Prolonged Gastrointestinal Manifestations After Recovery From COVID-19.

BACKGROUND & AIMS: Acute enteric infections are well known to result in long-term gastrointestinal (GI) disorders. Although COVID-19 is principally a respiratory illness, it demonstrates significant GI tropism, possibly predisposing to prolonged gut manifestations. We aimed to examine the long-term GI impact of hospitalization with COVID-19. METHODS: Nested within a large-scale observational cohort study of patients hospitalized with COVID-19 across North America, we performed a follow-up survey of 530 survivors 12-18 months later to assess for persistent GI symptoms and their severity, and for the development of disorders of gut-brain interaction (DGBIs). Eligible patients were identified at the study site level and surveyed electronically. The survey instrument included the Rome IV Diagnostic Questionnaire for DGBI, a rating scale of 24 COVID-related symptoms, the Gastrointestinal Symptoms Rating Scale, and the Impact of Events-Revised trauma symptom questionnaire (a measure of posttraumatic stress associated with the illness experience). A regression analysis was performed to explore the factors associated with GI symptom severity at follow-up. RESULTS: Of the 530 invited patients, 116 responded (52.6% females; mean age, 55.2 years), and 73 of those (60.3%) met criteria for 1 or more Rome IV DGBI at follow-up, higher than the prevalence in the US general population (P < .0001). Among patients who experienced COVID-related GI symptoms during the index hospitalization (abdominal pain, nausea, vomiting, or diarrhea), 42.1% retained at least 1 of these symptoms at follow-up; in comparison, 89.8% of respondents retained any (GI or non-GI) COVID-related symptom. The number of moderate or severe GI symptoms experienced during the initial COVID-19 illness by self-report correlated with the development of DGBI and severity of GI symptoms at follow-up. Posttraumatic stress disorder (Impact of Events-Revised score ≥33) related to the COVID-19 illness experience was identified in 41.4% of respondents and those individuals had higher DGBI prevalence and GI symptom severity. Regression analysis revealed that higher psychological trauma score (Impact of Events-Revised) was the strongest predictor of GI symptom severity at follow-up. CONCLUSIONS: In this follow-up survey of patients 12-18 months after hospitalization with COVID-19, there was a high prevalence of DGBIs and persistent GI symptoms. Prolonged GI manifestations were associated with the severity of GI symptoms during hospitalization and with the degree of psychological trauma related to the illness experience.

High-dimensional deconstruction of pancreatic cancer identifies tumor microenvironmental and developmental stemness features that predict survival.

Numerous cell states are known to comprise the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME). However, the developmental stemness and co-occurrence of these cell states remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) on a cohort of treatment-naive PDAC time-of-diagnosis endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) samples (n = 25). We then combined these samples with surgical resection (n = 6) and publicly available samples to increase statistical power (n = 80). Following annotation into 25 distinct cell states, cells were scored for developmental stemness, and a customized version of the Ecotyper tool was used to identify communities of co-occurring cell states in bulk RNA-seq samples (n = 268). We discovered a tumor microenvironmental community comprised of aggressive basal-like malignant cells, tumor-promoting SPP1+ macrophages, and myofibroblastic cancer-associated fibroblasts associated with especially poor prognosis. We also found a developmental stemness continuum with implications for survival that is present in both malignant cells and cancer-associated fibroblasts (CAFs). We further demonstrated that high-dimensional analyses predictive of survival are feasible using standard-of-care, time-of-diagnosis EUS-FNB specimens. In summary, we identified tumor microenvironmental and developmental stemness characteristics from a high-dimensional gene expression analysis of PDAC using human tissue specimens, including time-of-diagnosis EUS-FNB samples. These reveal new connections between tumor microenvironmental composition, CAF and malignant cell stemness, and patient survival that could lead to better upfront risk stratification and more personalized upfront clinical decision-making.

Threshold evaluation for optimal number of endoscopic treatment sessions to achieve complete eradication of Barrett's metaplasia.

