tbuckley/cabot-search huggingface dataset:
SNOW: Sitravatinib and nivolumab in oral cavity cancer (OCC) window of opportunity study.
Authors: Marc Oliva Bernal, Daniel Vilarim Araujo, Douglas Brian Chepeha, Amy Prawira, Anna Spreafico, Scott Victor Bratman, Tina Shek, John R de Almeida, Aaron Richard Hansen, Andrew J. Hope, David Paul Goldstein, Ilan Weinreb, Bayardo Perez-Ordonez, Trevor John Pugh, Pamela S Ohashi, Ben X Wang, Jonathan Crawford Irish, Hirak Der-Torossian, Isan Chen, Lillian L. Siu
Journal: Journal of Clinical Oncology (2020)

6569 Background: Sitravatinib (receptor TKI against TYRO3, AXL, MERTK and VEGF family of receptors) is predicted to increase M1-type tumor-associated macrophages (TAMs) and decrease MDSCs in the tumor microenvironment. SNOW is a window-of-opportunity study evaluating the immunogenic and antitumor effects of preoperative sitravatinib and nivolumab in patients (pts) with OCC. Early results demonstrated the combination was safe and active (Oliva et al, SITC 2019). Biomarker analyses and updated results are presented. Methods: Pts with untreated T2-4a, N0-2 or T1&gt;1cm-N2 OCC are eligible. All pts receive oral sitravatinib 120mg daily from day (D) 1 up to 48h pre-surgery and 1 dose of Nivolumab 240mg on D15. Surgery planned between D23-D30. Standard of care adjuvant radiotherapy given based on clinical stage. Tumor pictures, fresh tumor biopsies, blood samples taken at baseline, D15 and pre-surgery. Tumor flow cytometry and multiplex immunofluorescence staining performed on all biopsies to study changes in immune-cell populations. Tumor whole-exome sequencing (WES) performed on baseline biopsies. Results: As of Jan 31 st 2020, 10 out of 12 planned pts were enrolled. Study treatment was well-tolerated: only 1 pt had grade (G) &gt;3 toxicity (hypertension) and 1 pt required surgery delay due to G2 thrombocytopenia. None had intraoperative complications. 1 pt had wound infection and tracheostomy bleeding 11 days post-surgery, possibly-related to study drugs. All pts had tumor reduction, 9/10 had pathological downstaging, including 1 complete response (Table). All had clear margins with no extranodal extension; none required adjuvant chemotherapy. All pts are alive with no recurrence (median follow-up= 69 weeks). Lower % of MDSCs and increased % of M1-TAMs and M1:M2 ratio trend was seen at D15 and pre-surgery, with stronger effect in major responders. Best responders (Pts S1-S2) had higher % of PD-L1+ TAMs at baseline. Tumor WES revealed an HRAS G12D mutation in pt S2 and a BLM mutation (DNA repair) in pt S6 (no downstaging). Conclusions: Pharmacodynamic analyses support the antitumor and immune effects of sitravatinib and nivolumab in OCC. Immune pathological response assessment and transcriptomics are on-going. Clinical trial information: NCT03575598 . [Table: see text]
Use of self-rated health to identify frailty and predict mortality in older adults with cancer. Results from the care study.
Authors: Mustafa Al Obaidi, Smith Giri, Nabiel Mir, Kelly Kenzik, Andrew Michael McDonald, Crystal Young Smith, Olumide B. Gbolahan, Ravi Kumar Paluri, Smita Bhatia, Grant Richard Williams
Journal: Journal of Clinical Oncology (2020)

