Veterans with multiple risk factors for Barrett's esophagus are infrequently evaluated with upper endoscopy.

Recent guidelines recommend screening for patients with chronic gastroesophageal reflux disease who have three or more additional risk factors for Barrett's esophagus (BE). Failure to screen high-risk individuals represents a missed opportunity in esophageal adenocarcinoma prevention and early detection. We aimed to determine the frequency of upper endoscopy and prevalence of BE and esophageal cancer in a cohort of United States veterans who possessed four or more risk factors for BE. All patients at VA New York Harbor Healthcare System with at least four risk factors for BE between 2012 and 2017 were identified. Procedure records were reviewed for upper endoscopies performed between January 2012 and December 2019. Multivariable logistic regression was used to determine risk factors associated with undergoing endoscopy and factors associated with BE and esophageal cancer. 4505 patients with at least four risk factors for BE were included. 828 patients (18.4%) underwent upper endoscopy, of which 42 (5.1%) were diagnosed with BE and 11 (1.3%) with esophageal cancer (10 adenocarcinoma; 1 squamous cell carcinoma). Among individuals who underwent upper endoscopy, risk factors associated with undergoing endoscopy included obesity (OR, 1.79; 95% CI, 1.41-2.30; P < 0.001) and chronic reflux (OR, 3.86; 95% CI, 3.04-4.90; P < 0.001). There were no individual risk factors associated with BE or BE/esophageal cancer. In this retrospective analysis of patients with 4 or more risk factors for BE, fewer than one-fifth of patients underwent upper endoscopy, supporting the need for efforts aimed at improving BE screening rates.

Colonoscopy after a Positive Stool-based Test for Colon Cancer Screening: Moving Toward a Better Understanding of What to Expect.

Stool-based tests for colorectal cancer, including fecal immunochemical testing (FIT) and multitarget stool DNA testing (mt-sDNA), are among the recommended first-line screening options for patients at average risk for colorectal cancer and offer advantages over colonoscopy. However, stool-based tests have high false-positive rates, and the expected yield of colonoscopy after positive FIT compared with positive mt-sDNA is not well studied. As discussed in this issue of Cancer Prevention Research, the presence of a precancerous lesion in the majority of cases with either positive stool-based test is expected. In addition, a positive mt-sDNA is associated with a higher risk for finding any neoplasia on colonoscopy compared with positive FIT, and particularly associated with higher prevalence of clinically relevant serrated polyps compared with positive FIT. Further research is needed on what to expect from positive stool-based testing on average risk 45-49 years old patients, the newest cohort indicated for colorectal cancer screening. See related article, p. 455.

Impact of social determinants of health on colorectal cancer screening and surveillance in the COVID reopening phase.

BACKGROUND/AIMS: Procedural delays due to the coronavirus disease 2019 (COVID-19) pandemic may exacerbate disparities in colorectal cancer (CRC) preventive care. We aimed to measure racial and socioeconomic disparities in the prioritization of CRC screening or adenoma surveillance during the COVID reopening period. METHODS: We identified CRC screening or surveillance colonoscopies performed during two time periods: (1) 9 June 2019-30 September 2019 (pre-COVID) and (2) 9 June 2020-30 September 2020 (COVID reopening). We recorded the procedure indication, patient age, sex, race/ethnicity, primary language, insurance status and zip code. Multivariable logistic regression was used to determine factors independently associated with undergoing colonoscopy in the COVID reopening era. RESULTS: We identified 1473 colonoscopies for CRC screening or adenoma surveillance; 890 occurred in the pre-COVID period and 583 occurred in the COVID reopening period. In total 342 (38.4%) pre-COVID patients underwent adenoma surveillance and 548 (61.6%) underwent CRC screening; in the COVID reopening cohort, 257 (44.1%) underwent adenoma surveillance and 326 (55.9%) underwent CRC screening (P = 0.031). This increased proportion of surveillance procedures in the reopening cohort was statistically significant on multivariable analysis [odds ratio (OR), 1.26; 95% confidence interval (CI), 1.001-1.58]. Black patients comprised 17.4% of the pre-COVID cohort, which declined to 15.3% (P = 0.613). There was a trend toward an inverse association between reopening phase colonoscopy and Medicaid insurance compared with commercial insurance (OR, 0.71; 95% CI, 0.49-1.04). No significant associations were found between reopening phase colonoscopy and the remaining variables. CONCLUSIONS: During the COVID reopening period, colonoscopies for CRC fell by over one-third with significantly more surveillance than screening procedures. Nonwhite patients and non-English speakers comprised a shrinking proportion in the COVID reopening period.

