Oral Curcumin With Piperine as Adjuvant Therapy for the Treatment of COVID-19: A Randomized Clinical Trial.

Background: Coronavirus disease-2019 (COVID-19) has a wide range of pathophysiological effects. Curcumin, an active constituent of Curcuma longa (turmeric), has several properties, including anti-inflammatory, antioxidant, antiviral, anti-thrombotic, and anti-proliferative effects, which make it a promising candidate for the symptomatic treatment of COVID-19. Objective: We aimed to determine the effects of curcumin administered with piperine (to optimize absorption) on symptoms in patients with COVID-19 in a double-blind, randomized, controlled trial at a 30-bed dedicated COVID Health Center (DCHC) in Maharashtra, India. Methods: In addition to conventional COVID-19 treatment, patients in the control group received a dose of probiotics twice a day, and patients in the study group received curcumin (525 mg) with piperine (2.5 mg) in tablet form twice a day. The effects of curcumin/piperine treatment on primary and secondary outcomes were assessed for the duration of hospitalization. Results: Patients with mild, moderate, and severe symptoms who received curcumin/piperine treatment showed early symptomatic recovery (fever, cough, sore throat, and breathlessness), less deterioration, fewer red flag signs, better ability to maintain oxygen saturation above 94% on room air, and better clinical outcomes compared to patients of the control group. Furthermore, curcumin/piperine treatment appeared to reduce the duration of hospitalization in patients with moderate to severe symptoms, and fewer deaths were observed in the curcumin/piperine treatment group. Conclusions: Administration of oral curcumin with piperine as an adjuvant symptomatic therapy in COVID-19 treatment could substantially reduce morbidity and mortality, and ease the logistical and supply-related burdens on the healthcare system. Curcumin could be a safe and natural therapeutic option to prevent Post-Covid thromboembolic events. Clinicaltrials.gov identifier: CTRI/2020/05/025482.

Intravascular imaging and histological correlates of medial and intimal calcification in peripheral artery disease.

BACKGROUND: In peripheral artery disease, two different types of calcification are frequently observed, i.e., medial and intimal calcification. AIMS: The aim of this study was to determine the ability of intravascular ultrasound (IVUS) imaging and optical frequency domain imaging (OFDI) to detect medial and intimal calcification in human peripheral arteries. METHODS: We performed ex vivo intravascular imaging of cadaveric human peripheral arteries with calcifications. IVUS and OFDI images were co-registered with histology. A total of 12 legs from nine patients were examined, and 438 cross-sectional images were co-registered with histology. RESULTS: OFDI could detect 183 of 231 intimal calcifications by histology, whereas IVUS could detect 194 (OFDI: sensitivity 79%, specificity 86%, area under the curve [AUC] 0.83; IVUS: sensitivity 84%, specificity 85%, AUC 0.85). Of 245 medial calcifications by histology, 160 and 164 were detected by OFDI and IVUS, respectively (OFDI: sensitivity 65%, specificity 85%, AUC 0.75; IVUS: sensitivity 67%, specificity 80%, AUC 0.74). Medial calcification with overlying intimal calcification (overlapped calcification) and an unclear border between intima and media were the main reasons for misdiagnosis. Without those 89 overlapped calcifications, sensitivity in both OFDI and IVUS was improved (OFDI: sensitivity 81%, specificity 85%, AUC 0.83; IVUS: sensitivity 88%, specificity 80%, AUC 0.84). CONCLUSIONS: There are limitations in detecting medial calcification in overlapped intimal calcification and with an unclear border between intima and media by both IVUS and OFDI. It is important to distinguish medial calcification from intimal calcification before proceeding with endovascular therapy since different approaches will be required.

Anticoagulation in Pulmonary Arterial Hypertension: Do We Know the Answer?

