tbuckley/cabot-search huggingface dataset:
Racial disparities in definitive treatment and long-term mortality among US veterans with high-risk localized prostate cancer.
Authors: Ravi Bharat Parikh, Kyle William Robinson, Sumedha Chhatre, Elina Medvedeva, S. Bruce Malkowicz, Ravishankar Jayadevappa
Journal: Journal of Clinical Oncology (2020)

e19037 Background: Equal access to care may mediate racial disparities among men with localized prostate cancer. We examined the association between African-American race and long-term mortality among men with high-risk prostate cancer in a large equal-access health system. Methods: In this retrospective cohort study, we used the VA Corporate Data Warehouse to identify African-American (AA) and non-Hispanic White Veterans diagnosed with high-risk (prostate-specific antigen [PSA] ≥ 20 ng/mL, Gleason 8-10, or stage ≥ cT2c) localized prostate cancer between January 1 st , 2001 and December 31 st , 2011 and followed through January 1 st , 2019. Veterans who did not receive continuous VA care were excluded. We used descriptive statistics to compare type of therapy received and multivariable Cox proportional hazards regressions to estimate the association between mortality and race. Cox models were adjusted for age, pre-treatment PSA, year of diagnosis, enrollment priority (an individual-level proxy for income and disability need), marital status, Elixhauser comorbidity index, and primary treatment. Results: Among 14,877 Veterans (median age 67 years [interquartile range [IQR] 62-75]), 4,160 (28.0%) were AA. Median followup was 9.0 years (IQR 6.1-11.4). Compared to White men, AA men were more likely to have PSA ≥ 20 (49.9% vs. 40.9%), be unmarried (59.3% vs. 43.3%), have ≥3 comorbidities (46.4% vs. 41.0%), and have high disability and income need (22.0% vs. 18.6%) (all p &lt; 0.001). Over time, AA Veterans were consistently less likely to receive prostatectomy (18.9% vs. 24.9%). Crude mortality rates were 50.6 and 61.6 deaths per 1000 patient-years for AA and White Veterans, respectively. After adjusting for all covariates, AA Veterans had lower all-cause mortality (adjusted hazard ratio [aHR] 0.83, 95% CI 0.79-0.88, p &lt; 0.001) compared to White Veterans. This association was consistent across pre-specified subgroups (Table). Conclusions: Among men with high-risk prostate cancer who received continuous care within a large equal-access health system, African-Americans had lower all-cause mortality compared to Whites. Equal access to care may mitigate or reverse traditional racial disparities in mortality among men with prostate cancer. [Table: see text]
阿司匹林哮喘伴心绞痛一例
Authors: 成娟, 王福杰
Journal: BMJ (2008)

患者男,40岁,因思睡、头晕3个月入院.否认高血压、冠心病、糖尿病及支气管哮喘病史,吸烟25年,饮酒10年,青霉素过敏.查体:脉搏88次/min,血压130/80 mm Hg(1 mm Hg=0.133 kPa),体胖,心肺正常,四肢肌力正常.血甘油三酯4.01 mmol/L(154 ms/L).血液流变学检查:全血黏度中的高切、中切、低切升高。
Early ctDNA response assessment for prediction of platinum sensitivity in small cell lung cancer.
Authors: Yonina R. Murciano-Goroff, Angela B. Hui, Jacob J. Chabon, Everett J Moding, Emily S. Lebow, Jose A. Araujo-Filho, James M. Isbell, David Randolph Jones, Michelle S. Ginsberg, Mackenzie L. Myers, Michael Offin, Alexander E. Drilon, Matthew David Hellmann, Wei-Chu Victoria Lai, Jorge S. Reis-Filho, Pedram Razavi, Charles M. Rudin, Ash A. Alizadeh, Bob T. Li, Maximilian Diehn
Journal: Journal of Clinical Oncology (2020)

