Anish Wadhwa

Concordia University–Ann Arbor, Ann Arbor, Michigan, United States

Are you Anish Wadhwa?

Claim your profile

Publications (9)53.43 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Cytomegalovirus (CMV) infection increases morbidity and mortality in lung transplant recipients. Our center identified CMV-resistant (rCMV) disease resulting in the death of 3 out of 4 cases. We attributed rCMV to erratic dosing, inconsistent medication levels, and a shortened duration of valganciclovir (Val) prophylaxis. We describe the effect of changes in a prophylaxis protocol in order to prevent rCMV in at-risk patients.Methods and MaterialsThe Pre-intervention cohort (Pre 3/08-4/11) received prophylaxis with Val for 3 (D+ and D-/R+) to 6 (D+/R-) months; Val was held for WBC <4. The post-intervention cohort (Post, 11/10-9/11) had IV ganciclovir (Gan) induction for 2 weeks followed by Val for 6 months (D+/R- also received CMV-IVIg (150 mg/kg for 6 doses). Val was continued through leukopenia & IS was adjusted instead. A calcineurin inhibitor, anti-proliferative agent, and prednisone were used for primary immunosuppression (IS). Patients surviving >6 months and followed ≥12 months were included. Frequency of CMV events, time to first event (unadjusted and adjusted for changes in Val or IS), frequency of changes in Val dosing or IS (due to adverse effects) and frequency of rCMV were compared.Results54 Pre and 23 Post patients were included. CMV event frequency (Pre 23/54 (43%) vs. Post 9/23 (39%) (p=0.77)), median time to events (Pre 54 days, Post 69 days) and time to event analysis was not different between groups (HR 1.087, 95% CI 0.50-2.35). Changes in IS or Val dosing were not more frequent Pre (11/54 (20%)) versus Post (6/23 (26%)) (p=0.57). Pre was associated with development of rCMV in 4/54 (7%) patients, but rCMV in Post has not yet been detected.Conclusions Our combination therapy was successful in preventing rCMV in at-risk patients even though the frequency of CMV events and the changes in IS or Val dosing were unchanged. Our findings suggest that a longer duration of prophylaxis with consistent dosing and perhaps the addition of CMV-IVIg leads to a reduction in rCMV.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S129-S130. DOI:10.1016/j.healun.2013.01.286 · 6.65 Impact Factor
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • Natalie Walker · Anish Wadhwa · Kevin Chan · Vibha N. Lama
    American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Donor mesenchymal stromal/stem cell (MSC) expansion and fibrotic differentiation is associated with development of bronchiolitis obliterans syndrome (BOS) in human lung allografts. However, the regulators of fibrotic differentiation of these resident mesenchymal cells are not well understood. This study examines the role of endogenous and exogenous prostaglandin (PG)E2 as a modulator of fibrotic differentiation of human lung allograft-derived MSCs. Effect of PGE2 on proliferation, collagen secretion, and α-smooth muscle actin (α-SMA) expression was assessed in lung-resident MSCs (LR-MSCs) derived from patients with and without BOS. The response pathway involved was elucidated by use of specific agonists and antagonists. PGE2 treatment of LR-MSCs derived from normal lung allografts significantly inhibited their proliferation, collagen secretion, and α-SMA expression. On the basis of pharmacologic and small-interfering RNA approaches, a PGE2/E prostanoid (EP)2/adenylate cyclase pathway was implicated in these suppressive effects. Stimulation of endogenous PGE2 secretion by IL-1β was associated with amelioration of their myofibroblast differentiation in vitro, whereas its inhibition by indomethacin augmented α-SMA expression. LR-MSCs from patients with BOS secreted significantly less PGE2 than non-BOS LR-MSCs. Furthermore, BOS LR-MSCs were found to be defective in their ability to induce cyclooxygenase-2, and therefore unable to up-regulate PGE2 synthesis in response to IL-1β. BOS LR-MSCs also demonstrated resistance to the inhibitory actions of PGE2 in association with a reduction in the EP2/EP1 ratio. These data identify the PGE2 axis as an important autocrine-paracrine brake on fibrotic differentiation of LR-MSCs, a failure of which is associated with BOS.
    American Journal of Respiratory and Critical Care Medicine 09/2011; 185(1):77-84. DOI:10.1164/rccm.201105-0834OC · 13.00 Impact Factor
  • A. Wadhwa · N. Walker · L. Badri · K. Chan · V. Lama
    The Journal of Heart and Lung Transplantation 04/2011; 30(4). DOI:10.1016/j.healun.2011.01.574 · 6.65 Impact Factor
  • N. Walker · L. Badri · A. Wadhwa · V. Lama
    The Journal of Heart and Lung Transplantation 04/2011; 30(4). DOI:10.1016/j.healun.2011.01.232 · 6.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bronchoalveolar lavage fluid (BAL) from human lung allografts demonstrates the presence of a multipotent mesenchymal stromal cell population. However, the clinical relevance of this novel cellular component of BAL and its association with bronchiolitis obliterans syndrome (BOS), a disease marked by progressive airflow limitation secondary to fibrotic obliteration of the small airways, remains to be determined. In this study we investigate the association of number of mesenchymal stromal cells in BAL with development of BOS in human lung transplant recipients. Mesenchymal colony-forming units (CFUs) were quantitated in a cohort of 405 BAL samples obtained from 162 lung transplant recipients. Poisson generalized estimating equations were used to determine the predictors of BAL mesenchymal CFU count. Higher CFU counts were noted early post-transplantation; time from transplant to BAL of greater than 3 months predicted 0.4-fold lower CFU counts (P = 0.0001). BOS diagnosis less than or equal to 365 days before BAL was associated with a 2.11-fold higher CFU count (P = 0.02). There were 2.62- and 2.70-fold higher CFU counts noted in the presence of histologic diagnosis of bronchiolitis obliterans (P = 0.05) and organizing pneumonia (0.0003), respectively. In BAL samples obtained from BOS-free patients greater than 6 months post-transplantation (n = 173), higher mesenchymal CFU counts (≥10) significantly predicted BOS onset in both univariate (hazard ratio, 5.61; 95% CI, 3.03-10.38; P < 0.0001) and multivariate (hazard ratio, 5.02; 95% CI, 2.40-10.51; P < 0.0001) Cox regression analysis. Measurement of mesenchymal CFUs in the BAL provides predictive information regarding future BOS onset.
    American Journal of Respiratory and Critical Care Medicine 12/2010; 183(8):1062-70. DOI:10.1164/rccm.201005-0742OC · 13.00 Impact Factor
  • Chest 10/2010; 138(4 MeetingAbstracts):546A-546A. DOI:10.1378/chest.10964 · 7.48 Impact Factor
  • Clinical transplants 01/2009;