Clinical factors as prognostic variables among molecular subgroups of endometrial cancer

Background Clinical factors may influence endometrial cancer survival outcomes. We examined the prognostic significance of age, body mass index (BMI), and type 2 diabetes among molecular subgroups of endometrial cancer. Methods This was a single institution retrospective study of patients who underwent surgery for endometrial carcinoma between January 2007 and December 2012. Tumors were classified into four molecular subgroups by immunohistochemistry of mismatch repair (MMR) proteins and p53, and sequencing of polymerase-epsilon (POLE). Overall, cancer-related, and non-cancer-related mortality were estimated using univariable and multivariable survival analyses. Results Age >65 years was associated with increased mortality rates in the whole cohort (n = 515) and in the "no specific molecular profile" (NSMP) (n = 218) and MMR deficient (MMR-D) (n = 191) subgroups during a median follow-up time of 81 months (range 1-136). However, hazard ratios for cancer-related mortality were non-significant for NSMP and MMR-D. Diabetes was associated with increased overall and non-cancer-related mortality in the whole cohort and MMR-D subgroup. Overweight/obesity had no effect on outcomes in the whole cohort, but was associated with decreased overall and cancer-related mortality in the NSMP subgroup, and increased overall and non-cancer-related mortality in the MMR-D subgroup. Overweight/obesity effect on cancer-related mortality in the NSMP subgroup remained unchanged after controlling for confounders. High-risk uterine factors were more common, and estrogen and progesterone receptor expression less common in NSMP subtype cancers of normal-weight patients compared with overweight/obese patients. No clinical factors were associated with outcomes in p53 aberrant (n = 69) and POLE mutant (n = 37) subgroups. No cancer-related deaths occurred in the POLE mutant subgroup. Conclusions The prognostic effects of age, BMI, and type 2 diabetes do not appear to be uniform for the molecular subgroups of endometrial cancer. Our data support further evaluation of BMI combined with genomics-based risk-assessment.Peer reviewe

American Society of Anesthesiologists physical status score as a predictor of long-term outcome in women with endometrial cancer

Objective To study the association of the American Society of Anesthesiologists (ASA) physical status score with long-term outcome in endometrial cancer. Methods Overall, disease-specific and non-cancer-related survival were estimated using simple and multivariable Cox regression analyses and the Kaplan-Meier method. Results A total of 1166 patients were included in the study. Median follow-up time was 76 (range 1-136) months. All-cause and non-cancer-related mortality were increased in patients whose ASA physical status score was III (HRs 2.5 and 8.0, respectively) or IV (HRs 5.7 and 25, respectively), and cancer-related mortality was increased in patients whose score was IV (HR 2.7). Kaplan-Meier analyses demonstrated a worse overall, disease-specific and non-cancer-related survival for patients whose score was >= III (p= III in both subgroups of stages (p=0.003 and p=0.017 for stage I and stages II-IV, respectively). ASA physical status score remained an independent predictor of all-cause mortality (HR 2.2 for scores >= III), cancer-related mortality (HRs 1.7 and 2.2 for scores >= III and IV, respectively) and non-cancer related mortality (HR 3.1 for scores >= III) after adjustment for prognostically relevant clinicopathologic and blood-based covariates. ASA physical status score also remained an independent predictor of cancer-related mortality after exclusion of patients who were at risk for nodal involvement based on features of the primary tumor but who did not undergo lymphadenectomy, and patients with advanced disease who received suboptimal chemotherapy (HRs 1.6 and 2.5 for scores >= III and IV, respectively). Conclusions ASA physical status score independently predicts overall survival, disease-specific survival, and non-cancer-related survival in endometrial cancer.Peer reviewe

