Men with Crohn's disease may have an increased risk for head and neck squamous cell carcinoma - a nationwide register study

Objective Our goal was to study inflammatory bowel disease (IBD) patients' risk of head and neck squamous cell carcinoma (HNSCC), compared to general population.Materials and methods We performed a retrospective nationwide register-based study of Finnish individuals diagnosed with IBD between the years 1995 and 2015. The standardized incidence ratio (SIR) of HNSCC was calculated by comparing the cohort's complementary age-year-sex-person-year incidence to that of the whole Finnish population.Results About 70,567 patients were diagnosed with IBD (Crohn's disease or ulcerative colitis). Later, 89 of them were diagnosed with HNSCC with mean time of 6.82 years. The incidence of HNSCC was increased in IBD patients compared to the Finnish population expectation (SIR 1.3, 95% CI 1.065-1.614, P = 0.062). When calculating Crohn's disease and ulcerative colitis separately as well as men and women separately, the incidence was particularly increased for men with Crohn's disease (SIR 1.951, 95% CI 1.216-2.935, P = 0.025).Conclusion An increased risk for HNSCC was found in men with Crohn's disease compared to the Finnish population expectations.Clinical relevance This study provides information that would improve follow-up protocols and treatment guidelines of IBD.Peer reviewe

Malignant transformation of oral epithelial dysplasia in Southwest Finland

Oral epithelial dysplasia (OED) is considered a risk for oral squamous cell carcinoma (OSCC). A meta-analysis estimated a mean malignant transformation rate of 12.1% (95% CI 8.1-17.9). The main target of this study was to define how many OED patients develop OSCC in the hospital district of Southwest Finland. A total of 571 patients diagnosed with OED were identified. Their potential subsequent diagnosis of OSCC was derived from the Finnish Cancer Registry. The risk of OSCC development in OED patients was compared with that of the general population without OED. During a mean follow-up of 5.5 (range 0.1-29.0) years 10.9% of OED patients developed OSCC. OED patients had a 44.7-fold higher risk (95% CI 34.4-56.7) of developing OSCC than the general population. The risk was at its highest within two years of OED diagnosis. OED patients in Southwest Finland have a significantly increased risk of developing OSCC relative to the general population, especially within the first two years of dysplasia diagnosis.Peer reviewe

Human polyomavirus BKPyV and JCPyV serostatus has no impact on women´s human papillomavirus infection outcome

IntroductionPolyomaviruses have both structural and functional similarities with papillomaviruses. Accordingly, their role in human papillomavirus (HPV) associated malignancies has been studied with conflicting results. Our goal was to disclose any association between BK (BKPyV) and/or JC (JCPyV) polyomavirus serology and HPV data derived from Finnish women (327) in a 6-year prospective follow-up.MethodsGlutathione S-transferase fusion-protein-capture (ELISA) in combination with fluorescent bead technology was used to analyze antibodies to BKPyV and JCPyV. In the longitudinal setting, BKPyV or JCPyV serostatus was related to i) oral- and ii) genital low (LR)- and high risk (HR) HPV DNA detection, iii) HPV16 persistence at both these sites, iv) results of the Pap (Papanicolaou) smear taken at baseline, and v) development of incident CIN (cervical intraepithelial neoplasia) during the follow-up.ResultsBeing BKPyV or JCPyV seropositive was not significantly associated with HPV seropositivity to either LR- or HR-genotypes, genital- or oral HPV DNA positivity, persistence of genital- or oral HPV16 infection, grade of Pap smear, or development of incident CIN.DiscussionThus, the present study could not provide any confirmation to the concept that co-infections by HPyV and HPV have interactions that impact on the clinical manifestations or outcomes of HPV infections either in the genital tract or in the oral mucosa

Optimal sampling and analysis methods for clinical diagnostics of vaginal microbiome

