Monitoring and modulating the trajectory of eosinophilic esophagitis.

Current treatments of eosinophilic esophagitis (EoE) aim to eliminate esophageal mucosal inflammation and attenuate, stabilize, or reverse stricture formation. However, our ability to study the long-term course of esophageal strictures in patients with EoE is hampered by the short-term existence of this disease. It is unclear to what degree of control of inflammation is needed to prevent stricture formation. Additionally, identified phenotypes of EoE may ultimately dictate different levels of concern and time intervals for developing fibrosis. Currently, multiple methods are used to monitor patients' disease progression to fibrosis, as symptoms alone do not correlate with disease activity. Endoscopic findings and mucosal histology are used to monitor disease activity, but these focus on improvements in inflammation with inconsistent evaluation of underlying fibrosis. The use of functional lumen impedance planimetry, barium esophagraphy, and endoscopic ultrasound continues to expand in EoE. The rapid advancements in EoE have led to an armamentarium of measuring tools and therapies that holistically characterize disease severity and response to therapy. Nevertheless, our ability to evaluate gross esophageal fibrosis and stricture formation from a transmural rather than mucosal view should be a focus of future investigations because it is essential to monitoring and modulating the trajectory of EoE.

Peroral endoscopic myotomy for spastic esophageal dysmotility among opioid users: a multicenter propensity score matching study.

BACKGROUND AND AIMS: Opioid-induced esophageal dysfunction (OIED) often presents as spastic esophageal disorders (SEDs) and esophagogastric junction outflow obstruction (EGJOO). The aim of this study was to evaluate and compare clinical outcomes of peroral endoscopic myotomy (POEM) for SEDs and EGJOO among opioid users and nonusers. METHODS: This propensity score (PS) matching study included consecutive opioid users and nonusers who underwent POEM for SEDs and EGJOO between January 2018 and September 2022. The following covariates were used for the PS calculation: age, sex, duration of symptoms, Eckardt score, type of motility disorder, and length of myotomy during POEM. Clinical response was defined as a post-POEM Eckardt score ≤3. RESULTS: A total of 277 consecutive patients underwent POEM during the study period. PS matching resulted in the selection of 64 pairs of patients strictly matched 1:1 (n = 128) with no statistically significant differences in demographic, baseline, or procedural characteristics or in the parameters considered for the PS between the 2 groups. Clinical response to POEM was significantly lower among opioid users (51 of 64 [79.7%]) versus nonusers (60 of 64 [93.8%]) (P = .03) at a median follow-up of 18 months. Among opioid users, higher opioid dose (>60 morphine milligram equivalents per day) was associated with a higher likelihood of failure to respond to POEM (odds ratio, 4.59; 95% confidence interval, 1.31-3.98; P = .02). CONCLUSIONS: Clinical response to POEM for SEDs and EGJOO is significantly lower among opioid users versus nonusers. There was a dose-relationship between opioids and response to POEM, with higher daily opioid usage associated with a higher likelihood of treatment failure.

Current state of rumination syndrome.

Rumination syndrome (RS) is an underdiagnosed behavioral disorder of recurrent regurgitation. Regurgitation occurs in RS due to increased gastric pressure achieved by subconscious contraction of the abdominal musculature wall, reversing the pressure gradient between the esophagus and the stomach. RS is mainly diagnosed clinically by the Rome Criteria with symptoms of regurgitation without retching of recently ingested food into the mouth and subsequent spitting or re-mastication. When the diagnosis is unable to be made clinically, supportive testing including fed impedance manometry can be considered. RS occurs worldwide, affecting patients of all ages, races, and genders with a prevalence of 3.1-5.8%. There is significant overlap with RS and disorders of a gut-brain interaction and upright gastroesophageal reflux driven by aerophagia and supragastric belching. There is also an association with mood disorder, fibromyalgia, and eating disorders. RS may be misdiagnosed as a variety of other syndromes including gastroesophageal reflux disease, gastroparesis, achalasia, and bulimia nervosa. Once RS is diagnosed, the mainstay of treatment is diaphragmatic breathing to lower the intragastric pressure and increase the lower esophageal pressure. Diaphragmatic breathing can be supported with biofeedback and cognitive behavioral therapy as well as medication options for more refractory cases. Response to therapy overtime and changes in symptoms overtime can now be tracked with a validated questionnaire.