Tapaturmien ehkäisy peruskouluissa vuonna 2013

Koulujen ja oppilaitosten terveyden ja hyvinvoinnin edistämistä on seurattu vuodesta 2006 lähtien Terveyden ja hyvinvoinnin laitoksen ja Opetushallituksen toimesta. Peruskoulujen terveyden ja hyvinvoinnin edistäminen kartoitettiin valtakunnallisesti neljännen kerran syksyllä 2013. Tässä julkaisussa esitellään koulutapaturmiin ja niiden ehkäisyyn sekä turvallisuuteen liittyvät tulokset syksyllä 2013 tehdyn tiedonkeruun tuloksista. Tiedonkeruuseen vastasi 2022 (74 %) peruskoulua. Tulokset ovat tarkasteltavissa tietojensa julkaisemiseen luvan antaneiden 755 peruskoulun tuloksista koulukohtaisesti TEAviisari-verkkopalvelussa . Koululla on keskeinen merkitys kokonaisvaltaisen turvallisuuskulttuurin luomisessa ja turvallisuuskasvatuksen tarjoajana. Perusopetuslaki (628/1998) velvoittaa koulut tarjoamaan oppilaille turvallisen opiskeluympäristön. Turvallisen fyysisen kasvuympäristön lisäksi opetuksessa ja opetussuunnitelmissa olisi tärkeä huolehtia annettavan tapaturma- ja turvallisuuskasvatuksen johdonmukaisuudesta. Turvallisuutta tukevien taitojen oppiminen on läpi elämän kestävä prosessi

Molecular characterization in the prediction of disease extent in endometrial carcinoma

Objective: Patients with endometrial carcinoma are usually triaged to staging lymphadenectomy selectively based on estimated risk of lymphatic spread. The risk is generally assessed by the presence of uterine risk factors, but their preoperative and intraoperative identification remain a challenge. The objective of this study was to assess the capability of molecular classification, described by The Cancer Genome Atlas (TCGA), to predict the stage of endometrial carcinoma. Study design: Sequencing of polymerase-epsilon (POLE) and immunohistochemistry of mismatch repair (MMR) proteins and p53 were performed to stratify endometrial carcinomas into subgroups of POLE exonuclease domain mutation (EDM), MMR deficiency, abnormal p53 (p53 abn) and 'no specific molecular profile' (NSMP). NSMP was the reference subgroup for comparisons. Associations of molecular subgroups and uterine risk factors with stage were examined in univariable and multivariable analyses. Results: Six hundred and four patients were included in the study. None of the POLE EDM tumours extended beyond the uterine cervix. In an unadjusted analysis, p53 abn was associated with increased risk for stage IIIC-IV disease [odds ratio (OR) 4.6, 95% confidence interval (CI) 2.3-9.2; p <0.0005]. When controlling for uterine risk factors (histotype and grade, depth of myometrial invasion, tumour size, lymphovascular space invasion), p53 was not an independent predictor of advanced disease. In contrast, POLE EDM independently predicted local disease (OR 0.12, 95% CI 0.015-0.99; p = 0.049 for stage II-IV cancer). Of the molecular subgroups, p53 abn was most strongly associated with the presence of high-risk uterine factors (ORs between 2.2 and 19; p Conclusion: Of the TCGA-based molecular subgroups, POLE EDM independently predicted early stage endometrial carcinoma. Although p53 abn was not an independent predictor of advanced disease, its association with uterine risk factors could allow utilization of molecular data in deciding the type of staging surgery if knowledge of uterine factors is deficient. (C) 2020 Elsevier B.V. All rights reserved.Peer reviewe

No Association Between Ljungan Virus Seropositivity and the Beta-cell Damaging Process in the Finnish Type 1 Diabetes Prediction and Prevention Study Cohort

Background: Ljungan virus (LV) has not confirmed to associate with any human disease, but a possible connection with type 1 diabetes has been suggested. LV is a rodent-borne picornavirus that induces a diabetes-like condition in rodents. Approximately 30% of adults and 60% of children are seropositive in Finland. The Finnish Type 1 Diabetes Prediction and Prevention study enabled the use of very well characterized sample panels from children seroconverted to positivity for multiple islet autoantibodies during their prospective observation from birth; in addition, samples from age, sex, human leukocyte antigen (HLA), and residence area matched control children. Methods: We analyzed LV IgG seroprevalence in 102 case children (65 had also developed type 1 diabetes), in addition to nondiabetic control children. LV and human parechovirus (HPeV) immunofluorescence assays were used to analyze LV and HPeV-specific IgG from 102 plasma samples taken at the time of islet autoantibody appearance and from 204 samples from the matched control children. Results: Altogether 46.1% of the case and 50.7% of the control children were positive for LV IgG (odds ratio 0.8; 95% confidence interval, 0.47-1.36; P = 0.416) and 67.6% versus 79.8% were positive for HPeV IgG, respectively (odds ratio 0.49, 0.27-0.9, P = 0.023). Conclusions: Thus, no risk associations between LV or HPeV-specific IgG and islet autoimmunity were observed. However, a trend for significantly higher prevalence of HPeV antibodies in control children (P = 0.023) suggests a possible protective association of this virus with islet autoimmunity.Peer reviewe

