Galectin-3 in chronic kidney disease.

BACKGROUND AND AIMS: High serum galectin-3 has been associated with adverse outcomes among dialysis patients, although its prognostic role remains unclear among individuals with earlier-stage chronic kidney disease. The present systematic review aims to evaluate the association of serum galectin-3 with survival, cardiovascular disease and kidney disease progression among non-dialysis chronic kidney disease patients. METHODS: PubMed, Scopus, Web of Science, CENTRAL and Google Scholar were systematically searched till November 10, 2023. All observational studies assessing the prognostic role of serum galectin-3 in patients with non-dialysis chronic kidney disease were included. RESULTS: Overall, 12 studies (10 cohort, 2 cross-sectional) were included, comprising 9,349 patients. The endpoint of survival was assessed in 5 studies, indicating a significant association between increasing serum galectin-3 levels and higher all-cause mortality risk (Hazard ratio per unit: 1.22, 95 % confidence intervals-CI: 1.05-1.41, ≥6 ng/mL: 2.66, 95 % CI: 1.68-4.23). Current evidence coming from 4 studies was inconclusive regarding the potential link of galectin-3 and kidney function decline, yielding conflicting results. No significant associations between serum galectin-3 and heart failure, cardiovascular events or death were consistently reported. CONCLUSIONS: This systematic review supports the prognostic role of galectin-3 in chronic kidney disease, as its increased serum values may be associated with higher all-cause mortality risk. No clear role could be supported for serum galectin-3 regarding the prediction of cardiovascular disease or kidney disease progression.

The Complexity of Tobacco Smoke-Induced Mutagenesis in Head and Neck Cancer.

Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). Here, we further explore how tobacco exposure contributes to cancer development by mutational signature analysis of 265 whole-genome sequenced HNC from eight countries. Six tobacco-associated mutational signatures were detected, including some not previously reported. Differences in HNC incidence between countries corresponded with differences in mutation burdens of tobacco-associated signatures, consistent with the dominant role of tobacco in HNC causation. Differences were found in the burden of tobacco-associated signatures between anatomical subsites, suggesting that tissue-specific factors modulate mutagenesis. We identified an association between tobacco smoking and three additional alcohol-related signatures indicating synergism between the two exposures. Tobacco smoking was associated with differences in the mutational spectra and repertoire of driver mutations in cancer genes, and in patterns of copy number change. Together, the results demonstrate the multiple pathways by which tobacco smoke can influence the evolution of cancer cell clones.

Association of kidney function with physical performance: the Maastricht study.

BACKGROUND: Kidney failure has been associated with decreased physical capacity, although evidence regarding the physical performance of individuals with earlier stages of chronic kidney disease (CKD) remains limited. METHODS: Cross-sectional data were derived from the prospective, population-based Maastricht Study. Multivariate linear regression models were fitted to assess the association of estimated glomerular filtration rate (eGFR) and albuminuria categories with physical performance test outcomes. RESULTS: Overall, 7396 participants were included. Compared to eGFR 60-90 ml/min/1.73 m2, values < 60 ml/min/1.73 m2 were associated with significantly shorter 6-min walk distance (ß: - 13.04 m, 95% confidence intervals-CI - 19.95; - 6.13), worse timed chair rise stand test time (ß: 0.91 s, 95% CI 0.36; 1.47), lower maximal grip (ß: - 0.83 kg, 95% CI - 1.50; - 0.15) and elbow flexion (ß: - 3.64 Nm, 95% CI - 7.11; - 0.16) strength. Additionally, eGFR > 90 ml/min/1.73 m2 was linked to significantly shorter 6-min walk distance (ß: - 6.13 m, 95% CI - 9.44; - 2.82). Urinary albumin excretion > 30 mg/24 h was associated with shorter 6-min walk distance (ß: - 12.48 m, 95% CI - 18.28; - 6.68), worse timed chair rise stand test time (ß: 0.51 s, 95% CI 0.11; 1.06), lower maximal grip (ß: - 1.34 kg, 95% CI - 1.91; - 0.76) and elbow flexion strength (ß: - 3.31 Nm, 95% CI - 5.80; - 0.82). CONCLUSIONS: Reduced eGFR and higher albuminuria levels were associated with worse physical performance, especially shorter 6-min walk distance and lower muscle strength. The relationship between eGFR and physical function was non-linear, with also high eGFR values being associated with worse performance, especially in the six-minute walk test.