Esophagogastroduodenoscopy findings that do no not explain dysphagia are associated with underutilization of high-resolution manometry.

In patients with dysphagia that is not explained by upper endoscopy, high-resolution esophageal manometry (HRM) is the next logical step in diagnostic testing. This study investigated predictors of failure to refer for HRM after an upper endoscopy that was performed for but did not explain dysphagia. This was a retrospective cohort study of patients >18 years of age who underwent esophagogastroduodenoscopy (EGD) for dysphagia from 2015 to 2021. Patients with EGD findings that explained dysphagia (e.g. esophageal mass, eosinophilic esophagitis, Schatzki ring, etc.) were excluded from the main analyses. The primary outcome was failure to refer for HRM within 1 year of the index non-diagnostic EGD. We also investigated delayed referral for HRM, defined as HRM performed after the median. Multivariable logistic regression modeling was used to identify risk factors that independently predicted failure to refer for HRM, conditioned on the providing endoscopist. Among 2132 patients who underwent EGD for dysphagia, 1240 (58.2%) did not have findings to explain dysphagia on the index EGD. Of these 1240 patients, 148 (11.9%) underwent HRM within 1 year of index EGD. Endoscopic findings (e.g. hiatal hernia, tortuous esophagus, Barrett's esophagus, surgically altered anatomy not involving the gastroesophageal junction, and esophageal varices) perceived to explain dysphagia were independently associated with failure to refer for HRM (adjusted odds ratio 0.45, 95% confidence interval 0.25-0.80). Of the 148 patients who underwent HRM within 1 year of index EGD, 29.7% were diagnosed with a disorder of esophagogastric junction outflow, 17.6% with a disorder of peristalsis, and 2.0% with both disorders of esophagogastric outflow and peristalsis. The diagnosis made by HRM was similar among those who had incidental EGD findings that were non-diagnostic for dysphagia compared with those who had completely normal EGD findings. Demographic factors including race/ethnicity, insurance type, and income were not associated with failure to refer for HRM or delayed HRM. Patients with dysphagia and endoscopic findings unrelated to dysphagia have a similar prevalence of esophageal motility disorders to those with normal endoscopic examinations, yet these patients are less likely to undergo HRM. Provider education is indicated to increase HRM referral in these patients.

Questionnaire for diagnosis and response to therapy in rumination syndrome.

Rumination is a behavioral disorder characterized by regurgitation of food without retching. It is diagnosed clinically by the Rome Criteria and treated primarily by diaphragmatic breathing. Despite diagnosis and follow-up being based on symptomatic responses to therapies, there are no published or validated questionnaires. To address this care-gap, a rumination questionnaire was developed and reviewed by two expert esophagologists and five patients diagnosed with rumination. Ultimately, an eight-point questionnaire with scoring ranging from -1 to 10 was finalized. This newly developed questionnaire was implemented on five additional patients diagnosed clinically with rumination syndrome with improvement after interventions noted.

Gender Matters: Characteristics of Hepatocellular Carcinoma in Women From a Large, Multicenter Study in the United States.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, affecting men to women at a ratio of about 4:1. Risk factors, characteristics, and outcomes for HCC in women in the United States remain poorly understood; therefore, we aim to explore gender differences further. METHODS: Patients diagnosed with HCC between January 2000 and June 2014 at 5 large centers were identified. Clinical information, tumor characteristics, and survival data were extracted manually. The presence of underlying cirrhosis was assessed based on published criteria. RESULTS: Of 5,327 patients with HCC in our cohort, 1,203 (22.6%) were women. There were important differences in the underlying etiology of liver disease between the 2 genders (P < 0.0001): women had a significantly higher frequency of nonalcoholic fatty liver disease (23% vs 12%) and lower frequency of alcoholic liver disease (5% vs 15%). The proportion of noncirrhotic HCC was significantly higher among women (17% vs 10%, P < 0.0001). Women had less-advanced HCC at presentation by tumor, node, metastasis staging (P < 0.0001) and a higher proportion within Milan criteria (39% vs 35%, P = 0.002). Women had a greater overall survival (2.5 ± 2.9 years vs 2.2 ± 2.7 years, P = 0.0031). DISCUSSION: The frequency of underlying nonalcoholic fatty liver disease and noncirrhotic HCC were significantly higher in women than men in this large cohort. Women presented with less-advanced HCC and had a greater overall survival. Further investigation is warranted to explore potential mechanisms and implications for these gender differences, especially with noncirrhotic HCC (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/AJG/B535).

