tbuckley/cabot-search huggingface dataset:
结核性大叶性肺炎13例
Authors: 刘新华
Journal: BMJ (2004)

近年来结核病在全球呈上升趋势,我国同样面临着结核病防治的严峻挑战,一些非典型的肺结核患者出现在综合性医院,常易出现误诊.现就我院 1998～2000年收治的结核性大叶性肺炎 13例进行综合分析,以引起广大医师的重视。
Reflection on competence training of psychosomatic medical for general practitioners in China
Authors: Lei Huang, Qingwei Li, Lingjing Jin, Yi Shen, Shiyu Hu, Xudong Zhao
Journal: BMJ (2019)

本文阐述了临床医疗工作中开展心身医学服务的重要性和针对全科医师开展心身医学能力培训的必要性，提出目前我国全科医师心身医学能力培养存在的问题和构建新培养模式的建议，包括明确全科医师心身医学能力的培训目标，借鉴国外的培养体系和评价体系并进行本土化修订。
常见口腔黏膜病的临床表现
Authors: 刘宏伟
Journal: BMJ (2011)

口腔黏膜病是指发生在口腔黏膜及软组织上的除肿瘤以外的疾病.口腔黏膜病病损的临床表现多种多样.最常见的是溃疡及糜烂,其他如角化异常、疱疹、结节、坏死等亦可发生.而且在病程的不同阶段还可以发生病损类型的重叠,如疱疹破溃可形成溃疡,上皮剥脱后形成糜烂等.从病因来看也比较复杂.除极少数病种是单纯由局部原因引起外,大多数口腔黏膜病的发病和全身状况有着密切的关系.有些口腔黏膜病损是全身性疾病早期或晚期的一部分病征.还有许多口腔黏膜病病因不明,一些口腔黏膜和皮肤先后或同时发生病损的疾病.但无论哪种情况,口腔黏膜病往往都在身体抵抗力降低时发生.所以在诊治时要注意从口腔局部联系全身,从口腔黏膜病损的表现寻求疾病的本质,才不致因诊断不明而延误治疗[1].本文由于篇幅所限,仅对全科医师可能见到的常见口腔黏膜病按发病率由高向低进行介绍。
Translesion synthesis genes POLI and REV1 in breast tumors and response to neoadjuvant chemotherapy.
Authors: Patricia Thompson, Emma V Jones, Christina Preece, Jinyu Li, Jigna Bhalla, Jules Cohen, Lea N. Baer, Andrew Pierce, Alison Stopeck
Journal: Journal of Clinical Oncology (2020)

e12642 Background: Translesion synthesis (TLS) of DNA by specialized polymerases (POLs) and REV1, a scaffold protein that recruits other TLS DNA POLs for nascent strand extension, experimentally enable tumor cells to replicate through DNA damage. TLS POLs are hypothesized to contribute to treatment resistance. Methods: We conducted a discovery gene expression study using NanoString technology with a bespoke codeset enriched for DNA damage response genes and RNA from 12 TN, 10 HER2+ and 29 ER+/HER2- breast cancer patients before neoadjuvant chemotherapy (NACT) and when available, in the matching residual tumor. Eleven patients achieved a pathologic complete response (pCR), 12 had &lt; 1 cm residual disease (partial responders) and 28 patients had &gt; 1cm residual disease (non-responders). RNA counts were normalized and log-transformed for differential expression analyses corrected for false discovery. Results: DNA polymerase Iota ( POLI) was the top overexpressed gene in the pretreatment biopsy of non-responders independent of tumor subtype (p corrected = 0.0002). Expression of REV1 was also significantly higher in non-responders and positively correlated with POLI (r = 0.577, p &lt; 0.0001). Despite a small sample size, pretreatment expression levels of POLI and REV1 were significantly higher in ER+ (n = 38) than ER- (n = 13) tumors (p = 0.0006). When restricted to ER+ tumors, POL1 and REV1 expression levels were significantly higher in pretreatment biopsy of non-responders (n = 25) than partial and complete responders (n = 13). For ER+ patients, response by median POL1/REV1 expression levels are shown in Table. Pre/post treatment POL1 and REV1 expression did not change in patients with residual disease. Conclusions: In discovery, two genes involved in TLS of DNA (POLI and REV1) were found overexpressed in pretreatment biopsies from breast cancers poorly responsive to NACT, independent of tumor subtype. Overexpression was more common among ER+ tumors, which exhibit a high inherent resistance to chemotherapy. If confirmed, expressed levels of POLI and REV1 may identify a subgroup of breast cancers resistant to NACT for which targeted inhibition of mutagenic TLS may be beneficial. [Table: see text]
Phase I dose escalation of stereotactic body radiation therapy and concurrent cisplatin for re-irradiation of unresectable, recurrent head and neck squamous cell carcinoma.
Authors: Michelle Echevarria, Christine H. Chung, Kedar Kirtane, Jameel Muzaffar, John Arrington, Joaquim Farinhas, Jimmy J. Caudell
Journal: Journal of Clinical Oncology (2020)

