123 results on '"Sihag S"'
Search Results
2. Blood metabolites of murrah buffalo heifer on supplementation of different sources of rumen bypass proteins
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Kumari, A., Gulati, H.K., Kumar, S., Sihag, S., and Kumar, M.
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- 2021
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3. EP07.04-04 High-Risk Clinicopathologic and Genomic Features of Recurrence in Stage I Lung Adenocarcinoma
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Fick, C.N., primary, Dunne, E.G., additional, Mastrogiacomo, B., additional, Tan, K.S., additional, Toumbacaris, N., additional, Adusumilli, P.S., additional, Rocco, G., additional, Molena, D., additional, Huang, J., additional, Park, B.J., additional, Bott, M.J., additional, Rusch, V.R., additional, Sihag, S., additional, Isbell, J.M., additional, and Jones, D.R., additional
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- 2023
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4. Effect of dietary inclusion of spent grains on the performance of growing buffalo calves
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Kumar, S., primary, Sihag, S., additional, and Sihag, Z. S., additional
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- 2023
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5. FOLFOX-Based Chemoradiation as Non-Operative Management for Esophageal Adenocarcinoma
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Rouf, R., primary, Ku, G., additional, Cowzer, D., additional, Harrington, C., additional, Maron, S., additional, Janjigian, Y., additional, Ilson, D.H., additional, Molena, D., additional, Sihag, S., additional, Hajj, C., additional, Crane, C.H., additional, and Wu, A.J., additional
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- 2022
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6. SO-6 Novel frailty index predicts short-term outcomes after esophagectomy in elderly patients with esophageal cancer
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Boerner, T., primary, Tin, A., additional, Vickers, A., additional, Harrington, C., additional, Janjigian, Y., additional, Ilson, D., additional, Wu, A., additional, Bott, M., additional, Isbell, J., additional, Park, B., additional, Sihag, S., additional, Jones, D., additional, Downey, R., additional, Shahrokni, A., additional, and Molena, D., additional
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- 2022
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7. Changing Pattern of Prices and Arrivals of Agricultural Commodities Through e-NAM: A Case Study of Sirsa Apmc in Haryana
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Singh Abhey, Kiran, and Sihag Shakuntla
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e-nam ,agricultural commodities ,infrastructure facilities ,arrivals and price pattern ,towary rolne ,infrastruktura ,wzorce przywozów i cen ,l10 ,m31 ,Regional economics. Space in economics ,HT388 ,Economics as a science ,HB71-74 - Abstract
The study examined the market profile and status of Electronic National Agriculture Market (e-NAM) in Sirsa Agricultural Produce Market Committee (APMC) The study also analysed the arrival and price pattern of major agricultural commodities before and after the implementation of e-NAM in the study area.
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- 2023
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8. Survival and Patterns of Failure in Oligometastatic Esophagogastric Cancer
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Hilal, L., primary, Ku, G., additional, Molena, D., additional, Janjigian, Y., additional, Ilson, D.H., additional, Maron, S., additional, Sihag, S., additional, Yoon, S.S., additional, Strong, V., additional, Crane, C.H., additional, Gomez, D.R., additional, and Wu, A.J., additional
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- 2020
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9. COLON CAPSULE ENDOSCOPY (CCE) IS AN EFFECTIVE FILTER TEST FOR COLONIC POLYP SURVEILLANCE
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Semenov, S, additional, Manoharan, T, additional, Sihag, S, additional, Hazel, K, additional, Ismail, MS, additional, Molloy, D, additional, Ryan, B, additional, Breslin, N, additional, O’Connor, A, additional, and McNamara, D, additional
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- 2020
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10. SIMETHICONE CLEARS THE WAY FOR CAPSULES
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Douglas, A, additional, Sihag, S, additional, Semenov, S, additional, Ryan, B, additional, O’Connor, A, additional, Breslin, N, additional, and McNamara, D, additional
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- 2020
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11. SMALL BOWEL POLYPECTOMY FOR THE MANAGEMENT OF PEUTZ-JEGHER ASSOCIATED RECURRENT INTUSSUSCEPTION
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Ismail, MS, additional, Semenov, S, additional, Sihag, S, additional, and McNamara, D, additional
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- 2020
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12. THE ADDITION OF CASTOR OIL AS A BOOSTER IN COLON CAPSULE REGIMENS SIGNIFICANTLY IMPROVES COMPLETION RATES AND POLYP DETECTION
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Semenov, S, additional, Atiyekeogbebe, R, additional, Ismail, MS, additional, Sihag, S, additional, McCarthy, E, additional, Ryan, B, additional, Breslin, N, additional, O’Connor, A, additional, and McNamara, D, additional
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- 2020
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13. IMPROVING QUALITY IN COLON CAPSULE ENDOSCOPY; EFFECTS OF DIFFERENT BOWEL PREPARATION REGIMENS
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Syafiq Ismail, M, additional, Semenov, S, additional, Sihag, S, additional, Breslin, N, additional, O’Connor, A, additional, Ryan, B, additional, and McNamara, D, additional
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- 2020
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14. CLINICAL OUTCOME OF PATIENTS EXAMINED BY SMALL BOWEL CAPSULE ENDOSCOPY WITH NON-SPECIFIC ENTERITIS
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Sihag, S, additional, Tan, B, additional, Ismail, MS, additional, Semenov, S, additional, Ryan, B, additional, O’Connor, A, additional, Breslin, N, additional, and McNamara, D, additional
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- 2020
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15. IS IT WORTH REPEATING CAPSULE ENDOSCOPY (CE) IN SUSPECTED SMALL BOWEL BLEEDING?
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Sihag, S, additional, McCarthy, E, additional, Semenov, S, additional, Syafiq Ismail, M, additional, Molloy, D, additional, Ryan, B, additional, O’Connor, A, additional, Breslin, N, additional, and McNamara, D, additional
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- 2020
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16. P203 FIT and FC as a surrogate non-invasive marker for mucosal healing in inflammatory bowel disease
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ISMAIL, M S, primary, Murphy, G, additional, Kelly, C, additional, O’Riordan, F, additional, Semenov, S, additional, Sihag, S, additional, Breslin, N, additional, Anthony, O, additional, Ryan, B, additional, and McNamara, D, additional
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- 2020
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17. Genetic Determinants of Chemoradiation Response and Survival in Locally Advanced Esophageal Carcinoma Treated with Trimodality Therapy
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Pitter, K.L., primary, Casey, D.L., additional, Oh, P., additional, Setton, J., additional, Ku, G., additional, Ilson, D.H., additional, Janjigian, Y., additional, Bains, M.S., additional, Jones, D., additional, Molena, D., additional, Crane, C.H., additional, Sihag, S., additional, and Wu, A.J., additional
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- 2019
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18. Nutrigenomic evaluation of garlic (Allium sativum) and holy basil (Ocimum sanctum) leaf powder supplementation on growth performance and immune characteristics in broilers
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Sheoran, N., primary, Kumar, R., additional, Kumar, A., additional, Batra, K., additional, Sihag, S., additional, Maan, S., additional, and Maan, N. S., additional
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- 2017
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19. Gastric preconditioning via percutaneous angioembolization before esophagectomy in patients at high risk for esophageal leak.
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Bevers KC, Sewell M, Bott MJ, Sihag S, Park BJ, Ridouani F, Muñoz FG, Santos E, and Molena D
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- Humans, Male, Female, Middle Aged, Aged, Gastric Artery, Ischemic Preconditioning methods, Coloring Agents administration & dosage, Treatment Outcome, Preoperative Care methods, Esophagectomy adverse effects, Esophagectomy methods, Anastomotic Leak prevention & control, Anastomotic Leak etiology, Indocyanine Green administration & dosage, Esophageal Neoplasms surgery, Esophageal Neoplasms therapy, Embolization, Therapeutic methods, Embolization, Therapeutic adverse effects, Stomach blood supply, Stomach surgery, Feasibility Studies
- Abstract
Anastomotic leaks and stenoses remain critical complications in esophagectomy and are related to conduit perfusion. Surgical gastric preconditioning has been described but requires additional surgery and creates scar tissue, potentially hindering future operation. We sought to evaluate the feasibility and safety of percutaneous gastric preconditioning by angioembolization to improve perfusion of gastric conduits before esophagectomy in a high-risk patient cohort. Patients pending an esophagectomy for cancer and deemed to be high risk for anastomotic complications underwent preconditioning by image-guided angioembolization. Preconditioning was performed on an outpatient basis by means of superselective embolization of the left gastric and short gastric arteries. Intraoperative conduit perfusion evaluation with indocyanine green and postoperative surgical outcomes was reviewed. Seventeen patients underwent gastric preconditioning, with no complications observed. Thirteen of the 17 patients ultimately underwent esophagectomy; the remaining four patients were not candidates for an operation. Patients proceeded to surgery a median of 23 days (interquartile range, 21-27 days) after preconditioning. The intraoperative indocyanine green perfusion of all conduits was appropriate, with no tip demarcation and with a median time to dye uptake of 20s (interquartile range, 15-20s). There were no anastomotic stenoses or leaks noted within the series. Gastric conduit preconditioning by percutaneous angioembolization of the left gastric and short gastric arteries can be performed safely and without operative delay in high-risk patients. Further evaluation of preconditioning for conduit optimization is warranted to limit the critical complications of anastomotic leak and stenosis in esophagectomy., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2024
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20. Modeling lung adenocarcinoma metastases using patient-derived organoids.
