Temporal trends and outcomes of patients with chronic limb-threatening ischemia with and without history of coronary artery disease: insights from the us national inpatient sample database.

BACKGROUND: The burden and prognostic significance of coronary artery disease (CAD) in adults with peripheral artery disease and chronic limb-threatening ischemia (CLTI) is unknown. METHODS: Temporal trends in prevalence of significant CAD (history of myocardial infarction or coronary revascularizations) in hospitalizations for CLTI were determined using the 2000 to 2018 National Inpatient Sample (NIS) database. A multivariable regression analysis of outcomes was performed based on presence or absence of CAD. RESULTS: Among 13 575 099 hospitalizations for CLTI (41% female, 69% white, mean age 69 years), 23% had concomitant CAD, of which 11% underwent lower extremity arterial revascularization (43.6% endovascular and 56.4% surgical). The prevalence of concomitant CAD with CLTI increased from 15.3% in 2000 to 23.1% in 2018. Furthermore, the frequency of endovascular revascularization in adults with CAD and CLTI increased from 15.1% to 48.3%, while there was a decreasing trend of surgical revascularization, from 84.9% to 51.7%. After multivariate adjustments, CLTI with CAD was associated with increased risk of in-hospital mortality (OR, 1.40; 95% CI, 1.32-1.47; P less than .0001) and bleeding requiring transfusion (OR, 1.10; 95% CI, 1.06-1.12; P less than .0001) compared with patients with CLTI without CAD. As compared with surgical revascularization, endovascular revascularization was associated with lower risk of in-hospital mortality in both patients with CLTI with CAD (OR, 0.69; 95% CI, 0.63-0.76; P less than .001) and CLTI without CAD (OR, 0.71; 95% CI, 0.67-0.76; P less than .001). CONCLUSIONS: Prevalence of CAD has increased in adults presenting with CLTI and is associated with poor outcomes, warranting the need for effective interventions and secondary prevention in this high-risk population.

A novel computational predictive biological approach distinguishes Integrin ß1 as a salient biomarker for breast cancer chemoresistance.

Chemoresistance is a primary cause of breast cancer treatment failure, and protein-protein interactions significantly contribute to chemoresistance during different stages of breast cancer progression. In pursuit of novel biomarkers and relevant protein-protein interactions occurring during the emergence of breast cancer chemoresistance, we used a computational predictive biological (CPB) approach. CPB identified associations of adhesion molecules with proteins connected with different breast cancer proteins associated with chemoresistance. This approach identified an association of Integrin ß1 (ITGB1) with chemoresistance and breast cancer stem cell markers. ITGB1 activated the Focal Adhesion Kinase (FAK) pathway promoting invasion, migration, and chemoresistance in breast cancer by upregulating Erk phosphorylation. FAK also activated Wnt/Sox2 signaling, which enhanced self-renewal in breast cancer. Activation of the FAK pathway by ITGB1 represents a novel mechanism linked to breast cancer chemoresistance, which may lead to novel therapies capable of blocking breast cancer progression by intervening in ITGB1-regulated signaling pathways.

Exhaustion of coronary vasodilatory reserve in the resting state: Clinical characteristics and long-term outcomes after intervention.

OBJECTIVES/BACKGROUND: Resting coronary blood flow approximates flow with maximal vasodilation in very severe coronary stenosis. We studied the incidence of exhausted vasodilatory reserve by FFR, its clinical characteristics and long-term prognosis after FFR guided percutaneous coronary intervention (PCI). METHODS: Consecutive patients undergoing FFR-guided PCI for coronary stenosis with reduced resting blood flow (baseline Pd/Pa < 0.8) were included. Basal maximal vasodilation (BMV) was defined as less than 5% difference between resting Pd/Pa and FFR, that is, FFR-baseline Pd/Pa < 0.05. RESULTS: Of 658 vessels that underwent FFR-guided PCI in 602 patients, 151 vessels had resting blood flow in the ischemic range (baseline Pd/Pa ≤ 0.8) and were included in the analysis. Of these, 28 lesions in 28 patients met criteria for BMV (4.25% of the entire registry and 18.5% of those with the reduced basal coronary flow). Stenosis severity was a significant predictor of the presence of BMV. In long term follow-up (median 106 ± 3.6 months), BMV was not associated with increased target vessel revascularization (TVR) or major adverse cardiac event compared to non-BMV(OR 1.9, 95% CI 0.7-4.8, p-value 0.2 and OR 1.3, 95% CI 0.75-2.5, p = 0.3, respectively). CONCLUSION: Low baseline Pd/Pa that approximates fractional flow reserve (exhausted vasodilatory reserve) defines a subgroup of patients with severe coronary artery stenosis. Prognosis, when treated with PCI along with medical therapy, appears similar to those with intact vasodilatory reserve.

Systematic review of the evaluation and management of coronary pseudoaneurysm after stent implantation.

