HR Adj Research Articles

Female Infertility and Neurodevelopmental Disorders in Children: associations and evidence for familial confounding in Denmark.

Existing research suggests the impact of infertility on the risk of neurodevelopmental disorders in children, however, studies to date have failed to separate the impact of male and female infertility, often blurring the lines with proxies that encompass all forms of infertility. Moreover, while both health conditions co-occurring with infertility and genetic factors operating upstream have been suggested to influence the association between infertility and child outcomes, their roles and potential impact on observed associations remain unclear. The objectives of this study are to investigate the relationship between female infertility and autism in the child, differentiating it from the effects of male and the couple infertility; consider the role of various maternal and birth factors in the association; and examine the effects of shared familial confounders on the association. Danish population-based cohort study, including all singleton live births in Denmark 1998-2015, their parents and parents' siblings. The cohort was followed up until December 31, 2016. The exposure was a history of female infertility in the mother and the mother's sister. We examined four definitions of female infertility based on the ICD-10 codes derived from the Danish National Patient Register - any female infertility; specified female infertility; female exclusive infertility; and female or male infertility. The outcome was diagnosis of autism spectrum disorder (ASD) in the Danish Psychiatric Central Research Register or the national patient register. A multivariable Cox regression model was used to estimate the associations between female infertility and autism, accounting for child's sex, year of birth, maternal age, education level, chronic comorbidities, and pregnancy and birth complications. The effects of shared familial factors on the association were analyzed using exposure information from the child's maternal aunt. The cohort included 1,131,899 mother-child pairs, among which 18,374 children with ASD diagnosis. History of female infertility in the mother (all definitions) was significantly associated with autism in the child, with the association remaining robust after adjustment for covariates (HRadj=1.14 (95% CI, 1.03-1.26) for specified infertility). The diagnosis of infertility in a child's maternal aunt was also significantly linked to the child's autism risk, even after adjustment for maternal infertility (HRadj=1.10 (95% CI, 1.00-1.20). in This population-based birth cohort study, we found a slightly higher risk of autism in children born to mothers with a history of infertility, with the association remaining consistent across various definitions of female infertility and robust to adjustments for demographic, child, and maternal factors. The study suggests for the first time that shared familial factors, possibly both genetic and non-genetic, could be influencing both female infertility and the risk of autism in children, indicating a need for further investigation into these familial effects.

Immune Marker Spatial Distribution and Clinical Outcome after PD-1 Blockade in Mismatch Repair-deficient, Advanced Colorectal Carcinomas.

Targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) interaction has led to durable responses in fewer than half of patients with mismatch repair-deficient (MMR-d) advanced colorectal cancers. Immune contexture, including spatial distribution of immune cells in the tumor microenvironment (TME), may predict immunotherapy outcome. Immune contexture and spatial distribution, including cell-to-cell distance measurements, were analyzed by multiplex immunofluorescence (mIF) in primary colorectal cancers with d-MMR (N = 33) from patients treated with anti-PD-1 antibodies. By digital image analysis, density, ratio, intensity, and spatial distribution of PD-L1, PD-1, CD8, CD3, CD68, LAG3, TGFβR2, MHC-I, CD14, B2M, and pan-cytokeratin were computed. Feature selection was performed by regularized Cox regression with LASSO, and a proportional hazards model was fitted to predict progression-free survival (PFS). For predicting survival among patients with MMR-d advanced colorectal cancer receiving PD-1 blockade, cell-to-cell distance measurements, but not cell densities or ratios, achieved statistical significance univariately. By multivariable feature selection, only mean number of PD-1+ cells within 10 μm of a PD-L1+ cell was significantly predictive of PFS. Dichotomization of this variable revealed that those with high versus low values had significantly prolonged PFS [median not reached (>83 months) vs. 8.5 months (95% confidence interval (95% CI), 4.7-NR)] with a median PFS of 28.4 months for all patients [adjusted HR (HRadj) = 0.14; 95% CI, 0.04-0.56; P = 0.005]. Expression of PD-1 was observed on CD8+ T cells; PD-L1 on CD3+ and CD8+ T lymphocytes, macrophages (CD68+), and tumor cells. In d-MMR colorectal cancers, PD-1+ to PD-L1+ receptor to ligand proximity is a potential predictive biomarker for the effectiveness of PD-1 blockade.

