Canakinumab: Promises and Future in Cardiometabolic Diseases and Malignancy

Inflammation has proven in multiple studies to be responsible for the progression of cardiometabolic diseases and malignancies. The interleukin family has been critically associated with progression of atherosclerosis, insulin resistance, and various malignancies. Given the advent of pharmacologic interleukin-1 (IL-1) inhibition, this pathway can potentially be targeted to improve outcomes. In the recently concluded Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial, investigators looked at the potential role of IL-1 (especially IL-1β) inhibition in halting the progression of atherosclerosis. In the subset analysis of the data from this trial, IL-1β inhibition with canakinumab was found to have beneficial effects in other cardiometabolic diseases characterized by inflammation, like diabetes, stroke, and chronic kidney disease, and also in patients with lung cancer. In this article, we will try to review the current literature on the role of canakinumab in the treatment of cardiometabolic diseases and malignancies.     

Is stenting for atherosclerotic renal stenosis an effective technique?

IntroductionOne of the treatments for renal artery stenosis is endovascular intervention, but its effectiveness is controversial. The present study aims to analyze the experience of a working group in the endovascular treatment of selected patients with severe obstructive atherosclerotic lesions of the renal arteries, and to characterize early and late results.MethodsThis is a retrospective study of symptomatic patients with atherosclerotic renal artery stenosis who underwent endoluminal therapy between May 12, 1999 and March 12, 2015 at two institutions. Statistical analysis was performed using the PASW Statistics program.ResultsA total of 99 patients were treated, mean age 66 years and 76.8% male. The mean degree of stenosis measured by renal Doppler echocardiography was 83% and 64.6% were ostial lesions. Mean preoperative creatinine level was higher than the postoperative mean: 1.3 vs. 1.2 mg/dl (p=0.014). The number of antihypertensive drugs in the preoperative period was higher than in the postoperative period: 2.0 vs. 1.3 (p=0.001). The mean follow-up was 40 months (0-164). The mean peak systolic velocity over time in the postoperative period was 77 cm/s (40-250). The restenosis rate was 8%, and 30-day mortality was 0%.ConclusionsThe results demonstrated that the endovascular technique has a beneficial effect on blood pressure and renal function in selected patients, and is a safe technique associated with a high rate of technical success and few complications.     

Development of deep learning segmentation models for coronary X-ray angiography: Quality assessment by a new global segmentation score and comparison with human performance

Introduction and objectivesAlthough automatic artificial intelligence (AI) coronary angiography (CAG) segmentation is arguably the first step toward future clinical application, it is underexplored. We aimed to (1) develop AI models for CAG segmentation and (2) assess the results using similarity scores and a set of criteria defined by expert physicians.MethodsPatients undergoing CAG were randomly selected in a retrospective study at a single center. Per incidence, an ideal frame was segmented, forming a baseline human dataset (BH), used for training a baseline AI model (BAI). Enhanced human segmentation (EH) was created by combining the best of both. An enhanced AI model (EAI) was trained using the EH. Results were assessed by experts using 11 weighted criteria, combined into a Global Segmentation Score (GSS: 0–100 points). Generalized Dice Score (GDS) and Dice Similarity Coefficient (DSC) were also used for AI models assessment.Results1664 processed images were generated. GSS for BH, EH, BAI and EAI were 96.9+/-5.7; 98.9+/-3.1; 86.1+/-10.1 and 90+/-7.6, respectively (95% confidence interval, p<0.001 for both paired and global differences). The GDS for the BAI and EAI was 0.9234±0.0361 and 0.9348±0.0284, respectively. The DSC for the coronary tree was 0.8904±0.0464 and 0.9134±0.0410 for the BAI and EAI, respectively. The EAI outperformed the BAI in all coronary segmentation tasks, but performed less well in some catheter segmentation tasks.ConclusionsWe successfully developed AI models capable of CAG segmentation, with good performance as assessed by all scores.     

