tbuckley/cabot-search huggingface dataset:
KEYNOTE-B79 phase 1b trial to evaluate the allogeneic CAR T-cells CYAD-101 and pembrolizumab in refractory metastatic colorectal cancer patients.
Authors: Richard D. Kim, Hans Prenen, Sylvie Rottey, Dae Won Kim, Anne Flament, Frederic Lehmann, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2022)

TPS227 Background: The allogeneic chimeric antigen receptor (CAR) T-cell treatment CYAD-101 utilizes the NKG2D receptor that targets eight ligands expressed on tumor cells and also on stromal and immunosuppressive immune cells of the tumor microenvironment. CYAD-101 co-expresses a T-cell receptor (TCR) inhibitory peptide with the aim to eliminate the potential of graft versus host disease (GvHD), the main safety risk associated with engineered cells of allogeneic origin. In the previous alloSHRINK trial (NCT03692429), CYAD-101 was administered post FOLFOX preconditioning chemotherapy to 15 patients with progressive metastatic colorectal cancer (mCRC) who were previously treated with FOLFOX. Overall, the treatment was well tolerated with no evidence of GvHD. The disease control rate was 73.3% with two patients presenting a confirmed partial response per RECIST’s criteria (4 months and 8 months of duration from first CYAD-101 infusion) and nine had stable disease with a median duration of 4.6 months. Evidence of increase in the TCR repertoire and modulation of the cytokine profile post-treatment with CYAD-101 were observed implying that CYAD-101 may also be modulating the immune suppressive environment in patients mirroring what was demonstrated in pre-clinical models. We considered that a sequential therapy with the anti-PD1 monoclonal antibody pembrolizumab to further release the anti-tumor potential of this expanded T-cell population may drive deeper, more durable and new clinical responses beyond that currently demonstrated with the CAR T-cells alone. Methods: The phase 1b KEYNOTE-B79 trial (NCT04991948) will evaluate, according to a Simon’s two stage study design, the safety and clinical activity of three consecutive infusions of CYAD-101 (1x10 9 cells per infusion) post FOLFOX preconditioning chemotherapy with two-week interval between cycles, followed by pembrolizumab treatment (200 mg administered every three weeks for up to two years) in microsatellite stable/mismatch-repair proficient mCRC patients with recurrent/progressing disease after at least one metastatic line of therapy, which must include FOLFOX chemotherapy. The pembrolizumab treatment will be initiated 3 weeks after the last CYAD-101 infusion to fall outside the classical time window of potential CAR T-cell toxicities (e.g., cytokine release syndrome). The co-primary endpoints of the trial are the occurrence of dose-limiting toxicities (DLTs) at any time from the first FOLFOX preconditioning treatment up to 3 weeks after the first pembrolizumab treatment and the objective response rate (ORR) at the tumor assessment planned 6 weeks after the first pembrolizumab treatment administration. The KEYNOTE-B79 study will be initiated in Q4-2021 in five sites in USA and Europe. Clinical trial information: NCT04991948.
A prognostic model to predict the disappearance of left atrial thrombi among candidates for percutaneous transvenous mitral commissurotomy under oral anticoagulant therapy Songkwan Silaruks, Bandit Thinkhamrop, Wirote Tantikosum, Chaiyasith Wongvipaporn, Pyatat Tatsanavivat, Orathai Pacheerat, Virat Klungboonkrong. Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand
Journal: Journal of the American College of Cardiology (2001)
The role of germline polymorphisms in genes involved in the antioxidant system to predict the efficacy of cetuximab for patients with metastatic colorectal cancer (mCRC) enrolled in FIRE-3 trial.
Authors: Hiroyuki Arai, Joshua Millstein, Sebastian Stintzing, Jingyuan Wang, Francesca Battaglin, Natsuko Kawanishi, Priya Jayachandran, Shivani Soni, Zhang Wu, Volker Heinemann, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2022)

