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Objective: Despite various surgical and nonsurgical strategies for abdominal wall endometriosis, the lack of definitive guidance on optimal treatment choice leads to clinical uncertainty. This review scrutinizes the safety and efficacy of abdominal wall endometriosis treatments to aid in decision-making., Data Sources: We performed a systematic literature review of PubMed, Embase, and Cochrane Library databases from 1947 until December 2023., Methods of Study Selection: A comprehensive literature search identified studies that assessed both surgical and nonsurgical interventions, including high-intensity focused ultrasound (HIFU), cryoablation, radiofrequency ablation, and microwave ablation. This review is registered in NIHR-PROSPERO (CRD 42023494969). Local tumor control (LTC), local pain relief (LPR), and adverse events (AE) were recorded., Tabulation, Integration, and Results: This review included 51 articles among 831 identified. All study designs were considered eligible for inclusion. A total of 2674 patients are included: 2219 patients (83%) undergoing surgery, and 455 (17%) undergoing percutaneous interventions (342 HIFU, 103 cryoablation, 1 radiofrequency ablation, 9 microwave ablation). Follow-up length was 18 months in median, ranging from 1 to 235 months. Overall LTC rates ranged from 86% to 100%. Surgical interventions consistently demonstrated the highest rate of LTC with a median rate of 100%, and LPR with a median rate of 98.2% (95% confidence interval [CI]: 93.9-97.7). HIFU showed median LTC and LPR rates, respectively of 95.65% (95% CI, 87.7-99.9) and 76.1% (95% CI, 61.8-90.4); and cryoablation of 85.7% (95% CI, 66.0-99.9) and 79.2% (95% CI, 67.4-91.03). Minor AE was reported after surgery in 17.5% of patients (225/1284) including 15.9% (199/1284) of mesh implantation; 76.4% (239/313) after HIFU; and 8.7% (9/103) after cryoablation. Severe AE was reported in 25 patients in the surgery group and 1 in the percutaneous group., Conclusion: The safety profile and efficacy of nonsurgical interventions support their clinical utility for management of abdominal wall endometriosis., Competing Interests: Declaration of Competing Interest F.H. Cornelis is consultant for Boston Scientific, Varian, and IceCure., (Copyright © 2024 AAGL. Published by Elsevier Inc. All rights reserved.)

