Exposure to ambient air pollution and elevated blood levels of gamma-glutamyl transferase in a large Austrian cohort.

Gamma glutamyl transferase (GGT) is related to oxidative stress and an indicator for liver damage. We investigated the association between air pollution and GGT in a large Austrian cohort (N = 116,109) to better understand how air pollution affects human health. Data come from voluntary prevention visits that were routinely collected within the Vorarlberg Health Monitoring and Prevention Program (VHM&PP). Recruitment was ongoing from 1985 to 2005. Blood was drawn and GGT measured centralized in two laboratories. Land use regression models were applied to estimate individuals' exposure at their home address for particulate matter (PM) with a diameter of <2.5 µm (PM2.5), <10 µm (PM10), fraction between 10 µm and 2.5 µm (PMcoarse), as well as PM2.5 absorbance (PM2.5abs), NO2, NOx and eight components of PM. Linear regression models, adjusting for relevant individual and community-level confounders were calculated. The study population was 56 % female with a mean age of 42 years and mean GGT was 19.0 units. Individual PM2.5 and NO2 exposures were essentially below European limit values of 25 and 40 µg/m3, respectively, with means of 13.58 µg/m3 for PM2.5 and 19.93 µg/m3 for NO2. Positive associations were observed for PM2.5, PM10, PM2.5abs, NO2, NOx, and Cu, K, S in PM2.5 and PM10 fractions and Zn mainly in PM2.5 fraction. The strongest association per interquartile range observed was an increase of serum GGT concentration by 1.40 % (95 %-CI: 0.85 %; 1.95 %) per 45.7 ng/m3 S in PM2.5. Associations were robust to adjustments for other biomarkers, in two-pollutant models and the subset with a stable residential history. We found that long-term exposure to air pollution (PM2.5, PM10, PM2.5abs, NO2, NOx) as well as certain elements, were positively associated with baseline GGT levels. The elements associated suggest a role of traffic emissions, long range transport and wood burning.

Pharmacological targeting of host chaperones protects from pertussis toxin in vitro and in vivo.

Whooping cough is caused by Bordetella pertussis that releases pertussis toxin (PT) which comprises enzyme A-subunit PTS1 and binding/transport B-subunit. After receptor-mediated endocytosis, PT reaches the endoplasmic reticulum from where unfolded PTS1 is transported to the cytosol. PTS1 ADP-ribosylates G-protein α-subunits resulting in increased cAMP signaling. Here, a role of target cell chaperones Hsp90, Hsp70, cyclophilins and FK506-binding proteins for cytosolic PTS1-uptake is demonstrated. PTS1 specifically and directly interacts with chaperones in vitro and in cells. Specific pharmacological chaperone inhibition protects CHO-K1, human primary airway basal cells and a fully differentiated airway epithelium from PT-intoxication by reducing intracellular PTS1-amounts without affecting cell binding or enzyme activity. PT is internalized by human airway epithelium secretory but not ciliated cells and leads to increase of apical surface liquid. Cyclophilin-inhibitors reduced leukocytosis in infant mouse model of pertussis, indicating their promising potential for developing novel therapeutic strategies against whooping cough.

Intermediate-High Risk Pulmonary Embolism: The Use of Riociguat and Inferior Vena Cava Filter in a Situation of Recurrent Embolism following Insufficient Anticoagulation and Fibrinolytic Therapy.

Pulmonary embolism (PE) is associated with serious morbidity and mortality. In this case report, we describe a hemodynamically stable patient with submassive PE and a large thrombus in the inferior vena cava (IVC) protruding into the right atrium (RA), complicated by severe respiratory failure, elevated troponin T (TnT), and right ventricular (RV) dysfunction. The patient was stratified as intermediate-high risk of early death. Important issues regarding the initial choice of anticoagulation, rescue thrombolytic therapy, and benefits of adding riociguat to stimulate the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) pathway to improve the RV function are discussed. Finally, we address appropriate timing and the use of IVC filter in a situation of recurrent PE following anticoagulation and fibrinolytic therapy.

Development and reliability assessment of a new quality appraisal tool for cross-sectional studies using biomarker data (BIOCROSS).

BACKGROUND: Biomarker-based analyses are commonly reported in observational epidemiological studies; however currently there are no specific study quality assessment tools to assist evaluation of conducted research. Accounting for study design and biomarker measurement would be important for deriving valid conclusions when conducting systematic data evaluation. METHODS: We developed a study quality assessment tool designed specifically to assess biomarker-based cross-sectional studies (BIOCROSS) and evaluated its inter-rater reliability. The tool includes 10-items covering 5 domains: 'Study rational', 'Design/Methods', 'Data analysis', 'Data interpretation' and 'Biomarker measurement', aiming to assess different quality features of biomarker cross-sectional studies. To evaluate the inter-rater reliability, 30 studies were distributed among 5 raters and intraclass correlation coefficients (ICC-s) were derived from respective ratings. RESULTS: The estimated overall ICC between the 5 raters was 0.57 (95% Confidence Interval (CI): 0.38-0.74) indicating a good inter-rater reliability. The ICC-s ranged from 0.11 (95% CI: 0.01-0.27) for the domain 'Study rational' to 0.56 (95% CI: 0.40-0.72) for the domain 'Data interpretation'. CONCLUSION: BIOCROSS is a new study quality assessment tool suitable for evaluation of reporting quality from cross-sectional epidemiological studies employing biomarker data. The tool proved to be reliable for use by biomedical scientists with diverse backgrounds and could facilitate comprehensive review of biomarker studies in human research.

