1,607 results on '"Wayne, L."'
Search Results
2. Clinical Significance of [18F] Fluoro-2-Deoxy-d-Glucose/Computed Tomographic Avid Hilar Lymph Nodes in Esophageal Carcinoma Patients
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Ara A. Vaporciyan, David C. Rice, Jeremy J. Erasmus, Nicolas Zhou, Sonia L. Betancourt Cuellar, Ravi Rajaram, Stephen G. Swisher, Wayne L. Hofstetter, Mara B. Antonoff, Boris Sepesi, Garrett L. Walsh, Hope A. Feldman, and Reza J. Mehran
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Esophageal cancer ,medicine.disease ,Work-up ,Hilar lymph nodes ,Locally advanced disease ,Biopsy ,Carcinoma ,medicine ,Surgery ,Clinical significance ,Fdg pet ct ,Radiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background The assumption that increased [18F] fluoro-2-deoxy-d-glucose (FDG) uptake in hilar nodes on PET/CT imaging is indicative of distant metastasis can result in palliative rather than curative care in patients with esophageal cancer. This study aims to determine the significance of increased FDG uptake in hilar nodes in patients with potentially curable, locally advanced disease at initial staging. Methods We included patients with biopsy-proven esophageal carcinoma who had pretreatment FDG-PET/CT at initial staging, and follow-up imaging >1 year. We excluded patients with distant hematogeneous metastases. Hilar nodes were considered concerning for metastatic disease when SUV max was >2.5 or FDG uptake was visually > mediastinal background were examined. Results We reviewed FDG-PET CT scans from 806 patients treated for esophageal cancer from 2010-2018 and identified 42 patients with FDG avid hilar adenopathy. Thirteen patients underwent histological assessment and 29 were followed with imaging. None of the 42 patients were found to have distant metastatic disease on initial work up and all were treated curatively. In follow up, 2/42 patients eventually manifested hilar nodal metastases after treatment; one who had a biopsy-negative hilar node at initial staging and another who did not have a biopsy of the hilar node. Conclusions Increased FDG uptake in hilar nodes in patients with localized esophageal cancer was not indicative of non-regional nodal metastasis. Patients in these situations should be approached with curative intent. The need for biopsy of FDG avid hilar nodes in this cohort should be carefully considered due to the low diagnostic utility.
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- 2022
3. Modern Perioperative Practices May Mitigate Effects of Continued Smoking Among Lung Cancer Patients
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Nicolas Zhou, Wayne L. Hofstetter, Stephen G. Swisher, Kyle G. Mitchell, Garrett L. Walsh, Mara B. Antonoff, David C. Rice, Erin M. Corsini, Paul M. Cinciripini, Maher Karam-Hage, Boris Sepesi, Ara A. Vaporciyan, Reza J. Mehran, and Jack A. Roth
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,media_common.quotation_subject ,Disease ,Logistic regression ,Postoperative Complications ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Humans ,Medicine ,Lung cancer ,media_common ,business.industry ,Incidence ,Smoking ,Perioperative ,Abstinence ,medicine.disease ,Increased risk ,Cardiothoracic surgery ,Smoking cessation ,Smoking Cessation ,Surgery ,Neoplasm Recurrence, Local ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Although smokers are at an increased risk for postoperative pulmonary complications after thoracic surgery, the relationship between cessation timing and postoperative pulmonary complications has not been explored in an era of enhanced recovery protocols and active tobacco cessation programs. Because a strong preference exists among thoracic surgeons to delay surgery to continued smokers, we sought to evaluate this relationship in a modern era. Methods Patients undergoing lung resection for a diagnosis of non-small cell lung cancer from 2012 to 2017 were identified. Multivariable logistic regression was used to evaluate preoperative tobacco cessation timing to determine the impact on postoperative pulmonary complications. Results In all, 1038 ever smokers were identified. Patients were current smokers in 30 (3%) instances, and among former smokers, the preoperative cessation interval was 0 to 14 days in 10% (104), more than 14 days to 1 month in 6% (62), more than 1 month to 1 year in 18% (189), more than 1 to 5 years in 10% (107), and more than 5 years in 53% (546). Pulmonary complications occurred in 269 patients (26%). Multivariable analysis revealed that no group of recent or long-term quitters had superior outcomes in terms of pulmonary complications when evaluating various periods of abstinence in comparison with continued smokers and active quitters. Conclusions In an era of enhanced recovery protocols, minimally invasive surgery, and active tobacco cessation programs that may help patients to cut back, our data do not support the practice of delaying or denying surgery to patients who have difficulty quitting completely. Perioperative cessation counseling should be aimed at long-term benefits, including reduction of disease recurrence and secondary malignancies.
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- 2022
4. Synchronous Esophageal and Lung Cancers—Is Combined Anatomic Resection Appropriate?
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Tamar B. Nobel, Carmen L. Mueller, Jose Luis Ramirez-GarciaLuna, Hedi Zhao, Jonathan Cools-Lartigue, Lorenzo E. Ferri, Wayne L. Hofstetter, Manjit S. Bains, Daniela Molena, Jonathan Spicer, Ana Maria Misariu, and Stephen G. Swisher
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,Esophageal Neoplasms ,medicine.medical_treatment ,Anastomosis ,Postoperative Complications ,Humans ,Medicine ,Anatomic resection ,Neoadjuvant therapy ,Retrospective Studies ,Combined resection ,Lung ,business.industry ,Esophageal cancer ,medicine.disease ,Surgery ,Esophagectomy ,Treatment Outcome ,medicine.anatomical_structure ,Cohort ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background This study evaluates the safety and feasibility of combined resection for patients with synchronous pulmonary and esophageal cancer. Methods Patients undergoing esophagectomy between 1997 and 2019 were identified from prospectively collected databases at three tertiary referral centers, and those with combined anatomic lung resection at the same setting were identified. This cohort was then matched in a 1:3 ratio to esophagectomy alone cases, based on age, sex, pathologic stage, neoadjuvant therapy, and surgical procedure. Demographic data, peri-operative data, post-operative complications were compared. Statistical analysis included unpaired t-test, Fisher’s exact or chi-squared test and Gehan-Breslow analysis. Results Of 4729 esophagectomies, combined anatomic lung resection was performed in 18 patients with discrete pulmonary lesions. Matching yielded 49 patients who underwent esophagectomy only and was statistically similar compared to patients undergoing combined resections. Ivor Lewis esophagectomy and lobectomy were the most frequent procedures. Combined resections did not have a higher overall complication rate than esophagectomy alone, rather these patients had fewer overall complications (56% vs 84%; p=0.02). Specifically, there was not difference in anastomotic leak (17% vs. 18%) or pulmonary complications (39% vs. 33%) between combined resection and esophagectomy alone. No post-operative mortality was identified, and median overall survival was 4.1 years versus 6.5 years (p=0.10). Conclusions Patients with synchronous localized lung and esophageal cancer, although rare, should not be biased towards non-surgical therapy, as the morbidity associated with combined esophagectomy and anatomic lung resection does not differ significantly from esophagectomy alone in this highly selected group of patients.
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- 2022
5. Animating Human Athletics
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David C. Brogan, Jessica K. Hodgins, Wayne L. Wooten, and James F. O'Brien
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FOS: Computer and information sciences ,business.industry ,Computer science ,I.3.5 ,Animation ,Motion control ,Graphics (cs.GR) ,Motion (physics) ,Dynamic simulation ,Computer Science - Graphics ,Computer vision ,Artificial intelligence ,business ,Computer animation ,Simulation ,ComputingMethodologies_COMPUTERGRAPHICS - Abstract
This paper describes algorithms for the animation of men and women performing three dynamic athletic behaviors: running, bicycling, and vaulting. We animate these behaviors using control algorithms that cause a physically realistic model to perform the desired maneuver. For example, control algorithms allow the simulated humans to maintain balance while moving their arms, to run or bicycle at a variety of speeds, and to perform a handspring vault. Algorithms for group behaviors allow a number of simulated bicyclists to ride as a group while avoiding simple patterns of obstacles. We add secondary motion to the animations with spring-mass simulations of clothing driven by the rigid-body motion of the simulated human. For each simulation, we compare the computed motion to that of humans performing similar maneuvers both qualitatively through the comparison of real and simulated video images and quantitatively through the comparison of simulated and biomechanical data., Alternate location: http://graphics.berkeley.edu/papers/Hodgins-AHA-1995-08 8 pages, figures
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- 2023
6. Thrombosis in Extracorporeal Membrane Oxygenation (ECMO) Circuits
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Cristina A Figueroa Villalba, Wayne L. Chandler, Robyn C Reed, and David Michael McMullan
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medicine.medical_specialty ,Antifibrinolytic ,medicine.drug_class ,medicine.medical_treatment ,Biomedical Engineering ,Biophysics ,Bioengineering ,Oxygenators ,Biomaterials ,Extracorporeal Membrane Oxygenation ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Extracorporeal membrane oxygenation ,Humans ,cardiovascular diseases ,Thrombus ,Child ,Oxygenator ,Oxygenators, Membrane ,Bowel infarction ,business.industry ,Thrombosis ,General Medicine ,medicine.disease ,Venous thrombosis ,cardiovascular system ,Cardiology ,Complication ,business ,circulatory and respiratory physiology - Abstract
Thrombosis in extracorporeal membrane oxygenation (ECMO) circuits remains a frequent complication. We characterize the location, extent, structure, and clinical implications of thrombi in 53 ECMO circuits from 46 pediatric patients. The tubing, pump, and oxygenator were examined for visible thrombi. Representative samples of thrombi were collected for histologic, immunofluorescence, and immunohistochemical analysis. Thrombi were found in 81% of ECMO circuits. The most clinically significant were inflow oxygenator membrane surface thrombi (11% of circuits), arterial tubing thrombi (30%), and venous tubing (26%) or connector thrombi (26%). Oxygenator membrane surface thrombi resulted in rapidly increasing delta pressure across the oxygenator over 1-2 days, oxygenator failure, and circuit replacement. Oxygenator membrane surface thrombi were associated with intravascular venous thrombosis and bacterial infection before starting ECMO. Arterial cannula/tubing thrombi led in one case to aortic and mesenteric artery thrombosis followed by bowel infarction. In 11% of cases, venous tubing thrombi grew large enough to break off and embolize to the pump, resulting in increased hemolysis. Antifibrinolytic therapy during ECMO was associated with an increased risk of pump thromboembolism. Other less clinically significant thrombi included pump axle thrombi with thrombus fragments trapped in the oxygenator (45%), and deep oxygenator membrane thrombi (15%). Examination of ECMO circuits after removal is a useful quality improvement tool that can elucidate the cause of circuit problems, indicate patients at increased risk of thrombosis, and suggest areas for possible improvements.
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- 2021
7. Doxorubicin in combination with cisplatin, 5‐flourouracil, and vincristine is feasible and effective in unresectable hepatoblastoma: A Children's Oncology Group study
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Eugene D. McGahren, M. Beth McCarville, Howard M. Katzenstein, Carlos Rodriguez-Galindo, Rebecka L. Meyers, Jin Piao, Wayne L. Furman, Nadia Chung, Christopher B. Weldon, Mark Krailo, Alexander J. Towbin, Patrick A. Thompson, Allison F. O'Neill, Sarangarajan Ranganathan, Stephen P. Dunn, Marcio H. Malogolowkin, Milton J. Finegold, Jessica Randazzo, Angela D. Trobaugh-Lotrario, Max R. Langham, and Gregory M. Tiao
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Hepatoblastoma ,Oncology ,Cancer Research ,Vincristine ,medicine.medical_specialty ,Article ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Mucositis ,Humans ,Adverse effect ,Cisplatin ,business.industry ,Liver Neoplasms ,medicine.disease ,Clinical trial ,Regimen ,Treatment Outcome ,Doxorubicin ,Feasibility Studies ,business ,Febrile neutropenia ,medicine.drug - Abstract
Background The Children's Oncology Group (COG) adopted cisplatin, 5-flourouracil, and vincristine (C5V) as standard therapy after the INT-0098 legacy study showed statistically equivalent survival but less toxicity in comparison with cisplatin and doxorubicin. Subsequent experience demonstrated doxorubicin to be effective in patients with recurrent disease after C5V, and this suggested that it could be incorporated to intensify therapy for patients with advanced disease. Methods In this nonrandomized, phase 3 COG trial, the primary aim was to explore the feasibility and toxicity of a novel therapeutic cisplatin, 5-flourouracil, vincristine, and doxorubicin (C5VD) regimen with the addition of doxorubicin to C5V for patients considered to be at intermediate risk. Patients were eligible if they had unresectable, nonmetastatic disease. Patients with a complete resection at diagnosis and local pathologic evidence of small cell undifferentiated histology were also eligible for an assessment of feasibility. Results One hundred two evaluable patients enrolled between September 14, 2009, and March 12, 2012. Delivery of C5VD was feasible and tolerable: the mean percentages of the target doses delivered were 96% (95% CI, 94%-97%) for cisplatin, 96% (95% CI, 94%-97%) for 5-fluorouracil, 95% (95% CI, 93%-97%) for doxorubicin, and 90% (95% CI, 87%-93%) for vincristine. Toxicity was within expectations, with death as a first event in 1 patient. The most common adverse events were febrile neutropenia (n = 55 [54%]), infection (n = 48 [47%]), mucositis (n = 31 [30%]), hypokalemia (n = 39 [38%]), and elevated aspartate aminotransferase (n = 28 [27%]). The 5-year event-free and overall survival rates for the 93 patients who did not have complete resection at diagnosis were 88% (95% CI, 79%-93%) and 95% (95% CI, 87%-98%), respectively. Conclusions The addition of doxorubicin to the previous standard regimen of C5V is feasible, tolerable, and efficacious, and this suggests that C5VD is a good regimen for future clinical trials.
