299 results on '"Chowdhuri S"'
Search Results
2. Suppressed immune microenvironment and repertoire in brain metastases from patients with resected non-small-cell lung cancer
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Kudo, Y., Haymaker, C., Zhang, J., Reuben, A., Duose, D.Y., Fujimoto, J., Roy-Chowdhuri, S., Solis Soto, L.M., Dejima, H., Parra, E.R., Mino, B., Abraham, R., Ikeda, N., Vaporcyan, A., Gibbons, D., Lang, F.F., Luthra, R., Lee, J.J., Moran, C., Huse, J.T., Kadara, H., and Wistuba, I.I.
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- 2019
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3. Liquid biopsy assay for lung carcinoma using centrifuged supernatants from fine-needle aspiration specimens
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Hannigan, B., Ye, W., Mehrotra, M., Lam, V., Bolivar, A., Zalles, S., Barkoh, B.A., Duose, D., Hu, P.C., Broaddus, R., Stewart, J., Heymach, J., Medeiros, L.J., Wistuba, I., Luthra, R., and Roy-Chowdhuri, S.
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- 2019
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4. P2.11A.25 Clinicogenomic Profile of Different Resistance Patterns to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
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Hong, L., Aminu, M., Young, C., Rinsurongkawong, W., Li, H., Qin, K., Elamin, Y., Sepesi, B., Gibbons, D., Vaporciyan, A., Lee, J.J., Roy-Chowdhuri, S., Routbort, M., Le, X., Heymach, J., Wu, J., Zhang, J., and Vokes, N.
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- 2024
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5. Comparing seismic susceptibility models of the Himalayan terrain
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Som, S. K., Dasarwar, P., Mohan, Murali, Hindayar, J. N., Kumar, N. Thrideep, Chowdhuri, S. N., Darmwal, G. S., and Singh, Harbans
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- 2016
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6. Site response studies in Agartala Urban agglomeration
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Chowdhuri, S. N., Singh, O. P., and Majumdar, R. K.
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- 2011
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7. Frequent homozygous deletion of the LKB1/STK11 gene in non-small cell lung cancer
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Gill, R K, Yang, S-H, Meerzaman, D, Mechanic, L E, Bowman, E D, Jeon, H-S, Roy Chowdhuri, S, Shakoori, A, Dracheva, T, Hong, K-M, Fukuoka, J, Zhang, J-H, Harris, C C, and Jen, J
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- 2011
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8. Hypercapnia-induced vasodilation in the cerebral circulation is reduced in older adults with sleep-disordered breathing .
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Rastogi, R., Morgan, B. J., Badr, M. S., and Chowdhuri, S.
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OLDER people ,SLEEP apnea syndromes ,CEREBRAL circulation ,VASODILATION ,DOPPLER ultrasonography - Abstract
The prevalence of sleep-disordered breathing (SDB) is higher in older adults compared with younger individuals. The increased propensity for ventilatory control instability in older adults may contribute to the increased prevalence of central apneas. Reductions in the cerebral vascular response to CO
2 may exacerbate ventilatory overshoots and undershoots during sleep. Thus, we hypothesized that hypercapnia-induced cerebral vasodilation (HCVD) will be reduced in older compared with younger adults. In 11 older and 10 younger adults with SDB, blood flow velocity in the middle cerebral artery (MCAV) was measured using Doppler transcranial ultrasonography during multiple steady-state hyperoxic hypercapnic breathing trials while awake, interspersed with room air breathing. Changes in ventilation, MCAV, and mean arterial pressure (MAP) via finger plethysmography during the trials were compared with baseline eupneic values. For each hyperoxic hypercapnic trial, the change (Δ) in MCAV for a corresponding change in end-tidal CO2 and the HCVD or the change in cerebral vascular conductance (MCAV divided by MAP) for a corresponding change in end-tidal CO2 was determined. The hypercapnic ventilatory response was similar between the age groups, as was ΔMCAV/ΔPETCO . However, compared with young, older adults had a significantly smaller HCVD (1.3 ± 0.7 vs. 2.1 ± 0.6 units/mmHg, P = 0.004). Multivariable analyses demonstrated that age and nadir oxygen saturation during nocturnal polysomnography were significant predictors of HCVD. Thus, our data indicate that older age and SDB-related hypoxia are associated with diminished HCVD. We hypothesize that this impairment in vascular function may contribute to breathing instability during sleep in these individuals. [ABSTRACT FROM AUTHOR]2 - Published
- 2022
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9. Amelioration of sleep-disordered breathing with supplemental oxygen in older adults.
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Rastogi, Ruchi, Badr, M. S., Ahmed, A., and Chowdhuri, S.
- Abstract
Elderly adults demonstrate increased propensity for breathing instability during sleep compared with younger adults, and this may contribute to increased prevalence of sleep-disordered breathing (SDB) in this population. Hence, in older adults with SDB, we examined whether addition of supplemental oxygen (O
2 ) will stabilize breathing during sleep and alleviate SDB. We hypothesized that exposure to supplemental O2 during non-rapid eye movement (NREM) sleep will stabilize breathing and will alleviate SDB by reducing ventilatory chemoresponsiveness and by widening the carbon dioxide (CO2 ) reserve. We studied 10 older adults with mild-to-moderate SDB who were randomized to undergo noninvasive bilevel mechanical ventilation with exposure to room air or supplemental O2 (Oxy) to determine the CO2 reserve, apneic threshold (AT), and controller and plant gains. Supplemental O2 was introduced during sleep to achieve a steady-state O2 saturation ≥95% and fraction of inspired O2 at 40%-50%. The CO2 reserve increased significantly during Oxy versus room air (-4.2 ± 0.5 mmHg vs. -3.2 ± 0.5 mmHg, P = 0.03). Compared with room air, Oxy was associated with a significant decline in the controller gain (1.9 ± 0.4 L/min/mmHg vs. 2.5 ± 0.5 L/min/mmHg, P = 0.04), with reductions in the apnea-hypopnea index (11.8 ± 2.0/h vs. 24.4 ± 5.6/h, P = 0.006) and central apnea-hypopnea index (1.7 ± 0.6/h vs. 6.9 ± 3.9/h, P = 0.03). The AT and plant gain were unchanged. Thus, a reduced slope of CO2 response resulted in an increased CO2 reserve. In conclusion, supplemental O2 reduced SDB in older adults during NREM sleep via reduction in chemoresponsiveness and central respiratory events. NEW & NOTEWORTHY This study demonstrates for the first time in elderly adults without heart disease that intervention with supplemental oxygen in the clinical range will ameliorate central apneas and hypopneas by decreasing the propensity to central apnea through decreased chemoreflex sensitivity, even in the absence of a reduction in the plant gain. Thus, the study provides physiological evidence for use of supplemental oxygen as therapy for mild-to-moderate SDB in this vulnerable population. [ABSTRACT FROM AUTHOR]- Published
- 2020
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10. Comparative study of sequential combined spinal epidural anaesthesia versus spinal anaesthesia in high risk geriatric patients for major orthopaedic surgery
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Bhattacharya, Dipasri, Tewari, I., and Chowdhuri, S.
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Aged patients -- Care and treatment ,Peridural anesthesia -- Patient outcomes ,Peridural anesthesia -- Physiological aspects ,Orthopedic surgery -- Methods ,Orthopedic surgery -- Patient outcomes - Abstract
Byline: Dipasri. Bhattacharya, I. Tewari, S. Chowdhuri Sequential combined spinal epidural anaesthesia (Sequential CSEA) is probably the greatest advance in central neuraxial block in this decade for high risk geriatric [...]
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- 2007
11. 694P - Diagnostic value of digital multiplexed detection of single nucleotide variants in pancreatic cancer specimens collected by endoscopic ultrasound fine-needle aspiration
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Cazacu, I.M., Semaan, A., Stephens, B.M., Swartzlander, D.B., Guerrero, P.A., Singh, B.S., Lungulescu, C.V., Raileanu, S., Danciulescu, M.M., Roy-Chowdhuri, S., Maitra, A., Saftoiu, A., and Bhutani, M.S.
