tbuckley/cabot-search huggingface dataset:
Neurotoxicity preventive effect of oxaliplatin with lipoic acid plus sodium potassium magnesium calcium and glucose injection
Authors: Ran Lyu, Yongjie Li, Qingliang Feng
Journal: BMJ (2014)

A total of 218 patients on chemotherapeutic regimens containing oxaliplatin were randomly divided into experimental (n=120) and control (n=98) groups. The experimental group received an intravenous infusion of lipoic acid plus sodium potassium magnesium calcium and glucose injection. The control group had only normal saline. Overall incidence of neurotoxicity and toxicity grade of peripheral nerve were observed after 4, 8 and 12 cycles. Those with neurotoxic symptoms were followed up for 1 year. No significantly statistical difference existed in the incidence of peripheral neurotoxicity after 4, 8 cycles (P>0.05). After 12 cycles, 31 patients in the experimental group had an onset of neurotoxicity of grade 3 (n=8, 6.7%) & grade 4 (n=0) versus 21 cases of grade 3 (n=21, 21.4%) and grade 4 (n=5, 5.1%) in the control group. Statistically significant differences existed between grades 3 and 4 neurotoxicity (P<0.05). After 1 year of follow-up, the incidence of grade 1 of neurotoxicity was 2.5% (n=3) in the experimental group versus 23.7% (n=9) in the control group. And the inter-group difference was statistically significant (P<0.05). Lipoic acid plus sodium potassium magnesium, calcium and glucose injection can effectively prevent the occurrences of acute and chronic peripheral neurotoxicity associated with oxaliplatin.


Key words: 
Neurotoxicity; Oxaliplatin
Right-sided chest lead electrocardiographic abnormalities in acute pulmonary embolism
Authors: 于东祥, 张冬梅
Journal: BMJ (2005)

目的 探讨右胸导联心电图对急性肺栓塞的诊断价值.方法回顾分析1999年3月至2003年10月收治的98例可疑肺栓塞患者的标准12导联和右胸导联(V3R、V4R和V5R)心电图,对左、右胸导联心电图进行测量和比较.结果 98例中只有23例确诊为急性肺栓塞,其中男18例,女5例,平均年龄(48±10)岁.23例中18例(78%)左、右胸导联均有右心室劳损表现;13例(72%)的心电图异常改变在入院或症状发作后24 h内消失; 9例(39%)同时存在常规12导联心电图异常和右胸导联的ST段抬高;5例(22%)左胸导联心电图正常,而右胸导联ST段抬高并呈qr、QS型;右胸导联ST段抬高的发生率为56.5%(13/23); 20例(87%)V3R导联呈qr型.结论急性肺栓塞时常有右胸导联心电图的特征性改变.当怀疑肺栓塞时,特别是当常规12导联无典型改变时,应描记右胸导联心电图。
Establishment of accreditation standards for trainers of general practitioners in community health service centers
Authors: Juan Shou, Yao Liu, Xiangjie Zhang, Hua Yang, Jing Zhou, Qian Chen
Journal: BMJ (2014)

Objective
To establish a set of accreditation standards for trainers of general practitioner (GP) in community health service centers.


Methods
A modified Delphi expert consultation was conducted during December 2012 and September 2013.Thirty two experts of general practice from different teaching hospitals and community health service centers were invited for three rounds Delphi questionnaires.A set of accreditation standards for GP trainers in primary care was established through data analysis, synthesis and process.


Results
Expert activity coefficients were 100.0% for three rounds consultation, the authority coefficients were 0.894, 0.882 and 0.893, respectively.The opinion coordination coefficients of experts were 0.156, 0.166 and 0.215, respectively (P=0.000). The developed accreditation standards system comprised of three first-grade indicators and 14 second-grade indicators.The weight coefficients of three first-grade indicators, namely professional profiles, clinical competences in primary care and teaching abilities, were 0.339 8, 0.335 6 and 0.324 6, respectively.