Artificial intelligence–derived immune phenotypes for prediction of prognosis in patients with stage III colon cancer (NCCTG N0147; Alliance).

3542 Background: Solid tumors can be characterized by distinct immune phenotypes based on the level of T cell infiltration in the tumor microenvironment (TME) which may provide prognostic information and also inform strategies to restore the anti-tumor immune response. Immune phenotypes were determined using an artificial intelligence (AI) algorithm in digitized whole-slide images (WSI) of tumors with deficient (d) mismatch repair (MMR) vs proficient (p) MMR. Methods: Stage III colon carcinomas (N = 401; 393 met QC) from participants in a phase III trial of FOLFOX-based adjuvant chemotherapy were analyzed including all available tumors with dMMR (n = 196) and a randomly selected cohort of pMMR tumors (n = 195). Using an AI algorithm (Lunit SCOPE) previously trained on solid tumors, digitized tumors were categorized into three immune phenotypes based on epithelial and stromal TIL data-driven cutpoints in dMMR and pMMR (inflamed: TIL high in epithelium (> upper 25%); excluded: TIL high in stroma (>lower 25%), low in epithelium; and desert: TIL low in epithelium and stroma). Phenotypes were then examined in relationship to disease-free survival (DFS) using Kaplan-Meier methodology. Results: Of the 3 immune phenotypes in dMMR tumors, 25% were inflamed, 50% were immune-excluded, and 25% were immune-desert. Based on univariate results, multivariable modeling was performed incorporating immune phenotype in addition to age, histological grade, N stage, T stage, performance status, treatment arm, BRAF and KRAS status and identified immune phenotypes and N stage to be significantly associated with DFS. Among dMMR tumors, immune desert phenotype was associated with the poorest DFS (Desert: HR adj 1.95, 95%CI (1.01, 3.80); Excluded: HR adj 0.89, 95%CI (0.47, 1.69); Inflamed: ref; p:0.01). When compared to immune desert tumors, immune-excluded tumors had significantly better DFS (HR adj 0.49, 95%CI (0.27, 0.88), p:0.01). At a median follow-up of 60 months, 3-year DFS of patients with dMMR was 71.2% with Immune inflamed, 78.5% with Excluded, and 54.5% with Desert phenotypes. In contrast to dMMR, univariate analyses of data-driven cutpoints in pMMR tumors was not prognostic. Using a different data-driven cutpoint (15%), the revised immune phenotypes remained non-significant for DFS within pMMR tumors. Conclusions: Distinct AI-derived immune phenotypes in the TME were identified that were significantly prognostic in patients with dMMR, but not pMMR colon cancers. A data-driven immune-desert phenotype was identified in dMMR tumors that was associated with significantly poorer survival. Further investigation of the potential predictive utility of these phenotypes for immunotherapy are planned. Support: https://acknowledgments.alliancefound.org . ClinicalTrials.gov Identifier: NCT00079274 .

Pathological analysis of tumor microenvironmental features using deep learning to predict survival of colon carcinomas.