Roles of swallowing and belching in different phenotypes of gastroesophageal reflux disease.

BACKGROUND: The contributions of swallowing and belching to specific gastroesophageal reflux disease (GERD) phenotypes are unclear. METHODS: This study retrospectively analyzed esophageal pH/impedance studies, comparing reflux events preceded by gastric belching (GB), supragastric belching (SGB), air swallowing, and liquid/solid swallowing based on reflux position, lower esophageal sphincter (LES) pressure, and acid exposure time (AET). KEY RESULTS: 20 GERD patients and 10 controls were studied. Upright GERD patients and controls had a higher proportion of reflux events with a preceding swallow or belch (0.64, 0.64) than the supine group (0.38, p = 0.043). The upright group and controls trended toward a higher proportion of reflux events preceded by overall swallowing (0.61, 0.50) and air swallowing (0.55, 0.48) than the supine group (0.32, 0.31 p = 0.064, p = 0.11), but the three groups had similar rates of liquid/solid swallowing (0.032, 0.024, 0.017, p = 0.69). LES pressure did not correlate with reflux events preceded by swallowing (R2 = 0.021, p = 0.44). There was a higher rate of events preceded by gastric belching in the control group (0.14) than in the upright (0.032) and supine groups (0.066, p = 0.049). LES pressure did not correlate with the rate of events preceded by belching (R2 = 0.000093, p = 0.96). Normal AET patients had a higher rate of events preceded by GB (0.12) than those with increased acid exposure (0.030, p = 0.0083), but the two groups had similar rates of preceding air (0.43, 0.47, p = 0.68), liquid/solid (0.018, 0.032, p = 0.30), and overall swallowing (0.44, 0.53, p = 0.38). CONCLUSIONS AND INFERENCES: Swallowing more than belching is a dominant mechanism for reflux irrespective of GERD position, LES pressure, and AET.

Cross-Phenotype GWAS Supports Shared Genetic Susceptibility to Systemic Sclerosis and Primary Biliary Cholangitis.

Objective: An increased risk of primary biliary cholangitis (PBC) has been reported in patients with systemic sclerosis (SSc). Our study aims to investigate the shared genetic susceptibility between the two disorders and to define candidate causal genes using cross-phenotype GWAS meta-analysis. Methods: We performed cross-phenotype GWAS meta-analysis and colocalization analysis for SSc and PBC. We performed both genome-wide and locus-based analysis, including tissue and pathway enrichment analyses, fine-mapping, colocalization analyses with expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) datasets, and phenome-wide association studies (PheWAS). Finally, we used an integrative approach to prioritize candidate causal genes from the novel loci. Results: We detected a strong genetic correlation between SSc and PBC (rg = 0.84, p = 1.7 × 10-6). In the cross-phenotype GWAS meta-analysis, we identified 44 non-HLA loci that reached genome-wide significance (p < 5 × 10-8). Evidence of shared causal variants between SSc and PBC was found for nine loci, five of which were novel. Integrating multiple sources of evidence, we prioritized CD40, ERAP1, PLD4, SPPL3, and CCDC113 as novel candidate causal genes. The CD40 risk locus colocalized with trans-pQTLs of multiple plasma proteins involved in B cell function. Conclusion: Our study supports a strong shared genetic susceptibility between SSc and PBC. Through cross-phenotype analyses, we have prioritized several novel candidate causal genes and pathways for these disorders.

Diet for Functional Gastrointestinal Disorders/Disorders of Gut-Brain Interaction.

