tbuckley/cabot-search huggingface dataset:
A phase III trial-in-progress called REPLATINUM that compares RRx-001 + a platinum doublet to a platinum doublet in third-line or beyond small cell lung cancer.
Authors: Daniel Morgensztern, Chao Hui Huang, Christian Diego Rolfo, John C. Ruckdeschel, Konstantin H. Dragnev, Raid Aljumaily, Ralph J. Hauke, Tarek Mekhail, Mary J. Fidler, John Turner Hamm, Alberto Chiappori
Journal: Journal of Clinical Oncology (2020)

TPS9083 Background: Despite several recent checkpoint inhibitor approvals extensive stage small cell lung cancer (SCLC) is associated with a poor prognosis and remains an area of high unmet need. RRx-001 is a first-in-class, minimally toxic small molecule immunotherapeutic that inhibits c-Myc, downregulates the antiphagocytic checkpoint, CD47, repolarizes tumor associated macrophages (TAM) from protumor M2 to antitumor M1 and resensitizes to previously active first line therapies. On the basis of favorable results from a Phase 2 trial called QUADRUPLE THREAT (NCT02489903) in combination with a platinum doublet in later line SCLC, a Phase 3 trial called REPLATINUM was started in 3 rd line or beyond SCLC in Q4 2019. Enrollment is ongoing. Methods: This US-based, open-label, randomized, phase 3 study (NCT03777657) compares RRx-001 4mg + a platinum doublet (carboplatin or cisplatin + etoposide) versus a platinum doublet for pts with 3 rd line or beyond SCLC that have previously received a checkpoint inhibitor. Approximately 120 pts from 25 centers will be randomized 1:1 to receive RRx-001 4 mg in combination with a platinum doublet vs. a platinum doublet. The platinum doublet will be administered on both arms for up to 4 cycles; on the RRx-001 arm only patients with stable disease or better are eligible to continue on RRx-001 4 mg + carboplatin AUC 2-4 maintenance therapy. If radiologic progression occurs on the control arm prior to the 4 th cycle, patients are eligible to crossover to the RRx-001 treatment arm. PFS is the primary endpoint. Secondary endpoints include OS and ORR. Exploratory endpoints include c-Myc, CD-47 and PD-L1 on circulating tumor cells and SIRP-alpha expression on circulating monocytes. Clinical trial information: NCT03777657.
急性肾损伤
Authors: 吴东, 蔡建芳, 陈嘉林
Journal: BMJ (2012)

一、急性肾损伤,定义看步枪(RIFLE)急性肾损伤(acute kidney injury,AKI)指急性(48 h内)肾功能下降,临床主要表现为血清肌酐的升高或尿量减少.为早期发现并完整反映肾功能急性变化的连续过程,2002年急性透析质量倡议(Acute Dialysis Quality Initiative,ADQI)提出以AKI的概念取代急性肾衰竭(acute renal failure,ARF),并用RIFLE系统对其定义分级.2005年,急性肾损伤网络工作组(Acute Kidney Injury Network,AKIN)又基于RIFLE系统对AKI的定义及分级进行了修订。
Diagnosis and treatment of hydrometrocolpos in infants less than 6 months
Authors: Hongxia Ren, Yanli Zhang, Xiaobing Sun, Xiaoxia Wu, Baohong Zhao, Yuanyuan Jin, Min Yang, Liqiong Duan, Xue Sun
Journal: BMJ (2016)

Objective
To review the diagnosis and treatment of hydrometrocolpos in infants less than 6 months.


Methods
The clinical data of 6 infants aged 2 to 180 d (mean 57 d) with hydrometrocolpos admitted in our hospital between January 2011and June 2014 were retrospectively analyzed.


