Adjunctive therapies to reduce thrombotic events in patients with a history of myocardial infarction : role of vorapaxar

© 2015 Farag et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) LicenseAcute myocardial infarction (AMI) is generally attributed to coronary atherothrombotic disease. Platelet activation is essential for thrombus formation and is thus an important target for pharmacological intervention to prevent and treat AMI. Despite contemporary treatment with dual antiplatelet therapy, including acetylsalicylic acid and adenosine diphosphate receptor antagonists, patients with prior AMI remain at increased risk of future thrombotic events. This has stimulated the search for more potent antithrombotic agents. Among these is the oral protease-activated receptor-1 antagonist vorapaxar, which represents a new oral antiplatelet agent to reduce thrombotic risk in patients with atherothrombotic disease. The TRACER and the TRA 2°P-TIMI 50 trials concluded that vorapaxar in addition to standard therapy reduced ischemic adverse cardiac events. A remarkable benefit was observed in patients with stable atherosclerotic disease, particularly those with a previous history of AMI. Although favorable effects were seen in reduction of adverse cardiac events, this was associated with excess major and intracranial bleeding, particularly in patients at high risk of bleeding and those with a history of stroke or transient ischemic attack. Currently, the lack of a reliable individualized risk stratification tool to assess patients for thrombotic and bleeding tendencies in order to identify those who might gain most net clinical benefit has led to limited use of vorapaxar in clinical practice. Vorapaxar may find a niche as an adjunct to standard care in patients at high risk of thrombotic events and who are at low risk of bleeding.Peer reviewe

Selective Serotonin-Norepinephrine Reuptake Inhibitors-Induced Takotsubo Cardiomyopathy

CONTEXT: Takotsubo translates to octopus pot in Japanese. Takotsubo cardiomyopathy (TTC) is characterized by a transient regional systolic dysfunction of the left ventricle. Catecholamine excess is the one most studied and favored theories explaining the pathophysiology of TTC. CASE REPORT: We present the case of a 52-year-old Hispanic female admitted for venlafaxine-induced TTC with a review literature on all the cases of Serotonin-norepinephrine reuptake inhibitors (SNRI)-associated TTC published so far. CONCLUSION: SNRI inhibit the reuptake of catecholamines into the presynaptic neuron, resulting in a net gain in the concentration of epinephrine and serotonin in the neuronal synapses and causing iatrogenic catecholamine excess, ultimately leading to TTC

Robotic Surgery and Successful Set-Up: A Stepwise Approach

Robot purchase, implementation, and sustainability require a number of key challenges to overcome. We provide our experience of managing a potentially daunting task, summarizing the key steps to help deliver such an exciting project. We will take you through team approach options for purchase and safe implementation in the current financial climate

Delayed Spontaneous Recanalization of Chronic Total Occlusion of Left Anterior Descending Artery after Attempted but Failed Revascularization During Percutaneous Coronary Intervention

Chronic total occlusion (CTO) of coronary artery remains the Achilles heel of the interventional cardiologist and is present in a significant proportion of referrals for coronary artery bypass graft surgery (CABG); however, with the development and standardization of modern CTO recanalization techniques, it has been able to achieve excellent success while coping with lesions of increasing complexity. Nevertheless, failure to recanalize despite the development of new techniques still remains one of the challenges in the field of interventional cardiology. Spontaneous recanalization has been described in nonocclusive coronary artery dissections in detail; none has addressed the possibility of spontaneous recanalization after failed percutaneous coronary intervention (PCI). We report a case of spontaneous but delayed recanalization of CTO of left anterior descending artery 3 years after attempted but failed revascularization during PCI

