Evidence is accumulating that immune cells play a prominent role in pancreatic cancer etiology but prospective investigations are missing.
We conducted a nested case-control study within the European ...Prospective Investigation into Cancer and Nutrition (EPIC) study with 502 pairs of incident pancreatic cancer cases and matched controls. Relative counts of circulating immune cells (neutrophils and lymphocyte sublineages: total CD3
, CD8
, CD4
, and FOXP3
regulatory T cells (Tregs) relative to nucleated cells, (white blood cells) were measured by qRT-PCR. ORs with 95% confidence intervals were estimated using logistic regressions, modeling relative counts of immune cells on a continuous scale.
Neither relative counts of immune cell types taken individually, nor mutually adjusted for each other were associated with pancreatic cancer risks. However, in subgroup analyses by strata of lag-time, higher relative counts of Tregs and lower relative counts of CD8
were significantly associated with an increased pancreatic cancer risks in participants diagnosed within the first 5 years of follow-up.
These results might reflect reverse causation, due to higher relative counts of Tregs and lower counts of CD8
cells among individuals with more advanced stages of latent pancreatic cancer, who are closer to the point of developing clinical manifest disease.
We have shown, for the first time, that increased relative counts of regulatory T cells and lower relative counts of CD8
, cytotoxic T cells may be associated with pancreatic cancer risk or relatively late-stage tumor development.
.
Purpose
Studies attempting to link dietary non-enzymatic antioxidant activity (NEAC) and colorectal cancer (CRC) risk have reported mixed results. We examined this association in the Spanish ...Multicase–Control Study considering the likely influence of coffee and other dietary factors.
Methods
1718 CRC cases and 3312 matched-controls provided information about diet through a validated 140-item food frequency questionnaire. Dietary NEAC was estimated for three methods total radical-trapping antioxidant parameters (TRAP), ferric reducing/antioxidant power (FRAP) and TEAC-ABTS using published values of NEAC content in food, with and without coffee’s NEAC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated through unconditional logistic regression models adjusted for lifestyle and dietary factors.
Results
Overall dietary intake of NEAC was significantly lower in cases compared to controls and associated with a significantly reduced CRC risk, in both men (OR
Q5vsQ1
= 0.67, 95% CI 0.47–0.96 for FRAP) and women (OR
Q5vsQ1
= 0.53, 95% CI 0.32–085 for FRAP), in multivariate models with and without the antioxidant contribution from coffee. The effect was similar for all the NEAC methods evaluated and for both colon and rectum. The association between dietary NEAC and CRC risk became non-significant when adjusting for fiber intake. However, intakes of NEAC and fiber were correlated.
Conclusion
This study indicates that intake of an antioxidant-rich plant-based diet, both with and without NEAC from coffee, is associated with decreased CRC risk.
Abstract
Background
The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated the immunogenicity and ...safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy.
Methods
In this phase 3, randomized (1:1), observer-blind, multicenter trial, RT recipients were enrolled and received 2 doses of RZV or placebo 1–2 months (M) apart 4–18M posttransplant. Anti–glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post–dose 1, and 1M and 12M post–dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post–dose 2.
Results
Two hundred sixty-four participants (RZV: 132; placebo: 132) were enrolled between March 2014 and April 2017. gE-specific humoral and cell-mediated immune responses were higher in RZV than placebo recipients across postvaccination time points and persisted above prevaccination baseline 12M post–dose 2. Local AEs were reported more frequently by RZV than placebo recipients. Overall occurrences of renal function changes, rejections, unsolicited AEs, serious AEs, and pIMDs were similar between groups.
Conclusions
RZV was immunogenic in chronically immunosuppressed RT recipients. Immunogenicity persisted through 12M postvaccination. No safety concerns arose.
Clinical Trials Registration
NCT02058589.
The adjuvanted recombinant zoster vaccine was immunogenic in renal transplant recipients receiving daily immunosuppressive treatment. Humoral and cell-mediated immune responses persisted through 1 year postvaccination. Vaccination had no impact on renal function or rejection rate. No safety concerns arose.
IntroductionThe nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and sex differences in ...this regard are yet to be assessed.MethodsStudy including 611 men and 302 women from the Spanish multicentre AtheSpAin cohort to assess CV disease in axSpA. Data on CV disease risk factors were collected both at disease diagnosis and at enrolment, and data on disease activity, functional indices and carotid ultrasonography only at enrolment.ResultsAfter a median disease duration of 9 years, patients of both sexes who at disease diagnosis had elevated acute phase reactants (APRs), more frequently had hypertension and obesity. The same occurred with dyslipidaemia in men and with diabetes mellitus in women. At enrolment, CV risk factors were independently associated with APR and with activity and functional indices, with various sex differences. C reactive protein (CRP) values were inversely associated with HDL-cholesterol in men (β coefficient: −1.2 (95% CI: −0.3 to −0.07) mg/dL, p=0.001), while erythrocyte sedimentation rate values were positively associated with triglycerides in women (β coefficient: 0.6 (95% CI: 0.04 to 1) mg/dL, p=0.035). Furthermore, only women showed an independent relationship between insulin resistance parameters and APR or disease activity. Both men and women with high–very high CV risk according to the Systematic Assessment of Coronary Risk Evaluation 2 and CRP levels higher than 3 mg/L at diagnosis of the disease presented carotid plaques significantly more frequently than those with normal CRP levels at disease diagnosis.ConclusionInflammation is associated with atherosclerosis and CV disease in axSpA. A gender-driven effect is observed in this relationship.
