Saumini Srinivasan
University of Tennessee Health Science Center
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Cancer | 2012
Megan S Motosue; Liang Zhu; Kumar Srivastava; Dennis C. Stokes; Melissa M. Hudson; Valerie McPherson; Saumini Srinivasan; Matthew J. Krasin; Daniel M. Green; Sheri L. Spunt; Hiroto Inaba
Although whole lung irradiation is used to treat pulmonary metastases of pediatric solid malignancies, few studies have addressed its long‐term pulmonary consequences.
Journal of The American College of Surgeons | 2014
Jason W. Denbo; Liang Zhu; Deokumar Srivastava; Dennis C. Stokes; Saumini Srinivasan; Melissa M. Hudson; Kirsten K. Ness; Leslie L. Robison; Michael D. Neel; Bhaskar N. Rao; Fariba Navid; Andrew M. Davidoff; Daniel M. Green
BACKGROUND Complete resection of lung metastases improves survival in patients with osteosarcoma. We evaluated the long-term effect of metastasectomy on pulmonary function of patients treated for osteosarcoma during childhood. STUDY DESIGN We reviewed the medical records of patients who had pulmonary function tests (PFTs) after metastasectomy for osteosarcoma. Patient, tumor, and treatment variables were abstracted along with PFTs. The PFTs were recorded as a percentage of predicted value and were classified as abnormal for forced vital capacity (FVC) < 80%, forced expiratory volume in 1 second (FEV1) < 80%, total lung capacity (TLC) < 75%, and single breath diffusion capacity for carbon monoxide corrected for hemoglobin (DLCOcorr) < 75%. RESULTS Twenty-one patients had PFTs performed during follow-up. Mean age at diagnosis of osteosarcoma was 13.2 ± 4.7 years (SD). Fifteen patients had a single thoracotomy, and 6 patients had ≥2 thoracotomies (range 2 to 6). Eighty lesions were resected. Nine patients had ≤2 lesions resected and 12 patients had >2 lesions (range 3 to 12) resected. Mean time from the last surgical procedure to measurement of PFTs was 20.3 ± 9.0 years (SD). Total lung capacity was abnormal for 28.6%, DLCOcorr for 47.4%, FVC for 40%, and FEV1 for 47.6% of the cohort members. Individual PFTs were abnormal in 13.3% (TLC) to 46.7% (DLCOcorr) of patients who had 1 thoracotomy and in 50.0% (DLCOcorr) to 66.7% (FEV1, TLC) of patients with ≥2 thoracotomies. The number of thoracotomies was associated with abnormal TLC (p = 0.03). CONCLUSIONS Patients who underwent pulmonary metastasectomy for osteosarcoma as children often had abnormal PFTs on long-term follow-up, but the reduction in lung volumes and DLCOcorr was relatively mild. Multiple thoracotomies predicted greater impairment of pulmonary function.
Annals of the American Thoracic Society | 2014
Ashok Srinivasan; Saumini Srinivasan; Sudeep Sunthankar; Anusha Sunkara; Guolian Kang; Dennis C. Stokes; Wing Leung
RATIONALE Pulmonary complications are a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. OBJECTIVES The relationship between pretransplant pulmonary function tests (PFTs) and development of post-transplant pulmonary complications in children was studied. METHODS This is a retrospective single institution cohort study of 410 patients who underwent pretransplant PFT and were monitored to 10 years posttransplant. MEASUREMENTS AND MAIN RESULTS Pulmonary complications were observed in 174 (42%) patients. Children with pulmonary complications had significantly lower forced expiratory flow at 25-75% of vital capacity (P = 0.02) derived using conventional predicted equations for age, and the Global Lung Initiative-2012 predicted equations (P = 0.01). T-cell depletion (P = 0.001), acute grade 3-4 graft-versus-host disease (P = 0.008), and chronic graft-versus-host disease (P = 0.01) increased risk for pulmonary complications. Patients who had pulmonary complications had a 2.8-fold increased risk of mortality (P < 0.0001). The cumulative incidence of death due to pulmonary complications was significantly higher in children who had low lung volumes, FRC less than 50% (P = 0.005), TLC less than 50% (P = 0.0002), residual volume less than 50% (P = 0.007), and T-cell depletion (P = 0.01). Lower FEV1 (P = 0.0005), FVC (P = 0.0005), TLC (P < 0.0001), residual volume less than 50% (P = 0.01), and restrictive lung disease (P = 0.01) predicted worse overall survival. CONCLUSIONS Abnormal pretransplant PFT significantly increased risk after transplant. These patients may benefit from modified transplant strategies to reduce morbidity and mortality.
