Supervised Exercise Therapy for Intermittent Claudication: A Propensity Score Matched Analysis of Retrospective Data on Long Term Cardiovascular Outcomes.

OBJECTIVE: This study aimed to explore the long term outcomes of patients with intermittent claudication (IC) who completed supervised exercise therapy (SET) vs. those who declined or prematurely discontinued SET, focusing on the incidence of chronic limb threatening ischaemia (CLTI), revascularisation, major adverse limb events (MALE), and major adverse cardiovascular events (MACE). METHODS: A retrospective registry analysis of consecutive patients with IC who were referred for SET between March 2015 and August 2016 and followed up for a minimum of five years. Serial univariable analysis and logistic regression were performed to identify the statistically significant clinical variables that were independent predictors of each outcome measure. The resulting statistically significant variables were used to guide 1:1 propensity score matching (PSM) using the nearest neighbour method with a calliper of 0.2. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between SET and the outcomes of interest. RESULTS: Two hundred and sixty-six patients were referred to SET between March 2015 and August 2016. Of these, 64 patients completed SET and 202 patients did not. After PSM, 49 patients were analysed in each cohort. The Cox proportional hazards analysis revealed a significant association between completion of SET and revascularisation requirement (HR 0.46 95% CI 0.25 - 0.84; p = .011), completion of SET and progression to CLTI (HR 0.091, 95% CI 0.04 - 0.24; p < .001), completion of SET and MACE (HR 0.52; 95% CI 0.28 - 0.99; p = .05) and completion of SET and MALE (HR 0.28, 95% CI 0.13 - 0.65; p = .003). The Harrell's C index for all of these models was greater than 0.75, indicating good predictive accuracy. CONCLUSION: Completion of SET is associated with better outcomes in patients who completed SET compared with patients who declined or discontinued SET with respect to clinically important cardiovascular outcomes over seven years.

Regeneration of hyaline cartilage in osteochondral lesion model using L-lysine magnetic nanoparticles labeled mesenchymal stem cells and their in vivo imaging.

Treatment of osteochondral defects continues to pose a major challenge for patients and orthopedic surgeons due to the limited healing potential of articular cartilage. Mesenchymal stem cells (MSCs) possess therapeutic potential for the treatment of osteochondral pain and pathology. However, it is necessary to use proper labeling and imaging agent of stem cells that can decipher its role posttransplantation. A major limitation of routinely used contrast agents is signal dilution over a period of time which limits its use for further studies. At the same time, regeneration of fibrocartilage over native hyaline cartilage also limits the use of conventional therapies. The present study evaluates the efficacy of bone marrow-derived mesenchymal stem cells (BMSCs) for the treatment of osteochondral defect in rats with the regeneration of hyaline cartilage in situ and in vivo monitoring of the stem cells using L-lysine functionalized magnetic iron oxide nanoparticles (lys-IONPs). L-lysine stabilizes the iron oxide nanoparticles, enhances the biocompatibility, and provides functionalities for efficient stem cell labeling. in vitro toxic effects of lys-IONPs on mitochondrial impairment, morphological alterations, and actin cytoskeleton reveal minimum damage to BM-MSCs. Histological data (H and E, Masson's trichrome and immunohistochemistry) describe the early initiation of healing and regeneration of hyaline-like cartilage over fibrocartilage in stem cell treated groups. MR scans demonstrate generation of hypointense signals in lys-IONPs-BMSCs with improved signal intensity and minimum loss over 28 days revealing its use as a long-term stem cell labeling and imaging agent.

Fluoroless catheter ablation in adults: a single center experience.

BACKGROUND: Ablation procedures for arrhythmias have increased in frequency and complexity over the last decade. Improvements in technology have allowed for less reliance on fluoroscopy to guide these procedures. Ablation without fluoroscopy has been reported in small cohorts. We report a single center experience of fluoroless ablation after adoption of this technique for all endovascular ablations. METHODS: This retrospective study evaluated 107 consecutive patients who underwent a catheter ablation procedure for an atrial or ventricular arrhythmias after adoption of a completely fluoroless technique. No fluoroscopy was used in any case. A mapping system was utilized in all cases. Intracardiac echocardiography (ICE) catheters were utilized in 75 of the ablation cases (70.4%). Of the 107 patients who underwent EP study, three patients did not undergo ablation as they were non-inducible for SVT. Of the remaining 104 patients, 56 patients (53.8%) underwent ablation for atrial fibrillation, 23 patients (22.1%) for SVT, 10 patients (9.6%) for lone atrial flutter, and 16 patients (15.4%) for a ventricular arrhythmia including PVC, idiopathic VT or ventricular tachycardia. RESULTS: Catheters were able to be placed in 100% of patients without complication. Time to placement in the coronary sinus was 2.1 min ± 1.4 min. Mean transseptal time was 3.54 min ± 3 min. Mean procedure time for all ablations was 2 h 6 min ± 50 min. There were no complications in the series of patients. CONCLUSIONS: Fluoroless ablation is feasible and safe with acceptable procedure times. Adoption of this technique is encouraged in order to eliminate unnecessary risk of fluoroscopy.

