tbuckley/cabot-search huggingface dataset:
Results from MAGENTA: A national randomized four-arm noninferiority trial evaluating pre- and post-test genetic counseling during online testing for breast and ovarian cancer genetic risk.
Authors: Elizabeth M. Swisher, Nadine Rayes, Deborah Bowen, Christine B Peterson, Tara Coffin, Barbara Norquist, Kathleen Gavin, Deborah Polinsky, Jamie Crase, Jamie Nadine Bakkum-Gamez, Stephanie V. Blank, Mark F Munsell, Denise R Nebgen, Harsha Pradeep, Sherman Law, Olufunmilayo I. Olopade, Alicia Zhou, Douglas A. Levine, Alan D. D'Andrea, Karen H. Lu
Journal: Journal of Clinical Oncology (2020)

1506 Background: Hereditary breast and ovarian cancer (HBOC) is preventable when genetic risk is identified. We aimed to test whether pre and/or post-test genetic counseling is needed to optimally deliver online accessible genetic testing. Methods: MAGENTA (Making GENetic Testing Accessible) is a four-arm non-inferiority trial evaluating electronic genetic education and results delivery alone or combined with pre-test only, or post-test only telephone genetic counseling compared to mandatory pre- and post-test counseling (control arm) in women at risk of HBOC (NCT02993068). Regardless of assigned arm, all subjects with a pathogenic mutation received post-test telephone counseling. All subjects were enrolled electronically as part of either a family history cohort (FHC) or a cascade cohort (CC, known familial mutation). The primary outcome was cancer risk distress at 3 months and the trial was powered for the FHC. Secondary outcomes included completion of testing (i.e., received results), anxiety, depression, quality of life, and decisional regret, all measured by standardized scales. Results: Enrollment is complete and a total of 3,822 participants were randomized, 3,111 in FHC and 711 in CC. Participants were enrolled from all 50 states, but most were white/non-Hispanic (88%). Among participants that completed genetic testing, 173 (7.2%) had a mutation in a breast or ovarian cancer gene, with 114 (5.7%) of FHC and 59 (14.2%) of CC. In the primary intention-to-treat analysis of FHC, each of the three experimental arms was non-inferior to the control arm for distress at 3 months (p &lt; 0.025/3 = 0.0083). In the CC, no and pre-test only counseling were also non-inferior (p &lt; 0.025/3 = 0.0083). Distress was lowest in the arm with neither pre nor post-test counseling. Overall, 318 (18%) participants had very high distress at three month follow-up, and this rate was not significantly different across arms. Anxiety, depression and decisional regret did not have statistically significant differences across arms at follow-up. Test completion was highest in the no counseling arm (86.4%) and lowest in the control arm (60.6%). Conclusions: Electronic genetic education and results release without genetic counseling was non-inferior with regard to patient distress and was associated with higher test completion and lower distress. These results support use of a genetic testing paradigm providing individualized genetic counseling only for patients with positive test results. Clinical trial information: NCT02993068.
Can a Structured, Electronic Approach to Shared Decision-making Increase Attempted Trial of Labor?
Authors: Geeta K. Swamy, Chad A. Grotegut
Journal: JAMA (2020)

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
Relationship of uric acid levels with clinical outcomes in severe ischemic stroke patients treated with intravenous recombinant tissue plasminogen activator
Authors: Youyu Lin, Zhiping Hu, Yinhui Huang, Yafang Chen, Ruowei Cai, Jinying Zhang
Journal: BMJ (2016)

One hundred and seventy six consecutive patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator(rt-PA) in 4.5 hours from symptom onset during February 2009 to July 2013 were included in the study. Modified Rankin Scale was used to evaluate the recovery of neurological functions. Patients were divided into good (0-1) or poor (2-6) outcome groups according modified Rankin Scale score. Univariate analysis and multivariate logistic regression analysis were used to determine the differences of clinical data between the two groups. The age of patients with good outcome was significantly lower than that of poor outcome group [(61.4±11.5) vs. (69.0±13.2) years, P=0.000]. Compared to patients with poor outcomes, patients with good outcome group showed lower rate of diabetes[ 13%(12/93) vs. 29%(24/83), P=0.009], lower blood glucose level [(5.05±0.97) vs. (5.83±1.72) mmol/L, P=0.020], higher uric acid level[(404.4±151.7) vs. (345.6±107.5) μmol/L, P=0.028], shorter onset to treatment time [(1.92±0.94) vs. (2.30±1.01) h, P=0.019], lower baseline National Institute of Health Stroke Scale score [(14.0±5.2) vs. (16.0±6.2), P=0.025], lower systolic blood pressure level at 2 h[(140.8±18.3) vs.(149.0±18.9) mmHg(1 mmHg=0.133 kPa), P=0.005]and 24 h [(137.6±21.9) vs. (147.1±17.4) mmHg, P=0.009]after thrombolysis. Logistic regression analysis showed that uric acid levels were not related to hemorrhagic transformation independently (P=0.172, OR=0.965, 95%CI: 0.917-1.016), but were related to outcome independently (P=0.047, OR=0.957, 95%CI: 0.916-0.999).


