Search

Your search keyword '"Yvonne Meli"' showing total 23 results
Start Over Author "Yvonne Meli"
23 results on '"Yvonne Meli"'

1. Development of mRNA Manufacturing for Vaccines and Therapeutics: mRNA Platform Requirements and Development of a Scalable Production Process to Support Early Phase Clinical Trials

Author

Jill Whitley, Christopher Zwolinski, Christian Denis, Maureen Maughan, Leonie Hayles, David Clarke, Meghan Snare, Hong Liao, Sean Chiou, Tina Marmura, Holly Zoeller, Ben Hudson, John Peart, Monica Johnson, Amelia Karlsson, Yunfei Wang, Cynthia Nagle, Cherell Harris, Daniel Tonkin, Stephanie Fraser, Lieza Capiz, Christina L. Zeno, Yvonne Meli, Diana Martik, Daniel A. Ozaki, Amy Caparoni, Jason E. Dickens, Drew Weissman, Kevin O. Saunders, Barton F. Haynes, Gregory D. Sempowski, Thomas N. Denny, and Matthew R. Johnson

Subjects
Vaccines, SARS-CoV-2, Physiology (medical), Biochemistry (medical), Public Health, Environmental and Occupational Health, Animals, COVID-19, Humans, General Medicine, Review Article, RNA, Messenger
Abstract

The remarkable success of SARS CoV-2 mRNA-based vaccines and the ensuing interest in mRNA vaccines and therapeutics have highlighted the need for a scalable clinical-enabling manufacturing process to produce such products, and robust analytical methods to demonstrate safety, potency, and purity. To date, production processes have either not been disclosed or are bench-scale in nature and cannot be readily adapted to clinical and commercial scale production. To address these needs, we have advanced an aqueous-based scalable process that is readily adaptable to GMP-compliant manufacturing, and developed the required analytical methods for product characterization, quality control release, and stability testing. We also have demonstrated the products produced at manufacturing scale under such approaches display good potency and protection in relevant animal models with mRNA products encoding both vaccine immunogens and antibodies. Finally, we discuss continued challenges in raw material identification, sourcing and supply, and the cold chain requirements for mRNA therapeutic and vaccine products. While ultimate solutions have yet to be elucidated, we discuss approaches that can be taken that are aligned with regulatory guidance.

Published
2021

3. Quantitative Computed Tomography Assessment of Pectoralis and Erector Spinae Muscle Area and Disease Severity in Chronic Obstructive Pulmonary Disease Referred for Lung Volume Reduction

Author

Nicole Welch, Joe Zein, Yvonne Meli, Amy Attaway, Annette Bellar, Srinivasan Dasarathy, Ruchi Yadav, Mariëlle P.K.J. Engelen, and Umur Hatipoğlu

Subjects
Pulmonary and Respiratory Medicine, Lung volume reduction, medicine.medical_specialty, Sarcopenia, Lung Neoplasms, Pulmonary disease, Severity of Illness Index, Article, Cachexia, Pectoralis Muscles, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, Forced Expiratory Volume, Erector spinae muscles, Medicine, Humans, 030212 general & internal medicine, Quantitative computed tomography, Pneumonectomy, Lung, Early Detection of Cancer, Emphysema, COPD, medicine.diagnostic_test, business.industry, Skeletal muscle, respiratory system, medicine.disease, respiratory tract diseases, medicine.anatomical_structure, 030228 respiratory system, Pulmonary Emphysema, Cardiology, business, Tomography, X-Ray Computed
Abstract

Patients with advanced COPD develop skeletal muscle loss (sarcopenia) that is associated with adverse clinical outcomes including mortality. We evaluated if thoracic muscle area is associated with clinical outcomes in patients with severe COPD. We analyzed consecutive patients with severe COPD undergoing evaluation for lung volume reduction from 2015 to 2019 (n=117) compared to current and former smoking controls undergoing lung cancer screening with normal lung function (n=41). Quantitative assessments of pectoralis muscle (PM) and erector spinae muscle (ESM) cross sectional area (CSA) were related to clinical outcomes including composite endpoints. Our results showed a reduction in PM CSA but not ESM CSA was associated with the severity of GOLD stage of COPD. Current smokers demonstrated reduced PM CSA which was similar to that in COPD patients who were GOLD stages 3 and 4. PM CSA was associated positively with FEV1, FEV1% predicted, FVC, DLCO, and FEV1/FVC ratio, and was associated negatively with the degree of radiologic emphysema. ESM correlated positively with DLCO, RV/TLC (a marker of hyperinflation), and correlated negatively with radiologic severity of emphysema. Kaplan-Meier analysis showed that reductions in PM but not ESM CSA was associated with the composite end point of mortality, need for lung volume reduction, or lung transplant. In conclusion, in well-characterized patients with severe COPD referred for lung volume reduction, PM CSA correlated with severity of lung disease, mortality and need for advanced therapies. In addition to predicting clinical outcomes, targeting sarcopenia is a potential therapeutic approach in patients with severe COPD.

