66 results on '"Oromendia C"'
Search Results
2. Attributable Mortality of Acute Respiratory Distress Syndrome in Critically Ill Septic Patients: Estimation Using a Novel Causal Inference Method
- Author
-
Torres, L.K., primary, Hoffman, K., additional, Oromendia, C., additional, Diaz, I., additional, Schenck, E., additional, Higuera Moreno, A., additional, Pinilla Vera, M., additional, Baron, R.M., additional, Fredenburgh, L.E., additional, Huh, J.W., additional, Choi, A.M.K., additional, and Siempos, I.I., additional
- Published
- 2020
- Full Text
- View/download PDF
3. A Symptom-Based Approach to Defining Exacerbations Suggests High Burden of Exacerbation Events in SPIROMICS
- Author
-
Krishnan, J.K., primary, Oromendia, C., additional, Easthausen, I., additional, Muellerova, H., additional, Barjaktarevic, I., additional, Barr, R.G., additional, Bowler, R.P., additional, Dransfield, M.T., additional, Han, M.K., additional, Hansel, N.N., additional, Krishnan, J.A., additional, Marzan-McGill, R., additional, Paine, R., additional, Putcha, N., additional, Sack, C., additional, Sheffey, M., additional, Villarreal, M., additional, Woodruff, P., additional, Martinez, F.J., additional, and Christenson, S., additional
- Published
- 2020
- Full Text
- View/download PDF
4. An Analysis of the Respiratory Sub-Score of the Sequential Organ Failure Assessment (SOFA) Scoring System in Patients Treated with High Flow Nasal Cannula (HFNC)
- Author
-
Lee, S.F., primary, Torres, L.K., additional, Oromendia, C., additional, Sanchez, E., additional, Siempos, I.I., additional, and Schenck, E., additional
- Published
- 2020
- Full Text
- View/download PDF
5. Recurrent thrombosis in patients with antiphospholipid antibodies and arterial thrombosis on antithrombotic therapy
- Author
-
Giannakopoulos, B, Krilis, S, de Jesus, G, Levy, R, Rosa, R, Andrade, D, Fortin, Pf, Zhang, Z, Zuily, S, Wahl, D, Tektonidou, M, Nalli, C, Andreoli, L, Tincani, A, Chighizola, Cb, Gerosa, M, Meroni, P, Banzato, A, Pengo, V, Sciascia, S, De Ceulaer, K, Davis, S, Atsumi, T, Uthman, I, Derksen, R, Degroot, P, Ugarte, A, Ruiz Irastorza, G, Rodriguez-Pinto, I, Pons-Estel, G, Cervera, R, Rodriguez, E, Aguirre Zamorano MA, Lopez-Pedrera), R, Mackie, I, Efthymiou, M, Cohen, H, Bertolaccini, Ml, Cuadrado, M, Khamashta, M, Sanna, G, Petri, M, Roubey, R, Knight, Js, Ortel, T, Gonzalez, E, Willis, Jhon Raymond, Levine, S, Rand, J, Belmont, Hm, Barbhaiya, M, Erkan, D, Salmon, J, Lockshin, M, Branch, W, Jackson, Wg, Oromendia, C, Unlu, O, and Desancho, Mt
- Subjects
030203 arthritis & rheumatology ,medicine.medical_specialty ,biology ,medicine.drug_class ,business.industry ,Anticoagulant ,Hematology ,030204 cardiovascular system & hematology ,Single Center ,medicine.disease ,Thrombosis ,Thrombosis and Hemostasis ,Clinical trial ,03 medical and health sciences ,0302 clinical medicine ,Antiphospholipid syndrome ,Internal medicine ,Antithrombotic ,medicine ,biology.protein ,In patient ,Antibody ,business - Abstract
Management for patients with antiphospholipid syndrome (APS) and arterial thrombosis is controversial. There are no prospective data demonstrating the superiority of high- or moderate-intensity anticoagulation with vitamin K antagonists over antiplatelet agents. Using 2 antiphospholipid antibody databases (single center [New York Presbyterian Hospital] and multicenter [Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking]), we retrospectively collected demographic and clinical data of patients with APS and arterial thrombosis. The primary outcome was recurrent thrombosis rate after initial arterial thrombosis in patients with APS treated with antiplatelet and/or anticoagulant therapy. We identified 139 patients with a median follow-up time of 4.24 years after initial thrombosis. Thirty-seven patients (27.3%) received anticoagulants, 43 (30.9%) antiplatelets, and 58 (41.7%) combined therapy. Sixteen patients (37.2%) in the antiplatelet group, 9 (23.7%) in the anticoagulant group, and 4 (6.9%) in the combined therapy group experienced recurrent thrombosis. We estimate that 20% of patients will experience a recurrence by 3.4, 7.3, and 16.3 years, respectively, depending on assignment to antiplatelet, anticoagulant, or combined therapy. These results suggest that combined therapy decreases the rate of and increases the time to thrombosis recurrence in patients with APS presenting with arterial thrombosis.
- Published
- 2017
- Full Text
- View/download PDF
6. The Necroptosis Endotype in Neutropenic Critical Illness
- Author
-
Price, D., primary, Oromendia, C., additional, Sanchez, E., additional, Ma, K.C., additional, Schenck, E., additional, Nakahira, K., additional, Choi, M.E., additional, Baron, R.M., additional, Fredenburgh, L.E., additional, Higuera, A., additional, Pinilla Vera, M., additional, Huh, J.W., additional, Lee, J.Y., additional, Suh, G.Y., additional, Siempos, I.I., additional, and Choi, A.M.K., additional
- Published
- 2019
- Full Text
- View/download PDF
7. Mortality of Acute Hypoxemic Respiratory Failure Compared with Acute Respiratory Distress Syndrome in Critically Ill Patients
- Author
-
Torres, L., primary, Finkelsztein, E., additional, Oromendia, C., additional, Schenck, E., additional, Higuera, A., additional, Mayra, V., additional, Baron, R.M., additional, Fredenburgh, L.E., additional, Huh, J.W., additional, Choi, A.M.K., additional, and Siempos, I.I., additional
- Published
- 2019
- Full Text
- View/download PDF
8. An Analysis of the Respiratory Subscore of the Sequential Organ Failure Assessment (SOFA) Scoring System in the Weill Cornell-Critical Care Database for Advanced Research (WC-CEDAR)
- Author
-
Schenck, E., primary, Oromendia, C., additional, Sanchez, E., additional, Finkelzstein, E., additional, Hong, K.S., additional, Kabariti, J., additional, Flores, S., additional, Harrington, J.S., additional, Siempos, I.I., additional, Campion, T., additional, and Choi, A.M.K., additional
- Published
- 2019
- Full Text
- View/download PDF
9. Pedestrians struck by motor vehicles: In search of a target for intervention
- Author
-
Ferrari-Light, D., primary, Oromendia, C., additional, Melnic, G., additional, Sample, J., additional, and Saldinger, P., additional
- Published
- 2018
- Full Text
- View/download PDF
10. Phase I dose-escalation study of fractionated dose 177Lu-PSMA-617 for progressive metastatic castration resistant prostate cancer (mCRPC)
- Author
-
Tagawa, S.T., primary, Vallabhajosula, S., additional, Jhanwar, Y., additional, Hackett, A., additional, Oromendia, C., additional, Naiz, M.J., additional, Goldsmith, S.J., additional, Nanus, D.M., additional, Beltran, H., additional, Molina, A.M., additional, Faltas, B., additional, Sreekumar, J., additional, Babich, J., additional, Ballman, K., additional, and Bander, N.H., additional
- Published
- 2018
- Full Text
- View/download PDF
11. Clinico-genomic profiling and outcome prediction of neuroendocrine prostate cancer (NEPC)
- Author
-
Conteduca, V., primary, Oromendia, C., additional, Sigouros, M., additional, Sborner, A., additional, Nanus, D.M., additional, Tagawa, S.T., additional, Ballman, K., additional, and Beltran, H., additional
- Published
- 2018
- Full Text
- View/download PDF
12. A phase 2 study of the aurora kinase A inhibitor alisertib for patients with neuroendocrine prostate cancer (NEPC)
- Author
-
Beltran, H., primary, Danila, D., additional, Montgomery, B., additional, Szmulewitz, R., additional, Vaishampayan, U., additional, Armstrong, A., additional, Stein, M., additional, Hoimes, C., additional, Pinski, J., additional, Scher, H., additional, Puca, L., additional, Bareja, R., additional, Wong, W., additional, Rubin, M., additional, Mosquera, J.M., additional, Sboner, A., additional, Oromendia, C., additional, Nanus, D., additional, Ballman, K., additional, and Tagawa, S.T., additional
- Published
- 2016
- Full Text
- View/download PDF
13. Sequence of Radiation Therapy Versus Surgery on Outcomes in Gastroesophageal Junction Cancer
- Author
-
Kim, S.K., primary, Oromendia, C., additional, Christos, P., additional, Wernicke, A.G., additional, and Parashar, B., additional
- Published
- 2016
- Full Text
- View/download PDF
14. Changes in practice patterns in male infertility cases in the United States - the trend toward subspecialization
- Author
-
Bach, P.V., primary, Najari, B.B., additional, Oromendia, C., additional, Neto, F., additional, Goldstein, M., additional, Hu, J.C., additional, and Kashanian, J., additional
- Published
- 2016
- Full Text
- View/download PDF
15. 839P - Clinico-genomic profiling and outcome prediction of neuroendocrine prostate cancer (NEPC)
- Author
-
Conteduca, V., Oromendia, C., Sigouros, M., Sborner, A., Nanus, D.M., Tagawa, S.T., Ballman, K., and Beltran, H.
- Published
- 2018
- Full Text
- View/download PDF
16. 799PD - Phase I dose-escalation study of fractionated dose 177Lu-PSMA-617 for progressive metastatic castration resistant prostate cancer (mCRPC)
- Author
-
Tagawa, S.T., Vallabhajosula, S., Jhanwar, Y., Hackett, A., Oromendia, C., Naiz, M.J., Goldsmith, S.J., Nanus, D.M., Beltran, H., Molina, A.M., Faltas, B., Sreekumar, J., Babich, J., Ballman, K., and Bander, N.H.
- Published
- 2018
- Full Text
- View/download PDF
17. LBA29 - A phase 2 study of the aurora kinase A inhibitor alisertib for patients with neuroendocrine prostate cancer (NEPC)
- Author
-
Beltran, H., Danila, D., Montgomery, B., Szmulewitz, R., Vaishampayan, U., Armstrong, A., Stein, M., Hoimes, C., Pinski, J., Scher, H., Puca, L., Bareja, R., Wong, W., Rubin, M., Mosquera, J.M., Sboner, A., Oromendia, C., Nanus, D., Ballman, K., and Tagawa, S.T.
- Published
- 2016
- Full Text
- View/download PDF
18. Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort.