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Liu Y, Lankadasari M, Rosiene J, Johnson KE, Zhou J, Bapat S, Chow-Tsang LL, Tian H, Mastrogiacomo B, He D, Connolly JG, Lengel HB, Caso R, Dunne EG, Fick CN, Rocco G, Sihag S, Isbell JM, Bott MJ, Li BT, Lito P, Brennan CW, Bilsky MH, Rekhtman N, Adusumilli PS, Mayo MW, Imielinski M, and Jones DR
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- Humans, Animals, Mice, Neoplasm Metastasis, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) metabolism, Models, Biological, Leukocytes, Mononuclear metabolism, Organoids pathology, Adenocarcinoma of Lung pathology, Lung Neoplasms pathology, Lung Neoplasms secondary
- Abstract
Approximately 50% of patients with surgically resected early-stage lung cancer develop distant metastasis. At present, there is no in vivo metastasis model to investigate the biology of human lung cancer metastases. Using well-characterized lung adenocarcinoma (LUAD) patient-derived organoids (PDOs), we establish an in vivo metastasis model that preserves the biologic features of human metastases. Results of whole-genome and RNA sequencing establish that our in vivo PDO metastasis model can be used to study clonality and tumor evolution and to identify biomarkers related to organotropism. Investigation of the response of KRAS
G12C PDOs to sotorasib demonstrates that the model can examine the efficacy of treatments to suppress metastasis and identify mechanisms of drug resistance. Finally, our PDO model cocultured with autologous peripheral blood mononuclear cells can potentially be used to determine the optimal immune-priming strategy for individual patients with LUAD., Competing Interests: Declaration of interests G.R. has financial relationships with Scanlan, AstraZeneca, and Medtronic. S.S. is a member of the AstraZeneca Advisory Board. J.M.I. has stock ownership in LumaCyte and is a consultant/advisory board member for Roche Genentech. M.J.B. is a consultant for AstraZeneca, Iovance Biotherapeutics, and Intuitive Surgical and receives research support from Obsidian Therapeutics. B.T.L. has served as an uncompensated advisor and consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, and Lilly; has received research grants (institutional) from Amgen, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Hengrui USA, and Lilly; has received academic travel support from Amgen, Jiangsu Hengrui Medicine, and MORE Health; and has intellectual property rights as a book author at Karger Publishers and Shanghai Jiao Tong University Press. M.H.B. receives royalties from Globus Medical and DePuy Synthes. P.S.A. declares research funding from Atara Biotherapeutics; is a scientific advisory board member and consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPACT Bio, Johnson & Johnson, Orion, and Outpace Bio; has patents, royalties, and intellectual property on mesothelin-targeted chimeric antigen receptor and other T cell therapies, which have been licensed to Atara Biotherapeutics; and has an issued patent method for detection of cancer cells using virus and pending patent applications on PD-1 dominant negative receptor, a wireless pulse-oximetry device, and an ex vivo malignant pleural effusion culture system. MSK has licensed intellectual property related to mesothelin-targeted chimeric antigen receptors and T cell therapies to Atara Biotherapeutics and has associated financial interests. D.R.J. serves on a clinical trial steering committee for AstraZeneca and has research grant support from Merck., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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21. Real-world Decision-making Process for Stereotactic Body Radiotherapy Versus Minimally Invasive Surgery in Early-stage Lung Cancer Patients.
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Vanstraelen S, Tan KS, Adusumilli PS, Bains MS, Bott MJ, Downey RJ, Gomez DR, Gray KD, Huang J, Isbell JM, Molena D, Park BJ, Rimner A, Rusch VW, Shaverdian N, Sihag S, Wu AJ, Jones DR, and Rocco G
- Abstract
Objective: To generate a prediction model for selection of treatment modality for early-stage non-small cell lung cancer (NSCLC)., Summary Background Data: Stereotactic body radiotherapy (SBRT) and minimally invasive surgery (MIS) are used in the local treatment of early-stage NSCLC. However, selection of patients for either SBRT or MIS remains challenging, due to the multitude of factors influencing the decision-making process., Methods: We analyzed 1291 patients with clinical stage I NSCLC treated with intended MIS or SBRT from January 2020 to July 2023. A prediction model for selection for SBRT was created based on multivariable logistic regression analysis. The receiver operating characteristic curve analysis stratified the cohort into 3 treatment-related risk categories. Post-procedural outcomes, recurrence and overall survival (OS) were investigated to assess the performance of the model., Results: In total, 1116 patients underwent MIS and 175 SBRT. The prediction model included age, performance status, previous pulmonary resection, MSK-Frailty score, FEV1 and DLCO, and demonstrated an area-under-the-curve of 0.908 (95%CI, 0.876-0.938). Based on the probability scores (n=1197), patients were stratified into a low-risk (MIS, n=970 and SBRT, n=28), intermediate-risk (MIS, n=96 and SBRT, n=53) and high-risk category (MIS, n=10 and SBRT, n=40). Treatment modality was not associated with OS (HR of SBRT, 1.67 [95%CI: 0.80-3.48]; P=0.20)., Conclusion: Clinical expertise can be translated into a robust predictive model, guiding the selection of stage I NSCLC patients for MIS versus SBRT and effectively categorizing them into three distinct risk groups. Patients in the intermediate category could benefit most from multidisciplinary evaluation., Competing Interests: Disclosures: Prasad S. Adusumilli declares research funding from ATARA Biotherapeutics, is a scientific advisory board member and consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnson & Johnson, Orion, Outpace Bio, has patents, royalties, and intellectual property on mesothelin-targeted chimeric antigen receptor and other T-cell therapies, which have been licensed to ATARA Biotherapeutics, and has an issued patent method for detection of cancer cells using virus and pending patent applications on PD-1 dominant negative receptor, a wireless pulse-oximetry device, and an ex vivo malignant pleural effusion culture system. Daniel Gomez receives research funding from AstraZeneca and Varian. He has received personal fees from Varian, AstraZeneca, GRAIL, Johnson & Johnson, Medtronic, Physicians Education Resource, and Regeneron. Daniela Molena serves on a steering committee for AstraZeneca, as a consultant for Johnson & Johnson, Bristol-Myers Squibb, AstraZeneca, and Boston Scientific, and has been an invited speaker for Merck and Genentech. Bernard J. Park serves as a consultant for Intuitive Surgical, CEEVRA, Medtronic, and Becton Dickinson. Matthew J. Bott is a consultant for AstraZeneca Pharmaceuticals, Iovance Biotherapeutics, and Intuitive Surgical and receives research support from Obsidian Therapeutics. Andreas Rimner served on a steering committee for Merck, served as a consultant for AstraZeneca and Merck, and received grant support (institutional) from Varian Medical Systems, Boehringer Ingelheim, AstraZeneca, Merck, and Pfizer, payments from NIH/Coordinating Center for Clinical Trials. Valerie W. Rusch reports grant support (institutional) from Genelux and Genentech, travel support from Intuitive Surgical, and travel support and payments from NIH/Coordinating Center for Clinical Trials. Smita Sihag is a member of the AstraZeneca Advisory Board. James M. Isbell has served as an advisory board member for AstraZeneca and Merck, as an uncompensated steering board member for Genentech, has received institutional research support from ArcherDx/Invitae, Guardant Health, GRAIL, and Intuitive Surgical and travel support from Intuitive Surgical, and has equity/ownership interest in LumaCyte. David R. Jones is a member of the Advisory Council for AstraZeneca and receives research grant support from Merck. Gaetano Rocco has financial relationships with Scanlan International, Medtronic, and Merck. The other authors have no conflict of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
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22. Commission on Cancer Standards for Lymph Node Sampling and Oncologic Outcomes After Lung Resection.
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Resio BJ, Tan KS, Skovgard M, Dycoco J, Adusumilli PS, Bains MS, Bott MJ, Downey RJ, Gray KD, Huang J, Molena D, Park BJ, Rusch VW, Sihag S, Rocco G, Jones DR, and Isbell JM
- Abstract
Background: The newest Commission on Cancer standards recommend sampling 3 mediastinal and 1 hilar lymph node stations, 3 (N2) 1 (N1), for lung cancer resections. However, the relationship between the Commission on Cancer standards and outcomes has not been thoroughly investigated., Methods: A prospective institutional database was queried for clinical stage I-III lung resections before the implementation of the new standards. The relationship between the 3 (N2) 1 (N1) standard ("guideline concordant") and outcomes (upstaging, complications, receipt of adjuvant therapy, locoregional/distant recurrence, and survival) was assessed with multivariable models and stratified by stage., Results: Of 9289 pulmonary resections, 3048 (33%) were guideline concordant and 6241 (67%) were not. Compared with nonconcordant, those that were guideline concordant had higher rates of nodal upstaging (21% vs 13%; odds ratio [OR], 1.32 [95% CI, 1.14-1.51]; P < .001) and in-hospital complications (34% vs 27%; OR, 1.17 [95% CI, 1.05-1.30]; P = .004) but similar adjuvant systemic therapy administration (19% vs 13%; OR, 1.09 [95% CI, 0.95-1.24]; P = .2; 98% chemotherapy). Locoregional and distant recurrences were not significantly improved with guideline concordance across clinical stage I, II, and III subsets. Overall survival was similar in clinical stages I and II, but improved survival was observed for guideline concordant clinical stage III patients (hazard ratio, 0.85 [95% CI, 0.74-0.97]; P = .02)., Conclusions: Sampling 3 (N2) 1 (N1) was associated with increased upstaging and complications but not with decreased recurrence or mortality in clinical stage I or II patients. Survival was improved for concordant, clinical stage III patients. Further study is indicated to determine the ideal lymph node sampling strategy across heterogeneous lung cancer patients., Competing Interests: Disclosures James Isbell reports a relationship with LumaCyte that includes: equity or stocks; with Roche that includes: board membership; and with Genetech Biotech Co Ltd that includes: board membership and funding grants. Daniela Molena reports a relationship with Genetech Biotech Co Ltd that includes: board membership and funding grants; with AstraZeneca Pharmaceuticals LP that includes: board membership and consulting or advisory; with Johnson and Johnson Ltd that includes: consulting or advisory; with Bristol Myers Squibb Co that includes: consulting or advisory; and with Merck & Co Inc that includes: consulting or advisory. David Jones reports a relationship with Merck & Co Inc that includes: consulting or advisory; and with AstraZeneca Pharmaceuticals LP that includes: board membership and consulting or advisory. Matthew Bott reports a relationship with AstraZeneca Pharmaceuticals LP that includes: board membership and consulting or advisory. Prasad Adusumilli reports a relationship with Johnson and Johnson Ltd that includes: consulting or advisory; with Atara Biotherapeutics that includes: consulting or advisory; with Bayer Corporation that includes: consulting or advisory; with Carisma Therapeutics Inc that includes: consulting or advisory; with Imugene that includes: consulting or advisory; and with ImmPactBio that includes: consulting or advisory. Bernard Park reports a relationship with Intuitive Surgical Inc that includes: consulting or advisory; and with COTA, Inc that includes: consulting or advisory. Valerie Rusch reports a relationship with Genetech Biotech Co Ltd that includes: board membership and funding grants; with Intuitive Surgical Inc that includes: consulting or advisory; and with Genelux that includes: funding grants. Gaetano Rocco reports a relationship with AstraZeneca Pharmaceuticals LP that includes: board membership and consulting or advisory; with Scanlan International Inc that includes: consulting or advisory; and with Medtronic that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
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- 2024
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23. Bryophyllum pinnatum (Lam.) Oken: unravelling therapeutic potential and navigating toxicity.