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- 2021
8. Pharmacokinetically guided dosing of oral sorafenib in pediatric hepatocellular carcinoma: A simulation study
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John C. Panetta, Wayne L. Furman, Jessica Gartrell, Olivia Campagne, and Clinton F. Stewart
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Male ,Sorafenib ,030213 general clinical medicine ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Adolescent ,Dose ,Urology ,RM1-950 ,Models, Biological ,030226 pharmacology & pharmacy ,Article ,General Biochemistry, Genetics and Molecular Biology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,medicine ,Humans ,Dosing ,General Pharmacology, Toxicology and Pharmaceutics ,Child ,business.industry ,Research ,General Neuroscience ,Liver Neoplasms ,Infant ,Articles ,General Medicine ,Clinical trial ,Tolerability ,Child, Preschool ,Practice Guidelines as Topic ,Toxicity ,Female ,Therapeutics. Pharmacology ,Public aspects of medicine ,RA1-1270 ,business ,Pediatric Hepatocellular Carcinoma ,medicine.drug - Abstract
Sorafenib improves outcomes in adult hepatocellular carcinoma; however, hand foot skin reaction (HFSR) is a dose limiting toxicity of sorafenib that limits its use. HFSR has been associated with sorafenib systemic exposure. The objective of this study was to use modeling and simulation to determine whether using pharmacokinetically guided dosing to achieve a predefined sorafenib target range could reduce the rate of HFSR. Sorafenib steady‐state exposures (area under the concentration curve from 0 to 12‐h [AUC0–>12 h]) were simulated using published sorafenib pharmacokinetics at either a fixed dosage (90 mg/m2/dose) or a pharmacokinetically guided dose targeting an AUC0–>12 h between 20 and 55 h µg/ml. Dosages were either rounded to the nearest quarter of a tablet (50 mg) or capsule (10 mg). A Cox proportional hazard model from a previously published study was used to quantify HFSR toxicity. Simulations showed that in‐target studies increased from 50% using fixed doses with tablets to 74% using pharmacokinetically guided dosing with capsules. The power to observe at least 4 of 6 patients in the target range increased from 33% using fixed dosing with tablets to 80% using pharmacokinetically guided with capsules. The expected HFSR toxicity rate decreased from 22% using fixed doses with tablets to 16% using pharmacokinetically guided dosing with capsules. The power to observe less than 6 of 24 studies with HFSR toxicity increased from 51% using fixed dosing with tablets to 88% using pharmacokinetically guided with capsules. Our simulations provide the rationale to use pharmacokinetically guided sorafenib dosing to maintain effective exposures that potentially improve tolerability in pediatric clinical trials.
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- 2021
9. Interstitial lung disease in children with Rubinstein‐Taybi syndrome
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Mindy K. Ross, William A. Gower, Ceila E. Loughlin, Anil G. Jegga, Jagila Minso, Simon S. Wong, Wayne L. Furman, Lauraine H. Rivier, Lauren Bradford, Xiaoping Li, Gail H. Deutsch, Mateja Cernelc-Kohan, Timothy J. Vece, Caitlin Hurley, Dennis C. Stokes, James S. Hagood, and Katayoon Shayan
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Rubinstein-Taybi Syndrome ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Pathology ,Lung ,business.industry ,H&E stain ,Interstitial lung disease ,Surfactant protein C ,Lung biopsy ,respiratory system ,medicine.disease ,CREB-Binding Protein ,Staining ,medicine.anatomical_structure ,Fibrosis ,Mutation ,Exome Sequencing ,Pediatrics, Perinatology and Child Health ,medicine ,Humans ,Histopathology ,Child ,Lung Diseases, Interstitial ,business - Abstract
Introduction Rubinstein-Taybi syndrome (RSTS) is a rare genetic syndrome caused primarily by a mutation in the CREBBP gene found on chromosome 16. Patients with RSTS are at greater risk for a variety of medical problems, including upper airway obstruction and aspiration. Childhood interstitial lung disease (ILD) thus far has not been definitively linked to RSTS. Here we present three patients with RSTS who developed ILD and discuss possible mechanisms by which a mutation in CREBBP may be involved in the development of ILD. Methods Routine hematoxylin and eosin staining was performed on lung biopsy tissue for histological analysis. Immunofluorescent staining was performed on lung biopsy tissue for markers of fibrosis, surfactant deficiency and histone acetylation. Cases 1 and 2 had standard clinical microarray analysis. Case 3 had whole exome sequencing. Bioinformatics analyses were performed to identify possible causative genes using ToppGene. Results CT images in all cases showed consolidated densities overlying ground glass opacities. Lung histopathology revealed accumulation of proteinaceous material within alveolar spaces, evidence of fibrosis, and increased alveolar macrophages. Immunofluorescent staining showed increase in surfactant protein C staining, patchy areas of increased aSMA staining, and increased staining for acetylated histone 2 and histone 3 lysine 9. Discussion Clinical characteristics, radiographic imaging, lung histopathology, and immunofluorescent staining results shared by all cases demonstrated findings consistent with ILD. Immunofluorescent staining suggests two possible mechanisms for the development of ILD: abnormal surfactant metabolism and/or persistent activation of myofibroblasts. These two pathways could be related to dysfunctional CREBBP protein. This article is protected by copyright. All rights reserved.
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- 2021
10. Stereotactic ablative radiotherapy for operable stage I non-small-cell lung cancer (revised STARS): long-term results of a single-arm, prospective trial with prespecified comparison to surgery
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Mara B. Antonoff, Song Gao, Saumil Gandhi, John V. Heymach, Arlene M. Correa, Vivek Verma, Zhongxing Liao, James W. Welsh, Ravi Rajaram, Wayne L. Hofstetter, Ritsuko Komaki, Garrett L. Walsh, Lei Feng, Joe Y. Chang, Donald A. Berry, Aileen Chen, R Sadagopan, Stephen E. McRae, Peter A Balter, Reza J. Mehran, Matthew S. Ning, Jack A. Roth, Craig DeGraaf, Steven H. Lin, Melenda Jeter, Ara A. Vaporciyan, Xiaochun Wang, Paige L. Nitsch, Michael S. O'Reilly, Quynh-Nhu Nguyen, Boris Sepesi, Julianne M. Pollard-Larkin, David C. Rice, Stephen G. Swisher, and Percy Lee
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Male ,medicine.medical_specialty ,Time Factors ,Lung Neoplasms ,Radiosurgery ,SABR volatility model ,Article ,Carcinoma, Non-Small-Cell Lung ,medicine ,Clinical endpoint ,Humans ,Prospective Studies ,Progression-free survival ,Pneumonectomy ,Prospective cohort study ,Lung cancer ,Aged ,Neoplasm Staging ,Performance status ,Thoracic Surgery, Video-Assisted ,business.industry ,Hazard ratio ,Middle Aged ,medicine.disease ,Texas ,Progression-Free Survival ,Surgery ,Clinical trial ,Oncology ,Lymph Node Excision ,Female ,business - Abstract
Summary Background A previous pooled analysis of the STARS and ROSEL trials showed higher survival after stereotactic ablative radiotherapy (SABR) than with surgery for operable early-stage non-small-cell lung cancer (NSCLC), but that analysis had notable limitations. This study reports long-term results of the revised STARS trial, in which the SABR group was re-accrued with a larger sample size, along with a protocol-specified propensity-matched comparison with a prospectively registered, contemporary institutional cohort of patients who underwent video-assisted thoracoscopic surgical lobectomy with mediastinal lymph node dissection (VATS L-MLND). Methods This single-arm prospective trial was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and enrolled patients aged 18 years or older with a Zubrod performance status of 0–2, newly diagnosed and histologically confirmed NSCLC with N0M0 disease (squamous cell, adenocarcinoma, large cell, or NSCLC not otherwise specified), and a tumour diameter of 3 cm or less. This trial did not include patients from the previous pooled analysis. SABR dosing was 54 Gy in three fractions (for peripheral lesions) or 50 Gy in four fractions (for central tumours; simultaneous integrated boost to gross tumour totalling 60 Gy). The primary endpoint was the 3-year overall survival. For the propensity-matching analysis, we used a surgical cohort from the MD Anderson Department of Thoracic and Cardiovascular Surgery's prospectively registered, institutional review board-approved database of all patients with clinical stage I NSCLC who underwent VATS L-MLND during the period of enrolment in this trial. Non-inferiority could be claimed if the 3-year overall survival rate after SABR was lower than that after VATS L-MLND by 12% or less and the upper bound of the 95% CI of the hazard ratio (HR) was less than 1·965. Propensity matching consisted of determining a propensity score using a multivariable logistic regression model including several covariates (age, tumour size, histology, performance status, and the interaction of age and sex); based on the propensity scores, one patient in the SABR group was randomly matched with one patient in the VATS L-MLND group using a 5:1 digit greedy match algorithm. This study is registered with ClinicalTrials.gov , NCT02357992 . Findings Between Sept 1, 2015, and Jan 31, 2017, 80 patients were enrolled and included in efficacy and safety analyses. Median follow-up time was 5·1 years (IQR 3·9–5·8). Overall survival was 91% (95% CI 85–98) at 3 years and 87% (79–95) at 5 years. SABR was tolerated well, with no grade 4–5 toxicity and one (1%) case each of grade 3 dyspnoea, grade 2 pneumonitis, and grade 2 lung fibrosis. No serious adverse events were recorded. Overall survival in the propensity-matched VATS L-MLND cohort was 91% (95% CI 85–98) at 3 years and 84% (76–93) at 5 years. Non-inferiority was claimed since the 3-year overall survival after SABR was not lower than that observed in the VATS L-MLND group. There was no significant difference in overall survival between the two patient cohorts (hazard ratio 0·86 [95% CI 0·45–1·65], p=0·65) from a multivariable analysis. Interpretation Long-term survival after SABR is non-inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains promising for such cases but multidisciplinary management is strongly recommended. Funding Varian Medical Systems and US National Cancer Institute (National Institutes of Health).
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- 2021
11. Optimizing Discharge After Shorter Hospitalizations: Lessons Learned Through After-Hours Calls with Thoracic Surgical Patients
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Stephen G. Swisher, Alisa N. Blumenthaler, Mara B. Antonoff, Wayne L. Hofstetter, Kavita Parikh, David C. Rice, Ara A. Vaporciyan, Nicolas Zhou, Reza J. Mehran, Garrett L. Walsh, Ravi Rajaram, and Boris Sepesi
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Thoracic Surgical Procedure ,business.industry ,Patient demographics ,Aftercare ,General Medicine ,Postoperative recovery ,Thoracic Surgical Procedures ,Surgical procedures ,After discharge ,Patient Discharge ,Telephone ,Cardiothoracic surgery ,Emergency medicine ,Humans ,Medicine ,Surgery ,Cardiology and Cardiovascular Medicine ,business ,Minimally invasive procedures ,Retrospective Studies ,Surgical patients - Abstract
Objective Minimally invasive procedures coupled with enhanced recovery pathways enable faster postoperative recovery and shorter hospitalizations. However, patients may experience unexpected concerns after return home, prompting after-hours calls. We aimed to characterize concerns prompting after-hours calls to improve discharge strategies. Methods A single-institution, retrospective review was conducted of thoracic surgical patients from 11/4/2019 to 6/14/2020. Records were reviewed and elements of patient demographics, surgical procedures, postoperative courses, reasons for calls, and outcome of calls were collected. We compared characteristics of patients who made after-hours calls to those who did not, and performed multivariable analysis to identify characteristics associated with making an after-hours call. Results During the study period, 379 patients underwent thoracic surgical procedures, among whom 88 (23.2%) initiated after-hours calls. Of these, 62 (70%) addressed patient symptoms, while 26 (30%) addressed patient questions including drain management, medications, and hospital policy questions. Patients making after-hours calls more frequently had undergone complex operations (26.1% vs 8.2%, P = 0.001), and were less likely to have received a standardized, clinician-initiated post-discharge telephone follow-up (29.5% vs 54.3%, P < 0.001). Complex operations increased likelihood of after-hours calls (OR: 3.33, 95% CI: 1.69-6.57, P < 0.001), while receipt of clinician-initiated telephone follow-up decreased likelihood of after-hours calls (OR: 0.38, 95% CI: 0.22-0.64, P < 0.001). There were no differences in emergency visits between the 2 groups (11% vs 8%, P = 0.370). Conclusions Despite efforts to optimize patient symptoms and knowledge prior to discharge, a substantial number of patients still have concerns after discharge. Many after-hours calls are related to knowledge gaps that may be addressed with improved predischarge education. Moreover, clinician-initiated telephone follow-up shows benefit in reducing after-hours calls.
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- 2021
12. A 54-year-old woman with chronic lithium toxicity
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Emily Austin, Wayne L. Gold, Peter E. Wu, and Jane Kobylianskii
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Weakness ,Pediatrics ,medicine.medical_specialty ,Bipolar Disorder ,Bipolar I disorder ,Administration, Oral ,Lithium ,chemistry.chemical_compound ,Lithium Carbonate ,Altered Mental Status ,Renal Dialysis ,Humans ,Medicine ,Medical history ,Practice ,business.industry ,Lithium carbonate ,General Medicine ,Emergency department ,Middle Aged ,medicine.disease ,Antidepressive Agents ,Treatment Outcome ,chemistry ,Cases ,Toxicity ,Fluid Therapy ,Female ,Drug Overdose ,medicine.symptom ,business ,Chronic lithium - Abstract
KEY POINTS A 54-year-old woman presented to the emergency department with a 2-day history of altered mental status, weakness and involuntary movements. Her medical history included bipolar I disorder, which had been diagnosed 32 years previously. Her prescribed medications were lithium carbonate 900
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- 2021
13. Assessment of the safety, pharmacokinetics and pharmacodynamics of GSK3335065, an inhibitor of kynurenine monooxygenase, in a randomised placebo‐controlled first‐in‐human study in healthy volunteers
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Catherine Muya, Sara Soleman, Alexander W. Krug, Sarah Walsh, Xinyi Zhu, Nicola Robertson, Richard J. Dimelow, William J. Guiney, Madelein Crause, Disala Fernando, Iain Uings, Georgios Vlasakakis, Marylise Bergeal, Wayne L. Wright, Yi Cui, Connie Parker, and Ciara Gorey
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Male ,Tachycardia ,Pharmacology ,Ventricular tachycardia ,Placebo ,Mixed Function Oxygenases ,chemistry.chemical_compound ,Double-Blind Method ,Pharmacokinetics ,Humans ,Medicine ,Pharmacology (medical) ,Adverse effect ,Kynurenine ,Volume of distribution ,business.industry ,medicine.disease ,Healthy Volunteers ,Pancreatitis ,Tolerability ,chemistry ,Acute Disease ,medicine.symptom ,business - Abstract
GSK3335065 is an inhibitor of kynurenine monooxygenase (KMO) being developed for the treatment of acute pancreatitis. Healthy male volunteers were administered ascending doses of GSK3335065 or matched placebo as a single intravenous bolus injection to assess safety, tolerability, pharmacokinetics and pharmacodynamics. GSK3335065 displayed an apparent volume of distribution between 20.6 L and 44.6 L, a clearance between 0.462 L/h and 0.805 L/hr and a terminal half-life between 31.3 and 34.5 hr. In the single subject who received 1.3 mg GSK3335065, changes in tryptophan pathway metabolites were observed consistent with the changes seen in preclinical species suggesting that KMO enzyme activity was partially inhibited. However, a broad complex ventricular tachycardia was observed in this subject, which was judged to be a Serious Adverse Event (SAE) and resulted in early termination of the study. While development of GSK3335065 was subsequently discontinued, significant confounding factors hinder a clear interpretation that the tachycardia was directly related to administration of the compound.