Angiographic profile and outcomes in persistent non-valvular atrial fibrillation: A study from tertiary care center in North India

BackgroundThe relationship of atrial fibrillation (AF) with coronary artery disease (CAD) is well established, yet it is often missed. There is evidence of myocardial ischemia on stress imaging in AF patients in the absence of obstructive CAD. In this prospective cohort, we studied the angiographic profiles of non-valvular AF patients.MethodsThe study was a nonrandomized, prospective, single-center observational study of consecutive patients of persistent non-valvular AF. Patients symptomatic for AF despite optimal medical therapy for 3 months were recruited and all underwent coronary angiograms (CAG). Patients with prior history of CAD were excluded.ResultsA total of 70 patients were followed for a mean duration of 12 ± 1.4 months. The mean age of the study group was 66.07 (±11.49) years. Hypertension was the commonest comorbidity seen in 74% patients. Obstructive CAD was present in 32 (46%) patients, non-obstructive (<50% stenosis) CAD in 17 (24%) patients and normal coronaries in 21 (30%) patients. Overall 49 (70%) patients had evidence of CAD. Amongst patients without obstructive CAD, slow flow was seen in 16 (42%) patients. Lower baseline ejection fraction, lower haemoglobin & albumin levels and higher creatinine levels was associated with increased mortality. In patients without obstructive CAD, hospitalizations for fast ventricular rate were significantly increased in those having slow flow on CAG (p = 0.005).ConclusionsMajority (70%) of our patients had evidence of atherosclerotic CAD on CAG. A large proportion of patients without obstructive CAD had slow flow on CAG.     

解偶联蛋白1基因多态性与2型糖尿病心脑血管并发症的相关性

目的探讨解偶联蛋白1(UCP1)基因多态性与2型糖尿病(T2DM)心脑血管并发症的相关性。方法选取2019年7月—2020年7月住院治疗的T2DM 440例,根据有无心脑血管并发症分为观察组(T2DM合并心脑血管并发症)221例和对照组(单纯T2DM)219例。比较两组一般资料,UCP1在rs45539933、rs10011540及rs1800592位点的基因型分布与等位基因频率;通过多因素Logistic回归分析评估T2DM发生心脑血管事件的危险因素。结果观察组病程长于对照组,糖化血红蛋白水平高于对照组,而血清高密度脂蛋白胆固醇水平低于对照组(P<0.01)。观察组C/C基因型分布及C碱基频率均高于对照组(P<0.05)。C/C基因型是T2DM患者发生心脑血管并发症的危险因素(P<0.05)。结论UCP1基因多态性与T2DM心脑血管并发症的发生显著相关。     

Dimensional study of prostate cancer using stereological tools

This study analyzes the dimensional changes of the glands from prostate cancer by applying stereology to estimate the variations in volume, length, surface, and cellular densities of tumor acini. Normal and tumor acini were visualized using immunohistochemistry for cytokeratin18. On immunostained sections, parameters related to the dimensions and cell population of prostate acini were measured. The immunohistochemical expression of proliferative cell nuclear antigen was also measured to correlate the quantitative changes estimated with the proliferative activity of the epithelium. The average cell volume in normal and tumor epithelium was estimated using the method of the nucleator. The relative size of the acini was similar in the carcinoma compared with the normal prostate. Within the acini, the fraction of acinar volume occupied by the epithelium was significantly higher in cancer than in the nontumor prostate. Conversely, the glandular lumen of the cancer acini is lower than in the normal acini. The significant increase of acinar length density in the carcinoma indicates that the glandular tree's growth in the carcinoma is higher and with more branches than in the case of nonneoplastic glands. The basal surface density is higher in the carcinoma than in the controls. The number of epithelial cells per unit length of acini was significantly decreased in the neoplastic glands. This "dilution" of the cell population along the cancer acinus can be explained by the significant increase in the tumor cell's mean cell volume.