Metabolic Adaptation Establishes Disease Tolerance to Sepsis.

Sepsis is an often lethal syndrome resulting from maladaptive immune and metabolic responses to infection, compromising host homeostasis. Disease tolerance is a defense strategy against infection that preserves host homeostasis without exerting a direct negative impact on pathogens. Here, we demonstrate that induction of the iron-sequestering ferritin H chain (FTH) in response to polymicrobial infections is critical to establish disease tolerance to sepsis. The protective effect of FTH is exerted via a mechanism that counters iron-driven oxidative inhibition of the liver glucose-6-phosphatase (G6Pase), and in doing so, sustains endogenous glucose production via liver gluconeogenesis. This is required to prevent the development of hypoglycemia that otherwise compromises disease tolerance to sepsis. FTH overexpression or ferritin administration establish disease tolerance therapeutically. In conclusion, disease tolerance to sepsis relies on a crosstalk between adaptive responses controlling iron and glucose metabolism, required to maintain blood glucose within a physiologic range compatible with host survival.

Biopsy-verified vulvar lichen sclerosus: Incidence trends 1997-2022 and increased risk of vulvar squamous precancer and squamous cell carcinoma.

Population-based data on the epidemiology of vulvar lichen sclerosus (LS) are sparse and only few prospective studies have investigated the malignant potential of the disease. We used the nationwide Danish Pathology Registry to first assess the incidence of biopsy-verified vulvar LS in the period 1997-2022 and second to examine the incidence of vulvar high-grade squamous precancer and squamous cell carcinoma (SCC) in women with biopsy-verified vulvar LS (1978-2019) compared with that expected in the general female population. For the latter aim, we computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). During our study period, the age-standardized incidence rate of vulvar LS increased from 5.0 (1997-1998) to 35.7 (2021-2022) per 100,000 person-years. Compared with the general female population, women with biopsy-verified vulvar LS had significantly increased rates of vulvar high-grade squamous precancer (SIR = 8.5; 95% CI: 7.2-10.0) and SCC (SIR = 16.2; 95% CI: 14.2-18.4). The SIRs of vulvar high-grade squamous precancer and SCC did not vary substantially according to length of follow-up. This nationwide and population-based study shows a 7-fold increase in the incidence of biopsy-verified vulvar LS since 1997. Data also show that women with biopsy-verified vulvar LS have 8.5 and 16 times higher than expected incidence of vulvar high-grade squamous precancer and SCC, respectively. The substantially increased incidence of vulvar high-grade squamous precancer and SCC following LS is important in relation to the clinical management and follow-up of LS patients.

Prediagnostic use of menopausal hormone therapy and long-term survival of localized epithelial ovarian cancer: The Extreme study.

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.

Low-dose aspirin use and risk of ovarian cancer: a combined analysis from two nationwide studies in Denmark and Sweden.

BACKGROUND: Studies on association between low-dose aspirin use and ovarian cancer risk were mostly based on self-reported medication use and few had large enough sample size to investigate the potential modification effect by ovarian cancer risk factors. METHODS: In these two nationwide nested case-control studies among the Danish and Swedish female population, 11,874 women with ovarian cancer (30-84 years old) (Denmark: 7328 diagnosed in 2000-2019, Sweden: 4546 diagnosed in 2010-2018) were randomly age- matched with 473,960 female controls (293,120 from Denmark, and 181,840 from Sweden). We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) and combined the estimates based the fixed-effect assumption. Effect modification by inflammation-related risk factors and by indication (cardiovascular disease, CVD) were also investigated. RESULTS: Ever use of low-dose aspirin was not strongly associated with the overall risk of ovarian cancer (OR = 0.97; 95%CI: 0.92-1.03). However, the association differed according to parity (nulliparous: OR = 0.80, 95%CI: 0.70-0.92; parous: OR = 1.00, 95%CI: 0.94-1.07; p-interaction = 0.0024), and according to history of CVD (no CVD: OR = 0.91, 95%CI: 0.82-1.00; ever CVD: OR = 1.05, 95%CI: 0.97-1.13; p-interaction =0.0204). CONCLUSIONS: Low-dose aspirin use was associated with a decreased ovarian cancer risk especially in nulliparous women and in women without CVD diagnosis.