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- 2021
14. Esophagectomy or Total Gastrectomy for Siewert 2 Gastroesophageal Junction (GEJ) Adenocarcinoma? A Registry-Based Analysis
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Sheraz R. Markar, Wayne L. Hofstetter, Lorenzo E. Ferri, Alexander W. Phillips, Sivesh K. Kamarajah, and Ewen A. Griffiths
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education.field_of_study ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Hazard ratio ,Population ,030230 surgery ,medicine.disease ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Esophagectomy ,Surgical oncology ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,medicine ,Adenocarcinoma ,Surgery ,Gastrectomy ,business ,education ,Cohort study - Abstract
Backgrounds Due to a lack of randomized and large studies, the optimal surgical approach for Siewert 2 gastroesophageal junctional (GEJ) adenocarcinoma remains unknown. This population-based cohort study aimed to compare survival between esophagectomy and total gastrectomy for the treatment of Siewert 2 GEJ adenocarcinoma. Methods Data from the National Cancer Database (NCDB) from 2010 to 2016 was used to identify patients with non-metastatic Siewert 2 GEJ adenocarcinoma who received either esophagectomy (n = 999) or total gastrectomy (n = 8595). Propensity score-matching (PSM) and multivariable analyses were used to account for treatment selection bias. Results Comparison of the unmatched cohort’s baseline demographics showed that the patients who received esophagectomy were younger, had a lower burden of medical comorbidities, and had fewer clinical positive lymph nodes. The patients in the unmatched cohort who received gastrectomy had a significantly shorter overall survival than those who received esophagectomy (median, 47 vs. 68 months [p < 0.001]; 5-year survival, 45 % vs. 53 %). After matching, gastrectomy was associated with significantly reduced survival compared with esophagectomy (median, 51 vs. 68 months [p < 0.001]; 5-year survival, 47 % vs. 53 %), which remained in the adjusted analyses (hazard ratio [HR], 1.22; 95 % confidence interval [CI], 1.09–1.35; p < 0.001). Conclusions In this large-scale population study with propensity-matching to adjust for confounders, esophagectomy was prognostically superior to gastrectomy for the treatment of Siewert 2 GEJ adenocarcinoma despite comparable lymph node harvest, length of stay, and 90-day mortality. Adequately powered randomized controlled trials with robust surgical quality assurance are the next step in evaluating the prognostic outcomes of these surgical strategies for GEJ cancer.
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- 2021
15. Effect of primary colorectal cancer tumor location on survival after pulmonary metastasectomy
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Boris Sepesi, Stephen G. Swisher, Wayne L. Hofstetter, Reza J. Mehran, Garrett L. Walsh, Jack A. Roth, David C. Rice, Nicolas Zhou, Arlene M. Correa, Mara B. Antonoff, Van K. Morris, Erin M. Corsini, Ara A. Vaporciyan, and Kyle G. Mitchell
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Male ,Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Colorectal cancer ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Internal medicine ,medicine ,Humans ,Pneumonectomy ,Survival rate ,Aged ,Retrospective Studies ,Proportional hazards model ,business.industry ,Hazard ratio ,Middle Aged ,medicine.disease ,Primary tumor ,Confidence interval ,030228 respiratory system ,Female ,Surgery ,Metastasectomy ,Colorectal Neoplasms ,Cardiology and Cardiovascular Medicine ,business - Abstract
Objectives Although colorectal cancer bowel segment location has been shown to independently predict the outcomes in early stage disease, it has not been previously studied in the setting of pulmonary metastases. We sought to determine whether colorectal cancer location affects survival after pulmonary metastasectomy. Methods Patients who had undergone pulmonary metastasectomy for colorectal cancer at a single institution from 2011 to 2018 were reviewed. Univariable and multivariable Cox regression analyses were performed to identify predictors of overall survival and disease-free survival. The Kaplan-Meier survival method was used to determine differences between groups. Results A total of 194 patients were evaluated. The median follow-up, survival time, and 5-year survival rate were 36.8 months, 75.8 months, and 57%, respectively, and 122 patients (63%) had experienced disease recurrence at any location. On univariable analysis, age, primary tumor location, pulmonary nodule size, ≥3 pulmonary nodules, and intrathoracic nodal disease were associated with overall survival. On multivariable analysis, patients with left-sided tumors experienced a survival benefit (hazard ratio, 0.31; P = .036). Kaplan-Meier analysis revealed a median survival time of 90 months (95% confidence interval, 82 months to not reached) compared with 55 months (95% confidence interval, 49 months to not reached) for patients with left-sided and rectal tumors, respectively, after metastasectomy (P = .078). Location was not associated with disease-free survival on Cox multivariable regression. Conclusions We found that left-sided colorectal cancer is associated with prolonged survival after pulmonary metastasectomy. Future investigations are required to determine the validity of such findings, including the effect of location in the prognostication for patients who are candidates for pulmonary metastasectomy.
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- 2021
16. Probiotics and gut health: linking gut homeostasis and poultry productivity
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Wayne L. Bryden and Shaniko Shini
- Subjects
0301 basic medicine ,biology ,Gut barrier ,business.industry ,0402 animal and dairy science ,04 agricultural and veterinary sciences ,Gut flora ,Health benefits ,biology.organism_classification ,040201 dairy & animal science ,law.invention ,Biotechnology ,Structure and function ,03 medical and health sciences ,Probiotic ,030104 developmental biology ,law ,Barrier integrity ,Animal Science and Zoology ,business ,Productivity ,Gut homeostasis ,Food Science - Abstract
The use of probiotics in poultry production has increased rapidly, and this movement has been promoted by global events, such as the prohibition or decline in the use of antibiotic growth promotants in poultry feeds. There has been a persistent search for alternative feed additives, and probiotics have shown that they can restore the composition of the gut microbiota, and produce health benefits to the host, including improvements in performance. Probiotics have shown potential to increase productivity in poultry, especially in flocks challenged by stressors. However, the outcomes of probiotic use have not always been consistent. There is an increasing demand for well defined products that can be applied strategically, and currently, probiotic research is focusing on delineating their mechanisms of action in the gut that contribute to an improved efficacy. In particular, mechanisms involved in the maintenance and protection of intestinal barrier integrity and the role of the gut microbiota are being extensively investigated. It has been shown that probiotics modulate intestinal immune pathways both directly and through interactions with the gut microbiota. These interactions are key to maintaining gut homeostasis and function, and improving feed efficiency. Research has demonstrated that probiotics execute their effects through multiple mechanisms. The present review describes recent advances in probiotic use in poultry. It focuses on the current understanding of gut homeostasis and gut health in chickens, and how it can be assessed and improved through supplementation of poultry diets with probiotics in poultry diets. In particular, cellular and molecular mechanisms involved in the maintenance and protection of gut barrier structure and function are described. It also highlights important factors that influence probiotic efficacy and bird performance.
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- 2021
17. Interlaboratory Performance in Measurement of Dabigatran and Rivaroxaban
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Oksana Volod, Andrew J. Goodwin, Dong Chen, Huy P. Pham, James Alexander Isom, Karen A. Moser, John D. Olson, Russell A. Higgins, Amanda M. VanSandt, Kristi J. Smock, Geoffrey D. Wool, Thomas A. Long, Marian A. Rollins-Raval, Neil S Harris, and Wayne L. Chandler
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medicine.medical_specialty ,Pyridones ,Coefficient of variation ,Administration, Oral ,Thrombin time ,Gastroenterology ,Antithrombins ,Pathology and Forensic Medicine ,Dabigatran ,Rivaroxaban ,Internal medicine ,External quality assessment ,medicine ,Humans ,Prothrombin time ,medicine.diagnostic_test ,business.industry ,Anticoagulants ,General Medicine ,Medical Laboratory Technology ,Oral anticoagulant ,Pyrazoles ,Partial Thromboplastin Time ,Blood Coagulation Tests ,business ,Partial thromboplastin time ,medicine.drug - Abstract
Context.— Assessing direct oral anticoagulant (DOAC) drug levels by reliable laboratory assays is necessary in a number of clinical scenarios. Objective.— To evaluate the performance of DOAC-specific assays for various concentrations of dabigatran and rivaroxaban, assess the interlaboratory variability in measurement of these DOACs, and investigate the responsiveness of the routine clotting assays to various concentrations of these oral anticoagulants. Design.— College of American Pathologists proficiency testing survey data from 2013 to 2016 were summarized and analyzed. Results.— For dabigatran, the interlaboratory coefficient of variation (CV) of ecarin chromogenic assay was broad (ranging from 7.5% to 29.1%, 6.3% to 15.5%, and 6.8% to 9.0% for 100-ng/mL, 200-ng/mL, and 400-ng/mL targeted drug concentrations, respectively). The CV for diluted thrombin time for dabigatran was better overall (ranging from 11.6% to 17.2%, 9.3% to 12.3, and 7.1% to 11.2% for 100 ng/mL, 200 ng/mL, and 400 ng/mL, respectively). The rivaroxaban-calibrated anti-Xa assay CVs also showed variability (ranging from 11.5% to 22.2%, 7.2% to 10.9%, and 6.4% to 8.1% for 50-ng/mL, 200-ng/mL, and 400-ng/mL targeted drug concentrations, respectively). The prothrombin time (PT) and activated partial thromboplastin time (aPTT) showed variable dose- and reagent-dependent responsiveness to DOACs: PT was more responsive to rivaroxaban and aPTT to dabigatran. The undiluted thrombin time showed maximum prolongation across all 3 dabigatran concentrations, making it too sensitive for drug-level monitoring, but supporting its use as a qualitative screening assay. Conclusions.— DOAC-specific assays performed reasonably well. While PT and aPTT cannot be used safely to determine DOAC degree of anticoagulation, a normal thrombin time excludes the presence of dabigatran.
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- 2021
18. Monoclonal Antibody Therapies for High Risk Neuroblastoma
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Wayne L. Furman
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Oncology ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,anti-disialoganglioside ,Review ,Disease ,Monoclonal antibody ,neuroblastoma ,Rheumatology ,Antigen ,Internal medicine ,Neuroblastoma ,medicine ,Immunology and Allergy ,Pharmacology (medical) ,High risk neuroblastoma ,business.industry ,Gastroenterology ,Multimodal therapy ,Immunotherapy ,anti-GD2 ,medicine.disease ,Regimen ,chimeric ,effector cells ,immunotherapy ,business - Abstract
Monoclonal antibodies (mAbs) are part of the standard of care for the treatment of many adult solid tumors. Until recently none have been approved for use in children with solid tumors. Neuroblastoma (NB) is the most common extracranial solid tumor in children. Those with high-risk disease, despite treatment with very intensive multimodal therapy, still have poor overall survival. Results of treatment with an immunotherapy regimen using a chimeric (human/mouse) mAb against a cell surface disialoganglioside (GD2) have changed the standard of care for these children and resulted in the first approval of a mAb for use in children with solid tumors. This article will review the use of the various anti-GD2 mAbs in children with NB, methods that have been or are being evaluated for enhancing their efficacy, as well as review other promising antigenic targets for the therapeutic use of mAbs in children with NB.
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- 2021
19. Chemoradiotherapy Followed by Active Surveillance Versus Standard Esophagectomy for Esophageal Cancer
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Thomas N. Walsh, Berend J van der Wilk, Wayne L. Hofstetter, Carlo Castoro, Jaffer A. Ajani, Guillaume Piessen, Heidi Furlong, Bas P. L. Wijnhoven, Sjoerd M. Lagarde, J. Jan B. van Lanschot, Ben M Eyck, Sung-Bae Kim, Daan Nieboer, Jong H. Kim, Rita Alfieri, Surgery, and Public Health
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medicine.medical_specialty ,Randomization ,Esophageal Neoplasms ,business.industry ,medicine.medical_treatment ,Chemoradiotherapy ,Patient data ,Esophageal cancer ,medicine.disease ,Esophagectomy ,SDG 3 - Good Health and Well-being ,Internal medicine ,Meta-analysis ,Propensity score matching ,medicine ,Humans ,Surgery ,Patient Generated Health Data ,Progression-free survival ,Watchful Waiting ,business - Abstract
OBJECTIVE: To compare overall survival of patients with a cCR undergoing active surveillance versus standard esophagectomy.SUMMARY OF BACKGROUND DATA: One-third of patients with esophageal cancer have a pathologically complete response in the resection specimen after neoadjuvant chemoradiotherapy. Active surveillance may be of benefit in patients with cCR, determined with diagnostics during response evaluations after chemoradiotherapy.METHODS: A systematic review and meta-analysis was performed comparing overall survival between patients with cCR after chemoradiotherapy undergoing active surveillance versus standard esophagectomy. Authors were contacted to supply individual patient data. Overall and progression-free survival were compared using random effects meta-analysis of randomized or propensity score matched data. Locoregional recurrence rate was assessed. The study-protocol was registered (PROSPERO: CRD42020167070).RESULTS: Seven studies were identified comprising 788 patients, of which after randomization or propensity score matching yielded 196 active surveillance and 257 standard esophagectomy patients. All authors provided individual patient data. The risk of all-cause mortality for active surveillance was 1.08 [95% confidence interval (CI): 0.62-1.87, P = 0.75] after intention-to-treat analysis and 0.93 (95% CI: 0.56-1.54, P = 0.75) after per-protocol analysis. The risk of progression or all-cause mortality for active surveillance was 1.14 (95% CI: 0.83-1.58, P = 0.36). Five-year locoregional recurrence rate during active surveillance was 40% (95% CI: 26%-59%). 95% of active surveillance patients undergoing postponed esophagectomy for locoregional recurrence had radical resection.CONCLUSIONS: Overall survival was comparable in patients with cCR after chemoradiotherapy undergoing active surveillance or standard esophagectomy. Diagnostic follow-up is mandatory in active surveillance and postponed esophagectomy should be offered to operable patients in case of locoregional recurrence.
