tbuckley/cabot-search huggingface dataset:
Magrolimab and gemcitabine-cisplatin combination enhance phagocytic elimination of bladder cancer.
Authors: Bernhard Kiss, Anne Kathrin Volkmer, Dongdong Feng, Kelly Marie McKenna, Shirley Mihardja, Mark Chao, Chris H.M. Takimoto, Joseph C Liao, Jens-Peter Volkmer, Irving L. Weissman
Journal: Journal of Clinical Oncology (2020)

e17035 Background: CD47 is an antiphagocytic signal and macrophage checkpoint that bladder and other cancer cells over-express to evade innate immunity. Magrolimab (Hu5F9-G4) a CD47 blocking antibody, promotes phagocytosis of cancer cells by macrophages and is being tested in several clinical trials (NCT02953509, NCT03248479, NCT02953782, NCT03558139). Chemotherapies synergize with magrolimab by increasing “eat me” signals on cancer cells, and thus enhancing phagocytosis. This synergy has been shown in MDS and AML, whereby magrolimab+azacitidine has shown encouraging efficacy in pre-clinical and clinical studies. This study aimed to investigate the effect of magrolimab as monotherapy and in combination with gemcitabine-cisplatin chemotherapy in bladder cancer. Methods: Phagocytosis of urothelial bladder cancer cells (639V) was evaluated in vitro with magrolimab alone and in combination with chemotherapy (gemcitabine + cisplatin). Treatment in vivo was evaluated in a xenograft mouse model. 639V cells were transplanted into NSG mice and upon confirmation of engraftment mice were randomized into 4 treatment cohorts: control (PBS), magrolimab, chemotherapy (cisplatin + gemcitabine), and magrolimab in combination with chemotherapy. In the first experimental setup treatment was started early in small tumors and in the second experimental setup treatment was started late after tumors have grown to large size. Tumor growth was monitored by in vivo bioluminescent imaging. Metastases were evaluated postmortem. Results: Chemotherapy increased calreticulin on bladder cancer cells. Magrolimab enhanced phagocytosis of bladder cancer cells in vitro and combination of magrolimab with chemotherapy further increased phagocytosis compared to either therapy alone. Magrolimab and chemotherapy, each alone decreased tumor growth in vivo but only combination of magrolimab with chemotherapy showed a strong inhibition of tumor growth, resulting in a significantly prolonged survival compared to all other treatment cohorts. This was shown for both, small tumors and large tumors. Metastases formation in liver and lungs was completely inhibited by treatment with magrolimab, whereas mice treated with chemotherapy alone or PBS control showed metastases in these organs. Conclusions: Magrolimab treatment in combination with chemotherapy was efficacious in preclinical in vitro and in vivo studies in bladder cancer and provides a novel treatment opportunity for patients with bladder cancer and other solid tumors.
反复口干、多饮、多尿15年,加重一周
Authors: 顾莉清, 殷立敏, 刘帅, 祝墡珠
Journal: BMJ (2012)

