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Background. Knowledge about mortality rates (MRs) in patients with chronic hepatitis C (CHC) with cirrhosis is limited. This study aimed to estimate all-cause MRs among patients with CHC with or without cirrhosis in Denmark compared with the general population. Methods. Patients registered in the Danish Database for Hepatitis B and C with CHC and a liver fibrosis assessment were eligible for inclusion. Liver fibrosis was assessed by means of liver biopsy, transient elastography, and clinical cirrhosis. Up to 20 sex- and age-matched individuals per patient were identified in the general population. Data were extracted from nationwide registries. Results. A total of 3410 patients with CHC (1014 with cirrhosis), and 67 315 matched individuals were included. Adjusted MR ratios (MRRs) between patients with or without cirrhosis and their comparison cohorts were 5.64 (95% confidence interval [CI], 4.76–6.67) and 1.94 (1.55–2.42), respectively. Cirrhosis among patients was associated with an MRR of 4.03 (95% CI, 3.43–4.72). A cure for CHC was associated with an MRR of 0.64 (95% CI, 0.40–1.01) among cirrhotic patients and 2.33 (1.47–3.67) compared with the general population. Conclusions. MRs were high among patients with CHC with or without cirrhosis compared with the general population. Curing CHC was associated with a reduction in MR among cirrhotic patients, but the MR remained higher than the general population.

Attenuation correction (AC) of whole-body PET data in combined PET/MRI tomographs is expected to be a technical challenge. In this study, a potential solution based on a segmented attenuation map is proposed and evaluated in clinical PET/CT cases. Segmentation of the attenuation map into 4 classes (background, lungs, fat, and soft tissue) was hypothesized to be sufficient for AC purposes. The segmentation was applied to CT-based attenuation maps from (18)F-FDG PET/CT oncologic examinations of 35 patients with 52 (18)F-FDG-avid lesions in the lungs (n = 15), bones (n = 21), and neck (n = 16). The standardized uptake values (SUVs) of the lesions were determined from PET images reconstructed with nonsegmented and segmented attenuation maps, and an experienced observer interpreted both PET images with no knowledge of the attenuation map status. The feasibility of the method was also evaluated with 2 patients who underwent both PET/CT and MRI. The use of a segmented attenuation map resulted in average SUV changes of 8% +/- 3% (mean +/- SD) for bone lesions, 4% +/- 2% for neck lesions, and 2% +/- 3% for lung lesions. The largest SUV change was 13.1%, for a lesion in the pelvic bone. There were no differences in the clinical interpretations made by the experienced observer with both types of attenuation maps. A segmented attenuation map with 4 classes derived from CT data had only a small effect on the SUVs of (18)F-FDG-avid lesions and did not change the interpretation for any patient. This approach appears to be practical and valid for MRI-based AC.

Background The effect of peginterferon and ribavirin treatment on chronic hepatitis C virus (HCV) infection has been established in several controlled clinical studies. However, the effectiveness of treatment and predictors of treatment success in routine clinical practice remains to be established. Our aim was to estimate the effectiveness of peginterferon and ribavirin treatment in unselected HCV patients handled in routine clinical practice. The endpoint was sustained virological response (SVR), determined by the absence of HCV RNA 24 weeks after the end of treatment. Methods We determined the proportion of SVR in a nationwide, population-based cohort of 432 patients with chronic HCV infection who were starting treatment, and analyzed the impact of known covariates on SVR by using a logistic regression analysis. Results The majority of treated patients had genotype 1 (133 patients) and genotype 2/3 (285 patients) infections, with 44% and 72%, respectively, obtaining SVR. Other than genotype, the predictors of SVR were age ≤ 45 years at the start of treatment, completion of unmodified treatment, the absence of cirrhosis and non-European origin. Conclusions The effectiveness of peginterferon and ribavirin treatment for chronic hepatitis C in a routine clinical practice is comparable to that observed in controlled clinical trials, with a higher SVR rate in genotype 2 and 3 patients compared to genotype 1 patients. Our data further indicate that age at start of treatment is a strong predictor of SVR irrespective of HCV genotype, with patients 45 years or younger having a higher SVR rate.

Levels of neutral poly-/perfluoroalkyl substances (nPFASs) in air and snow collected from Ny-Ålesund were measured and their air-snow exchange was determined to investigate whether they could re-volatilize into the atmosphere driven by means of air-snow exchange. The total concentration of 12 neutral PFASs ranged from 6.7 to 39 pg m −3 in air and from 330 to 690 pg L −1 in snow. A significant log-linear relationship was observed between the gas/particle partition coefficient and vapor pressure of the neutral PFASs. For fluorotelomer alcohol (FTOHs) and fluorotelomer acrylates (FTAs), the air-snow exchange fluxes were positive, indicating net evaporative from snow into air, while net deposition into snow was observed for perfluorooctane sulfonamidoethanols (Me/EtFOSEs) in winter and spring of 2012. The air-snow exchange was snow-phase controlled for FTOHs and FTAs and controlled by the air-phase for FOSEs. Air-snow exchange may significantly interfere with atmospheric concentrations of neutral PFASs in the Arctic.