Purpose: This study assessed the safety and effectiveness of a technical modification that involves adding short gastric artery (SGA) embolization to left gastric artery (LGA) embolization., Material and Methods: This retrospective single-center study analyzed twenty obese patients (median age of 53.5 (30-73)) who were not eligible for bariatric surgery and underwent bariatric embolization with 300-500-µm microspheres in addition to a lifestyle counseling program between March 2021 and July 2022. Eight patients had LGA + SGA embolization, and twelve had LGA embolization alone. The primary outcome measure was total body weight loss (TBWL) at 6 months in the SGA + LGA and the LGA-only cohorts. Safety was assessed, defined as the 30-day adverse events rate according to the SIR classification., Results: The mean 6-month post-embolization TBWL in the SGA + LGA cohort was 7.3 kg (95%CI 2.1-12.4; p = .01) and 4.1 kg (95%CI 0.4-8.6; p = 0.034) in the LGA-only cohort (mean difference - 3.1 kg ± 2.8; 95%CI (- 9.1-2.8); p = .28). The mean 6-month post-embolization TBWL in the entire cohort was 5.3 kg (p < .01). The rate of complications was similar between the two groups., Conclusion: Combined SGA and LGA embolization is safe and effective to treat obesity. Larger studies are needed to determine whether SGA + LGA embolization results in more significant weight loss than LGA embolization alone., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: The aim of this observational, real-world evidence, modified intention-to-treat (mITT) study based on prospectively collected data from the VEDOIBD registry was to compare the effectiveness of vedolizumab (VEDO) vs antitumor necrosis factor (anti-TNF) in biologic-naïve Crohn's disease (CD) patients., Methods: Between 2017 and 2020, 557 CD patients starting therapy with VEDO or anti-TNF were consecutively enrolled in 45 IBD centers across Germany. Per study protocol, the analysis excluded biologic-experienced patients and those with a missing Harvey-Bradshaw Index score, resulting in a final sample of 327 biologic-naïve CD patients. Clinical remission was measured using the Harvey-Bradshaw Index at the end of induction therapy and after 1 and 2 years. Switching to a different therapy was considered an outcome failure. Propensity score adjustment with inverse probability of treatment weighting was used to correct for confounding., Results: The effectiveness of both VEDO (n = 86) and anti-TNF (n = 241) was remarkably high for induction treatment, but VEDO performed significantly less well than anti-TNF (clinical remission: 56.3% vs 73.9%, P < .05). In contrast, clinical remission after 2 years was significantly better for VEDO compared with anti-TNF (74.2% vs 44.7%; P < .05; odds ratio, 0.45; 95% CI, 0.22-0.94). Remarkably, only 17% of patients switched from VEDO to another biologic vs 44% who received anti-TNF., Conclusions: The results of this prospective, 2-year, real-world evidence study suggest that the choice of VEDO led to higher remission rates after 2 years compared with anti-TNF. This could support the role of VEDO as a first-line biologic therapy in CD., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: In addition to randomized controlled trials (RCTs), real-world studies on the effectiveness of ustekinumab (UST) in Crohn's disease (CD) are required inasmuch as RCTs are usually confined to selected patients, which may not represent everyday clinical practice. Within the framework of the prospective real-world RUN-CD registry, a total of approximately 900 CD patients from 44 inflammatory bowel disease centers from all over Germany starting a new therapy with UST or other biologics were screened for a real-world evidence (RWE) comparison of CD patients with UST vs antitumor necrosis factor (TNF)., Methods: A total of 618 CD patients with a nonrandomized biological therapy were qualified for this induction phase effectiveness RUN-CD study of UST vs anti-TNF. To reduce selection bias in estimations of treatment effects, the propensity score with inverse probability of treatment weighting was implemented. The results were reported as odds ratio (OR) and 95% confidence interval (CI)., Results: A total of 339 UST and 279 anti-TNF patients were analyzed. The effectiveness of UST vs anti-TNF in terms of clinical remission (UST 65.4% vs anti-TNF 63.0%; OR, 1.11; 95% CI, 0.71-1.74) and steroid-free remission (UST 51.0% vs anti-TNF 53.8%; OR, 0.94; 95% CI, 0.60-1.47) was comparable at the end of induction therapy. Similar results were observed in the bio-naïve and bio-experienced UST vs anti-TNF groups. For both, the remission rates were higher in the bio-naïve than in the bio-experienced groups (P < .05)., Conclusions: In this prospective, observational RUN-CD study, the RWE head-to-head comparison of UST vs anti-TNF showed similar induction effectiveness in both groups, remarkably higher than those found in prior RCTs., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: This observational real-world evidence (RWE) study is based on prospectively collected data from the VEDO IBD registry study., Aim: To compare the effectiveness of vedolizumab and anti-TNF agents in biologic-naïve patients with ulcerative colitis (UC) at the end of induction and during maintenance treatment., Methods: Between 2017 and 2020, we enrolled 512 patients with UC starting therapy with vedolizumab or an anti-TNF agent in 45 IBD centres across Germany. We excluded biologic-experienced patients and those with missing partial Mayo (pMayo) outcomes; this resulted in a final sample of 314 (182 on vedolizumab and 132 on an anti-TNF agent). The primary outcome was clinical remission measured using pMayo score; any switch to a different biologic agent was considered an outcome failure (modified ITT analysis). We used propensity score adjustment with inverse probability of treatment weighting to correct for confounding., Results: During induction therapy, clinical remission was relatively low and similar in vedolizumab- and anti-TNF-treated patients (23% vs. 30.4%, p = 0.204). However, clinical remission rates after two years were significantly higher for vedolizumab-treated patients than those treated with an anti-TNF agent (43.2% vs. 25.8%, p < 0.011). Among patients treated with vedolzumab, 29% switched to other biologics, versus 54% who had received an anti-TNF agent., Conclusion: After two years of treatment, vedolizumab resulted in higher remission rates than anti-TNF agents., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Objective: Under the assumption of irreversibility, the Montreal classification provides a unidirectional assessment of the complications and behaviour of Crohn's disease (CD) that does not allow for downstaging. We examined the use of a bidirectional Montreal classification system that can capture disease regression., Design: From the BioCrohn Registry, an inception cohort of patients with CD for ≤12 months duration was defined and followed up for 5-years. Cumulative probabilities for developing complications were estimated using the Kaplan-Meier method. Potential associations of explanatory variables with disease progression were estimated with Cox regression., Results: Among 393 incident CD patients (of whom 255 completed the entire follow-up), the 5-year cumulative probability of developing complications was 41.5% (15.6% and 25.9% for stricturing and penetrating complications respectively). Perianal disease (hazard ratio [95% confidence interval]: 8.45 [4.74-15.07]) and surgical resection of the intestine (2.71 [1.50-4.92]) in the very early phase of the disease were associated with a higher risk of developing a penetrating complication within the 5-year follow-up. The use of a bidirectional Montreal classification system which can account for disease regression demonstrated that 90% of patients exhibited inflammatory disease behaviour at 5 years, in contrast to 58%, if the hierarchical, unidirectional Montreal classification system was used., Conclusion: An additional bidirectional disease behaviour assessment capturing reversed or fully controlled complications may provide a more realistic appraisal of the complexity and unmet needs of patients treated with advanced therapies., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Purpose: We characterized the profile of Crohn's disease (CD) or ulcerative colitis (UC) biologic-naïve patients (starting a new therapy with vedolizumab or TNFα-antagonists), their baseline disease activity predictors, and their perception of the quality of life (HRQoL)., Methods: The VEDO IBD -Study is a real-world study on the effectiveness of vedolizumab vs other biologics as induction and maintenance therapy for CD and UC. A total of 627 CD and 546 UC patients were enrolled from IBD-experienced centers across Germany. In both biologic-naïve vedolizumab (n=397) and anti-TNF (n=359) patients, CD and UC disease severity and HRQoL predictors were analyzed with logistic regression. The results were reported as odds ratio (OR) and 95% confidence interval (CI)., Results: When compared to biologic-naïve anti-TNF patients, a first biological therapy with vedolizumab was considered for older CD patients, with a less complicated though longer disease course, and with a history of comorbidities. No differences in (unmet) needs were observed among patients with UC. The presence of extra-intestinal manifestations in biologic-naïve anti-TNF patients with CD (OR (95% CI): 3.83 (1.69-8.68)) and, in both biologic-naïve groups of patients with UC, stool frequency (2.00 (1.25-3.19); 1.82 (1.10-3.02), respectively) and rectal bleeding (2.24 (1.20-4.18); 1.92 (1.19-3.11), respectively) emerged as the most important predictors of disease severity, which in turn were also significantly associated with a worse HRQoL., Conclusion: This study highlights the existence of unmet medical needs of patients with CD or UC, for whom a new biological therapy is planned as part of the VEDO IBD -Study, which considerably impacts their HRQoL., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Socioeconomic status (SES) is strongly associated with childhood overweight. The underlying mechanism and the role of family and lifestyle factors as potential mediators of this relationship remain, however, unclear. Cross-sectional data of 4,772 girls and boys aged 5-16 years from the Kiel Obesity Prevention Study were considered in mediation analyses. Fat mass (FM) was assessed by bioelectrical impedance analysis and converted into a percent FM SD score (FM%-SDS). SES was defined by the parental educational level, classified as low, middle, or high. Characteristics of family and lifestyle factors were obtained via validated questionnaires and considered as mediators. In 3 different age groups, the product-of-coefficients method was used to examine age-specific mediator effects on the relationship between SES and FM%-SDS (c = total effects) and their ratio to total effects, adjusted for age, sex, puberty, and nationality. The prevalence of overweight was 6.9%. In all age groups, SES was inversely associated with FM%-SDS as follows: 5-7 years, c1 = -0.11 (95% CI -0.19 to -0.03); 9-11 years, c2 = -0.21 (95% CI -0.27 to -0.14); and 13-16 years, c3 = -0.23 (95% CI -0.28 to -0.17). The relationship between SES and FM%-SDS was fully (5-7 and 9-11 years) and partly (13-16 years) mediated by similar and age-specific mediators, including parental BMI, parental smoking habits, media consumption, physical activity, and shared meals. Overall, these variables resulted in a total mediating effect of 77.8% (5-7 years), 82.4% (9-11 years), and 70.6% (13-16 years). Consistent for both sexes, the relationship between SES and FM%-SDS was therefore mediated by parental weight status, risk-related behavior within families, and children's and adolescents' lifestyle factors. Strategies for obesity prevention, which are predominantly targeted at socially disadvantaged groups, should therefore address the family environment and lifestyle factors., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Initial evidence suggests that lithium might affect life expectancy and the risk for different disease conditions, but most studies were conducted in patients on lithium medication. Little is known about the association of blood lithium levels within the physiological range with cardiometabolic risk factors and diet. We measured plasma lithium in a community-based sample from Northern Germany (samples taken between 2010 and 2012). All participants (aged 25-82 years) underwent standardized examinations and completed a semi-quantitative food frequency questionnaire. Of several variables tested, the estimated glomerular filtration rate (eGFR) was statistically significantly (inversely) associated with lithium levels, mainly in individuals with slightly impaired renal function (eGFR < 75 mL/min/1.73 m 2 ). Besides, lithium levels were positively associated with age and alcohol intake. Using reduced rank regression, we identified a dietary pattern explaining 8.63% variation in plasma lithium levels. Higher lithium levels were associated with higher intakes of potatoes, leafy vegetables, root vegetables, fruits, tea, beer, wine and dietetic products and lower intakes of pasta, rice, pork, chocolate, sweets, soft drinks, other alcoholic beverages, sauces and snacks. Our observations suggest that plasma lithium levels are associated inversely with kidney function, particularly in individuals with slightly impaired renal function, and positively with age and alcohol intake. Lithium at physiological levels was moderately related to an exploratory dietary pattern.

