tbuckley/cabot-search huggingface dataset:
Multi-center clinical studies on pazufloxacin sodium chloride injection in treatment for acute bacterial infections
Authors: Jing Yang, Geng-zhi Ge, Tian Xia, Bao-yuan Chen, Xiao-wen Han, Bing Liu, Li-xian He, Xiao-qiang Ding, Zhong-yi Huang, Zhong-min Qiu, Jun Ma, Ce Shen, Nian-song Wang
Journal: BMJ (2008)

Objective To evaluate efficacy and safety of locally-produced pazufloxacin mesilate sodium chloride injection in the treatment of bacterial infections of respiratory and urinary tract.Methods A multi-center double-blind randomized controlled clinical trial was carried out to evaluate efficacy and safety of pazufloxacin mesilate sodium chloride in treatment for acute bacterial infection, as compared to those of levofloxacin hydrochloride and glucose injection as control treatment.A total of 244 patients with acute bacterial infection of respiratory and urinary tract were enrolled in the studies.120 in trial group and 120 in control group, with four withdrawals.Pazufloxacin mesilate and levofloxacin were administered intravenously by drip at a dose of 300 mg and 200 mg, every 12 hours for 7 to 14 days for trial and control groups, respectively.Resuits Overall efficacy of pazufloxacin mesilate was 77.0 percent and 93.5 percent in treatment for acute bacterial infections of respiratory and urinary tract.respectively, and that of levofloxacin was 80.6 percent and 89.6 percent, respectively.Overall bacterial clearance rate WaS 91.5 percent for pazufloxacin mesilate, 89.6 percent for respiratory tract infection and 94.1 percent for urinary tract infection, respectively.and 93.4 percent for levofloxacin, 97.3 percent for respiratory tract infection and 89.7 percent for urinary tract infection, respectively.No significant difference in adverse drug reactions between the two groups(P＞0.05)was found, with 4.88 percent and 7.44 percent for trial and control groups, respectively.Conclusions Pazufloxacin mesilate sodium chloride injection produced locally is a safe and effective antibiotic in treatment for acute infections of respiratory and urinary tract.

Key words: 
Quinolones;  Bacterial infections;  Randomized controlled trials
Correction of muscular dystrophies by CRISPR gene editing
Authors: Francesco Chemello, Rhonda Bassel-Duby, Eric N. Olson
Journal: Journal of Clinical Investigation (2020)

Muscular dystrophies are debilitating disorders that result in progressive weakness and degeneration of skeletal muscle. Although the genetic mutations and clinical abnormalities of a variety of neuromuscular diseases are well known, no curative therapies have been developed to date. The advent of genome editing technology provides new opportunities to correct the underlying mutations responsible for many monogenic neuromuscular diseases. For example, Duchenne muscular dystrophy, which is caused by mutations in the dystrophin gene, has been successfully corrected in mice, dogs, and human cells through CRISPR/Cas9 editing. In this Review, we focus on the potential for, and challenges of, correcting muscular dystrophies by editing disease-causing mutations at the genomic level. Ideally, because muscle tissues are extremely long-lived, CRISPR technology could offer a one-time treatment for muscular dystrophies by correcting the culprit genomic mutations and enabling normal expression of the repaired gene.
Correlation of DLL3 expression in gastroenteropancreatic neuroendocrine neoplasms with loss of RB1 and prognostic significance.
Authors: Chiara Liverani, Alberto Bongiovanni, Laura Mercatali, Federica Pieri, Chiara Spadazzi, Giacomo Miserocchi, Giandomenico Di Menna, Flavia Foca, Sara Ravaioli, Alessandro De Vita, Claudia Cocchi, Federica Recine, Toni Ibrahim
Journal: Journal of Clinical Oncology (2020)