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Sharma G, Jangra A, Sihag S, Chaturvedi S, Yadav S, and Chhokar V
- Abstract
Bryophyllum pinnatum (Lam.) Oken, a multipurpose medicinal herb, has drawn much interest for its therapeutic qualities from both traditional and modern medicine systems. Many active secondary metabolites, such as bufadienolides, triterpenes, phenols, alkaloids, glycosides, lipids, flavonoids, and organic acids, are responsible for the plant's curative properties. B. pinnatum exhibits a noteworthy significance in oncological research by exhibiting its ability to modify numerous pathways, which may suggest a potential anticancer impact. The herb is recommended for treating lithiasis, a common cause of renal failure, due to its effectiveness in dissolving stones and avoiding crystal formation. The plant has a major impact on diabetes, especially type II diabetes. Moreover, the versatility of B. pinnatum extends to its examination in connection to COVID-19. However, caution is warranted, as B. pinnatum has been reported to possess toxicity attributed to the presence of bufadienolides in its metabolic profile. A comprehensive investigation is essential to thoroughly understand and confirm the synthesis of potentially hazardous compounds. This is crucial for minimizing their presence and ensuring the safe consumption of B. pinnatum among diverse populations of organisms. This review highlights the various medical uses of B. pinnatum , including its ability to effectively treat kidney and liver diseases, as well as its anti-leishmanial, neuropharmacological, antibacterial, immunosuppressive, anti-tumour, and cytotoxic effects. While extensively employed in both traditional and scientific domains, the plant's complete medicinal potential, molecular mechanisms, safety profile, and pharmacodynamics remain ambiguous, rendering it an ideal candidate for pioneering research endeavours., Competing Interests: Conflict of interestThe authors have no relevant financial or non-financial interests to disclose., (© Prof. H.S. Srivastava Foundation for Science and Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
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- 2024
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24. A Real-World Assessment of Stage I Lung Cancer Through Electronic Nose Technology.
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Rocco G, Pennazza G, Tan KS, Vanstraelen S, Santonico M, Corba RJ, Park BJ, Sihag S, Bott MJ, Crucitti P, Isbell JM, Ginsberg MS, Weiss H, Incalzi RA, Finamore P, Longo F, Zompanti A, Grasso S, Solomon SB, Vincent A, McKnight A, Cirelli M, Voli C, Kelly S, Merone M, Molena D, Gray K, Huang J, Rusch VW, Bains MS, Downey RJ, Adusumilli PS, and Jones DR
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- Humans, Male, Female, Middle Aged, Aged, Prospective Studies, Lung Neoplasms pathology, Electronic Nose, Neoplasm Staging
- Abstract
Introduction: Electronic nose (E-nose) technology has reported excellent sensitivity and specificity in the setting of lung cancer screening. However, the performance of E-nose specifically for early-stage tumors remains unclear. Therefore, the aim of our study was to assess the diagnostic performance of E-nose technology in clinical stage I lung cancer., Methods: This phase IIc trial (NCT04734145) included patients diagnosed with a single greater than or equal to 50% solid stage I nodule. Exhalates were prospectively collected from January 2020 to August 2023. Blinded bioengineers analyzed the exhalates, using E-nose technology to determine the probability of malignancy. Patients were stratified into three risk groups (low-risk, [<0.2]; moderate-risk, [≥0.2-0.7]; high-risk, [≥0.7]). The primary outcome was the diagnostic performance of E-nose versus histopathology (accuracy and F1 score). The secondary outcome was the clinical performance of the E-nose versus clinicoradiological prediction models., Results: Based on the predefined cutoff (<0.20), E-nose agreed with histopathologic results in 86% of cases, achieving an F1 score of 92.5%, based on 86 true positives, two false negatives, and 12 false positives (n = 100). E-nose would refer fewer patients with malignant nodules to observation (low-risk: 2 versus 9 and 11, respectively; p = 0.028 and p = 0.011) than would the Swensen and Brock models and more patients with malignant nodules to treatment without biopsy (high-risk: 27 versus 19 and 6, respectively; p = 0.057 and p < 0.001)., Conclusions: In the setting of clinical stage I lung cancer, E-nose agrees well with histopathology. Accordingly, E-nose technology can be used in addition to imaging or as part of a "multiomics" platform., Competing Interests: Disclosure Dr. Rocco has a financial relationship with Scanlan, Merck, and Medtronic. Dr. Prasad S. Adusumilli serves as consultant for ATARA Biotherapeutics, Bayer, Carisma Therapeutics, Imugene, ImmPactBio, and Johnson & Johnson. Dr. Park has received honoraria from Intuitive Surgical, AstraZeneca, and Medtronic, serves as a consultant to Ceevra, and has received institutional research support from Intuitive Surgical. Dr. Bott is a consultant for AstraZeneca Pharmaceuticals, Iovance Biotherapeutics, and Intuitive Surgical and receives research support from Obsidian Therapeutics. Dr. Molena serves on a steering committee for AstraZeneca and as a consultant for Johnson & Johnson, Bristol-Myers Squibb, AstraZeneca, and Boston Scientific, and has been an invited speaker for Merck and Genentech. Dr. Isbell has served as an advisory board member for AstraZeneca and Merck and as an uncompensated steering board member for Genentech, has received institutional research support from ArcherDx/Invitae, Guardant Health, GRAIL, and Intuitive Surgical and travel support from Intuitive Surgical, and has equity or ownership interest in LumaCyte. Dr. Rusch receives grant support (institutional) from Genelux and Genentech, travel support from Intuitive Surgical, and travel support and payments from the National Institutes of Health/Coordinating Center for Clinical Trials. Dr. Solomon serves as a consultant for GE Healthcare and Merck and on the data monitoring committee for Candel Therapeutics and Impact Biotech. Dr. Jones is a member of the Advisory Council for AstraZeneca and Advisory Committee for More Health, has been a speaker for DAVA Oncology, and receives research grant support from Merck. The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
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- 2024
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25. Outcomes of Patients Undergoing Segmentectomy for Occult Node-Positive Clinical Stage IA Lung Cancer.
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Nobel TB, Tan KS, Adusumilli PS, Bains MS, Downey RJ, Gray K, Huang J, Isbell JM, Molena D, Park BJ, Rocco G, Rusch VW, Sihag S, Jones DR, and Bott MJ
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- Humans, Male, Female, Aged, Middle Aged, Treatment Outcome, Neoplasm Recurrence, Local epidemiology, Retrospective Studies, Survival Rate trends, Lymph Nodes pathology, Lymph Nodes surgery, Lung Neoplasms surgery, Lung Neoplasms pathology, Lung Neoplasms mortality, Pneumonectomy methods, Carcinoma, Non-Small-Cell Lung surgery, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, Neoplasm Staging, Lymphatic Metastasis
- Abstract
Background: Results of recent clinical trials suggest that segmentectomy may be an acceptable alternative to lobectomy for selected patients with early-stage non-small cell lung cancer (NSCLC). Increased use of segmentectomy may result in a concomitant increase in occult node-positive (N+) disease on surgical pathology examination. The optimal management for such patients remains unknown., Methods: Clinicopathologic data were abstracted from a prospective institutional database to identify patients with pathologic N+ disease after segmentectomy for cT1 N0 M0 NSCLC. Propensity score matching identified a comparable lobectomy cohort for assessment of cumulative incidence of recurrence and overall survival (OS)., Results: Of 759 included patients, 27 (4%) had nodal upstaging on the final pathology report. Of these 27 patients, 4 (15%) had skip metastasis to N2 stations, and 20 (74%) received adjuvant therapy; no completion lobectomies were performed. Ten patients (37%) had disease recurrence: 3 isolated locoregional (11%) and 7 distant (26%). The median time to recurrence among patients with recurrence was 1.8 years; OS after recurrence was 3.4 years. After 5:1 matching with 109 patients who underwent lobectomy, all variables were balanced between the groups, except pathologic N2 stage and open surgical approach. The 5-year cumulative incidence of recurrence was not significantly different between segmentectomy and lobectomy (42% vs 52%, respectively; Gray's P = .1). The 5-year OS (63% and 50%) and rate of locoregional recurrence (12% vs 13%) were not statistically different between the groups., Conclusions: Patients with occult N+ disease after segmentectomy for cT1 N0 M0 NSCLC had limited isolated locoregional recurrences and outcomes similar to those in patients who underwent lobectomy. Lobectomy may not provide an advantage in these patients., Competing Interests: Disclosures James M. Isbell has served as an advisory board member for AstraZeneca and Merck; has served as an uncompensated steering board member for Genentech; has received travel support from Intuitive Surgical; and has equity or ownership interest in LumaCyte. Daniela Molena has served on a steering committee for AstraZeneca; has served as a consultant for Johnson & Johnson, Bristol Myers Squibb, AstraZeneca, and Boston Scientific; and has been an invited speaker for Merck and Genentech. Bernard J. Park has received honoraria from Intuitive Surgical, AstraZeneca, and Medtronic; and has served as a consultant for Ceevra. Gaetano Rocco has a financial relationship with Scanlan, Merck, and Medtronic. Valerie W. Rusch has received other support from DaVinci Surgery; has received nonfinancial support from Bristol Myers Squibb; and has received personal fees from the NIH Coordinating Center for Clinical Trials. Smita Sihag has served as a member of the AstraZeneca advisory board. David R. Jones has served as a member of the advisory council for AstraZeneca and the Advisory Committee for More Health; and has been a speaker for DAVA Oncology. Matthew J. Bott has served as a consultant for AstraZeneca Pharmaceuticals, Iovance Biotherapeutics, and Intuitive Surgical., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
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- 2024
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26. Determinants of successful minimally invasive surgery for resectable non-small cell lung cancer after neoadjuvant therapy.