Key words: 
Uric acid, blood; Tissue plasminogen activator, recombinant; Stroke, ischemic
Prognostic differences of RAS mutations: Results from South Australian (SA) metastatic colorectal (mCRC) registry.
Authors: Timothy Jay Price, Cynthia Piantadosi, Amanda Rose Townsend, Rob Padbury, Amitesh Chandra Roy, James Moore, Guy Maddern, David Roder, Christos Stelios Karapetis
Journal: Journal of Clinical Oncology (2020)

4067 Background: Effective targeting of RAS mutations has proven elusive until recently. AMG 510, a novel agent which targets KRAS G12C mutations (G12C MT), has shown promise in early phase clinical trials that included patients with mCRC. Prior reports have suggested that G12C MT may be predictive of poor outcome. Methods: We aimed to assess the prognostic implications of individual RAS in a population-based registry. The SAmCRCR collects data from all patients diagnosed with mCRC in South Australia prospectively. Individual RAS mutation data from patients entered into the SAmCRCR between February 2006 and December 2018 was reviewed. Survival was analysed for the more frequent mutations using Kaplan Meier method. Results: 1605 (33%) of the 4905 patients entered onto the registry had RAS mutation results available. Of these, 658 (41%) had RAS MT. The nature of the RAS MT was available in 563 (85.7% of those with RAT MT). Patient characteristics, frequency of individual RAS MT and median overall survival (OS) per RAS MT are noted in table. Low frequency MT made up an additional 16.3%. There were numerical differences in survival however there was no statistical difference in survival when comparing the various RAS MT, including the comparison of G12C to G12S (p = 0.38). Conclusions: Whilst the G12S mutation was associated with the longest survival numerically, the observed survival for patients with the most common RAS mutations (G12C, G12V, G12A, G12D and G13D) did not significantly differ. [Table: see text]
Long-term follow-up of BMT CTN 0702 (STaMINA) of postautologous hematopoietic cell transplantation (autoHCT) strategies in the upfront treatment of multiple myeloma (MM).
Authors: Parameswaran Hari, Marcelo C. Pasquini, Edward Allen Stadtmauer, Raphael Fraser, Mingwei Fei, Steven Michael Devine, Yvonne Adeduni Efebera, Nancy Geller, Mary M. Horowitz, John Koreth, Heather Jolie Landau, Philip L. McCarthy, Muzaffar H. Qazilbash, Nina Shah, David H. Vesole, Dan T. Vogl, George Somlo, Amrita Y. Krishnan, Sergio Giralt
Journal: Journal of Clinical Oncology (2020)

