Procedural Safety and Long-Term Clinical Outcomes in Patients Receiving Ultra-Long Everolimus-Eluting Stent: A Single-Center Real-World Experience.

Background: Diffuse long coronary lesions are difficult to treat percutaneously. The aim of the present study was to assess the procedural safety and long-term efficacy of the ultra-long (48-mm) drug-eluting stent Xience Xpedition. Methods: This was an investigator-initiated, observational, all-comers study. A total of 92 patients with 93 lesions were enrolled in the study from October 2016 to October 2020. The primary outcome of the study was major adverse cardiac events (MACEs). Secondary outcomes were individual components of the primary outcome and procedural success. Results: The mean (standard deviation (SD)) age of the participants was 58.8 (10.8) years. More than half of the patients had ST-segment elevation myocardial infarction (STEMI) at presentation (55.4%). Ten patients were in cardiogenic shock (CGS; 10.8%). Most of the lesions were located in the left anterior descending artery (48.3%). American College of Cardiology/American Heart Association (ACC/AHA) type C was the most common lesion type amongst the intervened vessels (46.74%), with a mean syntax score (SD) of 16.99 (8.89). The mean stent diameter used was 2.77 mm (0.25). MACE was observed in 7.6% of patients studied at a median follow-up of 24 months. MACE was significantly lower in the population without CGS, occurring in only 2.4% of the patients; a significant difference in MACE was observed in patients with and without CGS (P < 0.001). Procedural success was obtained in 89.2% of total population; however, 96.3% of patients without CGS had procedural success. Conclusions: The deployment of the ultra-long 48-mm Xience Xpedition stent is feasible, safe, and effective; and it was associated with a good intermediate-term clinical outcome.

Clinical profile and management of patients with acute pulmonary thromboembolism - a single centre, large observational study from India.

Acute pulmonary thromboembolism is associated with high mortality, similar to that of myocardial infarction and stroke. We studied the clinical presentation and management of pulmonary thromboembolism in the Indian population. An analysis of 140 patients who presented with acute pulmonary thromboembolism at a large volume center in India from June 2015 through December 2018 was performed. The mean age of our study population was 50 years with 59% being male. Comorbidities including deep vein thrombosis, diabetes mellitus, hypertension, and chronic obstructive pulmonary disease were present in 52.9%, 40%, 35.7% and 7.14% of patients, respectively. Out of 140 patients, 40 (28.6%) patients had massive pulmonary thromboembolism, 36 (25.7%) sub-massive pulmonary thromboembolism, and 64 (45.7%) had low-risk pulmonary thromboembolism. Overall, in-hospital mortality was 25.7%. Multivariate regression analysis found chronic kidney disease and pulmonary thromboembolism severity to be the only independent risk factors. Thrombolysis was performed in 62.5% of patients with a massive pulmonary thromboembolism and 63.9% of patients with a sub-massive pulmonary thromboembolism. In the massive pulmonary thromboembolism group, patients receiving thrombolytic therapy had lower mortality compared with patients who did not receive therapy (p=0.022), whereas this difference was not observed in patients in the sub-massive pulmonary thromboembolism group. We conclude that patients with acute pulmonary thromboembolism in India presented more than a decade earlier than our western counterparts, and it was associated with poor clinical outcomes. Thrombolysis was associated with significantly reduced in-hospital mortality in patients with massive pulmonary thromboembolism.

Comparison of the effect of Morphine and Fentanyl in patients with acute coronary syndrome receiving Ticagrelor - The COMET (Comparison Morphine, Fentayl and Ticagrelor) randomized controlled trial.

