tbuckley/cabot-search huggingface dataset:
Gait speed and recommended treatment intensity among older adults with blood cancers.
Authors: Andrew Hantel, Oreofe O Odejide, Marlise Rachel Luskin, Adam Samuel Sperling, Tammy Hshieh, Clark DuMontier, Richard Chen, Robert Soiffer, Jane A. Driver, Gregory A. Abel
Journal: Journal of Clinical Oncology (2020)

12041 Background: Gait speed identifies frailty and predicts survival among older adults with hematologic malignancies (Liu, Blood, 2019). It is not known if gait speed correlates with the intensity of oncologists’ recommended treatment in this population. Methods: From 2/2015-11/2019, patients ≥75 years presenting for an initial hematologic malignancy consultation at the Dana-Farber Cancer Institute were approached for a screening frailty assessment including a 4-meter gait speed test, reported as &lt;0.4, 0.4-0.6, 0.6-0.8, or &gt;0.8 meters/second (m/s). Faster gait speed is associated with less frailty and predicts better survival. Gait speed was not reported to the oncologist. Treatment recommendations were categorized into standard, reduced, or no therapy based on NCCN guidelines, as applicable. Gait/treatment intensity “mismatches” were characterized as patients with lowest quartile gait speed recommended standard intensity and highest quartile not recommended standard intensity. Multivariable regression was performed to assess if gait speed predicted treatment intensity (controlling for age, sex, ECOG performance status [PS], and disease type). Results: Of 786 patients enrolled, 408 required active treatment where NCCN guidelines vary by fitness. Mismatches were seen in 26.7% of patients (Table: column percentages with 95% CI, mismatches starred): 10 (21.3%) with lowest quartile gait speed recommended standard intensity and 99 (55.0%) with highest quartile recommended reduced or no therapy. In multivariable analysis, PS was predictive of no therapy as compared to standard intensity (all p&lt;0.02) and age was predictive of reduced as compared to standard intensity (p&lt;0.01); gait speed was not reliably predictive in either case. Conclusions: In this large cohort of older adults with hematologic malignancies, gait/treatment intensity mismatches occurred in over one-quarter of patients. Oncologists’ recommendations were predicted by age and PS but not gait speed. Given that gait speed is a strong predictor of survival in this population, oncologists should integrate it to minimize over- and under-treatment when making treatment recommendations. [Table: see text]
PROREPAIR-A: Clinical and molecular characterization study of prostate cancer (PC) patients with and without previously known germline <i>BRCA1/2</i> mutations.
Authors: Rebeca Lozano, Elena Castro, Isabel Aragon, Heather Thorne, Fernando López-Campos, Alejandro Sanz, Concepción Alonso, Urbano Anido, Juan maria Jose, Ana Gutierrez Pecharroman, Miguel Ramirez-Backhaus, Judith Balmana Gelpi, Isabel Chirivella, Gemma Llort, Nuria Romero-Laorden, Sara Arevalo, Jose Rubio, Tomás Di Domenico, Shahneen Kaur Sandhu, David Olmos
Journal: Journal of Clinical Oncology (2020)