BACKGROUND: Endoscopic eradication therapy (EET) is the standard of care for Barrett's esophagus (BE)-associated neoplasia. Previous data suggest the mean number of EET sessions required to achieve complete eradication of intestinal metaplasia (CE-IM) is 3. This study aimed to define the threshold of EET sessions required to achieve CE-IM. METHODS: The TREAT-BE Consortium is a multicenter outcomes cohort including prospectively enrolled patients with BE undergoing EET. All patients achieving CE-IM were included. Demographic, endoscopic, and histologic data were recorded at treatment onset along with treatment details and surveillance data. Kaplan-Meier analysis was performed to define a threshold of EET sessions, with 95 %CI, required to achieve CE-IM. A secondary analysis examined predictors of incomplete response to EET using multiple logistic regression and recurrence rates. RESULTS: 623 patients (mean age 65.2 [SD 11.6], 79.6 % male, 86.5 % Caucasian) achieved CE-IM in a mean of 2.9 (SD 1.7) EET sessions (median 2) and a median total observation period of 2.7 years (interquartile range 1.4-5.0). After three sessions, 73 % of patients achieved CE-IM (95 %CI 70 %-77 %). Age (odds ratio [OR] 1.25, 95 %CI 1.05-1.50) and length of BE (OR 1.24, 95 %CI 1.17-1.31) were significant predictors of incomplete response. CONCLUSION: The current study found that a threshold of three EET sessions would achieve CE-IM in the majority of patients. Alternative therapies and further diagnostic testing should be considered for patients who do not have significant response to EET after three sessions.

Validation of choledocholithiasis predictors from the "2019 ASGE Guideline for the role of endoscopy in the evaluation and management of choledocholithiasis."

BACKGROUND AND AIMS: Identifying patients likely to have CDL is an important clinical dilemma because endoscopic retrograde cholangiopancreatography (ERCP), carries a 5-7% risk of adverse events. The purpose of this study was to compare the diagnostic test performance of the 2010 and 2019 ASGE criteria used to help risk stratify patients with suspected CDL. METHODS: Consecutive patients evaluated for possible CDL from 2013 to 2019 were identified from surgical, endoscopic, and radiologic databases at a single academic center. Inclusion criteria included all patients who underwent ERCP and/or cholecystectomy with intraoperative cholangiogram (IOC) for suspected CDL. We calculated the diagnostic test performance of criteria from both guidelines and compared their discrimination using the receiver operator curve. Univariate and multivariate analysis was used to identify the strongest component predictors. RESULTS: 1098 patients [age 57.9 ± 19.0 years, 62.8% (690) F] were included. 66.3% (728) were found to have CDL on ERCP and/or IOC. When using the 2019 guidelines, the sensitivity, specificity, PPV, NPV, and accuracy are 65.8, 78.9, 86.3, 54.1, and 70.4%, respectively. Using the 2010 guidelines, the sensitivity, specificity, PPV, NPV, and accuracy are 50.5, 78.9, 82.5, 44.8, and 60.1%, respectively. The AUC for high-risk criteria using the 2019 guidelines [0.726 (0.695, 0.758)] was greater than for the 2010 guidelines [0.647 (0.614, 0.681)]. The key difference providing the increased discrimination was the inclusion of stones on any imaging modality, which increased the sensitivity to 55.0% from 29.1%. Not including CDL on imaging or cholangitis, a dilated CBD was the strongest individual predictor of CDL on multivariate analysis (OR 3.70, CI 2.80, 4.89). CONCLUSION: Compared to 2010, the 2019 high-risk criterion improves diagnostic test performance, but still performs suboptimally. Less invasive tests, such as EUS or MRCP, should be considered in patients with suspected CDL prior to ERCP.

Circulant embedding with QMC: analysis for elliptic PDE with lognormal coefficients.

In a previous paper (Graham et al. in J Comput Phys 230:3668-3694, 2011), the authors proposed a new practical method for computing expected values of functionals of solutions for certain classes of elliptic partial differential equations with random coefficients. This method was based on combining quasi-Monte Carlo (QMC) methods for computing the expected values with circulant embedding methods for sampling the random field on a regular grid. It was found capable of handling fluid flow problems in random heterogeneous media with high stochastic dimension, but no convergence theory was provided. This paper provides a convergence analysis for the method in the case when the QMC method is a specially designed randomly shifted lattice rule. The convergence result depends on the eigenvalues of the underlying nested block circulant matrix and can be independent of the number of stochastic variables under certain assumptions. In fact the QMC analysis applies to general factorisations of the covariance matrix to sample the random field. The error analysis for the underlying fully discrete finite element method allows for locally refined meshes (via interpolation from a regular sampling grid of the random field). Numerical results on a non-regular domain with corner singularities in two spatial dimensions and on a regular domain in three spatial dimensions are included.