A comprehensive manually curated reaction map of RANKL/RANK-signaling pathway.

Receptor activator of nuclear factor-kappa B ligand (RANKL) is a member of tumor necrosis factor (TNF) superfamily that plays a key role in the regulation of differentiation, activation and survival of osteoclasts and also in tumor cell migration and bone metastasis. Osteoclast activation induced by RANKL regulates hematopoietic stem cell mobilization as part of homeostasis and host defense mechanisms thereby linking regulation of hematopoiesis with bone remodeling. Binding of RANKL to its receptor, Receptor activator of nuclear factor-kappa B (RANK) activates molecules such as NF-kappa B, mitogen activated protein kinase (MAPK), nuclear factor of activated T cells (NFAT) and phosphatidyl 3-kinase (PI3K). Although the molecular and cellular roles of these molecules have been reported previously, a systematic cataloging of the molecular events induced by RANKL/RANK interaction has not been attempted. Here, we present a comprehensive reaction map of the RANKL/RANK-signaling pathway based on an extensive manual curation of the published literature. We hope that the curated RANKL/RANK-signaling pathway model would enable new biomedical discoveries, which can provide novel insights into disease processes and development of novel therapeutic interventions.

Cardiac tamponade as a presenting manifestation of Sheehan syndrome.

We report a 38-year-old Syrian woman who presented with progressive breathlessness, hypotension and circulatory collapse. Echocardiogram revealed a large pericardial effusion with evidence of cardiac tamponade. There was a history of secondary amenorrhoea, loss of axillary and pubic hair following childbirth at 28 years of age. Investigations revealed low levels of gonadotrophins, oestrogen, prolactin and thyrotrophin but normal levels of basal and post-synacthen (ACTH) cortisol. An MRI of the sella showed atrophic changes of the pituitary. She was treated with intravenous fluids, dopamine infusion, intravenous hydrocortisone and thyroxine replacement. The clinical suspicion of Sheehan syndrome facilitated early administration of corticosteroids, adequate thyroxine replacement and rapid resolution of pericardial effusion.

Characterization of the inflammatory and apoptotic cells in the aortas of patients with ascending thoracic aortic aneurysms and dissections.

OBJECTIVE: The histopathologic abnormality underlying ascending aortic aneurysm and dissection is medial degeneration, a lesion that is described as the noninflammatory loss of smooth muscle cells and elastic fibers. This study sought to determine whether inflammatory cells are present in medial degeneration and assess any possible contribution of these cells to apoptosis of smooth muscle cells. METHODS: Aortic specimens were obtained from patients undergoing prophylactic surgical repair of an ascending aortic aneurysm (n = 9) and type A dissection (n = 7), along with control patients dying of causes unrelated to aortic disease (n = 5). Immunohistochemical staining was performed to evaluate the presence of lymphocytes and macrophages, and markers of apoptosis were assessed in the aortas of patients with ascending aortic aneurysm and dissection. RESULTS: Immunohistochemical study indicated significantly more CD3+ cells in the aortas of patients with aneurysms or dissections than in control aortas (P = .020 and P = .0022, respectively). In addition, aortas of patients with aneurysms or dissections had more CD68+ cells (P = .01 and P = .005, respectively). CD3+ cells were localized in the media and surrounding the vasa vasorum in the adventitia. Cells yielding a positive result on in situ terminal transferase-mediated deoxyuridine triphosphate nick end-labeling were found in increased numbers in the aortas of patients with aneurysms or dissections relative to control aortas (P = .005 and P = .002, respectively). Furthermore, Fas and FasL were increased in the aortic samples from patients with aneurysms and dissections relative to control aortas. CONCLUSION: The coexistence of inflammatory cells with markers of apoptotic vascular cell death in the media of ascending aortas with aneurysms and type A dissections raises the possibility that activated T cells and macrophages may contribute to the elimination of smooth muscle cells and degradation of the matrix associated with thoracic aortic aneurysms and dissections.