Epstein-Barr Virus DNA Is Associated With Conjunctival Squamous Cell Carcinomas: A Case-Control Study From Zimbabwe.

Incidence of conjunctival squamous cell carcinoma (cSCC) in Zimbabwe is >30-fold higher than the global average. cSCC risk is notably higher among people with human immunodeficiency virus, implicating impaired immune response and a yet unknown infectious etiology. Formalin-fixed, paraffin-embedded blocks from Zimbabwe, comprising conjunctival precancer (n = 78), invasive cSCC cases (n = 148) and nonmalignant eye lesions (n = 119), were tested for multiple DNA viruses using Luminex bead-based technology. Epstein-Barr virus (EBV) type 1 positivity was strongly associated with cSCC diagnosis (adjusted odds ratio [aOR], 5.6 [95% confidence interval {CI}, 3.0-10.4) and marginally associated with precancer (aOR, 2.1 [95% CI, 1.0-4.5]). On analyzing EBV transcriptional activity with any of LMP1, EBNA1, and BZLF1, RNA transcripts were detected in 5 of 112 controls, 3 of 67 precancers, and 10 of 139 cases and none were associated with conjunctival case status. Our EBV DNA data suggest that EBV may play a role in cSCC. However, the low detection rate of EBV RNA supports further investigation to infer causality.

Molecular epidemiology of HIV among people who inject drugs after the HIV-outbreak in Athens, Greece: Evidence for a 'slow burn' outbreak.

BACKGROUND: New diagnoses of HIV-1 infection among people who inject drugs (PWID) in Athens, Greece, saw a significant increase in 2011 and a subsequent decline after 2013. Despite this, ongoing HIV-1 transmission persisted from 2014 to 2020 within this population. Our objective was to estimate the time of infection for PWID in Athens following the HIV-1 outbreak, explore the patterns of HIV-1 dispersal over time, and determine the duration from infection to diagnosis. METHODS: Time from HIV-1 infection to diagnosis was estimated for 844 individuals infected within 4 PWID-specific clusters and for 8 PWID infected with sub-subtype A6 diagnosed during 2010-2019. Phylogeny reconstruction was performed using the maximum-likelihood method. HIV-1 infection dates were based on molecular clock calculations. RESULTS: In total 86 of 92 (93.5%) sequences from PWID diagnosed during 2016-2019 were either related to the previously identified PWID-specific clusters (n = 81) or belonged to a new A6 cluster (n = 5). The median time between infection and diagnosis was 0.42 years during the outbreak period and 0.70 years during 2016-2019 (p < 0.001). The proportion of clustered sequences from PWID was very low at 5.3% during the pre-outbreak period (1998-2009), saw an increase to 41.7% one year before the outbreak in 2010, and consistently remained high during the whole period after 2011, spanning the post-outbreak period (2016-2019) with a range from 92.9% to 100%. CONCLUSIONS: The substantial proportion of clustered infections (93.5%) during 2016-2019 implies a persistent 'slow burn' HIV outbreak among PWID in Athens, suggesting that the outbreak was not successfully eliminated. The consistently high proportion of clustered sequences since the onset of the outbreak suggests the persistence of ongoing HIV-1 transmission attributed to injection practices. Our findings underscore the importance of targeted interventions among PWID, considering the ongoing transmission rate and prolonged time from infection to diagnosis.

Association of soluble suppression of tumorigenicity 2 with mortality and adverse outcomes in chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Early risk stratification is necessary to prevent chronic kidney disease progression and complications. This systematic review aims to evaluate the association of soluble suppression of tumorigenicity 2 (sST2), a member of the interleukin-1 receptor family, with all-cause mortality, cardiovascular disease and renal function deterioration among chronic kidney disease patients. METHODS: PubMed, Scopus, Web of Science, CENTRAL and Google Scholar were systematically searched from inception to December 20, 2023. Cohort studies examining the prognostic role of sST2 levels in pre-dialysis and dialysis patients were included. In case of 3 or more studies per outcome, conventional and dose-response meta-analyses were conducted. RESULTS: Overall, 21 studies were included comprising 15,100 patients. In pre-dialysis patients, the qualitative synthesis of studies suggested that high sST2 is associated with significantly increased all-cause mortality, while evidence regarding cardiovascular events or kidney disease progression was conflicting. In the dialysis population, high sST2 was linked to an elevated risk of all-cause (Hazard ratio-HR: 3.00, 95% confidence intervals-CI: 1.95-4.61) and cardiovascular (HR: 2.38, 95% CI: 1.69-3.34) mortality. Dose-response meta-analysis suggested a log-linear association of sST2 with both all-cause (χ2: 34.65, p value < 0.001) and cardiovascular (χ2: 29.14, p value < 0.001) mortality, whereas findings regarding cardiovascular events were limited with mixed results. CONCLUSIONS: High sST2 values are associated with an increased risk of all-cause mortality in pre-dialysis and dialysis patients, as well as with an elevated risk of cardiovascular mortality in the dialysis population. Further studies are needed to elucidate its potential association with cardiovascular events and kidney disease progression.

