Cost-effectiveness of screening with polymerase chain reaction for Helicobacter pylori to prevent gastric cancer and peptic ulcers.

Background: Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer. Screening and treatment of H. pylori may reduce the risk of gastric cancer and peptic ulcer disease (PUD). Polymerase chain reaction (PCR) of gastric biopsies provides superior sensitivity and specificity for the detection of H. pylori. This study explores whether population-based H. pylori screening with PCR is cost-effective in the US. Methods: A Markov cohort state-transition model was developed to compare three strategies: no screening with opportunistic eradication, 13C-UBT population screening and treating of H. pylori, and PCR population screening and treating of H. pylori. Estimates of risks and costs were obtained from published literature. Since the efficacy of H. pylori therapy in gastric cancer prevention is not certain, we broadly varied the benefit 30-100% in sensitivity analysis. Results: PCR screening was cost-effective and had an incremental-cost effectiveness ratio per quality adjusted life-year (QALY) of $38,591.89 when compared to 13C-UBT strategy with an ICER of $2,373.43 per QALY. When compared to no screening, PCR population screening reduced cumulative gastric cancer incidence from 0.84% to 0.74% and reduced PUD risk from 14.8% to 6.0%. The cost-effectiveness of PCR screening was robust to most parameters in the model. Conclusions: Our modeling study finds PCR screening and treating of H. pylori to be cost-effective in the prevention of gastric cancer and PUD. However, the potential negative consequences of H. pylori eradication such as antibiotic resistance could change the balance of benefits of population screening.

Prevalence of Extensive and Limited Gastric Intestinal Metaplasia and Progression to Dysplasia and Gastric Cancer.

BACKGROUND AND AIMS: Guidelines cite extensive gastric intestinal metaplasia (GIM) as a bigger risk factor for gastric cancer (GC) than limited GIM and an indication for endoscopic surveillance. Data on progression of extensive GIM to GC in the USA are limited. This study aimed to estimate the prevalence and progression rates of extensive GIM in a US cohort. METHODS: This retrospective study assessed the prevalence of extensive GIM between 1/1/1990 and 8/1/2019 at a large academic medical center. Multivariable regression was used to identify predictors of extensive GIM. Incidence of GC on follow-up was calculated as number of new diagnoses divided by person-years of follow-up. Presence of GIM on subsequent follow-up endoscopy was assessed. RESULTS: Of 1256 individuals with GIM, 352 (28%) had extensive GIM and 904 (72%) had limited GIM. On multivariable analysis, older age (OR 1.01, 95% CI 1.00-1.02) and Hispanic ethnicity (OR 1.55, 95% CI 1.11-2.16) were predictive of extensive GIM. The annual incidence of GC for GIM overall was 0.09%. There was no difference in progression to GC between extensive or limited GIM (IRR 0, 95% CI 0-2.6), or to advanced lesions overall (IRR 0.37, 95% CI 0.04-1.62). 70% of individuals had persistent GIM on follow-up biopsy, and 22% with limited GIM had extensive GIM on follow-up biopsy. CONCLUSIONS: 28% of individuals with GIM have the extensive subtype, and are more likely to be older and of Hispanic ethnicity. There was no difference in progression to GC between extensive and limited GIM. Further research is needed to better assess risk of GIM in the US context.

Minimal Associations between Short-Term Dietary Intake and Salivary Microbiome Composition.

BACKGROUND: Increasing evidence points to the esophageal microbiome as an important co-factor in esophageal neoplasia. Esophageal microbiome composition is strongly influenced by the oral microbiome. Salivary microbiome assessment has emerged as a potential non-invasive tool to identify patients at risk for esophageal cancer, but key host and environmental factors that may affect the salivary microbiome have not been well-defined. This study aimed to evaluate the impact of short-term dietary intake on salivary microbiome composition. METHODS: Saliva samples were collected from 69 subjects prior to upper endoscopy who completed the Automated Self-Administered 24-Hour (ASA24) Dietary Assessment. Salivary microbiome composition was determined using 16S rRNA amplicon sequencing. RESULTS: There was no significant correlation between alpha diversity and primary measures of short-term dietary intake (total daily calories, fat, fiber, fruit/vegetables, red meat intake, and fasting time). There was no evidence of clustering on beta diversity analyses. Very few taxonomic alterations were found for short-term dietary intake; an increased relative abundance of Neisseria oralis and Lautropia sp. was associated with high fruit and vegetable intake, and an increased relative abundance of a taxon in the family Gemellaceae was associated with increased red meat intake. CONCLUSIONS: Short-term dietary intake was associated with only minimal salivary microbiome alterations and does not appear to have a major impact on the potential use of the salivary microbiome as a biomarker for esophageal neoplasia.