3527 Background: Advances in deep learning may improve the ability to evaluate and quantify pathological features in solid tumors to improve prediction of patient disease-free survival (DFS). We used an artificial intelligence (AI) algorithm to quantify morphological features in the tumor microenvironment of stage III colon cancers. Methods: We analyzed digitized stage III colon carcinomas (N = 402; 382 met QC) from participants in a phase III trial of FOLFOX-based adjuvant chemotherapy that included all available tumors with dMMR and a randomly selected cohort of pMMR tumors (median follow-up 60 months) [NCCTG N0147; Alliance for Clinical Trials in Oncology]. Fifteen morphological features were extracted using the QuantCRC algorithm that segments images into carcinoma (low-grade, high-grade, signet ring cell), stroma (immature, mature, and inflammatory), mucin, tumor/stroma ratio, tumor budding/poorly differentiated clusters (TB/PDC), necrosis, smooth muscle, fat, and tumor-infiltrating lymphocytes (TILs) and tumor area (mucin, epithelium and TB/PDC). Analysis of AI-derived features with clinical variables, molecular alterations ( BRAF/KRAS), and DFS were examined using Kaplan-Meier methodology and multivariable Cox regression. Results: Among the 15 AI-derived morphological features, the following differed significantly between dMMR (n = 191) and pMMR (n = 189) whereby dMMR tumors had lower mature stroma, but higher inflammatory stroma and tumor, higher tumor grade and increased mucin, TB/PDCs, signet ring cells, and TILs (all p< 0.05). Among dMMR tumors, multivariable analysis revealed that tumor area [mucin, epithelium and TB/PDC] (HR adj 0.45, 95%CI (0.24, 0.84), p:0.01, [Q2/3 vs Q1]) and N stage were the only significant and independent prognostic variables. Among pMMR tumors, multivariable analysis identified that tumor budding/poorly differentiated clusters (TB/PDCs) (HR adj 0.20, 95%CI (0.06, 0.61), p:0.01, [Q1 vs Q4]) was the strongest prognostic variable and the only morphological feature that was significantly associated with DFS along with age, N stage and T stage. Conclusions: Using AI, we can extract and quantify distinct morphological features in tumor sections that differ between dMMR and pMMR and multivariately, can significantly and robustly enhance prognostication within each MMR group. Among pMMR tumors, tumor budding/poorly differentiated clusters was the strongest predictor of DFS. Support: NIH U10CA180821, U10CA180882, U24CA196171, R01 CA210509 (to FAS). Study NCCTG N0147 received funds from Sanofi https://acknowledgments.alliancefound.org . ClinicalTrials.gov Identifier: NCT00079274 Key words Artificial Intelligence; Tumor Microenvironment; Colonic Neoplasms; Disease-free survival.

Impact of malnutrition on postoperative outcomes of patients undergoing gastrectomy for gastric cancer: A nationwide analysis between 2012 and 2017.

315 Background: Gastrectomy offers a curative treatment option for non-metastatic gastric cancers (GC). Unfortunately, cancer associated malnutrition is a common and potentially actionable problem in GC patients. In this nationwide study, we analyzed the impact of malnutrition on outcomes of patients undergoing gastrectomy for GC. Methods: The Nationwide inpatient Sample database (NIS) was used to identify patients who underwent gastrectomy for gastric cancer from 2012-2017 using ICD 9 and ICD 10 codes. The population was then divided into patients with or without PEM (Protein energy malnutrition) to compare their outcomes. Univariate and Multivariable logistic and linear regression models were used to analyze mortality and healthcare resource utilization. Results: Of the 6,620 patients identified, 4,607 (69.6%) patients were ≥ 60 years old and 3,972 (60%) were males. Majority were White (49.1%) followed by Asians (20.3%). 2,052 (31%) patients were malnourished. Patients with PEM had higher rates of sepsis [adjusted Odds ratio (aOR) 3.6(2.4-5.4), p =0.000], shock [aOR 2.9(1.9-4.5), p =0.000], acute kidney injury [aOR 2.1(1.5-2.9), P<0.001], ICU admissions [ aOR 1.9(1.3-2.9), p =0.001], and higher post operative mortality [aOR 2.5 (1.5-4.3), p =0.001]. Mean Length of stay was longer in PEM patients as compared to non-PEM patients (16.2 vs 9.4 days). On survival analysis, overall survival (OS) was significantly worse for patients with PEM undergoing gastrectomy [HR adj: 1.14 (p=0.04)]. A comparison of these outcomes has been detailed in the table. Conclusions: In this analysis, we highlight the importance of nutrition for gastric cancer patients undergoing gastrectomy. Ensuring adequate nutritional status prior to surgery can improve patient outcomes and decrease health care costs.[Table: see text]

Incidence and risk factors associated with falls among women with breast cancer during taxane-based chemotherapy.