Surgical anatomy of the pudendal nerve and its branches in South Africans

Dissection of the pudendal nerve (PN) and its branches in 71 cadavers revealed anatomic variations not previously described. Knowledge of this variation is necessary to prevent nerve injury resulting in sexual of sensory dysfunction. Because descriptions vary, this study re-evaluated the anatomy of the PN as implicated in perineal procedures in South Africans. The course of the PN from the gluteal region into the perineum was dissected in an adult sample of both sexes and of African and European ancestry. Distances between PN and branches to applicable landmarks were measured. Basic descriptive statistics and comparisons were carried out between groups. In 5/13 African females, the inferior rectal nerve (IRN) entered the gluteal region separately and in 12/13 cases it passed medial to the ischial spine with the PN. The dorsal nerve of the clitoris or penis (DNC/DNP) was closer to the bony frame in those of European ancestry. The IRN branches were more superficial in females, but deeper in males of European ancestry. In African females, a PN block and Richter stitch should be placed more medial. Outside-in transobturator tape procedures might endanger the DNC/DNP in obese individuals. In females of European ancestry the IRN branches are compromised during ischioanal abscess drainage. In males of European ancestry, the dorsal penile nerve block might be less effective. Predictions should be verified clinically.http://www.nature.com/ijir2015-12-31hb201

Determination of the bioavailability and biodistribution of a single dose of oral cholecalciferol/Calcirol® soft gelatin capsule by pharmacoscintigraphy- CalSci study

Background: It is required to study the bioavailability and biodistribution of specific cholecalciferol formulation before prescribing. Pharmacoscintigraphy is an established radiological-imaging technique that is used to map various drug formulations as they traverses the human body (biodistribution) in real-time. We evaluated the bioavailability and biodistribution pattern, transit time, and gastrointestinal clearance of a single dose of Calcirol® soft gelatin capsule 60,000 IU [an oral cholecalciferol (vitamin D) formulation] using pharmacoscintigraphy. Methods: Six male healthy adult volunteers were administered a single oral dose of Calcirol® soft gelatin capsule labelled with technetium-99m. Post-dosing, serial venous blood samples were collected till day 27 for the estimation of the plasma levels of 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol levels. Different pharmacokinetic parameters were calculated. Sequential static gamma imaging was performed to evaluate the biodistribution of Calcirol® soft gelatin capsule. Descriptive statistics was used. Various pharmacokinetic parameters were calculated from the concentration-time curves. Statistical analysis was carried out using Student’s t-test. Suitable multivariate analysis was performed based on the distribution of data. All statistical analyses were performed using SAS® Software (v 9.4). Results: The overall absorption of Calcirol® soft gelatin capsule was 93.23%, which was fully from the small intestine. It led to achieving a sufficient level of 25-hydroxycholecalciferol (>60 ng/ml) within 6 hours of oral intake. The levels of plasma 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol increased (maximum around 6 and 18 days, respectively). The small intestinal residence time was around 16 hours. No adverse event was noted. Conclusions: This was the first pharmacoscintigraphy study in the world which demonstrated the favourable bio-distribution of the Calcirol softgels supporting its role in vitamin D supplementation

Opposite changes in the expression of clathrin and caveolin-1 in normal and cancerous human prostate tissue: putative clathrin-mediated recycling of EGFR

Endocytosis, an important macromolecule uptake process in cells, is known to be dysregulated in cancer. Clathrin and caveolin-1 proteins play a major role in receptor-mediated endocytosis. We have used a quantitative, unbiased and semi-automated method to measure in situ protein expression of clathrin and caveolin-1 in cancerous and paired normal (cancer adjacent, non-cancerous) human prostate tissue. There was a significant (p < 0.0001) increase in the expression of clathrin in prostate cancer samples (N = 29, n = 91) compared to normal tissue (N = 29, n = 67) (N = number of patients, n = number of cores in tissue arrays). Conversely, there was a significant (p < 0.0001) decrease in expression of caveolin-1 in prostate cancer tissue compared to normal prostate tissue. The opposite change in expression of the two proteins was highly correlated to increasing cancer aggressiveness. There was also a concurrent increase in the expression of epidermal growth factor receptor (EGFR), a key receptor in carcinogenesis, with clathrin in prostate cancer tissue, indicating recycling of EGFR through clathrin-mediated endocytosis (CME). These results indicate that in prostate cancer, caveolin-1-mediated endocytosis (CavME) may be acting as a brake and increase in CME may facilitate tumorigenicity and aggressiveness of prostate cancer through recycling of EGFR. Changes in the expression of these proteins can also potentially be used as a biomarker for prostate cancer to aid in diagnosis and prognosis and clinical decision-making

Enhanced Recovery after Urological Surgery: A Contemporary Systematic Review of Outcomes, Key Elements, and Research Needs

