tbuckley/cabot-search huggingface dataset:
Safety and outcomes of immunotherapy re-challenge in lung cancer.
Authors: Xinyu Nan, Paulette Gabbai-Saldate, Sandip Pravin Patel, Lyudmila Bazhenova, William M. Mitchell, Kathryn A. Gold
Journal: Journal of Clinical Oncology (2020)

e19355 Background: Immune checkpoint inhibitors (CIs) have been shown to improve overall survival in lung cancer and are FDA approved in multiple settings, both as single agents and in combination with chemotherapy. Immune related adverse events (irAEs) are common and frequently manifest as dermatitis, pneumonitis, colitis, and hepatitis, among others. Managing grade 2 or higher irAEs often requires multiple outpatient visits and sometimes inpatient admissions, which can significantly increase patient morbidity and healthcare cost. There is limited evidence on the safety of restarting CIs after moderate to severe irAE. Identifying high-risk factors for developing severe irAEs again after re-challenge can improve patient care and cost efficiency. Methods: We searched our electronic medical records to identify patients with NSCLC and SCLC treated with one or more PD-1, PD-L1, or CTLA-4 CIs at our institution between 2013 and 2019. We reviewed 452 patients and identified 44 patients who developed irAE requiring treatment discontinuation. Of these 44 patients, 19 were re-challenged with same or different CIs. The primary end point of this study is to assess the rate of grade 2 or higher irAE after CI re-challenge. Secondary endpoints are mortality rate, overall survival, and disease status. Results: Median follow up for the 19 patients who were re-challenged with CI was 15 months. Median duration of CI treatment after re-challenge was 6 months (range 0.5 to 25 months). 7 patients (37%) developed irAEs (grade 2 or above) again (5 pts with same irAE as prior). Multivariate logistic regression analysis revealed that age≥70 and requirement of steroid for initial irAEs were associated with a higher risk of recurrent irAEs. Median overall survival has not yet been reached; 32% of patients have died. No deaths were related to irAE. After re-challenge with CIs, 42% of the patients had partial response or stable disease, and 58% had progression of disease. Conclusions: Our study demonstrated that re-challenge with immunotherapy is feasible in some patients who had treatment held due to irAEs, though recurrent irAEs were common. Caution should be taken when restarting CIs after moderate to severe toxicities, especially in older adults.
Prognostic role of filgrastim and derived neutrophil-to-lymphocyte ratio (dNLR) in the effectiveness of PD1/PDL1 inhibitors in previously treated non-small cell lung cancer.
Authors: Juan Francisco Marin Pozo, Carmen Lucia Muñoz Cid, Macarena Merino Almazán, Raquel Claramunt García, Elvira Marin Caba, Encarnación Pérez Cano, Ana Laura Ortega Granados
Journal: Journal of Clinical Oncology (2020)