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- 2021
20. Diuresis-Related Weight Loss Reflects Interstitial Compartment Decongestion with Minimal Impact on Intravascular Volume Expansion or Outcomes in Post-Acute Heart Failure
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Wayne L. Miller, Diane E. Grill, Brian P. Mullan, and Ronstan Lobo
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Confounding ,Diuresis ,medicine.disease ,Interquartile range ,Weight loss ,Interstitial fluid ,Internal medicine ,Heart failure ,medicine ,Intravascular volume status ,Cardiology ,Diuretic ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Findings from heart failure (HF) studies linking diuresis-related weight loss to clinical decongestion and outcomes are mixed. Differential responses of interstitial and intravascular volume compartments to diuretic therapy and heterogeneity in volume profiles may confound the clinical interpretation of weight loss in patients with HF. Methods and Results Data were prospectively collected in hospitalized patients requiring diuresis. Plasma volume (PV) was measured using I-131-labelled albumin indicator-dilution methodology. The cohort was stratified by tertiles of weight loss and analyzed for interstitial fluid loss relative to changes in PV and HF-related morality or first rehospitalization. Among 92 patients, the admission PV was expanded +42% (4.7 ± 1.2 L) above normal with significant variability (14% normal PV, 18% mild-moderate expansion, and 68% with large PV expansion [>+25% above normal]). With diuresis there were proportional decreases in interstitial volume (–6.5 ± 4.4%) and PV (–7.5 ± 11%); however, absolute decreases in the PV (–254 mL, interquartile range –11 to –583 mL) were less than 10% of interstitial volume loss (–5040 mL, interquartile range –2800 to –7989 mL); greater interstitial fluid loss did not translate into better outcomes (log-rank P = .430). Conclusions Diuresis-related decreases in weight reflect fluid loss from the interstitial compartment with only minor changes in the PV and without an impact on outcomes. Further, the degree of PV expansion at hospital admission does not drive the magnitude of the diuresis response, even with a wide spectrum of body weights; interstitial fluid overload is preferentially targeted and PV relatively preserved. Therefore, greater interstitial fluid loss reflects clinical decongestion, but not better outcomes, and a limited association with intravascular volume profiles potentially confounding weight loss as a prognostic metric in HF.
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- 2021
21. Immunotherapy in Patients With Locally Advanced Esophageal Carcinoma: ASCO Treatment of Locally Advanced Esophageal Carcinoma Guideline Rapid Recommendation Update
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Locally Advanced Esophageal Carcinoma Guideline Expert Panel, Wayne L. Hofstetter, Manish A. Shah, and Erin B. Kennedy
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Cancer Research ,medicine.medical_specialty ,Time Factors ,Esophageal Neoplasms ,medicine.medical_treatment ,Locally advanced ,MEDLINE ,Adenocarcinoma ,medicine ,Carcinoma ,Humans ,In patient ,Guideline development ,Intensive care medicine ,Immune Checkpoint Inhibitors ,Neoplasm Staging ,business.industry ,Cancer ,Immunotherapy ,Guideline ,medicine.disease ,Nivolumab ,Treatment Outcome ,Oncology ,Esophageal Squamous Cell Carcinoma ,business - Abstract
ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options.
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- 2021
22. Neoadjuvant chemoradiotherapy or chemotherapy alone for oesophageal cancer: population-based cohort study
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Lorenzo E. Ferri, Sivesh K. Kamarajah, Wayne L. Hofstetter, Alexander W. Phillips, and Sheraz R. Markar
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Esophageal Neoplasms ,medicine.medical_treatment ,Antineoplastic Agents ,Adenocarcinoma ,030230 surgery ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Propensity Score ,Survival rate ,Neoadjuvant therapy ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,business.industry ,Hazard ratio ,Cancer ,Middle Aged ,Esophageal cancer ,medicine.disease ,Survival Analysis ,Chemotherapy regimen ,Neoadjuvant Therapy ,Esophagectomy ,030220 oncology & carcinogenesis ,Cohort ,Carcinoma, Squamous Cell ,Female ,Surgery ,business - Abstract
Background Although both neoadjuvant chemoradiotherapy (nCRT) and chemotherapy (nCT) are used as neoadjuvant treatment for oesophageal cancer, it is unknown whether one provides a survival advantage over the other, particularly with respect to histological subtype. This study aimed to compare prognosis after nCRT and nCT in patients undergoing oesophagectomy for oesophageal adenocarcinoma (OAC) or squamous cell carcinoma (OSCC). Methods Data from the National Cancer Database (2006–2015) were used to identify patients with OAC and OSCC. Propensity score matching and Cox multivariable analyses were used to account for treatment selection biases. Results The study included 11 167 patients with OAC (nCRT 9972, 89.3 per cent; nCT 1195, 10.7 per cent) and 2367 with OSCC (nCRT 2155, 91.0 per cent; nCT 212, 9.0 per cent). In the matched OAC cohort, nCRT provided higher rates of complete pathological response (35.1 versus 21.0 per cent; P Conclusion Despite pathological benefits, including primary tumour response to nCRT, there was no prognostic benefit of nCRT compared with nCT for OAC suggesting that these two modalities are equally acceptable. However, for OSCC, nCRT followed by surgery appears to remain the optimal treatment approach.
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- 2021
23. Simultaneous versus staged resections for bilateral pulmonary metastases
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Wayne L. Hofstetter, Ara A. Vaporciyan, Mara B. Antonoff, Ravi Rajaram, Nicolas Zhou, Boris Sepesi, David C. Rice, Andres Zorrilla-Vaca, Reza J. Mehran, and Hope A. Feldman
- Subjects
Adult ,Male ,medicine.medical_specialty ,Lung Neoplasms ,Adolescent ,Coronavirus disease 2019 (COVID-19) ,medicine.medical_treatment ,030230 surgery ,03 medical and health sciences ,Pneumonectomy ,0302 clinical medicine ,medicine ,Humans ,Thoracotomy ,Aged ,Neoplasm Staging ,Retrospective Studies ,Thoracic Surgery, Video-Assisted ,business.industry ,Metastasectomy ,Retrospective cohort study ,General Medicine ,Perioperative ,Middle Aged ,Surgery ,Oncology ,030220 oncology & carcinogenesis ,Propensity score matching ,Cohort ,Female ,Colorectal Neoplasms ,business - Abstract
BACKGROUND: For patients with bilateral pulmonary metastases, staged resections have historically been the preferred surgical intervention. During the spring of 2020, the COVID-19 pandemic made patient travel to the hospital challenging and necessitated reduction in operative volume so that resources could be conserved. We report our experience with synchronous bilateral metastasectomies for the treatment of disease in both lungs. METHODS: Patients with bilateral pulmonary metastases who underwent simultaneous bilateral resections were compared with a cohort of patients who underwent staged resections. We used nearest-neighbor propensity score (1:1) matching to adjust for confounders. Perioperative outcomes were compared between groups using paired statistical analysis techniques. RESULTS: Between 1998 and 2020, 36 patients underwent bilateral simultaneous metastasectomies. We matched 31 pairs of patients. The length of stay was significantly shorter in patients undergoing simultaneous resection (median 3 vs. 8 days, p < .001) and operative time was shorter (156 vs. 235.5 min, p < .001) when compared to the sum of both procedures in the staged group. The groups did not significantly differ with regard to postoperative complications. CONCLUSION: In a carefully selected patient population, simultaneous bilateral metastasectomy is a safe option. A single procedure confers benefits for both the patient as well as the hospital resource system.
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- 2021
24. Plasma Volume Status and Its Association With In-Hospital and Postdischarge Outcomes in Decompensated Heart Failure
- Author
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W.H. Wilson Tang, Brooke Alhanti, Joseph B Lerman, Justin L. Grodin, Ambarish Pandey, Christopher M. O'Connor, Randall C. Starling, Marat Fudim, Robert J. Mentz, Faiez Zannad, Wayne L. Miller, Adrian F. Hernandez, Courtney Page, Patrick Rossignol, Robert M. Califf, Justin A. Ezekowitz, Nicolas Girerd, Duke University Medical Center, Canadian VIGOUR Centre, University of Alberta, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Texas Southwestern Medical Center, Mayo Clinic [Rochester], Cleveland Clinic, Inova Heart and Vascular Institute, PR, NG, and FZ are supported by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d’Avenir' program (reference: ANR-15-RHUS-0004), by the French PIA project 'Lorraine Universite d’Excellence' (reference: ANR-15-IDEX-04-LUE)., IMPACT GEENAGE, ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), and ANR-15-IDEX-0004,LUE,Isite LUE(2015)
- Subjects
medicine.medical_specialty ,Aftercare ,Heart failure ,030204 cardiovascular system & hematology ,Plasma volume ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Urine output ,plasma volume ,Cardiovascular mortality ,business.industry ,congestion ,Hazard ratio ,Odds ratio ,Prognosis ,medicine.disease ,Hospitals ,Patient Discharge ,3. Good health ,Weak correlation ,Cardiology ,Weak association ,Cardiology and Cardiovascular Medicine ,business - Abstract
International audience; Background: Prior analyses suggest an association between formula-based plasma volume (PV) estimates and outcomes in heart failure (HF). We assessed the association between estimated PV status by the Duarte-ePV and Kaplan Hakim (KH-ePVS) formulas, and in-hospital and postdischarge clinical outcomes, in the ASCEND-HF trial.Methods and results: The KH-ePVS and Duarte-ePV were calculated on admission. We assessed associations with in-hospital worsening HF, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality. There were 6373 (89.2%), and 6354 (89.0%) patients who had necessary characteristics to calculate KH-ePVS and Duarte-ePV, respectively. There was no association between PV by either formula with in-hospital worsening HF. KH-ePVS showed a weak correlation with N-terminal prohormone BNP, and with measures of decongestion such as body weight change and urine output (r < 0.3 for all). Duarte-ePV was trending toward an association with worse 30-day (adjusted odds ratio 1.07, 95% confidence interval [CI] 1.00-1.15, P = .058), but not 180-day outcomes (adjusted hazard ratio 1.03, 95% CI 0.97-1.09, P = .289). A continuous KH-ePVS of >0 (per 10-unit increase) was associated with improved 30-day outcomes (adjusted odds ratio 0.75, 95% CI 0.62-0.91, P = .004). The continuous KH-ePVS was not associated with 180-day outcomes (adjusted hazard ratio 1.05, 95% CI 0.98-1.12, P = .139).Conclusions: Baseline PV estimates had a weak association with in-hospital measures of decongestion. The Duarte-ePV trended toward an association with early clinical outcomes in decompensated HF, and may improve risk stratification in HF.
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- 2021
25. Esophageal Cancer
- Author
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Sonia L. Betancourt-Cuellar, Marcelo F. Benveniste, Wayne L. Hofstetter, and Diana P. Palacio
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Endoscopic ultrasound ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Esophagogastroduodenoscopy ,Cancer ,General Medicine ,TNM staging system ,Esophageal cancer ,medicine.disease ,Malignancy ,030218 nuclear medicine & medical imaging ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,medicine ,Adenocarcinoma ,Abdomen ,Radiology, Nuclear Medicine and imaging ,Radiology ,business - Abstract
Esophageal cancer is an uncommon malignancy that ranks sixth in terms of mortality worldwide. Squamous cell carcinoma is the predominant histologic subtype worldwide whereas adenocarcinoma represents the majority of cases in North America, Australia, and Europe. Esophageal cancer is staged using the American Joint Committee on Cancer and the International Union for Cancer Control TNM system and has separate classifications for the clinical, pathologic, and postneoadjuvant pathologic stage groups. The determination of clinical TNM is based on complementary imaging modalities, including esophagogastroduodenoscopy/endoscopic ultrasound; endoscopic ultrasound-fine-needle aspiration; computed tomography of the chest, abdomen, and pelvis; and fluorodeoxyglucose PET/computed tomography.
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- 2021
26. Contributions of cardiac dysfunction and volume status to central haemodynamics in chronic heart failure
- Author
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Barry A. Borlaug, Diane E. Grill, Hidemi Sorimachi, Wayne L. Miller, and Karen M. Fischer
- Subjects
Heart Failure ,Cardiac function curve ,medicine.medical_specialty ,business.industry ,Hemodynamics ,Central venous pressure ,Diastole ,Stroke Volume ,Blood volume ,030204 cardiovascular system & hematology ,medicine.disease ,Ventricular Function, Left ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Heart failure ,Cardiology ,Intravascular volume status ,Humans ,Medicine ,Pulmonary Wedge Pressure ,Cardiology and Cardiovascular Medicine ,business ,Pulmonary wedge pressure - Abstract
Elevated cardiac filling pressures producing clinical congestion in heart failure (HF) patients may be secondary to intravascular volume expansion or abnormalities in cardiac diastolic properties. The objective of this study was to assess the extent to which measures of myocardial function and intravascular volume correlate with haemodynamic abnormalities in chronic HF.Subjects underwent invasive haemodynamic assessment, measurement of total blood volume (TBV) using radiolabel indicator-dilution methodology, and echocardiography to evaluate cardiac structure and function. Patients were divided into those with hypervolaemia (defined as TBV +8% above referenced normal volume) and normal volume ('euvolaemia') (TBV ≤ + 8%). Of 66 patients, 39 (59%) were hypervolaemic and 27 (41%) normal TBV. Central venous pressure (CVP, P = 0.01) and pulmonary capillary wedge pressure (PCWP, P 0.001) were higher in hypervolaemic compared with euvolaemic patients; however, 15% of hypervolaemic patients displayed normal pressures. Of euvolaemic patients, 70% displayed elevated CVP and 63% elevated PCWP. PCWP was moderately correlated with TBV (r = 0.42), left ventricular diastolic function (e' velocity, r = -0.44), and left atrial strain (r = -0.47). In multivariable regression TBV, left ventricular e', and left atrial strain were independently associated with PCWP (all P 0.05).While hypervolaemic patients displayed elevations in filling pressures, a substantial proportion (15%) had normal pressures, and of all subjects with elevated filling pressures nearly one third had normal TBVs. Importantly, of patients with normal volumes, a majority (60%) display elevated filling pressures. Combined analysis of volume, pressure, and cardiac function may be helpful to guide comprehensive assessments of HF status.
