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Objective: Several reproductive factors are associated with ovarian cancer risk but the association with survival is less clear. The main aim was to examine the impact of pre-diagnostic reproductive factors on long-term ovarian cancer survival (≥10 years)., Methods: We included all women with epithelial ovarian cancer in Denmark, 1990-2014. Information on reproductive factors and covariates were obtained from nationwide registers. Using pseudo-values, we estimated the absolute and relative 10-year survival probabilities and 95% CIs for each reproductive factor and ovarian cancer overall, restricted to serous tumors and stratified into localized and non-localized tumors. A relative survival probability >1 indicates better survival. Adjusted models considered age, diagnosis year, histology, stage, comorbidity, and income. In a sub-population sensitivity analysis, we also adjusted for residual disease., Results: The cohort comprised 11,870 women. In the adjusted models, pre-diagnostic parity (relative survival probability 1.08, 95% CI 1.01 to 1.16) and endometriosis (relative survival probability 1.17, 95% CI 1.02 to 1.34) increased the likelihood of surviving ≥10 years in women with localized cancer. Previous infertility also improved the 10-year survival in women with localized ovarian cancer (relative survival probability 1.18, 95% CI 1.07 to 1.29) and in women with a non-localized tumor (relative survival probability 1.45, 95% CI 1.15 to 1.84). Pre-diagnostic pelvic inflammatory disease enhanced 10-year survival in women with localized serous (relative survival probability 1.24, 95% CI 1.03 to 1.49) and non-localized cancer (relative survival probability 1.35, 95% CI 1.04 to 1.76). Previous tubal ligation or hysterectomy were not significantly associated with 10-year survival. Adjustment for residual disease did not substantially change estimates, except for parity and pelvic inflammatory disease, where the associations disappeared., Conclusion: Pre-diagnostic reproductive factors, such as endometriosis or infertility, were associated with improved long-term survival. However, causality cannot be established in this observational study, and more research to confirm our findings and into potential mechanisms is warranted., Competing Interests: Declaration of Competing Interests None declared., (Copyright © 2024 European Society of Gynaecological Oncology and the International Gynecologic Cancer Society. Published by Elsevier Inc. All rights reserved.)

Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways. Several proteins were regulated with semaglutide, after accounting for changes in body weight and HbA 1c at end of trial, suggesting effects of semaglutide on the proteome beyond weight loss and glucose lowering. A comparison of semaglutide with real-world proteomic profiles revealed potential benefits on disease-specific proteomic signatures including the downregulation of specific proteins associated with cardiovascular disease risk, supporting its reported effects of lowering cardiovascular disease risk and potential drug repurposing opportunities. This study showcases the potential of proteomics data gathered from randomized trials for providing insights into disease mechanisms and drug repurposing opportunities. These data also highlight the unmet need for, and importance of, examining proteomic changes in response to weight loss pharmacotherapy in future trials., Competing Interests: Competing interests: L.S., K.S., M. Galanakis, M.T.I., J.S., A.S., L.B.K. and A.A.T. are employees and shareholders of Novo Nordisk. D.G., L.M. and M. Geybels were employees and shareholders of Novo Nordisk at the time of the analysis. M. Galanakis, M. Geybels and D.V. have received a grant from the Danish Innovation Fund (204000005B). J.Q.P. has received consulting fees from Boehringer Ingelheim and Novo Nordisk. L.Z. declares no competing interests., (© 2025. The Author(s).)

Universal screening for defective mismatch repair (dMMR) in colorectal cancer utilizes immunohistochemical staining for MLH1, MSH2, MSH6 and PSM2. Additionally, BRAF V600E mutations status and MLH1 hypermethylation should be performed to distinguish germline and somatic dMMR alterations. A decade of Danish population-based registries has been analysed regarding screening uptake, detection rate and referral to genetic counselling. MMR testing was performed in 71·8% (N = 34,664) of newly diagnosed colorectal cancers with an increasing trend to 88·8% coverage in the study's final year. The likelihood of undergoing MMR testing was reduced in males with 2% (95% CI 0·4-2·7, p = 0·008), with 4·1% in patients above age 70 years (95% CI 1·5-6·6, p = 0·003) compared in patients below age 51 years, with 16·3% in rectal cancers (95% CI 15·1-17·6, p < 0·001) and 1·4% left-sided colon cancers (95% CI 0·1-1·7, p = 0·03) compared to right-sided colon cancers. Tumour stage II and III increased the likelihood of being tested, with 3·7% for stage II (95% CI 2·2-5·6, p < 0·001) and 3·3% for stage III tumours (95% CI 1·8-4·8, p < 0·001) compared to stage I tumours, whereas the likelihood for stage IV tumours is reduced by 35·7% (95% CI 34·2-37·2, p < 0·001). Test rates significantly differed between the Danish health care regions. dMMR was identified in 15·1% (95% CI 14·8-15·6, p < 0·001) cases with somatic MMR inactivation in 6·7% of the cases. 8·3% tumours showed hereditary dMMR expression patterns, and 20·0% of those were referred to genetic counselling. Despite the high uptake rates, we found disparities between patient groups and missed opportunities for genetic diagnostics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Use of menopausal hormone therapy (MHT) prior to an epithelial ovarian cancer (EOC) diagnosis has been suggested to be associated with improved survival. In a recent nationwide cohort study, we found that prediagnostic long-term MHT use, especially estrogen therapy (ET), was associated with improved long-term survival in women with nonlocalized EOC. Our aim was to investigate the influence of prediagnostic MHT use on long-term survival among women with localized EOC in the same nationwide study. Our study cohort comprised all women aged 50 years or older with an EOC diagnosis in Denmark 2000-2014 (n = 2097) identified from the Extreme study. We collected information on usage of systemic ET and estrogen plus progestin therapy (EPT) from the Danish National Prescription Registry. By using pseudo-values, 5- and 10-year absolute and relative survival probabilities were estimated with 95% confidence intervals (CIs) while adjusting for histology, comorbidity, and income. Relative survival probabilities >1 indicate better survival. The 5-year absolute survival probabilities were 61% and 56%, respectively, among women who were nonusers and users of prediagnostic MHT, whereas these numbers were 46% and 41%, respectively, regarding 10-year survival. Use of MHT was not significantly associated with an improved 5- or 10-year survival in women with localized EOC (5-year relative survival probability = 0.95, 95% CI: 0.89-1.02; 10-year relative survival probability = 0.92, 95% CI: 0.84-1.02). Similar findings were seen for systemic ET or EPT use. Our findings do not suggest a positive benefit from prediagnostic MHT use on long-term survival of localized EOC., (© 2024 UICC.)

Objective: Patients with autoimmune disease may have impaired cancer survival. The aim was to investigate the association between autoimmune disease and ovarian cancer survival., Methods: From the Extreme study, we included women diagnosed with epithelial ovarian cancer (EOC) in Denmark during 1990-2014 (n = 11,870). Information on exposure and covariates was retrieved from nationwide registries. Using pseudo-values, we estimated absolute and relative 5- and 10-year survival probabilities with 95% confidence intervals (CIs) for autoimmune diseases combined and for the four most common individual disorders in our study population, namely type 1 diabetes, rheumatoid arthritis, Graves' disease, and inflammatory bowel disease., Results: The overall 5- and 10-year absolute survival probabilities were 35% and 24%, respectively, in women with EOC without autoimmune disease. Autoimmune diseases combined was not significantly associated with survival among women with EOC (5-year adjusted relative survival probability = 1.01, 95% CI: 0.94-1.09; 10-year adjusted relative survival probability = 0.90, 95% CI: 0.81-1.00). However, stratification by disease stage showed an impaired 10-year survival in women with autoimmune disease and a localized EOC (relative survival probability = 0.86, 95% CI: 0.76-0.97). None of the individual autoimmune diseases were statistically significantly associated with EOC survival., Conclusions: Only among women with localized EOC, there seemed to be a long-term survival loss associated with a history of autoimmune disease. In contrast, no significant association between a history of autoimmune disease and survival was observed in women with nonlocalized EOC where the survival is already low., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Little is known about employment status, occupation, and disposable income in adults with NF1., Methods: From the Danish National Patient Registry and database of two national Centers for Rare Diseases, we identified 1469 adults with NF1, who were matched to 11,991 randomly selected population comparisons on sex and birth year and month. Annual information on employment, occupation and disposable income was ascertained from national registries in 1980-2019., Results: Adults with NF1 had a lower odds ratio (OR) for employment [OR 0.71, 95% confidence interval (CI) 0.61-0.83] and higher OR for health-related unemployment (OR 2.94, 95% CI 2.16-3.96) at age 30 years than population comparisons, which persisted at age 40 and 50 years. Somatic diagnoses were associated with a higher OR for health-related unemployment in adults with NF1 than in the population comparisons. Adults with NF1 had a slightly lower disposable income, with a 14% (0.82-0.89) reduction observed among the youngest birth cohort. Furthermore, adults with NF1 were less likely to be in a high skilled occupation at ages 30, 40 and 50 years., Conclusion: Adults with NF1 have a lower employment rate, which was mainly due to health-related reasons and a slightly lower disposable income than adults without NF1. Thus, anticipation guidance for employment should be part of the management of NF1 families., (© 2023. The Author(s).)

The present study examined the association and complementary effect of self-compassion on the subjective happiness and psychological well-being of adults during the COVID-19 pandemic. The study was based on a concurrent correlational design to examine relationships between self-compassion, subjective happiness, psychological well-being, resilience, and the meaning in life. Data were collected via a battery of questionnaires and analyzed, focusing on the above variables. The sample of this study (N = 526) consisted of Greek professionals in education and university students. The results showed that there is a strong positive relationship between self-compassion and subjective happiness, and between self-compassion and psychological well-being. The findings suggest that an attitude of self-compassion may well influence the development of psychological well-being and increase the subjective happiness of adults during the distressing era of a long-term pandemic. The results also indicated a positive relationship between self-compassion and meaning in life and showed that self-compassion is a prerequisite for resilience, which in turn may serve as a moderator of psychological well-being and subjective happiness.

Background: The primary aim was to assess Health Related Quality of Life (HRQoL), anxiety and depression in patients and caregivers during follow-up care after curative treatment for cancer in the pancreas, duodenum, or bile ducts. The secondary aim was to assess dyadic coping and the burden of being a caregiver., Materials and Methods: In this prospective observational cohort study, we included patients and caregivers at first follow-up visit to conduct the following: Demographic characteristics, The European Organization for Research and Treatment of Cancer Quality of Life, the pancreas and bile duct module, EQ5D 3L, GAD-7 and PHQ-9 at baseline, and at six and nine-months follow-up visit. Demographic characteristics, Dyadic Coping Inventory and Zarit Caregiver Burden Questionnaire were conducted at baseline and at nine-months of follow-up visit., Results: The response rate was 42% with 104 of the 248 invited patients completing the questionnaires at baseline: 78 (75% of 104) after six and 69 (66% of 104) after nine months. The median (Q25,75) time for inclusion was 33.6 (13.4, 38) and 29.1 (18.3, 36) weeks after surgery for patients with pancreatic or duodenal cancer, and bile duct cancer, respectively. The response rate of caregivers was 88% with 75 of 85 completing the questionnaires. Fifty percent of patients with pancreatic or duodenal cancer had diarrhea at baseline. After six and nine months, this increased to 75%. Fatigue was the most prominent symptom in patients with bile duct cancer after nine months with 25% of patients scoring this as a clinical symptom., Conclusions: The study highlights the need to systematically screen physical and psychological symptoms in patients and caregivers during follow-up care after treatment for cancer in the pancreas, duodenum and bile ducts. Symptom management during follow-up care should be prioritized by clinicians.

