tbuckley/cabot-search huggingface dataset:
Project Orbis: Global Collaborative Review Program
Authors: R. Angelo de Claro, Dianne Spillman, Lauren Tesh Hotaki, Michael Shum, Laila Sofia Mouawad, Gustavo Mendes Lima Santos, Kelly Robinson, Melissa Hunt, Caroline Healy, Agnes Chan, Yee Hoo Looi, Clare Rodrigues, Ulrich-Peter Rohr, Chantal Walther, Richard Pazdur
Journal: Clinical Cancer Research (2020)

In 2019, the FDA Oncology Center of Excellence launched Project Orbis, a global collaborative review program to facilitate faster patient access to innovative cancer therapies across multiple countries. Project Orbis aims for concurrent submission, review, and regulatory action for high-impact clinically significant marketing applications among the participating partner countries. Current Project Orbis partners (POP) include the regulatory health authorities (RHA) of Australia, Brazil, Canada, Singapore, and Switzerland. Project Orbis leverages the existing scientific and regulatory partnerships between the various RHA under mutual confidentiality agreements. While FDA serves as the primary coordinator for application selection and review, each country remains fully independent on their final regulatory decision. In the first year of Project Orbis (June 2019 to June 2020), a total of 60 oncology marketing applications were received, representing 16 unique projects, and resulting in 38 approvals. New molecular entities, also known as new active substances, comprised 28% of the received marketing applications. The median time gap between FDA and Orbis submission dates was 0.6 months with a range of -0.8 to 9.0 months. Across the program, the median time-to-approval was similar between FDA (4.2 months, range 0.9-6.9, N = 18) and the POP (4.4 months, range 1.7-6.8, N = 20). Participating countries have signified a strong commitment for continuation and growth of the program. Project Orbis expansion considerations include the addition of more countries and management of more complex applications.
Patterns of Venous Thromboembolism Prophylaxis during Inpatient Treatment of Acute Leukemia: Results of a North American Web-Based Survey
Authors: Eun-Ju Lee, B. Douglas Smith, Jessica W Merrey, Alfred I Lee, Nikolai A. Podoltsev, Lisa Barbarotta, Mark R Litzow, Thomas Prebet, Selina Luger, Steven D. Gore, Michael B. Streiff, Amer M. Zeidan
Journal: Blood (2015)
SMBE Editors and Council
Authors: Walter Fitch, Masatoshi Nei, Marcy Uyenoyama, Elizabeth Raffaele, G Golding, Richard Lewontin, Howard Ochman, Jody Hey, Ken Wolfe, Michael Lynch, Manyuan Long, John Archibald, Ziheng Yang, Dan Graur, Robin Bush
Journal: Molecular Biology and Evolution (2010)
MYOFIBROMA UTERI.
Authors: HERMANN J. BOLDT
Journal: JAMA (1900)

The greater number of solid neoplasms of the uterus are fibromyomata; tumors, consisting of fibrous connective tissue only—fibroids—or of muscle only-myoma—are comparatively rare. It is the preponderance of one or the other of these tissues in a tumor on which the consistency depends, and to some extent the rapidity or slowness of its growth. The original seat of such neoplasms is, strictly speaking, interstitial; that is, the growth takes its starting-point in the parenchyma of the uterus, and subsequently grows in the direction of least resistance; thus subserous and submucous fibromyomata are formed. Real subserous tumors are freely movable, unless they become incarcerated in the true pelvis. They rarely cause symptoms, except when they attain a large size, or become incarcerated or twisted. Interstitial tumors are of two varieties: 1, the greatest number are encapsulated and may, therefore, be readily enucleated, if the capsule be incised; 2, those which are
An Unusual Presentation of Breast Implant Rupture
Authors: Anna Hudson, Richard K. J. Brown, Satoshi Minoshima, Dell Dunn
Journal: Clinical Nuclear Medicine (2022)