Abstract only
121
Background: Low-grade inflammation, characterized by high cytokine activity, plays a crucial role in tumorigenesis. Further, cytokines and other inflammatory biomarkers are closely ...implicated in tumor growth, angiogenesis, and metastasis. This metaanalysis of randomized controlled trials estimates the effects of exercise training in the control of the serum levels of cytokines and other inflammatory markers in breast cancer survivors. Methods: PRISMA statement and the Cochrane Handbook were followed. We searched MEDLINE, CENTRAL, EMBASE, Scopus and DARE database to retrieve randomized controlled trials published between 1980- March 2014 providing effect estimates of exercise interventions in the serum levels of cytokines, such as interleukin (IL) -2, IL-6, IL-8, tumoral necrosis factor alpha (TNF-α) and C-reactive protein (CRP) in breast cancer survivors. An Inverse of variance (IV) fixed-effects model was conducted in absence of heterogeneity (I
2
<50%); otherwise a random-effects model was selected. Mean Differences (MD) were calculated to estimate differences between groups (p<0.05 with 95% Confidence interval). Heterogeneity was measured with the Chi
2
test (p<0.10) and I
2
statistics. Results: A total of 15 studies were included (n=1,447; mean age= 51.6 years old). Exercise interventions resulted in positive effects for CRP (MD= 0.37, 95%CI, 0.04 to 0.71; p= 0.03; I
2
=15%), IL-2 (MD= -6.04, 85%CI, -11.41 to -0.67; p=0.03; I
2
=0%), IL-10 (-22.90, 95%CI, -41.27 to -4.53; p=0.001, I
2
=0%) and waist circumference as indicator of body composition (MD= -1.12, 95%CI, -2.06 to -0.18; p=0.02; I
2
=45%). Non-significant differences were observed for IL-6 and TNF-α. There was no evidence of publication bias. Conclusions: These findings suggest that exercise training improves the systemic pro-inflammatory profile in breast cancer survivors and consequently the immunological responses and the carcinogenic processes related to tumoral environment. The effects observed for IL-10 provide a novel focus of evidence for the role of exercise as an effective anti-inflammatory intervention in cancer survivors.
Abstract only
120
Background: Epidemiological data suggest that Insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) are associated with breast cancer risk, apoptosis and other ...carcinogenic mechanisms. This metaanalysis evaluates the effects of exercise interventions in controlling serum concentrations of Insulin-like growth factors (IGF1-IGF2) and IGFBP-3 in women with breast cancer. Methods: We incorporated the PRISMA statement. Databases of MEDLINE, Ovid, EMBASE and Cochrane Central Registers were searched to identify randomized controlled trials until March 2014, reporting effect estimates for IGF-1, IGF-2, IGFBP-3 and other secondary outcomes such as insulin, glucose and waist circumference as a body composition measure. An Inverse of variance (IV) with Mantel–Haenszel method was selected for analysis, and a random-effects models were used to assess the pooled estimates in addition to sensitivity analyses, whilst heterogeneity was evaluated using the Chi
2
test (P<0.10) and I
2
statistics (I
2
>50%).STATA 12.0 was used for metaanalysis procedures. Results: Six studies were included in the pooled analysis involving 321 patients. Effect estimates showed that exercise training improved IGF-1 (MD= -12.9, 95CI% -16.73 to -9.14, P<0.001), IGF-2 (MD= -43.4, 95CI% -58.5 to -28.3, P<0.001), IGFBP-3 (MD= -0.61, 95CI% -0.69 to -0.53, P<0.001) and waist circumference (MD= -1.133, 95CI% -2.20 to -0.05, P=0.03) in women with breast cancer. Conversely, non-significant differences were observed for Insulin (MD= 0.046, 95CI% -0.24 to 0.34, P=0.7), Glucose (MD=0.22, 95CI% -0.32 to 0.78, P=0.419) and Insulin Resistance (MD= 0.64, 95CI% -0.006 to 1.29, P= 0.06). There was no evidence of publication bias. Conclusions: Exercise is an effective and safe intervention in improving the serum concentrations of insulin like growth factors (IGF1-IGF2) and IGFBP-3 in women with breast cancer, strengthening the physiological effects of exercise in regulating cellular proliferation and apoptosis in breast cancer. Further evidences are encouraged.