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- 2019
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12. P1.04-07 Immune Suppressive Microenvironment and Highly Clonal Concordance of TCR Repertoire in Brain Metastases from Non-Small Cell Lung Cancer
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Kudo, Y., Haymaker, C., Zhang, J., Reuben, A., Duose, D., Fujimoto, J., Roy-Chowdhuri, S., Solis, L., Dejima, H., Cuentas, E. Parra, Mino, B., Ikeda, N., Luthra, R., Gibbons, D., Lang, F., Lee, J.J., Huse, J., Kadara, H., and Wistuba, I.
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- 2019
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13. Synchronization aspects of single phase SPWM inverters for microgrid mode of operation.
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Roy, Pritha, Bera, J. N., Chowdhuri, S., and Sarkar, G.
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- 2016
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14. A comparative study between different modulations techniques used in field oriented control induction motor drive.
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Banerjee, T., Bera, J. N., Chowdhuri, S., and Sarkar, G.
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- 2016
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15. Performance analysis of a three-phase Active Front-End PWM Rectifier without current loop PI controller.
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Mitra, A., Bhowmik, P. S., and Chowdhuri, S.
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- 2016
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16. Performance Studies of Fuzzy Logic Based PI-like Controller Designed for Speed Control of Switched Reluctance Motor.
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Chowdhuri, S., Biswas, S.K., and Mukherjee, A.
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- 2006
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17. Power Factor Management Of Industrial Power Distribution Systems.
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Cboudhury, T., Chowdbury, S.P., Mukhopadhyay, R.A., and Chowdhuri, S.
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- 1991
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18. Practice parameters for the surgical modifications of the upper airway for obstructive sleep apnea in adults.
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Aurora RN, Casey KR, Kristo D, Auerbach S, Bista SR, Chowdhuri S, Karippot A, Lamm C, Ramar K, Zak R, and Morgenthaler TI
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- 2010
19. Genetic Diversity Evaluation in Exotic Mulberry Germplasm.
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Ghosh, M. K., Sahu, P. K., Chowdhuri, S. Roy, Sil, S. K., Chakrabarti, S., and Bajpai, A. K.
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PLANT genetics ,PLANT diversity ,MULBERRY ,MORACEAE ,PLANT germplasm ,PLANT shoots ,PLANT physiology - Abstract
Mulberry (Morus sp.), belonging to moraceae family, is perennial in nature but maintained mostly as bushes for commercial purposes; its foliage serves as feed for silkworm. The present work was undertaken to study the variability among 29 exotic genotypes for yield and yield related traits, viz., total shoot length/plant/crop, fresh weight (g) of 100 leaves/plant/crop, fresh weight (g)/leaf and specific leaf weight (g) per square meter. Three-year data with five crops per year were used for the present study. Parameters like heritability (broad-sense), genetic coefficient of variation, phenotypic coefficient of variation, genotypic correlations, phenotypic correlations and environmental correlations suggested that the traits under study were under genetic control and could be used to improve mulberry. Mahalanobis divergence analysis, followed by Tocher method of clustering, provided three genotypic clusters. The analysis also revealed that mulberry varieties of different geographic origin might not be different genotypically. [ABSTRACT FROM AUTHOR]
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- 2009
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20. Electric Field Dependence on Charge Collection of CdZnTe X-Ray Detectors.
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Giakos, G. C., Pillai, B., Vedantham, S., Chowdhuri, S., Odogba, J., Dasgupta, A., Vega-Lozada, V., Guntupalli, R., Suryanarayanan, S., Endorf, R. J., Passalaqua, A., and Kollipara, S.
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- 1997
21. Optimization of Cd1-xZnxTe Detectors for Digital Radiography.
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Giakos, G. C., Pillai, B., Vedantham, S., Chowdhuri, S., Dasgupta, A., Richardson, R. B., Ghotra, P., Endorf, R. J., Passalaqua, A., and Davros, W. J.
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- 1997
22. DOZ047.70: Prevalence of abnormal triple endoscopy findings for tracheoesophageal fistula patients in a multidisciplinary aerodigestive clinic.
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Chowdhuri, S, Osterbauer, B, Bansal, M, Hochstim, C, and Bhardwaj, V
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FISTULA , *ESOPHAGEAL fistula , *CLINICS ,ESOPHAGEAL atresia - Published
- 2019
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23. Performance of new bivoltine hybrid in Keonjhar of Odisha.
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Purohit, K. M., Mohapatra, D. P. Das, Bindroo, B. B., Saha, A. K., and Chowdhuri, S. Roy
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SILKWORMS ,SERICULTURE ,FIELD research ,SILK ,SILK industry - Abstract
The article focuses on a field trial of bivoltine hybrid D6(P)N x SK4C conducted in Keonnijhar of Odisha, India between 2010-2012. Topics discussed include information on D6(P)N x SK4C, a high-yielding silkworm hybrid evolved by the Central Sericultural Research & Training Institute, the yield potential of D6(P)N x SK4C, and its important economic traits that make it superior to that of NB18 x SK4C.
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- 2013
24. Adrenal tumor presenting as precocious puberty.
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Chowdhuri, Swagata, Dharmalingam, Mala, Kumar, K., Chowdhuri, S, Dharmalingam, M, and Kumar, K M
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We present a case report of a two and a half-year-old boy who presented with precocious puberty. A clinical diagnosis of congenital adrenal hyperplasia was made. Patient was investigated and found to have an adrenocortical tumor. The tumor was about 7 cms in diameter. The tumor was secreting androgens, 17OHP and cortisol. This is an unusual array of hormones to be secreted by an adrenal tumor. [ABSTRACT FROM AUTHOR]
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- 2001
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25. An evolutionary approach to optimize speed controller of DC machines.
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Chowdhuri, S. and Mukherjee, A.
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- 2000
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26. INDO-AUSTRALIAN WOOL PARTNERSHIP HAILED AS "SUCCESS STORY.".
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Chowdhuri, S. K.
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Presents highlights of the Wool 2004 fashion show organized by the India-South East Asia regional offices of Woolmark Co. and the Australian High Commission on October 9, 2003. Clothes exhibited by Oswal Woollen Mills, Reid & Tailor and Ahujasons; Models featured in the show; Winner of the Godrej Ezee Banao Sweater Bano Star contest.