Helicobacter pylori and Gastric Cancer.

Helicobacter pylori is present in approximately one-half of the world's population. There are significant differences in prevalence based on region, age, race/ethnicity, and socioeconomic status. H pylori is the most common cause of infection-related cancers. Studies have demonstrated the relationship between H pylori infection and gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. H pylori has features and enzymatic properties allowing it to survive in the acidic stomach environment, and has specific virulence factors that promote an increased risk of gastric pathology. Eradication of H pylori is first-line therapy for mucosa-associated lymphoid tissue lymphoma and decreases the risk of gastric adenocarcinoma.

Heavy Alcohol Use Is Associated With Gastric Cancer: Analysis of the National Health and Nutrition Examination Survey From 1999 to 2010.

INTRODUCTION: Evidence regarding the association between alcohol use and gastric cancer (GC) has been inconsistent. METHODS: Adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010 were included. Multivariable regression was used to assess the association between GC and heavy alcohol use (≥5 alcoholic drinks daily). RESULTS: Of 470,168 individuals surveyed, 342 had a history of GC. Heavy alcohol use was associated with GC (odds ratio 3.13, 95% confidence interval 1.15-8.64) on multivariable analysis. DISCUSSION: This is the largest study to our knowledge to demonstrate an association between heavy alcohol use and GC in the United States.

Prevalence of Clostridioides difficile and Other Gastrointestinal Pathogens in Patients with COVID-19.

BACKGROUND: Gastrointestinal symptoms are common in patients with COVID-19, but prevalence of co-infection with enteric pathogens is unknown. AIMS: This study assessed the prevalence of enteric infections among hospitalized patients with COVID-19. METHODS: We evaluated 4973 hospitalized patients ≥ 18 years of age tested for COVID-19 from March 11 through April 28, 2020, at two academic hospitals. The primary exposure was a positive COVID-19 test. The primary outcome was detection of a gastrointestinal pathogen by PCR stool testing. RESULTS: Among 4973 hospitalized individuals, 311 were tested for gastrointestinal infections (204 COVID-19 positive, 107 COVID-19 negative). Patients with COVID-19 were less likely to test positive compared to patients without COVID-19 (10% vs 22%, p < 0.01). This trend was driven by lower rates of non-C.difficile infections (11% vs 22% in COVID-19 positive vs. negative, respectively, p = 0.04), but not C. difficile infection (5.1% vs. 8.2%, p = 0.33). On multivariable analysis, infection with COVID-19 remained significantly associated with lower odds of concurrent GI infection (aOR 0.49, 95% CI 0.24-0.97), again driven by reduced non-C.difficile infection. Testing for both C.difficile and non-C.difficile enteric infection decreased dramatically during the pandemic. CONCLUSIONS: Pathogens aside from C.difficile do not appear to be a significant contributor to diarrhea in COVID-19 positive patients.

Chemotherapy-Induced Peripheral Neuropathy Detection via a Smartphone App: Cross-sectional Pilot Study.

