tbuckley/cabot-search huggingface dataset:
Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer
Authors: Cora N. Sternberg, Karim Fizazi, Fred Saad, Neal D. Shore, Ugo De Giorgi, David F. Penson, Ubirajara Ferreira, Eleni Efstathiou, Katarzyna Madziarska, Michael P. Kolinsky, Daniel I. G. Cubero, Bettina Noerby, Fabian Zohren, Xun Lin, Katharina Modelska, Jennifer Sugg, Joyce Steinberg, Maha Hussain
Journal: New England Journal of Medicine (2020)

Preliminary trial results showed that enzalutamide significantly improved metastasis-free survival among men who had nonmetastatic, castration-resistant prostate cancer and rapidly increasing prostate-specific antigen (PSA) levels while taking androgen-deprivation therapy. Results from the final analysis of overall survival have not yet been reported. In this double-blind, phase 3 trial, men with nonmetastatic, castration-resistant prostate cancer (defined on the basis of conventional imaging and a PSA doubling time of ≤10 months) who were continuing to receive androgen-deprivation therapy were randomly assigned (in a 2:1 ratio) to receive enzalutamide at a dose of 160 mg or placebo once daily. Overall survival was assessed with a group sequential testing procedure and an O'Brien-Fleming-type alpha-spending function. As of October 15, 2019, a total of 288 of 933 patients (31%) in the enzalutamide group and 178 of 468 (38%) in the placebo group had died. Median overall survival was 67.0 months (95% confidence interval [CI], 64.0 to not reached) in the enzalutamide group and 56.3 months (95% CI, 54.4 to 63.0) in the placebo group (hazard ratio for death, 0.73; 95% CI, 0.61 to 0.89; P = 0.001). The exposure-adjusted rate of adverse events of grade 3 or higher was 17 per 100 patient-years in the enzalutamide group and 20 per 100 patient-years in the placebo group. Adverse events in the enzalutamide group were consistent with those previously reported for enzalutamide; the most frequently reported events were fatigue and musculoskeletal events. Enzalutamide plus androgen-deprivation therapy resulted in longer median overall survival than placebo plus androgen-deprivation therapy among men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level. The risk of death associated with enzalutamide was 27% lower than with placebo. Adverse events were consistent with the established safety profile of enzalutamide. (Funded by Pfizer and Astellas Pharma; PROSPER ClinicalTrials.gov number, NCT02003924.).
Value of electrocardiogram (ECG) in identifying acute occlusion sites of right coronary artery
Authors: Chunlin Huang
Journal: BMJ (2015)

Clinical data of 151 patients with acute occlusion of right coronary artery were retrospectively analyzed. Coronary angiography and electrocardiography (EEG) were performed in all 151 patients, angiography showed proximal-middle segment occlusion in 114 cases and distant segment occlusion in 37 cases. The correlation of ECG findings with coronary artery occlusion sites was analyzed. Results showed that EEG findings related to proximal-middle segment occlusion were: ST segment elevation in lead V4R ≥0.05 mV, Ⅲ degree atrioventricular block, ST segment depression in lead Ⅰ>0.1 mV, ST segment depression in lead AVL≥0.2 mV, ST segment elevation in lead Ⅲ≥0.25 mV, the total ST depression in lead V2,V3 and V4 ≥0.4 mV , the total ST depression in lead I and aVL ≥0.25 mV; among which ST depression of Lead Ⅰ>0.1 mV, ST elevation of Lead V4R≥0.05 mV and Ⅲ degree atrioventricular block were used to predict occlusion of proximal-middle segment of right coronary artery with 100% specificity. ECG findings related to distal segment occlusion were: ST depression in lead Ⅰ≤0.1 mV, ST segment depression in lead AVL<0.2 mV, ST elevation in lead Ⅲ≤0.25 mV, the total ST depression in lead V2,V3 and V4 <0.4 mV, ST segment were not depression in lead V1-V5,the total ST depression in lead I and aVL<0.25 mV. Based on a 4-step flow method, ECG might be adopted to identify the acute occlusion sites in proximal-middle segment and distal segment of right coronary.