Conclusions
The established accreditation standard system is credible, which would appropriately guide the selection of GP trainers in primary care from three dimensions and enhance the quality of standardized training of general practitioners.


Key words: 
General practitioner; Teacher training; Delphi technique; Standards
Gut microbiome diversity as an independent predictor of survival in cervical cancer patients receiving chemoradiation.
Authors: Travis T. Sims, Molly B. Alam, Tatiana Karpinets, Kyoko Yoshida-Court, Greyson W.G. Biegert, Mustapha Ahmed-Kaddar, Xiaogang Wu, Andrea Delgado Medrano, Bhavana Sree Vangara Chapman, Travis Solley, Mitra Aparna, Melissa P. Mezzari, Lois M. Ramondetta, Lilie L. Lin, Anuja Jhingran, Kathleen M. Schmeler, Nadim J Ajami, Jennifer Ann Wargo, Lauren Elizabeth Colbert, Ann Klopp
Journal: Journal of Clinical Oncology (2020)

6036 Background: Diversity of the gut microbiome is associated with response rates for patients receiving immunotherapy. Studies investigating the gut microbiome and outcomes in cancer patients often do not adjust for confounding patient and tumor characteristics. We sought to identify independent gut microbial risk factors in cervical cancer (CC) patients receiving chemoradiation (CRT) and to evaluate their impact on survival. Methods: We analyzed baseline 16S rDNA fecal microbiomes of CC patients receiving standard CRT. Patient and tumor characteristics were analyzed by univariate and multivariate Cox regression models for Recurrence-free survival (RFS) and Overall survival (OS) based on univariate p-value&gt;0.2. Characteristics included age, body mass index (BMI), race, stage, grade, histology, nodal status, and max tumor size. Alpha (within sample) diversity was evaluated using Shannon diversity index (SDI). Kaplan-Meier curves were generated for patients with normal BMI and overweight/obese BMI based on Cox analysis. Results: 55 CC patients were included. Univariate analysis identified older age (Hazard Ratio (HR) of 0.93 (95% CI = 0.87-0.98, p = 0.0096)), SDI (HR of 0.51 (95% CI = 0.23-1.1, p = 0.087)) and BMI (HR of 0.92 (95% CI = 0.84-1, p = 0.096)) as risk factors for RFS. Multivariate survival analyses identified BMI and SDI as independent prognostic factors for RFS with a HR of 0.87 (95% CI = 0.77-0.98, p = 0.02) and 0.36 (95% CI = 0.15-0.84, p = 0.018) respectively. For OS, multivariate survival analyses again identified BMI and SDI as independent prognostic factors with a HR of 0.78 (95% CI = 0.623-0.97, p = 0.025) and 0.19 (95% CI = 0.043-0.83, p = 0.028) respectively. Conclusions: Gut diversity is a significant factor for predicting OS in CC patients undergoing CRT when BMI is accounted for, and may help explain the “obesity paradox” in cancer response. Studies exploring the relationship between gut diversity, CRT, and treatment efficacy are needed to further understand the role of the gut microbiome in treatment outcomes. [Table: see text]
Investigating the impact of medical comorbidities in patients taking beta blockers and treated with immunotherapy for metastatic melanoma.
Authors: Paul Pyunggang Hong, Junjia Zhu, Joseph J. Drabick, Todd D. Schell
Journal: Journal of Clinical Oncology (2020)

