Browsing by Subject "Organ failure"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Cryo-EM confirms a common fibril fold in the heart of four patients with ATTRwt amyloidosis
    (bioRxiv, 2024-03-09) Nguyen, Binh An; Singh, Virender; Afrin, Shumaila; Singh, Preeti; Pekala, Maja; Ahmed, Yasmin; Pedretti, Rose; Canepa, Jacob; Lemoff, Andrew; Kluve-Beckerman, Barbara; Wydorski, Pawel; Chhapra, Farzeen; Saelices, Lorena; Pathology and Laboratory Medicine, School of Medicine
    ATTR amyloidosis results from the conversion of transthyretin into amyloid fibrils that deposit in tissues causing organ failure and death. This conversion is facilitated by mutations in ATTRv amyloidosis, or aging in ATTRwt amyloidosis. ATTRv amyloidosis exhibits extreme phenotypic variability, whereas ATTRwt amyloidosis presentation is consistent and predictable. Previously, we found an unprecedented structural variability in cardiac amyloid fibrils from polyneuropathic ATTRv-I84S patients. In contrast, cardiac fibrils from five genotypically-different patients with cardiomyopathy or mixed phenotypes are structurally homogeneous. To understand fibril structure's impact on phenotype, it is necessary to study the fibrils from multiple patients sharing genotype and phenotype. Here we show the cryo-electron microscopy structures of fibrils extracted from four cardiomyopathic ATTRwt amyloidosis patients. Our study confirms that they share identical conformations with minimal structural variability, consistent with their homogenous clinical presentation. Our study contributes to the understanding of ATTR amyloidosis biopathology and calls for further studies.
  • Thumbnail Image
    Item
    Introduction and Validation of a Novel Acute Pancreatitis Digital Tool: Interrogating Large Pooled Data From 2 Prospectively Ascertained Cohorts
    (Wolters Kluwer, 2020) Paragomi, Pedram; Spagnolo, Daniel M.; Breze, Cameron R.; Gougol, Amir; Talukdar, Rupjyoti; Kochhar, Rakesh; Goenka, Mahesh Kumar; Gulla, Aiste; Gonzalez, Jose A.; Singh, Vikesh K.; Ferreira, Miguel; Stevens, Tyler; Barbu, Sorin T.; Nawaz, Haq; Gutierrez, Silvia C.; Zarnescu, Narcis O.; Archibugi, Livia; Easler, Jeffrey J.; Triantafyllou, Konstantinos; Pelaez-Luna, Mario; Thakkar, Shyam; Ocampo, Carlos; de-Madaria, Enrique; Cote, Gregory A.; Wu, Bechien U.; Pothoulakis, Ioannis; Haupt, Mark; Whitcomb, David C.; Papachristou, Georgios I.; Medicine, School of Medicine
    Objectives: Acute pancreatitis (AP) is a sudden onset, rapidly evolving inflammatory response with systemic inflammation and multiorgan failure (MOF) in a subset of patients. New highly accurate clinical decision support tools are needed to allow local doctors to provide expert care. Methods: Ariel Dynamic Acute Pancreatitis Tracker (ADAPT) is a digital tool to guide physicians in ordering standard tests, evaluate test results and model progression using available data, propose emergent therapies. The accuracy of the severity score calculators was tested using 2 prospectively ascertained Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience cohorts (pilot University of Pittsburgh Medical Center, n = 163; international, n = 1544). Results: The ADAPT and post hoc expert-calculated AP severity scores were 100% concordant in both pilot and international cohorts. High-risk criteria of all 4 severity scores at admission were associated with moderately-severe or severe AP and MOF (both P < 0.0001) and prediction of no MOF was 97.8% to 98.9%. The positive predictive value for MOF was 7.5% to 14.9%. Conclusions: The ADAPT tool showed 100% accuracy with AP predictive metrics. Prospective evaluation of ADAPT features is needed to determine if additional data can accurately predict and mitigate severe AP and MOF.