Dietary intake of vitamin C and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Previous studies suggest that dietary vitamin C is inversely associated with gastric cancer (GC), but most of them did not consider intake of fruit and vegetables. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project, a consortium of epidemiological studies on GC. METHODS: Fourteen case-control studies were included in the analysis (5362 cases, 11,497 controls). We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the association between dietary intake of vitamin C and GC, adjusted for relevant confounders and for intake of fruit and vegetables. The dose-response relationship was evaluated using mixed-effects logistic models with second-order fractional polynomials. RESULTS: Individuals in the highest quartile of dietary vitamin C intake had reduced odds of GC compared with those in the lowest quartile (OR: 0.64; 95% CI: 0.58, 0.72). Additional adjustment for fruit and vegetables intake led to an OR of 0.85 (95% CI: 0.73, 0.98). A significant inverse association was observed for noncardia GC, as well as for both intestinal and diffuse types of the disease. The results of the dose-response analysis showed decreasing ORs of GC up to 150-200 mg/day of vitamin C (OR: 0.54; 95% CI: 0.41, 0.71), whereas ORs for higher intakes were close to 1.0. CONCLUSIONS: The findings of our pooled study suggest that vitamin C is inversely associated with GC, with a potentially beneficial effect also for intakes above the currently recommended daily intake (90 mg for men and 75 mg for women).

Association of serum galectin-3 levels with mortality and cardiovascular disease outcomes in hemodialysis patients: a systematic review and dose-response meta-analysis.

BACKGROUND: Galectin-3 has been proposed as a candidate marker for cardiovascular risk stratification, although its role in kidney failure is unclear. The aim of this systematic review was to assess the association of serum galectin-3 levels with overall survival and cardiovascular outcomes among hemodialysis patients. METHODS: Medline, Scopus, Web of Science and CENTRAL were systematically searched from inception till Aug 20, 2023. Observational studies evaluating the association of serum galectin-3 with mortality, cardiovascular disease and arterial stiffness in hemodialysis patients were included. The exposure-response relationship between galectin-3 and mortality was explored by dose-response meta-analysis using restricted cubic splines in a one-stage approach. RESULTS: Overall, 13 studies were included (9 cohort and 4 cross-sectional), comprising 6025 hemodialysis individuals. Increasing galectin-3 values were associated with greater all-cause mortality risk (χ2: 18.71, p-value < 0.001) and an insignificant trend toward higher cardiovascular mortality risk (χ2: 5.06, p-value: 0.079). Compared to a reference galectin-3 value of 10 ng/ml, all-cause mortality risk was significantly higher with levels of 20 ng/ml (Hazard ratio-HR: 2.62, 95% confidence intervals-CI: 1.66-4.15), 30 ng/ml (HR: 3.78, 95% CI: 2.05-6.97) and 40 ng/ml (HR: 4.01, 95% CI: 2.14-7.52). Qualitative synthesis of evidence indicated that serum galectin-3 may be linked to abdominal aortic calcification severity and progression, as well as to left ventricular systolic and diastolic dysfunction. CONCLUSIONS: This study suggests that high serum galectin-3 levels are associated with greater all-cause mortality risk among patients on maintenance hemodialysis. Preliminary cross-sectional evidence indicates that serum galectin-3 may be associated with arterial stiffness and left ventricular dysfunction.

The Mutographs biorepository: A unique genomic resource to study cancer around the world.