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Chu NQ, Tan KS, Dycoco J, Adusumilli PS, Bains MS, Bott MJ, Downey RJ, Gray KD, Huang J, Isbell JM, Molena D, Sihag S, Rocco G, Jones DR, Park BJ, and Rusch VW
- Abstract
Objective: Minimally invasive surgery (MIS) (video-assisted thoracoscopic surgery and robot-assisted thoracoscopic surgery) for pulmonary resection is standard in early-stage non-small cell lung cancer because it is associated with better perioperative outcomes than thoracotomy. MIS for resection of more advanced non-small cell lung cancer (Stages IB-IIIB) treated with neoadjuvant therapy has been utilized. However, the determinants of success are not well defined., Methods: A single institution retrospective review of a prospectively maintained database was conducted, querying for patients with clinical Stage IB through IIIB non-small cell lung cancer who had resection after neoadjuvant systemic therapy without radiation from 2013 to 2022. Patients were grouped by surgical approach; that is, open versus MIS. Successful MIS was defined by no conversion, R0 resection, and no major (grade 3 or greater) morbidity. Analyses by intent-to-treat assessed outcomes by Wilcoxon rank-sum test and Fisher exact test. (Multivariable regression analysis identified variables that contributed to successful MIS resection.) RESULTS: Of 627 eligible patients, 360 (57%) had open and 267 (43%) had MIS procedures. Most patients (79.1%) received neoadjuvant platinum-based chemotherapy, and 21.9% were treated with immunotherapy or targeted therapy alone or combined with chemotherapy. Among MIS resections, 179 (67%) were performed by video-assisted thoracoscopic surgery and 88 (33%) by robot-assisted thoracoscopic surgery. The conversion rate was 16% (n = 43). Successful MIS resection was achieved in 77% of patients. Multivariable regression analysis showed that pretreatment clinical N stage was a significant determinant of success, but not pretreatment clinical T stage or type of neoadjuvant therapy., Conclusions: Following neoadjuvant systemic therapy for clinical stage IB or IIIB non-small cell lung cancer, MIS resection can be successfully accomplished and should be considered in appropriate patients. Presence of pretreatment nodal disease is associated with higher odds of conversion, major morbidity, and incomplete resection., Competing Interests: Conflict of Interest Statement Dr Adusumilli declares research funding from ATARA Biotherapeutics; is a Scientific Advisory Board Member and consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnston & Johnston, Orion Pharma, and Outpace Bio; and holds patents, royalties, and intellectual property on mesothelin-targeted CAR and other T-cell therapies that have been licensed to ATARA Biotherapeutics, issued a patent method for detection of cancer cells using virus, and has pending patent applications on PD-1 dominant negative receptor, wireless pulse-oximetry device, and on an ex vivo malignant pleural effusion culture system. Memorial Sloan Kettering Cancer Center has licensed intellectual property related to mesothelin-targeted CARs and T-cell therapies to ATARA Biotherapeutics and has associated financial interests. Dr Bott is a consultant for AstraZeneca Pharmaceuticals, Iovance Biotherapeutics, and Intuitive Surgical and receives research support from Obsidian Therapeutics. Dr Isbell has served as an advisory board member for AstraZeneca and Merck, as an uncompensated steering board member for Genentech, has received institutional research support from ArcherDx/Invitae, Guardant Health, GRAIL, and Intuitive Surgical and travel support from Intuitive Surgical, and has equity/ownership interest in LumaCyte. Dr Molena serves on a steering committee for AstraZeneca, as a consultant for Johnson & Johnson, Bristol-Myers Squibb, AstraZeneca, and Boston Scientific, and has been an invited speaker for Merck and Genentech. Dr Sihag is a member of the AstraZeneca Advisory Board. Dr Rocco has received royalties from Scanlan International, has served as an uncompensated advisor for AstraZeneca, and has served as a consultant for Medtronic. Dr Jones is a member of the advisory council for AstraZeneca and receives research grant support from Merck. Dr Park has received honoraria from Intuitive Surgical, AstraZeneca, Medtronic, serves as a consultant to CEEVRA, and has received institutional research support from Intuitive Surgical. Dr Rusch reports unreimbursed participation in Data Safety and Monitoring Committees for Cancer Research UK MARS II and RAMONA trials. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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27. A Novel Frailty Index Can Predict the Short-Term Outcomes of Esophagectomy in Older Patients with Esophageal Cancer.
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Boerner T, Sewell M, Tin AL, Vickers AJ, Harrington-Baksh C, Bains MS, Bott MJ, Park BJ, Sihag S, Jones DR, Downey RJ, Shahrokni A, and Molena D
- Subjects
- Humans, Aged, Male, Female, Treatment Outcome, Postoperative Complications epidemiology, Aged, 80 and over, Esophagectomy methods, Esophageal Neoplasms surgery, Esophageal Neoplasms mortality, Frailty complications
- Abstract
Background: Frailty, rather than age, is associated with postoperative morbidity and mortality. We sought to determine whether preoperative frailty as defined by a novel scoring system could predict the outcomes among older patients undergoing esophagectomy. Methods: We identified patients 65 years or older who underwent esophagectomy between 2011 and 2021 at our institution. Frailty was assessed using the MSK-FI, which consists of 1 component related to functional status and 10 medical comorbidities. We used a multivariable logistic regression model to test for the associations between frailty and short-term outcomes, with continuous frailty score as the predictor and additionally adjusted for age and Eastern Cooperative Oncology Group performance status. Results: In total, 447 patients were included in the analysis (median age of 71 years [interquartile range, 68-75]). Most of the patients underwent neoadjuvant treatment (81%), an Ivor Lewis esophagectomy (86%), and minimally invasive surgery (55%). A total of 22 patients (4.9%) died within 90 days of surgery, 144 (32%) had a major complication, 81 (19%) were readmitted, and 31 (7.2%) were discharged to a facility. Of the patients who died within 90 days, 19 had a major complication, yielding a failure-to-rescue rate of 13%. The risk of 30-day major complications (OR, 1.24 [95% CI, 1.09-1.41]; p = 0.001), readmissions (OR, 1.31 [95% CI, 1.13-1.52]; p < 0.001), and discharge to a facility (OR, 1.86 [95% CI, 1.49-2.37]; p < 0.001) increased with increasing frailty. Frailty and 90-day mortality were not associated. Conclusions: Frailty assessment during surgery decision-making can identify patients with a high risk of morbidity.
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- 2024
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28. Lung resection after initial nonoperative treatment for non-small cell lung cancer.
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Dunne EG, Fick CN, Tan KS, Toumbacaris N, Mastrogiacomo B, Adusumilli PS, Rocco G, Molena D, Huang J, Park BJ, Bott MJ, Rusch VR, Sihag S, Isbell JM, Chaft JE, Li BT, Gomez D, Rimner A, Bains MS, and Jones DR
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Neoplasm Staging, Retrospective Studies, Progression-Free Survival, Time Factors, Risk Factors, Treatment Outcome, Databases, Factual, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung therapy, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung surgery, Carcinoma, Non-Small-Cell Lung secondary, Lung Neoplasms mortality, Lung Neoplasms pathology, Lung Neoplasms therapy, Lung Neoplasms surgery, Pneumonectomy adverse effects, Pneumonectomy mortality
- Abstract
Objectives: The study objectives were to assess the outcomes of lung resection in patients with non-small cell lung cancer previously treated with nonoperative treatment and to identify prognostic factors associated with survival., Methods: Patients who underwent surgery (2010-2022) after initial nonoperative treatment at a single institution were identified from a prospectively maintained database. Exclusion criteria included metachronous cancer, planned neoadjuvant therapy, and surgery for diagnostic or palliative indications. Cox models were constructed for overall survival and event-free survival. Survival of patients with stage IV disease was compared with survival of a nonstudy cohort who did not undergo surgery., Results: In total, 120 patients met the inclusion criteria. Initial clinical stage was early stage in 16%, locoregionally advanced in 25%, and metastatic in 59% of patients. The indication for surgery was recurrence in 18%, local persistent disease in 23%, oligoprogression in 22%, and local control of oligometastatic disease in 38% of patients. Grade 3 or greater complications occurred in 5% of patients; 90-day mortality was 3%. Three-year event-free survival and overall survival were 39% and 73%, respectively. Male sex and lymphovascular invasion were associated with shorter event-free survival and overall survival; younger age and prior radiation therapy were associated with shorter overall survival. Patients with stage IV disease who received salvage lung resection had better overall survival than similar patients who received subsequent systemic therapy and no surgery., Conclusions: In this selected, heterogeneous population, lung resection after initial nonoperative treatment for non-small cell lung cancer was safe. Surgery as local consolidative therapy was associated with encouraging outcomes and should be considered for these patients., Competing Interests: Conflict of Interest Statement Dr Adusumilli declares research funding from ATARA Biotherapeutics; is a scientific advisory board member and consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnson & Johnson, Orion, and Outpace Bio; has patents, royalties, and intellectual property on mesothelin-targeted chimeric antigen receptor and other T-cell therapies, which have been licensed to ATARA Biotherapeutics; and has an issued patent method for detection of cancer cells using virus and pending patent applications on PD-1 dominant negative receptor, a wireless pulse-oximetry device, and an ex vivo malignant pleural effusion culture system. MSK Cancer Center has licensed intellectual property related to mesothelin-targeted chimeric antigen receptors and T-cell therapies to ATARA Biotherapeutics and has associated financial interests. Dr Rocco has financial relationships with Scanlan International, Medtronic, and Merck. Dr Molena serves on a steering committee for AstraZeneca and as a consultant for Johnson & Johnson, Bristol Myers Squibb, Merck, and Genentech. Dr Park is a consultant for Intuitive Surgical, Medtronic, AstraZeneca, and CEEVRA. Dr Bott is a consultant for AstraZeneca. Dr Rusch reports grant support (institutional) from Genelux and Genentech, travel support from Intuitive Surgical, and travel support and payments from National Institutes of Health/Coordinating Center for Clinical Trials. Dr Sihag is a member of the AstraZeneca Advisory Board. Dr Isbell has stock ownership in LumaCyte and is a consultant/advisory board member for Roche Genentech. Dr Chaft serves as a consultant for AstraZeneca, Bristol Myers Squibb, Flame Biosciences, Regeneron-Sanofi, Guardant Health, and Arcus Biosciences and receives institutional research funding from AztraZeneca, Bristol Myers Squibb, Merck, and Novartis. Dr Li has served as an uncompensated advisor and consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, and Lilly; has received research grants to his institution from Amgen, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Hengrui USA, and Lilly; has received academic travel support from Amgen, Jiangsu Hengrui Medicine, and MORE Health; and has intellectual property rights as a book author at Karger Publishers and Shanghai Jiao Tong University Press. Dr Gomez reports research funding from Merck, AstraZeneca, Varian, and Bristol Myers Squibb and serves on the advisory boards of MedLearning Group, Medtronic, GRAIL, Johnson & Johnson, AstraZeneca, and Varian. Dr Rimner is a consultant for AstraZeneca, Merck, and MoreHealth, serves as an advisory board member for Merck, and reports institutional grant support from Varian Medical Systems, AstraZeneca, Merck, Pfizer, and Boehringer Ingelheim. Dr Jones serves as a consultant for Merck, AstraZeneca, Genentech, and DAVA Oncology. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)
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- 2024
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29. Assessment of Serum Insulin and VASPIN Levels Among Type 2 Diabetes Mellitus Patients with or Without Obesity: A Cross-sectional Analytical Study.
