Natural history study of patients with familial platelet disorder with associated myeloid malignancy.

ABSTRACT: Deleterious germ line RUNX1 variants cause the autosomal dominant familial platelet disorder with associated myeloid malignancy (FPDMM), characterized by thrombocytopenia, platelet dysfunction, and a predisposition to hematologic malignancies (HMs). We launched a FPDMM natural history study and, from January 2019 to December 2021, enrolled 214 participants, including 111 patients with 39 different RUNX1 variants from 45 unrelated families. Seventy of 77 patients had thrombocytopenia, 18 of 18 had abnormal platelet aggregometry, 16 of 35 had decreased platelet dense granules, and 28 of 55 had abnormal bleeding scores. Nonmalignant bone marrows showed increased numbers of megakaryocytes in 12 of 55 patients, dysmegakaryopoiesis in 42 of 55, and reduced cellularity for age in 30 of 55 adult and 17 of 21 pediatric cases. Of 111 patients, 19 were diagnosed with HMs, including myelodysplastic syndrome, acute myeloid leukemia, chronic myelomonocytic leukemia, acute lymphoblastic leukemia, and smoldering myeloma. Of those 19, 18 were relapsed or refractory to upfront therapy and referred for stem cell transplantation. In addition, 28 of 45 families had at least 1 member with HM. Moreover, 42 of 45 patients had allergic symptoms, and 24 of 30 had gastrointestinal (GI) symptoms. Our results highlight the importance of a multidisciplinary approach, early malignancy detection, and wider awareness of inherited disorders. This actively accruing, longitudinal study will genotype and phenotype more patients with FPDMM, which may lead to a better understanding of the disease pathogenesis and clinical course, which may then inform preventive and therapeutic interventions. This trial was registered at www.clinicaltrials.gov as #NCT03854318.

Small bowel disease prevalence on video capsule endoscopy in chronic granulomatous disease-associated inflammatory bowel disease.

BACKGROUND AND AIM: Patients with chronic granulomatous disease (CGD) may develop inflammatory bowel disease (IBD). Characterization of small bowel disease in this cohort is scarce. Here, we sought to determine the prevalence and characteristics of small bowel disease and evaluate the clinical utility of video capsule endoscopy (VCE) for its diagnosis. METHODS: A retrospective study was performed on patients with CGD who were evaluated for gastrointestinal disease with VCE as a part of ongoing natural history studies at a single academic center. VCEs were reviewed for inflammatory findings and severity of disease utilizing the Capsule Endoscopy Crohn's Disease Activity Index. Radiographic studies and endoscopies performed within 30 days of VCE were compared with small bowel inflammatory findings. RESULTS: Twenty-six VCEs corresponding to 25 patients were found. The majority of patients were male and White; mean age was 28 years old. The majority (85%) demonstrated presence of small bowel inflammatory findings on VCE including strictures, ulcers, erosions, and erythema. Duodenal and ileal inflammatory disease on endoscopy did not correlate with disease on VCE. Moderate-severe colonic disease correlated with moderate-severe disease on VCE. Radiography did not correlate with disease on VCE. Prolonged small bowel transit time correlated with moderate-severe small bowel disease. CONCLUSIONS: Small bowel IBD was highly prevalent in this cohort of patients with CGD. Limitations included small sample size. Given that radiology and duodenal/ileal disease did not correlate with VCE findings, VCE-driven investigation of small bowel disease should be considered in patients with CGD-associated IBD, particularly those with colonic disease.

Clinical, Endoscopic, and Histopathologic Gastrointestinal Disease in an American Cohort With Behçet's Disease.

