Potassium-competitive acid blockers and acid-related disorders.

PURPOSE OF REVIEW: Potassium-competitive acid blockers (PCABs) represent a new class of compounds for the treatment of acid-related disorders. Recent FDA approval of the PCAB vonoprazan for erosive esophagitis has started an important new approach to acid-related disorders. RECENT FINDINGS: Compared to conventional proton pump inhibitors (PPIs), PCABs provide more rapid, potent, and sustained suppression of gastric acid with faster and more durable symptom relief. Studies have demonstrated the efficacy of PCABs for erosive esophagitis, nonerosive reflux disease, and peptic ulcer disease including H. pylori. However, the PCAB vonoprazan was only approved in the US as part of combination therapy for eradication of H. pylori. Clinical trials have now demonstrated noninferiority of vonoprazan to lansoprazole for treatment of erosive esophagitis, particularly noting superiority of vonoprazan in patients with severe esophagitis resulting in FDA approval of vonoprazan for treatment of erosive esophagitis. Emerging data suggests a possible utility of vonoprazan for PPI-resistant gastroesophageal reflux disease (GERD) and on-demand therapy for nonerosive reflux disease. Vonoprazan is generally well tolerated but long-term safety data is not well established. SUMMARY: The PCAB vonoprazan is a newly FDA approved treatment option for erosive esophagitis. Its possible role in PPI-resistant GERD and nonerosive reflux disease warrants further investigation.

Initial Stage of Disease Similar for White and Black Patients With Early-Onset Colorectal Cancer at a Safety-Net Hospital.

BACKGROUND: Non-Hispanic Black (NHB) patients with early-onset colorectal cancer (EOCRC) are more likely to present with advanced-stage disease than their Non-Hispanic White (NHW) counterparts. To further elucidate whether differences in tumor biology or disparities in access to care may be responsible, we examined the association between race/ethnicity and initial stage of disease, time to diagnosis, and tumor characteristics among NHW and NHB patients with EOCRC cared for in a safety-net health care setting. METHODS: We performed a retrospective cohort study of NHW and NHB patients diagnosed with primary EOCRC who received care at Boston Medical Center between January 2000 and May 2020. We compared demographics, risk factors, presenting signs/symptoms, time to diagnosis, health care utilization, and tumor characteristics (stage, grade, location, and mutational status). RESULTS: We identified 103 patients (mean age 41.5±7.2 y, 53.4% men), including 40 NHWs and 63 NHBs, with EOCRC. NHB and NHW patients were similar with respect to demographics, presenting signs/symptoms, and risk factor distribution. There were also no significant differences between NHWs and NHBs with respect to the advanced stage of disease at presentation (45.0% vs. 42.9%, P =0.83), the median time to diagnosis [152 d (IQR, 40 to 341) vs. 160 d (IQR, 61 to 312), P =0.79] or tumor characteristics, except for a predilection for proximal disease among NHBs (30.2% vs. 15.0%). CONCLUSIONS: NHB patients were no more likely than NHW patients to present with advanced-stage disease, aggressive tumor histology, or experience delays in diagnosis within a safety-net health care system.

Long-term Continued Proton Pump Inhibitor Use is Common in Patients Diagnosed with Eosinophilic Esophagitis Despite Failure of Histologic Response: Data from a two-centre study: Long-term PPI Use in Patients with EoE.

Background and Aims: Treatment paradigms for proton pump inhibitors (PPIs) in eosinophilic esophagitis (EoE) are evolving. We aimed to determine patterns of long-term PPI use after EoE diagnosis in PPI histologic non-responders. Methods: We conducted a retrospective review at University of Colorado (UCH) and University of North Carolina (UNC) of EoE patients who were histologic non-responders to PPIs. Data were extracted from electronic medical records related to demographics, PPI use, and reasons for continuing or stopping PPI. Results: Of 67 patients in the UCH cohort, PPIs were initially discontinued in 9 (13%). Of 58 remaining on PPI, 48% were not instructed to discontinue therapy and 26% continued for symptom improvement. Of 675 patients at UNC, PPI was stopped in 185 (27%). Of patients remaining on PPI, 15% were not told to discontinue therapy and 62% were continued for symptom improvement. At last contact, >50% of patients remained on PPI at both centres with most common reasons for continuation being symptom improvement and not telling patients to discontinue. In the UNC cohort, clinical features associated with remaining on PPI included children younger than 18 years (p=0.01), males (p<0.001), heartburn symptoms (p<0.001) and hiatal hernia (p=0.004). Patients with dysphagia were less likely to remain on PPIs (p<0.001). Conclusions: Long-term PPI use is common in EoE patients even without histologic response. Failure to instruct patients to discontinue therapy was a common reason for long-term use, thus PPI use should be revisited in all EoE patients to confirm clinical benefit.