病史摘要患者,女性,83岁.因反复口干、多饮、多尿15年,加重1周于2010年10月20日收入闵行区华漕社区卫生中心.15年前反复出现口干、多饮、多尿,易疲倦,多次查空腹血糖8.O mmol/L,餐后血糖最高达18 mmol/L;糖化血红蛋白9.1％.明确诊断为2型糖尿病,予以饮食控制,服用格列吡嗪5 mg、阿卡波糖50 mg,血糖控制在8 mmol/L左右.近2年,患者未能严格控制饮食,门诊随访不规范,随机血糖常波动在15 ～ 20 mmol/L之间,未正规诊治.近1周来患者感口干、多饮、多食症状明显加重,尿量增多,随机血糖最高达26 mmol/L,伴泡沫尿,间歇性颜面部、双下肢浮肿.既往高血压痛10余年,最高180/80 mm Hg(1 mm Hg =0.133kPa),长期口服非洛地平片2.5 mg、2次/d治疗,血压控制在140～160/70～90 mm Hg.慢性支气管炎病史9年余,高血脂症5余年,双眼白内障史20余年.近2年来有反复尿路感染史.家族史:其母有糖尿病病史.否认巨大胎儿生产史.体格检查:血压160/80 mm Hg,BMI 20.03 kg/m2.神志清,营养可,眼睑稍浮肿,双肺呼吸音粗,双肺未闻及干湿性啰音,心界无扩大,心率76次/min,心律齐,心音正常,各瓣膜听诊区未闻及病理性杂音.腹部平坦,无压痛、反跳痛,肝脾肋下未触及,Murphy征(-),移动性浊音(-),肠鸣音正常,四肢肢体肌力5级,双侧肌张力正常,双下肢轻度凹陷性水肿,双侧足背动脉搏动正常.辅助检查:尿常规:尿蛋白(+++),尿糖(++),糖化血红蛋白9.1％,肌酐126 μmol/L,尿酸200 μmol/L,白蛋白24.7 g/L,空腹血糖10.84 mmol/L,TG 1.74 mmol/L,TC6.31 mmol/L,腹部B超示脂肪肝.心电图示T波改变.眼底检查:白内障,糖尿病视网膜病变(Ⅱ期).入院后予以精蛋白生物合成人胰岛素注射液预混30R(诺和灵30R)分别于早餐前14 U、晚餐前10 U皮下注射控制血糖及相应对症治疗,患者病情逐渐稳定.监测空腹血糖波动在7 mmol/L左右,餐后2h血糖波动在10 mmol/L左右,血压波动在130～ 140/70～ 90 mm Hg,尿常规提示:尿糖(+),尿蛋白(++).TC 1.65 mmol/L,TC 5.10 mmo]/L,肌酐96 μmol/L,尿酸250 μmol/L,白蛋白29.7 g/L.3个月后复查糖化血红蛋白7.6％.2011年4月21日患者突然出现发热、咳痰,体温波动在38.0 ～39.0℃,无畏寒、寒战,无胸闷、胸痛,无呼吸困难,小便次数较前增多,体检:咽稍红,双侧扁桃体无肿大,双肺呼吸音粗,两肺底可闻及湿性啰音,血常规:WBC 13.60×109/L,分类中性粒细胞0.896,CRP 56 mg/L.尿常规:WBC(+++),胸片提示两侧肺炎。
血气分析
Authors: 吴东, 陈嘉林
Journal: BMJ (2010)

一、判断呼吸性酸中毒病情pH值比PaCO2更重要 HCO3-和CO2是血液中最重要的一对缓冲物质,二者浓度比值保持恒定对维持人体酸碱平衡至关重要,而这又有赖于肺和肾的调节[1].慢性阻塞性肺疾病(COPD)是社区患者呼吸性酸中毒的主要病因.由于气道阻力增加,肺泡面积减少以及呼吸肌力不足,COPD患者有效肺通气量减少,动脉血PaCO2升高,从而发生呼吸性酸中毒.为代偿PaCO2的升高以维持pH值相对恒定,机体将通过肾脏增加HCO3-重吸收,增加血HCO3-浓度,该过程需要数天时间才能达成新的平衡。
自发性脑脊液鼻漏致化脓性脑膜炎一例
Authors: 赵振宇, 张玉珍
Journal: BMJ (2005)

患者男,49岁.因发热、寒战、头痛、恶心、呕吐3 d于2005年1月1日入院.患者于3 d前发热,体温达40℃,流涕、头痛、恶心、喷射性呕吐,吐出物为胃内容物,头痛以双颞侧及后枕部为著。
Genomic testing in early breast cancer (EBC) for low middle income countries (LMIC): Is it worth the cost?
Authors: Gunjan Shrivastav, Devavrat Arya, Aditi Chaturvedi, Charu Garg, Shubham Jain, Sheetal Mukhiya, Harit Kumar Chaturvedi, Nitesh Rohatgi
Journal: Journal of Clinical Oncology (2020)