A 99mTc-methylene diphosphate (MDP) bone scintigraphy scan was performed to follow up metastatic breast cancer. A circular region of radiotracer uptake in the location of the patient's left breast implant was seen. Review of the same-day chest CT and the prior CT showed that the patient's breast implant had ruptured in the interim. The 99mTc-MDP uptake in the capsule of the breast implant was attributed to rupture, likely secondary to inflammation. This is an example of an unusual presentation of breast implant rupture discovered on a 99mTc-MDP bone scintigraphy scan.
Saliva RT-PCR Sensitivity Over the Course of SARS-CoV-2 Infection
Authors: Anne L. Wyllie, Prem K. Premsrirut
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 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
Incorrect Data Reported in Text and Figure in: Comparison of Conventional-Dose vs High-Dose Conformal Radiation Therapy in Clinically Localized Adenocarcinoma of the Prostate: A Randomized Controlled Trial
Authors: Anthony Zietman
Journal: JAMA (2008)

data was needed.All of the original data had been collected, stored, and analyzed by the statistics department of the American College of Radiology (ACR).For one secondary analysis, the raw data were obtained from the ACR and the original Kaplan-Meier analysis of cancer-free survival was rerun.This outcome had been defined as freedom from 3 successive increases in the level of prostate-specific antigen (PSA).We were unable to reproduce the curves reported in the JAMA article and brought this to the attention of the ACR statisticians.They traced the problem to an error in the definition of PSA failure coded in the computer program.Although the primary outcome of the study was biochemical failure defined as 3 successive increases (as indicated in the "Methods" section of the article), the computer code identified any 3 increases as biochemical failure.This erroneously identified additional patients as "failures" along with those correctly classified.The data have now been reanalyzed using the correct definition.The risk of biochemical failure is lower in both arms of the trial than originally reported, although the differences between the 2 arms remain statistically significant.In the post hoc subgroup analyses, the risk reduction is no longer statistically significant for the higher-risk subgroup of patients overall but remains significant for the intermediate-risk subgroup.On behalf of my research team, I apologize to the JAMA editors and readers for the errors in our study and for any inconvenience caused by the publication of these incorrect data.
The prognostic value of stress technetium-99m sestamibi gated single photon emission computed tomography in patients with dilated cardiomyopathy Carol Y. Gemayel, Vijay K. Verma, Muthu Velusamy, April Mann, Deborah Katten, Alan Ahberg, Jeff Mather, Gary V. Heller. Hartford Hospital, Hospital, CT
Journal: Journal of the American College of Cardiology (2001)
Anti-HER2 therapy with pyrotinib and trastuzumab in refractory HER2-positive metastatic colorectal cancer: A preliminary report from HER2-FUSCC-G study.
Authors: Wenhua Li, Jinjia Chang, Midie Xu, Xiaodong Zhu
Journal: Journal of Clinical Oncology (2022)

97 Background: Dual-targeted HER2 therapy has led to a promising antitumor effect in HER2 positive metastatic colorectal cancer. The current study was aimed to evaluate the therapeutic efficacy of pyrotinib and trastuzumab in patients with HER2 positive colorectal cancer. Methods: HER2-FUSCC-G is an ongoing, open-label, non-randomised, phase 2a study. Patients in this subset were diagnosed as HER2 positive metastatic colorectal cancer refractory to standard chemotherapies. All the enrolled patients were treated with a loading dose of trastuzumab at 8 mg/kg followed by 6mg/kg once every three weeks, and oral pyrotinib at 400 mg per day until progression. ORR was set as the primary endpoint. Estimates of PFS (progression free survival) and OS (overall survival) were obtained with the Kaplan-Meier method and compared with log-rank test. Results: Between January 2020 to June 2021, 11 patients were enrolled in this study. The ORR was 45.5% in whole population, and 55.6% in RAS wild-type patients. At a median follow-up of 17.73 months, median PFS and OS were 7.80 and 14.97 months, respectively. The KRAS wild-type group of patients had prolonged survival (PFS: 9.97 vs. 7.73 months, P = 0.19; OS: 20.67 vs. 12.43 months, P = 0.021) compared with KRAS mutant group. Nine of 11 (81.8%) patients reported≥1 grade treatment-emergent adverse events (TATEs), while 4 (36.4%) patients reported grade 3/4 TATEs. Conclusions: The combination of trastuzumab and pyrotinib showed a promising anti-tumor response and prolonged long-term survival benefit in RAS wild-type and HER2 positive mCRC with acceptable tolerance. Clinical trial information: NCT04960943.
Prognostic effect of RAS/BRAF mutations in patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Haisam Abid, Aniko Szabo, Bradley W. Taylor, Aditya V. Shreenivas, Sakti Chakrabarti, Mandana Kamgar, James P. Thomas, Ben George
Journal: Journal of Clinical Oncology (2022)