This study aims to evaluate the falling incidence density and examine the potential risk factors associated with falling among women with breast cancer during taxane-based chemotherapy. One hundred and twenty-three women with breast cancer participated in this study. The fall incidence density, taxane-induced peripheral neuropathy (TIPN) symptoms, and physical performance tests were evaluated at five time points throughout chemotherapy treatment. A fall diary was used to record fall incidence during treatment. The fall incidence density was calculated by dividing the number of first fall occurrences by person-time at risk. The risk factors associated with time to first fall were analyzed using the Cox proportional hazards model. The Kaplan-Meier curve illustrated the probability of survival from a fall during chemotherapy treatment. Over the course of treatment, 29 (23.58%) participants reported falls. The fall incidence density was 3 per 1000 person-day. This study discovered a significant link between age (adjusted HR (HRadj) = 1.07; 95% CI: 1.02-1.13) and BMI (HRadj = 1.11; 95% CI: 1.02-1.21) and falling. Women with breast cancer could fall for the first time at any time after starting chemotherapy until the end of the follow-up period. Furthermore, time to first fall was associated with age and BMI. Early detection of falling in women with breast cancer, particularly among older persons and those with a high BMI, may be essential to preventing falls.

Transcatheter aortic valve implantation in patients with rheumatic aortic stenosis

BackgroundRheumatic heart disease (RHD) accounts for the highest number of deaths from valvular heart disease globally. Yet, rheumatic aortic stenosis (AS) was excluded from landmark studies investigating the safety and...

Significance of the dissection of common hepatic arterial lymph nodes in patients with oesophageal carcinoma: a multicentre retrospective study

ObjectivesTo explore the significance of intraoperative common hepatic arterial lymph node dissection in patients with ooesophageal squamous carcinoma (ESCC) without coeliac trunk lymph node metastasis indicated by abdominal enhanced CT.MethodsPatients...

Association between distance to tertiary hospital and cardiovascular outcomes in coronary artery disease patients

Abstract Background The impact of distance from residence to Tertiary Referral Hospital and cardiovascular (CV) outcomes in patients with coronary artery disease (CAD) is unknow. Despite longer travel distances hinder access to healthcare and may worsen CV outcomes, we hypothesize that Mediterranean lifestyle and behaviors in distant rural areas may be associated with a reduced risk of CV death and events. Purpose To investigate the association between travel distance to Tertiary Hospital and mid-term cardiovascular outcomes in a population of CAD patients in Southern Spain. Methods Retrospective study including all patients discharged after percutaneous coronary intervention (PCI) at a high-volume center in Southern Spain during 2018. Those belonging to another healthcare area were excluded. One-way driving distances from residence to hospital were computed using Google Maps Distance Matrix API with R package “gmapsdistance”. Patients were stratified into tertiles according to travel distance (short, STD; intermediate, ITD; and long, LTD). Kaplan-Meier (KM) and Multivariable Cox regression (adjusted for age, sex, atrial fibrillation, cancer history, prior revascularization and clinical presentation) were used to assess the impact of travel distance on CV death and a composite outcome of MACE (Myocardial Infarction, unplanned PCI and CV death). Results Of 1005 patients discharged after PCI during the study period, 966 met the selection criteria. Flowchart and baseline characteristics by distance groups are presented in Figure 1. Median travel distance tertiles were 6.1 (STD), 41.7 (ITD) and 78.4 (LTD). During a median follow-up of 31 (IQR 28–35) months, 50 cardiovascular deaths [STD 27 (8.4%), ITD 13 (4%), LTD 10 (3.1%), p=0.006)] and 63 MACE occurred [STD 45 (13.9%), ITD 37 (11.5%), LTD 26 (8.1%), p=0.060)]. KM curves for the three distance groups are shown in Figure 2. In univariable and multivariable Cox models, longer travel distances were associated with better outcomes, as for every 10 Km increase, there was a 11% and 7% decrease in the hazards of CV death (HR adj: 0.89, CI 0.82–0.98, p=0.029) and of MACE (HR adj: 0.93, CI 0.87–0.99, p=0.025), respectively. Conclusion Travel distance was inversely associated with CV events in a population of CAD patients in Southern Spain. Patients in the first tertile of distance had a higher rate of CV death. Multicenter studies involving other Mediterranean regions are needed to confirm these findings and to look for explanations. Funding Acknowledgement Type of funding sources: None. Flowchart and baseline characteristicsSurvival curves by distance groups

Comparison of clinical characteristics and survival outcomes in patients with malignant peritoneal and pleural mesothelioma.