e15162 Background: Combined administration of β-adrenergic antagonist with IL-2, anti-PD-1, and/or anti-CTLA-4 immunotherapy was associated with a better overall survival in metastatic melanoma patients. This result was also reinforced by the significant reduction in tumor growth in a murine melanoma model when a β2-selective antagonist was combined with anti-PD1/IL-2 immunotherapy. Here we sought to elucidate the impact of the various comorbidities behind the indications of β-blockers, and how they might have influenced the patients’ immunotherapy treatment response. Methods: A single-institution retrospective chart review was performed to examine the medical comorbidities with indications for β-blockers in the melanoma patients who received IL-2, αPD-1 and/or αCTLA-4 immunotherapy between January 2000 and March 2015. Two groups were identified: one that took a selective β-1 blocker (N = 41), and another that took a nonselective pan β-blocker (N = 17). The primary analysis compared the distribution of different comorbidity types between two groups, using the Fisher’s exact test. A secondary analysis examined the association of overall survival and the β-blocker groups by further controlling for comorbid conditions, using the multivariate Cox Proportional-Hazard regression model. Results: Seven different comorbidities with indications for β-blocker usage were identified. Of those comorbidities, only the presence of ischemic heart disease was marginally different between the two groups (β-1 group 19.5% vs. pan-β group 47.1%, p-value = 0.0697). There was no difference for overall survival between each of the comorbidity conditions. When performing the multivariate Cox Proportional-Hazard regression model, β-blocker usage still remained statistically significant for the overall survival (HR 0.27, CI 0.0966-0.768, p = 0.0139), even after controlling for the comorbid conditions. Conclusions: Immunotherapy with pan β-adrenergic blockade was associated with a significantly improved overall survival rate for metastatic melanoma. Furthermore, having a comorbid condition that indicated for the prescription of β-blockers was not a factor in establishing this survival rate.
Molecular predictors of response to selinexor in recurrent glioblastoma (GBM).
Authors: Christopher James Walker, Yao Shen, Morten Mau-Sørensen, Patrick Y. Wen, Martin J. Van Den Bent, Scott Randall Plotkin, Anna Maria Elisabeth Walenkamp, Adam Green, Andrea Califano, Hua Chang, Leah Henegar, Sharon Shacham, Mariano J Alvarez, Yosef Landesman, Andrew B. Lassman
Journal: Journal of Clinical Oncology (2020)

2565 Background: The nuclear export protein exportin 1 (XPO1) is overexpressed in many cancers, including GBM. Selinexor is an inhibitor of XPO1 that crosses the blood-brain-barrier and targets cancer cells by sequestering tumor suppressor proteins and oncoprotein mRNAs in the cell nucleus, inducing cancer cell apoptosis. Selinexor is FDA approved for treatment of patients (pts) with refractory multiple myeloma and is under evaluation for GBM. Methods: We previously reported encouraging results from a phase II clinical trial of selinexor for molecularly unselected pts with recurrent GBM (ASCO 2019). On available pre-treatment archival tumor tissue from 57 cases, we performed DNA exome and RNA transcriptome sequencing to use both gene mutations and expressions for exploring molecular correlates of response in selinexor treated pts, in a hypothesis generating, post-hoc, exploratory analysis. Pts with inadequate drug exposure were excluded ( &lt; 21 days or &lt; 3 doses). We compared OS and PFS between mutated and wild-type patients for genes mutated in at least 5 cases. RNAseq data were used to infer differential protein activities between patients with selinexor sensitive disease (defined as best response of partial or complete response, n = 7) vs. resistant disease (defined as progressive disease as best response, n = 23). Results: Two mutated genes were associated with longer survival in selinexor treated pts: DOCK8 (n = 7; progression free survival [PFS], P = 0.013, hazard ratio [HR] = 3.75 [1.32-10.62]; overall survival, P = 0.009, HR = 15.39 [2.00-118.34]) and PDX1 (n = 5, PFS, P = 0.014, HR = 4.468 [1.361-14.670]). Other commonly mutated genes in glioma, including IDH1 (n = 9) were observed but not associated with survival. Protein activities inferred from RNA sequencing data were also correlated with response to selinexor. In a machine learning model, ZC3H12A (also called MCPIP-1), a negative regulator of inflammation; RAB43, a member of the RAS family that binds GTP and regulates vesicle trafficking, and SOCS3, a suppressor of cytokine signaling that can antagonize JAK/STAT signaling and repress innate immunity, predicted clinical benefit from selinexor (area under the ROC curve from leave one out cross validation = 0.89, permutation test P &lt; 0.04). Conclusions: DOCK8 and PDX1 mutations were favorable prognostic factors in selinexor treated pts. Activity of three proteins (ZC3H12A, RAB43, and SOCS3) predicted clinical benefit from selinexor. Further studies with more pts are required to validate our findings. ClinicalTrials.gov: NCT01986348
Combination of tumor multinucleation and spatial arrangement of tumor-infiltrating lymphocytes to predict overall survival in oropharyngeal squamous cell carcinoma: A multisite study.
Authors: Can Koyuncu, Germán Corredor, Cheng Lu, Paula Toro, Kaustav Bera, Pingfu Fu, Shlomo A. Koyfman, Deborah Chute, David J. Adelstein, Wade Thorstad, Justin A. Bishop, Farhoud Faraji, James S. Lewis, Anant Madabhushi
Journal: Journal of Clinical Oncology (2020)

