Impact of time off anticoagulation in patients with continuous-flow left ventricular assist devices.

Patients with left ventricular assist devices (LVADs) receive anticoagulation to decrease the risk of thrombosis. Various circumstances require discontinuing anticoagulation in LVAD patients, but the risks entailed are not well defined. In a retrospective review of LVAD implantation procedures, we examined the effect of time off anticoagulation on thrombosis and mortality rates after implantation. An international normalized ratio ≤ 1.5 was used to screen for patients taken off anticoagulation. Patients were divided into three groups by the cumulative number of days off anticoagulation: no discontinuation, short-term discontinuation (< 30 days), and long-term discontinuation (≥ 30 days). Rates of ischemic stroke, pump thrombosis, and mortality were compared among groups. Of 245 patients who underwent LVAD implantation during the study, 70 (28.6%) were off anticoagulation during follow-up: 37 (15.1%) had short-term discontinuation (median, 11 days), and 33 (13.5%) had long-term discontinuation (median, 124 days). Patients with long-term discontinuation had a higher rate of ischemic stroke (adjusted hazard ratio 8.5, p = 0.001) and death (adjusted hazard ratio 3.9, p = 0.001). The three groups did not differ in pump thrombosis rate. We conclude that after LVAD implantation, discontinuing anticoagulation for ≥ 30 days is independently associated with an increased risk of ischemic stroke and death.

Central nervous system intravascular lymphoma leading to rapidly progressive dementia.

Intravascular lymphoma is an uncommon subtype of B-cell lymphoma with neoplastic cells limited to the lumen of small blood vessels. We report a case of a 52-year-old man who presented with constitutional symptoms and rapidly progressive dementia. He was found to have diffuse leptomeningeal and faint parenchymal enhancement on magnetic resonance imaging and was subsequently diagnosed with intravascular lymphoma following a brain biopsy. He responded remarkably well to systemic and intrathecal chemotherapy. The diagnosis and treatment of intravascular lymphoma have been guided by a few case reports and are largely based on expert opinion.

Complex Left Atrial Appendage Morphology Is an Independent Risk Factor for Cryptogenic Ischemic Stroke.

Importance: Ischemic strokes pose a significant health burden. However, the etiology of between 20 and 40% of these events remains unknown. Left atrial appendage morphology may influence the occurrence of thromboembolic events. Design: A retrospective cross-sectional study was conducted to investigate the role of LAA morphology in patients with atrial fibrillation (AF) and cardioembolic-associated stroke and patients with cryptogenic stroke without atrial fibrillation. LAA morphology is classified into two groups: (1) simple (chicken-wing) vs. (2) complex (non-chicken wing) based on transesophageal echocardiography (TEE) findings. In addition to the LAA morphology, left atrial parameters, including orifice diameter, depth, emptying velocity, and filling velocity, were collected for both groups. Mathematical, computational models were constructed to investigate flow velocities in chicken-wing and non-chicken wing morphological patterns to assess LAA function further. Findings: TEE values for volume, size, emptying, and filling velocities were similar between simple and complex LAA morphology groups. Patients with cryptogenic stroke without coexisting AF were noted to have significantly higher rates of complex LAA morphology. Chicken-wing LAA morphology was associated with four-fold higher flow rate (kg/s) in computational simulations. Conclusions: Complex LAA morphology may be an independent contributing factor for cryptogenic strokes. Further studies are warranted to investigate the mechanism involved in LAA morphology and thromboembolic events.

Anomalous Left Coronary Artery From the Right Sinus of Valsalva in a Patient Presenting with ST-Segment Elevation in Lead aVR: A Case Report.

BACKGROUND: Anomalous coronary artery origins appear in roughly 1% of coronary angiograms, and up to 15% of syncope and sudden cardiac death events can be attributed to anomalous coronaries. Patients with an anomalous coronary artery arising from the opposite sinus may initially present with syncope and electrocardiographic findings of ischemia. CASE REPORT: We describe a case in which an adolescent male presented with exercise-induced angina and syncope, and his initial electrocardiogram (ECG) showed diffuse ST-segment depression with ST-segment elevation in lead aVR. Cardiac catheterization revealed there was no coronary ostium in the left coronary cusp, and the left coronary artery had an anomalous origin from the right cusp. The patient received urgent left internal mammary artery-to-left anterior descending artery coronary bypass and a saphenous vein graft to the ramus intermedius. After he underwent 6 months of medical therapy with ß-blockade and angiotensin-receptor blockade, his left ventricular systolic function improved to low-normal level (left ventricular ejection fraction, approximately 50%). WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: ST-segment elevation in lead aVR is strongly prognostic for left main or triple-vessel coronary artery disease. However, in patients who present with syncope and few other coronary artery disease risk factors, this ECG finding should be suggestive of an ischemic event caused by an anomalous left coronary artery. Early recognition of this pattern of clinical signs and ECG findings by an emergency physician could be critical for making the correct diagnosis and risk stratifying the patient for early coronary angiography and urgent surgical revascularization.