460 Background: Malignant peritoneal mesothelioma (MPeM) is an aggressive tumor strongly associated with asbestos exposure. We analyzed a large nationwide database to better understand the differences in the demographic and clinical patterns of MPeM and pleural mesothelioma (MPlM). Methods: The National Cancer Database (NCDB) 2010-15 was queried to identify all patients diagnosed with MpeM and MPlM. The demographic and clinical characteristics were compared using Pearson’s chi-square test. Kaplan-Meier method and associated log-rank test were used to compare the unadjusted overall survival of the two malignant mesothelioma (MM) sites. A multivariate Cox regression analysis was done to determine survival difference between the 2 groups. Results: Of the 8,668 patients included in the study, 1,081 (12.5%) had MPeM and 7,587 (87.5%) had MPlM. The MPeM cohort was younger (median age at diagnosis 61 vs 73 years), predominantly females (45.7% vs 23.5%), had a lower Charlson Deyo Comorbidity Score ( > = 1: 24.5% vs 32.1%), had higher percentage of uninsured patients (4% vs 2.2%), was less likely to be treated at a community or comprehensive community center (36.1% vs 47.3%) and had lower proportion of sarcomatous or biphasic histology (9.3% vs 22.4%) compared to MPlM cohort. The MPeM cohort was more likely to receive surgery (56.5% vs 28%) and chemotherapy (68.4% vs 54.5%) but less likely to receive radiation (0.8% vs 11%). The p-value was < 0.001 for all comparisons. The median OS was 19.7 and 9.7 months for patients with MPeM and MPlM, respectively (log-rank p value < 0.001). On multivariate Cox proportional hazards analysis, OS was significantly worse for MPlP compared to MPeP [HR adj: 1.19, 95% confidence interval (CI): 1.09-1.30 (p < 0.001)]. Conclusions: There is paucity of data about clinical characteristics and outcomes of MPeM. Much of our current knowledge about MPeM is extrapolated from MPlM. Our study suggests significant differences in prognostic factors and survival outcomes between the two sites.

Cardiovascular and skeletal safety of zoledronic acid in osteoporosis observational, matched cohort study using Danish and Swedish health registries.

This observational safety study used national registers to compare the real world cardiovascular and skeletal safety of zoledronic acid (ZA) against oral bisphosphonates (oBP) and untreated population controls. Propensity score matched cohort study in Sweden and Denmark. Matched cohort 1 included 8739 ZA users and 25,577 oBP users while matched cohort 2 included 8731 ZA users and 25,924 untreated subjects. In comparison to oBP users, heart failure risk was higher in ZA users, with an adjusted HR (adj) (95%CI) of 1.17 (1.04;1.32) and a higher all-cause mortality (adj HR 1.24 (1.15; 1.34)), however, there was no increased risk of cardiovascular mortality. In the comparison to untreated subjects, ZA users showed a higher risk of atrial fibrillation, adj HR 1.18 (1.05;1.32), arrhythmias adj HR 1.18 (1.06;1.31), and heart failure, adj HR 1.38 (1.24;1.54). Cardiovascular mortality was lower in ZA users (adj HR 0.87 (0.77; 0.98)) and risk of adverse skeletal outcomes was significantly higher, reflecting more severe osteoporosis in these patients. There was no association of cardiovascular risk with increasing exposure time. Sensitivity analyses produced similar findings with no substantial changes in event rates. We noted an increased risk of heart failure, fractures and death among ZA users compared with oral BP. The risk of cardiovascular and skeletal outcomes was higher in ZA users than in matched population controls, but there was no increase in cardiovascular mortality in ZA users compared to oral BP or untreated controls. Despite propensity score matching, it is not possible to determine with certainty whether the increased risk of cardiovascular outcomes is consistent with a true drug effect or higher baseline risk in patients who begin ZA treatment.