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Sihag S, Mathur R, Bissa MS, and Bhawani J
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Introduction: A collection of diverse conditions together referred to as diabetes mellitus frequently manifest as periods of hyperglycemia and glucose intolerance, which can be caused by insufficient insulin, improper insulin action, or both. A medical condition known as obesity is the accumulation of excess body fat to the point that it may be harmful to one's health. It has been determined that the adipokine vaspin (visceral adipose tissue-derived serpin A12) belongs to the family of serine protease inhibitors. Insulin, a polypeptide hormone, is released by the pancreatic beta cells. This hormone is both anti-catabolic and anabolic. Insulin decreases blood glucose levels by preventing its synthesis and encouraging its storage and use., Methodology: In total, 125 male and female participants of various ages participated in the current study. They included 25 healthy controls, 50 non-obese and 50 obese non-insulin-dependent diabetes mellitus patients, who visited the MDM Hospital's outpatient clinic in Jodhpur, Rajasthan. Commercially available reagents and kits were utilized for the analysis of serum insulin and vaspin samples. Standard statistical tools were utilized to evaluate the parameters., Results and Discussion: When results were compared with healthy participants and non-obese NIDDM subjects, obese NIDDM subjects showed statistically significant higher fasting serum insulin and serum vaspin levels ( P < 0.0001)., Conclusion: Our study's conclusions demonstrated a strong correlation between blood insulin and vaspin levels and diabetes and obesity. Vaspin has a positive impact on insulin resistance, obesity, type 2 diabetes, and metabolic syndrome. It also enhances glucose tolerance and insulin sensitivity, reducing diabetes complications. This novel biomarker has the potential to enhance diabetes mellitus outcomes by facilitating prompt diagnosis, improved management, and reduction of complications., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)
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- 2024
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30. The Contemporary Management of Esophageal and Gastric Cancer.
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Sihag S and Merritt RE
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- Humans, Disease Management, Esophageal Neoplasms therapy, Stomach Neoplasms therapy
- Abstract
Competing Interests: Disclosure R.E. Merritt currently serves as a consultant for Astra Zeneca, and a speaker for Astra Zeneca. He does not have any conflicts of interest relevant to this publication.
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- 2024
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31. Advances in Diagnostic, Staging, and Restaging Evaluation of Esophageal and Gastric Cancer.
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Nobel T and Sihag S
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- Humans, Endosonography methods, Esophageal Neoplasms pathology, Esophageal Neoplasms diagnosis, Stomach Neoplasms pathology, Stomach Neoplasms diagnosis, Neoplasm Staging methods
- Abstract
The initial endoscopic and staging evaluation of esophagogastric cancers must be accurate and comprehensive in order to select the optimal therapeutic plan for the patient. Esophageal and gastric cancers (and treatment paradigms) are delineated by their proximity to the cardia (within 2 cm). The most frequent and important symptom that informs the initial staging evaluation is dysphagia, which is associated with at least cT3 or locally advanced disease. Endoscopic ultrasound is often needed if earlier stage disease is suspected, preferably in combination with endoscopic mucosal or submucosal resection or fine-needle aspiration of suspicious lymph nodes to enhance staging accuracy., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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32. Immunotherapy for Resectable Locally Advanced Esophageal Carcinoma.
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Fick CN, Dunne EG, Sihag S, Molena D, Cytryn SL, Janjigian YY, Wu AJ, Worrell SG, Hofstetter WL, Jones DR, and Gray KD
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- Humans, Neoadjuvant Therapy methods, Neoplasm Staging, Esophagectomy methods, Immune Checkpoint Inhibitors therapeutic use, Esophageal Neoplasms therapy, Esophageal Neoplasms pathology, Immunotherapy methods
- Abstract
Background: The current standard of care for locally advanced esophageal and gastroesophageal junction (GEJ) cancers includes neoadjuvant chemoradiotherapy or perioperative chemotherapy with surgical resection; however, disease-free survival in these patients remains poor. Immune checkpoint inhibitors (ICIs) are approved for adjuvant treatment of locally advanced esophageal and GEJ cancers, but their benefit in the perioperative and neoadjuvant settings remains under investigation., Methods: We used the PubMed online database to conduct a literature search to identify studies that investigated immunotherapy for locally advanced esophageal and GEJ carcinoma. A review of ClinicalTrials.gov yielded a list of ongoing trials., Results: Adjuvant nivolumab for residual disease after neoadjuvant chemoradiotherapy and surgery is the only approved immunotherapy regimen for locally advanced esophageal cancer. Early-phase trials investigating the addition of neoadjuvant or perioperative ICIs to standard-of-care multimodality approaches have observed pathologic complete response rates as high as 60%. Response rates are highest for ICIs plus chemoradiotherapy for esophageal squamous cell carcinoma and dual checkpoint inhibition in mismatch repair-deficient adenocarcinomas. Safety profiles are acceptable, with a pooled adverse event rate of 27%. Surgical morbidity and mortality with immunotherapy are similar to historical controls with no immunotherapy, and R0 resection rates are high. When reported, disease-free survival among patients treated with perioperative immunotherapy is promising., Conclusions: Outside of clinical trials, immunotherapy for resectable esophageal carcinoma is limited to the adjuvant setting. Phase III trials investigating neoadjuvant and perioperative immunotherapy are now underway and will provide much-needed data on survival that may ultimately lead to practice-changing recommendations., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
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- 2024
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33. Late recurrence of completely resected stage I to IIIA lung adenocarcinoma.
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Fick CN, Dunne EG, Toumbacaris N, Tan KS, Mastrogiacomo B, Park BJ, Adusumilli PS, Molena D, Gray KD, Sihag S, Huang J, Bott MJ, Rocco G, Isbell JM, and Jones DR
- Abstract
Objective: Research into the risk factors associated with late recurrence (>2 years after surgery) of lung adenocarcinoma is limited. We investigated the incidence of and clinicopathologic and genomic features associated with late recurrence of resected stage I-IIIA lung adenocarcinoma., Methods: We performed a retrospective analysis of patients with completely resected pathologic stage I-IIIA lung adenocarcinoma (2010-2019). Patients with a history of lung cancer, neoadjuvant therapy, or mucinous or noninvasive lung adenocarcinoma, or with follow-up of less than 2 years were excluded. Cox and logistic regression modeling were used to compare clinicopathologic variables among patients with no, early (≤2 years), and late recurrence. Comparisons of genomic mutations were corrected for multiple testing., Results: Of the 2349 patients included, 537 developed a recurrence during follow-up. Most recurrences (55% [297/537]) occurred early; 45% (240/537) occurred late. A larger proportion of late recurrences than early recurrences were locoregional (37% vs 29%; P = .047). Patients with late recurrence had more aggressive pathologic features (International Association for the Study of Lung Cancer grade 2 and 3, lymphovascular invasion, visceral pleural invasion) and higher stage than patients without recurrence. Pathologic features were similar between patients with early and late recurrence, except stage IIIA disease was more common in the early cohort. No genomic mutations were associated with late recurrence., Conclusions: Late recurrence of lung adenocarcinoma after resection is more common than previously reported. Patients without disease more than 2 years after surgery who had aggressive pathologic features at the time of resection have an elevated risk of recurrence and may benefit from more aggressive follow-up., Competing Interests: Conflict of Interest Statement B.J.P. has received honoraria from Intuitive Surgical, AstraZeneca, Medtronic, consultants for CEEVRA, and has received research support from Intuitive Surgical. P.S.A. declares research funding from ATARA Biotherapeutics, is a scientific advisory board member/consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnson & Johnson, Orion, and Outpace Bio, has patents, royalties, and intellectual property on T-cell therapies, licensed to ATARA Biotherapeutics, and has an issued patent method for detection of cancer cells using virus and pending patent applications on PD-1 dominant negative receptor, a wireless pulse-oximetry device, and an ex vivo malignant pleural effusion culture system. M.S.K. has licensed intellectual property related to mesothelin-targeted chimeric antigen receptors and T-cell therapies to ATARA Biotherapeutics. D.M. serves on a steering committee for AstraZeneca, consults for Johnson & Johnson, Bristol-Myers Squibb, AstraZeneca, and Boston Scientific, and has been an invited speaker for Merck and Genentech. S.S. serves on the AstraZeneca Advisory Board. M.J.B. consults for AstraZeneca Pharmaceuticals, Iovance Biotherapeutics, and Intuitive Surgical and receives research support from Obsidian Therapeutics. G.R. has financial relationships with Scanlan International, AstraZeneca, and Medtronic. J.M.I. has served on advisory boards for AstraZeneca and Merck, as an uncompensated steering board member for Genentech, has received research support from ArcherDx/Invitae, Guardant Health, GRAIL, and Intuitive Surgical and travel support from Intuitive Surgical, and has equity/ownership interest in LumaCyte. D.R.J. serves on the Advisory Council for AstraZeneca and receives research grant support from Merck. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)
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- 2024
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34. Low ppm NO 2 detection through advanced ultrasensitive copper oxide gas sensor.
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Sihag S, Dahiya R, Rani S, Berwal P, Jatrana A, Sisodiya AK, Sharma A, and Kumar V
- Abstract
The imperative development of a cutting-edge environmental gas sensor is essential to proficiently monitor and detect hazardous gases, ensuring comprehensive safety and awareness. Nanostructures developed from metal oxides are emerging as promising candidates for achieving superior performance in gas sensors. NO
2 is one of the toxic gases that affects people as well as the environment so its detection is crucial. The present study investigates the gas sensing capability of copper oxide-based sensor for 5 ppm of NO2 gas at 100 °C. The sensing material was synthesized using a facile precipitation method and characterized by XRD, FE-SEM, UV-visible spectroscopy, photoluminescence spectroscopy, XPS and BET techniques. The developed material shows a response equal to 67.1% at optimal temperature towards 5 ppm NO2 gas. The sensor demonstrated an impressive detection limit of 300 ppb, along with a commendable percentage response of 5.2%. Under optimized conditions, the synthesized material demonstrated its high selectivity, as evidenced by the highest percentage response recorded for NO2 gas among NO2 , NH3 , CO, CO2 and H2 S., (© 2024. The Author(s).)- Published
- 2024
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35. Genomic Landscape of Adenocarcinomas Across the Gastroesophageal Junction: Moving on from the Siewert Classification.