Key words: 
Coronary occlusion; Inferior wall myocardial infarction; Electrocardiography
Efficacy of immune checkpoint inhibitors for the treatment of metastatic melanoma (MM) in patients with concurrent chronic lymphocytic leukemia (CLL).
Authors: Veronica Guerra, Gabriel O. Ologun, Lauren Elaine Haydu, Emily Zhi-Yun Keung, Elizabeth M. Burton, Hussein Abdul-Hassan Tawbi, William G. Wierda, Michael A. Davies, Jennifer Ann Wargo, Alessandra Ferrajoli
Journal: Journal of Clinical Oncology (2020)

e22044 Background: Patients with CLL have immune impairment with abnormalities in T-cell subset composition and immune synapse formation. The impact of these defects on response to immune checkpoint inhibitors (CPI) is not known. Given the high incidence of melanoma in patients with CLL we sought to evaluate the response to CPI in patients with concomitant MM and CLL. Methods: Retrospective analysis of 24 patients (pts) with concurrent CLL and MM who received a total of 38 CPI therapies between July 1997 and July 2019. Primary objective was to determine objective response rate (ORR), defined as complete response (CR) or partial response (PR) by RECIST1.1. Secondary outcomes included event-free survival; overall survival (OS), and duration of response (DOR). Results: The median age at CLL and melanoma diagnosis was 62 and 63 years, respectively. 71% of patients were male. Most presented with early stage CLL at diagnosis (67%), 60% had mutated IGVH, and 47% had deletion of 13q by FISH. 71% remained on observation for their CLL. Median time from melanoma diagnosis to CPI initiation was 13.5 months. 83% had stage IV MM and 17% stage III MM at the time of therapy. 17% had increased LDH. The most common melanoma mutations were BRAF(35%), BRAFV600 (26%), TP53 (30%) and NRAS (26%). Median follow up was 37 months and the ORR was 24% (Table). Median DOR was 41 months and median OS is 26.4 months. Immune-mediated adverse events occurred in 42%, including 13% fever, 11% thrombotic events, 8% endocrine dysfunction. 13 pts are alive and 11 pts died (8 pts due to MM progression). There were no significant changes in absolute lymphocyte counts during CPI therapy. 2 pts received CPI while on ibrutinib or ibrutinib+venetoclax therapy with ongoing CLL responses. Conclusions: Our experience indicates that CPIs can be effective for the treatment of MM in patients with concurrent CLL, achieving durable responses. Immuno-mediated toxicities were frequently observed. A lower ORR was observed in first-line CPI in MM, however the numbers of pts are small. Further studies are needed to determine if initial or concurrent treatment for CLL could improve CPI outcomes and survival. Additional studies evaluating T cells function and tissue infiltration in these patients are ongoing. [Table: see text]
Selpercatinib (LOXO-292) in patients with <i>RET</i>-mutant medullary thyroid cancer.
Authors: Manisha H. Shah, Eric Jeffrey Sherman, Bruce Robinson, Benjamin J. Solomon, Hyunseok Kang, Jochen H. Lorch, Francis P. Worden, Marcia S. Brose, Sophie Leboulleux, Yann Godbert, Marie Meurer, John C. Morris, Taofeek Kunle Owonikoko, Daniel Shao-Weng Tan, Oliver Gautschi, Jyoti D. Patel, Luxi Yang, Jennifer Kherani, Maria E. Cabanillas, Lori J. Wirth
Journal: Journal of Clinical Oncology (2020)

