Soluble urokinase plasminogen activator receptor as a long-term prognostic biomarker in acute coronary syndromes

Abstract

Purpose: The aim of our study was to analyse the long-term prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in the setting of an acute coronary syndrome (ACS).

Methods: We included 340 patients with an ACS who underwent coronary angiography and plasma suPAR concentration was measured. Patients were classified into low suPAR concentrations (<2.6?ng/mL) and high suPAR concentrations (≥2.6?ng/mL) and long-term events were evaluated. suPAR prognostic value was assessed beyond a clinical model that included age, GRACE score, estimated glomerular filtration rate, cardiac troponin-I peak and left ventricular ejection fraction <40%.

Results: Higher suPAR concentrations were associated with an increased prevalence of cardiovascular risk factors. After multivariate adjustment, suPAR ≥2.6?ng/mL were independently associated with an increased risk of all-cause death (HR 2.3; 95%CI 1.2–4.4; p?=?.017), major adverse cardiovascular events (MACE) (HR 1.7; 95%CI 1.1–2.5; p?=?.020) and heart failure (HR 4.1; 95%CI 1.3–12.6; p?=?.015), but not with myocardial infarction. For long-term all-cause death significant improvement of reclassification and discrimination were seen after addition of suPAR to a clinical model.

Conclusions: In the setting of an ACS, suPAR is associated with long-term all-cause death, heart failure and MACE, and provides incremental prognostic value beyond traditional risks factors.     

Short-term effect of dust storms on the risk of mortality due to respiratory, cardiovascular and all-causes in Kuwait

This study aimed to investigate the impact of dust storms on short-term mortality in Kuwait. We analyzed respiratory and cardiovascular mortality as well as all-cause mortality in relation to dust storm events over a 5-year study period, using data obtained through a population-based retrospective ecological time series study. Dust storm days were identified when the national daily average of PM₁₀ exceeded 200 μg/m³. Generalized additive models with Poisson link were used to estimate the relative risk (RR) of age-stratified daily mortality associated with dust events, after adjusting for potential confounders including weather variables and long-term trends. There was no significant association between dust storm events and same-day respiratory mortality (RR = 0.96; 95 %CI 0.88–1.04), cardiovascular mortality (RR = 0.98; 95 %CI 0.96–1.012) or all-cause mortality (RR = 0.99; 95 %CI 0.97–1.00). Overall our findings suggest that local dust, that most likely originates from crustal materials, has little impact on short-term respiratory, cardiovascular or all-cause mortality.     

Predictive Value of Carotid Distensibility Coefficient for Cardiovascular Diseases and All-Cause Mortality: A Meta-Analysis

AimsThe aim of the present study is to determine the pooled predictive value of carotid distensibility coefficient (DC) for cardiovascular (CV) diseases and all-cause mortality.BackgroundArterial stiffness is associated with future CV events. Aortic pulse wave velocity is a commonly used predictor for CV diseases and all-cause mortality; however, its assessment requires specific devices and is not always applicable in all patients. In addition to the aortic artery, the carotid artery is also susceptible to atherosclerosis, and is highly accessible because of the surficial property. Thus, carotid DC, which indicates the intrinsic local stiffness of the carotid artery and may be determined using ultrasound and magnetic resonance imaging, is of interest for the prediction. However, the role of carotid DC in the prediction of CV diseases and all-cause mortality has not been thoroughly characterized, and the pooled predictive value of carotid DC remains unclear.MethodsA meta-analysis, which included 11 longitudinal studies with 20361 subjects, was performed.ResultsCarotid DC significantly predicted future total CV events, CV mortality and all-cause mortality. The pooled risk ratios (RRs) of CV events, CV mortality and all-cause mortality were 1.19 (1.06–1.35, 95%CI, 9 studies with 18993 subjects), 1.09 (1.01–1.18, 95%CI, 2 studies with 2550 subjects) and 1.65 (1.15–2.37, 95%CI, 6 studies with 3619 subjects), respectively, for the subjects who had the lowest quartile of DC compared with their counterparts who had higher quartiles. For CV events, CV mortality and all-cause mortality, a decrease in DC of 1 SD increased the risk by 13%, 6% and 41% respectively, whereas a decrease in DC of 1 unit increased the risk by 3%, 1% and 6% respectively.ConclusionsCarotid DC is a significant predictor of future CV diseases and all-cause mortality, which may facilitate the identification of high-risk patients for the early diagnosis and prompt treatment of CV diseases.     