BACKGROUND: Severe chemotherapy-induced peripheral neuropathy (CIPN) can cause long-term dysfunction of the hands and feet, interfere with activities of daily living, and diminish the quality of life. Monitoring to identify CIPN and adjust treatment before it progressing to a life-altering severity relies on patients self-reporting subjective symptoms to their clinical team. Objective assessment is not a standard component of CIPN monitoring due to the requirement for specially trained health care professionals and equipment. Smartphone apps have the potential to conveniently collect both subjective and objective CIPN data directly from patients, which could improve CIPN monitoring. OBJECTIVE: The objective of this cross-sectional pilot study was to assess the feasibility of functional CIPN assessment via a smartphone app in patients with cancer that have received neurotoxic chemotherapy. METHODS: A total of 26 patients who had completed neurotoxic chemotherapy were enrolled and classified as CIPN cases (n=17) or controls (n=9) based on self-report symptoms. All participants completed CIPN assessments within the NeuroDetect app a single time, including patient-reported surveys (CIPN20 [European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Chemotherapy-induced Peripheral Neuropathy 20-item scale] and PRO-CTCAE [Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events]) and functional assessments (Gait and Balance and 9-Hole Peg Test). Functional assessment data were decomposed into features. The primary analysis was done to identify features indicative of the difference between CIPN cases and controls using partial least squares analyses. Exploratory analyses were performed to test if any features were associated with specific symptom subtypes or patient-reported survey scores. Patient interviews were also conducted to understand the challenges they experienced with the app. RESULTS: Comparisons between CIPN cases and controls indicate that CIPN cases had shorter step length (P=.007), unique swaying acceleration patterns during a walking task, and shorter hand moving distance in the dominant hands during a manual dexterity task (variable importance in projection scores ≥2). Exploratory analyses showed similar signatures associated with symptoms subtypes, CIPN20, and PRO-CTCAE. The interview results showed that some patients had difficulties due to technical issues, which indicated a need for additional training or oversight during the initial app download. CONCLUSIONS: Our results supported the feasibility of remote CIPN assessment via a smartphone app and suggested that functional assessments may indicate CIPN manifestations in the hands and feet. Additional work is needed to determine which functional assessments are most indicative of CIPN and could be used for CIPN monitoring within clinical care.

Increased Risk of Pancreatitis after Endoscopic Retrograde Cholangiopancreatography Following a Positive Intraoperative Cholangiogram: A Single-Center Experience.

BACKGROUND/AIMS: To determine if patients with a positive intraoperative cholangiogram (IOC) who undergo a subsequent endoscopic retrograde cholangiopancreatography (ERCP) have an increased risk of post-ERCP pancreatitis (PEP) compared to those who undergo ERCP directly for suspected common bile duct stones. METHODS: A retrospective case-control study was performed from 2010 to 2016. Cases included inpatients with a positive IOC at cholecystectomy who underwent subsequent ERCP. The control group included age-sex matched cohorts who underwent ERCP for choledocholithiasis. Multivariate logistic regression was used to assess the association between PEP and positive IOC, adjusting for matching variables and additional potential confounders. RESULTS: Of the 116 patients that met the inclusion criteria, there were 91 women (78%) in each group. Nine patients (7.8%) developed PEP in the IOC group, compared to 3 patients in the control group (2.6%). The use of pancreatic duct stents and rectal indomethacin was similar in both groups. After adjusting for age, sex, total bilirubin levels, and any stent placement, patients with a positive IOC had a significantly increased risk of PEP (odds ratio, 4.79; 95% confidence interval, 1.05-21.89; p<0.05). CONCLUSION: In this single-center case-control study, there was a five-fold increased risk of PEP following a positive IOC compared to an age-sex matched cohort.

Disease Course and Outcomes of COVID-19 Among Hospitalized Patients With Gastrointestinal Manifestations.

BACKGROUND & AIMS: Our understanding of outcomes and disease time course of COVID-19 in patients with gastrointestinal (GI) symptoms remains limited. In this study we characterize the disease course and severity of COVID-19 among hospitalized patients with gastrointestinal manifestations in a large, diverse cohort from the Unites States. METHODS: This retrospective study evaluated hospitalized individuals with COVID-19 between March 11 and April 28, 2020 at two affiliated hospitals in New York City. We evaluated the association between GI symptoms and death, and also explored disease duration, from symptom onset to death or discharge. RESULTS: Of 2804 patients hospitalized with COVID-19, the 1,084 (38.7%) patients with GI symptoms were younger (aOR for age ≥75, 0.59; 95% CI, 0.45-0.77) and had more co-morbidities (aOR for modified Charlson comorbidity score ≥2, 1.22; 95% CI, 1.01-1.48) compared to those without GI symptoms. Individuals with GI symptoms had better outcomes, with a lower likelihood of intubation (aHR, 0.66; 95% CI, 0.55-0.79) and death (aHR, 0.71; 95% CI, 0.59-0.87), after adjusting for clinical factors. These patients had a longer median disease course from symptom onset to discharge (13.8 vs 10.8 days, log-rank p = .048; among 769 survivors with available symptom onset time), which was driven by longer time from symptom onset to hospitalization (7.4 vs 5.4 days, log-rank P < .01). CONCLUSION: Hospitalized patients with GI manifestations of COVID-19 have a reduced risk of intubation and death, but may have a longer overall disease course driven by duration of symptoms prior to hospitalization.

