RESUMEN
BACKGROUND AND AIM: Endoscopic mucosal resection (EMR) is an established technique for the diagnosis and treatment of high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) in Barrett's esophagus. Submucosal preinjection is not universally used or generally recommended when performing routine ligation-assisted EMR. Prior studies, however, have demonstrated evidence of at least superficial muscle injury on ligation-assisted EMR without submucosal injection. There are limited published data supporting any potential benefit of submucosal preinjection. Our aim was to review this technique and determine the rate of any degree of muscle injury in patients with Barrett's HGD and EAC treated with submucosal preinjection before ligation-assisted EMR. METHODS: Patients undergoing submucosal preinjection before ligation-assisted EMR for Barrett's esophagus at a single institution between 2012 and 2016 were identified. Data were collected regarding patient demographics and medical history, endoscopy and histopathology findings, adverse events, and subsequent outcomes. All EMR specimens were reviewed by an expert gastrointestinal pathologist. RESULTS: One hundred fifty consecutive EMR procedures were performed on 70 patients. Of 70 patients, 85.7% of patients were men, with a median age of 68 years. EAC was identified in 75 specimens (50%) and HGD in 44 specimens (29.3%). Deep resection margins were clear of adenocarcinoma in all specimens. Muscularis propria was not identified in any of the 150 specimens. There were no cases of post-EMR perforation. CONCLUSIONS: Preinjection before ligation-assisted EMR achieved complete excision with histologically clear margins, without histological evidence of any inadvertent muscularis propria.
RESUMEN
BACKGROUND: Rates of alcohol consumption and obesity are increasing in many Western populations. For some cancer types, both heavy alcohol consumption and obesity are independently associated with increased risk. Whether combined exposure to both synergistically increases an individual's risk of cancer is unclear. We performed a systematic review to assess whether alcohol and obesity interact to confer higher risk for cancer than the additive sum of their effects. METHODS: A systematic literature search was conducted from the inception date to 13 February 2024 of PubMed, Embase, Cochrane Library and Web of Science to identify studies of alcohol, obesity, and cancer risk. We aimed to undertake a meta-analysis if there were sufficient data. RESULTS: The literature search identified 17,740 potentially eligible studies. After review, 24 studies were included. Eleven reported on the association between alcohol consumption and cancer risk in individuals according to their body mass index (BMI), nine reported on the association between BMI and cancer risk in individuals according to their alcohol consumption, and six studies examined potential synergistic interactions between alcohol consumption and obesity on cancer risk. However, there were insufficient data and significant heterogeneity in the cancers studied to undertake meta-analysis, therefore a systemic review and narrative synthesis was conducted. Overall, there was no consistent pattern of interaction between alcohol use and overweight/obesity on cancer risk across cancer types. CONCLUSIONS: While alcohol and obesity are prevalent and important risk factors for a range of cancers, data are lacking on whether their combined exposure may synergistically increase an individual's risk for cancer. Further study across more cancer types is required to better understand the nature of interactions between alcohol use and obesity on cancer risk.