Lifestyle factors and quality of life among primary health care physicians in Madinah,Saudi Arabia

BackgroundPhysicians are considered to be a high-risk population for a poor quality of life (QoL), but few studies of lifestyle factors include the QoL among them.ObjectivesThis study aimed to investigate the relationship between lifestyle factors and a positive QoL among primary health care (PHC) physicians.MethodsA cross-sectional study was conducted at 20 primary healthcare centers in Madinah, Saudi Arabia. A self-administered questionnaire was used, including sociodemographic characteristics, lifestyle data, and the short version of the World Health Organization Quality of Life questionnaire. Appropriate statistical analyses were used, including multivariate logistic regression models.ResultsThe response rate was 85.7% (72/84) physicians. The mean score of the total QoL and its four studied domains (physical, psychological, social, and environmental) was relatively high, with no statistically significant difference between the consultants and general practitioners. The positive total QoL in this study was significantly lower among physicians with obesity (OR = 0.55, 95%CI = 0.25–0.97), those using butter and animal fat for cooking (OR = 0.10, 95%CI = 0.02–0.81), and those eating meals out > 3 times per week (OR = 0.30, 95%CI = 0.10–0.90). Although non-significant, vegetable consumption and a high level of physical activity were associated with a positive QoL, with adjusted ORs of 2.5 (95%CI = 0.82–7.58) and 1.5 (95%CI = 0.33–6.65), respectively.ConclusionThe findings indicate a relatively good QoL among the participating physicians; however, a lower QoL was associated with unhealthy lifestyle factors. QoL was significantly associated with obesity, cooking practices, and eating meals from restaurants.     

Reproductive factors,obesity and risk of colorectal cancer in a cohort of Asian women

BackgroundThis study evaluated reproductive factors and obesity in relation to colorectal cancer (CRC) in Asian women.MethodsThe study cohort comprised 28191 women who were recruited between 1994 and 1997. During 18 years of prospective follow-up, 404 and 212 women developed colon cancer (CC) and rectal cancer (RC) respectively. Cox proportional hazards regression was used.ResultsMenstrual factors were not related to the risk of CRC, CC and RC. Gravidity and parity were not associated with CRC or RC, but women who were ever pregnant had a HR of 1.87 (95%CI 1.12–3.14) compared to those never pregnant, and parous women had a HR of 1.79 (95% CI 1.10–2.92) compared to nulliparous women for CC. Use of oral contraceptives and hormone replacement therapy were not associated with CRC, CC or RC.Compared to women with normal BMI, women who were obese had HRs of 1.39 (95%CI 1.12–1.74) and 1.64 (95%CI 1.24–2.16) for CRC and CC respectively. No increased risk was seen for RC. Adjusted for BMI, for colonic cancer, women in the highest quartile for Waist Circumference had a HR of 2.14 (95%CI 1.42–3.25) compared to the lowest quartile, for Waist Hip Ratio, a HR of 1.74 (95%CI 1.30–2.34), and for Waist-Height ratio, a HR of 1.80 (1.26–2.57). None of these measures were significantly associated with RC.ConclusionsObesity is positively associated with CC but not RC, and abdominal obesity exerts an independent effect. Reproductive factors had at best a weak effect on CC and RC.     

Effects of Metabolic Syndrome with or without Obesity on Outcomes after Coronary Artery Bypass Graft. A Cohort and 5-Year Study