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Nakauchi M, Walch HS, Nussenzweig S, Carr R, Vos E, Berger MF, Schultz N, Janjigian Y, Wu A, Tang L, Shah P, Jones DR, Coit D, Strong VE, Molena D, and Sihag S
- Abstract
Objective: To investigate how the Siewert classification of gastroesophageal junction adenocarcinomas correlates with genomic profiles., Summary/background Data: Current staging and treatment guidelines recommend that tumors with an epicenter less than 2 cm into the gastric cardia be treated as esophageal cancers, while tumors with epicenter greater than 2 cm into the cardia be staged and treated as gastric cancers. To date, however, few studies have compared the genomic profiles of the 3 Siewert classification groups to validate this distinction., Methods: Using targeted tumor sequencing data on patients with adenocarcinoma of the gastroesophageal junction previously treated with surgery at our institution, we compared genomic features across Siewert classification groups., Results: A total of 350 patients were included: 121 had Siewert type I, 170 type II, and 59 type III. Comparisons by Siewert location revealed that Siewert type I and II were primarily characterized as the chromosomal instability (CIN) molecular subtype and displayed Barrett's metaplasia and p53 and cell cycle pathway dysregulation. Siewert type III tumors, by contrast, were more heterogeneous, including higher proportions of microsatellite instability (MSI) and genomically stable (GS) tumors and more frequently displayed ARID1A and somatic CDH1 alterations, signet ring cell features, and poor differentiation. Overall, Siewert type I and II tumors demonstrated greater genomic overlap with lower esophageal tumors, while Siewert type III tumors shared genomic features with gastric tumors., Conclusions: Overall, our results support recent updates in treatment and staging guidelines. Ultimately, however, molecular rather than anatomic classification may prove more valuable in determining staging, treatment, and prognosis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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36. Advances in the Surgical Management of Esophageal Cancer.
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Sihag S
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- Humans, Combined Modality Therapy, Disease Management, Esophagectomy, Lymph Node Excision, Esophageal Neoplasms surgery, Esophageal Neoplasms pathology, Esophageal Neoplasms therapy
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Radical esophagectomy with two or three-field lymphadenectomy remains the mainstay of curative treatment for localized esophageal cancer, often in combination with systemic chemotherapy and/or radiotherapy. In this article, we describe notable advances in the surgical management of esophageal cancer over the past decade that have led to an improvement in both surgical and oncologic outcomes. In addition, we discuss new approaches to surgical management currently under investigation that have the potential to offer further benefits to appropriately selected patients. These incremental breakthroughs primarily include advances in endoscopic and minimally invasive techniques, perioperative management protocols, as well as the application of local therapies, including surgery, to oligometastatic disease., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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37. High-risk features associated with recurrence in stage I lung adenocarcinoma.
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Fick CN, Dunne EG, Vanstraelen S, Toumbacaris N, Tan KS, Rocco G, Molena D, Huang J, Park BJ, Rekhtman N, Travis WD, Chaft JE, Bott MJ, Rusch VW, Adusumilli PS, Sihag S, Isbell JM, and Jones DR
- Abstract
Objective: There is a lack of knowledge regarding the use of prognostic features in stage I lung adenocarcinoma (LUAD). Thus, we investigated clinicopathologic features associated with recurrence after complete resection for stage I LUAD., Methods: We performed a retrospective analysis of patients with pathologic stage I LUAD who underwent R0 resection from 2010 to 2020. Exclusion criteria included history of lung cancer, induction or adjuvant therapy, noninvasive or mucinous LUAD, and death within 90 days of surgery. Fine and Gray competing-risk regression assessed associations between clinicopathologic features and disease recurrence., Results: In total, 1912 patients met inclusion criteria. Most patients (1565 [82%]) had stage IA LUAD, and 250 developed recurrence: 141 (56%) distant and 109 (44%) locoregional only. The 5-year cumulative incidence of recurrence was 12% (95% CI, 11%-14%). Higher maximum standardized uptake value of the primary tumor (hazard ratio [HR], 1.04), sublobar resection (HR, 2.04), higher International Association for the Study of Lung Cancer grade (HR, 5.32 [grade 2]; HR, 7.93 [grade 3]), lymphovascular invasion (HR, 1.70), visceral pleural invasion (HR, 1.54), and tumor size (HR, 1.30) were independently associated with a hazard of recurrence. Tumors with 3 to 4 high-risk features had a higher cumulative incidence of recurrence at 5 years than tumors without these features (30% vs 4%; P < .001)., Conclusions: Recurrence after resection for stage I LUAD remains an issue for select patients. Commonly reported clinicopathologic features can be used to define patients at high risk of recurrence and should be considered when assessing the prognosis of patients with stage I disease., Competing Interests: Conflict of Interest Statement Dr Rocco has financial relationships with Scanlan International, AstraZeneca, and Medtronic. Dr Molena serves on a steering committee for AstraZeneca, consults for Johnson & Johnson, Bristol-Myers Squibb, AstraZeneca, Boston Scientific, and has been an invited speaker for Merck and Genentech. Dr Park has received honoraria from Intuitive Surgical, AstraZeneca, Medtronic, consults for CEEVRA, and has received research support from Intuitive Surgical. Dr Chaft consults for AstraZeneca, Bristol-Myers Squibb, Merck, Regeneron-Sanofi, Guardant Health, and Lily and receives research funding from AztraZeneca, Bristol-Myers Squibb, Merck, and Beigene. Dr Bott consults for AstraZeneca, Iovance Biotherapeutics, Intuitive Surgical, and receives research support from Obsidian Therapeutics. Dr Rusch reports grant support from Genelux and Genentech, and travel support from Intuitive Surgical and National Institutes of Health/Coordinating Center for Clinical Trials. Dr Adusumilli declares research funding from ATARA Biotherapeutics; is a scientific advisory board member and consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnson & Johnson, Orion, and Outpace Bio; has patents, royalties, and intellectual property on T-cell therapies licensed to ATARA Biotherapeutics; and has an issued patent method for detection of cancer cells using virus and pending patent applications on PD-1 dominant negative receptor, a wireless pulse-oximetry device, and an ex vivo malignant pleural effusion culture system. Dr Sihag serves on the AstraZeneca advisory board. Dr Isbell has served on advisory boards for AstraZeneca and Merck; as an uncompensated steering board member for Genentech; has received research support from ArcherDx/Invitae, Guardant Health, GRAIL, Intuitive Surgical; has received travel support from Intuitive Surgical; and has equity/ownership interest in LumaCyte. Dr Jones serves on the advisory council for AstraZeneca and receives research grant support from Merck. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)
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- 2024
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38. Comparison of Hemopoietic Biochemical Parameters in the First, Second, and Third Trimester of Pregnant Females Attending a Tertiary Care Hospital of Western Rajasthan.
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Bissa MS, Rawtani J, Sihag S, and Bissa R
- Abstract
Background: Pregnant women constitute a high-risk group for nutrient deficiency anemia which may be associated with detrimental effects on maternal and infant health., Objectives: This study aimed to assess and compare hematological and biochemical changes across trimesters in pregnant women, considering parameters such as hemoglobin, serum iron, unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), ferritin, vitamin B12, and folic acid. The research sought to identify mean value differences, correlations, and potential implications for maternal healthcare practices., Methods: A hospital-based prospective observational study was conducted, involving 60 primigravida women with singleton pregnancies. The subjects were assessed during the first, second, and third trimesters. Biochemical parameters were assessed using standard methods, and statistical analysis was performed to identify significance and correlations., Results: The study revealed a significant decline in hemoglobin, serum iron, ferritin, vitamin B12, and folic acid as pregnancy advanced. Hemoglobin levels decreased from 11.40 g/dl (first trimester) to 10.43 g/dl (third trimester). Serum iron exhibited a decline from 109.73 µg/dl (first trimester) to 94.03 µg/dl (third trimester). Serum ferritin decreased from 24.93 ng/ml (first trimester) to 18.21 ng/ml (third trimester). Vitamin B12 levels dropped from 255.92 pg/ml (first trimester) to 92.13 pg/ml (third trimester). Folic acid levels decreased from 13.82 ng/ml (first trimester) to 11.77 ng/ml (third trimester). UIBC and TIBC concentrations increased progressively across trimesters. Statistical evaluations confirmed the significance of these trends. The coefficient of correlation indicated positive relationships between hemoglobin and serum iron, ferritin, folic acid, and vitamin B12. Positive correlation between serum iron and ferritin, vitamin B12, and negative with folic acid. Serum ferritin negatively correlated with vitamin B12 and folic acid. Serum folic acid and vitamin B12 are positively correlated., Conclusion: The findings emphasize the dynamic nature of hematological and biochemical changes during pregnancy. The observed trends have profound implications for maternal healthcare practices, urging targeted interventions, early monitoring, and supportive supplementation. Recognizing these variations contributes to the optimization of health outcomes for both mother and child., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Bissa et al.)
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- 2024
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39. Treatment of esophageal adenocarcinoma in patients with a history of bariatric surgery.
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Nobel T, Sewell M, Boerner T, Bains MS, Bott MJ, Gerdes H, Gray K, Nishimura M, Park BJ, Shah P, Sihag S, Jones DR, and Molena D
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- Humans, Middle Aged, Obesity complications, Obesity surgery, Gastrectomy adverse effects, Retrospective Studies, Barrett Esophagus etiology, Barrett Esophagus surgery, Barrett Esophagus diagnosis, Esophageal Neoplasms etiology, Esophageal Neoplasms surgery, Esophageal Neoplasms diagnosis, Adenocarcinoma etiology, Adenocarcinoma surgery, Adenocarcinoma diagnosis, Bariatric Surgery adverse effects, Gastroesophageal Reflux surgery, Gastroesophageal Reflux complications, Obesity, Morbid surgery
- Abstract
Background: The relationship among obesity, bariatric surgery, and esophageal adenocarcinoma (EAC) is complex, given that some bariatric procedures are thought to be associated with increased incidence of reflux and Barrett's esophagus. Previous bariatric surgery may complicate the use of the stomach as a conduit for esophagectomy. In this study, we presented our experience with patients who developed EAC after bariatric surgery and described the challenges encountered and the techniques used., Methods: We conducted a retrospective review of our institutional database to identify all patients at our institution who were treated for EAC after previously undergoing bariatric surgery., Results: In total, 19 patients underwent resection with curative intent for EAC after bariatric surgery, including 10 patients who underwent sleeve gastrectomy. The median age at diagnosis of EAC was 63 years; patients who underwent sleeve gastrectomy were younger (median age, 56 years). The median time from bariatric surgery to EAC was 7 years. Most patients had a body mass index (BMI) score of >30 kg/m
2 at the time of diagnosis of EAC; approximately 40% had class III obesity (BMI score > 40 kg/m2 ). Six patients (32%) had known Barrett's esophagus before undergoing a reflux-increasing bariatric procedure. Sleeve gastrectomy patients underwent esophagectomy with gastric conduit, colonic interposition, or esophagojejunostomy. Only 1 patient had an anastomotic leak (after esophagojejunostomy)., Conclusion: Endoscopy should be required both before (for treatment selection) and after all bariatric surgical procedures. Resection of EAC after bariatric surgery requires a highly individualized approach but is safe and feasible., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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40. Mucinous Carcinoma of the Breast: A Case Report.
