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Funding Acknowledgements Type of funding sources: None. Introduction The risk of a severe course of COVID-19 infection increases with age and body weight, is higher in men and in the chronically ill. Patients with cardiovascular diseases, including heart failure (HF), are at risk of severe (various) infections with a higher risk of complications leading to death. The current guidelines of the European Society of Cardiology recommend prophylactic vaccinations in this group of patients against both SARS-COV-2 and other pathogens. Purpose The aim of the study was to analyze the vaccination coverage against pneumococcus, influenza and COVID-19, as well as to assess the incidence and course of COVID-19 infections in the population of patients with HF hospitalized after an episode of acute heart failure (AHF) between 03.2021 and 03.2022. Methods As a part of the prospective Acute Heart Failure Registry (OP-AHF), in the period from 06.2019, data were obtained from 122 patients hospitalized in the ICCU. Inclusion criteria were hospitalization for AHF and the need to use at least one of: intravenous diuretics, catecholamines or mechanical circulatory support. Data on vaccinations against COVID-19 (a/C19), influenza (a/I) and pneumococcus (a/P), as well as COVID-19 incidence, were collected in a 12-month follow-up from 90 patients. Results COVID-19 infection occurred in 27% of patients (24 of 90 patients). In the studied population, fewer cases of the disease occurred in patients over 65 years of age compared to the younger ones (20% vs 36%, p = 0.08) and a significant proportion of them were male (96% vs 4% women).Among patients with a history of COVID-19 infection [C19(+)] compared to patients without infection [C19(-)], slightly more patients were active smokers (42% vs 39%, p = 0.85), more had diabetes (42% vs 27%, p = 0.19) and hypertriglyceridemia (25% vs 8%, p = 0.03). Patients C19(+) had a higher BMI (34 vs 29 in C19(-), p = 0.01) and lower left ventricle ejection fraction at discharge (33 vs 40, p = 0.18). The most common etiologies of HF in C19(+) patients were ischemic (10 of 24 patients, 42%) and valvular (10 of 24 patients, 42%). The vaccination coverage a/C19 in the whole group of patients was 69% (62 out of 90), of which a higher percentage of vaccinations was in patients over 65 years of age (75% vs 62%, p = 0.19). The a/I vaccination rate was 11%, with a slightly lower percentage in patients over 65 years of age (10% vs 13%, p = 0.65). Among the studied patients, 58% (52 of 90) were vaccinated with both a/C19 and a/I. However, all patients vaccinated a/I were also vaccinated a/C19. None of the examined patients was vaccinated a/P. Conclusion The COVID-19 pandemic and the widely available information on cardiovascular complications resulted in an increase in vaccination among a group of patients at high risk for complications. However, there is still unsufficient awareness of the need for influenza and pneumococcal vaccination as a prevention of serious post-infection complications.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by a grant from the Institute of Medical Sciences, University of Opole, Poland. Background Acute heart failure (AHF) is a life-threatening multifaceted clinical condition requiring intensive and expensive treatment. Earlier studies highlighted the difference in characteristics and prognosis of new onset AHF (NO- AHF) and acute decompensated heart failure (ADHF). Protein Klotho and FGF23 could be attractive tools in the evaluation of patients with AHF. GDF-15 is a recognized marker of the risk of death and complications, including bleeding in many cardiovascular diseases. Aim The aim of the study was to compare selected biomarkers (Protein Klotho, FGF-23, GDF-15) with clinical characteristics and 12-month outcomes of patients with NO-AHF and ADHF. Methods As part of the prospective Acute Heart Failure Registry (OP-AHF), data from 112 patients hospitalized in Intensive Cardiac Care Unit (ICCU) were collected from June 2019. Inclusion criteria were: hospitalization for AHF and the use of at least one of: intravenous diuretics, catecholamines or mechanical circulatory support. Blood samples were collected on admission, at discharge as well as at the 30-day. Patients were than follow-up for one year. Results Patients with NO-AHF constituted 46% of the study group (52 out of 112) and compared to patients with ADHF they were more often aged under 65 years (44% vs. 30%, p=0.12), better educated (25% vs. 8%, p=0.03), less frequently with diabetes (31% vs. 43%, p=0.17), hypertension (58% vs. 83%, p=0.03), and prior myocardial infarction (19% vs. 45%, p=0.004). In both groups there were more men (69% vs. 80%,p=0.19) and ischemic etiology of heart failure were more frequent (33% vs. 51%, p=0.42) in NO-AHF and ADHF, respectively. Left ventricular ejection fraction (LVEF) was insignificantly higher in patients with NO-AHF on admission (30% vs. 26%, p=0.6) and at discharge (35% vs. 30%, p=0.27).Only patient with NO-AHF improved LVEF at the 12- month follow–up (50% vs. 35%, p=0,003).It was no signifcant differences between median value of Klotho protein in both groups at admission, discharge and 30–day follow up visit. We observed significant reduction in FGF-23 and GDF-16 at tree time points (Table 1). 12-month mortality in patients with NO-AHF was insignificantly lower (17% vs. 28% in ADHF HR=1,7 (95% Cl=0.25-1.18)),also after correction for age, sex and ,LVEF- 20% vs. 25%, respectively, p=0.58; HR=1,26 (0.3-1.8). In the Cox multivariate model, the risk of death was presented as hazard ratio (HR) and was highest for GDF-15 in both groups (Table2). Conclusion Patients with the NO- AHF have different clinical profile than patients with acute decompensated heart failure with a tendency to lower 12-month mortality. There were no significant differences in the median value of Klotho protein in both groups. Reduction of the FGF-23 during hospitalization can serve as a marker of AHF compensation, thus FGF-23 could be a valuable tool for assessing response to treatment. GDF-15 seems to be the strongest predictor of death in both groups of AHF.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant from the Institute of Medical Sciences, University of Opole, Poland. Introduction Acute heart failure (AHF) is one of the most common causes of hospitalizations and deaths in the developed countries. Advances in the diagnosis and treatment of heart diseases and the increase of life expectancy have resulted in the fact that we are increasingly hospitalizing elderly patients, often with multi-diseases, which is a significant challenge for health care. Purpose The aim of the study was to analyze the clinical characteristics, treatment and outcomes of patients with AHF over 65 years of age compared to the younger ones. Methods As part of the prospective Acute Heart Failure Registry (OP-AHF), data from 122 patients hospitalized in ICCU were collected from June 2019. Inclusion criteria were hospitalization for AHF and the use of at least one of: intravenous diuretics, catecholamines or mechanical circulatory support. All patients were then followed for 12 months. Results Patients older than 65 years constituted 64% of patients with AHF (78 out of 122 people). Compared to younger ones, they were more often males (36% vs 14%, p = 0.01), smokers (85% vs 55%, p Conclusions Elderly patients >65 years of age have higher risk of death within 12 months after an episode of acute heart failure than younger ones. However, despite greater burden of comorbidities, they are not more often rehospitalized due to cardiovascular reasons. Fig. Actual and adjusted for age, sex, LVEF and NT-pro BNP 12- month survival of patient over 65 years of age