5511 Background: Germline BRCA1/2 (g BRCA1/2) mutations are associated with poor clinical outcomes in PC. Previous studies showed that g BRCA2 carriers present more CNV in several genes associated with more aggressive disease. These aberrations may explain the poor clinical outcomes of these patients, but larger studies are needed to confirm these findings. Methods: PROREPAIR-A is a multicenter case-control study in which g BRCA2 carriers with available diagnostic timor-tissue were matched 1:2 by Gleason and stage at diagnosis (M0 vs M1) with known non-carriers (NC). A minimum of 120 controls-60 cases were required to prove a 5yr Cause Specific Survival (CSS)-rate of 85% vs 60%. The primary endpoint was to confirm the independent prognostic value of g BRCA2 in PC CSS. In addition, we explored the prognostic role of g BRCA1 and somatic events in BRCA2, RB1, MYC, PTEN and TMPRSS2-ERG by FISH. Χ 2 , Kaplan-Meier, log-rank and cox-regression models were carried out to identify associations with baseline characteristics and outcomes: Metastases Free Survival (MFS), Time to Castration-Resistance (TTCR) and CSS. Results: A total of 80:160 matched cases-controls were initially included, but tumor tissue and clinical data were only available in 73 g BRCA2 and 127 NC. 14 g BRCA1 were also included. At diagnosis, g BRCA2 were younger (median 62.6 vs 64.5, p = 0.02) and had cT3-4 disease more often than NC (31.5% vs 9.4%, p &lt; 0.01), but no other significant differences were found. Somatic BRCA2-RB1 codeletion (40.8% vs 11.8%, p &lt; 0.01) and MYC amplification (51.4% vs 22.8%, p &lt; 0.01) were more frequent in g BRCA2 compared to NC, but no significant differences in PTEN and TMPRSS2-ERG were observed. g BRCA2 mutations as well as somatic BRCA2-RB1 codel and MYC amplif were significantly associated with shorter CSS, MFS and TTCR (Table). MVA model confirmed the independent prognostic value of g BRCA2 (HR 1.94, p = 0.03), BRCA2-RB1 codel (HR 3.16, p &lt; 0.01), MYC amplif (HR 2.36, p &lt; 0.01), Gleason ≥8 (p &lt; 0.01) and M1 at diagnosis (p &lt; 0.01) for CSS. Conclusions: PROREPAIR-A confirmed the independent prognostic value of g BRCA2 for CSS. Somatic BRCA2, RB1 and MYC aberrations were more frequent in g BRCA2 carriers. Those alterations are associated with shorter CSS, MFS and TTCR, and may contribute to poor clinical outcomes in g BRCA2 and NC. [Table: see text]
CCTG HN.10: A phase II single-arm trial of elective volume adjusted de-escalation radiotherapy (EVADER) in patients with low-risk HPV-related oropharyngeal squamous cell carcinoma (NCT03822897).
Authors: Scott Victor Bratman, Eric Berthelet, James B. Butler, John R de Almeida, Irene Karam, Ur Metser, Robert Anton Olson, Craig Pochini, John Waldron, Eugene Yu, Andrea McNiven, Winson Y. Cheung, Marc Gaudet, Sarah Hunter, Bingshu E. Chen, Wendy R. Parulekar
Journal: Journal of Clinical Oncology (2020)

TPS6592 Background: Treatment for HPV positive(+) oropharyngeal squamous cell carcinoma (OSCC) is highly effective but associated with significant short and long term treatment related morbidity. We hypothesize that decreasing the regions of elective nodal irradiation (ENI) in the neck will lead to less toxicity and better quality of life/functional outcomes while maintaining high disease control rates in patients with favourable prognosis HPV+ OSCC. Methods: HN.10 is a Canadian Cancer Trials Group phase II trial with a primary objective to evaluate the efficacy of primary definitive radiotherapy (RT) or chemoradiotherapy (CRT) utilizing volume reduced ENI as measured by 2-year event-free survival (EFS) in patients with low-risk HPV+ OPSCC. Secondary objectives include to evaluate overall survival, local control, regional control, locoregional control, out-of-field regional control, distant metastasis free survival, early and late toxicities of treatment, subjective swallowing functions, quality of life, utilization of healthcare resources, work productivity, and prognostic biomarkers. An imaging and biospecimen bank will be compiled as part of trial conduct. Key eligibility criteria include: pathologically proven diagnosis of HPV+ OPSCC; HPV association determined locally by either p16 immunohistochemistry or direct detection of HPV DNA sequences (e.g. by PCR or in situ hybridization) performed on a core needle or surgical biopsy specimen of the primary tumour or involved cervical lymph node; clinical stage T1-3 N0-1 M0 (UICC/AJCC 8th Ed.); fit for radiotherapy +/-chemoradiotherapy. Statistical Design: The primary endpoint is 2-year EFS. Assuming 2-year EFS to be 91% (Ha) for low-risk HPV-related OPSCC with standard treatment, and that the experimental treatment will be considered as ineffective if the 2-year EFS is ≤ 85% (H0), with one-sided alpha of 0.1, a sample size of 100 patients will have 80% power to detect a 6% difference of 2-year EFS. With 3 years of accrual and 2 years of follow-up, the total duration of this study will be 5 years. A total of 304.7 person-years of follow-up is needed for the final analysis. The null hypothesis (H0) will be rejected when the observed survival rate is 88.85% or higher (i.e. if there are 18 or fewer EFS events observed). Conduct to Date: Study activation February 20, 2019. Enrollment as of January 29 2020: 23. Clinical trial information: NCT03822897 .
脑脊液检查结果的临床解读
Authors: 张健
Journal: BMJ (2008)

