tbuckley/cabot-search huggingface dataset:
Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study
Authors: Steven F. Powell, Kathryn A. Gold, Mark M. Gitau, Christopher J. Sumey, Michele M. Lohr, Steven C. McGraw, Ryan K. Nowak, Ashley W. Jensen, Miran J. Blanchard, Christopher D. Fischer, Julie Bykowski, Christie A. Ellison, Lora J. Black, Paul A. Thompson, Juan L. Callejas-Valera, John H. Lee, Ezra E. W. Cohen, William C. Spanos
Journal: Journal of Clinical Oncology (2020)

PURPOSE Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC. PATIENTS AND METHODS Eligible patients included those with oral cavity (excluding lip), oropharyngeal, hypopharyngeal, or laryngeal stage III to IVB HNSCC (according to American Joint Committee on Cancer, 7th edition, staging system) eligible for cisplatin-based, standard-dose (70 Gy) chemoradiotherapy. Pembrolizumab was administered concurrently with and after chemoradiotherapy with weekly cisplatin. Safety was the primary end point and was determined by incidence of chemoradiotherapy adverse events (AEs) and immune-related AEs (irAEs). Efficacy was defined as complete response (CR) rate on end-of-treatment (EOT) imaging or with pathologic confirmation at 100 days postradiotherapy completion. Key secondary end points included overall (OS) and progression-free survival (PFS). RESULTS The study accrued 59 patients (human papillomavirus [HPV] positive, n = 34; HPV negative, n = 25) from November 2015 to October 2018. Five patients (8.8%) required discontinuation of pembrolizumab because of irAEs, all of which occurred during concurrent chemoradiotherapy; 98.3% of patients completed the full planned treatment dose (70 Gy) of radiotherapy without any delays ≥ 5 days; 88.1% of patients completed the goal cisplatin dose of ≥ 200 mg/m 2 . EOT CR rates were 85.3% and 78.3% for those with HPV-positive and -negative HNSCC, respectively. CONCLUSION Pembrolizumab in combination with weekly cisplatin-based chemoradiotherapy is safe and does not impair delivery of curative radiotherapy or chemotherapy in HNSCC. Early efficacy data support further investigation of this approach.
There is a slight increase in incident diabetes risk with the use of statins, but benefits likely outweigh any adverse effects in those with moderate-to-high cardiovascular risk
Authors: Lokpal, Bhatia, Christopher, Byrne, 范维琥
Journal: BMJ (2010)

他汀类药物是使用范围最广的一类药物，仅在2008年，英国就大约开出了5千万张他汀类药物的处方。他汀类药物能显著减少中-高危病人的心血管事件，其在一级和二级预防中的有效性和安全性已经确立。常见报道的不良反应包括肌痛和肝酶升高，但总体上他汀类药物治疗中不良反应的发生率甚低，其耐受性良好。不过，
家庭监护血糖
Authors: 洪靖, 杨文英
Journal: BMJ (2011)

良好的血糖控制对于预防或延缓糖尿病的并发症很重要.家庭监护血糖有助于评估糖尿病患者糖代谢紊乱的程度,了解降糖药物治疗的效果,制定和调整降糖措施.常用的糖代谢控制的监测指标包括糖化血红蛋白(HbA1c)、尿糖、利用血糖仪进行的自我血糖监测以及动态血糖监测。
Health anxiety
Authors: Hedman-Lagerlöf Erik, Tyrer Peter, Hague John, Tyrer Helen, 杨旭, 高畅
Journal: BMJ (2019)

46岁男性，因胸闷、胸痛就诊于全科门诊。近期冠状动脉计算机断层扫描（CT）结果正常。在过去的一年中，患者多次因不同症状于多名全科医生处就诊，这些症状常在医生解释或进行检查后得到缓解。
Abstract 16584: Racial Variation in Diabetes-Related Cardiovascular Mortality Since 2002 in the United States
Authors: Sridharan Raghavan, Yuk-Lam Ho, Jason L Vassy, David Gagnon, Peter W Wilson, Lawrence S Phillips
Journal: Circulation (2017)