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by a grant from the Institute of Medical Sciences, Univeristy of Opole, Poland Background Klotho is an antiaging protein with pleiotropic actions that exerts organ protection. There is evidence that Klotho protein acts as a human aging-suppression molecule and correlates with life span, coronary artery disease, atherosclerosis, and osteoporosis. In laboratory models of damage, an increased expression of Klotho protein in human cardiac myocytes and release of Klotho protein into the extracellular space suggests a potential compensatory and cardioprotective effect. The aim of the present study was to assess changes of Klotho protein levels during an episode of acute heart failure (AHF) as well as its long-term prognostic utility in population of AHF patients compared to other biomarkers. Methods We analysed 112 consecutive patients admitted to ICCU between June 2019 and January 2021 due to hight-risk AHF. Blood samples were collected on admission, at discharge as well as at the 30-day. Patients were then followed-up for all-cause mortality and rehospitalizations due to heart failure. Results Patients (N=112; median age 68 years, 75% men, median left ventricular ejection fraction 30% [IQR 20-38%]) had median admission levels of Klotho protein = 670 pg/ml [501-851], FGF-23 = 1278 pg/ml [283-4429], NT-proBNP = 5361 ng/l [3019-13182], and GDF-15 = 4582 pg/ml [3028-9081]. Klotho protein decreased by 19% from admission to discharge and then increased by 13% from discharge to 30-day (P Conclusion The levels of Klotho protein in patients with AHF are higher compared to healthy population and they show dynamics dependent on the clinical state what indicates the utility of Klotho as a typical biomarker. Lower values of Klotho protein in AHF patients are associated with higher mortality which may suggests protective effect of higher Klotho levels.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant from the Institute of Medical Sciences, Univeristy of Opole, Poland Background FGF-23 is a well-known marker for phosphate metabolism and independent risk marker for cardiovascular mortality. FGF-23 can stimulate pro-fibrotic factors in myocytes and finally promote cardiac fibrosis. There is also evidence that FGF-23 levels can predict the response to the therapies in acute heart failure (AHF) patients. The aim of the study was to assess whether FGF-23 level change during an episode of AHF as well as its long-term prognostic utility in population of AHF patients. Additionally, we also aimed to evaluate correlations of FGF-23 levels with the response to therapy. Methods We analysed 112 consecutive patients admitted to ICCU between June 2019 and January 2021 due to high-risk AHF. Guidelines guided therapy of heart failure was introduced. Blood samples were collected on admission, at discharge as well as at the 30-day. Patients were then followed-up for all-cause mortality and rehospitalisations due to heart failure. Results Patients (N=112; median age 68 years, 75% men, median left ventricular ejection fraction 30% [IQR 20-38%]) had median admission levels of FGF-23 = 1278 pg/ml [283-4429], Klotho protein = 670 pg/ml [501-851], NT-proBNP = 5361 ng/l [3019-13182], and GDF-15 = 4582 pg/ml [3028-9081]. FGF-23 decreased by 70% from admission to discharge (P Conclusion Levels of FGF-23 on admission in patients with AHF are significantly elevated and lowers during appropriate effective therapy what indicates the utility of FGF-23 as a typical biomarker. High values of FGF-23 are associated with higher 6-month mortality. Reduction of the FGF-23 during hospitalization can serve as a marker of AHF compensation, thus FGF-23 could be a valuable tool for assessing response to treatment.