- Author
-
Zhang WZ, Rice MC, Hoffman KL, Oromendia C, Barjaktarevic IZ, Wells JM, Hastie AT, Labaki WW, Cooper CB, Comellas AP, Criner GJ, Krishnan JA, Paine R 3rd, Hansel NN, Bowler RP, Barr RG, Peters SP, Woodruff PG, Curtis JL, Han MK, Ballman KV, Martinez FJ, Choi AM, Nakahira K, Cloonan SM, and Choi ME
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Cohort Studies, Biomarkers urine, Spirometry, DNA, Mitochondrial genetics, DNA, Mitochondrial urine, Pulmonary Disease, Chronic Obstructive urine, Pulmonary Disease, Chronic Obstructive genetics, Pulmonary Disease, Chronic Obstructive diagnosis
- Published
- 2024
- Full Text
- View/download PDF
19. Serum proteomic profiling of rheumatoid arthritis-interstitial lung disease with a comparison to idiopathic pulmonary fibrosis.
- Author
-
Wu X, Jeong Y, Poli de Frías S, Easthausen I, Hoffman K, Oromendia C, Taheri S, Esposito AJ, Quesada Arias L, Ayaub EA, Maurer R, Gill RR, Hatabu H, Nishino M, Frits ML, Iannaccone CK, Weinblatt ME, Shadick NA, Dellaripa PF, Choi AMK, Kim EY, Rosas IO, Martinez FJ, and Doyle TJ
- Subjects
- Humans, Proteomics, Lung Diseases, Interstitial complications, Idiopathic Pulmonary Fibrosis genetics, Idiopathic Pulmonary Fibrosis complications, Arthritis, Rheumatoid genetics, Arthritis, Rheumatoid complications
- Abstract
Although interstitial lung disease (ILD) causes significant morbidity and mortality in rheumatoid arthritis (RA), it is difficult to predict the development or progression of ILD, emphasising the need for improved discovery through minimally invasive diagnostic tests. Aptamer-based proteomic profiling was used to assess 1321 proteins from 159 patients with rheumatoid arthritis with interstitial lung disease (RA-ILD), RA without ILD, idiopathic pulmonary fibrosis and healthy controls. Differential expression and gene set enrichment analyses revealed molecular signatures that are strongly associated with the presence and severity of RA-ILD and provided insight into unexplored pathways of disease. These warrant further study as non-invasive diagnostic tools and future therapeutic targets., Competing Interests: Competing interests: The authors have reported the following conflicts of interest, all outside the submitted work: ST reports medical advisory group membership of Novo Nordisk and board membership at Droobi Health, Qatar. RG receives grant support from Canon Medical Systems. HH reports grants from Canon Medical Systems and Konica Minolta, and personal fees from Mitsubishi Chemical Co and Canon Medical Systems Inc. MN reports grants from AstraZeneca, Daiichi Sankyo, Canon Medical Systems, Merck investigator studies program; personal fees from Daiichi Sankyo and AstraZeneca. MEW receives research support from Amgen, Bristol Myers Squibb and Eli Lilly and consultation fees from AbbVie, Aclaris, Amgen, Arena, Bayer, Bristol Myers Squibb, Corvitas, Eqrx, Genosco, GSK, Gilead, Horizon, Johnson & Johnson, Kiniksa, Lilly, Novartis, Pfizer, Rami Therapeutics, R Pharma, Roche, Sanofi, Scipher, Sci Rhom, Set Point and Tremeau. He holds stock/stock options of CanFite, Inmedix, Vorso and Scipher. NAS reports grants and other support from Bristol-Myers Squibb, grants from Mallinckrodt, Sanofi, Crescendo Biosciences, Lilly and Amgen. PFD reports grants from Bristol-Myers Squibb and Genentech, and other support from Boehringer Ingelheim. AMKC is a cofounder and equity stock holder for Proterris, which develops therapeutic uses for carbon monoxide, and also has a use patent on CO and a patent in chronic obstructive pulmonary disease. EYK is a member of the steering committees for and receives no financial remuneration from NCT04409834 (Prevention of arteriovenous thrombotic events in critically ill COVID-19 patients, TIMI group) and REMAP-CAP ACE2 renin–angiotensin system modulation domain, and receives unrelated research funding from Bayer AG, Roche Pharma Research and Early Development, Windtree Therapeutics, the US National Institutes of Health, the US Agency for International Development, the American Heart Association, American Lung Association and the Bell Family Fund. IOR reports grants from Genentech. FJM reports personal fees, non-financial support and other support from AstraZeneca, other support from Afferent/Merck, personal fees, non-financial support and other support from Boehringer Ingelheim, other support from Bristol Myers Squibb, other support from Chiesi, personal fees and non-financial support from the Canadian Respiratory Society, personal fees and non-financial support from CME Outfitters, personal fees and non-financial support from CSL Behring, personal fees from Dartmouth University, personal fees from France Foundation, personal fees from Gala, personal fees and non-financial support from Genentech, grants, personal fees, non-financial support and other support from GlaxoSmithKline, personal fees and non-financial support from Inova Fairfax, personal fees and non-financial support from MD Magazine, personal fees and non-financial support from NYP Methodist Hospital Brooklyn, personal fees and non-financial support from Miller Communications, personal fees and non-financial support from National Association for Continuing Education/Integritas, other support from Nitto, personal fees and non-financial support from Novartis, personal fees from New York University, personal fees and non-financial support from Patara/Respivant, personal fees from Pearl, personal fees and non-financial support from Peer View, personal fees from Physicians Education Resource, personal fees from ProMedior, personal fees and non-financial support from Rare Diseases Healthcare Communications, personal fees from Rockpointe Communications, personal fees and non-financial support from Sanofi/Regeneron, other support from Biogen, personal fees and non-financial support from Sunovion, personal fees and non-financial support from Teva, other support from two XAR, personal fees from University of Birmingham Alabama, personal fees from UpToDate, non-financial support from Veracyte, personal fees from Vindico, personal fees and non-financial support from WebMD/MedScape, non-financial support and other support from Zambon, non-financial support from ProTerrix Bio, and personal fees from IQVIA, Raziel, Abvie and Verona. TJD has received grant support from Bristol Myers Squibb, consulting fees from Boehringer Ingelheim and L.E.K. consulting, and has been part of a clinical trial funded by Genentech. The remaining authors have reported no conflicts of interest., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2022
- Full Text
- View/download PDF
20. The genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy.
- Author
-
van der Mijn JC, Eng KW, Chandra P, Fernandez E, Ramazanoglu S, Sigaras A, Oromendia C, Gudas LJ, Tagawa ST, Nanus DM, Faltas BF, Beltran H, Sternberg CN, Elemento O, Sboner A, Mosquera JM, and Molina AM
- Subjects
- DNA Copy Number Variations genetics, F-Box-WD Repeat-Containing Protein 7 genetics, Genomics, Humans, Mutation genetics, Nuclear Proteins metabolism, RNA-Binding Proteins genetics, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology
- Abstract
Primary clear cell renal cell carcinoma (ccRCC) has been previously characterized, but the genomic landscape of metastatic ccRCC is largely unexplored. Here, we performed whole exome sequencing (WES) in 68 samples from 44 patients with ccRCC, including 52 samples from a metastatic site. SETD2, PBRM1, APC and VHL were the most frequently mutated genes in the metastatic ccRCC cohort. RBM10 and FBXW7 were also among the 10 most frequently mutated genes in metastatic tissues. Recurrent somatic copy number variations (CNV) were observed at the previously identified regions 3p25, 9p21 and 14q25, but also at 6p21 (CDKN1A) and 13q14 (RB1). No statistically significant differences were found between samples from therapy-naïve and pretreated patients. Clonal evolution analyses with multiple samples from 13 patients suggested that early appearance of CNVs at 3p25, 9p21 and 14q25 may be associated with rapid clinical progression. Overall, the genomic landscapes of primary and metastatic ccRCC seem to share frequent CNVs at 3p25, 9p21 and 14q25. Future work will clarify the implication of RBM10 and FBXW7 mutations and 6p21 and 13q14 CNVs in metastatic ccRCC., (© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Published
- 2022
- Full Text
- View/download PDF
21. Characterizing COPD Symptom Variability in the Stable State Utilizing the Evaluating Respiratory Symptoms in COPD Instrument.
- Author
-
Krishnan JK, Ancy KM, Oromendia C, Hoffman KL, Easthausen I, Leidy NK, Han MK, Bowler RP, Christenson SA, Couper DJ, Criner GJ, Curtis JL, Dransfield MT, Hansel NN, Iyer AS, Paine Iii R, Peters SP, Wedzicha JA, Woodruff PG, Ballman KV, and Martinez FJ
- Abstract
Rationale: It has been suggested that patients with chronic obstructive pulmonary disease (COPD) experience considerable daily respiratory symptom fluctuation. A standardized measure is needed to quantify and understand the implications of day-to-day symptom variability., Objectives: To compare standard deviation with other statistical measures of symptom variability and identify characteristics of individuals with higher symptom variability., Methods: Individuals in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) Exacerbations sub-study completed an Evaluating Respiratory Symptoms in COPD (E-RS) daily questionnaire. We calculated within-subject standard deviation (WS-SD) for each patient at week 0 and correlated this with measurements obtained 4 weeks later using Pearson's r and Bland Altman plots. Median WS-SD value dichotomized participants into higher versus lower variability groups. Association between WS-SD and exacerbation risk during 4 follow-up weeks was explored., Measurements and Main Results: Diary completion rates were sufficient in 140 (68%) of 205 sub-study participants. Reproducibility (r) of the WS-SD metric from baseline to week 4 was 0.32. Higher variability participants had higher St George's Respiratory Questionnaire (SGRQ) scores (47.3 ± 20.3 versus 39.6 ± 21.5, p =.04) than lower variability participants. Exploratory analyses found no relationship between symptom variability and health care resource utilization-defined exacerbations., Conclusions: WS-SD of the E-RS can be used as a measure of symptom variability in studies of patients with COPD. Patients with higher variability have worse health-related quality of life. WS-SD should be further validated as a measure to understand the implications of symptom variability., (JCOPDF © 2022.)
- Published
- 2022
- Full Text
- View/download PDF
22. Attributable mortality of acute respiratory distress syndrome: a systematic review, meta-analysis and survival analysis using targeted minimum loss-based estimation.