Introduction: The population distributions of hemoglobin A1c(HbA1c) differ across races for individuals without and with diabetes. In addition, the rates of cardiovascular mortality differin black ...
老年期急性起病的克-雅病一例并文献复习
Authors: 郑维红, 刘肇绩, 陈中杰, 陈星宇
Journal: BMJ (2011)

患者男,73岁,因视力下降4周,行走不稳1周于2006年9月7日入院.患者4周前出现视物模糊,视力进行性下降,2周内由1.0下降至0.1,眼科诊断为白内障、玻璃体变性,双眼屈光不正.1周前出现头晕、行走不稳、坐不稳、易摔倒,偶有呛水,伴言语减少且缓慢,症状渐加重,以共济失调待查入本院.既往高血压病史10余年,无外伤手术史,家族中无类似病史.入院体格检查:言语略缓慢,说话少,反应较慢,记忆力差,尤以即时记忆为甚.双瞳孔等大等圆,直径2.5mm,左侧对光反射迟钝,右侧对光反射灵敏,眼前指数辨别不能,无眼震,左侧鼻唇沟稍浅,伸舌偏右.四肢肌力、肌张力、腱反射和感觉正常,双侧病理征(-).右指鼻试验不准,双侧跟膝胫试验欠稳准,闭目难立征阳性。
Phase II study of consolidative intensity-modulated radiation therapy following first-line palliative systemic chemotherapy for de novo previously untreated metastatic (M1) nasopharyngeal carcinoma.
Authors: Victor Ho-Fun Lee, Ann SY Chan, Dora LW Kwong, To-Wai Leung, Sherry CY Ng, Chi-Chung Tong, Ka-On Lam, Varut Vardhanabhuti, Sik-Kwan Chan, Cheuk-Wai Choi, Tsz Him So, Wing-Lok Chan, Mai-Yee Luk, Pek-Lan Khong, Anne WM Lee
Journal: Journal of Clinical Oncology (2020)

6524 Background: The prognosis of de novo previously untreated metastatic (M1) nasopharyngeal carcinoma (NPC) at diagnosis is poor, and the role of consolidative intensity-modulated radiation therapy (IMRT) to the primary tumor and the neck following first-line palliative chemotherapy remains unknown. We report a phase II study of consolidative IMRT after first-line chemotherapy in previously untreated M1 NPC. Methods: Consolidative IMRT was given in prospectively recruited patients whose previously untreated M1 NPC did not progress after 6 cycles of first-line chemotherapy with gemcitabine and cisplatin. The primary study objective was overall survival (OS). Secondary objectives included progression-free survival (PFS), local relapse-free survival (LRFS), regional relapse-free survival (RRFS), response and toxicity. Results: Sixty-nine consecutive patients were enrolled. Sixty-four (92.8%) patients received first-line chemotherapy, of which 8 (12.5%) developed progressive disease and another 8 (12.5%) did not receive IMRT despite non-progression to first-line chemotherapy. The remaining 48 patients whose disease controlled after chemotherapy received IMRT, including 18 (37.5%) who received concurrent chemoradiation. OS was significantly better in those who received IMRT (35.1 versus 14.2 months; P &lt; 0.001), after a median follow-up duration of 3.40 years (range 0.43 years to 12.14 years). PFS, LRFS, and RRFS were also significantly longer in those who received IMRT. Multivariable analyses revealed that IMRT was the only prognostic factor of all survival endpoints. Grade 3 adverse events were observed in 10 (20.8%) patients, mainly mucositis, dysphagia and desquamation. Conclusions: Consolidative IMRT was associated with an OS benefit and favorable tolerability among previously untreated M1 NPC patients who had non-progressive disease following first-line chemotherapy. These results support the rationale to further investigate IMRT as part of the initial treatment in this setting. Clinical trial information: NCT02476669 .
Improved latissimus dorsi muscle perforator flaps transplantation with T-shaped cross-bridge vascular anastomosis for repairing of soft tissue defect in legs
Authors: Gong-lin Zhang, Ke-ming Chen
Journal: BMJ (2010)