Introduction Running the marathon may be followed by post-exercise “cardiac fatigue” manifesting as transient right ventricular (RV) systolic and diastolic impairment. It is the thin-walled RV that is predominantly affected by the exercise-induced overload, with little if any, impact on the left ventricle (LV) [1]. The 2-D echocardiographic (ECHO) assessment of RV is challenging and may be incomplete since conventional measures reflect only the longitudinal motion (displacement of tricuspid annulus towards the apex) [2]. The mechanics of RV can be separated into two more components, anteroposterior (stretching RV wall by contracting septum) and radial (internal relocation of the RV free wall) [2]. The significance and relative contribution of motion components to global RV function may not be equal, and their interplay can vary depending on concomitant diseases [3]. Purpose We aimed to analyse the pathophysiology of RV exhaustion associated with a marathon run with 3-D ECHO, which allows precise estimation of all RV motion components and their contribution to RV global function. Methods The study included 34 healthy males (mean age of 40±8 years), amateurs, who finished the marathon in northern Poland. The 3-D ECHO was performed 2 weeks before (stage I), at the marathon finish line (stage II) and 2 weeks after the competition (stage III). According to the ReVISION method (Right ventricular separate wall motion quantification) the global RV function was decomposed to longitudinal (L_), anteroposterior (AP_) and radial (R_) [3]. By dividing componential ejection fractions (EF) with global RV EF, L_EFi, AP_EFi, and R_EFi ratios were obtained. Results When comparing results from stage I and III there were no significant differences (Table 1). The analysis revealed post-run decline in RV EF with no changes in LV EF. The quantification of the RV motion components showed reduction in R_EF after the marathon with no changes in AP_EF or L_EF. The relative contribution of componential EF to global RV function were permanent and was not influenced by the competition. Conclusions Marathon run resulted in transient RV dysfunction arising from decline in radial shortening. Noteworthy, the componential interplay between wall motion compartments was preserved in pre- and post-run assessment. The ReVISION method enables the comprehensive analysis of the competing RV. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): The study was supported by the project POWR.03.05.00-00-z082/18 co-financed by the European Union through the European Social Fund under the Operational Programme Knowledge Education Development 2014–2020