Low sodium diet for gastric cancer prevention in the United States: Results of a Markov model.

BACKGROUND AND AIMS: High sodium consumption has been associated with an increased risk of gastric cancer. The mean daily sodium intake in the United States substantially exceeds the national recommended amount. The low sodium-DASH diet has been shown to decrease the risk of cardiovascular disease in the United States, but its impact on gastric cancer has not been well studied. We therefore aimed to model the impact and cost-effectiveness of the low sodium-DASH diet for gastric cancer prevention in the U.S. METHODS: A Markov cohort state-transition model was developed to simulate the impact of the low sodium-DASH diet on gastric cancer outcomes for the average 40-year-old in the United States compared to no intervention. Primary outcomes of interest were gastric cancer incidence and incremental cost-effectiveness ratios (ICER). RESULTS: Our model found that compared to the no intervention cohort, the risk of gastric cancer decreased by 24.8% for males and 21.2% for females on the low sodium-DASH diet. 27 cases and 14 cases per 10,000 individuals were prevented for males and females, respectively, in the intervention group. The ICER for the low sodium-DASH diet strategy was $287,726 for males and $423,878 for females compared to the no intervention strategy. CONCLUSIONS: Using a Markov model of gastric cancer risk, we found that adherence to a low sodium-DASH diet could decrease the risk of gastric cancer. This intervention was not cost-effective due to the high cost of a low sodium-DASH accordant diet, but significantly improved for high-risk populations and when the cost of the diet became slightly more affordable.

Risk of Adverse Outcomes in Hospitalized Patients With Autoimmune Disease and COVID-19: A Matched Cohort Study From New York City.

OBJECTIVE: To examine the effect of autoimmune (AI) disease on the composite outcome of intensive care unit (ICU) admission, intubation, or death from COVID-19 in hospitalized patients. METHODS: Retrospective cohort study of 186 patients hospitalized with COVID-19 between March 1, 2020, and April 15, 2020 at NewYork-Presbyterian Hospital/Columbia University Irving Medical Center. The cohort included 62 patients with AI disease and 124 age- and sex-matched controls. The primary outcome was a composite of ICU admission, intubation, and death, with secondary outcome as time to in-hospital death. Baseline demographics, comorbidities, medications, vital signs, and laboratory values were collected. Conditional logistic regression and Cox proportional hazards regression were used to assess the association between AI disease and clinical outcomes. RESULTS: Patients with AI disease were more likely to have at least one comorbidity (87.1% vs 74.2%, P = 0.04), take chronic immunosuppressive medications (66.1% vs 4.0%, P < 0.01), and have had a solid organ transplant (16.1% vs 1.6%, P < 0.01). There were no significant differences in ICU admission (13.7% vs 19.4%, P = 0.32), intubation (13.7% vs 17.7%, P = 0.47), or death (16.1% vs 14.5%, P = 0.78). On multivariable analysis, patients with AI disease were not at an increased risk for a composite outcome of ICU admission, intubation, or death (ORadj 0.79, 95% CI 0.37-1.67). On Cox regression, AI disease was not associated with in-hospital mortality (HRadj 0.73, 95% CI 0.33-1.63). CONCLUSION: Among patients hospitalized with COVID-19, individuals with AI disease did not have an increased risk of a composite outcome of ICU admission, intubation, or death.

Racial and ethnic disparities in mortality from gastric and esophageal adenocarcinoma.