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Rey J, Shukla S, Acharya S, Gadkari P, and Sihag S
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This case report presents the diagnostic journey of a 65-year-old female presenting with symptoms suggestive of breast pathology, ultimately diagnosed with mucinous carcinoma, following comprehensive clinical evaluation and histopathological confirmation. Initial assessments indicated a fibroadenoma; however, subsequent histopathological examination revealed mucinous carcinoma, highlighting the importance of histopathological confirmation in establishing definitive diagnoses. The case underscores the challenges in distinguishing between benign and malignant breast lesions based on clinical presentation and imaging findings alone. The multidisciplinary approach facilitated discussions regarding treatment options tailored to the patient's clinical and pathological characteristics. This case emphasizes the significance of a comprehensive diagnostic approach, integrating clinical evaluation, imaging studies, and histopathological analysis, in ensuring accurate diagnosis and guiding optimal management strategies for patients with breast cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Rey et al.)
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- 2024
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41. A Case Report of Malignant Mesenchymal Tumor Presenting As Anterior Thigh Swelling: A Diagnostic Challenge.
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Rey J, Shukla S, Acharya S, Gadkari P, and Sihag S
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This case report describes the presentation, diagnostic challenges, and management of a 64-year-old male with a malignant mesenchymal tumor presenting as a swelling in the anterior thigh. Despite initial misdiagnosis and treatment at a local hospital, the swelling worsened, leading to referral to a specialized hospital. Further investigations, including blood tests, ultrasonography (USG), and MRI, revealed a large solid cystic lesion compressing adjacent muscles, indicative of soft tissue sarcoma (STS). A skin biopsy confirmed the diagnosis of a malignant mesenchymal tumor. The patient, also suffering from hypertension and diabetes mellitus, was subsequently referred to the oncology department for further management. This case underscores the importance of thorough evaluation and histopathological confirmation for accurate diagnosis and management of STS, particularly in the context of atypical presentations and comorbidities., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Rey et al.)
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- 2024
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42. Clinical and molecular characteristics of early-onset vs average-onset esophagogastric cancer.
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Lumish MA, Walch H, Maron SB, Chatila W, Kemel Y, Maio A, Ku GY, Ilson DH, Won E, Li J, Joshi SS, Gu P, Schattner MA, Laszkowska M, Gerdes H, Jones DR, Sihag S, Coit DG, Tang LH, Strong VE, Molena D, Stadler ZK, Schultz N, Janjigian YY, and Cercek A
- Subjects
- Humans, Female, Adolescent, Young Adult, Adult, Middle Aged, Aged, Aged, 80 and over, Cardia metabolism, Esophagogastric Junction metabolism, Esophagogastric Junction pathology, Retrospective Studies, Esophageal Neoplasms epidemiology, Esophageal Neoplasms genetics, Stomach Neoplasms diagnosis, Stomach Neoplasms epidemiology, Stomach Neoplasms genetics, Adenocarcinoma epidemiology, Adenocarcinoma genetics, Carcinoma, Signet Ring Cell metabolism, Carcinoma, Signet Ring Cell pathology
- Abstract
Background: The rate of esophagogastric cancer is rising among individuals under 50 years of age. It remains unknown whether early-onset esophagogastric cancer represents a unique entity. This study investigated the clinical and molecular characteristics of early-onset and average-onset esophagogastric cancer ., Methods: We reviewed the Memorial Sloan Kettering Cancer Center gastric, esophageal, and gastroesophageal junction cancer database. Associations between baseline characteristics and tumor and germline molecular alterations were compared between those with early-onset and average-onset esophagogastric cancer using Fisher exact tests and the Benjamini-Hochberg method for multiple-hypothesis correction., Results: We included 1123 patients with early-onset esophagogastric cancer (n = 219; median age = 43 years [range = 18-49 years]) and average-onset esophagogastric cancer (n = 904; median age = 67 years [range = 50-94 years]) treated between 2005 and 2018. The early-onset group had more women (39% vs 28%, P = .002). Patients with early-onset esophagogastric cancer were more likely to have a gastric primary site (64% vs 44%, P < .0001). The signet ring cell and/or diffuse type was 3 times more common in the early-onset esophagogastric cancer group (31% vs 9%, P < .0001). Early-onsite tumors were more frequently genomically stable (31% vs 18%, P = .0002) and unlikely to be microsatellite instability high (2% vs 7%, P = .003). After restricting to adenocarcinoma and signet ring cell and/or diffuse type carcinomas, we observed no difference in stage (P = .40) or overall survival from stage IV diagnosis (median = 22.7 vs 22.1 months, P = .78)., Conclusions: Our study supported a preponderance of gastric primary disease sites, signet ring histology, and genomically stable molecular subtypes in early-onset esophagogastric cancer. Our findings highlight the need for further research to define the underlying pathogenesis and strategies for early detection and prevention., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2024
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43. Biologic versus synthetic prosthesis for chest wall reconstruction: a matched analysis.
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Vanstraelen S, Bains MS, Dycoco J, Adusumilli PS, Bott MJ, Downey RJ, Huang J, Isbell JM, Molena D, Park BJ, Rusch VW, Sihag S, Allen RJ Jr, Cordeiro PG, Coriddi MR, Dayan JH, Disa JJ, Matros E, McCarthy CM, Nelson JA, Stern C, Shahzad F, Mehrara B, Jones DR, and Rocco G
- Subjects
- Humans, Postoperative Complications epidemiology, Postoperative Complications surgery, Postoperative Complications etiology, Treatment Outcome, Prostheses and Implants adverse effects, Retrospective Studies, Thoracic Wall surgery, Biological Products
- Abstract
Objectives: The aim of this study was to compare postoperative outcomes between biologic and synthetic reconstructions after chest wall resection in a matched cohort., Methods: All patients who underwent reconstruction after full-thickness chest wall resection from 2000 to 2022 were reviewed and stratified by prosthesis type (biologic or synthetic). Biologic prostheses were of biologic origin or were fully absorbable and incorporable. Integer matching was performed to reduce confounding. The study end point was surgical site complications requiring reoperation. Multivariable analysis was performed to identify associated risk factors., Results: In total, 438 patients underwent prosthetic chest wall reconstruction (unmatched: biologic, n = 49; synthetic, n = 389; matched: biologic, n = 46; synthetic, n = 46). After matching, the median (interquartile range) defect size was 83 cm2 (50-142) for the biologic group and 90 cm2 (48-146) for the synthetic group (P = 0.97). Myocutaneous flaps were used in 33% of biologic reconstructions (n = 15) and 33% of synthetic reconstructions (n = 15) in the matched cohort (P = 0.99). The incidence of surgical site complications requiring reoperation was not significantly different between biologic and synthetic reconstructions in the unmatched (3 [6%] vs 29 [7%]; P = 0.99) and matched (2 [4%] vs 4 [9%]; P = 0.68) cohorts. On the multivariable analysis, operative time [adjusted odds ratio (aOR) = 1.01, 95% confidence interval (CI), 1.00-1.01; P = 0.006] and operative blood loss (aOR = 1.00, 95% CI, 1.00-1.00]; P = 0.012) were associated with higher rates of surgical site complications requiring reoperation; microvascular free flaps (aOR = 0.03, 95% CI, 0.00-0.42; P = 0.024) were associated with lower rates., Conclusions: The incidence of surgical site complications requiring reoperation was not significantly different between biologic and synthetic prostheses in chest wall reconstructions., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)
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- 2023
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44. Expression profiling of immune genes associated with black pepper ( Piper nigrum ) powder supplementation in the diets of broiler chickens.
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Chalana G, Sihag S, Kumar A, and Magotra A
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- Animals, Powders, Escherichia coli, Toll-Like Receptor 2, Toll-Like Receptor 4, Diet veterinary, Dietary Supplements, Animal Feed analysis, Chickens genetics, Piper nigrum
- Abstract
The present study was conducted on three hundred commercial broiler chicks with the aim to evaluate the effect of black pepper supplementation on expression of TLR gene where the negative control (T1) group was given basal diet without antibiotic and in the control group (T2) basal diet with antibiotic was fed, third (T3), fourth (T4), fifth (T5) and sixth (T6) groups were supplemented with black pepper powder (BPP) at levels 0.25, 0.5, 0.75 and 1%, respectively in diet. After 42 days, a significant reduction ( p < 0.05) in ileal E. coli count and a higher value of Lactobacilli was recorded in the various black pepper powder supplemented groups, and they differed significantly ( p < 0.05) from negative control. The mRNA expression levels of Toll-like receptors (TLR 2 and TLR 4) had shown significant ( p < 0.05) changes in experimental groups. The TLR 2 and TLR 4 genes revealed differential expression in all black pepper supplemented groups in comparison to negative control and control group, while TLR 7 did not show any significant change. Thus, supplementation of black pepper powder can be exploited as an immunomodulator to enhance adaptive immune response of broiler chicks after validation on large number of samples.
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- 2023
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45. Operative Time is Associated With Postoperative Complications After Pulmonary Lobectomy.
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de Angelis P, Tan KS, Chudgar NP, Dycoco J, Adusumilli PS, Bains MS, Bott MJ, Downey RJ, Huang J, Isbell JM, Molena D, Park BJ, Rusch VW, Sihag S, Jones DR, and Rocco G
- Subjects
- Humans, Female, Aged, Male, Operative Time, Retrospective Studies, Pneumonectomy adverse effects, Pneumonectomy methods, Postoperative Complications etiology, Lung, Thoracic Surgery, Video-Assisted adverse effects, Thoracic Surgery, Video-Assisted methods, Length of Stay, Lung Neoplasms surgery
- Abstract
Objective: To investigate the association between operative time and postoperative outcomes., Background: The association between operative time and morbidity after pulmonary lobectomy has not been characterized fully., Methods: Patients who underwent pulmonary lobectomy for primary lung cancer at our institution from 2010 to 2018 were reviewed. Exclusion criteria included clinical stage ≥IIb disease, conversion to thoracotomy, and previous ipsilateral lung treatment. Operative time was measured from incision to closure. Relationships between operative time and outcomes were quantified using multivariable mixed-effects models with surgeon-level random effects., Results: In total, 1651 patients were included. The median age was 68 years (interquartile range, 61-74), and 63% of patients were women. Median operative time was 3.2 hours (interquartile range, 2.7-3.8) for all cases, 3.0 hours for open procedures, 3.3 hours for video-assisted thoracoscopies, and 3.3 hours for robotic procedures ( P =0.0002). Overall, 488 patients (30%) experienced a complication; 77 patients (5%) had a major complication (grade ≥3), and 5 patients (0.3%) died within 30 days of discharge. On multivariable analysis, operative time was associated with higher odds of any complication [odds ratio per hour, 1.37; 95% confidence interval (CI), 1.20-1.57; P <0.0001] and major complication (odds ratio per hour, 1.41; 95% CI, 1.21-1.64; P <0.0001). Operative time was also associated with longer hospital length of stay (β, 1.09; 95% CI, 1.04-1.14; P =0.001)., Conclusions: Longer operative time was associated with worse outcomes in patients who underwent lobectomy. Operative time is a potential risk factor to consider in the perioperative phase., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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46. Prognostic value of circumferential radial margin involvement in esophagectomy for esophageal cancer: a case series.
