Esophageal cancer is the 7th leading cause of cancer deaths worldwide. While squamous cell carcinoma is the most prevalent histology internationally, adenocarcinoma of the distal esophagus accounts for nearly 50% of cases in developed countries due to the differences in the etiologic factors such as gastroesophageal reflux disease (GERD) and obesity that predominate. While surgery is the mainstay of treatment of this disease, the utilization of chemoradiation, either used postoperatively or neoadjuvantly, has become a standard practice in the United States. What is the optimal management approach is still an area of contention, however, and may be different in different regions around the world. This article reviews some of these controversies, including the role for surgery in patients treated with definitive chemoradiation. At the end, we will also outline recommendations regarding radiotherapy procedures and techniques.
Adenocarcinoma ; diagnosis ; epidemiology ; pathology ; therapy ; Carcinoma, Squamous Cell ; diagnosis ; epidemiology ; pathology ; therapy ; Chemoradiotherapy ; Esophageal Neoplasms ; diagnosis ; epidemiology ; pathology ; therapy ; Esophagectomy ; methods ; Humans ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Risk Factors

Objective: Heart rate variability (HRV) evaluates small beat-to-beat time interval (BBI) differences produced by the heart and suggested as a marker of the autonomic nervous system. Artifact produced by movement with wrist worn devices can significantly impact the validity of HRV analysis. The objective of this study was to determine the impact of small errors in BBI selection on HRV analysis and produce a foundation for future research in mental health wearable technology. Methods: This was a sub-analysis from a prospective observational clinical trial registered with clinicaltrials.gov (NCT03030924). A cohort of 10 subject’s HRV tracings from a wearable wrist monitor without any artifact were manipulated by the study team to represent the most common forms of artifact encountered. Results: Root mean square of successive differences stayed below a clinically significant change when up to 5 beats were selected at the wrong time interval and up to 36% of BBIs was removed. Standard deviation of next normal intervals stayed below a clinically significant change when up to 3 beats were selected at the wrong time interval and up to 36% of BBIs were removed. High frequency HRV shows significant changes when more than 2 beats were selected at the wrong time interval and any BBIs were removed. Conclusion Time domain HRV metrics appear to be more robust to artifact compared to frequency domains. Investigators examining wearable technology for mental health should be aware of these values for future analysis of HRV studies to improve data quality.

BACKGROUND/AIMS: Optimal bowel preparation is essential for successful screening or for surveillance colonoscopy (SC). Inadequate bowel preparation is associated with older age, the male gender, and the presence of certain comorbidities. However, the association between patients' functional status and bowel preparation quality has not been studied. We prospectively examined the relationship between functional status, namely, the ability to perform activities of daily living (ADLs) and ambulate, and the quality of bowel preparation in elderly patients undergoing SC. METHODS: Before undergoing SC, 88 elderly patients were surveyed regarding their functional status, specifically regarding their ability to perform ADLs and ambulate a quarter of a mile. Gastroenterologists then determined the quality of the bowel preparation, which was classified as either adequate or inadequate. Then, the frequency of inadequate bowel preparation in patients who did or did not experience difficulty performing ADLs and ambulating was calculated. RESULTS: Difficulty ambulating (unadjusted odds ratio [OR], 4.83; p<0.001), difficulty performing ADLs (OR, 2.93; p=0.001), and history of diabetes (OR, 2.88; p=0.007) were significant univariate predictors of inadequate bowel preparation. After adjusting for the above variables, only difficulty ambulating (adjusted OR, 5.78; p=0.004) was an independent predictor of inadequate bowel preparation. CONCLUSIONS: Difficulty with ambulation is a strong predictor of inadequate bowel preparation in elderly patients undergoing SC.
Activities of Daily Living ; Aged* ; Colonoscopy* ; Comorbidity ; Humans ; Male ; Mass Screening* ; Odds Ratio ; Prospective Studies ; Walking

BACKGROUNDGenetic factors account for approximately 50% of the individual variation in plasma low-density lipoprotein cholesterol (LDL-C) concentrations in the general population. Several candidate genes have been proposed but their relative contributions to the variance in LDL-C are not known, except for apolipoprotein E (apoE). We report here an investigation of the relationship between LDL-C and cholesterol 7alpha-hydroxylase (CYP7), as well as apoE and low-density lipoprotein receptor (LDLR), three pivotal genes in LDL metabolism.

METHODSOur study population included more than 200 nuclear families with increased coronary heart disease (CHD) risk from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Variance-component linkage methods, a measured genotype approach, and a variance-component linkage analysis conditional on a measured genotype association were used.

RESULTSThe results showed significant linkage between a genetic determinant of plasma LDL-C concentrations and a polymorphism near CYP7 with its allelic variation accounting for 27% of the total LDL-C variation. There is significant association between plasma LDL-C concentrations and apoE genotypes. Conditional on the apoE association, the total LDL-C variation accounted by allelic variation of a polymorphism near CYP7 was increased significantly.