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- 2003
27. Reference standards for gene fusion molecular assays on cytological samples: an international validation study
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Elena Vigliar, Eugenio Gautiero, Annalisa Altimari, Reinhard Büttner, Birgit Weynand, Carlos E. de Andrea, Philippe Vielh, Francesco Pepe, Claudio Bellevicine, Paul Hofman, Miguel Angel Molina Vila, Rossella Bruno, Fernando Schmitt, Véronique Hofman, Giancarlo Troncone, Francesc Tresserra, Luis Cirnes, Rafael Rosell, Ruth Román, Sabine Merkelbach-Bruse, David Gentien, Fabio Pagni, Dario de Biase, Catherine I. Dumur, Giulia Anna Carmen Vita, Kajsa Ericson Lindquist, Gabriella Fontanini, Sinchita Roy-Chowdhuri, Janna Siemanowski, Maria D. Lozano, Clara Mayo-de-las-Casas, Pasquale Pisapia, Sara Vander Borght, Antonino Iaccarino, Hans Brunnström, Umberto Malapelle, Giovanni Tallini, Malapelle, U, Pepe, F, Pisapia, P, Altimari, A, Bellevicine, C, Brunnström, H, Bruno, R, Büttner, R, Cirnes, L, De Andrea, C, de Biase, D, Dumur, C, Ericson Lindquist, K, Fontanini, G, Gautiero, E, Gentien, D, Hofman, P, Hofman, V, Iaccarino, A, Lozano, M, Mayo-de-Las-Casas, C, Merkelbach-Bruse, S, Pagni, F, Roman, R, Schmitt, F, Siemanowski, J, Roy-Chowdhuri, S, Tallini, G, Tresserra, F, Vander Borght, S, Vielh, P, Vigliar, E, Vita, G, Weynand, B, Rosell, R, Molina Vila, M, Troncone, G, Malapelle, Umberto, Pepe, Francesco, Pisapia, Pasquale, Altimari, Annalisa, Bellevicine, Claudio, Brunnström, Han, Bruno, Rossella, Büttner, Reinhard, Cirnes, Lui, De Andrea, Carlos E, de Biase, Dario, Dumur, Catherine I, Ericson Lindquist, Kajsa, Fontanini, Gabriella, Gautiero, Eugenio, Gentien, David, Hofman, Paul, Hofman, Veronique, Iaccarino, Antonino, Lozano, Maria Dolore, Mayo-de-Las-Casas, Clara, Merkelbach-Bruse, Sabine, Pagni, Fabio, Roman, Ruth, Schmitt, Fernando C, Siemanowski, Janna, Roy-Chowdhuri, Sinchita, Tallini, Giovanni, Tresserra, Francesc, Vander Borght, Sara, Vielh, Philippe, Vigliar, Elena, Vita, Giulia Anna Carmen, Weynand, Birgit, Rosell, Rafael, Molina Vila, Miguel Angel, and Troncone, Giancarlo
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Validation study ,Staining and Labeling ,Oncogene Proteins, Fusion ,May-Grunwald giemsa ,cytological techniques ,molecular ,molecular biology ,pathology ,Papanicolaou stain ,General Medicine ,Reference Standards ,Amplicon ,Biology ,Molecular biology ,Pathology and Forensic Medicine ,Staining ,Fusion gene ,Cytological Techniques ,Neoplasms ,Humans ,cytological technique ,Reference standards - Abstract
AimsGene fusions assays are key for personalised treatments of advanced human cancers. Their implementation on cytological material requires a preliminary validation that may make use of cell line slides mimicking cytological samples. In this international multi-institutional study, gene fusion reference standards were developed and validated.MethodsCell lines harbouringEML4(13)–ALK(20) andSLC34A2(4)–ROS1(32) gene fusions were adopted to prepare reference standards. Eight laboratories (five adopting amplicon-based and three hybridisation-based platforms) received, at different dilution points two sets of slides (slide A 50.0%, slide B 25.0%, slide C 12.5% and slide D wild type) stained by Papanicolaou (Pap) and May Grunwald Giemsa (MGG). Analysis was carried out on a total of 64 slides.ResultsFour (50.0%) out of eight laboratories reported results on all slides and dilution points. While 12 (37.5%) out of 32 MGG slides were inadequate, 27 (84.4%) out of 32 Pap slides produced libraries adequate for variant calling. The laboratories using hybridisation-based platforms showed the highest rate of inadequate results (13/24 slides, 54.2%). Conversely, only 10.0% (4/40 slides) of inadequate results were reported by laboratories adopting amplicon-based platforms.ConclusionsReference standards in cytological format yield better results when Pap staining and processed by amplicon-based assays. Further investigation is required to optimise these standards for MGG stained cells and for hybridisation-based approaches.
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- 2023
28. Precipitating activity of lectins against human and animal sera
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Chowdhuri, S., Bhattacharya, S.K., and Chatterjee, P.C.
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- 1975
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29. Consistency and reproducibility of next-generation sequencing and other multigene mutational assays: A worldwide ring trial study on quantitative cytological molecular reference specimens
- Author
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Malapelle, Umberto, Mayo de Las Casas, Clara, Molina Vila, Miguel A, Rosell, Rafael, Savic, Spasenija, Bihl, Michel, Bubendorf, Lukas, Salto Tellez, Manuel, de Biase, Dario, Tallini, Giovanni, Hwang, David H, Sholl, Lynette M, Luthra, Rajyalakshmi, Weynand, Birgit, Vander Borght, Sara, Missiaglia, Edoardo, Bongiovanni, Massimo, Stieber, Daniel, Vielh, Philippe, Schmitt, Fernando, Rappa, Alessandra, Barberis, Massimo, Pepe, Francesco, Pisapia, Pasquale, Serra, Nicola, Vigliar, Elena, Bellevicine, Claudio, Fassan, Matteo, Rugge, Massimo, de Andrea, Carlos E, Lozano, Maria D, Basolo, Fulvio, Fontanini, Gabriella, Nikiforov, Yuri E, Kamel Reid, Suzanne, da Cunha Santos, Gilda, Nikiforova, Marina N, Roy Chowdhuri, Sinchita, Troncone, Giancarlo, Malapelle, Umberto, Mayo de Las Casas, Clara, Molina Vila, Miguel A., Rosell, Rafael, Savic, Spasenija, Bihl, Michel, Bubendorf, Luka, Salto Tellez, Manuel, DE BIASE, Dario, Tallini, Giovanni, Hwang, David H., Sholl, Lynette M., Luthra, Rajyalakshmi, Weynand, Birgit, Vander Borght, Sara, Missiaglia, Edoardo, Bongiovanni, Massimo, Stieber, Daniel, Vielh, Philippe, Schmitt, Fernando, Rappa, Alessandra, Barberis, Massimo, Pepe, Francesco, Pisapia, Pasquale, Serra, Nicola, Vigliar, Elena, Bellevicine, Claudio, Fassan, Matteo, Rugge, Massimo, de Andrea, Carlos E., Lozano, Maria D., Basolo, Fulvio, Fontanini, Gabriella, Nikiforov, Yuri E., Kamel Reid, Suzanne, da Cunha Santos, Gilda, Nikiforova, Marina N., Roy Chowdhuri, Sinchita, Troncone, Giancarlo, Malapelle, U, Mayo-de-Las-Casas, C, Molina-Vila, Ma, Rosell, R, Savic, S, Bihl, M, Bubendorf, L, Salto-Tellez, M, de Biase, D, Tallini, G, Hwang, Dh, Sholl, Lm, Luthra, R, Weynand, B, Vander Borght, S, Missiaglia, E, Bongiovanni, M, Stieber, D, Vielh, P, Schmitt, F, Rappa, A, Barberis, M, Pepe, F, Pisapia, P, Serra, N, Vigliar, E, Bellevicine, C, Fassan, M, Rugge, M, de Andrea, Ce, Lozano, Md, Basolo, F, Fontanini, G, Nikiforov, Ye, Kamel-Reid, S, da Cunha Santos, G, Nikiforova, Mn, Roy-Chowdhuri, S, and Troncone, G
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Proto-Oncogene Proteins B-raf ,Cancer Research ,cytological molecular reference ,cytology ,lung cancer ,molecular cytopathology ,multigene mutational assay ,next-generation sequencing ,Class I Phosphatidylinositol 3-Kinases ,DNA Mutational Analysis ,Real-Time Polymerase Chain Reaction ,Proto-Oncogene Mas ,Cell Line ,GTP Phosphohydrolases ,Proto-Oncogene Proteins p21(ras) ,Phosphatidylinositol 3-Kinases ,Gene Frequency ,Cell Line, Tumor ,Humans ,High-Throughput Nucleotide Sequencing ,Membrane Proteins ,Reproducibility of Results ,Sequence Analysis, DNA ,ErbB Receptors ,Oncology ,Colonic Neoplasms - Abstract
Molecular testing of cytological lung cancer specimens includes, beyond epidermal growth factor receptor (EGFR), emerging predictive/prognostic genomic biomarkers such as Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral [v-ras] oncogene homolog (NRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA). Next-generation sequencing (NGS) and other multigene mutational assays are suitable for cytological specimens, including smears. However, the current literature reflects single-institution studies rather than multicenter experiences.Quantitative cytological molecular reference slides were produced with cell lines designed to harbor concurrent mutations in the EGFR, KRAS, NRAS, BRAF, and PIK3CA genes at various allelic ratios, including low allele frequencies (AFs; 1%). This interlaboratory ring trial study included 14 institutions across the world that performed multigene mutational assays, from tissue extraction to data analysis, on these reference slides, with each laboratory using its own mutation analysis platform and methodology.All laboratories using NGS (n = 11) successfully detected the study's set of mutations with minimal variations in the means and standard errors of variant fractions at dilution points of 10% (P = .171) and 5% (P = .063) despite the use of different sequencing platforms (Illumina, Ion Torrent/Proton, and Roche). However, when mutations at a low AF of 1% were analyzed, the concordance of the NGS results was low, and this reflected the use of different thresholds for variant calling among the institutions. In contrast, laboratories using matrix-assisted laser desorption/ionization-time of flight (n = 2) showed lower concordance in terms of mutation detection and mutant AF quantification.Quantitative molecular reference slides are a useful tool for monitoring the performance of different multigene mutational assays, and this could lead to better standardization of molecular cytopathology procedures. Cancer Cytopathol 2017;125:615-26. © 2017 American Cancer Society.