BACKGROUND: Racial/ethnic differences in mortality have not been well studied for either non-cardia gastric cancer (NCGC) or cardia gastric cancer (CGC). The aim of this study was to examine the US mortality rates for these cancer subtypes, as well as esophageal adenocarcinoma (EAC) as a comparator. METHODS: We identified 14 164 individuals who died from NCGC, 5235 from CGC, and 13 982 from EAC in the Surveillance, Epidemiology, and End Results database between 2004 and 2016. Age-adjusted incidence-based mortality rates and corresponding annual percent changes (APCs) were calculated. Analyses were stratified by race/ethnicity, age, and stage of disease at diagnosis. RESULTS: The mortality rate in NCGC was two- to threefold higher in blacks, Hispanics, and Asians/Pacific Islanders (PI) than non-Hispanic whites, and was significant across all age groups and stages of disease (P < .01). Mortality in CGC was higher in non-Hispanic whites than blacks and Asians/PI, particularly in individuals in the 50-64 year age group and those with stage IV disease. Mortality in EAC was two- to sixfold higher in non-Hispanic whites than all other groups across all age groups and stages of disease. From 2004 to 2016, mortality rates were stable across all racial/ethnic groups in NCGC and CGC, and in minority groups with EAC, but have been rising in non-Hispanic whites with EAC (APC 3.03, 95% CI 0.17-5.96). CONCLUSIONS: This is the largest study of incidence-based mortality in CGC and NCGC and demonstrates racial/ethnic differences in mortality between these subtypes. Mortality rates for NCGC are highest in minority groups, and have been stable in recent years despite declining incidence. Mortality rates for CGC are marginally higher in middle-aged non-Hispanic whites with advanced disease, though have remained stable. In contrast, mortality in EAC has been rising for non-Hispanic whites, in parallel to incidence. Further studies are needed to refine prevention strategies for high-risk individuals dying from these specific cancer subtypes.

Enteric tube placement in patients with esophageal varices: Risks and predictors of postinsertion gastrointestinal bleeding.

BACKGROUND AND AIM: Enteric tube (ET) placement is approached with caution in patients with esophageal varices (EV) due to concern of causing variceal bleeding. Data are limited on rates and predictors of gastrointestinal bleeding (GIB) in these patients. This study aims to assess the rate and predictors of bleeding from EV after ET placement. METHODS: We performed a retrospective chart review on patients requiring ET access with known EV. Inclusion criteria were age >18 with endoscopically proven EV who required ET placement. Patients who were admitted with, or developed a GIB prior to placement of ET were excluded, as were patients admitted for liver transplantation. Primary outcome was incidence of GIB within 48 h of tube placement. Secondary outcome was a >2 g/dL drop in hemoglobin within 48 h of placement without evidence of bleed. Statistical analysis was performed using Fischer's exact test, Mann-Whitney U test, and univariate logistic regression model. RESULTS: A total of 75 patients were included in the analysis. The most common etiology of cirrhosis was alcohol (44%). The most common location of EV was in the lower third of the esophagus (61%). The primary outcome was observed in 11 (14.6%) patients. The secondary outcome was found in eight (10.6%) patients. On univariate analysis, GIB was associated with higher MELD-Na (P = 0.026) and EV located in the lower third of the esophagus (P = 0.048). CONCLUSION: ET placement in patients with EV is associated with low risk of bleeding. Elevated MELD-Na and lower EV location conferred a higher risk of bleeding after ET placement.

Strategies for Effective Discontinuation of Proton Pump Inhibitors.

PURPOSE OF REVIEW: Proton pump inhibitors (PPIs) are effective for many conditions but are often overprescribed. Recent concerns about long-term risks have made patients re-evaluate their need to take PPIs chronically, though these population-based studies have methodological weaknesses. The goal of this review is to provide evidenced-based strategies for discontinuation of PPI therapy. RECENT FINDINGS: Given that some patients experience rebound symptoms when abruptly stopping continuous PPI therapy due to its effect on hypergastrinemia, strategies focus on avoiding rebound. Tapering the PPI and then initiating a "step-down" approach with the use of alternative medications may be effective. "On-demand therapy" provides patients with the option to take intermittent PPI courses, reducing overall use and cost while preserving patient satisfaction. It is important for providers to consider ambulatory pH or pH/impedance testing to rule out diagnoses that may require alternative medications like neuromodulators. A number of studies reviewed here can provide guidance in counseling patients on PPI discontinuation. It is important for the provider to obtain a baseline needs assessment for PPI therapy and to elucidate predictors of difficulty in discontinuation prior to initiating a strategy.

