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Item Modeling the effect of ascites-induced compression on ovarian cancer multicellular aggregates(The Company of Biologists, 2018-09-25) Klymenko, Yuliya; Wates, Rebecca B.; Weiss-Bilka, Holly; Lombard, Rachel; Liu, Yueying; Campbell, Leigh; Kim, Oleg; Wagner, Diane; Ravosa, Matthew J.; Stack, M. Sharon; Mechanical and Energy Engineering, School of Engineering and TechnologyEpithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. EOC dissemination is predominantly via direct extension of cells and multicellular aggregates (MCAs) into the peritoneal cavity, which adhere to and induce retraction of peritoneal mesothelium and proliferate in the submesothelial matrix to generate metastatic lesions. Metastasis is facilitated by the accumulation of malignant ascites (500 ml to >2 l), resulting in physical discomfort and abdominal distension, and leading to poor prognosis. Although intraperitoneal fluid pressure is normally subatmospheric, an average intraperitoneal pressure of 30 cmH2O (22.1 mmHg) has been reported in women with EOC. In this study, to enable experimental evaluation of the impact of high intraperitoneal pressure on EOC progression, two new in vitro model systems were developed. Initial experiments evaluated EOC MCAs in pressure vessels connected to an Instron to apply short-term compressive force. A Flexcell Compression Plus system was then used to enable longer-term compression of MCAs in custom-designed hydrogel carriers. Results show changes in the expression of genes related to epithelial-mesenchymal transition as well as altered dispersal of compressed MCAs on collagen gels. These new model systems have utility for future analyses of compression-induced mechanotransduction and the resulting impact on cellular responses related to intraperitoneal metastatic dissemination.This article has an associated First Person interview with the first authors of the paper.Item Outcomes After TIPS for Ascites and Variceal Bleeding in a Contemporary Era-An ALTA Group Study(Wolters Kluwer, 2021) Boike, Justin Richard; Mazumder, Nikhilesh Ray; Kolli, Kanti Pallav; Ge, Jin; German, Margarita; Jest, Nathaniel; Morelli, Giuseppe; Spengler, Erin; Said, Adnan; Lai, Jennifer C.; Desai, Archita P.; Couri, Thomas; Paul, Sonali; Frenette, Catherine; Verna, Elizabeth C.; Rahim, Usman; Goel, Aparna; Gregory, Dyanna; Thornburg, Bartley; VanWagner, Lisa B.; Advancing Liver Therapeutic Approaches (ALTA) Study Group; Medicine, School of MedicineIntroduction: Advances in transjugular intrahepatic portosystemic shunt (TIPS) technology have led to expanded use. We sought to characterize contemporary outcomes of TIPS by common indications. Methods: This was a multicenter, retrospective cohort study using data from the Advancing Liver Therapeutic Approaches study group among adults with cirrhosis who underwent TIPS for ascites/hepatic hydrothorax (ascites/HH) or variceal bleeding (2010-2015). Adjusted competing risk analysis was used to assess post-TIPS mortality or liver transplantation (LT). Results: Among 1,129 TIPS recipients, 58% received TIPS for ascites/HH and 42% for variceal bleeding. In patients who underwent TIPS for ascites/HH, the subdistribution hazard ratio (sHR) for death was similar across all Model for End-Stage Liver Disease Sodium (MELD-Na) categories with an increasing sHR with rising MELD-Na. In patients with TIPS for variceal bleeding, MELD-Na ≥20 was associated with increased hazard for death, whereas MELD-Na ≥22 was associated with LT. In a multivariate analysis, serum creatinine was most significantly associated with death (sHR 1.2 per mg/dL, 95% confidence interval [CI] 1.04-1.4 and 1.37, 95% CI 1.08-1.73 in ascites/HH and variceal bleeding, respectively). Bilirubin and international normalized ratio were most associated with LT in ascites/HH (sHR 1.23, 95% CI 1.15-1.3; sHR 2.99, 95% CI 1.76-5.1, respectively) compared with only bilirubin in variceal bleeding (sHR 1.06, 95% CI 1.00-1.13). Discussion: MELD-Na has differing relationships with patient outcomes dependent on TIPS indication. These data provide new insights into contemporary predictors of outcomes after TIPS.Item Portal Hypertension and Ascites Due to an Arterioportal Fistula: Sequela of a Remote Traumatic Liver Laceration(American College of Gastroenterology, 2016-08) Hulkower, Benjamin M.; Butty, Sabah; Ghabril, Marwan; Department of Medicine, School of MedicineArterioportal fistulas (APFs) are a group of vascular disorders, in which systemic arteries communicate with the portal circulation, presenting as a congenital syndrome or more commonly acquired from iatrogenic instrumentation or abdominal trauma. We report the case of a 58-year-old man who developed ascites without underlying risk factors for portal hypertension, which was attributed to an APF found on imaging, manifesting 43 years after sustaining a liver laceration. After angiographic embolization of the APF, the patient's ascites resolved completely. The prolonged latent period between the patient's abdominal trauma and eventual presentation with ascites highlights the need to consider vascular malformations in the differential diagnosis of unexplained noncirrhotic portal hypertension.Item Portal vein thrombosis, mortality and hepatic decompensation in patients with cirrhosis: A meta-analysis(Baishideng Publishing Group Co (World Journal of Hepatology), 2015-11-28) Stine, Jonathan G.; Shah, Puja M.; Cornella, Scott L.; Rudnick, Sean R.; Ghabril, Marwan S.; Stukenborg, George J.; Northup, Patrick G.; Department of Medicine, IU School of MedicineAIM: To determine the clinical impact of portal vein thrombosis in terms of both mortality and hepatic decompensations (variceal hemorrhage, ascites, portosystemic encephalopathy) in adult patients with cirrhosis. METHODS: We identified original articles reported through February 2015 in MEDLINE, Scopus, Science Citation Index, AMED, the Cochrane Library, and relevant examples available in the grey literature. Two independent reviewers screened all citations for inclusion criteria and extracted summary data. Random effects odds ratios were calculated to obtain aggregate estimates of effect size across included studies, with 95%CI. RESULTS: A total of 226 citations were identified and reviewed, and 3 studies with 2436 participants were included in the meta-analysis of summary effect. Patients with portal vein thrombosis had an increased risk of mortality (OR = 1.62, 95%CI: 1.11-2.36, P = 0.01). Portal vein thrombosis was associated with an increased risk of ascites (OR = 2.52, 95%CI: 1.63-3.89, P < 0.001). There was insufficient data available to determine the pooled effect on other markers of decompensation including gastroesophageal variceal bleeding or hepatic encephalopathy. CONCLUSION: Portal vein thrombosis appears to increase mortality and ascites, however, the relatively small number of included studies limits more generalizable conclusions. More trials with a direct comparison group are needed.Item Total Serum Bilirubin within 3 Months of Hepatoportoenterostomy Predicts Short-Term Outcomes in Biliary Atresia(Elsevier, 2016-03) Shneider, Benjamin L.; Magee, John C.; Karpen, Saul J.; Rand, Elizabeth B.; Narkewicz, Michael R.; Bass, Lee M.; Schwarz, Kathleen; Whitington, Peter F.; Bezerra, Jorge A.; Kerkar, Nanda; Haber, Barbara; Rosenthal, Philip; Turmelle, Yumirle P.; Molleston, Jean P.; Murray, Karen F.; Nguyen, Vicky L.; Wang, Kasper S.; Romero, Rene; Squires, Robert H.; Arnon, Ronen; Sherker, Averell H.; Moore, Jeffrey; Ye, Wen; Sokol, Ronald J.; Department of Pediatrics, IU School of MedicineOBJECTIVES: To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. STUDY DESIGN: Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB <2.0, all others TB ≥ 2) after HPE was examined as a biomarker, using Kaplan-Meier survival and logistic regression. RESULTS: Fifty percent (68/137) of infants had TB < 2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB < 2.0 group vs TB ≥ 2 (86% vs 20%, P < .0001). Infants with TB ≥ 2 had diminished weight gain (P < .0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9-14.1, P < .0001), hypoalbuminemia (OR 7.6, 95% CI 3.2-17.7, P < .0001), coagulopathy (OR 10.8, 95% CI 3.1-38.2, P = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P < .0001), or LT or death (OR 16.8, 95% CI 7.2-39.2, P < .0001). CONCLUSIONS: Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB <2.0 mg/dL within 3 months of HPE may enhance early outcomes.Item Trends in Racial and Ethnic Disparities in the Receipt of Lifesaving Procedures for Hospitalized Patients With Decompensated Cirrhosis in the US, 2009-2018(American Medical Association, 2023-07-03) Nephew, Lauren D.; Knapp, Shannon M.; Mohamed, Kawthar A.; Ghabril, Marwan; Orman, Eric; Patidar, Kavish R.; Chalasani, Naga; Desai, Archita P.; Medicine, School of MedicineImportance: Patients with decompensated cirrhosis are hospitalized for acute management with temporizing and lifesaving procedures. Published data to inform intervention development in this area are more than a decade old, and it is not clear whether there have been improvements in disparities in the receipt of these procedures over time. Objective: To evaluate the associations of race and ethnicity with receipt of procedures to treat decompensated cirrhosis over time in the US. Design, setting, and participants: This retrospective cross-sectional study analyzed National Inpatient Sample data on cirrhosis admissions among patients with portal hypertension-related complications from 2009 to 2018. All hospital discharges for individuals aged 18 years and older from 2009 to 2018 were assessed for inclusion. Admissions were included if they contained at least 1 cirrhosis-related International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code and at least 1 cirrhosis-related complication ICD-9-CM or ICD-10-CM code (ie, ascites, hepatic encephalopathy, variceal hemorrhage [VH], and hepatorenal syndrome [HRS]). Data were analyzed from January to June 2022. Exposure: Hospitalization for decompensated cirrhosis. Main outcomes and measures: The outcomes of interest were trends in the odds ratios (ORs) for receiving procedures (upper endoscopy, transjugular portosystemic shunt [TIPS], hemodialysis, and liver transplantation [LT]) for decompensated cirrhosis and mortality by race and ethnicity, modeled over time. Multivariable logistic regression was used to assess these outcomes. Results: Among 717 580 admissions (median [IQR] age, 58 [52-67] years), 345 644 patients (9.8%) were Black, 623 991 patients (17.6%) were Hispanic, and 2 340 031 patients (47.4%) were White. Based on the modeled trends, by 2018, there were no significant differences by race or ethnicity in the odds of receiving upper endoscopy for VH. However, Black patients remained less likely than White patients to undergo TIPS for VH (OR, 0.54; 95% CI, 0.47-0.62) and ascites (OR, 0.34; 95% CI, 0.31-0.38). The disparity in receipt of LT improved for Black and Hispanic patients over the study period; however, by 2018, both groups remained less likely to undergo LT than their White counterparts (Black: OR, 0.66; 95% CI, 0.61-0.70; Hispanic: OR, 0.74; 95% CI, 0.70-0.78). The odds of death in Black and Hispanic patients declined over the study period but remained higher in Black patients than White patients in 2018 (OR, 1.08; 95% CI, 1.05-1.11). Conclusions and relevance: In this cross-sectional study of individuals hospitalized with decompensated cirrhosis, there were racial and ethnic disparities in receipt of complex lifesaving procedures and in mortality that persisted over time.