tbuckley/cabot-search huggingface dataset:
Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab (T) in combination with durvalumab (D) for patients (pts) with advanced hepatocellular carcinoma (aHCC).
Authors: Robin Kate Kelley, Bruno Sangro, William Proctor Harris, Masafumi Ikeda, Takuji Okusaka, Yoon-Koo Kang, Shukui Qin, Wai Meng David Tai, Ho Yeong Lim, Thomas Yau, Wei-Peng Yong, Ann-Lii Cheng, Antonio Gasbarrini, Filippo G. De Braud, Jordi Bruix, Mitesh J. Borad, Philip He, Alejandra Negro, Masatoshi Kudo, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2020)

4508 Background: The combination of dual immune checkpoint inhibitors (ICI) T (anti–CTLA-4) and D (anti–PD-L1) showed tolerability with a promising objective response rate (ORR) in the initial cohort of this study (NCT02519348). Subsequent evaluation of pts with solid tumors treated with increasing doses of T suggested priming with a higher dose of T may induce a stronger immune response and enhance anti-tumor activity. Thus, the randomized expansion cohorts comprised 4 arms evaluating T and D as monotherapies and 2 T+D regimens, including a novel T+D regimen featuring a single, priming dose of T. Methods: ICI-naïve pts with aHCC who progressed on, were intolerant to, or refused sorafenib were randomized to one of two T+D combinations: T300+D (T 300 mg + D 1500 mg 1 dose followed by D Q4 weekly [Q4W]) or T75+D (T 75 mg Q4W + D 1500 mg Q4W [4 doses] followed by D Q4W); or single agent D (1500 mg Q4W) or T (750 mg Q4W). Safety was the primary endpoint. ORR by blinded, independent central review using RECIST v1.1, duration of response (DoR), circulating lymphocytes, and overall survival (OS) were assessed. Results: At data cut-off (09/02/2019), 332 pts were enrolled. Median follow-ups were 11.7 months (mo) for T300+D, 14.6 (T75+D), 8.9 (D), and 15.8 (T). Treatment-related adverse event (trAE) incidences are shown (Table); no deaths were attributed to trAEs for T300+D or T. The T300+D arm had the highest confirmed ORR (DoR not reached [NR]) and longest OS (Table). A unique proliferative T cell profile was identified for pts in the T300+D arm, suggesting additive biologic activity for the combination, and showed pts with an OR exhibited high cytotoxic (CD8) counts. Conclusions: The encouraging clinical activity and tolerable safety profile suggest T300+D provides the best benefit-risk profile as opposed to T75+D or monotherapies. The unique pharmacodynamic activity of the T300+D regimen further supports its use in aHCC. T300+D and D are being evaluated in the ongoing phase III HIMALAYA study (NCT03298451) in first-line HCC vs sorafenib. Funding: AstraZeneca. Clinical trial information: NCT02519348 . [Table: see text]
巩膜板层迂回缝线人工晶体固定法临床观察
Authors: 李元彬, 高磊, 姜鹏飞
Journal: BMJ (2011)

随着眼科显微手术学的发展,常规的人工晶体植入技术已变得十分成熟和简单,但是在临床上仍然会碰到一些复杂的病例需要通过缝线技术进行人工晶体的悬吊固定.我们采用巩膜板层迂回缝线技术进行人工晶体悬吊,取得了良好的效果,现总结如下。
Effectiveness on blood pressure control for hypertensive patients with Mobile Health Management in community
Authors: Jianxia Zhu, Mingcheng Lu, Jinsheng Zeng, Fuyi Zhou, Yulan Li, Zhuohua Liang, Chao Tang, Shaohua Lyu
Journal: BMJ (2015)

Objectives
To evaluate the effectiveness of mobile internet technology in management of hypertensive patients in community.


Methods
Total 556 hypertensive patients in community were randomly divided into mobile health management group (management group, n=270) and control group (n=286). Conventional antihypertensive medication was given for both groups. In management group additional mobile health management was performed, including real-time monitoring of blood pressure, reminding of medication by voice reminder and SMS through the information platform of automatic warning system. The blood pressure and blood lipid were measured, quality of life was evaluated by Nottingham Health Profile (NHP) and Life Satisfaction Index Z (LSIZ) scales; the incidence of complications, hospitalization or emergency admission related to hypertension were documented during the 1 year of follow up.