Association Between Peripheral Adipokines and Inflammation Markers: A Systematic Review and Meta-Analysis.

OBJECTIVE: Obesity-induced inflammation potentially promotes a variety of chronic conditions. This study aimed to summarize cross-sectional associations between adipose tissue-derived hormones (leptin and adiponectin) and inflammatory biomarkers (C-reactive protein [CRP], interleukin [IL]-6, and tumor necrosis factor [TNF]-α) by means of meta-analysis. METHODS: A systematic search of the databases EMBASE and MEDLINE (PubMed) up to January 2017 was conducted. Data were independently extracted and evaluated by two reviewers. Pooled effect sizes and 95% confidence intervals were calculated using random-effects models. RESULTS: After the initial search, 5,907 publications were retrieved; of these, an overall 60 studies with 45,210 participants were deemed eligible for inclusion in the meta-analysis. Positive correlations with inflammatory biomarkers were observed for leptin (pooled Rho = 0.35, 0.20, and 0.20 for CRP, IL-6, and TNF-α, respectively), whereas the respective correlations with adiponectin were negative (pooled Rho = -0.18, -0.14, and -0.12 for CRP, IL-6, and TNF-α, respectively). Stratification by age showed that the observed correlations tended to be weaker with the increasing age of participants. No apparent differences were observed by sex and adiposity status. CONCLUSIONS: This is the first quantitative synthesis of human studies on the association between circulating adipokines and inflammation biomarkers. Potential influence of age on these associations requires further evaluation.

Ultrasound in evaluation of post-interventional femoral vein obstruction: a case report.

Ultrasound is the preferred imaging modality in diagnosis of vascular complications following cardiac catheterization and intervention. In some cases, however, bleeding surrounding the femoral vessels, may severely distort the color Doppler images, making detection of venous complications especially difficult. This report refers to such a case where post-catheterization haematoma was suspected to cause an obstruction of the femoral vein. Spectral Doppler recordings of blood flow in the common femoral vein, up-stream, distal to the hemorrhagic area, confirmed the diagnosis of obstruction by demonstrating changes in the venous flow pattern in the common femoral vein, consistent with venous hypertension. Due to the poor quality of the ultrasound images, the exact cause of the obstruction had to be established by another imaging modality, not affected by haemorrhages. CT showed that the common femoral vein was compressed at the puncture site by surrounding haemorrhages. Thus, when bleeding due to cardiac catheterization is associated with possible venous obstruction and findings by color Doppler are equivocal due to degradation of the color-Doppler image, detection of venous hypertension by spectral Doppler, performed distal to the bleeding area, strongly supports the presence of venous obstruction where the exact cause may be established by CT.

Treatment of a hepatic artery aneurysm by endovascular stent-grafting.

Aneurysms of the visceral arteries are rare. Traditional treatment has been surgical or endovascular with coil embolization. Recently, however, reports on endovascular therapy with stent-grafts have been published. We report the case of a 61-year-old man who was successfully treated with a stent-graft for a symptomatic combined celiac/hepatic artery aneurysm.

[Use of stents in abdominal aortic aneurysms]. / Bruk av stentgraft ved abdominale aortaaneurismer.

BACKGROUND: Endovascular treatment of aortic aneurysms has acquired a widespread application. We present the results of endovascular treatment of infrarenal, abdominal aortic aneurysms in our hospital from 1995 through 2002. MATERIAL AND METHOD: Seventy-one stent graft procedures were performed on 69 patients (64 men), mean age 72 years (range 48-96 years). Mean aneurysm diameter was 57 mm (range 35-100 mm). Sixty-nine procedures were elective and two were emergency procedures. All data were registered prospectively. RESULTS: Two procedures failed initially because of technical problems. Both patients underwent a successful procedure later. Immediate conversion to open surgery was done in one case because of a collapse of the graft into the aneurysm sac. There was no 30-day mortality for elective procedures. The conversion rate after a mean observation time of 42 months was 11%. Late complications resulted in 47 re-interventions in 29 patients, of which 96% were done in cases treated with Stentor or Vanguard prostheses. CONCLUSION: Endovascular treatment of aortic aneurysms is an alternative to open surgery. Stent graft failure can be serious and difficult to predict. This treatment should not be recommended to patients younger than 70 years and fit for open surgery.

[Stenting of failing above-knee femoropopliteal percutaneous transluminal angioplasty]. / Stentbehandling i det femoropopliteale segmentet ovenfor kneet.

BACKGROUND: Percutaneous transluminal angioplasty (PTA) is increasingly used in the treatment of stenoses and short occlusions of the superficial femoral and proximal popliteal arteries. Routine treatment with arterial stents does not seem to improve the results compared to PTA without stent but the efficacy of stenting as a repair procedure of a failing PTA is not known. PATIENTS AND METHODS: In our hospital, intraluminal arterial stenting of the above knee femoropopliteal segment has been used as a repair procedure when PTA alone fails because of dissection or recoil. From 1995 to 2001, 264 above-knee femoropopliteal PTAs were performed in 203 patients. Fifteen procedures were considered failures; these cases are reported in this study. RESULTS: Arterial stents were successfully implanted in all fifteen patients. One year postoperatively, five stents had occluded, seven reconstructions were still patent. Three patients could not be followed up; they were diseased at the time of the study. INTERPRETATION: In spite of the limited patency achieved, intraluminal arterial stenting in the above-knee femoropopliteal segment can be useful as a repair procedure when PTA alone fails.