INTRODUCTION: Dual antiplatelet therapy (DAPT) remains the cornerstone of acute coronary syndrome (ACS) management, and ticagrelor is one of the commonly used second antiplatelet agents. There is some evidence to suggest that morphine may reduce the antiplatelet effect of ticagrelor. METHODS AND RESULTS: In a single-center, randomized controlled trial, we compared the effect of morphine and fentanyl on platelet aggregation (PA) among patients with ACS treated with ticagrelor. Platelet aggregation was studied by automated light transmittance aggregometry (LTA) at baseline, and at 2 h after ticagrelor loading. The primary outcome was the difference in the maximal inhibition of platelet aggregation [IPA(%)] between the groups at 2 h. Pain relief, and drug-related adverse events were secondary outcomes. Of 136 patients randomized, 70 received fentanyl and 66 received morphine. At baseline, the median (IQR) platelet aggregation [61.35% (54.6 to 70) Vs. 58.8% (52.7 to 72.9)] were comparable between the groups. There was no statistically significant difference between the fentanyl and the morphine groups in IPA at 2-h [85.88%(64.65-98.16) and 81.93%(44.2-98.03), p = 0.09]. However, morphine use was independently associated with a PA of >30% at 2 h (p < 0.009). There was no difference in adverse events. CONCLUSION: In patients with ACS, there was no significant difference between the use of fentanyl or morphine on the effect of ticagrelor on PA. (CTRI/2018/04/013423).

Clinicopathologic implications of epithelial cell adhesion molecule expression across molecular subtypes of breast carcinoma.

BACKGROUND: Epithelial cell adhesion molecule (EpCAM), a type I transmembrane protein of the epithelial tissues and known cell adhesion molecule, has been demonstrated to have critical role in carcinogenesis. In breast cancer, EpCAM expression has been associated with poor prognosis. The expression pattern of EpCAM across molecular subtypes of breast carcinoma has been studied in patients reporting to a South Indian multispecialty tertiary care hospital. The prognostic significance of EpCAM expression pattern and probable response to therapy has also been addressed. MATERIALS AND METHODS: EpCAM expression was assessed by immunohistochemical studies on 200 breast carcinoma tissue samples of different molecular subtypes, including luminal A, luminal B, Her2Neu, and triple-negative breast cancer (TNBC). The expression was scored using the standard scoring system. A correlation was drawn with detailed clinicopathologic annotation and available outcomes data to analyze the influence of EpCAM on prognosis. RESULTS: EpCAM expression varied significantly in the different intrinsic subtypes of breast carcinoma. Differential expression was also established with different grades of breast carcinoma with varying levels of differentiation. We observed strong EpCAM expression in TNBC among other subtypes. CONCLUSION: The differential expression of EpCAM among intrinsic subtypes of breast cancer and the correlation of EpCAM expression with high-grade breast carcinoma shown in the study have important implications in understanding the role of EpCAM and might form the basis for developing targeted therapies in breast cancer in the future.

Targeting the cancer epigenome: synergistic therapy with bromodomain inhibitors.

Epigenetic and genomic alterations regulate the transcriptional landscape of cells during cancer onset and progression. Recent clinical studies targeting the epigenetic 'readers' (bromodomains) for cancer therapy have established the effectiveness of bromodomain (BRD) and extraterminal (BET) inhibitors in treating several types of cancer. In this review, we discuss key mechanisms of BET inhibition and synergistic combinations of BET inhibitors with histone deacetylase inhibitors (HDACi), histone methyltransferase inhibitors (HMTi), DNA methyltransferase inhibitors (DNMTi), kinase, B-cell lymphoma 2 (Bcl-2) and proteosome inhibitors, and immunomodulatory drugs for cancer therapy. We also highlight the potential of such combinations to overcome drug resistance, and the evolving approaches to developing novel BET inhibitors.

Histone Deacetylase (HDAC) Inhibitors - emerging roles in neuronal memory, learning, synaptic plasticity and neural regeneration.

Epigenetic regulation of neuronal signalling through histone acetylation dictates transcription programs that govern neuronal memory, plasticity and learning paradigms. Histone Acetyl Transferases (HATs) and Histone Deacetylases (HDACs) are antagonistic enzymes that regulate gene expression through acetylation and deacetylation of histone proteins around which DNA is wrapped inside a eukaryotic cell nucleus. The epigenetic control of HDACs and the cellular imbalance between HATs and HDACs dictate disease states and have been implicated in muscular dystrophy, loss of memory, neurodegeneration and autistic disorders. Altering gene expression profiles through inhibition of HDACs is now emerging as a powerful technique in therapy. This review presents evolving applications of HDAC inhibitors as potential drugs in neurological research and therapy. Mechanisms that govern their expression profiles in neuronal signalling, plasticity and learning will be covered. Promising and exciting possibilities of HDAC inhibitors in memory formation, fear conditioning, ischemic stroke and neural regeneration have been detailed.