- Published
- 2017
30. Deciphering inhibitory activity of marine algae Ecklonia cava phlorotannins against SARS CoV-2 main protease: A coupled in-silico docking and molecular dynamics simulation study.
- Author
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Chakraborty A, Ghosh R, Barik S, Mohapatra SS, Biswas A, and Chowdhuri S
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- Humans, COVID-19 virology, Antiviral Agents pharmacology, Antiviral Agents chemistry, Dioxins, Molecular Dynamics Simulation, Molecular Docking Simulation, Phaeophyceae chemistry, SARS-CoV-2 drug effects, SARS-CoV-2 enzymology, Coronavirus 3C Proteases antagonists & inhibitors, Coronavirus 3C Proteases chemistry, Coronavirus 3C Proteases metabolism, Tannins pharmacology, Tannins chemistry
- Abstract
The onset of COVID-19 due to the SARS CoV-2 virus has spurred an urgent need for potent therapeutics and vaccines to combat this global pandemic. The main protease (Mpro) of the virus, crucial in its replication, has become a focal point in developing anti-COVID-19 drugs. The cysteine protease Mpro in SARS CoV-2 bears a significant resemblance to the same protease found in SARS CoV-1. Previous research highlighted phlorotannins derived from Ecklonia cava, an edible marine algae, as inhibitors of SARS CoV-1 Mpro activity. However, it remains unclear whether these marine-derived phlorotannins also exert a similar inhibitory effect on SARS CoV-2 Mpro. To unravel this, our study utilized diverse in-silico methodologies. We explored the pharmacological potential of various phlorotannins (phloroglucinol, triphloretol-A, eckol, 2-phloroeckol, 7-phloroeckol, fucodiphloroethol G, dieckol, and phlorofucofuroeckol-A) and assessed their binding efficacies alongside established Mpro inhibitors (N3 and lopinavir) through molecular docking studies. Among these compounds, five phlorotannins (eckol, 2-phloroeckol, 7-phloroeckol, dieckol, and phlorofucofuroeckol-A) exhibited potent binding affinities comparable to or surpassing N3 and lopinavir, interacting especially with the catalytic residues His41 and Cys145 of Mpro. Moreover, molecular dynamics simulations revealed that these five Mpro-phlorotannin complexes displayed enhanced stability and maintained comparable or slightly reduced compactness. They exhibited reduced conformational changes and increased expansion relative to the Mpro-N3 and/or Mpro-lopinavir complex. Our MM-GBSA analysis further supported these findings. Overall, our investigation highlights the potential of these five phlorotannins in inhibiting the proteolytic function of SARS CoV-2 Mpro, offering promise for anti-COVID-19 drug development., Competing Interests: Declaration of competing interest The authors 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 Elsevier B.V. All rights reserved.)
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- 2024
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31. The American Cancer Society National Lung Cancer Roundtable strategic plan: Methods for improving turnaround time of comprehensive biomarker testing in non-small cell lung cancer.
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Roy-Chowdhuri S, Mani H, Fox AH, Tsao A, Sholl LM, Farjah F, Johnson BE, Osarogiagbon RU, Rivera MP, Silvestri GA, Smith RA, and Wistuba II
- Abstract
Comprehensive biomarker testing for patients with non-small cell lung cancer is critical for selecting appropriate targeted therapy or immunotherapy. Ensuring timely ordering, processing, and reporting is key to optimizing patient outcomes. However, various factors can prevent or delay patients from being offered the option of treatment selection based on comprehensive biomarker testing. These factors include problems with access to testing, tissue adequacy, turnaround time, and health insurance coverage and billing practices. Turnaround time depends on several logistical and tissue handling factors, which involve institutional policies, processes, resources, testing methodology, and testing algorithms that vary across different practices. In this article, the authors identify key factors that prolong biomarker testing turnaround time, propose strategies to reduce it, and present a process map to aid physicians and key organizational stakeholders in improving testing efficiency., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)
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- 2024
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32. Repurposing of antimycobacterium drugs for COVID-19 treatment by targeting SARS CoV-2 main protease: An in-silico perspective.
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Chakraborty A, Ghosh R, Soumya Mohapatra S, Barik S, Biswas A, and Chowdhuri S
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- Humans, Antiviral Agents pharmacology, Antiviral Agents chemistry, Anti-Bacterial Agents pharmacology, Minocycline pharmacology, Rifampin pharmacology, COVID-19 virology, Computer Simulation, Drug Repositioning, Molecular Docking Simulation, COVID-19 Drug Treatment, SARS-CoV-2 drug effects, SARS-CoV-2 enzymology, Coronavirus 3C Proteases antagonists & inhibitors, Coronavirus 3C Proteases metabolism, Coronavirus 3C Proteases chemistry, Molecular Dynamics Simulation
- Abstract
The global mortality rate has been significantly impacted by the COVID-19 pandemic, caused by the SARS CoV-2 virus. Although the pursuit for a potent antiviral is still in progress, experimental therapies based on repurposing of existing drugs is being attempted. One important therapeutic target for COVID-19 is the main protease (Mpro) that cleaves the viral polyprotein in its replication process. Recently minocycline, an antimycobacterium drug, has been successfully implemented for the treatment of COVID-19 patients. But it's mode of action is still far from clear. Furthermore, it remains unresolved whether alternative antimycobacterium drugs can effectively regulate SARS CoV-2 by inhibiting the enzymatic activity of Mpro. To comprehend these facets, eight well-established antimycobacterium drugs were put through molecular docking experiments. Four of the antimycobacterium drugs (minocycline, rifampicin, clofazimine and ofloxacin) were selected by comparing their binding affinities towards Mpro. All of the four drugs interacted with both the catalytic residues of Mpro (His41 and Cys145). Additionally, molecular dynamics experiments demonstrated that the Mpro-minocyline complex has enhanced stability, experiences reduced conformational fluctuations and greater compactness than other three Mpro-antimycobacterium and Mpro-N3/lopinavir complexes. This research furnishes evidences for implementation of minocycline against SARS CoV-2. In addition, our findings also indicate other three antimycobacterium/antituberculosis drugs (rifampicin, clofazimine and ofloxacin) could potentially be evaluated for COVID-19 therapy., Competing Interests: Declaration of competing interest The authors 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 Elsevier B.V. All rights reserved.)
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- 2024
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33. Palbociclib in Solid Tumor Patients With Genomic Alterations in the cyclinD-cdk4/6-INK4a-Rb Pathway: Results From National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice Trial Arm I (APEC1621I).
