Epidemiology and Racial Differences of EoE Patients in a U.S. Veterans Population.

BACKGROUND: Eosinophilic esophagitis (EoE) is increasing in prevalence but there is a lack of population-based studies. We sought to determine the prevalence, demographics, and associated atopic diseases in the Veterans Affairs (VA) population. METHODS: A nationwide analysis of data from the VA patient population was done using a Veterans Health Administration database. EoE was identified using ICD9 (530.13) and ICD10 (K20.0) codes from October 2008 to June 2020. Demographic data, smoking status, BMI, treatment, and ICD codes for atopic diagnoses were collected. Two sample proportion z-tests, Chi-square tests, two-sample t tests, and one-way ANOVA were used to assess associations across demographic categories. RESULTS: We identified a total of 11,775 patients with an EoE diagnosis: 91% male, 83% White, 8.6% Black, and 5% were of Hispanic ethnicity. The prevalence of EoE increased over time. At diagnosis, the mean age was 48.5 years overall, 51.6 years for Black patients, 45.3 years for Hispanic patients, and 48.2 years for Whites. Dysphagia was the most common symptom overall, but a higher percentage of Blacks and females were found to report chest pain (p < 0.0001, h = 0.32). With the exception of urticaria and atopic dermatitis, both Blacks and Hispanics had a higher incidence of atopic conditions compared to other races and ethnicities (p < 0.0001). CONCLUSION: While EoE is seen primarily in White males, our study shows that a notable percentage of patients were Black or Hispanic, suggesting that EoE should be considered in non-white patients. The later age of diagnosis in this group could represent a lack of awareness about EoE among non-white patients. More research is needed to study these associations.

The Impact of Obesity on the Fibrostenosis Progression of Eosinophilic Esophagitis in a U.S. Veterans Cohort.

Whether obesity is protective against progression of EoE is unknown. The aim of this study was to assess factors that alter the progression of EoE and determine if BMI is correlated with reduced disease severity. In this retrospective analysis of the Department of Veterans Affairs electronic health records, patients with EoE who received at least one dilation were identified using ICD and CPT codes. Kaplan-Meier curves determined the relationship between BMI and time to second esophageal dilation as a measurement of severity of disease. Cox proportional hazards models assessed the risk of second dilation adjusted for potential confounders. Of 2890 patients with EoE and at least one dilation, 40% were obese (n = 1165). There were no clinically significant differences in demographics between obese and non-obese patients. Non-obese patients were more likely to be smokers and had a higher mean average of the number of dilation visits compared to obese patients (p < 0.05). When stratified by obesity, non-obese individuals had a median time to next dilation of 6.53 years (95% CI (5.83, 7.79)) compared to 9.24 years for obese individuals (95% CI (7.40, 15.04)). When stratified by six BMI categories, median time to second dilation increased with increasing BMI. The hazard ratio of second dilation for obese individuals was 0.81 (95% CI (0.72-0.92)). EoE patients with a higher BMI were less likely to undergo a second dilation compared to those with a lower BMI. Obesity may have a protective role in EoE or severe strictures may lead to malnourishment. Further research into these possibilities is needed.

Prevalence of Advanced Colorectal Neoplasia in Veterans: Effects of Age, Sex, and Race/Ethnicity.

GOAL: We sought to quantify the independent effects of age, sex, and race/ethnicity on risk of colorectal cancer (CRC) and advanced neoplasia (AN) in Veterans. STUDY: We conducted a retrospective, cross-sectional study of Veterans aged 40 to 80 years who had diagnostic or screening colonoscopy between 2002 and 2009 from 1 of 14 Veterans Affairs Medical Centers. Natural language processing identified the most advanced finding and location (proximal, distal). Logistic regression was used to examine the adjusted, independent effects of age, sex, and race, both overall and in screening and diagnostic subgroups. RESULTS: Among 90,598 Veterans [mean (SD) age 61.7 (9.4) y, 5.2% (n=4673) were women], CRC and AN prevalence was 1.3% (n=1171) and 8.9% (n=8081), respectively. Adjusted CRC risk was higher for diagnostic versus screening colonoscopy [odds ratio (OR)=3.79; 95% confidence interval (CI), 3.19-4.50], increased with age, was numerically (but not statistically) higher for men overall (OR=1.53; 95% CI, 0.97-2.39) and in the screening subgroup (OR=2.24; 95% CI, 0.71-7.05), and was higher overall for Blacks and Hispanics, but not in screening. AN prevalence increased with age, and was present in 9.2% of men and 3.9% of women [adjusted OR=1.90; 95% CI, 1.60-2.25]. AN risk was 11% higher in Blacks than in Whites overall (OR=1.11; 95% CI, 1.04-1.20), was no different in screening, and was lower in Hispanics (OR=0.74; 95% CI, 0.55-0.98). Women had more proximal CRC (63% vs. 39% for men; P=0.03), but there was no difference in proximal AN (38.3% for both genders). CONCLUSIONS: Age and race were associated with AN and CRC prevalence. Blacks had a higher overall prevalence of both CRC and AN, but not among screenings. Men had increased risk for AN, while women had a higher proportion of proximal CRC. These findings may be used to tailor when and how Veterans are screened for CRC.

