Oral microbiome and risk of malignant esophageal lesions in a high-risk area of China:A nested case-control study

Objective:We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk.Methods:We conducted a case-control study nested within a population-based cohort with up to 8 visits of oral swab collection for each subject over an 11-year period in a high-risk area for esophageal cancer in China.The oral microbiome was evaluated with 16 S ribosomal RNA(rRNA)gene sequencing in 428 pre-diagnostic oral specimens from 84 cases with esophageal lesions of severe squamous dysplasia and above(SDA)and 168 matched healthy controls.DESeq analysis was performed to identify taxa of differential abundance.Differential oral species together with subject characteristics were evaluated for their potential in predicting SDA risk by constructing conditional logistic regression models.Results:A total of 125 taxa including 37 named species showed significantly different abundance between SDA cases and controls(all P<0.05&false discovery rate-adjusted Q<0.10).A multivariate logistic model including 11 SDA lesion-related species and family history of esophageal cancer provided an area under the receiver operating characteristic curve(AUC)of 0.89(95%CI,0.84-0.93).Cross-validation and sensitivity analysis,excluding cases diagnosed within 1 year of collection of the baseline specimen and their matched controls,or restriction to screenendoscopic-detected or clinically diagnosed case-control triads,or using only bacterial data measured at the baseline,yielded AUCs>0.84.Conclusions:The oral microbiome may play an etiological and predictive role in esophageal cancer,and it holds promise as a non-invasive early warning biomarker for risk stratification for esophageal cancer screening programs.

Hospital contacts with alcohol problems prior to liver cirrhosis or pancreatitis diagnosis

AIM To evaluate prior hospital contacts with alcohol problems in patients with alcoholic liver cirrhosis and pancreatitis. METHODS This was a register-based study of all patients diagnosed with alcoholic liver cirrhosis or pancreatitis during 2008-2012 in Denmark. Hospital contacts with alcohol problems(intoxication, harmful use, or dependence) in the 10-year period preceding the diagnosis of alcoholic liver cirrhosis and pancreatitis were identified.RESULTS In the 10 years prior to diagnosis, 40% of the 7719 alcoholic liver cirrhosis patients and 40% of the 1811 alcoholic pancreatitis patients had at least one prior hospital contact with alcohol problems. Every sixth patient(15%-16%) had more than five contacts. A similar pattern of prior hospital contacts was observed for alcoholic liver cirrhosis and pancreatitis. Around 30% were diagnosed with alcohol dependence and 10% with less severe alcohol diagnoses. For the majority, admission to somatic wards was the most common type of hospital care with alcohol problems. Most had their first contact with alcohol problems more than five years prior to diagnosis.CONCLUSION There may be opportunities to reach some of the patients who later develop alcoholic liver cirrhosis or pancreatitis with preventive interventions in the hospital setting.

Association of obesity with hypertension and type 2 diabetes mellitus in India:A meta-analysis of observational studies

AIM To perform a meta-analysis of the association of obesity with hypertension and type 2 diabetes mellitus(T2DM) in India among adults. METHODS To conduct meta-analysis, we performed comprehensive, electronic literature search in the PubM ed, CINAHL Plus, and Google Scholar. We restricted the analysis to studies with documentation of some measure of obesity namely; body mass index, waist-hip ratio, waist circumference and diagnosis of hypertension or diagnosis of T2DM. By obtaining summary estimates of all included studies, the meta-analysis was performed using both RevM an version 5 and "metan" command STATA version 11. Heterogeneity was measured by I^2 statistic. Funnel plot analysis has been done to assess the study publication bias.RESULTS Of the 956 studies screened, 18 met the eligibility criteria. The pooled odds ratio between obesity and hypertension was 3.82(95%CI: 3.39 to 4.25). The heterogeneity around this estimate(I^2 statistic) was 0%, indicating low variability. The pooled odds ratio from the included studies showed a statistically significant association between obesity and T2DM(OR = 1.14, 95%CI: 1.04 to 1.24) with a high degree of variability.CONCLUSION Despite methodological differences, obesity showed significant, potentially plausible association with hypertension and T2DM in studies conducted in India. Being a modifiable risk factor, our study informs setting policy priority and intervention efforts to prevent debilitating complications.

