessment tools are usually applied, and prediction indicated that they will not be used.

Conclusion

Efforts should be focused on questions with high divergence between wishes and predictions, defining actions that will improve PMO management. Collaboration between scientific societies and health authorities to address the identified opportunities of improvement is proposed.

Funding

Amgen S.A.

     

Review of morphology,development, and evolution of the notarium in birds

The notarium is a rigid bony structure, which resulted from the fusion of thoracic vertebrae of some pterosaurs and birds. It is high variable, ranging from two to six fused thoracic vertebrae. In this study, we reviewed and analyzed approximately 270 specimens of neornithine birds (representing 80% of the living orders) and some fossils in order to identify the number of fused vertebrae, degree and sites of vertebral fusion, occurrence of sutures, and other structures of potential phylogenetic and functional significance. These data were analyzed using a recent time-calibrated molecular phylogenetic tree and principal component analyses analysis evaluating the relationship with long bones in order to reconstruct macroevolutionary trends related to the evolution of the notarium. The occurrence of this structure shows a mosaic distribution over neornithine phylogeny, originating several times independently, especially during the Paleogene, in predominantly ground-dwelling forms. The notarium of these groups is characterized by: neural spines fused into single structure, intervertebral openings small to absent, large ventral keels forming ventral plates, and fused transverse processes. Derived neornithines, such as aquatic forms and long-legged birds, have a tendency to display a decreased degree of fusion between the vertebrae, which may indicate a reduction or disappearance of the notarium.     

Clinical Utility and Economic Impact of Conventional Transbronchial Needle Aspiration of Mediastinal Lymphadenopathies in Bronchogenic Carcinoma

ObjectivesTo analyse the clinical utility and economic impact of conventional transbronchial needle aspiration (TBNA) in patients with diagnosis of bronchogenic carcinoma (BC) and mediastinal lymphadenopathies in thoracic computed tomography (CT). To assess the predictive factors of valid aspirations.Patients and methodsRetrospective observational study between 2006 and 2011 of all TBNA performed in patients with final diagnosis of BC and accessible hilar or mediastinal lymphadenopathies on thoracic CT.ResultsWe performed TBNA on 267 lymphadenopathies of 192 patients. In 34.9% of patients, two or more lymph nodes were biopsied. Valid aspirations were obtained in 153 patients (79.7%) that were diagnostic in 124 patients (64.6%). Multivariate analysis showed that factors associated with valid or diagnostic results are the diameter of the lymph node and the number of lymph nodes explored. TBNA was the only endoscopic technique that provided the diagnosis of BC in 54 patients (28.1%). Staging mediastinoscopy was avoided in 67.6% of patients. The prevalence of mediastinal lymph node involvement was 74.4%, sensitivity of TBNA was 86.2% and negative predictive value was 63.6%. Including mediastinoscopy and other avoided diagnostic techniques, TBNA saved 451.57 € per patient.ConclusionsTBNA is a clinically useful, cost-effective technique in patients with BC and mediastinal or hilar lymphadenopathies. It should therefore be performed on a regular basis during diagnostic bronchoscopy of these patients.     

Topical application of the lectin Artin M accelerates wound healing in rat oral mucosa by enhancing TGF‐β and VEGF production

The lectin Artin M has been shown to accelerate the wound‐healing process. The aims of this study were to evaluate the effects of Artin M on wound healing in the palatal mucosa of rats and to investigate the effects of Artin M on transforming growth factor beta (TGF‐β) and vascular endothelial growth factor (VEGF) secretion by rat gingival fibroblasts. A surgical wound was created on the palatal mucosa of 72 rats divided into three groups according to treatment: C—Control (nontreated), A—Artin M gel, and V—Vehicle. Eight animals per group were sacrificed at 3, 5, and 7 days postsurgery for histology, immunohistochemistry and determination of the levels of cytokines, and growth factors. Gingival fibroblasts were incubated with 2.5 μg/mL of Artin M for 24, 48, and 72 hours. The expression of VEGF and TGF‐β was determined by enzyme‐linked immunosorbent assay. Histologically, at day 7, the Artin M group showed earlier reepithelialization, milder inflammatory infiltration, and increased collagen fiber formation, resulting in faster maturation of granular tissue than in the other groups (p < 0.05). Artin M–induced cell proliferation in vivo and promoted a greater expression of TGF‐β and VEGF in both experiments (p < 0.05). Artin M was effective in healing oral mucosa wounds in rats and was associated with increased TGF‐β and VEGF release, cell proliferation, reepithelialization, and collagen deposition and arrangement of fibers.