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- 2021
27. Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial
- Author
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Cheuk Hong Leung, Wayne L. Hofstetter, John V. Heymach, Alexandre Reuben, Myrna C.B. Godoy, Ara A. Vaporciyan, Padmanee Sharma, Yasir Elamin, Neda Kalhor, Robert R. Jenq, Junya Fujimoto, Tina Cascone, Anne S. Tsao, William N. William, Charles Lu, Frank E. Mott, Nadim J. Ajami, Don L. Gibbons, Jack A. Roth, David C. Rice, Luisa M. Solis, Hai T. Tran, Brett W. Carter, Lauren Averett Byers, Andrew Futreal, Lorenzo Federico, Annikka Weissferdt, Garrett L. Walsh, Reza J. Mehran, Chantale Bernatchez, George R. Blumenschein, Jennifer A. Wargo, Heather Lin, Cara Haymaker, Xiuning Le, Jonathan M. Kurie, Mehmet Altan, James P. Allison, Stephen G. Swisher, Edwin R. Parra, Boris Sepesi, Hitoshi Dejima, Frank V. Fossella, Jianjun Zhang, Bonnie S. Glisson, Mara B. Antonoff, Abdul Wadud Khan, Apar Pataer, Alejandro Francisco-Cruz, Ignacio I. Wistuba, Humam Kadara, J. Jack Lee, and Ferdinandos Skoulidis
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Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Ipilimumab ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,Clinical endpoint ,Carcinoma ,Humans ,Medicine ,Lung cancer ,Neoadjuvant therapy ,Aged ,Chemotherapy ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Neoadjuvant Therapy ,Clinical trial ,Nivolumab ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,business ,medicine.drug - Abstract
Ipilimumab improves clinical outcomes when combined with nivolumab in metastatic non-small cell lung cancer (NSCLC), but its efficacy and impact on the immune microenvironment in operable NSCLC remain unclear. We report the results of the phase 2 randomized NEOSTAR trial (NCT03158129) of neoadjuvant nivolumab or nivolumab + ipilimumab followed by surgery in 44 patients with operable NSCLC, using major pathologic response (MPR) as the primary endpoint. The MPR rate for each treatment arm was tested against historical controls of neoadjuvant chemotherapy. The nivolumab + ipilimumab arm met the prespecified primary endpoint threshold of 6 MPRs in 21 patients, achieving a 38% MPR rate (8/21). We observed a 22% MPR rate (5/23) in the nivolumab arm. In 37 patients resected on trial, nivolumab and nivolumab + ipilimumab produced MPR rates of 24% (5/21) and 50% (8/16), respectively. Compared with nivolumab, nivolumab + ipilimumab resulted in higher pathologic complete response rates (10% versus 38%), less viable tumor (median 50% versus 9%), and greater frequencies of effector, tissue-resident memory and effector memory T cells. Increased abundance of gut Ruminococcus and Akkermansia spp. was associated with MPR to dual therapy. Our data indicate that neoadjuvant nivolumab + ipilimumab-based therapy enhances pathologic responses, tumor immune infiltrates and immunologic memory, and merits further investigation in operable NSCLC. Neoadjuvant treatment with nivolumab plus ipilimumab is well tolerated and demonstrates clinical efficacy in patients with early stage lung cancer.
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- 2021
28. Intestinal Metaplasia in the Esophageal Remnant Is Rare After Ivor Lewis Esophagectomy
- Author
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Mara B. Antonoff, Wayne L. Hofstetter, Garrett L. Walsh, Boris Sepesi, Jack A. Roth, Ravi Rajaram, Ara A. Vaporciyan, David C. Rice, Stephen G. Swisher, Kyle G. Mitchell, Erin M. Corsini, Nicolas Zhou, and Reza J. Mehran
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Gastroenterology ,Reflux ,Intestinal metaplasia ,medicine.disease ,digestive system diseases ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Esophagectomy ,Interquartile range ,030220 oncology & carcinogenesis ,Internal medicine ,Metaplasia ,Barrett's esophagus ,Medicine ,Adenocarcinoma ,030211 gastroenterology & hepatology ,Surgery ,medicine.symptom ,Esophagus ,business - Abstract
Most patients undergoing esophagectomy will experience intermittent reflux of gastric and biliary content into the remnant esophagus postoperatively. The incidence of new or recurrent intestinal metaplasia following chemoradiation and surgery has not been well-described. Furthermore, post-resection guidelines do not exist regarding surveillance for metaplasia in the esophageal remnant. Patients undergoing Ivor Lewis esophagectomy after concurrent chemoradiation for a diagnosis of esophageal adenocarcinoma from 2006 to 2018 were identified. Pathology records were reviewed for the presence of intestinal metaplasia on pretreatment biopsies, surgical specimen, or post-resection biopsies. In total, 619 patients met inclusion criteria, including 267 (43%) who had intestinal metaplasia noted either prior to or at the time of esophagectomy. The median duration of metaplastic disease prior to resection was 4.4 months. During a median follow-up time of 28 months (interquartile range, 12–60), intestinal metaplasia was noted in the remnant esophagus in 12 (2%) patients, 7 of whom had a prior history of metaplasia. Local recurrence of adenocarcinoma was also uncommon, and occurred in 37/577 (6%) of patients with complete resections, with similar event rates among those with and without a prior history of metaplasia (14/249 [6%] vs. 23/328 [7%], p = 0.614). Our findings suggest that despite several factors predisposing to mucosal damage following esophagectomy, occurrence of new intestinal metaplasia after trimodality therapy in our patient population appears to be rare, even among patient with a previous history of this pathologic finding, which may have significant implications for surveillance and cost-savings after resection.
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- 2021
29. Targeting cancer stem cells with a pan-BCL-2 inhibitor in preclinical and clinical settings in patients with gastroesophageal carcinoma
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Ying Wang, Arlene M. Correa, Boyi Gan, Randy L. Johnson, Ailing W. Scott, Cordelia Y Li, Melissa Pool Pizzi, Jeannelyn S. Estrella, Longfei Huo, Shaozhong Wei, Lianchun Xiao, Brian Weston, Namita Shanbhag, Shumei Song, Yuan Li, Wayne L. Hofstetter, Guang Lei, Lang Ma, Jaffer A. Ajani, Manoop S. Bhutani, Bin Liu, Jeffrey H. Lee, Qiongrong Chen, and Jiankang Jin
- Subjects
Male ,0301 basic medicine ,Esophageal Neoplasms ,Apoptosis ,Pilot Projects ,Docetaxel ,Molecular oncology ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Stomach Neoplasms ,In vivo ,Cancer stem cell ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Gastrointestinal cancer ,YAP1 ,business.industry ,Gossypol ,Gastroenterology ,Cancer ,Middle Aged ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Disease Models, Animal ,030104 developmental biology ,Proto-Oncogene Proteins c-bcl-2 ,030220 oncology & carcinogenesis ,Neoplastic Stem Cells ,Cancer research ,Female ,business ,medicine.drug - Abstract
ObjectiveGastro-oesophageal cancers (GEC) are resistant to therapy and lead to poor prognosis. The cancer stem cells (CSCs) and antiapoptotic pathways often confer therapy resistance. We sought to elucidate the antitumour action of a BCL-2 inhibitor, AT101 in GEC in vitro, in vivo and in a clinical trial.MethodsExtensive preclinical studies in vitro and in vivo were carried out to establish the mechanism action of AT101 on targeting CSCs and antiapoptotic proteins. A pilot clinical trial in patients with GEC was completed with AT-101 added to standard chemoradiation.ResultsOverexpression of BCL-2 and MCL-1 was noted in gastric cancer tissues (GC). AT-101 induced apoptosis, reduced proliferation and tumour sphere formation in MCL-1/BCL-2 high GC cells. Interestingly, AT101 dramatically downregulated genes (YAP-1/Sox9) that control CSCs in GEC cell lines regardless of BCL-2/MCL-1 expression. Addition of docetaxel to AT-101 amplified its antiproliferation and induced apoptosis effects. In vivo studies confirmed the combination of AT101 and docetaxel demonstrated stronger antitumour activity accompanied with significant decrease of CSCs biomarkers (YAP1/SOX9). In a pilot clinical trial, 13 patients with oesophageal cancer (EC) received AT101 orally concurrently with chemoradiation. We observed dramatic clinical complete responses and encouraging overall survival in these patients. Clinical specimen analyses revealed that AT-101 dramatically reduced the expression of CSCs genes in treated EC specimens indicating antitumour activity of AT101 relies more on its anti-CSCs activity.ConclusionsOur preclinical and clinical data suggest that AT-101 overcomes resistance by targeting CSCs pathways suggesting a novel mechanism of action of AT101 in patients with GEC.
- Published
- 2021
30. Anastomotic Leak is Increased With Clostridium difficile Infection After Colectomy: Machine Learning-Augmented Propensity Score Modified Analysis of 46 735 Patients
- Author
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David A. Margolin, Dominique J. Monlezun, Wayne L. Ambroze, and Sarah Baker
- Subjects
Leak ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Propensity score matching ,medicine ,General Medicine ,Clostridium difficile ,Anastomosis ,business ,Surgical Infections ,Colectomy ,Surgery - Abstract
Background Clostridium difficile infection (CDI) is now the most common cause of healthcare-associated infections, with increasing prevalence, severity, and mortality of nosocomial and community-acquired CDI which makes up approximately one third of all CDI. There are also increased rates of asymptomatic colonization particularly in high-risk patients. C difficile is a known collagenase-producing bacteria which may contribute to anastomotic leak (AL). Methods Machine learning-augmented multivariable regression and propensity score (PS)–modified analysis was performed in this nationally representative case-control study of CDI and anastomotic leak, mortality, and length of stay for colectomy patients using the ACS-NSQIP database. Results Among 46 735 colectomy patients meeting study criteria, mean age was 61.7 years (SD 14.38), 52.2% were woman, 72.5% were Caucasian, 1.5% developed CDI, 3.1% developed anastomotic leak, and 1.6% died. In machine learning (backward propagation neural network)-augmented multivariable regression, CDI significantly increases anastomotic leak (OR 2.39, 95% CI 1.70-3.36; P < .001), which is similar to the neural network results. Having CDI increased the independent likelihood of anastomotic leak by 3.8% to 6.8% overall, and in dose-dependent fashion with increasing ASA class to 4.3%, 5.7%, 7.6%, and 10.0%, respectively, for ASA class I to IV. In doubly robust augmented inverse probability weighted PS analysis, CDI significantly increases the likelihood of AL by 4.58% (95% CI 2.10-7.06; P < .001). Conclusions This is the first known nationally representative study on CDI and AL, mortality, and length of stay among colectomy patients. Using advanced machine learning and PS analysis, we provide evidence that suggests CDI increases AL in a dose-dependent manner with increasing ASA Class.
- Published
- 2020
31. Induction Chemotherapy With an Anti-GD2 Monoclonal Antibody (Dinutuximab) and Cytokines in Children With Newly Diagnosed High-risk Neuroblastoma: A Case Series
- Author
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Wayne L. Furman, Sara M. Federico, Jessica Gartrell, Kenneth J. Caldwell, Sara Helmig, and Barry L. Shulkin
- Subjects
Male ,Oncology ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Antineoplastic Agents ,Disease ,Monoclonal antibody ,Neuroblastoma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Retrospective Studies ,Chemotherapy ,business.industry ,Antibodies, Monoclonal ,Infant ,Dinutuximab ,Induction chemotherapy ,Induction Chemotherapy ,Hematology ,medicine.disease ,Minimal residual disease ,Regimen ,Child, Preschool ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Cytokines ,Female ,business ,030215 immunology - Abstract
Although outcomes for patients with high-risk neuroblastoma improved after the addition of a chimeric anti-GD2 monoclonal antibody (dinutuximab) as treatment for minimal residual disease, nearly half of these patients die of disease. Recent studies demonstrated efficacy of the combination of chemotherapy with anti-GD2 mAb in patients with relapsed or newly diagnosed disease. This retrospective case series describes 6 patients treated at St Jude Children's Research Hospital with an induction regimen containing dinutuximab and chemotherapy, followed by consolidation and postconsolidation therapy. The treatment was well tolerated with expected toxicities. All patients completed induction therapy and demonstrated a clinical response. Further studies are warranted.
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- 2020
32. LKB1/STK11 Expression in Lung Adenocarcinoma and Associations With Patterns of Recurrence
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Kyle G. Mitchell, Edwin R. Parra, Jiexin Zhang, David B. Nelson, Erin M. Corsini, Pamela Villalobos, Cesar A. Moran, Ferdinandos Skoulidis, Ignacio I. Wistuba, Junya Fujimoto, Jack A. Roth, Mara B. Antonoff, J. Jack Lee, Ara A. Vaporciyan, Wayne L. Hofstetter, Reza J. Mehran, Stephen G. Swisher, David C. Rice, Boris Sepesi, Garrett L. Walsh, Carmen Behrens, Neda Kalhor, Annikka Weissferdt, John V. Heymach, null AstraZeneca, null Bayer, and null GlaxoSmithKline
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,STK11 ,Adenocarcinoma of Lung ,Protein Serine-Threonine Kinases ,030204 cardiovascular system & hematology ,Disease-Free Survival ,Article ,03 medical and health sciences ,0302 clinical medicine ,AMP-Activated Protein Kinase Kinases ,Internal medicine ,PD-L1 ,Biomarkers, Tumor ,medicine ,Humans ,Clinical significance ,Aged ,Neoplasm Staging ,Retrospective Studies ,Lung ,Tissue microarray ,biology ,Cluster of differentiation ,business.industry ,FOXP3 ,Middle Aged ,Prognosis ,medicine.disease ,medicine.anatomical_structure ,030228 respiratory system ,biology.protein ,Adenocarcinoma ,Female ,Surgery ,Neoplasm Recurrence, Local ,Cardiology and Cardiovascular Medicine ,business - Abstract
BACKGROUND: Mutations in the serine-threonine kinase LKB1/STK11 have been implicated in mediating resistance to checkpoint blockade among patients with advanced lung adenocarcinoma. We sought to examine the associations between clinicopathologic characteristics, tumor LKB1 expression, features of the immune microenvironment, and postoperative prognosis among patients with early-stage lung adenocarcinoma undergoing surgical therapy. METHODS: Formalin-fixed, paraffin-embedded specimens of patients undergoing resection of stage I-III, chemotherapy-naïve adenocarcinomas (1997–2008) were analyzed using tissue microarray sectioning. Sublobar resections were excluded. Intratumoral LKB1/STK11 expression was quantified as H-score. In a subset, tumor associated immune cell populations were quantified using whole tumor sections in peritumoral and intratumoral compartments. RESULTS: 104 patients met inclusion criteria. LKB1/STK11 expression (median H-score 102.9) was higher in women (median 123.3) than men (100.0, p=0.004) and in never-smokers (median 145.0) than former/current smokers (100.0, p=0.002). LKB1/STK11 expression was positively correlated with intratumoral infiltration of CD3(+) (r=0.351, P=0.005), CD4(+) (r=0.436, P
- Published
- 2020
33. Operations research: Applications and algorithms, by Wayne L. Winston, Duxbury press, Boston, 1987, 1025 pages
- Author
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Pace Plaza and Jack Yurkiewicz
- Subjects
Engineering ,Operations research ,Computer Networks and Communications ,Hardware and Architecture ,business.industry ,business ,Software ,Information Systems - Published
- 1988
34. A phase I trial of talazoparib and irinotecan with and without temozolomide in children and young adults with recurrent or refractory solid malignancies
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Mary Beth McCarville, Victor M. Santana, Elizabeth Stewart, Armita Bahrami, Rachel C. Brennan, Clinton F. Stewart, Wayne L. Furman, Sara Helmig, Michael W. Bishop, Jessica Gartrell, April Sykes, Alberto S. Pappo, Michael R. Clay, Kimberly Godwin, Sue C. Kaste, Olivia Campagne, Sara M. Federico, Natasha Sahr, Anang A. Shelat, and Dana Hawkins
- Subjects
Adult ,Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Poly(ADP-ribose) Polymerase Inhibitors ,Neutropenia ,Irinotecan ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Neoplasms ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Temozolomide ,medicine ,Humans ,Child ,business.industry ,medicine.disease ,Synovial sarcoma ,030104 developmental biology ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Phthalazines ,Female ,Sarcoma ,business ,Schlafen family member 11 ,Febrile neutropenia ,medicine.drug - Abstract
Background Talazoparib combined with irinotecan and temozolomide demonstrated efficacy in a murine Ewing sarcoma model. Based on these data, we conducted a phase I trial of talazoparib and irinotecan with/without temozolomide in paediatric patients with recurrent/refractory solid malignancies. Patients and methods Cohorts of 3–6 patients with recurrent/refractory solid malignancies received escalating doses of oral talazoparib and intravenous irinotecan (arm A) and oral talazoparib, oral temozolomide and intravenous irinotecan (arm B) in a 3 + 3 design. Talazoparib was administered on days 1–6, and intravenous irinotecan and oral temozolomide were administered on days 2–6, of a 21-day course. Serum for talazoparib and irinotecan pharmacokinetics was obtained during course 1. UGT1A1 polymorphism and Schlafen family member 11 (SLFN11) immunohistochemical staining were performed. Results Forty-one patients (20 males; median age, 14.6 years; 24 with recurrent disease) were evaluable for dose escalation. Twenty-nine and 12 patients were treated on arm A and arm B, respectively, for a total of 208 courses. The most common diagnosis was Ewing sarcoma (53%). The most common ≥grade III haematologic toxicities in arms A and B included neutropenia (78% and 31%, respectively) and thrombocytopenia (42% and 31%, respectively). In arms A and B, febrile neutropenia (24% and 14%, respectively) and diarrhoea (21% and 7%, respectively) were the most common ≥grade III non-hematologic toxicities. Six patients (Ewing sarcoma [5 patients] and synovial sarcoma [1 patient]) had a response (1 with a complete response, 5 with a partial response). The objective response rates were 10.3% (arm A) and 25% (arm B). Pharmacokinetic testing demonstrated no evidence of drug-drug interaction between talazoparib and irinotecan. UGT1A1 was not related to response. SLFN11 positivity was associated with best response to therapy. Conclusions The combination of talazoparib and irinotecan with/without temozolomide is feasible and active in Ewing sarcoma, and further investigation is warranted.
