Panax ginseng Modulates Cytokines in Bone Marrow Toxicity and Myelopoiesis: Ginsenoside Rg1 Partially Supports Myelopoiesis

In this study, we have demonstrated that Korean Panax ginseng (KG) significantly enhances myelopoiesis in vitro and reconstitutes bone marrow after 5-flurouracil-induced (5FU) myelosuppression in mice. KG promoted total white blood cell, lymphocyte, neutrophil and platelet counts and improved body weight, spleen weight, and thymus weight. The number of CFU-GM in bone marrow cells of mice and serum levels of IL-3 and GM-CSF were significantly improved after KG treatment. KG induced significant c-Kit, SCF and IL-1 mRNA expression in spleen. Moreover, treatment with KG led to marked improvements in 5FU-induced histopathological changes in bone marrow and spleen, and partial suppression of thymus damage. The levels of IL-3 and GM-CSF in cultured bone marrow cells after 24 h stimulation with KG were considerably increased. The mechanism underlying promotion of myelopoiesis by KG was assessed by monitoring gene expression at two time-points of 4 and 8 h. Treatment with Rg1 (0.5, 1 and 1.5 µmol) specifically enhanced c-Kit, IL-6 and TNF-α mRNA expression in cultured bone marrow cells. Our results collectively suggest that the anti-myelotoxicity activity and promotion of myelopoiesis by KG are mediated through cytokines. Moreover, the ginsenoside, Rg1, supports the role of KG in myelopoiesis to some extent

Sex differences in atrial fibrillation in India: Insights from the Kerala-AF registry

Background: Much data informing sex differences in atrial fibrillation (AF) comes from Western cohorts. In this analysis, we describe sex differences in Kerala, India, using the Kerala-AF registry—the largest AF registry from the Indian subcontinent. Methods: Patients aged ≥18 years were recruited from 53 hospitals across Kerala. Patients were compared for demographics, treatments, and 12-month outcomes, including major adverse cardiovascular events (MACE) and bleeding. Results: Male patients were more likely to have a smoking and/or alcohol history and had more ischaemic heart disease (46.2% vs. 25.5%; p < 0.001). Female patients had more valvular AF (35.1% vs. 18.0%; p < 0.001), and more use of calcium-channel blockers (23.3% vs. 16.5%; p < 0.001) or digoxin (39.6% vs. 28.5%; p < 0.001). Almost one in four patients were not anticoagulated despite raised CHA2DS2-VASc scores. 12-month MACE outcomes did not differ by sex (male: 30.2% vs. female: 29.4%; p = 0.685), though bleeding events were more common in male patients (2.4% vs. 1.3%; p = −0.038), driven by minor bleeding (1.2% vs. 0.5%). Conclusion: In this large AF cohort from India, male patients had a higher prevalence of ischaemic heart disease, smoking, and alcohol use, while female patients had a higher prevalence of valvular heart disease. MACE did not differ by sex, though bleeding was more common in males. Almost a quarter of patients were not anticoagulated despite raised thromboembolic risk

Phenotypes of South Asian patients with atrial fibrillation and holistic integrated care management: cluster analysis of data from KERALA-AF Registry

Background: Patients with atrial fibrillation (AF) frequently experience multimorbidity. Cluster analysis, a machine learning method for classifying patients with similar phenotypes, has not yet been used in South Asian AF patients. Methods: The Kerala Atrial Fibrillation Registry is a prospective multicentre cohort study in Kerala, India, and the largest prospective AF registry in South Asia. Hierarchical clustering was used to identify different phenotypic clusters. Outcomes were all-cause mortality, major adverse cardiovascular events (MACE), and composite bleeding events within one-year follow-up. Findings: 3348 patients were included (median age 65.0 [56.0–74.0] years; 48.8% male; median CHA2DS2-VASc 3.0 [2.0–4.0]). Five clusters were identified. Cluster 1: patients aged ≤65 years with rheumatic conditions; Cluster 2: patients aged >65 years with multi-comorbidities, suggestive of cardiovascular-kidney-metabolic syndrome; Cluster 3: patients aged ≤65 years with fewer comorbidities; Cluster 4: heart failure patients with multiple comorbidities; Cluster 5: male patients with lifestyle-related risk factors. Cluster 1, 2 and 4 had significantly higher MACE risk compared to Cluster 3 (Cluster 1: OR 1.36, 95% CI 1.08–1.71; Cluster 2: OR 1.79, 95% CI 1.42–2.25; Cluster 4: OR 1.76, 95% CI 1.31–2.36). The results for other outcomes were similar. Atrial fibrillation Better Care (ABC) pathway in the whole cohort was low (10.1%), especially in Cluster 4 (1.9%). Overall adherence to the ABC pathway was associated with reduced all-cause mortality (OR 0.26, 95% CI 0.15–0.46) and MACE (OR 0.45, 95% CI 0.31–0.46), similar trends were evident in different clusters. Interpretation: Cluster analysis identified distinct phenotypes with implications for outcomes. There was poor ABC pathway adherence overall, but adherence to such integrated care was associated with improved outcomes. Funding: Kerala Chapter of Cardiological Society of India