Quark Mass Dependence of Heavy Quark Diffusion Coefficient from Lattice QCD.

We present the first study of the quark mass dependence of the heavy quark momentum and spatial diffusion coefficients using lattice QCD with light dynamical quarks corresponding to a pion mass of 320 MeV. We find that, for the temperature range 195 MeV

History of autoimmune disease and long-term survival of epithelial ovarian cancer: The extreme study.

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.

Risk of nonovarian cancer in a nationwide-based study of nearly 5000 women with borderline ovarian tumors in Denmark.

Evidence regarding cancer risk after borderline ovarian tumors (BOTs) is limited. We conducted a nationwide cohort study examining the incidence of nonovarian cancers in women with serous or mucinous BOTs compared with the general female population with up to 41 years of follow-up. Through the nationwide Pathology Registry, we identified nearly 5000 women with BOTs (2506 serous and 2493 mucinous) in Denmark, 1978 to 2018. We computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) as relative risk estimates of specific nonovarian cancers. Compared with general female population rates, women with serous BOTs had increased rates of particularly malignant melanoma (SIR = 1.9; 95% CI: 1.3-2.6), thyroid cancer (SIR = 3.0; 95% CI: 1.4-5.4) and myeloid leukemia (SIR = 3.2; 95% CI: 1.5-5.8), and women with mucinous BOTs had elevated rates of lung cancer (SIR = 1.7; 95% CI: 1.3-2.1), pancreatic cancer (SIR = 1.9; 95% CI: 1.2-2.9) and myeloid leukemia (SIR = 2.3; 95% CI: 0.9-4.7). We found no convincing association with neither breast nor colorectal cancer in women with BOTs. This is the first large nationwide study showing that women with specific types of BOTs have increased risks of several nonovarian cancers, likely due to some shared risk factors or genetic characteristics.

Heavy Quark Diffusion from 2+1 Flavor Lattice QCD with 320 MeV Pion Mass.

We present the first calculations of the heavy flavor diffusion coefficient using lattice QCD with light dynamical quarks corresponding to a pion mass of around 320 MeV. For temperatures 195 MeV

External validation of the hospital frailty risk score among hospitalised home care clients in Canada: a retrospective cohort study.

BACKGROUND: The Hospital Frailty Risk Score (HFRS) is scored using ICD-10 diagnostic codes in administrative hospital records. Home care clients in Canada are routinely assessed with Resident Assessment Instrument-Home Care (RAI-HC) which can calculate the Clinical Frailty Scale (CFS) and the Frailty Index (FI). OBJECTIVE: Measure the correlation between the HFRS, CFS and FI and compare prognostic utility for frailty-related outcomes. DESIGN: Retrospective cohort study. SETTING: Alberta, British Columbia and Ontario, Canada. SUBJECTS: Home care clients aged 65+ admitted to hospital within 180 days (median 65 days) of a RAI-HC assessment (n = 167,316). METHODS: Correlation between the HFRS, CFS and FI was measured using the Spearman correlation coefficient. Prognostic utility of each measure was assessed by comparing measures of association, discrimination and calibration for mortality (30 days), prolonged hospital stay (10+ days), unplanned hospital readmission (30 days) and long-term care admission (1 year). RESULTS: The HFRS was weakly correlated with the FI (ρ 0.21) and CFS (ρ 0.28). Unlike the FI and CFS, the HFRS was unable to discriminate for 30-day mortality (area under the receiver operator characteristic curve (AUC) 0.506; confidence interval (CI) 0.502-0.511). It was the only measure that could discriminate for prolonged hospital stay (AUC 0.666; CI 0.661-0.673). The HFRS operated like the FI and CFI when predicting unplanned readmission (AUC 0.530 CI 0.526-0.536) and long-term care admission (AUC 0.600; CI 0.593-0.606). CONCLUSIONS: The HFRS identifies a different subset of older adult home care clients as frail than the CFS and FI. It has prognostic utility for several frailty-related outcomes in this population, except short-term mortality.