In Denmark, vaccination against human papillomavirus (HPV) has been implemented in the children's vaccination program (January 2009) and in multiple catch-up cohorts (October 2008 in girls 13-15 years and in August 2012 in women up to 27 years). In the present study we estimate incidence of cervical intraepithelial neoplasia grade 3 (CIN3), adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma (AC) during 2000-2019. All cases of CIN3 and AIS were identified from the nationwide Pathology Data Bank, while SCC and AC were identified from the Danish Cancer Registry. We calculated age-standardized incidence rates and estimated annual percentage change (EAPC) with corresponding 95% confidence interval (CI) for the periods before vaccination implementation (2000-2005), early after implementation of childhood HPV vaccination and the first catch-up vaccination program (2006-2012), and after implementation of the second catch-up program (2013-2019). For CIN3 and AIS, age-specific incidence rates and EAPCs were calculated. An increasing age-standardized incidence was observed before introduction of HPV vaccination (2000-2005) for CIN3 [EAPC CIN3 : 3.0 (95% CI 1.7 to 4.3)] and AIS [EAPC AIS : 3.5 (95% CI 0.7 to 6.4)]. In the most recent period (2013-2019), following implementation of the second catch-up program, a decrease was observed for both CIN3 [EAPC CIN3 : -6.5 (95% CI -8.3 to -4.8)], AIS [EAPC AIS : -8.7 (95% CI -12.3 to -5.1)] and for SCC [EAPC SCC : -3.9 (95% CI -7.5 to -0.2)]. In this study we document a decrease in the incidence of CIN3, AIS and SCC in the period after implementation of multi-cohort HPV vaccination in Denmark., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Prediagnostic use of menopausal hormone therapy (MHT) has been suggested to be associated with improved survival of epithelial ovarian cancer (EOC). We investigated the potential long-term survival benefit of prediagnostic MHT use in women ≥50 years with nonlocalized EOC using the Extreme study including all women in Denmark registered with nonlocalized EOC during 2000 to 2014 (N = 3776). We obtained individual-level information on prediagnostic use of systemic estrogen therapy (ET) and estrogen plus progestin therapy (EPT) from the National Prescription Registry and estimated absolute and relative 5- and 10-year survival probabilities with 95% confidence intervals (CIs) using pseudo-values, taking into account histology, comorbidity, income and residual disease. Among women not having used prediagnostic MHT, 5- and 10-year absolute survival probabilities were 19% and 11%, respectively. Compared to MHT nonusers, prediagnostic systemic ET use for 3 to 4 years and ≥ 5 years was associated with 1.43 (95% CI: 1.01-2.02) and 1.22 (95% CI: 0.96-1.55) times higher 5-year survival probabilities, respectively. Ten-year survival probabilities were also increased but not statistically significantly. Among prediagnostic EPT users, increased 5-year (1.14, 95% CI: 0.85-1.53) and 10-year (1.38, 95% CI: 0.91-2.08) survival probabilities were observed after use for 3 to 4 years compared to MHT nonuse, whereas EPT use for ≥5 years was not associated with long-term survival of nonlocalized EOC. Our findings may suggest a better long-term survival of nonlocalized EOC in women having used long-term prediagnostic ET. However, the statistical precision of our results did not allow firm conclusions and more studies are needed., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: As Greece is a country which has introduced the 13-valent pneumococcal conjugate vaccine (PCV13) both in the infant and in the adult immunization programs, the aim of the study was to investigate age-specific and serotype-specific trends of pneumococcal meningitis over an 11-year period (2010-2020)., Materials and Methods: Data are reported from pneumococcal meningitis cases [notified to the National Public Health Organization (NPHO)], with clinical samples and bacterial isolates sent for pneumococcal identification and serotyping at the National Meningitis Reference Laboratory (NMRL). Pneumococcal identification was performed directly on clinical samples or bacterial isolates by multiplex PCR (mPCR) assay, while serotyping was carried out by application of the Capsular Sequence Typing (CST) method with the combination of single tube PCR assays., Results: A total of 427 pneumococcal meningitis cases were notified to the NPHO between 2010 and 2020. Among those, 405 (94.8%) were microbiologically confirmed, while samples from 273 patients were sent to the NMRL for identification and/or further typing. The annual notification rate peaked at 0.47/100,000 in 2016 and since then has been decreasing. The incidence was highest in infants and in older adults. Pneumococcal serotypes were identified in 260/273 (95.2%) cases, where clinical samples were sent to the NMRL. The most prevalent serotypes (≥5%) were 3, 19A, 23B, 15B/C, 11A/D, 23A, 22F. During the study period there has been a decrease of PCV13 serotypes combined with an increase of non-PCV13 serotypes (p = 0.0045)., Conclusions: This is the first study to report serotypes for pneumococcal meningitis across all ages in the post-PCV13 era in Greece. There is a need to enhance surveillance, by close monitoring of the emerging serotypes and the impact of vaccination programs. Higher-valency PCVs may help to improve the coverage of pneumococcal disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)