Journal of Pediatric Gastroenterology and Nutrition | 2017
Andres Carrion; Drucy Borowitz; Steven D. Freedman; Christopher M. Siracusa; Jennifer L. Goralski; Denis Hadjiladis; Saumini Srinivasan; Dennis C. Stokes
ABSTRACT The effect of ivacaftor in patients with cystic fibrosis (CF) with recurrent pancreatitis is unknown. We conducted a multicenter retrospective study of patients with CF taking ivacaftor who had a history of recurrent pancreatitis. During the first 3 months of therapy, only 1 of the 6 patients had an episode of pancreatitis, which was managed on an outpatient basis. Between 3 and 12 months on ivacaftor therapy, none of the patients had recurrence of pancreatitis or required hospitalization. The use of ivacaftor was associated with a reduced frequency and recurrence rate of pancreatitis in patients with CF.
PLOS ONE | 2015
James D. Tutor; Saumini Srinivasan; Memorie M. Gosa; Thomas Spentzas; Dennis C. Stokes
Background Swallowing dysfunction can lead to recurring aspiration and is frequently associated with chronic symptoms such as cough and wheezing in infants. Our objective was to describe the characteristics of infants with swallowing dysfunction, determine if pulmonary function abnormalities are detectable, and if they improve after therapy. Methods We studied 38 infants with a history of coughing and wheezing who had pulmonary function tests performed within two weeks of their diagnosis of swallowing dysfunction. The raised lung volume rapid thoracoabdominal compression technique was used. After 6 months of therapy, 17 of the infants repeated the tests. Results Initially, 25 had abnormal spirometry, 18 had abnormal plethysmography, and 15 demonstrated bronchodilator responsiveness. Six months later test were repeated for seventeen patients. Ten patients had continued abnormal spirometry, two patients remained normal, three patients’ abnormal spirometry had normalized, and two patients’ previously normal studies became abnormal. Eight of the 17 patients had continued abnormal plethysmography, six had continued normal plethysmography, and three patients’ normal plethysmography became abnormal. After 6 months of treatment, eight patients demonstrated bronchodilator responsiveness, of which five continued to demonstrate bronchodilator responsiveness and three developed responsiveness. The remainder either continued to be non- bronchodilator responsive (two) or lost responsiveness (three.) The findings of the abnormal tests in most infants tested is complicated by frequent occurrence of other co-morbidities in this population, including gastroesophageal reflux in 23 and passive smoke exposure in 13 of the infants. Conclusions The interpretation of lung function changes is complicated by the frequent association of swallowing dysfunction with gastroesophageal reflux and passive smoke exposure in this population. Six months of medical therapy for swallowing dysfunction/gastroesophageal reflux did not significantly improve pulmonary function in these infants. Long-term studies will be necessary to determine which of these changes persists into adulthood.