e21729 Background: A neutrophil/lymphocyte ratio (NLR)&gt; 5 or its derivative (dNLR)&gt; 3 have been proposed as a prognostic factor for non-effectiveness of nivolumab in non-small-cell lung cancer (NSCLC). Filgrastim (GSGF) increases the absolute counts of neutrophils in patients (pts) with neutropenia. The aim of this study is to determine whether the use of GSGF, during the first line therapy of nSCLC, influences the effectiveness of the anti-PD1/PDL1 inhibitors (aPD1-i) used in subsequent line. Methods: We designed a single center, observational and retrospective study. We included NSCLC pts treated with Nivolumab (NIV), Pembrolizumab (PEM) or Atezolizumab (ATE) between January-16 and November-19 after primary platinum-based chemotherapy at one hospital from south Spain. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Results were assessed using Kaplan-Meier method for GSGF-use stratified by NLR, dNLR, or aPD1-i. Results: 79 pts were enrolled (91% men), mean age was 66.7 years, 78.8% of pts had ECOG = 0-1. NIV was used at 55.7%, ATE 25.3% and PEM 19.0% of pts. 50.6 % of tumors were squamous histology. GSGF was used at 19 pts (24.1%). The mean WBC at the start of therapy with aPD1-I was 9300 cell/µL (sd=3900), range 3600-25800 cell/µL. NLR was less than 5 in 46 pts (58.2%) and dNLR was less than 3 in 51 pts (64.6%). The mean time from the start of line previously to start the treatment with aPD1-i was 9.7 months (sd=8.6). The median for treatment duration was 4.1 months [IC 95%; 2.3-5.8].OS was 7.3 months [IC 95%:3.4-11.3] and PFS was 4.4 months [IC95%:2.3-6.5]. We found statistically significant difference in OS between patients with dNLR &lt;3, median 13.9 months [IC95%; 5.4-22.4] vs patients with dNLR&gt; 3, median 3.6 months [IC95%; 2.4-4.7], p=0.037. The median OS was higher in pts GSGF-treated (6.1 months) vs pts no GSGF-treated (3.3 months), p=0.347, no reaching statistical significance. No difference was found in OS by NLR. The analysis for OS by GSGF use stratified by dNLR is shown in the table. Conclusions: The effectiveness of aPD1-i in nSCLC patients previously treated and with dNLR&gt;3, a priori poor prognosis, is greater in the group of patients treated with GSGF, reaching OS like pts with dNLR &lt;3. [Table: see text]
Phase III study of the hypoxia-inducible factor 2α (HIF-2α) inhibitor MK-6482 versus everolimus in previously treated patients with advanced clear cell renal cell carcinoma (ccRCC).
Authors: Toni K. Choueiri, Laurence Albiges, Li Fan, Rodolfo F. Perini, Naseem J. Zojwalla, Thomas Powles, Brian I. Rini
Journal: Journal of Clinical Oncology (2020)

TPS5094 Background: In RCC, the Von Hippel-Lindau ( VHL) tumor suppressor gene is inactivated in most cases, resulting in the accumulation and overactivation of HIF-2α. HIF-2α is a key oncogenic driver in RCC and is involved in the activation of genes associated with angiogenesis, tumor progression, and metastasis, such as vascular endothelial growth factor A ( VEGFA), cyclin D1, and CXCR4. MK-6482 is a potent and selective small molecule inhibitor of HIF-2α, and it has shown antitumor activity in a phase 1/2 study in patients with previously treated advanced ccRCC. Methods: The current study (NCT04195750) is a phase 3, open-label, multicenter, randomized, active-controlled trial to compare the efficacy and safety of MK-6482 with everolimus in patients with previously treated advanced ccRCC. Adults aged ≥18 years will be eligible if they have unresectable, locally advanced, or metastatic ccRCC; have measurable disease per RECIST v1.1; and received ≤3 prior systemic regimens, which must include a PD-1/PD-L1 inhibitor (≥2 doses) and a VEGF-targeted therapy, for locally advanced or metastatic RCC. Approximately 736 patients will be randomly assigned 1:1 to receive MK-6482 120 mg orally once daily or everolimus 10 mg orally once daily. At randomization, patients will be stratified by International Metastatic RCC Database prognostic scores (0 vs 1-2 vs 3-6) and by the number of prior anti-VEGF–targeted therapies received for advanced RCC (1 vs 2-3). Responses will be assessed by CT or MRI per RECIST v1.1 by blinded independent central review at week 9 from the date of randomization, then every 8 weeks through week 49, and then every 12 weeks thereafter. Treatment will continue until documented disease progression, withdrawal of consent, or other discontinuation event. Dual primary endpoints are progression-free survival per RECIST v1.1 and overall survival. Key secondary endpoints include objective response rate, duration of response, patient-reported outcomes, and safety. Clinical trial information: NCT04195750 .
First-in-human phase I/II clinical trial of ONC-392: Preserving CTLA-4 immune tolerance checkpoint for safer and more effective cancer immunotherapy.
Authors: Christian Diego Rolfo, Soren Bentzen, Martin Devenport, Yang Liu, Pan Zheng
Journal: Journal of Clinical Oncology (2020)

