Utility of Intraprocedural Luminal Diameter and Distensibility Measurements During the Esophageal Peroral Endoscopic Myotomy Procedure.

GOALS: Through evaluation of the lower esophageal sphincter immediately before and after myotomy using an endoluminal functional lumen imaging probe (EFLIP), our study aimed to determine the clinical response to peroral endoscopic myotomy (POEM) and the incidence of postprocedure reflux. BACKGROUND: Achalasia is a rare esophageal motility disorder characterized by impaired relaxation of the lower esophageal sphincter (LES) and diminished peristalsis. POEM is a therapeutic option for durable management of achalasia. However, symptomatic acid reflux and esophagitis are well-known adverse effects of the procedure. STUDY: Electronic medical records of 168 patients who underwent POEM for achalasia at 2 tertiary care referral centers from May 2014 to May 2021 were reviewed. EFLIP was used at a range of catheter fill volumes to assess LES dynamics. Preprocedure and postprocedure Eckardt Symptom Scores were recorded. RESULTS: Significant clinical improvement from POEM was sustained in over 94% of patients after 1 year. EFLIP changed intraprocedural management 5% of the time by means of myotomy extension. In patients with reflux>1 year following POEM, there was no significant difference in post-POEM LES diameter or change in LES diameter compared with those without reflux. However, post-POEM LES distensibility index (DI) was significantly higher in patients with reflux after 1 year compared with those without reflux. CONCLUSIONS: POEM is a safe and increasingly effective therapy for patients with symptomatic achalasia. Intraprocedural EFLIP measurements suggest that post-POEM reflux may be correlated more with DI than LES diameter. Yet, more data is needed to substantiate these outcomes.

The influence of hospitalization and HIV severity on gastrointestinal PCR panel evaluation of HIV-related acute diarrhea in New York City: a retrospective, cross-sectional study.

Introduction: Diarrhea is common in persons living with HIV (PLWH)/AIDS. With the increasing utilization of multiplex gastrointestinal PCR panel (GI panel) testing, we aimed to characterize the roles of CD4 count and hospitalization in GI panel assessments of PLWH with acute diarrhea. Methods: We performed a cross-sectional study of adult PLWH with acute diarrhea who underwent GI panel testing at two urban academic centers. Demographic, HIV disease, GI panel result, and hospitalization data were collected, and patients were cohorted by CD4 count (CD4 < 200, CD4 200-499, CD4 > = 500). The primary outcome was enteric infection as detected by GI panel, and hospitalization. Results: Of 298 PLWH, 119 (39.9%) had a CD4 count below 200, 195 (65.4%) were hospitalized, and 137 (46.0%) had enteric infection. Bacterial infection correlated with higher CD4 count (41.9% (CD4 > = 500) vs 31.2% (CD4 200-499) vs 25.2% (CD4 < 200), p = 0.041). Hospitalization correlated with poorly controlled HIV and fewer enteric infections (34.4% vs 68.0%, p < 0.001). After adjusting for HIV disease severity, a negative GI panel remained independently associated with hospitalization (adjusted odds ratio (aOR) 5.32, 95% confidence interval (CI) 2.72-10.9), even in patients tested within 72 hours of hospitalization. Despite better HIV control, men who have sex with men (MSM) had more frequent infectious diarrhea, including from E. coli, giardiasis, and multiple pathogens. MSM status independently predicted enteric infection (aOR 1.93, 95% CI: 1.02-3.67). Conclusions: GI panel results vary by HIV disease severity and hospitalization in PLWH. Clinicians - especially in the inpatient setting - should carefully consider these factors when interpreting GI panel results. Further characterization of diarrheal etiology in PLWH with a negative GI panel is needed. Plain Language Summary: PCR stool test results are affected by certain factors in HIV-related diarrhea Diarrhea is common in people living with HIV (PLWH) and has a variety of causes, including infections, medications, and HIV itself. Multiplex polymerase chain reaction (PCR) stool testing simultaneously evaluates for a variety of common viral, bacterial, and parasitic infections of the gastrointestinal tract, and is increasingly being used in patients with diarrhea. However, patients with HIV and diarrheal illness may have uncommon infections not typically present in those with normal immune function - and thus not routinely evaluated for in stool testing. It is not known what factors, if any, might affect the results of PCR testing in HIV-related diarrhea.In this study, we examined all PLWH who underwent stool PCR testing for diarrhea over a 4-year period. We separated the patients into groups based on HIV disease severity as measured by CD4 T-cell count, or the count of the immune cells affected by HIV. We examined whether there were differences among groups in infection rates as detected by PCR stool testing. Separately, we studied the role of hospitalization in stool PCR test results.Of 298 PLWH who underwent stool PCR testing for diarrhea, 119 had a CD4 count less than 200 (low CD4 count), 195 were hospitalized at time of testing, and 137 had a positive stool PCR test. Compared to those with a low CD4 count, subjects with less severe HIV disease were more likely to have a bacterial infection on stool PCR testing and less likely to be hospitalized. Hospitalized patients were more likely to have a negative PCR stool test, regardless of CD4 count. Many patients with a low CD4 count had diarrheal etiologies not evaluated by multiplex stool PCR. In PLWH who experience diarrhea, stool PCR testing results vary by CD4 count and hospitalization. Providers should be mindful of these factors when interpreting stool PCR test results.