Long-term survival of nonlocalized epithelial ovarian cancer among women using menopausal hormone therapy prior to diagnosis: The extreme study.

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.

Risk of Anal High-grade Squamous Intraepithelial Lesions Among Renal Transplant Recipients Compared With Immunocompetent Controls.

BACKGROUND: Renal transplant recipients (RTRs) have increased risk of human papillomavirus (HPV)-related cancers, including anal cancer. We investigated the prevalence of anal high-grade intraepithelial lesions (HSILs) in RTRs compared with immunocompetent controls and risk factors for anal HSIL in RTRs. METHODS: We included 247 RTRs and 248 controls in this cross-sectional study. We obtained anal samples for HPV testing with INNO-LiPA and performed high-resolution anoscopy on all participants. The participants completed a questionnaire on lifestyle and sexual habits. We used logistic regression to estimate odds ratios (ORs) of histologically confirmed anal HSIL in RTRs vs controls and risk factors for anal HSIL in RTRs, stratified by sex and anal high-risk (hr) HPV status, adjusting for age, smoking, lifetime sexual partners, and receptive anal sex. RESULTS: RTRs had higher anal HSIL prevalence than controls, both among men (6.5% vs 0.8%; adjusted OR [aOR], 11.21 [95% confidence interval {CI}, 1.46-291.17]) and women (15.4% vs 4.0%; aOR, 6.41 [95% CI, 2.14-24.10]). Among those with anal hrHPV, RTRs had higher anal HSIL prevalence than controls (33.8% vs 9.5%; aOR, 6.06 [95% CI, 2.16-20.27]). Having had receptive anal sex (aOR, 6.23 [95% CI, 2.23-19.08]) or genital warts (aOR, 4.21 [95% CI, 1.53-11.48]) were risk factors for anal HSIL in RTRs. All HSIL cases occurred in individuals with anal hrHPV. CONCLUSIONS: RTRs had increased risk of anal HSIL compared with immunocompetent controls, with particularly high prevalence in female RTRs. Receptive anal sex, previous genital warts, and anal hrHPV infection were risk factors for anal HSIL in RTRs. Screening for anal HSIL in RTRs should be considered. CLINICAL TRIALS REGISTRATION: NCT03018927.

Prognostic impact of socioeconomic status on long-term survival of non-localized epithelial ovarian cancer ꟷ The Extreme study.

OBJECTIVE: To examine the influence of socioeconomic status (SES) on long-term survival of non-localized ovarian cancer. METHODS: All women in Denmark with a first diagnosis of non-localized epithelial ovarian cancer 1982-2007 were identified in the Cancer Registry and/or the Pathology Registry and followed up until December 2017. The survival probability was estimated after respectively 5 and 10 years, using so-called pseudo observations, and analyzed according to education, income, and marital status defined from nationwide registries. RESULTS: The study cohort included 6486 women, and the estimated 5- and 10-year survival probabilities were 21.4% and 12.7%, respectively. Compared to women with short education, the 5-year survival probability was 7% higher for women with medium (relative survival probability = 1.07, 95% CI: 0.97, 1.19) and long education (relative survival probability = 1.07, 95% CI: 0.93, 1.24). Compared with married women, the 5-year survival probability for divorced women/widower was slightly lower (0.85, 95% CI: 0.69, 1.04) and for unmarried women slightly higher (1.08, 95% CI: 0.94, 1.23). Finally, the probability of being alive 5 years after diagnosis was 1.09 times higher (95% CI: 0.95, 1.24) for medium-income women and 1.23 times higher (95% CI: 1.08, 1.41) for high-income women compared with low-income women. Similar patterns were observed for 10-year survival. CONCLUSIONS: Non-localized ovarian cancer patients have a poor prognosis. Our data suggest that among Danish women with advanced ovarian cancer, higher personal income is associated with slightly higher probability of long-term survival, whereas education and marital status did not affect the probability of long-term survival.

Follow-up after abnormal cervical cancer screening in immigrants compared with Danish-born women - A nationwide register study.