INTRODUCTION: Behçet's disease (BD) is a chronic systemic vasculitis characterized by oral and genital ulcers, uveitis, and skin lesions. Patients with BD may develop gastrointestinal (GI) disease; however, characterization of GI disease in American cohorts is lacking. In this article, we present clinical, endoscopic, and histopathologic GI findings in an American cohort of patients with BD. METHODS: Patients with established BD were evaluated prospectively at the National Institutes of Health. Demographic and clinical data were collected including BD manifestations and GI symptoms. Endoscopy with histopathologic sampling was performed for both clinical and research indications with written consent. RESULTS: Eighty-three patients were evaluated. The majority were female (83.1%) and white (75.9%). Mean age was 36 ± 14.8 years. GI symptoms were reported in 75% of cohort with nearly half of reporting abdominal pain (48.2%) and significant numbers reporting acid reflux, diarrhea, and nausea/vomiting. Esophagogastroduodenoscopy was performed in 37 patients; erythema and ulcers were the most common found abnormalities. Colonoscopy was performed in 32 patients with abnormalities including polyps, erythema, and ulcers. Endoscopy was normal in 27% of esophagogastroduodenoscopies and 47% of colonoscopies. Vascular congestion was demonstrated on the majority of random biopsies throughout the GI tract. Inflammation was not highly prevalent on random biopsies except in the stomach. Wireless capsule endoscopy was performed on 18 patients; ulcers and strictures were the most common abnormalities. DISCUSSION: GI symptoms were common in this cohort of American patients with BD. Endoscopic examination was often normal; however, histopathologic examination demonstrated vascular congestion throughout the GI tract.

COVID-19 is not associated with worse long-term inflammatory bowel disease outcomes: a multicenter case-control study.

Background: Inflammatory bowel disease (IBD) is not associated with worse coronavirus disease 2019 (COVID-19) outcomes. However, data are lacking regarding the long-term impact of severe acute respiratory syndrome coronavirus 2 infection on the disease course of IBD. Objectives: We aimed to investigate the effect of COVID-19 on long-term outcomes of IBD. Design: We performed a multicenter case-control study of patients with IBD and COVID-19 between February 2020 and December 2020. Methods: Cases and controls were individuals with IBD with presence or absence, respectively, of COVID-19-related symptoms and confirmatory testing. The primary composite outcome was IBD-related hospitalization or surgery. Results: We identified 251 cases [ulcerative colitis (n = 111, 45%), Crohn's disease (n = 139, 55%)] and 251 controls, with a median follow-up of 394 days. The primary composite outcome of IBD-related hospitalization or surgery occurred in 29 (12%) cases versus 38 (15%) controls (p = 0.24) and on multivariate Cox regression, COVID-19 was not associated with increased risk of adverse IBD outcomes [adjusted hazard ratio (aHR): 0.84, 95% confidence interval [CI]: 0.44-1.42]. When stratified by infection severity, severe COVID-19 was associated with a numerically increased risk of adverse IBD outcomes (aHR: 2.43, 95% CI: 1.00-5.86), whereas mild-to-moderate COVID-19 was not (aHR: 0.68, 95% CI: 0.38-1.23). Conclusion: In this case-control study, COVID-19 did not have a long-term impact on the disease course of IBD. However, severe COVID-19 was numerically associated with worse IBD outcomes, underscoring the continued importance of risk mitigation and prevention strategies for patients with IBD during the ongoing COVID-19 pandemic.

Crohn's disease active inflammation assessment with iodine density from dual-energy CT enterography: comparison with endoscopy and conventional interpretation.