Asunto(s)
Consumo de Bebidas Alcohólicas , Neoplasias , Obesidad , Humanos , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Índice de Masa Corporal , Neoplasias/epidemiología , Neoplasias/etiología , Obesidad/epidemiología , Obesidad/complicaciones , Factores de RiesgoRESUMEN
Background: First Nations populations have poorer colorectal cancer (CRC) survival compared to non-First Nations populations. Whilst First Nations populations across the world are distinct, shared experiences of discrimination and oppression contribute to persistent health inequities. CRC screening improves survival, however screening rates in First Nations populations are poorly described. This study seeks to define participation rates in CRC screening in First Nations populations worldwide. Methods: A systematic literature search was conducted of PubMed, Embase, Cochrane Library, CINAHL, MEDLINE, grey literature, national registries and ClinicalTrials.gov. All sources were searched from their inception date to 18 February 2024. Studies were included if they reported CRC screening rates in adult (≥18 years) First Nations populations. We aimed to undertake a meta-analysis if there were sufficient data. Quality of papers were assessed using the Joanna Briggs Institute (JBI) appraisal tool. The study was registered with PROSPERO, CRD42020210181. Findings: The literature search identified 1723 potentially eligible published studies. After review, 57 studies were included, 50 from the United States (US), with the remaining studies from Australia, Aotearoa New Zealand (NZ), Canada, Dominica and Guatemala. Additionally, eleven non-indexed reports from national programs in Australia and NZ were included. There were insufficient data to undertake meta-analysis, therefore a systematic review and narrative synthesis were conducted. CRC screening definitions varied, and included stool-based screening, sigmoidoscopy and colonoscopy. US First Nations screening rates ranged between 4.0 and 79.2%, Australia reported 10.6-35.2%, NZ 18.4-49%, Canada 22.4-53.4%, Guatemala 2.2% and Dominica 4.2%. Fifty-five studies were assessed as moderate or high quality and two as low quality. Interpretation: Our findings suggested that there is wide variation in CRC screening participation rates across First Nations populations. Screening data are lacking in direct comparator groups and longitudinal outcomes. Disaggregation of screening data are required to better understand and address First Nations CRC outcome inequities. Funding: None.
RESUMEN
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Much of the recognised health-care burden occurs in the minority of people with NAFLD who progress towards cirrhosis and require specialist follow-up, including risk stratification and hepatocellular carcinoma surveillance. NAFLD is projected to become the leading global cause of cirrhosis and hepatocellular carcinoma, but the frequency of non-cirrhotic hepatocellular carcinoma provides a challenge to existing surveillance strategies. Deaths from extrahepatic cancers far exceed those from hepatocellular carcinoma in NAFLD. Unlike hepatocellular carcinoma, the increased extrahepatic cancer risk in NAFLD is not dependent on liver fibrosis stage. Given that almost 30% of the world's adult population has NAFLD, extrahepatic cancer could represent a substantial health and economic issue. In this Review, we discuss current knowledge and controversies regarding hepatocellular carcinoma risk stratification and surveillance practices in people with NAFLD. We also assess the associations of extrahepatic cancers with NAFLD and their relevance both in the clinic and the wider community.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Adulto , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/patología , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/patología , Factores de Riesgo , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/patología , Cirrosis Hepática/complicaciones , FibrosisRESUMEN
BACKGROUND: The Balance Tracking System (BTrackS) Limits of Stability (LOS) protocol is a relatively new means of evaluating unconstrained dynamic postural control ability. While the reliability of this protocol has previously been established, reference data is currently unavailable to assist in the interpretation of results. RESEARCH QUESTION: What are typical reference values for the BTrackS LOS protocol with respect to sex, height, and BMI? METHODS: A cross= -section of 800 healthy, young adults (aged 18-29 years; 368 men, 432 women) were administered the BTrackS LOS protocol. Sex, height and weight variables were also captured for the participants. RESULTS: Results of a stepwise linear regression showed that the outcome measure for BTrackS LOS testing (i.e. LOS Area) was larger in taller individuals and in men. Based on these findings, four percentile ranking categories were established and associated look-up tables created. SIGNIFICANCE: The reference values provided by this study offer much needed guidance to clinicians and researchers for the determination of dynamic balance abnormalities based on BTrackS LOS testing.