Cervical cancer screening is offered free-of-charge to women aged 23-64 years in Denmark. Immigrants participate less in screening than Danish-born women, but little is known about their participation in follow-up after abnormal screening results. In this registry-based cohort study, we examined the likelihood of timely follow-up after an abnormal cervical cytology in immigrants from different countries and regions compared with Danish-born women. In nationwide registers, we identified women aged 23-64 years with high-grade (n = 74,335) or low-grade (n = 174,038) abnormal cytology during 1997-2017. Timely follow-up was defined as a new examination within six months for high-grade and 18 months for low-grade abnormalities. We calculated the probability of timely follow-up by country and region of origin and estimated odds ratios (ORs) of timely follow-up between immigrants and Danish-born women. The proportions with timely follow-up after high-grade abnormalities ranged from 90.6%-95.1% in immigrants from different countries or regions, compared with 95.5% in Danish-born women. For low-grade abnormalities, follow-up ranged from 75.2%-92.8% in immigrants, compared with 90.6% in Danish-born women. Women from Sub-Saharan Africa had low probability of timely follow-up after both high-grade (90.9%) and low-grade (75.2%) abnormalities. The differences between immigrants and Danish-born women remained when adjusting for age, year, income, employment and marital status. In conclusion, immigrants from most countries and regions were slightly less likely than Danish-born women to receive timely follow-up after abnormal cervical cytology, also after adjusting for socioeconomic differences. Efforts should be made to improve follow-up of abnormal screening results in immigrant groups with low attendance.

Concurrent Validity Between Electronically Administered Physical Activity Questionnaires and Objectively Measured Physical Activity in Danish Community-Dwelling Older Adults.

AIM: To investigate the concurrent validity of the International Physical Activity Questionnaire-short form (IPAQ-SF) and the Nordic Physical Activity Questionnaire-short (NPAQ-short) when compared with objectively measured daily steps among older adults. METHODS: Spearman's ρ between IPAQ-SF and NPAQ-short and objectively measured steps using Garmin Vivofit 3 physical activity monitors. RESULTS: A total of 54 participants were included. The IPAQ-SF subscales' moderate physical activity (PA), moderate to vigorous PA (MVPA), and sedentary time showed little or no correlation with daily steps. The NPAQ-short subscales' vigorous PA, moderate PA, and MVPA showed little or no correlation. The IPAQ-SF subscales' vigorous PA and walking showed fair correlation. Only the IPAQ-SF metabolic equivalent of task minutes showed moderate to good correlation with daily steps. The IPAQ-SF categories and NPAQ-short categorization of World Health Organization compliance were significantly different, but the magnitudes were small and distributions indicated problems with the categorization. CONCLUSION: The concurrent validity is low, as the scores did not reflect objectively measured daily steps.

Non-participation in cervical cancer screening according to health, lifestyle and sexual behavior: A population-based study of nearly 15,000 Danish women aged 23-45 years.

High participation in cervical cancer screening is essential for an effective screening program. In this population-based study, we investigated associations between general health, lifestyle and sexual behavior, and non-participation in cervical cancer screening in Denmark. During 2011-2012, a random sample of women aged 18-45 years from the general female population were invited to participate in a survey regarding health, lifestyle and sexual habits. Altogether 18,631 women responded (response rate: 75.1%), of whom 14,271 women aged 23-45 years were included in this analysis. Information on screening participation within four years after response, and data on sociodemographic characteristics, was obtained from nationwide registers. Logistic regression was used to calculate odds ratios (ORs) for non-participation, crude and adjusted for sociodemographic characteristics. Overall, 13.9% of the women were not screened during follow-up. The odds of non-participation was increased in women who were overweight (ORadj. = 1.20; 95% CI, 1.06-1.35), obese (ORadj. = 1.46; 95% CI, 1.27-1.67), perceived themselves as much too fat (ORadj. = 1.50; 95% CI, 1.29-1.74), had poor self-perceived health (ORadj. = 1.22; 95% CI, 1.03-1.45) or smoked daily (ORadj. = 1.81; 95% CI, 1.61-2.03). Conversely, women with previous genital warts or other sexually transmitted infections, and young women with ≥10 lifetime sexual partners or ≥2 new recent partners, had decreased odds of non-participation. In conclusion, obesity, poor self-perceived health and daily smoking were associated with lower participation in cervical cancer screening. Interventions targeting these groups are needed.