8506 Background: STaMINA was a phase III trial comparing progression-free survival (PFS) among 758 pts randomized to: 1. second autoHCT then lenalidomide (Len) maintenance (Auto/Auto, n = 247); 2. consolidation with Len/bortezomib/ dexamethasone (RVD) followed by Len maintenance (Auto/RVD, 254); 3. Len maintenance (Auto/Len, 257). All three arms were similar (Stadtmauer JCO 2018). Len maintenance was designed to continue for 3 years and amended to allow continuation until disease progression through a follow up protocol (07LT, NCT#02322320). We report 6 yr follow up for STaMINA and the results of Len discontinuation beyond 3 years. Methods: 07LT was offered to pts who were progression-free at 38 mo; completed planned Len maintenance and were within 4 years of BMT CTN 0702 follow up. Among 431 07LT eligible patients, 273 enrolled and 179 opted to continue maintenance until disease progression. All patients enrolled in STaMINA were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) and long-term outcomes for patients not enrolled on 07LT (N = 166) were available through this mechanism. Before combining 07LT data and CIBMTR data for LTFU analysis, outcomes in both databases were analyzed separately and confirmed to be comparable. Results: Using intent-to-treat (ITT), 6yr PFS and overall survival (OS) was the same among Auto/Auto (43.9%; 73.1%), Auto/RVD (39.7%, 74.9%) and Auto/Len (40.9%, 76.4%)(p = 0.6; p = 0.8). Protocol defined high risk disease, (HR = 1.53, p &lt; 0.0001) and age (p = 0.03) were adverse risks for PFS. In as treated analysis, 6yr PFS were 49.4%, 39.7% and 38.6% for Auto/auto (170), Auto/RVD (222) and Auto/Len (361), respectively (p = 0.01). 6yr PFS in high risk pts as treated analysis were 43.6% and 26% for Auto/auto and Auto/Len, respectively (p = 0.03). Landmark analysis at 38 mo included 215 pts who continued Len maintenance (either on 07LT study or commercial Len) vs. 207 who stopped. Baseline demographics; study arm on 0702, induction pre-autoHCT were similar. Len discontinuation after 38 mo was associated with inferior PFS (79.5% vs. 61% at 5yr; HR = 1.91, p = 0.0004) but similar OS. Incidence of all second primary malignancies (SPM)(81 cases with 43 heme-malignancies) was associated with age. Conclusions: Long term outcomes are similar using ITT, but as treated analysis suggested a PFS benefit for tandem autoHCT, driven mainly by pts with high risk MM. Len discontinuation even at 38 mo was associated with inferior PFS. Clinical trial information: NCT02322320 .
Characterization of the immune tumor microenvironment of HER2-positive breast cancer following treatment with entinostat and immune checkpoint inhibition.
Authors: Evanthia T. Roussos Torres, Dimitrios N Sidiropoulos, Emily Davis-Marcisak, Luciane Tsukamoto Kagohara, Roisin M. Connolly, Vered Stearns, Elizabeth M. Jaffee, Elana J. Fertig
Journal: Journal of Clinical Oncology (2020)

e15061 Background: HER2+ breast cancers are known to be less-immunogenic and associated with low response rates to immune checkpoint inhibitors (ICIs). A combination of immunosuppressive signals that prevent cytotoxic T cells from infiltrating the tumor microenvironment (TME) and, low tumor antigen expression, contribute to immunotherapy resistance in this population. Epigenetic modulators can both reexpress tumor antigens and rewire the immunosuppressive environment. We previously used a histone deacetylase inhibitor, entinostat (ENT), in combination with ICIs to reverse the immunosuppressive TME and increase tumor antigen expression in a NeuN HER2+ mouse model of breast cancer. Our results showed that ENT in combination with anti-PD-1, anti-CTLA-4, provided a significant survival benefit compared to either treatment alone. Methods: This current study employs single cell RNA-sequencing on whole tumor samples from mice treated with ICIs and entinostat to investigate the role of epigenetic inhibitors in rewiring the expression of tumor antigens and the cellular landscape of the TME. We generate single cell data over 54,000 cells from 20 tumors treated with entinostat alone or in combination with anti-PD1 and anti-CTLA4 and their combination. Results: Analysis of cells in the TME identifies consistent proportion of monocytes, macrophages, T-cells, Myeloid Derived Suppressor Cells (MDSCs) and Cancer Associated Fibroblasts (CAFs) before and after treatment. Differential expression analysis within the cell types identifies distinct subpopulations and we explore those that are either proportionally higher or lower in each treatment group. Notably, pathway analysis on differentially expressed genes of each cell type identified that combination entinostat and checkpoint treatment increased T cell activation, leukocyte proliferation, myeloid leukocyte and neutrophil migration, and decreased Wnt signaling and histone modifications in tumor cells. These results are being corroborated in patient samples from a parallel clinical trial to provide translational relevance. Conclusions: Our current work provides insights into the transcriptional network within a breast tumor after treatment with ENT+ICIs. We predict our findings will bring us closer to identifying additional therapeutic targets and ultimately improve survival rates of patients with less-immunogenic tumors.
Diagnosis and treatment of patients with esophageal perforation and rupture
Authors: Guo-wen Wang, Zu-yi Wang, Tao Tao, Xue-gang Liu, Zhen Tang
Journal: BMJ (2013)

We retrospectively analyzed the clinical data of 17 patients with esophageal perforation and rupture from August 2007 to December 2011. Among them, there were spontaneous esophageal rupture (n=6), esophageal perforation caused by foreign bodies (n=8) and iatrogenic injury (n=3). Family members gave up treatment because of critical illness (n=2), conservative treatment was offered for surgical intolerance (n=1) and all others (n=14) underwent operation (thoractomy, n=13; neck incision, n=1). One patient with conservative treatment and another two surgical cases died. The other 12 cases recovered. Therefore individualized treatment is essential for the patients with esophageal perforation and rupture.