e12521 Background: Chemotherapy is crucial for EBC management but has toxicities. Attempts are made to identify patients where chemotherapy can be safely skipped. Genomic testing offers advantage over clinico-pathological tools but given the cost, its utility in clinical practise, especially in LMIC remains questionable. Methods: 50 EBC patients who underwent risk stratification by oncotypeDX were retrospectively studied. Their clinico-pathological characteristics, Nottingham prognostic index (NPI) and PREDICT recommendation (v 2.1) were recorded. Tumor board(TB) made treatment recommendations based on age and histopathology, blinded to recurrence score(RS). The results were compared. Results: 32% patients were &lt; 50 years, 68% were &gt; 50 years. 32% and 68% patients were pre and post menopausal respectively. On pathological examination, T1, T2 &amp; T3 comprised 26%, 70% and 4% respectively. 96% were node negative, 2% node positive, 2% had unknown nodal status. Tumors had Grade 1, 2 and 3 in 8%, 88% and 4% respectively. 4% had unknown estrogen receptor (ER), progesterone receptor (PR) score. ER and PR were low (Allred 3-5) in 2% and 12% respectively. NPI was low ( &lt; 3.4) in 96% and intermediate (3.5- 5.4) in 4%. On PREDICT, all showed low benefit of chemotherapy ( &lt; 3% at 10 years). TB prescribed chemotherapy in 58% and hormonal therapy (HT) in 42% patients. RS was low, intermediate and high in 66%, 26% and 8% patients respectively. Patients with low and high RS were supposed to receive HT and chemotherapy respectively. In the intermediate group, 4% patients were recommended HT as per age. 22% patients could not be assigned a treatment based on RS alone. In remaining 78%, TB’s decision matched RS recommendation in 38% (19) patients. In 2% (1), TB recommended HT while OncotypeDX showed high RS. In 38% (19) patients, TB recommended chemotherapy while OncotypeDX showed low RS. Despite all having low/intermediate NPI with &lt; 3% chemotherapy benefit on PREDICT, 8% showed chemotherapy benefit on OncotypeDX. In 40%, OncotypeDX recommendation deferred from TB. In more than one third patients, when TB recommended chemotherapy, RS came low. In these patients we could avoid chemotherapy, saving ~900 USD treatment costs. As 68% patients were elderly ( &gt; 50), genomic testing avoided chemotherapy in this subgroup, likely to suffer treatment toxicities. Conclusions: In LMIC where all patients don’t have access to hospitals with adequate infrastructure for chemotherapy administration, genomic testing has significant implications. We recommend using it more in clinical practise.
A phase II study of atezolizumab and cobimetinib in PD-1/PD-L1 inhibitor resistant or refractory non-small cell lung cancer: ETCTN #10166.
Authors: Stephen V. Liu, Richard Delmar Hall, Andreas Nicholas Saltos, Gregory Alan Otterson, Ming Tony Tan, Sacha Gnjatic, Ryan D. Gentzler, Tawee Tanvetyanon, Helen X. Chen, Elad Sharon
Journal: Journal of Clinical Oncology (2020)

TPS9638 Background: Use of checkpoint inhibitors, alone or with chemotherapy, has emerged as the preferred standard treatment for patients with advanced, driver-negative non-small cell lung cancer (NSCLC). While outcomes are superior to chemotherapy alone, only a subset of patients achieve durable response and long term survival. One potential mechanism of primary resistance to checkpoint inhibitors is the lack of tumor-infiltrating lymphocytes. Inhibition of mitogen-activated protein kinase (MAPK) kinase (MEK) increases the number of CD8+ T-cell within a tumor and has shown synergy with anti-programmed death-ligand 1 (PD-L1) antibodies. The combination of the MEK inhibitor cobimetinib and the PD-L1 antibody atezolizumab has led to limited responses in colorectal cancer, a tumor typically non-responsive to checkpoint inhibition. This phase II trial explores the combination of cobimetinib and atezolizumab in patients with PD(L)1-refractory NSCLC. Methods: This phase II study is being conducted through the Experimental Therapeutics Clinical Trials Network (ETCTN #10166). Eligible patients have advanced NSCLC with primary resistance to anti-PD(L)1 therapy (defined as progression noted within 6 months of initiating therapy) and tumor amenable to serial core biopsy. Patients will receive atezolizumab 840mg intravenously every 2 weeks and cobimetinib 60mg orally for 21 days in 28-day cycles. Two cohorts will enroll in parallel, defined by presence or absence of a KRAS mutation. Each cohort will employ a Simon two-stage design to test a null rate of 5% vs. 25% (power = 0.90, □ = 0.10). If &gt; 1 of 9 patients in stage 1 achieve a partial response, an additional 15 patients are enrolled and if &gt; 3 patients achieve a durable response, the combination will be worthy of further investigation. The primary endpoint is durable (&gt; 6 months) response rate. Secondary endpoints are overall response rate, progression free survival, overall survival, duration of response and adverse events. Biopsies performed at baseline and after 3 weeks of therapy will assess the change in the density of tumoral CD8+ T-cells. Whole exome sequencing and immune cell profiling will also be performed on serial samples. Enrollment was initially limited to KRAS-mutant NSCLC. Prespecified activity goal for the first stage of accrual has been met; second stage accrual began in September 2019. Enrollment to the KRAS wild-type cohort will commence. Clinical trial information: NCT03600701 .
Prospective study for usefulness of circulating-free DNA on prediction of third generation EGFR tyrosine kinase inhibitors.
Authors: Hironori Yoshida, Chiho Nakashima, Naohisa Matsumoto, Kentaro Iwanaga, Noriyuki Ebi, Akihiro Nishiyama, Kazuhiro Yatera, Minoru Fukuda, Sunao Ushijima, Hitomi Umeguchi, Daijiro Harada, Shoichi Kuyama, Kosuke Kashiwabara, Takayuki Suetsugu, Nobukazu Fujimoto, Katsumi Nakatomi, Fumihiro Tanaka, Hidetaka Uramoto, Chiharu Yoshii, Naoko Sueoka-Aragane
Journal: Journal of Clinical Oncology (2020)