Worldwide trends in esophageal cancer survival,by sub-site,morphology,and sex:an analysis of 696,974 adults diagnosed in 60 countries during 2000-2014(CONCORD-3)

Background Esophageal cancer survival is poor worldwide,though there is some variation.Differences in the distribution of anatomical sub-site and morphological sub-type may help explain international differences in survival for all esophageal cancers combined.We estimated survival by anatomic sub-site and morphological sub-type to understand further the impact of topography and morphology on international comparisons of esophageal cancer survival.Methods We estimated age-standardized one-year and five-year net survival among adults(15-99 years)diagnosed with esophageal cancer in each of 60 participating countries to monitor survival trends by calendar period of diagnosis(2000-2004,2005-2009,2010-2014),sub-site,morphology,and sex.Results For adults diagnosed during 2010-2014,tumors in the lower third of the esophagus were the most common,followed by tumors of overlapping sub-site and sub-site not otherwise specified.The proportion of squamous cell carcinomas diagnosed during 2010-2014 was generally higher in Asian countries(50%-90%),while adenocarcinomas were more common in Europe,North America and Oceania(50%-60%).From 2000-2004 to 2010-2014,the proportion of squamous cell carcinoma generally decreased,and the proportion of adenocarcinoma increased.Over time,there were few improvements in age-standardized five-year survival for each sub-site.Age-standardized one-year survival was highest in Japan for both squamous cell carcinoma(67.7%)and adenocarcinoma(69.0%),ranging between 20%-60%in most other countries.Age-standardized five-year survival from squamous cell carcinoma and adenocarcinoma was similar for most countries included,around 15%-20%for adults diagnosed during 2010-2014,though international variation was wider for squamous cell carcinoma.In most countries,survival for both squamous cell carcinoma and adenocarcinoma increased by less than 5%between 2000-2004 and 2010-2014.Conclusions Esophageal cancer survival remains poor in many countries.The distributions of sub-site and morphological sub-type vary between countries,but these differences do not fully explain international variation in esophageal cancer survival.

Pancreatic cancer survival trends in the US from 2001 to 2014:a CONCORD-3 study

Background:Survival from pancreatic cancer is low worldwide.In the US,the 5-year relative survival has been slightly higher for women,whites and younger patients than for their counterparts,and differences in age and stage at diagnosis[Corrections added Nov 16,2022,after first online publication:a new affiliation is added to Maja Nikšić]may contribute to this pattern.We aimed to examine trends in survival by race,stage,age and sex for adults(15-99 years)diagnosed with pancreatic cancer in the US.Methods:This population-based study included 399,427 adults registered with pancreatic cancer in 41 US state cancer registries during 2001-2014,with followup to December 31,2014.We estimated age-specific and age-standardized net survival at 1 and 5 years.Results:Overall,12.3%of patients were blacks,and 84.2%were whites.About 9.5%of patients were diagnosed with localized disease,but 50.5%were diagnosed at an advanced stage;slightly more among blacks,mainly among men.No substantial changes were seen over time(2001-2003,2004-2008,2009-2014).In general,1-year net survival was higher in whites than in blacks(26.1%vs.22.1%during 2001-2003,35.1%vs.31.4%during 2009-2014).This difference was particularly evident among patients with localized disease(49.6%in whites vs.44.6%in blacks during 2001-2003,60.1%vs.55.3%during 2009-2014).The survival gap between blacks and whites with localized disease was persistent at 5 years after diagnosis,and it widened over time(from 24.0%vs.21.3%during 2001-2003 to 39.7%vs.31.0%during 2009-2014).The survival gap was wider among men than among women.Conclusions:Gaps in 1-and 5-year survival between blacks and whites were persistent throughout 2001-2014,especially for patients diagnosed with a localized tumor,for which surgery is currently the only treatment modality with the potential for cure.

科学、医学与未来基因组学向改进医疗保健的转化

本文要点 至今，大多数常见病的遗传学基础仍然难以捉摸 如今，全基因组关联分析已揭示了人类DNA中有成千上万个区域，这些区域中的基因序列变异影响机体对常见病的易感性 常见的与疾病相关的单核苷酸多态性分布在多重的染色体区域里，