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.

Efficacy and safety of statin therapy in kidney transplant recipients: a systematic review and meta-analysis.

BACKGROUND: Dyslipidemia represents an important risk factor for cardiovascular diseases, although its optimal management after kidney transplantation remains unclear. The present meta-analysis aimed to shed light on the efficacy and safety of statins among kidney transplant recipients, evaluating their potential effects on the risk of cardiovascular events, mortality and graft survival. METHODS: Medline, Scopus, Web of Science, CENTRAL, Clinicaltrials.gov and Google Scholar were systematically searched from their inception through April 20, 2024. Both randomized controlled trials and observational studies evaluating the effects of statin administration after kidney transplantation were held eligible. Random-effects models were fitted using the maximum likelihood method, while the certainty of evidence was appraised following the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. RESULTS: Overall, 27 studies (10 randomized controlled trials and 17 observational studies) were included. Statin use compared to no use was associated with a lower risk of major adverse cardiovascular events [Relative risk (RR): 0.87, 95% confidence interval (CI): 0.67-0.96, moderate certainty] and overall mortality (RR: 0.84, 95% CI: 0.74-0.94, low certainty). The risk of graft loss did not differ between the compared groups (RR: 0.72, 95% CI: 0.48-1.08, very low certainty). Regarding safety endpoints, statin use was associated with a lower risk of hepatotoxicity (RR: 0.81, 95% CI: 0.70-0.93, moderate certainty), but with a greater risk of rhabdomyolysis (RR: 1.37, 95% CI: 1.10-1.70, low certainty) and cataract (RR: 1.22, 95% CI: 1.14-1.31, moderate certainty). No statistically significant differences between the compared groups with and without statin use were observed concerning the risk of creatine kinase elevation, post-transplant diabetes mellitus, hip fracture, venous thromboembolism, or cancer. CONCLUSIONS: Among kidney transplant recipients, statin use is associated with a lower risk of cardiovascular events and better patient survival, presenting an acceptable safety profile. Further large-scale studies are needed to determine the optimal statin dosing strategy and lipid-lowering goals, depending on comorbidities and immunosuppression regimens. REGISTRATION: https://doi.org/10.17504/protocols.io.5qpvok3yzl4o/v1 .

Safety of COVID-19 vaccines in multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Data are sparse regarding the safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (MS). OBJECTIVE: To estimate (1) the pooled proportion of MS patients experiencing relapse among vaccine recipients; (2) the rate of transient neurological worsening, adverse events, and serious adverse events; (3) the previous outcomes of interest for different SARS-CoV-2 vaccine types. METHODS: Systematic review and meta-analysis of pharmacovigilance registries and observational studies. RESULTS: Nineteen observational studies comprising 14,755 MS patients who received 23,088 doses of COVID-19 vaccines were included. Mean age was 43.3 years (95% confidence interval (CI): 40-46.6); relapsing-remitting, secondary-progressive, primary-progressive MS and clinically isolated syndrome were diagnosed in 82.6% (95% CI: 73.9-89.8), 12.6% (95% CI: 6.3-20.8), 6.7% (95% CI: 4.2-9.9), and 2.9% (95% CI: 1-5.9) of cases, respectively. The pooled proportion of MS patients experiencing relapse at a mean time interval of 20 days (95% CI: 12-28.2) from vaccination was 1.9% (95% CI: 1.3%-2.6%; I2 = 78%), with the relapse risk being independent of the type of administered SARS-CoV-2-vaccine (p for subgroup differences = 0.7 for messenger RNA (mRNA), inactivated virus, and adenovector-based vaccines). After vaccination, transient neurological worsening was observed in 4.8% (95% CI: 2.3%-8.1%) of patients. Adverse events and serious adverse events were reported in 52.8% (95% CI: 46.7%-58.8%) and 0.1% (95% CI: 0%-0.2%) of vaccinations, respectively. CONCLUSION: COVID-19 vaccination does not appear to increase the risk of relapse and serious adverse events in MS. Weighted against the risks of SARS-CoV-2-related complications and MS exacerbations, these safety data provide compelling pro-vaccination arguments for MS patients.

Changes in Stroke Hospital Care During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

[Figure: see text].

Dietary Supplement Use after Cancer Diagnosis in Relation to Total Mortality, Cancer Mortality and Recurrence: A Systematic Review and Meta-Analysis.