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Boerner T, Carr R, Hsu M, Tan KS, Sigel C, Tang L, Harrington C, Ku GY, Ilson DH, Janjigian YY, Wu AJ, Sihag S, Bains MS, Bott MJ, Isbell JM, Park BJ, Jones DR, and Molena D
- Subjects
- Humans, Prognosis, Margins of Excision, Neoplasm, Residual surgery, Neoplasm Staging, Retrospective Studies, Esophagectomy adverse effects, Esophageal Neoplasms
- Abstract
Background: Residual tumor at the proximal or distal margin after esophagectomy is associated with worse survival outcomes; however, the significance of the circumferential resection margin (CRM) remains controversial. In this study, we sought to evaluate the prognostic significance of the CRM in patients with esophageal cancer undergoing resection., Materials and Methods: We identified patients who underwent esophagectomy for pathologic T3 esophageal cancer from 2000 to 2019. Patients were divided into three groups: CRM- (residual tumor >1 mm from the CRM), CRM-close (residual tumor >0 to 1 mm from the CRM), and CRM+ (residual tumor at the surgical CRM). CRM was also categorized and analyzed per the Royal College of Pathologists (RCP) and College of American Pathologists (CAP) classifications., Results: Of the 519 patients included, 351 (68%) had CRM-, 132 (25%) had CRM-close, and 36 (7%) had CRM+. CRM+ was associated with shorter disease-free survival [DFS; CRM+ vs. CRM-: hazard ratio (HR), 1.53 [95% CI, 1.03-2.28]; P =0.034] and overall survival (OS; CRM+ vs. CRM-: HR, 1.97 [95% CI, 1.32-2.95]; P <0.001). Survival was not significantly different between CRM-close and CRM-. After adjustment for potential confounders, CAP+ was associated with poor oncologic outcomes (CAP+ vs. CAP-: DFS: HR, 1.47 [95% CI, 1.00-2.17]; P =0.050; OS: HR, 1.93 [95% CI, 1.30-2.86]; P =0.001); RCP+ was not (RCP+ vs. RCP-: DFS: HR, 1.21 [95% CI, 0.97-1.52]; P =0.10; OS: HR, 1.21 [95% CI, 0.96-1.54]; P =0.11)., Conclusion: CRM status has critical prognostic significance for patients undergoing esophagectomy: CRM+ was associated with worse outcomes, and outcomes between CRM-close and CRM- were similar., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2023
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47. Investigating the impact of linseed supplementation, rich in omega-3 fatty acids, on the expression of immune genes in Beetal Goats.
- Author
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Shunthwal J, Sihag ZS, Magotra A, Meetu, and Sihag S
- Abstract
The present study investigated the effect of linseed supplementation on serum profiling and differential expression levels of IL-2 and TLR 2 genes involved in the immune system of lactating goats. The study was conducted on 15 lactating Beetal goats for 3 months, which were divided into three groups. Treatment group T
1 was kept as a control group with no linseed supplementation, whereas treatment group T2 received ground linseed at the rate 10% of concentrate per day per animal, and treatment group T3 received 20% ground linseed. The concentration of triglycerides, cholesterol and LDL concentration were found to be significantly lower (P < 0.05) in both 10% and 20% linseed supplemented group than the control group. Whereas, HDL concentration in T2 and T3 group were found to be significantly higher than the control group. The differential expression of targeted genes comparatively revealed highest relative expression in the group that received 20% linseed supplementation. Although the study did not show a significant effect of linseed supplementation on the expression of TLR-2 and IL-2 genes in goats, it highlights the potential benefits of omega-3 PUFA supplementation on immune system modulation in animals.- Published
- 2023
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48. Identification and functional characterization of a novel aldo-keto reductase from Aloe vera.
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Jangra A, Chaturvedi S, Sihag S, Sharma G, Tiwari S, and Chhokar V
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- Aldo-Keto Reductases genetics, Alcohol Oxidoreductases genetics, Alcohol Oxidoreductases metabolism, Phylogeny, NADP genetics, Plants metabolism, Aldehyde Reductase genetics, Aldehyde Reductase chemistry, Aldehyde Reductase metabolism, Aloe genetics, Aloe metabolism
- Abstract
Main Conclusion: The present investigation profoundly asserted the catalytic potential of plant-based aldo-ketoreductase, postulating its role in polyketide biosynthesis and providing new insights for tailored biosynthesis of vital plant polyketides for therapeutics. Plants hold great potential as a future source of innovative biocatalysts, expanding the possibilities within chemical reactions and generating a variety of benefits. The aldo-keto reductase (AKR) superfamily includes a huge collection of NAD(P)H-dependent oxidoreductases that carry out a variety of redox reactions essential for biosynthesis, detoxification, and intermediary metabolism. The present study involved the isolation, cloning, and purification of a novel aldo-ketoreductase (AvAKR) from the leaves of Aloe vera (Aloe barbadensis Miller) by heterologous gene expression in Escherichia coli based on the unigene sequences of putative ketoreductase and cDNA library screening by oligonucleotide hybridization. The in-silico structural analysis, phylogenetic relationship, and molecular modeling were outranged to approach the novelty of the sequence. Additionally, agroinfiltration of the candidate gene tagged with a green fluorescent protein (GFP) was employed for transient expression in the Nicotiana benthamiana to evaluate the sub-cellular localization of the candidate gene. The AvAKR preferred cytoplasmic localization and shared similarities with the known plant AKRs, keeping the majority of the conserved active-site residues in the AKR superfamily enzymes. The enzyme facilitated the NADPH-dependent reduction of various carbonyl substrates, including benzaldehyde and sugars, proclaiming a broad spectrum range. Our study successfully isolated and characterized a novel aldo-ketoreductase (AvAKR) from Aloe vera, highlighting its versatile NADPH-dependent carbonyl reduction proficiency therewith showcasing its potential as a versatile biocatalyst in diverse redox reactions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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49. Explainable Brain Age Prediction using coVariance Neural Networks.
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Sihag S, Mateos G, McMillan C, and Ribeiro A
- Abstract
In computational neuroscience, there has been an increased interest in developing machine learning algorithms that leverage brain imaging data to provide estimates of "brain age" for an individual. Importantly, the discordance between brain age and chronological age (referred to as "brain age gap") can capture accelerated aging due to adverse health conditions and therefore, can reflect increased vulnerability towards neurological disease or cognitive impairments. However, widespread adoption of brain age for clinical decision support has been hindered due to lack of transparency and methodological justifications in most existing brain age prediction algorithms. In this paper, we leverage coVariance neural networks (VNN) to propose an explanation-driven and anatomically interpretable framework for brain age prediction using cortical thickness features. Specifically, our brain age prediction framework extends beyond the coarse metric of brain age gap in Alzheimer's disease (AD) and we make two important observations: (i) VNNs can assign anatomical interpretability to elevated brain age gap in AD by identifying contributing brain regions, (ii) the interpretability offered by VNNs is contingent on their ability to exploit specific eigenvectors of the anatomical covariance matrix. Together, these observations facilitate an explainable and anatomically interpretable perspective to the task of brain age prediction.
- Published
- 2023
50. Unique Genomic Alterations and Microbial Profiles Identified in Patients With Gastric Cancer of African, European, and Asian Ancestry: A Novel Path for Precision Oncology.
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Abate M, Walch H, Arora K, Vanderbilt CM, Fei T, Drebin H, Shimada S, Maio A, Kemel Y, Stadler ZK, Schmeltz J, Sihag S, Ku GY, Gu P, Tang L, Vardhana S, Berger MF, Brennan MF, Schultz ND, and Strong VE
- Subjects
- Humans, Precision Medicine, Phosphatidylinositol 3-Kinases genetics, Proto-Oncogene Proteins p21(ras) genetics, Genomics, Mutation, Stomach Neoplasms genetics, Stomach Neoplasms pathology
- Abstract
Objective: Here, we characterize differences in the genetic and microbial profiles of GC in patients of African (AFR), European, and Asian ancestry., Background: Gastric cancer (GC) is a heterogeneous disease with clinicopathologic variations due to a complex interplay of environmental and biological factors, which may affect disparities in oncologic outcomes.., Methods: We identified 1042 patients with GC with next-generation sequencing data from an institutional Integrated Mutation Profiling of Actionable Cancer Targets assay and the Cancer Genomic Atlas group. Genetic ancestry was inferred from markers captured by the Integrated Mutation Profiling of Actionable Cancer Targets and the Cancer Genomic Atlas whole exome sequencing panels. Tumor microbial profiles were inferred from sequencing data using a validated microbiome bioinformatics pipeline. Genomic alterations and microbial profiles were compared among patients with GC of different ancestries., Results: We assessed 8023 genomic alterations. The most frequently altered genes were TP53 , ARID1A , KRAS , ERBB2 , and CDH1 . Patients of AFR ancestry had a significantly higher rate of CCNE1 alterations and a lower rate of KRAS alterations ( P < 0.05), and patients of East Asian ancestry had a significantly lower rate of PI3K pathway alterations ( P < 0.05) compared with other ancestries. Microbial diversity and enrichment did not differ significantly across ancestry groups ( P > 0.05)., Conclusions: Distinct patterns of genomic alterations and variations in microbial profiles were identified in patients with GC of AFR, European, and Asian ancestry. Our findings of variation in the prevalence of clinically actionable tumor alterations among ancestry groups suggest that precision medicine can mitigate oncologic disparities., Competing Interests: C.M.V. is an uncompensated consultant and shareholder in Paige AI. S.V. is an advisor for Immunai and has been a consultant for Koch Disruptive Technologies. M.F. Berger has provided services to AstraZeneca, Eli Lilly and Company, and PetDx, Inc. M.F. B. has ownership in Kazia Therapeutics, Ltd. and a fiduciary role in the de Beaumont Foundation. N.D.S. has provided services to Cambridge Innovation Institute, Harvard T.H. Chan School of Public Health, Innovation in Cancer Informatics, and Seoul National University. V.E.S. has received speaking honoraria from Merck Pharmaceuticals. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2023
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