Results
After 1 year of follow up, the blood pressure and blood lipid decreased significantly (P 0.05). Score of knowledge related to health education in management group was significantly higher than that of pre-management (90.5±3.1 vs. 31.1±5.9, P 0.05). The scores of life satisfaction degree measured by LSIZ in management group and in control group were 9.53±3.03 and 8.30±2.96, respectively (P<0.01).


Conclusion
Mobile Health Management can effectively control blood pressure, reduce incidence of complications, enhance compliance of patients and improve quality of life for hypertensive patients in community.


Key words: 
Hypertension; Disease managment; Community health services
End-of-life health care utilization (EOLHCU) in patients with thoracic, head and neck cancers with or without phase I study participation at a single institution.
Authors: Dominic Min-Tran, Annika Gustafson, Keith D. Eaton, Elizabeth Trice Loggers, Cristina P. Rodriguez, Rafael Santana-Davila
Journal: Journal of Clinical Oncology (2020)

e19153 Background: Several retrospective studies suggest patients enrolled in clinical trials have more end-of-life health care utilization (EOLHCU). This is particularly concerning for phase I clinical trial participants who are known to have therapeutic misconceptions about the purpose and benefits of phase I clinical trial participation. Methods: We identified all phase I participants at the Seattle Cancer Care Alliance (SCCA) with thoracic, head and neck cancers (THNC) who died between July 1, 2014 and June 30, 2018(P1C). We compared them to 139 randomly selected THNC patients who died within the same time period without phase I study participation (NP1C). Patient records were abstracted from the electronic health record (and Epic Care Everywhere if patients received EOL care outside of SCCA). A chi-square test was used to compare categorial variables and t-tests were used for numerical variables. Results: 67 P1C patients were identified; 3 patients had no outside records at the end of life and were removed from the database. No statistically significant differences in gender, ethnicity, marital status, or form of insurance were found between the two groups. P1C patients were younger (median age of 62 (interquartile range (IQR) 55-69) vs. 66 (IQR 59-72), p=0.008) and had more lines of therapy from diagnosis until death (median 4 (IQR 1-3) vs. 2 (IQR 1-3), p=&lt;0.0001). No difference in end-of-life care or quality of death metrics were found between the two groups, however a trend toward more referrals to palliative care were noted in phase I participants. (Table). Conclusions: At our center no differences in EOLHCU or quality of death parameters were seen in THNC patients who did or did not participate in phase I studies. [Table: see text]
假性动脉瘤的临床诊治
Authors: 陈力, 陈华, 田华, 龚渭华, 陶思丰
Journal: BMJ (2004)

假性动脉瘤发生于各种损伤,常与伤后处理不当有关,医源性假性动脉瘤发病近年有增多的趋势.彩色多普勒超声检查是首选的方法,对多数患者手术是惟一有效的治疗手段.我科收治的33例患者中因锐器刺击伤者19例,闭合性创伤6例,医源性损伤8例,均行手术治疗后痊愈。
Targeting CD33 in Chemoresistant AML Patient-Derived Xenografts by CAR-CIK Cells Modified with an Improved SB Transposon System
Authors: Maria Caterina Rotiroti, Chiara Buracchi, Silvia Arcangeli, Stefania Galimberti, Maria Grazia Valsecchi, Vincenzo Maria Perriello, Tamas Rasko, Gaia Alberti, Chiara Francesca Magnani, Claudia Cappuzzello, Felix Lundberg, Amit Pande, Giuseppe Dastoli, Martino Introna, Marta Serafini, Ettore Biagi, Zsuzsanna Izsvák, Andrea Biondi, Sarah Tettamanti
Journal: Molecular Therapy (2020)