Results
Among 6 cases, there were 2 case of urogenital sinus malformation, 1 case combined with cloacal deformities, 1 case combined with Muckusick-Kaufman syndrome, 1 case combined with oblique vaginal syndrome and 1 case combined with obliteration of hymen. There were 3 cases with unilateral hydronephrosis, 1 case with bilateral renal seeper and pouch colon, 1 case with hands and foot polydactyly-syndactylia and congenital heart disease and 1 case combined double uterus, vagina and cystic renal masses. Abdominal and pelvic ultrasonographic examination was performed in all 6 cases, abdominal CT or MRI scans of genital tract were performed in 5 cases. Three cases received cystoscopy, 4 cases underwent laparoscopic exploration. All 6 cases underwent uterine vaginal fluid drainage; one patient received hymen incision, one case received incision of longitudinal vaginal septum and fluid drainage; 4 cases received fluid drainage under laparoscopy, including one case undergoing colostomy. The clinical symptoms of all six cases disappeared during 6 months to 3 years follow-up, no patient had recurrence.


Conclusions
Hydrometrocolpos is relatively rare in neonates or young infants. The clinical manifestations are mainly abdominal distension, defecate difficulty and abnormal perineum. Detailed physical examination and ultrasound examination, CT or MRI scan, imaging, endoscopy are helpful for the diagnosis. Comprehensive investigation and individualized treatment strategy are important.


Key words: 
Genital diseases, female; Infant; Diagnosis; Treatment
A template for generic asssessment of tumor response: "myRECIST".
Authors: Stephen Raskin, Tehila Kharizman, Tatyana Rachutin Zalogin, Aliza Ackerstein, Eli Konen, Raanan Berger, Michal Amitai
Journal: Journal of Clinical Oncology (2020)

e14149 Background: Oncologists often need an objective, quantitative assessment of a patient's response to therapy. Lacking a standardized format, the oncologist may request a RECIST (Response Evaluation Criteria in Solid Tumors) analysis. RECIST, however, was developed to provide standardized assessment in the context of randomized clinical trials. RECIST is based on the prospective analysis of a limited sample of tumor lesions or lymph nodes, whereas the clinician naturally makes clinical decisions retrospectively. Furthermore, RECIST has definitions, rules, and criteria for classifying responses that may not apply in the clinical setting, and it does not include consistent rules for merging or splitting lymph nodes, mixed tumor responses, lesions that may cavitate, and a wide range of individualistic responses encountered in clinical practice. Methods: To address these issues, we have modified our working Excel-based template for RECIST 1.1 assessment to include a "myRECIST" feature, so that the radiologist can enter data and examine a range of pre-defined or customizable scenarios, including RECIST1.1, iRECIST, Lugano, volumetric and other parametric protocols. With a few interactions, this template can produce exportable tables and graphs of tumor responses that can guide therapy, as shown in the attached image. Definitions are standardized and linked to RADLEX ontology for specificity and subsequent analysis. Results: This template has been developed for clinical use and is available for downloading from our institutional web-site. Conclusions: We have developed, for public use, a free, easy-to-use, down-loadable Excel template for evaluating prospective or retrospective scenarios of tumor response to therapy that avoids the restrictions of the RECIST methodology. This template may prove useful to oncologists both in and out of the context of randomized clinical trials. We call this "myRECIST."
Health insurance status and cancer stage at diagnosis and survival in the United States.
Authors: Jingxuan Zhao, Xuesong Han, Leticia Nogueira, Ahmedin Jemal, Michael T. Halpern, K Robin Yabroff
Journal: Journal of Clinical Oncology (2020)