Key words: 
Esophageal perforation; Esophageal rupture
艾滋病合并弓形虫脑病37例临床分析
Authors: 李品银, 张金桥
Journal: BMJ (2010)

艾滋病(AIDS)是世界性的公共卫生问题和社会问题,已对人类生存和发展构成严重威胁,AIDS患者并发各种机会性感染是就诊、入院、死亡的重要原因.弓形虫脑病是中枢系统并发症其中之一,可为原隐匿感染的激活,亦可为原发感染[1].本研究回顾性分析我院收治的37例AIDS并弓形虫脑病的临床资料,探讨其临床特点及转归,以提高对本病的认识。
A phase Ib, open-label, dose-escalation trial of naptumomab estafenatox (Nap) in combination with durvalumab (MEDI4736) in subjects with selected advanced or metastatic solid tumors.
Authors: Ravit Geva, Corinne Maurice-Dror, Mor Tal Moskovitz, Eitan Ben-Ami, Ari Raphael, Ilana Lorber, Marcel Rozencweig, Talia Golan
Journal: Journal of Clinical Oncology (2020)

TPS3160 Background: Immunotherapy with the anti-PD-(L)1 checkpoint inhibitors (CPIs) has been largely ineffective in so-called non-immunogenic “cold tumors”. Facilitating T cell infiltration is necessary to invoke an immune response which may be augmented or complemented by the activity of CPIs like durvalumab. Selective T cell Redirection Proteins (STRs) are fusion proteins that consist of genetically engineered Superantigen (Sag) linked to Fragment antigen binding (Fab) moieties directed to tumor-associated antigens. Nap is a first in class STR compound, recognizing the tumor-associated oncofetal antigen 5T4, whereas the SAg moiety selectively engages the T cell receptor β variable (TRBV) 7-9. Nap has been shown to induce specific T cells expansion, activation and infiltration into the tumor in pre-clinical and clinical studies. Pre-clinical data demonstrated that the combination of STR with CPI may lead to long term durable responses not possible in most patients receiving single agent CPI therapy and suggests that combining CPIs with STR may be a promising therapeutic strategy for patients with solid tumors. Methods: Patients will be treated with the combination of Nap and durvalumab using a flat dose of durvalumab (1120 mg) and the 3+3 design for Nap dose escalation (2, 5, 10, 15 and 20 mcg/kg). The MTD of Nap for the combination treatment will be established based on DLTs occurring during the first treatment cycle. The dose escalation part will be followed by MTD expansion cohort in which 10–15 patients will be treated with MTD of Nap and 1120 mg durvalumab (Clinical trial registry number NCT03983954). Major eligibility criteria include patients with pretreated advanced or metastatic, 5T4 expressing solid tumors, including patients previously progressed on CPI therapy. As of January 2020, enrollment to dose levels 2, 5 and 10 mcg/kg has been completed without DLT, enrollment to dose level 15 mcg/kg will start on February 2020. Clinical trial information: NCT03983954 .
超声心动图评价胸腔积液抽液前后的心脏结构和功能
Authors: 宋维, 方平, 李兵, 谭跃萍, 周长林, 袁志忠, 林继军
Journal: BMJ (2004)

采用多普勒超声仪评价71例不同量及不同部位胸腔积液患者抽液前后的心脏结构和功能.提示双侧大量胸腔积液对心脏结构和功能可产生明显影响;右侧胸腔不仅对右心结构和功能产生明显影响,且对左心功能有影响;左侧胸腔积液主要对左心结构和功能产生影响,抽液后明显改善。
中西医结合治疗中心性浆液性脉络膜视网膜病变66例
Authors: 温安东, 聂翔
Journal: BMJ (2007)