143 Background: Reactive oxygen species activate RAS/MAPK signaling either through inactivation of phosphatases or by direct oxidation of kinases. We hypothesized that functional genetic variants in genes involved in the antioxidant system may be associated with the efficacy of cetuximab in mCRC patients. Methods: We analyzed genomic and clinical data from FIRE-3, a phase III trial which compared cetuximab and bevacizumab in combination with FOLFIRI in untreated mCRC patients. Genomic DNA extracted from blood samples was genotyped using an OncoArray (Illumina, Inc., San Diego, CA, USA). Candidate 13 functional single nucleotide polymorphisms (SNPs) ( TXN rs2301242, TXN rs2301241, TXN2 rs4821494, TXN2 rs9619611, TXN2 rs59841625, CAT rs7943316, CAT rs564250, CAT rs11604331, CAT rs1001179, CAT rs769217, GPX4 rs757229, GPX4 rs4807542, and GPX4 rs713041) were tested for association with progression-free survival and overall survival (OS), using log-rank test and Cox proportional hazards model. To confirm the predictive value, the treatment-by-SNP interaction was tested. Results: A total of 236 patients were available for the SNP analyses (cetuximab arm, n = 129; bevacizumab arm, n = 107). In the cetuximab arm, two SNPs were significantly associated with clinical outcomes in univariate analyses: TXN2 rs4821494 (T/T vs any G allele, hazard ratio [HR] on OS = 2.17, 95% confidence interval [CI] = 1.04–4.56, log-rank p = 0.04) and GPX4 rs4807542 (G/G vs any A allele, HR on OS = 2.04, 95% CI = 1.05–3.98, log-rank p = 0.03). Multivariate analysis confirmed the significance in TXN2 rs4821494 (T/T vs any G allele, HR on OS = 2.47, 95% CI = 1.06–5.72, p = 0.03). In the bevacizumab arm, univariate analyses did not detect any significant associations between the SNPs and clinical outcomes. Treatment-by-SNP interaction test showed the significant predictive value of TXN2 rs4821494 in terms of OS ( p = 0.03). Conclusions: TXN2 rs4821494 involved in the antioxidant system may predict the efficacy of cetuximab, in comparing with bevacizumab, in the first-line treatment of mCRC. Our novel findings warrant further validation studies.
Role of glycolysis in the energy production for the nonmechanical myocardial work in isolated pig hearts KarimBbendjelid, Emmanuelle Canet, Cendrine Casali, Annie Desenfant, Jean Francois Obadia, Didier Revel, Marc Janier. CERMEP, Lyon, France, UMR 5515 (CREATIS), Lyon, France
Journal: Journal of the American College of Cardiology (2001)
Abstract 17293: Functional Outcomes After Acute Pulmonary Embolism
Authors: Yevgeniy Brailovsky, Siri Kunchakarra, Katerina Porcaro, Demetrios Doukas, Andrew Stiff, Carlos Bechara, John Lopez, Verghese Mathew, Jawed Fareed, Amir Darki
Journal: Circulation (2018)