Background. Coinfection with hepatitis C virus (HCV) in human immunodeficiency virus (HIV) type 1—infected patients may decrease the effectiveness of highly active antiretroviral therapy. We determined the impact of HCV infection on response to highly active antiretroviral therapy and outcome among Danish patients with HIV-1 infection. Methods. This prospective cohort study included all adult Danish HIV-1—infected patients who started highly active antiretroviral therapy from 1 January 1995 to 1 January 2004. Patients were classified as HCV positive (positive HCV serological test and/or HCV PCR results [443 patients {16%}]), HCV negative (consistent negative HCV serological test results [2183 patients {80%}]) and HCV-U (never tested for HCV [108 patients {4%}]). The study end points were viral load, CD4+ cell count, and mortality. Results. Compared with the HCV-negative group, overall mortality was significantly higher in the HCV-positive group (mortality rate ratio, 2.4; 95% confidence interval [CI], 1.9–3.0), as was liver disease—related mortality (mortality rate ratio, 16; 95% CI, 7.2–33). Furthermore, patients in the HCV-positive group had a higher risk of dying with a prothrombin time <0.3, from acquired immunodeficiency syndrome—related disease, and if they had a history of alcohol abuse. Although we observed no difference in viral load between the HCV-positive and HCV-negative groups, the HCV-positive group had a marginally lower absolute CD4+ cell count. Conclusions. HIV-HCV—coinfected patients are compromised in their response to highly active antiretroviral therapy. Overall mortality, as well as mortality from liver-related and acquired immunodeficiency syndrome—related causes, is significantly increased in this patient group.

Genetic variation upstream of the apoptosis pathway has been associated with outcome of hepatitis C virus (HCV) infection. We investigated genetic polymorphisms in the intrinsic apoptosis pathway to assess their influence on sustained virological response (SVR) to pegylated interferon-α and ribavirin (pegIFN/RBV) treatment of HCV genotypes 1 and 3 infections. We conducted a candidate gene association study in a prospective cohort of 201 chronic HCV-infected individuals undergoing treatment with pegIFN/RBV. Differences between groups were compared in logistic regression adjusted for age, HCV viral load and interleukin 28B genotypes. Four single nucleotide polymorphisms (SNPs) located in the B-cell lymphoma 2-like 1 (BCL2L1) gene were significantly associated with SVR. SVR rates were significantly higher for carriers of the beneficial rs1484994 CC genotypes. In multivariate logistic regression, the rs1484994 SNP combined CC + TC genotypes were associated with a 3.4 higher odds ratio (OR) in SVR for the HCV genotype 3 (p = 0.02). The effect estimate was similar for genotype 1, but the association did not reach statistical significance. In conclusion, anti-apoptotic SNPs in the BCL2L1 gene were predictive of SVR to pegIFN/RBV treatment in HCV genotypes 1 and 3 infected individuals. These SNPs may be used in prediction of SVR, but further studies are needed.

Concentrations of neutral poly- and perfluoroalkyl substances (PFASs), such as fluorotelomer alcohols (FTOHs), perfluoroalkane sulfonamides (FASAs), perfluoroalkane sufonamidoethanols (FASEs), and fluorotelomer acrylates (FTACs), have been simultaneously determined in surface seawater and the atmosphere of the North Sea. Seawater and air samples were taken aboard the German research vessel Heincke on the cruise 303 from 15 to 24 May 2009. The concentrations of FTOHs, FASAs, FASEs, and FTACs in the dissolved phase were 2.6–74, <0.1–19, <0.1–63, and <1.0–9.0 pg L −1 , respectively. The highest concentrations were determined in the estuary of the Weser and Elbe rivers and a decreasing concentration profile appeared with increasing distance from the coast toward the central part of the North Sea. Gaseous FTOHs, FASAs, FASEs, and FTACs were in the range of 36–126, 3.1–26, 3.7–19, and 0.8–5.6 pg m −3 , which were consistent with the concentrations determined in 2007 in the North Sea, and approximately five times lower than those reported for an urban area of Northern Germany. These results suggested continuous continental emissions of neutral PFASs followed by transport toward the marine environment. Air–seawater gas exchanges of neutral PFASs were estimated using fugacity ratios and the two-film resistance model based upon paired air–seawater concentrations and estimated Henry's law constant values. Volatilization dominated for all neutral PFASs in the North Sea. The air–seawater gas exchange fluxes were in the range of 2.5 × 10 3 –3.6 × 10 5  pg m −2 for FTOHs, 1.8 × 10 2 –1.0 × 10 5  pg m −2 for FASAs, 1.1 × 10 2 –3.0 × 10 5  pg m −2 for FASEs and 6.3 × 10 2 –2.0 × 10 4  pg m −2 for FTACs, respectively. These results suggest that the air–seawater gas exchange is an important process that intervenes in the transport and fate for neutral PFASs in the marine environment.