The successful implementation of chimeric antigen receptor (CAR)-T cell therapy in the clinical context of B cell malignancies has paved the way for further development in the more critical setting of acute myeloid leukemia (AML). Among the potentially targetable AML antigens, CD33 is insofar one of the main validated molecules. Here, we describe the feasibility of engineering cytokine-induced killer (CIK) cells with a CD33.CAR by using the latest optimized version of the non-viral Sleeping Beauty (SB) transposon system "SB100X-pT4." This offers the advantage of improving CAR expression on CIK cells, while reducing the amount of DNA transposase as compared to the previously employed "SB11-pT" version. SB-modified CD33.CAR-CIK cells exhibited significant antileukemic activity in vitro and in vivo in patient-derived AML xenograft models, reducing AML development when administered as an "early treatment" and delaying AML progression in mice with established disease. Notably, by exploiting an already optimized xenograft chemotherapy model that mimics human induction therapy in mice, we demonstrated for the first time that CD33.CAR-CIK cells are also effective toward chemotherapy resistant/residual AML cells, further supporting its future clinical development and implementation within the current standard regimens.
PD-L1 expression landscape and its relationship with tumor mutation burden in Chinese cancer patients.
Authors: Haihua Yang, Longgang Cui, Yuzi Zhang, Zhengyi Zhao, Yuezong Bai, Wenzhuan Xie
Journal: Journal of Clinical Oncology (2020)

e15267 Background: Little is known about the pan-cancer PD-L1 expression landscape in Chinese patients although PD-L1 expression has been approved by FDA as a diagnosis for anti-PD-(L)1 therapy in several types of cancer. We did a cross-sectional analysis to assess the PD-L1 expression landscape in Chinese patients and its relationship with Tumor mutation burden (TMB). Methods: Tissue samples were collected from more than 8,000 consecutive cases in China between January, 2017, and August, 2019 and were analyzed by 3D Medicines, a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. The method for NGS sequencing and tumor mutational burden (TMB) measurement were described previously. Clinical data and PD-L1 expression profiles were obtained from 8,063 patients whose tissue samples assed quality control. IHC staining for PD-L1 expression was performed using PD-L1 IHC 22C3 pharmDx assay (Dako North America, Carpentaria, CA, U.S.) or Ventana PD-L1 SP263 assay (Ventana Medical Systems, Tucson, AZ, U.S.). PD-L1 expression was determined using Tumor Proportion Score (TPS), the percentage of viable tumor cells stained. Results: PD-L1 expression was examined for 8,063 tissue samples collected from more than 18 different types of solid tumors. There were 4,866 (60%) male and 3,197 (40%) female patients. Their median age was 59 (IQR range, 50-66) years. Given the significance of different cut-points of PD-L1 expression in predicting clinical outcomes, expression levels of PD-L1 were arranged into the following intervals: &lt; 1%, 1%-5%, 5%-50% and ≥50% for each cancer type. Small cell lung cancer (SCLC) had the lowest and Squamous Carcinoma of Head and Neck (HNSC) had the highest levels of PD-L1 expression. Spearman correlation analysis indicated no correlation between PD-L1 and tumor mutational burden (TMB) for Chinese cancer patients (R = 0.1, P &lt; 0.01), which is in line with the previous reports that PD-L1 and TMB were two independent predictors in immunotherapy. Conclusions: The landscape of PD-L1 expression among Chinese cancer population in this study will further assist the utilization of PD-L1 as a predictive biomarker in clinical practice.
先天性背部皮肤窦道伴脊髓纵裂与脂肪瘤一例
Authors: 赵国栋, 李放, 赵广民, 李小强
Journal: BMJ (2009)

患者女,17岁.因发现背部皮肤窦道于2008年7月15日就诊.患者二便正常.查体:神清,智力正常,正常步态,腰椎活动度可,腰背部可见一8 cm×8 cm突出肿物、质软、皮温不高、活动度可、无压痛部位,其卜缘可及约直径4 mm皮肤窦道、无分泌物(图1),四肢感觉、肌力正常,脊柱曲度尚可,生理征可引出,病理征阴性,直腿抬高试验及股神经牵拉试验(-)。
Identification of SDHA germline mutations in sporadic SDHA mutant gastrointestinal stromal tumors (GIST): The need of a genetic counselling.
Authors: Margherita Nannini, Milena Urbini, Valentina Indio, Angela Schipani, Bruno Vincenzi, Marianna Silletta, Giovanni Grignani, Francesco Tolomeo, Alessandro Rizzo, Elena Fumagalli, Elena Conca, Maristella Saponara, Annalisa Astolfi, Maria A. Pantaleo
Journal: Journal of Clinical Oncology (2020)