CONCLUSIONOur results suggest the apoE and CYP7 may be two important genes accounting for the genetic variation of plasma LDL-C concentrations in a population with cardiovascular diseases.

Adult ; Aged ; Alleles ; Apolipoproteins E ; genetics ; Cholesterol 7-alpha-Hydroxylase ; genetics ; Cholesterol, LDL ; blood ; Coronary Disease ; genetics ; Female ; Genetic Linkage ; Genetic Variation ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, LDL ; genetics ; Risk Factors

Objective: Suicide is the 2nd leading cause of death in adolescence, and acute pediatric mental health emergency department (ED) visits have doubled in the past decade. The objective of this study was to evaluate physiologic parameters relationship to suicide severity. Methods: This was a prospective, observational study from April 2018 thru November 2019 in a tertiary care pediatric emergency department (ED) and inpatient pediatric psychiatric unit enrolling acutely suicidal adolescent patients. Patients wore a wrist device that used photoplethysmography for 7 days during their acute hospitalization to measure heart rate variability (HRV). During that time, Columbia Suicide Severity Scores (CSSRS) were assessed at 3 time points. Results: There was complete device data and follow-up for 51 patients. There was an increase in the high frequency (HF) component of HRV in patients that had a 25% or greater decrease in their CSSRS (mean difference 11.89 ms/ Hz ; p-value 0.005). Patients with a CSSRS≥15 on day of enrollment had a lower, although not statistically significant, HF component (mean difference -8.34 ms/ Hz; p-value 0.071). Conclusion We found an inverse correlation between parasympathetic activity measured through the HF component and suicidality in an acutely suicidal population of adolescents. Wearable technology may have the ability to improve outpatient monitoring for earlier detection and intervention.

The prevalence of allergic diseases is increasing globally, most particularly in middle- to low-income countries. This article examines the burden of allergic rhinitis and chronic urticaria in the Asia-Pacific region, unmet clinical needs, and the potential role of bilastine in the management of these conditions. An International Advisory Group meeting was convened in association with the Asian Pacific Society of Respirology Annual Congress in November 2014, followed by a literature review, and consensus-based outcomes from the meeting and literature review are described. Regional estimates of the prevalence of allergic rhinitis range from 10% to 50%, while little is known regarding the burden of urticaria in the Asia-Pacific region. A survey of allergy patients in the region identified fast, complete, and long-lasting symptom relief as the medication attributes most important to patients. International treatment guidelines for allergic rhinitis and urticaria advocate the first-line use of second-generation, no-sedating H1-antihistamines, such as bilastine, over their first-generation counterparts and a range of these agents are available to Asia-Pacific patients. The newer agents possess many of the properties of an "ideal" antihistamine (once daily administration, rapid and complete symptom relief, limited potential for drug-drug interactions, minimal side effects). The burgeoning prevalence of allergic diseases in the Asia-Pacific region and the uncontrolled symptoms that these patients experience demand a new antihistamine that offers the highest number of positive features according to the international guidelines.
Asia ; Asian Continental Ancestry Group ; Consensus ; Group Processes ; Histamine Antagonists ; Humans ; Hypersensitivity ; Prevalence ; Rhinitis, Allergic ; Urticaria

OBJECTIVEA randomized trial of breast self-examination (BSE) program was carried out to evaluate whether the intensive BSE can reduce the death number of women from breast cancer.

METHODSA total of 266,064 women (age of 30 to 64 years) associated with 519 textile factories in Shanghai had been randomly assigned to a BSE instruction group (132,979 women) or a control group (133,085 women) since 1989. Initial instruction in BSE group included demonstration of proper palpation techniques. It was followed by 2 reinforcement sessions during the subsequent 4 years including video shows, BSE instruction sessions and BSE practice under medical supervision. These activities were continued for 5 years. Attendance at all events was recorded. The cohort was followed through July 2000 for development of breast diseases, and the breast cancer cases were followed up through 2001 for vital status. The data analysis methods used included Kaplan-Meier plots, Log-rank test and Cox modeling.

RESULTSAmong women under instruction, 864 breast cancers were detected and 133 breast cancer deaths occurred, and 896 breast cancers were detected and 130 deaths recorded in the control group. The tumor size (P = 0.07), TNM stage (P = 0.39) and cumulative breast cancer mortality rate (P = 0.72) were not significantly different between the 2 groups. However, more and smaller fibroadenomas were detected in the instruction group than in the control group (P < 0.01).

CONCLUSIONIntensive instruction in BSE can not reduce mortality rate of breast cancer, but more and smaller benign breast lumps can be detected.