Background Accumulating evidence indicates that trimethylamine-N-oxide (TMAO) may play a causal role in cardiovascular disease (CVD), chronic kidney disease (CKD) and type 2 diabetes (T2D). TMAO plasma concentrations show considerable intra- and inter-individual variation, underscoring the need for a reference interval in the general population to identify elevated TMAO concentrations. Methods TMAO concentrations were determined using an LC-MS/MS assay in a community-based sample of the PopGen control cohort consisting of 694 participants (54% men; aged 25-82 years) free of clinical CVD, CKD and T2D. We defined reference intervals for TMAO concentrations in human plasma using the 2.5th and 97.5th percentiles. Using multivariable regression analysis we analyzed the association of estimated glomerular filtration rate (eGFR), sex, and dietary intake and TMAO plasma concentrations. Results TMAO plasma concentrations were positively skewed and differed by sex. The median TMAO plasma concentration in men was 3.91 (Q1-Q3: 2.87-6.10) μmol/L and the reference interval 1.28-19.67 μmol/L (2.5th-97.5th percentile). In women median TMAO plasma concentration was 3.56 (Q1-Q3: 2.41-5.15) μmol/L and the reference interval 1.08-17.12 μmol/L. In multivariable regression analysis plasma TMAO was associated with sex, renal function and diet. The association of TMAO and diet was significant for intake of fish and shellfish in men only. Conclusions In a community-based sample free of apparent CVD and renal disease, we report the distribution of TMAO plasma concentrations with sex, renal function and diet as factors associated with plasma TMAO, and suggest reference intervals. These data may facilitate standardized comparisons of TMAO across populations.

Context: CD36 is a class B scavenger-receptor involved in the uptake of fatty acids in liver and adipose tissue. It is unknown whether plasma CD36 levels are related to liver fat content or adipose tissue in the general population., Methods: We measured plasma CD36 from 575 participants of the community-based PopGen cohort who underwent MRI to quantify visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and liver signal intensity (LSI), a proxy for liver fat content. Nonalcoholic fatty liver disease (NAFLD) was defined as LSI ≥3.0 in the absence of high alcohol intake. The relations between plasma CD36 and body mass index (BMI), VAT, SAT, LSI, and NAFLD were evaluated via multivariable-adjusted linear and logistic regression analysis., Results: Plasma CD36 concentrations were correlated with BMI (r = 0.11; P = 0.01), SAT (r = 0.16; P < 0.001), and VAT (r = 0.15, P < 0.001) but not with LSI (P = 0.44). In multivariable-adjusted regression models, mean BMI values rose across CD36 quartiles [quartile 1 (Q1), 27.8 kg/m2; Q4, 28.9 kg/m2; P-trend = 0.013). Similarly, VAT (Q1, 4.13 dm3; Q4, 4.71 dm3; P-trend < 0.001), and SAT (Q1, 7.61 dm3; Q4, 8.74 dm3; P-trend < 0.001) rose across CD36 quartiles. Plasma CD36 concentrations were unrelated to LSI (P-trend = 0.36) and NAFLD (P-trend = 0.64). Participants with NAFLD and elevated alanine aminotransferase (ALT), a marker for liver damage, had higher CD36 compared with participants with NAFLD and normal ALT., Conclusions: Higher plasma concentrations of CD36 were associated with greater general and abdominal adiposity but not with liver fat content or NAFLD in this community-based sample. However, plasma CD36 may reflect more severe liver damage in NAFLD., (Copyright © 2019 Endocrine Society.)

Purpose: Selenoprotein P (SELENOP) has been previously related to various metabolic traits with partially conflicting results. The identification of SELENOP-associated metabolites, using an untargeted metabolomics approach, may provide novel biological insights relevant to disentangle the role of SELENOP in human health., Methods: In this cross-sectional study, 572 serum metabolites were identified by comparing the obtained LC-MS/MS spectra with spectra stored in Metabolon's spectra library. Serum SELENOP levels were measured in 832 men and women using an ELISA kit., Results: Circulating SELENOP levels were associated with 24 out of 572 metabolites after accounting for the number of independent dimensions in the metabolomics data, including inverse associations with alanine, glutamate, leucine, isoleucine and valine, an unknown compound X-12063, urate and the peptides gamma-glutamyl-leucine, and N-acetylcarnosine. Positive associations were observed between SELENOP and several lipid compounds. Of the identified metabolites, each standard deviation increase in the branched-chain amino acids (isoleucine, leucine, valine), alanine and gamma-glutamyl-leucine was related to higher odds of having T2DM [OR (95% CI): 1.96 (1.41-2.73); 1.62 (1.15-2.28); 1.94 (1.45-2.60), 1.57 (1.17-2.11), and 1.52 (1.13-2.05), respectively]., Conclusions: Higher serum SELENOP levels were associated with an overall healthy metabolomics profile, which may provide further insights into potential mechanisms of SELENOP-associated metabolic disorders.

Aim: Assessment of the feasibility and reliability of immune-inflammatory biomarker measurements. Methods: The following biomarkers were assessed in 207 predominantly healthy participants at baseline and after 4 months: MMF, TGF-β, suPAR and clusterin. Results: Intraclass correlation coefficients (95% CIs) ranged from good for TGF-β (0.75 [95% CI: 0.33-0.90]) to excellent for MMF (0.81 [95% CI: 0.64-0.90]), clusterin (0.83 [95% CI: 0.78-0.87]) and suPAR (0.91 [95% CI: 0.88-0.93]). Measurement of TGF-β was challenged by the large number of values below the detection limit. Conclusion: Single measurements of suPAR, clusterin and MMF could serve as feasible and reliable biomarkers of immune-inflammatory pathways in biomedical research.

Purpose: The association of complex dietary patterns with circulating selenoprotein P (SELENOP) levels in humans is unknown. In a general population sample, we aimed to identify a dietary pattern explaining inter-individual variation in circulating SELENOP concentrations and to study this pattern in relation to prevalent diabetes, metabolic syndrome (MetS), MRI-determined total volumes of visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, and liver signal intensity/fatty liver disease., Methods: In this cross-sectional study, serum SELENOP levels were measured in 853 individuals. In a subsample of 553 participants, whole-body MRI was performed to assess body fat distribution and liver fat. Dietary intake was assessed by a self-administered food frequency questionnaire and the dietary pattern identified using reduced-rank regression (RRR). Multivariable linear and logistic regressions were used to investigate associations between dietary pattern score and metabolic traits., Results: Characterized by high intake of fruit, vegetables and antioxidant beverages, the RRR-derived dietary pattern displayed inverse associations with VAT, SAT, MetS, and prevalent diabetes in multivariable-adjusted restricted cubic splines. Each unit increase in dietary pattern score was associated with 31% higher SELENOP levels, 12% lower VAT (95% CI: - 19%; - 5%), 13% (95% CI: - 20%; - 6%) lower SAT values and 46% (95% CI: 27%; 60%) and 53% (95% CI: 22%; 72%) lower odds of having MetS or diabetes, respectively. No meaningful relations were observed between the dietary pattern and liver traits., Conclusions: Our observations propose diet-related regulation in SELENOP levels and that the identified dietary pattern is inversely related to VAT, SAT, MetS, and prevalent diabetes.

Importance: Inflammatory processes have been suggested to have an important role in colorectal cancer (CRC) etiology. Chemerin is a recently discovered inflammatory biomarker thought to exert chemotactic, adipogenic, and angiogenic functions. However, its potential link with CRC has not been sufficiently explored., Objective: To evaluate the prospective association of circulating plasma chemerin concentrations with incident CRC., Design, Setting, and Participants: Prospective case-cohort study based on 27 548 initially healthy participants from the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam cohort who were followed for up to 16 years. Baseline study information and samples were collected between August 23, 1994, and September 25, 1998. Recruitment was according to random registry sampling from the geographical area of Potsdam, Germany, and surrounding municipalities. The last date of study follow-up was May 10, 2010. Statistical analysis was conducted in 2018., Main Outcomes and Measures: Incident CRC, colon cancer, and rectal cancer. Baseline chemerin plasma concentrations were measured by enzyme-linked immunosorbent assay., Results: A random subcohort of 221 incident CRC cases and 2329 participants free of CRC with available blood sample measurements were included in the analysis. The participants' mean (SD) age was 50 (9) years, 62.1% were female, and 16.5% had a body mass index greater than 30. In multivariable-adjusted Cox proportional hazards regression models taking into account established CRC risk factors, higher chemerin concentrations were associated with a greater risk of CRC, with a hazard ratio (HR) of 1.81 (95% CI, 1.08-3.05; P for trend = .007) for the highest chemerin quartile vs the lowest. Analyses by cancer subsite indicated a stronger association with colon cancer (HR, 2.27; 95% CI, 1.18-4.34 for the highest quartile vs the lowest; P for trend = .005) compared with rectal cancer (HR, 1.27; 95% CI, 0.57-2.85; P for trend = .35). The association was particularly strong for proximal colon cancer (HR, 3.97; 95% CI, 1.51-10.50; P for trend = .001)., Conclusions and Relevance: This study found that the association between chemerin concentration and the risk of incident CRC was linear and independent of established CRC risk factors. Further studies are warranted to evaluate chemerin as a novel immune-inflammatory agent in colorectal carcinogenesis.

Background: The group of colorectal cancer (CRC) survivors continues to grow worldwide. Understanding health-related quality of life (HRQOL) determinants and consequences of HRQOL impairments in long-term CRC survivors may help to individualize survivorship care plans. We aimed to i) examine the HRQOL status of CRC long-term survivors, ii) identify cross-sectional sociodemographic and clinical correlates of HRQOL, and iii) investigate the prospective association of HRQOL after CRC diagnosis with all-cause mortality., Methods: We assessed HRQOL within a Northern German cohort of 1294 CRC survivors at a median of 6 years after CRC diagnosis using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Cross-sectional correlates of different HRQOL dimensions were analyzed using multivariable-adjusted logistic regression models with HRQOL as a binary variable. With multivariable-adjusted Cox proportional hazards regression models, hazard ratios (HR) of all-cause mortality were estimated per 10-point-increments of an HRQOL summary score, a global quality of life scale, and HRQOL functioning and symptom domains., Results: The median HRQOL summary score was 87 (interquartile range: 75-94). Sex, age, education, tumor location, metastases, other cancers, type of therapy, and current stoma were identified as correlates of different HRQOL scales. After a median follow-up time of 7 years after HRQOL assessment, 175 participants had died. Nearly all HRQOL domains, except for cognitive functioning and diarrhea, were significantly associated with all-cause mortality. A 10-point-increment in the summary score decreased the risk of death by 24% (HR: 0.76; 95% CI: 0.70-0.82)., Conclusions: HRQOL in CRC survivors appeared to be relatively high in the long term. Various clinical and sociodemographic factors were cross-sectionally associated with HRQOL in long-term CRC survivors. Lower HRQOL was associated with increased all-cause mortality. Individualized healthcare programs for CRC survivors (including psychosocial screening and interventions) are needed to detect decreased HRQOL and to further improve long-term HRQOL and survival.

Background Fibroblast growth factor-23 (FGF-23) has been hypothesized to play a role in the increased risk of cardiovascular disease in patients with CKD. Methods We identified prospective studies reporting associations between FGF-23 concentration and risk of cardiovascular events. Maximally adjusted risk ratios (RRs) were extracted for each outcome and scaled to a comparison of the top versus bottom third of the baseline FGF-23 concentration, and the results aggregated. Results Depending on the assay used, median FGF-23 concentrations were 43-74 RU/ml and 38-47 pg/ml in 17 general population cohorts; 102-392 RU/ml in nine cohorts of patients with CKD not requiring dialysis; and 79-4212 RU/ml and 2526-5555 pg/ml in eight cohorts of patients on dialysis. Overall, comparing participants in the top and bottom FGF-23 concentration thirds, the summary RRs (95% confidence intervals [95% CIs]) were 1.33 (1.12 to 1.58) for myocardial infarction, 1.26 (1.13 to 1.41) for stroke, 1.48 (1.29 to 1.69) for heart failure, 1.42 (1.27 to 1.60) for cardiovascular mortality, and 1.70 (1.52 to 1.91) for all-cause mortality. The summary RR for noncardiovascular mortality, calculated indirectly, was 1.52 (95% CI, 1.28 to 1.79). When studies were ordered by average differences in FGF-23 concentration between the top and bottom thirds, there was no trend in RRs across the studies. Conclusions The similarly-sized associations between increased FGF-23 concentration and cardiovascular (atherosclerotic and nonatherosclerotic) and noncardiovascular outcomes, together with the absence of any exposure-response relationship, suggest that the relationship between FGF-23 and cardiovascular disease risk may be noncausal., (Copyright © 2018 by the American Society of Nephrology.)

In addition to well-established risk factors like older age, female gender, and adiposity, oxidative stress may play a role in the pathophysiology of gallstone disease. Since vitamin E exerts important anti-oxidative functions, we hypothesized that circulating vitamin E levels might be inversely associated with prevalence of gallstone disease. In a cross-sectional study, we measured plasma levels of α- and γ-tocopherol using high performance liquid chromatography in a community-based sample (582 individuals; median age 62 years; 38.5% women). Gallstone disease status was assessed by ultrasound. Multivariable-adjusted logistic regression models were used to estimate the association of circulating α- and γ-tocopherol/cholesterol ratio levels with prevalent gallstone disease. Lower probabilities of having gallstone disease were observed in the top (compared to the bottom) tertile of the plasma α-tocopherol/cholesterol ratio in multivariable-adjusted models (OR (Odds Ratio): 0.31; 95% CI (Confidence Interval): 0.13-0.76). A lower probability of having gallstone disease was also observed for the γ-tocopherol/cholesterol ratio, though the association did not reach statistical significance (OR: 0.77; 95% CI: 0.35-1.69 for 3rd vs 1st tertile). In conclusion, our observations are consistent with the concept that higher vitamin E levels might protect from gallstone disease, a premise that needs to be further addressed in longitudinal studies., Competing Interests: The authors declare no conflict of interest.

Little is known about the distribution and determinants of circulating vitamin E levels in a German population. In this cross-sectional study we assessed the distribution of both α- and γ-tocopherol levels, identified their clinical and biochemical correlates, and assessed their relationships with a priori and a posteriori derived dietary patterns. Plasma α- and γ-tocopherol concentrations were measured using high performance liquid chromatography (HPLC) with fluorescence detection in 641 individuals (mean-age: 61 years; 40.6% women). Correlates of both markers were determined using linear regression with backward selection. Using a validated food-frequency questionnaire (FFQ), an a priori defined vitamin E-rich dietary pattern was constructed, and three a posteriori derived dietary patterns were identified by principal component analysis. Each pattern was related to α- and γ-tocopherol levels using linear regression. Median concentrations of α- and γ-tocopherol were 31.54 μmol/L and 1.35 µmol/L, respectively. 57.6% of participants had α-tocopherol levels >30 µmol/L. Triglycerides, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, and vitamin E supplementation were identified as correlates of vitamin E levels. After excluding supplement users, a dietary pattern rich in meat, bread, fats, potatoes, and sugar/confectionery was inversely related to α-tocopherol levels (β, -0.032, SE = 0.016; p = 0.047). Prospective studies are warranted to evaluate the actual impact of the reported findings in terms of nutrition and health outcomes., Competing Interests: The authors declare no conflict of interest.

The adipokines chemerin and omentin-1 have been suggested to influence cardiovascular function. The study aimed to investigate the longitudinal association between chemerin, omentin-1 concentrations and risk of incident heart failure (HF), respectively. We conducted a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 27548) including a randomly drawn subsample and all incident HF cases during a mean follow-up of 8.2 ± 1.5 years. A total of 212 incident HF cases and 2168 individuals free of HF cases were included in the study. After multivariable adjustment for established cardiovascular risk factors chemerin was strongly associated with risk of HF (HR per doubling chemerin: 4.91; 95%-CI: 2.57-9.39; p < 0.0001). Omentin-1 was not significantly related to HF risk in the overall study population. However, the association between omentin-1 and HF risk was modified by prevalent coronary heart disease (CHD), showing that the shape of the association was linear in participants without prevalent CHD (HR doubling omentin-1: 2.11; 95%-CI: 1.36-3.27; p linear = 0.0009) and U-shaped in participants with pre-existing CHD (p non-linear = 0.006). Our study provides first evidence for a strong positive association between chemerin and risk of HF. The association between the adipokine omentin-1 and risk of HF may differ according to pre-existing CHD.

Background: Lifestyle recommendations for cancer survivors are warranted to improve survival. In this study, we aimed to examine the association of total physical activity, different types of physical activity, hours of sleeping at day and night, and hours spent watching television (TV) with all-cause mortality in long-term colorectal cancer (CRC) survivors., Methods: We assessed physical activity in 1376 CRC survivors (44% women; median age, 69 years) at median 6 years after CRC diagnosis using a validated questionnaire. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) for all-cause mortality according to categories of physical activities, sleep duration, and TV watching., Results: During a median follow-up time of 7 years, 200 participants had died. Higher total physical activity was significantly associated with lower all-cause mortality (HR: 0.53; 95% CI: 0.36-0.80, 4th vs. 1st quartile). Specifically, sports, walking, and gardening showed a significant inverse association with all-cause mortality (HR: 0.34; 95% CI: 0.20-0.59, HR: 0.65; 95% CI: 0.43-1.00, and HR: 0.62; 95% CI: 0.42-0.91, respectively for highest versus lowest category). Individuals with ≥2 h of sleep during the day had a significantly increased risk of all-cause mortality compared to individuals with no sleep at day (HR: 2.22; 95% CI: 1.43-3.44). TV viewing of ≥4 h per day displayed a significant 45% (95% CI: 1.02-2.06) higher risk of dying compared to ≤2 h per day of watching TV., Conclusions: Physical activity was inversely related to all-cause mortality; specific activity types might be primarily responsible for this association. More hours of sleep during the day and a higher amount of TV viewing were each associated with higher all-cause mortality. Based on available evidence, it is reasonable to recommend CRC survivors to engage in regular physical activity.

We aimed to relate circulating α- and γ-tocopherol levels to a broad spectrum of adiposityrelated traits in a cross-sectional Northern German study. Anthropometric measures were obtained, and adipose tissue volumes and liver fat were quantified by magnetic resonance imaging in 641 individuals (mean age 61 years; 40.6% women). Concentrations of α- and γ-tocopherol were measured using high performance liquid chromatography. Multivariable-adjusted linear and logistic regression were used to assess associations of circulating α- and γ-tocopherol/cholesterol ratio levels with visceral (VAT) and subcutaneous adipose tissue (SAT), liver signal intensity (LSI), fatty liver disease (FLD), metabolic syndrome (MetS), and its individual components. The α- tocopherol/cholesterol ratio was positively associated with VAT (β scaled by interquartile range (IQR): 0.036; 95%Confidence Interval (CI): 0.0003; 0.071) and MetS (Odds Ratio (OR): 1.83; 95% CI: 1.21-2.76 for 3rd vs. 1st tertile), and the γ-tocopherol/cholesterol ratio was positively associated with VAT (β scaled by IQR: 0.066; 95% CI: 0.027; 0.104), SAT (β scaled by IQR: 0.048; 95% CI: 0.010; 0.087) and MetS (OR: 1.87; 95% CI: 1.23-2.84 for 3rd vs. 1st tertile). α- and γ-tocopherol levels were positively associated with high triglycerides and low high density lipoprotein cholesterol levels (all Ptrend < 0.05). No association of α- and γ-tocopherol/cholesterol ratio with LSI/FLD was observed. Circulating vitamin E levels displayed strong associations with VAT and MetS. These observations lay the ground for further investigation in longitudinal studies.

Chemerin is a recently discovered adipokine with inflammatory and metabolic actions relevant for chronic disease development. However, evidence from human research on the role of chemerin in chronic disease risk is still lacking. We assessed the reliability of plasma chemerin concentrations measured on two occasions over a 4-month period in 207 apparently healthy participants. In addition, we explored the cross-sectional associations between chemerin and inflammatory biomarkers using Spearman partial correlation and multivariable linear regression analyses. Intra-individual reproducibility of chemerin measurements was assessed by calculating intraclass correlation coefficients (ICCs) and exploration of Bland-Altman plots. Reliability analyses revealed good reproducibility of chemerin measurements (ICC: 0.72 (95%-CI 0.65, 0.78)). Visual inspection of Bland-Altman plots confirmed that the two time point measurements had a high level of agreement. In correlation analyses, chemerin was positively correlated with adiposity measures (body mass index and waist circumference). In addition, independent of adiposity measures, chemerin was correlated with the biomarkers C-reactive protein, fatty acid-binding protein 4 and progranulin (Rho-s ranging from 0.23 to 0.37). In multivariable linear regression analysis, a combination of correlated factors including body mass index, waist circumference, C-reactive protein, progranulin and fatty acid-binding protein-4 explained 28.0% of chemerin concentrations. These findings demonstrate methodological utility of chemerin concentrations in population-based research setting. Human studies are highly warranted in order to provide further insights into the role of chemerin as a biomarker linking immunity and metabolism in relation to chronic disease risk., (© 2017 The authors.)

Objective: Association studies of selenoprotein P (SELENOP) with cardiometabolic traits in humans are relatively scarce and, in part, conflicting. A general population sample from Northern Germany was evaluated for cross-sectional associations of circulating SELENOP concentrations with metabolic syndrome (MetS), total volumes of MRI-determined visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, liver signal intensity, and fatty liver disease (FLD)., Methods: Nine hundred and five participants received comprehensive clinical and molecular phenotyping along with measurement of serum SELENOP; 584 individuals received MRI., Results: Multivariable-adjusted restricted cubic regression splines displayed statistically significant inverse relations of SELENOP levels with MetS, VAT, and SAT (P < 0.0001 for all). Compared with the second quartile of SELENOP distribution, the MetS odds ratios for the first, third, and fourth quartiles were 1.62 (95% confidence interval [CI]: 1.08-2.43), 0.85 (95% CI: 0.57-1.26), and 0.41 (95% CI: 0.27-0.62), respectively. Furthermore, participants in the second, third, and fourth SELENOP quartiles had significantly lower VAT and SAT volumes as compared to those in the first biomarker quartile. A J-shaped relation was observed for SELENOP levels and liver signal intensity/FLD (P = 0.01)., Conclusions: The findings suggest inverse associations of circulating SELENOP concentrations with several metabolic traits, to be further investigated in longitudinal studies., (© 2017 The Obesity Society.)