Introduction The long-term endurance training is associated with an increased risk of both right (RV) and left ventricular (LV) dysfunction. However, males and females exhibit different cardiac adaptation to exercise. The aim of our study was to evaluate three-dimensional (3D) echocardiographic parameters of ventricular function before and after the marathon in male and female amateur athletes, and compare them between sexes. Methods The study included 40 male (39±8 years) and 27 female (40±7 years) amateur athletes. Echocardiography was performed 2–3 weeks before (Stage 1) and immediately after (Stage 2) the marathon run. RV and LV area and function were assessed using standard and 3D echocardiography. Results After the marathon, there was a significant increase in the RV size (indexed RV end-diastolic volume, 51.1±12.0 vs. 59.0±9.1 ml/m2, p=0.003 in males; 48.8±11.0 vs. 60.0±11.1 ml/m2, p Conclusions In both male and female amateur athletes, marathon running resulted in RV dilatation and reduction in function, with concomitant decrease in LV dimensions. However, 3D analysis revealed that strenuous exercise alters LV systolic function to a greater degree in men relative to women. Funding Acknowledgement Type of funding sources: None.

Background/Introduction Postprocedural radial artery occlusion (RAO) is still the Achilles' heel of conventional transradial approach (cTRA) as it limits its reuse for future coronary procedures. A distal transradial access (dTRA) via the anatomical snuffbox has been proposed as an alternative. It is hypothesised that dTRA may reduce the incidence of RAO. Purpose To assess whether routine dTRA reduce the risk of RAO in consecutive patients undergoing coronary angiography or intervention, in comparison with cTRA. Methods Out of 465 subjects, 400 patients were included in a prospective, single-center, randomized (1:1) study. Hemodynamic instability, ST-elevation myocardial infarction, forearm artery occlusion or prior radial access failure were the exclusion criteria. Ultrasound-guided follow-up was obtained after 1 day and 60 days to evaluate the incidence of acute and late RAO. Results Baseline characteristics of patients were matched. Results are presented in table 1. Conclusion(s) The incidence of postprocedural acute and late RAO after routine dTRA and cTRA is low and occur with similar frequency when evaluated by ultrasound. Funding Acknowledgement Type of funding sources: None. Table 1

Background Pulmonary hypertension constitutes a rare disease characterized by a severe development and a high risk of premature death. One of its main clinical types is pulmonary arterial hypertension (PAH), in which the highest percentage of patients are affected by idiopathic PAH. The pathogenesis of this disease has not completely been discovered and elucidated so far, and non-specific clinical symptoms make the diagnosis of PAH a serious problem. Currently, PAH is confirmed with invasive examination based on right heart catheterization. Purpose The main aim of the study was to evaluate and compare both plasma and urine fingerprints of PAH patients and control group with the use of an untargeted metabolomics approach. The study also focused on correlation analysis between the observed metabolic changes and the clinical parameters to select specific indicators of PAH disease. Methods An untargeted metabolomics approach was applied to the plasma and urine samples with the use of gas chromatography coupled to triple quadrupole mass spectrometry (GC-QqQ/MS) and advanced statistical tests were applied to evaluate the potential metabolic indicators of PAH. The PAH patients (n=40) and healthy controls (n=39) were matched for age, sex, BMI and included in the study. The obtained raw datasets were properly processed (data deconvolution, signal correction using QCSVR method and PQN normalization) and subsequently subjected to uni- and multivariate statistical tests (Student's t-test, Welch's test, U Mann-Whitney test, PCA and OPLS-DA). The identification of the statistically significant metabolites was performed using universal libraries, such as: Fiehn's and NIST11. Results The statistically significant metabolites (n=10 and 11 for urine and plasma samples, respectively)originate from various biochemical pathways associated with the carbohydrate, amino acid, lipid, fatty acid and pyrimidine metabolism. The metabolic changes observed in the urine samples of PAH patients (compared to the control group) included different concentrations in: threonic acid, hippuric acid, acetic acid, sorbitol, butanoic acid and propionic acid. The metabolic alterations in the plasma samples covered changes in the levels of valine, leucine, lactic acid, hydroxybutanoic acid, nonanoic acid, cholesterol and octadecanoic acid. Metabolites representing the highest correlation with mean pulmonary arterial pressure include, for instance: propionic acid (r=0.85), valine (r=0.75) and lactic acid (r=0.63) Conclusions The observed metabolic changes are related to various biological processes that are disturbed in the course of PAH, namely: proliferation of pulmonary vascular cells or the functions of cardiomyocytes and the right ventricle of the heart. The obtained results confirmed the potential of a metabolomics approach to uncover and explain the underlying molecular mechanisms of PAH. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Science and High Education of Poland