Asunto(s)
Estado de Salud , Equilibrio Postural , Masculino , Adulto Joven , Humanos , Femenino , Valores de Referencia , Reproducibilidad de los Resultados , Diseño Interior y MobiliarioRESUMEN
Successful hitting performance may be related to perceptual processing of visual information. The purpose of this investigation was to examine the relationship between preseason cognitive assessments, off-field preseason hitting assessment, and in-game batting performing in collegiate baseball and softball athletes. Collegiate varsity baseball (n = 10, 20.5 ± 1.0 years) and softball (n = 16, 20.3 ± 1.3 years) underwent Flanker Task and Trail Maker Tests A (TMT-A) and B (TMT-B) 24 hours prior to a pre-seasoning indoor hitting assessment. During pre-season hitting assessment, athletes selected 10 underhand pitches and were outfitted with commercially available measurement tools (i.e., HitTrax and The Blast) to quantify swing characteristics. Batting average (BA), slugging percentage (SLUG) and on-base percentage (OBP) was obtained from subsequent 14 non-conference baseball and softball games. The data from this study demonstrated a relationship between the ball's exit velocity (r = .501), bat velocity (r = .524) and average distance traveled (r = .449) during the hitting assessment and in-game BA, p < 0.05. No relationship between hitting assessment outcomes and OBP or SLUG were detected, p > 0.05. Furthermore, the Flanker-Task, TMT-A and TMT-B were not related to in game batting outcomes, p > 0.05. Therefore, these data suggest that off-season preparation should be designed to maximize swing velocity while maintaining performance (i.e., skill) of the coordinated swing.
RESUMEN
BACKGROUND AND AIMS: The role of gastroscopy to investigate the upper GI (UGI) tract in subjects with a positive fecal occult blood test (FOBT+) result is controversial. We conducted a systematic review and meta-analysis, which aimed to determine the prevalence of UGI lesions in FOBT+ subjects. METHODS: Databases were searched until March 31, 2022 for studies reporting UGI lesions in FOBT+ subjects undergoing colonoscopy and gastroscopy. Pooled prevalence rates of UGI cancers and clinically significant lesions (CSLs; lesions potentially explaining occult blood loss), odds ratio (OR), and 95% confidence intervals (CIs) were calculated. RESULTS: We included 21 studies with 6993 FOBT+ subjects. Pooled prevalence of UGI cancers was .8% (95% CI, .4-1.6) and UGI CSLs was 30.4% (95% CI, 20.7-42.2), and that of colonic cancers and CSLs was 3.3% (95% CI, 1.8-6.0) and 31.9% (95% CI, 23.9-41.1), respectively. There was no significant difference in the prevalence of UGI CSL and UGI cancers in FOBT+ subjects with/without colonic pathology (ORs of 1.2 [95% CI, .9-1.6; P = .137] and 1.6 [95% CI, .5-5.5; P = .460]). Anemia in FOBT+ subjects was associated with UGI cancers (OR, 6.3; 95% CI, 1.3-31.5; P = .025) and UGI CSLs (OR, 4.3; 95% CI, 2.2-8.4; P = .0001). GI symptoms were not associated with UGI CSLs (OR, 1.3; 95% CI, .6-2.8; P = .511). CONCLUSIONS: There is an appreciable prevalence of UGI cancers and other CSLs in FOBT+ subjects. Anemia but not symptoms or colonic pathology are linked to UGI lesions. Although the data suggest that same-day gastroscopy in FOBT+ subjects undergoing colonoscopy yields approximately 25% more malignancies as colonoscopy alone, prospective data are required to determine the cost-efficacy of dual endoscopy as a standard of care for all FOBT+ subjects.
Asunto(s)
Anemia , Neoplasias Colorrectales , Humanos , Sangre Oculta , Estudios Prospectivos , Colonoscopía , Endoscopía Gastrointestinal , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/complicaciones , Anemia/epidemiología , Tamizaje MasivoRESUMEN
AIMS: People with severe mental illness (SMI) have a greater risk of dying from colorectal cancer (CRC), even though the incidence is lower or similar to that of the general population This pattern is unlikely to be solely explained by lifestyle factors, while the role of differences in cancer healthcare access or treatment is uncertain. METHODS: We undertook a systematic review and meta-analysis on access to guideline-appropriate care following CRC diagnosis in people with SMI including the receipt of surgery, chemo- or radiotherapy. We searched for full-text articles indexed by PubMed, EMBASE, PsychInfo and CINAHL that compared CRC treatment in those with and without pre-existing SMI (schizophrenia, schizoaffective, bipolar and major affective disorders). Designs included cohort or population-based case-control designs. RESULTS: There were ten studies (sample size = 3501-591 561). People with SMI had a reduced likelihood of surgery (RR = 0.90, 95% CI 0.92-0.97; p = 0.005; k = 4). Meta-analyses were not possible for the other outcomes but in results from individual studies, people with SMI were less likely to receive radiotherapy, chemotherapy or sphincter-sparing procedures. The disparity in care was greatest for those who had been psychiatric inpatients. CONCLUSIONS: People with SMI, including both psychotic and affective disorders, receive less CRC care than the general population. This might contribute to higher case-fatality rates for an illness where the incidence is no higher than that of the general population. The reasons for this require further investigation, as does the extent to which differences in treatment access or quality contribute to excess CRC mortality in people with SMI.