- Published
- 2020
35. Preoperative Chemoradiation Versus Chemotherapy in Gastroesophageal Junction Adenocarcinoma
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Yi Ju Chiang, Wayne L. Hofstetter, Brian D. Badgwell, Syed Nabeel Zafar, Jaffer A. Ajani, Mariela A. Blum, Jeannelyn S. Estrella, Paul F. Mansfield, Bruce D. Minsky, Prajnan Das, and Naruhiko Ikoma
- Subjects
Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Esophageal Neoplasms ,medicine.medical_treatment ,Adenocarcinoma ,030204 cardiovascular system & hematology ,Gastroesophageal Junction Adenocarcinoma ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Stomach Neoplasms ,Internal medicine ,Preoperative Care ,Humans ,Medicine ,Retrospective Studies ,Chemotherapy ,business.industry ,Hazard ratio ,Cancer ,Chemoradiotherapy, Adjuvant ,Middle Aged ,medicine.disease ,Primary tumor ,Confidence interval ,Regimen ,030228 respiratory system ,Propensity score matching ,Female ,Surgery ,Esophagogastric Junction ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background The incidence of lower esophageal and gastroesophageal junction adenocarcinoma has sharply increased over the past several decades and is a serious public health problem. Preoperative therapy with either chemotherapy or chemoradiation is recommended, but the optimal regimen is unknown. We used the National Cancer Database and propensity score matching to investigate whether preoperative chemoradiation therapy offers an advantage over chemotherapy alone for patients with these tumors. Methods From the National Cancer Database esophageal and gastric dataset, we selected patients with either lower esophageal or gastric cardia adenocarcinomas who had undergone definitive resection after chemotherapy or chemoradiation. We used propensity score matching to balance groups based on the preoperative treatment they received. We then used conditional multivariable logistic regression and Cox proportional hazard models to examine the association between preoperative therapy regimen and pathological response, overall survival (OS), and postoperative outcomes. Results Our study included 13,783 patients; 12,129 (89.0%) had received preoperative chemoradiation. Propensity score matching created 1650 pairs. Patients receiving chemoradiation were 2.7 (95% confidence interval, 1.29-3.23) times more likely to achieve complete response in the primary tumor than were those receiving chemotherapy alone; however, chemoradiation was not associated with improved OS (hazard ratio, 1.01; 95% confidence interval, 0.91-1.12). Short-term outcomes (length of stay, mortality, and readmissions) were similar between the 2 groups. Conclusions Preoperative chemoradiation was associated with a higher complete response rate in the primary tumor but not with improved OS in lower esophageal and gastroesophageal junction adenocarcinoma.
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- 2020
36. Agreement on Major Pathological Response in NSCLC Patients Receiving Neoadjuvant Chemotherapy
- Author
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J. Jack Lee, John V. Heymach, Cesar A. Moran, Jack A. Roth, Ignacio I. Wistuba, Apar Pataer, Ara A. Vaporciyan, Boris Sepesi, Arlene M. Correa, Neda Kalhor, Stephen G. Swisher, Tina Cascone, Annikka Weissferdt, Jitesh B. Shewale, and Wayne L. Hofstetter
- Subjects
Adult ,Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Pathological response ,Article ,03 medical and health sciences ,0302 clinical medicine ,Neoadjuvant treatment ,Major Pathologic Response ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Lung cancer ,Aged ,Retrospective Studies ,Aged, 80 and over ,Chemotherapy ,business.industry ,Surrogate endpoint ,Hazard ratio ,Middle Aged ,Prognosis ,medicine.disease ,Neoadjuvant Therapy ,Survival Rate ,Clinical trial ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,business ,Follow-Up Studies - Abstract
Introduction We have suggested that major pathologic response (MPR) could serve as a surrogate endpoint for survival and provide rapid means of comparing different neoadjuvant treatment regimens. Here, we confirm that MPR is predictive of long-term overall survival (OS) in patients with non–small-cell lung cancer (NSCLC) who underwent neoadjuvant chemotherapy and surgical resection, to assess agreement on MPR between 2 observers, and to determine the minimum number of slides needed to obtain an accurate determination of MPR. Patients and Methods We identified 151 patients with NSCLC who had been treated with neoadjuvant chemotherapy followed by complete surgical resection from 2008 to 2012. Tissue specimens were retrospectively evaluated by 2 pathologists who had been blinded to patients’ treatment and outcome. We assessed the relationships between MPR and OS, the levels of agreement between the pathologists, and determined the number of slides needed to obtain an accurate determination of MPR. Results Our results reveal that MPR examined by either observer 1 (experienced) or by observer 2 (trained) was significantly predictive of long-term OS after neoadjuvant chemotherapy. MPR was associated with long-term OS in patients with NSCLC undergoing neoadjuvant chemotherapy on multivariable analysis (hazard ratio 2.68; P = .01). The levels of agreement between 2 pathologists were high after direct in-person training by one pathologist or the other (R2 = 0.994). Our data suggest that at least 3 slides should be read to accurately determine MPR. Conclusions MPR is significantly predictive of long-term OS in neoadjuvant chemotherapy–treated patients with NSCLC. MPR may serve as a surrogate endpoint for evaluating novel chemotherapies and immunotherapy response in biomarker-driven translational clinical trials.
- Published
- 2020
37. Locoregional Control, Overall Survival, and Disease-Free Survival in Stage IIIA (N2) Non–Small-Cell Lung Cancer: Analysis of Resected and Unresected Patients
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Tina Cascone, Ting Xu, Quynh Nhu Nguyen, David C. Rice, Jack A. Roth, Saumil Gandhi, Wayne L. Hofstetter, Zhongxing Liao, Arlene M. Correa, Mara B. Antonoff, Anne S. Tsao, Ara A. Vaporciyan, Reza J. Mehran, Ravi Rajaram, Stephen G. Swisher, Boris Sepesi, Vassiliki A. Papadimitrakopoulou, and Garrett L. Walsh
- Subjects
Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Durvalumab ,medicine.medical_treatment ,Adenocarcinoma of Lung ,03 medical and health sciences ,Pneumonectomy ,0302 clinical medicine ,Unresected ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Lung cancer ,Aged ,Retrospective Studies ,Chemotherapy ,business.industry ,Mortality rate ,Cancer ,Middle Aged ,Prognosis ,medicine.disease ,Surgery ,Survival Rate ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Female ,Neoplasm Recurrence, Local ,Outcomes research ,business ,Follow-Up Studies - Abstract
Introduction The standard of care for stage IIIA (N2) non–small-cell lung cancer (NSCLC) includes concurrent definitive chemoradiation (dCRT) followed by durvalumab, thus challenging the role of surgery in resectable patients. We assessed locoregional disease control and survival in patients with surgically resected and unresected stage IIIA (N2) NSCLC disease. Patients and Methods We conducted a retrospective analysis from prospectively collected databases at MD Anderson Cancer Center. Patients undergoing neoadjuvant chemotherapy and surgery or dCRT for clinical stage IIIA (N2) disease (2004-2014) were evaluated. Primary outcomes included locoregional disease control, disease-free survival (DFS), and overall survival (OS). Kaplan-Meier outcome analyses were performed. Results Of the 159 resected patients, the majority had lobectomy (82.4%), followed by pneumonectomy (11.9%) and sublobar resection (5.7%). The 30- and 90-day mortality rates were 0.6% and 1.3%, respectively. At median follow-up of 52.8 months, recurrence was 55.3%, with 44.0% having distant and 15.1% locoregional recurrence. At 5 years, OS was 50.8% and DFS was 33.1% Median OS was 61.2 months. A total of 366 patients underwent dCRT, with intensity-modulated radiation in 64.5%, proton therapy in 26.0%, and 3-dimensional conformal radiotherapy in 9.6%. The mean dose was 68.1 Gy. At median follow-up of 20.8 months, recurrence was 53.6%, with distant and locoregional recurrence of 40.7% and 30.3%, respectively. At 5 years, OS was 29.2% and DFS was 20.5%. Median OS was 27.5 months. Conclusion Stage IIIA (N2) NSCLC continues to be a heterogeneous disease, and patients with surgically resected and unresected disease represent different risk populations. Ongoing immunotherapy trials may further redefine treatment algorithms in this complex patient population.
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- 2020
38. Gentamicin Vestibulotoxicity: Further Insights From a Large Clinical Series
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John Rutka, Terence S Fu, Ophir Ilan, Wanda Dillon, David D. Pothier, Simon D. Carr, Jerome A. Leis, Wayne L. Gold, Iqbal Mohammed Syed, and Paul Douglas-Jones
- Subjects
medicine.medical_specialty ,Vestibular evoked myogenic potential ,Nephrotoxicity ,Neurotology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Videonystagmography ,Dosing ,Saccule and Utricle ,030223 otorhinolaryngology ,Retrospective Studies ,medicine.diagnostic_test ,Cumulative dose ,business.industry ,Osteomyelitis ,medicine.disease ,Vestibular Evoked Myogenic Potentials ,Semicircular Canals ,Sensory Systems ,Otorhinolaryngology ,Anesthesia ,Gentamicin ,Neurology (clinical) ,Gentamicins ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
OBJECTIVE To review insights gained from a 21-year experience with gentamicin-induced vestibulotoxicity including differences in vestibulotoxicity between single daily dosing (SDD) and multiple daily dosing (MDD) regimens. STUDY DESIGN Retrospective case series. SETTING Tertiary care center. PATIENTS Patients with gentamicin vestibulotoxicity referred to the Hertz Multidisciplinary Neurotology Clinic between January 1993 and September 2014. INTERVENTION None. MAIN OUTCOME MEASURES Spectrum of vestibular dysfunction measured using videonystagmography, vestibular evoked myogenic potentials, video head impulse testing, and magnetic scleral search coil testing. RESULTS Of 53 patients with gentamicin-induced vestibulotoxicity, 24 received SDD and 29 received MDD treatment. The most common indications for treatment were sepsis, endocarditis, and osteomyelitis. Angular acceleration receptor function (semicircular canals) was more commonly affected than linear acceleration receptor function (otolithic organ of the saccule; 100% vs. 62%). A significant proportion of patients (53%) developed vestibulotoxicity in the absence of nephrotoxicity and 40% experienced vestibulotoxicity in a delayed fashion up to 10 days posttreatment cessation (mean 3.9 ± 0.7). Therapeutic monitoring did not necessarily prevent delayed vestibulotoxicity. Nephrotoxicity was less common for SDD compared with MDD (60% vs. 35%, p = 0.01). However, the SDD group experienced vestibulotoxicity at a lower cumulative dose (6.3 vs. 7.0 g, p = 0.04) and shorter duration of therapy (20.7 vs 29.4 d, p = 0.02). CONCLUSIONS Our study further highlights important insights regarding gentamicin-induced vestibulotoxicity. While SDD is associated with decreased risk for nephrotoxicity compared with MDD, it confers a higher risk for vestibulotoxicity.