3594 Background: Selpercatinib (LOXO-292) is a highly selective and potent small molecule RET kinase inhibitor. Here we report an update on the efficacy and safety of selpercatinib in RET-mutant medullary thyroid cancer (MTC). Methods: Patients with RET-mutant MTC were enrolled to the Phase 1/2 LIBRETTO-001 trial (NCT03157128), a global, multicenter trial (16 countries, 89 sites). Following the Phase 1 dose escalation portion of the trial, patients received the recommended dose of 160 mg orally twice daily. Each cycle was 28 days. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints included duration of response (DoR) and safety. Per health authority agreement, the primary analysis set was defined as the first 55 consecutively enrolled patients previously treated with multikinase inhibitors cabozantinib and/or vandetanib. Patients naïve to cabozantinib and vandetanib treatment were analyzed separately. All analyses were based on a 16-Dec-2019 data cutoff date. Results: In the primary analysis set of prior cabozantinib and/or vandetanib-treated patients with MTC (n = 55), the ORR by investigator assessment was 62% (95% CI 47.7–74.6, n = 34/55) and the median DoR was not reached (95% CI 18.4 months–not estimable) despite a median follow-up of 14.8 months. In cabozantinib/vandetanib treatment-naïve patients (n = 88), the ORR by investigator assessment was 69% (95% CI 58.6–78.7, n = 61/88, including 2 responses pending confirmation). Of the 59 confirmed responding patients, with a median follow-up of 8 months, responses were ongoing for 57 responders at the time of the analysis. In the safety analysis set consisting of all selpercatinib dosed patients (N = 702), the most common treatment-related adverse events (TRAEs) that occurred in ≥15% of patients were dry mouth (33.3%), increased AST (24.5%), increased ALT (23.8%), hypertension (23.2%), diarrhea (19.7%), and fatigue (16.8%). Only 2% (14 of 702) of patients discontinued selpercatinib for TRAEs. Conclusions: Selpercatinib use was associated with marked and durable antitumor activity in prior cabozantinib and/or vandetanib-treated patients and in cabozantinib/vandetanib-naïve patients with RET-mutant MTC, with the majority of responses ongoing in both cohorts. Selpercatinib was well tolerated. Efficacy data assessed by independent review committee based on the 16-Dec-2019 data cutoff date will be presented. Clinical trial information: NCT03157128 .
Current trends in the management of lacrimal gland tumors: A National Cancer Database study.
Authors: Prashanth Ashok Kumar, Dongliang Wang, Abirami Sivapiragasam
Journal: Journal of Clinical Oncology (2020)

e18573 Background: Lacrimal Gland (LG) tumors are rare with data limited to very few comparative trials. The original treatment is Orbital Exenteration followed by Radiotherapy (RT). Contemporary strategies like orbit sparing surgeries and Neoadjuvant Intra-arterial Chemotherapy (CT) are gaining popularity but remains controversial given the paucity of data. Our aim was to determine the pathological distribution and compare the treatment modalities used in LG tumors with the help of a large national database. Methods: From the 2004-2016 National Cancer Database (NCDB), we included Epithelial LG tumors. We excluded Lymphomas, Melanomas, Sarcomas and other metastatic lesions. Descriptive statistics, Hazard Ratio (HR) estimates and Kaplan Meier (KM) survival analysis were used. Results: A total of 669 LG tumors were identified. The distribution based on Pathology and treatment strategies used is represented in the table. The point survival estimate comparison between the surgical types and the various treatment groups showed no significance. Conclusions: SCC was the most common histological type. There was no difference in the overall outcome between radical and orbit sparing procedures. Adjuvant RT and adjuvant chemoradiation did not confer any additional survival benefit over surgery alone. Mallen-St Clair et. using the SEER database (321 LG patients) showed that RT improves Disease Specific Survival in SCC. Moving forward, larger population-based studies and prospective trials are needed to determine the most ideal management option. The NCDB is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The data used in the study are derived from a de-identified NCDB file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology employed, or the conclusions drawn from these data by the investigator. [Table: see text]
Veliparib (V) monotherapy after progression on placebo (PL) + carboplatin/paclitaxel (CP) in patients with advanced HER2-negative g<i>BRCA</i>-associated breast cancer: Crossover outcomes and exploratory biomarker analyses in BROCADE3.
Authors: Shannon L Puhalla, Veronique Dieras, Banu Arun, Bella Kaufman, Hans Wildiers, Hyo S. Han, Jean-Pierre M. Ayoub, Vered Stearns, Yuan Yuan, Teresa L. Helsten, Bridget Riley-Gillis, Erin Murphy, Madan Gopal Kundu, Meijing Wu, David Maag, Christine Ratajczak, Cyril Ramathal, Michael Friedlander
Journal: Journal of Clinical Oncology (2020)