Dietary interventions may alleviate symptoms related to functional gastrointestinal disorders, now termed disorders of gut-brain interaction. We reviewed which interventions have high-quality data to support their use in gastroesophageal reflux disease (GERD), functional dyspepsia (FD), irritable bowel syndrome, and chronic idiopathic constipation.

Achalasia: Diagnosis, Management and Surveillance.

Achalasia is a rare chronic esophageal motility disorder characterized by incomplete relaxation of the lower esophageal sphincter and abnormal peristalsis. This abnormal motor function leads to impaired bolus emptying and symptoms of dysphagia, regurgitation, chest pain, or heartburn. After an upper endoscopy to exclude structural causes of symptoms, the gold standard for diagnosis is high-resolution esophageal manometry. However, complementary diagnostic tools include barium esophagram and functional luminal impedance planimetry. Definitive treatments include pneumatic dilation, Heller myotomy with fundoplication, and peroral endoscopic myotomy.

Hepatocellular Carcinoma in Hispanic Patients: Trends and Outcomes in a Large United States Cohort.

Hepatocellular carcinoma (HCC) has a strong racial and ethnic association, with Hispanic patients having a higher incidence and mortality. However, there are limited data regarding clinical features and outcomes. This study includes Hispanic and non-Hispanic White patients with HCC diagnosed between January 2000 and June 2014 from five United States academic medical centers. The chi-square test for categorical variables and analysis of variance for continuous variables were used for statistical analysis, with two-tailed P < 0.05 considered statistically significant. Of 5,327 patients, 4,217 met inclusion criteria, of whom 12.3% were Hispanic patients. Compared to their non-Hispanic White counterparts, Hispanic patients were older at age of diagnosis (mean ± SD, 64.2 ± 10.9 vs. 61.9 ± 10.5 years; P < 0.0001), with higher body mass index (29.6 ± 6.5 vs. 28.8 ± 5.9 kg/m2; P = 0.01), and were more likely to have diabetes and hypertension. Hispanic patients had significantly more nonalcoholic fatty liver disease and alcohol-related liver disease (both P < 0.0001). Hispanic patients presented with larger tumors, more advanced stage disease, and increased rates of macrovascular invasion and extrahepatic spread. HCCs in Hispanic patients were less likely to be within Milan criteria (26% vs. 38%; P < 0.0001) and were less likely to be treated with resection (9% vs. 13%; P = 0.03) or transplantation (8% vs. 19%; P < 0.0001). Hispanic patients had a median overall survival of 1.4 years (95% confidence interval [CI], 1.22-1.56), which was similar to that of non-Hispanic White patients (1.3 years; 95% CI, 1.26-1.41; P = 0.07). Conclusion: Hispanic patients with HCC were more likely to have metabolic risk factors for chronic liver disease, including obesity. Despite diagnosis at more advanced stages with less curative intervention than non-Hispanic White patients, median overall survival was similar between groups.

Health Care Costs After Cardiac Arrest in the United States.

BACKGROUND: This study was designed to estimate the costs of index hospitalizations after cardiac arrest in the United States. METHODS AND RESULTS: We used the US Nationwide Inpatient Sample (2003-2012) to identify patients with cardiac arrest. Log transformation of inflation-adjusted cost was determined for care to patient outcomes. Overall, an estimated 1 387 396 patients were hospitalized after cardiac arrest. The mean age of the cohort was 66 years, 45% were women, and the majority were white. Inpatient procedures included coronary angiography (15%), percutaneous coronary intervention (7%), intra-aortic balloon pump (4.4%), therapeutic hypothermia (1.1%), and mechanical circulatory support (0.1%). The rates of therapeutic hypothermia increased from zero in 2003 to 2.7% in 2012 (P<0.001). Both hospital charges and inflation-adjusted cost increased linearly over time. In a multivariate analysis, predictors of inflation-adjusted cost included large hospital size, urban teaching hospital, and length of stay. Among comorbidities, atrial fibrillation or fluid and electrolytes imbalance was most associated with cost. Among selected interventions, the cost was significantly increased with automatic implantable cardioverter defibrillators (odds ratio, 1.83; P<0.001), intra-aortic balloon pump (odds ratio, 1.50; P<0.001), hypothermia (odds ratio, 1.28; P<0.001), and extracorporeal membrane oxygenation (odds ratio, 2.38; P<0.001). CONCLUSIONS: In the period between 2003 and 2012, postcardiac arrest hospitalizations resulted in a steady rise in associated health care cost, likely related to increased length of stay, medical procedures, and systems of care. Although targeted cost containment for postarrest interventions may reduce the finance burden, there is an increasing need for funding research into prediction and prevention of cardiac arrest, which offers greater societal benefit.