7026 Background: While previous studies demonstrated associations between Medicaid coverage or no health insurance with both advanced stage at cancer diagnosis and worse survival, access to health care in the U.S. has changed substantially in the past decade. This study examined associations of health insurance status with stage at diagnosis and survival among 17 common cancers using recent national data. Methods: We identified 1,427,532 cancer patients aged 18-64 years newly diagnosed with 17 common cancers from the 2010-2013 National Cancer Database. Multivariable logistic regression models were used to examine the distribution of stage at diagnosis by health insurance status (private, Medicare, Medicaid, dual Medicare/Medicaid, and uninsured) overall and for each cancer site. Cox models compared stage-specific survival by health insurance for each site. Results: Compared to privately insured patients, Medicaid and uninsured patients were significantly more likely to be diagnosed with advanced-stage cancer (III/IV) for all the 17 cancers combined (adjusted odds ratio [AOR]: 2.27, 95% confidence interval [95CI]: 2.24-2.29; AOR: 2.39, 95CI: 2.36-2.42, respectively) and for all included cancer sites separately. Medicare and Medicare-Medicaid patients were also more likely to be diagnosed at advanced-stage for all the 17 cancers combined, but results varied by cancer site. Compared to the privately insured patients, worse survival was observed for patients with all other insurance types and uninsured at each stage for all the 17 cancers combined and most cancer sites. For example, among patients diagnosed at stage I, adjusted mortality hazard ratios for Medicare, Medicaid, Medicare-Medicaid, and uninsured patients were 1.72 (95CI: 1.70-1.75), 1.73 (95CI: 1.71-1.76), 2.07 (95CI: 2.02-2.17) and 1.56 (95CI: 1.53-1.58), respectively, compared with privately-insured patients. Conclusions: Patients with non-private insurance were more likely to be diagnosed with cancer at advanced stage and have worse survival. Improving access to health insurance with adequate coverage is crucial for receiving appropriate cancer screening, diagnosis, and quality care.
Proteome-wide biomarker quantification and target screening.
Authors: Qimin Quan, John Geanacopoulos, Joshua Ritchey, Mark Clenow, Joe Wilkinson, John Boyce
Journal: Journal of Clinical Oncology (2020)

e15205 Background: Existing drug development programs are represented by only a few hundred protein targets. A large subset of the ~20,000 proteins encoded by the human genome remain undiscovered. Proteome-wide “druggability” screening may lead to new targets for therapeutics. Methods: The NanoMosaic platform is a digital immunoassay technology that achieves sub-pg/ml level sensitivity, whole-proteome level multiplexing capability, and 7 logs of dynamic range. The platform overcomes the sensitivity and dynamic range limitations of traditional protein arrays and mass spectrometry. Results: The NanoMosaic technology is powered by silicon nanoneedle biosensors that are densely integrated on a plate and manufactured with CMOS-compatible nanofabrication processes. Each nanoneedle is a label-free biosensor, functionalized with capture antibodies. Its scattering spectrum changes when an antigen binds to its surface. Each analyte specific sensing area consists a total of ~23k nanoneedles divided into a digital region (~20k nanoneedles) and an analog region (~3k nanoneedles). The digital nanoneedles provide the single molecule sensitivity. Therefore, at ultra-low concentration when antigens that are captured by the nanoneedles follow Poisson statistics, the number of antigens can be quantitated by counting the presence or absence of color changes of individual nanoneedles in a binary fashion. As the protein concentrations increase, the binding event counts increase accordingly and achieve saturation when all nanoneedles capture more than one protein. Above the digital saturation concentration, an adjacent section of analog nanoneedles perform quantitative analysis based on the level of color change, thus providing a wider dynamic range up to 1ug/ml. Ultrahigh level multiplex can be achieved by parallelizing the detection in a microarray format without loss of the sensitivity and dynamic range. A 20,000-plex proteome-wide study can be achieved with a total of 5 billion nanoneedles on a ~70mm by 70mm chip. Conclusions: In conclusion, proteome-wide biomarker quantification and target discovery can be performed on the NanoMosaic platform at higher sensitivity, wider dynamic range, lower cost and higher throughput than is currently possible by mass spectrometry or traditional immunoassays.
关于基层高血压防治指南中有关血压测量问题的答复
Authors: 王文, 吴兴田
Journal: BMJ (2010)