Asunto(s)
Neoplasias Colorrectales , Trastornos Mentales , Esquizofrenia , Humanos , Canal Anal , Tratamientos Conservadores del Órgano , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , Trastornos Mentales/psicología , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/terapiaRESUMEN
BACKGROUND: Hepatocellular (HCC) and extrahepatic cancers have been associated with non-alcoholic fatty liver disease (NAFLD); however, the extent and nature of these relationships remain unclear. We aimed to estimate the absolute incidence rates of these cancers in adults with NAFLD with respect to key demographic and clinical factors. METHODS: We searched PubMed, Embase, Cochrane Library and Web of Science databases for studies reporting the incidence rates of any cancer in adults with NAFLD from inception to 31 August 2020. The main meta-analysis outcomes were pooled incidences of cancers in NAFLD using random-effects modelling. Subgroup analyses examined the effects of NAFLD disease stage. FINDINGS: In total, 64 studies were eligible for analysis of HCC and extrahepatic cancer incidence including 625,984 and 41,027 patients, respectively. The pooled HCC incidence rate was 1.25 per 1000 person-years (95% CI 1.01 to 1.49; I2 = 94.8%). In patients with NAFLD with advanced liver fibrosis or cirrhosis, the HCC incidence rate was 14.46 per 1000 person-years (95% CI 10.89 to 18.04; I2 = 91.3%). The pooled extrahepatic cancer incidence rate was 10.58 per 1000 person-years (95% CI 8.14 to 13.02; I2 = 97.1%). The most frequently occurring extrahepatic cancers were uterine, breast, prostate, colorectal, and lung. Extrahepatic cancer incidence rates were not higher in patients with NAFLD with advanced liver fibrosis or cirrhosis. INTERPRETATION: The rate of HCC development in patients with NAFLD who have progressed to advanced liver fibrosis or cirrhosis supports current HCC surveillance recommendations targeted for this group. Extrahepatic cancers are over eight-fold more frequent than HCC in NAFLD and not associated with liver fibrosis stage. As the global prevalence of NAFLD is approximately 25% and increasing, these findings support a focus on its prevention and the early detection of cancer in adults with NAFLD.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Adulto , Carcinoma Hepatocelular/diagnóstico , Fibrosis , Humanos , Incidencia , Cirrosis Hepática , Neoplasias Hepáticas/diagnóstico , Masculino , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND AND AIM: Symptoms of small intestinal bacterial overgrowth (SIBO) and celiac disease (CeD) often overlap, and studies suggest a link between SIBO and CeD. We thus conducted a systematic review and meta-analysis to compare SIBO prevalence in CeD patients and controls and assessed effects of antimicrobial therapy on gastrointestinal symptoms in SIBO positive CeD patients. METHODS: Electronic databases were searched until February 2022 for studies reporting SIBO prevalence in CeD. Prevalence rates, odds ratio (OR), and 95% confidence intervals (CI) of SIBO in CeD and controls were calculated. RESULTS: We included 14 studies, with 742 CeD patients and 178 controls. The pooled prevalence of SIBO in CeD was 18.3% (95% CI: 11.4-28.1), with substantial heterogeneity. Including case-control studies with healthy controls, SIBO prevalence in CeD patients was significantly increased (OR 5.1, 95% CI: 2.1-12.4, P = 0.0001), with minimal heterogeneity. Utilizing breath tests, SIBO prevalence in CeD patients was 20.8% (95% CI: 11.9-33.7), almost two-fold higher compared with culture-based methods at 12.6% (95% CI: 5.1-28.0), with substantial heterogeneity in both analyses. SIBO prevalence in CeD patients nonresponsive to a gluten free diet (GFD) was not statistically higher as compared with those responsive to GFD (OR 1.5, 95% CI: 0.4-5.0, P = 0.511). Antibiotic therapy of SIBO positive CeD patients resulted in improvement in gastrointestinal symptoms in 95.6% (95% CI: 78.0-99.9) and normalization of breath tests. CONCLUSIONS: This study suggests a link between SIBO and CeD. While SIBO could explain nonresponse to a GFD in CeD, SIBO prevalence is not statistically higher in CeD patients non-responsive to GFD. The overall quality of the evidence is low, mainly due to substantial "clinical heterogeneity" and the limited sensitivity/specificity of the available diagnostic tests.
