Impact of interferon-free regimens on the glomerular filtration rate during treatment of chronic hepatitis C in a real-life cohort.

Little data are available on renal toxicity exerted by direct-acting antivirals (DAAs) in real life. The aim of this study was to assess the impact of direct-acting antivirals against hepatitis C virus infection currently used in Spain and Portugal on the estimated glomerular filtration rate (eGFR) in clinical practise. From an international, prospective multicohort study, patients treated with DAAs for at least 12 weeks and with eGFR ≥30 mL/min per 1.73 m2 at baseline were selected. eGFR was determined using the CKD-EPI formula. A total of 1131 patients were included; 658 (58%) were HIV/HCV-coinfected patients. Among the 901 patients treated for 12 weeks, median (interquartile range) eGFR was 100 (87-107) at baseline vs 97 (85-105) mL/min per 1.73 m2 at week 12 of follow-up (FU12) post-treatment (P < .001). For HIV-coinfected subjects who received tenofovir plus a ritonavir-boosted HIV protease inhibitor (PI/r), baseline vs FU12 eGFR were 104 (86-109) vs 104 (91-110) mL/min per 1.73 m2 (P = .913). Among subjects receiving ombitasvir/paritaprevir with or without dasabuvir, eGFR did not show any significant change. Of 1100 subjects with eGFR >60 mL/min per 1.73 m2 at baseline, 22 (2%) had eGFR <60 mL/min per 1.73 m2 at FU12, but none presented with eGFR <30 mL/min per 1.73 m2 . In conclusion, eGFR slightly declines during therapy with all-oral DAAs and this effect persists up to 12 weeks after stopping treatment in subjects with normal to moderately impaired renal function, regardless of HIV status. Concomitant use of tenofovir plus PI/r does not seem to have an impact on eGFR.

Core amino acid variation at position 110 is associated with sustained virological response in Caucasian patients with chronic hepatitis C virus 1b infection.

The aim of this study was to analyze the impact of core variations on sustained virological response (SVR) to pegylated interferon plus ribavirin (PEG-IFN/RBV) and its association with predictive factors of response in Caucasian patients infected with genotype 1 hepatitis C virus (HCV-1). Full-length core sequences were analyzed in 100 Caucasian HCV-1-infected patients who received therapy with PEG-IFN/RBV. The associations between variations in the core protein and SVR, as well as with predictors of SVR, were analyzed. Variations at core 62, 70 and 110 were selected as candidates. There were almost no variations at these positions among patients harboring HCV-1a. However, they were identified in 10 (30.3 %), 21 (63.6 %) and 13 (39.4 %) subjects with HCV-1b, respectively. Among the HCV-1b patients, 39.1 % individuals carrying core R62 and 70 % subjects with core R62G showed SVR (p = 0.141), and 66.7 % of HCV-1b patients harboring core R70 and 38.1 % with core R70Q achieved SVR (p = 0.157), whereas the rate of SVR was 70 % for individuals with core T110 and 15.4 % for those with core T110N (p = 0.004). No statistical interaction between core variations and IL28B genotype was observed. Patients with R70 showed higher median (interquartile range) baseline plasma levels of low-density-lipoprotein cholesterol (LDL-C) than those with R70Q (96 [86-118] mg/dL vs. 76 [54-88] mg/dL, p = 0.014). We concluded that a substitution at core 110 is associated with a lower rate of SVR in Caucasian HCV-1b-infected patients receiving PEG-IFN/RBV. Furthermore, the variation at the core 70 position is related to plasma levels of LDL-C in these patients.

Combined use of aspartate aminotransferase, platelet count and matrix metalloproteinase 2 measurements to predict liver fibrosis in HIV/hepatitis C virus-coinfected patients.

OBJECTIVE: Noninvasive tests that can be used in place of liver biopsy to diagnose fibrosis have major limitations. They either leave a significant proportion of patients without a definitive diagnosis or produce inaccurate results. Moreover, the performance of these tests is lower in HIV/hepatitis C virus (HCV) coinfection. Against this background, we examined the utility of serum matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 1 (TIMP-1) measurements in combination with routine clinical data to predict fibrosis in HIV/HCV-coinfected patients. METHODS: Patients with a liver biopsy who had not received anti-HCV therapy were included in the study. A model including variables independently associated with fibrosis was constructed. Diagnostic accuracy was determined by measuring the area under the receiver operating characteristic curve (AUROC). Positive (PPV) and negative (NPV) predictive values were calculated. RESULTS: Ninety patients were included in the study. Aspartate aminotransferase (AST), platelet count and MMP-2 were predictors of significant fibrosis (F≥2) and cirrhosis (F4). A score constructed using these variables yielded an AUROC of 0.76 for F≥2 and 0.88 for F4. Score cut-offs detected (value ≥3.5) and excluded (value ≤1.5) F≥2 with a PPV of 87% and an NPV of 88%. Thirty-one patients (34%) were correctly diagnosed using these cut-offs, with four (13%) incorrect classifications. Cirrhosis was excluded with a certainty of 98% and diagnosed with a probability of 83%. Two (17%) of 12 patients were misclassified as having cirrhosis. The AST to platelet count index and MMP-2 levels were sequentially applied to detect F≥2. Forty-one patients (46%) were identified with this approach, with six (15%) misclassifications. CONCLUSION: MMP-2 levels can be used in combination with AST and platelet count to aid the diagnosis of liver fibrosis in HIV/HCV-coinfected patients.

Supplementation of flaxseed oil diminishes skin sensitivity and improves skin barrier function and condition.