Metformin Use Is Inversely Associated with Prevalent, but Not Incident Colorectal Adenomas.

BACKGROUND: Chemoprevention for colorectal neoplasia has attracted growing interest, with multiple medications investigated. Metformin may decrease the overall incidence of cancer in patients with diabetes and may decrease the incidence of colorectal cancer. AIMS: We aimed to determine the impact of metformin use on the behavior of colorectal adenomas in a US veteran population. METHODS: All patients with at least two high-quality colonoscopies between January 1997 and December 2013 at Veterans Affairs New York Harbor Healthcare System were identified. Outpatient prescription records were used to determine metformin exposure, and colonoscopy findings were recorded. Multivariable logistic regression was used to determine factors associated with adenoma detection on baseline and interval colonoscopy. RESULTS: In total, 1869 patients with two successive colonoscopies (median 4.5 years) were included. Four hundred and sixty patients had metformin exposure prior to baseline and/or interval colonoscopy. Overall adenoma detection rate was 59.7% at baseline and 45.9% at interval colonoscopy. On multivariable analysis, metformin use was associated with decreased adenoma prevalence at baseline (OR 0.68; 95% CI 0.51-0.92; p = 0.015). Metformin did not impact adenoma incidence at interval colonoscopy whether prescribed before baseline (OR 1.26; 95% CI 0.60-2.67), after baseline (OR 1.25; 95% CI 0.91-1.72), or before and after baseline (OR 1.14; 95% CI 0.82-1.58). CONCLUSIONS: In this retrospective analysis of an average-risk cohort, metformin use was associated with a decreased prevalence of colorectal adenomas at baseline colonoscopy. This inverse association did not persist on interval colonoscopy. Prospective studies are needed to evaluate potential chemoprotective effects of metformin over time.

Prevalence of Adenomas on Surveillance Colonoscopies for Patients with a History of Colonic Polyps of Unknown Histology.

BACKGROUND: Guidelines for surveillance colonoscopy depend on polyp histology. When patients present to a new healthcare system and report a personal history of "colon polyps," however, information on polyp histology is frequently unavailable. AIMS: To assess adenoma prevalence in patients with a history of colonic polyps of unknown histology and to compare it to patients undergoing either screening colonoscopy or surveillance colonoscopy for known adenomatous polyps. METHODS: This cohort study evaluated colonoscopies of patients ≥ 50 years of age over a 14-year period at a single institution. The exposure of interest was colonoscopy indication, categorized into three groups: screening colonoscopy, surveillance colonoscopy for history of colonic polyp(s) of unknown histology, and surveillance colonoscopy for history of adenoma(s). The primary outcome was adenoma detection rate. Multivariable logistic regression was used to assess the association between colonoscopy indication and adenoma detection rate. RESULTS: Of 31,856 colonoscopies, the adenoma prevalence was 26.1% for patients undergoing screening colonoscopy, 32.9% for patients with a history of polyps of unknown histology, and 41.9% for patients with a history of known adenomatous polyps. Relative to screening colonoscopies, there were higher odds of adenoma detection in surveillance colonoscopies for polyps of unknown histology (aOR compared to screening 1.42, 95% CI 1.30-1.55) and even higher odds among surveillance colonoscopies for a history of adenoma (aOR compared to screening 1.89, 95% CI 1.75-2.05). CONCLUSION: The adenoma prevalence on surveillance colonoscopy for patients with polyps of unknown histology was higher than that of screening colonoscopies but lower than that of surveillance colonoscopies for patients with adenomatous polyps.

Oral Microbiome Alterations and SARS-CoV-2 Saliva Viral Load in Patients with COVID-19.