首先衷心感谢广大医生关注基层高血压防治指南,深入学习和讨论,并提出宝贵意见,以不断修改完善. 1.有关非同日3次血压测量的理解:基层高血压指南与指南解读的撰稿人为同一人,主题理念是一致的,没有矛盾.基层指南力求简明扼要,故可能在某些方面表述不完善;可能在解读某一方面问题时,侧重点有所不同,表述方式有差异。
Computerized features of spatial arrangement of tumor-infiltrating lymphocytes from H&amp;E images predicts survival and response to checkpoint inhibitors in gynecologic cancers.
Authors: Sepideh Azarianpour Esfahani, Germán Corredor, Kaustav Bera, PingFu Fu, Amy Joehlin-Price, Haider Mahdi, Anant Madabhushi
Journal: Journal of Clinical Oncology (2020)

6074 Background: Immune checkpoint inhibitors (ICI) have demonstrated success in solid tumors. In gynecologic cancers (GC), the response rate is still low (~10-15%) except in MSI-H endometrial cancer (~ 50%). Current biomarkers (e.g. PDL1 expression) have limited utility in identifying benefit from ICI in GC. In this work we evaluated the ability of computational measurements of spatial arrangement of tumor infiltrating lymphocytes (TIL) from H&amp;E slide images in predicting overall survival (OS) and response to ICI in ovarian, cervical and endometrial cancers. Methods: The study included 151 patients, including 102 ovarian carcinomas treated with surgery and chemotherapy (D1) and another set (D2) of n=49 patients (n=14 ovarian, n=27 endometrial and n=8 cervical), treated with different ICI agents (Pembrolizumab, Nivolumab, Ipilimumab, Avelumab) in the second line setting. Progressors and non-progressors in D2 were classified according to clinical improvement and radiologic assessment by RECIST. A machine learning approach was employed to identify tumor regions on the diagnostic slides from D1 and D2 and then used to automatically identify TILs within the tumor regions. Subsequently machine learning was used to define TIL clusters based on TIL proximity, and graph network theory was used to capture measurements relating to spatial arrangement of TIL clusters. The multivariable Cox regression model (MCRM) was trained on n=51 patients from D1 to predict OS and then independently evaluated in predicting (1) OS on the hold-out n=51 patients in D1 and (2) response and progression-free survival (PFS) in D2. Results: Statistical analysis identified 7 prognostic features relating to interaction of TIL clusters with cancer nuclei. MCRM was prognostic of OS on the n=51 hold out patients in D1 (hazard ratio (HR)=2.06, 95% confidence interval [1.04- 4.07], p=0.008) and predictive of PFS in D2 (HR=2.24, CI=[1.13-4.44], p=0.03). The AUC for MCRM in predicting progression in D2 was 82%. Conclusions: Computerized features of spatial arrangement of TILs on H&amp;E images were prognostic of OS and PFS and predicted response to ICI in three gynecological cancers. These findings need to be validated in larger, multi-site validation sets. [Table: see text]
Evaluation on validity of Manual of Home-Based Rehabilitation Mode for Stroke Patients in Community
Authors: Yongxiang Zhou, Yan Qin, Hong Zhang, Yu'e Zhang, Yin Chen, Jianping Wu
Journal: BMJ (2017)

The evaluation tools were developed based on the theory of validity, the development process and results of the Manual of Home-Based Rehabilitation Mode for Stroke Patients were evaluated by a panel of experts, and the opinions and suggestions for improvement were collected from the evaluation experts. The results showed that the average score for development process and results of the manual were >4 points in structural validity, content validity and surface validity, indicating that the manual was of high quality, and the development of the manual was scientific and the results were practical. The manual may provide the guidance for the home-based rehabilitation in community. At the same time, this study has enriched the reviewing tools and evaluation method of manuals, and provided reference for the peers.