CT-based attenuation correction is a widely used option in commercial PET/CT scanners. However, as a result of a nonsimultaneous acquisition and differences in temporal resolution between both modalities, a potential misregistration between the PET and CT, especially in the thorax and the upper abdomen, can be found. We observed a substantial number of apparent perfusion defects in spatial coincidence with the misregistered segments of the heart and assumed these defects were related to an incorrect attenuation correction. The purpose of this work was to assess the clinical impact of emission-transmission misalignment in myocardial perfusion imaging with PET/CT and to investigate potential solutions. Twenty-eight coronary artery disease patients underwent PET/CT (13)NH3 rest/stress examinations. The emission-transmission misalignment was corrected by manual registration and the PET studies were reconstructed again using the realigned CT images for attenuation correction. The effects of the registration were evaluated by quantitative analysis of the local tracer uptake on a polar map basis. In addition to manual registration, 2 alternative realignment methods were evaluated: mutual information-based image registration and emission-driven correction based on the outline of the heart in the PET image. Manual realignment resulted in a change in the defect size of >10% of the left ventricle in 6 of 28 studies (21.4%); in 5 of the studies, this resulted in the disappearance of large apparent perfusion defects (15%-46% of the left ventricle), which were fully due to emission-transmission misregistration. Automatic image registration was unable to realign the datasets, whereas the emission-driven correction showed a good agreement with manual registration. Misregistration of PET and CT images is common in cardiac PET/CT studies and results in artifacts on the attenuation-corrected PET images, which appear to be corrected by repeating the PET reconstruction after manual realignment of the CT image data. In contrast to manual realignment, an automated emission-driven correction appears to be a promising approach.

BackgroundSeveral blood-based tests have been suggested to improve prostate cancer testing. The Stockholm3 test has been shown to reduce the number of prostate biopsies, to decrease detection of low-grade cancer and to maintain the detection rate of ISUP Gleason Group (GG) ≥ 2 cancer in a screening-by-invitation setting. We aimed to validate the performance of the Stockholm3 test in an independent, clinical practice cohort.MethodsThe study-population consisted of 533 men in ages 45–75 without previous diagnosis of prostate cancer scheduled for prostate biopsy at any of three centers in Norway and Sweden. Blood samples for Stockholm3 analysis were drawn prior to systematic prostate biopsies. Clinically significant prostate cancer was defined as any finding of ISUP Grade Group (GG) 2 or higher. We calculated area under the curve (AUC) for predicting prostate cancer at biopsy and calculated. Models including PSA and PSA-density (PSA/prostate volume) were compared to a model including also clinical information, protein levels and single nucleotide polymorphisms (SNP).Results263 of 533 (49%) participants were diagnosed with prostate cancer. 162 men had prostate cancer with GG ≥ 2. The Stockholm3 test discriminated better for GG ≥ 2 prostate cancer than PSA in combination with PSA-density AUC 8.9 (95% CI 82.7–89.2) and AUC 74.8 (95% CI 70.3–79.3). Using a Stockholm3 cut-off of 10% risk of GG ≥ 2 cancer, 38% of the biopsy procedures were saved, however delaying diagnosis for 6% (n = 10) of men with GG ≥ 2 cancer. Using PSA-density 0.1 as cut-off for biopsy saved 35% of biopsies, delaying diagnosis for 16% (n = 26) of men with GG ≥ 2 cancer.ConclusionA prediction model including clinical information, protein levels and SNPs was independently validated in a clinical practice cohort and reduces the number of un-necessary biopsies while delaying diagnosis for a limited number of men.

China is one of the largest producers, consumers, and traders for pesticides in the world. Currently, there are more than 600 pesticide-active substances registered in China, whereas few studies were conducted to improve our understanding of the occurrence and environmental impact of current-use pesticides (CUPs) in China’s environment. In this work, 72 surface sediment samples were taken from the coastal and offshore of Bohai and Yellow seas and were analyzed for six CUPs (trifluralin, dacthal, quintozene, endosulfan, chlorpyrifos, and dicofol) and two metabolites (pentachloroanisole and endosulfan sulfate). Sediment samples were categorized as estuarine or near-shore sediments (Laizhou Bay, Taozi Bay, Sishili Bay, and Jiaozhou Bay) and offshore sediments. Trifluralin, α-endosulfan, endosulfan sulfate, chlorpyrifos, dicofol, and pentachloroanisole were detected in more than 60 % of the samples. Dicofol was the predominant compound with concentrations mostly higher than 100 pg/g dry weight (dw) with the highest concentration of 18,000 pg/g dw. Concentrations of other compounds were mainly below 100 pg/g dw. CUP levels were much lower than the sediment screening benchmark calculated. The highest levels of α-endosulfan, endosulfan sulfate, trifluralin, and chlorpyrifos existed at Laizhou Bay, whereas pentachloroanisole and dicofol had highest mean concentrations at Jiaozhou Bay. Generally, no correlation between pesticide concentrations and total organic carbon was observed either for offshore samples or for near-shore samples.