Bacterial-viral interactions in saliva have been associated with morbidity and mortality for respiratory viruses such as influenza and SARS-CoV. However, such transkingdom relationships during SARS-CoV-2 infection are currently unknown. Here, we aimed to elucidate the relationship between saliva microbiota and SARS-CoV-2 in a cohort of newly hospitalized COVID-19 patients and controls. We used 16S rRNA sequencing to compare microbiome diversity and taxonomic composition between COVID-19 patients (n = 53) and controls (n = 59) and based on saliva SARS-CoV-2 viral load as measured using reverse transcription PCR (RT-PCR). The saliva microbiome did not differ markedly between COVID-19 patients and controls. However, we identified significant differential abundance of numerous taxa based on saliva SARS-CoV-2 viral load, including multiple species within Streptococcus and Prevotella. IMPORTANCE Alterations to the saliva microbiome based on SARS-CoV-2 viral load indicate potential biologically relevant bacterial-viral relationships which may affect clinical outcomes in COVID-19 disease.

Association of patient gender and gastroenterologists' diagnosis and management choices in gastroesophageal reflux disease.

Symptom severity and prevalence of erosive disease in gastroesophageal reflux disease (GERD) differ between genders. It is not known how gastroenterologists incorporate patient gender in their decision-making process. We aimed to evaluate how gender influences the diagnosis and management recommendations for patients with GERD. We invited a nationwide sample of gastroenterologists via voluntary listservs to complete an online survey of fictional patient scenarios presenting with different GERD symptoms and endoscopic findings. Patient gender for each case was randomly generated. Study participants were asked for their likelihood of a diagnosis of GERD and subsequent management recommendations. Results were analyzed using chi-square tests, Fisher Exact tests, and multivariable logistic regression. Of 819 survey invitations sent, 135 gastroenterologists responded with 95.6% completion rate. There was no significant association between patient gender and prediction for the likelihood of GERD for any of the five clinical scenarios when analyzed separately or when all survey responses were pooled. There was also no significant association between gender and decision to refer for fundoplication, escalate PPI therapy, or start of neuromodulation/behavioral therapy. Despite documented symptomatic and physiologic differences of GERD between the genders, patient gender did not affect respondents' estimates of GERD diagnosis or subsequent management. Further outcomes studies should validate whether response to GERD treatment strategies differ between women and men.

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.

Unsedated Colonoscopy: Impact on Quality Indicators.

BACKGROUND: In the USA, sedation is commonly used for colonoscopies; though colonoscopy can be successfully performed without sedation, outcomes data in this setting are scarce. AIMS: To determine patient characteristics associated with undergoing unsedated colonoscopy and whether adenoma detection rate (ADR) and cecal intubation rate (CIR) differ between sedated and unsedated colonoscopy. METHODS: Using a single-center electronic endoscopy database, we identified patients who underwent outpatient colonoscopy between 2011 and 2018 with or without sedation. We used multivariable logistic regression to determine factors associated with unsedated colonoscopy, CIR, and ADR. RESULTS: We identified 24,795 patients who underwent colonoscopy during the study period. Of these, 179 patients (0.7%) underwent unsedated colonoscopy. ADR was 27.4% in sedated and 21.2% in unsedated colonoscopies (p = 0.06); CIR was 95.8% in sedated and 85.5% in unsedated patients (p < 0.01). On multivariable analysis, male sex (OR 2.06, CI 1.52-2.79) and suboptimal bowel preparation (OR 1.75, CI 1.24-2.45) were associated with undergoing unsedated colonoscopy, while higher BMI was inversely associated with unsedated colonoscopy (BMI 25-29.9: OR 0.44, CI 0.25-0.77). On multivariable analysis, colonoscopy with sedation was associated with CIR (OR 3.79, CI 2.39-6.00) and ADR (OR 1.45, OR 1.00-2.10). CONCLUSION: We found that undergoing outpatient colonoscopy with sedation as opposed to no sedation was significantly associated with a higher CIR and ADR. Our findings suggest sedation is necessary to meet current CIR and ADR guidelines; however, given the potential cost and safety benefits of unsedated colonoscopy, further investigation into methods to improve patient selection and colonoscopy quality indicators is warranted.

Patient and Physician Factors Associated with Adenoma and Sessile Serrated Lesion Detection Rates.