BackgroundMetabolic syndrome (MetS) and obesity are risk factors for cardiovascular disease, however, it remains unclear about effects of MetS with or without obesity on perioperative and long-term morbidity and mortality after coronary artery bypass graft (CABG).MethodsAn observational cohort study was performed on 4,916 consecutive patients receiving isolated primary CABG in Fuwai hospital. Of all patients, 1238 patients met the inclusion criteria and were divided into three groups: control, MetS with obesity and MetS without obesity (n = 868, 76 and 294 respectively). The patient’s 5-year survival and major adverse cerebral and cardiovascular events (MACCE) were studied.ResultsAmong all three groups, there were no significant differences in in-hospital postoperative complications, epinephrine use, stroke, ICU stay, ventilation time, atrial fibrillation, renal failure, coma, myocardial infarction, repeated revascularization, and long-term stroke. The patients in MetS without obesity group were not associated with increased perioperative or long-term morbidities and mortality. In contrast, the patients in MetS with obesity group were associated with significant increased perioperative complications including MACCE (30.26% vs. 20.75%, 16.7%, p = 0.0074) and mortality (11.84% vs. 3.74%, 3.11%, p = 0.0007) respectively. Patients in MetS with obesity group was associated with significantly increased long-term of MACCE (adjusted OR:2.040; 95%CI:1.196–3.481; P＜0.05) and 5-years of mortality (adjusted HR:4.659; 95%CI:1.966–11.042; P＜0.05).ConclusionsPatients with metabolic syndrome and obesity are associated with significant increased perioperative and long-term complications and mortality, while metabolic syndrome without obesity do not worsen outcomes after CABG.     

Efficacy and safety of leadless pacemaker: A systematic review,pooled analysis and meta-analysis

BackgroundLeadless pacemakers have been designed as an alternative to transvenous systems which avoid some of the complications associated with transvenous devices. We aim to perform a systematic review of the literature to report the safety and efficacy findings of leadless pacemakers.MethodsWe searched MEDLINE and EMBASE to identify studies reporting the safety, efficacy and outcomes of patients implanted with a leadless pacemaker. The pooled rate of adverse events was determined and random-effects meta-analysis was performed to compare rates of adverse outcomes for leadless compared to transvenous pacemakers.ResultsA total of 18 studies were included with 2496 patients implanted with a leadless pacemaker and success rates range between 95.5 and 100%. The device or procedure related death rate was 0.3% while any complication and pericardial tamponade occurred in 3.1% and 1.4% of patients, respectively. Other complications such as pericardial effusion, device dislodgement, device revision, device malfunction, access site complications and infection occurred in less than 1% of patients. Meta-analysis of four studies suggests that there was no difference in hematoma (RR 0.67 95%CI 0.21–2.18, 3 studies), pericardial effusion (RR 0.59 95%CI 0.15–2.25, 3 studies), device dislocation (RR 0.33 95%CI 0.06–1.74, 3 studies), any complication (RR 0.44 95%CI 0.17–1.09, 4 studies) and death (RR 0.45 95%CI 0.15–1.35, 2 studies) comparing patients who received leadless and transvenous pacemakers.ConclusionLeadless pacemakers are safe and effective for patients who have an indication for single chamber ventricular pacing and the findings appear to be comparable to transvenous pacemakers.     

Pilot study of DNA methylation-derived neutrophil-to-lymphocyte ratio and survival in pediatric medulloblastoma

IntroductionMethylation-derived neutrophil-to-lymphocyte ratio (mdNLR) has been identified as a potential prognostic biomarker of outcomes in various cancers. We evaluated the prognostic value of blood-derived mdNLR within a retrospective cohort of pediatric medulloblastoma patients.Materials and methodsDNA methylation was measured in archival peripheral blood samples collected on 56 pediatric medulloblastoma patients. Hazard ratios (HR) and 95% confidence intervals (CI) for the association between mdNLR and survival were evaluated using Cox proportional hazard models.ResultsCompared to patients who were alive at last follow-up (n = 43), the mean mdNLR value was slightly higher in deceased patients (n = 13) (12.3 vs. 5.2,P = 0.163). Elevated log-transformed mdNLR was suggestively associated with an increased likelihood of death in unadjusted models (HR=1.43, 95%CI: 0.92–2.22) and significantly associated with mortality in adjusted models (HR=1.61, 95%CI: 1.01–2.58).DiscussionFuture work is warranted to investigate the relationship between mdNLR outcomes in specific pediatric medulloblastoma molecular subgroups.     

Asymmetric and Symmetric Dimethylarginine as Risk Markers for Total Mortality and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Studies

BackgroundA growing number of studies linked elevated concentrations of circulating asymmetric (ADMA) and symmetric (SDMA) dimethylarginine to mortality and cardiovascular disease (CVD) events. To summarize the evidence, we conducted a systematic review and quantified associations of ADMA and SDMA with the risks of all-cause mortality and incident CVD in meta-analyses accounting for different populations and methodological approaches of the studies.MethodsRelevant studies were identified in PubMed until February 2015. We used random effect models to obtain summary relative risks (RR) and 95% confidence intervals (95%CIs), comparing top versus bottom tertiles. Dose-response relations were assessed by restricted cubic spline regression models and potential non-linearity was evaluated using a likelihood ratio test. Heterogeneity between subgroups was assessed by meta-regression analysis.ResultsFor ADMA, 34 studies (total n = 32,428) investigating associations with all-cause mortality (events = 5,035) and 30 studies (total n = 30,624) investigating the association with incident CVD (events = 3,396) were included. The summary RRs (95%CI) for all-cause mortality were 1.52 (1.37–1.68) and for CVD 1.33 (1.22–1.45), comparing high versus low ADMA concentrations. Slight differences were observed across study populations and methodological approaches, with the strongest association of ADMA being reported with all-cause mortality in critically ill patients. For SDMA, 17 studies (total n = 18,163) were included for all-cause mortality (events = 2,903), and 13 studies (total n = 16,807) for CVD (events = 1,534). High vs. low levels of SDMA, were associated with increased risk of all-cause mortality [summary RR (95%CI): 1.31 (1.18–1.46)] and CVD [summary RR (95%CI): 1.36 (1.10–1.68) Strongest associations were observed in general population samples.ConclusionsThe dimethylarginines ADMA and SDMA are independent risk markers for all-cause mortality and CVD across different populations and methodological approaches.     

Health conditions associated with metabolic syndrome after cancer at a young age: A nationwide register-based study

PurposeChildhood cancer survivors are at risk for developing metabolic syndrome (MetS), which subsequently leads to cardiovascular morbidity and excess mortality. Our aim was to investigate the purchases of medications associated with MetS among 7551 early onset cancer patients compared to siblings.MethodsOur nationwide Finnish population-based registry study analyzed the drug purchase of medication among early onset cancer patients diagnosed with cancer below the age of 35 years between 1994 and 2004 compared to siblings by linkage to the drug purchase registry, allowing for a maximal follow-up of 18 years.ResultsThe hazard ratios (HRs) for purchasing antihypertensives and diabetes drugs were higher after both childhood (HR 4.6, 95%CI 3.1–7.0; HR 3.0, 95%1.5–6.1) and young adulthood (YA) cancer (HR 1.5, 95%CI 1.3–1.8; HR 1.6, 95%CI 1.1–2.2) compared to siblings. The HRs for purchasing lipid-lowering drugs were elevated both after childhood (HR 4.3,95%CI 0.9–19.5) and YA cancer (HR 1.6, 95%CI 1.04–2.5), but only reached significance in YA cancer patients. Among specific cancer diagnosis groups, highest HR values for antihypertensives were found in childhood acute lymphoblastic leukemia (ALL) (HR 6.1, 95%CI 3.7–10.3) and bone tumor (HR 4.3, 95%CI 1.9–9.4), and YA ALL (HR 4.8, 95%CI 3.1–7.0) and acute myeloid leukemia (AML) (HR 3.4, 95%CI 2.5–5.1) patients. Moreover, childhood ALL (HR 6.3, 95%CI 2.7–14.8), AML (HR 7.6, 95%CI 1.9–24.5) and central nervous system (CNS)-tumor (HR 3.5, 95%CI 1.3–9.2) and YA ALL (HR 3.7, 95%CI 1.2–9.5) patients showed the strongest likelihood of purchasing diabetes drugs compared to siblings.ConclusionThe purchase of medications associated with MetS was increased after early onset cancer and highly dependent on the age at cancer diagnosis and the cancer diagnosis. Prevention strategies are imperative for reducing potentially life-threatening cardiovascular complications after early onset cancer.     

Population-level cure of colorectal cancer in Malta: An analysis of patients diagnosed between 1995 and 2004

AimThe aim of this study was to estimate the population-level ‘cure’ of Maltese colorectal cancer patients diagnosed between 1995 and 2004, and to estimate the median survival time for the ‘uncured’ patients.Methods and study populationAnalysis was conducted on 1470 cases registered by the Malta National Cancer Register between 1995 and 2004 and followed up to end of 2010. The mean age of the patients was 66.4 (95%CI 65.8–67.1), and the number of men and women were equal. Background mortality for 1995–2010 was extracted from publicly available life tables. A mixture model with Weibull survival distribution and identity link was used to model ‘cure’.ResultsThe overall ‘cured’ proportion for the patients diagnosed in 1995–1999 was 45.3% (95%CI 40.2–50.5) while the ‘cured’ proportion for the patients diagnosed in 2000–2004 was 52.3% (95%CI 47.2–57.5). Median survival time for the ‘uncured’ patients increased in the second calendar period from 1.25 years (95%CI 1.04–1.45) to 1.42 years (95%CI 1.15–1.76).ConclusionIn Malta, as in the rest of Europe, improvements have been made in short- and long-term survival over the 15-year period under study. To continue this improvement, differences by age that still persist must be investigated and efforts focused to reduce any gaps between Malta and other European countries.     

Impact of comorbidity on survival by tumour location: Breast,colorectal and lung cancer (2000–2014)

BackgroundTo assess the impact of comorbidity, measured by the Charlson Comorbidity Index (CCI), on survival in breast, colorectal and lung cancer.MethodsWe identified 3455 breast cancer, 3336 colorectal cancer and 2654 lung cancer patients through the Hospital del Mar cancer registry. The prevalence of comorbidities according to the CCI was calculated. Kaplan-Meier curves and the log-rank test were used to compare survival curves for each cancer location. Cox regression was used to calculate survival hazard ratios and 1-, 3- and 5-year mortality rate ratios adjusted by age, sex, CCI, place of first consultation, stage, treatment and period of diagnosis.ResultsThe overall unadjusted 5-year follow-up survival proportion was 82.6% for breast cancer, 55.7% for colorectal cancer, and 16.3% for lung cancer. Overall survival was associated with CCI ≥ 3 in breast cancer (HR: 2.33 95%CI: 1.76–3.08), colorectal cancer (HR: 1.39; 95%CI: 1.13–1.70) and lung cancer (HR: 1.22; 95%CI: 1.06–1.40). In breast cancer, the higher the CCI, the higher the adjusted mortality rate ratio and differences were greater in 5-year than in 1-year follow-up survival.ConclusionsComorbidity is a significant predictor of overall survival in cancer patients; however, it has a stronger impact on survival in breast cancer than in colorectal and lung cancer.     

Partial nephrectomy vs cryoablation for T1a renal cell carcinoma: A comparison of survival benefit stratified by tumour size

ObjectiveWe compared the impact on survival outcomes of partial nephrectomy (PN) and cryoablation (CA) for patients diagnosed with T1a renal cell carcinoma (RCC).Patients and MethodsAmong patients diagnosed between 2004 and 2014 in the Surveillance, Epidemiology and End Results program, we identified histologically confirmed T1aN0M0 RCC treated with PN (n = 17644) or CA (n = 868). Propensity score matching (PSM) was performed. Kaplan-Meier method, Cox proportional hazards model were used to calculate cancer specific mortality (CSM) and overall mortality (OM) in the unmatched and matched cohort, and in subgroups based on tumour size (< 2 cm, 2-3 cm, 3-4 cm). Sensitivity analyses were performed.ResultsA total of 18512 patients were identified: PN (93.88%) and CA (6.12%). In the propensity-score matched cohort, for tumours ≤ 2 cm, the CA and PN groups had similar CSM (HR: 1.41, 95% CI: 0.32–6.31, p = 0.65) and OM (HR 0.97, 95%CI: 0.47–2.01, p = 0.93). For tumours 2-3 cm, CA was associated with similar CSM (HR 1.64, 95%CI: 0.67–4.03, p = 0.28) but higher OM (HR 2.05, 95%CI: 1.35–3.11, p < 0.001), compared with PN. For tumours 3-4 cm, CA was associated with increased CSM (HR: 3.76, 95% CI: 1.62–8.69, p = 0.002) and OM (HR 2.17, 95%CI: 1.48–3.18, p < 0.001).ConclusionFor RCC ≤ 2 cm, PN and CA are equal in survival outcomes. For RCC 2-4 cm, PN may have a possible advantage over CA.     

Toxoplasma gondii infection/exposure and the risk of brain tumors: A systematic review and meta-analysis

BackgroundBrain tumors are among the most fatal cancers with substantial morbidity and mortality worldwide. Epidemiologic evidence suggests that infectious agents, especially, protozoan parasite Toxoplasma gondii could be a possible risk factor or contributor. Here, we performed a systematic review and meta-analysis to evaluate the possible association between T. gondii infection/exposure and risk of brain tumors.MethodsWe searched the PubMed, Embase, Scopus, and Web of Science collection databases from inception through 1st of December 2021. Pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were generated using random effects models. We did the subgroup analysis according to tumor types. Statistical tests for heterogeneity and sensitivity analyses were applied.ResultsA total of seven eligible studies comprising 2323 patients diagnosed with brain tumors and 5131 healthy controls were included in the meta-analysis. T. gondii infection/exposure prevalence was 24.2% (95%CI, 12.7%–41.2) in cases and 12.9% (95%CI, 7.0–22.6%) in control subjects. Pooled analysis showed an overall OR of 1.96 (95%CI, 1.37–2.80), indicating a significant increased risk of brain tumors associated with T. gondii infection/exposure. In subgroup analysis T. gondii infection/exposure was significantly associated with gliomas (OR: 1.64, 95%CI, 1.15–2.33), meningioma (OR: 2.30, 95%CI, 1.0–5.27) and other types of brain tumors (OR: 2.19, 95%CI, 1.02–4.71).ConclusionThis study provides suggestive evidence for an association between T. gondii infection/exposure and brain tumors. Our findings should be further confirmed by well-designed cohort studies with strict control of confounders. Moreover, we suggest that future studies also focus on the effect of T. gondii infection/exposure to the types of brain tumors.     

Lack of significant associations between single nucleotide polymorphisms in LPAL2-LPA genetic region and all cancer incidence and mortality in Japanese population: The Japan public health center-based prospective study

BackgroundHigh lipoprotein (a) level is an established cardiovascular risk, but its association with non-cardiovascular diseases, especially cancer, is controversial. Serum lipoprotein (a) levels vary widely by genetic backgrounds and are largely determined by the genetic variations of apolipoprotein (a) gene, LPA. In this study, we investigate the association between SNPs in LPA region and cancer incidence and mortality in Japanese.MethodsA genetic cohort study was conducted utilizing the data from 9923 participants in the Japan Public Health Center-based Prospective Study (JPHC Study). Twenty-five SNPs in the LPAL2-LPA region were selected from the genome-wide genotyped data. Cox regression analysis adjusted for the covariates and competing risks of death from other causes, were used to estimate the relative risk (hazard ratios (HR) with 95% confidence intervals (CI)) of overall and site-specific cancer incidence and mortality, for each SNP.ResultsNo significant association was found between SNPs in the LPAL2-LPA region and cancer incidence or mortality (overall/site-specific cancer). In men, however, HRs for stomach cancer incidence of 18SNPs were estimated higher than 1.5 (e.g., 2.15 for rs13202636, model free, 95%CI: 1.28–3.62) and those for stomach cancer mortality of 2SNPs (rs9365171, rs1367211) were estimated 2.13 (recessive, 95%CI:1.04–4.37) and 1.61 (additive, 95%CI: 1.00–2.59). Additionally, the minor allele for SNP rs3798220 showed increased death risk from colorectal cancer (CRC) in men (HR: 3.29, 95% CI:1.59 – 6.81) and decreased CRC incidence risk in women (HR: 0.46, 95%CI: 0.22–0.94). Minor allele carrier of any of 4SNPs could have risk of prostate cancer incidence (e.g., rs9365171 dominant, HR: 1.71, 95%CI: 1.06–2.77).ConclusionsNone of the 25 SNPs in the LPAL2-LPA region was found to be significantly associated with cancer incidence or mortality. Considering the possible association between SNPs in LPAL2-LPA region and colorectal, prostate and stomach cancer incidence or mortality, further analysis using different cohorts is warranted.     