Published
2021

4. Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial

Author

Wesley H, Self, Matthew W, Semler, Lindsay M, Leither, Jonathan D, Casey, Derek C, Angus, Roy G, Brower, Steven Y, Chang, Sean P, Collins, John C, Eppensteiner, Michael R, Filbin, D Clark, Files, Kevin W, Gibbs, Adit A, Ginde, Michelle N, Gong, Frank E, Harrell, Douglas L, Hayden, Catherine L, Hough, Nicholas J, Johnson, Akram, Khan, Christopher J, Lindsell, Michael A, Matthay, Marc, Moss, Pauline K, Park, Todd W, Rice, Bryce R H, Robinson, David A, Schoenfeld, Nathan I, Shapiro, Jay S, Steingrub, Christine A, Ulysse, Alexandra, Weissman, Donald M, Yealy, B Taylor, Thompson, Samuel M, Brown, Jay, Steingrub, Howard, Smithline, Bogdan, Tiru, Mark, Tidswell, Lori, Kozikowski, Sherell, Thornton-Thompson, Leslie, De Souza, Peter, Hou, Rebecca, Baron, Anthony, Massaro, Imoigele, Aisiku, Lauren, Fredenburgh, Raghu, Seethala, Lily, Johnsky, Richard, Riker, David, Seder, Teresa, May, Michael, Baumann, Ashley, Eldridge, Christine, Lord, Nathan, Shapiro, Daniel, Talmor, Thomas, O’Mara, Charlotte, Kirk, Kelly, Harrison, Lisa, Kurt, Margaret, Schermerhorn, Valerie, Banner-Goodspeed, Katherine, Boyle, Nicole, Dubosh, Michael, Filbin, Kathryn, Hibbert, Blair, Parry, Kendall, Lavin-Parsons, Natalie, Pulido, Brendan, Lilley, Carl, Lodenstein, Justin, Margolin, Kelsey, Brait, Alan, Jones, James, Galbraith, Rebekah, Peacock, Utsav, Nandi, Taylor, Wachs, Michael, Matthay, Kathleen, Liu, Kirsten, Kangelaris, Ralph, Wang, Carolyn, Calfee, Kimberly, Yee, Gregory, Hendey, Steven, Chang, George, Lim, Nida, Qadir, Andrea, Tam, Rebecca, Beutler, Joseph, Levitt, Jenny, Wilson, Angela, Rogers, Rosemary, Vojnik, Jonasel, Roque, Timothy, Albertson, James, Chenoweth, Jason, Adams, Skyler, Pearson, Maya, Juarez, Eyad, Almasri, Mohamed, Fayed, Alyssa, Hughes, Shelly, Hillard, Ryan, Huebinger, Henry, Wang, Elizabeth, Vidales, Bela, Patel, Adit, Ginde, Amiran, Baduashvili, Jeffrey, McKeehan, Lani, Finck, Carrie, Higgins, Michelle, Howell, Ivor, Douglas, Jason, Haukoos, Terra, Hiller, Carolynn, Lyle, Alicia, Cupelo, Emily, Caruso, Claudia, Camacho, Stephanie, Gravitz, James, Finigan, Christine, Griesmer, Pauline, Park, Robert, Hyzy, Kristine, Nelson, Kelli, McDonough, Norman, Olbrich, Mark, Williams, Raj, Kapoor, Jean, Nash, Meghan, Willig, Henry, Ford, Jayna, Gardner-Gray, Mayur, Ramesh, Montefiore, Moses, Michelle, Ng Gong, Michael, Aboodi, Ayesha, Asghar, Omowunmi, Amosu, Madeline, Torres, Savneet, Kaur, Jen-Ting, Chen, Aluko, Hope, Brenda, Lopez, Kathleen, Rosales, Jee, Young You, Jarrod, Mosier, Cameron, Hypes, Bhupinder, Natt, Bryan, Borg, Elizabeth, Salvagio Campbell, R Duncan, Hite, Kristin, Hudock, Autumn, Cresie, Faysal, Alhasan, Jose, Gomez-Arroyo, Abhijit, Duggal, Omar, Mehkri, Andrei, Hastings, Debasis, Sahoo, Francois, Abi Fadel, Susan, Gole, Valerie, Shaner, Allison, Wimer, Yvonne, Meli, Alexander, King, Thomas, Terndrup, Matthew, Exline, Sonal, Pannu, Emily, Robart, Sarah, Karow, Catherine, Hough, Bryce, Robinson, Nicholas, Johnson, Daniel, Henning, Monica, Campo, Stephanie, Gundel, Sakshi, Seghal, Sarah, Katsandres, Sarah, Dean, Olivia, Krol, Milad, Jouzestani, Peter, Huynh, Donald, Yealy, Denise, Scholl, Peter, Adams, Bryan, McVerry, David, Huang, Derek, Angus, Jordan, Schooler, Steven, Moore, Clark, Files, Chadwick, Miller, Kevin, Gibbs, Mary, LaRose, Lori, Flores, Lauren, Koehler, Caryn, Morse, John, Sanders, Caitlyn, Langford, Kristen, Nanney, Masiku, MdalaGausi, Phyllis, Yeboah, Peter, Morris, Jamie, Sturgill, Sherif, Seif, Evan, Cassity, Sanjay, Dhar, Marjolein, de Wit, Jessica, Mason, Andrew, Goodwin, Greg, Hall, Abbey, Grady, Amy, Chamberlain, Samuel, Brown, Joseph, Bledsoe, Lindsay, Leither, Ithan, Peltan, Nathan, Starr, Melissa, Fergus, Valerie, Aston, Quinn, Montgomery, Rilee, Smith, Mardee, Merrill, Katie, Brown, Brent, Armbruster, Estelle, Harris, Elizabeth, Middleton, Robert, Paine, Stacy, Johnson, Macy, Barrios, John, Eppensteiner, Alexander, Limkakeng, Lauren, McGowan, Tedra, Porter, Andrew, Bouffler, J. Clancy, Leahy, Bennet, deBoisblanc, Matthew, Lammi, Kyle, Happel, Paula, Lauto, Wesley, Self, Jonathan, Casey, Matthew, Semler, Sean, Collins, Frank, Harrell, Christopher, Lindsell, Todd, Rice, William, Stubblefield, Christopher, Gray, Jakea, Johnson, Megan, Roth, Margaret, Hays, Donna, Torr, Arwa, Zakaria, David, Schoenfeld, Taylor, Thompson, Douglas, Hayden, Nancy, Ringwood, Cathryn, Oldmixon, Christine, Ulysse, Richard, Morse, Ariela, Muzikansky, Laura, Fitzgerald, Samuel, Whitaker, Adrian, Lagakos, Roy, Brower, Lora, Reineck, Neil, Aggarwal, Karen, Bienstock, Michelle, Freemer, Myron, Maclawiw, Gail, Weinmann, Laurie, Morrison, Mark, Gillespie, Richard, Kryscio, Daniel, Brodie, Wojciech, Zareba, Anne, Rompalo, Michael, Boeckh, Polly, Parsons, Jason, Christie, Jesse, Hall, Nicholas, Horton, Laurie, Zoloth, Neal, Dickert, and Deborah, Diercks

Subjects
Adult, Male, medicine.medical_specialty, Randomization, Science, Pneumonia, Viral, Placebo, 01 natural sciences, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Interquartile range, Internal medicine, medicine, Humans, Treatment Failure, 030212 general & internal medicine, 0101 mathematics, Pandemics, Aged, Original Investigation, business.industry, SARS-CoV-2, 010102 general mathematics, Politics, Hydroxychloroquine, General Medicine, Odds ratio, Middle Aged, Interim analysis, Intensive care unit, COVID-19 Drug Treatment, Female, business, medicine.drug
Abstract

Importance Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. Objective To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. Design, Setting, and Participants This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Interventions Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). Main Outcomes and Measures The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Results Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, −0.2% [95% CI, −5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Conclusions and Relevance Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults. Trial Registration ClinicalTrials.gov:NCT04332991

Published
2020

5. Lower lobe lung volume reduction surgery: a case report

Author

Mohammed Al-Jaghbeer, Umur Hatipoğlu, Atul C. Mehta, Sid Murthy, and Yvonne Meli

Subjects
medicine.medical_specialty, Pulmonary disease, Case Report, 030204 cardiovascular system & hematology, Lung volume reduction surgery, Microbiology, omcrep/2200, omcrep/2100, 03 medical and health sciences, 0302 clinical medicine, Medicine, Volume reduction, COPD, business.industry, Walk distance, Objective Improvement, medicine.disease, Surgery, Discontinuation, respiratory tract diseases, Infectious Diseases, 030228 respiratory system, Lower lobe lung, Parasitology, business, AcademicSubjects/MED00010
Abstract

Lung volume reduction surgery (LVRS) is an option for select patients with advanced chronic obstructive pulmonary disease (COPD). Current guidelines recommend LVRS for patients with appropriate physiology and heterogeneous distribution of emphysema predominately involving upper lobes. We present an unusual case of a 72-year-old male with an advanced COPD who suffered with recurrent exacerbations despite optimal medical management. He underwent a two-stage bilateral lower lobe LVRS for heterogeneous lower lobe emphysema via video-assisted thoracoscopic (VATS) approach. This resulted in a significant subjective as well as objective improvement in his pulmonary functions, 6-min walk distance and subsequent discontinuation of supplemental oxygen.

