Background: A history of cancer is incorporated into the surgical risk assessment of patients undergoing surgical aortic valve replacement through the Society for Thoracic Surgeons score. However, the prognostic significance of cancer in patients treated with transcatheter aortic valve replacement (TAVR) is unclear. As the cancer survivorship population increases, it is imperative to establish the efficacy and safety of TAVR in patients with severe symptomatic aortic stenosis (AS) and a history of malignancy. Objectives: The primary goal of this study was to assess the periprocedural outcomes and long-term mortality in patients with a history of cancer undergoing TAVR. Methods: A systematic review of PubMed, MEDLINE, and EMBASE was conducted to identify studies reporting outcomes in patients with a history of malignancy undergoing TAVR. A meta-analysis was performed using a random-effects model with a primary outcome of all-cause mortality and cardiac mortality at the longest followup. On secondary analyses, procedural safety was assessed. Results: A total of 13 observational studies with 10,916 patients were identified in the systematic review. Seven studies including 6,323 patients were included in the quantitative analysis. Short-term mortality (relative risk [RR] 0.61, 95%CI 0.36-1.01; p = .06) and long-term all-cause mortality (RR 1.24, 95%CI 0.95-1.63; p = .11) were not significantly different when comparing patients with and without a history of cancer. No significant difference in the rate of periprocedural complications including stroke, bleeding, acute kidney injury, and pacemaker implantation was noted. Conclusion: In patients with severe AS undergoing TAVR, a history of cancer was not associated with adverse short or long-term survival. Based on these findings, TAVR should be considered in all patients with severe symptomatic AS, irrespective of their history of malignancy.
Background: Spontaneous cervical artery dissection (sCAD) is a leading cause of ischemic stroke in young patients. Studies using high-resolution magnetic resonance imaging and positron emission tomography have suggested vessel wall inflammation to be a pathogenic factor in sCAD. Computed tomography (CT) attenuation of perivascular adipose tissue (PVAT) is an established non-invasive imaging biomarker of inflammation in coronary arteries, with higher attenuation values reflecting a greater degree of vascular inflammation. Objectives: We evaluate the CT attenuation of PVAT surrounding the internal carotid artery (PVAT<sub>carotid</sub>) with and without spontaneous dissection. Methods: Single-centre prospective observational study of 56 consecutive patients with CT-verified spontaneous dissection of the internal carotid artery (ICA) admitted between 2011 and 2018. Of these patients, 6 underwent follow-up CTA. 22 patients who underwent CTA for acute neurological symptoms but did not have dissection formed the control group. Using semiautomated research software, PVAT<sub>carotid</sub> was measured as the mean Hounsfield Unit (HU) attenuation of adipose tissue within a defined volume of interest surrounding the ICA. Results: PVAT<sub>carotid</sub> was significantly higher around dissected ICA compared with non-dissected contralateral ICA in the same patients (-58.7±10.2 vs. -68.9±8.1 HU, P<0.0001) and ICA of patients without dissection (-58.7±10.2 vs. -69.3±9.3 HU, P<0.0001). After a median follow-up of 89 days, there was a significant reduction in PVAT<sub>carotid</sub> around dissected ICA (from -57.5±13.4 to -74.3±10.5 HU, P<0.05); while no change was observed around non-dissected contralateral ICA (from -71.0±4.4 to -74.1±4.1 HU, P=0.19). ICA dissection was an independent predictor of PVAT<sub>carotid</sub> following multivariable adjustment for age and the presence of ICA occlusion. Conclusion: PVAT<sub>carotid</sub> is elevated in the presence of sCAD and may decrease following the acute event.
Didanosine (ddI) is currently used in the management of patients infected by the human immunodeficiency virus. Rifabutin (RBT) is being extensively used for prophylaxis against Mycobacterium avium complex (MAC) infections. Due to its acid-labile characteristics, ddI must be administered with a buffer. Recent reports have indicated that absorption of ketoconazole, ciprofloxacin, and dapsone, etc., in the gut is altered by concomitant ddI dosing. We have assessed whether concomitant dosing of ddI as antiretroviral therapy modifies RBT absorption in the gut, its steady-state pharmacokinetics, and/or safety in 15 patients with AIDS. Of the 15 patients enrolled, 12 completed the study and 3 receiving 600 mg of RBT with concomitant ddI administration withdrew prematurely from the study. Steady-state RBT pharmacokinetics were assessed on day 13 (ddI plus RBT) and day 16 (RBT alone). The ddI doses (adjusted for body weight) were 167 to 375 mg twice daily, while RBT was administered as a single 300- or 600-mg daily dose. No statistically significant (P > 0.05) differences were seen in RBT absorption parameter estimates between days 13 and 16: maximum concentration in plasma (Cmax; 511 +/- 341 ng/ml versus 525 +/- 254 ng/ml) and the time at which Cmax was observed (3.0 versus 2.5 h). The mean RBT estimates for area under the concentration-time curve from 0 to 24 h (AUC(0-tau)) (5,650 versus 5,023 ng x h/ml) and for oral clearance (1.28 versus 1.18 liter/h/kg) on both study days were also similar. Assessment based on urinary recovery of RBT (3.1 versus 3.7 mg) and its predominant deacetyl metabolite, LM565 (1.6 versus 1.4 mg), showed no apparent effect of ddI. The fraction of the RBT dose converted to LM565, as suggested by the ratio of AUC of the metabolite to AUC of the parent drug, was also unaltered (0.15 versus 0.12). A ratio analysis (day 13/day 16) of the RBT pharmacokinetic estimates showed that the 95% confidence intervals for all parameters were inclusive of one. Furthermore, the brief interruption of ddI therapy over this short study period at steady state produced no clinically significant changes in body weight, hematology, and renal and pancreatic functions. Therefore, concomitant administration of ddI appears not to affect RBT absorption in the gut and its disposition or safety in patients with AIDS.
vs 72620, p=0.01). Additionally, SLE patients had significantly lower GLS (%) (-16.762.8) when compared to healthy controls (-21.362) (p,0.0001) despite normal LVEF in both groups. Conclusions: Our results suggest that SLE patients show evidence of subclinical cardiac dysfunction, despite a normal LVEF and absence of cardiac disease. These patients may benefit from routine echocardiographic assessments and early cardiac preventative interventions.
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