The MIPAM trial: a 12-week intervention with motivational interviewing and physical activity monitoring to enhance the daily amount of physical activity in community-dwelling older adults - a study protocol for a randomized controlled trial.

BACKGROUND: Physical Activity Monitors (PAMs) have been shown to effectively enhance level of physical activity (PA) in older adults. Motivational interviewing is a person-centred model where participants are guided using self-reflection and counselling, and addresses the behavioural and psychological aspects of why people initiate health behaviour change by prompting increases in motivation and self-efficacy. The addition of motivational interviewing to PA interventions may increase the effectiveness of PAMs for older adults. METHODS: This motivational interviewing and PA monitoring trial is designed as an investigator-blinded, two arm parallel group, randomized controlled superiority trial with primary endpoint after 12 weeks of intervention. The intervention group will receive a PAM-based intervention and motivational interviewing and the control group will only receive the PAM-based intervention. The primary outcome is PA, objectively measured as the average daily number of steps throughout the intervention period. Secondary outcome measures include self-reported PA health-related quality of life, loneliness, self-efficacy for exercise, outcome expectancy for exercise, and social relations. The outcomes will be analysed with a linear regression model investigating between-group differences, adjusted for baseline scores. Following the intention to treat principle, multiple imputation will be performed to handle missing values. DISCUSSION: A moderate effect of daily PA measured using PAMs is expected in this superiority RCT investigating the effect of adding motivational interviewing to a PAM intervention. According to the World Health Organization, walking and cycling are key activities in regular PA and should be promoted. To increase the general public health and lower the burden of inactivity in older adults, cost-beneficial solutions should be investigated further. If this RCT shows that motivational interviewing can enhance the effect of PAM-based interventions, it might be included as an add-on intervention when appropriate. No matter what the results of this study will be, the conclusions will be relevant for clinicians as the dependence on technology is increasing, especially in relation to public health promotion. TRIAL REGISTRATION: NCT03906162 , April 1, 2019.

Participation in cervical cancer screening among immigrants and Danish-born women in Denmark.

In this nationwide register-based cohort study, we examined cervical cancer screening participation among immigrants in Denmark by country and region of origin. Furthermore, we assessed whether differences in screening participation between immigrants and Danish-born women were explained by sociodemographic or health-related characteristics, and examined predictors of participation among immigrants. Using high-quality registries, we identified women invited for cervical cancer screening during 2008-2009 and retrieved individual-level data on sociodemographic-, health- and immigration-related characteristics. A total of 610,907 women were followed for up to 2.9 years after screening invitation. We estimated the probability of participation using the Aalen-Johansen estimator and the hazard ratios (HRs) of participation using Cox regression. The probability of participation within follow-up was 74.5% (95% CI, 74.4%-74.6%) in Danish-born women; 61.2% (95% CI, 60.4%-62.1%) in Western immigrants; and 61.3% (95% CI, 60.9%-61.8%) in non-Western immigrants. Participation in immigrants varied by region of origin from 44.3% (95% CI, 41.4%-47.4%) in immigrants from North America, New Zealand and Australia to 67.8% (95% CI, 65.4%-70.3%) in immigrants from South- and Central America. Substantial variation was seen between specific countries of origin. Differences in participation between immigrants and Danish-born women were not explained by sociodemographic or health-related characteristics. Predictors of low participation in immigrants included lower income, unemployment, being unmarried, having a history of schizophrenia or other psychoses, and ≤5 years' stay in Denmark. In conclusion, cervical cancer screening participation in immigrants varied by region and country of origin, but all immigrant groups had lower participation than Danish-born women.

Associations between fatigue, physical activity, and QoL in patients with myeloproliferative neoplasms.