4611 Background: Neuroendocrine neoplasms (NENs) are a rare subgroup of tumors with challenging management due to their unpredictable and heterogeneous behaviour. The identification of clinically useful biomarkers is a top priority need in this disease. The negative notch regulator DLL3 has gained increasing attention in small cell lung carcinoma, large cell neuroendocrine carcinoma and neuroendocrine prostate cancer, confirming the tumor suppressor function of Notch-1 signaling in neuroendocrine cells. Methods: A retrospective immunohistochemical analysis of DLL3, PD-L1 and RB1 was performed on FFPE samples from 43 patients with gastroenteropancreatic (GEP)-NENs and correlated with clinical characteristics. Results: DLL3 was expressed in high-grade (G3) GEP-NENs. The presence of DLL3 was significantly associated with poorly differentiated NEC (77.8% positive tumors), while none of the patients with well-differentiated NET expressed this marker. Expression of DLL3 was correlated with loss of RB1 and negative 68 Ga-PET/CT scan. The 85.7% of DLL3- positive tumors showed loss of RB1 expression, while only 1 out of 35 DLL3- negative tumors had RB1 loss. DLL3 was expressed in 75% of patients with negative 68 Ga-PET/CT, while only in 25% of patients with positive 68 Ga-PET/CT scan. The presence of DLL3 was negatively associated with PFS and OS. Median PFS was 41.9 months in DLL3-negative patients versus 7.9 months in DLL3-positive patients; median OS was 72.9 months in DLL3-negative patients versus 11.7 months in DLL3-positive patients. No correlation was found with DLL3 and PD-L1 expression. The presence of PD-L1 was not associated with any clinical characteristics. Conclusions: DLL3 is expressed in high grade GEP-NENs and is associated with loss of RB1, negative 68 Ga-PET/CT scan and unfavourable clinical outcome. The presence of DLL3 discriminates poorly differentiated NEC from well-differentiated NET. DLL3 could represent the ideal prognostic factor to stratify patients with GEP-NENs and a candidate therapeutic target in NEC patients.
淡水淹溺患者抢救成功一例
Authors: 孙丽, 苏海华, 温冰
Journal: BMJ (2008)

患者男,17岁,因溺水后神志不清半小时,于2007年8月10日入院治疗.患者于入院前半小时游泳时不慎溺水后出现神志不清,烦躁,恶心,呕吐,呕吐物为胃内容物.由120急救送入我院.人院时患者咯粉红色泡沫样痰。
Germline and somatic DNA damage repair gene mutations potentially predict the efficacy of relevant treatment in Chinese patients with pancreatic ductal adenocarcinoma.
Authors: Lin Shui, Yang Peng, Shuangshuang Li, Jiangfang Tian, Dan Cao
Journal: Journal of Clinical Oncology (2020)

e16732 Background: PDAC is a fatal disease with molecular heterogeneity, inducing differences in biological behaviour and therapeutic strategy. We conducted a study to reveal the mutation landscape of Chinese PDAC patients, and investigate the predictive role of germline and somatic DNA damage repair (DDR) status in precise treatment. Methods: 195 PDAC patients were enrolled from multiple medical centers of China between Jan 2016 to Nov 2019. Baseline clinical or genetic characteristics, and survival status were collected. NGS were performed on paraffin-embedded resected tissues or peripheral blood using a panel of 417 genes, including 50 DDR-related genes. Survival analysis was conducted using Kaplan-Meier, and Cox proportional hazard regression model. Results: The main driver genes were KRAS, TP53, CDKN2A, and SMAD4. Patients with KRAS mutation showed worse OS than those without (p = 0.048). DDR deficiency were identified in 15.38% of overall patients, mainly occurred in BRCA2 (4.62%), ATM (4.10%), RAD50 (1.54%) and MLH1 genes (1.03%). No significant improvement of OS existed between patients with or without DDR mutations (p = 0.88). Treatment with olaparib (adjusted HR, 0.2550; P = 0.0720) or platinum-based chemotherapy (adjusted HR, 0.1308; P = 0.0185) respectively decreased hazard of death in patients with DDR mutation. Besides BRCA gene, ATM mutant patients treated with olaparib harbored prolonged median OS than those without olaparib treatment (22.25 vs 15.2 month). Despite a little higher PD-L1 expression rate were seen in DDR mutant patients (29.17% vs 20.51%), no statistical correlation between tumor mutation burden level and DDR mutation was identified. And in patients treated with PD-1 blockade, 2 patients of DDR wild-type group both had SD, whereas of the remaining 5 patients with DDR deficiency, 1 was evaluated as PR, 3 as SD, and 1 as PD (ORR, 0 wt vs 20% mut). Conclusions: In this multi-center retrospective study, we deciphered the intra-tumoral genetic heterogeneity in Chinese PDAC population, which differs from western patients cohort to some extent. We found the potential role of germline and somatic DDR mutation status in predicting the response to olaparib and platinum-based chemotherapy, especially with BRCA or ATM mutation. However, DDR alteration was limited in prediction of hypermutational status and sensitivity to PD-1 blockade. Our study may provide a valuable evidence for clinical application of DDR mutation as a potential biomarker for precise treatment.
A gentle therapy: Weekly epirubicin, as second-line treatment in elderly patients with malignant pleural mesothelioma (MPM).
Authors: Roberto Bollina, Paolo Belloni, Michela Pelliccione
Journal: Journal of Clinical Oncology (2020)