Pseudoaneurysm (PSA) formation is a rare but well-known complication of coronary stenting. It develops after a procedural perforation disrupts the integrity of the vessel wall but is contained by a single wall layer, usually pericardium, extravascular thrombosis and later fibrosis. Medical literature of PSA consists primarily of case reports. A systematic review of pseudoaneurysm after coronary stenting was performed to summarize its presentation, diagnostic imaging modalities, natural history, and management approaches. Clinical presentations range from asymptomatic to hemodynamic collapse, size from small to "giant," and treatment approaches from surgical or percutaneous exclusion to "watchful waiting" and imaging surveillance. Based on current information, a management algorithm is provided recommending urgent to emergent exclusion for symptomatic PSA, elective exclusion for large and giant PSA, and "watchful waiting" and periodic imaging surveillance for small to moderate sized PSA.

Boosting phosphorylation site prediction with sequence feature-based machine learning.

Protein phosphorylation is one of the essential posttranslation modifications playing a vital role in the regulation of many fundamental cellular processes. We propose a LightGBM-based computational approach that uses evolutionary, geometric, sequence environment, and amino acid-specific features to decipher phosphate binding sites from a protein sequence. Our method, while compared with other existing methods on 2429 protein sequences taken from standard Phospho.ELM (P.ELM) benchmark data set featuring 11 organisms reports a higher F1 score = 0.504 (harmonic mean of the precision and recall) and ROC AUC = 0.836 (area under the curve of the receiver operating characteristics). The computation time of our proposed approach is much less than that of the recently developed deep learning-based framework. Structural analysis on selected protein sequences informs that our prediction is the superset of the phosphorylation sites, as mentioned in P.ELM data set. The foundation of our scheme is manual feature engineering and a decision tree-based classification. Hence, it is intuitive, and one can interpret the final tree as a set of rules resulting in a deeper understanding of the relationships between biophysical features and phosphorylation sites. Our innovative problem transformation method permits more control over precision and recall as is demonstrated by the fact that if we incorporate output probability of the existing deep learning framework as an additional feature, then our prediction improves (F1 score = 0.546; ROC AUC = 0.849). The implementation of our method can be accessed at http://cse.iitkgp.ac.in/~pralay/resources/PPSBoost/ and is mirrored at https://cosmos.iitkgp.ac.in/PPSBoost.

Effects of Virtual Reality training on medical students' learning motivation and competency.

OBJECTIVES: To determine the need of contemporary immersive approaches (Virtual Reality) in teaching and training at medical sector. The main objective of this study was to explore the effects of text, video and immersive technologies learning methodologies for participants' learning in public and private medical colleges and universities of Pakistan. METHODS: In this quantitative research 87 medical students of 4th year from three public and five private medical colleges and universities participated. A laparoscopy operation was selected in consultation with senior medical consultants for this experiment. The experimental material was arranged in virtual reality, video and text based learning. At completion of each of which, participants completed a questionnaire about learning motivation and learning competency through the different mediums. RESULTS: Statistical t-test was selected for the analysis of this study. By comparing the mean values of virtual reality, video, and text based learning methodologies in medical academics; result of virtual reality is at top of others. All performed model are statistically significant (P=0.000) and results can be applied at all population. CONCLUSION: Through this research, we contribute to medical students learning methodologies. In medical studies, both theoretical and practical expertise has a vital role, while repetition of hands-on practice can improve young doctors' professional competency. Virtual reality was found best for medical students in both learning motivation and learning competency. Medical students and educationist may select virtual reality as new learning methodology for curriculum learning.

Acquired Von Willebrand Syndrome (AVWS) in cardiovascular disease: a state of the art review for clinicians.

Von Willebrand Factor (vWF) is a large glycoprotein with a broad range of physiological and pathological functions in health and disease. While vWF is critical for normal hemostasis, vascular integrity and repair, quantitative and qualitative abnormalities in the molecule can predispose to serious bleeding and thrombosis. The heritable form of von Willebrand Disease was first described nearly a century ago, but more recently, recognition of an acquired condition known as acquired von Willebrand Syndrome (AVWF) has emerged in persons with hematological, endocrine and cardiovascular diseases, disorders and conditions. An in-depth understanding of the causes, diagnostic approach and management of AVWS is important for practicing clinicians.

Inflammation and coronary artery disease: from pathophysiology to Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS).

The worldwide prevalence of cardiovascular disease in general and atherosclerotic coronary artery disease in particular is a health and economic concern of unparalleled proportion. Despite a long history of astute observations beginning in 1575 made by Fallopius, followed by those of von Rokatansky, Virchow, Osler, and Ross, and incremental knowledge of the pathobiology of atherosclerosis to include varying stages of inflammation, response to internally and externally mediated vascular injury, and impaired homeostasis, gaps in the field's understanding persist. Here, we summarize the current scope of the problem for coronary artery disease, emerging constructs in its pathobiology and common clinical phenotypes, potentially useful biomarkers, clinical trials designed specifically to test the 'inflammation hypothesis' of disease, and the interface of pathobiology and precision medicine as a foundation for diagnosis, management, and future advances in the diagnosis, prognosis, natural history, prevention, and optimal management.