Large-scale biorepositories and databases are essential to generate equitable, effective, and sustainable advances in cancer prevention, early detection, cancer therapy, cancer care, and surveillance. The Mutographs project has created a large genomic dataset and biorepository of over 7,800 cancer cases from 30 countries across five continents with extensive demographic, lifestyle, environmental, and clinical information. Whole-genome sequencing is being finalized for over 4,000 cases, with the primary goal of understanding the causes of cancer at eight anatomic sites. Genomic, exposure, and clinical data will be publicly available through the International Cancer Genome Consortium Accelerating Research in Genomic Oncology platform. The Mutographs sample and metadata biorepository constitutes a legacy resource for new projects and collaborations aiming to increase our current research efforts in cancer genomic epidemiology globally.

Aspirin for the Primary Prevention of Cardiovascular Diseases in Patients with Chronic Kidney Disease: An Updated Meta-analysis.

AIM: Chronic kidney disease is associated with increased risk of cardiovascular diseases (CVD). This meta-analysis aims to evaluate the efficacy and safety of aspirin administered for primary prevention of CVD in patients with chronic kidney disease. METHODS: PubMed, Scopus, Web of Science, CENTRAL and Clinicaltrials.gov were systematically searched from inception to 22 June 2023. Randomized controlled trials (RCTs) and cohort studies evaluating aspirin as primary prevention of CVD in chronic kidney disease were included. Meta-analysis was conducted using random-effects models. RESULTS: Overall, 11 studies (6 RCTs and 5 cohort studies) with 24,352 patients were included. The meta-analysis of RCTs indicated that aspirin was associated with lower risk of major adverse cardiovascular events [hazard ratio (HR): 0.79; 95% confidence intervals (CI): 0.64-0.97] and higher risk of major bleeding [risk ratio (RR): 1.35; 95% CI 1.15-1.58]. Incorporating observational evidence led to statistically non-significant findings in terms of risk of both cardiovascular events (pooled HR: 0.97; 95% CI 0.75-1.25; low certainty) and major bleeding (pooled RR: 1.21; 95% CI 0.99-1.48; moderate certainty). No statistically significant differences between aspirin and placebo were observed in the outcomes of mortality, coronary heart disease, stroke and renal events. CONCLUSIONS: RCT evidence points to a possible benefit in cardiovascular event reduction from aspirin administration, at the cost of increased major bleeding risk. This finding was not confirmed when the existing observational evidence was incorporated. Further research should determine the most appropriate subpopulation of chronic kidney disease patients that would benefit the most from prophylactic aspirin therapy. REGISTRATION:  The study protocol has been prospectively registered and is publicly available from: https://doi.org/10.17504/protocols.io.261ged63jv47/v1 .

Diagnostic accuracy of HPV16 early antigen serology for HPV-driven oropharyngeal cancer is independent of age and sex.

A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV-driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk-factor analysis based on serology was conducted, comparing HPV-driven to non-HPV-driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1-88.3) and specificity of 91.2% (95% CI 88.6-93.4) for HPV-driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack-years (72.1%). The risk-factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack-years, TNM-T and TNM-N stage. HPV serology is a robust biomarker for HPV-driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels.

Reproductive factors, hormonal interventions, and gastric cancer risk in the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Gastric cancer incidence is higher in men, and a protective hormone-related effect in women is postulated. We aimed to investigate and quantify the relationship in the Stomach cancer Pooling (StoP) Project consortium. METHODS: A total of 2,084 cases and 7,102 controls from 11 studies in seven countries were included. Summary odds ratios (ORs) and 95% confidence intervals (CIs) assessing associations of key reproductive factors and menopausal hormone therapy (MHT) with gastric cancer were estimated by pooling study-specific ORs using random-effects meta-analysis. RESULTS: A duration of fertility of ≥ 40 years (vs. < 20), was associated with a 25% lower risk of gastric cancer (OR = 0.75; 95% CI: 0.58-0.96). Compared with never use, ever, 5-9 years and ≥ 10 years use of MHT in postmenopausal women, showed ORs of 0.73 (95% CI: 0.58-0.92), 0.53 (95% CI: 0.34-0.84) and 0.71 (95% CI: 0.50-1.00), respectively. The associations were generally similar for anatomical and histologic subtypes. CONCLUSION: Our results support the hypothesis that reproductive factors and MHT use may lower the risk of gastric cancer in women, regardless of anatomical or histologic subtypes. Given the variation in hormones over the lifespan, studies should address their effects in premenopausal and postmenopausal women. Furthermore, mechanistic studies may inform potential biological processes.

Association of physical activity with endothelial dysfunction among adults with and without chronic kidney disease: The Maastricht Study.