Key words: 
Stroke; Rehabilitation; Community health service
从三个病例看临床思维
Authors: 刘凤奎, 姜民慧
Journal: BMJ (2010)

刘凤奎:本讲通过三个病例来分析临床体检与临床思维. 例1为50岁男性,因为左上腹疼四五天,从千里之外来求诊.根据患者的主诉,从腹痛的角度入手考虑,应该了解其腹痛的部位、特点、程度与性质(阵发、持续、可否忍受等)、有无诱因,另外疼痛有无放射、是否可缓解等.疼痛部位在上腹,首先考虑胃、胆、胰腺等消化道疾病,询问病史.其次为非消化系统,如胸腔疾病,胸膜炎、肺炎可放射到上腹出现疼痛,故需了解有无呼吸道症状及与呼吸有关的一些表现;心绞痛、心肌梗死(心梗)也可致上腹疼痛。
Establishing the common oncology data model for the national biobank consortium of Taiwan.
Authors: Yang Yi-Hsin, Li-Tzong Chen, Shiu-Feng Huang
Journal: Journal of Clinical Oncology (2020)

e19283 Background: Taiwan has 32 biobanks under Government’ governance. The Ministry of Health and Welfare have established a National Biobank Consortium of Taiwan to unify the specimen quality and the medical record database. The total recruited participants exceed 350,000. The National Health Research Institutes in Taiwan hold the responsibility of establish a common data model for aggregating data elements from electronic health records (EHRs) of institutes through direct feeds. The goals are to assemble a set of common oncology data elements and to facilitate cancer data interoperability for patient care and research across institutes of Biobank Consortium. Methods: We first conduct a thorough review of available EHR data elements for patient characteristics, diagnosis/staging, treatments, laboratory results, vital signs and outcomes. The data dictionary was organized based on HL7 FHIR and also included data elements from Taiwan Cancer Registry (TCR) and National Health Insurance (NHI) Program, which the common definition has already been established and implemented for years. Data elements suggested by ASCO CancerLinQ and minimal Common Oncology Data Elements (mCODE) are also referenced during planning. The final common model was then reviewed by a panel of experts consisting oncologists as well as data science specialists. Results: There are finally 9 data tables with 281 data elements, in which 248 of them are from the routinely uploaded data elements to government agencies (TCR &amp; NHI) and 33 elements are collected with partial common definition among institutes. There are 164 data elements which are to be collected one observation per case, while 117 elements will be accumulated periodically. Conclusions: A comprehensive understanding of genetics, phenotypes, disease variation as well as treatment responses is crucial to fulfill the needs of real-world studies, which potentially would lead to personalized treatment and drug development. At the first stage of this project, we aim to accumulate available EHR structured data elements and to maintain sufficient cancer data quality. Consequently, the database can provide real-world evidence to promote evidence-based &amp; data-driven cancer care.
Studies on the biological and pathogenical characteristics of Trichophyton rubrum
Authors: 傅裕, 鲍迎秋, 常建民, 李若瑜
Journal: BMJ (2007)

皮肤癣菌是一类能入侵角质层和角质组织的真菌,在人和动物可引起表浅感染.常引起感染的皮肤癣菌主要有红色毛癣菌、须癣毛癣菌、犬小孢子菌、石膏小孢子菌和絮状表皮癣菌.红色毛癣菌是一种最常见的亲人性致病性皮肤癣菌[1],呈世界性分布,也是我国最常见的皮肤癣菌.红色毛癣菌可以引起皮肤、毛发、指(趾)甲感染,且常引起足和指(趾)甲的慢性难治性感染.有研究统计它可以导致皮肤癣菌病中90%的慢性感染[2],培养阳性率达到67%[3].因此,红色毛癣菌是一种非常重要的致病菌,了解它的生物学特性和致病特点对红色毛癣菌引起的皮肤癣菌病的诊断、治疗有十分重要的意义。
Assessment of community health service ability of general practitioners after standardized training in Shanghai
Authors: Hui Li, Minghui Peng, Shijie Fu, Xiangjie Zhang, Yao Liu
Journal: BMJ (2016)

Objective
To assess community health service ability of general practitioners(GPs) with the Standardized General Practitioner Training(SGPT)in Shanghai.