11537 Background: SDH- deficient GIST, as defined by the loss of expression of SDHB, account up to about 10% of all gastric GIST and generally affect younger population. Germline mutations in SDHB, SDHC, and SDHD occur in about 20–30% of SDH- deficient, that may be referred to a hereditary condition known as hereditary GIST-paraganglioma syndrome (Carney-Stratakis Syndrome), whereas germline SDHA mutations have been rarely described in apparently sporadic cases. Currently, even germline testing is recommended for SDH- deficient GIST, there are no clear guidelines for genetic counselling and follow-up of SDH x mutation carriers and relatives, especially for SDHA mutant GIST not yet linked to well-defined hereditary syndrome. The aim of this work was to study the SDHA gene in the normal DNA of patients with SDHA mutant GIST. Methods: Thirteen patients carrying SDHA-mutant GIST were studied (8F/5M). Median age of diagnosis was 45,9 years (range 25-74). All GIST were located in the stomach and 3 patients out 13 presented a metastatic disease. In all cases except one, the GIST was the only cancer presentation and no personal or familial history of cancer was revealed. All cases were negative for SDHB immunohistochemistry. Germline mutations were identified through Sanger sequencing of SDHA in the normal counterpart. Results: Germline mutations were identified in all patients for which normal counterpart was available: 4 cases harboured truncating mutations (S384X, R31X and W119X); 5 cases carried pathogenic missense mutations (G233V, R171H, R589Q, G257A and R600Q) and 2 cases had splice site alterations (c.457-3_457-1 delCAG and c.456+9 C &gt; T). In 8 cases the tumor DNA showed the loss of the corresponding wild-type allele, while in the other 3 cases compound heterozygosity for an additional somatic mutation was detected (R589W, R451C,and R171C). In 2 patients, unfortunately, normal DNA was not available, however both tumours carried two mutational hits on SDHA (one with heterozygous G419R and E564K, and one with homozygous R585Q). Of note, 5 patients presented un-usaul SDHA related clinical characteristics as were not young adult ( &gt; 50 years-old) or no multifocal GIST. Conclusions: We demonstrated that germline SDHA mutations are highly frequent in SDHA- deficient GIST. Therefore, although a clear syndrome has not been defined, genetic counselling and follow-up of SDHA mutation carriers and relatives should be clarified.
High-dose osimertinib for CNS progression in EGFR+ non-small cell lung cancer (NSCLC): A multi-institutional experience.
Authors: Andrew Piper-Vallillo, Julia K Rotow, Jacqueline V Aredo, Khvaramza Shaverdashvili, Jia Luo, Jennifer W Carlisle, Hatim Husain, Alona Muzikansky, Rebecca Suk Heist, Deepa Rangachari, Suresh S. Ramalingam, Heather A. Wakelee, Helena Alexandra Yu, Lecia V. Sequist, Joshua Bauml, Joel W. Neal, Zofia Piotrowska
Journal: Journal of Clinical Oncology (2020)