Introduction Endurance athletes have an increased risk of atrial remodeling and atrial arrhythmias. However, data regarding atrial adaptation to physical exercise in non-elite athletes are limited. We aimed to assess exercise-induced alternations in atrial morphology and function in male and female amateur marathon runners, using real-time three-dimensional (3D) echocardiography. Methods The study group consisted of 40 male (39±8 years) and 27 female (40±7 years) amateur athletes. 3D echocardiography was performed 2–3 weeks before (Stage 1) and immediately after (Stage 2) the marathon run. Right (RA) and left atrial (LA) remodeling was assessed by volumetric measures, total ejection fraction (EF) and volume (EV). Speckle tracking was used to determine the temporal evaluation of atrial function by strain analysis. Results The main results are presented in Table 1. At rest, male athletes demonstrated greater RA size and decreased RA contractility, as assessed by EF and atrial strains, in comparison to females. At Stage 1, LA morphology and function did not differ significantly between genders. After the marathon, a remarkable increase in RA maximal volume (RAVmax, 32.9±8.6 vs. 36.4±8.2 ml/m2, p=0.016) and RAEF (49.5±9.7 vs. 57.3±9.2%, p=0.002) was observed only in female athletes (p Conclusions In amateur athletes, marathon running promotes biatrial remodelling with significant gender discrepancies. Females are more susceptible to exercise-induced morphological and functional changes of RA, while postrace alternations in males concern principally LA. 3D echocardiography of the atria is a useful indicator of exercise capacity, not only in elite, but also in amateur athletes. Funding Acknowledgement Type of funding sources: None.

Background and Aims The study investigates the practical utility of whole-blood gene expression profiling to diagnose inflammatory bowel diseases [IBDs]. Methods The discovery cohorts included 102 and 51 paediatric IBD patients and controls, and 95 and 46 adult IBD patients and controls, respectively. The replication cohorts included 447 and 76 paediatric IBD patients and controls, and 271 and 108 adult IBD patients and controls, respectively. In the discovery phase, RNA samples extracted from whole peripheral blood were analysed using RNA-Seq, and the predictive values of selected biomarkers were validated using quantitative polymerase chain reaction [qPCR]. Results In all, 15 differentially expressed transcripts [adjusted p ≤0.05] were selected from the discovery sequencing datasets. The receiver operating characteristic curves and area under the curve [ROC-AUC] in replication analyses showed high discriminative power [AUC range, 0.91–0.98] for 11 mRNAs in paediatric patients with active IBD. By contrast, the AUC-ROC values ranged from 0.63 to 0.75 in comparison among inactive paediatric IBDs and active/inactive adult IBDs, indicating a lack of discriminative power. The best multi-mRNA diagnostic classifier showed moderate discriminative power [AUC = 0.81] for paediatric inactive IBD, but was not able to discriminate active or inactive adult IBD patients from controls. The AUC-ROC values did not confirm an ability of the mRNAs abundances to discriminate between active ulcerative colitis and active Crohn’s disease in paediatric or adult populations. Conclusions This study identifies and validates blood transcriptional biomarkers that could be used in clinical settings as diagnostic predictors of IBD clinical activity in paediatric, but not adult, IBD patients.

We report measurements of the flux-integrated ν̅μ and ν̅μ + νμ charged-current cross-sections on water and hydrocarbon targets using the T2K anti-neutrino beam with a mean beam energy of 0.86 GeV. The signal is defined as the (anti-)neutrino charged-current interaction with one induced $\mu^\pm$ and no detected charged pion or proton. These measurements are performed using a new WAGASCI module recently added to the T2K setup in combination with the INGRID Proton Module. The phase space of muons is restricted to the high-detection efficiency region, $p_{\mu}>400~{\rm MeV}/c$ and $\theta_{\mu}200~{\rm MeV}/c$, $\theta_{\pi}600~{\rm MeV}/c$, $\theta_{\rm p}