近20年来,随着神经生物学、病理学、影像学及相关学科的迅猛发展,针对神经系统疾病的临床检查手段日益增多,临床上进行腰椎穿刺(简称腰穿)操作的数量已明显减少,但脑脊液检查对一些神经系统疾病的诊断仍有它不可替代的作用,如中枢神经系统感染性疾病、脑膜癌、吉兰-巴雷综合征、中枢神经系统脱髓鞘病、影像学检查不能确定的蛛网膜下腔出血等。
Assessment of cardiopulmonary exercise testing prior to lobectomy in patients over 60 years old
Authors: Yunfeng Li, Songyang Yu
Journal: BMJ (2014)

A total of 92 patients aged over scheduled for lobectomy patients underwent cardiopulmonary exercise testing and follow-up observations. The values of first second forced expiratory volume (FEV1) (%) and diffusing capacity of CO (DLco) for 14 patients with intra/postoperative cardiopulmonary complications were lower than those of 78 complication-free counterparts. And ECG exercise test load was significantly higher than those without complications.


Key words: 
Pneumonectomy; Exercise test
Quantitative analysis of the therapeutic effect of topical medication for seborrheic dermatitis
Authors: Wenjing Jiang, Hanghang Zhu
Journal: BMJ (2018)

Fifty one female outpatients with facial seborrheic dermatitis attending in Xuanwu Hospital during February 2016 to July 2016 were randomly assigned in two groups: 28 patients were treated with hyaluronic acid gel (study group) and 23 patients were treated with tacrolimus ointment (control group) for 28 days. The improvement of symptoms after treatment was observed by a questionnaire, and VISIA was used to quantify the skin index of the patients. There was no difference in the therapeutic effect between the study group and control group after 28 days (P>0.05). The facial spots and red areas were decreased in both groups, compared to those before treatment (P<0.05). The results indicate that hyaluronic acid gel is safe, non-irritating and effective in treatment of seborrheic dermatitis, and VISIA provides an objective and effective method for assessing the skin lesions seborrheic dermatitis.


Key words: 
Dermatitis, seborrheic; Gels, hyaluronic acid; Tacrolimus
Effects of intravenous metoprolol by two injection methods on atrial fibrillation and rapid ventricular rates complicated with heart failure
Authors: 凌峰, 彭文辉, 杨俊, 潘浩, 徐海鹰, 王宁夫, 李佩璋, 张邢炜, 吴欣
Journal: BMJ (2007)

目的 探讨不同方式静脉注射美托洛尔对心房颤动(房颤)快速心室率(快室率)伴心力衰竭(心衰)的疗效及安全性.方法 90例房颤快室率伴心衰的患者经常规抗心衰药物治疗后,观察0.5 h,如心率仍＞100次/min、血压≥100/60 mm Hg(1 mm Hg=0.133 kPa)者,随机分3组:①美托洛尔注射液10 mg稀释后经微泵静脉滴注(微泵组)1 h;②美托洛尔注射液5 mg于10 min缓慢静脉推注(推注组),观察10 min,如心率仍大于100次/min,血压≥90/60 mm Hg,则再重复一次;③生理盐水对照组.当患者心率≤60 次/min、血压＜90/60 mm Hg时注射停止.各组静脉注射药物前及开始时给予美托洛尔注射液或生理盐水后1 h观察症状、体征、心率、血压、肺部啰音、无创血流动力学和血清脑钠肽、心钠肽等指标.结果 美托洛尔2种静脉注射方式给药后,大多数患者心衰症状、体征明显改善,心率、脑钠肽显著下降(F值分别为15.929、14.534,均P＜0.01)且比对照组明显(F值分别为5.011,4.559,均P＜0.05),收缩压、舒张压有所降低但与对照组差异无统计学意义;无创心功能参数中,微泵组心脏指数、心输出量、每搏指数、每搏输出量、左室射血时间增加且比对照组明显(F值分别为4.435、4.726、3.965、3.450、5.966,均P＜0.05),推注组无类似效应.结论 美托洛尔2种静脉注射方式治疗房颤快室率伴心衰均是有效和安全的,微泵方式给药有更好的血流动力学效应。
Tepotinib inhibits the epithelial-mesenchymal transition and tumor growth of gastric cancers via increasing GSK3β, ECAD, MUC5AC, and MUC6.
Authors: Dae Young Zang, Sung-Hwa Sohn, Bohyun Kim, Hee Jung Sul, Jinhui Jeong, Bum Jun Kim, Hyeong Su Kim
Journal: Journal of Clinical Oncology (2020)