Next-generation sequencing-based microbiological analysis is a complex way to profile vaginal microbiome samples since each step affects the results gained. Methodologies for sample collection lack golden standards. We compared Puritan DNA/RNA swab (PS) and Copan FLOQ swab (CS) and provided consistent and reliable microbiome profiles analyzed by 16S rRNA gene sequencing. We collected two consecutive vaginal samples utilizing PS with room temperature storing and CS with instant freezing from 26 women. Variable region 4 of bacterial 16S rRNA gene was amplified with single PCR by custom-designed dual-indexed primers and sequenced with Illumina MiSeq system. Read quality control, operational taxonomic unit tables, and alpha and beta diversities analysis were performed, and community richness, diversity, and evenness were evaluated and compared between the two samplings and tests. Nineteen sample pairs produced detectable, intact DNA during the extraction protocol and/or further microbial profiles. Alpha bacterial diversity indices were independent on the collection protocol. No significant statistical differences were found in the measured beta diversity metrics between the collection methods. Of the women, 43% had Lactobacillus-dominated vaginal microbiome profile despite of collection method. Previously reported important vaginal microbiome phyla Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Proteobacteria were present in the sample set although their relative abundances varied among individuals. PS and CS enable constant vaginal microbiota sampling. The PS method with no need for instant freezing is suitable for on-site collections at clinics. Furthermore, it seems to be possible to take two samples instead of one with constant microbiological results.Peer reviewe

Men with Crohn's disease may have an increased risk for head and neck squamous cell carcinoma - a nationwide register study

Objective Our goal was to study inflammatory bowel disease (IBD) patients' risk of head and neck squamous cell carcinoma (HNSCC), compared to general population.Materials and methods We performed a retrospective nationwide register-based study of Finnish individuals diagnosed with IBD between the years 1995 and 2015. The standardized incidence ratio (SIR) of HNSCC was calculated by comparing the cohort's complementary age-year-sex-person-year incidence to that of the whole Finnish population.Results About 70,567 patients were diagnosed with IBD (Crohn's disease or ulcerative colitis). Later, 89 of them were diagnosed with HNSCC with mean time of 6.82 years. The incidence of HNSCC was increased in IBD patients compared to the Finnish population expectation (SIR 1.3, 95% CI 1.065-1.614, P = 0.062). When calculating Crohn's disease and ulcerative colitis separately as well as men and women separately, the incidence was particularly increased for men with Crohn's disease (SIR 1.951, 95% CI 1.216-2.935, P = 0.025).Conclusion An increased risk for HNSCC was found in men with Crohn's disease compared to the Finnish population expectations.Clinical relevance This study provides information that would improve follow-up protocols and treatment guidelines of IBD.</p

Malignant transformation of oral epithelial dysplasia in Southwest Finland

Oral epithelial dysplasia (OED) is considered a risk for oral squamous cell carcinoma (OSCC). A meta-analysis estimated a mean malignant transformation rate of 12.1% (95% CI 8.1-17.9). The main target of this study was to define how many OED patients develop OSCC in the hospital district of Southwest Finland. A total of 571 patients diagnosed with OED were identified. Their potential subsequent diagnosis of OSCC was derived from the Finnish Cancer Registry. The risk of OSCC development in OED patients was compared with that of the general population without OED. During a mean follow-up of 5.5 (range 0.1-29.0) years 10.9% of OED patients developed OSCC. OED patients had a 44.7-fold higher risk (95% CI 34.4-56.7) of developing OSCC than the general population. The risk was at its highest within two years of OED diagnosis. OED patients in Southwest Finland have a significantly increased risk of developing OSCC relative to the general population, especially within the first two years of dysplasia diagnosis

Increased B-Type Natriuretic Peptide Concentration Is Associated with Reduced Coronary Vasoreactivity in Patients with Dilated Cardiomyopathy but Not in Healthy Young Subjects

Background/Aims. Natriuretic peptides are associated with the cardiovascular disease risk under a range of different circumstances. However, less is known about whether this association is found also in young healthy subjects. Methods. 9 patients with dilated cardiomyopathy and 26 healthy young subjects were studied. The myocardial blood flow measurements were performed basally and during adenosine infusion using PET. Results. S-proBNP concentrations were significantly higher (2153 ± 1964 versus 28 ± 17 ng/L, P = .000002) and adenosine-stimulated flow lower (1.6 ± 0.8 versus 3.6 ± 1.1 mL·g−1·min−1, P = .00001) in patients with dilated cardiomyopathy when compared to healthy subjects. S-proBNP concentration was inversely associated with adenosine stimulated flow in patients with dilated cardiomyopathy (r = −0.75, P = .019) but not in healthy subjects (r = −0.06, P = .84). Conclusions. Natriuretic peptides are inversely associated with coronary vasoreactivity in patients with dilated cardiomyopathy but not in healthy young subjects. Since reduced coronary vasoreactivity seems to be one of the earliest abnormalities in the development of coronary artery disease, this might indicate that natriuretic peptides are not predictor of cardiovascular disease risk in healthy young subjects

Is There an Association between Long-Term Sick Leave and Disability Pension and Unemployment beyond the Effect of Health Status? – A Cohort Study