191 Background: Somatic alterations in KRAS and BRAF have prognostic as well as predictive impact in pts with mCRC; however, the differential impact of various somatic alterations in these genes need further characterization. We analyzed the prognostic impact of specific somatic mutations in K RAS and BRAF in mCRC pts. Methods: We retrospectively reviewed the electronic medical records of pts with mCRC at our institution who underwent comprehensive genomic profiling (CGP) utilizing the Foundation One assay. Prevalence of genetic alterations was estimated using proportions and compared between groups using a chi-squared test. Patients were followed for survival from metastatic diagnosis until death or last follow-up, with left truncation at the time of CGP. Kaplan-Meier estimates were used to estimate overall survival, and groups were compared using a Cox-regression based likelihood ratio test. Results: 192 pts were identified - median age at diagnosis was 55 years, 62% (119/192) presented with metachronous metastatic disease, and 28% (54/192) had a rectal primary. Somatic mutations in KRAS were found in 49% (95/192) pts, and 53% (50/95) had a left sided primary (p = 0.3). Majority of the KRAS mutations localized to codon 12 (72/95 -76%), KRAS G12C comprised 12% (11/95). Median Overall Survival (mOS) of KRAS mutated pts was 3.0 years compared to 3.5 years for KRAS wild type (WT) pts (p = 0.5). Median OS of pts with different KRAS mutations were as follows: codon 12 mutations (excluding G12C) - 2.7 years; KRAS G12C – 5.2 years; non-codon 12 KRAS mutations - 4.8 years. BRAF mutations were identified in 7.8% (15/192) pts, and 67% (10/15) had a right sided primary (p = 0.062). BRAF V600E represented the most common alteration in BRAF – 87% (13/15). Patients with BRAF mutation had a mOS of 1.8 years compared to 3.1 years for BRAF WT pts (p = 0.2). Median OS of pts with different BRAF mutations were as follows: BRAF V600E – 1.8 years and BRAF non V600E - 2.1 years (p = 0.4). Conclusions: The numerically higher mOS in pts with KRAS G12C and non-codon 12 KRAS mutations merit further biologic characterization with functional assays. Individualized therapeutic strategies must be conceptualized for mCRC pts with specific RAS/BRAF mutations, considering their widely disparate prognosis and putative downstream signaling mechanisms. Dynamic molecular simulation to understand conformational changes in proteins associated with specific mutations will be pivotal to optimizing precision therapeutic strategies.
A Rare Case of Pituitary Carcinoma With Bone Metastases
Authors: Nuh Filizoglu, Salih Ozguven
Journal: Clinical Nuclear Medicine (2022)

Abstract Pituitary carcinomas are extremely rare and aggressive tumors that comprise only 0.2% of all pituitary tumors. Because of its rarity, pituitary carcinomas are difficult to diagnose. Conventional imaging methods are inadequate to detect metastatic lesions. Pituitary carcinomas are neuroendocrine tumors and express somatostatin receptors; therefore, 68 Ga-DOTATATE PET/CT may be used in the staging of these rare tumors. Herein, we present an exceptional case of pituitary carcinoma with sclerotic skeletal metastases showing 68 Ga-DOTATATE uptake.
PARIS LETTER.
Authors: None A. B.
Journal: JAMA (1885)