•Identifying pro-atherogenic factors in rheumatic diseases can help prevent cardiovascular events.•Axial spondyloarthritis features associated with atherosclerosis remain unclear.•Inflammation and ...disease severity are associated with atherosclerosis in axial spondyloarthritis.
To identify disease-related factors associated with subclinical atherosclerosis and cardiovascular (CV) events in a large series of patients with axial spondyloarthritis (axSpA) and to identify possible differences in the effect of the potential pro-atherogenic factors between ankylosing spondylitis (AS) non-radiographic axSpA (nr-axSpA).
This is a cross-sectional observational study of the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Subclinical atherosclerosis determined by carotid ultrasound included assessment of carotid intima-media thickness (cIMT) and plaque detection.
639 AS and 167 nr-axSpA patients were recruited. CV risk factors (CRF) and several disease-related factors showed a statistically significant association with subclinical atherosclerosis in the crude analysis. After adjustment for age, sex, and smoking (model 1), associations remained statistically significant for spinal mobility, inflammatory bowel disease, use of prednisone, and Disease-modifying antirheumatic drugs (DMARD) when assessing carotid plaques and for acute phase reactants (APR) at diagnosis, use of prednisone, DMARD, and TNF-inhibitors when measuring cIMT. In model 2, which also included classic CRF as confounding factors to identify axSpA features with a potential independent pro-atherogenic effect, the functional status was the only variable significantly associated with plaques and the use of prednisone and APR at diagnosis with cIMT. No association differences were found between both subtypes of patients. Besides, APR at diagnosis were also associated with subsequent development of CV events that had occurred in 33 patients.
Apart from CRF, atherosclerotic disease in AxSpA is associated with disease-related factors such as inflammatory response and disease severity, with no differences between AS and nr-axSpA.
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To compare the atherosclerosis disease burden between ankylosing spondylitis (AS) and non-radiographic (nr) axial spondyloarthritis (axSpA) and establish a model that allows to identify ...high-cardiovascular (CV) risk in axial spondyloarthritis patients.
Cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort aimed to study atherosclerosis in axSpA. Carotid ultrasound (US) was performed to determine the carotid intima-media wall thickness (cIMT) and detect the presence of carotid plaques. The European cardiovascular disease risk assessment model, the Systematic COronary Risk Evaluation (SCORE), was also applied.
A set of 639 patients with AS and 167 patients with nr-axSpA without history of CV events were recruited. AS patients were older showing more CV risk factors and higher values of C reactive protein and erythrocyte sedimentation rate (ESR) than those with nr-axSpA. However, no difference in the prevalence of carotid plaques or in the cIMT was found between both groups in the adjusted analysis. The percentage of patients reclassified from the low and moderate CV risk categories to the very high-risk category due to the presence of carotid plaques was comparable in AS and nr-axSpA (10.7% versus 10.1% and 40.5% versus 45.5%, respectively). A model containing age, BASFI and ESR applied to moderate risk axSpA patients identified 41% of these patients as having very high-risk patients with high specificity (88%).
The atherosclerosis burden is similar in nr-axSpA and AS. As occurred for AS, more than 40% of axSpA patients included in the category of moderate CV risk according to the SCORE are reclassified into very high risk after carotid US, and a clinically relevant proportion of them can be detected by applying a model containing age, BASFI and ESR.
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Smoking is an established risk factor for pancreatic cancer, previously investigated by the means of questionnaires. Using cotinine as a biomarker for tobacco exposure allows more accurate ...quantitative analyses to be performed. This study on pancreatic cancer, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC cohort), included 146 cases and 146 matched controls. Using liquid chromatography‐mass spectrometry, plasma cotinine levels were analyzed on average 8.0 years before cancer onset (5–95% range: 2.8–12.0 years). The relation between plasma cotinine levels and pancreatic cancer was analyzed with conditional logistic regression for different levels of cotinine in a population of never and current smokers. This was also done for the self‐reported number of smoked cigarettes per day at baseline. Every increase of 350 nmol/L of plasma cotinine was found to significantly elevate risk of pancreatic cancer odds ratio (OR): 1.33, 95% confidence interval (CI): 1.11–1.60. People with a cotinine level over 1187.8 nmol/L, a level comparable to smoking 17 cigarettes per day, have an elevated risk of pancreatic cancer, compared to people with cotinine levels below 55 nmol/L (OR: 3.66, 95% CI: 1.44–9.26). The results for self‐reported smoking at baseline also show an increased risk of pancreatic cancer from cigarette smoking based on questionnaire information. People who smoke more than 30 cigarettes per day showed the highest risk compared to never smokers (OR: 4.15, 95% CI: 1.02–16.42). This study is the first to show that plasma cotinine levels are strongly related to pancreatic cancer.
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