Asunto(s)
Enfermedad Celíaca , Antibacterianos/uso terapéutico , Pruebas Respiratorias , Estudios de Casos y Controles , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/microbiología , Humanos , Intestino Delgado/microbiología , PrevalenciaRESUMEN
BACKGROUND: Mechanisms for how Helicobacter pylori infection affects risk of gastroesophageal reflux disease (GERD) and Barrett's esophagus are incompletely understood and might differ by sex. METHODS: In a case-control study nested in the Melbourne Collaborative Cohort Study with 425 GERD cases and 169 Barrett's esophagus cases (identified at 2007-2010 follow-up), we estimated sex-specific odds ratios for participants who were H. pylori seronegative versus seropositive at baseline (1990-1994). To explore possible mechanisms, we (i) compared patterns of H. pylori-induced gastritis by sex using serum pepsinogen-I and gastrin-17 data and (ii) quantified the effect of H. pylori seronegativity on Barrett's esophagus mediated by GERD using causal mediation analysis. RESULTS: For men, H. pylori seronegativity was associated with 1.69-fold [95% confidence interval (CI), 1.03-2.75] and 2.28-fold (95% CI, 1.27-4.12) higher odds of GERD and Barrett's esophagus, respectively. No association was observed for women. H. pylori-induced atrophic antral gastritis was more common in men (68%) than in women (56%; P = 0.015). For men, 5 of the 15 per 1,000 excess Barrett's esophagus risk from being seronegative were mediated by GERD. CONCLUSIONS: Men, but not women, who were H. pylori seronegative had increased risks of GERD and Barrett's esophagus. A possible explanation might be sex differences in patterns of H. pylori-induced atrophic antral gastritis, which could lead to less erosive reflux for men. Evidence of GERD mediating the effect of H. pylori on Barrett's esophagus risk among men supports this proposed mechanism. IMPACT: The findings highlight the importance of investigating sex differences in the effect of H. pylori on risk of GERD and Barrett's esophagus in future studies.
Asunto(s)
Esófago de Barrett , Gastritis , Reflujo Gastroesofágico , Infecciones por Helicobacter , Helicobacter pylori , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Reflujo Gastroesofágico/complicaciones , Infecciones por Helicobacter/complicaciones , Humanos , MasculinoRESUMEN
We examined demographic and lifestyle risk factors for incidence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) in an Australian cohort of 20,975 participants aged 40-63 at recruitment (1990-1994). Information on GERD and BE was collected between 2007 and 2010. GERD symptoms were defined as self-reported heartburn or acid regurgitation. BE was defined as endoscopically confirmed columnar-lined esophagus. Risk factors for developing GERD symptoms, BE diagnosis, age at symptom onset, and age at BE diagnosis were quantified using regression. During a mean follow-up of 15.8 years, risk of GERD symptoms was 7.5% (n = 1,318) for daily, 7.5% (n = 1,333) for 2-6 days/week, and 4.3% (n = 751) for 1 day/week. There were 210 (1.0%) endoscopically diagnosed BE cases, of whom 141 had histologically confirmed esophageal intestinal metaplasia. Female sex, younger age, lower socioeconomic position (SEP) and educational attainment, and former smoking were associated with higher GERD risk. Male sex and smoking were associated with earlier GERD symptom onset. Men, older participants, those with higher SEP, and former smokers were at higher BE risk. There was some evidence higher SEP was associated with earlier BE diagnosis. GERD and BE had different demographic risk factors but shared similar lifestyle factors. Earlier GERD symptom onset for men and smokers might have contributed to higher BE risk. The SEP patterns observed for GERD and BE suggest potential inequity in access to care. These findings would be important in the development of clinical risk prediction models for early detection of BE.