6566 Background: Oropharyngeal squamous cell carcinoma patients can have major morbidity from current treatment regimens, necessitating accurate identification of patients with aggressive versus indolent tumors. In this study, we sought to evaluate whether the combination of computer extracted features of tumor cell multinucleation (MN) and spatial interplay of tumor-infiltrating lymphocytes (TILs) is prognostic of overall survival (OS) in OPSCC patients. Methods: OPSCC specimens from 688 patients were retrospectively collected from 3 different sites. 141 patients from site 1 formed the training set (D1) and 322 patients from site 2 and 225 patients from site 3 formed the independent validation cohort (D2, n = 547). A machine learning (ML) model was employed to automatically calculate a Multi-nucleation risk index (MNI), which is the ratio of the number of MN to the number of epithelial cells, to each patient. A separate ML model was also used to capture measurements related to the interplay between TILs and tumor cells (SpaTIL), which were then used to compute a risk score using a Cox regression model. The median value of both the MNIs and the SpaTIL risk scores in D2 were used to identify patients as either low- or high-risk. A definitive label was assigned to each patient by combining the class labels obtained from the MNI and SpaTIL models using a logical AND operation. Results: In D2, the patients with high-risk scores had statistically significantly worse survival in univariate analysis. The univariate analysis yielded an HR = 1.91 (95% CI: 1.25-2.93, p = 0.0027) for D. Multivariate analysis controlling the effect of different clinical variables is shown in the table. Conclusions: We presented a computational pathology approach to prognosticate disease outcome in OPSCC by combining features relating to density of multinucleation and spatial arrangement of TILs and validated the approach on a large multi-site dataset. With additional validation the approach could potentially help identify OPSCC patients who could benefit from de-escalation of therapy. [Table: see text]
Functional and Genomic Variation between Human-Derived Isolates of Lachnospiraceae Reveals Inter- and Intra-Species Diversity
Authors: Matthew T. Sorbara, Eric R. Littmann, Emily Fontana, Thomas U. Moody, Claire E. Kohout, Mergim Gjonbalaj, Vincent Eaton, Ruth Seok, Ingrid M. Leiner, Eric G. Pamer
Journal: Cell Host & Microbe (2020)
EUROQoL-5D as a valid patient-reported outcome measurement (PROM) tool to predict health-related quality of life (HRQoL) and survival in patients with hematological malignancies.
Authors: Raul Cordoba, Adriana Pascual, Javier Martinez-Peromingo, Ana-Isabel Hormigo, Elham Askari, Carola Diaz-Aizpun, Pilar Llamas, Marta Perez-Albacete, Maria Jarana, Miguel-Angel Bonillo, Susana Cruz, Alberto Pardo, Antonio Herrero, Marta del Olmo, Javier Arcos
Journal: Journal of Clinical Oncology (2020)