Adult ; Breast Neoplasms ; diagnosis ; epidemiology ; prevention & control ; Breast Self-Examination ; China ; epidemiology ; Female ; Humans ; Incidence ; Mass Screening ; Middle Aged

This review deals with the characteristics of various inflammatory mediators identified in the middle ear during otitis media and in cholesteatoma. The role of each inflammatory mediator in the pathogenesis of otitis media and cholesteatoma has been discussed. Further, the relation of each inflammatory mediator to the pathophysiology of the middle and inner ear along with its mechanisms of pathological change has been described. The mechanisms of hearing loss including sensorineural hearing loss (SNHL) as a sequela of otitis media are also discussed. The passage of inflammatory mediators through the round window membrane into the scala tympani is indicated. In an experimental animal model, an application of cytokines and lipopolysaccharide (LPS), a bacterial toxin, on the round window membrane induced sensorineural hearing loss as identified through auditory brainstem response threshold shifts. An increase in permeability of the blood-labyrinth barrier (BLB) was observed following application of these inflammatory mediators and LPS. The leakage of the blood components into the lateral wall of the cochlea through an increase in BLB permeability appears to be related to the sensorineural hearing loss by hindering K+ recycling through the lateral wall disrupting the ion homeostasis of the endolymph. Further studies on the roles of various inflammatory mediators and bacterial toxins in inducing the sensorineumral hearing loss in otitis media should be pursued.
Bacterial Toxins ; Chemokines ; Cholesteatoma ; Cochlea ; Cytokines ; Ear, Inner ; Ear, Middle ; Endolymph ; Evoked Potentials, Auditory, Brain Stem ; Hearing Loss ; Hearing Loss, Sensorineural ; Homeostasis ; Membranes ; Models, Animal ; Otitis ; Otitis Media ; Permeability ; Recycling ; Scala Tympani

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a multifaceted disorder that afflicts millions of individuals worldwide. IBS is currently diagnosed based on the presence/duration of symptoms and systematic exclusion of other conditions. A more direct manner to identify IBS is needed to reduce healthcare costs and the time required for accurate diagnosis. The overarching objective of this work is to identify gene expression-based biological signatures and biomarkers of IBS. METHODS: Gene transcripts from 24 tissue biopsy samples were hybridized to microarrays for gene expression profiling. A combination of multiple statistical analyses was utilized to narrow the raw microarray data to the top 200 differentially expressed genes between IBS versus control subjects. In addition, quantitative polymerase chain reaction was employed for validation of the DNA microarray data. Gene ontology/pathway enrichment analysis was performed to investigate gene expression patterns in biochemical pathways. Finally, since vitamin D has been shown to modulate serotonin production in some models, the relationship between serum vitamin D and IBS was investigated via 25-hydroxyvitamin D (25[OH]D) chemiluminescence immunoassay. RESULTS: A total of 858 genetic features were identified with differential expression levels between IBS and asymptomatic populations. Gene ontology enrichment analysis revealed the serotonergic pathway as most prevalent among the differentially expressed genes. Further analysis via real-time polymerase chain reaction suggested that IBS patient-derived RNA exhibited lower levels of tryptophan hydroxylase-1 expression, the enzyme that catalyzes the rate-limiting step in serotonin biosynthesis. Finally, mean values for 25(OH)D were lower in IBS patients relative to non-IBS controls. CONCLUSIONS: Values for serum 25(OH)D concentrations exhibited a trend towards lower vitamin D levels within the IBS cohort. In addition, the expression of select IBS genetic biomarkers, including tryptophan hydroxylase 1, was modulated by vitamin D. Strikingly, the direction of gene regulation elicited by vitamin D in colonic cells is “opposite” to the gene expression profile observed in IBS patients, suggesting that vitamin D may help “reverse” the pathological direction of biomarker gene expression in IBS. Thus, our results intimate that IBS pathogenesis and pathophysiology may involve dysregulated serotonin production and/or vitamin D insufficiency.
Biomarkers ; Biopsy ; Cohort Studies ; Colon ; Diagnosis ; Gene Expression Profiling ; Gene Expression ; Gene Ontology ; Health Care Costs ; Humans ; Immunoassay ; Irritable Bowel Syndrome ; Luminescence ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction ; RNA ; Serotonin ; Transcriptome ; Tryptophan ; Tryptophan Hydroxylase ; Vitamin D ; Vitamins

As COVID-19 pandemic approaching its third year, more data have shown that obesity and hypertriglyceridemia are the high-risk factors for the major complications such as acute respiratory distress syndrome, thromboembolism, coagulopathy and cytokine storm, which are responsible for the majority of disease severity and mortality. In this review article, we have analyzed the public available clinical reports and laboratory research results of the COVID-19 studies by researchers and clinicians of many nations around the world. Many of these reports covered COVID-19 patients of different ethnic groups. We suggested that obesity and high triglycerides are high risks for severe COVID-19 and death. We also summarized the possible underlying molecular mechanism likely connecting the severe COVID-19 with obesity and hypertriglyceridemia. From public health perspective, we highlight the importance of the healthy diet and lifestyle in fighting against SARS-CoV-2 virus in long period of time.
Humans ; COVID-19 ; Pandemics ; SARS-CoV-2 ; Hypertriglyceridemia ; Obesity ; Severity of Illness Index