Background/Introduction Conventional transradial approach (c-TRA) at the wrist is considered as the default strategy for catheter-based procedures providing less serious access-related complications and better patients' comfort than transfemoral route. A novel distal transradial artery approach (d-TRA) via the anatomical snuffbox has been proposed recently as an noteworthy alternative. It is hypothesised that d-TRA may provide additional benefits without losing the efficacy of c-TRA. Purpose To assess consecutive patients' comfort undergoing coronary angiography or intervention by novel d-TRA in comparison with c-TRA. Methods In a span of 4 months, out of 465 caucasian subjects, 400 patients were included in a prospective, single-center, randomized (1:1) distAl vs traditioNal Transradial Access for coRonary procEdures Study (ANTARES). Hemodynamic instability, ST-elevation myocardial infarction, forearm artery occlusion or prior radial access failure were the exclusion criteria. An artery was punctured with anterior wall modified Seldinger technique, and standard 5F or 6F vascular sheaths were used. Pain/discomfort when access gaining, radial spasm, early (within 24 hours) postprocedural local neuropathy (thumb numbness) were the analyzed parameters determining patients' comfort in both groups. Results Baseline characteristics of patients were matched. Conclusion(s) Coronary procedures performed in consecutive patients via novel d-TRA are associated with worse patient's comfort determined by higer rate of radial spasm and early postprocedural local neuropathy, and greater pain/discomfort when access gaining, in comparison with c-TRA. Funding Acknowledgement Type of funding source: None

Generalized convulsive status epilepticus is a life-threatening emergency, because recurrent convulsions can cause death or injury. A common form of generalized convulsive status epilepticus is of focal onset. The neuronal circuits activated during seizure spread from the hippocampus, a frequent site of seizure origin, to the bilateral motor cortex, which mediates convulsive seizures, have not been delineated. Status epilepticus was initiated by electrical stimulation of the hippocampus. Neurons transiently activated during seizures were labelled with tdTomato and then imaged following brain slice clearing. Hippocampus was active throughout the episode of status epilepticus. Neuronal activation was observed in hippocampus parahippocampal structures: subiculum, entorhinal cortex and perirhinal cortex, septum, and olfactory system in the initial phase status epilepticus. The tdTomato-labelled neurons occupied larger volumes of the brain as seizures progressed and at the peak of status epilepticus, motor and somatosensory cortex, retrosplenial cortex, and insular cortex also contained tdTomato-labelled neurons. In addition, motor thalamic nuclei such as anterior and ventromedial, midline, reticular, and posterior thalamic nuclei were also activated. Furthermore, circuits proposed to be crucial for systems consolidation of memory: entorhinal cortex, retrosplenial cortex, cingulate gyrus, midline thalamic nuclei and prefrontal cortex were intensely active during periods of generalized tonic-clonic seizures. As the episode of status epilepticus waned, smaller volume of brain was activated. These studies suggested that seizure spread could have occurred via canonical thalamocortical pathway and many cortical structures involved in memory consolidation. These studies may help explain retrograde amnesia following seizures.

Several epidemiologic studies have indicated an increased risk of lung cancer among welders. We used the SYNERGY project database to assess welding as a risk factor for developing lung cancer. The database includes data on 15,483 male lung cancer cases and 18,388 male controls from 16 studies in Europe, Canada, China, and New Zealand conducted between 1985 and 2010. Odds ratios and 95% confidence intervals between regular or occasional welding and lung cancer were estimated, with adjustment for smoking, age, study center, and employment in other occupations associated with lung cancer risk. Overall, 568 cases and 427 controls had ever worked as welders and had an odds ratio of developing lung cancer of 1.44 (95% confidence interval: 1.25, 1.67) with the odds ratio increasing for longer duration of welding. In never and light smokers, the odds ratio was 1.96 (95% confidence interval: 1.37, 2.79). The odds ratios were somewhat higher for squamous and small cell lung cancers than for adenocarcinoma. Another 1,994 cases and 1,930 controls had ever worked in occupations with occasional welding. Work in any of these occupations was associated with some elevation of risk, though not as much as observed in regular welders. Our findings lend further support to the hypothesis that welding is associated with an increased risk of lung cancer. © The Author 2013.