PURPOSE: To compare terminal ileum (TI) mucosal iodine density obtained at dual-energy CT enterography (DECTE) with conventional CT interpretation and endoscopy in patients with Crohn's disease (CD). MATERIALS AND METHODS: Twenty-three CD patients (14 men; mean[SD] age:48.1[16.7] years) with endoscopy within 30 days of DECTE were retrospectively identified. An inflammatory bowel disease gastroenterologist reviewed endoscopic images. Two radiologists qualitatively assessed the presence of active TI inflammation. Mean iodine density normalized to the aorta (I%), mean absolute iodine density (I), and iodine density standard deviation (ISD) from the distal 2 cm ileum (TI) mucosa obtained using semiautomatic prototype software were compared with endoscopic assessment using Mann Whitney tests. The optimal threshold I% and I were determined from receiver operating curves (ROC). Sensitivity and specificity of conventional interpretation and determined iodine thresholds were compared using McNemar's test. Inter-reader agreement was assessed using kappa. A p < 0.05 indicated statistical significance. RESULTS: Twelve (52.1%) patients had endoscopic active inflammation. I% was 37.9[13.3]% for patients with and 21.7[7.5]% for patients without endoscopic active inflammation (p = 0.001). The optimal ROC threshold 24.6% had 100% sensitivity and 81.8% specificity (AUC = 0.909, 95% CI 0.777-1). I was 2.44[0.73]mg/mL for patients with and 1.77[1.00]mg/mL for patients without active endoscopic inflammation (p = 0.0455). The optimal ROC threshold 1.78 mg/mL I had 91.7% sensitivity and 63.6% specificity (AUC = 0.75, 95% CI 0.532-0.968). ISD was similar for patients with and without endoscopic active inflammation (0.82[0.33]mg/mL and 0.77[0.28]mg/mL, respectively, p = 0.37). Conventional interpretation sensitivity and specificity (R1/R2) were 83.3%/91.7% and 72.7%/54.5%, respectively (all p > 0.05) with moderate inter-reader agreement (Κ = 0.542[95% CI 0.0202-0.088]). CONCLUSION: Mean normalized iodine density is highly sensitive and specific for endoscopic active inflammation. DECTE could be considered as a surrogate to endoscopy in CD patients. Despite trends towards improved sensitivity and specificity compared with conventional interpretation, future larger studies are needed.

Diagnosis and Monitoring of Ulcerative Colitis.

Ulcerative colitis is one of the two main subtypes of inflammatory bowel disease, along with Crohn's disease. Understanding the clinical and endoscopic features of ulcerative colitis is critical in achieving a timely diagnosis. An initial evaluation includes assessing clinical symptoms, inflammatory markers, endoscopic findings, and determination of the presence or absence of extraintestinal manifestations. Initial disease management should consider disease severity at the time of diagnosis as well as prognostication, or the determination of risk factors present with a high likelihood of severe disease in the future. Once appropriate therapy has been initiated, ongoing monitoring is crucial, which may include repeated clinical assessments over time, measuring noninvasive markers of inflammation, and endoscopic and histologic reevaluation. An important aspect of disease monitoring in ulcerative colitis is dysplasia surveillance; there are many patient-specific risk factors which influence surveillance strategies. Utilizing appropriate surveillance techniques is necessary for early detection of dysplasia and colorectal neoplasia.

Safety and Efficacy of Ustekinumab in the Inflammatory Bowel Disease of Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by mutations encoding the NADPH oxidase complex.1 Those affected are at increased risk of bacterial and fungal infections and require antimicrobial prophylaxis. Dysregulated inflammation may cause inflammatory bowel disease (IBD), termed CGD-associated IBD or CGD colitis, a distinct entity from Crohn's disease (CD) or ulcerative colitis (UC).

Gastrointestinal Computed Tomography Findings in Chronic Granulomatous Disease with Subgroup Clinicopathologic Analysis.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency which can lead to gastrointestinal (GI) complications including inflammatory bowel disease. Radiographic findings in this cohort have not been well described. AIMS: To describe the frequency and spectrum of gastrointestinal abnormalities seen on computed tomography (CT) in patients with CGD and determine whether radiography was predictive of endoscopic or histopathologic inflammatory findings. METHODS: A retrospective review was conducted on 141 consecutive CGD patients seen at the National Institutes of Health between 1988 and 2011. All corresponding CTs were reviewed for gastrointestinal abnormalities including wall thickening. Endoscopic and histopathologic findings were reviewed in subjects with documented endoscopy within 30 days of an imaging study. Findings were compared between patients with and without wall thickening on CT to determine whether bowel wall thickening was predictive of endoscopic or histologic inflammatory findings. RESULTS: Two hundred and ninety-two CTs were reviewed. GI wall thickening was present on CT in 61% of patients (n = 86). Among a subgroup of 20 patients who underwent endoscopy at the time of their imaging, there was a statistically significant correlation between radiographic gastrointestinal wall thickening and endoscopic inflammation in the same intestinal segment (p = 0.035). Additionally, there was a significant correlation between radiographic gastrointestinal wall thickening and inflammatory features on histopathology (p = 0.02). CONCLUSIONS: GI abnormalities are commonly observed on CT in CGD patients. Bowel wall thickening correlates with endoscopic and histopathologic evidence of inflammation. These findings may be used to better facilitate directed endoscopic assessment and histopathologic sampling in patients with CGD.