The Lkb1 metabolic sensor maintains haematopoietic stem cell survival.

Haematopoietic stem cells (HSCs) can convert between growth states that have marked differences in bioenergetic needs. Although often quiescent in adults, these cells become proliferative upon physiological demand. Balancing HSC energetics in response to nutrient availability and growth state is poorly understood, yet essential for the dynamism of the haematopoietic system. Here we show that the Lkb1 tumour suppressor is critical for the maintenance of energy homeostasis in haematopoietic cells. Lkb1 inactivation in adult mice causes loss of HSC quiescence followed by rapid depletion of all haematopoietic subpopulations. Lkb1-deficient bone marrow cells exhibit mitochondrial defects, alterations in lipid and nucleotide metabolism, and depletion of cellular ATP. The haematopoietic effects are largely independent of Lkb1 regulation of AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling. Instead, these data define a central role for Lkb1 in restricting HSC entry into cell cycle and in broadly maintaining energy homeostasis in haematopoietic cells through a novel metabolic checkpoint.

Intra-abdominal esophageal duplication cysts: a review.

Esophageal duplication cysts (EDCs) are well described within the literature, normally occurring within the mediastinum. Intra-abdominal EDCs are rare and typically occur near the intra-abdominal esophagus. Herein, we describe two cases of intra-abdominal EDCs: a 60-year-old man who was incidentally found to have a retro-duodenal cystic mass and a 50-year-old woman with a cystic lesion near the body and tail of her pancreas causing left flank pain. Both patients underwent enucleation of their respective masses. Pathology revealed ciliated pseudostratified columnar epithelium with scattered mucus-secreting cells and two smooth muscle layers in the cyst wall of both patients, consistent with EDCs. Although intra-abdominal EDCs have been reported in the literature, our two cases and a review of the literature indicate that these lesions are not always adherent to or even near the intra-abdominal esophagus.

A CD8 DE loop peptide analog prevents graft-versus-host disease in a multiple minor histocompatibility antigen-mismatched bone marrow transplantation model.

Donor CD8(+) T cells can be potent mediators of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation to either major histocompatibility complex (MHC) class I-or multiple minor histocompatibility antigen-mismatched recipients. To develop small molecular inhibitors of CD8(+) T-cell activity, theoretical structural analysis of the human CD8 alpha molecule was previously used to identify potential functional surface epitopes that interact with the MHC class I molecule. The DE loop (p71-78) was identified as such a target region, and a panel of synthetic cyclized peptide mimics of this region were tested for their inhibitory effects on cytotoxic T lymphocyte activity in human cell-mediated lympholysis assays. Peptide 1109 (CKRLGDTFVC) was most effective at inhibiting specific target cell lysis. Accordingly, studies were conducted to determine whether there was sufficient cross-species homology in the DE loop region and its nonpolymorphic interactive site on the beta(2)-microglobulin domain of the MHC class I molecule to allow similar inhibition of murine CD8(+) cytotoxic T lymphocyte activity. On the basis of strong in vitro inhibitory activity of 1109 in the murine system, the capacity of the peptide to inhibit in vivo CD8(+) T-cell effector functions in skin and hematopoietic stem cell transplantation models was examined. In the C57BL/6 anti-bm1 skin allograft rejection model, across an MHC class I barrier, a single injection of 1109 at the time of transplantation significantly prolonged graft survival. Moreover, 1109 administered at the time of transplantation in the multiple minor histocompatibility antigen-disparate B10.BR-->CBA GVHD model significantly prolonged the survival of lethally irradiated mice that underwent transplantation with donor bone marrow cells and CD8(+) T cells. Histopathologic analysis confirmed that mice treated with the synthetic peptide exhibited diminution of epithelial target cell injury. Specificity of the peptide effect was evidenced by draining lymph node cells from B10.BR mice that had been challenged with CBA lymphocytes and simultaneously treated with 1109. These cells could not generate secondary proliferative responses in vitro upon stimulation with CBA splenocytes but could respond to third-party C57BL/6 stimulation. Thus, the 1109 peptide has potential application in the prevention of CD8-mediated GVHD development.