CXCR7 expression is associated with disease-free and disease-specific survival in cervical cancer patients

Background:The CXC chemokine receptor (CXCR)7 is involved in tumour development and metastases formation. The aim of the present study was to determine protein expression of CXCR7, its putative co-receptors epidermal growth factor receptor (EGFR) and CXCR4, its predominant ligand CXCL12, their co-dependency and their association with survival in cervical cancer patients.Methods:CXC chemokine receptor 7, EGFR, CXCR4 and CXCL12 expression were determined immunohistochemically in 103 paraffin-embedded, cervical cancers. Subsequently, associations with patient characteristics were assessed and survival analyses were performed.Results:CXC chemokine receptor 7 was expressed by 43% of tumour specimens, in a large majority of cases together with either EGFR or CXCR4 (double positive), or both (triple positive). The CXCR7 expression was associated with tumour size (P=0.013), lymph node metastasis (P=0.001) and EGFR expression (P=0.009). CXC chemokine receptor 7 was independently associated with disease-free survival (hazard ratio (HR)=4.3, 95% confidence intervals (CI) 1.7-11.0, P=0.002), and strongly associated with disease-specific survival (HR=3.9, 95% CI 1.5-10.2, P=0.005).Conclusion:CXC chemokine receptor 7 expression predicts poor disease-free and disease-specific survival in cervical cancer patients, and might be a promising new therapeutic marker. In a large majority of cases, CXCR7 is co-expressed with CXCR4 and/or EGFR, supporting the hypothesis that these receptors assist in CXCR7 signal transduction.Cervix cance

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Cumulation and permit issuance for SVHCs

Bedrijven krijgen van de overheid een vergunning voor de hoeveelheid chemische stoffen die ze mogen uitstoten, waaronder Zeer Zorgwekkende Stoffen (ZZS). Deze vergunning wordt meestal voor één stof gegeven maar bedrijven stoten vaak mengsels van verschillende stoffen tegelijk uit. Mensen en het milieu kunnen hieraan worden blootgesteld (cumulatie). De kans dat een mengsel schadelijke effecten heeft, kan groter zijn dan de effecten van één stof. Hoe groot die kans is, hangt af van de samenstelling, de concentraties en de schadelijkheid van de stoffen. Het effect van een mengsel wordt nu nauwelijks meegenomen bij de vergunningverlening, zo blijkt uit een verkenning van het RIVM. Daarin is ook geïnventariseerd welke mogelijkheden er zijn om daar wat aan te doen. Dit is gedaan in opdracht van het ministerie van Infrastructuur en Waterstaat (IenW). Het RIVM beschrijft welke methoden overheden kunnen gebruiken om de effecten van stoffenmengsels voor mens en milieu te kunnen inschatten en voor de vergunningverlening te gebruiken. Ook is gekeken hoe landen rondom Nederland, zoals Denemarken, België (Vlaanderen) en Duitsland, het effect van mengsels erin betrekken. Het RIVM beveelt aan te onderzoeken in welke stappen van het vergunningsverleningsproces de cumulatie-effecten het beste kunnen worden meegenomen. Het is hierbij belangrijk rekening te houden met veiligheidsmarges die er al zijn. Ook is het nodig de voorstellen uit te werken met betrokken partijen, zoals omgevingsdiensten. Dan zijn ze beter uit te voeren in de praktijk. Daarnaast geeft het RIVM aanbevelingen voor vervolgonderzoek. Bijvoorbeeld om in kaart te brengen op welke plekken in Nederland ZZS en andere chemische stoffen het meest voorkomen, zodat deze locaties als eerste kunnen worden aangepakt. Ook is aandacht nodig voor de hoeveelheid vergunde stoffen die uit de lucht in de bodem en het water terechtkomt. De neerslag op bodem en water blijft nu grotendeels buiten beeld, en dus ook het cumulatie-effect daarvan. Tot slot benadrukt het RIVM in het algemeen om zo min mogelijk ZZS naar de leefomgeving uit te stoten. Dat verkleint de mogelijke cumulatieve effecten van ZZS voor mens en milieu.The government issues permits to companies specifying the quantity of chemical substances that they are allowed to emit, including substances of very high concern (SVHCs). These permits are usually issued for a single substance, but companies often emit mixtures of various substances simultaneously. People and the environment can be exposed to these (cumulation). The probability that a mixture will have harmful effects could be higher than the probability of the constituent substances having harmful effects individually. How high that probability is will depend on the composition, concentrations and harmfulness of the substances. A study conducted by the National Institute for Public Health and the Environment (RIVM) reveals that the effects of mixtures receive scant attention within the permit issuance process at present. The study, which was commissioned by the Ministry of Infrastructure and Water Management, also identified options to address this. RIVM sets out the methods that authorities can use both for the permit issuance process and to enable them to gauge the effects of mixtures of substances on humans and the environment. The study also looked at how nearby countries and regions such as Denmark, Belgium (Flanders) and Germany factor in the effects of mixtures. RIVM would recommend investigating which steps within the permit issuance process would be the best ones to factor the cumulative effects into. In this regard, it is important to give due consideration to the safety margins already in place. It will also be necessary to flesh out the proposals with parties involved, such as environmental agencies, thus ensuring that they are more readily implementable in practice. RIVM also makes recommendations for follow-up research, such as charting the places in the Netherlands where SVHCs and other chemical substances are most prevalent, making it possible to tackle these locations first. In addition, attention will need to be given to the quantity of the licensed substances ending up in the soil and water from the air. As things currently stand, precipitation onto soil and water is largely unmonitored, as is the cumulative effect thereof. Finally, RIVM is keen to stress in general that levels of SVHCs emitted into the living environment should be minimised. This will reduce the potential cumulative effects of these SVHCs on humans and the environment

Alterations in classical and nonclassical HLA expression in recurrent and progressive HPV-induced usual vulvar intraepithelial neoplasia and implications for immunotherapy

TI9 - Endometriumpathologi

Predictive Performance of Cardiovascular Disease Risk Prediction Algorithms in People Living With HIV

Immunogenetics and cellular immunology of bacterial infectious disease

Progression of liver fibrosis following acute hepatitis C virus infection in HIV-positive MSM

Molecular basis of virus replication, viral pathogenesis and antiviral strategie