Influence of Total Coronary Occlusion on Clinical Outcomes (from the Bypass Angioplasty Revascularization Investigation 2 DiabetesTrial).

Our aim was to evaluate the influence of chronic total occlusions (CTOs) on long-term clinical outcomes of patients with coronary heart disease and diabetes mellitus. We evaluated patients with coronary heart disease and diabetes mellitus enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes, who underwent either prompt revascularization (PR) with intensive medical therapy (IMT) or IMT alone according to the presence or absence of CTO. Of 2,368 patients enrolled in the trial, 972 patients (41%) had CTO of coronary arteries. Of those, 482 (41%) and 490 (41%) were in the PR with IMT versus IMT only groups, respectively. In the PR group, patients with CTO were more likely to be selected for the coronary artery bypass grafting stratum (coronary artery bypass grafting 62% vs percutaneous coronary intervention 31%, p <0.001). Compared to the non-CTO group, patients with CTO had more abnormal Q wave, abnormal ST depression, and abnormal T waves. The myocardial jeopardy score was higher in the CTO versus non-CTO group (52 [36 to 69] vs 37 [21 to 53], p <0.001). After adjustment, 5-year mortality rate was significantly higher in the CTO group in the entire cohort (hazard ratio [HR] 1.35, p = 0.013) and in patients with CTO managed with IMT (HR 1.46, p = 0.031). However, the adjusted risk of death was not increased in patients managed with PR (HR 1.26, p = 0.180). In conclusion, CTO of coronary arteries is associated with increased mortality in patients treated medically. However, the presence of a CTO may not increase mortality in patients treated with revascularization. Larger randomized trials are needed to evaluate the effects of revascularization on long-term survival in patients with CTO.

Thrombus formation following transcatheter aortic valve replacement.

OBJECTIVES: This paper reviews the published data and reports 3 cases of thrombosis involving CoreValve (Medtronic, Minneapolis, Minnesota) and 1 involving Edward Sapien (Edwards Lifesciences, Irvine, California) devices. Three of these cases had pathological findings at autopsy. BACKGROUND: Only a limited number of cases of valve dysfunction with rapid increase of transvalvular aortic gradients or aortic insufficiency post-transcatheter aortic valve replacement (TAVR) have been described. This nonstructural valvular dysfunction has been presumed to be because of early pannus formation or thrombosis. METHODS: Through reviews of the published reports and 4 clinical cases, pathological and clinical findings of early valve thrombosis are examined to elucidate methods for recognition and identifying potential causes and treatments. RESULTS: This paper presents 4 cases, 2 of which had increasing gradients post-TAVR. All 3 pathology cases showed presence of a valve thrombosis in at least 2 TAV leaflets on autopsy, but were not visualized by transthoracic echocardiogram or transesophageal echocardiogram. One case was medically treated with oral anti coagulation with normalization of gradients. The consequence of valve thrombosis in all 3 pathology patients either directly or indirectly played a role in their early demise. At least 18 case reports of early valve thrombosis have been published. In 12 of these cases, the early treatment with anticoagulation therapy resolved the thrombus formation and normalized aortic pressures gradients successfully. CONCLUSIONS: These 4 cases elucidate the occurrence of valve thrombosis post-TAVR. Consideration should be given to treatment with dual antiplatelet therapy and oral anticoagulation in patients post-TAVR with increasing mean pressure gradients and maximum aortic valve velocity. Further research should be conducted to create guidelines for antithrombotic therapy following TAVR procedure.