- Author
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Macy ME, Mody R, Reid JM, Piao J, Saguilig L, Alonzo TA, Berg SL, Fox E, Weigel BJ, Hawkins DS, Mooney MM, Williams PM, Patton DR, Coffey BD, Roy-Chowdhuri S, Takebe N, Tricoli JV, Janeway KA, Seibel NL, and Parsons DW
- Subjects
- Humans, Child, Adolescent, Female, Male, Young Adult, Child, Preschool, Cyclin D genetics, Pyridines therapeutic use, Piperazines therapeutic use, Cyclin-Dependent Kinase 4 antagonists & inhibitors, Cyclin-Dependent Kinase 4 genetics, Neoplasms drug therapy, Neoplasms genetics, Cyclin-Dependent Kinase 6 antagonists & inhibitors, Cyclin-Dependent Kinase 6 genetics
- Abstract
Purpose: The National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice trial assigned patients age 1-21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase II treatment arms of molecularly targeted therapies on the basis of genetic alterations detected in their tumor. Patients with tumors that harbored prespecified genomic alterations in the cyclinD-CDK4/6-INK4a-Rb pathway with intact Rb expression were assigned and treated with the cdk4/6 inhibitor palbociclib., Methods: Patients received palbociclib orally once daily for 21 days of 28-day cycles until disease progression, intolerable toxicity, or up to 2 years. The primary end point was objective response rate; secondary end points included safety/tolerability and progression-free survival., Results: Twenty-three patients (median age, 15 years; range, 8-21) were enrolled; 20 received protocol therapy and were evaluable for toxicity and response. Of the evaluable patients, the most common diagnoses were osteosarcoma (n = 9) and rhabdomyosarcoma (n = 6). A single actionable gene amplification was found in 19 tumors ( CDK4 , n = 11, CDK6 , n = 2, CCND3 , n = 6), with one tumor harboring two amplifications ( CDK4 and CCND2 ). Hematologic toxicities were the most common treatment-related events. No objective responses were seen. Two patients with tumors harboring CDK4 amplifications (neuroblastoma and sarcoma) had best response of stable disease for six and three cycles. Six-month progression was 10% (95% CI, 1.7 to 27.2)., Conclusion: The CDK4/6 inhibitor palbociclib at 75 mg/m
2 orally daily was tolerable in this heavily pretreated cohort. No objective responses were observed in this histology-agnostic biomarker-selected population with treatment-refractory solid tumors, demonstrating that pathway alteration alone is insufficient in pediatric cancers to generate a response to palbociclib monotherapy.- Published
- 2024
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34. Phase II Study of Samotolisib in Children and Young Adults With Tumors Harboring Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Pathway Alterations: Pediatric MATCH APEC1621D.
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Laetsch TW, Ludwig K, Williams PM, Roy-Chowdhuri S, Patton DR, Coffey B, Reid JM, Piao J, Saguilig L, Alonzo TA, Berg SL, Mhlanga J, Fox E, Weigel BJ, Hawkins DS, Mooney MM, Takebe N, Tricoli JV, Janeway KA, Seibel NL, and Parsons DW
- Subjects
- Humans, Child, Adolescent, Female, Male, Young Adult, Child, Preschool, Infant, Neoplasms drug therapy, Neoplasms genetics, MTOR Inhibitors therapeutic use, Phosphatidylinositol 3-Kinases genetics, Pyrimidines, Bridged Bicyclo Compounds, Heterocyclic, TOR Serine-Threonine Kinases
- Abstract
Purpose: Patients age 1-21 years with relapsed or refractory solid and CNS tumors were assigned to phase II studies of molecularly targeted therapies on the National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial. Patients whose tumors harbored predefined genetic alterations in the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway and lacked mitogen-activated protein kinase pathway activating alterations were treated with the PI3K/mTOR inhibitor samotolisib., Methods: Patients received samotolisib twice daily in 28-day cycles until disease progression or unacceptable toxicity. A rolling 6 limited dose escalation was performed as, to our knowledge, this was the first pediatric study of samotolisib. The primary end point was the objective response rate; secondary end points included progression-free survival (PFS) and the recommended phase II dose and toxicity of samotolisib in children., Results: A total of 3.4% (41/1,206) of centrally tested patients were matched to this arm. Seventeen patients were treated. Among treated patients, the most common diagnoses included osteosarcoma (n = 6) and high-grade glioma (n = 5) harboring alterations in phosphatase and tensin homolog (n = 6), PIK3CA (n = 5), and tuberous sclerosis complex 2 (n = 3). No objective responses or prolonged stable disease were observed. Three-month PFS was 12% (95% CI, 2 to 31). Two patients experienced dose-limiting toxicities (mucositis and pneumonitis). Dose level 2 (115 mg/m
2 /dose twice daily) was determined to be the recommended phase II dose of samotolisib in children., Conclusion: This nationwide study was successful at identifying patients and evaluating the efficacy of molecularly targeted therapy for rare molecular subgroups of patients in a histology-agnostic fashion. Unfortunately, there was no activity of samotolisib against tumors with PI3K/mTOR pathway alterations. Prospective trials such as the NCI-COG Pediatric MATCH are necessary to evaluate the efficacy of molecularly targeted therapies given their increasing use in clinical practice.- Published
- 2024
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35. TDP1 phosphorylation by CDK1 in mitosis promotes MUS81-dependent repair of trapped Top1-DNA covalent complexes.
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Paul Chowdhuri S and Das BB
- Subjects
- Phosphorylation, Humans, DNA metabolism, HeLa Cells, DNA Damage, Mitosis, Phosphoric Diester Hydrolases metabolism, Phosphoric Diester Hydrolases genetics, CDC2 Protein Kinase metabolism, CDC2 Protein Kinase genetics, DNA-Binding Proteins metabolism, DNA-Binding Proteins genetics, DNA Topoisomerases, Type I metabolism, DNA Topoisomerases, Type I genetics, Endonucleases metabolism, Endonucleases genetics, DNA Repair
- Abstract
Topoisomerase 1 (Top1) controls DNA topology, relieves DNA supercoiling during replication and transcription, and is critical for mitotic progression to the G1 phase. Tyrosyl-DNA phosphodiesterase 1 (TDP1) mediates the removal of trapped Top1-DNA covalent complexes (Top1cc). Here, we identify CDK1-dependent phosphorylation of TDP1 at residue S61 during mitosis. A TDP1 variant defective for S61 phosphorylation (TDP1-S61A) is trapped on the mitotic chromosomes, triggering DNA damage and mitotic defects. Moreover, we show that Top1cc repair in mitosis occurs via a MUS81-dependent DNA repair mechanism. Replication stress induced by camptothecin or aphidicolin leads to TDP1-S61A enrichment at common fragile sites, which over-stimulates MUS81-dependent chromatid breaks, anaphase bridges, and micronuclei, ultimately culminating in the formation of 53BP1 nuclear bodies during G1 phase. Our findings provide new insights into the cell cycle-dependent regulation of TDP1 dynamics for the repair of trapped Top1-DNA covalent complexes during mitosis that prevents genomic instability following replication stress., (© 2024. The Author(s).)
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- 2024
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36. Phase II study of vemurafenib in children and young adults with tumors harboring BRAF V600 mutations: NCI-COG pediatric MATCH trial (APEC1621) Arm G.
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Nelson MV, Kim A, Williams PM, Roy-Chowdhuri S, Patton DR, Coffey BD, Reid JM, Piao J, Saguilig L, Alonzo TA, Berg SL, Ramirez NC, Jaju A, Fox E, Weigel BJ, Hawkins DS, Mooney MM, Takebe N, Tricoli JV, Janeway KA, Seibel NL, and Parsons DW
- Subjects
- Humans, Male, Female, Child, Adolescent, Young Adult, Adult, Child, Preschool, Neoplasms drug therapy, Neoplasms genetics, Proto-Oncogene Proteins B-raf genetics, Vemurafenib therapeutic use, Vemurafenib administration & dosage, Mutation
- Abstract
Background: This is a phase II subprotocol of the NCI-COG Pediatric MATCH study evaluating vemurafenib, a selective oral inhibitor of BRAF V600 mutated kinase, in patients with relapsed or refractory solid tumors harboring BRAF V600 mutations., Methods: Patients received vemurafenib at 550 mg/m2 (maximum 960 mg/dose) orally twice daily for 28-day cycles until progression or intolerable toxicity. The primary aim was to determine the objective response rate and secondary objectives included estimating progression-free survival and assessing the tolerability of vemurafenib., Results: Twenty-two patients matched to the subprotocol and 4 patients (18%) enrolled. Primary reasons for non-enrollment were ineligibility due to exclusions of low-grade glioma (n = 7) and prior BRAF inhibitor therapy (n = 7). Enrolled diagnoses were one each of histiocytosis, ameloblastoma, Ewing sarcoma, and high-grade glioma, all with BRAF V600E mutations. Treatment was overall tolerable with mostly expected grade 1/2 adverse events (AE). Grade 3 or 4 AE on treatment were acute kidney injury, hyperglycemia, and maculopapular rash. One patient came off therapy due to AE. One patient (glioma) had an objective partial response and remained on protocol therapy for 15 cycles., Conclusion: There was a low accrual rate on this MATCH subprotocol, with only 18% of those who matched with BRAFV600 mutations enrolling, resulting in early termination, and limiting study results (ClinicalTrials.gov Identifier: NCT03220035)., (© The Author(s) 2024. Published by Oxford University Press.)