12046 Background: Poor self-rated health (SRH) is a known predictor of mortality in the general adult population, but little is known about its use in older adults with cancer. The purpose of this study was to examine the association and ability of SRH to identify frail older adults and assess its ability to predict mortality in older adults with cancer. Methods: Using participants from the Cancer &amp; Aging Resilience Evaluation (CARE) Registry who had undergone a geriatric assessment, we examined SRH using a single-item from the Patient-Reported Outcomes Measurement Information System (PROMIS) global health scale. SRH scores were dichotomized into Poor (poor and fair) and Good (good, very good, and excellent). Multivariable logistic regression analyses were used to examine associations between SRH and frailty (based on frailty index) and specific geriatric impairments adjusting for age, sex, comorbidity, cancer type and stage. Finally, the impact of SRH on all-cause mortality was assessed with a multivariable cox regression model. Results: A total of 708 participants with malignancy were included, median age was 68y, 41.5% male, and 74.6% White. Colorectal cancer was the most common cancer (27.1%) and 48.2% of the participants had Stage IV disease. Poor SRH was reported by 42% of participants and was associated with significantly higher odds of frailty (adjusted Odds Ratio [aOR] = 21.8; 95%CI 13.7-34.8). Similarly, poor SRH was independently associated with higher odds of impairments in Activities of Daily Living (ADL) (aOR = 5.6, 95%CI, 3.6-8.9), independent ADL (aOR = 8.4, 95%CI, 5.8-12.4), cognition (aOR = 4.6, 95%CI 2.3-9.3), malnutrition (aOR = 4.5, 95%CI 3.2-6.4), falls (aOR = 3.6, 95%CI 2.4-5.4), anxiety (aOR = 4.6, 95%CI 2.9-7.3), and depression (aOR = 5.4, 95%CI 3.0-9.7). The SRH demonstrated high sensitivity (84.3%) and specificity (78.4%) for identifying frailty, with a positive predictive value of 67% and negative predictive value of 90.6%. The 1y survival rate in those with Poor SRH was significantly worse (64.7% vs 84.3%, log rank p value &lt; 0.001). In a multivariate cox regression analysis, poor SRH remained an independent predictor of worse survival (adjusted Hazard Ratio 2.29 [1.6-3.2], p&lt; 0.01) after adjusting for age, sex, race, cancer type, stage, comorbidity, and planned treatment. Conclusions: Poor SRH is highly associated with frailty and could be a simple tool to identify frail older patients with cancer at risk for adverse events and increased mortality.
Evaluation of a New Criterion for Detecting Prion Disease With Diffusion Magnetic Resonance Imaging
Authors: Alberto Bizzi, Riccardo Pascuzzo, Janis Blevins, Marina Grisoli, Raffaele Lodi, Marco E. M. Moscatelli, Gianmarco Castelli, Mark L. Cohen, Lawrence B. Schonberger, Aaron Foutz, Jiri G. Safar, Brian S. Appleby, Pierluigi Gambetti
Journal: JAMA Neurology (2020)

Early diagnosis is a requirement for future treatment of prion diseases. Magnetic resonance imaging (MRI) with diffusion-weighted images and improved real-time quaking-induced conversion (RT-QuIC) in cerebrospinal fluid (CSF) have emerged as reliable tests.To assess the sensitivity and specificity of diffusion MRI for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) with a new criterion (index test) of at least 1 positive brain region among the cortex of the frontal, parietal, temporal, and occipital lobes; the caudate; the putamen; and the thalamus.This diagnostic study with a prospective and a retrospective arm was performed from January 1, 2003, to October 31, 2018. MRIs were collected from 1387 patients with suspected sCJD consecutively referred to the National Prion Disease Pathology Surveillance Center as part of a consultation service.Magnetic resonance imaging. Four neuroradiologists blinded to the diagnosis scored the MRIs of 200 randomly selected patients. One neuroradiologist scored the MRIs of all patients.Sensitivity and specificity of the index test compared with currently used criteria and CSF diagnostic (improved RT-QuIC, 14-3-3, and tau CSF tests).A total of 872 patients matched the inclusion criteria (diffusion MRI and autopsy-confirmed diagnosis), with 619 having sCJD, 102 having other prion diseases, and 151 having nonprion disease. The primary analysis included 200 patients (mean [SD] age, 63.6 [12.9] years; 100 [50.0%] male). Sensitivity of the index test of 4 neuroradiologists was 90% to 95% and superior to sensitivity of current MRI criteria (69%-76%), whereas specificity was 90% to 100% and unchanged. Interrater reliability of the 4 neuroradiologists was high (κ = 0.81), and individual intrarater reliability was excellent (κ ≥0.87). The sensitivity of the index test of 1 neuroradiologist for 770 patients was 92.1% (95% CI, 89.7%-94.1%) and the specificity was 97.4% (95% CI, 93.4%-99.3%) compared with a sensitivity of 69.8% (95% CI, 66.0%-73.4%; P < .001) and a specificity of 98.0% (95% CI, 94.3%-99.6%; P > .99) according to the current criteria. For 88 patients, index test sensitivity (94.9%; 95% CI, 87.5%-98.6%) and specificity (100%; 95% CI, 66.4%-100%) were similar to those of improved RT-QuIC (86.1% [95% CI, 76.5%-92.8%] and 100% [95% CI, 66.4%-100%], respectively). Lower specificities were found for 14-3-3 and tau CSF tests in 452 patients.In this study, the diagnostic performance of diffusion MRI with the new criterion was superior to that of current standard criteria and similar to that of improved RT-QuIC. These results may have important clinical implications because MRI is noninvasive and typically prescribed at disease presentation.
Patterns of disease progression to checkpoint inhibitor immunotherapy in patients with stage IV non-small cell lung cancer.
Authors: Naomi Fei, Christina Attia, Mohammed Almubarak, Patrick C. Ma, Malcolm David Mattes
Journal: Journal of Clinical Oncology (2020)

e21674 Background: The purpose of this study was to assess patterns of disease progression for patients with metastatic non-small cell lung cancer (NSCLC) on checkpoint inhibitor immunotherapy in order to help guide effective use of targeted radiation therapy to sites of gross disease most likely to progress. Methods: This single center, retrospective study included all patients diagnosed with Stage IV NSCLC between June 2015 and February 2019 who received at least 2 cycles of nivolumab, pembrolizumab, or atezolizumab, with or without concurrent chemotherapy. Immune RECIST criteria were used to assess patterns of disease progression, and progression-free survival (PFS), excluding irradiated tumors. Descriptive statistics were used to report baseline patient and tumor characteristics. The Chi square and log-rank tests were used to determine whether any baseline clinical characteristics were associated with progressive disease in initial sites only (vs. new or combined sites), and PFS, respectively. Factors assessed included initial metastatic sites, tumor histology, performance status, PD-L1 expression, untreated primary tumor, history of brain metastasis, number of metastatic sites involved, and use of concurrent chemo-immunotherapy. Results: Among 143 eligible patients with a median follow-up of 11 months, 97 (68%) developed disease progression. Of these, 67 patients (69.1%) progressed only at initial disease site(s), 10 patients (10.3%) progressed only at new disease site(s), and 20 patients (20.6%) progressed in both initial and new sites. Rates of disease progression based on tumor location were higher for liver (64%) and lung metastases (61%) than for other metastatic sites (33-36%) or the primary tumor (24%). Only higher PD-L1 expression ( p= 0.002) and absence of lung metastasis ( p= 0.048) at baseline were associated with improved PFS. No baseline characteristics significantly impacted the probability of initial disease site-only progression, though a trend was observed for untreated primary tumor (72% vs. 56%, p= 0.169). Conclusions: The dominant pattern of disease progression for patients with metastatic NSCLC on checkpoint inhibitor immunotherapy is in the initial sites of disease alone, whereas only 10% of patients progressed in new disease site(s) alone, suggesting a potential role for local radiation therapy as a complementary treatment modality. Pre-treatment patient and tumor characteristics did not predict patients most likely to benefit.
Twenty-five-year trends in gender disparity for obesity and overweight by using WHO and IOTF definitions among Chinese school-aged children: a multiple-cross-sectional study
Authors: 宋逸, 王海俊, 董彬, 马军, 王志强, Agardh Anette
Journal: BMJ (2017)

目的
探索1985—2010年中国城乡儿童肥胖和超重率性别差异的长期趋势。


方法
研究对象来自全国学生体质与健康调研，该调研是中国最大的可代表全国学龄儿童的调研，包括1 280 239名7~18岁儿童。按照世界卫生组织（WHO）和国际肥胖工作组（IOTF）的标准对肥胖和超重进行判定。使用Logistic回归对不同年度超重、肥胖率的性别差异进行估计。


结果
过去25年以来，中国城乡儿童肥胖率迅速增长（WHO标准：从0.10%上升到4.3%；IOTF标准：从0.03%上升到2.2%），在每一调查年男生肥胖率均高于女生（P<0.01）。各年龄组均出现增长趋势（P<0.01）。尽管肥胖率在男女生中都出现增长，但是男生的增长速度快于女生。肥胖率的男女生性别比有随时间增加的趋势，在每一调查年，城市地区肥胖率的男女生性别比都高于乡村地区。


结论
在城乡地区逐步增加的性别差异显示男生的肥胖和超重，特别是城市男生的肥胖和超重，导致了儿童肥胖和超重的比例不断增加。
颈椎病的基本概念、分型及诊治原则
Authors: 张永刚, 张宏志
Journal: BMJ (2007)

颈椎病(cervical spondylosis)是脊柱外科的常见病和多发病.其概念易混淆,分型和临床症状也较为复杂,须仔细鉴别诊断.因此有必要对颈椎病的基本概念、分型及诊治原则做一简单的阐述。
窄谱中波紫外线联合外用药物治疗白癜风患者细胞因子的改变
Authors: 方芳, 曾义斌, 梅莉红, 干慧慧, 权哲, 王红枫, 翁孟武
Journal: BMJ (2011)

对白癜风的发病机制还不明,治疗上也缺少有效的方法.我们对21例白癜风患者应用窄谱中波紫外线(NUVB)并联合0.1%他克莫司软膏或卤米松软膏等外搽,于治疗前后观测某些细胞因子的变化。
ONC201 in previously irradiated pediatric H3 K27M-mutant glioma or newly diagnosed DIPG.
Authors: Sharon L. Gardner, Carl Johannes Koschmann, Rohinton Tarapore, Jeffrey C. Allen, Wafik Tharwat Zaky, Yazmin Odia, Matthew Hall, Doured Daghistani, Ziad Khatib, Dolly Aguilera, Tobey J. MacDonald, Maryam Fouladi, Susan Lynne McGovern, Cassie Kline, Nicholas A Vitanza, Guangrong Lu, Wolfgang Oster, Joshua E. Allen, Soumen Khatua
Journal: Journal of Clinical Oncology (2020)

3619 Background: ONC201 is a first-in-class DRD2 antagonist and ClpP agonist that has demonstrated promising activity in high-grade glioma preclinical models and radiographic regressions with single agent ONC201 in recurrent H3 K27M-mutant glioma patients . The recommended phase 2 dose (RP2D) of 625mg ONC201 orally once a week has been established in adult patients as well tolerated and biologically active. ONC201 efficacy has been shown in high-grade glioma preclinical models and radiographic regressions with single agent ONC201 have been reported in adult recurrent H3 K27M-mutant glioma patients. We report results from the first Phase I pediatric clinical trial of ONC201. Methods: This open-label, multi-center trial for pediatric H3 K27M-mutant glioma or non-biopsied DIPG employed a 3+3 dose-escalation and dose-expansion design with 6 arms. Arms A and E, which have completed accrual, determined the RP2D of ONC201 using oral capsule and liquid formulations in post-radiation pediatric H3 K27M-mutant glioma patients ONC201, respectively. Arm B aims to determine the RP2D for ONC201 in combination with radiotherapy in patients with newly diagnosed DIPG. Arms C and D aim to measure intratumoral ONC201 concentrations in midline glioma patients and the impact of ONC201 on H3 K27M DNA levels in CSF, respectively. Arm F was recently opened to study ONC201 as a single agent in patients with progressive H3 K27M-mutant tumors (excluding DIPG and spinal cord tumors) following radiotherapy. After determining the RP2D, a dose-expansion cohort will evaluate the safety, radiographic response, and activity of ONC201. Results: An RP2D of weekly 625mg ONC201 scaled by body weight as a capsule or in liquid formulation was established in the primary endpoints of arms A, B and E alone or in combination with radiation, without incidence of dose-limiting toxicity (DLT). Pharmacokinetic profiles were similar to those observed in adults (T 1/2 : 8.4h; T max : 2.1h; C max : 2.3ug/mL; AUC 0-tlast : 16.4ug/mL), with similar exposure across body weights. Conclusions: ONC201 was well tolerated without DLTs at the same adult RP2D scaled by body weight as monotherapy or in combination with radiotherapy in pediatric H3 K27M-mutant glioma patients. Further investigation of ONC201 to treat H3 K27M-mutant glioma and DIPG is warranted. Clinical trial information: NCT03416530 .
人文因素对疾病的影响
Authors: 曾昭耆
Journal: BMJ (2012)

各种社会性、人文性差异,确乎可能对医生诊断治疗的各个环节发生影响,而最终必然影响到患者的疗效和预后.重视人文方面的个体差异性,有利于提高诊断准确性,有助于医生制订出适宜的医疗保健措施,也有利于改善患者对医嘱的依从性,达到进一步提高疗效、改善预后的目的。
他山之石:英国的全科医生培养和科研
Authors: 邵隽一
Journal: BMJ (2012)

在2011年10月18日至19日北京大学全科医学学科建设研讨会上,来自英国伯明翰大学的郑家强教授、剑桥大学临床医学院副院长约翰·本森( Dr.John Benson)、牛津大学初级卫生系主任理查德·霍布斯( Dr.Richard Hobbs)等多位医学教育专家,对英国本科医学教育中的全科医学课程设置、初级卫生学科发展、全科医生培训、全科医生师资培养和英国初级卫生保健体系的成功与不足、国家初级卫生研究院的发展等方面做了介绍.英国初级卫生体系之所以能够成为该国国民卫生系统(NHS,成立于1948年)的基石、承担起绝大多数民众的基本医疗,除了有来自政府的持续支持外,全科医学学科研究与发展起着重要的支撑作用,全科医学学科有自己的研究机构——国家初级卫生研究院,有一套完善的全科医生培养体系……经过严格训练出来的全科医生具有相当的专业能力,且有职业归属感.我谨将研讨会上有关英国全科教育体系和全科医生培养、全科医学科研归纳介绍一二。
Vision impairment and eye diseases in the elderly: a report from a community health center
Authors: Xiao-jun Zhao
Journal: BMJ (2011)

The dada of 987 out-patients aged 60 or over,who visited Bajiao Community Health Center of Beijing Shijingshan District from January 2006 to December 2009,were retrospectively analyzed.The results revealed that there was no gender difference in the prevalence of low vision and blindness ( χ2 =2.719,P = 0.606); the severity of low vision and blindness was correlated with the age of patients ( χ2 =138.389,P = 0.000); cataract was the main cause of low vision and blindness,accounting for 49.6%(62/125) of low vision and 64.3% (36/56) of blindness.

Key words: 
Aged; Vision,low
Interventional therapy of postpartum hemorrhage: report of 19 cases
Authors: Xi-fen Shu, Yong Zuo
Journal: BMJ (2008)

This investigation was to evaluate the implication of interventional therapy in postpartum hemorrhage at emergency settings. Due to the failure of conservative therapy, nineteen postpartum hemorrhage cases received digital subtraction angiography(DSA)followed by internal iliac or uterine artery embolization by using gelatin sponge. As a result, all of 19 patients showed good response to the treatment, and no recurrence Was found after 6 months' follow-up. Our findings suggested that artery embolization is a safe, effective and micro-invasive treatment strategy for intractable postpartum hemorrhage, which could reduce mortality and avoid hysterectomy as well.

Key words: 
Postpartum hemorrhage; Embolization,therapeutic
Triple-Negative Breast Cancer Drug Receives Approval
Authors: Rebecca Voelker
Journal: JAMA (2020)

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Effect of neoadjuvant chemotherapy and early chemotherapeutic response evaluation for low/intermediated-risk mid-low stage II/III rectal cancer: A prospective, open-label, single-arm, phase II trial.
Authors: Xiangbing Deng, Liang Bi, Qingbin Wu, Du He, Hongfeng Gou, Bing Wu, Yongyang Yu, Wenjian Meng, Qiu Meng, Ziqiang Wang
Journal: Journal of Clinical Oncology (2020)

e16133 Background: Neoadjuvant chemoradiotherapy (NCRT) is the standard of care for stage II/III rectal cancer (RC) for its local-control effect. As advancement in surgery, local relapse was no longer the primary cause of failures, especially in low/intermediated-risk stage II/III RCs, in which benefit of radiotherapy in local control wasn’t shown in our previous trial. Distant relapse has become the major form of recurrences, and occurs at an increased rate when chemotherapy was delayed. This trial explores the effect of neoadjuvant chemotherapy (NCT), and the possibility of early assessment of chemotherapeutic response in low/intermediated-risk stage II/III RCs. Methods: This prospective, single arm, phase II trial planned to enroll 60 low/intermediate-risk stage II/III mid-low RCs (low: cT3a-bN0-1M0 MRF(-); mid: cT3a-c or T4aN0-1M0). 4 cycles of CAPOX NCT were scheduled. Rectal MRI, transanal US, endoscopy, CT were examined prior to treatment and after every two cycles. The primary outcome was the clinicopathological response, defined as pathological TRG0-1, TRG2 without tumor length increase, or TRG3 with tumor length regression over 30%. This study was approved by the Ethics Committees of West China Hospital and registered at ClinicalTrials.gov (NCT03666442). Results: From Dec. 2017 to Oct. 2019, 61 eligible patients were enrolled. Two patients received 3 cycles and 2 had only 2 cycles of chemotherapy due to intolerable adverse effects; 57 cases finished 4 cycles. In pathological evaluation, 13 patients (21.3%) were complete response (pTRG0) with one positive node in one patient; 5 cases were pTRG1; 26 were pTRG2; 17 had no response (pTRG3). 48 cases (78.7%) were responders. In the ROC curve predicting the responder via the 2-cycle regression in tumor length, the AUC was 0.864 (95%CI (0.764,0.963), p &lt; 0.001), and the best cutoff regression rate after 2 cycles NCT was 27%. With this cutoff, the sensitivity was 83.3%; specificity was 84.6%; accuracy was 83.6%; positive likelihood ratio was 5.42; negative likelihood ratio was 0.20. Conclusions: NCT achieve more favorable pCR and tumor response rate in low/intermediated-risk stage II/III RCs, comparing to previous studies. The tumor regression after 2 cycles NCT had good accuracy in diagnosing the chemotherapeutic response. This early assessed chemosensitivity may become another feature for tailored use of neoadjuvant treatments, further cohort study will be conducted. Clinical trial information: NCT03666442 .