Published
2020

6. Multi-Disciplinary Evaluation for Therapeutic Interventions in Patients with Chronic Obstructive Pulmonary Disease

Author

Mohammed Al-Jaghbeer, Joseph Cicenia, Bohdan Pichurko, Loutfi S. Aboussouan, Sudish C. Murthy, K. Nicolacakis, Richard Rice, Yvonne Meli, Thomas R. Gildea, Scott Marlow, Usman Ahmad, Atul C. Mehta, P. Curtis, Umur Hatipoğlu, A. Attaway, James K. Stoller, and Michael Machuzak

Subjects
medicine.medical_specialty, Multi disciplinary, business.industry, medicine, Psychological intervention, Pulmonary disease, In patient, Intensive care medicine, business
Published
2020
Full Text
View/download PDF

7. Effect of Zephyr Endobronchial Valves on Dyspnea, Activity Levels, and Quality of Life at One Year. Results from a Randomized Clinical Trial

Author

Mark T. Dransfield, Justin L. Garner, Surya P. Bhatt, Dirk-Jan Slebos, Karin Klooster, Frank C. Sciurba, Pallav L. Shah, Nathaniel T. Marchetti, Richard D. Sue, Shawn Wright, Hiram Rivas-Perez, Tanya A. Wiese, Momen M. Wahidi, Hugo Goulart de Oliveira, Brian Armstrong, Sri Radhakrishnan, Narinder S. Shargill, Gerard J. Criner, Lewis Katz, Francis Cordova, Parag Desai, Nathaniel Marchetti, Victor Kim, Kartik Shenoy, John Travaline, Jiji Thomas, Lii-Yoong H. Criner, Richard Sue, Aaron Thornburg, Terry Thomas, Mark Dransfield, Surya Bhatt, James Michael Wells, Necole Seabron-Harris, Umair Gauhar, Crissie Despirito, Frank Sciurba, Jessica Bon Field, Divay Chandra, Joseph Leader, Roy Semaan, Christina Ledezma, Pallav Shah, Samuel Kemp, Justin Garner, Arafa Aboelhassan, Karthi Srikanthan, Eric Tenda, Anita Abraham, Cai Sim, Momen Wahidi, Kamran Mahmood, Scott Shofer, Kathleen Coles, Guilherme Augusto Oliveira, Betina Machado, Igor Benedetto, Fabio Svartman, Amarilio de Macedo Neto, Leonardo Schreiner, Taiane Vieira, Brian Morrissey, Ken Yoneda, Tina Tham, Daniel Tompkins, Paulo F. Guerreiro Cardoso, Rodrigo Athanazio, Felipe Nominando, Samia Rached, Luciana Cassimiro, Steven Hays, Eric Seeley, Pavan Shrestha, Gabriela R. Dincheva, Adnan Majid, Daniel Alape-Moya, Mihir Parikh, Alichia Paton, Alexis Agnew, Nicholas Pastis, Charlie Strange, Tatsiana Beiko, Danielle Woodford, Mary Blanton, Lisa Kopas, Timothy Connolly, Jose Fernando Santacruz, Bhavin Shah, Mark Vollenweider, Luis Herrera, Rumi Khan, Kristine Sernulka, P. Michael McFadden, Richard Barbers, Michelle Hernandez, Michael Machuzak, Francisco Almeida, Joseph Cicenia, Thomas Gildea, Atul Mehta, Sonali Sethi, Yvonne Meli, David Hsia, Richard Casaburi, William Stringer, Leticia Diaz, Arthur Sung, Meghan Ramsey, Ryan Van Wert, Karen Morris, Nabil Jarad, Tim Batchelor, Iara Sequeiros, Katy Tucker, Malgorzata Kornaszweska, Hazem Fallouh, Ramsey Sabit, Hatam Naase, Joseph George, Azin Salimian, Helen Dyer, Stephen Hazelrigg, Kristal Adams, Karen Bade, Ganesh Krishna, Bryan S. Benn, Michelle Canfield, Sharmila Vetri Villalan, Travis Stewart, Dirk-Ja n Slebos, Nick H. T. ten Hacken, Jorine Hartman, Sonja Augustijn, and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
Male, Exacerbation, medicine.medical_treatment, EMPHYSEMA, Bronchoscopic lung volume reduction, law.invention, 0302 clinical medicine, Randomized controlled trial, Quality of life, law, Forced Expiratory Volume, Surveys and Questionnaires, interventional bronchoscopy, Medicine, PREDICTS MORTALITY, 030212 general & internal medicine, LUNG-VOLUME-REDUCTION, Pneumonectomy, Zephyr Valve, Lung function, Original Research, Rehabilitation, Exercise Tolerance, Patient-centered outcomes, Prostheses and Implants, respiratory system, Middle Aged, Treatment Outcome, Pulmonary Emphysema, patient-reported outcomes, Anesthesia, Female, Pulmonary and Respiratory Medicine, REHABILITATION, Adult, Bronchi, Severe copd, OBSTRUCTIVE PULMONARY-DISEASE, CAPACITY, chronic obstructive pulmonary disease, 03 medical and health sciences, severe emphysema, SEVERE COPD, Bronchoscopy, PATIENT-CENTERED OUTCOMES, Humans, Aged, business.industry, respiratory tract diseases, PHYSICAL-ACTIVITY, 030228 respiratory system, EXACERBATION, Quality of Life, business, Adult Pulmonary
Abstract

Rationale: Bronchoscopic lung volume reduction with Zephyr Valves improves lung function, exercise tolerance, and quality of life of patients with hyperinflated emphysema and little to no collateral ventilation. Objectives: Post hoc analysis of patient-reported outcomes (PROs), including multidimensional measures of dyspnea, activity, and quality of life, in the LIBERATE (Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema) study are reported. Methods: A total of 190 patients with severe heterogeneous emphysema and little to no collateral ventilation in the target lobe were randomized 2:1 to the Zephyr Valve or standard of care. Changes in PROs at 12 months in the two groups were compared: dyspnea with the Transitional Dyspnea Index (TDI), focal score; the Chronic Obstructive Pulmonary Disease Assessment Test (CAT; breathlessness on hill/stairs); Borg; the EXAcerbations of Chronic pulmonary disease Tool–PRO, dyspnea domain; activity with the TDI, magnitude of task/effort/functional impairment, CAT (limited activities), and the St. George’s Respiratory Questionnaire (SGRQ), activity domain; and psychosocial status with the SGRQ, impacts domain, and CAT (confidence and energy). Results: At 12 months, patients using the Zephyr Valve achieved statistically significant and clinically meaningful improvements in the SGRQ; CAT; and the TDI, focal score, compared with standard of care. Improvements in the SGRQ were driven by the impacts and activity domains (P