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- 2024
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37. Opioid-Related Sleep Disordered Breathing: Correlates and Conundrums.
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Chowdhuri S and Badr MS
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- 2024
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38. Olaparib for childhood tumors harboring defects in DNA damage repair genes: arm H of the NCI-COG Pediatric MATCH trial.
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Glade Bender JL, Pinkney K, Williams PM, Roy-Chowdhuri S, Patton DR, Coffey BD, Reid JM, Piao J, Saguilig L, Alonzo TA, Berg SL, Ramirez NC, Fox E, Weigel BJ, Hawkins DS, Mooney MM, Takebe N, Tricoli JV, Janeway KA, Seibel NL, and Parsons DW
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Infant, Male, Young Adult, Ataxia Telangiectasia Mutated Proteins genetics, BRCA1 Protein genetics, BRCA2 Protein genetics, DNA Damage drug effects, DNA-Binding Proteins genetics, Germ-Line Mutation, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use, Poly(ADP-ribose) Polymerase Inhibitors adverse effects, DNA Repair drug effects, DNA Repair genetics, Neoplasms drug therapy, Neoplasms genetics, Phthalazines therapeutic use, Phthalazines adverse effects, Phthalazines administration & dosage, Piperazines therapeutic use, Piperazines administration & dosage, Piperazines adverse effects
- Abstract
Background: The National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice (MATCH) precision oncology platform trial enrolled children aged 1-21 years with treatment-refractory solid tumors and predefined actionable genetic alterations. Patients with tumors harboring alterations in DNA damage repair (DDR) genes were assigned to receive olaparib., Methods: Tumor and blood samples were submitted for centralized molecular testing. Tumor and germline sequencing were conducted in parallel. Olaparib was given twice daily for 28-day cycles starting at a dose 30% lower than the adult recommended phase 2 dose (RP2D). The primary endpoint was the objective response., Results: Eighteen patients matched (1.5% of those screened) based on the presence of a deleterious gene alteration in BRCA1/2, RAD51C/D, or ATM detected by tumor sequencing without germline subtraction or analysis of loss of heterozygosity (LOH). Eleven (61%) harbored a germline mutation, with only one exhibiting LOH. Six patients enrolled and received the olaparib starting dose of 135 mg/m2/dose. Two participants were fully evaluable; 4 were inevaluable because <85% of the prescribed dose was administered during cycle 1. There were no dose-limiting toxicities or responses. Minimal hematologic toxicity was observed., Conclusion: Most DDR gene alterations detected in Pediatric MATCH were germline, monoallelic, and unlikely to confer homologous recombination deficiency predicting sensitivity to olaparib monotherapy. The study closed due to poor accrual., Clinicaltrials.gov Identifier: NCT03233204. IRB approved: initial July 24, 2017., (© The Author(s) 2024. Published by Oxford University Press.)
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- 2024
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39. Molecular Pathology of Lung Cancer.
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Roy-Chowdhuri S
- Subjects
- Humans, Biomarkers, Tumor genetics, Molecular Diagnostic Techniques, Lung pathology, Lung Neoplasms diagnosis, Lung Neoplasms pathology, Lung Neoplasms genetics
- Abstract
The identification of targetable genomic alterations in lung cancer is required as standard of care to guide optimal therapy selection. With a constantly evolving landscape of ancillary molecular and biomarker testing in lung cancer, pathologists need to be aware of what specimens to test, how the testing should be performed, and which targets to test for to provide the clinically relevant genomic information necessary to treat these patients. Several guideline statements on the topic are currently available to help pathologists and laboratory personnel best use the small specimens obtained from patients with lung cancer for ancillary molecular testing., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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40. Plasmacytoid urothelial carcinoma of the urinary bladder-A clinicopathological and molecular analysis of 52 cases.
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Zheng L, Chen H, Zhao J, Roy-Chowdhuri S, Kamat AM, Alhalabi O, Gao J, Siefker-Radtke A, Hansel DE, Czerniak B, and Guo CC
- Subjects
- Humans, Male, Aged, Middle Aged, Female, Adult, Aged, 80 and over, DNA Mutational Analysis, Immunohistochemistry, TOR Serine-Threonine Kinases genetics, TOR Serine-Threonine Kinases metabolism, Urothelium pathology, In Situ Hybridization, Fluorescence, Tumor Suppressor Protein p53 genetics, Telomerase genetics, Carcinoma, Transitional Cell genetics, Carcinoma, Transitional Cell pathology, Receptor, ErbB-2 genetics, Receptor, ErbB-2 metabolism, Genetic Predisposition to Disease, Urinary Bladder Neoplasms genetics, Urinary Bladder Neoplasms pathology, Urinary Bladder Neoplasms mortality, Mutation, Biomarkers, Tumor genetics, Biomarkers, Tumor analysis, DNA Copy Number Variations
- Abstract
Plasmacytoid urothelial carcinoma (UC) is a rare histologic subtype of bladder cancer that is associated with an aggressive clinical behavior. We analyzed the clinicopathologic and molecular features of plasmacytoid UC in 52 patients from a single institute. The patients included 44 men and 8 women, with a mean age of 64 years (range, 41-91 years). All bladder cancers were high-grade UC, and plasmacytoid component accounted for a mean of 47% of bladder tumors (range, 5-100%). Distinct gene mutations were found in most plasmacytoid UCs (n = 49); the most common mutations were TP53 (n = 30), followed by TERT (n = 20), and CDH1 (n = 18). Copy number analysis was performed in 34 patients, and 13 of them showed copy number variations. Expression of HER2 was analyzed in 18 patients by immunohistochemistry, and 3 of them showed HER2 overexpression, which was confirmed by fluorescence in situ hybridization analysis. Thirty-two patients died of disease in a median of 15 months (range, 1-45 months). No individual gene mutations were significantly associated with clinical outcome, but mutations in the mammalian target of rapamycin (mTOR) pathway, including PICK3CA and PIK3R1 mutations, were associated with a significantly shorter survival duration (p < 0.05). Plasmacytoid UC is an aggressive histologic subtype that demonstrates frequent somatic gene mutations and CNVs, which may underlie its oncogenesis and progression. Gene mutations of the mTOR pathway are associated with poor outcome in a subset of patients with plasmacytoid UC., Competing Interests: Declaration of competing interest All authors declare they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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41. Spitz melanocytic neoplasms with MLPH::ALK fusions: Report of two cases with previously unreported features and literature review.