Balloon tamponade for control of myotomy bleeding during peroral endoscopic myotomy.

Video 1Balloon tamponade for control of bleeding during peroral endoscopic myotomy.

Probiotic Use in Celiac Disease: Results from a National Survey.

BACKGROUND AND AIMS: Patients with celiac disease (CD) commonly use supplements for perceived health benefits despite scant evidence. We aimed to characterize the prevalence and predictors of probiotic use among CD patients. METHODS: We analyzed data from iCureCeliac®; a patient-powered research network questionnaire distributed by the Celiac Disease Foundation. We included adults with self-reported CD who answered questions regarding demographics, diagnosis, symptoms, and treatment. We compared probiotic users versus probiotic non-users and subsequently performed multivariable logistic regression, assessing for independent predictors of probiotic use. RESULTS: 4,909 patients met the criteria for inclusion in the study. Of these, 1,160 (23.6%) responded to a question regarding probiotic use. The mean age of participants was 38.8 years and 82% were female. 381 patients (33%) reported using probiotics. More probiotic users sought nutritional counseling at time of diagnosis (36% vs. 30%, p=0.05) and remained symptomatic despite a gluten-free diet (40% vs. 25%, p <0.001). Probiotic users had lower scores on the pain subscale of the SF36 (63.7±21.6 vs. 69.5±22.1, p=0.006). On multivariable analysis, patients diagnosed after age 50 (OR=2.04, 95%CI: 1.37-3.04), and those with persistent symptoms despite a gluten-free diet (OR=1.94, 95%CI: 1.44-2.63) were more likely to use probiotics. CONCLUSION: In this large study of a national CD registry, roughly one-third of CD patients reported using probiotics. Patients diagnosed later in life were more likely to use probiotics and those who remained symptomatic despite a gluten-free diet were twice as likely to take probiotics. Patients may be seeking additional means of treatment for persistent symptoms.

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.

Numbers and Features of Patients With a Diagnosis of Celiac Disease Without Duodenal Biopsy, Based on a National Survey.