Background: Studies have shown that long-term sick leave is a strong predictor of disability pension. However, few have aimed to disentangle the effect of sick leave and of health status. The objective of this study was to investigate whether there is an association between long-term sick leave and disability pension and unemployment, when taking health status into account. Methods/Principal Findings: The study was based on the Stockholm Public Health Cohort, restricted to 13,027 employed individuals (45.9 % men) aged 18–59 in 2002 and followed until 2007. Hazard ratios (HR) with 95 % Confidence Interval (CI) were estimated by Cox regression models adjusting for socio-demographic factors and five measures of health status. Having been on long-term sick leave increased the risk of disability pension (HR 4.01; 95 % CI 3.19–5.05) and longterm unemployment (HR 1.45; 95 % CI 1.05–2.00), after adjustment for health status. The analyses of long-term sick leave due to specific illness showed that the increased risk for long-term unemployment was confined to the group on sick leave due to musculoskeletal (HR 1.70 95 % CI 1.00–2.89) and mental illness (HR 1.80 95 % CI 1.13–2.88) and further that there was an increased risk for short-term unemployment in the group on sick leave due to mental illness (HR1.57 95%CI 1.09–2.26). Conclusions/Significance: Long-term sick leave increases the risks of both disability pension and unemployment even when taking health status into account. The results support the hypothesis that long-term sick leave may start a process o

Knowledge Hub on the Integrated Assessment of Chemical Contaminants and their Effects on the Marine Environment

In a time of environmental awareness, spurred on by the possibility that our world is threatened by climate change, it is important to remember that there are other anthropogenic pressures, which are also essential for addressing the protection of the marine and coastal environment. Pollution is a global, complex issue that contributes to biodiversity loss and poor environmental health and comes from the production and release of many of the synthetic chemicals that we use in our daily lives. Chemical contaminants are often underrepresented as a major contributor of environmental deterioration. The Joint Programming Initiative Healthy and Productive Seas and Oceans (JPI Oceans) established in 2018 the JPI Oceans Knowledge Hub on the integrated assessment of chemical contaminants and their effects on the marine environment. The purpose of the Knowledge Hub was to provide recommendations on how to improve the methodological basis for marine chemical status assessment. The work has resulted in the following policy paper which focuses on improving the efficiency and implementation of integrated assessment methodology of effects of chemicals of emerging concern. Substantial additional knowledge of biological effects is needed to achieve Good Environmental Status (GES) of our oceans and coastal areas. The Knowledge Hub is represented by highly skilled scientists and policy makers, appointed by the JPI Oceans Management Board, to ensure that the recommendations provided are useful for policy making

The pharmacokinetics of the interstitial space in humans

BACKGROUND: The pharmacokinetics of extracellular solutes is determined by the blood-tissue exchange kinetics and the volume of distribution in the interstitial space in the different organs. This information can be used to develop a general physiologically based pharmacokinetic (PBPK) model applicable to most extracellular solutes. METHODS: The human pharmacokinetic literature was surveyed to tabulate the steady state and equilibrium volume of distribution of the solutes mannitol, EDTA, morphine-6-glucuronide, morphine-3-glucuronide, inulin and β-lactam antibiotics with a range of protein binding (amoxicillin, piperacillin, cefatrizine, ceforanide, flucloxacillin, dicloxacillin). A PBPK data set was developed for extracellular solutes based on the literature for interstitial organ volumes. The program PKQuest was used to generate the PBPK model predictions. The pharmacokinetics of the protein (albumin) bound β-lactam antibiotics were characterized by two parameters: 1) the free fraction of the solute in plasma; 2) the interstitial albumin concentration. A new approach to estimating the capillary permeability is described, based on the pharmacokinetics of the highly protein bound antibiotics. RESULTS: About 42% of the total body water is extracellular. There is a large variation in the organ distribution of this water – varying from about 13% of total tissue water for skeletal muscle, up to 70% for skin and connective tissue. The weakly bound antibiotics have flow limited capillary-tissue exchange kinetics. The highly protein bound antibiotics have a significant capillary permeability limitation. The experimental pharmacokinetics of the 11 solutes is well described using the new PBPK data set and PKQuest. CONCLUSIONS: Only one adjustable parameter (systemic clearance) is required to completely characterize the PBPK for these extracellular solutes. Knowledge of just this systemic clearance allows one to predict the complete time course of the absolute drug concentrations in the major organs. PKQuest is freely available