BACKGROUND: Skin sensitivity is a common problem in the Western population correlated with changes of skin properties like skin barrier function, hydration and skin physiology. Skin properties can be modulated by dietary fatty acids (FA), especially poly-unsaturated FA. The present study was performed to evaluate the effect of daily supplementation with flaxseed oil and safflowerseed oil on healthy volunteers with sensitive skin. METHODS: The study was designed as a randomized, double-blind 12-week intervention with 2 female treatment groups (n = 13). Plasma FA profile, skin sensitivity, skin hydration, transepidermal water loss (TEWL) and skin surface were evaluated on day 0, week 6 and week 12. RESULTS: Supplementation with flaxseed oil led to significant decreases in sensitivity (after nicotinate irritation), TEWL, skin roughness and scaling, while smoothness and hydration were increased. Concomitantly, the ratio of n-6/n-3 FA in plasma decreased. Upon supplementation with safflowerseed oil, only a significant improvement in skin roughness and hydration was observed; however, the effects were less pronounced and determined at a later point in time than with flaxseed oil. The plasma n-6/n-3 FA ratio increased. CONCLUSION: The data provide evidence that daily intake of flaxseed oil modulates skin condition.

Large thoracic wall hematoma following sternal reconstruction with transversal plate fixation after deep sternal wound infection.

We present the case of a 53-year-old male patient with a rare complication of a thoracic wall hematoma following thoracic wall reconstruction with transverse plate fixation and pectoralis advancement flaps. The patient could be subsequently discharged after surgical re-placement and an uneventful would healing. This case marks one of two complications occurring in a series of six patients treated for deep sternal wound infection with a combination of vacuum-assisted therapy and plate fixation.

Intraoperative embolus formation during cardiopulmonary bypass affects the release of S100B.

BACKGROUND: Intraoperative thromboembolism and the systemic inflammatory reaction are thought to play a role in causing cerebral dysfunction following cardiopulmonary bypass (CPB). Increased levels of S100B, an astroglial protein, have been linked to neuropsychological deficits after CPB. The present study investigated whether S100B release correlates with intraoperative embolus formation, thrombin formation, or the release of inflammatory parameters. METHODS: 40 patients undergoing coronary artery bypass grafting were included. Blood samples were taken before, during, and after CPB, and levels of S100B, thrombin-antithrombin complex (TAT), complement C5a, and interleukin 8 were analysed. Embolus formation was assessed by Doppler ultrasound at the arterial line of CPB. RESULTS: The release of S100B correlated with embolus count (r = 0.42; p = 0.009) and TAT formation (r = 0.71; p = 0.0001). The correlation of S100B with interleukin 8 (r = 0.58; p = 0.0001) was due to the dependence of both parameters on bypass time (r = 0.29; p = 0.075, partial correlation). A correlation of S100B with C5a formation could not be observed. CONCLUSIONS: S100B release is related to embolus and thrombin formation during CPB, indicating that thrombofibrinous embolism is involved in perioperative brain damage. Inflammatory parameters (i.e. interleukin 8 and C5a) seem to have no influence on S100B release.

Reduced release of tissue factor by application of a centrifugal pump during cardiopulmonary bypass.

The application of a centrifugal pump might lead to a reduced release of tissue factor (TF) due to less blood cell damage. This could result in a decrease in activation of the extrinsic pathway of coagulation and embolus formation. In the present study, 60 patients undergoing coronary artery bypass grafting were randomly assigned to a centrifugal or a roller pump. Plasma concentrations of TF, thrombin-antithrombin complex (TAT), and prothrombin fragments F1 + 2 were investigated before, during, and after cardiopulmonary bypass (CPB). Embolus detection was performed at the arterial line of CPB and transcranially by Doppler ultrasound. The centrifugal pump group revealed a lower TF release (area under the curve during CPB) when compared with the roller pump group [5661 (696-10359) vs 12681 (6383-17538) microg x min/l; median (lower - upper quartiles); P = 0.009]. In contrast, TAT and F1 + 2 formation did not differ between the groups, and neither did the total embolus count of both Doppler systems. Embolus counts did not correlate with TAT or F1 + 2 formation. In conclusion, the reduction in TF release by the application of a centrifugal pump seems to have little consequence on total thrombin formation. Since the applied Doppler systems seem to detect mainly microbubbles, conclusions regarding differences between the two pumps in the formation of thrombofibrinous clots cannot be drawn.

Centrifugal and roller pumps--are there differences in coagulation and fibrinolysis during and after cardiopulmonary bypass?

A number of hemostatic parameters reflecting the activation of coagulation and fibrinolysis were investigated in a prospective study of 24 patients undergoing cardiopulmonary bypass (CPB) during heart surgery. The patients were randomized to a group in which either a roller (group 1) or a centrifugal pump (group 2) was used. Blood samples were taken preoperatively, at the onset of and every 20 min during CPB, after the administration of protamine, and 4, 20, 44, and 68 h postoperatively. The groups did not differ significantly in hematocrit, fibrinogen, factor XIII, and antithrombin III. Significant differences in favor of group 2 during and after CPB were found in prothrombin fragment F1 + 2, plasmin-antiplasmin complex (PAP), thrombin-antithrombin complex (TAT), and D-dimer (F1 + 2 P < 0.01 after 80-min CPB, PAP P < 0.005 after 40-min CPB, TAT and D-dimer P < 0.05 after 100-min CPB, D-dimer and PAP P < 0.05 after protamine administration, TAT and F1 + 2 4 h after CPB). These findings indicate the activation of fibrinolysis preceding thrombin generation during cardiopulmonary bypass. In addition, we conclude that centrifugal blood pumping is beneficial in avoiding excessive activation of both coagulation and fibrinolysis.