Distal esophagus is the most commonly involved site for strictures in patients with eosinophilic esophagitis.

While strictures are common in eosinophilic esophagitis (EoE), there are few data on stricture distribution and characteristics. Our primary aim was to characterize strictures by location in the esophagus in EoE and associated clinical, endoscopic, and histologic features. This was a retrospective study from the UNC EoE Clinicopathologic Database of subjects with esophageal strictures or narrowing from 2002 to 2017. Strictures were categorized as distal esophagus/gastroesophageal junction, mid-esophagus, proximal esophagus, or diffusely narrowed. Stricture location was assessed and compared with clinical, endoscopic, and histologic features, and also with treatment response to diet or topical steroids. Efficacy of combination therapy with dilation and intralesional steroid injection was assessed in a sub-group of patients with strictures. Of 776 EoE cases, 219 (28%) had strictures, 45% of which were distal, 30% were proximal, 5% were mid-esophageal, and 20% had diffuse narrowing. Those with mid-esophageal strictures were younger (P = 0.02) and had shorter symptom duration (P < 0.01). Those with diffuse esophageal narrowing were more likely to be women (57%) and have abdominal pain (25%). There was no association between other clinical, endoscopic, and histologic findings and treatment response based on stricture location. Fourteen patients (8%) received intralesional triamcinolone injection and subsequently achieved a higher mean dilation diameter after injection (13.7 vs. 15.5 mm; P < 0.01). In conclusion, almost half of strictures in EoE patients were in the distal esophagus. Therefore, EoE should be a diagnostic consideration in patients with focal distal strictures and not presumed to be secondary to gastroesophageal reflux disease.

Increased prevalence of autonomic dysfunction due to postural orthostatic tachycardia syndrome in patients with eosinophilic gastrointestinal disorders.

BACKGROUND AND AIMS: Eosinophilic gastrointestinal disorders (EGIDs) have been linked with atopic conditions, connective tissue disorders, and autoimmunity, but the association between EGIDs and autonomic dysfunction has not been extensively described. We aimed to assess this association and determine the prevalence of autonomic dysfunction in our EGID population. METHODS: In this retrospective cohort study, we analyzed adult patients in the University of North Carolina Eosinophilic Esophagitis (EoE)/EGID database who also had a diagnosis of comorbid autonomic dysfunction (postural orthostatic tachycardia syndrome [POTS] or gastroparesis). The electronic medical record was abstracted and disease characteristics summarized. RESULTS: We identified seven patients who had EGID and autonomic dysfunction. All had POTS and were Caucasian, and five (71%) were female; 2 also had gastroparesis. Onset of autonomic symptoms coincided with onset of EGID symptoms in 3 patients (43%) or with an acute EGID flare in 3. In no cases did successful control of EGID lead to improvement of autonomic symptoms. Two subjects (29%) had comorbid Ehlers-Danlos syndrome and mast cell activation syndrome. The prevalence of POTS in EGID patients was 7/560 (1.25%), compared to an estimated 0.17% prevalence of POTS in the general population. CONCLUSIONS: The prevalence of autonomic dysfunction was 5-10-fold higher in EGID than expected in the general population, suggesting an association between the two conditions, though the underlying mechanism is unclear. Providers should consider comorbid autonomic dysfunction in patients with EGID, particularly when symptoms persist despite treatment.

Longitudinal Growth Outcomes Following First-line Treatment for Pediatric Patients With Eosinophilic Esophagitis.