Occupation as a welder has been associated with a 25%-40% increase in lung cancer risk. This study aims to elucidate to what extent confounding by smoking and asbestos drives this association and to evaluate the role of welding-related exposures such as chromium. The study included 2,197 male incident lung cancer cases and 2,295 controls from Romania, Hungary, Poland, Russia, Slovakia, the Czech Republic, and the United Kingdom from 1998 to 2001. Information on risk factors was collected through face-to-face interviews. Experts assessed exposure to 70 agents, and risk estimates were adjusted for smoking and occupational exposures. Occupation as a welder/flame cutter (prevalence controls: 3.7%) was associated with an odds ratio of 1.36 (95% confidence interval (CI): 1.00, 1.86) after adjustment for smoking and occupational exposures including asbestos. An odds ratio of 1.18 (95% CI: 1.01, 1.38) was found for welding fumes (prevalence controls: 22.8%), increasing to 1.38 for more than 25 exposure years (95% CI: 1.09, 1.75). A duration-response association was also observed for mild steel welding without chromium exposure. In this population, occupational exposure to welding fumes accounted for approximately 4% of lung cancer cases, to which both stainless and mild steel welding contributed equally. Given that welding remains a common task for many workers, exposure to welding fumes represents an important risk factor for lung cancer. © The Author 2012. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.

In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P=5 5.75× 3 10 -8, per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17-1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10 -14) and rs12617313 (P = 7.48 × 10 -12), both highly correlated withrs9679290 (r 2 > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r 2 < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10 -9, per-allele OR = 1.28, 95% CI: 1.18-1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants. Published by Oxford University Press 2011.

Background: Analysis of candidate genes in individual studies has had only limited success in identifying particular gene variants that are conclusively associated with lung cancer risk. In the International Lung Cancer Consortium (ILCCO), we conducted a coordinated genotyping study of 10 common variants selected because of their prior evidence of an association with lung cancer. These variants belonged to candidate genes from different cancerrelated pathways including inflammation (IL1B), folate metabolism (MTHFR), regulatory function (AKAP9 and CAMKK1), cell adhesion (SEZL6) and apoptosis (FAS, FASL, TP53, TP53BP1 and BAT3). Methods: Genotype data from 15 ILCCO case-control studies were available for a total of 8431 lung cancer cases and 11 072 controls of European descent and Asian ethnic groups. Unconditional logistic regression was used to model the association between each variant and lung cancer risk. Results: Only the association between a non-synonymous variant of TP53BP1 (rs560191) and lung cancer risk was significant (OR = 0.91, P = 0.002). This association was more striking for squamous cell carcinoma (OR = 0.86, P = 6 × 10-4). No heterogeneity by center, ethnicity, smoking status, age group or sex was observed. In order to confirm this association, we included results for this variant from a set of independent studies (9966 cases/11 722 controls) and we reported similar results. When combining all these studies together, we reported an overall OR = 0.93 (0.89-0.97) (P = 0.001). This association was significant only for squamous cell carcinoma [OR = 0.89 (0.85-0.95), P = 1 × 10-4]. Conclusion: This study suggests that rs560191 is associated to lung cancer risk and further highlights the value of consortia in replicating or refuting published genetic associations. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.

MicroRNA 26a (miR-26a) reduces cell viability in several cancers, indicating that miR-26a could be used as a therapeutic option in patients. We demonstrate that miR-26a not only inhibits G1-S cell cycle transition and promotes apoptosis, as previously described, but also regulates multiple cell cycle checkpoints. We show that sustained miR-26a over-expression in both breast cancer (BC) cell lines and mouse embryonic fibroblasts (MEFs) induces oversized cells containing either a single-large nucleus or two nuclei, indicating defects in mitosis and cytokinesis. Additionally, we demonstrate that miR-26a induces aneuploidy and centrosome defects and enhances tumorigenesis. Mechanistically, it acts by targeting G1-S transition genes as well as genes involved in mitosis and cytokinesis such as CHFR, LARP1 and YWHAE. Importantly, we show that only the re-expression of CHFR in miR-26a over-expressing cells partially rescues normal mitosis and impairs the tumorigenesis exerted by miR-26a, indicating that CHFR represents an important miR-26a target in the regulation of such phenotypes. We propose that miR-26a delivery might not be a viable therapeutic strategy due to the potential deleterious oncogenic activity of this miRNA.

