Browsing by Author "Hage, Chadi A."

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    Antifungal Prophylaxis for Adult Recipients of Veno-Venous Extracorporeal Membrane Oxygenation: A Cautionary Stance During the COVID-19 Pandemic
    (Wolters Kluwer, 2021-03) Epelbaum, Oleg; Carmona, Eva M.; Evans, Scott E.; Hage, Chadi A.; Jarrett, Benjamin; Knox, Kenneth S.; Limper, Andrew H.; Pennington, Kelly M.; Medicine, School of Medicine
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    Associations between the stanford integrated psychosocial assessment for transplant and one-year lung transplant medical and psychosocial outcomes
    (Springer Nature, 2023-06-12) Hinton-Froese, Kendra E.; Teh, Lisa; Henderson, Danielle R.; Hage, Chadi A.; Chernyak, Yelena; Psychiatry, School of Medicine
    The Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) is a standardized measure of the psychosocial risk profile of solid organ transplant candidates. While studies have found associations between this measure and transplant outcomes, to date this has not been examined in lung transplant recipients. We examined relations between pre-transplant SIPAT scores and 1-year lung transplant medical and psychosocial outcomes in a sample of 45 lung transplant recipients. The SIPAT was significantly associated with 6-minute walk test (χ2(1) = 6.47, p = .010), number of readmissions (χ2(1) = 6.47, p = .011), and mental health services utilization (χ2(1) = 18.15, p < .001). It was not a significantly associated with the presence of organ rejection or mortality (ps > 0.10). Results suggest that the SIPAT can help identify patients who are at an elevated risk for transplant complications and thus would benefit from services to mitigate risk factors and improve outcomes.
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    Characterization of the Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) in Lung Transplant Candidates
    (Springer, 2022-03) Chernyak, Yelena; Henderson, Danielle R.; Teh, Lisa; Powell, Anna-Leigh; Hinton, Kendra E.; Hage, Chadi A.; Psychiatry, School of Medicine
    The SIPAT is a standardized measure for pre-transplant psychosocial evaluation. Previous SIPAT studies utilized a relatively small lung transplant sample and only included listed patients. This study characterized the SIPAT in 147 lung transplant candidates to better elucidate its utility. The average score corresponded to a minimally acceptable rating and nearly half of the patients had relative or absolute contraindications. Interstitial Lung Disease (ILD) patients scored more favorably than non-ILD patients (U = 7.69, p < .05). The Total (β = − .05, SE = .018, p < .01), Social Support Subscale (β = − .133, SE = .058, p < .05), and Psychosocial Stability and Psychopathology Subscale (β = − .103, SE = .040, p < .05) significantly predicted listing status. The SIPAT has a unique profile in lung transplant candidates and demonstrated utility for guiding transplant decisions. Future research should examine which lung transplant outcomes are significantly associated with SIPAT scores.
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    Contemporary trends in PGD incidence, outcomes, and therapies
    (Elsevier, 2022) Cantu, Edward; Diamond, Joshua M.; Cevasco, Marisa; Suzuki, Yoshi; Crespo, Maria; Clausen, Emily; Dallara, Laura; Ramon, Christian V.; Harmon, Michael T.; Bermudez, Christian; Benvenuto, Luke; Anderson, Michaela; Wille, Keith M.; Weinacker, Ann; Dhillon, Gundeep S.; Orens, Jonathan; Shah, Pali; Merlo, Christian; Lama, Vibha; McDyer, John; Snyder, Laurie; Palmer, Scott; Hartwig, Matt; Hage, Chadi A.; Singer, Jonathan; Calfee, Carolyn; Kukreja, Jasleen; Greenland, John R.; Ware, Lorraine B.; Localio, Russel; Hsu, Jesse; Gallop, Robert; Christie, Jason D.; Medicine, School of Medicine
    Background: We sought to describe trends in extracorporeal membrane oxygenation (ECMO) use, and define the impact on PGD incidence and early mortality in lung transplantation. Methods: Patients were enrolled from August 2011 to June 2018 at 10 transplant centers in the multi-center Lung Transplant Outcomes Group prospective cohort study. PGD was defined as Grade 3 at 48 or 72 hours, based on the 2016 PGD ISHLT guidelines. Logistic regression and survival models were used to contrast between group effects for event (i.e., PGD and Death) and time-to-event (i.e., death, extubation, discharge) outcomes respectively. Both modeling frameworks accommodate the inclusion of potential confounders. Results: A total of 1,528 subjects were enrolled with a 25.7% incidence of PGD. Annual PGD incidence (14.3%-38.2%, p = .0002), median LAS (38.0-47.7 p = .009) and the use of ECMO salvage for PGD (5.7%-20.9%, p = .007) increased over the course of the study. PGD was associated with increased 1 year mortality (OR 1.7 [95% C.I. 1.2, 2.3], p = .0001). Bridging strategies were not associated with increased mortality compared to non-bridged patients (p = .66); however, salvage ECMO for PGD was significantly associated with increased mortality (OR 1.9 [1.3, 2.7], p = .0007). Restricted mean survival time comparison at 1-year demonstrated 84.1 days lost in venoarterial salvaged recipients with PGD when compared to those without PGD (ratio 1.3 [1.1, 1.5]) and 27.2 days for venovenous with PGD (ratio 1.1 [1.0, 1.4]). Conclusions: PGD incidence continues to rise in modern transplant practice paralleled by significant increases in recipient severity of illness. Bridging strategies have increased but did not affect PGD incidence or mortality. PGD remains highly associated with mortality and is increasingly treated with salvage ECMO.