- Author
-
Torres LK, Hoffman KL, Oromendia C, Diaz I, Harrington JS, Schenck EJ, Price DR, Gomez-Escobar L, Higuera A, Vera MP, Baron RM, Fredenburgh LE, Huh JW, Choi AMK, and Siempos II
- Subjects
- Critical Illness, Hospital Mortality, Humans, Intensive Care Units, Survival Analysis, Respiratory Distress Syndrome
- Abstract
Background: Although acute respiratory distress syndrome (ARDS) is associated with high mortality, its direct causal link with death is unclear. Clarifying this link is important to justify costly research on prevention of ARDS., Objective: To estimate the attributable mortality, if any, of ARDS., Design: First, we performed a systematic review and meta-analysis of observational studies reporting mortality of critically ill patients with and without ARDS matched for underlying risk factor. Next, we conducted a survival analysis of prospectively collected patient-level data from subjects enrolled in three intensive care unit (ICU) cohorts to estimate the attributable mortality of critically ill septic patients with and without ARDS using a novel causal inference method., Results: In the meta-analysis, 44 studies (47 cohorts) involving 56 081 critically ill patients were included. Mortality was higher in patients with versus without ARDS (risk ratio 2.48, 95% CI 1.86 to 3.30; p<0.001) with a numerically stronger association between ARDS and mortality in trauma than sepsis. In the survival analysis of three ICU cohorts enrolling 1203 critically ill patients, 658 septic patients were included. After controlling for confounders, ARDS was found to increase the mortality rate by 15% (95% CI 3% to 26%; p=0.015). Significant increases in mortality were seen for severe (23%, 95% CI 3% to 44%; p=0.028) and moderate (16%, 95% CI 2% to 31%; p=0.031), but not for mild ARDS., Conclusions: ARDS has a direct causal link with mortality. Our findings provide information about the extent to which continued funding of ARDS prevention trials has potential to impart survival benefit., Prospero Registration Number: CRD42017078313., Competing Interests: Competing interests: AMKC is a cofounder and stock holder of and serves on the Scientific Advisory Board for Proterris, which develops therapeutic uses for carbon monoxide. He also has a use patent on carbon monoxide. He served as a consultant for an advisory board meeting of Teva Pharmaceutical Industries, July 2018. RMB serves on the Advisory Board for Merck. LEF reports clinical trials support from Asahi Kasei Pharma America. None declared: LKT, KH, CO, ID, JSH, EJS, DRP, LG-E, AH, MPV, JWH and IIS., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2021
- Full Text
- View/download PDF
23. A Comparative Analysis of the Respiratory Subscore of the Sequential Organ Failure Assessment Scoring System.
- Author
-
Schenck EJ, Hoffman KL, Oromendia C, Sanchez E, Finkelsztein EJ, Hong KS, Kabariti J, Torres LK, Harrington JS, Siempos II, Choi AMK, and Campion TR Jr
- Subjects
- Humans, Intensive Care Units, Oxygen, Prognosis, ROC Curve, Retrospective Studies, Organ Dysfunction Scores, Oximetry
- Abstract
Rationale: The Sequential Organ Failure Assessment (SOFA) tool is a commonly used measure of illness severity. Calculation of the respiratory subscore of SOFA is frequently limited by missing arterial oxygen pressure (Pa
O ) data. Although missing Pa2 O data are commonly replaced with normal values, the performance of different methods of substituting Pa2 O for SOFA calculation is unclear. Objectives: The study objective was to compare the performance of different substitution strategies for missing Pa2 O data for SOFA score calculation. Methods: This retrospective cohort study was performed using the Weill Cornell Critical Care Database for Advanced Research from a tertiary care hospital in the United States. All adult patients admitted to an intensive care unit (ICU) from 2011 to 2019 with an available respiratory SOFA score were included. We analyzed the availability of the Pa2 O /fraction of inspired oxygen (Fi2 O ) ratio on the first day of ICU admission. In those without a Pa2 O /Fi2 O ratio available, the ratio of oxygen saturation as measured by pulse oximetry to Fi2 O was used to calculate a respiratory SOFA subscore according to four methods (linear substitution [Rice], nonlinear substitution [Severinghaus], modified respiratory SOFA, and multiple imputation by chained equations [MICE]) as well as the missing-as-normal technique. We then compared how well the different total SOFA scores discriminated in-hospital mortality. We performed several subgroup and sensitivity analyses. Results: We identified 35,260 unique visits, of which 9,172 included predominant respiratory failure. Pa2 O data were available for 14,939 (47%). The area under the receiver operating characteristic curve for each substitution technique for discriminating in-hospital mortality was higher than that for the missing-as-normal technique (0.78 [0.77-0.79]) in all analyses (modified, 0.80 [0.79-0.81]; Rice, 0.80 [0.79-0.81]; Severinghaus, 0.80 [0.79-0.81]; and MICE, 0.80 [0.79-0.81]) ( P < 0.01). Each substitution method had a higher accuracy for discriminating in-hospital mortality (MICE, 0.67; Rice, 0.67; modified, 0.66; and Severinghaus, 0.66) than the missing-as-normal technique. Model calibration for in-hospital mortality was less precise for the missing-as-normal technique than for the other substitution techniques at the lower range of SOFA and among the subgroups. Conclusions: Using physiologic and statistical substitution methods improved the total SOFA score's ability to discriminate mortality compared with the missing-as-normal technique. Treating missing data as normal may result in underreporting the severity of illness compared with using substitution. The simplicity of a direct oxygen saturation as measured by pulse oximetry/Fi2 O ratio-modified SOFA technique makes it an attractive choice for electronic health record-based research. This knowledge can inform comparisons of severity of illness across studies that used different techniques.2 - Published
- 2021
- Full Text
- View/download PDF
24. Evaluation of Technology-Enabled Monitoring of Patient-Reported Outcomes to Detect and Treat Toxic Effects Linked to Immune Checkpoint Inhibitors.
- Author
-
Msaouel P, Oromendia C, Siefker-Radtke AO, Tannir NM, Subudhi SK, Gao J, Wang Y, Siddiqui BA, Shah AY, Aparicio AM, Campbell MT, Zurita AJ, Shaw LK, Lopez LP, McCord H, Chakraborty SN, Perales J, Lu C, Van Alstine ML, Elashoff M, and Logothetis C
- Subjects
- Adult, Aged, Aged, 80 and over, Biological Monitoring instrumentation, Cohort Studies, Female, Humans, Male, Middle Aged, Texas, Toxicity Tests instrumentation, Biological Monitoring methods, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors toxicity, Mobile Applications, Patient Reported Outcome Measures, Toxicity Tests methods, Urogenital Neoplasms drug therapy
- Abstract
Importance: Immune checkpoint inhibitors can produce distinct toxic effects that require prompt recognition and timely management., Objective: To develop a technology-enabled, dynamically adaptive protocol that can provide the accurate information needed to inform specific remedies for immune toxic effects in patients treated with immune checkpoint inhibitors., Design, Setting, and Participants: An open-label cohort study was conducted at a single tertiary referral center from September 6, 2019, to September 3, 2020. The median follow-up duration was 63 (interquartile range, 35.5-122) days. Fifty patients with genitourinary cancers treated with immune checkpoint inhibitors were enrolled., Interventions: A fit-for-purpose electronic platform was developed to enable active patient and care team participation. A smartphone application downloaded onto patients' personal mobile devices prompted them to report their symptoms at least 3 times per week. The set of symptoms and associated queries were paired with alert thresholds for symptoms requiring clinical action., Main Outcomes and Measures: The primary end point of this interim analysis was feasibility, as measured by patient and care team adherence, and lack of increase in care team staffing. Operating characteristics were estimated for each symptom alert and used to dynamically adapt the alert thresholds to ensure sensitivity while reducing unnecessary alerts., Results: Of the 50 patients enrolled, 47 had at least 1 follow-up visit and were included in the analysis. Median age was 65 years (range, 37-86), 39 patients (83%) were men, and 39 patients (83%) had metastatic cancer, with the most common being urothelial cell carcinoma and renal cell carcinoma (22 [47%] patients each). After initial onboarding, no further care team training or additional care team staffing was required. Patients had a median study adherence rate of 74% (interquartile range, 60%-86%) and 73% of automated alerts were reviewed within 3 days by the clinic team. Symptoms with the highest positive predictive value for adverse events requiring acute intervention included dizziness (21%), nausea/vomiting (26%), and shortness of breath (14%). The symptoms most likely to result in unnecessary alerts were arthralgia and myalgia, fatigue, and cough., Conclusions and Relevance: The findings of this cohort study suggest an acceptable and fiscally sound method can be developed to create a dynamic learning system to detect and manage immune-related toxic effects.
- Published
- 2021
- Full Text
- View/download PDF
25. Association of plasma mitochondrial DNA with COPD severity and progression in the SPIROMICS cohort.
- Author
-
Zhang WZ, Hoffman KL, Schiffer KT, Oromendia C, Rice MC, Barjaktarevic I, Peters SP, Putcha N, Bowler RP, Wells JM, Couper DJ, Labaki WW, Curtis JL, Han MK, Paine R 3rd, Woodruff PG, Criner GJ, Hansel NN, Diaz I, Ballman KV, Nakahira K, Choi ME, Martinez FJ, Choi AMK, and Cloonan SM
- Subjects
- Aged, DNA, Mitochondrial blood, Disease Progression, Exercise Tolerance, Female, Forced Expiratory Volume, Humans, Longitudinal Studies, Lung physiopathology, Male, Middle Aged, NADH Dehydrogenase blood, Prospective Studies, Pulmonary Disease, Chronic Obstructive blood, Pulmonary Disease, Chronic Obstructive diagnosis, Pulmonary Disease, Chronic Obstructive physiopathology, Severity of Illness Index, Smokers, Smoking adverse effects, Surveys and Questionnaires, Time Factors, United States, Walk Test, DNA, Mitochondrial genetics, NADH Dehydrogenase genetics, Pulmonary Disease, Chronic Obstructive genetics
- Abstract
Background: There is a lack of mechanism-driven, clinically relevant biomarkers in chronic obstructive pulmonary disease (COPD). Mitochondrial dysfunction, a proposed disease mechanism in COPD, is associated with the release of mitochondrial DNA (mtDNA), but plasma cell-free mtDNA has not been previously examined prospectively for associations with clinical COPD measures., Methods: P-mtDNA, defined as copy number of mitochondrially-encoded NADH dehydrogenase-1 (MT-ND1) gene, was measured by real-time quantitative PCR in 700 plasma samples from participants enrolled in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Associations between p-mtDNA and clinical disease parameters were examined, adjusting for age, sex, smoking status, and for informative loss to follow-up., Results: P-mtDNA levels were higher in participants with mild or moderate COPD, compared to smokers without airflow obstruction, and to participants with severe COPD. Baseline increased p-mtDNA levels were associated with better CAT scores in female smokers without airflow obstruction and female participants with mild or moderate COPD on 1-year follow-up, but worse 6MWD in females with severe COPD. Higher p-mtDNA levels were associated with better 6MWD in male participants with severe COPD. These associations were no longer significant after adjusting for informative loss to follow-up., Conclusion: In this study, p-mtDNA levels associated with baseline COPD status but not future changes in clinical COPD measures after accounting for informative loss to follow-up. To better characterize mitochondrial dysfunction as a potential COPD endotype, these results should be confirmed and validated in future studies., Trial Registration: ClinicalTrials.gov NCT01969344 (SPIROMICS).
- Published
- 2021
- Full Text
- View/download PDF
26. Effect of Neutropenic Critical Illness on Development and Prognosis of Acute Respiratory Distress Syndrome.
- Author
-
Price DR, Hoffman KL, Oromendia C, Torres LK, Schenck EJ, Choi ME, Choi AMK, Baron RM, Huh JW, and Siempos II
- Subjects
- Adult, Aged, Cohort Studies, Female, Humans, Male, Middle Aged, New York, Prognosis, Republic of Korea, Utah, Neutropenia complications, Neutropenia diagnosis, Neutropenia physiopathology, Respiratory Distress Syndrome diagnosis, Respiratory Distress Syndrome etiology, Respiratory Distress Syndrome physiopathology, Respiratory Distress Syndrome therapy
- Published
- 2021
- Full Text
- View/download PDF
27. Increased platelet activation in sleep apnea subjects with intermittent hypoxemia.
- Author
-
Krieger AC, Anand R, Hernandez-Rosa E, Maidman A, Milrad S, DeGrazia MQ, Choi AJ, Oromendia C, Marcus AJ, and Drosopoulos JHF
- Subjects
- Adult, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Platelet Aggregation, Sleep Apnea, Obstructive complications, Hypoxia complications, Platelet Activation, Sleep Apnea, Obstructive blood, Sleep Apnea, Obstructive physiopathology
- Abstract
Purpose: Obstructive sleep apnea (OSA) is independently associated with increased risk for stroke and other cardiovascular diseases. Since activated platelets play an important role in cardiovascular disease, the objective of this study was to determine whether platelet reactivity was altered in OSA subjects with intermittent nocturnal hypoxemia., Methods: Thirty-one subjects, without hypertension or cardiovascular disease and not taking medication, participated in the study. Subjects were stratified based on OSA-related oxygen desaturation index (ODI) recorded during overnight polysomnography. Platelet reactivity to a broad panel of agonists (collagen, thrombin, protease-activated receptor1 hexapeptide, epinephrine, ADP) was measured by monitoring platelet aggregation and ATP secretion. Expression of platelet activation markers CD154 (CD40L) and CD62P (P-selectin) and platelet-monocyte aggregates (PMA) was quantified by flow cytometry., Results: Epinephrine-induced platelet aggregation was substantially decreased in OSA subjects with significant intermittent hypoxemia (ODI ≥ 15) compared with subjects with milder hypoxemia levels (ODI < 15) (area under curve, p = 0.01). In addition, OSA subjects with ODI ≥ 15 exhibited decreased thrombin-induced platelet aggregation (p = 0.02) and CD40L platelet surface expression (p = 0.05). Platelet responses to the other agonists, CD62P platelet surface expression, and PMA levels were not significantly different between groups. Reduction in platelet responses to epinephrine and thrombin, and decreased CD40L surface marker expression in significant hypoxemic OSA individuals, is consistent with their platelets being in an activated state., Conclusions: Increased platelet activation was present in otherwise healthy subjects with intermittent nocturnal hypoxemia due to underlying OSA. This prothrombotic milieu in the vasculature is likely a key contributing factor toward development of thrombosis and cardiovascular disease., Trial Registration: NCT00859950.
- Published
- 2020
- Full Text
- View/download PDF
28. Increased airway iron parameters and risk for exacerbation in COPD: an analysis from SPIROMICS.
- Author
-
Zhang WZ, Oromendia C, Kikkers SA, Butler JJ, O'Beirne S, Kim K, O'Neal WK, Freeman CM, Christenson SA, Peters SP, Wells JM, Doerschuk C, Putcha N, Barjaktarevic I, Woodruff PG, Cooper CB, Bowler RP, Comellas AP, Criner GJ, Paine R 3rd, Hansel NN, Han MK, Crystal RG, Kaner RJ, Ballman KV, Curtis JL, Martinez FJ, and Cloonan SM
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers blood, Bronchoalveolar Lavage Fluid chemistry, Disease Progression, Female, Ferritins metabolism, Forced Expiratory Volume, Humans, Iron physiology, Iron-Binding Proteins physiology, Lung metabolism, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive metabolism, Respiratory Function Tests, Risk Factors, Severity of Illness Index, Iron metabolism, Iron-Binding Proteins metabolism, Pulmonary Disease, Chronic Obstructive physiopathology
- Abstract
Levels of iron and iron-related proteins including ferritin are higher in the lung tissue and lavage fluid of individuals with chronic obstructive pulmonary disease (COPD), when compared to healthy controls. Whether more iron in the extracellular milieu of the lung associates with distinct clinical phenotypes of COPD, including increased exacerbation susceptibility, is unknown. We measured iron and ferritin levels in the bronchoalveolar lavage fluid (BALF) of participants enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD (SPIROMICS) bronchoscopy sub-study (n = 195). BALF Iron parameters were compared to systemic markers of iron availability and tested for association with FEV
1 % predicted and exacerbation frequency. Exacerbations were modelled using a zero-inflated negative binomial model using age, sex, smoking, and FEV1 % predicted as clinical covariates. BALF iron and ferritin were higher in participants with COPD and in smokers without COPD when compared to non-smoker control participants but did not correlate with systemic iron markers. BALF ferritin and iron were elevated in participants who had COPD exacerbations, with a 2-fold increase in BALF ferritin and iron conveying a 24% and 2-fold increase in exacerbation risk, respectively. Similar associations were not observed with plasma ferritin. Increased airway iron levels may be representative of a distinct pathobiological phenomenon that results in more frequent COPD exacerbation events, contributing to disease progression in these individuals.- Published
- 2020
- Full Text
- View/download PDF
29. Prognostic value of the SPOP mutant genomic subclass in prostate cancer.
- Author
-
Shoag J, Liu D, Ma X, Oromendia C, Christos P, Ballman K, Angulo C, Cai PY, Gaffney C, Klein E, Karnes J, Den RB, Liu Y, Davicioni E, and Barbieri CE
- Subjects
- Cohort Studies, Genomics, Humans, Male, Prognosis, Prospective Studies, Prostatic Neoplasms mortality, Retrospective Studies, Survival Rate, Mutation, Nuclear Proteins genetics, Prostatic Neoplasms classification, Prostatic Neoplasms genetics, Repressor Proteins genetics
- Abstract
Background: Speckle-type POZ protein (SPOP) mutation defines one of the dominant prostate cancer genomic subtypes, yet the impact of this mutation on clinical prognosis is unknown., Methods: We defined SPOP mutation status either by DNA sequencing or by transcriptional signature in a pooled retrospective multi-institutional cohort, the Decipher retrospective cohort, the Decipher Genomics Resource Information Database prospective cohort, and The Cancer Genome Atlas. Kaplan-Meier survival analysis and multivariable Cox models were used to assess the independent impact of SPOP mutation on survival, biochemical recurrence and time to metastasis. The Decipher retrospective cohort was also used to assess the impact of the addition of SPOP mutation status to a model predicting adverse pathology at prostatectomy which was then validated in the Decipher prospective cohort., Results: A fixed-effect model incorporating results from multivariable Cox regression including 5,811 subjects demonstrated that SPOP mutation was associated with a lower rate of adverse pathology at radical prostatectomy (odds ratios 0.57, 95% confidence interval 0.34-0.93), independent of preoperative prostate-specific antigen, age, and pathologic Gleason score. SPOP was not associated with biochemical recurrence, metastasis-free survival, or cancer-specific survival independent of pathologic information. The addition of SPOP status to prognostic models reclassified a large proportion of patients with the mutation (55%) into a favorable risk group when used to predict adverse pathology., Conclusion: While the clinical utility of delineating any single molecular alteration in prostate cancer remains unclear, these results illustrates the importance of genomic subtypes in prostate cancer behavior and potential role in prognostic tools., Competing Interests: Conflict of interest YL and ED are employees of GenomeDx., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
30. Alveolar Macrophage Immunometabolism and Lung Function Impairment in Smoking and Chronic Obstructive Pulmonary Disease.
- Author
-
O'Beirne SL, Kikkers SA, Oromendia C, Salit J, Rostmai MR, Ballman KV, Kaner RJ, Crystal RG, and Cloonan SM
- Subjects
- Adult, Female, Healthy Volunteers, Humans, Male, Middle Aged, Lung immunology, Lung physiopathology, Macrophages, Alveolar metabolism, Pulmonary Disease, Chronic Obstructive chemically induced, Pulmonary Disease, Chronic Obstructive immunology, Pulmonary Disease, Chronic Obstructive physiopathology, Smoking adverse effects
- Published
- 2020
- Full Text
- View/download PDF
31. Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort.
- Author
-
Zhang WZ, Rice MC, Hoffman KL, Oromendia C, Barjaktarevic IZ, Wells JM, Hastie AT, Labaki WW, Cooper CB, Comellas AP, Criner GJ, Krishnan JA, Paine R 3rd, Hansel NN, Bowler RP, Barr RG, Peters SP, Woodruff PG, Curtis JL, Han MK, Ballman KV, Martinez FJ, Choi AM, Nakahira K, Cloonan SM, and Choi ME
- Subjects
- Aged, Biomarkers urine, Cohort Studies, Female, Humans, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive physiopathology, DNA, Mitochondrial urine, Pulmonary Disease, Chronic Obstructive urine
- Abstract
BACKGROUNDMitochondrial dysfunction, a proposed mechanism of chronic obstructive pulmonary disease (COPD) pathogenesis, is associated with the leakage of mitochondrial DNA (mtDNA), which may be detected extracellularly in various bodily fluids. Despite evidence for the increased prevalence of chronic kidney disease in COPD subjects and for mitochondrial dysfunction in the kidneys of murine COPD models, whether urine mtDNA (u-mtDNA) associates with measures of disease severity in COPD is unknown.METHODSCell-free u-mtDNA, defined as copy number of mitochondrially encoded NADH dehydrogenase-1 (MTND1) gene, was measured by quantitative PCR and normalized to urine creatinine in cell-free urine samples from participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Urine albumin/creatinine ratios (UACR) were measured in the same samples. Associations between u-mtDNA, UACR, and clinical disease parameters - including FEV1 % predicted, clinical measures of exercise tolerance, respiratory symptom burden, and chest CT measures of lung structure - were examined.RESULTSU-mtDNA and UACR levels were measured in never smokers (n = 64), smokers without airflow obstruction (n = 109), participants with mild/moderate COPD (n = 142), and participants with severe COPD (n = 168). U-mtDNA was associated with increased respiratory symptom burden, especially among smokers without COPD. Significant sex differences in u-mtDNA levels were observed, with females having higher u-mtDNA levels across all study subgroups. U-mtDNA associated with worse spirometry and CT emphysema in males only and with worse respiratory symptoms in females only. Similar associations were not found with UACR.CONCLUSIONU-mtDNA levels may help to identify distinct clinical phenotypes and underlying pathobiological differences in males versus females with COPD.TRIAL REGISTRATIONThis study has been registered at ClinicalTrials.gov ( NCT01969344).FUNDINGUS NIH, National Heart, Lung and Blood Institute, supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from AstraZeneca/MedImmune, Bayer, Bellerophon Therapeutics, Boehringer-Ingelheim Pharmaceuticals Inc., Chiesi Farmaceutici S.p.A., Forest Research Institute Inc., GlaxoSmithKline, Grifols Therapeutics Inc., Ikaria Inc., Novartis Pharmaceuticals Corporation, Nycomed GmbH, ProterixBio, Regeneron Pharmaceuticals Inc., Sanofi, Sunovion, Takeda Pharmaceutical Company, and Theravance Biopharma and Mylan.