BACKGROUND & AIMS: According to guidelines, individuals with symptoms of celiac disease should undergo duodenal biopsy analysis to establish a diagnosis, but little is known about physician adherence to these guidelines. We used a patient-powered research network (PPRN) to compare demographics, diagnoses, symptoms, and treatment between groups of patients with celiac disease diagnosed by biopsy analysis and patients with a diagnosis based on results of serology tests. METHODS: We analyzed data from iCureCeliac-a voluntary, PPRN hosted and distributed by the Celiac Disease Foundation, from January 30, 2016, through August 25, 2016. We compared data from adults with a diagnosis of celiac disease (mean age, 43.4 years; 85.6% female) based on biopsy analysis (n = 780) vs patients with a diagnosis based on only serologic analysis (n = 202) using univariate and multivariable analyses. We collected demographic information, as well as data on type of health care practitioner, where patients obtain their primary information about celiac disease, and the Celiac Disease Quality of Life score, nutritionist referral rates, adherence to the gluten-free diet, ongoing symptoms and use of supplements. RESULTS: Among patients with a diagnosis based on serology results, 33.3% were diagnosed by non-gastroenterologists vs 20.7% in the biopsy diagnosed group (P < .001). Fewer patients with a diagnosis based on serology results sought nutritional counseling at the time of diagnosis (40.1%) than patients with a diagnosis based on biopsy (58.9%) (P < .001). A higher proportion of patients diagnosed by serology without biopsy took dietary supplements to aid in digestion of gluten (19.8%) than patients with a diagnosis based on biopsy (8.9%) (P < .001). After we adjusted for age and sex, patients with a diagnosis based on serology were less likely to seek nutritional counseling after diagnosis (odds ratio [OR], 0.45; 95% CI, 0.33-0.63), less likely to receive a diagnosis from a gastroenterologist (OR, 0.16; 95% CI, 0.07-0.37), and more likely to use digestive supplements (OR, 2.61; 95%, CI 1.62-4.19). CONCLUSIONS: In an analysis of data from a PPRN, we found that 21% of adult participants with celiac disease did not have a diagnosis based on a duodenal biopsy. Patients with a diagnosis based on serology results were more likely to be diagnosed by non-gastroenterologists, less likely to seek nutritional counseling, and more likely to use dietary supplements. Patients require more education about management of celiac disease and referral to gastroenterologists for duodenal biopsy confirmation of their disease.

Enteric Infections Are Common in Patients with Flares of Inflammatory Bowel Disease.

OBJECTIVES: Few studies have examined the role of non-Clostridium difficile enteric infections in flares of inflammatory bowel disease (IBD). Our objective was to investigate enteric infection detected by multiplex PCR stool testing in patients with IBD. METHODS: We performed a cross-sectional analysis of 9403 patients who underwent 13,231 stool tests with a gastrointestinal pathogen PCR panel during a diarrheal illness from March 2015 to May 2017. Our primary outcome was the presence of an infection. Secondary outcomes included endoscopic and histologic predictors of infection, and IBD outcomes following testing. RESULTS: A total of 277 patients with Crohn's disease (CD), 300 patients with ulcerative colitis (UC), and 8826 patients without IBD underwent 454, 503, and 12,275 tests, respectively. Compared to patients without IBD, patients with IBD were less likely to test positive (CD 18.1%, UC 16.1%, no IBD 26.6%, p < 0.001). Compared to patients without IBD, CD had a higher prevalence of norovirus (p = 0.05) and Campylobacter (p = 0.043), whereas UC had a lower prevalence of norovirus (p = 0.001) and a higher prevalence of Campylobacter (p = 0.013), Plesiomonas (p = 0.049), and Escherichia coli species (p < 0.001). Of 77 patients who underwent endoscopy, there were no major endoscopic or histologic predictors of a positive test. Patients who tested negative were more likely to have IBD therapy escalated (p = 0.004). Enteric infection did not impact IBD outcomes following testing (log-rank 0.224). CONCLUSIONS: Non-Clostridium difficile enteric infections were identified in 17% of symptomatic patients with IBD. Endoscopic and histologic findings may not differentiate flare from infection. Norovirus and E.coli may play an important role in flare of IBD.

The Distribution of Enteric Infections Utilizing Stool Microbial Polymerase Chain Reaction Testing in Clinical Practice.