From September 2006 to January 2008,5 patients with soft tissue defect of the legununderwent reconstruction with the improved bridge anastomosis vascular latissimus dorsi muscle perforatorflflaps transplantation. The latissimus dorsi muscle perforator flaps was elevated with subscapular andcicircumflex scapular vessels. The vascular pedicle of the latissimus dorsi muscle perforator flaps wereananastomosed to the two vascular ends of the posterior tibial artery of contralateral leg by end-to-endananastomosis. The flaps survived completely after transplantation. Patients were followed up for 8 months -33. 5 years ( mean 2. 7 years) postoperatively. There was no remarkable donor site morbidity, Dopplereexamination showed the patency of the posterior tibial artery of contralateral legs. This technique ispparticularly useful in leg reconstructive surgery when only one vessel remains. The patency of the posteriortibial artery of contralateral leg is preserved in transplantation of the bridge free flap.

Key words: 
Reconstructive surgical procedures;  Skine transplantation
A novel approach to quantitatively synthesize subgroup findings from multiple trials.
Authors: Devon J Boyne, Paul Arora, Darren Brenner
Journal: Journal of Clinical Oncology (2020)

e14081 Background: The identification of characteristics that stratify patients according to the likelihood of treatment response is a key goal of precision oncology research. Within randomized trials, effect modification is typically examined through subgroup analyses or the inclusion of an interaction term(s) in a multivariable regression model. To date, systematic reviews of such findings have relied upon qualitative summaries or subgroup-specific meta-analyses. Such approaches are problematic because they do not quantify the magnitude or the degree of uncertainty in the difference in the treatment effects between subgroups. To address this gap, we propose a novel approach that can be used to quantitatively pool subgroup findings from multiple trials. Methods: Our procedure is focused on the estimation of the pooled difference between the subgroup-specific treatment effects within a two-stage meta-analysis. In the first stage, the magnitude and standard error of the difference between the subgroup-specific treatment effects is estimated for each study. When studying relative effect measures, this difference can be estimated on the log-scale, e.g., study-specific difference = log(RR subgroup A ) – log(RR subgroup B ). The standard error of this difference can then be estimated using subgroup-specific 95% CIs. A meta-analysis of the study-specific differences is then conducted. When the differences are estimated on the log-scale, the pooled quantity can be re-expressed as the ratio of the subgroup specific ORs, RRs, or HRs whereby a ratio equal to 1.00 indicates that the subgroup-specific estimates are equal in magnitude. Results: Case-studies and empirical simulations highlighting the application of our approach will be presented. Potential extensions of this methodology will also be discussed. Such extensions include the use of dose-response models to address subgroup categories of a continuous variable and the inclusion of three or more treatments within a network meta-analysis. Conclusions: This method may help to better identify and quantify the degree of heterogeneity of subgroup differences across trials, particularly in settings where the number of patients within each trial is limited.
DURTRERAD: A phase II open-label study evaluating feasibility and efficacy of durvalumab (D) and durvalumab and tremelimumab (DT) in combination with radiotherapy (RT) in non-resectable locally advanced HPV-negative HNSCC—Results of the preplanned feasibility interim analysis.
Authors: Konrad Friedrich Klinghammer, Thomas Christoph Gauler, Carmen Stromberger, Grzegorz Kofla, Maike de Wit, Johannes Gollrad, Izabella Rauer, Peter Martus, Inge Tinhofer, Volker Budach, Ulrich Keilholz, Susen Burock
Journal: Journal of Clinical Oncology (2020)