9053 Background: MPM is a rapidly progressive tumor with a poor prognosis. Treatment options are limited for patients (pts) with PMP who experience disease progression after first-line pemetrexed-based chemotherapy (CT). This retrospective study wants to evaluate, in the age of immunotherapy, whether a gentle CT can be used as second line of treatment in elderly pts, above all maintaining quality of life (safety and tolerability ) and improving progession free survival (PFS ). Currently second-line CT is increasingly use, because many elderly pts are fit at the progression of the disease. No standard second/further line CT exist for MPM after failure of first-line pemetrexed based CT. The purpose of the study is to evaluate the clinical activity of weekly epirubicin as second-line CT in elderly with MPM. Methods: From July 2015 to March 2019, in Medical Oncology Dept. of ASST Rhodense 98 pts were elegible for analysis. Pts had histologically confermed unresectable MPM. Histology was epithelioid in 86 pts, sarcomatoid in 7 and biphasic in 5 pts. A Carboplatin(AUC4)-pemetrexed doublet was administered in 70 pts and 28 received gemcitabine as single agent how first line. A quality of life questionnaire was administered to each pt and geriatric comprehensive assessment (GCA) was performed. Epirubicin ( E ) was always administered with a schedule at 20 mg/msq day 1,8,15 every 28 until disease progression or intolerance. The primary endpoint was PFS, and secondary endpoints were the overall response rate (ORR) and QofL an overall survival (OS). Results: Of the 98 elegible pts, 71 was males, and 27 was female . Median age: 78 (range 72-86) PS: 0/1/2 was respectively in 32%, 60% and 8% of pts. A median of 5 cycles of E (range 2 -16) was delivered; 3% of pts required dose modification. PFS was of 7 months (range 3-16) . ORR was as follow: 0 CR, 18 PR (17%), 44 SD (44%) and PD occurred in 36 pts (39%). OS was 11 months (range 5-22). No life threatening event occurred. No grade 3-4 toxicities were observed . Liver toxicity grade 1-2in 10 pts (10%), thrombocytopenia grade 1 in 9 pts (9%), neutropenia grade 1-2 in 40 pts (40%), fatigue grade 2 in 33pts (32%), nausea grade 1 in 20 pts (20%). The analitical and stratified data will be exposed. Conclusions: Also in the era of immunotherapy, a simple treatment, E in weekly schedule has demonstrated to be a gentle therapy with a possibility to treat in second line, pre-treated elderly pts with MPM in progression after first line therapy, with an acceptable profile . Now this schedule could be considered as a safe and standard secon-line CT in elderly pts.
从中心动脉压解读降压质量
Authors: 姜一农
Journal: BMJ (2007)