BACKGROUND: Gastrointestinal infection is a major cause of morbidity. We sought to characterize the pathogenic etiologies of gastrointestinal infection to identify seasonal patterns and predictors of specific infections utilizing a multiplex PCR assay in clinical practice. METHODS: We performed a cross-sectional study of 9403 patients who underwent 13,231 stool tests with a FilmArray gastrointestinal pathogen PCR panel during an episode of diarrhea from March 2015 to May 2017. Our primary outcome was the presence of a positive panel. Logistic regression was used to test for associations between season and infections. RESULTS: A positive result was found in 3426 tests (25.9%) in 2988 patients (31.8%), yielding 4667 pathogens consisting of 1469 viruses (31.5%), 2925 bacteria (62.7%), and 273 parasites (5.8%). Age less than 50 years was associated with a higher prevalence of pathogens compared to age ≥ 50 (p < 0.0001). The overall prevalence of a positive result for bacteria peaked in the summer (635, 29.2%), and the prevalence of viruses peaked in the winter (446, 31.8%). Compared to the winter, testing in the summer yielded a higher prevalence of bacteria (OR 1.52, 95% CI 1.33, 1.73, p < 0.0001) and lower odds of viruses (OR 0.69, 95% CI 0.58, 0.81, p < 0.0001), primarily driven by E. coli species and norovirus. CONCLUSIONS: Season was a major determinant in detecting specific pathogens. Our substantially lower positivity rate than previous reports in the literature on multiplex PCR assays may more accurately reflect true clinical practice. Recognizing the temporal distribution of enteric pathogens may help facilitate empiric treatment decisions in certain clinical situations.

The Effect of Depressive Symptoms on the Association between Gluten-Free Diet Adherence and Symptoms in Celiac Disease: Analysis of a Patient Powered Research Network.

BACKGROUND: The prevalence of depression in celiac disease (CD) is high, and patients are often burdened socially and financially by a gluten-free diet. However, the relationship between depression, somatic symptoms and dietary adherence in CD is complex and poorly understood. We used a patient powered research network (iCureCeliac®) to explore the effect that depression has on patients' symptomatic response to a gluten-free diet (GFD). METHODS: We identified patients with biopsy-diagnosed celiac disease who answered questions pertaining to symptoms (Celiac Symptom Index (CSI)), GFD adherence (Celiac Dietary Adherence Test (CDAT)), and a 5-point, scaled question regarding depressive symptoms relating to patients' celiac disease. We then measured the correlation between symptoms and adherence (CSI vs. CDAT) in patients with depression versus those without depression. We also tested for interaction of depression with regard to the association with symptoms using a multiple linear regression model. RESULTS: Among 519 patients, 86% were female and the mean age was 40.9 years. 46% of patients indicated that they felt "somewhat," "quite a bit," or "very much" depressed because of their disorder. There was a moderate correlation between worsened celiac symptoms and poorer GFD adherence (r = 0.6, p < 0.0001). In those with a positive depression screen, there was a moderate correlation between worsening symptoms and worsening dietary adherence (r = 0.5, p < 0.0001) whereas in those without depression, the correlation was stronger (r = 0.64, p < 0.0001). We performed a linear regression analysis, which suggests that the relationship between CSI and CDAT is modified by depression. CONCLUSIONS: In patients with depressive symptoms related to their disorder, correlation between adherence and symptoms was weaker than those without depressive symptoms. This finding was confirmed with a linear regression analysis, showing that depressive symptoms may modify the effect of a GFD on celiac symptoms. Depressive symptoms may therefore mask the relationship between inadvertent gluten exposure and symptoms. Additional longitudinal and prospective studies are needed to further explore this potentially important finding.

Mechanisms of Acquired Resistance to BRAF V600E Inhibition in Colon Cancers Converge on RAF Dimerization and Are Sensitive to Its Inhibition.

BRAF V600E colorectal cancers are insensitive to RAF inhibitor monotherapy due to feedback reactivation of receptor tyrosine kinase signaling. Combined RAF and EGFR inhibition exerts a therapeutic effect, but resistance invariably develops through undefined mechanisms. In this study, we determined that colorectal cancer progression specimens invariably harbored lesions in elements of the RAS-RAF-MEK-ERK pathway. Genetic amplification of wild-type RAS was a recurrent mechanism of resistance in colorectal cancer patients that was not seen in similarly resistant melanomas. We show that wild-type RAS amplification increases receptor tyrosine kinase-dependent activation of RAS more potently in colorectal cancer than in melanoma and causes resistance only in the former. Currently approved RAF inhibitors inhibit RAF monomers but not dimers. All the drug-resistant lesions we identified activate BRAF V600E dimerization directly or by elevating RAS-GTP. Overall, our results show that mechanisms of resistance converge on formation of RAF dimers and that inhibiting EGFR and RAF dimers can effectively suppress ERK-driven growth of resistant colorectal cancer. Cancer Res; 77(23); 6513-23. ©2017 AACR.