OBJECTIVES: No formal comparative effectiveness studies have been conducted to evaluate the effect of eosinophilic esophagitis (EoE) treatment choice on long-term growth in pediatric patients. Long-term studies of inhaled corticoid steroids in asthma, however, suggest possible effects on linear growth. The aim of this study was to compare longitudinal, anthropometric growth in children with EoE according to treatment approach. METHODS: We conducted a retrospective, multicenter cohort study of anthropometric growth (height and body mass index [BMI] z scores) in pediatric (<18 years of age) patients newly diagnosed with EoE across 5 clinical sites between 2005 and 2014. We compared differences in growth according to treatment approach over a 12-month period. Modification by sex and age was examined and sensitivity analyses were conducted to assess robustness of results given study assumptions. RESULTS: In the 409 patients identified, the mean age and proportion male differed by treatment (P =  < 0.01 and P = 0.04, respectively). Baseline growth measures were associated with slight impairment of height at diagnosis (median baseline height z score of -0.1 [interquartile range -0.9, 0.8]). In general, treatment approach was not associated with any significant increase or decrease in expected growth over a 12-month period. Subtle decrease in linear growth was observed with treatment using a combined elemental and topical steroid (Δ height z score [adjusted]: -0.04; 95% confidence interval [CI]: -0.08, -0.01). Differences in linear growth differed by sex (P for interaction <0.01). For elemental formula in combination with topical steroids, only girls exhibited a significant decline in linear growth (Δ height z score [adjusted]: -0.24; 95% CI: -0.32, -0.17). A slight reduction in BMI was observed for patients treated with a combination of elemental diet and dietary elimination (Δ BMI z score [adjusted]: -0.07; 95% CI: -0.13, -0.01). CONCLUSIONS: Treatment of EoE, in general, is not associated with major anthropometric growth changes in most pediatric patients. Slight linear growth impairment was observed for topical steroid treatment, and sex differences in growth by treatment approach were observed. Future prospective studies should evaluate the effect of treatment on optimal growth and development and over a longer period of follow-up.

Practice Pattern Variation in Pediatric Eosinophilic Esophagitis in the Carolinas EoE Collaborative: A Research Model in Community and Academic Practices.

OBJECTIVES: Differences in the initial management of pediatric eosinophilic esophagitis (EoE) by practice setting have not been well characterized. We aimed to characterize these differences for sites in the Carolinas EoE Collaborative (CEoEC), a multicenter network of academic and community practices. METHODS: We performed a retrospective cohort study of pediatric EoE patients at five CEoEC sites: University of North Carolina (UNC) Hospital, Charlotte Asthma and Allergy Specialists, Greenville Health Systems, Wake Forest Baptist Medical Center, and the Medical University of South Carolina Hospital. Cases of EoE were defined by consensus guidelines. Data were extracted from electronic medical records. We tested for differences among sites and used a multinomial model (polytomous regression) to assess associations between treatment and site, adjusting on patient factors. RESULTS: We identified 464 children with EoE across the CEoEC sites. The median age was highest at Wake Forest (11.4 years), the median eosinophil count was highest at UNC (69 eos/hpf), and UNC had the most male patients (82%). UNC used topical steroids for initial treatment in 86% of cases, compared with <1% in Greenville (P < 0.01). Greenville used dietary elimination more frequently than UNC (81% vs 2%, P < 0.01). Differences in treatment approach held after adjusting for potential baseline confounders. There was no significant association between patient factors and initial treatment approach. CONCLUSIONS: Significant differences in EoE patient factors and treatment approaches were identified across CEoEC sites and were not explained by patient or practice factors. This suggests that institutional or provider preferences drive initial treatment approaches, and that more data are needed to drive best practice decisions.

The Six-Food Elimination Diet for Eosinophilic Esophagitis Increases Grocery Shopping Cost and Complexity.

The six-food elimination diet (SFED), where dairy, wheat, eggs, soy, nuts, and seafood are avoided, is an effective treatment for eosinophilic esophagitis (EoE). Patient-related costs of this approach, however, are unknown. We aimed to assess the cost of and ease of shopping for an SFED compared to an unrestricted diet. A dietitian with expertise in EoE generated menus meeting dietary requirements for a week's worth of meals for the SFED and an unrestricted diet. We compared prices and the number of missing items for both diets at standard and specialty grocery stores. The average weekly price of the SFED at a standard supermarket was $92.54 compared to $79.84 for an unrestricted diet (p = 0.0001). A patient shopping at a standard grocery store needed a higher proportion of items from a second store compared to an unrestricted diet (32 vs. 3 %, p = 0.0001). The prices of the SFED and unrestricted diet using a specialty supermarket were comparable ($106.47 vs. $105.96, p = 0.81), as was the percentage of items requiring a trip to a second store (6 vs. 2 % items, p = 0.03). Shopping at a specialty grocery store increased weekly grocery costs by $13.93 (p = 0.04) for the SFED and $26.12 (p = 0.03) for the unrestricted diet. In conclusion, for patients shopping at standard grocery stores, the cost of an SFED is higher, and an SFED requires more items from a second store. These differences disappear at specialty grocery stores, but costs were significantly higher. This cost and logistical burden can inform patients when selecting dietary therapy.