BACKGROUND: Patients with Philadelphia chromosome-negative Myeloproliferative Neoplasms (MPNs) report fatigue as the most common symptom and contributing significantly to reduction in their quality of life (QoL). Targeted non-pharmacological intervention to increase levels of physical activity is suggested as a fatigue-reducing and QoL-enhancing intervention in MPN patients. The interrelationship between physical activity, fatigue, and QoL has, to our knowledge, never been reported. METHODS: We analyzed data from 1807 MPN patients. The primary analysis included a multiple regression model allowing fatigue to mediate the relationship between physical activity and QoL. RESULTS: We herein report the first and the largest study of patients with MPNs, in whom we have investigated the interrelationship between fatigue, physical activity, and QoL. Sedentary patients were more likely to report fatigue compared to highly active patients. There was a negative association between fatigue and QoL, and there was a positive association between physical activity and QoL. There was no interaction between fatigue and physical activity in the association with QoL. CONCLUSION: We found positive associations between level of physical activity and QoL, independently of fatigue being present. More research is needed before physical activity can be introduced as a targeted intervention to reduce fatigue and increase QoL in the management of patients.

Quantitative tumor heterogeneity assessment on a nuclear population basis.

Immunohistochemistry Ki-67 stain is widely used for visualizing cell proliferation. The common method for scoring the proliferation is to manually select and score a hot spot. This method is time-consuming and will often not give reproducible results due to subjective selection of the hotspots and subjective scoring. An automatic hotspot detection and proliferative index scoring would be time-saving, make the determination of the Ki-67 score easier and minimize the uncertainty of the score by introducing a more objective and standardized score. Tissue Micro Array cores stained for Ki-67 and their neighbor slide stained for Pan Cytokeratin were aligned and Ki-67 positive and negative nuclei were identified inside tumor regions. A heatmap was calculated based on these and illustrates the distribution of the heterogenous response of Ki-67 positive nuclei in the tumor tissue. An automatic hot spot detection was developed and the Ki-67 score was calculated. All scores were compared with scores provided by a pathologist using linear regression models. No significant difference was found between the Ki-67 scores guided by the developed heatmap and the scores provided by a pathologist. For comparison, scores were also calculated at a random place outside the hot spot and these scores were found to be significantly different from the pathologist scores. A heatmap visualizing the heterogeneity in tumor tissue expressed by Ki-67 was developed and used for an automatic identification of hot spots in which a Ki-67 score was calculated. The Ki-67 scores did not differ significantly from scores provided by a pathologist. © 2017 International Society for Advancement of Cytometry.

Anthropometry, DXA, and leptin reflect subcutaneous but not visceral abdominal adipose tissue on MRI in 197 healthy adolescents.

BackgroundAbdominal fat distribution is associated with the development of cardio-metabolic disease independently of body mass index (BMI). We assessed anthropometry, serum adipokines, and DXA as markers of abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) using magnetic resonance imaging (MRI).MethodsWe performed a cross-sectional study that included 197 healthy adolescents (114 boys) aged 10-15 years nested within a longitudinal population-based cohort. Clinical examination, blood sampling, DXA, and abdominal MRI were performed. SAT% and VAT% were adjusted to total abdominal volume.ResultsGirls had a higher SAT% than did boys in early and late puberty (16 vs. 13%, P<0.01 and 20 vs. 15%, P=0.001, respectively), whereas VAT% was comparable (7% in both genders, independently of puberty). DXA android fat% (standard deviation score (SDS)), suprailiac skinfold thickness (SDS), leptin, BMI (SDS), waist-to-height ratio (WHtR), and waist circumference (SDS) correlated strongly with SAT% (descending order: r=0.90-0.55, all P<0.001) but weakly with VAT% (r=0.49-0.06). Suprailiac skinfold was the best anthropometric marker of SAT% (girls: R2=48.6%, boys: R2=65%, P<0.001) and VAT% in boys (R2=16.4%, P<0.001). WHtR was the best marker of VAT% in girls (R2=7.6%, P=0.007).ConclusionsHealthy girls have a higher SAT% than do boys, whereas VAT% is comparable, independently of puberty. Anthropometry and circulating leptin are valid markers of SAT%, but not of VAT%.