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- 2020
39. Phase I expansion cohort to evaluate the combination of bevacizumab, sorafenib and low-dose cyclophosphamide in children and young adults with refractory or recurrent solid tumours
- Author
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Vinay M. Daryani, Andrew M. Davidoff, Wayne L. Furman, Jianrong Wu, Clinton F. Stewart, Sara M. Federico, Alberto S. Pappo, Kenneth J. Caldwell, Mary Beth McCarville, Victor M. Santana, Fariba Navid, and Shenghua Mao
- Subjects
Adult ,Male ,0301 basic medicine ,Sorafenib ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Maximum Tolerated Dose ,Cyclophosphamide ,Bevacizumab ,Neutropenia ,Gastroenterology ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Tissue Distribution ,Child ,Salvage Therapy ,business.industry ,Soft tissue sarcoma ,Infant ,Common Terminology Criteria for Adverse Events ,Prognosis ,medicine.disease ,Rash ,Survival Rate ,030104 developmental biology ,Oncology ,Drug Resistance, Neoplasm ,Response Evaluation Criteria in Solid Tumors ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,Neoplasm Recurrence, Local ,medicine.symptom ,business ,Follow-Up Studies ,medicine.drug - Abstract
Background Angiogenesis is critical for tumour growth and metastasis. Dual inhibition of vascular endothelial growth factors and platelet-derived growth factor receptors suppresses angiogenesis. This expansion cohort of a phase I study targeted angiogenesis with sorafenib, bevacizumab and low-dose cyclophosphamide in children and young adults with recurrent solid tumours. Methods An expansion cohort including patients with refractory or recurrent solid tumours was enrolled and received bevacizumab (15 mg/kg IV, day 1), sorafenib (90 mg/m2 po twice daily, days 1–21) and low-dose cyclophosphamide (50 mg/m2 po daily, days 1–21). Each course was 21 days. Toxicities were assessed using Common Terminology Criteria for Adverse Events, v3.0, and responses were evaluated by Response Evaluation Criteria in Solid Tumors criteria. Serial bevacizumab pharmacokinetic (PK) studies were performed during course 1. Results Twenty-four patients (15 males; median age 14.5 yrs; range 1–22 yr) received a median of 6 courses (range 1–18). Twelve patients had a bone or soft tissue sarcoma. The most common grade III/IV non-haematologic toxicities were hypertension (N = 4), hand/foot rash (N = 3) and elevated lipase (N = 3). The most common grade III/IV haematologic toxicities were neutropenia (N = 7) and lymphopenia (N = 17). Three patients (2 synovial sarcoma, 1 rhabdoid tumour) achieved a partial response and 18 had stable disease. The progression-free survival at 3 and 6 months were 78.1% (95% confidence interval [CI] 60.6–95.6%) and 54% (95% CI 30.2–78.2%), respectively. Bevacizumab PKs in 15 patients was similar to published adult PK results. Conclusions Intravenous bevacizumab combined with oral sorafenib and low-dose cyclophosphamide was tolerated and demonstrated promising activity in a subset of childhood solid tumours.
- Published
- 2020
40. Importance of resection for locoregional disease control in Masaoka stage IVA thymic neoplasms
- Author
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Erin M. Corsini, David C. Rice, Ara A. Vaporciyan, Kyle G. Mitchell, Jack A. Roth, Mara B. Antonoff, Stephen G. Swisher, Wayne L. Hofstetter, Boris Sepesi, Garrett L. Walsh, and Reza J. Mehran
- Subjects
Adult ,Male ,medicine.medical_specialty ,Thymoma ,Pleural Neoplasms ,medicine.medical_treatment ,Disease ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Stage (cooking) ,Thymic carcinoma ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Thymic Neoplasms ,Proportional hazards model ,business.industry ,Thymus Neoplasms ,General Medicine ,Middle Aged ,Thoracic Surgical Procedures ,Thymectomy ,medicine.disease ,Surgery ,Oncology ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,030211 gastroenterology & hepatology ,Neoplasm Recurrence, Local ,Masaoka Stage IVa ,business - Abstract
Background and objectives It is unclear if a specific strategy for simultaneous treatment of primary thymic neoplasms and pleural metastases confers benefit for Masaoka stage IVA disease. We reviewed our experience with thymic neoplasms with concurrent pleural metastases to identify factors influencing outcomes. Methods Records of patients who presented with stage IVA thymic neoplasms from 2000 to 2018 were assessed. Multivariate Cox proportional hazards analyses were completed to determine predictors of progression-free and overall survival. Results Forty-eight patients were identified, including 34 (71%) who underwent surgery. Median overall and progression-free survival were 123 and 21 months, respectively. The extent of resection varied, and was most commonly thymectomy plus partial pleurectomy (22, 65%). Median progression-free survival for patients who underwent surgical resection versus those who had not was 24 versus 12 months (P = .018). Following surgical resection, mediastinal recurrence was uncommon (2, 6%, vs 7, 50% nonoperatively). Five-year survival rates in these groups were suggestive of possible benefit to surgery (87% vs 68%). Conclusions Thymic neoplasms with pleural dissemination represents a treatment challenge. As part of a multidisciplinary approach, surgery appears to be associated with more favorable long-term results, although selection bias may account for some of the survival differences observed.
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- 2020
41. Time trends and predictors of survival in surgically resected early‐stage non–small cell lung cancer patients
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Eric L. Brown, Garrett L. Walsh, Reza J. Mehran, Luis G LeonNovelo, Jack A. Roth, Jitesh B. Shewale, Arlene M. Correa, Ara A. Vaporciyan, Wayne L. Hofstetter, Boris Sepesi, Erin M. Corsini, Mara B. Antonoff, Stephen G. Swisher, David C. Rice, and Alan G. Nyitray
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Coronary artery disease ,Young Adult ,03 medical and health sciences ,Pneumonectomy ,Sex Factors ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Humans ,Thoracotomy ,Stage (cooking) ,Lung cancer ,Neoadjuvant therapy ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Retrospective Studies ,Aged, 80 and over ,Proportional hazards model ,business.industry ,Age Factors ,General Medicine ,Middle Aged ,Nomogram ,medicine.disease ,Survival Rate ,Nomograms ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Surgery ,business - Abstract
Background The improvement in the management of lung cancer have the potential to improve survival in patients undergoing resection for early-stage (stage I and II) non-small cell lung cancer (NSCLC), but few studies have evaluated time trends and identified predictors of overall survival (OS). Methods We identified surgically resected early-stage NSCLC between 1998 and 2016. The 3-year OS (1998-2014) and 5-year OS (1998-2012) rates were calculated for each year. Joinpoint regression was used to calculate annual percentage changes (APC) and to test time trends in OS. Multivariable Cox regression was used to identify predictors of OS. Results There was a significant upward trend in the 3-year (1998, 56%; 2014, 83%; APC = 1.8) and 5-year (1998, 47%; 2012, 76%; APC = 3.1) OS. Older age; male sex; history of diabetes, coronary artery disease, and chronic obstructive pulmonary disease; high ASA score; smoking pack-years; high-grade tumor; pneumonectomy; thoracotomy; neoadjuvant therapy; nodal disease; and positive tumor margin were predictors of poor OS. Conclusion The upward time trend in OS suggests that improved staging, patient selection, and management have conferred a survival benefit in early-stage NSCLC patients. The prediction model of OS could be used to refine selection criteria for resection and improve survival outcomes.
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- 2020
42. 18F-fluorodeoxyglucose positron emission tomography correlates with tumor immunometabolic phenotypes in resected lung cancer
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Tina Cascone, Brett W. Carter, Ara A. Vaporciyan, Kyle G. Mitchell, David Piwnica-Worms, Carmen Behrens, Stephen G. Swisher, Edwin R. Parra, Weiyi Peng, Jing Wang, Yunfei Wang, Alexandre Reuben, John V. Heymach, Cesar A. Moran, Wayne L. Hofstetter, Pamela Villalobos, Annikka Weissferdt, Behrang Amini, Myrna C.B. Godoy, Boris Sepesi, William N. William, Don L. Gibbons, J. Jack Lee, Garrett L. Walsh, Junya Fujimoto, Patrick Hwu, Humam Kadara, and Ignacio I. Wistuba
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Cancer Research ,Tumor microenvironment ,medicine.diagnostic_test ,business.industry ,T cell ,Immunology ,Cell ,Gene signature ,medicine.disease ,Article ,Immune system ,medicine.anatomical_structure ,Oncology ,Positron emission tomography ,medicine ,Cancer research ,Immunology and Allergy ,Immunohistochemistry ,Lung cancer ,business - Abstract
Enhanced tumor glycolytic activity is a mechanism by which tumors induce an immunosuppressive environment to resist adoptive T cell therapy; therefore, methods of assessing intratumoral glycolytic activity are of considerable clinical interest. In this study, we characterized the relationships among tumor (18)F-fluorodeoxyglucose (FDG) retention, tumor metabolic and immune phenotypes, and survival in patients with resected non-small cell lung cancer (NSCLC). We retrospectively analyzed tumor preoperative positron emission tomography (PET) (18)F-FDG uptake in 59 resected NSCLCs and investigated correlations between PET parameters (SUV(Max), SUV(Total), SUV(Mean), TLG), tumor expression of glycolysis- and immune-related genes, and tumor-associated immune cell densities that were quantified by immunohistochemistry. Tumor glycolysis-associated immune gene signatures were analyzed for associations with survival outcomes. We found that each (18)F-FDG PET parameter was positively correlated with tumor expression of glycolysis-related genes. Elevated (18)F-FDG SUV(Max) was more discriminatory of glycolysis-associated changes in tumor immune phenotypes than other (18)F-FDG PET parameters. Increased SUV(Max) was associated with multiple immune factors characteristic of an immunosuppressive and poorly immune infiltrated tumor microenvironment, including elevated PD-L1 expression, reduced CD57(+) cell density, and increased T cell exhaustion gene signature. Elevated SUV(Max) identified immune-related transcriptomic signatures that were associated with enhanced tumor glycolytic gene expression and poor clinical outcomes. Our results suggest that (18)F-FDG SUV(Max) has potential value as a noninvasive, clinical indicator of tumor immunometabolic phenotypes in patients with resectable NSCLC and warrants investigation as a potential predictor of therapeutic response to immune-based treatment strategies.
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- 2020
43. A phase 1 trial of everolimus and bevacizumab in children with recurrent solid tumors
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Olivia Campagne, Natasha Sahr, Lisa M. McGregor, April Sykes, Wayne L. Furman, Ruth G. Tatevossian, Clinton F. Stewart, Sujuan Jia, and Victor M. Santana
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Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Maximum Tolerated Dose ,Bevacizumab ,Angiogenesis Inhibitors ,Antineoplastic Agents ,Peripheral blood mononuclear cell ,Gastroenterology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Neoplasms ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Everolimus ,030212 general & internal medicine ,Child ,PI3K/AKT/mTOR pathway ,business.industry ,Prognosis ,medicine.disease ,Progression-Free Survival ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Toxicity ,Biomarker (medicine) ,Female ,Neoplasm Recurrence, Local ,business ,Progressive disease ,medicine.drug - Abstract
Background The prognosis for children with recurrent solid tumors generally is poor. Targeting mammalian target of rapamycin (mTOR) and vascular endothelial growth factor A with everolimus and bevacizumab, respectively, synergistically improves progression-free survival and is well tolerated in adults with solid tumors. Methods In the current phase 1 study, a total of 15 children with recurrent or refractory solid tumors were treated with bevacizumab and everolimus to establish the maximum tolerated dose, toxicity, and preliminary antitumor response (ClinicalTrials.gov identifier NCT00756340). The authors also evaluated everolimus-mediated inhibition of the mTOR pathway in the peripheral blood mononuclear cells of treated patients. Results Tumors predominantly were soft tissue and/or bone sarcomas (8 cases) and brain tumors (5 cases). The first 2 patients enrolled at dose level 1 (10 mg/kg of bevacizumab and 4 mg/m2 of everolimus) experienced dose-limiting toxicities (DLTs). The next 5 patients were enrolled at dose level 0 (8 mg/kg of bevacizumab and 4 mg/m2 of everolimus), and DLTs occurred in 2 patients. The authors then modified the protocol to permit expansion of dose 0, and 8 additional patients were added, with no DLTs reported. Of all the patients, stable disease occurred in 4 patients (30.8%; median, 2 courses), and progressive disease occurred in 9 patients (69.2%). Overall survival was 0.59 years (95% CI, 0.24-1.05 years). The mTOR biomarker phospho-4EBP1 Thr/37/46 significantly decreased from baseline to day 27 in peripheral blood mononuclear cells (P = .045). Phospho-AKT levels also decreased from those at baseline. Conclusions The maximum tolerated dose of cotreatment with bevacizumab and everolimus was 8 mg/kg of bevacizumab and 4 mg/m2 of everolimus in a 4-week cycle for children with recurrent solid tumors.
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- 2020
44. Diagnostic criteria and symptom grading for delayed gastric conduit emptying after esophagectomy for cancer
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Mats Lindblad, B. P. L. Wijnhoven, J. J. B. van Lanschot, M. I. van Berge Henegouwen, Camiel Rosman, Suzanne S. Gisbertz, Philippe Nafteux, Wolfgang Schröder, H. Van Veer, Donald E. Low, P. Pattyn, Gail E. Darling, S. M. Griffin, Lorenzo E. Ferri, M A Chaudry, M Konradsson, K Moorthy, Paul M. Schneider, M. Luyer, Christiane J. Bruns, Bruno Sgromo, Miguel A. Cuesta, M Nilsson, Wayne L. Hofstetter, Yuukou Kitagawa, R. van Hillegersberg, Stuart Mercer, Nelson Ndegwa, Arnulf H. Hölscher, C A Gutschow, Christopher R. Morse, Edward Cheong, G A P Nieuwehuijzen, Jari Räsänen, Jelle P. Ruurda, Surgery, AGEM - Re-generation and cancer of the digestive system, AGEM - Endocrinology, metabolism and nutrition, CCA - Imaging and biomarkers, HUS Heart and Lung Center, III kirurgian klinikka, University of Helsinki, and Helsinki University Hospital Area
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Male ,Delphi Technique ,Esophageal Neoplasms ,medicine.medical_treatment ,Modified delphi ,Gastric emptying ,law.invention ,PYLORIC DRAINAGE ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,Postoperative Complications ,0302 clinical medicine ,QUALITY-OF-LIFE ,law ,Gastroenterology ,General Medicine ,Middle Aged ,3. Good health ,Treatment Outcome ,Esophagectomy ,030220 oncology & carcinogenesis ,Vomiting ,Original Article ,Female ,030211 gastroenterology & hepatology ,Symptom Assessment ,medicine.symptom ,Adult ,medicine.medical_specialty ,Consensus ,Nausea ,malnutrition ,03 medical and health sciences ,gastric emptying ,SDG 3 - Good Health and Well-being ,MANAGEMENT ,Journal Article ,medicine ,Humans ,Esophageal Motility Disorders ,Radiogram ,Grading (tumors) ,business.industry ,General surgery ,Gastric conduit ,Malnutrition ,3126 Surgery, anesthesiology, intensive care, radiology ,consensus ,3121 General medicine, internal medicine and other clinical medicine ,RISK-FACTORS ,esophagectomy ,business - Abstract
Contains fulltext : 225948.pdf (Publisher’s version ) (Open Access) Delayed gastric conduit emptying (DGCE) after esophagectomy for cancer is associated with adverse outcomes and troubling symptoms. Widely accepted diagnostic criteria and a symptom grading tool for DGCE are missing. This hampers the interpretation and comparison of studies. A modified Delphi process, using repeated web-based questionnaires, combined with live interim group discussions was conducted by 33 experts within the field, from Europe, North America, and Asia. DGCE was divided into early DGCE if present within 14 days of surgery and late if present later than 14 days after surgery. The final criteria for early DGCE, accepted by 25 of 27 (93%) experts, were as follows: >500 mL diurnal nasogastric tube output measured on the morning of postoperative day 5 or later or >100% increased gastric tube width on frontal chest x-ray projection together with the presence of an air-fluid level. The final criteria for late DGCE accepted by 89% of the experts were as follows: the patient should have 'quite a bit' or 'very much' of at least two of the following symptoms; early satiety/fullness, vomiting, nausea, regurgitation or inability to meet caloric need by oral intake and delayed contrast passage on upper gastrointestinal water-soluble contrast radiogram or on timed barium swallow. A symptom grading tool for late DGCE was constructed grading each symptom as: 'not at all', 'a little', 'quite a bit', or 'very much', generating 0, 1, 2, or 3 points, respectively. For the five symptoms retained in the diagnostic criteria for late DGCE, the minimum score would be 0, and the maximum score would be 15. The final symptom grading tool for late DGCE was accepted by 27 of 31 (87%) experts. For the first time, diagnostic criteria for early and late DGCE and a symptom grading tool for late DGCE are available, based on an international expert consensus process.