- Published
- 2020
- Full Text
- View/download PDF
32. Bronchoscopic delivery of aminocaproic acid as a treatment for pulmonary bleeding: A case series.
- Author
-
Simon RP, Oromendia C, Sanso LM, Ramos LG, and Rajwani K
- Subjects
- Aged, Female, Hemoptysis drug therapy, Humans, Lung drug effects, Male, Middle Aged, Postoperative Complications, Retrospective Studies, Tranexamic Acid administration & dosage, Tranexamic Acid therapeutic use, Treatment Outcome, Aminocaproic Acid administration & dosage, Aminocaproic Acid therapeutic use, Antifibrinolytic Agents administration & dosage, Antifibrinolytic Agents therapeutic use, Bronchoscopy adverse effects, Hemorrhage drug therapy
- Abstract
Objective: Bronchoscopy is an essential therapeutic modality in the treatment of pulmonary bleeding. Although numerous endoscopic treatments exist, topical ε-aminocaproic acid has not been described in the literature. This study documents the use of this novel treatment for pulmonary bleeding and compares it to available evidence for tranexamic acid, a similar anti-fibrinolytic agent., Design: Case-series study., Setting: ICU and general inpatient floors of a tertiary medical center., Patients: Forty-six patients receiving endobronchial ε-aminocaproic acid for the treatment or prevention of pulmonary bleeding., Measurements and Main Results: Of the 46 patients included in the study, 41.6% and 13% presented with non-massive and massive hemoptysis, respectively. In patients with active pulmonary bleeding, endobronchial application of ε-aminocaproic acid and accompanying therapies resulted in cessation of bleeding in 94.7% of cases. A total of six patients received ε-aminocaproic acid monotherapy; in three patients with active bleeding, 100% achieved hemostasis after treatment. Of the 36 patients successfully treated for active pulmonary bleeding, 27.8% had recurrent bleeding within 30 days. Thirty-day adverse events were as follows: death (10 patients), deep vein thrombosis (2 patients), renal failure (2 patients), and stroke (2 patients)., Conclusions: Endobronchial administration of ε-aminocaproic acid during bronchoscopy may be a safe and efficacious option in the treatment and prevention of pulmonary bleeding. Further studies are necessary to better define ε-aminocaproic acid's safety profile, optimal routes of administration, and comparative effectiveness to tranexamic acid., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
33. Persistent severe acute respiratory distress syndrome for the prognostic enrichment of trials.
- Author
-
Sanchez E, Price DR, Chung KP, Oromendia C, Choi AMK, Schenck EJ, and Siempos II
- Subjects
- Adult, Arterial Pressure physiology, Female, Humans, Hypoxia complications, Hypoxia diagnosis, Hypoxia physiopathology, Male, Middle Aged, Oxygen metabolism, Partial Pressure, Randomized Controlled Trials as Topic, Respiratory Distress Syndrome complications, Respiratory Distress Syndrome diagnosis, Respiratory Distress Syndrome physiopathology, Hypoxia epidemiology, Prognosis, Respiratory Distress Syndrome epidemiology
- Abstract
Background: Acute respiratory distress syndrome (ARDS) is heterogeneous. As an indication of the heterogeneity of ARDS, there are patients whose syndrome improves rapidly (i.e., within 24 hours), others whose hypoxemia improves gradually and still others whose severe hypoxemia persists for several days. The latter group of patients with persistent severe ARDS poses challenges to clinicians. We attempted to assess the baseline characteristics and outcomes of persistent severe ARDS and to identify which variables are useful to predict it., Methods: A secondary analysis of patient-level data from the ALTA, EDEN and SAILS ARDSNet clinical trials was conducted. We defined persistent severe ARDS as a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) of equal to or less than 100 mmHg on the second study day following enrollment. Regularized logistic regression with an L1 penalty [Least Absolute Shrinkage and Selection Operator (LASSO)] techniques were used to identify predictive variables of persistent severe ARDS., Results: Of the 1531 individuals with ARDS alive on the second study day after enrollment, 232 (15%) had persistent severe ARDS. Of the latter, 100 (43%) individuals had mild or moderate hypoxemia at baseline. Usage of vasopressors was greater [144/232 (62%) versus 623/1299 (48%); p<0.001] and baseline severity of illness was higher in patients with versus without persistent severe ARDS. Mortality at 60 days [95/232 (41%) versus 233/1299 (18%); p<0.001] was higher, and ventilator-free (p<0.001), intensive care unit-free [0 (0-14) versus 19 (7-23); p<0.001] and non-pulmonary organ failure-free [3 (0-21) versus 20 (1-26); p<0.001] days were fewer in patients with versus without persistent severe ARDS. PaO2:FiO2, FiO2, hepatic failure and positive end-expiratory pressure at enrollment were useful predictive variables., Conclusions: Patients with persistent severe ARDS have distinct baseline characteristics and poor prognosis. Identifying such patients at enrollment may be useful for the prognostic enrichment of trials., Competing Interests: The corresponding author has read the journal’s policy and the authors of this manuscript have the following competing interests: AMC is a co-founder of Proterris and serving as a consultant for an advisory board meeting of Teva Pharmaceutical Industries, July 2018. None declared (ES, DRP, KPC, CO, EJS, IIS). This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2020
- Full Text
- View/download PDF
34. Validation of risk factors for recurrence of renal cell carcinoma: Results from a large single-institution series.
- Author
-
van der Mijn JC, Al Hussein Al Awamlh B, Islam Khan A, Posada-Calderon L, Oromendia C, Fainberg J, Alshak M, Elahjji R, Pierce H, Taylor B, Gudas LJ, Nanus DM, Molina AM, Del Pizzo J, and Scherr DS
- Subjects
- Aged, Carcinoma, Renal Cell pathology, Female, Humans, Kidney Neoplasms pathology, Male, Middle Aged, Neoplasm Grading, Neoplasm Recurrence, Local pathology, Nephrectomy, Prognosis, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Survival Analysis, Carcinoma, Renal Cell surgery, Diabetes Mellitus epidemiology, Kidney Neoplasms surgery, Neoplasm Recurrence, Local epidemiology
- Abstract
Purpose: To validate prognostic factors and determine the impact of obesity, hypertension, smoking and diabetes mellitus (DM) on risk of recurrence after surgery in patients with localized renal cell carcinoma (RCC)., Materials and Methods: We performed a retrospective cohort study among patients that underwent partial or radical nephrectomy at Weill Cornell Medicine for RCC and collected preoperative information on RCC risk factors, as well as pathological data. Cases were reviewed for radiographic evidence of RCC recurrence. A Cox proportional-hazards model was developed to determine the contribution of RCC risk factors to recurrence risk. Disease-free survival and overall survival were analyzed using the Kaplan-Meier method and log-rank test., Results: We identified 873 patients who underwent surgery for RCC between the years 2000-2015. In total 115 patients (13.2%) experienced a disease recurrence after a median follow up of 4.9 years. In multivariate analysis, increasing pathological T-stage (HR 1.429, 95% CI 1.265-1.614) and Nuclear grade (HR 2.376, 95% CI 1.734-3.255) were independently associated with RCC recurrence. In patients with T1-2 tumors, DM was identified as an additional independent risk factor for RCC recurrence (HR 2.744, 95% CI 1.343-5.605). Patients with DM had a significantly shorter median disease-free survival (1.5 years versus 2.6 years, p = 0.004), as well as median overall survival (4.1 years, versus 5.8 years, p<0.001)., Conclusions: We validated high pathological T-stage and nuclear grade as independent risk factors for RCC recurrence following nephrectomy. DM is associated with an increased risk of recurrence among patients with early stage disease., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
- Full Text
- View/download PDF
35. Clinical features of neuroendocrine prostate cancer.
- Author
-
Conteduca V, Oromendia C, Eng KW, Bareja R, Sigouros M, Molina A, Faltas BM, Sboner A, Mosquera JM, Elemento O, Nanus DM, Tagawa ST, Ballman KV, and Beltran H
- Subjects
- Adenocarcinoma mortality, Adenocarcinoma pathology, Aged, Biopsy, Carcinoma, Small Cell mortality, Carcinoma, Small Cell pathology, Cohort Studies, Disease Progression, Humans, Male, Middle Aged, Neoplasm Metastasis, Prognosis, Retrospective Studies, Survival Analysis, Treatment Outcome, Carcinoma, Neuroendocrine diagnosis, Carcinoma, Neuroendocrine mortality, Carcinoma, Neuroendocrine pathology, Carcinoma, Neuroendocrine therapy, Prostatic Neoplasms diagnosis, Prostatic Neoplasms mortality, Prostatic Neoplasms pathology, Prostatic Neoplasms therapy
- Abstract
Background: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may arise de novo or in patients previously treated with hormonal therapies for prostate adenocarcinoma as a mechanism of resistance. Despite being important to recognise, the clinical features of NEPC are poorly defined and could help guide when to perform a biopsy to look for NEPC histologic transformation., Methods: We reviewed baseline, treatment and outcome data of 87 patients with metastatic prostate cancer and tumour biopsy confirming NEPC histology. Forty-seven (54.0%) NEPC cases presented de novo, and 40 (46.0%) were therapy-related (t-NEPC). Thirty-six (41.4%) were classified as pure small-cell carcinoma, and 51 (58.6%) demonstrated mixed features with both small-cell carcinoma and adenocarcinoma present. Genomic data were available for 47 patients., Results: The median age at time of NEPC was 68.1 years, median prostate-specific antigen (PSA) was 1.20 ng/ml (0.14 ng/mL small-cell carcinoma, 1.55 ng/mL mixed carcinoma) and sites of metastases included bone (72.6%), lymph node (47.0%), and viscera (65.5%). Median time from adenocarcinoma to t-NEPC diagnosis was 39.7 months (range, 24.5-93.8) with a median of two lines of prior systemic therapy. Platinum chemotherapy was used to treat 57.5% of patients, with a median progression-free survival of 3.9 months. Small-cell carcinoma was associated with worse overall survival (OS) than mixed histology (8.9 months from NEPC diagnosis versus 26.1 months, P < 0.001). Median OS of de novo NEPC was shorter than that of t-NEPC (16.8 months from prostate cancer diagnosis versus 53.5 months, P = 0.043). An average PSA rise per month of ≤0.7 ng/ml before t-NEPC; elevated lactate dehydrogenase levels, RB1 and TP53 loss and liver metastases were poor prognostic features., Conclusions: We describe the clinical features of a cohort of patients with NEPC. These characteristics may inform future diagnostic strategies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
36. Paired Associative Stimulation as a Tool to Assess Plasticity Enhancers in Chronic Stroke.
- Author
-
Silverstein J, Cortes M, Tsagaris KZ, Climent A, Gerber LM, Oromendia C, Fonzetti P, Ratan RR, Kitago T, Iacoboni M, Wu A, Dobkin B, and Edwards DJ
- Abstract
Background and Purpose: The potential for adaptive plasticity in the post-stroke brain is difficult to estimate, as is the demonstration of central nervous system (CNS) target engagement of drugs that show promise in facilitating stroke recovery. We set out to determine if paired associative stimulation (PAS) can be used (a) as an assay of CNS plasticity in patients with chronic stroke, and (b) to demonstrate CNS engagement by memantine, a drug which has potential plasticity-modulating effects for use in motor recovery following stroke., Methods: We examined the effect of PAS in fourteen participants with chronic hemiparetic stroke at five time-points in a within-subjects repeated measures design study: baseline off-drug, and following a week of orally administered memantine at doses of 5, 10, 15, and 20 mg, comprising a total of seventy sessions. Each week, MEP amplitude pre and post-PAS was assessed in the contralesional hemisphere as a marker of enhanced or diminished plasticity. Strength and dexterity were recorded each week to monitor motor-specific clinical status across the study period., Results: We found that MEP amplitude was significantly larger after PAS in baseline sessions off-drug, and responsiveness to PAS in these sessions was associated with increased clinical severity. There was no observed increase in MEP amplitude after PAS with memantine at any dose. Motor threshold (MT), strength, and dexterity remained unchanged during the study., Conclusion: Paired associative stimulation successfully induced corticospinal excitability enhancement in chronic stroke subjects at the group level. However, this response did not occur in all participants, and was associated with increased clinical severity. This could be an important way to stratify patients for future PAS-drug studies. PAS was suppressed by memantine at all doses, regardless of responsiveness to PAS off-drug, indicating CNS engagement.
- Published
- 2019
- Full Text
- View/download PDF
37. Thrombotic risk factors in patients with antiphospholipid syndrome: a single center experience.
- Author
-
Abu-Zeinah G, Oromendia C, and DeSancho MT
- Subjects
- Adult, Anticoagulants therapeutic use, Antiphospholipid Syndrome drug therapy, Autoimmune Diseases complications, Black People, Female, Humans, Male, Middle Aged, Precision Medicine methods, Recurrence, Retrospective Studies, Thrombosis ethnology, Antiphospholipid Syndrome complications, Risk Factors, Thrombosis etiology
- Abstract
Patients with primary or secondary antiphospholipid syndrome (APS) have an increased risk of recurrent venous, arterial thrombosis and pregnancy complications. Therefore, determining thrombotic risk is important when individualizing antithrombotic therapy in patients with APS. To identify thrombotic risk factors in a cohort of APS patients. We conducted a retrospective review of APS patients who received care at a Hematology clinic of a university medical center from 2004 to 2017. Demographics, clinical features, antithrombotic therapy and thrombotic outcomes were collected. Time to event analysis identified clinical risk factors for thrombosis. The time varying effects of antithrombotic treatments on thrombosis outcome were analyzed. We identified 84 subjects with APS with a median age at diagnosis of 40.7 years [interquartile range [IQR] 33.5-57.6]. The majority were female (n = 63, 75%) and White (n = 45, 54%). Twenty-eight (33%) patients had concomitant autoimmune disease (AID) and of these, 15 (54%) had systemic lupus erythematosus. A thrombotic event occurred in 15 (18%) patients during a median follow-up of 48 months. A significantly higher rate of thrombotic events was observed in APS patients with AID compared to those without AID (hazard ratio (HR) 4.93, 95% CI 1.7-14.3, p = 0.04), and in black patients compared to whites (HR 5.94, 95% CI 1.1-32.1, p = 0.039). Patients on therapeutic anticoagulation regardless of type (warfarin, low molecular weight heparin or direct oral anticoagulants) were significantly less likely to have a recurrent thrombotic event compared to those on prophylactic anticoagulation (HR 0.11, 95% confidence interval [CI] 0.031-0.395, p = 0.001). However the numbers are too small to draw conclusions. Our study suggests that APS patients with concomitant AID and of Black race are at increased risk of recurrent thrombotic events.
- Published
- 2019
- Full Text
- View/download PDF
38. Circulating cell death biomarker TRAIL is associated with increased organ dysfunction in sepsis.
- Author
-
Schenck EJ, Ma KC, Price DR, Nicholson T, Oromendia C, Gentzler ER, Sanchez E, Baron RM, Fredenburgh LE, Huh JW, Siempos II, and Choi AM
- Subjects
- Adolescent, Adult, Aged, Cell Death, Critical Illness, Female, Hospital Mortality, Humans, Intensive Care Units, Male, Middle Aged, New York, Receptor-Interacting Protein Serine-Threonine Kinases metabolism, Sepsis mortality, Shock, Septic blood, Young Adult, Apoptosis, Biomarkers blood, Multiple Organ Failure blood, Sepsis blood, TNF-Related Apoptosis-Inducing Ligand blood
- Abstract
Background: In sepsis, there may be dysregulation in programed cell death pathways, typified by apoptosis and necroptosis. Programmed cell death pathways may contribute to variability in the immune response. TRAIL is a potent inducer of apoptosis. Receptor-interacting serine/threonine protein kinase-3 (RIPK3) is integral to the execution of necroptosis. We explored whether plasma TRAIL levels were associated with in-hospital mortality, organ dysfunction, and septic shock. We also explored the relationship between TRAIL and RIPK3., Methods: We performed an observational study of critically ill adults admitted to intensive care units at 3 academic medical centers across 2 continents, using 1 as derivation and the other 2 as validation cohorts. Levels of TRAIL were measured in the plasma of 570 subjects by ELISA., Results: In all cohorts, lower (<28.5 pg/ml) versus higher levels of TRAIL were associated with increased organ dysfunction (P ≤ 0.002) and septic shock (P ≤ 0.004). Lower TRAIL levels were associated with in-hospital mortality in 2 of 3 cohorts (Weill Cornell-Biobank of Critical Illness, P = 0.012; Brigham and Women's Hospital Registry of Critical Illness, P = 0.011; Asan Medical Center, P = 0.369). Lower TRAIL was also associated with increased RIPK3 (P ≤ 0.001)., Conclusion: Lower levels of TRAIL were associated with septic shock and organ dysfunction in 3 independent ICU cohorts. TRAIL was inversely associated with RIPK3 in all cohorts., Funding: NIH (R01-HL055330 and KL2-TR002385).
- Published
- 2019
- Full Text
- View/download PDF
39. Retrospective single-center study evaluating clinical and dermoscopic features of longitudinal melanonychia, ABCDEF criteria, and risk of malignancy.
- Author
-
Ko D, Oromendia C, Scher R, and Lipner SR
- Subjects
- Adult, Aged, Biopsy, Diagnosis, Differential, Female, Humans, Male, Melanoma pathology, Middle Aged, Nail Diseases pathology, Retrospective Studies, Skin Neoplasms pathology, Young Adult, Dermoscopy, Melanoma diagnostic imaging, Nail Diseases diagnostic imaging, Nails pathology, Skin Neoplasms diagnostic imaging
- Abstract
Background: Longitudinal melanonychia (LM) is a common finding in clinical practice; however, it has a broad differential diagnosis, including subungual melanoma (SUM), which can be difficult to distinguish clinically from benign conditions., Objective: To identify clinical and dermoscopic features that distinguish histopathologically diagnosed SUM from benign LM and to evaluate the validity of the ABCDEF criteria among patients on whom a biopsy was performed., Methods: Retrospective cohort study of consecutive patients who underwent nail matrix biopsy for LM at a single center from January 2011 to November 2017., Results: A total of 84 cases in which biopsy was performed (8 cases of SUM and 76 benign) were included in the analysis. The patients with SUM were younger (P = .011), had their melanonychia longer (P = .017), and presented with a wider band (P = .002) and greater width percentage (P < .001) than patients with benign LM did. The number of ABCDEF criteria met did not differ between the groups., Limitations: Retrospective single-center study; patients who did not undergo biopsy could not be studied., Conclusions: In the cases of LM in which biopsy was performed, SUM usually presented with a wider band and greater width percentage than benign LM did. The number of ABCDEF criteria met was not different between the groups. Because many of the clinical and dermoscopic signs were less consistent, biopsy should be performed in cases with any concerning band, especially in those with width percentage higher than 40%., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
40. To Code or Not To Code: Teaching Multidisciplinary Clinicians to Conduct Code Status Discussions.
- Author
-
Palathra BC, Kawai F, Oromendia C, Bushan A, Patel Y, Morris J, and Pan CX
- Subjects
- Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, New York City, Young Adult, Cardiopulmonary Resuscitation education, Cardiopulmonary Resuscitation psychology, Clinical Competence, Communication, Health Personnel education, Health Personnel psychology, Physician-Patient Relations
- Abstract
Background: Code status discussions (CSDs) can be challenging for many clinicians. Barriers associated with them include lack of education, comfort level, and experience. Objective: To conduct an educational intervention to improve knowledge and communication approaches related to CSDs. Design: A cross-sectional multidisciplinary educational intervention was conducted over one year consisting of an interactive presentation, live role-play, and pre- and post-intervention tests to measure impact of the formal training. Evaluations and comments were also collected. Setting/Subjects: Attending physicians, nurses, residents, fellows, and physician assistants (PAs) at an urban community teaching hospital of 500 beds serving an ethnically diverse population. Measurements: Data from pre- and post-intervention tests evaluating knowledge and communication approach regarding CSDs were collected. Participants completed a qualitative evaluation of the program. Results: There were 165 participants: 29 attending physicians, 26 residents, 17 fellows, 18 PAs, and 75 nurses. All (100%) completed the pre-intervention test and 154 (93.3%) completed the post-intervention test. There was an overall improvement in scores, 43.8% pre-intervention to 75.6% post-intervention ( p -values <0.005). Attending physicians and fellows had the highest pre-intervention scores, while nurses and PAs had the lowest. Most participants (97%) reported they learned new information and 91% stated they would change patient management. Conclusions: Our study found that a brief educational intervention with multipronged teaching tools improved knowledge concerning CSDs. Participants felt it provided new insights and would change their practice. This study contributes to the literature by examining CSD training across different disciplines, allowing for cross-group comparisons. Future studies should try to correlate educational interventions and clinician knowledge with clinical practice outcomes.
- Published
- 2019
- Full Text
- View/download PDF
41. Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials.
- Author
-
Schenck EJ, Oromendia C, Torres LK, Berlin DA, Choi AMK, and Siempos II
- Subjects
- Airway Extubation methods, Critical Care methods, Female, Humans, Male, Middle Aged, Oxygen blood, Oxygen Consumption, Predictive Value of Tests, Prevalence, Prognosis, Respiration, Artificial methods, Severity of Illness Index, Time Factors, Treatment Outcome, Bilirubin blood, Respiratory Distress Syndrome diagnosis, Respiratory Distress Syndrome epidemiology, Respiratory Distress Syndrome physiopathology, Respiratory Distress Syndrome therapy, Vasoconstrictor Agents therapeutic use
- Abstract
Background: Observational studies suggest that some patients meeting criteria for ARDS no longer fulfill the oxygenation criterion early in the course of their illness. This subphenotype of rapidly improving ARDS has not been well characterized. We attempted to assess the prevalence, characteristics, and outcomes of rapidly improving ARDS and to identify which variables are useful to predict it., Methods: A secondary analysis was performed of patient level data from six ARDS Network randomized controlled trials. We defined rapidly improving ARDS, contrasted with ARDS > 1 day, as extubation or a Pao
2 to Fio2 ratio (Pao2 :Fio2 ) > 300 on the first study day following enrollment., Results: The prevalence of rapidly improving ARDS was 10.5% (458 of 4,361 patients) and increased over time. Of the 1,909 patients enrolled in the three most recently published trials, 197 (10.3%) were extubated on the first study day, and 265 (13.9%) in total had rapidly improving ARDS. Patients with rapidly improving ARDS had lower baseline severity of illness and lower 60-day mortality (10.2% vs 26.3%; P < .0001) than ARDS > 1 day. Pao2 :Fio2 at screening, change in Pao2 :Fio2 from screening to enrollment, use of vasopressor agents, Fio2 at enrollment, and serum bilirubin levels were useful predictive variables., Conclusions: Rapidly improving ARDS, mostly defined by early extubation, is an increasingly prevalent and distinct subphenotype, associated with better outcomes than ARDS > 1 day. Enrollment of patients with rapidly improving ARDS may negatively affect the prognostic enrichment and contribute to the failure of therapeutic trials., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
42. Automated expiratory ventilation assistance through a small endotracheal tube can improve venous return and cardiac output.
- Author
-
Berlin DA, Manoach S, Oromendia C, and Heerdt PM
- Abstract
Background: Positive pressure ventilation can decrease venous return and cardiac output. It is not known if expiratory ventilation assistance (EVA) through a small endotracheal tube can improve venous return and cardiac output., Results: In a porcine model, switching from conventional positive pressure ventilation to (EVA) with - 8 cmH
2 0 expiratory pressure increased the venous return and cardiac output. The stroke volume increased by 27% when the subjects were switched from conventional ventilation to EVA [53.8 ± 7.7 (SD) vs. 68.1 ± 7.7 ml, p = 0.003]. After hemorrhage, subjects treated with EVA had higher median cardiac output, higher mean systemic arterial pressure, and lower central venous pressure at 40 and 60 min when compared with subjects treated with conventional ventilation with PEEP 0 cmH2 0. The median cardiac output was 41% higher in the EVA group than the control group at 60 min [2.70 vs. 1.59 L/min, p = 0.029]., Conclusion: EVA through a small endotracheal tube increased venous return, cardiac output, and mean arterial pressure compared with conventional positive pressure ventilation. The effects were most significant during hypovolemia from hemorrhage. EVA provided less effective ventilation than conventional positive pressure ventilation.- Published
- 2019
- Full Text
- View/download PDF
43. Clinical improvement with intensive robot-assisted arm training in chronic stroke is unchanged by supplementary tDCS.
- Author
-
Edwards DJ, Cortes M, Rykman-Peltz A, Chang J, Elder J, Thickbroom G, Mariman JJ, Gerber LM, Oromendia C, Krebs HI, Fregni F, Volpe BT, and Pascual-Leone A
- Subjects
- Adult, Aged, Aged, 80 and over, Arm physiopathology, Brain Ischemia physiopathology, Brain Ischemia rehabilitation, Chronic Disease, Double-Blind Method, Evoked Potentials, Motor, Female, Follow-Up Studies, Humans, Male, Middle Aged, Pyramidal Tracts physiopathology, Robotics, Stroke physiopathology, Treatment Outcome, Stroke Rehabilitation, Therapy, Computer-Assisted, Transcranial Direct Current Stimulation
- Abstract
Background: Intensive robot-assisted arm training in the chronic phase of stroke recovery can lead to clinical improvement. Combinatorial therapeutic approaches are sought to further optimize stroke recovery. Transcranial direct current stimulation (tDCS) is one candidate to combine with robotic training, as transient increases in excitability and improvements in motor behavior have separately been reported., Objective: To determine whether tDCS, delivered prior to robotic training, could augment clinical improvement., Methods: We conducted a dual-site, randomized controlled trial in 82 chronic ischemic stroke patients (inclusion > 6 m post-injury, dominant hemisphere, first stroke; residual hemiparesis) who were split into two groups to receive tDCS (M1-SO montage, anode ipsilesional, 5×7 cm electrodes, 2 mA, 20 mins) or sham tDCS, prior to robotic upper-limb training (12 weeks; 36 sessions; shoulder-elbow robot or wrist robot on alternating sessions). The primary end-point was taken after 12 weeks of training, and assessed with the Upper Extremity Fugl-Meyer impairment scale (FM). Corticomotor conduction was assessed with transcranial magnetic stimulation (TMS)., Results: For the combined group (n = 82; post-training) robotic training increased the FM by 7.36 points compared to baseline (p < 0.0001). There was no difference in the FM increase between the tDCS and sham groups (6.97 and 7.73 respectively, p = 0.46). In both groups, clinically meaningful improvement (≥5 points) from baseline was evident in the majority of patients (56/77), was sustained six months later (54/72), and could be attained in severe, moderate and mild baseline hemiparesis. Clinical improvement was associated with increased excitability in the affected hemisphere as assessed by resting motor threshold (pre-post p = 0.029; pre-post 6 months p = 0.029), but not with threshold-adjusted assessment of MEP amplitude (pre-post p = 0.09; pre-post 6 months p = 0.15). Participants with motor evoked potentials were more likely to improve clinically than those without (17/18, 94%, versus 39/59, 66%, p = 0.018)., Conclusions: Our study confirms the benefit of intensive robot-assisted training in stroke recovery, and indicates that conventional tDCS does not confer further advantage to robotic training. We also showed that corticospinal integrity, as assessed by TMS, is a predictor of clinically meaningful response to intensive arm therapy in chronic stroke.
- Published
- 2019
- Full Text
- View/download PDF
44. Delays in Initiating Post-operative Prophylactic Biologic Therapy Are Common Among Crohn's Disease Patients.
- Author
-
Cohen-Mekelburg S, Gold S, Schneider Y, Dennis M, Oromendia C, Yeo H, Michelassi F, Scherl E, and Steinlauf A
- Subjects
- Adalimumab therapeutic use, Adult, Antibodies, Monoclonal, Humanized therapeutic use, Cecum surgery, Certolizumab Pegol therapeutic use, Cohort Studies, Colectomy, Crohn Disease surgery, Female, Humans, Ileum surgery, Infliximab therapeutic use, Insurance, Health statistics & numerical data, Intestine, Small surgery, Logistic Models, Male, Medicaid, Medicare, Middle Aged, Multivariate Analysis, Preoperative Care statistics & numerical data, Retrospective Studies, Risk Factors, Secondary Prevention, United States, Biological Products therapeutic use, Crohn Disease prevention & control, Digestive System Surgical Procedures, Postoperative Care statistics & numerical data, Time-to-Treatment statistics & numerical data
- Abstract
Background: Studies have shown that prophylactic biologic therapy can reduce post-surgical Crohn's disease recurrence., Aims: We aimed to identify the frequency of delay and risk factors associated with a delay in the initiation of prophylactic post-surgical biologic therapy in high-risk patients., Methods: We performed a cohort study of Crohn's disease patients who underwent a bowel resection. We identified those at risk of recurrence and explored multiple characteristics for those with and without a delay post-operatively., Results: A total of 84 patients were included in our analysis of which 69.0% had a greater than 4-week delay and 56.0% a greater than 8-week delay in post-surgical biologic prophylaxis. Publicly insured patients had a 100% delay in post-surgical prophylaxis initiation (p = 0.039, p = 0.003 at 4 and 8 weeks, respectively). Patients on a biologic pre-surgery were less likely to have a delay (p < 0.001) in post-operative prophylaxis. Care at an inflammatory bowel disease (IBD) center was associated with timely therapy when considering a post-operative immunomodulator or biologic strategy., Conclusions: There are a substantial number of delays in initiating post-operative prophylactic biologic therapy in high-risk patients. Identifying susceptible patients by insurance type or absence of pre-operative therapy can focus future improvement efforts. Additionally, consultation with IBD-specialized providers should be considered in peri-surgical IBD care.
- Published
- 2019
- Full Text
- View/download PDF
45. A Phase II Trial of the Aurora Kinase A Inhibitor Alisertib for Patients with Castration-resistant and Neuroendocrine Prostate Cancer: Efficacy and Biomarkers.
- Author
-
Beltran H, Oromendia C, Danila DC, Montgomery B, Hoimes C, Szmulewitz RZ, Vaishampayan U, Armstrong AJ, Stein M, Pinski J, Mosquera JM, Sailer V, Bareja R, Romanel A, Gumpeni N, Sboner A, Dardenne E, Puca L, Prandi D, Rubin MA, Scher HI, Rickman DS, Demichelis F, Nanus DM, Ballman KV, and Tagawa ST
- Subjects
- Aged, Aged, 80 and over, Aurora Kinase A antagonists & inhibitors, Azepines adverse effects, Carcinoma, Neuroendocrine genetics, Carcinoma, Neuroendocrine pathology, Disease Progression, Humans, Male, Middle Aged, Orchiectomy, Prostate pathology, Prostatic Neoplasms, Castration-Resistant genetics, Prostatic Neoplasms, Castration-Resistant pathology, Pyrimidines adverse effects, Receptors, Androgen genetics, Signal Transduction drug effects, Aurora Kinase A genetics, Azepines administration & dosage, Carcinoma, Neuroendocrine drug therapy, N-Myc Proto-Oncogene Protein genetics, Prostatic Neoplasms, Castration-Resistant drug therapy, Pyrimidines administration & dosage
- Abstract
Purpose: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may develop de novo or as a mechanism of treatment resistance. N-myc is capable of driving NEPC progression. Alisertib inhibits the interaction between N-myc and its stabilizing factor Aurora-A, inhibiting N-myc signaling, and suppressing tumor growth., Patients and Methods: Sixty men were treated with alisertib 50 mg twice daily for 7 days every 21 days. Eligibility included metastatic prostate cancer and at least one: small-cell neuroendocrine morphology; ≥50% neuroendocrine marker expression; new liver metastases without PSA progression; or elevated serum neuroendocrine markers. The primary endpoint was 6-month radiographic progression-free survival (rPFS). Pretreatment biopsies were evaluated by whole exome and RNA-seq and patient-derived organoids were developed., Results: Median PSA was 1.13 ng/mL (0.01-514.2), number of prior therapies was 3, and 68% had visceral metastases. Genomic alterations involved RB1 (55%), TP53 (46%), PTEN (29%), BRCA2 (29%), and AR (27%), and there was a range of androgen receptor signaling and NEPC marker expression. Six-month rPFS was 13.4% and median overall survival was 9.5 months (7.3-13). Exceptional responders were identified, including complete resolution of liver metastases and prolonged stable disease, with tumors suggestive of N-myc and Aurora-A overactivity. Patient organoids exhibited concordant responses to alisertib and allowed for the dynamic testing of Aurora-N-myc complex disruption., Conclusions: Although the study did not meet its primary endpoint, a subset of patients with advanced prostate cancer and molecular features supporting Aurora-A and N-myc activation achieved significant clinical benefit from single-agent alisertib., (©2018 American Association for Cancer Research.)