Rye and health - Where do we stand and where do we go?

Background: High whole grain intake has consistently been associated with lowered risk of developing a number of chronic diseases. Among cereals, rye has highest content of dietary fiber, together with a wide variety of bioactive compounds. There is accumulating evidence from intervention studies of physiological effects of rye foods with potential health benefits. Scope and approach: This review summarizes the state of the art of rye and health and identifies future directions for research and innovation, based partly on findings presented at the international conference "The Power of Rye", angstrom land, Finland, 7-8 June 2017. Key findings and conclusions: Rye foods have well-established beneficial effects on insulin metabolism compared with wheat bread under isocaloric conditions and at standardized amounts of available carbohydrates, which may have positive implications for diabetes prevention. Recent findings suggest that alterations in blood glucose flux partly explain these effects. Moreover, several studies have shown beneficial effects of rye-based foods on satiety, which is one plausible mechanism behind recently demonstrated beneficial effects on weight management. Emerging results indicate beneficial effects of rye intake on inflammation and blood lipids. More research is needed to uncover underlying mechanisms for other demonstrated effects and the long-term implications for health. A challenge with rye-based foods is making them palatable and widely acceptable to consumers. Development of innovative and tasty rye products and targeted communication strategies is crucial in increasing awareness and consumption of rye foods. Novel results in this regard are presented in this review.Peer reviewe

Aluekehittämisen verkostoyhteistyön toiminta- ja rahoitusmallit: Kohti vaikuttavaa verkostotyötä

Aluekehittämisessä kyse on useimmiten joko ”ilkeistä ongelmista” tai ”monitahoisista mahdollisuuksista”, joiden ratkaiseminen tai hyödyntäminen ei ole mahdollista vain yhden toimijan kyvyillä, osaamisella ja resursseilla. Tämä korostaa verkostomaista otetta kehittämistyöhön. Hallitusohjelman mukaisen alue- ja kaupunkikehittämisen sekä kansallisten alueiden kehittämisen painopisteiden ja instrumenttien valmistelun tueksi on tarvittu analyysiä erilaisista verkostoyhteistyön toiminta- ja rahoitusmalleista. VALUMA-hankkeessa on rakennettu kokonaiskuvaa verkostomaisesta alueiden kehittämisestä sekä koottu oppeja aluekehittämisen verkostoista Suomessa ja muissa maissa. Lisäksi selvityksessä on analysoitu erilaisten verkostoyhteistyön toimintamallien mahdollisia vaikutuksia aluekehittämisen kokonaisuudessa sekä valtion roolia ja mahdollisen kannustin- tai ohjelmarahoituksen merkitystä. Selvityksen perusteella kansallisesti vaikuttava aluekehittämisen verkostotyön kokonaisuus vaatii aluekehittämistoimijoiden yhteistyönä rakennetun tietopohjan, selkeän tavoitteen ja poliittisen tuen aluekehittämiselle, aluekehittämisen kyvykkyyksien ja vertaisoppimisen vahvistamista sekä ilmiö- ja teemapohjaisen rahoituksen järjestämistä verkostotyölle.Tämä julkaisu on toteutettu osana valtioneuvoston selvitys- ja tutkimussuunnitelman toimeenpanoa(tietokayttoon.fi). Julkaisun sisällöstä vastaavat tiedon tuottajat, eikä tekstisisältö välttämättä edusta valtioneuvoston näkemystä