Childhood brain tumours,early infections and immune stimulation: A pooled analysis of the ESCALE and ESTELLE case-control studies (SFCE,France)

BackgroundFew studies have investigated whether early infections and factors potentially related to early immune stimulation might be involved in the aetiology of childhood brain tumours (CBT). In this study, we investigated the associations between CBT with early day-care attendance, history of early common infections, atopic conditions (asthma/wheezing, eczema, allergic rhinitis), early farm residence/visits and contact with animals.MethodsWe pooled data from two nationwide French case-control studies, the ESCALE and ESTELLE studies. Children with a CBT diagnosed between 1 and 14 years of age were identified directly from the French National Registry of Childhood Cancers, while population controls were recruited from telephone subscribers. Odds-ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression adjusted for potential confounders.ResultsThe analyses included 469 cases and 2719 controls. We found no association between attending a day-care centre (OR: 0.9, 95%CI: 0.7–1.2) or having had repeated common infections (OR: 0.9, 95%CI: 0.7–1.2) in the first year of life and the risk of CBT. There was also no association with a history of asthma/wheezing (OR: 0.8, 95%CI: 0.56–1.1). Farm visits (OR: 0.6, 95%CI: 0.5–0.8) as well as contact with pets (OR: 0.8, 95%CI: 0.6–1.0) in the first year of life were inversely associated with CBT.ConclusionsOur findings suggest a protective effect of early farm visits and contact with pets, but not with other markers of early immune stimulation. This might be related to immune stimulation but needs further investigation.     

Modulation of Mutational Landscape in HER2-Positive Breast Cancer after Neoadjuvant Chemotherapy

IntroductionIn early-stage HER2 positive breast cancer (BC) patients, tumor response to neoadjuvant chemotherapy (NACT) predict survival outcomes. Patients achieving less than pathological complete response (pCR) have a worse prognosis, however, this group is heterogeneous. Nowadays limited data on predictive/prognostic biomarkers in patients with residual cancer disease are available.MethodsUsing next-generation sequencing technology, we evaluated a panel of 21 cancer genes in a group of HER2 positive BC patients with residual disease after NACT. A control group of patients who achieved the pCR was selected too. The BC mutational profile was analyzed on both the tumor diagnostic biopsy and matched residual disease.ResultsOverall, the detection rate of mutations was 79% in the No-pCR group versus 90% in the pCR cohort and 98% in the residual BC. The most mutated genes were TP53 and PIK3CA. No correlations between single gene mutations and survival outcomes were found. In no-pCR cohort, 52% of patients had different mutational profile after NACT, 69% of them had an increased in the number of mutated genes. Mutational profile changes from diagnostic biopsy to residual BC were a negative prognostic factor in term of relapse free survival: recurrence probability in different gene profile sub-group was 42% vs 0% in the same profile one (P = .019).ConclusionsTreatment selective pressure on tumor cells due to NACT changed the gene mutational profile in more than half of BC patient with residual tumor disease. Treatment-induced gene mutations significantly increase the risk of relapse. Profiling primary and residual BC is a major step in order to further personalized adjuvant treatment strategy.     

The validity of self-reported cancer in a population-based cohort compared to that in formally registered sources

BackgroundSelf-reported cancer has been validated with heterogeneous results across populations. The aim was to assess the validity of self-reported cancer in the Lifelines population-based cohort and to search for explanations for not reporting cancer.MethodsData from adult participants (n = 152,780) from Lifelines was linked to the Dutch-Nationwide pathology databank (PALGA), which has nearly 100% coverage of cancer diagnoses in the Netherlands and is considered as the gold standard for ascertainment of cancer diagnosis in this study. Sensitivity and positive predictive value (PPV) for self-reported cancers -reported as hand-written free text- were described. Logistic regressions analyses were performed to evaluate whether socio-demographic factors were associated with the presence of self-reported cancer when there was a diagnosis in PALGA.Results6611 (4.50%) participants had at least one self-reported diagnosis of cancer, where 9960 (6.97%) participants had at least one cancer diagnosis in PALGA. The sensitivity of self-reported cancer was 64.68% [95%CI:63.71–65.66], and 70.18% [95%CI:68.83–71.56] after excluding skin and cervical cancers. Skin and cervical cancers represented 61.24% of non-self-reported cancers. The overall PPV was 97.45% [95%CI:97.45–97.81], and 97.33% [95%CI:96.72–97.82] after the exclusion of skin and cervical cancers. Participants who did not self-report their cancer were more likely to be male, had longer time since diagnosis and lower educational level.ConclusionOverall, the reports of cancer in Lifelines have a high positive predictive value and moderate sensitivity. One third of the cancers were not reported, mainly skin and cervical cancers. Male participants, those with a lower educational level and those with longer time since diagnosis were less likely to self-report a diagnosed cancer.