Asunto(s)
Esófago de Barrett , Reflujo Gastroesofágico , Australia/epidemiología , Esófago de Barrett/epidemiología , Esófago de Barrett/etiología , Femenino , Reflujo Gastroesofágico/epidemiología , Reflujo Gastroesofágico/etiología , Humanos , Incidencia , Estilo de Vida , Masculino , Factores de RiesgoRESUMEN
ABSTRACT: Kendall, BJ, Siekirk, NJ, and Lai, Q. Effects of acute high-intensity interval training on information processing speed. J Strength Cond Res 36(11): 3081-3086, 2022-This study investigated the effects of acute exercise on reaction time (RT), premotor time (i.e., central processing), and motor time (i.e., peripheral processing) using surface electromyography to fractionate RT. Fifty-eight young adults (27 men, 31 women) between the age of 18 and 40 years participated in 2 testing sessions. During visit one, subjects performed a simple RT task under regular (i.e., consistent timing) and irregular (i.e., variable timing) foreperiods. Subjects were then randomized to either an aerobic-only high-intensity interval training (HIIT) group (HIIT-A), an aerobic/resistance HIIT group (HIIT-AR), or a resting control group (CG). Both exercise groups performed a 20-minute, digital video disc-delivered HIIT exercise protocol. After exercise or rest, when controlling for cardiovascular fitness, no statistical differences were observed for the regular foreperiod conditions ( p > 0.05). For the irregular foreperiod conditions, the HIIT-A group (M = 219.8, SE = 6.5) and the HIIT-AR group (M = 218.2, SE = 5.8) had significantly faster mean RTs than the CG (M = 248.1, SE = 8.1). In addition, the HIIT-A (M = 172.1, SE = 4.6) and HIIT-AR exercise groups (M = 171.3, SE = 4.8) had significantly faster mean PMTs than the CG (M = 189.7, SE = 5.7). These findings suggest that tasks dependent on central processing may benefit from an acute bout of exercise.
Asunto(s)
Sistema Cardiovascular , Entrenamiento de Intervalos de Alta Intensidad , Adulto Joven , Masculino , Humanos , Femenino , Adolescente , Adulto , Entrenamiento de Intervalos de Alta Intensidad/métodos , Ejercicio Físico , CogniciónRESUMEN
Symptoms related with gastro-esophageal reflux disease (GERD) were previously shown to be linked with increased risk for the 2019 coronavirus disease (COVID-19). We aim to interrogate the possibility of a shared genetic basis between GERD and COVID-19 outcomes. Using published GWAS data for GERD (78 707 cases; 288 734 controls) and COVID-19 susceptibility (up to 32 494 cases; 1.5 million controls), we examined the genetic relationship between GERD and three COVID-19 outcomes: risk of developing severe COVID-19, COVID-19 hospitalization and overall COVID-19 risk. We estimated the genetic correlation between GERD and COVID-19 outcomes followed by Mendelian randomization (MR) analyses to assess genetic causality. Conditional analyses were conducted to examine whether known COVID-19 risk factors (obesity, smoking, type-II diabetes, coronary artery disease) can explain the relationship between GERD and COVID-19. We found small to moderate genetic correlations between GERD and COVID-19 outcomes (rg between 0.06 and 0.24). MR analyses revealed a OR of 1.15 (95% CI: 0.96-1.39) for severe COVID-19; 1.16 (1.01-1.34) for risk of COVID-19 hospitalization; 1.05 (0.97-1.13) for overall risk of COVID-19 per doubling of odds in developing GERD. The genetic correlation/associations between GERD and COVID-19 showed mild attenuation towards the null when obesity and smoking was adjusted for. Susceptibility for GERD and risk of COVID-19 hospitalization were genetically correlated, with MR findings supporting a potential causal role between the two. The genetic association between GERD and COVID-19 was partially attenuated when obesity is accounted for, consistent with obesity being a major risk factor for both diseases.
