The association of pre-operative biomarkers of endothelial dysfunction with the risk of post-operative neurocognitive disorders: results from the BioCog study.

INTRODUCTION: Endothelial dysfunction (ED) promotes the development of atherosclerosis, and studies suggest an association with age-related neurocognitive disorders. It is currently unclear whether ED is also associated with the risk of perioperative neurocognitive disorders. METHOD: We included 788 participants aged ≥ 65 years of the BioCog study. Patients were scheduled to undergo elective surgery with expected duration > 60 min. Blood was collected before surgery for measurement of 5 biomarkers of ED: asymmetric and symmetric dimethylarginine (ADMA; SDMA), intercellular and vascular adhesion molecule (ICAM-1, VCAM-1), and von Willebrand factor (vWF). Patients were monitored for the occurrence of postoperative delirium (POD) daily until the 7th postoperative day. 537 (68.1%) patients returned for a 3-month follow-up. Post-operative cognitive dysfunction (POCD) was defined from the change in results on a battery of 6 neuropsychological tests between baseline and 3 months, compared to the change in results of a control group during the 3-month interval. The associations of each of the 5 ED biomarkers with POD and POCD respectively were determined using multiple logistic regression analyses with adjustment for age, sex, surgery type, pre-morbid IQ, body mass index, hypertension, diabetes, HbA1C, triglyceride, total and HDL cholesterol. RESULTS: 19.8% of 788 patients developed POD; 10.1% of 537 patients had POCD at 3 months. Concentrations of ED biomarkers were not significantly associated with a POD. A higher VCAM-1 concentration was associated with a reduced POCD risk (adjusted odds ratio 0.55; 95% CI: 0.35-0.86). No further statistically significant results were found. CONCLUSION: Pre-operative concentrations of ED biomarkers were not associated with POD risk. We unexpectedly found higher VCAM-1 to be associated with a reduced POCD risk. Further studies are needed to evaluate these findings.

Diet and physical activity as risk-reducing factors for hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a multifactorial inflammatory skin disease that is considered to be an immune-mediated inflammatory disease (IMID). Up till now, the impact of lifestyle on (the development of) HS has not been thoroughly investigated. OBJECTIVES: To investigate the effect of dietary intake and physical activity (PA) on (the development of) HS. MATERIALS AND METHODS: A nested case-control study was performed within the longitudinal Lifelines Cohort Study, that took place in the Northern Netherlands, and identified 1004 adult eligible HS patients and 5000 age-matched controls. Dietary data were collected using a validated food frequency questionnaire, subsequently translated to the Lifelines Diet Score (LLDS), alternate Mediterranean Diet Score (aMED) and Dutch Dietary Guidelines score (DDG), with higher scores reflecting healthier dietary habits. PA was measured by the Short Questionnaire to Assess Health-enhancing PA score. Logistic regression analyses were performed between dietary/PA scores, and the prevalence/development and severity of HS. RESULTS: Compared to controls, HS patients scored lower on the LLDS [OR = 0.98; 95% CI 0.96-0.99], aMED [0.93; 0.89-0.97] and DDG [0.93; 0.88-0.97] with multivariable regression analysis. Overall, this indicates less adherence to dietary recommendations and consumption of a low-quality diet in the HS population. Lower adherence to the LLDS and DDG was also significantly associated with a higher likelihood to HS development in univariable regression analysis [0.96; 0.94-0.99 and 0.91; 0.84-0.99, respectively], and a trend of decreased adherence to the aMED [0.93; 0.85-1.02] was noted. Besides, PA levels were found significantly lower in HS patients (p ≤ 0.001). CONCLUSIONS AND RELEVANCE: Poor diet quality and lower quantities of PA were associated with HS in the general population. Identifying dietary and PA habits of HS patients can contribute to the development of prevention strategies for HS specifically, and for IMIDs in general.

Vitamin D Status and Risk of All-Cause and Cause-Specific Mortality in Osteoarthritis Patients: Results from NHANES III and NHANES 2001-2018.

Objectives: The role of Vitamin D (VD) in calcium balance and bone health makes VD a vital factor in osteoarthritis (OA). Studies that have evaluated the effect of VD on OA patients have mainly been performed on a short-term basis. In this analysis, we aimed to evaluate whether VD was associated with mortality, a long-term outcome, in OA patients. Methods: Participants with self-reported OA from NHANES III and NHANES 2001−2018 were included. Associations of 25(OH)D concentrations with mortality risk were assessed continuously using restricted cubic splines and by categories (i.e., <25.0, 25.0−49.9, 50.0−74.9, and ≥75.0 nmol/L) using the Cox regression model. Sensitivity and stratified analyses were performed to evaluate the robustness of the results. Results: A total of 4570 patients were included, of which 1388 died by 31 December 2019. An L-shaped association was observed between 25(OH)D concentrations and all-cause mortality, whereas an inverse association was found for cardiovascular disease (CVD) mortality. The adjusted hazard ratios (95% confidence intervals) across four categories were 1.00 (reference), 0.49 (0.31, 0.75), 0.45 (0.29, 0.68), and 0.43 (0.27, 0.69) for all-cause mortality and 1.00 (reference), 0.28 (0.14, 0.59), 0.25 (0.12, 0.51), and 0.24 (0.11, 0.49) for CVD-specific mortality; no significant associations were found for cancer-specific mortality. Similar results were observed when stratified and sensitivity analyses were performed. Conclusions: Compared with patients with insufficient or deficient serum 25(OH)D, those with sufficient 25(OH)D concentrations had a lower risk of all-cause and CVD mortality, supporting a beneficial role of VD on a long-term basis.

Ferritin Trajectories over Repeated Whole Blood Donations: Results from the FIND+ Study.

BACKGROUND: Depending on post-donation erythropoiesis, available iron stores, and iron absorption rates, optimal donation intervals may differ between donors. This project aims to define subpopulations of donors with different ferritin trajectories over repeated donations. METHODS: Ferritin levels of 300 new whole blood donors were measured from stored (lookback) samples from each donation over two years in an observational cohort study. Latent classes of ferritin level trajectories were investigated separately using growth mixture models for male and female donors. General linear mixed models assessed associations of ferritin levels with subsequent iron deficiency and/or low hemoglobin. RESULTS: Two groups of donors were identified using group-based trajectory modeling in both genders. Ferritin levels showed rather linear reductions among 42.9% of male donors and 87.7% of female donors. For the remaining groups of donors, steeper declines in ferritin levels were observed. Ferritin levels at baseline and the end of follow-up varied greatly between groups. CONCLUSIONS: Repeated ferritin measurements show depleting iron stores in all-new whole blood donors, the level at which mainly depends on baseline ferritin levels. Tailored, less intensive donation strategies might help to prevent low iron in donors, and could be supported with ferritin monitoring and/or iron supplementation.

A computational model for prediction of ferritin and haemoglobin levels in blood donors.

Blood donors are at risk of iron deficiency anaemia. While this risk is decreased through ferritin-based deferral, ideally ferritin monitoring should also aid in optimising donation frequencies. We extended an existing model of haemoglobin (Hb) synthesis with iron homeostasis and validated the model on a cohort of 300 new donors whose ferritin levels were measured from stored blood samples collected over a 2-year period. We then used the donor's gender, body weight, height, and baseline Hb and ferritin levels to predict subsequent Hb and ferritin levels. The prediction error was within measurement variability in 88% of Hb level predictions and 64% of ferritin level predictions. A sensitivity analysis of the model revealed that baseline ferritin level was the most important in predicting future ferritin levels. Finally, we used the model to calculate the annual donation frequency at which donors would keep their ferritin level >15 ng/ml when measured after donating for 2 years. The mean annual donation frequency would then be 1.9 for women and 4.1 for men. The computational model, requiring baseline values only, can predict future Hb and ferritin levels remarkably well. This enables determination of optimal donation frequencies for individual donors at the start of their donation career.

Diet quality indices and gastrointestinal cancer risk: results from the Lifelines study.

OBJECTIVE: To investigate the long-term association between four dietary quality indices and the risk of gastrointestinal (GI) cancer. METHODS: Baseline details of the dietary intake of participants, assessed by a single food frequency questionnaire from the prospective Lifelines population-based cohort were translated to diet quality scores using several dietary and dietary-lifestyle indices. Incident cases of GI cancer were then assessed by linkage to the Dutch nationwide histo-cytopathology registry. The association between GI cancer risk and diet quality (defined as higher quintiles on dietary indices compared to the first quintile) was assessed by multivariable Cox proportional hazard models. RESULTS: We included 72,695 participants aged 51.20 ± 8.71 years with a median follow-up to cancer diagnosis of 8 years (interquartile range 2 years). During follow-up, 434 colorectal cancers and 139 upper GI cancers were diagnosed. There was a significant reduction in colorectal cancer risk for high categories in the American Cancer Society (ACS) Index (hazard ratio 0.62; 95% CI 0.46-0.84). However, high dietary index scores were not associated with strong beneficial effects on upper GI cancer risk. CONCLUSION: High quintiles on the ACS Index were associated with a significantly reduced risk of colorectal cancer. This index may be of use in a colorectal cancer prevention program.

Staple Food Fortification with Folic Acid and Iron and Gastrointestinal Cancers: Critical Appraisal of Long-Term National Fortification.

The co-occurrence of wheat flour fortification with folic acid and iron and gastrointestinal cancer incidences were critically assessed in the East Azerbaijan province in Northwest of Iran. In an ecological design, overall gastrointestinal cancer rate ratios and their 95% confidence intervals (95% CI) were calculated as primary outcome before (2004-2006) and after (2007-2015) the introduction of fortification. No consistent changes were observed in esophageal and gastric cancer, but the rate ratios of colorectal cancer increased significantly after fortification in the 35-54 years age group (women: 2.07, 95% CI: 1.79-2.49; men: 1.59, 95% CI: 1.33-1.89) and the 55-74 years age group (women 1.50, 95% CI: 1.27-1.76; men: 2.51, 95% CI: 2.13-2.95). The increased incidence of colorectal cancer was contemporary with long-term fortification; further investigation is required to establish the associations.

Systematic review and meta-analysis of diet quality and colorectal cancer risk: is the evidence of sufficient quality to develop recommendations?

The quality of existing evidence about the impact of diet quality on colorectal cancer (CRC) risk has only rarely been assessed. In the current review, we searched PubMed, EMBASE, Web of Science, Cochrane, and the resulting references (up to January 2020) for studies that evaluated the role of high diet quality by extreme dietary index categorization and the risk of CRC. Two researchers independently performed the study selection, data extraction, and quality assessment. We then applied a random-effects meta-analysis to estimate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) for CRC at the extremes of each dietary index, and we assessed the quality of the pooled results using the Grading of Recommendations Assessment, Development and Evaluation approach. A high diet quality was significantly associated with reduced CRC risk when patients had a low Diet Inflammatory Index score (OR, 0.66; 95%CI, 0.56-0.78), a high Mediterranean Diet Score (OR, 0.84; 95%CI, 0.78-0.90), high Dietary Approaches to Stop Hypertension adherence (OR, 0.83; 95%CI, 0.78-0.89), and a high Healthy Eating Index score (OR, 0.72; 95%CI, 0.64-0.80). The pooled results for all dietary indices were rated as being of low quality due to concerns over inconsistency or imprecision. We conclude that, despite a high diet quality appearing to have a preventive role in CRC, the evidence is currently of insufficient quality to develop dietary recommendations.

Assessment of Diet Quality and Adherence to Dietary Guidelines in Gastrointestinal Cancer Survivors: A Cross-Sectional Study.

Diet quality among short- and long-term gastrointestinal (GI) cancer survivors with different tumor sites was investigated compared to a reference population cohort. Diet quality of GI cancer survivors (n = 307) was compared to an age- and sex-matched reference population with no history of cancer (n = 3070). All were selected from Lifelines, a population-based cohort. GI cancers were defined as having a history of cancer of the bowel, esophagus, or stomach. Diet quality was assessed by a self-administrated food frequency questionnaire in terms of: (i) Lifelines Diet (LLD) scores, where higher scores indicate higher diet quality; (ii) the adherence to dietary guidelines, quantified by the percentage of meeting dietary recommendations, as given by Dutch dietary guidelines; and (iii) the mean daily intake of food components. All analyses were adjusted for lifestyle factors. Diet scores in GI cancer survivors were not different from the reference population (OR = 0.97, 95% CI: 0.73-1.23). Stratification for time since diagnosis and tumor site gave similar results. The intake of vegetables, unsweetened dairies, and nuts and legumes was almost 50% lower than the recommended amount, and the mean intake of unhealthy food components was at least one serving/day among GI cancer survivors, as well as in the reference population. In the long run, GI cancer survivors do not differ from the reference population in their diet quality. In conclusion, both groups can improve their diet quality.

Diet Quality and Upper Gastrointestinal Cancers Risk: A Meta-Analysis and Critical Assessment of Evidence Quality.

We aimed to assess the effect of a high-quality diet on the risk of upper gastrointestinal cancer and to evaluate the overall quality of our findings by searching PubMed, EMBASE, Web of Science, Cochrane, and the references of related articles to February 2020. Two reviewers independently retrieved the data and performed the quality assessments. We defined the highest-quality diet as that with the lowest Diet Inflammatory Index category and the highest Mediterranean Diet Score category. Overall odds ratios and 95% confidence intervals were estimated for upper gastrointestinal cancer risk comparing the highest- versus lowest-diet quality. A random-effects meta-analysis was then applied with Review Manager, and the quality of the overall findings was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation approach. The highest-quality diets were significantly associated with reduced risk of upper gastrointestinal cancers, achieving odds ratios of 0.59 (95% confidence interval: 0.48-0.72) for the Diet Inflammatory Index, pooling the findings from nine studies, and 0.72 (95% confidence interval: 0.61-0.88) for the Mediterranean Diet Score, pooling the findings from 11 studies. We observed a minimum of 69% heterogeneity in the pooled results. The pooled results were graded as low quality of evidence. Although it may be possible to offer evidence-based general dietary advice for the prevention of upper gastrointestinal cancers, the evidence is currently of insufficient quality to develop dietary recommendations.

Folic Acid Supplement Intake and Risk of Colorectal Cancer in Women; A Case Control Study.

Background: An ongoing controversy exists on the role of folic acid supplementation in colorectal cancer risk among epidemiological studies. Objective: To assess the association between maternal folic acid supplementation and colorectal cancer risk. Methods: A paired matched case control study of 405 subjects was performed, including women residing in 135 villages of East Azerbaijan, Iran. Per area, subjects were followed regularly in local healthcare centers, where health- and social-related information have been collected prospectively in face to face interviews by well-trained health workers. We extracted folic acid supplement intake, baseline characteristics, and confounders from healthcare records. The data for study participants were linked to national cancer registry repositories, from which we retrieved the data of 135 women diagnosed with colorectal cancer between 2005 to 2015. Two hundred seventy controls were individually matched with cases in terms of residing village, age, and gender. We applied multivariate conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Findings: There was no significant association between folic acid supplementation and colorectal cancer risk in those with history of folic acid intake compared to those with no history of intake (OR 0.95; 95% CI 0.59 to 1.53), in those with less than five years of folic acid (0.79; 0.45 to 1.39) or in those with ≥5 years intake (1.09; 0.52 to 2.26). This risk did not change after adjustment for covariates or further stratification. Conclusions: Maternal folic acid supplementation did not affect colorectal cancer risk in a population where supplemental folic acid is prescribed with regular intervals for women of child-bearing age.

Immunomodulatory and anti-inflammatory effects of probiotics in multiple sclerosis: a systematic review.

Multiple sclerosis (MS) is an inflammatory and autoimmune neurological disorder which leads to demyelination. Although the etiology of MS is yet to be known, it appears that regulating the immune system and suppressing inflammatory pathways may possibly have a favorable effect on the healing of this disease. Evidence suggests that probiotics consumption via gut microbiome alteration devises beneficial effects in improving immune and inflammatory responses in MS. All articles were systematically searched (in the main databases) for this paper. Two investigators independently scrutinized full texts of the potentially eligible articles. The quality of the study was evaluated using standardized tools. The methodological quality of seven studies included in this review ranged from fair to good. The findings illustrated that there were statistically significant improvements in the static and dynamic balance in patients and animals with MS. In the paper in hand, the effects of probiotics administration on immune and inflammatory markers in MS disease are evaluated. In addition, the limitations and knowledge gaps were reported while proposing a possible mechanism of probiotics therapy in modulating immune and inflammatory responses. This systematic review indicated that the probiotics could improve immune and inflammatory parameters, the cytokines and cells in MS disease. Probiotics may have efficient effects in management and treatment of MS. More studies are required to clarify the effect of supplementation with probiotics and their mechanisms in MS disease.

Folic acid intake and folate status and colorectal cancer risk: A systematic review and meta-analysis.

BACKGROUND & AIMS: To evaluate the controversies among the studies assessing the association between folic acid intake or folate status and colorectal cancer risk. METHODS: PubMed, Cochrane library and references of related articles were searched from January 2000 to September 2016. Studies on folic acid intake or folate status and colorectal cancer or adenoma risk were included. Full text review was conducted for potentially eligible studies. Quality assessment was performed. Random-effects meta-analysis was used to estimate risk ratio and 95% Confidence Intervals. Analysis was conducted by Comprehensive Meta-Analysis software. RESULTS: Folic acid supplement intake showed no significant effect on colorectal cancer risk in meta-analysis of randomized controlled trials, RR: 1.07 (95% CI: 0.86-1.43). The effect on risk was not significant in cohort studies either; RR = 0.96 (95% CI: 0.76-1.21). However, there was significant reduced colorectal cancer risk in total folate intake in cohort studies; 0.71 (95% CI: 0.59-0.86). Odds Ratio was also significantly reduced in case control studies; 0.77 (95% CI: 0.62-0.95). Nevertheless once folate status was measured as Red Blood Cell folate content, no significant effect on colorectal cancer risk was observed; 1.05 (95% CI: 0.85-1.30). CONCLUSION: The differences in bioavailability and metabolism of synthetic folic acid and natural dietary folate as well as variation in the baseline characteristics of subjects and various methods of folate status assessment might be the main reasons for these controversies. Findings of present study highlight the importance of individualized folic acid supplement intake given the fact that the beneficiary effects of long term folic acid supplementation is not confirmed.

Association of Mood Disorders with Serum Zinc Concentrations in Adolescent Female Students.

Among various factors influencing mood disorders, the impact of micronutrient deficiencies has attracted a great attention. Zinc deficiency is considered to play a crucial role in the onset and progression of mood disorders in different stages of life. The main objective of this study was to assess the correlation between serum zinc levels and mood disorders in high school female students. This cross-sectional study was conducted on a random sample of 100 representative high school female students. The participants completed 24-h food recall questionnaires to assess the daily zinc intakes. Serum zinc status was assessed using flame atomic absorption spectrometry, and zinc deficiency was defined accordingly. Mood disorders were estimated by calculating the sum of two test scores including Beck's depression inventory (BDI) and hospital anxiety depression scale (HADS) tests. General linear model (GLM) and Pearson's regression test were applied to show the correlation of serum zinc levels and mood disorder scores and the correlation between zinc serum levels and BDI scores, respectively. Dietary zinc intake was higher in subjects with normal zinc concentrations than that of zinc-deficient group (p = 0.001). Serum zinc levels were inversely correlated with BDI and HADS scores (p < 0.05). Each 10 µg/dL increment in serum zinc levels led to 0.3 and 0.01 decrease in depression and anxiety scores, respectively (p < 0.05). Serum zinc levels were inversely correlated with mood disorders including depression and anxiety in adolescent female students. Increasing serum levels of zinc in female students could improve their mood disorders.

High Risk Infants Follow-Up: A Case Study in Iran.

Background. A follow-up program for high risk infants was initiated in Alzahra Maternity Hospital in Tabriz city, Iran, in 2013. The aim of this paper is to give a brief report of the program. Material and Methods. Two groups of high risk neonates were studied. The first group comprising 509 infants received services in Alzahra Maternity Hospital implemented by the follow-up program. This included a full package for family to look after high risk infant and periodic clinical evaluation at two and four weeks after birth and then two, three, four, five, and six months later again. The second group including 131 infants in Taleqani Maternity Hospital received routine services after birth with no specific follow-up care. Results. Some anthropometric indices showed a significant improvement in the intervention hospital compared to control group. These included the following: head circumference at first and second months; weight in the first, fourth, fifth, and sixth months; and height in sixth month only. Clinical evaluation of infants showed an improvement for some of the medical conditions. Conclusion. Follow-up care program for a minimum of six months after discharge from maternity hospitals may help to avoid adverse and life threatening consequences in high risk infants.