tbuckley/cabot-search huggingface dataset:
Temporal trends in opioid prescribing patterns among oncologists in the Medicare population.
Authors: Vikram Jairam, Daniel X. Yang, Saamir Pasha, Pamela R. Soulos, Cary Philip Gross, James B. Yu, Henry Soo-Min Park
Journal: Journal of Clinical Oncology (2020)

12022 Background: In the wake of the United States (U.S.) opioid epidemic, there have been significant governmental and societal efforts to curb opioid prescribing. However, it is unknown whether these efforts have affected prescribing among oncologists, whose patient population often requires narcotics for symptom management. We investigated temporal patterns in opioid prescribing for Medicare patients among oncologists. Methods: We queried the Centers for Medicare and Medicaid Services Part D prescriber dataset to identify independently practicing physicians between January 1, 2013 and December 31, 2017. We used population-averaged multivariable negative binomial regression to estimate the association between time and per-provider opioid prescribing rate, defined as number of opioid claims (original prescriptions and refills) per 100 patients, among oncologists and non-oncologists on both a national and statewide level. All models were adjusted for provider characteristics and annual total patient count per provider. Results: The final study sample included 20,513 oncologists and 711,636 non-oncologists. From 2013 to 2017, the national opioid prescribing rate declined by 19.3% (68.8 to 55.5 opioid prescriptions per 100 patients; P&lt; 0.001) among oncologists and 20.4% (50.7 to 40.3 prescriptions per 100 patients; P&lt; 0.001) among non-oncologists. During this timeframe, 40 U.S. states experienced a significant ( P&lt; 0.05) decrease in opioid prescribing among oncologists, most notably in Vermont (-43.2%), Idaho (-34.5%), and Maine (-32.8%). In comparison, all 50 states exhibited a significant decline ( P&lt; 0.05) in opioid prescribing among non-oncologists. In 5 states, opioid prescribing decreased more among oncologists than non-oncologists, including Oklahoma (-24.6% vs. -7.1%), Idaho (-34.5% vs. -17.8%), Utah (-31.7% vs. -18.7%), Texas (-19.9% vs. -14.7%), and New York (-24.0% vs. -19.7%) (all P&lt; 0.05). Conclusions: Between 2013 and 2017, the opioid prescribing rate decreased by approximately 20% nationwide among both oncologists and non-oncologists. These findings raise concerns about whether opioid prescribing legislation and guidelines intended for the non-cancer population are being applied inappropriately to patients with cancer and survivors.
FLT3 ligand (CDX-301) and stereotactic radiotherapy for advanced non-small cell lung cancer.
Authors: Nitin Ohri, Balazs Halmos, Madhur Garg, Jeffrey M Levsky, Haiying Cheng, Rasim A. Gucalp, William Raymond Bodner, Rafi Kabarriti, Aviva Berkowitz, Michael Jay Yellin, Tibor Keler, Shalom Kalnicki, Chandan Guha
Journal: Journal of Clinical Oncology (2020)

9618 Background: In a murine non-small cell lung cancer (NSCLC) model, we demonstrated synergy between localized radiotherapy and the dendritic cell growth factor fms-like tyrosine kinase 3 (FLT3) ligand. We now present results from a phase II study testing this combination in patients with advanced and treatment-refractory NSCLC. Methods: Advanced NSCLC patients with multifocal active disease after at least one line of systemic therapy and ECOG performance status 0-2 received 5 daily subcutaneous injections of CDX-301 (75 µg/kg) concurrent with stereotactic body radiotherapy (SBRT, 30-54 Gy in 1-5 fractions based on target size and location) directed at a single site of disease. Additional “cycles” of SBRT and CDX-301 could be administered at least four months after the initial study treatment, at the discretion of the treating physicians. The primary endpoint was progression-free survival four months after treatment initiation (PFS4), with a hypothesis that the PFS4 rate would exceed 40%. Secondary endpoints included overall survival (OS) duration, responses on PET (PERCIST criteria) and CT (RECIST criteria), and dose-limiting toxicities (grade ≥3 adverse events within 30 days). Lesions targeted with SBRT were excluded from response assessments. The intended sample size was 29 subjects. Blood samples were obtained for flow cytometry and other analyses of immune activation. Results: Twenty-nine subjects received study therapy between October 2016 and January 2020. Subjects received a median of 3 lines (range: 1-5) of systemic therapy prior to study enrollment, including immune checkpoint inhibitors targeting the PD-1/PD-L1 axis in 26 subjects (90%). At the time of this analysis, the actuarial PFS4 rate is 60%, which exceeds our pre-specified efficacy objective. With a median follow-up duration for living patients of 12 months, the actuarial 12-month OS rate is 55%. Partial response of lesions not targeted with SBRT (“abscopal effect”) was observed in 9 subjects (31%) using PET criteria and in 4 subjects (14%) using CT criteria. Seven subjects (24%) received a second course of SBRT and CDX-301 after initial study therapy. No dose-limiting toxicities have been observed. Only six subjects (21%) have received additional chemotherapy or immunotherapy after study treatment. Conclusions: The combination of CDX-301 and SBRT is well-tolerated and has activity as systemic therapy for advanced NSCLC. Additional studies to maximize the efficacy of this in situ vaccination approach with the addition of an agonist anti-CD40 antibody (CDX-1140) are planned. Clinical trial information: NCT02839265 .
反复咳嗽、咳痰、气喘十余年,加重两天
Authors: 陈远虹, 崔明, 韩一平, 祝墡珠
Journal: BMJ (2012)

病史摘要患者,男性,75岁.因“反复咳嗽、咳痰、气喘10余年,加重2d”于2010年12月24日入院.患者10余年前开始出现反复发作咳嗽、咳痰,冬春季及季节变化时为甚,每年发作持续时间超过2个月,抗炎平喘等治疗有效.近年有活动后气促.2d前患者又出现咳嗽、咳痰,为白黏痰,不易咳出,伴气促,不伴发热、胸痛、咯血、盗汗、刺激性干咳、夜间阵发性呼吸困难、少尿、下肢浮肿等.曾至我院门诊就治,查血常规:WBC 10.8×109/L,分类中性粒细胞0.675,CRP35 mg/L;胸片:两肺纹理增多,予头孢呋辛钠、二羟丙茶碱等治疗,症状未好转,现为进一步诊治,拟“慢性支气管炎急性发作”收入病房.入院后经抗感染、止咳平喘、控制血压等治疗后病情稳定.入院第4天晨8点患者在安静状态下突发气促,即予以头孢他啶、左氧氟沙星抗感染,氨溴索化痰,二羟丙茶碱、甲基泼尼松龙静脉推注,呋塞米降压等治疗。
Differential expression of micro-RNA in tumor and non-tumor tissues of patients with colorectal cancer.
Authors: Inna A. Novikova, Natalya N. Timoshkina, Oleg Ivanovich Kit, Sergey I. Poluektov, Andrey V. Dashkov, Dmitry Haragezov, Roman E. Tolmakh, Evgeniy N. Kolesnikov, Vladimir A. Dontsov, Dmitry S. Petrov, Natalya V. Soldatkina, Yuriy A. Gevorkyan, Denis S. Kutilin
Journal: Journal of Clinical Oncology (2020)

e13516 Background: The colorectal cancer (CRC) incidence is steadily increasing. Moreover, the problem of its early diagnosis remains unresolved due to the low specificity of known tumor markers, and the problem of creating new therapeutic approaches is due to the lack of a complete understanding of the mechanisms of regulation of gene expression in this oncopathology. The study of micro-RNAs (short non-coding RNAs that regulate gene expression) can be the solution to both problems. The aim of the study was to analyze micro-RNA differential expression in the tumor and non-tumor tissues of CRC patients. Methods: 5 patients with CRC (colon adenocarcinoma, G2) were selected for the multiple parallel micro-RNA sequencing. The mirVana miRNA Isolation Kit protocol was used to isolate small RNA fractions. The miRNA library was prepared using the TruSeq Small RNASample Preparation Kit. Sequencing of the nucleotide sequences of cDNA libraries was performed using a MiSeq (Illumina, USA). The copy numbers of micro-RNA were determined by comparing the nucleotide sequence of the sequenced molecules in each sample with the known nucleotide sequences of micro-RNA presented in the databases. When analyzing the differential expression of micro-RNA, the DESeq2 method implemented in R medium was used. Results: Six differentially expressed micro-RNAs were detected (p &lt; 0.05): 2 that decrease expression (hsa-miR-143-3p,hsa-miR-26a-5p) and 4 increase expression in the tumor relative to non-tumor (hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-21-5p, hsa-let-7i-5p). The highest level of expression in both tumor and non-tumor tissue was observed for hsa-miR-143-3p, the lowest one for hsa-let-7i-5p. Moreover, the largest difference in micro-RNA expression in tumor tissue relative to non-tumor was shown for hsa-miR-92a-3p (4.5 times, p = 0.02), the smallest for hsa-miR-143-3p (2.4 times, p = 0.04). For miRNAs that differentially changed their expression, a search was made for target genes using the miRWalk 3.0 database. 14573 target genes were found, of which 3346 were for hypo-expressed micro-RNAs and 11228 for hyper-expressed micro-RNAs. Conclusions: Sequencing revealed 6 differentially expressed micro-RNAs (hsa-miR-143-3p, hsa-miR-26a-5p, hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-21-5p, hsa-let-7i-5p) in the tumor tissue is relatively non-tumor tissues of the colon. The data obtained expand the understanding of the mechanisms of gene regulation in the context of this oncopathology and may possibly become the basis for highly specific tumor markers panel.
Translational relevance of androgen receptor immunohistochemistry scoring systems for data harmonization in triple negative breast cancer (TNBC).
Authors: Suhail Sayeed Mufti, Bhanu Prakash Lalkota, Tejaswini BN, Hrishi Varayathu, Vinu Sarathy, Lalnun Puii, Lalram Sangi, Beulah Elsa Thomas, Diganta Hazarika, Satheesh Chiradoni Thungappa, Sriniivas Bj, Shekar Patil, Radheshyam Naik, Basavalinga Sadasivaiah Ajaikumar
Journal: Journal of Clinical Oncology (2020)

1078 Background: Androgen receptor (AR) expressing triple negative breast cancer (TNBC) is a sub-set of TNBC with an evolving prognostic and predictive behaviour. AR immunohistochemical threshold for positivity has not been standardized and a wide range of cut-offs have been used across studies ( &gt; 0% to 75%). In this study we explored AR immunohistochemistry thresholds in relation to disease free survival (DFS) and clinical outcomes in non-metastatic TNBC using the Allred and H-Score systems. Increasing interest in AR as a therapeutic target for TNBC and the use of digital tissue image analysis makes it important to standardize AR immunohistochemistry reporting. Methods: 100 FFPE (formalin-fixed paraffin-embedded) tumour blocks were retrieved for non-metastatic TNBCs diagnosed between January 2015 and May 2017 and immunostained using AR441 (IgG1) mouse monoclonal antibody. Clinical follow-up ranged from 59 to 31 months and DFS was calculated. Cut-off scores were explored using Evaluate Cutpoints ( R maxstat package) and X-tile software. The score with maximum split in DFS (based on log-rank statistics and lowest p-value) was chosen as the cut-off. Descriptive and survival statistics was performed. Results: The median age was 51 (SD 11.262; range 28 to 82) years. Using Evaluate Cutpoints ≥3 was found as the threshold for AR by Allred Score. 36% cases were AR positive using Allred score (HR 0.508; CI 0.234 - 1.11; p-value 0.08). Using Evaluate Cutpoints ≥30 was found as the threshold for AR by H-Score (HR 0.624, CI 0.306 - 1.27; p-value 0.19). 35% cases were AR positive using H-Score. X-tile analysis also found the cut-offs as ≥3 and ≥30 for Allred and H-Score respectively (p &lt; 0.05). A significant correlation was seen between the two scoring systems (Pearson Correlation 0.935; p &lt; 0.01). A significantly higher number of grade III TNBCs were AR negative (n = 55/76) compared to grade II (n = 9/24) (p = 0.002). Cut-off for Ki67 was 75 (HR 1.61, CI 0.85-3.04, p-value 0.141) with a significantly higher number of AR negatives in the Ki67≥75 group (21/26; p &lt; 0.05). The overall median DFS was 51.9 months. There was no significant difference in DFS for the AR negative (median: 47.4 months; mean: 39.39 months) and AR positive (Median survival not reached; mean: 41.3 months) groups(p = 0.23). Conclusions: AR immunohistochemistry cut-offs using the Allred (≥3) and H-Score (≥30) are close to the ones used for ER/PR immunohistochemistry as per ASCO/CAP guidelines, making a strong case for universal application of these systems for harmonization of AR data.
Two-year survival with nivolumab in previously treated, advanced non-small cell lung cancer: A pooled analysis of real-world patients from France, Germany and Canada.
Authors: Martin Sebastian, Clarisse Audigier-Valette, Charles Andrew Butts, Didier Debieuvre, Adrien Dixmier, Andreas Gröschel, Sylvia Gutz, Rosalyn A. Juergens, Catherine Labbe, Denis Moro-Sibilot, Maurice Perol, Christian Schumann, Ariadna Juarez-Garcia, Khalid Lakhdari, John R. Penrod, Filippa Pettersson, Dorothee Reynaud, Daniela Waldenberger, Victoria Allan, Fabrice Barlesi
Journal: Journal of Clinical Oncology (2020)

e21714 Background: Data from clinical studies demonstrate a long-term survival benefit of nivolumab in previously treated advanced non-small cell lung cancer (NSCLC) patients with overall survival (OS) at two-years of 27%, however real-world data are limited. We report OS in patients pooled from two prospective multi-centre observational cohort studies in France (EVIDENS, NCT03382496) and Germany (ENLARGE, NCT02910999) and a third retrospective registry of patients treated through expanded access to nivolumab in Canada. Methods: Individual patient data from each cohort were pooled and harmonised in eligibility criteria and variable definitions. Included patients had locally advanced or metastatic (stage IIIB/IV) NSCLC, received nivolumab after at least one prior systemic therapy and had no other concurrent primary cancers. OS was estimated from nivolumab initiation until death or censoring using Kaplan-Meier method. Equality of survival distributions across cohorts was measured using log-rank test. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated from unstratified Cox proportional hazards regression models to explore survival among subgroups. Data on bone and liver metastases, PD-L1 and safety were available and analysed for France and Germany only. Results: Data from 2582 patients (48% France; 34% Germany; 18% Canada) were pooled. Baseline characteristics were: median age 66 years, 64% male, 82% ECOG 0-1, 69% 1 prior line of therapy, 68% non-squamous histology, and 18% with brain metastases (treated or untreated). Median follow-up was 8 months. No difference in OS was observed between countries. The 2-year OS was 28% (95%CI 25-31) for all patients, 26% (95%CI 21-31) for squamous histology and 29% (95%CI 26-33) for non-squamous histology. Bone metastases (HR 1.42; 95%CI 1.26-1.60; P= &lt; .0001) and liver metastases (HR 1.60; 95%CI 1.39-1.85; P= &lt; .0001) were associated with shorter survival, while ECOG PS 0-1 (HR 0.61; 95%CI 0.52-0.71; P= &lt; .0001) and PD-L1 positivity (HR 0.75; 95%CI 0.60-0.93; P= &lt; .0001) were associated with prolonged survival. Rates of any grade and grade 3/4 treatment-related adverse events (TRAE) were 32% and 7% respectively. Conclusions: In this three-country pooled analysis of nivolumab in previously treated advanced NSCLC, real-world overall survival at 2-years was consistent with pivotal nivolumab trials overall and in subgroups. Rates of grade 3/4 TRAEs were comparable, but events of lower grade may be underreported in the real world.
Metastases resection in colorectal cancer patients with mutation in oncogene BRAF or tumors located on the right side: Experience at the HGUGM.
Authors: Laura Ortega, Marianela Bringas Beranek, Natalia Gutiérrez Alonso, Javier Soto Alsar, Manuel Alva Bianchi, Marta Arregui Valles, Inmaculada Aparicio Salcedo, Iria Gallego Gallego, Gonzalo García González, Gabriela Torres Pérez-Solero, Andres J. Muñoz Martín, Aitana Calvo Ferrándiz, Montserrat Blanco-Codesido, Miguel Martin, Pilar Garcia-Alfonso
Journal: Journal of Clinical Oncology (2020)

4041 Background: Approximately 25% of patients with colorectal cancer (CRC) debut with metastatic disease. In addition, 25-35% of patients with localized disease at diagnosis develop metastatic lesions during the evolution of their disease. Consequently, approximately 50-60% of patients with CRC will present metastatic lesions at some point in their lives. Metastasis resection has improved the prognosis of these patients, achieving overall survival (OS) that exceed 40 months. However, there are doubts about the benefit of this approach in patients with mutations in oncogene BRAF or tumors located on the right-side, due their poor prognosis. The aim of the study is to analyze the impact of metastases resection on OS of these populations. Methods: We conducted a retrospective analysis of patients with mCRC attended in the Medical Oncology Department of the Hospital General Universitario Gregorio Marañón (Spain) between January 2010 and 2018. Results: 487 patients were identified and included in the analysis. Median age was 71 years (62-81). Most patients were males (62.4%). 55.2% had metastatic lesions at diagnosis. Most patients had ECOG 0-1 at diagnosis of metastatic disease (91.0%). 8.9% of patients had BRAF mutations (n = 21) and 31.8% of patients had primary tumors located on the right-side (n = 152). 474 patients received first-line chemotherapy (97.3%). OS of the entire cohort was 29.67 months; 30.69 months in BRAF mutated patients vs 35.89 in wild-type patients (p = 0.161); 25.29 months in right-side tumors vs 31.02 in left-side tumors (p = 0.044). 306 patients (62.8%) underwent metastases resection. Most common location was liver (51.4%). 147 patients (30.2%) underwent a second metastases resection. Mean number of metastases surgeries was 1.35 (+/-1.40). OS since metastases resection was 24.83 months in BRAF mutated patients vs 41.55 months in wild-type patients (p = 0.020). According to location, it was 35.49 months in right-side tumors vs 43.78 months in left-side tumors (p = 0.106). In BRAF mutated patients, OS was 38.19 months in patients underwent metastases resection vs 18.52 months in non-surgical patients (p = 0.043); 41.51 months vs 16.18 months respectively in patients with tumors located on the right-side (p &lt; 0.001). Conclusions: Metastases resection has a positive impact on overall survival of patients with mutations in oncogene BRAF or right-side tumors, even though their prognosis is still poor compared to patients without these alterations.
Ultrasonography in prenatal screening of brachydactyly
Authors: Jiaqi Hu, Yuguo Zhang, Juan He, Yi Liu, Jia Huang
Journal: BMJ (2019)

From November. 2015 to December 2016, targeted hand ultrasonographic examinations were carried out on 532 fetuses with family history, suspected limb deformities or other abnormalities. The number, size and shape of metacarpal and phalangeal bones were observed from coronal, axial and sagittal view. Three-dimensional ultrasound examination was performed on the suspected short fingers of fetal hands. Follow-up data were obtained in 382 cases. In 6 cases of prenatally detected brachydactyly, 5 were bilateral and 1 case was unilateral. In these cases, more than one ossification centers of phalanxes were not present or significantly smaller. In 6 cases of brachydactyly, the termination of pregnancy was performed in 4 (including 2 cases with multiple malformations, and 2 cases with brachydactyly family history but without other abnormalities), while in other 2 cases without other abnormalities the pregnancy was retained until birth. X-rays and autopsies confirmed the prenatal diagnosis of brachydactyly in 4 cases of pregnancy termination, but duplicated distal phalanges of bilateral thumbs of 1 case was missed in prenatal scan. It is suggested that the targeted ultrasonographic scan of the fetal hands in high-risk population during pregnancy helps to detect severe brachydactyly.


