This study aimed at analyzing circulating levels of inflammatory and profibrogenic cytokines in patients with hepatitis C virus (HCV) chronic infection undergoing therapy with direct-acting antiviral agents (DAA) and correlating these immune biomarkers with liver disease status. We studied 88 Brazilian monoinfected chronic hepatitis C patients receiving interferon- (IFN-) free sofosbuvir-based regimens for 12 or 24 weeks, followed-up before therapy initiation and three months after the end of treatment. Liver disease was determined by transient elastography, in addition to APRI and FIB-4 indexes. Analysis of 30 immune mediators was carried out by multiplex or enzymatic immunoassays. Sustained virological response rate was 98.9%. Serum levels of cytokines were increased in HCV-infected patients when compared to control group. CCL-2, CCL-3, CCL-4, CXCL-8, CXCL-10, IL-1β, IL-15, IFN-γ, IL-4, IL-10, TGF-β, FGFb, and PAI-1 decreased significantly after antiviral therapy, reaching values similar to noninfected controls. TGF-βand suPAR levels were associated with fibrosis/cirrhosis. Also, we observed amelioration in hepatic parameters after DAA treatment. Together, our results suggest that viral control induced by IFN-free DAA therapy restores inflammatory mediators in association with improvement in liver function.
Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of kidney injury. We sought to assess the prognostic value of this biomarker in patients with stable chronic heart failure (HF). We studied 61 patients with chronic systolic HF who had been receiving optimal medical treatment for at least six months. Biomarkers were measured at baseline and included plasma NGAL, microalbuminuria, serum creatinine, and B-type natriuretic peptide (BNP). Estimated glomerular filtration rate (eGFR) was also calculated. Mean follow-up was 10.6±6.6 months. The primary endpoint was time to first cardiovascular event, defined as a combination of cardiovascular death, HF hospitalization or emergency department visit due to HF. Variables independently related to events were determined using a Cox proportional hazards model. Fifteen (24.6%) patients reached the primary endpoint. Patients with events were more likely to have worse renal function at baseline and also higher NGAL levels (median 316 [interquartile range 122-705] vs. 107 [78-170]; p=0.006). NGAL correlated significantly with creatinine (r=0.50; p<0.0001), albuminuria (r=0.33; p=0.008), and eGFR (r=-0.47; p=0.0001) but not with BNP (r=0.003; p=0.97). The best NGAL cutoff as determined by ROC curve analysis was 179 ng/ml. Event-free survival was lower in patients with NGAL above this cutoff. Variables independently related to events were NGAL (HR 1.0035, 95% CI 1.0019-1.0052; p<0.0001) and male gender (HR 5.9, 95% CI 1.22-28.6; p=0.028). NGAL correlated with other biomarkers of renal function but not with BNP and was independently associated with outcomes.
27 October 2017 in International Journal of Clinical Pharmacy
Gunshot wounds require surgeons to decide whether to remove or leave bullet fragments in the body. Surgeons also decide how to follow up with patients who have lead fragments retained in their body. Current literature recommends to remove only intra-articular fragments without the need for a follow-up for patients with the metal retained. Therefore, this study investigates chronic lead toxicity for gunshot wounds. The study was performed in the metropolitan area of Rio de Janeiro/Brazil, between 2013 and 2015. It was a case-control study that included 45 victims of gunshot lesions with metallic fragments retained for more than 6 months. The 45 controls were matched for gender, age, and race. We compared the lead blood levels and frequency of symptoms. The control group had average blood lead levels of 2.17 μg/dL (95% Confidence Interval [CI]; 1.71–2.63) and median 2.1 μg/dL. The case group had average values of 9.01 μg/dL (CI; 6.07–11.96) and median values of 6.5 μg/dL with p-values < = 0.001. The case group reported the following more frequently: irritancy, bad mood, headache, memory losses, daylight drowsiness, myalgia, weakness, abdominal pain, joint pain, trembling, tingling limbs. There was statistical significance for the differences of symptoms frequencies and for odds ratio between groups. Although the mean lead levels found were lower than the current laboratory references, low levels have been associated with both rising morbidity and mortality. The WHO stated: “There is no known level of lead exposure that is considered safe”. In conclusion, this work showed that bullets retained in the body are not innocuous. There are impacts in the blood lead levels and symptoms related to it, even with few fragments, extra-articular located or existing with low blood lead levels.