- Published
- 2019
- Full Text
- View/download PDF
46. A phase I trial of low-dose inhaled carbon monoxide in sepsis-induced ARDS.
- Author
-
Fredenburgh LE, Perrella MA, Barragan-Bradford D, Hess DR, Peters E, Welty-Wolf KE, Kraft BD, Harris RS, Maurer R, Nakahira K, Oromendia C, Davies JD, Higuera A, Schiffer KT, Englert JA, Dieffenbach PB, Berlin DA, Lagambina S, Bouthot M, Sullivan AI, Nuccio PF, Kone MT, Malik MJ, Porras MAP, Finkelsztein E, Winkler T, Hurwitz S, Serhan CN, Piantadosi CA, Baron RM, Thompson BT, and Choi AM
- Subjects
- Adult, Aged, Biomarkers blood, Blood Gas Analysis, Carboxyhemoglobin, DNA, Mitochondrial, Female, Humans, Male, Middle Aged, Administration, Inhalation, Carbon Monoxide administration & dosage, Respiratory Distress Syndrome drug therapy, Respiratory Therapy methods, Sepsis drug therapy
- Abstract
Background: Acute respiratory distress syndrome (ARDS) is a prevalent disease with significant mortality for which no effective pharmacologic therapy exists. Low-dose inhaled carbon monoxide (iCO) confers cytoprotection in preclinical models of sepsis and ARDS., Methods: We conducted a phase I dose escalation trial to assess feasibility and safety of low-dose iCO administration in patients with sepsis-induced ARDS. Twelve participants were randomized to iCO or placebo air 2:1 in two cohorts. Four subjects each were administered iCO (100 ppm in cohort 1 or 200 ppm in cohort 2) or placebo for 90 minutes for up to 5 consecutive days. Primary outcomes included the incidence of carboxyhemoglobin (COHb) level ≥10%, prespecified administration-associated adverse events (AEs), and severe adverse events (SAEs). Secondary endpoints included the accuracy of the Coburn-Forster-Kane (CFK) equation to predict COHb levels, biomarker levels, and clinical outcomes., Results: No participants exceeded a COHb level of 10%, and there were no administration-associated AEs or study-related SAEs. CO-treated participants had a significant increase in COHb (3.48% ± 0.7% [cohort 1]; 4.9% ± 0.28% [cohort 2]) compared with placebo-treated subjects (1.97% ± 0.39%). The CFK equation was highly accurate at predicting COHb levels, particularly in cohort 2 (R2 = 0.9205; P < 0.0001). Circulating mitochondrial DNA levels were reduced in iCO-treated participants compared with placebo-treated subjects., Conclusion: Precise administration of low-dose iCO is feasible, well-tolerated, and appears to be safe in patients with sepsis-induced ARDS. Excellent agreement between predicted and observed COHb should ensure that COHb levels remain in the target range during future efficacy trials., Trial Registration: ClinicalTrials.gov NCT02425579., Funding: NIH grants P01HL108801, KL2TR002385, K08HL130557, and K08GM102695.
- Published
- 2018
- Full Text
- View/download PDF
47. Robotic Arm Rehabilitation in Chronic Stroke Patients With Aphasia May Promote Speech and Language Recovery (but Effect Is Not Enhanced by Supplementary tDCS).
- Author
-
Buchwald A, Falconer C, Rykman-Peltz A, Cortes M, Pascual-Leone A, Thickbroom GW, Krebs HI, Fregni F, Gerber LM, Oromendia C, Chang J, Volpe BT, and Edwards DJ
- Abstract
Objective: This study aimed to determine the extent to which robotic arm rehabilitation for chronic stroke may promote recovery of speech and language function in individuals with aphasia. Methods: We prospectively enrolled 17 individuals from a hemiparesis rehabilitation study pairing intensive robot assisted therapy with sham or active tDCS and evaluated their speech ( N = 17) and language ( N = 9) performance before and after a 12-week (36 session) treatment regimen. Performance changes were evaluated with paired t -tests comparing pre- and post-test measures. There was no speech therapy included in the treatment protocol. Results: Overall, the individuals significantly improved on measures of motor speech production from pre-test to post-test. Of the subset who performed language testing ( N = 9), overall aphasia severity on a standardized aphasia battery improved from pre-test baseline to post-test. Active tDCS was not associated with greater gains than sham tDCS. Conclusions: This work indicates the importance of considering approaches to stroke rehabilitation across different domains of impairment, and warrants additional exploration of the possibility that robotic arm motor treatment may enhance rehabilitation for speech and language outcomes. Further investigation into the role of tDCS in the relationship of limb and speech/language rehabilitation is required, as active tDCS did not increase improvements over sham tDCS.
- Published
- 2018
- Full Text
- View/download PDF
48. Acute respiratory distress syndrome without identifiable risk factors: A secondary analysis of the ARDS network trials.
- Author
-
Harrington JS, Schenck EJ, Oromendia C, Choi AMK, and Siempos II
- Subjects
- Adult, Age Factors, Aged, Female, Humans, Intensive Care Units, Male, Middle Aged, Randomized Controlled Trials as Topic, Respiration, Artificial, Respiratory Distress Syndrome etiology, Respiratory Distress Syndrome mortality, Risk Factors, United States epidemiology, Length of Stay, Patient Selection, Respiratory Distress Syndrome epidemiology
- Abstract
Purpose: We examined whether patients with acute respiratory distress syndrome (ARDS) lacking risk factors are enrolled in therapeutic trials and assessed their clinical characteristics and outcomes., Methods: We performed a secondary analysis of patient-level data pooled from the ARMA, ALVEOLI, FACTT, ALTA and EDEN ARDSNet randomized controlled trials obtained from the Biologic Specimen and Data Repository Information Coordinating Center of the National Heart, Lung and Blood Institute. We compared baseline characteristics and clinical outcomes (before and after adjustment using Poisson regression model) of ARDS patients with versus without risk factors., Results: Of 3733 patients with ARDS, 81 (2.2%) did not have an identifiable risk factor. Patients without risk factors were younger, had lower baseline severity of illness, were more likely to have the ARDS resolve rapidly (i.e., within 24 h) (p < 0.001) and they had more ventilator-free days (median 21; p = 0.003), more intensive care unit-free days (18; p = 0.010), and more non-pulmonary organ failure-free days (24; p < 0.001) than comparators (17, 14 and 18, respectively). Differences persisted after adjustment for potential confounders., Conclusions: Patients with ARDS without identifiable risk factors are enrolled in therapeutic trials and may have better outcomes, including a higher proportion of rapidly resolving ARDS, than those with risk factors., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
49. Reclassification of Acute Respiratory Distress Syndrome: A Secondary Analysis of the ARDS Network Trials.
- Author
-
Oromendia C and Siempos II
- Subjects
- Adult, Aged, Cause of Death, Female, Humans, Intensive Care Units statistics & numerical data, Length of Stay statistics & numerical data, Male, Middle Aged, Oxygen Inhalation Therapy, Partial Pressure, Randomized Controlled Trials as Topic, Respiration, Artificial statistics & numerical data, Respiratory Distress Syndrome metabolism, Respiratory Distress Syndrome therapy, Severity of Illness Index, Treatment Outcome, Mortality, Oxygen metabolism, Respiratory Distress Syndrome classification
- Published
- 2018
- Full Text
- View/download PDF
50. Circulating RIPK3 levels are associated with mortality and organ failure during critical illness.
- Author
-
Ma KC, Schenck EJ, Siempos II, Cloonan SM, Finkelsztein EJ, Pabon MA, Oromendia C, Ballman KV, Baron RM, Fredenburgh LE, Higuera A, Lee JY, Chung CR, Jeon K, Yang JH, Howrylak JA, Huh JW, Suh GY, and Choi AM
- Subjects
- Aged, Apoptosis, Female, Hospital Mortality, Humans, Intensive Care Units, Logistic Models, Male, Middle Aged, Multivariate Analysis, Necrosis, Odds Ratio, Republic of Korea, Severity of Illness Index, Survival Analysis, United States, Critical Illness mortality, Multiple Organ Failure blood, Multiple Organ Failure mortality, Receptor-Interacting Protein Serine-Threonine Kinases blood, Receptor-Interacting Protein Serine-Threonine Kinases metabolism
- Abstract
Background: Necroptosis is a form of programmed necrotic cell death that is rapidly emerging as an important pathophysiological pathway in numerous disease states. Necroptosis is dependent on receptor-interacting protein kinase 3 (RIPK3), a protein shown to play an important role in experimental models of critical illness. However, there is limited clinical evidence regarding the role of extracellular RIPK3 in human critical illness., Methods: Plasma RIPK3 levels were measured in 953 patients prospectively enrolled in 5 ongoing intensive care unit (ICU) cohorts in both the USA and Korea. RIPK3 concentrations among groups were compared using prospectively collected phenotypic and outcomes data., Results: In all 5 cohorts, extracellular RIPK3 levels in the plasma were higher in patients who died in the hospital compared with those who survived to discharge. In a combined analysis, increasing RIPK3 levels were associated with elevated odds of in-hospital mortality (odds ratio [OR] 1.7 for each log10-unit increase in RIPK3 level, P < 0.0001). When adjusted for baseline severity of illness, the OR for in-hospital mortality remained statistically significant (OR 1.33, P = 0.007). Higher RIPK3 levels were also associated with more severe organ failure., Conclusions: Our findings suggest that elevated levels of RIPK3 in the plasma of patients admitted to the ICU are associated with in-hospital mortality and organ failure., Funding: Supported by NIH grants P01 HL108801, R01 HL079904, R01 HL055330, R01 HL060234, K99 HL125899, and KL2TR000458-10. Supported by Samsung Medical Center grant SMX1161431.
- Published
- 2018
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.