1097 Background: In BROCADE3 (NCT02163694), addition of the PARP inhibitor (PARPi) V to CP improved PFS in patients (pts) with g BRCA-associated advanced breast cancer (hazard ratio 0.71 [95% CI 0.57–0.88], p = 0.002). Reversion mutations may account for resistance to platinum-based CT and PARPi. Efficacy, safety, and exploratory biomarker analyses for pts randomized to PL + CP who received crossover (Cx) V monotherapy after progression are reported. Methods: 513 total pts were randomized 2:1 to V + CP or PL + CP. V/PL, C, and P could be discontinued independently prior to progression, leading to varying platinum-free intervals at the time of progression. After progression, pts in the PL + CP arm could receive open-label Cx V monotherapy (300–400 mg BID continuous), beginning within 60 d of progression and continuing to second progression. Adverse events (AEs) and activity during Cx V were assessed. Exploratory analysis of BRCA reversion mutations restoring BRCA1/2 protein function that emerged during PL + CP treatment was performed on plasma circulating tumor DNA using targeted-amplicon next generation sequencing. Results: At data cutoff, 75 pts initially randomized to PL + CP had ≥1 dose of Cx V. Mean (range) duration of Cx V was 154 d (2–966). Activity during Cx V is in the Table. Mean (range) platinum-free interval at time of first dose of Cx V was 3.1 mos (0.4–10.9) vs 8.1 mos (1.0–34.9) in pts who had progressed vs had not progressed by 24 wks after first dose of Cx V. BRCA reversion analysis was completed for 18 Cx pts. Reversion mutations were identified in 1/18 pts (5.6%). This patient had Cx V duration of 19 d and had progressed by 24 wks. BRCA reversion analysis on additional Cx pts will be presented. Most common AEs during Cx V were nausea (61%), vomiting (29%), fatigue (24%), and diarrhea (21%). Any grade anemia, neutropenia, and thrombocytopenia occurred in 7%, 15%, and 7% of pts. Three pts (4%) experienced a convulsion event. Conclusions: Platinum-free interval may influence efficacy of subsequent PARPi. Impact of BRCA reversion mutations warrants further evaluation. Cross-resistance may limit PARPi efficacy after platinum failure. Clinical trial information: NCT02163694 . [Table: see text]
偏头痛的治疗
Authors: 李焰生
Journal: BMJ (2007)

偏头痛是-种常见和慢性的神经血管性疾患,有着相当大的危害,不仅因频繁和严重的头痛导致患者的学习与工作能力下降、生存质量降低,而且多与脑卒中、情感障碍等多种疾患相关[1-2].WHO将严重偏头痛定为最致残的慢性疾病,类同于痴呆、四肢瘫痪和严重精神病。
Double-balloon endoscopy facilitates efficient endoscopic resection of duodenal and jejunal polyps in patients with familial adenomatous polyposis
Authors: Mariko Sekiya, Hirotsugu Sakamoto, Tomonori Yano, Shoko Miyahara, Manabu Nagayama, Yasutoshi Kobayashi, Satoshi Shinozaki, Keijiro Sunada, Alan Kawarai Lefor, Hironori Yamamoto
Journal: Endoscopy (2020)