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Salah HT, Yang RK, Roy-Chowdhuri S, Ross MI, Aung PP, Rothrock AT, Torres-Cabala CA, Curry JL, Prieto VG, Nagarajan P, and Cho WC
- Subjects
- Adult, Female, Humans, Adaptor Proteins, Signal Transducing, Oncogene Proteins, Fusion genetics, Anaplastic Lymphoma Kinase genetics, Melanoma genetics, Melanoma pathology, Nevus, Epithelioid and Spindle Cell genetics, Nevus, Epithelioid and Spindle Cell pathology, Skin Neoplasms genetics, Skin Neoplasms pathology
- Abstract
ALK-fused Spitz melanocytic neoplasms are a distinct subgroup of melanocytic lesions exhibiting unique histopathologic characteristics. These lesions often manifest as exophytic or polypoid tumors, characterized by fusiform-to-epithelioid melanocytes arranged in a nested, fascicular, or plexiform growth pattern. Several fusion partners of the ALK gene have been identified in spitzoid melanocytic neoplasms, with TPM3 and DCTN1 being the most prevalent. Less common fusion partners include NPM1, TPR, CLIP1, GTF3C2, EEF2, MYO5A, KANK1, and EHBP1. The MLPH gene, which encodes melanophilin (MLPH), playing a crucial role in regulating skin pigmentation by acting as a linker between RAB27A and myosin Va during melanosome transport, has also recently been recognized as a rare fusion partner of ALK in Spitz melanocytic neoplasms. Currently, there exists a sparse documentation within English literature, illustrating a limited number of cases featuring MLPH::ALK fusion in Spitz melanocytic neoplasms. In this report, we present two additional cases, including a previously unreported instance of Spitz melanoma, contributing to the expanding knowledge on ALK-fused Spitz melanocytic neoplasms. In addition, we provide a comprehensive review of the clinical, histopathologic, and molecular features observed in documented cases with this novel fusion., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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42. Principles of Analytic Validation of Immunohistochemical Assays: Guideline Update.
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Goldsmith JD, Troxell ML, Roy-Chowdhuri S, Colasacco CF, Edgerton ME, Fitzgibbons PL, Fulton R, Haas T, Kandalaft PL, Kalicanin T, Lacchetti C, Loykasek P, Thomas NE, Swanson PE, and Bellizzi AM
- Subjects
- Humans, Reproducibility of Results, United States, Evidence-Based Medicine standards, Practice Guidelines as Topic standards, Pathology, Clinical standards, Pathology, Clinical methods, Immunohistochemistry standards, Immunohistochemistry methods
- Abstract
Context.—: In 2014, the College of American Pathologists developed an evidence-based guideline to address analytic validation of immunohistochemical assays. Fourteen recommendations were offered. Per the National Academy of Medicine standards for developing trustworthy guidelines, guidelines should be updated when new evidence suggests modifications., Objective.—: To assess evidence published since the release of the original guideline and develop updated evidence-based recommendations., Design.—: The College of American Pathologists convened an expert panel to perform a systematic review of the literature and update the original guideline recommendations using the Grading of Recommendations Assessment, Development and Evaluation approach., Results.—: Two strong recommendations, 1 conditional recommendation, and 12 good practice statements are offered in this updated guideline. They address analytic validation or verification of predictive and nonpredictive assays, and recommended revalidation procedures following changes in assay conditions., Conclusions.—: While many of the original guideline statements remain similar, new recommendations address analytic validation of assays with distinct scoring systems, such as programmed death receptor-1 and analytic verification of US Food and Drug Administration approved/cleared assays; more specific guidance is offered for validating immunohistochemistry performed on cytology specimens., Competing Interests: Authors’ disclosures of potential conflicts of interest and author contributions are found in the Appendix at the end of this article., (© 2024 College of American Pathologists.)
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- 2024
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43. Phase II Study of Ulixertinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Alterations: APEC1621J of the National Cancer Institute-Children's Oncology Group Pediatric MATCH Trial.
- Author
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Vo KT, Sabnis AJ, Williams PM, Roy-Chowdhuri S, Patton DR, Coffey B, Reid JM, Piao J, Saguilig L, Alonzo TA, Berg SL, Jaju A, Fox E, Weigel BJ, Hawkins DS, Mooney MM, Takebe N, Tricoli JV, Janeway KA, Seibel NL, and Parsons DW
- Subjects
- Humans, Adolescent, Child, Female, Male, Young Adult, Child, Preschool, Infant, United States, Mitogen-Activated Protein Kinases genetics, National Cancer Institute (U.S.), MAP Kinase Signaling System drug effects, MAP Kinase Signaling System genetics, Aminopyridines, Pyrroles, Neoplasms drug therapy, Neoplasms genetics
- Abstract
Purpose: The National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric MATCH trial assigns patients age 1-21 years with refractory malignancies to phase II treatment arms of molecularly targeted therapies on the basis of genetic alterations detected in their tumor. Patients with activating alterations in the mitogen-activated protein kinase pathway were treated with ulixertinib, an extracellular signal-regulated kinase (ERK)1/2 inhibitor., Methods: As there were no previous pediatric data, ulixertinib was initially tested in a dose escalation cohort to establish the recommended phase II dose (RP2D) before proceeding to the phase II cohort. Ulixertinib was administered at 260 mg/m
2 /dose orally twice a day (dose level 1 [DL1], n = 15) or 350 mg/m2 /dose orally twice a day (DL2, n = 5). The primary end point was objective response rate; secondary end points included safety/tolerability and progression-free survival (PFS)., Results: Twenty patients (median 12 years; range, 5-20) were treated, all evaluable for response. CNS tumors comprised 55% (11/20) of diagnoses, with high-grade glioma and low-grade glioma most common (n = 5 each). All CNS tumors except one harbored BRAF fusions or V600E mutations. Rhabdomyosarcoma (n = 5) was the most frequent non-CNS diagnosis. DL1 was declared the RP2D in the dose escalation cohort after dose-limiting toxicities in Cycle 1 occurred in 1/6 patients at DL1 and 2/5 patients at DL2, including fatigue, anorexia, rash, nausea, vomiting, diarrhea, dehydration, hypoalbuminemia, and hypernatremia. No objective responses were observed. Six-month PFS was 37% (95% CI, 17 to 58). Three patients with BRAF -altered CNS tumors achieved stable disease >6 months., Conclusion: Ulixertinib, a novel targeted agent with no previous pediatric data, was successfully evaluated in a national precision medicine basket trial. The pediatric RP2D of ulixertinib is 260 mg/m2 /dose orally twice a day. Limited single-agent efficacy was observed in a biomarker-selected cohort of refractory pediatric tumors.- Published
- 2024
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44. Exploratory pilot study to characterize the immune landscapes of malignant pleural effusions and their corresponding primary tumors from patients with breast carcinoma and lung adenocarcinoma.
- Author
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Laberiano-Fernandez C, Gan Q, Wang SM, Tamegnon A, Wistuba I, Yoon E, Roy-Chowdhuri S, and Parra ER
- Subjects
- Humans, Female, Pilot Projects, Middle Aged, Aged, B7-H1 Antigen immunology, B7-H1 Antigen metabolism, Male, Adenocarcinoma pathology, Adenocarcinoma immunology, Adenocarcinoma diagnosis, Adult, Aged, 80 and over, Biomarkers, Tumor immunology, Breast Neoplasms immunology, Breast Neoplasms pathology, Breast Neoplasms diagnosis, Pleural Effusion, Malignant immunology, Pleural Effusion, Malignant pathology, Lung Neoplasms pathology, Lung Neoplasms immunology, Adenocarcinoma of Lung pathology, Adenocarcinoma of Lung immunology, Adenocarcinoma of Lung diagnosis
- Abstract
Introduction: Malignant pleural effusion (MPE) is a frequent complication of advanced malignancies. In this pilot study, we characterized the immune landscapes of MPEs, compared them to their primary tumor (PT) samples from breast carcinoma (BC) and lung adenocarcinoma (LADC), and tested the utility of multiplexed image technology in cytological samples., Materials and Methods: We evaluated the immune contexture of 6 BC and 5 LADC MPEs and their PTs using 3 multiplex immunofluorescence panels. We explored the associations between sample characteristics and pleural effusion-free survival., Results: No MPE samples had positive programmed death-ligand 1 expression in malignant cells, although 3 of 11 PTs has positive programmed death-ligand 1 expression (more than 1% expression in malignant cells). Overall, in LADC samples, cluster of differentiation 3 (CD3)+ T cells and CD3+CD8+ cytotoxic T cells predominated (median percentages for MPEs versus PTs: 45.6% versus 40.7% and 4.7% versus 6.6%, respectively) compared with BC. CD68+ macrophages predominated in the BC samples (medians for MPEs 61.2% versus PTs for 57.1%) but not in the LADC samples. Generally in PTs, CD3+CD8+ forkhead box P3+ T cells and the median distances from the malignant cells to CD3+CD8+Ki67+ and CD3+ programmed cell death protein 1 + T cells correlated to earlier MPE after PT diagnosis., Conclusions: The immune cell phenotypes in the MPEs and PTs were similar within each cancer type but different between BC versus LADC. An MPE analysis can potentially be used as a substitute for a PT analysis, but an expanded study of this topic is essential., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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45. Updated Analysis of a Phase 2 Trial of Cytoreduction, Gastrectomy, and Hyperthermic Intraperitoneal Perfusion with Chemotherapy for Patients with Peritoneal Carcinoma from Gastric Cancer.