e21510 Background: Most non-small lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations develop resistance when exposed to EGFR-tyrosine kinase inhibitors (TKIs). T790M develops in about half of patients treated with TKI and can be detected by tumor tissue and cfDNA hotspot tests. However, co-occurring mutations at other loci may impact efficacy. We conducted a prospective, multi-center, observational study to assess the detection rates and predictive values of plasma-based EGFR T790M detection methods for Japanese NSCLC patients treated with osimertinib. Methods: NSCLC patients with tumor EGFR mutations and disease progression after treatment with 1st- or 2nd-generation EGFR-TKI were enrolled. Plasma was collected at the time of clinical disease progression, before osimertinib treatment. The collected plasma was tested for EGFR T90M by in-house plasma MBP-QP and ddPCR assays and compared to clinically tested cobas (Roche) results (including tissue, plasma). The primary endpoint was to demonstrate comparability of our MBP-QP system to cobas using plasma-based EGFR T790M detection to predict the therapeuitic effect of osimertinib via objective response rate (ORR) and disease control rate (DCR). As an exploratory analysis, we used Guardant360 to retrospectively test available banked plasma samples collected describe time points. Results: From Feb 2017 to Jan 2019, 145 patients enrolled. T790M was detected by cobas in 57 cases (44 tissue, 16 plasma, 3 both). ORR and DCR in plasma cobas-positive cases were 62.5% and 81.3%, respectively. MBP-QP found T790M in 9 patients with ORR and DCR 66.7% and 77.8%. ddPCR found 17 cases with ORR and DCR 70.6% and 82.4%. ORR was not correlated to AF. In plasma samples from 54 patients, Guardant360 detected T790M in 57%. Co-occurring alterations such as amplification or minor mutations in EGFR or other genes such as TP53 did not impact ORR, but in the group with poor response to osimertinib, the number of detected gene alterations tended to be large. Two patients with small cell carcinoma transformation had RB1 mutations and MYC amplification. Conclusions: Regardless of the test system, the detection of T790M could predict a good therapeutic effect of osimertinib, but there was no difference in response to osimertinib depending on EGFR T790M AF. Compared to single-gene assessment of EGFR, NGS of cfDNA may be useful for guiding treatment decisions for patients with TKI-resistant NSCLC. Clinical trial information: UMIN000025930.
生物制剂在风湿性疾病中的应用
Authors: 杨春花, 黄烽
Journal: BMJ (2006)

生物制剂用于治疗风湿性疾病二十余年已经取了重要的研究成果,并开发出了一系列全新和鼓舞人心的生物制剂,其中包括:①针对促炎细胞因子生物制剂,如已经广泛应用于临床的抗肿瘤坏死因子(Tumor necrosis factor,TNF)抑制剂(Adalimumab、Etanercept和Infliximab)、白细胞介素(IL)-1受体拮抗剂和抗IL-6受体单克隆抗体;②针对抗B细胞的特异性抑制剂,如已经开发出成品并正在被尝试用于治疗风湿性疾病的抗CD20单克隆抗体Rituximab、抗CD40配体的单克隆抗体、B淋巴细胞刺激因子(BLys)家族的单克隆抗体;③抗T细胞特异性抑制剂,如细胞毒性T淋巴细胞抗原4-免疫球蛋白(Cytotoxic T lymphocyte antigen 4-immuno-globulin,CTLA4-Ig)。
他是否需要使用抗生素
Authors: 金世红
Journal: BMJ (2006)