The authors pooled data from 15 case-control studies of head and neck cancer (9,107 cases, 14,219 controls) to investigate the independent associations with consumption of beer, wine, and liquor. In particular, they calculated associations with different measures of beverage consumption separately for subjects who drank beer only (858 cases, 986 controls), for liquor-only drinkers (499 cases, 527 controls), and for wine-only drinkers (1,021 cases, 2,460 controls), with alcohol never drinkers (1,124 cases, 3,487 controls) used as a common reference group. The authors observed similar associations with ethanol-standardized consumption frequency for beer-only drinkers (odds ratios (ORs) = 1.6, 1.9, 2.2, and 5.4 for =5, 6-15, 16-30, and >30 drinks per week, respectively; Ptrend < 0.0001) and liquor-only drinkers (ORs = 1.6, 1.5, 2.3, and 3.6; P < 0.0001). Among wine-only drinkers, the odds ratios for moderate levels of consumption frequency approached the null, whereas those for higher consumption levels were comparable to those of drinkers of other beverage types (ORs = 1.1, 1.2, 1.9, and 6.3; P < 0.0001). Study findings suggest that the relative risks of head and neck cancer for beer and liquor are comparable. The authors observed weaker associations with moderate wine consumption, although they cannot rule out confounding from diet and other lifestyle factors as an explanation for this finding. Given the presence of heterogeneity in study-specific results, their findings should be interpreted with caution.

This study investigated associations between occupational pesticide exposure and renal cell carcinoma (RCC) risk. To follow-up on a previous report by Buzio et al., we also considered whether this association could be modified by glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) genotypes. About 1097 RCC cases and 1476 controls from Central and Eastern Europe were interviewed to collect data on lifetime occupational histories. Occupational information for jobs held for at least 12 months duration was coded for pesticide exposures and assessed for frequency and intensity of exposure. GSTM1 and GSTT1 gene deletions were analyzed using TaqMan® assays. A significant increase in RCC risk was observed among subjects ever exposed to pesticides [odds ratio (OR): 1.60; 95% confidence interval (CI): 1.00-2.55]. After stratification by genotypes, increased risk was observed among exposed subjects with at least one GSTM1 active allele (OR: 4.00; 95% CI: 1.55-10.33) but not among exposed subjects with two GSTM1 inactive alleles compared with unexposed subjects with two inactive alleles (P-interaction: 0.04). Risk was highest among exposed subjects with both GSTM1 and GSTT1 active genotypes (OR: 6.47; 95% CI: 1.82-23.00; P-interaction: 0.02) compared with unexposed subjects with at least one GSTM1 or T1 inactive genotype. In the largest RCC case-control study with genotype information conducted to date, we observed that risk associated with pesticide exposure was exclusive to individuals with active GSTM1/T1 genotypes. These findings further support the hypothesis that glutathione S-transferase polymorphisms can modify RCC risk associated with occupational pesticide exposure. © The Author 2008. Published by Oxford University Press. All rights reserved.

Poor oral health has been reported as a risk factor in the etiology of head and neck cancer. Data on oral health were ascertained as part of two multicenter case-control studies comprising 924 cases and 928 controls in central Europe and 2,286 cases and 1,824 controls in Latin America. Incident cases of squamous cell carcinoma of the head and neck (oral cavity, pharynx, larynx) and esophagus, as well as age (in quinquennia)- and sex frequency-matched controls, were enrolled from 1998 to 2003. Poor condition of the mouth (central Europe: odds ratio (OR) = 2.89, 95% confidence interval (CI): 1.74, 4.81; Latin America: OR = 1.89, 95% CI: 1.47, 2.42), lack of toothbrush use (Latin America: OR = 2.36, 95% CI: 1.28, 4.36), and daily mouthwash use (Latin America: OR = 3.40, 95% CI: 1.96, 5.89) emerged as risk factors for head and neck cancer, independent of tobacco use and alcohol consumption. Missing between six and 15 teeth was an independent risk factor for esophageal cancer (central Europe: OR = 2.84, 95% CI: 1.26, 6.41; Latin America: OR = 2.18, 95% CI: 1.04, 4.59). These results indicate that periodontal disease (as indicated by poor condition of the mouth and missing teeth) and daily mouthwash use may be independent causes of cancers of the head, neck, and esophagus. © The Author 2007. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved.