articles+ search results

Lung, Lung Cancer, Cancer, Prevention, Carcinoma, Non-Small-Cell Lung, ErbB Receptors, Humans, Lung Neoplasms, Mutation, Survival Analysis, Medical and Health Sciences, and Epidemiology

BackgroundSomatic EGFR mutations define a subset of non-small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches.MethodsThrough analysis of the International Lung Cancer Consortium (ILCCO) epidemiologic datasets, we developed a regression model for EGFR-status; we then applied a clinical-restriction approach using the optimal cut-point, and a second epidemiologic, multiple imputation approach to ILCCO survival analyses that did and did not account for EGFR-status.ResultsOf 35,356 ILCCO patients with NSCLC, EGFR-mutation-status was available in 4,231 patients. A model regressing known EGFR-mutation-status on clinical and demographic variables achieved a concordance index of 0.75 (95% CI, 0.74-0.77) in the training and 0.77 (95% CI, 0.74-0.79) in the testing dataset. At an optimal cut-point of probability-score = 0.335, sensitivity = 69% and specificity = 72.5% for determining EGFR-wildtype status. In both restriction-based and imputation-based regression analyses of the individual roles of BMI on overall survival of patients with NSCLC, similar results were observed between overall and EGFR-mutation-negative cohort analyses of patients of all ancestries. However, our approach identified some differences: EGFR-mutated Asian patients did not incur a survival benefit from being obese, as observed in EGFR-wildtype Asian patients.ConclusionsWe introduce a pragmatic method to evaluate the potential impact of EGFR-status on epidemiological analyses of NSCLC.ImpactThe proposed method is generalizable in the common occurrence in which EGFR-status data are missing.

Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Lung Cancer, Tobacco, Prevention, Cancer, Genetics, Clinical Research, Tobacco Smoke and Health, Lung, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Case-Control Studies, Chromosomes, Human, Pair 5, Europe, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotyping Techniques, Humans, Lung Neoplasms, Membrane Proteins, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Telomerase, Lung cancer, Never smokers, Genome-wide association study, Genetic susceptibility, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Oncology & Carcinogenesis, Clinical sciences, and Oncology and carcinogenesis

IntroductionInherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer.MethodsWe conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer.ResultsWe detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722-0.820; p value 5.31 × 10-16), rs380286 (OR: 0.770, 95% CI: 0.723-0.820; p value 4.32 × 10-16), and rs4975616 (OR: 0.778, 95% CI: 0.730-0.829; p value 1.04 × 10-14). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate.ConclusionsWe found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease.

Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Oncology and Carcinogenesis, Genetics, Lung, Nutrition, Tobacco Smoke and Health, Prevention, Cancer, Tobacco, Obesity, Clinical Research, Lung Cancer, Aetiology, 2.1 Biological and endogenous factors, Body Mass Index, Fasting, Humans, Insulin, Insulin Resistance, Likelihood Functions, Lipids, Lung Neoplasms, Mendelian Randomization Analysis, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, and General Science & Technology

BackgroundAssessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.Methods and findingsWe identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results.ConclusionsOur results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.

Lung, Human Genome, Genetics, Cancer, Prevention, Lung Cancer, 2.1 Biological and endogenous factors, Aetiology, Case-Control Studies, Chromosome Mapping, Chromosomes, Human, Pair 5, Female, Genetic Loci, Genetic Predisposition to Disease, Genotyping Techniques, Humans, Lung Neoplasms, Male, Middle Aged, Oncology and Carcinogenesis, and Oncology & Carcinogenesis

Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)), rs112290073 (OR = 1.85, P = 1.27×10(-5)), rs138895564 (OR = 2.16, P = 2.06×10(-5); among young cases, OR = 3.77, P = 8.41×10(-4)). In addition, we found that rs139852726 (P = 1.44×10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(-7)) and lung cancer (P = 2.37×10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.

monkeypox, conjunctivitis, eye discharge, case report, Ophthalmology, and RE1-994

A 38-year-old male with recently diagnosed HIV and gonorrhea presented with umbilicated facial lesions and blepharoconjunctivitis of the right eye. Polymerase chain reaction test was performed of the skin were positive for Monkeypox (MPX). The patients’ ocular symptoms improved with acyclovir, azithromycin, gemifloxacin, and tecovirimat after 3 weeks of treatment. The incidence of MPX has been on the rise in 2022, and this case represents a unique presentation and an addition to the pool of data pertinent to diagnosis and treatment of MPX and its ocular manifestations. Due to the MPX reemergence, it is imperative for ophthalmologists to keep MPX on the differential for patients presenting with blepharoconjunctivitis.