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    Detection of (1,3)-β-d-Glucan in Cerebrospinal Fluid in Histoplasma Meningitis
    (American Society for Microbiology, 2018-09-25) Myint, Thein; Chow, Felicia C.; Bloch, Karen C.; Raymond-Guillen, Luke; Davis, Thomas E.; Wright, Patty W.; Woc-Colburn, Laila; Khairy, Raed N.; Street, Alan C.; Yamamoto, Tomotaka; Albers, Amanda; Wheat, L. Joseph; Hage, Chadi A.; Medicine, School of Medicine
    The diagnosis of central nervous system (CNS) histoplasmosis is often difficult. Although cerebrospinal fluid (CSF) (1,3)-β-d-glucan (BDG) is available as a biological marker for the diagnosis of fungal meningitis, there are limited data on its use for the diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection, using the Fungitell assay, in patients with CNS histoplasmosis and controls. A total of 47 cases and 153 controls were identified. The control group included 13 patients with a CNS fungal infection other than histoplasmosis. Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. The median CSF BDG level was 85 pg/ml for cases, compared to <31 pg/ml for all controls (P < 0.05) and 82 pg/ml for controls with other causes of fungal meningitis (P = 0.27). The sensitivity for detection of BDG in CSF was 53.2%, whereas the specificity was 86.9% versus all controls and 46% versus other CNS fungal infections. CSF BDG levels of ≥80 pg/ml are neither sensitive nor specific to support a diagnosis of Histoplasma meningitis.
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    Diagnosis of Histoplasmosis Using the MVista Histoplasma Galactomannan Antigen Qualitative Lateral Flow–Based Immunoassay: A Multicenter Study
    (Oxford University Press, 2021-08-31) Abdallah, Wassim; Myint, Thein; LaRue, Richard; Minderman, Melissa; Gunn, Suphansa; Wheat, L. Joseph; Hage, Chadi A.; Medicine, School of Medicine
    Background: Accurate and timely methods for the diagnosis of histoplasmosis in resource-limited countries are lacking. Histoplasma antigen detection by enzyme immunoassay (EIA) is widely used in the United States (US) but not in resource-limited countries, leading to missed or delayed diagnoses and poor outcomes. Lateral flow assays (LFAs) can be used in this setting. Methods: Frozen urine specimens were submitted to MiraVista diagnostics for antigen testing from 3 medical centers in endemic areas of the US. They were blinded and tested for the MVista Histoplasma LFA. Patients were classified as controls or cases of histoplasmosis. Cases were divided into proven or probable; pulmonary or disseminated; immunocompetent or immunosuppressed; and mild, moderate, or severe. Results: Three hundred fifty-two subjects were enrolled, including 66 cases (44 proven, 22 probable) and 286 controls. Most of the cases were immunocompromised (71%), and 46 had disseminated and 20 had pulmonary histoplasmosis. Four cases were mild, 42 moderate, and 20 severe. LFA and EIA were highly concordant (κ = 0.84). Sensitivity and specificity of the LFA were 78.8% and 99.3%, respectively. LFA sensitivity was higher in proven cases (93.2%), patients with disseminated (91.3%), moderate (78.6%), and severe disease (80%), and those with galactomannan levels >1.8 ng/mL (97.8%). Specificity was 99.3% in proven cases, 99.3% in patients with moderate or severe disease, and 96.8% in those with galactomannan levels >1.8 ng/mL. Cross-reactivity was noted with other endemic mycoses. Conclusions: The MVista Histoplasma LFA meets the need for accurate rapid diagnosis of histoplasmosis in resource-limited countries, especially in patients with high disease burden, potentially reducing morbidity and mortality.