6574 Background: DURTRERAD is a randomized phase II study evaluating feasibility and efficacy of durvalumab (anti-PD-L1) vs. durvalumab and tremelimumab (anti-CTLA-4) in combination with radiotherapy as primary treatment for locally advanced HPV negative HNSCC. (NCT03624231). Concurrent chemo-RT with a platinum-based regimen is considered the standard treatment, although efficacy and long-term toxicity are not satisfactory. Combining immunotherapy with RT might result in improved efficacy with limited long-term toxicity. Methods: The phase II study planned to enroll 120 pts, 60 pts (1:1) in each treatment arm. Treatment with DT (1500mg/75 mg, arm DT),or D (1500mg, arm D) both in combination with RT (70Gy) was considered to be feasible if less than 10% of the patients treated will discontinue treatment due to on-treatment toxicities. A first interim analysis for feasibility and efficacy was planned after randomisation of 20 patients. Results: So far 23 patients have been screened, 16 patients have been randomised and started their allocated treatment, 10 in arm D and 6 in arm DT. Of 10 patients in arm D 1 patient stopped infusional treatment due to immune related toxicity. Out of 6 patients in the DT arm, however, 5 patients stopped treatment due to treatment related AEs, 2 pts due to immune related toxicity with one Grade 5 AE. Three patients stopped due to non-immune related AE. The grade 5 AE prompted the interim analysis, which revealed non-feasibility as well as safety-issues of the DT+radiotherapy combination . As a result, the DT arm was prematurely terminated. Conclusions: Even though in the recurrent/metastatic setting DT was not associated with increased toxicity, DT in combination with RT was not feasible in our poor prognostic, vulnerable patient cohort of advanced HPV negative unresectable HNSCC, warranting early disclosure of these results. No increase in toxicity was observed in the D monotherapy arm, and the trial continued with D monotherapy in combination with RT. Clinical trial information: NCT03624231 .
Clinical characteristics and outcomes of signet ring cell carcinoma of the stomach: A retrospective analysis of SEER database.
Authors: Moataz Ellithi, Radowan Elnair, Hafez Mohammad Abdullah
Journal: Journal of Clinical Oncology (2020)

e16572 Background: Signet ring cell carcinoma (SRCC) of the stomach accounts for 8 to 30% of all gastric cancers, however the incidence has been rising. We performed a Surveillance, Epidemiology and End Results (SEER) database analysis to further characterize the biology and clinical aspects of this entity, in comparison to gastric adenocarcinoma (AC). Methods: Surveillance, Epidemiology and End Results (SEER) 18 database was used to obtain data on age, gender, ethnicity, survival, and tumor characteristics of 5,424 US patients diagnosed with gastric SRCC between 2012-2016 and these were compared to 40,657 patients with other gastric adenocarcinoma (AC) subtypes diagnosed during the same period. Results: The gender distribution of both types of cancer was similar with males making up 51.8% of gastric SRCC and 48.3% of gastric AC patients. Median age of diagnosis was 63 years for gastric SRCC as compared to 65 years for gastric AC patients. The age of diagnosis distribution for both types was similar with patient &lt;40 years (7.2% versus 6.2% respectively), 40-60 years (34% versus 32% respectively), 60-80 years (44.6% versus 45.15% respectively) and at &gt; 80 years (14.4% versus 16.6% respectively). Among the SRCC patients, 70.9 % were Caucasians, 15.5% were Asians/Pacific Islanders, and 11.6% were African-Americans. Amongst gastric AC patients, Caucasians made up 76% of the patients, while African-Americans made up 12.9% and Asian/Pacific Islanders made up 9.2 % of the patients. Median OS was 10 months for gastric SRCC compared to 24 months (p &lt; 0.001) for gastric AC. Racial differences in overall survival (OS) was noted. The median OS in Caucasians, African-American, Asian/Pacific Islander, and Native American populations was 11,11,15,7 months respectively (p &lt; 0.001). Conclusions: Gastric SRCC has significantly worse survival as compared to AC with median OS of 10 months vs 24 months. It is more common in patients with Asian/Pacific Islander ancestry as compared to gastric AC. There is a significant racial disparity in survival outcomes with significantly shorter survival in patients with Native american ancestry.
未婚青少年流产后咨询与教育
Authors: 张帝开, 秦君璞, 陈姗, 周莉
Journal: BMJ (2010)