BACKGROUND AND AIMS: Physical activity (PA) constitutes an established protective factor while sedentary behavior (SB) an emerging independent risk factor for cardiovascular diseases. This study evaluated the association of PA and SB with endothelial dysfunction (ED) depending on kidney function status. METHODS: Cross-sectional data from the prospective, population-based Maastricht Study were used. PA and SB were measured using the ActivPAL3 accelerometer 24h/day for eight consecutive days. ED was evaluated by plasma levels of soluble vascular cell adhesion protein-1, intercellular adhesion molecule-1, E-selectin and von Willebrand factor, which were combined into an ED score with higher values depicting higher ED. RESULTS: Overall, 2,668 participants, 323 with chronic kidney disease, were included. In normal kidney function individuals, the ED score presented a significant negative association with total, lower-intensity and moderate-to-vigorous PA duration and a positive association with total sedentary time, sedentary breaks and sedentary bout duration. In participants with chronic kidney disease, a significant negative association of ED score with total [ß: -4.42, 95% confidence intervals (95% CI): -7.98; -0.87] and lower-intensity (ß: -7.08, 95% CI: -13.41; -0.74) PA duration, as well as a positive association of ED score with sedentary bout duration (ß: 43.72, 95% CI: 9.85; 77.59) were noted. The strength of associations did not significantly differ across kidney function subgroups (p > 0.05). CONCLUSIONS: This analysis showed that PA duration is inversely associated with ED both among patients with normal kidney function and chronic kidney disease. In chronic kidney disease, longer sedentary bouts were associated with greater endothelial dysfunction.

The interaction of human immunodeficiency virus-1 and human endogenous retroviruses in patients (primary cell cultures) and cell line models.

IMPORTANCE: In this work, we demonstrated that human immunodeficiency virus (HIV) infection leads to the modification of the human endogenous retrovirus (HERV) expression. Differential expression of multiple HERVs was found in peripheral blood mononuclear cells derived from HIV-infected patients compared to healthy donors and HIV-infected T cell cultures compared to non-infected. The effect of HIV presence on HERV expression appears to be more restricted in cells of monocytic origin, as only deregulation of HERV-W and HERV-K (HML-6) was found in these cell cultures after their infection with HIV. Multiple factors contribute to this aberrant HERV expression, and its levels appear to be modified in a time-dependent manner. Further studies and the development of optimized in vitro protocols are warranted to elucidate the interactions between HIV and HERVs in detail.

Attitudes and Practices Related to COVID-19 Vaccination with the Second Booster Dose among Members of Athens Medical Association: Results from a Cross-Sectional Study.

BACKGROUND: There are limited data on the attitudes and acceptance of the second booster (fourth dose) of the COVID-19 vaccination among physicians. METHODS: A cross-sectional, questionnaire-based, online study was conducted among members of the Athens Medical Association (A.M.A.) who were invited to participate anonymously over the period from January to March 2023. RESULTS: From the 1224 members who participated in the survey, 53.9% did not receive the fourth dose of the COVID-19 vaccine. The main reasons for no vaccination were the lack of obligation to receive the fourth dose, the history of three doses of the COVID-19 vaccine and the lack of sufficient information about the effectiveness of the fourth dose. Over half of the three-dose-vaccinated participants were willing to receive the fourth dose in the near future. Interestingly, the vaccination coverage among participants who had been informed about the fourth dose through scientific sources was low. CONCLUSIONS: The low vaccination coverage with the fourth dose reported in this study can lead to broad and serious consequences, such as increase in COVID-19 infections, reduction of available healthcare staff and increased caseloads of COVID-19 in hospitals. Furthermore, hesitant physicians will adversely influence the vaccination uptake among the general population due to their key role in informing and recommending the vaccine. The healthcare system administration should acknowledge and address physician's concerns through effective communication and better support.

Yoghurt Intake and Gastric Cancer: A Pooled Analysis of 16 Studies of the StoP Consortium.