Methods
One hundred and four GPs receiving SGPT and matched 102 GPs without SGPT were enrolled in this retrospective cohort study from September to November in 2014. Community health service ability, including abilities in basic medical service and public health service were assessed and compared between two groups. Written examination was applied in the public health services ability assessment. Objective structured clinical examination (OSCE) was applied for evaluation of basic medical service abilities.


Results
The scores of written examination in GPs with SGPT were higher than those without SGPT[(66±4) vs. (62±7), P 0.05).


Conclusions
GPs with SGPT have better basic medical service and public health service ability. But some aspects of basic medical service ability need to be strengthened in the training and practice.


Key words: 
Community health services; Clinical competence; General practitioners; Standardized general practitioner training
伏立康唑致骨髓抑制一例
Authors: 李淑杰
Journal: BMJ (2008)

患者女,51岁.持续高热10 d入院.体温39.5 ℃左右.7年前因脑梗死卧床.近45 d一直因肺炎应用多种抗生素(如青霉素、头孢他啶、头孢三嗪).查体:体温39.4℃,体重50 kg,神志模糊,口角皲裂,舌体光滑无苔,左下肺闻及湿啰音,右侧肢体肌力0级,左侧肢体肌力3级。
MAX Functions as a Tumor Suppressor and Rewires Metabolism in Small Cell Lung Cancer
Authors: Arnaud Augert, Haritha Mathsyaraja, Ali H. Ibrahim, Brian Freie, Michael J. Geuenich, Pei-Feng Cheng, Sydney P. Alibeckoff, Nan Wu, Joseph B. Hiatt, Ryan Basom, Adi Gazdar, Lucas B. Sullivan, Robert N. Eisenman, David MacPherson
Journal: Cancer Cell (2020)
Medicaid expansion and trends in cancer stage at diagnosis.
Authors: John Withington, Angela Tramontano, Deborah Schrag
Journal: Journal of Clinical Oncology (2020)

e14129 Background: Cancer stage distribution offers an early window into the effect of the ACA’s 2014 Medicaid expansion. If Medicaid expansion enabled uninsured adults to access preventive care, then the proportion of cancers diagnosed at early stage should be higher in states that adopted it. Methods: Patient level data were retrieved from SEER-18, New York and Texas cancer registries from January 2010 to December 2015, for eight common tumor types; including N = 2,493,589 (breast, cervical, colorectal, prostate, lung) screen detectable and N = 369,203 (testis, kidney and uterine corpus) not detected by routine screening. Patients were categorized by residence in states that were: 1) Non-expanders; 2) Expanders - income eligibility thresholds increased from 0% to 138% of the federal poverty level (FPL) in 2014; and 3) Pre-Expanders, with pre-2014 eligibility thresholds &gt; 70% of FPL. Stage distributions were compared before and after January 2014, categorized by AJCC stage and using ordinal stage equivalent (OSE) which assigns a numeric score based on AJCC stage. Difference in difference in difference (D3) methods compared patients ≥65 versus &lt; 65, and screen-detectable versus not. Multivariable logistic regression was used to adjust for variation in age, sex, race, ethnicity and tumor site across states. Results: No differences in stage distribution were observed across the three categories of state. (Table). D3 analysis revealed no difference between trends in the over 65s, or for screen-detectable cancers. Adjustment for age, sex, race, ethnicity and tumor site made no significant difference to these results. Conclusions: States’ Medicaid expansion status in 2014 was not associated with a significant difference in early stage diagnoses for adults with cancer diagnosed before age 65. Obstacles to early cancer detection other than financial access must be addressed to improve population-level outcomes. [Table: see text]