Paris, Jan. 9, 1885. In his thesis for the doctorate, " On the Conditions for Surgical Intervention in the External Localizations of Tuberculosis," Dr. Coudray formulates certain rules which the surgeon might attend to with advantage to himself as well as to his patient. In a general way, the author states that external tuberculoses necessitate intervention only in such cases as do not present a spontaneous tendency to cure. The natural tendency to cure, which is frequent in a certain class of patients, constitutes, on the contrary, the exception with those who frequent the hospitals. The formation of secondary foci, consecutive to operations, may be considered a rare circumstance, if not exceptional. The doctrine of auto-inoculation, according to the same author, is no argument against intervention. The rule by which a tuberculous lesion should be removed as soon as it becomes a cause of wasting debility, is, according to Dr. Coudray,
Changes Reflecting Corrections to Related Article
Authors: Nora Pashayan, Paul Pharoah
Journal: JAMA Oncology (2022)

We disagree with the statement that polygenic risk score (PRS) must differentiate between incident and lethal cancers to be used as a risk stratifier in population-based cancer screening programs.To reduce cancer death, a screening program first needs to detect cancer.By identifying the subgroup of the population at higher risk for cancer, screening could be targeted to those more likely to derive benefits from screening (ie, those who are more likely to have cancer), and subsequently more cancer deaths could be prevented among this subgroup receiving screening, even when the relative mortality reduction associated with screening does not vary by risk.At a population level, with less screening, there would be fewer false findings and fewer overdiagnoses.Population-based breast cancer screening programs use age for risk stratification and targeted screening.Combining age with PRS and other risk factors further refines the risk stratification and promises to improve the benefit-harm tradeoff of screening for breast cancer.There are ongoing personalized breast cancer screening trials 3-5 that would generate empirical evidence on the benefits and harms of risk-based screening and provide empirical data to inform whether and how overdiagnosis varies by risk.To address our errors and the related concerns, we have reestimated overdiagnosed cases with the assumption that a fixed proportion of the screen-detected cases are overdiagnosed, whatever the prior risk.This results in corrections to the numbers of overdiagnoses reported in the Abstract, Results, Table , Figure 1, and eTable 2 in the Supplement of our original article. 2 These corrections do not change the article's conclusions or interpretations that "not offering breast cancer screening to women at lower risk could improve the cost-effectiveness of the screening program, reduce overdiagnosis, and maintain the benefits of screening." 2(p.
Dose-dependent effects of folic acid on plasma homocysteine levels among 723 individuals with coronary heart disease: the PACIFIC study Bruce Neal, Stephen MacMahon, Andrew Tonkin, Nicholas Dudman, David Hunt, Mark Richards, John Simes, David Wilcken, Alan Brnabic, Judy Murphy, Yvonne Cleverley, on behalf of the PACIFIC study collaborative group. Institute for international health, Sydney, Australia
Journal: Journal of the American College of Cardiology (2001)
Trajectories of Blood Pressure in Midlife Women: Does Menopause Matter?
Authors: Saad Samargandy, Karen A. Matthews, Maria M. Brooks, Emma Barinas-Mitchell, Jared W. Magnani, Rebecca C. Thurston, Samar R. El Khoudary
Journal: Circulation Research (2022)

Whether changes in blood pressure (BP) over women's midlife are more driven by chronological aging or the menopause transition has been debated. We sought to determine whether women can be classified into distinct trajectory groups based on pattern and level of systolic BP (SBP), diastolic BP, pulse pressure (PP), and mean arterial pressure (MAP) over the menopause transition, and to assess whether menopause-related factors predict the group and level of BP measures.Participants were from the SWAN (Study of Women's Health Across the Nation). Group-based trajectory modeling was used to identify women who shared distinct BP trajectories over time relative to menopause onset and to assess associations of menopause-related factors with trajectory group and level of BP measures. An accelerated rise relative to menopause onset suggests a menopause contribution.The study included 3302 multiracial and multiethnic women with BP measures over 17 follow-up visits (baseline age [SD]: 46.3 [2.7]). Women were classified into either low, medium, or high trajectory group in each BP measure. The low SBP, PP, and MAP trajectories (in 35%, 53%, and 28% of the cohort, respectively) were rising slowly before menopause but showed a significant accelerated rise 1 year after menopause, indicating a menopause contribution. The remaining BP trajectories were rising up until menopause and either continued with the same rise or declined after menopause. A younger menopause age predicted the low SBP, PP, and MAP trajectories. A greater follicle-stimulating hormone level predicted lower SBP and PP levels, while vasomotor symptoms occurrence predicted higher SBP, PP, and MAP levels over time. Estradiol did not predict trajectory or level of any BP measure.Distinct BP trajectories over the menopause transition exist that revealed a group of women whose SBP, PP, and MAP trajectories are consistent with a menopause contribution. Our findings support frequent monitoring of BP during the menopause transition.
Poorly differentiated histology as a predictive biomarker in patients with advanced gastrointestinal (GI) cancers treated with immunotherapy.
Authors: Amber Draper, Emily Jung, Yichun Cao, Rami Atallah, Jeffrey M. Switchenko, Olatunji B. Alese
Journal: Journal of Clinical Oncology (2022)