TPS3159 Background: A major paradigm in cancer immunotherapy is to use checkpoint inhibitors to break regulatory mechanisms that guard the host against autoimmune diseases. CTLA-4-targeting immunotherapy was the first example to establish this paradigm. However, the clinically tested anti-CTLA-4 antibodies exhibit suboptimal efficacy but high toxicity. Our recent studies have demonstrated that immunotherapy-related adverse events (irAE) and the cancer immunotherapeutic effect (CITE) represent distinct and therapeutically separable activities of anti-CTLA-4 antibodies. The irAEs are attributable to inactivation of the CTLA-4 checkpoint, while the CITE is effective through selective depletion of regulatory T cells (Treg) in the tumor microenvironment. We hypothesize that a safer and more effective CTLA-4-targeting immunotherapy should preserve the CTLA-4 checkpoint while enhancing the efficacy and selectivity of Treg-depletion in tumor microenvironment. In preparation to test this ground-breaking hypothesis clinically, we have generated a next generation of anti-CTLA-4 antibody that preserves the CTLA-4 immune checkpoint by avoiding lysosomal degradation of CTLA-4. The new antibody, ONC-392, has dramatically lower irAEs in a humanized mouse model and significantly more potent activity in depleting tumor-infiltrating Tregs, resulting in more effective CITE. Methods: This is an open label Phase IA/IB clinical study to test the safety, pharmacokinetics (PK), and efficacy of ONC-392 as a single agent and in combination with Pembrolizumab in advanced solid tumors and non-small cell lung cancer patients. The study consists of two linked parts: Part A is a dose-finding rapid titration study, with ONC-392 as a single agent in patients with advanced disease of various histology. The aim of this trial is to define the recommended Phase II dose for ONC-392 monotherapy (RP2D-M), Part B is a Phase IA/IB trial of ONC-392 in combination with a standard dose of 200 mg Pembrolizumab in patients with NSCLC. The trial consists of a dose-finding, dose escalation or de-escalation, Phase IA component aimed at defining the recommended phase II dose for ONC-392 in combination with a standard dose of Pembrolizumab (RP2D-C), then progressing into two parallel, single arm, Phase IB expansion cohorts to test for safety and initial efficacy in two groups of patients with NSCLC: Stage IV NSCLC anti-PD(L)1 immunotherapy naïve with PD-L1-positive (PD-L1 TPS ≥ 1%); Stage IV NSCLC refractory/resistant to anti-PD(L)1 immunotherapy. Clinical trial information: NCT04140526 .
间质性肺疾病的高分辨CT表现
Authors: 马大庆
Journal: BMJ (2011)

问质性肺疾病(TLD)种类繁多,发病原因有:吸入粉尘和有害气体,药物治疗反应,放射性损伤,感染,慢性心、肾疾病和癌性淋巴管炎等;原因未明确者有:特发性间质性肺炎(IIP)、结节病、胶原血管病、血管炎、淋巴增殖性疾病和遗传性疾病等[1].高分辨CT(HRCT)和薄层CT是主要的影像检查方法。
医院的优质服务战略
Authors: 吴春容
Journal: BMJ (2005)

在计划经济时代,医院之间主要靠规模、设备、技术、专家争取发展优势,极少有医院在优质服务上做文章,因为那时的医疗市场是供方市场,而不是需方市场,老百姓没有选择的余地,医院在缺医少药的年代主要以提供技术服务为主.直到现在,优质服务的发展战略还没有引起综合性医院的重视.而老百姓在医疗资源相对过剩的市场经济时代,对服务的要求越来越多,不满情绪越来越明显,优质服务已经成为老百姓的基本追求,也是老百姓选择就医单位的重要依据。
Using web search queries to monitor influenza-like illness: an exploratory retrospective analysis, Netherlands, 2017/18 influenza season
Authors: Paul P Schneider, Christel JAW van Gool, Peter Spreeuwenberg, Mariëtte Hooiveld, Gé A Donker, David J Barnett, John Paget
Journal: Eurosurveillance (2020)

BackgroundDespite the early development of Google Flu Trends in 2009, standards for digital epidemiology methods have not been established and research from European countries is scarce.AimIn this article, we study the use of web search queries to monitor influenza-like illness (ILI) rates in the Netherlands in real time.MethodsIn this retrospective analysis, we simulated the weekly use of a prediction model for estimating the then-current ILI incidence across the 2017/18 influenza season solely based on Google search query data. We used weekly ILI data as reported to The European Surveillance System (TESSY) each week, and we removed the then-last 4 weeks from our dataset. We then fitted a prediction model based on the then-most-recent search query data from Google Trends to fill the 4-week gap ('Nowcasting'). Lasso regression, in combination with cross-validation, was applied to select predictors and to fit the 52 models, one for each week of the season.ResultsThe models provided accurate predictions with a mean and maximum absolute error of 1.40 (95% confidence interval: 1.09-1.75) and 6.36 per 10,000 population. The onset, peak and end of the epidemic were predicted with an error of 1, 3 and 2 weeks, respectively. The number of search terms retained as predictors ranged from three to five, with one keyword, 'griep' ('flu'), having the most weight in all models.DiscussionThis study demonstrates the feasibility of accurate, real-time ILI incidence predictions in the Netherlands using Google search query data.
北京市海淀区社区口腔医生临床技能考试浅析
Authors: 牛光良, 曾东, 刘宇, 刘刚, 刘颖, 蒋保季, 李新球
Journal: BMJ (2007)

对社区口腔医生培训中临床技能考试存在的问题进行了分析.结果发现:考生成绩参差不齐,职称和医院级别是影响考试成绩的两个因素.不同级别医院间考生成绩差异较大,而不同职称间考试成绩差异无统计学意义。
Association of State Medicaid Expansion With Hospital Community Benefit Spending
Authors: Genevieve P. Kanter, Bardia Nabet, Meredith Matone, David M. Rubin
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Medicaid expansion was widely expected to alleviate the financial stresses faced by hospitals by providing additional revenue in the form of Medicaid reimbursements from patients previously receiving uncompensated care. Among nonprofit hospitals, which receive tax-exempt status in part because of their provision of uncompensated care, Medicaid expansion could have released hospital funds toward other community benefit activities. <h3>Objective</h3> To examine changes in nonprofit hospital spending on community benefit activities after Medicaid expansion. <h3>Design, Setting, and Participants</h3> This cohort study used difference-in-differences analysis of 1666 US nonprofit hospitals that filed Internal Revenue Service Form 990 Schedule H detailing their community benefit expenditures between 2011 and 2017. The analysis was conducted from February to September 2019. <h3>Exposures</h3> State Medicaid expansion between 2011 and 2017. <h3>Main Outcomes and Measures</h3> Percentage of hospital operating expenditures attributable to charity care and subsidized care, bad debt (ie, unreimbursed spending for care of patients who did not apply for charity care), unreimbursed Medicaid spending, noncare direct community spending, and total community benefit spending. <h3>Results</h3> Of 1478 hospitals in the sample in 2011, nearly half (653 [44.2%]) were small hospitals with fewer than 100 beds, and nearly 70% of hospitals (1023 [69.2%]) were in urban areas. Among the 1666 nonprofit hospitals, Medicaid expansion was associated with a decrease in spending on charity care and subsidized care (−0.68 [95% CI, −0.99 to −0.37] percentage points from a baseline mean [SD] of 3.6% [4.0%] of total hospital expenditures;<i>P</i> &lt; .001) and in bad debt (−0.17 [95% CI, −0.32 to −0.01] percentage points). There was an increase in unreimbursed spending attributable to caring for Medicaid patients (0.85 [95% CI, 0.60 to 1.10] percentage points;<i>P</i> = .04), which canceled out uncompensated care savings from the expansion. Noncare direct community expenditures decreased overall (−0.24 [95% CI, −0.48 to 0.00] percentage points;<i>P</i> = .049). Direct community expenditures remained more stable in small hospitals (–0.07 [95% CI, –0.20 to 0.05] percentage points;<i>P</i> =.26) compared with large hospitals (–0.37 [95% CI, –0.86 to 0.12] percentage points;<i>P</i> = .14) and in nonurban hospitals (0.02 [95% CI, −0.09 to 0.14] percentage points;<i>P</i> = .70) compared with urban hospitals (–0.36 [95% CI, –0.73 to 0.01] percentage points;<i>P</i> = .06). <h3>Conclusions and Relevance</h3> In this study, Medicaid expansion was associated with a decrease in nonprofit hospitals’ burden of providing uncompensated care, but this financial relief was not redirected toward spending on other community benefits.
Females as surgical oncologists in Taiwan: A nationwide population-based study.
Authors: Weiming Cheng, Yu-Hua Fan
Journal: Journal of Clinical Oncology (2020)