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- 2020
45. Hospital readmissions after pulmonary resection: post-discharge nursing telephone assessment identifies high risk patients
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Arlene M. Correa, Wayne L. Hofstetter, David C. Rice, Reza J. Mehran, Garrett L. Walsh, Stephen G. Swisher, Mara B. Antonoff, Jack A. Roth, Robert M. Van Haren, Ara A. Vaporciyan, and Boris Sepesi
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Pulmonary and Respiratory Medicine ,education.field_of_study ,High risk patients ,business.industry ,Post discharge ,medicine.medical_treatment ,Population ,030204 cardiovascular system & hematology ,Chest tube ,03 medical and health sciences ,Patient safety ,0302 clinical medicine ,Nursing ,Patient experience ,Medicine ,Original Article ,030212 general & internal medicine ,Pulmonary resection ,business ,education ,Resource utilization - Abstract
BACKGROUND: We previously reported that post-discharge nursing telephone assessments identified a frequent number of patient complaints. Our aim was to determine if telephone assessments can identify patients at risk for emergency room (ER) visits or hospital readmissions. METHODS: A single-institution, retrospective review was performed on all patients undergoing pulmonary resection over a 12-month period. Standardized nursing telephone calls were conducted and records were reviewed to determine postoperative issues. ER visits and readmissions within 30 and 90 days were recorded. RESULTS: In total, 521 patients underwent pulmonary resection and 245 (47%) were reached for telephone assessment. ER visits within 30/90 days were 8.1% (n=42) and 12.1% (n=63). Readmissions within 30/90 days were 3.1% (n=16) and 6% (n=31). For those reached by telephone assessment, patients with major issue demonstrated increased 30-day ER visits: 22.6% (n=7) vs. 8.0% (n=17), P=0.019. For all patients, those with 90-day ER visit and/or readmission were more likely to have pulmonary complications during initial admission (43.8% vs. 21.2%, P
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- 2020
46. When all life counts in conservation
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Erick J. Lundgren, Scott P. Carroll, Daniel Ramp, Wayne L. Linklater, Chelsea Batavia, Arian D. Wallach, Jamie Steer, Michael Paul Nelson, Esty Yanco, Danielle Celermajer, and Kate Brandis
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0106 biological sciences ,Ecology ,business.industry ,010604 marine biology & hydrobiology ,media_common.quotation_subject ,Immigration ,Wildlife ,Biodiversity ,Distribution (economics) ,15. Life on land ,010603 evolutionary biology ,01 natural sciences ,Emigration ,Geography ,Threatened species ,IUCN Red List ,Species richness ,business ,Socioeconomics ,Ecology, Evolution, Behavior and Systematics ,Nature and Landscape Conservation ,media_common - Abstract
Conservation science involves the collection and analysis of data. These scientific practices emerge from values that shape who and what is counted. Currently, conservation data are filtered through a value system that considers native life the only appropriate subject of conservation concern. We examined how trends in species richness, distribution, and threats change when all wildlife count by adding so-called non-native and feral populations to the International Union for Conservation of Nature Red List and local species richness assessments. We focused on vertebrate populations with founding members taken into and out of Australia by humans (i.e., migrants). We identified 87 immigrant and 47 emigrant vertebrate species. Formal conservation accounts underestimated global ranges by an average of 30% for immigrants and 7% for emigrants; immigrations surpassed extinctions in Australia by 52 species; migrants were disproportionately threatened (33% of immigrants and 29% of emigrants were threatened or decreasing in their native ranges); and incorporating migrant populations into risk assessments reduced global threat statuses for 15 of 18 species. Australian policies defined most immigrants as pests (76%), and conservation was the most commonly stated motivation for targeting these species in killing programs (37% of immigrants). Inclusive biodiversity data open space for dialogue on the ethical and empirical assumptions underlying conservation science.
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- 2020
47. Monitoring Hemostasis During Extracorporeal Life Support
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David Michael McMullan, Wayne L. Chandler, Dana C. Matthews, Thomas V. Brogan, Christopher R. Burke, Larissa Yalon, and Nabiha Huq Saifee
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Male ,Biomedical Engineering ,Biophysics ,Activated clotting time ,Hemorrhage ,Bioengineering ,030204 cardiovascular system & hematology ,Pharmacology ,Antithrombins ,Biomaterials ,03 medical and health sciences ,Extracorporeal Membrane Oxygenation ,0302 clinical medicine ,Humans ,Medicine ,Blood Coagulation ,Blood coagulation test ,Prothrombin time ,Hemostasis ,medicine.diagnostic_test ,business.industry ,Antithrombin ,Anticoagulants ,Thrombosis ,General Medicine ,Heparin ,030228 respiratory system ,Coagulation ,Female ,Blood Coagulation Tests ,business ,medicine.drug ,Partial thromboplastin time - Abstract
To balance the risk of bleeding versus circuit thrombosis during extracorporeal life support (ECLS), it is important to monitor anticoagulants and hemostasis. We evaluated the prothrombin time (PT), partial thromboplastin time (PTT), activated clotting time (ACT), and antifactor Xa heparin activity (aXa) correlation with changes in coagulation factor and heparin levels using in vitro and in vivo samples. aXa correlated with heparin (r = 0.97) and antithrombin (r = 0.98) but was unaffected by other parameters. PT correlated with coagulation factors (r = 0.88) but was minimally affected by heparin or other parameters. When single parameters were changed, ACT was insensitive to
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- 2020
48. Natriuretic Peptides to Predict Short-Term Mortality in Patients With Sepsis: A Systematic Review and Meta-analysis
- Author
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Zhen Wang, Allan S. Jaffe, Shashaank Vallabhajosyula, Kianoush Kashani, Saraschandra Vallabhajosyula, Saarwaani Vallabhajosyula, Wayne L. Miller, Pranathi R. Sundaragiri, and M. Hassan Murad
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medicine.medical_specialty ,medicine.drug_class ,Renal function ,Review ,030204 cardiovascular system & hematology ,law.invention ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,law ,Internal medicine ,AUROC, area under the receiver operating characteristic curve ,medicine ,Natriuretic peptide ,Sn, sensitivity ,030212 general & internal medicine ,BNP, B-type natriuretic peptide ,lcsh:R5-920 ,NT-proBNP, N-terminal pro-B-type natriuretic peptide ,Receiver operating characteristic ,Septic shock ,business.industry ,medicine.disease ,Intensive care unit ,3. Good health ,Systematic review ,Meta-analysis ,Sp, specificity ,ROC, receiver operating characteristic curve ,lcsh:Medicine (General) ,business - Abstract
Data are conflicting regarding the optimal cutoffs of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) to predict short-term mortality in patients with sepsis. We conducted a comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus) for English-language reports of studies evaluating adult patients with sepsis, severe sepsis, and septic shock with BNP/NT-proBNP levels and short-term mortality (intensive care unit, in-hospital, 28-day, or 30-day) published from January 1, 2000, to September 5, 2017. The average values in survivors and nonsurvivors were used to estimate the receiver operating characteristic curve (ROC) using a parametric regression model. Thirty-five observational studies (3508 patients) were included (median age, 51-75 years; 12%-74% males; cumulative mortality, 34.2%). A BNP of 622 pg/mL had the greatest discrimination for mortality (sensitivity, 0.695 [95% CI, 0.659-0.729]; specificity, 0.907 [95% CI, 0.810-1.003]; area under the ROC, 0.766 [95% CI, 0.734-0.797]). An NT-proBNP of 4000 pg/mL had the greatest discrimination for mortality (sensitivity, 0.728 [95% CI, 0.703-0.753]; specificity, 0.789 [95% CI, 0.710-0.867]; area under the ROC, 0.787 [95% CI, 0.766-0.809]). In prespecified subgroup analyses, identified BNP/NT-proBNP cutoffs had higher discrimination if specimens were obtained 24 hours or less after admission, in patients with severe sepsis/septic shock, in patients enrolled after 2010, and in studies performed in the United States and Europe. There was inconsistent adjustment for renal function. In this hypothesis-generating analysis, BNP and NT-proBNP cutoffs of 622 pg/mL and 4000 pg/mL optimally predicted short-term mortality in patients with sepsis. The applicability of these results is limited by the heterogeneity of included patient populations.
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- 2020
49. Clinically ascertained health outcomes, quality of life, and social attainment among adult survivors of neuroblastoma: A report from the St. Jude Lifetime Cohort
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Matthew J. Ehrhardt, Kirsten K. Ness, Matthew J. Krasin, Wayne L. Furman, Leslie L. Robison, Melissa M. Hudson, Daniel M. Green, Sujuan Huang, Nickhill Bhakta, Tara M. Brinkman, Carmen L. Wilson, Geehong Hyun, and Cathleen Marie Cook
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Hypercholesterolemia ,Pain ,Anxiety ,Psychological Distress ,Article ,Neuroblastoma ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Cancer Survivors ,Quality of life ,Internal medicine ,Outcome Assessment, Health Care ,Confidence Intervals ,medicine ,Humans ,Obesity ,030212 general & internal medicine ,Marriage ,Hearing Loss ,Somatoform Disorders ,Hypertriglyceridemia ,Cancer survivor ,business.industry ,Common Terminology Criteria for Adverse Events ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Distress ,Social Class ,Oncology ,Unemployment ,030220 oncology & carcinogenesis ,Chronic Disease ,Hypertension ,Cohort ,Quality of Life ,Female ,Independent Living ,Nervous System Diseases ,business ,Somatization - Abstract
BACKGROUND The objective of this study was to characterize chronic disease, health-related quality of life (HRQOL), emotional distress, and social attainment among long-term survivors of neuroblastoma. METHODS Chronic health conditions among 136 ≥10-year neuroblastoma survivors (median age, 31.9 years; range, 20.2-54.6 years) and 272 community controls (median age, 34.7 years; range, 18.3-59.6 years) were graded with a modified version of the Common Terminology Criteria for Adverse Events (version 4.03). HRQOL and emotional distress were assessed with the Medical Outcomes Study 36-Item Short Form Health Survey and the Brief Symptom Inventory-18. Log-binomial regression and logistic regression were used to compare the prevalence of chronic conditions and the frequency of reduced HRQOL, distress, and social attainment between survivors and controls. The cumulative burden approach was used to estimate multimorbidity. RESULTS By the age of 35 years, survivors had experienced, on average, 8.5 grade 1 to 5 conditions (95% confidence interval [CI], 7.6-9.3), which was higher than the average for controls (3.3; 95% CI, 2.9-3.7). Compared with controls, survivors had a higher prevalence of any pulmonary (P = .003), auditory (P
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- 2020
50. Persistent Opioid Use Among the Elderly After Lung Resection: A SEER-Medicare Study
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Reza J. Mehran, Sharon H. Giordano, Jiangong Niu, David B. Nelson, Kyle G. Mitchell, Boris Sepesi, Wayne L. Hofstetter, David C. Rice, and Mara B. Antonoff
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Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Population ,030204 cardiovascular system & hematology ,Medicare ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Epidemiology ,Carcinoma ,medicine ,Humans ,education ,Aged ,Retrospective Studies ,Aged, 80 and over ,Pain, Postoperative ,education.field_of_study ,Chemotherapy ,business.industry ,Incidence ,Incidence (epidemiology) ,Retrospective cohort study ,Opioid-Related Disorders ,medicine.disease ,United States ,Analgesics, Opioid ,030228 respiratory system ,Opioid ,Female ,Surgery ,Lung resection ,Cardiology and Cardiovascular Medicine ,business ,SEER Program ,medicine.drug - Abstract
Background Opioids represent the mainstay for treating postsurgical pain but can cause significant morbidity in addition to dependency. The aim of the study was to determine the incidence of persistent opioid use after lung surgery. Methods Patients who underwent lung resection from 2008 to 2013 for non-small cell lung cancer were identified in the Surveillance, Epidemiology and End Results-Medicare database. Patients were categorized as being chronic, intermittent, or naive preoperative opioid users using information obtained from part D records. Persistent opioid use was defined as having a filled opioid prescription between 3 and 6 months after lung resection. Results A total of 6948 patients were identified, among whom 3946 (56.8%) were opioid naive, 2017 (29.0%) were intermittent opioid users, and 985 (14.2%) were chronic opioid users preoperatively. Persistent opioid use (3-6 months) after lung resection was high (31%), even among opioid-naive patients (17%). Among those who were previously opioid naive, independent predictors of persistent opioid use were receipt of adjuvant radiation or chemotherapy, less than 70 years of age, Charlson comorbidity score of 1 or 2, and residence in zip codes associated with lower education. Conversely, patients who underwent minimally invasive surgery were less likely to have persistent opioid use. Those with persistent opioid use after surgery did not show any trend toward returning to preoperative opioid utilization for at least the first postoperative year. Conclusions Opioid dependence after lung resection in the population over 65 years of age is high but was significantly lower among those who received minimally invasive surgery, in addition to other factors.
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- 2020
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