Biology (General) and QH301-705.5

Abstract The ability to perform sophisticated, high-throughput optogenetic experiments has been greatly enhanced by recent open-source illumination devices that allow independent programming of light patterns in single wells of microwell plates. However, there is currently a lack of instrumentation to monitor such experiments in real time, necessitating repeated transfers of the samples to stand-alone analytical instruments, thus limiting the types of experiments that could be performed. Here we address this gap with the development of the optoPlateReader (oPR), an open-source, solid-state, compact device that allows automated optogenetic stimulation and spectroscopy in each well of a 96-well plate. The oPR integrates an optoPlate illumination module with a module called the optoReader, an array of 96 photodiodes and LEDs that allows 96 parallel light measurements. The oPR was optimized for stimulation with blue light and for measurements of optical density and fluorescence. After calibration of all device components, we used the oPR to measure growth and to induce and measure fluorescent protein expression in E. coli. We further demonstrated how the optical read/write capabilities of the oPR permit computer-in-the-loop feedback control, where the current state of the sample can be used to adjust the optical stimulation parameters of the sample according to pre-defined feedback algorithms. The oPR will thus help realize an untapped potential for optogenetic experiments by enabling automated reading, writing, and feedback in microwell plates through open-source hardware that is accessible, customizable, and inexpensive.

Medicine and Science

Abstract Prolonged fasting prior to oesophagogastroduodenoscopy (OGDS) could be noxious to patients’ well-being. Strict fasting protocol has been used prior to OGDS with the concern of reduced visibility or suboptimal endoscopic assessment. Maltodextrin beverages were also commonly used as the pre-operative carbohydrate loading in enhanced recovery after surgery (ERAS) protocol. Our study aimed to look for the effects of maltodextrin beverage 2 h before OGDS on gastric residual volume and patient’s well-being scores. This was a single-blinded, stratified randomised controlled trial, comparing control group (A, received 400 ml of plain water) and carbohydrate loading group (B, received 400 ml of Carborie). The primary objectives were to measure the gastric residual volume (GRV) and patient’s well-being scores using visual analogue scale (VAS) scores for hunger, thirst, anxiety, tiredness and general discomfort. Of 80 randomised patients, 78 completed the study (38 received plain water and 40 Carborie). The median (IQR) GRV was not significantly different between group A and B (5.0 ml (20) vs 4.0 ml (19), p = 0.777). Both groups showed significant reduction in VAS scores in all five parameters (p ≤ 0.001). There were no complications attributed to endoscopy in either group. Pre-endoscopy maltodextrin beverage is as safe as clear water with improved patient’s well-being in both groups. Clinical Trial Registration: NCT05106933.

rectal neoplasms, low anterior resection syndrome, low anterior resection syndrome score, tumor height, functional outcome, Diseases of the digestive system. Gastroenterology, and RC799-869

Purpose Oncological outcomes following rectal cancer surgery have improved significantly over recent decades with lower recurrences and longer overall survival. However, many of the patients experienced low anterior resection syndrome (LARS). This study identified the prevalence and risk factors associated with the development of LARS. Methods This cross-sectional study involved patients who were diagnosed with rectal cancer and had undergone sphincter-preserving low anterior resection from January 2011 to December 2020. Upon clinic follow-up, patients were asked to complete an interviewed based questionnaire (LARS score) designed to assess bowel dysfunction after rectal cancer surgery. Results Out of 76 patients, 25 patients (32.9%) had major LARS, 10 patients (13.2%) had minor LARS, and 41 patients (53.9%) had no LARS. The height of tumor from anal verge showed an association with the development of major LARS (P=0.039). Those patients with less than 8 cm tumor from anal verge had an increased risk of LARS by 3 times compared to those with 8 cm and above (adjusted odds ratio, 3.11; 95% confidence interval, 1.06–9.13). Conclusion Results from our study show that low tumor height was a significant risk factor that has a negative impact on bowel function after surgery. The high prevalence of LARS emphasizes the need for study regarding risk factors and the importance of understanding the pathophysiology of LARS, in order for us to improve patient bowel function and quality of life after rectal cancer surgery.

Pulmonary transit time, Cardiac MRI, Heart failure, Left ventricular ejection fraction, Diseases of the circulatory (Cardiovascular) system, and RC666-701

Abstract Background Longer pulmonary transit time (PTT) is closely associated with hemodynamic abnormalities. However, the implications on heart failure (HF) risk have not been investigated broadly in patients with diverse cardiac conditions. In this study we examined the long-term risk of HF hospitalization associated with longer PTT in a large prospective cohort with a broad spectrum of cardiac conditions. Methods All subjects were prospectively recruited to undergo cardiac magnetic resonance (CMR). The dynamic images of first-pass perfusion were acquired to assess peak-to-peak pulmonary transit time (PTT) which was subsequently normalized to RR interval duration. The risk of HF was examined using Cox proportional hazards models adjusted for baseline confounding risk factors. Results Among 506 consecutively consented patients undergoing clinical cardiac MR with diverse cardiac conditions, the mean age was 63 ± 14 years and 373 (73%) were male. After a mean follow up duration of 4.5 ± 3.0 years, 70 (14%) patients developed hospitalized HF and of these 6 died. A normalized PTT ≥ 8.2 was associated with a significantly increased adjusted HF hazard ratio of 3.69 (95% CI 2.02, 6.73). The HF hazard ratio was 1.26 (95% CI 1.18, 1.33) for each 1 unit increase in PTT which was higher among those preserved (1.70, 95% CI 1.20, 2.41) compared to those with reduced left ventricular ejection fraction (