To study post-diagnosis dietary supplement use in relation to total mortality, cancer mortality and recurrence among cancer survivors. PubMed and Cochrane Library were searched until April 2019 for observational studies (OS) and randomized clinical trials (RCT). Pooled risk ratios (RR) were calculated using random-effects models. Compared to no supplementation, calcium supplementation was associated with lower total (RR = 0.88, 95% confidence interval (CI): 0.77-1.00, I2=0%, four OS) and cancer mortality (RR = 0.71, 95% CI: 0.53-0.95, I2=0%, three OS) among all cancer survivors, and cancer mortality among colorectal cancer survivors (RR = 0.66, 95% CI: 0.47-0.94, I2=0%, two OS). Vitamin D supplementation was associated with lower total mortality (RR = 0.86, 95% CI: 0.76-0.99, I2=0%, three OS and two RCT). Among breast cancer survivors, supplementation with vitamin C (RR = 0.79, 95% CI: 0.68-0.92, I2=0%, four OS), D (RR = 0.85, 95% CI: 0.72-0.99, I2=0%, two OS), and E (RR = 0.76, 95% CI: 0.64-0.90, I2=0%, three OS) was associated with lower total mortality, while multivitamins (RR = 0.79, 95% CI: 0.64-0.97, I2=0%, two OS), vitamin C (RR = 0.76, 95% CI: 0.64-0.91, I2=0%, two OS), and E (RR = 0.69, 95% CI: 0.55-0.85, I2=0%, two OS) with lower cancer recurrence. Conclusions: Findings are mostly based on OS. More RCTs are needed to justify any recommendation for use.

Food insecurity among people who inject drugs in Athens, Greece: a study in the context of ARISTOTLE programme.

OBJECTIVE: To measure the prevalence of food insecurity and explore related characteristics and behaviours among people who inject drugs (PWID). DESIGN: Cross-sectional analysis of a community-based programme for HIV infection among PWID (ARISTOTLE programme). Food insecurity was measured by the Household Food Insecurity Access Scale. Computer-assisted interviews and blood samples were also collected. SETTING: A fixed location in Athens Metropolitan Area, Greece, during 2012-2013. PARTICIPANTS: In total, 2834 unique participants with history of injecting drug use in the past 12 months were recruited over four respondent-driven sampling rounds (approximately 1400/round). RESULTS: More than 50 % of PWID were severely or moderately food insecure across all rounds. PWID were more likely to be severely food insecure if they were older than 40 years [adjusted OR (aOR): 1·71, 95 % CI: 1·33-2·19], were women (aOR: 1·49, 95 % CI: 1·17-1·89), from Middle East countries (aOR v. from Greece: 1·80, 95 % CI: 1·04-3·11), had a lower educational level (primary or secondary school v. higher education; aOR: 1·54, 95 % CI: 1·29-1·84), had no current health insurance (aOR: 1·45, 95 % CI: 1·21-1·73), were homeless (aOR: 17·1, 95 % CI: 12·3-23·8) or were living with another drug user (aOR: 1·55, 95 % CI: 1·26-1·91) as compared with those living alone or with family/friends. HIV-infected PWID were more likely to be severely food insecure compared with uninfected (59·0 % v. 51·0 %, respectively, P = 0·002); however, this difference was attributed to the confounding effect of homelessness. CONCLUSIONS: Moderate/severe food insecurity was a significant problem, reaching > 50 % in this sample of PWID and closely related to socio-demographic characteristics and especially homelessness.

The effect of facemask in patients with unilateral cleft lip and palate: a systematic review and meta-analysis.

BACKGROUND: Patients with cleft lip and palate usually present a Class III skeletal pattern. Facemask (FM) is one of the conventional orthodontic treatment modalities used to address the skeletal discrepancy in cleft patients. OBJECTIVE: To investigate the potential effectiveness of FM in unilateral cleft lip and palate (UCLP) patients. SEARCH METHODS: Search without restrictions except language in seven databases since inception and hand searching until January 2019 was conducted. Detailed search strategies were developed for each database which were based on the PubMed strategy and adapted accordingly. SELECTION CRITERIA: Controlled studies assessing the effect of FM in UCLP patients were to be included. DATA COLLECTION AND ANALYSIS: After retrieval and selection of the studies, data extraction was performed. Both angular and linear cephalometric measurements were collected. Weighted mean differences (WMDs) and 95% confidence intervals (CΙs) between treated and untreated UCLP patients concerning the pre- and post-treatment angular measurements of each group were calculated using a random-effects meta-analysis model. The risk of bias in individual studies was assessed using the ROBINS-I tool. RESULTS: From nine eligible studies, five were included in the meta-analysis investigating the use of FM in patients and controls with UCLP (with and without maxillary expansion). Statistically significant differences were evident for SNA/S-N-ss, SNB/S-N-sm, ANB/ss-N-sm, and SN-MP. FM was found to induce an increase of SNA (WMD = 2.12 degrees, 95% CI: 1.58 to 2.66), ANB (WMD = 4.17 degrees, 95% CI: 3.60 to 4.74), and SN-MP angles (WMD = 2.60 degrees, 95% CI: 1.10 to 4.10) and a decrease of SNB angle (WMD = -1.94 degrees, 95% CI: -2.48 to -1.40) in UCLP patients. Low to moderate heterogeneity was observed. LIMITATIONS: They emerge due to risk of bias, exclusion of non-English papers and methodological characteristics of the included papers. CONCLUSIONS: According to the available data, FM seems to improve the sagittal skeletal relationships in UCLP patients, increasing the SNA and ANB angles and decreasing the SNB angle. Moreover, in the vertical dimension, FM increases the SN-MP angle. Regarding dental measurements, there are controversial results. More high-quality studies need to be conducted in order to further clarify the impact of FM on UCLP patients. REGISTRATION NUMBER: PROSPERO: CRD42019131619.

Incidence of incisor root resorption associated with the position of the impacted maxillary canines: A cone-beam computed tomographic study.

INTRODUCTION: The purpose of this study was to examine the incidence and position of lateral and central incisor root resorption owing to the impaction of maxillary canines by means of cone-beam computed tomography and to investigate parameters associated with the respective resorption. METHODS: Sixty-one patients presenting with unilateral or bilateral impacted maxillary canines were evaluated in a university clinic in Athens, Greece, using cone-beam computed tomography scan. No patient had undergone any type of orthodontic treatment in the past. Eleven different parameters related to the existence, grade, and localization of resorption were examined. Logistic regression analysis was used to evaluate potential associations. RESULTS: In our study, canine impaction caused lateral root resorption in 18.5% of the cases examined. Age was associated with localization of the impacted maxillary left canine in a palatal-buccal direction. More specifically, in younger patients, the impacted left canine was more likely to be located in the middle of the maxillary bone, whereas in older patients, it was more likely to be located in the palatal or buccal side of the bone. Lateral root resorption in the apical or middle third was more common in the younger ages, whereas lateral root resorption in the incisal third more common in the older ages. Lateral root resorption increased as the angle between the longitudinal axis of the impacted canine and the adjacent lateral incisor also increased. CONCLUSIONS: Incidence of lateral root resorption was 18.5% in this study population. In younger patients, the impacted canines appear more often in the middle of the maxillary bone, whereas in older patients, the canines are located more often in the palatal or buccal side of the maxilla.

National Dietary Guidelines of Greece for children and adolescents: a tool for promoting healthy eating habits.

OBJECTIVE: Dietary guidelines are an essential policy tool for facilitating optimal dietary patterns and healthy eating behaviours. We report: (i) the methodological approach adopted for developing the National Dietary Guidelines of Greece (NDGGr) for Infants, Children and Adolescents; and (ii) the guidelines for children aged 1-18 years. DESIGN: An evidence-based approach was employed to develop food-based recommendations according to the methodologies of the WHO, FAO and European Food Safety Authority. Physical activity recommendations were also compiled. Food education, healthy eating tips and suggestions were also provided. SETTING: The NDGGr encompass food-based nutritional and physical activity recommendations for promoting healthy dietary patterns and eating behaviours and secondarily to serve as a helpful tool for the prevention of childhood overweight and obesity. RESULTS: The NDGGr include food-based recommendations, food education and health promotion messages regarding: (i) fruits; (ii) vegetables; (iii) milk and dairy products; (iv) cereals; (v) red and white meat; (vi) fish and seafood; (vii) eggs; (viii) legumes; (ix) added lipids, olives, and nuts; (x) added sugars and salt; (xi) water and beverages, and (xii) physical activity. A Nutrition Wheel, consisting of the ten most pivotal key messages, was developed to enhance the adoption of optimal dietary patterns and a healthy lifestyle. The NDGGr additionally provide recommendations regarding the optimal frequency and serving sizes of main meals, based on the traditional Greek diet. CONCLUSIONS: As a policy tool for promoting healthy eating, the NDGGr have been disseminated in public schools across Greece.

Separate and combined associations of obesity and metabolic health with coronary heart disease: a pan-European case-cohort analysis.

Aims: The hypothesis of 'metabolically healthy obesity' implies that, in the absence of metabolic dysfunction, individuals with excess adiposity are not at greater cardiovascular risk. We tested this hypothesis in a large pan-European prospective study. Methods and results: We conducted a case-cohort analysis in the 520 000-person European Prospective Investigation into Cancer and Nutrition study ('EPIC-CVD'). During a median follow-up of 12.2 years, we recorded 7637 incident coronary heart disease (CHD) cases. Using cut-offs recommended by guidelines, we defined obesity and overweight using body mass index (BMI), and metabolic dysfunction ('unhealthy') as ≥ 3 of elevated blood pressure, hypertriglyceridaemia, low HDL-cholesterol, hyperglycaemia, and elevated waist circumference. We calculated hazard ratios (HRs) and 95% confidence intervals (95% CI) within each country using Prentice-weighted Cox proportional hazard regressions, accounting for age, sex, centre, education, smoking, diet, and physical activity. Compared with metabolically healthy normal weight people (reference), HRs were 2.15 (95% CI: 1.79; 2.57) for unhealthy normal weight, 2.33 (1.97; 2.76) for unhealthy overweight, and 2.54 (2.21; 2.92) for unhealthy obese people. Compared with the reference group, HRs were 1.26 (1.14; 1.40) and 1.28 (1.03; 1.58) for metabolically healthy overweight and obese people, respectively. These results were robust to various sensitivity analyses. Conclusion: Irrespective of BMI, metabolically unhealthy individuals had higher CHD risk than their healthy counterparts. Conversely, irrespective of metabolic health, overweight and obese people had higher CHD risk than lean people. These findings challenge the concept of 'metabolically healthy obesity', encouraging population-wide strategies to tackle obesity.

Tumor-associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation.

Immuno-proteomic screening has identified several tumor-associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01-0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited.

Mediterranean diet and its components in relation to all-cause mortality: meta-analysis.

The beneficial association of the Mediterranean diet (MedDiet) with longevity has been consistently demonstrated, but the associations of MedDiet components have not been accordingly evaluated. We performed an updated meta-analysis of prospective cohort studies published up to 31 December 2017, to quantify the association of adherence to MedDiet, expressed as an index/score (MDS) and of its components with all-cause mortality. We estimated summary relative risks (SRR) and 95 % CI using random effects models. On the basis of thirty studies (225 600 deaths), SRR for the study-specific highest/lowest and per 1sd MDS increment were 0·79 (95 % CI 0·77, 0·81, Ι 2=42 %, P-heterogeneity 0·02) and 0·92 (95 % CI 0·90, 0·94, Ι 2 56 %, P-heterogeneity <0·01), respectively. Inversely, statistically significant associations were evident in stratified analyses by country, MDS range and publication year, with some evidence for heterogeneity across countries overall (P-heterogeneity 0·011), as well as across European countries (P=0·018). Regarding MDS components, relatively stronger and statistically significant inverse associations were highlighted for moderate/none-excessive alcohol consumption (0·86, 95 % CI 0·77, 0·97) and for above/below-the-median consumptions of fruit (0·88, 95 % CI 0·83, 0·94) and vegetables (0·94, 95 % CI 0·89, 0·98), whereas a positive association was apparent for above/below-the-median intake of meat (1·07, 95 % CI 1·01, 1·13). Our meta-analyses confirm the inverse association of MedDiet with mortality and highlight the dietary components that influence mostly this association. Our results are important for better understanding the role of MedDiet in health and proposing dietary changes to effectively increase adherence to this healthy dietary pattern.

Reliability of different radiographic methods for the localization of displaced maxillary canines.

INTRODUCTION: The purpose of this study was to evaluate the reliability of the radiographic images of the main conventional x-ray techniques compared with the information from cone-beam computed tomography (CBCT). METHODS: Twenty patients with unilateral or bilateral impaction of the maxillary canines had radiographic examinations by means of periapical x-rays, occlusal x-rays, panoramic x-rays, and CBCT scans. Three experienced orthodontists examined all x-rays from each patient and evaluated the radiographic images of the impacted canines. The examiners were asked to detect resorption in adjacent teeth and the buccal-palatal position of the impacted canines. Agreement between examiners was statistically tested. RESULTS: Different diagnoses were produced by the 3 examiners regarding localization of the impacted canines and the presence or absence of root resorption of the adjacent teeth in conventional radiographic images. It appears that whereas panoramic x-ray is more sensitive in detecting resorption and tooth position, occlusal and periapical imaging have higher specificity and positive predictive value. The examiners were in good or excellent agreement when occlusal and periapicals were used for the definite diagnosis of resorption and tooth position. There was no disagreement of the examiners in CBCT images, which were used as the gold standard. CONCLUSIONS: Conventional radiographic methods demonstrated a more subjective diagnostic procedure compared with CBCT images. CBCT is a more accurate and precise examination method compared with conventional radiography for the localization of impacted teeth and root resorption of the adjacent teeth.

Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe.

BACKGROUND: We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence. METHODS: This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively. Harmonised individual participant data from all seven cohorts were analysed separately and alternatively for each anthropometric indicator using multivariable Cox proportional hazards models. RESULTS: After a median follow-up period of 12 years, 1656 first-incident obesity-related cancers (defined as postmenopausal female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the meta-analysis of all studies, associations between indicators of adiposity, per s.d. increment, and risk for all obesity-related cancers combined yielded the following summary hazard ratios: 1.11 (95% CI 1.02-1.21) for BMI, 1.13 (95% CI 1.04-1.23) for WC, 1.09 (95% CI 0.98-1.21) for HC, and 1.15 (95% CI 1.00-1.32) for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%, respectively per s.d. of BMI, WC, HC, and WHR. Effect modification by hormone therapy (HT) use was observed for postmenopausal breast cancer (Pinteraction<0.001), where never HT users showed an ∼20% increased risk per s.d. of BMI, WC, and HC compared to ever users. CONCLUSIONS: BMI, WC, HC, and WHR show comparable positive associations with obesity-related cancers combined and with colorectal cancer in older adults. For postmenopausal breast cancer we report evidence for effect modification by HT use.

Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort.

Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (phet = 0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; phet = 0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.

Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC).

Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval-CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer.

Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer.

UNLABELLED: Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however, there are little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intrahepatic bile duct (IBD), and gallbladder and biliary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Over an average of 7.7 years, 296 participants developed HCC (n=125), GBTC (n=137), or IBD (n=34). Using risk-set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, and time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured, and incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection, and adiposity measures, higher concentrations of CRP, IL-6, C-peptide, and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations=1.22; 95% CI=1.02-1.46; P=0.03; 1.90; 95% CI=1.30-2.77; P=0.001; 2.25; 95% CI=1.43-3.54; P=0.0005; and 2.09; 95% CI=1.19-3.67; P=0.01, respectively). CRP was associated also with risk of GBTC (IRR=1.22; 95% CI=1.05-1.42; P=0.01). GLDH was associated with risks of HCC (IRR=1.62; 95% CI=1.25-2.11; P=0.0003) and IBD (IRR=10.5; 95% CI=2.20-50.90; P=0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide, and non-HMW adiponectin and 0.46 for GLDH, indicating good predictive ability of these biomarkers. CONCLUSION: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.

Immigrant status as important determinant of breastfeeding practice in southern Europe.

AIM: Breastfeeding is universally accepted as the optimal way to nourish infants. There is evidence that socio-demographic factors, including immigrant status, are related to infant feeding practices. The aim of the present study was to identify the factors which are associated with breastfeeding initiation and duration, with special focus on the role of immigrant status of the mother in breastfeeding practice. A sample of mothers giving birth and living in Athens, Greece, was investigated. METHODS: 428 mothers (438 infants) were recruited in the maternity ward of a Tertiary University Hospital, and were interviewed using a structured questionnaire. Monthly telephone interviews were subsequently conducted until the sixth postpartum month. Multivariate logistic regression models were used to quantify the association of socio-demographic parameters with breastfeeding initiation. Cox regression analysis was employed to assess related factors that might influence breastfeeding duration. RESULTS: Being an immigrant was positively associated with exclusive as well as partial breastfeeding initiation (OR 7.97, 95% CI 1.02-62.19). Immigrant mothers were also 0.35 times less likely (95% Ci 0.21-0.58) to stop breastfeeding earlier, compared to the native ones. Several other factors were deemed important either for breastfeeding initiation or its duration but not for both aspects of breastfeeding practice. CONCLUSION: Maternal immigrant status was found to be consistently associated with breastfeeding initiation and duration in this study sample. Health professionals, health policy makers and politicians should remain attuned to the cultural backgrounds which have created strong breastfeeding traditions, to further promote breastfeeding practice in Western countries.