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.

Acute blood loss anemia after COVID-19 nasopharyngeal sampling.

ABSTRACT: Long-term care residents with novel coronavirus disease 2019 (COVID-19) experience high mortality rates and require frequent screening. Most resident testing occurs via nasopharyngeal swab that potentially causes epistaxis with rates of 5% to 8% in healthy populations. It is estimated that 48% of long-term care residents receive oral anticoagulation that increases risk of bleeding. A long-term care resident receiving oral anticoagulation experienced an episode of acute blood loss anemia after nasopharyngeal sampling. Current medications were not reviewed before testing, and oral anticoagulation was not held resulting in acute blood loss anemia. A medication review is indicated for skilled nursing and assisted living residents to identify oral anticoagulation before nasopharyngeal testing. Less invasive testing may be recommended or should bleeding occur, discontinuation of oral anticoagulation for a short term may be appropriate.

To Study Acute Changes in Brain Oxygenation on MRI in Healthcare Workers Using N95 Mask and PPE Kits for Six Hours a Day.

Background Due to long working hours wearing an N95 mask and PPE kit during the COVID-19 pandemic, the healthcare workers (HCWs) complained of headaches, confusion, and exhaustion. This study was therefore performed to study the changes in brain oxygenation. Aim To compare brain oxygenation in health care workers wearing an N95 mask with a PPE kit versus a three-ply mask during an intensive care setting for 6 hours. Materials and Methods Thirty clinicians and 30 paramedical staff participated in the study. The control (three-ply mask) and subject (N95 mask with PPE) groups included 15 clinicians and 15 paramedical staff. A comparative analysis of brain oxygenation using a 3T magnetic resonance imaging (MRI) machine was performed in these two groups at the beginning and the end of their work shift. Results The mean age of the individuals in the control and subject groups was 30.8 and 30.13 years, respectively. The median value of brain oxygenation in the control and subject groups in the pre-shift was between 33 and 31 and post-shift was 30 and 24. The drop in brain oxygenation in subjects was more than the controls ( p = 0.004) in the post-shift assessments. The cerebral blood flow (CBF) in the bilateral middle cerebral artery (MCA) using arterial spin labeling (ASL) showed a rise in CBF in both groups post-shift as compared with the pre-shift values. The median values of the right and left MCA in the control and subject groups pre-shift were 82.75/83.45 and 89.75/106.65. The post-shift median values of both MCAs of the control and subject groups were 115.65/115.55 and 109.60/119.49. Conclusion MRI-BOLD imaging revealed a significant drop in brain oxygenation in the subject group as compared with the control group. Multiphasic-ASL showed a compensatory rise in CBF in both groups.

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.

A comparison of manual electrocardiographic interval and waveform analysis in lead 1 of 12-lead ECG and Apple Watch ECG: A validation study.

Background: The Apple Watch Series 4 (AW) can detect atrial fibrillation and perform a single-lead electrocardiogram (ECG), but the clinical accuracy of AW ECG waveforms compared to lead 1 of a 12-lead ECG is unclear. Objective: The purpose of this study was to assess the accuracy of interval measurements on AW ECG tracings in comparison to lead 1 on a 12-lead ECG. Methods: We obtained ECGs at a university hospital of healthy volunteers age >18 years. ECG waveforms were measured with calipers to the nearest 0.25 mm. When possible, 3 consecutive waveforms in lead 1 were measured. Waveform properties, including intervals, were recorded. Concordance correlation coefficients and Bland-Altman plots were used to assess level of agreement between devices. Results: Twelve-lead (n = 113) and AW (n = 129) ECG waveforms from 43 volunteers (mean age 31 years; 65% female) were analyzed. Sinus rhythm interpretation between devices was 100% concordant. No arrhythmias were recorded. Mean difference (d) for heart rate was 1.16 ± 4.33 bpm (r = 0.94); 3.83 ± 113.54 ms for RR interval (r = 0.79); 5.43 ± 17 ms for PR interval (r = 0.83); -6.89 ± 14.81 ms for QRS interval (r = 0.65); -11.27 ± 22.9 ms for QT interval (r = 0.79); and -11.67 ± 27 ms for QTc interval (r = 0.57). There was moderate (d <40 ms) to strong (d <20 ms or < 5 bpm) agreement between devices represented by Bland-Altman plots. Conclusion: The AW produces accurate ECGs in healthy adults with moderate to strong agreement of basic ECG intervals.

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.

Rotors in patients with persistent atrial fibrillation: case report of a left atrial appendage rotor identified by a novel computational mapping algorithm integrated into 3-dimensional mapping and termination of atrial fibrillation with ablation.

Recent clinical trials using panoramic mapping techniques have shown success in targeting rotors and focal impulses in atrial fibrillation (AF). Ablations directed toward these organized sources improve outcomes in AF. The left atrial appendage (LAA) has been suspected as a possible extrapulmonary source of AF, and ablation within the LAA or electrical isolation of the LAA improves outcomes in certain cases. This case highlights a unique example of panoramic imaging created with a computational mapping algorithm integrated in 3-dimensional mapping, which identified rotors within the LAA. Furthermore, ablations performed near an identified rotor core within the LAA terminated AF.

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.

Multiscale imaging of the human heart: Building the foundation for human systems physiology and translational medicine.

The development of human cardiovascular systems physiology is inhibited by the lack of multiscale functional physiological data, which represents human heart physiology at the molecular, cellular, tissue, organ, and system levels. We have developed an experimental approach to study explanted human hearts in vitro at multiple physiological scales with a wide array of imaging modalities. This approach has already yielded data indicating significant differences between animal models of diseases and actual human heart disease. Our data provides a quantitative foundation for multiscale physiological models of the cardiovascular system and will allow improvement in translation of medical technology and pharmacology from animal models to therapy.

Anatomy and electrophysiology of the human AV node.

The atrioventricular node (AVN) has mystified generations of investigators over the last century and continues today to be at the epicenter of debates among anatomists, experimentalists, and electrophysiologists. Over the years, discrepancies have remained in regard to correlating components of AVN structure to function, as evidenced by studies from microelectrodes, optical mapping, and the electrophysiology laboratory. Historically, the AVN has been defined by classical histological methods; however, with recent advances in molecular biology techniques, a more precise characterization of structure is becoming attainable. Distinct molecular compartments are becoming apparent based on connexin staining and genotyping, providing new insight into previously characterized functional aspects of the AVN and its surrounding structures. Advances in optical mapping have provided a unique opportunity for correlating structure and function--unmasking properties of the native AVN pacemaker and providing further insight into basic mechanisms involved in AV conduction. Additionally, procurement of explanted human hearts have provided a unique opportunity to further characterize the human AVN structurally and functionally with both molecular biology techniques and optical mapping. With the elucidation of basic elements of both structure and function via molecular investigation and optical mapping, new opportunities are becoming apparent in utilizing the unique properties of the AVN for pursuing novel clinical applications relevant to clinical electrophysiology.

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.