e19141 Background: Patient-Reported Outcome Measurement (PROM) is the way to collect not only Health-Related Quality of Life (HRQoL) but also symptoms. EUROQOL-5D is a PROM tool explored widely in patients with cancer, although is not specific for cancer patients. The primary end-point of this project is to analyse the significance of impairments in EUROQOL-5D domains in overall survival of patients with hematological malignances, and the utility to incorporate as a PROM tool in a daily clinical practice. Methods: Patients with hematologic malignancies attended at Fundacion Jimenez Diaz University Hospital were assessed with EUROQOL-5D prior to receive any therapy. Self-reported health status stated as better, equal or worse was recorded at the time of assessment. Other variables such as age, sex, diagnosis and ECOG was collected to analyze their impact in survival. Results: From January 1, 2017 to December 31, 2019, 390 consecutive patients were included. Median age was 72 years (range 18-92), 194 (49.7%) were female, with a diagnosis of lymphoma in 257 (65.9%) and myeloma in 70 (17.9%), and ECOG 0-1 in 78.2% of patients. With a median follow-up of 10.5 months (range 0-32 months), we registered 72 events for overall survival. In the univariate analysis, age &gt; 76 years (AUC 0.739, Likelyhood Ratio 3.321, p &lt; 0.0001), ECOG 2-4 (OR 11.161, 95% CI 5.276-23.610, p &lt; 0.0001), impairment in EUROQOL-5D domains such us mobility (OR 2.896, 95%CI 1.406-5.967, p = 0.003), self-care (OR 3.959, 95%CI 1.732-9.050, p = 0.001) and usual activities (OR 3.190, 95%CI 1.573-6.467, p = 0.001), but not pain/disconfort nor anxiety/depression were identified as prognostic factors for shorter survival. Self-reported health status (OR 3.975, 95%CI 1.845-8.565, p &lt; 0.0001) was also a prognostic factor for survival. Impairments in EUROQOL-5D were also prognostic in patients with ECOG 0-1 (p &lt; 0.001). In the multivariate analysis, only ECOG 2-4 and self-reported health status remained with statistical significance. Conclusions: EUROQOL-5D is a valid tool to be incorporated as a PROM tool in pacients with hematological malignancies. Impairments in mobility, self-care and usual activities will identify a poorer prognosis group that would need closer monitoring.
Promoting genetic counseling among African American women with hereditary risk for breast cancer.
Authors: Pooja Parekh, Vida Henderson, Kent Hoskins, LeChaun Kendall, Jessica Madrigal, Jennifer Newsome, Vickii Coffey, Giesela Grumbach, DeLawnia Comer-Hagans, Carolyn Rogers
Journal: Journal of Clinical Oncology (2020)

e13639 Background: Breast cancer (BC) mortality is substantially higher for African American (AA) women compared to their white counterparts. Genetic counseling (GC) is a key step in management of women with hereditary BC risk, but medically underserved women of color are less likely to receive these services. We report preliminary data from a pilot study examining the impact of a culturally sensitive, multimedia educational video created to motivate AA women with hereditary BC risk to attend GC. Development of the intervention was guided by the Integrative Model of Behavioral Prediction and qualitative research with the target audience. Methods: AA women eligible for GC for hereditary BC according to national criteria were identified through cancer genetic risk assessment (CGRA) performed at the time of a screening mammogram at the University of Illinois Health System in Chicago, IL, and were invited to participate in the study. Participants completed a baseline survey, viewed the educational intervention, and completed a post-intervention survey. The surveys included five-item Likert scales on intentions to act on the information presented, normative beliefs about GC, knowledge, and acceptability of the intervention. Responses were summarized as frequencies and proportions, and changes pre/post-intervention were evaluated using McNemar’s test. Results: The proportion of participants (n = 30) who rated they were “Extremely Likely” to make an appointment with a genetic counselor increased from 50% at baseline to 70% following the intervention (p = 0.04). After viewing the video, the proportion who rated they were “Extremely Likely” to speak with their doctor about genetic counseling increased from 60% to 77% (p = 0.10). There was a 16.6% increase (p = 0.05) in the proportion of women who indicated their family would be interested in learning more about GC, and 96.6% and 90% of participants agreed that the intervention video was enjoyable to watch and that they could relate to what the actors were saying, respectively. Changes in intentions to act on the information presented were not accompanied by changes in knowledge. Conclusions: A culturally sensitive multimedia intervention based on a theoretical model of health behavior increased intentions to attend GC among high risk AA women. The intervention was enjoyable for minority women to watch and increased intentions to discuss GC with family members. These findings indicate that culturally tailored motivational interventions have the potential to increase uptake of GC in underserved communities.
Use of real-world data to understand barriers to interventional clinical trial enrollment in community oncology clinics (COC).
Authors: Johnetta Blakely, Lucio N. Gordan, Lee S. Schwartzberg, Jacqueline Gutman, Blythe J.S. Adamson, Ariel B. Bourla, Neal J. Meropol, Scott David Ramsey, Robert J. Green
Journal: Journal of Clinical Oncology (2020)