Characterization of Mycophenolate Mofetil Gastrointestinal Toxicity and Risk Factors for Severe Disease and Poor Prognosis.

Authors performed a chart review to identify cases of mycophenolate mofetil gastrointestinal toxicity at our institution. In this cohort, friability was associated with severe disease; and nausea and erythema were associated with poor prognosis.

Validity of Secretin Stimulation Testing on Proton Pump Inhibitor Therapy for Diagnosis of Zollinger-Ellison Syndrome.

INTRODUCTION: Zollinger-Ellison syndrome (ZES) is characterized by gastrinoma-induced hypergastrinemia causing excessive gastric acid secretion. Secretin stimulation tests (SSTs) are required for diagnosis in the majority of patients. Two case reports suggest that proton pump inhibitors (PPIs) cause false SST results. Consequently, PPIs are discontinued to allow hyperchlorhydria to recur; however, uncontrolled acidity can cause life-threatening complications in those with underlying undiagnosed ZES. The aim of this study was to determine whether PPIs influence the validity of SSTs for the diagnosis of ZES. METHODS: A retrospective chart review was performed. Charts of patients who underwent SSTs were reviewed to determine whether they were performed on or off PPI and the test's accuracy by comparing the results with gold standard tests (diagnostic laboratory testing performed off PPI or surgical pathology consistent with gastrinoma). Sensitivity, specificity, and positive predictive value (PPV) of SST on PPI were calculated and results compared with SST off PPI using noninferiority analyses. RESULTS: Twenty-eight patients corresponding to 29 SSTs were performed on PPI, and 70 patients corresponding to 107 SSTs were performed off PPI. Most of them were female and white and had multiple endocrine neoplasia type 1. We found no false-positive or false-negative SSTs on PPI. Sensitivity, specificity, and PPV of SSTs on PPI were determined to be noninferior to SSTs off PPI (P ≤ 0.05 for all). DISCUSSION: In our cohort, SSTs on PPI compared with SSTs off PPI were noninferior for sensitivity, specificity, and PPV. These results suggest that PPI withdrawal before SSTs may not be necessary.

Social Media and Research Publication Activity During Early Stages of the COVID-19 Pandemic: Longitudinal Trend Analysis.