e16562 Background: Aberrant expression of mucins can promote the epithelial-mesenchymal transition (EMT), which leads to enhanced tumorigenesis. Carcinogenesis-related pathways involving c-MET and beta-catenin involve mucins. This study characterized expressions of MET, MUC5AC, MUC5B, and MUC6 EMT signaling in human gastric cancer (GC) cell lines, and further characterized the differential susceptibility of these cell lines to tepotinib. Methods: We assessed the antitumor activity of tepotinib in GC cell lines. The effect of tepotinib on cell viability (IC 50 ), apoptotic cell death, the EMT, and c-MET and beta-catenin signaling were evaluated by MTS assay, flow cytometry, western blotting, and qRT-PCR. Antitumor efficacy was assessed in MKN45 xenograft mice. Results: Tepotinib treatment showed dose-dependent growth inhibition of c-MET-amplified SNU620, MKN45, and KATO III cells with concomitant induction of apoptosis, but tepotinib treatment did not have an effect on c-MET-reduced MKN28 and AGS cells. Tepotinib treatment also significantly reduced expressions of phospho-c-MET, total c-MET, phospho-ERK, total ERK, beta-catenin, and c-Myc protein in SNU620 and MKN45 cells. In contrast, this drug was only slightly active against KATO III cells. Notably, tepotinib significantly reduced the expressions of EMT promotion genes such as MMP7, COX-2, WNT1, MUC5B, and c-Myc in c-MET-expressed GC cells, and increased expressions of EMT suppression genes such as MUC5AC, MUC6, GSK3beta, and ECAD. In a murine xenograft model, tumor volumes were significantly reduced in the tepotinib-treated group, when administered by daily oral gavage at a dose of 10mg/kg/day. Histologically, tepotinib induced more necrosis than in the control group. Conclusions: These data show the possibility that tepotinib may have therapeutic effects in c-MET-amplified GC, suggesting that clinical studies need to confirm the therapeutic effect.
Correlation of ultrasound findings with clinical pathological types of adrenal cortical tumors
Authors: Yi Zhang, Xinsheng Wang, Mei Yuan, Lijiang Sun, Wei Wang, Yali Zhou, Wenxiao Li
Journal: BMJ (2018)

Objective
To investigate the correlation between ultrasound findings and clinical pathological types of adrenal cortical tumors (ACT).


Methods
The clinical data and ultrasonographic finding of 138 ACT patients undergoing surgical treatment in Affiliated Hospital of Qingdao University from January 2006 to December 2015 were retrospectively reviewed. The correlation between ultrasonic signs and pathological types of ACT was analyzed with Spearman method.


Results
There were 65 males and 73 females aged 18-71 years old. Among 138 cases, 90 patients were characterized by hypertension, Cushing signs, Coon signs and abnormal sexual character, with the clinical diagnosis of adrenal cortical hyperplasia or adenoma; while 48 asymptomatic patients were first detected by ultrasonography. The coincidence rate of ultrasound and clinical pathological diagnosis was 92.0%(127/138), and 11 cases were misdiagnosed. The coincidence rate of ultrasound and surgical diagnosis was 94.2%(130/138), and 8 cases were misdiagnosed. The coincidence rate for no functional adenoma was 95.8%(46/48), for cortisol cortical adenoma was 94.1 %(32/34), for aldosterone cortical adenoma was 93.6%(29/31), for cortical cysts was 9/10, for no functional adenocarcinoma was 5/6, for sexual abnormal cortical adenocarcinoma was 3/4, for cortisol cortical adenocarcinoma was 2/3, for mucous cortical adenoma was 1/2. The diameter of ACT was 0.6-11.5 cm. The low echo nodules of the adrenal region with a diameter  5.0 cm were associated with cortical adenocarcinoma (r= 0.595, P=0.01).