BACKGROUND AND AIMS: Sessile serrated lesions (SSLs) have been increasingly recognized as precursors to colorectal cancer. Unlike adenoma detection rate (ADR), there is currently no agreed-upon benchmark for SSL detection rate (SSLDR), and data on factors that impact SSL detection are limited. We aimed to identify patient, endoscopist, and procedural factors associated with SSL and adenoma detection. METHODS: We used a single-center electronic endoscopy database to identify all patients ages ≥ 50 years who underwent outpatient screening colonoscopy from January 1, 2012, to June 30, 2018. Univariable Chi-square analysis was used to determine patient, endoscopist, and procedure-related factors associated with SSL or adenoma detection. We used logistic regression with generalized estimating equations, accounting for clustering by individual endoscopist, to determine factors independently associated with ADR and SSLDR. RESULTS: We identified 10,538 unique patients who underwent colonoscopy performed by 28 endoscopists. Overall SSLDR was 2.2%, and overall ADR was 29.1%. On multivariable analysis, patient age, sex, BMI, smoking, endoscopist withdrawal time, and year of colonoscopy were independent predictors of ADR. Smoking and year of colonoscopy were independent predictors of SSLDR. Sub-optimal bowel preparation was inversely associated with SSL detection but not ADR. CONCLUSIONS: In this large study of patients undergoing average-risk screening colonoscopy, overall SSLDR was low, indicating that methods for increasing SSLDR are needed. Our findings suggest that endoscopists may take into account risk factors for SSLs, such as smoking history, and recognize that the detection of such lesions, even more so than for adenomas, is dependent on optimal bowel preparation.

Symptoms and demographic factors associated with early-onset colorectal neoplasia among individuals undergoing diagnostic colonoscopy.

BACKGROUND: The incidence and mortality of colorectal cancer (CRC) are increasing in adults under 50 years. Risk factors associated with early-onset colorectal neoplasia (CRN) are uncertain. We aimed to identify clinical predictors associated with the presence of CRN detected by diagnostic colonoscopy in symptomatic individuals under 50 years of age. METHODS: We used a single-center endoscopy database to identify symptomatic patients 18-49 years of age who underwent ambulatory colonoscopy between 2007 and 2017. Pathology reports identified CRN as adenomas, advanced adenomas (based on size or histology), or adenocarcinomas. Multivariable analysis was used to determine factors associated with CRN. RESULTS: We identified 4333 eligible patients of whom 363 (8.4%) had any CRN and 48 (1.1%) had advanced neoplasia (advanced adenoma or adenocarcinoma). Factors associated with any CRN on multivariable analysis included male sex [odds ratio (OR) 1.50 (1.19-1.88)], older age group [compared to 18-29 years, OR for 30-39: 3.12 (1.93-5.04); OR for 40-49: 4.68 (2.97-7.36)], obesity [OR for BMI 30-34.9 compared to 18-24.9: 1.44 (1.04-2.01)], and any tobacco use [OR 1.63 (1.18-2.23)]. Anemia was associated with advanced neoplasia [OR 3.11 (1.32-7.34)]. Of the advanced neoplastic lesions, 38 of 48 (79.2%) were located in the distal colon. CONCLUSIONS: In the largest study to date of symptomatic individuals under 50 years of age undergoing colonoscopy in the USA, advanced CRN was most often detected in the distal colon and was associated with anemia, but not with abnormal bowel habits or abdominal pain. We also found that patients with CRN under 50 years of age were more likely to be male, smokers, and obese. These findings should prompt further investigation of these risk factors alone and in combination.

Outcomes of patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study.