Electromagnetic Interference from Swimming Pool Generator Current Causing Inappropriate ICD Discharges.

Electromagnetic interference (EMI) includes any electromagnetic field signal that can be detected by device circuitry, with potentially serious consequences: incorrect sensing, pacing, device mode switching, and defibrillation. This is a unique case of extracardiac EMI by alternating current leakage from a submerged motor used to recycle chlorinated water, resulting in false rhythm detection and inappropriate ICD discharge. A 31-year-old female with arrhythmogenic right ventricular cardiomyopathy and Medtronic dual-chamber ICD placement presented after several inappropriate ICD shocks at the public swimming pool. Patient had never received prior shocks and device was appropriate at all regular follow-ups. Intracardiac electrograms revealed unique, high-frequency signals at exactly 120 msec suggestive of EMI from a strong external source of alternating current. Electrical artifact was incorrectly sensed as a ventricular arrhythmia which resulted in discharge. ICD parameters including sensing, pacing thresholds, and impedance were all normal suggesting against device malfunction. With device failure and intracardiac sources excluded, EMI was therefore strongly suspected. Avoidance of EMI source brought complete resolution with no further inappropriate shocks. After exclusion of intracardiac interference, device malfunction, and abnormal settings, extracardiac etiologies such as EMI must be thoughtfully considered and excluded. Elimination of inappropriate shocks is to "first, do no harm."

Testosterone therapy, thrombophilia, and hospitalization for deep venous thrombosis-pulmonary embolus, an exploratory, hypothesis-generating study.

Our hypothesis was that testosterone therapy (TT) interacts with previously undiagnosed thrombophilia-hypofibrinolysis, leading to hospitalization for deep venous thrombosis (DVT)-pulmonary emboli (PE). We determined the prevalence of DVT-PE associated with TT 147 men hospitalized in the last 12 months for DVT-PE. Of the 147 men, 2 (1.4%) had TT before and at the time of their DVT-PE. Neither had risk factors for thrombosis. Neither smoked. Case #1 (intramuscular T 50mg/week) had 2 PE, 6 and 24 months after starting TT. DVT-PE in case #2 (T gel 100mg/day) occurred 24 months after starting T. Both men were found to have previously undiagnosed familial thrombophilia (protein S deficiency, homocysteinemia, high Factor VIII). In case #2, on 100mg T gel/day, serum estradiol was high, 51 pg/ml (upper normal limit 42.6 pg/ml). At least 1.4% of men hospitalized for DVT-PE were on TT and had previously undiagnosed thrombophilia, suggesting a thrombotic interaction between exogenous T and thrombophilia-hypofibrinolysis. Given the increasing use of TT, our preliminary findings should facilitate design of a much-needed, multi-center, prospective study of pro-thrombotic interactions between T therapy and thrombophilia for subsequent thrombotic events including DVT-PE.

Testosterone, thrombophilia, thrombosis.

We assessed previously undiagnosed thrombophilia-hypofibrinolysis in 11 testosterone (T)-taking men, five of whom developed deep venous thrombosis (DVT), four pulmonary embolism, one spinal cord infarction, and one osteonecrosis 3.5 months (median) after starting T gel (50-160 mg/day) or T intramuscular (50-250 mg/week). In the order of referral because of thrombosis after starting T, thrombophilia-hypofibrinolysis was studied in 11 men, and, separately, in two control groups without thrombosis - 44 healthy normal male controls and 39 healthy men taking T. Nine men had DVT or DVT-pulmonary embolism after 3.5 months (median) on T, one spinal cord infarction after 5 days on T, and one had osteonecrosis (knee and then hip osteonecrosis after 6 and 18 months on T). Four of the 11 men (36%) had high factor VIII (≥150%) vs. one of 42 (2%) controls (P = 0.005), and vs. one of 25 (4%) T-controls, (P = 0.023). Of the 11 men, two (18%) had factor V Leiden heterozygosity vs. none of 44 controls, (P = 0.04) and vs. none of 39 T-controls(P = 0.045). Of the 11 men, three had 4G4G plasminogen activator inhibitor-1 homozygosity, one prothrombin G20210A heterozygosity, one low protein S, and one high factor XI. When T was continued, second DVT-pulmonary embolism recurred in three of 11 men despite adequate anticoagulation. T interacts with thrombophilia-hypofibrinolysis leading to thrombosis. Men sustaining DVT-pulmonary embolism-osteonecrosis on T should be studied for thrombophilia. Continuation of T in thrombophilic men appears to be contraindicated because of recurrent thrombosis despite adequate anticoagulation. Before starting T, to prevent T-associated thrombosis, we recommend measures of factor V Leiden, factor VIII, and the prothrombin gene.