Asunto(s)
COVID-19/genética , Diabetes Mellitus Tipo 2/genética , Reflujo Gastroesofágico/genética , Predisposición Genética a la Enfermedad , Índice de Masa Corporal , COVID-19/complicaciones , COVID-19/virología , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/virología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/virología , Femenino , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/virología , Estudio de Asociación del Genoma Completo , Hospitalización , Humanos , Masculino , Análisis de la Aleatorización Mendeliana , Obesidad/complicaciones , Obesidad/genética , Obesidad/virología , Polimorfismo de Nucleótido Simple , Factores de Riesgo , SARS-CoV-2/genética , SARS-CoV-2/patogenicidad , Índice de Severidad de la Enfermedad , Fumar/efectos adversosRESUMEN
OBJECTIVE: Gastro-oesophageal reflux disease (GERD) has heterogeneous aetiology primarily attributable to its symptom-based definitions. GERD genome-wide association studies (GWASs) have shown strong genetic overlaps with established risk factors such as obesity and depression. We hypothesised that the shared genetic architecture between GERD and these risk factors can be leveraged to (1) identify new GERD and Barrett's oesophagus (BE) risk loci and (2) explore potentially heterogeneous pathways leading to GERD and oesophageal complications. DESIGN: We applied multitrait GWAS models combining GERD (78 707 cases; 288 734 controls) and genetically correlated traits including education attainment, depression and body mass index. We also used multitrait analysis to identify BE risk loci. Top hits were replicated in 23andMe (462 753 GERD cases, 24 099 BE cases, 1 484 025 controls). We additionally dissected the GERD loci into obesity-driven and depression-driven subgroups. These subgroups were investigated to determine how they relate to tissue-specific gene expression and to risk of serious oesophageal disease (BE and/or oesophageal adenocarcinoma, EA). RESULTS: We identified 88 loci associated with GERD, with 59 replicating in 23andMe after multiple testing corrections. Our BE analysis identified seven novel loci. Additionally we showed that only the obesity-driven GERD loci (but not the depression-driven loci) were associated with genes enriched in oesophageal tissues and successfully predicted BE/EA. CONCLUSION: Our multitrait model identified many novel risk loci for GERD and BE. We present strong evidence for a genetic underpinning of disease heterogeneity in GERD and show that GERD loci associated with depressive symptoms are not strong predictors of BE/EA relative to obesity-driven GERD loci.
Asunto(s)
Esófago de Barrett , Neoplasias Esofágicas , Esofagitis Péptica , Reflujo Gastroesofágico , Esófago de Barrett/complicaciones , Esófago de Barrett/diagnóstico , Esófago de Barrett/genética , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/genética , Estudio de Asociación del Genoma Completo , Humanos , Obesidad/complicaciones , Obesidad/genéticaRESUMEN
BACKGROUND: Postural control is critical for body sway control and is subserved by three sources of sensory feedback (ie, vision, proprioception and vestibulation). A method for determining the relative contribution of each sensory feedback source to postural control is the modified clinical test of sensory integration and balance for the balance tracking system (BTrackS). However, this method has not yet been evaluated for test-retest reliability. PURPOSE: To determine the test-retest reliability of the modified clinical test of sensory integration and balance protocol for the BTrackS across multiple time intervals. METHODS: Three groups of healthy young adults performed the BTrackS modified clinical test of sensory integration and balance protocol four times separated by either one day, one week or one month. Within each time duration group, and condition, differences in total center of pressure path length were determined from one test session to the next and intra class correlation coefficient categorizations were made. RESULTS: In all but one case, no significant difference in performance was seen from one testing session to the next. The one significant difference found was a decrease in total center of pressure path length from day 1 to day 2 in the vestibular condition of the group tested daily. Intra class correlation coefficient results largely indicated fair-good reliability across time durations and test conditions. CONCLUSION: The present study largely supports use of the BTrackS modified clinical test of sensory integration and balance protocol as a means of probing the sensory contributions to balance performance across multiple time durations.
