Peri-interventional Triple Therapy With Dabigatran Improves Vasomotion and Promotes Endothelialization in Porcine Coronary Stenting Model

Objective: We evaluated the short and long-term effect of peri-interventional dabigatran therapy on vasomotion, endothelialization, and neointimal formation in a porcine coronary artery stenting model.Background: Stenting of coronary arteries induces local inflammation, impairs vasomotion and delays endothelialization.Methods: Twenty-eight animals underwent percutaneous coronary intervention (PCI) with drug eluting stents. Sixteen pigs started dabigatran therapy 4 days prior to PCI and continued for 4 days post-stenting, while 12 animals served as controls. Post-stenting dual antiplatelet therapy (75 mg clopidogrel and 100 mg aspirin) was continued in both groups until termination. Immediately post-stenting and at day 3 optical coherence tomography (OCT) was performed in all animals, followed by euthanasia of 8 dabigatran and 4 control animals. The remaining pigs (8 of each group) were followed up for 1 month, with control angiography and OCT. Tissue burden (degree of peri-strut structure—thrombus and/or fibrin) was evaluated. After euthanasia coronary arteries were harvested for in-vitro myometry and histology.Results: Thrombin generation was lower (p < 0.001) and tissue burden (0.83 ± 0.98 vs. 3.0 ± 2.45; p = 0.031) was significantly decreased in dabigatran treated animals. After 3 days post-PCI endothelium-dependent vasodilation was significantly improved (77 ± 40% vs. 41 ± 31%, p = 0.02) in dabigatran animals. Neither quantitative angiography nor histomorphometry showed differences between the groups. Endothelialization was faster in the dabigatran group as compared with controls (p = 0.045).Conclusion: Short-term peri-interventional triple therapy with dabigatran, aspirin, and clopidogrel led to an enhanced endothelium dependent vasodilation and faster endothelialization. However, neointimal formation 1-month after stent implantation was comparable between groups.

Piscirickettsia salmonis shedding and tissue burden, and hematological responses during cohabitation infections in chum Oncorhynchus keta, pink O. gorbuscha and Atlantic salmon Salmo salar

Background Salmonid rickettsial septicemia is an emergent and geographically widespread disease of marine-farmed salmonids caused by infection with the water-borne bacterium Piscirickettsia salmonis. Very little is known about the route, timing, or magnitude of bacterial shedding from infected fish. Methodology/principal findings A cohabitation challenge model was used to assess shedding from chum Oncorhynchus keta, pink O. gorbuscha and Atlantic salmon Salmo salar. Infections in donor fish were established by intraperitoneal injection of P. salmonis. Naïve recipients were cohabitated with donor fish after which cumulative percent morbidity and mortality (CMM) was monitored, and bacterial burdens in kidney and in tank water were measured by qPCR. All donor fish died with mean days-to-death (MDD) among species ranging from 17.5 to 23.9. Among recipients, CMM ranged from 42.7% to 77.8% and MDD ranged from 49.7 to 56.4. In each trial, two peaks of bacterial DNA concentrations in tank water closely aligned with the MDD values of donor and recipient fish. Bacterial tissue burden and shedding rate, and plasma physiological parameters were obtained from individual donors and recipients. Statistically significant positive correlations between the shedding rate and P. salmonis kidney burden were measured in donor pink and in donor and recipient chum salmon, but not in donor or recipient Atlantic salmon. In Atlantic salmon, there was a negative correlation between kidney bacterial burden and hematocrit, plasma Ca++ and Mg++ values, whereas in infected chum salmon the correlation was positive for Na+ and Cl- and negative for glucose. Conclusions A dependency of bacterial shedding on species-specific patterns of pathogenesis was suggested. The coincidence of bacterial shedding with mortality will inform pathogen transmission models.

