Browsing by Author "Sloan, Ian"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    High-dimensional deconstruction of pancreatic cancer identifies tumor microenvironmental and developmental stemness features that predict survival
    (Springer Nature, 2023-10-19) Storrs, Erik P.; Chati, Prathamesh; Usmani, Abul; Sloan, Ian; Krasnick, Bradley A.; Babbra, Ramandeep; Harris, Peter K.; Sachs, Chloe M.; Qaium, Faridi; Chatterjee, Deyali; Wetzel, Chris; Goedegebuure, Peter; Hollander, Thomas; Anthony, Hephzibah; Ponce, Jennifer; Khaliq, Ateeq M.; Badiyan, Shahed; Kim, Hyun; Denardo, David G.; Lang, Gabriel D.; Cosgrove, Natalie D.; Kushnir, Vladimir M.; Early, Dayna S.; Masood, Ashiq; Lim, Kian-Huat; Hawkins, William G.; Ding, Li; Fields, Ryan C.; Das, Koushik K.; Chaudhuri, Aadel A.; Medicine, School of Medicine
    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.
  • Thumbnail Image
    Item
    Prolonged Gastrointestinal Manifestations After Recovery From COVID-19
    (Elsevier, 2023) Elmunzer, B. Joseph; Palsson, Olafur S.; Forbes , Nauzer; Zakaria , Ali; Davis, Christian; Canakis, Andrew; Qayed, Emad; Bick, Benjamin; Pawa, Swati; Tierney, William M.; McLeod, Caroline G.; Taylor, Jason; Patel, Harsh; Mendelsohn, Robin B.; Bala, Gokul; Sloan, Ian; Merchant, Ambreen A.; Smith, Zachary L.; Sendzischew Shane, Morgan A.; Aroniadis, Olga C.; Ordiah, Collins O.; Ruddy, Johannah M.; Simren, Magnus; Tack, Jan; Drossman, Douglas; Medicine, School of Medicine
    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.