高血压与心血管事件的密切关系已经临床流行病学反复证实.降压带来的心血管事件减少的获益也已经大量循证医学研究证实.但近年来,基础与临床研究都不断提供这样一个事实,高血压不仅仅是一个压力问题,同时,血压还与血管密切相连,因此有学者提出血管-血压-预防(VHP)的观念,将血压从单纯的数值扩展到对内皮、血管壁的结构和功能改变的认识层面。
Caring for transgender cancer patients: Shortcomings of medical education.
Authors: Ernesto Gil Deza, Mariana Abal, Lourdes Gil Deza, Carlos Garcia Gerardi, Gaston Martin Reinas, Flavio Tognelli, Daniela Gercovich, Cesar Gonzalez, María del Huerto Jaunarena, Rubén Lovisolo, Alfredo Navigante, Monica Montiel, Marcelo Andres Nunell, Leonel Smolje, Mariano G Fernandez, Estefania E Kaminski, Marcelo Muino, Inés Danussi, Eduardo L. Morgenfeld, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2020)

11002 Background: Caring for transgender patients requires specific knowledge and skills. Medical schools spend less than 5 hours on average training for treatment of LGBT patients (Obedin-Maliver, JAMA, 306 (9), 971). This paper assesses the knowledge on the topic and skills of postgraduate Oncology students from Universidad del Salvador at the Observational Standard Clinical Examination (OSCE) 2019 (JCO 34 (15), Abstract e18150, 2017). Methods: At one of the stations of OSCE 2019, students had thirty minutes to complete a clinical record of a simulated transman patient with ovarian cancer stage IIIC. Based on the real case of Robert Eads, actors were trained with the documentary on his life “Southern Comfort”. Students were assessed on: A) knowledge of the transman condition, B) use of preferred gender pronoun by the patient, C) discontinuation of testosterone treatment, D) recommendation of genetic study, E) treatment of ovarian cancer according to NCCN guidelines, F) moral discomfort with LGBT patient care. All interviews were filmed or recorded by an observer. All films, recordings and clinical records were reviewed to rate the students' performance. Results: A total of 25 postgraduate Oncology students took the OSCE 2019. Assessment: A) 5/25 (20%) lacked knowledge of the transman condition, B) 3/25 (12%) did not use the patient's preferred gender pronoun, C) 17/25 (68%) discontinued testosterone, D) 23/25 (92%) requested genetic study, E) all students treated ovarian cancer according to NCCN guidelines, F) none expressed moral discomfort with LGBT patient care. Conclusions: 1) It is feasible to assess the knowledge and skills required for treatment of transgender patients in Oncology. 2) We found shortcomings of student's medical training regarding transgender patients: one in five did not understand the patient's condition, three did not use the patient´s preferred gender pronoun during the interview and more than half suspended the necessary hormone therapy for their condition. 3) This emphasizes the need to deepen our medical and communication skills in order to assist the transgender population and should be included in future ASCO-ASH milestones for specialty accreditation.
Cooperation between cancer-specialized hospital and community healthcare institutions in tiered referral system
Authors: Shuwen Zheng, Jian Yang, Jianhui Ma, Ai Wang, Jie He
Journal: BMJ (2016)

公立医院与基层医院的分工协作是新医改的主要内容之一，中国医学科学院肿瘤医院在肿瘤防治领域的分级诊疗和医学协作方面做了一些有益探索，主要通过合作办医、组建医疗联合体、对口支援、开展肿瘤防控项目等，加强了对基层医疗机构的指导、协作，提升了基层医疗机构的肿瘤诊治水平，为肿瘤专科医院与基层医院在分级诊疗及协作发展方面积累了经验。
A phase I and randomized phase II etctn study of KW-0761 (Mogamulizumab) and MK-3475 (Pembrolizumab) in relapsed and refractory diffuse large B-cell lymphoma.
Authors: Erel Joffe, Santosha Adipudi Vardhana, Anita Kumar, Mehrdad Abedi, Rasmus Hoeg, Elad Sharon, Anas Younes
Journal: Journal of Clinical Oncology (2020)