A Prospective Analysis of Red and Processed Meat Consumption and Risk of Colorectal Cancer in Women.

Red and processed meats have been implicated as risk factors in the development of colorectal cancer in U.S. women, but associations with cooking practices are less well established. Data are from the Sister Study, a cohort of women ages 35 to 74 years from the United States and Puerto Rico who have a sister diagnosed with breast cancer. Red and processed meat consumption, meat cooking practices, and intake of common meat products were collected at baseline using self-administered questionnaires (N = 48,704). Multivariable HRs (HRadj) and 95% confidence intervals (95% CI) were estimated. During a median 8.7 years' follow-up (range <1-12.7 years), 216 colorectal cancer cases were diagnosed. In categorical analyses, an increased risk of colorectal cancer was seen in the highest quartile of processed meat consumption compared with the lowest [HRadj = 1.52 (95% CI, 1.01-2.30); P trend = 0.02], and for specific meat products, including breakfast sausages [HRadj = 1.85 (95% CI, 1.30-2.64)] and bacon [HRadj = 1.46 (95% CI, 1.01-2.11)]. The HRadj for the highest quartile of red meat consumption was 1.04 (95% CI, 0.68-1.60), and little evidence of association was observed for cooking practices or doneness of red meat. We observed positive associations with specific red meat products when cooking methods were considered, for example, grilled/barbequed steaks [HRadj = 2.23 (95% CI, 1.20-4.14)] and hamburgers [HRadj = 1.98 (95% CI, 1.00-3.91)]. Higher reported daily intake of processed meats and consumption of barbecued/grilled red meat products were associated with increased risk of colorectal cancer in women. Variability in colorectal risk risk by meat type and cooking method should be considered when evaluating meat consumption.

Postoperative venous thromboembolism and mortality in patients with pancreatic surgery.

Pancreatic cancer is strongly associated with thrombosis. We investigated early postoperative venous thromboembolism (PVTE) mortality among patients with pancreatic surgery and compared outcomes in adenocarcinoma pancreatic cancer (ACPC) to non-adenocarcinoma pancreatic neoplasm (NACPN). We analyzed a prospectively collected database of patients who underwent pancreatic cancer or neoplasm-related surgery. As NACPN is underrepresented in other studies, we selected NACPN patients and a random sample of ACPC patients. PVTEwas defined as VTE occurring within 3 months of surgical intervention. Statistical analysis was performed using Cox proportional hazards regression. A total of 441 pancreatic surgery patients were included, with 331 ACPC and 110 NACPN. Median follow-up was 449 days during which 90 (20.4%) patients developed VTE. PVTE occurred in 53 (12.0%) patients, including 41 (12.4%) ACPC patients and 12 (10.9%) NACPN patients. Those with PVTE had 60% higher mortality rate. A multivariable analysis found that PVTE is an independent predictor of increased mortality (HR Adj, 1.6; 95% CI, 1.1-2.2; P < .01). The mortality impact was not consistent between ACPC (HR, 3.2; 95% CI, 1.3-7.9) and NACPN groups (HR, 1.3;95% CI, 0.9-1.8). Postoperative venous thromboembolism is an independent predictor of increased mortality in pancreatic surgery, specifically in adenocarcinoma pancreatic cancer surgery.

Postmenopausal breast cancer and occupational exposure to chemicals.

Objectives The aim of this study was to investigate if exposure to chemicals in the workplace was associated with an increased risk of postmenopausal breast cancer. Methods The study comprised women born 1923-1950 living in Malmö city, Sweden, 1991-1996, and enrolled for a prospective population cohort study. Occupational exposure to various chemicals was assessed from job-exposure matrices. An extensive set of individual data on hormonal breast cancer risk factors were collected via a baseline questionnaire and used for confounding control. First time diagnoses of invasive breast cancer were identified through the Swedish Cancer Registry until end of follow-up on 31 December 2013. Results Of 16 084 women, 1011 were diagnosed with breast cancer. Women exposed to chemicals in their occupational environment had a statistically significant increased risk [adjusted hazard ratio (HR adj) 1.26, 95% confidence interval (CI) 1.02-1.54] of breast cancer, and the risk correlated with duration of exposure. Investigation of risk in association with specific chemicals showed a non-significantly elevated risk after exposure to organic solvents. More than ten years of exposure to diesel exhaust was associated with an increased risk (HR adj1.69, 95% CI 1.01-2.82). Occupational chemical exposures account for 2% of the breast cancer cases in this population. Conclusions Occupational exposure to chemicals in general was associated with an elevated risk of breast cancer. A slight elevation of risk was seen after exposure to organic solvents. A statistically significant elevation of risk after >10 years of exposure to diesel exhaust was an unexpected finding.