2061 Background: Increasing enrollment in clinical trials remains a national priority, yet there are limited data from COCs on the degree to which common trial exclusion criteria (EC) and socioeconomic factors play a role in low enrollment rates. Methods: We analyzed data from the nationwide Flatiron Health electronic health record (EHR) derived de-identified database. COC were eligible if they had given a clinical trial study drug to ≥2 patients (pts)/year. We included pts with one of eight advanced or metastatic solid tumors who received ≥1 line of systemic anticancer therapy between 1/1/2014 and 11/30/2019. We defined EC as either: creatinine &gt; 1.5 mg/dl or Ccl &lt; 45 ml/min, Hb &lt; 9 g/dL, ANC &lt; 1500/ul, plts &lt; 100,000/ul, bilirubin &gt; 1.5 upper limit of normal (uln) or AST/ALT &gt; 2.5 uln within 30 days or ECOG performance status (PS) ≥ 2 within 60 days prior to start of therapy. We calculated the percentage of pts with ≥1 EC relative to the group of candidate pts, stratified by therapy line (1L, 2L, 3L+). We used multivariate logistic regression models to evaluate the effect of EC and socioeconomic factors (age, race, Medicaid) on the likelihood of receiving a clinical study drug for each line of therapy. Results: In this sample of 35 COCs, 26,988 pts received ≥1 systemic therapy. Pts with ≥ 1 EC: 28.4% in 1L, 34.2% in 2L, 37.4% in 3L. Percentages of pts with an ECOG PS ≥ 2 were: 15.6% (1L), 18.2% (2L), 19.8% (3L). Pts receiving a clinical study drug: 1.7% of 26,988 in 1L, 2.0% of 12,738 in 2L, 2.9% of 5,333 in 3L+, and 3.1% in any line. Excluding pts with ≥1 EC from the denominator modestly improved overall accrual: 2.0% of 19,729 in 1L, 2.3% of 8,588 in 2L, 3.7% of 3,470 in 3L+. In multivariate logistic regression, ECOG PS ≥ 2 was strongly associated with not receiving a study drug [odds ratio (95% CI); 1L: 0.25 (0.16-0.4); 2L: 0.28 (0.17-0.49); 3L: 0.21 (0.1-0.44)]. The likelihood of receiving a clinical study drug (any line) was lower for pts who are Black [0.63 (0.48-0.82)], Latino [0.49 (0.32-0.75)], and pts older than 70 years [0.63 (0.54-0.72)]. Medicaid pts were not significantly less likely to receive study drug [0.83 (0.64-1.07)]. Conclusions: In COC, common trial EC reduce pt availability for trials by &gt; 25%. Poor PS is highly prevalent and influential. These EC and complex trial requirements challenge COC’s ability to recruit representative pt populations. Future efforts to increase enrollment in trials must consider common EC along with well known barriers to enrollment of unrepresented groups.