  • Thumbnail Image
    Item
    Mortality in acute pancreatitis with persistent organ failure is determined by the number, type, and sequence of organ systems affected
    (Wiley, 2021-03) Machicado, Jorge D.; Gougol, Amir; Tan, Xiaoqing; Gao, Xiaotian; Paragomi, Pedram; Pothoulakis, Ioannis; Talukdar, Rupjyoti; Kochhar, Rakesh; Goenka, Mahesh K.; Gulla, Aiste; Gonzalez, Jose A.; Singh, Vikesh K.; Ferreira, Miguel; Stevens, Tyler; Barbu, Sorin T.; Nawaz, Haq; Gutierrez, Silvia C.; Zarnescu, Narcis O.; Capurso, Gabriele; Easler, Jeffrey J.; Triantafyllou, Konstantinos; Pelaez-Luna, Mario; Thakkar, Shyam; Ocampo, Carlos; de-Madaria, Enrique; Cote, Gregory A.; Wu, Bechien U.; Conwell, Darwin L.; Hart, Phil A.; Tang, Gong; Papachristou, Georgios I.; Medicine, School of Medicine
    Background: Persistent organ failure (POF) is the strongest determinant of mortality in acute pancreatitis (AP). There is a paucity of data regarding the impact of different POF attributes on mortality and the role of different characteristics of systemic inflammatory response syndrome (SIRS) in the risk of developing POF. Objective: We aimed to assess the association of POF dynamic features with mortality and SIRS characteristics with POF. Methods: We studied 1544 AP subjects prospectively enrolled at 22 international centers (APPRENTICE consortium). First, we estimated the association of onset, duration, and maximal score of SIRS with POF. Then, we evaluated the risk of mortality based on POF onset, duration, number, type, and sequence of organs affected. Analyses were adjusted for potential confounders. Results: 58% had SIRS, 11% developed POF, and 2.5% died. Early SIRS, persistent SIRS, and maximal SIRS score ≥ 3 were independently associated with higher risk of POF (p < 0.05). Mortality risk in POF was higher with two (33%, odds ratio [OR] = 10.8, 3.3-34.9) and three (48%, OR = 20.2, 5.9-68.6) organs failing, in comparison to single POF (4%). In subjects with multiple POF, mortality was higher when the cardiovascular and respiratory systems failed first or concurrently as compared to when the renal system failed first or concurrently with other organ (p < 0.05). In multivariate regression model, the number and sequence of organs affected in POF were associated with mortality (p < 0.05). Onset and duration of POF had no impact mortality. Conclusion: In AP patients with POF, the risk of mortality is influenced by the number, type, and sequence of organs affected. These results are useful for future revisions of AP severity classification systems.
  • Thumbnail Image
    Item
    Pancreatitis associated anxiety, depression, and stress: Hypothesis, definition, and intervention
    (Elsevier, 2022-07-02) McGuire, Sean P.; Montero, Anne Mary; McGreevy, Kathleen A.; Zyromski, Nicholas J.; Surgery, School of Medicine
    Necrotizing pancreatitis is characterized by a prolonged disease course requiring frequent hospitalization and intervention. Necrotizing pancreatitis patients have high rates of intensive care unit admission and organ failure. Critical illness is an identified risk factor for the development of anxiety, depression, and posttraumatic stress disorder. Limited literature examines quality of life in necrotizing pancreatitis patients, and studies examining psychiatric sequalae of necrotizing pancreatitis including depression, anxiety, and posttraumatic stress disorder are virtually nonexistent. Here, we review critical literature examining risk factors for poor mental health outcomes during and after necrotizing pancreatitis, identify several screening instruments to quantify mental health outcomes, and propose an intervention to improve mental health outcomes in patients with necrotizing pancreatitis. We conclude that establishing the incidence of mental health disorders and implementing strategies to improve mental health outcomes are critical to holistic care of necrotizing pancreatitis patients.