Abstract Background Many patients with familial adenomatous polyposis (FAP) have adenomatous polyps of the duodenum and the jejunum. We aimed to elucidate the long-term outcomes after double-balloon endoscopy (DBE)-assisted endoscopic resection of duodenal and jejunal polyps in patients with FAP. Methods We retrospectively reviewed patients who underwent more than two sessions of endoscopic resection using DBE from August 2004 to July 2018. Results A total of 72 DBEs were performed in eight patients (median age 30 years, range 12–53; 1.4 DBE procedures/patient-year) during the study period, and 1237 polyps were resected. The median observation period was 77.5 months (range 8–167). There were 11 adverse events, including seven delayed bleeds and four episodes of acute pancreatitis. No delayed bleeding occurred after cold polypectomy. Although, in one patient, one endoscopically resected duodenal polyp was diagnosed as being intramucosal carcinoma, none of the patients developed an advanced duodenal or jejunal cancer during the study period. Conclusions Endoscopic resection of duodenal and jejunal polyposis using DBE in patients with FAP can be performed safely, efficiently, and effectively.
血清氨基转移酶异常的临床解读
Authors: 刘凤奎
Journal: BMJ (2008)

肝脏有近千种酶,氨基转移酶(转氨酶)有数十种,其中临床最常检查的是丙氨酸氨基转移酶(ALT),门冬氨酸氨基转移酶(AST). 许多脏器和组织也含有这两种转氨酶,但两者分布的多少不一样。
Efficacy of lumbar spine posterior medial branch block combined with shockwaves therapy for treating lumbar facet joint syndrome
Authors: Yanping Luo, Yong Fei, Min Fang, Yanbo Yu, Bing Huang, Ming Yao
Journal: BMJ (2018)

采用前瞻性观察方法对2017年7月至2018年1月在桐乡市第二人民医院疼痛科门诊诊断的30例顽固性腰椎小关节综合征患者，采用腰脊神经后内侧支阻滞联合冲击波治疗观察。治疗1、2、4、8周的视觉模拟评分(VAS)及腰椎功能障碍指数(ODI)与治疗前比较，差异均有统计学意义(均P<0.05)；与治疗2周比较，治疗4周VAS、ODI均降低，差异均有统计学意义(均P<0.05)；所有患者在治疗前后未出现药物不良反应及并发症。提示腰脊神经后内侧支阻滞联合冲击波治疗顽固性腰椎小关节综合征能显著缓解患者疼痛，安全性高。
Bevacizumab plus S-1 and raltitrexed for refractory metastatic colorectal cancer.
Authors: Ye Chen, Jiyan Liu, Hongfeng Gou
Journal: Journal of Clinical Oncology (2020)

e16024 Background: There are lack of effective drugs and regimens for refractory metastatic colorectal cancer (mCRC), especially in China. Dihydropyrimidine dehydrogenase (DPD) is the rate limiting enzyme of 5-FU catabolic pathway. Thymidylate synthase (TS) is the target of 5-FU anti-tumor mechanism. Several studies have shown the up-regulation of the two enzymes after the use of 5-FU in colorectal cancer, which may be closely related to the 5-FU resistance. The preliminary research of our center has shown the efficacy and safety of S-1 (containing a DPD inhibitor) plus raltitrexed (a TS inhibitor) in refractory mCRC. The aim of this study is to evaluate the efficacy and safety of bevacizumab plus S-1 and raltitrexed for patients with mCRC after failure to fluoropyrimidine, irinotecan and oxaliplatin. Methods: This study is a one-center, single-arm, prospective phase II trial, being carried out in the Cancer Center, West China Hospital, Sichuan University, China. The patients who have progressed after the treatment of fluoropyrimidine, irinotecanand oxaliplatin, have at least one measurable lesion according to RECIST 1.1 criteria were enrolled. Patients receive bevacizumab 7.5mg/kg and raltitrexed 3 mg/m 2 on days 1 plus S-1 80, 100 or 120 mg/d according to body-surface area on days 1 through 14 of a 21-day cycle. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicity. Results: From Sep 2015 to Nov 2019, 44 patients were enrolled. By Feb 5, 2020, eleven patients were alive. Tumor response evaluation was available in 44 patients at the time of the analysis. There was no complete response, ORR was 15.9%(7/14) and disease control rate was 54.5%(24/44). mPFS and mOS were 110 days (95% confidence interval, 65.0-155.0) and 367 days (95% confidence interval, 310.4-423.6). The most common adverse events were bone marrow depression, dysfunction of digestive system abnormality of liver function and bleeding. Most of these adverse events were mild to moderate. Conclusions: Bevacizumab plus S-1 and raltitrexed further showed its moderate effect for refractory mCRC. Most of the adverse effects were mild to moderate, which could be well controlled. This combined regimen is worthy of further study as third or later line therapy in mCRC. Clinical trial information: ChiCTR1900020485 .
Association between blood cell ratios and lower extremity arterial ultrasonography abnormalities in patients with type 2 diabetes mellitus
Authors: Yuhong Li, Yu Chen, Zhenqian Fan
Journal: BMJ (2018)