9067 Background: Small cell lung cancer (SCLC) is an aggressive disease, characterized by inevitable chemotherapy resistance and rapid progression. We hypothesized that circulating tumor DNA (ctDNA) analysis can rapidly identify sensitivity to platinum-based therapy. Methods: Patients with SCLC at Memorial Sloan Kettering Cancer Center underwent serial plasma collections, including prior to the start of treatment and prior to Cycle 2 Day 1 of therapy (C2D1). Tumor mutations were identified from pre-treatment biopsies by MSK-IMPACT and/or pre-treatment plasma by CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). Median variant allele fraction (VAF) of all mutations was monitored on subsequent blood draws using CAPP-Seq. Progression free survival (PFS) was measured from the time of first pre-treatment blood draw. Results: Plasma was collected from 19 patients treated with carboplatin and etoposide, including three who received concurrent atezolizumab. Seven were female, and mean age was 64.5 years. ctDNA was detected in 17 patients (89%), including in the two patients in our series with limited stage disease. The most common mutations were in TP53 and RB1 in 14 and 6 patients, respectively. Fourteen patients had available plasma at C2D1. At baseline prior to treatment, median VAF did not differ significantly between radiologic responders and non-responders (9.4% versus 30.3%, p = 0.35). After one cycle of chemotherapy, the VAF percent decrease was significantly more in responders versus non-responders (-96.9% versus -10.3%, p &lt; 0.001). Median VAF was therefore significantly lower by C2D1 in patients who responded compared to non-responders (0.51% versus 27.2%, p = 0.02). Those who ultimately responded to therapy all had a &gt; 2 fold decrease in VAF by C2D1. With a median follow-up of 180 days, PFS was significantly longer in patients with &gt; 2 fold decrease in VAF by C2D1 (6.4 versus 1.9 months, log rank p &lt; 0.001). Conclusions: A 2-fold decrease in plasma VAF by C2D1 predicted platinum-sensitivity in SCLC and was associated with longer PFS. ctDNA may permit early assessment of benefit and expedite alternative treatment options for those without significant decrease in median VAF after one cycle of therapy.
Contamination status and cleaning frequency of stethoscopes in community health institutions
Authors: Zhou-ping Kuang, Guang-lai Deng, Xu-dong Liang
Journal: BMJ (2011)

Stethoscope diaphragms were sampled randomly for bacteria culture and identification from nursing and medical staff in 3 community health institutions in Zhongshan city. Anonymous filling in questionnaire was taken for investigating frequency of cleaning stethoscope by staff. A total of 100 stethoscope diaphragms were sampled, and a total of 523 bacteria strains were isolated. Eighty-six percent of stethoscopes surveyed were contaminated with bacteria, among the isolated organisms, G+ bacteria and G-bacteria accounted for 78% and 22% respectively. The Bacterial contamination rate and G- rate of stethoscopes used by inpatient staff were 6. 2 strains and 2. 1 strains per stethoscope respectively, which were significantly higher than those used by outpatient staff (4. 8 strain and 1. 1 strain per stethoscope, P ＜0. 05 and P < 0. 01, respectively). A total of 105 questionnaires showed that 21% (6/28) of nursing staff cleaned stethoscope monthly, meanwhile 12% (7/56) of outpatient medical staff and 14% (3/21) of inpatient medical staff (P ＜0. 01) did so; 29% (8/28) of nursing staff cleaned their stethoscopes once a year or never, meanwhile, the figures for outpatient and inpatient medical staff were 55% (31/56) and 57% (12/21) respectively (P ＜0. 01). Results indicate that there is high rate of bacterial contamination in stethoscopes, and G- is more frequently found in stethoscopes used by inpatient staff than outpatient. In general, the frequency of stethoscope cleaning is low, however, more frequently for nursing staff than medical staff.

Key words: 
Stethoscope;  Bacterial contaminated
Clinical relevance of detecting anti-infliximab antibodies with a drug-tolerant assay: post hoc analysis of the TAXIT trial
Authors: Van Stappen Thomas, Vande Casteele Niels, Van Assche Gert, Ferrante Marc, Vermeire Séverine, Gils Ann, 李佳宁, 吴东
Journal: BMJ (2018)

目的
评估在药物谷浓度（trough concentration，TC）调整后的英夫利昔单抗治疗随机对照试验（TAXIT）事后分析中，使用药物耐受性检测法测定药物抗体水平的临床相关性。