BACKGROUND AND AIMS: The treatment of submucosal (T1b) esophageal adenocarcinoma (EAC) remains in evolution, with some evidence supporting endoscopic management of low-risk lesions. Using a multicenter cohort, we evaluated outcomes of patients with T1b EAC and predictors of survival. METHODS: Patients diagnosed between 2001 and 2016 with T1b EAC were identified from 3 academic medical centers in the United States. Demographic, clinical, and outcome data were collected. Outcomes studied were overall and cancer-free survival. Cox proportional hazards models were constructed to assess independent predictors of survival. RESULTS: One hundred forty-one patients were included, of whom 68 (48%) underwent esophagectomy and 73 (52%) were treated endoscopically. Most patients (85.8%) had high-risk histologic features. Thirty-day operative mortality was 2.9%. Median follow-up in the esophagectomy and endoscopic cohorts was 49.4 and 43.4 months, respectively. Patients treated endoscopically were older with higher comorbidity scores, with 46 (63%) achieving histologic remission. Nineteen patients (26.0%) also received chemoradiation. Five-year overall survival rates in the surgical and endoscopic cohorts were 89% and 59%, respectively, whereas 5-year cancer-free survival rates were 92% and 69%. Presence of high-risk histologic features was associated with reduced overall survival. CONCLUSIONS: In this large multicenter study of patients with T1b EAC, esophagectomy was associated with improved overall but not cancer-free survival. High-risk histologic features were associated with poorer survival.

No Increased Risk of Colorectal Adenomas in Spouses of Patients with Colorectal Neoplasia.

Although genetic factors such as family history have been associated with increased risk of developing colorectal cancer (CRC), multiple lifestyle and environmental risk factors for CRC have been identified, including smoking, diet, obesity, and physical activity.1,2 Although couples typically have different genetic backgrounds, spouses are likely to share lifestyle and environmental exposures over the course of years, including similar home environments, geographical locations of residence, dietary exposures, and smoking exposures.3 As such, one might expect that an increased CRC incidence would be seen among spouses of patients with CRC; however, studies on this topic have inconsistent results.3-6 By using a large cohort of spouses who have undergone colonoscopy, we aimed to determine whether the risk of colorectal adenomas is increased among spouses of those with colorectal neoplasia (CRN) on colonoscopy.

Anesthesia Assistance in Screening Colonoscopy and Adenoma Detection Rate Among Trainees.

BACKGROUND AND AIMS: The use of anesthesia assistance (AA) for screening colonoscopy has been increasing substantially over the past decade, raising concerns about procedure safety and cost without demonstrating a proven improvement in overall quality indicators such as adenoma detection rate (ADR). The effect of AA on ADR has not been extensively studied among trainees learning colonoscopy. We aimed to determine whether type of sedation used during screening colonoscopy affects trainee ADR. METHODS: Using the electronic endoscopy databases of two hospitals in our medical center, we identified colonoscopies performed by 15 trainees from 2014 through 2018, including all screening examinations in which the cecum was reached. Multivariable logistic regression was used to determine factors associated with adenoma detection. RESULTS: We identified 1420 unique patients who underwent screening colonoscopy by a trainee meeting the inclusion criteria. Of these, 459 (32.3%) were performed with AA. Overall trainee ADR was 39.6%, with ADR increasing from 35.0% in year one of training to 42.8% in year three (p = 0.047). ADR for cases with AA was 37.9%, while ADR for conscious sedation cases was 32.0% (p = 0.374). Despite this 5.9% absolute difference, the use of AA was not associated with finding an adenoma on multivariable analysis when controlling for patient age, sex, smoking status, body mass index, trainee year of training, mean withdrawal time, supervising attending ADR, and bowel preparation quality (OR 0.85; 95% CI 0.67-1.09). CONCLUSIONS: Despite providing the ability to more consistently sedate patients, the use of AA did not affect trainee ADR. These results on trainee ADR and sedation type suggest that the overall lack of association between AA use and ADR is applicable to the trainee setting.

Substantial Increase in Anesthesia Assistance for Outpatient Colonoscopy and Associated Cost Nationwide.