Key words: 
Ultrasonography, prenatal; Prenatal diagnosis; Hand deformities; Brachydactyly
Accurate diagnosis and reasonable treatment for functional dyspepsia
Authors: 陈旻湖
Journal: BMJ (2008)

消化不良是临床最常见的症候群,主要表现为上腹部疼痛、饱胀和早饱,可伴食欲不振、嗳气、恶心或呕吐等症状.各级医院、各科医生在日常工作中均有机会碰到表现为消化不良的患者.消化不良症状既可由器质性病变引起,如常见的消化性溃疡、胃癌、胆石症、慢性肝病等,也可由代谢性疾病如糖尿病、药物如非甾类抗炎药等引起。
细节决定诊断
Authors: 吴东, 王迁
Journal: BMJ (2009)

英国作家柯南·道尔塑造了福尔摩斯这样一个家喻户晓的文学形象.小说中的福尔摩斯以细致的观察,敏锐的直觉和严密的推理,破获了诸多疑案,一百多年来倾倒了全世界无数读者.然而很少有人想到,临床医生的工作某种程度上也和福尔摩斯类似.为了明确诊断,医生需要详细采取病史,仔细查体,形成初步的诊断假设,在此基础上再安排针对性的检查,最后综合分析各种资料得出结论.这与福尔摩斯勘察现场、与证人谈话、追踪线索、进行法医学检验等破案步骤有着惊人的相似。
Premature complex-induced chronic cough:case report and literature review
Authors: Kefang Lai, Jun Li, Qingling Zhang, Ling Lin, Jinru Gong, Wei Luo, Dongxiao Lu, Yanping Yang, Nanshan Zhong
Journal: BMJ (2019)

The clinical presentation, chest image and electrocardiogram of 4 cases of premature complex-induced chronic cough admitted in the First Affiliated Hospital of Guangzhou Medical University from March 2008 to February 2009, were retrospectively analyzed. And other 6 cases of premature complex-induced chronic cough were retrieved for literature review. In total 10 patients, there were 3 males and 7 females aged 58(36-74) years,with a disease duration of 10.5 (3.0,264.0) months. The main clinical presentations were chronic dry cough with post-sternal thump and premature beats as shown by auscultation and 24 h-electrocardiogram examination. Cough was relieved after the premature beats were controlled with the treatment of arrhythmia drugs or radiofrequency ablation. Premature complex-induced cough is rare but it should be considered when the chief complaint of patients with premature beat is chronic cough.


Key words: 
Atrial premature complexes; Ventricular premature complexes; Cough
Identification of high-risk patients with chest pain in primary care
Authors: Yihong Sun
Journal: BMJ (2019)

基层医生面对胸痛患者最重要的是做好初步的鉴别诊断,筛查出高危患者并积极转诊。简要介绍《胸痛基层诊疗指南（2019年）》制定的背景和主要内容，并以急性冠脉综合征和肺栓塞为例，强调规范胸痛患者的筛查流程的重要性。
胃窦Dieulafoy病一例
Authors: 杜荣莲, 丁伟, 柴同海
Journal: BMJ (2006)

患者男,47岁,因黑便1 d入当地医院,进院后又黑便2 000 g,呕血2 000ml,为喷射状鲜血,含血凝块,伴头晕、心悸,出冷汗.经输血、补液、止血治疗并予三腔两囊管压迫后,仍少量黑便,未再呕血,转本院.既往有乙型肝炎(乙肝)病史20年。
The Bendamustine Plus Rituximab Regimen Is Active and Safe in Previously Untreated Patients with Waldenström Macroglobulinemia, a Study on Behalf of the French Innovative Leukemia Organization (FILO)
Authors: Kamel Laribi, Stéphanie Poulain, Lise Willems, Fatiha Merabet, Charles Herbaux, Damien Roos-Weil, Alix Baugier de Materre, Xavier Roussel, Sabine Tricot, Jehan Dupuis, Ronan Le Calloch, Benoit Bareau, Marie C Bene, Veronique Leblond
Journal: Blood (2017)