Aspergillus endocarditis of the mitral valve with ventricular myocardial invasion, cerebral vasculitis, and intracranial mycotic aneurysm formation in a patient with hemophagocytic lymphohistiocytosis.

Aspergillus endocarditis is a rare infection and reported mainly in immunocompromised hosts. We report a case of mitral valve aspergillus endocarditis with ventricular myocardial invasion, cerebral vasculitis and intracranial fungal aneurysm formation in a patient with hemophagocytic lymphohistiocytosis (HLH). This case illustrates the importance of prompt investigation and treatment of masses seen on an echocardiogram for rare infections such as Aspergillus endocarditis in immunocompromised patients.

Disseminated Pasteurella multocida infection: Cellulitis, osteomyelitis, and myositis.

A 67-year-old man with poorly controlled type II diabetes mellitus was evaluated for right lower extremity erythema and swelling and left-sided lower back pain. He was found to have Pasteurella multocida bacteremia; magnetic resonance imaging showed osteomyelitis of the lumbar spine with myositis in the adjacent left paraspinal muscles. He was initially treated with intravenous antibiotics and was later transitioned to oral amoxicillin. He recovered completely with six weeks of antimicrobial therapy.

Hedgehog signaling regulates the generation of ameloblast progenitors in the continuously growing mouse incisor.

In many organ systems such as the skin, gastrointestinal tract and hematopoietic system, homeostasis is dependent on the continuous generation of differentiated progeny from stem cells. The rodent incisor, unlike human teeth, grows throughout the life of the animal and provides a prime example of an organ that rapidly deteriorates if newly differentiated cells cease to form from adult stem cells. Hedgehog (Hh) signaling has been proposed to regulate self-renewal, survival, proliferation and/or differentiation of stem cells in several systems, but to date there is little evidence supporting a role for Hh signaling in adult stem cells. We used in vivo genetic lineage tracing to identify Hh-responsive stem cells in the mouse incisor and we show that sonic hedgehog (SHH), which is produced by the differentiating progeny of the stem cells, signals to several regions of the incisor. Using a hedgehog pathway inhibitor (HPI), we demonstrate that Hh signaling is not required for stem cell survival but is essential for the generation of ameloblasts, one of the major differentiated cell types in the tooth, from the stem cells. These results therefore reveal the existence of a positive-feedback loop in which differentiating progeny produce the signal that in turn allows them to be generated from stem cells.

Respiratory physiology of the Oniscidea: aerobic capacity and the significance of pleopodal lungs.

The radiation of the terrestrial isopods (sub-order Oniscidea) has been accompanied by evolution of pleopodal lungs in the sections Tylida and Crinocheta. To understand the significance of such lungs for aerobic respiration, comparative studies were conducted using 6 species. Ligia occidentalis, lacking lungs, behaved as a metabolic conformer in reduced PO(2), and showed decreased V(.-)O(2) in low humidity and following dehydration. In species possessing lungs, metabolism was insensitive to dehydration. However, lung development did not show a clear relationship to metabolic regulation: Porcellio dilatatus was a metabolic conformer while Tylos punctatus and Armadillidium vulgare were efficient regulators. The metabolic conformers did not accumulate lactate during moderate hypoxia (10% O(2)), indicating that reduced V(.-)O(2) is not compensated with anaerobic glycolysis. In contrast, Alloniscus perconvexus, a littoral species with limited metabolic regulation, showed the largest lactate accumulation during hypoxia and also possessed the highest tissue LDH activity. It is hypothesized that these are adaptations to periodic hypoxia in sand burrows and the high metabolic cost of burrowing. Differences in lactate accumulation during immersion were curious, with the largest increases occurring in L. occidentalis and A. perconvexus that tolerate prolonged immersion in seawater. Possible functions of this lactate accumulation may include modulation of hemocyanin oxygen affinity.