TPS8072 Background: Diffuse large B-cell lymphoma (DLBCL) escapes host immune responses via inhibition of the B2M and CD58 pathways and upregulation of PD-1 ligands. However, treatment results with PD-1 blockade have been disappointing. One potential mechanism is the recruitment of intra-tumoral regulatory T-cells (Tregs) which suppress anti-tumor immunity and inhibit NK cell cytotoxicity. Targeting regulatory T cells with the CCR4 antibody mogamulizumab (KW-0761) represents a molecularly informed strategy to overcome this resistance. Mogamulizumab has been safely administered in combination with pembrolizumab (MK-3475) in patients with solid malignancies and may promote CD8 T-cell dependent effector and NK cell-dependent cytotoxicity in lymphomas. Methods: This is a multi-center NIH-ETCTN phase Ib/randomized phase II study. The phase I will evaluate the safety and tolerability of mogamulizumab in combination with pembrolizumab in patients with R/R DLBCL and determine the recommended phase II dose (RP2D). A traditional 3+3 design with a starting dose of pembrolizumab 200mg IV on day 1 of a 21-day cycle and mogamulizumab 1mg/kg IV on days 1, 8, 15 and then 1.5 mg/kg IV every 21 days. The phase II will evaluate the efficacy of the combination by PFS (primary endpoint) ORR and CR (secondary endpoints). This will be a randomized 1:1 study with allowed crossover, comparing the combination to single agent pembrolizumab Correlative studies will evaluate the association of tumor infiltrating CD8 and NK cells with response to treatment, somatic mutations in B2M and CD58 and with MHC-I expression on DLBCL cells. Functional characterization of circulating immune cells in the peripheral blood and measurement of pro and anti-inflammatory cytokines will be used to assess the levels, activation status and effector function of Tregs and circulating T cells. Inclusion criteria include measurable disease, ≥2 prior lines of therapy including or ineligible for autologous stem cell transplant, ECOG ≤ 2 and normal organ function. Prior or planned allogeneic stem cell transplant, as well as prior treatment with an anti PD-1/PD-L1/CTLA4 antibody, preexisting autoimmune disease or CNS involvement by lymphoma are exclusion criteria. The study aims to enroll up to 12 patients on the phase I and up to 58 patients on the phase II and can be opened at any ETCTN participating site. To date it has been opened at two sites and is accruing the first patients for the phase I portion. Clinical trial information: NCT03309878 .
头部碰撞的严重后果
Authors: 曾昭耆
Journal: BMJ (2009)

一位85岁男性,20多年前曾有头晕、走路不自觉向左偏.当时查体,除悬雍垂反射迟钝外,无阳性体征.被诊断为椎基底动脉供血轻度不足.经输液治疗2周后,症状消失,其后间断使用口服药巩固.患者平日身体基本健康。
Treatment-related adverse events of combination immune checkpoint inhibitors: Systematic review and meta-analysis.
Authors: Robin Park, Laércio Lopes da Silva, Ivy Riano, Cagney Cristancho, Anwaar Saeed
Journal: Journal of Clinical Oncology (2020)

e15060 Background: Despite increasing clinical experience with immune checkpoint inhibitors and the recent publication of clinical practice guidelines for managing treatment-related adverse events, precise and nuanced checkpoint inhibitor data in the setting of combination therapy is lacking. Herein we have conducted a systematic review and meta-analysis of treatment-related adverse event data from clinical trials evaluating combination immune checkpoint inhibitors. Methods: Studies published in PubMed, Embase, and Cochrane Database from conception to September 28, 2019 were included in the meta-analysis. Studies were eligible for inclusion if combination immune checkpoint inhibitor therapy was evaluated in advanced unresectable cancer and treatment-related adverse event data were available. For comparison of severity of adverse events in combination versus monotherapy, only the studies containing monotherapy arms as a control population were included, while all were included for calculation of pooled incidence of selected adverse events. Pooled risk ratio (RR) was used for the comparison of combination versus monotherapy and the logit transformed proportion for calculation of pooled incidence. Between-study risk of bias was evaluated using the Begg's funnel plot and Egger's regression test. Subgroup analysis was conducted by combination regimen, cancer type, and dosing regimen. Results: A total of 18 studies comprising 2767 patients across 10 cancer types were included in the final analysis. Combination ICI was associated with a slightly higher risk of all-grade adverse events (RR 1.07 [95% CI 1.03-1.11]) and markedly greater risk of grade 3 or higher adverse events (RR 2.21 [95% CI 1.57-3.10]) compared to monotherapy ICI. Subgroup analyses showed significant differences in risk of grade 3 or higher adverse events between treatment type (PD-1+CTLA-4 and PD-L1+CTLA-4), among cancer types, and among dosing regimens (N1I3, N3I1 and D20T1). Incidence of all-grade adverse events was 0.905 [95% CI 0.842-0.945] and grade 3 or higher events/all-grade adverse events was 0.396 [95% CI 0.315-0.483]. The most common all-grade TRAEs were diarrhea/colitis, fatigue/asthenia, nausea/vomiting, rash, and pruritis. Conclusions: Combination ICI therapy has a significantly different treatment-related adverse event profile compared to monotherapy.
Association of neoadjuvant chemotherapy on survival in locally advanced gallbladder cancer.
Authors: Syed Mohammad Ali Kazmi, Suleyman Yasin Goksu, Muhammet Ozer, Nina Niu Sanford, Matthew R. Porembka, Sam C. Wang, John C. Mansour, David Hsieh, Todd Anthony Aguilera, Aravind Sanjeevaiah, Leticia Khosama, Mary Claire Maxwell, Muhammad Shaalan Beg
Journal: Journal of Clinical Oncology (2020)