Introduction: Pulmonary embolism (PE) is associated with significant acute morbidity, mortality, and long term functional limitations. There is paucity of data on acute and short term functional assessment after acute PE. Hypothesis: Functional capacity will improve from baseline to follow up among patients with acute PE. Methods: We prospectively analyzed patients who underwent evaluation by the pulmonary embolism response team (PERT) at Loyola University Medical Center between 2016 and 2018. We included patients with acute PE who underwent six-minute walk test (6MWT) at discharge and during outpatient follow up (50±72 days post discharge). We collected demographic and clinical characteristics. We used paired sampled t-test to compare continuous variables. Results: Among the 204 patients evaluated by PERT, 38 patients (18.6%) underwent 6MWT at baseline and follow up. Patients were classified as low risk (6 patients), submassive (29 patients), and massive (3 patients). Mean age was 61.3±14.2, 50% were female, 60.5% were white, 26.3% were black, 29% had cancer, and 68.4% had concomitant DVT, mean BMI 36.4±10.3, and mean PESI score was 96.8+44.4. Overall the mean 6MWT distance increased significantly from a baseline of 726.9±73.7 feet to 1042±72.8 feet at follow up (p&lt;0.001). Low risk (786±204 to 1115.8+177.6 p=0.63), Submassive (700.2±85 to 995.6±82.8 p&lt;0.001), and Massive PE (859±261.7 to 1343.3±307 p=0.168) groups all demonstrated improvement in 6MWT distance. Conclusions: Functional capacity as measured by 6MWT significantly improved during follow up after acute PE. Future studies are needed to determine predictors of favorable functional outcome and best treatment strategies.
Women with acute anterior myocardial infarction have less precordial ST elevation than men independent of age of presentation R.S. Wright, Wayne L. Miller, Ihor Gussak, David L. Dvorak, Thomas P. Aufdenheide, John H. Haley, Stephen L. Kopecky, Guy S. Reeder, Stephen C. Hammill. Mayo Clinic, Rochester, MN
Journal: Journal of the American College of Cardiology (2001)
Alcohol amplifies the association between common variants at<i>PRSS1–PRSS2</i>locus and chronic pancreatitis in a dose-dependent manner
Authors: Yuan-Chen Wang, Xiao-Tong Mao, Dong Yu, Sheng-Han Mao, Zhao-Shen Li, Wen-Bin Zou, Zhuan Liao
Journal: Gut (2022)
Resource utilization and total cost of care among Medicare advantage patients with metastatic pancreatic cancer receiving NCCN category 1 preferred regimens.
Authors: Gabriela Dieguez, Samantha Tomicki, David DeStephano, Benjamin Hsu, Paul Cockrum
Journal: Journal of Clinical Oncology (2022)

531 Background: Medicare Advantage accounts for almost 40% of Medicare beneficiaries in 2021. There is limited research evaluating utilization and cost for Medicare Advantage patients with metastatic pancreatic cancer (m-PANC) receiving various NCCN Category 1 preferred regimens. Methods: We used ICD-10 diagnosis codes to identify patients with m-PANC without end-stage renal disease in the 2016-2019 Milliman Consolidated Health Cost Guidelines Sources Database (CHSD) claims files. Study patients had 2+ claims with a pancreatic cancer diagnosis and Medicare Advantage coverage for 3 months pre- and 1 month post-metastasis diagnosis. Patients with stand-alone Part D plan coverage or aged&lt;65 years were excluded. Total cost of care (TCOC) was the sum of the average paid by the insurer and patient. Study patients were treated with NCCN Category 1 preferred regimens: 1L gemcitabine/nab-paclitaxel (gem/nab), 1L gemcitabine monotherapy (gem mono), 1L FOLFIRINOX (FFX), and 2L+ liposomal irinotecan (5FU was not included in this analysis; see Limitations for further details). Results: Of the approximately 2.5 million patients covered by Medicare Advantage in CHSD, there were 946 patients that received an NCCN Category 1 chemotherapy regimen between 2016 and 2019. Among NCCN Category 1 preferred regimens, patients receiving 2L+ liposomal irinotecan had the lowest mean admissions per beneficiary and mean readmission rate (0.5 and 8%) compared to patients receiving gem/nab (0.8 and 12%), gem mono (0.6 and 8%), or FFX (0.6 and 9%). Patients receiving 2L+ liposomal irinotecan also had the shortest length of stay per inpatient admission in days (2.9) compared to patients receiving gem/nab (5.1), gem mono (3.6), or FFX (4.3). Mean claims per beneficiary for emergency department observations was lowest among patients receiving 2L+ liposomal irinotecan (0.7), compared to patients receiving gem/nab (0.9), gem mono (1.0), or FFX (0.89). Patients receiving 2L+ liposomal irinotecan had lower median TCOC ($31,885) than patients receiving gem/nab ($39,479) or FFX ($32,632). Conclusions: Patients with Medicare Advantage receiving 2L+ liposomal irinotecan-based regimens to treat m-PANC had lower healthcare resource utilization in key categories and lower median total costs than patients receiving other NCCN Category 1 preferred regimens. Limitations: Analysis of different populations or time periods may yield different results. Our study used claims data and not electronic health records (EHRs), so we could not control for clinical covariates. Patient characteristics and regimen performance might influence which regimens patients receive. We did not adjust TCOC or utilization for LOT durations. We did not study whether liposomal irinotecan-based therapy patients received concomitant 5FU or prior gemcitabine-based therapy.
PUBLIC HEALTH.
Journal: JAMA (1894)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Natural history of patients with advanced cholangiocarcinoma and FGFR2 gene fusions/rearrangements.
Authors: Rachna T. Shroff, Francesca Avogadri, Richard Weng, Ai Li, Carl L. Dambkowski, Angela Lamarca
Journal: Journal of Clinical Oncology (2022)