Biology of Blood and Marrow Transplantation | 2017
Ashok Srinivasan; Anusha Sunkara; William Mitchell; Sudeep Sunthankar; Guolian Kang; Dennis C. Stokes; Saumini Srinivasan
Abnormal pulmonary function is prevalent in survivors of allogeneic hematopoietic cell transplantation (HCT). Post-transplantation recovery of pulmonary function, and its effect on survival, in children are not known. This retrospective cohort study of 308 children followed for 10 years after HCT at a single institution included 2 groups of patients. Group 1 comprised 188 patients with 3 or more pulmonary function test (PFT) results, of which at least 1 was abnormal, and group 2 comprised 120 patients with 3 or more PFTs, all of which were normal. Pulmonary function normalized post-transplantation in 51 patients (27%) in group 1. Obstructive lung disease, restrictive lung disease, mixed lung disease, and normal pattern were seen in 43%, 25%, 5%, and 27% of patients, respectively, at a median of 5 years (range, 0.5 to 11.9 years) post-transplantation. Lung volumes recovered better than spirometric indices. Pulmonary complications were seen in 80 patients (43%) in group 1. Patients who recovered pulmonary function had better overall survival (P = .006), which did not differ significantly from that in patients in group 2 with normal lung function post-transplantation (P = .80). After adjusting for duration of follow-up, pulmonary complications (P = .01), and lower pretransplantation forced vital capacity z-scores (P = .01) were associated with poor recovery. T cell depletion (P < .001), lower pretransplantation forced expired volume in 1 second z-scores (P = .006), and chronic graft-versus-host disease (P < .001) increased the risk for pulmonary complications. Nonrecovery of lung function with pulmonary complications (P = .03), acute graft-versus-host disease (P = .004), and mechanical ventilation (P < .001) were risk factors for nonrelapse mortality. Normalization of pulmonary function is possible in long-term survivors of allogeneic HCT. Strategies to decrease the risk of pulmonary complications may improve outcomes.
American Journal of Physiology-lung Cellular and Molecular Physiology | 2016
Kavisha Arora; Sunitha Yarlagadda; Weiqiang Zhang; Changsuk Moon; Erin Bouquet; Saumini Srinivasan; Chunying Li; Dennis C. Stokes; Anjaparavanda P. Naren
Cystic fibrosis (CF) is a life-shortening disease caused by the mutations that generate nonfunctional CF transmembrane conductance regulator (CFTR) protein. A rare serine-to-tyrosine (S1045Y) CFTR mutation was earlier reported to result in CF-associated fatality. We identified an African-American patient with the S1045Y mutation in CFTR, as well as a stop-codon mutation, who has a mild CF phenotype. The underlying mechanism of CF caused by S1045Y-CFTR has not been elucidated. In this study, we determined that S1045Y-CFTR exhibits twofold attenuated function compared with wild-type (WT)-CFTR. We report that serine-to-tyrosine mutation leads to increased tyrosine phosphorylation of S1045Y-CFTR, followed by recruitment and binding of E3-ubiquitin ligase c-cbl, resulting in enhanced ubiquitination and passage of S1045Y-CFTR in the endosome/lysosome degradative compartments. We demonstrate that inhibition of tyrosine phosphorylation partially rescues S1045Y-CFTR surface expression and function. Based on our findings, it could be suggested that consuming genistein (a tyrosine phosphorylation inhibitor) would likely ameliorate CF symptoms in individuals with S1045Y-CFTR, providing a unique personalized therapy for this rare CF mutation.
Annals of the American Thoracic Society | 2016
Daniel M. Green; Liang Zhu; Mingjuan Wang; Kirsten K. Ness; Matthew J. Krasin; Nickhill Bhakta; M. Beth McCarville; Saumini Srinivasan; Dennis C. Stokes; Deokumar Srivastava; Rohit P. Ojha; Kyla Shelton; Ching-Hon Pui; Gregory T. Armstrong; Daniel A. Mulrooney; Monika L. Metzger; Sheri L. Spunt; Fariba Navid; Andrew M. Davidoff; Bhaskar N. Rao; Leslie L. Robison; Melissa M. Hudson
American Journal of Respiratory and Critical Care Medicine | 2012
Sunitha Yarlagadda; Weiqiang Zhang; Himabindu Penmatsa; Aixia Ren; Kavisha Arora; Anjaparavanda P. Naren; Fatima Anmol I. Khan; Catherine A. Donnellan; Saumini Srinivasan; Dennis C. Stokes; John C. Kappes
american thoracic society international conference | 2010
James D. Tutor; Saumini Srinivasan; Linda Mallory; LaVonda Redd; Michelle Jones; Susan Kneeshaw; Renda Curry; Stephen M. Davis; Memorie M. Gosa; Barbara Culbreath; Michael Christensen; Robert A. Schoumacher; Dennis C. Stokes