Published
2020

8. A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE)

Author

Gerard J. Criner, Richard Sue, Shawn Wright, Mark Dransfield, Hiram Rivas-Perez, Tanya Wiese, Frank C. Sciurba, Pallav L. Shah, Momen M. Wahidi, Hugo Goulart de Oliveira, Brian Morrissey, Paulo F. G. Cardoso, Steven Hays, Adnan Majid, Nicholas Pastis, Lisa Kopas, Mark Vollenweider, P. Michael McFadden, Michael Machuzak, David W. Hsia, Arthur Sung, Nabil Jarad, Malgorzata Kornaszewska, Stephen Hazelrigg, Ganesh Krishna, Brian Armstrong, Narinder S. Shargill, Dirk-Jan Slebos, Francis Cordova, Parag Desai, Nathaniel Marchetti, Victor Kim, Kartik Shenoy, John Travaline, Jiji Thomas, Lii-Yoong H. Criner, Aaron Thornburg, Terry Thomas, Surya Bhatt, James Michael Wells, Necole Seabron-Harris, Umair Gauhar, Crissie Despirito, Frank Sciurba, Jessica Bon Field, Divay Chandra, Joseph Leader, Roy Semaan, Christina Ledezma, Pallav Shah, Samuel Kemp, Justin Garner, Arafa Aboelhassan, Karthi Srikanthan, Eric Tenda, Anita Abraham, Cai Sim, Momen Wahidi, Kamran Mahmood, Scott Shofer, Kathleen Coles, Guilherme Augusto Oliveira, Betina Machado, Igor Benedetto, Fabio Svartman, Amarilio de Macedo Neto, Leonardo Schreiner, Taiane Vieira, Ken Yoneda, Tina Tham, Daniel Tompkins, Paulo F. Guerreiro Cardoso, Rodrigo Athanazio, Felipe Nominando, Samia Rached, Luciana Cassimiro, Eric Seeley, Pavan Shrestha, Gabriela R. Dincheva, Daniel Alape-Moya, Mihir Parikh, Alichia Paton, Alexis Agnew, Charlie Strange, Tatsiana Beiko, Danielle Woodford, Mary Blanton, Timothy Connolly, Jose Fernando Santacruz, Bhavin Shah, Luis Herrera, Rumi Khan, Kristine Sernulka, Richard Barbers, Michelle Hernandez, Francisco Almeida, Joseph Cicenia, Thomas Gildea, Atul Mehta, Sonali Sethi, Yvonne Meli, David Hsia, Richard Casaburi, William Stringer, Leticia Diaz, Meghan Ramsey, Ryan Van Wert, Karen Morris, Tim Batchelor, Iara Sequeiros, Katy Tucker, Malgorzata Kornaszweska, Hazem Fallouh, Ramsey Sabit, Hatam Naase, Joseph George, Azin Salimian, Helen Dyer, Kristal Adams, Karen Bade, Bryan S. Benn, Michelle Canfield, Sharmila Vetri Villalan, Travis Stewart, Nick H. T. ten Hacken, Karin Klooster, Jorine Hartman, Sonja Augustijn, and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
Male, Pulmonary and Respiratory Medicine, CLINICAL-OUTCOMES, medicine.medical_specialty, Randomization, SURGERY, lung reduction, Bronchi, Critical Care and Intensive Care Medicine, OBSTRUCTIVE PULMONARY-DISEASE, chronic obstructive pulmonary disease, MEDICAL THERAPY, Collateral ventilation, law.invention, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Randomized controlled trial, law, Forced Expiratory Volume, Surveys and Questionnaires, Internal medicine, Bronchoscopy, Correspondence, Humans, COPD, Medicine, 030212 general & internal medicine, LUNG-VOLUME-REDUCTION, Respiratory system, Exercise Tolerance, IMPORTANT DIFFERENCE, business.industry, Walk distance, OPERATIVE MORTALITY, Endobronchial valve, Equipment Design, Prostheses and Implants, Middle Aged, NATIONAL EMPHYSEMA, medicine.disease, Treatment Outcome, emphysema, Pulmonary Emphysema, 030228 respiratory system, TESTS, Female, business
Abstract

Rationale: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months.Objectives: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe.Methods: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the Delta EBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores.Measurements and Main Results: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a Delta FEV1 greater than or equal to 15% (P Conclusions: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe.

Published
2018
Full Text
View/download PDF

9. Rapamycin Reduced Ischemic Brain Damage in Diabetic Animals Is Associated with Suppressions of mTOR and ERK1/2 Signaling

Author

Xiao Yang, Jianguo Niu, P. Andy Li, Tao Sun, Ping Liu, Changchun Hei, and Yvonne Meli

Subjects
Blood Glucose, Male, 0301 basic medicine, medicine.medical_specialty, Programmed cell death, MAP Kinase Signaling System, Blotting, Western, Ischemia, DNA Fragmentation, AMP-Activated Protein Kinases, Applied Microbiology and Biotechnology, Neuroprotection, Brain Ischemia, Diabetes Mellitus, Experimental, Brain ischemia, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, In Situ Nick-End Labeling, Animals, Medicine, Rapamycin, Rats, Wistar, Molecular Biology, Ecology, Evolution, Behavior and Systematics, PI3K/AKT/mTOR pathway, Cerebral Cortex, Sirolimus, ERK1/2, business.industry, TOR Serine-Threonine Kinases, Diabetes, Cell Biology, Cerebral ischemia, medicine.disease, Rats, 030104 developmental biology, Endocrinology, mTOR, business, 030217 neurology & neurosurgery, Research Paper, Developmental Biology, medicine.drug
Abstract

The objectives of the present study are to investigate the activation of mTOR and ERK1/2 signaling after cerebral ischemia in diabetic rats and to examine the neuroprotective effects of rapamycin. Ten minutes transient global cerebral ischemia was induced in straptozotocin-induced diabetic hyperglycemic rats and non-diabetic, euglycemic rats. Brain samples were harvested after 16 h of reperfusion. Rapamycin or vehicle was injected 1 month prior to the induction of ischemia. The results showed that diabetes increased ischemic neuronal cell death and associated with elevations of p-P70S6K and Ras/ERK1/2 and suppression of p-AMPKα. Rapamycin ameliorated diabetes-enhanced ischemic brain damage and suppressed phosphorylation of P70S6K and ERK1/2. It is concluded that diabetes activates mTOR and ERK1/2 signaling pathways in rats subjected to transient cerebral ischemia and inhibition of mTOR by rapamycin reduces ischemic brain damage and suppresses the mTOR and ERK1/2 signaling in diabetic settings.

Published
2016
Full Text
View/download PDF

10. The Long-Term Oxygen Treatment Trial for Chronic Obstructive Pulmonary Disease: Rationale, Design, and Lessons Learned

Author

Roger D. Yusen, Gerard J. Criner, Alice L. Sternberg, David H. Au, Anne L. Fuhlbrigge, Richard K. Albert, Richard Casaburi, James K. Stoller, Kathleen F. Harrington, J. Allen D. Cooper, Philip Diaz, Steven Gay, Richard Kanner, Neil MacIntyre, Fernando J. Martinez, Steven Piantadosi, Frank Sciurba, David Shade, Thomas Stibolt, James Tonascia, Robert Wise, William C. Bailey, Ernestina Sampong, Karin Sloan, Ashley Wagner, Susan Anderson, Marilyn Moy, Osarenoma Okunbor, Scott Marlow, Yvonne Meli, Richard Rice, Loutfi S. Aboussouan, Robert Castele, Joseph Parambil, Sumita Khatri, Aman Pande, Joe Zein, Thomas Olbrych, Stephan Alkins, Christine Jocko, Franck Rahaghi, Jean Barton, Jennifer Underwood, Barry Make, John Davies, Richard Mularski, Allison Naleway, Sarah Vertrees, Janos Porszasz, Peggy Walker, Renee Indelicato, Lennard Specht, Kathleen Ellstrom, Jamie Portillo, David Horak, Brian Tiep, Mary Barnett, Janice Drake, Mahasti Rittinger, Rachael Compton, Scott Miller, Ralph J. Panos, Laura A. Lach, Gerard Criner, Carla Grabianowski, Francis Cordova, Parag Desai, Samuel Krachman, James Mamary, Nathaniel Marchetti, Aditi Satti, Eileen Mumm, Michelle Vega-Olivo, Jenny Hua, Vanna Tauch, Lii-Yoong Criner, Michael Jacobs, Peter Rising, Paul Simonelli, Michele Mitchell, Matthew Lammi, Connie Romaine, Howard Lee, Mary Ianacone, Steven Scharf, Wanda Bell-Farrell, M. Jeffery Mador, Ayesha Rahman, Mumtaz Zaman, Lisa Hill, Alec Platt, J. Allen Cooper, Kathleen Harrington, Mark Dransfield, Patti Smith, Donald Davis, Peruvemba Sriram, Katherine Herring, Fernando Martinez, Meilan Han, Kelly Rysso, Catherine Meldrum, K. P. Ravikrishnan, Daniel Keena, Jennifer DeRidder, Beth Kring, Antonio Anzueto, Alex Aguilera, Timothy Houlihan, Reda Girgis, Jennifer Cannestra, Benjamin Kelly, Mary Beth Scholand, G. Martin Villegas, Judy Carle, Edmunds Udris, Randall Curtis, David Au, Laura C. Feemster, Richard Goodman, Brianna Moss, Lynn Reinke, Moira Aitken, Bruce Culver, Mario Castro, Brigitte Mittler, Jeanne Heaghney, Myron Jacobs, Min Joo, Nina Bracken, Edward Diamond, Mary K. Joseph, Xavier Soler, Arianna Villa, Daniel Layish, Edwin Silverman, Roxanne Kelly, Daniel Cossette, Patricia Belt, Amanda Blackford, Betty Collison, John Dodge, Michele Donithan, Cathleen Ewing, Rosetta Jackson, K Patrick May, Jill Meinert, Girlie Reyes, Michael Smith, Mark Van Natta, Laura Wilson, Annette Wagoner, Katherine P. Yates, Rosemarie Hakim, Antonello Punturieri, Julie Bamdad, Thomas Croxton, Joanne Deshler, Pamela McCord-Reynolds, Mario Stylianou, Gail Weinmann, Gordon Bernard, James Anderson, Bernard Lo, Andrew Ries, Stuart Stoloff, Byron Thomashow, Barbara Tilley, and Kevin Weiss