391 Background: Cholangiocarcinoma (CCA) is a rare malignancy associated with poor survival. Molecular profiling is important to inform treatment choices and FGFR2 fusions or other rearrangements are common, occurring in 10–16% of patients with intrahepatic CCA (iCCA). There is limited real-world data on the natural history of patients with advanced CCA and FGFR2 fusions/rearrangements receiving therapies for advanced disease. The primary objective of this retrospective, observational natural history study was to compare real-world overall survival in patients with advanced CCA and FGFR2 fusions/rearrangements vs. those with wild-type (WT) FGFR2 from the index date of diagnosis of advanced CCA to date of death. A secondary objective was to analyze overall survival in the subgroup of patients with CCA and FGFR2 fusions/rearrangements from the index date of start of second-line therapy to date of death. Methods: This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine clinico-genomic database. Data originated from approx. 280 US cancer clinics (̃800 sites of care). Patients were ≥18 years of age, had chart-confirmed advanced CCA, comprehensive genomic profiling demonstrating FGFR2 fusion/rearrangement, and had ≥2 visits within the Flatiron Health network since January 1, 2011. Results: As of May 2020, 571 patients met the inclusion criteria; 75 patients with FGFR2 fusions/rearrangements (median age 63 years; 64% female; 95% iCCA; 68% stage IV at initial diagnosis), and 496 patients with WT FGFR2 (median age 65 years; 48% female; 74% iCCA; 55% stage IV at initial diagnosis). Median overall survival from the index date of diagnosis was numerically higher, but not statistically different, for patients with FGFR2 fusions/rearrangements vs. WT FGFR2 (12.1 months [95% CI 8.5−17.1] vs. 7.1 months [95% CI 5.7−8.8]; log rank p = 0.184). 50 patients with FGFR2 fusions/rearrangements (median age 62 years; 70% female; 94% iCCA; 70% stage IV at diagnosis) received second-line therapy. Median real-world overall survival from the index date of second-line therapy was 8.5 months (95% CI 4.1−12.4 months). Conclusions: These real-world overall survival findings did not demonstrate a survival advantage for patients with CCA and FGFR2 fusions/rearrangements vs. WT FGFR2 receiving therapies for advanced disease, although a non-significant trend towards longer overall survival was observed in patients with FGFR2 fusions/rearrangements. FGFR2 status was not a significant predictor of overall survival after adjusting for potential prognostic covariates. An additional analysis is ongoing to compare overall survival from the start of second-line therapy in patients with advanced CCA and FGFR2 fusions/rearrangements vs. those with WT FGFR2.
Important Contribution to Egyptian Medicine
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Placement of a Double-Lumen Endotracheal Tube
Authors: David Hao, Daniel Saddawi-Konefka, Sarah Low, Paul Alfille, Keith Baker
Journal: New England Journal of Medicine (2021)

Placement of a double-lumen endotracheal tube is an airway management technique that permits isolation and selective ventilation of an individual lung. This video demonstrates placement of a double-lumen endotracheal tube, which is indicated for the prevention of damage to or contamination of a healthy lung.
News Beyond Our Pages
Authors: Marc E. Rothenberg, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (2020)