9586 Background: High-dose osimertinib 160 mg QD (osi160) has activity in osi-naïve, EGFR+ NSCLC pts with CNS or leptomeningeal disease (LMD) per the BLOOM trial, but the role of dose-escalation for CNS progression (PD) and/or LMD that develops while on 80 mg QD (osi80) is unclear. We describe here our multi-institutional experience with osi160. Methods: 105 pts from 8 institutions with advanced EGFR+ NSCLC treated with osi160 were retrospectively reviewed. To assess the CNS efficacy of dose escalation for CNS PD, we focused on pts who escalated from osi80 to osi160 for CNS PD without the addition of chemo and/or RT during dose escalation (cohort A, 24 pts). We also examined osi escalation for CNS PD while receiving chemo and/or RT (cohort B, 34 pts) and those who started on osi160 for CNS PD as the initial osi dose without overlapping therapies (cohort C, 11 pts). Radiographic responses were clinically assessed via chart review of scan reports. Kaplan-Meier analysis was used for time-to-event endpoints. We defined median duration of CNS disease control (MedDurCNSCon) on osi160 as time from the start of osi160 to CNS PD or discontinuation of osi160. Results: Among the 105 pts, 69 (26M, 43F; median age 57) EGFR+ NSCLC pts (29 del19, 31 L858R, 9 other) received osi160 for CNS PD between 10/2013 and 1/2020. Median lines of therapy pre-osi was 1 (range 0-8). While all 69 pts had CNS PD at the start of osi160, 61 (90%) had isolated CNS/LMD PD, without systemic PD. In cohort A, osi160 monotherapy had a MedDurCNSCon of 3.8 mos (95% CI, 1.7 – 5.8). Cohort A pts with isolated LMD (11) had MedDurCNSCon 5.8 mos (95% CI, 1.7 – 9) while those with parenchymal mets only (11) had MedDurCNSCon of 2 mos (95% CI, 1 - 4.9). In cohort B, osi160 in combination with RT (22) and/or chemo (14), had a MedDurCNSCon of 5.1 mos (95% CI, 3.1 – 6.5). In cohort C, osi160 monotherapy had a MedDurCNSCon of 4.2 mos (95% CI, 1.6 – NA). Pts on osi160 had no severe or life-threatening side effects. Conclusions: In this real-world cohort of EGFR+ NSCLC pts with CNS and/or LMD PD on osi80, dose escalation to 160 provided modest benefit with median 3.8 mos added CNS disease control. Dose escalation appeared more effective in pts with LMD versus parenchymal disease (MedDurCNSCon of 5.8 vs 2 mos). Treatment intensification with osi escalation plus RT and/or chemo appeared to confer about 1 month additional CNS disease control (power for comparison limited). Osi naïve pts started at 160 for CNS PD derived similar benefit. While limited by small numbers and retrospective design, this study suggests we need improved strategies to optimally manage CNS PD arising on osi80.
Phase III study of pembrolizumab (pembro) plus enzalutamide (enza) and androgen deprivation therapy (ADT) for patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC): KEYNOTE-991.
Authors: Christian Gratzke, Joseph E Burgents, Cuizhen Niu, Christian Heinrich Poehlein, Charles G. Drake
Journal: Journal of Clinical Oncology (2020)

TPS5595 Background: Pembro, an anti–PD-1 antibody, has shown antitumor activity as monotherapy and in combination with other agents in metastatic castration-resistant prostate cancer (mCRPC). As the antitumor effects of enza may be pro-immunogenic, we hypothesized that combining pembro and enza could show additive or synergistic antitumor activity. Furthermore, pembro + enza previously showed antitumor activity in pts with mCRPC for whom abiraterone failed (KEYNOTE-365, NCT02861573) and in pts with mCRPC for whom enza monotherapy failed (KEYNOTE 199, NCT02787005). These data warrant further evaluation of the combination of pembro + enza when given at the initiation of ADT. Methods: KEYNOTE-991 (NCT04191096) is a phase III trial to evaluate the efficacy and safety of enza + ADT + either pembro or placebo in patients with mHSPC. Approximately 1232 pts will be randomly assigned 1:1 to receive enza 160 mg orally once daily + ADT + pembro 200 mg IV every 3 weeks (Q3W) or enza 160 mg orally once daily + ADT + placebo IV Q3W. ADT is receipt of an LHRH agonist or antagonist during study treatment or bilateral orchiectomy. Treatment will be stratified by prior docetaxel therapy (yes or no) and presence of high-volume disease (yes or no). Pts with mHSPC, with ≥2 bone lesions and/or visceral disease, who are naive to next-generation hormone agents, and who have ECOG PS 0 or 1 are eligible. Pts must provide tissue for biomarker analysis. Responses will be assessed by CT or MRI and radionuclide bone imaging per Prostate Cancer Working Group 3 (PCWG3)–modified RECIST v1.1 by blinded independent central review (BICR) Q12W from the date of randomization. Treatment will continue with pembro for up to 35 cycles, and treatment with enza will proceed continuously from day 1 of cycle 1 until disease progression, unacceptable toxicity, or withdrawal of consent. Dual primary end points are radiographic progression-free survival (PFS) per PCWG3-modified RECIST v1.1 assessed by BICR and overall survival. Secondary end points are time to first subsequent anticancer therapy, time to symptomatic skeletal-related event, PFS2 (progression after next line of therapy or death), prostate-specific antigen (PSA) response rate, time to PSA progression, PSA undetectable rate, objective response rate, duration of response, and time to radiographic soft tissue progression. Other end points are safety and patient-reported outcomes (eg, time to pain progression). Clinical trial information: NCT04191096 .
中医应对外感发热和外感咳嗽
Authors: 张雪亮
Journal: BMJ (2011)