在我和Peter医生一起学习、工作的2年时间里,有一个特别大的收获就是学会如何科学地、合理地使用抗生素.Peter医生在使用抗生素方面非常慎重,适应证掌握得很准确,该用的地方用,不该用的地方绝对不滥用。
咳嗽的诊断和治疗
Authors: 贺正一, 朱丽琳
Journal: BMJ (2008)

贺正一:首先我们先从咳嗽的分类和原因开始.咳嗽通常按时间分为3类:急性咳嗽时间<3周,亚急性咳嗽3～8周,慢性咳嗽≥8周.咳嗽是由多种原因所致,并非单一原因,所以治疗咳嗽的关键在于病因治疗,咳嗽消失是治疗成功的标志。
Rhabdomyosarcoma of the female genital tract: Long-term outcome and association with <i>DICER1</i> variation.
Authors: Rejin Kebudi, Sema Bay Buyukkapu, Omer Gorgun, Ozlem Dural, Semen Onder, Bilge Bilgic, Ismail Yilmaz, Ayca Iribas, Carola A. S. Arndt, Anne Harris, Amanda Field, Kris Ann Pinekenstein Schultz, Ashley Hill, Emin Darendeliler
Journal: Journal of Clinical Oncology (2020)

10538 Background: Rhabdomyosarcoma (RMS) of the female genital tract is rare, accounting for 3.5% of cases of rhabdomyosarcomas. Germline DICER1 mutations are associated with predisposition to pleuropulmonary blastoma and other tumors including sarcomas. Recently DICER1-associated RMS of the uterus/ovary has ben reported.. The aim of this study is to evaluate demographic characteristics, molecular pathogenesis, treatment and long term outcome of female genital tract rhabdomyosarcoma. Methods: Files of children with RMS of the female genital tract diagnosed at the Istanbul University, Oncology Institute during 1990-2019 were reviewed. Molecular genetic sequencing was performed by polymerase chain reaction amplification of genomic DNA extracted from the formalin-fixed, paraffin embedded tumors, followed by Sanger sequencing. Genetic testing for DICER1 variants of the proband and family members was performed if DICER1 mutation was detected in the tumor of the proband. Results: Of 210 RMS cases, 11 arose from the female genital tract. The median age at diagnosis was 52 months (10 months-15 years). Primary sites were vaginal (n = 5), uterus (n = 4), and ovary(n = 2). Presenting symptoms included vaginal mass (n = 6), vaginal bleeding (n = 5), and abdominal pain (n = 3). Four had group 1, five group 3, two group 2 disease and all received chemotherapy (vincristine, actinomycinD + cyclophosphamide).Three received radiotherapy; three underwent hysterectomy. DICER1 mutation was detected in tumor tissue in three patients:[ c.5113G &gt; A (p.E1705K); c.5428G &gt; T (p.D1810Y); c.1870C &gt; T (p.Arg624Ter)] Genetic testing revealed germline DICER1 pathogenic variation in two patients and their family members, one of whom had cystic nephroma in infancy and history of Wilms tumor in an uncle. They were referred for surveillance for the DICER1 related diseases. A patient with metachronous bilateral ovarian RMS died. Two are married, one has children. The 5 year survival for RMS of the female genital tract was 85.7 % at a median follow-up of 34 (4-298) months. Conclusions: Rhabdomyosarcoma of the female genital tract is associated with a favorable prognosis, however some individuals undergo aggressive local therapies. Individuals with RMS of the female genital tract should be tested for DICER1 pathogenic variation. The detection of a DICER1 mutation in an individual or family members is important to facilitate surveillance for related tumors, so that they may be detected at the earliest possible stage, potentially increasing survival and decreasing risks of late effects.
Myeloablative fludarabine and busulfan regimen in myelofibrosis: Long term outcomes and analysis of prognostic factors.
Authors: Jacinth Joseph, Denai R. Milton, Julianne Chen, Gheath Alatrash, Amin Majid Alousi, Qaiser Bashir, Stefan O. Ciurea, May Daher, Jin Seon Im, Rohtesh S. Mehta, Betul Oran, Amanda Leigh Olson, Neeraj Saini, Samer Ali Srour, Borje Andersson, Richard E. Champlin, Uday R. Popat
Journal: Journal of Clinical Oncology (2020)