研究设计
本研究共纳入76名已入组TAXIT试验的，初筛时英夫利昔单抗药物谷浓度<3 μg/ml的患者血清样本（n=221）在进行优化处理后对血清样本进行了再分析，研究末亦进行了药物耐受性法检测。随机化分组前这些患者们接受了更高剂量的药物治疗，提升英夫利昔单抗药物谷浓度至治疗浓度范围即（3~7）μg/ml。根据测定的抗药抗体滴度将患者分组（四分位分组法，Q1~4）。


结果
应用药物耐受性检测法，初筛时免疫原性检测阳性率从21%（药物敏感性检测法）提升至63%，优化处理后自0%升至51%，而TAXIT试验末这一组数字为3%与42%。抗药抗体第4四分位组患者为达药物谷浓度目标范围需更大的英夫利昔单抗累积用药剂量[2 390 mg（880~2 998）]，从而导致更高的药物相关花费[10 712欧元（4 120~13 596）]。而抗药抗体阴性患者及抗药抗体第1/第2四分位组患者药物相关花费低至平均2 060欧元（1 648~3 296）与2 060欧元（1 648~4 120）/2 060欧元（1 751~3 296），P<0.001。然而，除1名抗药抗体第4四分位组的患者外，所有的患者药物敏感性检测中抗药抗体均阳性。


结论
强化药物剂量后，随着时间推移，药物敏感性测定法无法检出的低浓度抗药抗体在超过半数的患者中消失，且与临床无相关性。相反，在药物敏感性测定中亦可检测出的高浓度抗药抗体，不会随着时间推移消失，且以上患者需更高的药物累积剂量及更多的药物相关性花费。在这样的患者中，主动更换药物可能更具成本效益。


临床试验登记
2011-002061-38；事后结果。
A Literature review measuring quality of life in HIV and AIDS and influencing factors
Authors: 喻达, 刘民
Journal: BMJ (2006)

随着人类免疫缺陷病毒(HIV)感染者和艾滋病(AIDS)患者生命的延长,生存质量(quality of life , QOL)这一反映健康的指标日益受到关注和重视.2000年,WHO和联合国艾滋病规划署(UNAIDS)提出,在降低发病率和死亡率的同时,把提高与健康相关的生存质量作为关怀和支持HIV感染者和艾滋病患者的第3个目标[1].作者就近年来HIV感染者和艾滋病患者生存质量研究方面的进展进行综述。
Comprehensive modeling of longitudinal circulating tumor DNA dynamics to predict clinical response to first-line immunotherapy and chemoimmunotherapy in advanced non-small cell lung cancer.
Authors: Joseph Christopher Murray, Lamia Rhymee, Kristen Marrone, Jarushka Naidoo, Benjamin Philip Levy, Leonardo Ferreira, Samuel Rosner, Mara Lanis, Christine L. Hann, Josephine Louella Feliciano, Vincent K. Lam, David S. Ettinger, Peter Bela Illei, Chenguang Wang, Julie R. Brahmer, Patrick M. Forde, Victor E. Velculescu, Robert B. Scharpf, Valsamo Anagnostou
Journal: Journal of Clinical Oncology (2020)

9525 Background: First-line immunotherapy (IO) and chemo-immunotherapy (chemo-IO) are approved for PD-L1-expressing advanced non-small cell lung cancer (NSCLC), but PD-L1 expression does not reliably predict therapeutic response. Therefore, accurate on-therapy response assessment is needed to guide clinical decision-making. Conventional radiographic imaging is the gold-standard, but may not capture the nature and timing of an immune-mediated response. We investigated whether comprehensive longitudinal circulating tumor DNA (ctDNA) dynamics could enhance prediction of clinical response. Methods: We conducted targeted error correction sequencing (TEC-Seq) of longitudinal plasma specimens and matched white blood cells (WBCs) in patients with NSCLC treated with first-line IO or chemo-IO. Plasma ctDNA variants were identified by filtering out clonal hematopoiesis (CH) and germline (GL) variants found in matched WBCs. Clinical and pathological data, including PD-L1 tumor proportion score (TPS), and imaging response by RECIST1.1 were assessed. ctDNA dynamics were modeled to predict durable clinical benefit (at 6 months), progression-free survival (PFS), and overall survival (OS). Results: A total of 143 longitudinal plasma and 24 white blood cell samples underwent TEC-Seq for 31 patients with NSCLC treated with IO (n = 17) or chemo-IO (n = 14). ctDNA variants were found in 77% (n = 24) of patients after filtering out CH and GL variants, which comprised 53% (n = 196 of 373) of all variants. Molecular response, signified by elimination of ctDNA variants, was detected in 32% (n = 10) of patients and associated with improved PFS (p = 0.0004, log rank) and OS (p = 0.017, log rank). Time to molecular response was shorter than time to best RECIST response (median 3 vs. 7.71 weeks, p = 0.048, Mann-Whitney U test). A logistic regression model incorporating molecular response, recrudescence, or emergence of new variants predicted durable clinical benefit (sensitivity 84%, specificity 76%, AUC 0.88) better than PD-L1 TPS (AUC 0.67, p = 0.046, bootstrap method). Conclusions: Comprehensive modeling of ctDNA variant dynamics predicts clinical outcome independent of PD-L1 status in patients with advanced NSCLC treated with first-line IO or chemo-IO. Verification of bona fide ctDNA variants by matched WBC sequencing is essential. Molecular response can be identified earlier than imaging response and could enable on-therapy decision-making to alter clinical outcomes.
Prognostic impact of high stromal tumor-infiltrating lymphocytes (sTIL) in the absence of pathologic complete response (pCR) to neoadjuvant therapy (NAT) in early stage triple negative breast cancer (TNBC).
Authors: Nour Abuhadra, Ryan Sun, Jennifer Keating Litton, Gaiane M Rauch, Alastair Mark Thompson, Bora Lim, Beatriz E Adrada, Elizabeth A. Mittendorf, Jason B White, Elizabeth Ravenberg, Senthil Damodaran, Rosalind P Candelaria, Banu Arun, Naoto T. Ueno, Lumarie Santiago, Rashmi Krishna Murthy, Nuhad K. Ibrahim, William Fraser Symmans, Stacy L. Moulder, Lei Huo
Journal: Journal of Clinical Oncology (2020)

583 Background: Pathologic complete response is an excellent surrogate for disease-free survival (DFS) and overall survival (OS) in TNBC. High sTIL is associated with improved pCR rates in TNBC. Recent data suggest that high sTIL is also associated with improved outcomes in patients who received no chemotherapy for early stage TNBC (Park, Annals of Oncology, 2019). Thus, we hypothesized that high sTIL may have prognostic impact in patients who do not achieve pCR to NAT. Methods: Pretreatment core biopsies from 182 patients with early-stage TNBC enrolled on the ARTEMIS trial (NCT02276443) were evaluated for sTIL by H&amp;E. Patients were stratified according to sTIL (low &lt; 30%, and high &gt; 30%) and pCR (patients with pCR vs. no pCR). The primary outcome measure was DFS, defined from the date of diagnosis to the first local recurrence, distant metastases or death. Cox proportional hazards regression model was used. During follow-up 33 events for DFS were observed. Results: Among subjects who achieve pCR, DFS was excellent regardless of sTIL status and significantly better than those without pCR (p &lt; 0.05). However, patients with high sTIL and no pCR demonstrated significantly worse DFS compared to all subjects having pCR (HR 0.18, 95% CI 0.04-0.76, p = 0.02). Additionally, we did not find a significant difference between high and low sTIL patients who did not achieve pCR. Conclusions: In early TNBC receiving NAT, for patients failing to achieve pCR, high sTIL was not associated with improved DFS; outcomes were comparable to those with low sTIL without pCR. Thus, high sTIL at baseline does not appear to confer an intrinsic prognostic benefit in the absence of pCR.
An automated EHR-based tool for identification of patients (pts) with metastatic disease to facilitate clinical trial pt ascertainment.
Authors: Jeffrey J. Kirshner, Kelly Cohn, Steven Dunder, Karri Donahue, Madeline Richey, Peter Larson, Lauren Sutton, Evelyn Siu, Janet Donegan, Zexi Chen, Caroline Nightingale, James Hamrick
Journal: Journal of Clinical Oncology (2020)

2051 Background: Efforts to facilitate patient identification for clinical trials in routine practice, such as automating electronic health record (EHR) data reviews, are hindered by the lack of information on metastatic status in structured format. We developed a machine learning tool that infers metastatic status from unstructured EHR data, and we describe its real-world implementation. Methods: This machine learning model scans EHR documents, extracting features from text snippets surrounding key words (ie, ‘Metastatic’ ‘Progression’ ‘Local’). A regularized logistic regression model was trained, and used to classify patients across 5 metastatic status inference categories: highly-likely and likely positive, highly-likely and likely negative, and unknown. The model accuracy was characterized using the Flatiron Health EHR-derived de-identified database of patients with solid tumors, where manually abstracted information served as standard accurate reference. We assessed model accuracy using sensitivity and specificity (patients in the ‘unknown’ category omitted from numerator), negative and positive predictive values (NPV, PPV; patients ‘unknown’ included in denominator), and its performance in a real-world dataset. In a separate validation, we evaluated the accuracy gained upon additional user review of the model outputs after integration of this tool into workflows. Results: This metastatic status inference model was characterized using a sample of 66,532 patients. The model sensitivity and specificity (95%CI) were 82.% (82, 83) and 95% (95, 96), respectively; PPV was 89% (89, 90) and NPV was 94% (94, 94). In the validation sample (N = 200 originated from 5 distinct care sites), and after user review of model outputs, values increased to 97% (85, 100) for sensitivity, 98% (95, 100) for specificity, 92 (78, 98) for PPV and 99% (97, 100) for NPV. The model assigned 163/200 patients to the highly-likely categories, which were deemed not to require further EHR review by users. The prevalence of errors was 4% without user review, and 2% after user review. Conclusions: This machine learning model infers metastatic status from unstructured EHR data with high accuracy. The tool assigns metastatic status with high confidence in more than 75% of cases without requiring additional manual review, allowing more efficient identification of clinical trial candidates and clinical trial matching, thus mitigating a key barrier for clinical trial participation in community clinics.
Genetics of Hepatocellular Carcinoma: Approaches to Explore Molecular Diversity
Authors: Stefano Caruso, Daniel R. O’Brien, Sean P. Cleary, Lewis R. Roberts, Jessica Zucman‐Rossi
Journal: Hepatology (2020)

Hepatocellular carcinomas (HCCs) are highly heterogeneous malignancies with different risk factors, including alcohol abuse, chronic hepatitis B (HBV) and C (HCV) infection, fatty liver disease and other genetic disorders. Despite recent progress in HCC management, most are diagnosed at advanced stages, when therapeutic options are limited. Currently, multikinase inhibitors (sorafenib, lenvatinib, cabozantinib and regorafenib), human monoclonal antibodies (ramucirumab), and immune checkpoint inhibitors (nivolumab, pembrolizumab) are the only systemic therapies approved for the treatment of unresectable HCC (1). However, these drugs show low response rates and limited survival benefit of 2-3 months. Tumor heterogeneity, characterized by distinct molecular alterations in different sub-clones within each tumor or among tumors from different patients, contributes to drug resistance (2). Consequently, improved understanding of tumor heterogeneity and mechanisms of resistance to systemic treatments is required. Advances in next-generation sequencing have increased our understanding of the molecular complexity of HCC, delineating a molecular landscape which includes recurrent genetic alterations that drive tumor expansion, as well as inherited variants that increase HCC risk. This review provides an overview of the genetic changes during HCC development and progression, with a special focus on the role of the tumor heterogeneity. We also discuss the latest advances in the establishment of preclinical models to investigate the molecular diversity of HCC and their use for developing effective personalized therapies.
Retrospective cohort study of real-world treatment patterns and overall survival in patients with chronic lymphocytic leukemia (CLL) diagnosed between 2010 to 2017 in Ontario, Canada.
Authors: Shazia Hassan, Manjusha Hurry, Soo Jin Seung, Ryan Walton, Ashlie Elnoursi, Krystin Scheider, Jonathan Edwin, Dennis Wagner, Andrew Ta Wei Aw
Journal: Journal of Clinical Oncology (2020)