中心性浆液性脉络膜视网膜病变(简称中浆)是临床常见的眼底病,目前尚无有效的方法治疗和预防复发.根据中医理论及现代医学对本病的认识,自2002年10月至2004年6月,我们拟定了五苓四物汤加西药治疗本病,并设西药组作为对照进行疗效比较。
National evidence-based oncology navigation metrics: <i>Multisite exploratory study to demonstrate value and sustainability of navigation programs</i>.
Authors: Tricia Strusowski, Danelle Johnston
Journal: Journal of Clinical Oncology (2020)

e14040 Background: As evidence guides practice, it is essential for navigation programs to identify core metrics and standardize data collection to demonstrate program outcomes. Through extensive literature review three main areas of measurements have been defined as patient experience (PE), clinical outcomes (CO), and business performance or return-on-investment (ROI) metrics. To advance the field towards the goal of standardized metrics, a team from Academy of Oncology Nurse &amp; Patient Navigators (AONN+), American Cancer Society (ACS), and The Chartis Group, Chartis Oncology Solutions Practice conducted a first of its kind pilot study to assess the extent to which navigation programs could implement 10 of the 35 AONN+ national evidence-based metrics with the goal of validating these metrics and establishing benchmarks. Methods: Using a mixed methods approach, the study team selected eight sites to collect the metrics over a six-month period. Metrics data were uploaded into the ONC iQ NAV metrics cloud-based business intelligence platform to create participant-specific dashboards. Prior to study launch, sites also submitted three years of historical data, as available. Qualitative data on facilitators and barriers to metrics. Results: The following are the results of the study, (total patients navigated 4682). 10,295 total barriers identified, 2.2 barriers/pt. Time to treatment decreased by 11 days (initial 57 days decreased to 43 days). Readmission rates decreased: 30-day readmission 10.8%-9.8%, 60-day readmission 15.5%-14.3%, 90-day readmission 17.9% - 16.3%. Psychosocial distress screens: 1,987 completed (42% of patients screened). Social support referrals: 0.4/patient. Palliative care referrals: 687 pts. 15%. Satisfaction/Patient Experience survey: discuss goals 82%, encouraged participation in decisions 90%, listened to your needs 82%, listen to emotional concerns 82%, assisted with additional needs 74%. Conclusions: Further research will be needed in navigation metrics.
Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice
Authors: Kevin M. Huang, Alix F. Leblanc, Muhammad Erfan Uddin, Ji Young Kim, Mingqing Chen, Eric D. Eisenmann, Alice A. Gibson, Yang Li, Kristen W. Hong, Duncan DiGiacomo, Sherry H. Xia, Paola Alberti, Alessia Chiorazzi, Stephen N. Housley, Timothy C. Cope, Jason A. Sprowl, Jing Wang, Charles L. Loprinzi, Anne Noonan, Maryam B. Lustberg, Guido Cavaletti, Navjot Pabla, Shuiying Hu, Alex Sparreboom
Journal: Journal of Clinical Investigation (2020)

Peripheral neurotoxicity is a debilitating condition that afflicts up to 90% of patients with colorectal cancer receiving oxaliplatin-containing therapy. Although emerging evidence has highlighted the importance of various solute carriers to the toxicity of anticancer drugs, the contribution of these proteins to oxaliplatin-induced peripheral neurotoxicity remains controversial. Among candidate transporters investigated in genetically engineered mouse models, we provide evidence for a critical role of the organic cation transporter 2 (OCT2) in satellite glial cells in oxaliplatin-induced neurotoxicity, and demonstrate that targeting OCT2 using genetic and pharmacological approaches ameliorates acute and chronic forms of neurotoxicity. The relevance of this transport system was verified in transporter-deficient rats as a secondary model organism, and translational significance of preventive strategies was demonstrated in preclinical models of colorectal cancer. These studies suggest that pharmacological targeting of OCT2 could be exploited to afford neuroprotection in cancer patients requiring treatment with oxaliplatin.
Analysis of 31 cases with ribs fracture combined with delayed hemothorax
Authors: Run-qing Zhan, Wen-feng Zhang, Shi-jie Li
Journal: BMJ (2011)

The clinical data of 31 patients with delayed hemothorax between August 2003 to November 2010 was retrospectively analyzed. All patients had chest pain, difficult breathing in 14 cases (45％), heart rate increased in 19 patients (61％), fever in 16 cases (52％), abdomen pain in 3 patients (10％), and shock in 1 case (3％). Haemothorax was medium to massive and combined with pneumothorax in 9 cases. Twenty one patients received closed chest drainage, 4 recieved chest puncture to eliminate fluid, 5 were treated conservatively, and 1 had surgery for diaphragmatic hernia and hemorrhage.All patients recovered eventually. The key of diagnosis and treatment for delayed hemothorax is to take chest X-ray for patients with rib fractures in 2 to 9 days after chest trauma, and carefully observing the changes of chest signs, breathing, heart rate and body temperature.

Key words: 
Rib fractures;  Hemothorax