The shear stress and hypoxia in the pulmonary artery in patients with pulmonary arterial hypertension(PAH) causes endothelial dysfunction, smooth muscle proliferation and activation of thrombotic pathways leading to in situ thrombosis. Targeting the thrombotic pathways is a proposed mechanism to slow disease progression and improve survival. Over the years, the survival in patients with PAH has improved due to multiple factors with the increased use of anticoagulation as one of them. Both European Respiratory Society/European Society of Cardiology and American College of Cardiology/American Heart Association guidelines make grade II recommendations for using anticoagulation in PAH. The guidelines are based on weak observational studies with high risk of bias which have only studied warfarin as the choice of anticoagulation. In this article, we review the pathophysiology, rationale and the current literature investigating the role of anticoagulation in PAH.

Healthy Strut Coverage After Coronary Stent Implantation: An Ex Vivo Human Autopsy Study.

BACKGROUND: Struts have been considered as covered when tissue overlying the struts is >0 µm by optical coherence tomography (OCT). However, there is no confirmatory study to validate this definition by histology which is the gold standard. The aim of the present study was to assess the appropriate cutoff value of neointimal thickness of stent strut coverage by OCT with histology confirmation. METHODS: We performed ex vivo OCT imaging of human coronary arteries with stents at autopsy. A total of 46 stents in 39 vessels from 25 patients were examined in this study, and a total of 165 cross-sectional images were co-registered with histology to determine the optimal cutoff value for strut coverage by OCT which was defined as luminal endothelial cells with 2 abluminal layers of smooth muscles cells and matrix. Considering the resolution of OCT is 10 to 20 µm, the cutoff values were assessed at ≥20, ≥40, and ≥60 µm. RESULTS: A total of 2235 struts were reviewed by histology, 1216 were considered as well-matched struts which were analyzed in this study. By histology, 160 struts were identified as uncovered, while 1056 struts were covered. The OCT assessment without consideration of neointimal thickness yielded a poor specificity of 37.5% and sensitivity 100%. Of 3 cutoff values, the cutoff value of ≥40 µm yielded the best sensitivity (99.3%), specificity (91.0%), positive predictive value (98.6%), and negative predictive value (95.6%) as compared with ≥20 and ≥60 µm. CONCLUSIONS: Neointimal thickness ≥40 µm by OCT yielded the most accurate cutoff value to identify stent strut coverage validated by histology.

Detection of cholesterol crystals by optical coherence tomography.

AIMS: The aim of this study was to determine the ability of optical frequency domain imaging (OFDI)/optical coherence tomography (OCT) imaging systems to visualise the presence of cholesterol crystals (CCR) in human atherosclerotic coronary arteries. METHODS AND RESULTS: We performed ex vivo imaging of human coronary arteries by OFDI/OCT. A total of 559 cross-sectional images from 45 autopsy cases were co-registered with histology; 117 histologic sections showed presence of necrotic core with cholesterol clefts (CC). We modified a previously used OFDI/OCT definition for identification of CCRs which we now define as a linear and discrete high-intensity signal (bright area) within the plaque with sharp borders between it and adjacent low-/intermediate-intensity tissue. Additionally, the high-intensity signal is not a spot but a well-defined area distinguishing it from macrophages which lack sharp borders. OFDI/OCT imaging identified the presence of CCR in 30 of the 117 histologic sections. The sensitivity and specificity of OFDI/OCT for detection of CCR was 25.6% and 100.0%, respectively. By multivariate analysis, significant predictors to visualise CCR by OCT/OFDI were 1) an overlying fibrous plaque, and 2) the presence of stacked CC, defined as CC arranged one on top of another with >3 layers of CC. The prevalence of complicated plaques (i.e., plaque haemorrhage and late necrotic core) was significantly higher in detectable CCR by OFDI/OCT as compared to undetectable CCR. CONCLUSIONS: The presence of stacked CCs is required to detect CCR by OFDI/OCT. Detection of CCR by OCT/OFDI may help us to identify the late stages of atherosclerotic coronary plaque progression and improve risk stratification.