In order to promote precision medicine, Kolmert et al (Am J Respir Crit Care Med. 2020 Jul 15. https://doi.org/10.1164/rccm.201909-1869oc) characterized expression of urinary lipid mediators in patients with type 2 asthma. Levels of multiple types of eicosanoids, including leukotriene E4 (LTE4) and prostaglandin D2, positively correlated with severity of asthma and type 2 inflammation. Notably, eicosanoid levels were independent of oral corticosteroid treatment status but were decreased in subjects on anti-IgE therapy.
Childhood obesity beyond COVID-19
Authors: None The Lancet Public Health
Journal: The Lancet Public Health (2021)

The global rise in childhood obesity is a serious, long-term public health challenge and one that—warns a policy briefing from the World Obesity Federation published in November, 2020—could be exacerbated by the COVID-19 pandemic response. Given how dramatically the pandemic has affected food systems, the economy, and children's daily lives over the past 2 years, the potential impact of the pandemic on childhood obesity warrants careful scrutiny and a plan to get back on track towards reducing childhood obesity as part of the pandemic recovery.
Editorial Correspondence.
Authors: John B. Hamilton
Journal: JAMA (1894)

Galesburg, Ill., May 28, 11 P.M. The Association train left Chicago via Santa Fe line promptly at 5P.M., May 28. There were ninety persons on board bound for San Francisco, as follows: J. A. Work and wife,Elkhart, Ind.; Dr. L. Duncan Bulkley, New York; J. B. Roberts, Philadelphia; C. C. Roberts and wife, Philadelphia; Miss Roberts, Philadelphia; Mrs. A. L. Massey, Philadelphia; Miss Massey, Philadelphia; Miss Willard, Philadelphia; Alonzo Garcelon and J. A. Donovan and wife. Lewiston, Me.; Allen Pierson and wife, Spen cer, Ind.; Mrs. C. A. Garcelon, Chicago; H. McColl, Lapeer, Mich.; Geo. Davenport, East Randolph, Vt.; C. S. Talbot, Chicago; G. W. Jenkins, wife and daughter, Kilbourn City, Wis.; John L. Crofts, Little Falls, N. Y.; Mrs. Katherine R. Evans and Miss S. E. Clark, West Brattleboro, Vt.; H. D. Holton and wire, Brattleboro, Vt.; C. F. Jenne and wife, Brattleboro, Vt.; Joseph Eastman and daughter,
MISCELLANY
Journal: JAMA (1952)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Functional genomics analysis identifies T and NK cell activation as a driver of epigenetic clock progression
Authors: Thomas H. Jonkman, Koen F. Dekkers, Roderick C. Slieker, Crystal D. Grant, M. Arfan Ikram, Marleen M. J. van Greevenbroek, Lude Franke, Jan H. Veldink, Dorret I. Boomsma, P. Eline Slagboom, B. I. O. S. Consortium, Bastiaan T. Heijmans
Journal: Genome biology (2022)

Abstract Background Epigenetic clocks use DNA methylation (DNAm) levels of specific sets of CpG dinucleotides to accurately predict individual chronological age. A popular application of these clocks is to explore whether the deviation of predicted age from chronological age is associated with disease phenotypes, where this deviation is interpreted as a potential biomarker of biological age. This wide application, however, contrasts with the limited insight in the processes that may drive the running of epigenetic clocks. Results We perform a functional genomics analysis on four epigenetic clocks, including Hannum’s blood predictor and Horvath’s multi-tissue predictor, using blood DNA methylome and transcriptome data from 3132 individuals. The four clocks result in similar predictions of individual chronological age, and their constituting CpGs are correlated in DNAm level and are enriched for similar histone modifications and chromatin states. Interestingly, DNAm levels of CpGs from the clocks are commonly associated with gene expression in trans . The gene sets involved are highly overlapping and enriched for T cell processes. Further analysis of the transcriptome and methylome of sorted blood cell types identifies differences in DNAm between naive and activated T and NK cells as a probable contributor to the clocks. Indeed, within the same donor, the four epigenetic clocks predict naive cells to be up to 40 years younger than activated cells. Conclusions The ability of epigenetic clocks to predict chronological age involves their ability to detect changes in proportions of naive and activated immune blood cells, an established feature of immuno-senescence. This finding may contribute to the interpretation of associations between clock-derived measures and age-related health outcomes.