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Randomization, Time Factors, medicine.medical_treatment, Population, law.invention, Hypoxemia, Treatment and control groups, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Patient Admission, Randomized controlled trial, law, Oxygen therapy, Medicine, Humans, Multicenter Studies as Topic, 030212 general & internal medicine, education, Aged, Randomized Controlled Trials as Topic, Clinical Study Design, Aged, 80 and over, education.field_of_study, Geography, business.industry, Oxygen Inhalation Therapy, Middle Aged, Long-Term Care, United States, Clinical trial, Oxygen, 030228 respiratory system, Sample size determination, Emergency medicine, Physical therapy, Quality of Life, Female, medicine.symptom, business
Abstract

The Long-Term Oxygen Treatment Trial demonstrated that long-term supplemental oxygen did not reduce time to hospital admission or death for patients who have stable chronic obstructive pulmonary disease and resting and/or exercise-induced moderate oxyhemoglobin desaturation, nor did it provide benefit for any other outcome measured in the trial. Nine months after initiation of patient screening, after randomization of 34 patients to treatment, a trial design amendment broadened the eligible population, expanded the primary outcome, and reduced the goal sample size. Within a few years, the protocol underwent minor modifications, and a second trial design amendment lowered the required sample size because of lower than expected treatment group crossover rates. After 5.5 years of recruitment, the trial met its amended sample size goal, and 1 year later, it achieved its follow-up goal. The process of publishing the trial results brought renewed scrutiny of the study design and the amendments. This article expands on the previously published design and methods information, provides the rationale for the amendments, and gives insight into the investigators' decisions about trial conduct. The story of the Long-Term Oxygen Treatment Trial may assist investigators in future trials, especially those that seek to assess the efficacy and safety of long-term oxygen therapy. Clinical trial registered with clinicaltrials.gov (NCT00692198).