11042 Background: Operations for malignancy are stereotypically viewed as the field of men, especially in eastern countries. In recent decades, more and more women devoted themselves to be surgical oncologists. However, they face many challenges, especially when they treating patients with sex organ-related malignancies. In the present study, we compared the disparities between female and male surgical oncologists in urology, general surgery, and gynecology by analyzing a nationwide, population-based database in Taiwan. Methods: National Health Insurance covers more than 99.6% of population in Taiwan. The system’s claim data are released as the National Health Insurance Research Database. One of its database, the Longitudinal Health Insurance Database 2000, contains all the original data of one million randomly-selected beneficiaries enrolled in year 2000. We recruited the yearly inpatient and outpatient service volumes, oncological surgical volumes, revenue, and sex ratio of patients of each female and male attending general surgeons, gynecologists, and urologists with practice more than five years from 1995 to 2013. The differences of these factors between male and female physicians in each specialty were compared with Mann-Whitney U-test. P &lt; 0.05 was viewed as statistically significant. Results: There are 13, 87, and 191 female urologists, general surgeons, and gynecologists included, accounting for 6.7%, 7.0%, and 51.3% of physicians in each specialty in Taiwan respectively. Female urologists and general surgeons had significantly more female patients (p = 0.004 and &lt; 0.001 respectively). Female urologists had insignificantly less patient service numbers, oncological surgical volumes, and revenues (p = 0.285, 0.718, 0.077 respectively), while female general surgeons and gynecologists performed worse than corresponding male physicians (all p value &lt; 0.001). Of noted, female general surgeons have significantly less patient service (66.0±57.1 vs. 94.8±98.9 patients, p &lt; 0.001) and total surgical volumes (2.30±2.50 vs. 3.28±3.33 surgeries, p = 0.001) but more oncological surgeries (0.33±0.64 vs. 0.17±0.41 surgeries, p = 0.003); however, there is no differences after exclusion of surgeries for breast cancer (0.07±0.22 vs. 0.12±0.32 surgeries, p = 0.057). Conclusions: Patients tend to seek medical help from same-sex physicians in Taiwan. Females could have a comparable career with males in urology, while gender inequality remains significant in general surgery and gynecology. Female surgical oncologists may have advantages in breast cancer treatment.
Levels of tumor necrosis factor (TNF) -α and soluble TNF-R55, 75 in plasma and induced sputum in patients with acute exacerbations of chronic obstructive pulmonary disease
Authors: 曾勉, 黄建强, 卢桂芳, 王辉, 关开泮, 吴健锋, 柯彩霞, 张国娟, 贺云鹏
Journal: BMJ (2007)

