Morphological findings in frozen non-neoplastic kidney tissues of patients with kidney cancer from large-scale multicentric studies on renal cancer.

Funder: FP7 Ideas: European Research Council; doi: http://dx.doi.org/10.13039/100011199; Grant(s): 241669There are unexplained geographical variations in the incidence of kidney cancer with the high rates reported in Baltic countries, as well as eastern and central Europe. Having access to a large and well-annotated collection of "tumor/non-tumor" pairs of kidney cancer patients from the Czech Republic, Romania, Serbia, UK, and Russia, we aimed to analyze the morphology of non-neoplastic renal tissue in nephrectomy specimens. By applying digital pathology, we performed a microscopic examination of 1012 frozen non-neoplastic kidney tissues from patients with renal cell carcinoma. Four components of renal parenchyma were evaluated and scored for the intensity of interstitial inflammation and fibrosis, tubular atrophy, glomerulosclerosis, and arterial wall thickening, globally called chronic renal parenchymal changes. Moderate or severe changes were observed in 54 (5.3%) of patients with predominance of occurrence in Romania (OR = 2.67, CI 1.07-6.67) and Serbia (OR = 4.37, CI 1.20-15.96) in reference to those from Russia. Further adjustment for comorbidities, tumor characteristics, and stage did not change risk estimates. In multinomial regression model, relative probability of non-glomerular changes was 5.22 times higher for Romania and Serbia compared to Russia. Our findings show that the frequency of chronic renal parenchymal changes, with the predominance of chronic interstitial nephritis pattern, in kidney cancer patients varies by country, significantly more frequent in countries located in central and southeastern Europe where the incidence of kidney cancer has been reported to be moderate to high. The observed association between these pathological features and living in certain geographic areas requires a larger population-based study to confirm this association on a large scale

Genetic Analysis of Lung Cancer and the Germline Impact on Somatic Mutation Burden

International audienceBackground Germline genetic variation contributes to lung cancer (LC) susceptibility. Previous genome-wide association studies (GWAS) have implicated susceptibility loci involved in smoking behaviors and DNA repair genes, but further work is required to identify susceptibility variants. Methods To identify LC susceptibility loci, a family history-based genome-wide association by proxy (GWAx) of LC (48 843 European proxy LC patients, 195 387 controls) was combined with a previous LC GWAS (29 266 patients, 56 450 controls) by meta-analysis. Colocalization was used to explore candidate genes and overlap with existing traits at discovered susceptibility loci. Polygenic risk scores (PRS) were tested within an independent validation cohort (1 666 LC patients vs 6 664 controls) using variants selected from the LC susceptibility loci and a novel selection approach using published GWAS summary statistics. Finally, the effects of the LC PRS on somatic mutational burden were explored in patients whose tumor resections have been profiled by exome (n = 685) and genome sequencing (n = 61). Statistical tests were 2-sided. Results The GWAx–GWAS meta-analysis identified 8 novel LC loci. Colocalization implicated DNA repair genes (CHEK1), metabolic genes (CYP1A1), and smoking propensity genes (CHRNA4 and CHRNB2). PRS analysis demonstrated that these variants, as well as subgenome-wide significant variants related to expression quantitative trait loci and/or smoking propensity, assisted in LC genetic risk prediction (odds ratio = 1.37, 95% confidence interval = 1.29 to 1.45; P < .001). Patients with higher genetic PRS loads of smoking-related variants tended to have higher mutation burdens in their lung tumors. Conclusions This study has expanded the number of LC susceptibility loci and provided insights into the molecular mechanisms by which these susceptibility variants contribute to LC development

Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma.

BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13). CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma

Sähköinen kirjaaminen heräämön hoitotyössä

Opinnäytetyön tarkoituksena on tehdä Nokian terveyskeskuksen leikkausosaston heräämön sairaanhoitajille kirjaamisrunko sähköiseen potilastietojärjestelmään, jonka avulla osaston sairaanhoitajat jäsentävät hoitotyön kirjaamistaan heräämöhoidon aikana. Opinnäytetyön tehtävänä on selvittää, mitkä asiat ovat olennaisia sairaanhoitajan kirjata potilaan päiväkirurgisen heräämöhoidon aikana hyvän hoidon jatkuvuuden kannalta. Tavoitteena on saada yhtenäistettyä kirjaamiskäytäntöjä kyseisessä yksikössä, sekä auttaa sairaanhoitajia kirjaamaan tehokkaasti, mutta laadukkaasti. Työ toteutettiin kirjallisuuden pohjalta, sekä työelämäyhteyttä haastatellen teemahaastattelulla ja heidän aikai-simpia materiaalejaan hyväksikäyttäen. Työssä käsitellään postoperatiivista hoitoa, päiväkirurgisen potilaan heräämöhoidon erityispiirteitä, kirjaamista sekä potilasturvallisuutta. Potilaan välitön leikkauksen jälkeinen hoito tapahtuu erityisvalvonnassa eli heräämössä, jossa päiväkirurgiset potilaat toipuvat anestesiasta ja lopulta kuntoutuvat kotikuntoisiksi. Tällöin hoitosuhde on lyhyt, ja sairaanhoitajan vuorovaikutustaidot sekä kirjaamisen merkitys korostuvat potilasturvallisuuden kannalta. Hyvä tiedonkulku on tärkeä perustekijä turvallisessa ja laadukkaassa hoidossa. Omaan tuotokselliseen lopputulokseemme valitsimme kirjauksen pääkohdiksi postoperatiivisen hoidon seitsemän tärkeintä osa-aluetta, joita sairaanhoitaja heräämöhoitotyössä seuraa. Liitimme mukaan myös päiväkirurgisen potilaan kotiutumiskriteerit, joita sairaanhoitaja voi kirjaamisen yhteydessä hyödyntää tarkistuslistan tyyppisesti.The purpose of this thesis was to create a template for electronic documentation of nursing work for nurses in the postoperative care unit in Nokia. The aim was to standardize documentation of nursing work in the unit. Information for this thesis was gathered from recent literature and by interviewing the nurses of the postoperative care unit. The theoretical section discusses postoperative nursing, day surgery, electronic nursing documentation and patient safety. Immediate postoperative care takes place in a postop-erative care unit, from where outpatients are discharged. The care outpatients receive is very short-term, thus nursing documentation and the communication skills of the nurse are very important. The seven most important points of postoperative nursing were chosen as the main titles in the template, under which the nurse can document all the important information of the care the patient has received. The discharge criteria of an outpatient was also included in the template, enabling it to simultaneously act as a checking list for the nurse responsible of the discharging

Genetic Analysis of Lung Cancer and the Germline Impact on Somatic Mutation Burden.

BACKGROUND: Germline genetic variation contributes to lung cancer (LC) susceptibility. Previous genome-wide association studies (GWAS) have implicated susceptibility loci involved in smoking behaviors and DNA repair genes, but further work is required to identify susceptibility variants. METHODS: To identify LC susceptibility loci, a family history-based genome-wide association by proxy (GWAx) of LC (48&nbsp;843 European proxy LC patients, 195&nbsp;387 controls) was combined with a previous LC GWAS (29&nbsp;266 patients, 56&nbsp;450 controls) by meta-analysis. Colocalization was used to explore candidate genes and overlap with existing traits at discovered susceptibility loci. Polygenic risk scores (PRS) were tested within an independent validation cohort (1 666 LC patients vs 6 664 controls) using variants selected from the LC susceptibility loci and a novel selection approach using published GWAS summary statistics. Finally, the effects of the LC PRS on somatic mutational burden were explored in patients whose tumor resections have been profiled by exome (n = 685) and genome sequencing (n = 61). Statistical tests were 2-sided. RESULTS: The GWAx-GWAS meta-analysis identified 8 novel LC loci. Colocalization implicated DNA repair genes (CHEK1), metabolic genes (CYP1A1), and smoking propensity genes (CHRNA4 and CHRNB2). PRS analysis demonstrated that these variants, as well as subgenome-wide significant variants related to expression quantitative trait loci and/or smoking propensity, assisted in LC genetic risk prediction (odds ratio = 1.37, 95% confidence interval = 1.29 to 1.45; P &lt; .001). Patients with higher genetic PRS loads of smoking-related variants tended to have higher mutation burdens in their lung tumors. CONCLUSIONS: This study has expanded the number of LC susceptibility loci and provided insights into the molecular mechanisms by which these susceptibility variants contribute to LC development