Enhanced Recovery after Surgery (ERAS) programs are multimodal care pathways that aim to decrease intra-operative blood loss, decrease postoperative complications, and reduce recovery times

Implementation of PSMA PET/CT and alignment of ordering to SNMMI appropriate use criteria in a large network system

INTRODUCTION: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides appropriate use criteria (AUC) for prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) which include guidance on imaging in newly diagnosed prostate cancer and in patients with biochemically recurrent (BCR) disease. This study aims to examine trends in PSMA implementation and the prevalence and outcomes of scans ordered in scenarios deemed rarely appropriate or not meeting SNMMI AUC. METHODS: We retrospectively identified patients who were diagnosed with presumptive National Comprehensive Cancer Network unfavorable intermediate, high, or very high risk prostate cancer, patients who underwent staging for BCR, and all patients staged with PSMA between July 2021 and March 2023. Positivity was validated by adherence to a predetermined reference standard. RESULTS: The frequency of PSMA use increased in initial staging from 24% to 80% and work-up of BCR from 91% to 99% over our study period. In addition, 5% (17/340) of PSMA scans ordered for initial staging did not meet AUC and 3% (15/557) of posttreatment scans were deemed rarely appropriate. Initial staging orders not meeting SNMMI AUC resulted in no positivity (0/17), while rarely appropriate posttreatment scans were falsely positive in 75% (3/4) of cases. Urologists (53%, 17/32) comprised the largest ordering specialty in rarely appropriate use. CONCLUSION: The frequency of PSMA use rose across the study period. A significant minority of patients received PSMA PET/CT in rarely appropriate scenarios yielding no positivity in initial staging and significant false positivity post-therapy. Further education of providers and electronic medical record-based interventions could help limit the rarely appropriate use of PET imaging

Paediatric reference values for total psoas muscle area

Background: Sarcopenia, the unintentional loss of skeletal muscle mass, is associated with poor outcomes in adult patient populations. In adults, sarcopenia is often ascertained by cross-sectional imaging of the psoas muscle area (PMA). Although children with chronic medical illnesses may be at increased risk for muscle loss because of nutritional deficiencies, physical deconditioning, endocrine anomalies, and systemic inflammation, consistent quantitative definitions for sarcopenia in children are lacking. We aimed to generate paediatric reference values for PMA at two intervertebral lumbar levels, L3–4 and L4–5. Methods: In this cross-sectional study, we analysed abdominal computed tomography scans of consecutive children presenting to the emergency department. Participants were children 1–16 years who required abdominal cross-sectional imaging after paediatric trauma between January 1, 2005 and December 31, 2015 in a large Canadian quaternary care centre. Children with a documented chronic medical illness or an acute spinal trauma at presentation were excluded. Total PMA (tPMA) at levels L3–4 and L4–5 were measured in square millimetres (mm2) as the sum of left and right PMA. Age-specific and sex-specific tPMA percentile curves were modelled using quantile regression. Results: Computed tomography images from 779 children were included. Values of tPMA at L4–5 were significantly larger than at L3–4 at all ages, but their correlation was high for both girls (r = 0.95) and boys (r = 0.98). Amongst girls, tPMA 50th percentile values ranged from 365 to 2336 mm2 at L3–4 and from 447 to 2704 mm2 for L4–5. Amongst boys, 50th percentile values for tPMA ranged between 394 and 3050 mm2 at L3–4 and from 498 to 3513 mm2 at L4–5. Intraclass correlation coefficients were excellent at L3–4 (0.97, 95% CI 0.94 to 0.981) and L4–5 (0.99, 95% CI 0.986 to 0.995). Weight and tPMA were correlated, stratified by sex for boys (L3–4 r = 0.90; L4–5 r = 0.90) and for girls (L3–4 r = 0.87; L4–5 r = 0.87). An online application was subsequently developed to easily calculate age-specific and sex-specific z-scores and percentiles. Conclusions: We provide novel paediatric age-specific and sex-specific growth curves for tPMA at intervertebral L3–4 and L4–5 levels for children between the ages of 1-16 years. Together with an online tool (https://ahrc-apps.shinyapps.io/sarcopenia/), these tPMA curves should serve as a reference enabling earlier identification and targeted intervention of sarcopenia in children with chronic medical conditions