Conclusion
The ultrasound image of ACT is related to different clinical pathological types, which can provide important information for clinical diagnosis and selection of surgical modalities.


Key words: 
Adrenal cortex neoplasms; Ultrasonography; Pathological, clinical
A retrospective study evaluating clinical and molecular predictors of duration of response (DoR) to immune checkpoint inhibitors (ICI) in patients with advanced non-small cell lung cancer (NSCLC).
Authors: Yahya Ibrahim, Keerthana Sankar, Seongho Kim, Amy Haddad, Hirva Mamdani
Journal: Journal of Clinical Oncology (2020)

e21581 Background: ICI with/without chemotherapy has become the standard of care for the treatment of advanced NSCLC. Little is known about the clinical and molecular predictors of DoR to these agents. We previously reported clinical predictors of DoR to ICI in NSCLC patients (pts). Here we report the correlation of molecular alterations with DoR and clinical/molecular characteristics of super responders (DoR ≥ 2yr) to ICI. Methods: A retrospective chart review of pts with advanced NSCLC treated with ICI based therapy between 2015-2018 at Karmanos Cancer Institute was conducted. Clinical, tumor, and molecular characteristics data were collected. DoR was grouped into: &lt; / = 6 weeks, &gt; 6weeks-6months, &gt; 6mo-1yr, &gt; 1yr, and super responders. Results: Of 147 pts, 68% had adenocarcinoma, 61% received prior radiation, 21% had brain metastasis (mets), 26% developed irAEs, 33% were on statin, 27% were on aspirin, 83% were current or former smokers, 55% had right sided primary tumor, ICI was 1st line treatment (tx) in 20% and 2nd line tx in 52%. Overall median DoR was 168 days (95% CI, 132-231 days). Pts with right sided primary tumors and those who received ICI as 1st line tx had longer DoR (p = 0.012 and p = 0.017; respectively). Other aforementioned covariates, including brain mets, had no significant relationship with DoR. Molecular profile (MP) of 592 genes was available for 57 (38.8%) pts. PD-L1 ≥50%, CDKN2A and NOTCH1 mutations were associated with statistically significant longer DoR. Mutations/alterations in EGFR, ALK, ROS1, MET, RET, HER2, KRAS, STK11 and TP53 did not appears to have an impact on the DoR, although some of the analysis was limited because of very small number of pts. Of the 10 super responders, majority had adenocarcinoma, received prior radiation and were current/former smokers. Two had brain mets. Most did not have concurrent use of anti-inflammatory agents (statin or ASA). Only 2 of the super responders had MP available with negative NOTCH1 and CDKN2A mutations. Conclusions: Receiving ICI as 1st line of therapy and having right sided primary tumors predicted longer DoR. Presence of brain mets did not adversely affect the DoR. Super responders were more likely to have adenocarcinoma, prior radiation therapy, and current/former smoking history. PD-L1 expression ≥ 50%, CDKN2A, and NOTCH1 were associated with longer DoR. Presence of actionable genomic alterations, STK11, KRAS and TP53 did not appear to impact DoR to ICI.
右旋美托咪定的镇静效应及其对呼吸和循环的影响
Authors: 斯妍娜, 石莉, 张媛, 鲍红光
Journal: BMJ (2011)