Athlete’s heart, Seasonal variation, Cardiac screening, Echocardiography, Speckle tracking echocardiography, Diseases of the circulatory (Cardiovascular) system, and RC666-701

Abstract Background Pre-participation cardiac screening (PCS) of “Super-League” rugby football league (RFL) athletes is mandatory but may be completed at any time point. The aim of this study was to assess cardiac electrical, structural and functional variation across the competitive season. Methods Elite, male, RFL athletes from a single Super-League club underwent cardiac evaluation using electrocardiography (ECG), 2D echocardiography and speckle tracking echocardiography (STE) at four time points across the RFL season; (1) End pre-season (ENDPRE), (2) mid-season (MIDCOMP), (3) end-season (ENDCOMP) and (4) End off-season (ENDOFF). Training loads for each time point were also determined. One-way ANOVA with post-hoc Bonferroni were used for statistical analyses. Results Total workload undertaken by athletes was lower at both MIDCOMP and ENDCOMP compared to ENDPRE (P

Extraskeletal myxoid chondrosarcoma, EMC, Sarcoma, Paralabral cyst, Medical physics. Medical radiology. Nuclear medicine, and R895-920

Extraskeletal myxoid chondrosarcoma (EMC) is a malignant cartilage neoplasm usually encountered in the proximal extremities. We report the case of a 58-year-old male who presented initially with a 3-month history of cough. Initial staging demonstrated a right upper lobe mass with bilateral pulmonary nodules and moderate tracer uptake in the right lung mass and right groin on positron emission tomography imaging. Endobronchial ultrasound biopsy confirmed a histological diagnosis of EMC for which the patient underwent right upper lobe wedge resection. Pelvic MRI revealed a peripherally enhancing juxta-articular lesion within the region of the right obturator externus bursa, which was thought initially to represent either a ganglion or paralabral cyst. However, ultrasound-guided biopsy yielded identical histology to the resected lung mass leading to the diagnosis of primary EMC in the right groin with pulmonary metastases. The patient underwent surgical excision of the right groin mass with no local recurrence on the surveillance computed tomography at 5, 12, and 18 months but eventual disease recurrence in the right groin and further progression of the pulmonary metastases at 29 months. We emphasize that the contrast enhancement pattern of EMC can mimic a benign cystic lesion, in particular, when in a juxta-articular location, which has the potential to mislead radiologists and delay diagnosis and definitive treatment.

IgG4-related disease, Autoimmunity, Immunoglobulins, Sialadenitis, Retroperitoneal fibrosis, Medical physics. Medical radiology. Nuclear medicine, and R895-920

We present the case of periaortitis which presented initially with left flank pain. A diagnosis of IgG4-related disease (IgG4-RD) was subsequently made and managed as such. IgG4-RD is rare, can be difficult to diagnose, and requires clinical, serological, radiological and pathological correlation, particularly given that serum IgG4 levels may be normal. Immunosuppression is the mainstay treatment for this chronic condition alongside regular rheumatology input.

COVID-19 vaccination, Pregnancy, Multimorbidity, Smoking status, Vaccine uptake, Vaccine hesitancy, Infectious and parasitic diseases, and RC109-216

Abstract Background Multimorbidity, smoking status, and pregnancy are identified as three risk factors associated with more severe outcomes following a SARS-CoV-2 infection, thus vaccination uptake is crucial for pregnant women living with multimorbidity and a history of smoking. This study aimed to examine the impact of multimorbidity, smoking status, and demographics (age, ethnic group, area of deprivation) on vaccine hesitancy among pregnant women in Wales using electronic health records (EHR) linkage. Methods This cohort study utilised routinely collected, individual-level, anonymised population-scale linked data within the Secure Anonymised Information Linkage (SAIL) Databank. Pregnant women were identified from 13th April 2021 to 31st December 2021. Survival analysis was employed to examine and compare the length of time to vaccination uptake in pregnancy by considering multimorbidity, smoking status, as well as depression, diabetes, asthma, and cardiovascular conditions independently. The study also assessed the variation in uptake by multimorbidity, smoking status, and demographics, both jointly and separately for the independent conditions, using hazard ratios (HR) derived from the Cox regression model. Results Within the population cohort, 8,203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, with 8,572 (34.1%) remaining unvaccinated throughout the follow-up period, and 8,336 (33.2%) receiving the vaccine postpartum. Women aged 30 years or older were more likely to have the vaccine in pregnancy. Those who had depression were slightly but significantly more likely to have the vaccine compared to those without depression (HR = 1.08, 95% CI 1.03 to 1.14, p = 0.002). Women living with multimorbidity were 1.12 times more likely to have the vaccine compared to those living without multimorbidity (HR = 1.12, 95% CI 1.04 to 1.19, p = 0.001). Vaccine uptakes were significantly lower among both current smokers and former smokers compared to never smokers (HR = 0.87, 95% CI 0.81 to 0.94, p