BACKGROUND: Yoghurt can modify gastrointestinal disease risk, possibly acting on gut microbiota. Our study aimed at exploring the under-investigated association between yoghurt and gastric cancer (GC). METHODS: We pooled data from 16 studies from the Stomach Cancer Pooling (StoP) Project. Total yoghurt intake was derived from food frequency questionnaires. We calculated study-specific odds ratios (ORs) of GC and the corresponding 95% confidence intervals (CIs) for increasing categories of yoghurt consumption using univariate and multivariable unconditional logistic regression models. A two-stage analysis, with a meta-analysis of the pooled adjusted data, was conducted. RESULTS: The analysis included 6278 GC cases and 14,181 controls, including 1179 cardia and 3463 non-cardia, 1191 diffuse and 1717 intestinal cases. The overall meta-analysis revealed no association between increasing portions of yoghurt intake (continuous) and GC (OR = 0.98, 95% CI = 0.94-1.02). When restricting to cohort studies, a borderline inverse relationship was found (OR = 0.93, 95% CI = 0.88-0.99). The adjusted and unadjusted OR were 0.92 (95% CI = 0.85-0.99) and 0.78 (95% CI = 0.73-0.84) for any vs. no yoghurt consumption and GC risk. The OR for 1 category of increase in yoghurt intake was 0.96 (95% CI = 0.91-1.02) for cardia, 1.03 (95% CI = 1.00-1.07) for non-cardia, 1.12 (95% CI = 1.07-1.19) for diffuse and 1.02 (95% CI = 0.97-1.06) for intestinal GC. No effect was seen within hospital-based and population-based studies, nor in men or women. CONCLUSIONS: We found no association between yoghurt and GC in the main adjusted models, despite sensitivity analyses suggesting a protective effect. Additional studies should further address this association.

Mushroom consumption and risk of gastric cancer: a pooled analysis within the stomach cancer pooling project and a combined meta-analysis with other observational studies.

Edible mushrooms have high concentrations of vitamins and minerals. They are considered 'functional foods' for their disease-prevention properties. Mushroom consumption may reduce the risk of gastric cancer, the fifth most common cancer worldwide. We investigated the association between mushroom consumption and gastric cancer risk in a pooled analysis within the Stomach Cancer Pooling (StoP) Project and in a meta-analysis that also included previously published studies. A total of 3900 gastric cancer cases and 7792 controls from 11 studies were included in the StoP analysis. Mushroom consumption was measured using food frequency questionnaires. Higher mushroom consumption was associated with a lower risk of gastric cancer [relative risk (RR) for the highest vs. lowest consumption categories, 0.82; 95% confidence interval (CI), 0.71-0.95]. The corresponding RRs were 0.59 (95% CI, 0.26-1.33) in a meta-analysis of four previously published studies and 0.77 for all studies combined (95% CI, 0.63-0.95; n = 15 studies). In geographic subgroup analysis, the pooled risk in Western Pacific countries was (RR, 0.59; 95% CI, 0.40-0.87; n = 6). The stronger effect in Asian countries may reflect high level of antioxidants in mushroom species consumed in Asia.

Prevalence and predictors of arthralgia after initiation of vedolizumab in patients with inflammatory bowel disease: a retrospective cohort study.

OBJECTIVES: Vedolizumab is a mAb used for the treatment of moderate to severe ulcerative colitis and Crohn's disease. There is evidence that administration of vedolizumab has been associated with either new onset or reactivation of extra-intestinal manifestations, among which arthralgia is the most prominent. We aimed to study the incidence, characteristics and predictors for the occurrence of arthralgias in patients with inflammatory bowel disease (IBD) who receive vedolizumab. METHODS: A retrospective cohort study was implemented in patients with IBD. The occurrence of new-onset and recurrent arthralgias were recorded. Multivariate Cox proportional-hazards models were used to identify factors associated with the endpoints of interest. RESULTS: A total of 115 vedolizumab-treated IBD patients (male = 50.4%; ulcerative colitis = 70.4%; median follow-up = 12.7 months) participated. New-onset arthralgia occurred in 20.9%, and recurrent in 46.7% (45 patients at risk). Among patients with ulcerative colitis, multivariate Cox's proportional-hazards models showed, that new onset arthralgia was significantly associated with extensive colitis (hazard ratio = 2.91; 95% confidence interval, 1.04-8.12). Of 15 patients with concomitant treatment of azathioprine, no one manifested new-onset arthralgia (X2P = 0.03; Fisher's exact test P = 0.038). No predictors were identified for recurrent arthralgia. CONCLUSION: Arthralgias is a common manifestation of vedolizumab treatment. Patients with extensive ulcerative colitis demonstrate a higher risk for new-onset arthralgia, whereas, concomitant treatment with azathioprine appears to be protective. These associations may be mediated by re-directed lymphocyte trafficking and may support concomitant immunomodulator administration in specific patient subpopulations who commence treatment with vedolizumab.