临床上常用的镇静药丙泊酚和咪达唑仑对呼吸均有抑制作用.右旋美托咪定(dexmedetomidine,Dex)是新型的高度选择性的α2肾上腺素能受体激动剂,具有催眠、抗焦虑、镇静、镇痛和抗交感等多种作用[1-3].本研究观察Dex的镇静效果及其对呼吸、循环的影响。
Clinical and analytical validation of FoundationOne Liquid CDx, a novel 324-gene blood-based comprehensive genomic profiling assay.
Authors: Ryan Woodhouse, Lucas Dennis, Meijuan Li, Christine Burns, Pei Ma, Wei Meng, Ninad Dewal, Christine Vietz, Priti Hegde
Journal: Journal of Clinical Oncology (2020)

e13685 Background: As the availability of precision therapies expand, a well-validated blood-based comprehensive genomic profiling (CGP) assay has the potential to provide considerable value as a complement to tissue-based testing to ensure that potentially life-extending therapies are administered to the patients most likely to benefit. Comprehensive clinical and analytical validity data for blood-based assays are crucial to enabling physicians to understand the true performance of available testing options. Methods: The FoundationOne Liquid CDx assay is a blood-based CGP assay that has been validated for a Premarket Approval (PMA) submission to the Food and Drug Administration (FDA). Validation studies included &gt; 9,000 tests and &gt; 30,000 unique variants across &gt; 300 genes and &gt; 50 cancer types, allowing for a comprehensive assessment of performance. Results: The results of these extensive studies demonstrate a 95% limit of detection (LoD) of 0.40% variant allele fraction (VAF) for select short variants (subs and indels), 0.37% VAF for select rearrangements, 21.7% tumor fraction (TF) for select copy number amplifications, and 30.4% TF for copy number losses. LoD for complex biomarkers such as microsatellite instability (MSI) and blood tumor mutational burden (bTMB) were also determined. The limit of blank (LoB) was shown to be the ideal value of zero. Reproducibility of variant calling was determined to be 99.59% with two-sided exact CI of (99.58%, 99.60%). In comparison with an orthogonal method, an overall PPA (95% CI) of 96.3% (94.8, 97.4%) and NPA (95% CI) of &gt; 99.9% (99.9%, 100.0%) was observed. Critically, clinical validity and concordance with tissue-based CGP results across multiple tumor types were also evaluated. Conclusions: The results of these studies demonstrate that FoundationOne Liquid CDx accurately and reproducibly detects the major types of genomic alterations (short variants, rearrangements, and copy number alterations), as well as complex biomarkers, such as MSI, bTMB, and tumor fraction. These data demonstrate that the assay can identify genomic variants that may inform therapeutic decisions for cancer patients with any solid tumor using a single blood sample. Additionally, clinical validation results establish FoundationOne Liquid CDx as an additional tool for physicians in the therapeutic management of cancer patients.
Practice and exploration of continuing education of practical emergency medicine at community hospitals
Authors: Tiancheng Ren, Rong Mao, Yitang Wang, Xiang Gao
Journal: BMJ (2015)

A total of 180 community medical staff in Jiangning District of Nanjing received continuous education in practical emergency medicine through theory teaching, practice and scene simulation once a year from 2011 to 2013. And the training outcomes were evaluated before and after training and the feedbacks of community medical staff collected each time. The assessment results of theory and practical skills after training in 2013 were better than before training in 2011 [theory: (61.72±5.03) vs. (92.11±5.56) points; operation skills (55.28±6.18) vs. (93.33±3.45) points] (P<0.05). And the total satisfaction rate was 98.0%.


Key words: 
Education, continuing; Education, professional, retraining
Application of transesophageal ultrasound-guided minimally invasive surgical closure for congenital heart disease
Authors: Yongfeng Ren, Zhou Wang, Dehai Chen, Tiangang Zhu, Jian Li, Jing Lu, Shanshan Wang
Journal: BMJ (2019)

The clinical data of 31 patients with congenital heart disease (CHD) receiving minimally invasive surgical closure through chest or femoral venous catheter from June 2016 to September 2017 were analyzed retrospectively. All patients were diagnosed with esophageal echocardiography before operation. During the operation, the insert of guide wire and the sheath tube, and the placement of the sealing parasol were monitored and guided by transesophageal echocardiography (TEE). Satisfactory results were obtained in 30 patients. In 1 patients, the sealing parasol was detached, and open chest surgery was performed to remove the detached parasol and to repair the defect. TEE-guided minimally invasive surgical closure through chest or femoral vein catheter is safe and effective in the treatment of congenital heart disease and has certain clinical applicative value.


Key words: 
Surgical; Congenital heart disease; Minimally invasive block; Transesophageal echocardiography