Multi-center colonoscopy quality measurement utilizing natural language processing.

BACKGROUND: An accurate system for tracking of colonoscopy quality and surveillance intervals could improve the effectiveness and cost-effectiveness of colorectal cancer (CRC) screening and surveillance. The purpose of this study was to create and test such a system across multiple institutions utilizing natural language processing (NLP). METHODS: From 42,569 colonoscopies with pathology records from 13 centers, we randomly sampled 750 paired reports. We trained (n=250) and tested (n=500) an NLP-based program with 19 measurements that encompass colonoscopy quality measures and surveillance interval determination, using blinded, paired, annotated expert manual review as the reference standard. The remaining 41,819 nonannotated documents were processed through the NLP system without manual review to assess performance consistency. The primary outcome was system accuracy across the 19 measures. RESULTS: A total of 176 (23.5%) documents with 252 (1.8%) discrepant content points resulted from paired annotation. Error rate within the 500 test documents was 31.2% for NLP and 25.4% for the paired annotators (P=0.001). At the content point level within the test set, the error rate was 3.5% for NLP and 1.9% for the paired annotators (P=0.04). When eight vaguely worded documents were removed, 125 of 492 (25.4%) were incorrect by NLP and 104 of 492 (21.1%) by the initial annotator (P=0.07). Rates of pathologic findings calculated from NLP were similar to those calculated by annotation for the majority of measurements. Test set accuracy was 99.6% for CRC, 95% for advanced adenoma, 94.6% for nonadvanced adenoma, 99.8% for advanced sessile serrated polyps, 99.2% for nonadvanced sessile serrated polyps, 96.8% for large hyperplastic polyps, and 96.0% for small hyperplastic polyps. Lesion location showed high accuracy (87.0-99.8%). Accuracy for number of adenomas was 92%. CONCLUSIONS: NLP can accurately report adenoma detection rate and the components for determining guideline-adherent colonoscopy surveillance intervals across multiple sites that utilize different methods for reporting colonoscopy findings.

The Association Between Race and Stroke Prevalence in a Patient Cohort in Mississippi.

The risk factors for stroke, including hypertension, high cholesterol, heart disease, diabetes, heavy alcohol use, and prior history of stroke, are well known. In Mississippi, there is often a wider gulf of socioeconomic disparities between racial groups than in other regions within the United States. This increases the effect of these disparities in minority populations. The goal of this research is to determine whether there is an increased risk of stroke prevalence in the black community than in the white population. The odds ratio of 1.5 (CI 1.3818 - 1.5591) was returned for this analysis. White patients diagnosed with stroke represented 38 percent of the cohort while black patients totaled 62 percent of this cohort. There is a higher prevalence of stroke in the black population compared to the white population in this study cohort. The importance of this finding is apparent upon consideration of deficiencies in the management of risk factors. Note: The University of Mississippi Medical Center Patient Cohort explorer database search used for this study uses a data filter set for 'black' or 'African-American' in the search query. This study includes those patients designated 'black' or 'African-American' admitted with stroke at the University of Mississippi Medical Center. For clarity, this cohort will be identified in this paper as 'black Americans.'

Preoperative physiological esophageal assessment for anti-reflux surgery: A guide for surgeons on high-resolution manometry and pH testing.

Gastroesophageal reflux disease (GERD) is one of the most commonly encountered digestive diseases in the world, with the prevalence continuing to increase. Many patients are successfully treated with lifestyle modifications and proton pump inhibitor therapy, but a subset of patients require more aggressive intervention for control of their symptoms. Surgical treatment with fundoplication is a viable option for patients with GERD, as it attempts to improve the integrity of the lower esophageal sphincter (LES). While surgery can be as effective as medical treatment, it can also be associated with side effects such as dysphagia, bloating, and abdominal pain. Therefore, a thorough pre-operative assessment is crucial to select appropriate surgical candidates. Newer technologies are becoming increasingly available to help clinicians identify patients with true LES dysfunction, such as pH-impedance studies and high-resolution manometry (HRM). Pre-operative evaluation should be aimed at confirming the diagnosis of GERD, ruling out any major motility disorders, and selecting appropriate surgical candidates. HRM and pH testing are key tests to consider for patients with GERD like symptoms, and the addition of provocative measures such as straight leg raises and multiple rapid swallows to HRM protocol can assess the presence of underlying hiatal hernias and to test a patient's peristaltic reserve prior to surgery.