- Author
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Badgwell B, Estrella J, Roy-Chowdhuri S, Ikoma N, Blum Murphy M, Ajani J, and Mansfield P
- Subjects
- Humans, Cytoreduction Surgical Procedures, Perfusion, Gastrectomy, Combined Modality Therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Survival Rate, Stomach Neoplasms drug therapy, Stomach Neoplasms surgery, Carcinoma, Peritoneal Neoplasms therapy, Hyperthermia, Induced
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- 2024
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46. Changing digital and telecytology practices post COVID-19 comparing ASC survey results from 2016 to 2023.
- Author
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Chen-Yost HI, Bammert C, Hao W, Heymann JJ, Lin DM, Marotti J, Waraksa-Deutsch T, Huang M, Krishnamurti U, Lin O, Ly A, Moatamed N, Pantanowitz L, and Roy-Chowdhuri S
- Subjects
- Humans, Surveys and Questionnaires, SARS-CoV-2, Attitude of Health Personnel, Societies, Medical, Cytodiagnosis methods, United States, Pandemics, COVID-19 epidemiology, Telepathology methods
- Abstract
Introduction: During the COVID-19 pandemic, the need for digital pathology tools became more urgent. However, there needs to be more knowledge of the use in cytology. We aimed to evaluate current digital cytology practices and attitudes and compare the results with a pre-COVID-19 American Society of Cytopathology (ASC) survey., Materials and Methods: Fourteen survey questions assessing current attitudes toward digital cytology were developed from a 2016 ASC Digital Pathology Survey. Ten new survey questions were also created to evaluate telecytology use. The survey was e-mailed to ASC members over 6 weeks in 2023., Results: A total of 123 individuals responded (116 in 2016). Attitudes toward digital cytology were unchanged; most participants stated digital cytology is beneficial (87% 2023 versus 90% 2016). The percentage of individuals using digital cytology was unchanged (56% in 2016 and 2023). However, telecytology for rapid onsite assessment (ROSE) is now considered the best application (55% 2023 versus 31% 2016). Forty-three institutions reported using digital and telecytology tools; 40% made implementations after 2020; most did not feel that COVID-19 affected digital cytology (56%). Telecytology for ROSE is the most common application now (78%) compared with education (30%) in 2016. Limitations for implementing digital imaging in cytology included inability to focus (38%) and expense (33%)., Conclusions: General attitudes toward digital tools by the cytology community have essentially remained the same between 2016 and now. However, telecytology for ROSE is increasingly being used, which supports a need for validation and competency guidelines., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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47. Cancer biomarkers: Emerging trends and clinical implications for personalized treatment.
- Author
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Passaro A, Al Bakir M, Hamilton EG, Diehn M, André F, Roy-Chowdhuri S, Mountzios G, Wistuba II, Swanton C, and Peters S
- Subjects
- Humans, Medical Oncology methods, Tumor Microenvironment, Biomarkers, Tumor, Neoplasms therapy, Neoplasms drug therapy, Precision Medicine methods
- Abstract
The integration of cancer biomarkers into oncology has revolutionized cancer treatment, yielding remarkable advancements in cancer therapeutics and the prognosis of cancer patients. The development of personalized medicine represents a turning point and a new paradigm in cancer management, as biomarkers enable oncologists to tailor treatments based on the unique molecular profile of each patient's tumor. In this review, we discuss the scientific milestones of cancer biomarkers and explore future possibilities to improve the management of patients with solid tumors. This progress is primarily attributed to the biological characterization of cancers, advancements in testing methodologies, elucidation of the immune microenvironment, and the ability to profile circulating tumor fractions. Integrating these insights promises to continually advance the precision oncology field, fostering better patient outcomes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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48. The updated College of American Pathologists principles of analytic validation of immunohistochemical assays: A step forward for cytopathology.
- Author
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Roy-Chowdhuri S
- Published
- 2024
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49. Prevalence of central sleep apnea among veterans and response rate to continuous positive airway pressure therapy.
- Author
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Ibrahim NA, Sankari A, Aldwaikat A, Pandya N, Chowdhuri S, Salloum A, Martin JL, Zeineddine S, and Badr MS
- Abstract
Study Objectives: Sleep-disordered breathing (SDB) is common in the Veteran population. In this retrospective study, we investigated the prevalence of comorbid central and obstructive SDB and the response rate to PAP among Veterans., Methods: Veterans were screened from a single VA medical center who had polysomnography (PSG) study from 2017 to 2021 to ascertain the presence, severity, and type of SDB by measuring the apnea-hypopnea index (AHI) and central apnea index (CAI). Patients were excluded if they did not have complete studies (diagnostic and PAP titration studies). The inclusion criteria for these analyses were central sleep apnea (CSA) defined as AHI ≥ 10 events/hour and CAI ≥ 5 events/hour. Diagnostic "CSA only" was defined as AHI ≥ 10 events/hour and CAI ≥ 50% of AHI. "OSA only" was defined if AHI ≥ 10 events/hour and CAI < 5 events/hour. Comorbid central and obstructive sleep apnea (COSA) was defined if AHI ≥ 10 events/hour and CAI > 5 events/hour but < 50% of AHI. The responsiveness to PAP therapy was determined based on the CAI < 5 events/hour on the titration study., Results: A total of 90 patients met the inclusion criteria and from those 64 Veterans were found to have COSA (71%), 18 (20%) were CSA only, and 8 (9%) were OSA only. A total of 22 (24.4%) Veterans diagnosed with CSA or COSA were responsive to PAP therapy. Sixty days after treatment initiation, both responsive and nonresponsive groups had significant decreases in AHI and CAI ( p < 0.05)., Conclusions: Comorbid central and obstructive SDB is common among Veterans. The response to PAP therapy is suboptimal but improves over time., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)
- Published
- 2024
- Full Text
- View/download PDF
50. A Clinical Study of Malignant Sino-Nasal Tumors.
- Author
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Chowdhuri S, Nikam S, Keche P, Katre M, and Dhanajkar P
- Abstract
The sino-nasal cavities represent an anatomical region affected by a variety of tumors with clinical, etiological, genetic and pathological features, which are distinct from tumors commonly encountered in the area of head and neck cancers. We have undertaken this study with the aim of assessing clinical profile, various treatment modalities and outcome of patients with malignant sino-nasal tumors. In this prospective study of two years, done in a rural tertiary care hospital of India, 40 patients with malignant neoplastic tumors of nasal cavity, sinuses and nasopharynx were analyzed for their clinic-pathological and radiological profile and surgical management. The age range found was 10-78 years. There was a significant male preponderance with 23 (57.5%) male patients. Most common histological type seen in our study was Squamous cell carcinoma amongst 32 (80%) of cases. Maximum number of patients were managed with combination therapy of Surgery and Radiotherapy i.e. in 21 patients (52.5%). Multimodality treatment has been deemed the most efficacious choice of treatment which would improve disease free survival for the patients., Competing Interests: Conflict of InterestThere was no source of funding in our study and there was no any conflict of interest., (© Association of Otolaryngologists of India 2023. 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.)
- Published
- 2024
- Full Text
- View/download PDF
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