生殖健康不仅关系到人们的性健康和生育健康,同时也与下一代的健康密切相关.随着我国改革开放和社会经济的发展,性观念的开放,未婚性活动、婚前同居日趋增多,未婚人工流产、重复流产较前增加,严重影响了青少年的生殖健康,已经成为影响全国青少年女性生殖健康的一个重大的公共卫生问题。
Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b/2, multicentre, randomised trial
Authors: Yi-Long Wu, Ying Cheng, Jianying Zhou, Shun Lu, Yiping Zhang, Jun Zhao, Dong-Wan Kim, Ross Andrew Soo, Sang-We Kim, Hongming Pan, Yuh-Min Chen, Chih-Feng Chian, Xiaoqing Liu, Daniel Shao Weng Tan, Rolf Bruns, Josef Straub, Andreas Johne, Jürgen Scheele, Keunchil Park, James Chih-Hsin Yang, Yi-Long Wu, Xiaoqing Liu, Zhe Liu, Shun Lu, Xi Chen, Hongming Pan, Mengzhao Wang, Shiying Yu, Helong Zhang, Yiping Zhang, Jian Fang, Wei Li, Jianying Zhou, Jun Zhao, Ying Cheng, Chih-Hsin Yang, Gee-Chen Chang, Yuh-Min Chen, Te-Chun Hsia, Chih-Feng Chian, Cheng-Ta Yang, Chin-Chou Wang, Sang-We Kim, Keunchil Park, Dong-Wan Kim, Byoung Chul Cho, Ki Hyeong Lee, Young-Chul Kim, Ho Jung An, In Sook Woo, Jae Yong Cho, Sang Won Shin, Jong-Seok Lee, Joo-Hang Kim, Seung Soo Yoo, Terufumi Kato, Naofumi Shinagawa, Ross Andrew Soo, Shao Weng Daniel Tan, Lynette Si-Mien Ngo, Kananathan Ratnavelu, Azura Rozila Ahmad, Chong Kin Liam, Filippo de Marinis, Pierfrancesco Tassone, Amelia Insa Molla, Antonio Calles Blanco, Martin Emilio Lazaro Quintela, Enriqueta Felip Font, Anne-Marie Dingemans, Lynne Bui
Journal: The Lancet Respiratory Medicine (2020)
Meta-analysis on the efficacy and safety of Danhong injection in the treatment of cerebral infarction
Authors: Yang Yang, Ling-xia Zeng
Journal: BMJ (2012)

To evaluate the clinical efficacy and safety of Danhong injection in the treatment of cerebral infarction.A total of 27 randomized controlled trials were retrieved from the literature and analyzed by Meta-analysis with RevMan 5.0 software.All were at level B or above after quality assessment.The clinical efficacy of Danhong injection was better than that of the control group in the treatment of cerebral infarction( RR =1.21,95％ CI:1.17 - 1.26 ).After the administration of Danhong injection,the score of National Institute of Neurological Disorders and Stroke (NIHSS) and hemorrheologic indices were significantly lower than those of the control group (P ＜0.01 ).There was no obvious adverse reaction.The clinical efficacy and safety of Danhong injection have marked advantages over Danshen and Fufang Dansheng injection in the treatment of cerebral infarction.

Key words: 
Cerebrovascular disorders;  Meta-analysis
Receptor tyrosine kinases and growth factors expression in tumor thrombus cells in patients with renal cell carcinoma (RCC).
Authors: Maria Volkova, Ilya Tsimafeyeu, Dmitry Khochenkov, Anna Olshanskaia, Niko Vashakmadze, Yulia Khochenkova, Elyso Solomko, Saida Ashuba, Vsevolod Borisovich Matveev
Journal: Journal of Clinical Oncology (2020)