Hazard Indices and Human Health Risks Associated with Toxic Element Contaminants in Bivalve Shellfish from Niger Delta, Nigeria

The quality of coastal waters in Niger delta have increasingly and adversely impacted by varieties of contaminants occasioned by environmental degradation and aquatic perturbation posed by petroleum exploration activities. This tends to undermine nutritional and health benefits derived from consumption of shellfish harvested from these waters. This study investigated tissue burden, hazard indices and human health risks associated with toxic element contaminants in bivalve shellfish harvested from coastal waters of Niger delta. Four species of bivalve shellfish; bloody cockle (Anadara senilis), donax clam (Donax rugosus), knife clam (Tagelus adansonaii) and mangrove oyster (Crassosstra gasar) collected from four locations were assessed for levels of toxic element contaminants as well as hazard indices and human health risk associated with their consumption. The tissue burden of toxic element contaminants was determined using atomic absorption spectrometer while United State Environmental Protection Agency (US EPA) method was employed to estimate hazard indices and human health risk. Results indicated lead concentrations were within the 1.5mg/kg acceptable limits while levels of cadmium, arsenic and mercury were higher than FAO limits of 0.5, 0, 0.5 mg/kg respectively. The estimated human health risk indicated non-carcinogenic values and hazard indices higher than threshold value of one for cadmium, total arsenic and methyl mercury while values for inorganic arsenic at some locations were higher than stipulated one in one million (1.0x10-6) chances. This implies that toxic elements apart from lead in bivalves shellfish from these locations can induce potential deleterious health effects at consumption of 48g/day of bivalve shellfish.

The Value of Voltage Histogram Analysis Derived Right Atrial Scar Burden in the Prediction of Left Atrial Scar Burden

Introduction. Growing evidence suggests that fibrotic changes can be observed in atrial fibrillation (AF) in both atria. Quantification of the scar burden during electroanatomical mapping might have important therapeutic and prognostic consequences. However, as the current invasive treatment of AF is focused on the left atrium (LA), the role of the right atrium (RA) is less well understood. We aimed to characterize the clinical determinates of the RA low-voltage burden and its relation to the LA scaring. Methods. We have included 36 patients who underwent catheter ablation for AF in a prospective observational study. In addition to LA mapping and ablation, high-density RA bipolar voltage maps (HD-EAM) were also reconstructed. The extent of the diseased RA tissue (≤0.5 mV) was quantified using the voltage histogram analysis tool (CARTO®3, Biosense Webster). Results. The percentage of RA diseased tissue burden was significantly higher in patients with a CHA2DS2-VASc score ≥ 2 p=0.0305, higher indexed LA volume on the CTA scan and on the HD‐EAM (p=0.0223 and p=0.0064, respectively), or higher indexed RA volume on the HD‐EAM p=0.0026. High RA diseased tissue burden predicted the presence of high LA diseased tissue burden (OR = 7.1, CI (95%): 1.3–38.9, p=0.0145), and there was a significant correlation of the same (r = 0.6461, p<0.0001). Conclusions. Determining the extent of the right atrial low-voltage burden might give useful clinical information. According to our results, the diseased tissue burden correlates well between the two atria: the right atrium mirrors the left atrium.

Virulence and Resistance to Antifungal Therapies of Scopulariopsis Species

ABSTRACTScopulariopsisis an emerging opportunistic fungus characterized by its high resistance to antifungal therapies. We have developed a murine model of disseminated infection in immunosuppressed animals by intravenous inoculation ofScopulariopsis brevicaulisandScopulariopsis brumptii, the most clinically relevant species, in order to evaluate their virulence and their responses to conventional antifungal treatments. Survival and tissue burden studies showed thatS. brumptiiwas more virulent thanS. brevicaulis. The three drugs tested, liposomal amphotericin B, posaconazole, and voriconazole, prolonged the survival of mice infected withS. brumptii, but none showed efficacy againstS. brevicaulis. The different therapies were only able to modestly reduce the fungal burden of infected tissue; however, in general, despite the high serum levels reached, they showed poor efficacy in the treatment of the infection. Unfortunately, the most effective therapy forScopulariopsisinfections remains unresolved.