Published
2018

11. CT Metrics of Airway Disease and Emphysema in Severe COPD

Author

James Walter, David Godwin, Joyce Canterbury, Thomas E. Hartman, Yen Pin Chiang, Jeanne Smith, John J. Reilly, Hope Livingston, Abby M. Krichman, Mahasti Rittinger, Karma L. Kreizenbeck, Kymberley Anable, Ameena Al-Amin, Colleen Witt, Karen McVearry, Claude Deschamps, Selim M. Arcasoy, Liz Roessler, James K. Stoller, Yahya M. Berkmen, Paul J. Friedman, Enrique Fernandez, Laura Kotler-Klein, Chris Piker, Robert E. Hyatt, Mark J. Krasna, Priscilla McCreight, Jo Anna Baldwin, Jennifer M Lamb, Francisco Alvarez, Janet R. Maurer, Rodney Simcox, Gerald O'Brien, Iris Moskowitz, Marianne C. Fahs, Judd Gurney, A. Mark Fendrick, Mike Mantinaos, Sanjay Kalra, Robert M. Kaplan, Kevin R. Flaherty, Timothy Gilbert, James K. Garrett, Kathy Mieras, Kapreena Owens, Trina Limberg, Patricia Belt, Rolf D. Hubmayr, Roger Barnette, James Carter, Phillip M. Boiselle, Brian Woodcock, Anne Marie Kuzma, Brian F. Mullan, Dean Follmann, Mary Ellen Kleinhenz, Judith Harle, Ubaldo J. Martin, Bonnie Edwards, Fernando I. Martinez, Sandy Do, Alejandro A. Diaz, F.C. Sciurba, William Russell, David J. Sugarbaker, Theresa Alcorn, Susan Borosh, Patricia McDowell, Carolyn Wheeler, Blake Wood, Edwin K. Silverman, Alan J. Moskowitz, John F. Plankeel, William F. Bria, Susan Clark, Patricia Ward, Scott D. Ramsey, Barry J. Make, David H Kupferberg, Chinh T. Q. Nguyen, Stanley Aukberg, Elisabeth L. George, Steven Piantadosi, Geoffrey McLennan, Carl D. Mottram, Martin Zamora, Marvin Pomerantz, Ella A. Kazerooni, Jennifer Propst, Bessie Kachulis, Carol Fanning, Valentina Yegyan, Kenneth Silver, James P. Kiley, Sabine Duffy, David H. Harpole, Junfeng Guo, Donald C. Oxorn, Andrew L. Ries, Paramjit Gill, Bruce H. Culver, Todd M. Officer, Catherine Wood Larsen, John Hansen-Flaschen, Patrick Ross, Mindi Steiger, Lori Hanson, Rose Butanda, Paul F. Simonelli, Neil W. Brister, Amy Chong, Charles L. White, Eric A. Jensen, Cynthia Raymond, Mark K. Ferguson, Moulay Meziane, Mary Milburn-Barnes, James D. Luketich, Douglas E. Wood, A. John McSweeny, Woo Jin Kim, Kim Stavrolakes, John A. Waldhausen, Gregory L. Aughenbaugh, Chul Kwak, Sara L. Bartling, Joan Osterloh, Larry R. Kaiser, John S. Howe, Michael I. Lewis, Andrew Bowdle, Mark A. Gerhardt, Richard O'Connell, Brian R. Lawlor, Neil R. MacIntyre, David A. Lynch, Milton Joyner, Louie Boitano, James P. Utz, Everett Hood, Paul J. Smith, Joshua O. Benditt, John Apostolakis, Frances L. Brogan, Robert McKenna, Berend Mets, Phyllis Dibbern, Kevin Carney, Joan M. Lacomis, Kevin McCarthy, A. Laurie Shroyer, Mitchell K. O’Shea, Barry Make, Dora Greene, Janice Willey, Catherine Ramirez, Gwendolyn B. Vance, Philip R. Karsell, David DeMets, Angela DiMango, Peter Rising, Erik J. Kraenzler, Michael F. Keresztury, Laurie Ney Silfies, Michael Magliocca, Vivian Knieper, Betsy Ann Bozzarello, Marlene Edgar, Madelina Lorenzon, Deb Andrist, Sophia Chatziioannou, Darryl Atwell, Sally Frese, Ruth Etzioni, Stephen I. Marglin, Maria Shiau, Thomas Schroeder, Vincent J. Carey, Vladmir Formanek, Robert Levine, Cindy Chwalik, David Rittinger, Kenneth Martay, Brett A. Simon, Nancy Kurokawa, Anne L. Fuhlbrigge, Peter J. Julien, Michelle T. Toshima, Sean D. Sullivan, Joanne Deshler, Margaret Wu, Anthony Norris, David A. Lipson, Scott J. Swanson, Diane Lockhart, Omar A. Minai, Joseph l. Reeves-Viets, Raed A. Dweik, Keith S. Naunheim, Angela Delsing, Minnie Ellisor, Jane Whalen-Price, Victor F. Tapson, Leonard Rossoff, Susan M. Peterson, Deborah Nowakowski, David M. Shade, Susanne Snedeker, Susan Craemer, Anne Marie G. Sykes, Jennifer Norten, Manmohan S. Biring, Diane C. Strollo, Beth Elliot, Kedren Williams, Heather Sheaffer, Sheila Shearer, Robert P. Hoffman, Robert Quaife, J. Mendez, Donald A. Mahler, Janice Cook-Granroth, Scott Marlow, Zab Mosenifar, Malcolm M. DeCamp, Paul J. Christensen, Rosetta Jackson, Wissam Chatila, Robert Schilz, Glenda DeMercado, Peter B. O'Donovan, Kimberly Dubose, Robert J. Keenan, Satoshi Furukawa, Theodore Kopp, Gerald T. Ayres, Betty Collison, Stephen J. Swensen, Jennifer Stone-Wynne, Nicole Jenson, Stanley S. Siegelman, Tina Bees, Owen B. Wilson, R. Duane Davis, Pierre A. DeVilliers, Marcia Katz, Carolyn M. Clancy, Eddie L. Hoover, Bryan Benedict, Karen Kirsch, Philip M. Hartigan, Simon C. Body, Mark Stafford-Smith, David A. Zisman, Jeanne M. Hoffman, Fernando J. Martinez, Clarence Weir, Jeffrey D. Edelman, William Stanford, Zab Mohsenifar, Michael P. Donahoe, Michele Donithan, Catherine A. Meldrum, William A. Slivka, Lori Zaremba, Michael W. Smith, Martin D. Abel, Robert B Gerber, Sarah Hooper, Steven M. Scharf, Karen A. Hanson, Katherine P. Grichnik, J. Sanford Schwartz, Margaret L. Snyder, Charles J. Hearn, Joe Chin, Tammy Ojo, Gregory D.N. Pearson, Vera Edmonds, George R. Washko, Christine Young, Jennifer Minkoff-Rau, Ron Daniele, Chun Yip, Gregory L. Foster, Harold I. Palevsky, Joan E. Sexton, Dev Pathak, Pamela Fox, Paul E. Kazanjian, Karen King, Jacqueline Pfeffer, Imran Nizami, Judith Wagner, Catherine Wrona, John H. M. Austin, Karla Conejo-Gonzales, Sharon Bendel, Amir Sharafkhaneh, Carol Geaga, Denise Vilotijevic, Thomas H. Sisson, Steven H. Sheingold, Ryan Colvin, Elaine Baker, Karen Collins, Charles F. Emery, Mark Ginsburg, Abass Alavi, David D. Frankville, Joseph M. Reinhardt, Jan Drake, John M. Travaline, Rafael Espada, Kathy Lautensack, Leslie E. Quint, Jeffrey T. Chapman, Rosemary Lann, Steven M. Berkowitz, Alice L. Sternberg, Thurman Gillespy, Nadia Howlader, Frank J. Papatheofanis, Robert Frantz, Manuel L. Brown, Sarah Shirey, Yvonne Meli, Andra E. Ibrahim, Patricia A. Jellen, Rebecca Crouch, Warren B. Gefter, Michael J. Reardon, Jonathan B. Orens, Neal S. Kleiman, Marilyn L. Moy, Daniel L. Miller, Julie Fuller, Reuben M. Cherniack, Claudette Sikora, Lynn Bosco, Harry Handelsman, R. Edward Coleman, Judith M. Aronchick, James Tonascia, Delmar J. Gillespie, Patricia Berkoski, David P. Kapelanski, Cesar A. Keller, Amanda L. Blackford, Charles C. Miller, Kelly M. Campbell, Jill Meinert, Carl R. Fuhrman, Gordon R. Bernard, Connie Hudson, Roger Russell, Lewis Poole, Dale Williams, Magdy Younes, Shing Lee, Steven L. Sax, Martin Carlos, Diane C. Saunders, John Dodge, Matthew N. Bartels, Amy Jahn, Karen Taylor, Gregg L Ruppel, Wallace T. Miller, Mary Gilmartin, Tanisha Carino, Alfred P. Fishman, Gerene Bauldoff, Frank C. Sciurba, Gerard J. Criner, John Haddad, Mark D. Iannettoni, Terri Durr, Gordon F. Harms, Susan Golden, Norman E. Torres, Lisa Geyman, Alan Hibbit, Paul Rysso, Gilbert E. D'Alonzo, Henry E. Fessler, Mark L. Van Natta, Peter Wahl, James H. Harrell, Willard Chamberlain, Roger D. Yusen, Boleyn Hammel, Dawn E. Sassi-Dambron, Mark S. Allen, Jennifer Cutler, Shangqian Qi, Susan Rinaldo-Gallo, John D. Newell, June Hart, Raúl San José Estépar, Kerri McKeon, Staci Opelman, Eric S. Edell, Kathy Winner, Joe R. Rodarte, Mark A. King, Eric A. Hoffman, Laura A. Wilson, Phil Cagle, Jennifer Meyers, Kristin Berry, Mark P. Steele, Katherine Hale, Peter Barnard, Charles Soltoff, Melissa Weeks, Arfa Khan, Cary Stolar, Jeanine P. Wiener-Kronish, Jeannie Ricketts, Nancy Battaglia, Francine L. Jacobson, Satish G. Jhingran, Robert B. Teague, Mary Louise Dempsey, Leighton Chan, Philip T. Diaz, David Hicks, David E. Midthun, Charlene Levine, Andetta R. Hunsaker, Tomeka Simon, Jered Sieren, Susan Lubell, Scott A. Schartel, H P McAdams, Francis Cordova, Kris Bradt, Jeffery J. Johnson, Kenneth White, Mercedes True, Erin A. Sullivan, Byron Thomashow, Gail Weinmann, Robert A. Wise, Donna Tsang, Robert M. Kotloff, Atul C. Mehta, Gregory Tino, and Angela Wurster

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, Critical Care and Intensive Care Medicine, Risk Assessment, Sensitivity and Specificity, Severity of Illness Index, Cohort Studies, Pulmonary Disease, Chronic Obstructive, Predictive Value of Tests, Forced Expiratory Volume, Internal medicine, medicine, Humans, Lung volumes, Respiratory system, Aged, Probability, Original Research, Analysis of Variance, Univariate analysis, COPD, business.industry, Total Lung Capacity, Respiratory disease, Middle Aged, respiratory system, Airway obstruction, medicine.disease, Respiratory Function Tests, respiratory tract diseases, Airway Obstruction, Dyspnea, medicine.anatomical_structure, Pulmonary Emphysema, Multivariate Analysis, Cardiology, Female, Pulmonary Ventilation, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business, Airway, Respiratory tract
Abstract

Background CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV 1 and percent predicted value of FEV 1 with CT scan measures of emphysema and airway disease. Results In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT ( r = −0.28, p = 0.0001) and SRWA ( r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV 1 % predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV 1 % predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.