e19520 Background: Scoring systems, such as DIPSS-plus, prognosticate outcomes of myelofibrosis (MF) at diagnosis and at transplant. In this study, we evaluated the impact of individual components of these scoring systems, along with other factors previously reported to significantly prognosticate transplant outcomes in patients with MF. Methods: We identified 65 consecutive patients conditioned uniformly with Fludarabine(40 mg/m2X4days)/Busulfan(AUC-4000X4days) and ATG(MUD), tacroliumus and methotrexate for GVHD prophylaxis for allo-SCT during 2007-2019 at MD Anderson Cancer Center, USA. Associations between factors of interest and overall survival(OS), cumulative-incidence-of-relapse(relapse) and non-relapse mortality(NRM) were evaluated. Results: At transpant, median age was 61(range = 27-73) years; 42% were transfusion-dependent, 31% had secondary MF and 53% patients were intermediate2 and 42% were high-risk by DIPSS-plus. Forty percent of the 35 patients who had 28-gene panel tested had atleast one high-molecular-risk mutation, per MIPSS. Median follow-up for survivors was 35.6 months(range = 0.5-123). One-year and 5-year rates for OS were 78% and 51%, for relapse were 21% and 30%, and for NRM were 16% and 28%, respectively. Our multivariate analysis shows the following significant prognostic factors: HCT-CI &gt; 3[hazard ratio(95% CI):5.63(1.48-21.27)p = 0.011], peripheral-blood blasts≥5%[5.98(1.33-26.89)p = 0.020] and prior splenectomy[6.41(1.83-22.47)p = 0.004] were associated with worse OS. Matched-unrelated donor[4.07 (1.38-12.08)p = 0.011) and mismatched-unrelated donor[7.36 (1.36-39.83)p = 0.021] versus matched-related donor as well as peripheral blasts≥5%[4.10(1.00-16.83)p = 0.05] were associated with worse NRM. Diagnosis to transplant duration &gt; 12months[5.81(1.33-25.420)p = 0.020] was associated with higher relapse. Presence of 2 or more poor-risk mutations [6.39(1.35-30.21)p = 0.019] predicted higher relapse on univariate analysis and was not included in multivariate analysis(as data was available in 35 patients only). Conclusions: Of the IPSS-components used at diagnosis, only peripheral-blood blasts(at threshold ≥5%) was associated with worse outcome(OS and NRM). Unrelated-donor source was associated with higher NRM. Diagnosis to transplant duration &gt; 12months predicted higher relapse. The effect of mutations needs to be validated in a bigger study.
Decompressing Stoma vs Stent in Left-Sided Obstructive Colon Cancer
Authors: Antonio V. Sterpetti
Journal: JAMA Surgery (2020)

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Denomination and classification of atrial fibrillation
Authors: 汤日波, 马长生
Journal: BMJ (2007)

心房颤动(房颤)的命名和分类存在多种方案,这在一定程度上反映了目前对房颤机制的认识存在差异.这种差异对于房颤的学术交流和临床工作颇为不利,我们在此复习房颤的命名与分类,以期方便大家进行学术、临床沟通。
激光电凝术治疗下肢静脉曲张的临床观察
Authors: 周炳刚, 苏刚, 范玉琢, 徐强, 马德强, 黄允宁, 王炜
Journal: BMJ (2007)

为探讨激光电凝术治疗下肢静脉曲张(LEV)的临床效果,对106例(128条肢体)行激光电凝术和85例(98条肢体)行大隐静脉高位结扎+剥脱术治疗的LEV患者的临床资料进行分析.结果 ,激光电凝术治疗在手术时间、手术切口、术后疼痛、住院时间等方面明显优于传统手术治疗,而并发症、1年复发率两者相似.提示激光电凝术治疗LEV安全、有效、简便、微创。