Coffee Is Associated With Lower Breast Tumor Insulin-Like Growth Factor Receptor 1 Levels in Normal-Weight Patients and Improved Prognosis Following Tamoxifen or Radiotherapy Treatment.

Coffee is associated with decreased breast cancer risk, but the impact of body mass index (BMI) in combination with coffee consumption on prognosis is unclear. The suppressive effect of coffee constituents on the insulin-like growth factor receptor 1 (IGF1R) levels in breast cancer cells may play a role. The aim was to investigate the prognostic impact of coffee consumption and possible associations with tumor-specific IGF1R protein expression and BMI in a population-based cohort in Sweden, comprising 1,014 primary breast cancer patients without pretreatment enrolled 2002–2012 and followed for up to 13 years. Patients with higher coffee consumption had lower tumor IGF1R levels (P = 0.025), but only among the normal-weight patients (P = 0.005). Coffee did not impact the recurrence-risk overall. However, tamoxifen-treated patients with ER+ tumors drinking ≥ 2 cups of coffee/day had lower recurrence-risk [adjusted HR (HRadj) 0.57, 95% CI, 0.34–0.97] compared with patients with lower intake, although only among normal-weight patients (HRadj 0.37, 95% CI: 0.17–0.78; Pinteraction = 0.039). Similarly, coffee consumption ≥ 2 cups/day was associated with significantly lower recurrence-risk among the 640 radiotherapy-treated patients irrespective of BMI (HRadj 0.59, 95% CI 0.36–0.98) and in the 296 normal-weight patients (HRadj 0.36, 95% CI 0.17–0.76) but not in the 329 overweight or obese patients (HRadj 0.88, 95% CI 0.42–1.82) although the interaction was not significant (Pinteraction = 0.093). In conclusion, coffee consumption was negatively associated with tumor-specific IGF1R levels only among normal-weight patients. Though, IGF1R did not explain the association between coffee intake and improved prognosis among normal-weight tamoxifen- or radiotherapy-treated patients. Studies of IGF1R-targeting therapies may benefit from taking BMI and coffee consumption into account.

Association of serum cotinine levels and lung cancer mortality in non-smokers.

This study was performed to quantify the association between mortality and known and unknown secondhand smoke (SHS) exposure as measured by cotinine levels in non-smokers. Data collected from 1999 to 2010 in the National Health and Nutrition Examination Survey (NHANES) were linked to the National Death Index. Self-reported non-smokers aged ≥20 years ( N = 20 175) were studied. Serum cotinine was measured at recruitment; non-smokers were those with cotinine below the reported race-specific cut-off points (5.92, 4.85 and 0.84ng/ml for non-Hispanic blacks, non-Hispanic whites and Mexican Americans, and 3.08ng/ml for all other groups). Serum cotinine levels were significantly associated with overall survival (HR adj 1.17, 95% CI: 1.13-1.22 per natural-log unit change in cotinine), death for all medical causes, lung cancer, all cancers and heart diseases, after adjustment for gender, race/ethnicity, body mass index, smoking history and education. Similar results were observed when non-smokers reporting no SHS exposure at home or work were analyzed. There was a statistically significant trend in years of life lost (YLL), adjusted for confounders, across cotinine categories both in non-smokers (YLL adj : 5.6, 6.4, 6.8, 7.5; P for trend < 0.0001) and non-smokers reporting no SHS exposure (YLL adj : 5.5, 6.1, 6.3, 6.7; P for trend = 0.002). Serum cotinine levels identify SHS-attributable mortality in subjects who would have otherwise been overlooked by questionnaire data, providing further evidence that the economic toll of SHS may be substantially higher than what was reported based on questionnaires.