Published
2009
Full Text
View/download PDF

12. Bronchoscopic Approach to COPD

Author

Michael Machuzak, Demet Karnak, Atul C. Mehta, Thomas R. Gildea, Hina Sahi, and Yvonne Meli

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, COPD, Lung, medicine.diagnostic_test, business.industry, medicine.medical_treatment, medicine.disease, Pulmonary Disease, Chronic Obstructive, Pneumonectomy, Bronchoscopes, medicine.anatomical_structure, Quality of life, Bronchoscopy, Humans, Medicine, Smoking cessation, Lung volumes, business, Intensive care medicine, Airway
Abstract

Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition that has frequent morbidity and mortality, with associated costs of US $ 2.5 billion annually and nearly 14,000 deaths each year. In the most advanced stages it causes debilitating breathlessness which is not improved despite maximal medical therapy including smoking cessation, bronchodilators, steroids and supplemental oxygen. Limitations of medical therapy led to the development of several surgical techniques to improve quality of life. However, surgical techniques still carry substantial morbidity even if the mortality is low at centers with larger experience; hence investigators are vigorously pursuing research into innovative, alternative methods for achieving lung volume reduction (LVR), in recent years. Endoscopic techniques for LVR are proposed, based on two main approaches, either closing of anatomical airway passages into destroyed lobe/segment of the lung to affect a collapse and reduction in volume or opening extra-anatomical airway passages, aimed at improving expiratory collateral flow from hyper-inflated areas bypassing the flow limited segments of the emphysematous airways. This article reviews the available endoscopic devises and the evidence supporting their use in the treatment of COPD.

Published
2008
Full Text
View/download PDF

13. Abstract T P85: Mammalian Target of Rapamycin (mTOR) Signaling Pathway Mediates Cerebral Ischemic Brain Damage

Author

ChangChun Hei, Xiao Yang, Ping Liu, Yvonne Meli, Haining Li, Eugene Yap, WanRui Ma, and P. Andy Li

Subjects
Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

BACKGROUND: Mammalian target of rapamycin (mTOR) signaling regulates cell energy metabolism and cell proliferation. Recent studies have demonstrated that mTOR activation is associated with increased cardiac infarct volume and necroptosis. The role of mTOR in cerebral ischemia has not been studied. The aim of this study is to explore how mTOR pathway behavior after cerebral ischemia and whether inhibition of mTOR reduces or increases ischemic brain damage. METHODS: Ten minutes of global ischemia was induced in Wistar rats (2-3 months old). Animals were either treatment with mTOR inhibitor rapamycin (6 mg/kg) or its vehicle. Animal brains were harvested after 3 hrs, 16 hrs and 7 days for histopathology and protein analyses. Sham-operated non-ischemic rats were used as control. Rapamycin was i.p. injected 1 hr after reperfusion in 7-day subgroups and injected 7 days prior to ischemia in 3 and 16 hrs subgroups. RESULTS: 10 minutes of global ischemia caused neuronal damage to the striatum, hippocampal CA1, and neocortical regions at 7 days of reperfusion. Levels of p-mTOR, p-S6K were increased significantly after 3 and 16 hrs in both the hippocampus and cortex. In addition, p-Akt and cytochrome c were elevated in the hippocampi after 3 hrs, peaked at 16 hrs and remained elevated after 7 days of reperfusion. Post-ischemic treatment with rapamycin 1 hrs after reperfusion significantly reduced brain damage in the CA1 and cortical areas at 7 days of reperfusion. Levels of p-mTOR, p-S6K, p-Akt and cytochrome c were significantly suppressed by rapamycin in non-ischemic and ischemic animals. CONCLUSION: Cerebral ischemia activates mTOR signaling pathway and inhibition of mTOR activativity reduces ischemic brain damage.

Published
2015
Full Text
View/download PDF

14. Role of Flexible Bronchoscopy in Immunocompromised Patients With Lung Infiltrates

Author

James K. Stoller, Prasoon Jain, Sunder Sandur, Atul C. Mehta, Alejandro C. Arroliga, and Yvonne Meli

Subjects
Adult, Lung Diseases, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung biopsy, Opportunistic Infections, Critical Care and Intensive Care Medicine, Risk Assessment, Sensitivity and Specificity, Gastroenterology, Serology, Cohort Studies, Immunocompromised Host, Bronchoscopy, Fraction of inspired oxygen, Internal medicine, Biopsy, Confidence Intervals, medicine, Fiber Optic Technology, Humans, Prospective Studies, Prospective cohort study, Aged, Analysis of Variance, medicine.diagnostic_test, business.industry, Biopsy, Needle, Pneumonia, Middle Aged, medicine.disease, Surgery, Pneumothorax, Female, Safety, Cardiology and Cardiovascular Medicine, business, Bronchoalveolar Lavage Fluid, Empiric therapy
Abstract

Study objective: To study the diagnostic role of flexible bronchoscopy (FB) in immunocompromised patients with pulmonary infiltrates. Design: Prospective, observational study. Setting: Tertiary care hospital. Patients: A total of 104 consecutive non-HIV-infected immunocompromised patients with lung infiltrates in whom FB was performed. Methods: The primary outcome measure was the diagnostic yield of FB, which was derived as the number of the diagnoses made using FB results divided by all final diagnoses. Final diagnoses were established using data from FB, surgical lung biopsy (SLB), and microbiology and serology testing, and by the clinical response to empiric therapy. We also studied the diagnostic yields of individual sampling procedures such as BAL, transbronchial biopsy (TBB), and protectedspecimen brush (PSB) sampling. Results: Overall, 128 diagnoses were made in 104 patients. The overall diagnostic yield of FB was 56.2% (95% confidence interval [CI], 47 to 64%). FB provided at least one diagnosis in 53 of 104 patients (51%; 95% CI, 40 to 62%). FB was more likely to establish the diagnosis when the lung infiltrate was due to an infectious agent (81%; 95% CI, 67 to 90%) than to a noninfectious process (56%; 95% CI, 43 to 67%; p 0.011). The diagnostic yields of BAL (38%; 95% CI, 30 to 47%) and TBB (38%; 95% CI, 27 to 51%) were similar (p 0.94). The diagnostic yield of PSB sampling was lower (13%; 95% CI 6 to 24%; p 0.001) than that of BAL. The combined diagnostic yield of BAL and TBB (70%; 95% CI, 57 to 80%) was higher than that of BAL alone (p < 0.001). Finally, the diagnostic yield of FB with PSB sampling, BAL, and TBB was similar to that of FB with BAL and TBB. The complication rate from FB was 21% (95% CI, 15 to 31%). Minor bleeding (13%) and pneumothorax (4%) were the most common complications. Conclusions: FB has a high diagnostic yield in immunocompromised patients with pulmonary infiltrates. Based on our results, we recommend performing TBB in these patients, whenever possible. (CHEST 2004; 125:712–722)

Published
2004
Full Text
View/download PDF

15. Electromagnetic Navigation Bronchoscopy Paired With Cone-Beam CT Confirmation for Biopsy of Difficult Peripheral Lung Lesions: A Prospective Pilot Trial