张雪亮:这讲是从中医的角度探讨外感发热和咳嗽.大家知道,每隔几年总要有一次病毒性感冒流行,中医叫做发热性外感疾病.有人对中医治疗发热感冒不屑一顾,怀疑中医的疗效.绝大部分人感冒发热都会去看西医,认为打针输液来得快,一挂瓶心里就踏实.实际上大家肯定有同感,用药后虽然很快热度退了,但2小时以后又升上来了。
Abrrant expression of a subset of epithelial–mesenchymal transition genes in triple-negative breast cancer before and after EC-T neoadjuvant chemotherapy.
Authors: Liyuan Wei, Li Wang, Xiaojun Zhang, Xu Dong Zhang, Jinnan Gao
Journal: Journal of Clinical Oncology (2020)

e12617 Background: Pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) is associated with favorable outcomes of patients with triple-negative breast cancer (TNBC). However, the heterogeneous nature of the disease often results in diverse responses to the same NACT protocol. In particular, a proportion of patients with residual disease (RD) develop metastasis at early stages after treatment. Further stratification of TNBC patients without pCR to NACT is needed for the development of novel strategies in the management of these patients. Methods: A retrospective series of ten TNBC patients with locally residual disease after NACT with the EC-T regimen at Shanxi Bethune Hospital between 2014 and 2018 were included. Total RNA from FFPE pre-NACT core biopsies and paired surgical specimens was subjected to the Affymetrix Human Transcriptome Array. Gene Set Enrichment Analysis (GSEA) was used to identify signal pathways and gene signatures associated with early metastasis after NACT followed by surgery. The Cox proportional hazard model and Kaplan-Meier survival curves on DMFS (distant metastasis-free survival) were employed to assess the prognostic value of the identified signature in TNBC patients from GEO datasets. Results: The epithelial-mesenchymal transition (EMT) pathway was markedly more enriched in pre- (NES = 1.92; p.adjust = 0.019) and post-NACT samples (NES = 2.02; p.adjust = 0.010) from patients who developed metastasis at relatively early stages ( &lt; 18 months) after surgery compared with those who had been disease-free. Noticeably, the EC-T NACT differentially affected the expression of EMT genes resulting in global promotion or inhibition of the pathway in a case-dependent manner. Nevertheless, a subset of 6 EMT genes including LUM, SFRP4, DCN, MMP2, CXCL12, and HTRA1 was expressed constantly at higher levels in samples from patients who progressed to metastasis. The potential of this 6-EMT gene signature to predict TNBC metastasis was validated in the MDACC neoadjuvant series (GSE25066) that contained 113 TNBC patients with RD (55 with metastasis; p = 0.0008; HR = 0.36; 95% CI: 0.200-0.685) and the ICO–UMGC dataset (GSE103091) including 107 TNBC patients (31 with metastasis; p = 0.032, HR = 0.46, 95% CI:0.225-0.937). Conclusions: The expression of the 6-EMT gene signature at diagnosis may be a predictive value of metastasis of TNBC. Moreover, the persistently high expression of the signature may signal early metastasis in TNBC patients with residual disease after EC-T NACT.