BACKGROUND AND AIMS: The use of anesthesia assistance (AA) for outpatient colonoscopy has been increasing over the past decade, raising concern over its effects on procedure safety, quality, and cost. We performed a nationwide claims-based study to determine regional, patient-related, and facility-related patterns of anesthesia use as well as cost implications of AA for payers. METHODS: We analyzed the Premier Perspective database to identify patients undergoing outpatient colonoscopy at over 600 acute-care hospitals throughout the United States from 2006 through 2015, with or without AA. We used multivariable analysis to identify factors associated with AA and cost. RESULTS: We identified 4,623,218 patients who underwent outpatient colonoscopy. Of these, 1,671,755 (36.2%) had AA; the proportion increased from 16.7% in 2006 to 58.1% in 2015 (P < .001). Factors associated with AA included younger age (odds ratios [ORs], compared to patients 18-39 years old: 0.94, 0.82, 0.77, 0.72, and 0.77 for age groups 40-49 years, 50-59 years, 60-69 years, 70-79 years, and ≥80 years, respectively); and female sex (OR, 0.96 for male patients compared to female patients; 95% CI, 0.95-0.96). Black patients were less likely to receive AA than white patients (OR, 0.81; 95% CI, 0.81-0.82), although this difference decreased with time. The median cost of outpatient colonoscopy with AA was higher among all payers, ranging from $182.43 (95% CI, $180.80-$184.06) higher for patients with commercial insurance to $232.62 (95% CI, $222.58-$242.67) higher for uninsured patients. CONCLUSIONS: In an analysis of a database of patients undergoing outpatient colonoscopy throughout the United States, we found that the use of AA during outpatient colonoscopy increased significantly from 2006 through 2015, associated with increased cost for all payers. The increase in anesthesia use mandates evaluation of its safety and effectiveness in colorectal cancer screening programs.

Ethnic Variations in Duodenal Villous Atrophy Consistent With Celiac Disease in the United States.

BACKGROUND & AIMS: Celiac disease is a common disorder with a worldwide distribution, although the prevalence among different ethnicities varies. We aimed to measure the prevalence of duodenal villous atrophy among patients of different ethnicities throughout the United States. METHODS: We performed a cross-sectional study of all patients who had duodenal biopsies submitted to a national pathology laboratory between January 2, 2008 and April 30, 2015. The prevalence of villous atrophy was calculated for the following ethnicities by using a previously published algorithm based on patient names: North Indian, South Indian, East Asian, Hispanic, Middle Eastern, Jewish, and other Americans. RESULTS: Among all patients (n = 454,885), the median age was 53 years, and 66% were female. The overall prevalence of celiac disease was 1.74%. Compared with other Americans (n = 380,163; celiac disease prevalence, 1.83%), celiac disease prevalence was lower in patients of South Indian (n = 177, 0%; P = .08), East Asian (n = 4700, 0.15%; P ≤ .0001), and Hispanic (n = 31,491, 1.06%; P ≤ .0001) ethnicities. Celiac disease was more common in patients from the Punjab region (n = 617, 3.08%) than in patients from North India (n = 1195, 1.51%; P = .02). The prevalence of celiac disease among patients of Jewish (n = 17,806, 1.80%; P = .78) and Middle Eastern (n = 1903, 1.52%; P = .33) ethnicities was similar to that of other Americans. Among Jewish individuals (n = 17,806), the prevalence of celiac disease was 1.83% in Ashkenazi persons (n = 16,440) and 1.39% in Sephardic persons (n = 1366; P = .24). CONCLUSIONS: Among patients undergoing duodenal biopsy, individuals from the Punjab region of India constitute the ethnic group in the United States with the highest prevalence of villous atrophy consistent with celiac disease. Compared with other Americans, villous atrophy prevalence on duodenal biopsy is significantly lower among U.S. residents of South Indian, East Asian, and Hispanic ancestry.

Nonceliac Gluten Sensitivity.

Nonceliac gluten sensitivity (NCGS) refers to a clinical phenotype in which patients experience intestinal and extraintestinal symptoms related to ingesting a gluten-containing diet after a diagnosis of celiac disease (CD) or wheat allergy has been excluded. CD, an autoimmune disease characterized by villous atrophy triggered by the ingestion of gluten, has increased in prevalence in recent decades, although the majority of patients remain undiagnosed. There is now an increasing public awareness of NCGS and growing interest in the health effects of gluten among health professionals and the lay public. Several randomized controlled trials have explored NCGS but have left many questions unanswered surrounding the pathophysiology, biomarkers, and established diagnostic approach to patients with this condition. Future studies are necessary to establish biomarkers and to elucidate the pathophysiology of this condition because at present, NCGS likely comprises a heterogeneous patient population. In this review, we outline the clinical trials of NCGS as well as the approach to patients with possible NCGS as recommended by an international expert panel. Because maintaining a gluten-free diet has important health, social, and economic consequences, it is necessary for medical professionals to provide practical and evidence-based advice to patients with this condition.