e16716 Background: Gallbladder cancer (GBC) is an uncommon but highly fatal malignancy. Surgery remains the only potentially curative treatment for GBC. The role of neoadjuvant chemotherapy in patients with locally advanced GBC undergoing surgery is unknown. We studied the association of neoadjuvant chemotherapy on survival in locally advanced GBC patients who underwent resection. Methods: We identified adult patients with locally advanced (stage III-IV) GBC who underwent definitive surgery between 2004 and 2016 using the National Cancer Database. Treatment was categorized as neoadjuvant chemotherapy plus surgery (NAT), surgery plus adjuvant therapy (AT), and surgery alone (SA). Categorical variables were compared using the chi-square test with Bonferroni correction. Kaplan-Meier and Cox regression were used for survival analyses. We used 1:3 nearest neighbor propensity score matching based on NAT for each group. Results: Out of a total of 5,962 patients, 122 (2.2%) received NAT, 2934 (53.6%) AT, and 2421 (44.2%) SA. NAT was associated with private insurance and treatment at an academic/research facility (all p &lt; .001) while SA patients were older, Hispanic, had government insurance, and higher comorbidities (all p &lt; .001). Although all groups had similar lymph node assessment (NAT: 45%, AT: 46%, SA: 37%, p &lt; .001), NAT was associated with lymph node negative disease (NAT 23%, AT 13.2%, SA 13.2%, p &lt; .001). Median overall survival was higher in NAT compared to AT or SA (21 vs. 14 vs. 6 months, p &lt; .001) which persisted after propensity score matching (21 vs. 15 vs. 9 months, p &lt; .001) and multivariable regression analysis (Table). In node positive GBC, NAT was associated with improved median overall survival (NAT 24, AT 18, SA 8 months, p &lt; .001). Conclusions: NAT is infrequently used in patients with locally advanced GBC. NAT is associated with improved median overall survival compared to AT and SA, and appears to be most beneficial in node positive disease. Prospective studies are needed to evaluate the role of neoadjuvant chemotherapy in locally advanced GB. [Table: see text]
Treatment of ectopic pregnancy by two dosages of mifepristoned plus methotrexate
Authors: Cui-mei Li, Zhi-ping Deng
Journal: BMJ (2013)

The clinical efficacy of two dosages of mifepristone plus methotrexate (MTX) in the treatment of ectopic pregnancy was compared. One hundred and fifty patients with ectopic pregnancy patients were stratified randomly into 200 mg's single oral group (n=77) and 150 mg graded oral group (n=73). The results showed that, when the Fernandez scores ≤12 points, the difference of treatment success rate was not statistically significant (98% vs 100%, P>0.05); and when >12 points, two groups had statistical significance difference (10/13, 3/11, P 0.05).


Key words: 
Mifepristone; Pregnancy, ectopic