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    Distinct immunologic and radiographic patterns in etanercept-induced lung injury
    (Elsevier, 2013-01-12) Serban, Karina; Muzoora, Michael; Hage, Chadi A.; Lahm, Tim; Department of Medicine, School of Medicine
    Nonspecific clinical presentation of non-infectious, immune-mediated pulmonary complications of etanercept therapy makes the diagnosis difficult. While bronchoalveolar lavage fluid (BALF) cell analysis is frequently used in diagnosing drug-induced lung disease, BALF patterns in etanercept-induced lung injury (EILI) are not well established. Furthermore, previous reports of EILI diagnosis relied on transbronchial or surgical lung biopsies. Here, we report two patients who developed pulmonary toxicity after etanercept treatment. Both patients were diagnosed with EILI. While one patient presented with CD4(+)-predominant lymphocytic alveolitis (consistent with a sarcoid-like pattern), the other patient exhibited a CD8(+)-predominant pattern (consistent with hypersensitivity pneumonitis-like reaction). The different BAL patterns were accompanied by distinct radiographic findings. Both patients significantly improved after etanercept discontinuation and corticosteroid initiation. We propose that EILI can present with distinct immunologic and radiographic phenotypes. In addition, early BALF analysis with lymphocyte immunophenotyping can further define the underlying immunologic abnormalities, and thereby, avoid more invasive procedures.
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    Endemic mycosis
    (Springer Nature, 2005) Hage, Chadi A.; Knox, Kenneth S.; Sarosi, George A.; Department of Medicine, Indiana University School of Medicine
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    Extracorporeal photopheresis to attenuate decline in lung function due to refractory obstructive allograft dysfunction
    (Wiley, 2021) EPI Study Group; Hage, Chadi A.; Klesney-Tait, Julia; Wille, Keith; Arcasoy, Selim; Yung, Gordon; Hertz, Marshall; Chan, Kevin M.; Morrell, Matt; Goldberg, Hilary; Vedantham, Suresh; Derfler, Mary Clare; Commean, Paul; Berman, Keith; Spitznagel, Ed; Atkinson, Jeff; Despotis, George; Medicine, School of Medicine
    Background: This study was designed to prospectively evaluate the efficacy of extracorporeal photopheresis (ECP) to attenuate the rate of decline of FEV1 in lung transplant recipients with refractory bronchiolitis obliterans. Due to an observed higher than expected early mortality, a preliminary analysis was performed. Study design and methods: Subjects from 10 lung transplant centres were assigned to ECP treatment or to observation based on spirometric criteria, with potential crossover for those under observation. The primary endpoint of this study was to assess response to ECP (i.e., greater than a 50% decrease in the rate of FEV1 decline) before and 6 months after initiation of ECP. Mortality was also evaluated 6 and 12 months after enrolment as a secondary endpoint. Results: Of 44 enrolled subjects, 31 were assigned to ECP treatment while 13 were initially assigned to observation on a non-random basis using specific spirometric inclusion criteria (seven of the observation patients subsequently crossed over to receive ECP). Of evaluable patients, 95% of patients initially assigned to treatment responded to ECP with rates of FEV1 decline that were reduced by 93% in evaluable ECP-treated patients. Mortality rates (percentages) at 6 and 12 months after enrolment was 32% and 41%, respectively. The most common (92%) primary cause of death was respiratory or graft failure. Significantly (p = 0.002) higher rates of FEV1 decline were observed in the non-survivors (-212 ± 177 ml/month) when compared to the survivors (-95 ± 117 ml/month) 12 months after enrolment. In addition, 18 patients with bronchiolitis obliterans syndrome (BOS) diagnosis within 6 months of enrolment had lost 38% of their baseline lung function at BOS diagnosis and 50% of their lung function at enrolment. Conclusions: These analyses suggest that earlier detection and treatment of BOS should be considered to appreciate improved outcomes with ECP.
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    Histoplasmosis complicating tumor necrosis factor-α blocker therapy: a retrospective analysis of 98 cases
    (Oxford University Press, 2015-08-01) Vergidis, Paschalis; Avery, Robin K.; Wheat, L. Joseph; Dotson, Jennifer L.; Assi, Maha A.; Antoun, Smyrna A.; Hamoud, Kassem A.; Burdette, Steven D.; Freifeld, Alison G.; McKinsey, David; Money, Mary E.; Myint, Thein; Andes, David R.; Hoey, Cynthia A.; Kaul, Daniel A.; Dickter, Jana K.; Liebers, David E.; Miller, Rachel A.; Muth, William E.; Prakash, Vidhya; Steiner, Frederick T.; Walker, Randall C.; Hage, Chadi A.; Department of Medicine, IU School of Medicine
    BACKGROUND: Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. METHODS: We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. RESULTS: The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. CONCLUSIONS: In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.