664 Background: Checkpoint inhibitors (CPI) have significantly improved survival among patients with various cancer types. Prior studies have showed a correlation between immune cell infiltration and poorly differentiated cancers. We evaluated the impact of poorly differentiated histology on survival in patients with advanced GI malignancies treated with immunotherapy. Methods: We performed a retrospective, single institution analysis of patients with poorly differentiated GI tumors treated with CPI between 2016 and 2021. Univariate (UVA) and multivariable analyses (MVA) were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor/patient characteristics, progression free survival (PFS) and overall survival (OS). Results: A total of 123 patients were included. Median age was 66years. Majority had stage IV disease (88.2%), were White (65.5%) and male (64.5%). Most common diagnoses were HCC (28.5%), gastric (15.4%) and esophageal (14.6%) adenocarcinomas. About 32% were MSI-H, with 10% BRAF mutation rate. About 25% received CPI as initial treatment and 35.5% received 2 or more prior lines of therapy. Compared with well and moderately differentiated histology, poorly differentiated tumors had shorter mPFS (3.4 vs 2.5 vs. 2.2months; p = 0.29) and mOS (not reached [NR] vs. 20.9 vs. 14.2 months; p = 0.14) respectively. On UVA, the degree of tumor differentiation did not correlate with mPFS or mOS. Female patients (HR: 0.55, CI: 0.34-0.90, p = 0.018) and ECOG of 1 vs. ≥2 had significantly longer mPFS (HR: 0.58, CI: 0.35-0.97, p = 0.036). ECOG 1 correlated with better mOS (HR: 0.47, CI: 0.23-0.94, p = 0.034). Microsatellite stable (MSS) tumors had significantly shorter mPFS (HR: 5.74, CI: 2.41-13.63, p &lt; 0.001) and mOS (HR: 5.45, CI: 1.64-18.12, p = 0.006). Number of prior systemic therapies was also associated with shorter mPFS (HR: 1.19, CI: 1.03-1.39, p = 0.022) and mOS (HR: 1.23, CI: 1.01-1.50, p = 0.045). On MVA, ECOG status of 0/1 vs. ≥2 and MSI-H vs. MSS remained significantly associated with longer mPFS and mOS. There was no correlation with race or mutations such as BRAF or KRAS. Conclusions: Poorly differentiated histology did not predict for PFS or OS. Treatment naïve patients, female gender, ECOG 1 and MSI-H were most likely to benefit from CPI.
Update to living systematic review on drug treatments for covid-19
Journal: BMJ (2020)

Update to living systematic review on drug treatments for covid-19This living systematic review by Siemieniuk and colleagues (BMJ 2020;370:m2980) has been updated.For the latest update, visit doi:.The latest version of this living systematic review includes results for new interventions azithromycin, colchicine, interferon beta, interferon gamma, interferon kappa plus trefoil factor 2, rhG-CSF, tocilizumab (but certainty is low or very low); evidence that remdesivir may not reduce mortality (low certainty) or time to symptom resolution (moderate certainty); evidence that glucocorticoids probably reduce length of ICU stay (low certainty) and increase ventilator-free days (moderate certainty).
Medical Education, Registration and Hospital Service
Journal: JAMA (1926)

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