Enteric Infection in Relapse of Inflammatory Bowel Disease: The Utility of Stool Microbial PCR Testing.

BACKGROUND: The similar presentations in relapse of inflammatory bowel disease (IBD) and enteric infection pose substantial barriers to diagnosis and treatment. The objective of this study was to investigate the incidence, etiology, predictors, and treatment of enteric infection in patients with IBD. METHODS: We reviewed the records of 214 patients with IBD who underwent 295 gastrointestinal pathogen panel and Clostridium difficile infection (CDI) polymerase chain reaction (PCR) stool tests during an exacerbation of symptoms. We collected baseline characteristics, PCR outcomes, and medication exposures. We tested for associations via the Chi-square test and the t-test. Logistic regression analysis was used to identify predictors of enteric infection. RESULTS: Of 295 PCR tests ordered during an exacerbation of symptoms, 38 (12.9%) were positive for CDI and 41 (13.8%) were positive for 14 other pathogens, with E. coli species as the most common. A previous history of CDI or colonic involvement of IBD predicted CDI, whereas a previous colectomy predicted negative testing for CDI. The majority with CDI (24, 63.2%) received oral vancomycin and 15 (37.5%) with other enteric pathogens were treated for their infection. Patients with CDI had a longer median length of hospital stay (8.5 versus 4 days, P = 0.041). Patients who tested negative for enteric infections were more likely to have IBD medications added or up-titrated (P = 0.027). CONCLUSIONS: Enteric infection was detected in 79 (26.8%) symptomatic patients with IBD , with CDI the most frequent followed by E. coli. Negative stool PCR testing was associated with changes in IBD management. Broad enteric PCR testing should be considered during relapse of IBD.

Safety and Efficacy of Treatment of Hepatitis C in Kidney Transplant Recipients With Directly Acting Antiviral Agents.

BACKGROUND: With the development of all oral, interferon-free directly acting antiviral (DAA) medications, treatment of hepatitis C virus (HCV) infection in renal transplant recipients is possible, but limited data exists on its safety and efficacy. METHODS: We performed a retrospective cohort analysis of patients transplanted at our center with HCV who have been started on DAAs. Primary endpoints included sustained virologic response as defined as negative viral load at 12 weeks postcompletion of therapy and allograft function. RESULTS: A total of 31 patients met inclusion criteria. The most commonly used regimen was sofosbuvir and ledipasvir (n = 21). Of the treated patients, 100% had undetectable viral load at the completion of therapy. Of the 31 patients treated, 30 (97%) achieved sustained virologic response. Both graft and patient survivals at most recent follow-up was 100%. There was no significant change in glomerular filtration rate (GFR) before or after therapy (64.2 ± 16.5 mL/min per body surface area before vs. 58.9 ± 17.5 mL/min per body surface area after therapy; P = 0.22); however, 3 patients now have GFR less than 20. A total of 6 (19.3%) of 31 patients had worsening proteinuria during or shortly after therapy. Patients with more than 500 mg/g of proteinuria at the start of treatment were significantly more likely to develop worsening proteinuria than those with less than 500 mg/g of proteinuria at the start of therapy (P < 0.001). Retrospective review of 20 untreated HCV patients did not demonstrate worsening allograft function and proteinuria during a median follow-up time of 1386 days (range, 332-6254). CONCLUSIONS: Our preliminary data demonstrate that DAAs can be used safely and effectively in patients after kidney transplantation. Patients with proteinuria or lower GFR should be monitored more closely.