Author

Thomas R. Gildea, Louis Lam, Michael Machuzak, and Yvonne Meli

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung, Electromagnetics, medicine.diagnostic_test, business.industry, Pilot trial, Critical Care and Intensive Care Medicine, Peripheral, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030228 respiratory system, Bronchoscopy, Biopsy, Medicine, 030212 general & internal medicine, Radiology, Cardiology and Cardiovascular Medicine, business, Cone beam ct, Electromagnetic navigation bronchoscopy
Published
2016
Full Text
View/download PDF

18. Erosion of Implantable Cardioverter Defibrillator Patch Electrode Into Airways

Author

Atul C. Mehta, Thomas W. Rice, Patrick J. Tchou, Herbert P. Wiedemann, Yvonne Meli, and Asok Dasgupta

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung, Heart disease, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Respiratory disease, Critical Care and Intensive Care Medicine, medicine.disease, Implantable cardioverter-defibrillator, Surgery, medicine.anatomical_structure, Bronchoscopy, Ventricle, medicine, Differential diagnosis, Cardiology and Cardiovascular Medicine, business, Complication
Abstract

A 74-year-old man presented with a 9-month history of recurrent hemoptysis. He had implantable cardioverter defibrillator (ICD) patch electrodes placed 4 years before. A chest x-ray film showed crinkling of his posteriorly placed ICD patch which also appeared to have separated from his ventricle on a CT scan of the chest. Bronchoscopy localized the ICD patch electrode to the lower lobe of the left lung. He underwent a lobectomy and was treated with antibiotics at home. In patients with known ICD implantation, patch erosion into the airways should be considered in the differential diagnosis of recurrent hemoptysis.

Published
1998
Full Text
View/download PDF

19. Management of Benign Tracheal Stenosis: Gentle vs Rigid Dilation

Author

Sonali Sethi, Thomas R. Gildea, Joseph Cicenia, Danai Khemasuwan, Yvonne Meli, Wissam Jaber, Juan Wang, Michael Machuzak, Francisco A. Almeida, Atul Mehta, and Abdul Hamid Alraiyes

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Muscle Rigidity, business.industry, Internal medicine, medicine, Cardiology, Dilation (morphology), Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine, business, Tracheal Stenosis, Surgery
Published
2014
Full Text
View/download PDF

20. Utility of transbronchial needle aspiration in the diagnosis of endobronchial lesions

Author

Prasoon Jain, Asok Dasgupta, Yvonne Meli, Omar A. Minai, Atul C. Mehta, Alejandro C. Arroliga, and Sunder Sandur

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung Neoplasms, Bronchi, Critical Care and Intensive Care Medicine, Malignancy, Bronchial brushing, Bronchoscopy, Biopsy, medicine, Humans, Endobronchial Lesion, Prospective Studies, Prospective cohort study, Bronchus, medicine.diagnostic_test, business.industry, Respiratory disease, Biopsy, Needle, medicine.disease, carbohydrates (lipids), medicine.anatomical_structure, lipids (amino acids, peptides, and proteins), Radiology, Cardiology and Cardiovascular Medicine, business
Abstract

Background The utility of transbronchial needle aspiration (TBNA) in visible endobronchial lesions presenting as either an exophytic mass lesion (EML) or submucosal and peribronchial disease (SPD) is not well established. Objective To compare the yield of conventional diagnostic procedures (CDP) (bronchial washing, bronchial brushing, and endobronchial forceps biopsy) with that obtained from a combination of CDP and TBNA (CDP + TBNA). Design Prospective study of 55 patients. Setting Tertiary-care referral hospital. Results Of the 55 patients in whom malignancy was confirmed, CDP + TBNA identified 53 (96%) vs 42 (76%) identified by CDP (p = 0.001). The highest yield from any individual procedure was obtained by TBNA. Of the 23 patients with SPD, 22 (96%) were diagnosed using CDP + TBNA compared with 15 (65%) by CDP (p = 0.016); the yield from TBNA alone (22 of 23) in this group surpassed the combined yield from all other procedures. Although no statistically significant difference in yield was observed for EML, the use of TBNA identified four additional patients compared with CDP. Conclusion We conclude that the addition of TBNA to CDP increases diagnostic yield in patients with visible endobronchial lesions.

Published
1999

21. Uterine rhabdomyosarcoma metastatic to mediastinal lymph nodes: diagnosis by transbronchial needle aspiration

Author

Mani S. Kavuru, Yvonne Meli, Ralph J. Tuthill, Atul C. Mehta, and Lawrence S. Goldstein

Subjects
medicine.medical_specialty, Mediastinal lymphadenopathy, Mediastinal Neoplasms, Bronchoscopy, hemic and lymphatic diseases, Biopsy, Rhabdomyosarcoma, medicine, Humans, neoplasms, Lymph node, Aged, medicine.diagnostic_test, business.industry, Biopsy, Needle, Mediastinum, General Medicine, medicine.disease, Surgery, body regions, medicine.anatomical_structure, Lymphatic Metastasis, Uterine Neoplasms, Female, Radiology, Sarcoma, Chest radiograph, business
Abstract

Uterine rhabdomyosarcoma is rare, with only 60 reported cases. We describe an asymptomatic patient with metastatic uterine rhabdomyosarcoma manifested as extensive mediastinal lymphadenopathy. This 73-year-old woman had been previously treated for endometrial rhabdomyosarcoma and was referred to us when a right hilar density was seen on a chest radiograph; computed tomography showed a nodule in the right upper lobe and extensive right hilar and subcarinal lymphadenopathy. The diagnosis of metastatic rhabdomyosarcoma was made by fiberoptic bronchoscopy using transbronchial needle aspiration (TBNA). The patient is well 11 months after completing five cycles of chemotherapy. This is the first reported case of uterine rhabdomyosarcoma with metastasis to the mediastinum and the first case diagnosed with TBNA, which avoided the need for an invasive diagnostic procedure.

Published
1999

23. Clinical characteristics and prediction of pulmonary hypertension in severe emphysema

Author

Benjamin Nutter, Yvonne Meli, Omar A. Minai, Steven M. Scharf, Malcolm M. DeCamp, James K. Stoller, Gerard J. Criner, and Henry E. Fessler

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Hypertension, Pulmonary, Comorbidity, Pulmonary Artery, 030204 cardiovascular system & hematology, Doppler echocardiography, Hypoxemia, Pulmonary hypertension, 03 medical and health sciences, 0302 clinical medicine, DLCO, Forced Expiratory Volume, Internal medicine, medicine.artery, Prevalence, medicine, Humans, In patient, Aged, Emphysema, Carbon Monoxide, medicine.diagnostic_test, business.industry, Chronic obstructive pulmonary disease, Middle Aged, respiratory system, medicine.disease, Echocardiography, Doppler, 3. Good health, respiratory tract diseases, Oxygen, Pulmonary Emphysema, 030228 respiratory system, Lung disease, Pulmonary artery, Cardiology, Room air distribution, Female, medicine.symptom, Tomography, X-Ray Computed, business
Abstract

SummaryBackgroundWe explored the prevalence, clinical and physiologic correlates of pulmonary hypertension (PH), and screening strategies in patients with severe emphysema evaluated for the National Emphysema Treatment Trial (NETT).MethodsPatients undergoing Doppler echocardiography (DE) and right heart catheterization were included. Patients with mean pulmonary arterial pressure ≥25 mmHg (PH Group) were compared to the remainder (non-PH Group).ResultsOf 797 patients, 302 (38%) had PH and 18 (2.2%) had severe PH. Compared to the non-PH Group, patients with PH had lower % predicted FEV1 (p

Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results