Repeated artemisinin-based combination therapies in a malaria hyperendemic area of Mali: efficacy, safety, and public health impact

Artemisinin-based combination therapies (ACTs) are the first-line treatment of uncomplicated malaria. The public health benefit and safety of repeated administration of a given ACT are poorly studied. We conducted a randomized trial comparing artemether-lumefantrine, artesunate plus amodiaquine (AS+AQ) and artesunate plus sulfadoxine-pyrimethamine (AS+SP) in patients 6 months of age and older with uncomplicated malaria in Mali from July 2005 to July 2007. The patient received the same initial treatment of each subsequent uncomplicated malaria episode except for treatment failures where quinine was used. Overall, 780 patients were included. Patients in the AS+AQ and AS+SP arms had significantly less risk of having malaria episodes; risk ratio (RR) = 0.84 (P = 0.002) and RR = 0.80 (P = 0.001), respectively. The treatment efficacy was similar and above 95% in all arms. Although all drugs were highly efficacious and well tolerated, AS+AQ and AS+SP were associated with less episodes of malaria.     

Critical role of CD4 T cells in maintaining lymphoid tissue structure for immune cell homeostasis and reconstitution

Loss of the fibroblastic reticular cell (FRC) network in lymphoid tissues during HIV-1 infection has been shown to impair the survival of naive T cells and limit immune reconstitution after antiretroviral therapy. What causes this FRC loss is unknown. Because FRC loss correlates with loss of both naive CD4 and CD8 T-cell subsets and decreased lymphotoxin-β, a key factor for maintenance of FRC network, we hypothesized that loss of naive T cells is responsible for loss of the FRC network. To test this hypothesis, we assessed the consequences of antibody-mediated depletion of CD4 and CD8 T cells in rhesus macaques and sooty mangabeys. We found that only CD4 T-cell depletion resulted in FRC loss in both species and that this loss was caused by decreased lymphotoxin-β mainly produced by the CD4 T cells. We further found the same dependence of the FRC network on CD4 T cells in HIV-1-infected patients before and after antiretroviral therapy and in other immunodeficiency conditions, such as CD4 depletion in cancer patients induced by chemotherapy and irradiation. CD4 T cells thus play a central role in the maintenance of lymphoid tissue structure necessary for their own homeostasis and reconstitution.     

Early and mid-term clinical outcome of emergency PCI in patients with STEMI due to unprotected left main coronary artery disease

Objectives: Evaluation of acute and mid‐term outcomes of patients with ST‐elevation myocardial infarction (STEMI) undergoing emergency PCI due to unprotected left main coronary artery (ULMCA) disease. Background: STEMI patients due to ULMCA disease represent a rare, high risk group. Percutaneous coronary intervention (PCI) may be the preferred strategy of myocardial revascularization but there are few data about this topic. Methods: We analyzed 30‐day and mid‐term mortality of 58 patients with STEMI and ULMCA disease as culprit lesion treated in our centre by emergency PCI between 2000 to 2010. Results: Mean age was 67.3 ± 11.5 years. Thirty (51.7%) patients had cardiogenic shock on admission. PCI success was achieved in 54 patients (93.1%). Mean follow‐up was 15.8 ± 10.9 months (median 14, range 6–45). Thirty‐day and mid‐term mortality rates were 39.7% and 44%. Backward binary logistic regression model identified cardiogenic shock at presentation (OR 12.6, 95% CI 2.97–53.6, P < 0.001), age ≥75 years (OR 5.9, 95% CI 1.3–26.5, P = 0.019) and post‐PCI TIMI flow grade <3 (OR 2.9, 95% CI 1.8–5.7 P = 0.02) as independent predictors of 30‐day mortality. Cox proportional hazard ratio (HR) identified shock at presentation (HR 5.2, 95% CI 1.8–14.3, P < 0.002), age ≥75 years (HR 3.9, 95% CI 1.8–8.7, P < 0.001), post‐PCI TIMI flow grade <3 (HR 4.9, 95% CI 1.6–14.6; P < 0.005) as independent predictors of mid‐term mortality. Conclusions: In patients with STEMI and ULMCA as culprit lesion, emergency PCI is a valuable therapeutic strategy. Early and mid‐term survival depends on cardiogenic shock, advanced age, and PCI failure. Patients surviving the first month have good mid‐term prognosis. (J Interven Cardiol 2012;25:215–222)     

Stroke and renal dysfunction: are we always conscious of this relationship?

Cerebrovascular disease may represent an important clinical presentation of atherosclerosis in chronic kidney disease (CKD), and atherosclerosis is frequently encountered in CKD. In fact, kidney disease is now considered a risk factor for development of cardiovascular disease. Although guidelines for primary prevention of stroke have been recently published, CKD is hardly mentioned. Based on a series of available studies, we analyzed the relationship between reduced renal function, end-stage renal disease (ESRD), and stroke. Reduced renal function and risk of stroke appear to be related to the highest risk of patients on dialysis treatment. Primary and secondary prevention of stroke should be encouraged in participants with renal dysfunction.