目的 观察慢性阻塞性肺疾病(COPD)急性加重期患者治疗前后诱导痰及血浆中肿瘤坏死因子α(TNF-α)和可溶性肿瘤坏死因子受体55、75(sTNF-R55、sTNF-R75)水平的变化.方法 检测并分析48例COPD急性加重期患者治疗前后(A1组和A2组)及28例健康志愿者诱导痰及血浆中TNF-α、sTNF-R55、sTNF-R75水平及其肺功能.结果 COPD急性加重期患者治疗前后诱导痰及血浆中TNF-α和sTNF-R55、sTNFR75的水平均高于健康组;治疗前后痰TNF-α浓度(0.82±0.34)μg/L和(0.48±0.27)μg/L,血(0.82±0.35)μg/L和(0.60±0.46)μg/L,均有明显下降(P＜0.01);sTNF-R55、sTNF-R75浓度上升,血中浓度水平与肺功能无相关性(P＞0.05),诱导痰中浓度水平与肺功能呈正相关性(P＜0.05);TNF-α浓度与第1秒用力呼气容积和其占预计值百分数呈负相关(P=0.000).结论 COPD患者急性加重与全身和局部炎性介质和抗炎介质的失衡有关.全身炎症反应与气流受限关系不大,而局部炎症反应与气流受限密切相关。
Doctors, patients, and the drug industry: Partners, friends, or foes?
Authors: Angell Marcia
Journal: BMJ (2009)

药品企业、学者、医疗专家和患者之间的关系一直以来都不被人看好，这些群体都希望能改善彼此间的关系。皇家外科学院本周提出了42条建议，旨在促进各方和药品企业建立更有成效的关系。这里我们列出有关药品企业和医生与患者之间应该具有什么理想关系的5种观点以及需要采取的相应措施。
Evaluation of a mobile cervical cancer screening program in São Luis, Maranhão, Brazil: Impact and challenges.
Authors: Rachel Jorge Dino Cossetti Leal, Emanuel Cabral Pereira, Thamires Sales Ribeiro, Monalisa Leal Matta Machado, Roseline Braga de Carvalho, Larisa Machado Neme, Deborah Costa Alves, Plinio da Cunha Leal, Luciane Maria Oliveira Brito, Maria Bethânia da Costa Chein
Journal: Journal of Clinical Oncology (2020)

1558 Background: Cervical cancer (CC) still represents a public health priority in Brazil, with estimated incidence of 15,43 cases per 100.000 women. CC is the most frequent cause of cancer and cancer-related mortality in women in the state of Maranhão. The Brazilian national screening program recommends cervical cytology (Pap test) every 3 years in women 25-64 years old. Although of public access, the screening program continues to be non-organized. This was a real-life CC screening intervention through a mobile screening unit (MSU) in communities of São Luis, Maranhão. Methods: Prospective, intervention-based, analytic study, from April to August, 2018. Women in the assisted communities were offered Pap tests. Tests were collected and results were retrieved within 4 weeks along with further screening recommendations. Quality control and monitoring of the test were done. A structured questionnaire was applied. Results: 960 tests were collected and 545 women answered the questionnaire. Median age: 43 (34 – 52), with 88.2% of women within the target age. Socioeconomic charachteristics: 47.3% completed high school education; 37.8% were housewives, 16.1% were unemployed; 56.3% were married; 59.8% had a monthly family-income up to 1 minimum wage ($ 250,00). Previous Pap tests and difficulties: 94.1% had at least one previous test; 78,2% had a test within the past 3 years; 48.4% referred to dificculties to scheduling, 23.3% time constraints, 11.2% being ashamed, and 10.4% financial restrains. There were 65 (6.9%) abnormal results (LSIL in 3%, HSIL in 0.7%, and in situ adenocarcinoma in 1 case), for whom further investigation was recommended. Follow-up was possible in 31 of these cases. More than 50% were still awaiting for additional screening tests at time of contact (&gt;6 month interval). Conclusions: MSU strategy faccilitated the access to Pap tests, their results and recommendations. Although Pap test was easily available, the non-organized process of invitation, follow-up and referal of positive cases for further investigation, as offered by the Brazilian public health services, limit screening efficacy and CC control.