e17073 Background: To our knowledge, this is a first study describing the expression of the receptor tyrosine kinases (RTKs) and growth factors (GFs) in venous tumor thrombus cells and comparing results with the expression in primary RCC. Methods: Formalin-fixed paraffin-embedded specimens of tumor thrombus and primary tumor removed from 25 untreated pT3a-T4N0-1M0-1 RCC patients were evaluated by immunohistochemistry with primary antibodies to VEGF-A, FGF2, VEGFR1, VEGFR2, FGFR1, FGFR2, PDGFRα, and PDGFRβ (Abcam/Santa Cruz Biotech) and REAL™ EnVision™ Detection System (Agilent). The extent of expression was compared with 25 specimens of primary tumor tissue (selected from the same patients). Significant differences in the expression among these groups were assessed by chi-squared and Fisher's exact tests using a semi-quantitative method (H-score). The analysis of the correlation between expression levels and RCC characteristics was also performed. Results: Mean age was 62.0 (35-74) years. pT3a, pT3b, pT3c and pT4 stages were detected in 4 (16.0%), 13 (52.0%), 7 (28.0%), and 1 (4.0%) patients. Lymph node metastases were found in 9 (36.0%) cases, 15 (60.0%) patients had 1 or more metastatic sites. All RTKs and GFs were heavily expressed in primary tumor cells. Tumor thrombus cells were characterized by significant lower expression levels of VEGFR1, VEGFR2, and PDGFRα (p &lt; 0.05 for all). Tendency to lower expression of VEGF-A (p = 0.06), FGF-2 (p = 0.046), FGFR1 (p = 0.077), and FGFR2 (p = 0.09) was observed in tumor thrombus cells (Table). VEGFR2 expression levels were 2-times reduced in patients with supradiaphragmatic thrombus (H-score = 21.4±12.0) compared to infradiaphragmatic thrombus (H-score = 55.0±8.5, p = 0.042). Furman grade correlated with the expression levels of VEGFR1 (p = 0.035) and FGFR1 (p = 0.022) in primary tumor cells; tumor invasion into venous wall correlated with the expression levels of VEGFR1 (p = 0.023) and FGFR2 (p = 0.005) in thrombus cells. Conclusions: RCC invasion into veins is accompanied by a decrease in expression of RTKs and GFs. Further studies are needed to understand the biological significance. [Table: see text]
RESTORE: A single-arm, open-label phase II trial of bipolar androgen therapy (BAT) in men with metastatic castration resistant prostate cancer (mCRPC)—A comparison of post-abiraterone (Abi) versus post-enzalutamide (Enza) patients (Pts).
Authors: Mark Christopher Markowski, Hao Wang, Michael Thomas Schweizer, Michael Anthony Carducci, Channing Judith Paller, Benjamin A. Teply, Mario A. Eisenberger, Jun Luo, Emmanuel S. Antonarakis, Samuel R. Denmeade
Journal: Journal of Clinical Oncology (2020)

5576 Background: A paradoxical inhibition of cell growth has been observed in both androgen-sensitive and castration resistant prostate cancer cell lines following the addition of high-dose testosterone.We have conducted several clinical trials investigating a mode of supraphysiologic testosterone therapy termed, BAT, in which testosterone levels are rapidly driven to the supraphysiologic range followed by a return to near-castrate levels over 28-day treatment cycles with favorable results. We previously reported the efficacy of BAT in mCRPC pts that were progressing on enza. In this study, we compared the effect of BAT in mCRPC pts whose last therapy was abi vs. enza. In addition, we examined the benefit of abi or enza rechallenge after progression on BAT. Methods: 59 mCRPC pts (n = 29 post abi; n = 30 post enza) were enrolled and received at lease one dose of BAT monotherapy, 400mg intramuscularly every 28 days. After clinical or radiographic progression on BAT, pts were rechallenged with the AR targeted therapy to which they were most recently resistant. The co-primary endpoints were a 50% decline in PSA from baseline (PSA50) for BAT and for enza/abi rechallenge. Results: 5/29 (17.2%) of post-abi pts compared to 9/30 (30%) in the post enza group achieved a PSA50 response (P = 0.36). Post BAT rechallenge with abi (n = 19) or enza (n = 22) resulted in a PSA50 response rate of 15.8% (n = 3) and 68.2% (n = 15), respectively (P = 0.001). The total duration of benefit (i.e. PFS on BAT + PFS on rechallenge = “PFS2”) was significantly longer in the post enza vs. post-abi patients (Median PFS2: 12.75 vs. 8.125 months; P = 0.04. Lastly, AR-V7 negative (n = 42) pts has a significantly longer median PFS2 compared to AR-V7 positive (n = 10) pts. (10.3 vs. 7.1 months, P = 0.005). Conclusions: Our data suggest that BAT may be more effective at resensitizing mCRPC to direct AR antagonists (i.e. enza) compared to abi. Detection of AR-V7 portended a worse outcome on BAT/rechallenge. Further clinical study is warranted. Clinical trial information: NCT02090114 . [Table: see text]