e20003 Background: With recent advances in treatment of CLL, it is important to understand emerging treatment patterns and associated outcomes. A population-based study was undertaken to describe the management and survival of CLL patients in Ontario, Canada. Methods: Patients diagnosed with CLL between January 1, 2010 and December 31, 2017 were identified in the Ontario Cancer Registry and linked to provincial administrative databases. Treatment patterns by line of therapy were characterized, including analyses of time to initiation and between therapies. Overall survival was calculated. Results: 2,887 CLL patients were identified (median age 68yr; 67% male). The mean time from diagnosis to first line (1L) treatment was 651 days with 35% of patients receiving fludarabine-cyclophosphamide-rituximab (FCR) based treatment. During the study period, 71% of patients did not yet receive second line (2L) therapy and did not have subsequent follow up, while 19% received 2L ibrutinib. Median time to 2L initiation from 1L treatment discontinuation was 636 days. The table summarizes 1L and 2L therapies. Of the 827 patients on 2L therapy, 65% received ibrutinib. After the introduction of publicly funded novel agents in 2015, a shift in treatment patterns away from FCR and chlorambucil based regimens was observed. Overall mean survival for the cohort from diagnosis was 6.8yrs, and mean 5 year probability of survival was 72.4%. Conclusions: A shift in treatment patterns for CLL can be seen with the introduction of newer therapies, such as ibrutinib. The results can support healthcare decision-makers by characterizing the size of this patient population, real world treatment patterns and survival outcomes for patients with CLL. [Table: see text]
Morbidity, mortality and healthcare use among siblings of children with cancer: A population-based study.
Authors: Aditi Desai, Cindy Lau, Rinku Sutradhar, Douglas Lee, Paul C. Nathan, Sumit Gupta
Journal: Journal of Clinical Oncology (2020)

7040 Background: Siblings of children with cancer are at increased risk of adverse mental health outcomes; impact of the childhood cancer experience on these siblings’ physical health is unclear. We characterized the long-term risk of adverse physical health outcomes and healthcare use among siblings of children with cancer. Methods: Pediatric cancer patients in Ontario diagnosed between 1988 and 2016 were linked to their biological siblings to form the siblings/case cohort. Cases were matched to population controls based on sex, age, and residence area. Index date for cases was the date of their brother’s or sister’s cancer diagnosis (controls had the same index date as cases). After individual linkage to health services data, we compared several outcomes between these two groups: 1) physical health conditions (e.g. cancer, hypertension, injuries, death); 2) acute healthcare use (hospitalization, emergency department [ED] visits), and; 3) preventative healthcare use (periodic health checkups, influenza vaccinations). Predictors of outcomes, including demographics and characteristics of the cancer-affected child, were examined in cases. Cox proportional hazards, recurrent event, or logistic regression models were used as appropriate. Results: We identified 8,529 cases and 30,364 matched controls [median age at index: 6 years, interquartile range (IQR) 0-10; median follow-up time: 9 years, IQR 5-15]. Compared to controls, cases had increased risk of hypertension [hazard ratio (HR) 1.8; 95% confidence interval (95CI) 1.1-2.9; p = 0.01]. They also had higher rates of ED visits [rate ratio 1.1; 95CI 1.1-1.2; p &lt; 0.001] and increased risk of hospitalization [HR 1.1; 95CI 1.1-1.2; p &lt; 0.001]. Cases were more likely to undergo periodic health checkups [odds ratio (OR) 1.1; 95CI 1.0-1.1; p = 0.01] and influenza vaccinations [OR 1.5; 95CI 1.4-1.6; p &lt; 0.001]. In multivariable analysis restricted to cases, rurality and bereavement, among other predictors, were associated with increased use of acute healthcare. Conclusions: Increased risk of hypertension and hospitalization in cases suggests that these siblings are experiencing poorer physical health compared to their peers. Increased rates of ED visits and preventive healthcare suggests parental anxiety surrounding these siblings’ health. Siblings at highest risk of adverse outcomes could be identified through demographic characteristics, among others. Siblings would benefit from targeted surveillance and further investigation to elucidate underlying mechanisms influencing their health.
Eearly identification of Parkinson disease
Authors: 陈海波
Journal: BMJ (2008)

帕金森病是以运动迟缓、静止性震颤、肌强直及姿势平衡障碍为特征的进行性进展的神经系统变性疾病.由于缺乏客观的诊断性生物学标志,目前诊断主要依赖临床症状和体征,在疾病中晚期出现典型症状时不难诊断。