Colonoscopy and colorectal cancer rates among octogenarians and nonagenarians: nationwide study of US veterans.

BACKGROUND: According to Surveillance, Epidemiology and End Results (SEER) database, colorectal cancer (CRC) is the fourth most common type of cancer and second highest in cancer-related death after lung cancer. The SEER database is geographically limited, currently present in only 10-12 states. Though this gives a good approximation about the overall direction of CRC incidence and prevalence, we need more nationwide data to compare numbers. Furthermore, colonoscopies and CRC rates in the Veterans Affair (VA) geriatric population have not been studied. OBJECTIVES AND METHODS: Our aim was to study the rate of colonoscopies and CRC in octogenarians and nonagenarians and to find the prevalence of CRC in this population. The goal was to obtain data in this subset of patients in order to further expand CRC screening guidelines. A retrospective data analysis was performed consisting of US male veterans who underwent colonoscopy in the VA Health Care System from 2000 to 2015. RESULTS AND CONCLUSION: A total of 458,224 patients aged ≥80 years were identified from the database between years 2000 and 2015. This was divided into three groups of age 80-84 years (89,621 patients), 85-90 years (248,155 patients), and >90 years (120,448 patients). A total of 81,946 patients underwent colonoscopies of which 9,365 were diagnosed with CRC. There was a statistically significant linear increase in rate of colonoscopies with increase in age suggesting that these veterans who end up living to a higher age eventually get a colonoscopy for one reason or the other. The drop in CRC percentage and prevalence observed in age group 85-90 years is statistically different when compared to that in 80-84 years and >90 years groups; however, its clinical significance remains to be elucidated.

Staging and survival of colorectal cancer (CRC) in octogenarians: Nationwide Study of US Veterans.

BACKGROUND: The US Preventive Services Task Force of Colorectal Cancer (USPSTF) recommends against continuing screening for colorectal cancer (CRC) past 75 years in adequately screened individuals. Survival and staging data for CRC that compares elderly vs. younger populations has not been published. This study aims to compare staging (0-4) of CRC in groups of 60-69, 70-79 and 80-89-year-old; also, to compare surgical and no treatment (i.e., no surgery) survival outcomes (5-10 years) in these age groups. METHODS: Male veterans within groups 60-69, 70-79 and 80-89 years of age who were diagnosed with CRC between 2000 and 2015 were selected from Veterans affairs national cancer cube registry. RESULTS: Their staging, surgery or no treatment, and 5-10 years survival data was obtained from the cancer cube. Surgical and survival data was obtained only for stage 0-2 as surgery is currently the standard of treatment for these stages. CONCLUSIONS: Highest number of CRC cases diagnosed across each age group was stage 1 with stage 2 being second. In surgical treatment group the survival was statistical different for 80-89 age group as compared to 60-69 (34.4%) and 70-79 (30.86%) although octogenarians did have a surprisingly high mean of 25.45%. The 5-10-year survival data for no treatment group (i.e., no surgery) was very poor.

Mutations in fast skeletal troponin I, troponin T, and beta-tropomyosin that cause distal arthrogryposis all increase contractile function.

Distal arthrogryposes (DAs) are a group of disorders characterized by congenital contractures of distal limbs without overt neurological or muscle disease. Unexpectedly, mutations in genes encoding the fast skeletal muscle regulatory proteins troponin T (TnT), troponin I (TnI), and beta-tropomyosin (beta-TM) have been shown to cause autosomal dominant DA. We tested how these mutations affect contractile function by comparing wild-type (WT) and mutant proteins in actomyosin ATPase assays and in troponin-replaced rabbit psoas fibers. We have analyzed all four reported mutants: Arg63His TnT, Arg91Gly beta-TM, Arg174Gln TnI, and a TnI truncation mutant (Arg156ter). Thin filaments, reconstituted using actin and WT troponin and beta-TM, activated myosin subfragment-1 ATPase in a calcium-dependent, cooperative manner. Thin filaments containing either a troponin or beta-TM DA mutant produced significantly enhanced ATPase rates at all calcium concentrations without alternating calcium-sensitivity or cooperativity. In troponin-exchanged skinned fibers, each mutant caused a significant increase in Ca2+ sensitivity, and Arg156ter TnI generated significantly higher maximum force. Arg91Gly beta-TM was found to have a lower actin affinity than WT and form a less stable coiled coil. We propose the mutations cause increased contractility of developing fast-twitch skeletal muscles, thus causing muscle contractures and the development of the observed limb deformities.

Autopsy tissue trace elements in 8 long-term parenteral nutrition patients who received the current U.S. Food and Drug Administration formulation.

Iron, zinc, copper, manganese, chromium, and selenium levels were measured in autopsy tissues of 8 people with short bowel syndrome who received home parenteral nutrition (HPN) and the U.S. Food and Drug Administration (FDA)-approved trace element formulation for an average duration of 14 years (range, 2-21). Iron, zinc, copper, manganese and selenium were measured by inductively coupled plasma methods; chromium, by graphite furnace atomic absorption spectrometry. The levels in the 4 tissues studied, heart, skeletal muscle, liver, and kidney, were compared with levels in 45 controls who died without chronic gastrointestinal disorders. Results showed normal HPN patient values for iron and selenium, mild elevation of zinc, and major elevations of copper, manganese, and chromium. The implications of these results for trace-element supplements in long-term PN adult patients are discussed, and the need for reformulation of commercially available multi-trace element products in the United States is stressed.

Effects of troponin C isoform on the action of the cardiotonic agent EMD 57033.

The effects of the cardiotonic potentiator EMD 57033 on different TnC (troponin C) isoforms were investigated. Endogenous skeletal TnC was extracted from glycerinated, permeabilized rabbit psoas fibres and replaced with either purified native rabbit psoas TnC (fast TnC) or human recombinant cTnC (cardiac TnC) (3 mg/ml in relaxing solution for 30 min). In both conditions, 10 microM EMD 57033 increased maximal calcium-activated force (Pmax) and gave a leftward shift in the pCa-tension curve. With cTnC, the increase in Pmax was much greater (228%) compared with the effect seen for fast TnC (137%), which was the same as that in unextracted control fibres. When the whole troponin was replaced rather than just TnC, the effects of EMD 57033 on fibres replaced with cTn were the same as with the cTnC subunit alone, except that the force at low Ca2+ concentrations was not increased as much. If TnC was only partially extracted, it was found that the degree of extraction did not influence the effect of EMD 57033, except when force was decreased to below 10% of the pre-extraction Pmax. Dynamic stiffness was not altered by EMD 57033 in any of the preparations. The rate of tension recovery following a release-restretch method (ktr) was decreased by EMD 57033. We conclude that EMD 57033 acts by a rate-modulating effect, and that the quantitative response of this effect is dependent on the TnC isoform present.

Endothelin Opens Potassium Channels in Glial Cells.

Endothelin-1 (ET-1), an autocrine hormone synthesized by astrocytes, and endothelin-3 (ET-3), a highly homologous peptide produced by neurons, have both been shown previously to cause proliferation of these astrocytes in culture [Supattapone et al. (1989) Biochem. Biophys. Res. Commun., 165, 1115 - 1122; MacCumber et al. (1990) Proc. Natl. Acad. Sci. USA, 87, 2359 - 2363]. We now demonstrate, using 86Rb+ influx assays and single channel patch-clamp recording, that both endothelins-ET-3 and ET-1-can also open a charybdotoxin-sensitive, calcium-activated K+ channel of 15 - 40 pS in glial cells. The opening of this channel may be important for the regulation of [K+] in the brain microenvironment. Thus, the endothelins may be a general mediator of astroglial response to neuronal injury.

Potential P-glycoprotein pharmacokinetic interaction of telaprevir with morphine or methadone.

Telaprevir (TVR) effects on P-glycloprotein and cytochrome P450 (CYP) may significantly elevate serum levels of morphine and methadone. Recent literature points to major interactions when combining TVR with warfarin or rifampin. Opioid interactions are especially dangerous in hepatitis C patients, as coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) occurs in 50-90% of HIV-infected drug users that are prescribed opioids for chronic pain and/or methadone for maintenance. TVR has been shown to significantly inhibit the active transport enzyme pGP and may therefore increase intestinal morphine absorption. TVR also inhibits hepatic CYP3A4 that are responsible for metabolizing methadone. Patients requiring opioid analgesics must be carefully monitored because of potential for elevated opioid levels and overdose risk. Current recommendations minimize potential drug interactions between telaprevir and opioids, especially methadone, based on a single 7-day trial. We outline the various pharmacokinetic mechanisms involved when combining TVR with methadone or morphine and recommend that current data are not sufficiently robust to minimize the potentially significant interaction with opioids, especially methadone. Clinicians must be mindful of these understated interactions, know that the opioid dose may need to be significantly increased or reduced, and use caution during upward titration of opioids affected by these enzyme systems.

Neutrophilic myositis as a manifestation of celiac disease: a case report.

A 42-year-old white man presented with recurrent attacks of muscle pain and swelling. Clinically, he looked like he had severe pyogenic infection. He failed to respond to multiple courses of wide-spectrum antibiotics. Repeated cultures from muscle lesions and from the blood were negative. Hospital course was very hectic and life threatening at times. Upon further questioning, the patient gave a history of frequent loose-bowel movements for many years. A duodenal biopsy with villous blunting and positive antiglidin antibodies confirmed the diagnosis of celiac disease. The patient had complete recovery and remained in remission on a gluten-free diet.

DCM troponin C mutant Gly159Asp blunts the response to troponin phosphorylation.

Dilated cardiomyopathy (DCM) can be caused by a Gly159Asp mutation in cardiac troponin C (cTnC). Our previous work found that partial replacement of endogenous troponin in skinned muscle fibres with human cardiac troponin containing Gly159Asp cTnC had no significant effect on maximum force generation, Ca(2+)-sensitivity or cooperativity, but halved the activation rate. In order to examine whether the mutant affected contractility when troponin was phosphorylated, Gly159Asp cTnC was introduced in the presence of a phosphomimic of protein kinase A phosphorylation of troponin I (Ser23Asp,Ser24Asp). The increased force production of the muscle fibres caused by this phosphomimic was significantly depressed. Furthermore, in the presence of the protein kinase C phosphomimic of troponin T (Thr203Glu), Gly159Asp mutant significantly reversed the decrease in Ca(2+)-sensitivity. We conclude that this DCM mutant significantly blunts the contractile response to phosphorylation and this novel mechanism may contribute to its pathogenic effect.

Dilated cardiomyopathy mutations in three thin filament regulatory proteins result in a common functional phenotype.

Dilated cardiomyopathy (DCM), characterized by cardiac dilatation and contractile dysfunction, is a major cause of heart failure. Inherited DCM can result from mutations in the genes encoding cardiac troponin T, troponin C, and alpha-tropomyosin; different mutations in the same genes cause hypertrophic cardiomyopathy. To understand how certain mutations lead specifically to DCM, we have investigated their effect on contractile function by comparing wild-type and mutant recombinant proteins. Because initial studies on two troponin T mutations have generated conflicting findings, we analyzed all eight published DCM mutations in troponin T, troponin C, and alpha-tropomyosin in a range of in vitro assays. Thin filaments, reconstituted with a 1:1 ratio of mutant/wild-type proteins (the likely in vivo ratio), all showed reduced Ca(2+) sensitivity of activation in ATPase and motility assays, and except for one alpha-tropomyosin mutant showed lower maximum Ca(2+) activation. Incorporation of either of two troponin T mutants in skinned cardiac trabeculae also decreased Ca(2+) sensitivity of force generation. Structure/function considerations imply that the diverse thin filament DCM mutations affect different aspects of regulatory function yet change contractility in a consistent manner. The DCM mutations depress myofibrillar function, an effect fundamentally opposite to that of hypertrophic cardiomyopathy-causing thin filament mutations, suggesting that decreased contractility may trigger pathways that ultimately lead to the clinical phenotype.

Management of complications in patients receiving home parenteral nutrition.

Patients receiving long-term home parenteral nutrition tend to fall under the care of adult and pediatric gastroenterologists. This article reviews the management of potential infectious, mechanical and metabolic complications and describes common psychosocial issues related to the therapy. The point at which to refer the patient to an intestinal failure program offering autologous bowel reconstruction and small bowel transplantation is discussed.

Nutrition in the perioperative patient.

The association of malnutrition with surgical morbidity and mortality is well recognized. The question of whether this relationship is causal or simply an association in sick patients has been hotly debated. The field of nutrition support has grown out of the belief that correcting malnutrition will modify associated risks for poor outcome. It has been easier to substantiate this belief in some clinical situations than in others. The evidence for nutrition support during the perioperative period is reviewed and recommendations are made about where nutrition support is most useful and where it may be counterproductive. Some of the important unanswered questions about perioperative nutrition support are raised.