BACKGROUND: The COVID-19 pandemic has highlighted the importance of rapid dissemination of scientific and medical discoveries. Current platforms available for the distribution of scientific and clinical research data and information include preprint repositories and traditional peer-reviewed journals. In recent times, social media has emerged as a helpful platform to share scientific and medical discoveries. OBJECTIVE: This study aimed to comparatively analyze activity on social media (specifically, Twitter) and that related to publications in the form of preprint and peer-reviewed journal articles in the context of COVID-19 and gastroenterology during the early stages of the COVID-19 pandemic. METHODS: COVID-19-related data from Twitter (tweets and user data) and articles published in preprint servers (bioRxiv and medRxiv) as well as in the PubMed database were collected and analyzed during the first 6 months of the pandemic, from December 2019 through May 2020. Global and regional geographic and gastrointestinal organ-specific social media trends were compared to preprint and publication activity. Any relationship between Twitter activity and preprint articles published and that between Twitter activity and PubMed articles published overall, by organ system, and by geographic location were identified using Spearman's rank-order correlation. RESULTS: Over the 6-month period, 73,079 tweets from 44,609 users, 7164 journal publications, and 4702 preprint publications were retrieved. Twitter activity (ie, number of tweets) peaked in March 2020, whereas preprint and publication activity (ie, number of articles published) peaked in April 2020. Overall, strong correlations were identified between trends in Twitter activity and preprint and publication activity (P<.001 for both). COVID-19 data across the three platforms mainly concentrated on pulmonology or critical care, but when analyzing the field of gastroenterology specifically, most tweets pertained to pancreatology, most publications focused on hepatology, and most preprints covered hepatology and luminal gastroenterology. Furthermore, there were significant positive associations between trends in Twitter and publication activity for all gastroenterology topics (luminal gastroenterology: P=.009; hepatology and inflammatory bowel disease: P=.006; gastrointestinal endoscopy: P=.007), except pancreatology (P=.20), suggesting that Twitter activity did not correlate with publication activity for this topic. Finally, Twitter activity was the highest in the United States (7331 tweets), whereas PubMed activity was the highest in China (1768 publications). CONCLUSIONS: The COVID-19 pandemic has highlighted the potential of social media as a vehicle for disseminating scientific information during a public health crisis. Sharing and spreading information on COVID-19 in a timely manner during the pandemic has been paramount; this was achieved at a much faster pace on social media, particularly on Twitter. Future investigation could demonstrate how social media can be used to augment and promote scholarly activity, especially as the world begins to increasingly rely on digital or virtual platforms. Scientists and clinicians should consider the use of social media in augmenting public awareness regarding their scholarly pursuits.

Acute oesophageal necrosis in multiple endocrine neoplasia type 1: an undescribed complication.

Acute oesophageal necrosis (AEN) is a rare entity that most commonly presents as upper gastrointestinal bleeding. Complex pathophysiology may include oesophageal ischaemia as well as reflux of acidic gastric contents causing oesophageal mucosal injury. Management is supportive and directed at underlying comorbidities however prognosis is poor with complications such as oesophageal perforation, stricture and stenosis. Here we present the case of a 56-year-old man with multiple endocrine neoplasia type 1 (MEN1) and gastro-oesophageal reflux disease who developed AEN as a result of undiagnosed Zollinger-Ellison syndrome (ZES), duodenal ulcer-induced obstruction and hypotension from new-onset atrial fibrillation. AEN as the presentation of MEN1-associated ZES is an unusual presentation of this disease which clinicians, particularly endocrinologists and endoscopists, should be aware of.

COVID-19: An analysis of social media and research publication activity during the early stages of the pandemic.

Objectives: The COVID-19 pandemic has highlighted the importance of rapid dissemination of scientific and medical discovery. Social media (SoMe) has become an invaluable platform in science and medicine. This study analyzed activity of SoMe (Twitter), preprints, and publications related to COVID-19 and gastroenterology (GI) during the COVID-19 pandemic. Methods: Data from Twitter, preprint servers and PubMed was collected and analyzed from December 2019 through May 2020. Global and regional geographic and gastrointestinal organ specific social media trends were compared to preprint and publication activity; any associations were identified. Results: Over the 6-month period, there were 73,079 tweets from 44,609 users, 7,164 publications, and 4,702 preprints. Twitter activity peaked during March while preprints and publications peaked in April 2020. Strong correlations were identified between Twitter and both preprints and publications activity (p<0.001 for both). While COVID-19 data across the 3 platforms concentrated on pulmonology/critical care, the majority of GI tweets pertained to pancreatology, most publications focused on hepatology, and most preprints covered hepatology and luminal GI (LGI). There were significant associations between Twitter activity and research for all GI subfields (p=0.009 for LGI, p=0.006 for hepatology and IBD, p=0.007 for endoscopy), except pancreatology (p=0.2). Twitter activity was highest in the US (7,331 tweets) whereas PubMed activity was highest in China (1,768 publications). Conclusions: The COVID-19 pandemic has highlighted the utility of SoMe as a vehicle for disseminating scientific information during a public health crisis. Scientists and clinicians should consider the use of SoMe in augmenting public awareness of their scholarly pursuits.