RESUMEN
The current endoscopy and biopsy diagnosis of esophageal adenocarcinoma (EAC) and its premalignant condition Barrett's esophagus (BE) is not cost-effective. To enable EAC screening and patient triaging for endoscopy, we developed a microfluidic lectin immunoassay, the EndoScreen Chip, which allows sensitive multiplex serum biomarker measurements. Here, we report the proof-of-concept deployment for the EAC biomarker Jacalin lectin binding complement C9 (JAC-C9), which we previously discovered and validated by mass spectrometry. A monoclonal C9 antibody (m26 3C9) was generated and validated in microplate ELISA, and then deployed for JAC-C9 measurement on EndoScreen Chip. Cohort evaluation (n = 46) confirmed the expected elevation of serum JAC-C9 in EAC, along with elevated total serum C9 level. Next, we asked if the small panel of serum biomarkers improves detection of EAC in this cohort when used in conjunction with patient risk factors (age, body mass index and heartburn history). Using logistic regression modeling, we found that serum C9 and JAC-C9 significantly improved EAC prediction from AUROC of 0.838 to 0.931, with JAC-C9 strongly predictive of EAC (vs. BE OR = 4.6, 95% CI: 1.6-15.6, p = 0.014; vs. Healthy OR = 4.1, 95% CI: 1.2-13.7, p = 0.024). This proof-of-concept study confirms the microfluidic EndoScreen Chip technology and supports the potential utility of blood biomarkers in improving triaging for diagnostic endoscopy. Future work will expand the number of markers on EndoScreen Chip from our list of validated EAC biomarkers.
RESUMEN
INTRODUCTION: Colorectal cancer (CRC) mortality is significantly higher in those with severe mental illness (SMI) compared with the general population, despite similar incidence rates, suggesting that barriers to optimal screening and cancer care may contribute to disparities in CRC mortality in those with SMI. This study aims to compare participation in Australia's National Bowel Cancer Screening Programme (NBCSP) in those with SMI and those in the general population. We will also investigate treatment pathways after diagnosis to determine whether treatment variations could explain differences in CRC mortality. METHODS AND ANALYSIS: We will undertake a retrospective cohort study of Australians using linked administrative data to assess differences in screening and cancer care between those with and without SMI, aged 50-74 years on or after 1 January 2006. People with SMI will be defined using antipsychotic medication prescription data. The comparison group will be people enrolled in Medicare (Australia's universal healthcare system) who have not been prescribed antipsychotic medication. Data on outcomes (NBCSP participation, follow-up colonoscopy, CRC incidence and CRC-cause and all-cause mortality) and confounders will be obtained from national-based and state-based administrative health datasets. All people in New South Wales, aged 50-74 with a new diagnosis of CRC on or after 1 January 2006, will be ascertained to examine stage at diagnosis and cancer treatment in those with and without SMI. Poisson regression will be used to calculate incidence rates and rate ratios for each outcome. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the University of Queensland Human Research Ethics Committee, the Australian Institute of Health and Welfare Ethics Committee and data custodians from every Australian State/Territory. Findings will be disseminated via publications in peer-reviewed journals and presented at appropriate conferences. TRIAL REGISTRATION NUMBER: ACTRN12620000781943.