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Item does not contain fulltext, BACKGROUND: Folate-mediated 1-carbon metabolism requires several nutrients, including vitamin B6. Circulating biomarker concentrations indicating high vitamin B6 status are associated with a reduced risk of colorectal cancer (CRC). However, little is known about the effect of B6 status in relation to clinical outcomes in CRC patients. OBJECTIVES: We investigated survival outcomes in relation to vitamin B6 status in prospectively followed CRC patients. METHODS: A total of 2031 patients with stage I-III CRC participated in 6 prospective patient cohorts in the international FOCUS (folate-dependent 1-carbon metabolism in colorectal cancer recurrence and survival) Consortium. Preoperative blood samples were used to measure vitamin B6 status by the direct marker pyridoxal 5'-phosphate (PLP), as well as the functional marker HK-ratio (HKr)[3'-hydroxykynurenine: (kynurenic acid + xanthurenic acid + 3'-hydroxy anthranilic acid + anthranilic acid)]. Using Cox proportional hazards regression, we examined associations of vitamin B6 status with overall survival (OS), disease-free survival (DFS), and risk of recurrence, adjusted for patient age, sex, circulating creatinine concentrations, tumor site, stage, and cohort. RESULTS: After a median follow-up of 3.2 y for OS, higher preoperative vitamin B6 status as assessed by PLP and the functional marker HKr was associated with 16-32% higher all-cause and disease-free survival, although there was no significant association with disease recurrence (doubling in PLP concentration: HROS, 0.68; 95% CI: 0.59, 0.79; HRDFS, 0.84; 95% CI: 0.75, 0.94; HRRecurrence, 0.96; 95% CI: 0.84, 1.09; HKr: HROS, 2.04; 95% CI: 1.67, 2.49; HRDFS, 1.56; 95% CI: 1.31, 1.85; HRRecurrence, 1.21; 95% CI: 0.96,1. 52). The association of PLP with improved OS was consistent across colorectal tumor site (right-sided colon: HROS, 0.75; 95% CI: 0.59, 0.96; left-sided colon: HROS, 0.71; 95% CI: 0.55, 0.92; rectosigmoid junction and rectum: HROS, 0.61; 95% CI: 0.47, 0.

Item does not contain fulltext, BACKGROUND: We investigated whether preoperative and postoperative levels of inflammation markers, which have mechanistically been linked to colorectal cancer progression, were associated with recurrence and all-cause mortality in patients with colorectal cancer. METHODS: Data of two prospective cohort studies were used. For the current analysis, patients with stage I to III colorectal cancer were considered. Data on inflammation [IL6, IL8, IL10, TNFα, high-sensitivity C-reactive protein (hsCRP), and a combined inflammatory z-score] were available for 747 patients before surgery and for 614 patients after surgery. The associations between inflammation marker levels and colorectal cancer recurrence and all-cause mortality were examined using multivariable Cox proportional hazard regression models, considering patient characteristics and clinical and lifestyle factors. RESULTS: Higher preoperative and postoperative hsCRP levels were associated with a higher risk of recurrence [HR(per doubling) (95% CI), 1.15 (1.02-1.30) and 1.34 (1.16-1.55)] and all-cause mortality [HR(per doubling) (95% CI) 1.13 (1.01-1.28) and 1.15 (0.98-1.35)]. A doubling in IL8 levels (preoperative levels HR = 1.23; 95% CI, 1.00-1.53 and postoperative levels HR = 1.61; 95% CI, 1.23-2.12) and a higher combined inflammatory z-score (preoperative HR(per doubling) = 1.39; 95% CI, 1.03-1.89 and postoperative HR(per doubling) = 1.56; 95% CI, 1.06-2.28) were associated with a higher risk of all-cause mortality, but not recurrence. No associations between IL6, IL10, and TNFα and recurrence or all-cause mortality were observed. CONCLUSIONS: Preoperative and postoperative levels of specific inflammation markers were associated with recurrence and/or all-cause mortality. IMPACT: The complex role of inflammation in cancer recurrence merits further elucidation by investigating local inflammation at the tumor site.

Contains fulltext : 238985.pdf (Publisher’s version ) (Open Access), PURPOSE: Persistent fatigue among colorectal cancer (CRC) patients might be associated with unfavorable body composition, but data are sparse and inconsistent. We studied how skeletal muscle index (SMI), skeletal muscle radiodensity (SMR), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) at diagnosis are associated with fatigue up to 24 months post-diagnosis in stage I-III CRC patients. METHODS: SMI, SMR, VAT, and SAT were assessed among 646 CRC patients using pre-treatment computed tomography images. Fatigue at diagnosis, at 6, and 24 months post-diagnosis was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The association of SMI, SMR, VAT, and SAT with fatigue (yes/no) was assessed using confounder-adjusted restricted cubic spline analyses. RESULTS: Prevalence of fatigue at diagnosis was 18%, at 6 months 25%, and at 24 months 12%. At diagnosis, a significant (p = 0.01) non-linear association of higher levels of SAT with higher prevalence of fatigue was observed. Lower levels of SMR were linearly associated with higher prevalence of fatigue at 6 months post-diagnosis (overall association p = 0.02). None of the body composition parameters were significantly associated with fatigue at 24 months. CONCLUSION: Having more SAT was associated with more fatigue at diagnosis, while low levels of SMR were associated with more fatigue at 6 months post-diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Our results suggest that it may be interesting to investigate whether interventions that aim to increase SMR around the time of diagnosis may help to lower fatigue. However, more knowledge is needed to understand the mechanisms behind the association of SMR with fatigue.

Contains fulltext : 238999.pdf (Publisher’s version ) (Open Access), PURPOSE: Emerging evidence suggests that diet is linked to survival in colorectal cancer patients, although underlying mechanisms are not fully understood. The aim of this study was to evaluate whether dietary exposures are associated with metabolite concentrations in colorectal cancer patients. METHODS: Concentrations of 134 metabolites of the Biocrates Absolute(IDQ) p180 kit were quantified in plasma samples collected at diagnosis from 195 stage I-IV colorectal cancer patients. Food frequency questionnaires were used to calculate adherence to the World Cancer Research Fund (WCRF) dietary recommendations and the Dutch Healthy Diet (DHD15) index as well as to construct dietary patterns using Principal Component Analysis. Multivariable linear regression models were used to determine associations between dietary exposures and metabolite concentrations. All models were adjusted for age, sex, body mass index, smoking status, analytical batch, cancer stage, and multiple testing using false discovery rate. RESULTS: Participants had a mean (SD) age of 66 (9) years, were mostly men (60%), and mostly diagnosed with stage II and III cancer. For the dietary pattern analyses, Western, Carnivore, and Prudent patterns were identified. Better adherence to the WCRF dietary recommendations was associated with lower concentrations of ten phosphatidylcholines. Higher intake of the Carnivore pattern was associated with higher concentrations of two phosphatidylcholines. The DHD15-index, Western pattern, or Prudent pattern were not associated with metabolite concentrations. CONCLUSION: In the current study, the WCRF dietary score and the Carnivore pattern are associated with phosphatidylcholines. Future research should elucidate the potential relevance of phosphatidylcholine metabolism in the colorectal cancer continuum. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT03191110.

Purpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. Materials & methods: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. Results: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. Conclusions: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients.

Background: B vitamins have been associated with the risk and progression of colorectal cancer (CRC), given their central roles in nucleotide synthesis and methylation, yet their association with quality of life in established CRC is unclear.Objectives: To investigate whether quality of life 6 months postdiagnosis is associated with: 1) circulating concentrations of B vitamins and related biomarkers 6 months postdiagnosis; 2) changes in these concentrations between diagnosis and 6 months postdiagnosis; 3) B-vitamin supplement use 6 months postdiagnosis; and 4) changes in B-vitamin supplement use between diagnosis and 6 months postdiagnosis.Methods: We included 1676 newly diagnosed stage I-III CRC patients from 3 prospective European cohorts. Circulating concentrations of 9 biomarkers related to the B vitamins folate, riboflavin, vitamin B6, and cobalamin were measured at diagnosis and 6 months postdiagnosis. Information on dietary supplement use was collected at both time points. Health-related quality of life (global quality of life, functioning scales, and fatigue) was assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 6 months postdiagnosis. Confounder-adjusted linear regression analyses were performed, adjusted for multiple testing.Results: Higher pyridoxal 5'-phosphate (PLP) was cross-sectionally associated with better physical, role, and social functioning, as well as reduced fatigue, 6 months postdiagnosis. Associations were observed for a doubling in the hydroxykynurenine ratio [3-hydroxykynurenine: (kynurenic acid + xanthurenic acid + 3-hydroxyanthranilic acid + anthranilic acid); an inverse marker of vitamin B6] and both reduced global quality of life (beta = -3.62; 95% CI: -5.88, -1.36) and worse physical functioning (beta = -5.01; 95% CI: -7.09, -2.94). Dose-response relations were observed for PLP and quality of life. No associations were observed for changes in biomarker concentrations between diagn

Contains fulltext : 236794.pdf (Publisher’s version ) (Open Access)

Purpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. Materials & methods: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. Results: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. Conclusions: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients.

Contains fulltext : 229884.pdf (publisher's version ) (Open Access), Fatigue is very common among colorectal cancer (CRC) patients. We examined the association between adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) lifestyle recommendations and fatigue among stage I-III CRC patients, and whether inflammation mediated this association. Data from two prospective cohort studies were used. Adherence to the WCRF/AICR recommendations was expressed as a score ranging from 0-7, and assessed shortly after diagnosis. Six months post-diagnosis, fatigue was assessed with the European Organization for Research and Treatment of Cancer quality of life questionnaire C30 (EORTC QLQ-C30), and in a subpopulation, the plasma levels of inflammation markers (IL6, IL8, TNFα, and hsCRP) were assessed. Multiple linear regression analyses were performed to investigate the association between adherence to the WCRF/AICR recommendations and fatigue. To test mediation by inflammation, the PROCESS analytic tool developed by Hayes was used. A higher WCRF/AICR adherence score was associated with less fatigue six months after diagnosis (n = 1417, β -2.22, 95%CI -3.65; -0.78). In the population of analysis for the mediation analyses (n = 551), the total association between lifestyle and fatigue was (β -2.17, 95% CI -4.60; 0.25). A statistically significant indirect association via inflammation was observed (β -0.97, 95% CI -1.92; -0.21), explaining 45% of the total association between lifestyle and fatigue (-0.97/-2.17 × 100). Thus, inflammation is probably one of the underlying mechanisms linking lifestyle to fatigue.

Contains fulltext : 218303.pdf (Publisher’s version ) (Open Access), Objective: Chronic Chemotherapy-Induced Peripheral Neuropathy (CIPN) is highly prevalent among colorectal cancer (CRC) patients. Ergothioneine (ET) - a dietary antioxidant -protected against CIPN in experimental models, but human studies are lacking. We explored whether whole blood ET levels were associated with chronic peripheral neuropathy among CRC patients who had completed chemotherapy.Methods: At diagnosis, median ET-concentration in whole blood of 159 CRC patients was 10.2 mug/ml (7.2-15.8). Patients completed questionnaires on peripheral neuropathy 6 months after completion of chemotherapy. We calculated prevalence ratios (PR) to assess associations of ET-concentrations and prevalence of peripheral neuropathy and used linear regression to assess associations with severity of peripheral neuropathy.Results: Prevalence of total and sensory peripheral neuropathy were both 81%. Higher ET-concentrations tended to be associated with lower prevalence of total and sensory peripheral neuropathy, but not statistically significant (highest versus lowest tertile of ET: PR = 0.93(0.78, 1.11) for total neuropathy, and PR = 0.84(0.70, 1.02) for sensory neuropathy). ET-concentrations were not associated with severity of neuropathy.Conclusion: Statistically significant associations were not observed, possibly because of limited sample size. Although data may putatively suggest higher levels of ET to be associated with a lower prevalence of neuropathy, analyses should be repeated in larger populations with larger variability in ET-concentrations.

Contains fulltext : 220955.pdf (Publisher’s version ) (Open Access), Colorectal cancer is the second most common cause of cancer-related death globally, with marked differences in prognosis by disease stage at diagnosis. We studied circulating metabolites in relation to disease stage to improve the understanding of metabolic pathways related to colorectal cancer progression. We investigated plasma concentrations of 130 metabolites among 744 Stages I-IV colorectal cancer patients from ongoing cohort studies. Plasma samples, collected at diagnosis, were analyzed with liquid chromatography-mass spectrometry using the Biocrates AbsoluteIDQ™ p180 kit. We assessed associations between metabolite concentrations and stage using multinomial and multivariable logistic regression models. Analyses were adjusted for potential confounders as well as multiple testing using false discovery rate (FDR) correction. Patients presented with 23, 28, 39 and 10% of Stages I-IV disease, respectively. Concentrations of sphingomyelin C26:0 were lower in Stage III patients compared to Stage I patients (p(FDR) < 0.05). Concentrations of sphingomyelin C18:0 and phosphatidylcholine (diacyl) C32:0 were statistically significantly higher, while citrulline, histidine, phosphatidylcholine (diacyl) C34:4, phosphatidylcholine (acyl-alkyl) C40:1 and lysophosphatidylcholines (acyl) C16:0 and C17:0 concentrations were lower in Stage IV compared to Stage I patients (p(FDR) < 0.05). Our results suggest that metabolic pathways involving among others citrulline and histidine, implicated previously in colorectal cancer development, may also be linked to colorectal cancer progression.

Contains fulltext : 229382.pdf (publisher's version ) (Open Access), BACKGROUND: Folates, including folic acid, may play a dual role in colorectal cancer development. Folate is suggested to be protective in early carcinogenesis but could accelerate growth of premalignant lesions or micrometastases. Whether circulating concentrations of folate and folic acid, measured around time of diagnosis, are associated with recurrence and survival in colorectal cancer patients is largely unknown. METHODS: Circulating concentrations of folate, folic acid, and folate catabolites p-aminobenzoylglutamate and p-acetamidobenzoylglutamate were measured by liquid chromatography-tandem mass spectrometry at diagnosis in 2024 stage I-III colorectal cancer patients from European and US patient cohort studies. Multivariable-adjusted Cox proportional hazard models were used to assess associations between folate, folic acid, and folate catabolites concentrations with recurrence, overall survival, and disease-free survival. RESULTS: No statistically significant associations were observed between folate, p-aminobenzoylglutamate, and p-acetamidobenzoylglutamate concentrations and recurrence, overall survival, and disease-free survival, with hazard ratios ranging from 0.92 to 1.16. The detection of folic acid in the circulation (yes or no) was not associated with any outcome. However, among patients with detectable folic acid concentrations (n = 296), a higher risk of recurrence was observed for each twofold increase in folic acid (hazard ratio = 1.31, 95% confidence interval = 1.02 to 1.58). No statistically significant associations were found between folic acid concentrations and overall and disease-free survival. CONCLUSIONS: Circulating folate and folate catabolite concentrations at colorectal cancer diagnosis were not associated with recurrence and survival. However, caution is warranted for high blood concentrations of folic acid because they may increase the risk of colorectal cancer recurrence.

Contains fulltext : 215400.pdf (publisher's version ) (Open Access), PURPOSE: A healthy lifestyle after colorectal cancer (CRC) diagnosis may improve prognosis. Data related to lifestyle change in CRC survivors are inconsistent and potential interrelated changes are unknown. METHODS: We assessed dietary intake, physical activity, body mass index (BMI), waist circumference, and smoking among 1072 patients diagnosed with stages I-III CRC at diagnosis, 6 months and 2 years post-diagnosis. An overall lifestyle score was constructed based on the 2018 World Cancer Research Fund/American Institute of Cancer Research recommendations (range 0-7). We used linear mixed models to analyze changes in lifestyle over time. RESULTS: Participants had a mean (+/- SD) age of 65 +/- 9 years and 43% had stage III disease. In the 2 years following CRC diagnosis, largest changes were noted for sugary drinks (- 45 g/day) and red and processed meat intake (- 62 g/week). BMI (+ 0.4 kg/m(2)), waist circumference (+ 2 cm), and dietary fiber intake (- 1 g/day) changed slightly. CRC survivors did not statistically significant change their mean intake of fruits and vegetables, alcohol, or ultra-processed foods nor did they change their physical activity or smoking behavior. Half of participants made simultaneous changes that resulted in improved concordance with one component as well as deteriorated concordance with another component of the lifestyle score. Overall lifestyle score changed from a mean 3.4 +/- 0.9 at diagnosis to 3.5 +/- 0.9 2 years post-diagnosis. CONCLUSIONS: CRC survivors hardly improve their overall lifestyle after diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Given the importance of a healthy lifestyle, strategies to effectively support behavior changes in CRC survivors need to be identified.

Contains fulltext : 190939.pdf (publisher's version ) (Open Access), Chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe side-effect in colorectal cancer (CRC) patients. This study assessed the association between habitual dietary intake of magnesium or calcium and prevalence and severity of chronic CIPN in CRC patients receiving adjuvant chemotherapy. For this prospective cohort study, 196 CRC patients were considered. Magnesium and calcium intake was determined using a food frequency questionnaire at diagnosis, during and after chemotherapy. Chronic CIPN was assessed 12 months after diagnosis using the quality of life questionnaire CIPN20. Prevalence ratios were calculated to assess the association between magnesium or calcium intake and the prevalence of CIPN. Multivariable linear regression analysis was used to assess the association between magnesium or calcium intake and severity of CIPN. CIPN was reported by 160 (82%) patients. Magnesium intake during chemotherapy was statistically significantly associated with lower prevalence of CIPN (prevalence ratio (PR) 0.53, 95% confidence interval (CI) 0.32, 0.92). Furthermore, higher dietary intake of magnesium during (beta -1.08, 95% CI -1.95, -0.22) and after chemotherapy (beta -0.93, 95% CI -1.81, -0.06) was associated with less severe CIPN. No associations were found for calcium intake and the prevalence and severity of CIPN. To conclude, we observed an association between higher dietary magnesium intake and lower prevalence and severity of CIPN in CRC patients.