Clinical data of 380 patients with type 2 diabetes mellitus (T2DM) admitted in the Second Hospital of Tianjin Medical University from October 2014 to June 2017 were retrospectively reviewed. Patients were divided into 3 groups according to the results of lower extremity arterial ultrasonography: 103 patients without lower extremity arterial disease (group A), 132 patients with mild arterial disease (group B), 145 patients with moderate to severe lower extremity arterial disease (group C); and 100 healthy subjects served as control group. Blood routine parameters and blood biochemistry were measured; the results showed that blood cell ratios in T2DM patients were significantly higher than those in control group (P<0.05), and blood cell ratios in group B and group C were higher than those in group A (P<0.05). Pearson correlation analyses indicated that neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), hs-CRP, HbA1c, LDL-C were significantly associated with lower extremity arterial disease in T2DM patients. Logistic analysis showed that NLR (OR=2.01, 95%CI: 1.15-3.63, P<0.05) and PLR (OR=1.75, 95%CI: 1.04-3.28, P<0.05) were risk factors for lower extremity arterial disease in patients with type 2 diabetes mellitus.


Key words: 
Diabetes mellitus, type 2; Peripheral vascular diseases, lower extremity; Blood cell count
斑秃诊断与治疗
Authors: 陈慧, 朱威
Journal: BMJ (2010)

斑秃是一种临床常见的皮肤病,表现为突然发生的斑状脱发,脱发区皮肤无红肿热痛等炎症表现,无瘢痕及自觉症状. 1.病因:斑秃的病因尚未完全清楚.遗传易感性可能是病因之一,尤其是具有斑秃家族史的患者,人类白细胞抗原D(HLA-D)等位基因可能与发病的早晚、病情轻重相关.精神和神经因素是斑秃发病的诱因之一.很多患者发病前有精神压力大、抑郁、焦虑、生活不规律,睡眠质量差,或者遭遇严重精神创伤.自身免疫可能也参与了本病的发生,病理检查发现进展期毛球和毛乳头血管周围有以淋巴细胞为主的浸润,而疾病恢复期炎症细胞数量减少,毛囊数量增多.斑秃患者合并白癜风、桥本甲状腺炎、糖尿病等自身免疫性疾病的几率较正常人高。
Prevalence of the metabolic syndrome in middle-aged and elderly individuals
Authors: Wei Tang, Yuan Gao, Dan Yu, Hong-wen Zhou, Tao Yang
Journal: BMJ (2011)

Totally 1136 individuals aged over 40 underwent health check up in March to May 2009. Fasting blood glucose, 2-h post-challenge blood glucose, glycated hemoglobin A1c ( HbA1c), total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and serum uric acid were measured. The diagnosis of metabolic syndrome was based on the International Diabetes Federation Criteria. The results shows that total body fat, region body fat indices, blood pressure, blood glucose and serum uric acid levels increased with the age ( P < 0.01) . The prevalence rate of metabolic syndrome in this group of individuals were 15. 1% (171/1136) , and increased with age (P<0.01). The most common combination of metabolic syndrome was central obesity-hypertension-dyslipidemia (40. 9% , 70/171). Unconditional logistic regression revealed that waist-hip-ratio, body mass index and uric acid were the risk factors for metabolic syndrome. 

Key words: 
Metabolic syndrome X;  Reference standards