Presence of minor and major mental health impairment in adolescence and death from suicide and unintentional injuries/accidents in men: a national longitudinal cohort study

ObjectiveTo examine the association between minor and major mental health impairment in late adolescence and death from suicide and unintentional injuries/accidents in men.MethodsIn Norway, all men attend a compulsory military...

Sickness absence and permanent work disability in relation to upper- and lower-body pain and occupational mechanical and psychosocial exposures.

The aim of this study was to examine if combined pain (pain in the upper and lower body), high occupational mechanical exposures, and job strain predict sickness absence and permanent work disability, particularly if co-occurring. This longitudinal study was based on the musculoskeletal research database at the Danish Ramazzini Centre. We linked baseline information from 2001-2004 on musculoskeletal pain, job titles, and covariates with register information on sickness absence and permanent work disability. Mechanical and psychosocial exposure estimates were obtained from job exposure matrices. We used multivariable Cox regression. The study included 25 292 persons. Compared to low occupational mechanical exposures and no pain, low mechanical exposures and combined pain showed an adjusted hazard ratio (HR adj) of 1.81 [95% confidence interval (95% CI) 1.58-2.08], while high mechanical exposures and combined pain showed HR adj3.71 (95% CI 3.24-4.25) for sickness absence. The corresponding values for permanent work disability were 3.35 (95% CI 1.74-6.45) and 4.59 (95% CI 2.36-8.94). Job strain showed an association with sickness absence [HR adj1.24 (95% CI 1.10-1.39)], while low social support was associated with both sickness absence and permanent work disability [HR adj1.30 (95% CI 1.19-1.41) and 2.19 (95% CI 1.41-3.41), respectively]. Combined pain in the upper and lower body was associated with sickness absence and permanent work disability, and high occupational mechanical exposures further increased the risk. Job strain showed a modest association with sickness absence, while low social support at work was associated with both outcomes, especially permanent work disability.

Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFα inhibitors and rituximab

ObjectivesTo investigate the impact of disease activity, the course of the disease, its treatment over time, comorbidities and traditional risk factors on survival.MethodsData of the German biologics register RABBIT were...

Sex Differences in the Treatment and Outcome of Patients with Acute Coronary Syndrome After Percutaneous Coronary Intervention: A Population-Based Study

This study was performed to assess the influence of sex on drug therapy and long-term outcomes in acute coronary syndrome (ACS) patients who underwent percutaneous coronary intervention (PCI). This is a retrospective cohort study of ACS patients who underwent PCI [women (n=8,884) and men (n=23,937)] between January 1, 2006, and December 31, 2007, with at least a 1-year follow-up, based on the National Health Insurance Research Database in Taiwan. Propensity score was used to identify a 1:1 matched cohort (n=17,768) for multivariable adjustment. The influence of sex on drug therapy and outcomes was examined by multivariate logistic regression and multivariable Cox proportional hazards regression. Female patients had an 18% and 12% lower likelihood of receiving aspirin (adjusted odds ratio [OR(adj)]=0.82, 95% confidence interval [CI]=0.77-0.88) and clopidogrel (OR(adj)=0.88, 95% CI=0.81-0.95), respectively, than male patients but had a 17% and 22% higher likelihood of receiving beta-blockers (OR(adj)=1.17, 95% CI=1.10-1.24) and statins (OR(adj)=1.22, 95% CI=1.14-1.29), respectively, than male patients in the matched cohort. The adjusted hazard ratio (HR(adj)) of rehospitalization for revascularization in women was 0.84 (95% CI=0.79-0.90) compared with men after at least a 1-year follow-up in the matched cohort. Female patients with ACS who underwent PCI were less likely to receive aspirin and clopidogrel but were more likely to receive beta-blockers and statins than male patients. Male sex was associated with a higher risk of rehospitalization for revascularization than female sex.