6543 Background: For patients with unresectable, previously radiated, locoregionally recurrent head and neck cancer, stereotactic body radiation therapy (SBRT) has become an attractive option. The use of high daily doses of radiotherapy may overcome the inherent radioresistance of these recurrent cancers. Given the resistant and advanced nature of many of these cancers, the addition of chemotherapy to radiotherapy is typically recommended as a radiosensitizer. We therefore performed a phase I clinical trial in order to establish a maximum tolerated dose of SBRT with concurrent chemotherapy in locoregionally recurrent head and neck cancer. Methods: Major inclusion criteria were recurrence of previous squamous cell carcinoma of the head and neck in patients who had previously undergone radiotherapy to doses ≥ 45 Gy to the area of recurrence, ≥ 6 months prior to enrollment, and who were medically unfit for surgery, deemed unresectable, or refused surgery. Patients were treated with radiation therapy every other day for five fractions at three dose levels; 30 Gy, 35 Gy, and 40 Gy. Cisplatin was given prior to every SBRT fraction at a dose of 15 mg/m2. Patients were monitored for safety and tolerability for any grade 4 or greater toxicity (per CTCAE v4.0) that occurred within 3 months from the start of SBRT. Primary end point was maximum tolerated dose (MTD). Results: Twenty patients were enrolled and of those 17 patients were evaluable for the primary endpoint. Nine patients had a primary tumor in the oropharynx, four patients in the oral cavity, three in the neck, one in the larynx, and one simultaneously in the larynx and neck. Of the three patients that were not evaluable two withdrew consent, and one patient in the 30 Gy dose level died of unknown causes two weeks following completion of treatment. Due to safety concerns the 30 Gy dose level was expanded an additional three patients, and no further dose limiting toxicities (DLTs) were observed. At the 35 Gy and 40 Gy dose level there were no reported grade 4 or 5 adverse events (per CTCAE v4.0). There were 5 (27%) reported grade 3 toxicities and 12 (66%) grade 2 toxicities. Conclusions: This phase I study demonstrates that 40 Gy SBRT with concurrent cisplatin at a dose of 15mg/m2 is feasible, safe, and well tolerated. Patients continue to be followed for secondary outcomes of local control and overall survival. Clinical trial information: NCT02158234 .
Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis
Authors: Yongyan Wu, Yuliang Zhang, Xiwang Zheng, Fengsheng Dai, Yan Lu, Li Dai, Min Niu, Huina Guo, Wenqi Li, Xuting Xue, Yunfeng Bo, Yujia Guo, Jiangbo Qin, Yixiao Qin, Hongliang Liu, Yu Zhang, Tao Yang, Li Li, Linshi Zhang, Rui Hou, Shuxin Wen, Changming An, Huizheng Li, Wei Xu, Wei Gao
Journal: Molecular Cancer (2020)

Abstract Background Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck. LSCC patients have seriously impaired vocal, respiratory, and swallowing functions with poor prognosis. Circular RNA (circRNA) has attracted great attention in cancer research. However, the expression patterns and roles of circRNAs in LSCC remain largely unknown. Methods RNA sequencing was performed on 57 pairs of LSCC and matched adjacent normal mucosa tissues to construct circRNA, miRNA, and mRNA expression profiles. RT-PCR, qPCR, Sanger sequencing, and FISH were undertaken to study the expression, localization, and clinical significance of circCORO1C in LSCC tissues and cells. The functions of circCORO1C in LSCC were investigated by RNAi-mediated knockdown, proliferation analysis, EdU staining, colony formation assay, Transwell assay, and apoptosis analysis. The regulatory mechanisms among circCORO1C , let-7c-5p , and PBX3 were investigated by luciferase assay, RNA immunoprecipitation, western blotting, and immunohistochemistry. Results circCORO1C was highly expressed in LSCC tissues and cells, and this high expression was closely associated with the malignant progression and poor prognosis of LSCC. Knockdown of circCORO1C inhibited the proliferation, migration, invasion, and in vivo tumorigenesis of LSCC cells. Mechanistic studies revealed that circCORO1C competitively bound to let-7c-5p and prevented it from decreasing the level of PBX3 , which promoted the epithelial–mesenchymal transition and finally facilitated the malignant progression of LSCC. Conclusions circCORO1C has an oncogenic role in LSCC progression and may serve as a novel target for LSCC therapy. circCORO1C expression has the potential to serve as a novel diagnostic and prognostic biomarker for LSCC detection.
Pilot study on outcome and antitumor efficacy of an autologous cancer cell vaccine applied in patients with advanced solid tumors.
Authors: Eglys Gonzalez Marcano, Leona Kröhle, Joachim Ahlers, Joachim Drevs
Journal: Journal of Clinical Oncology (2020)

3000 Background: In the last decade cancer immunotherapy has emerged as the most promising anti-tumor approach. The most commonly used immunotherapies are vaccines and checkpoint inhibitors. An autologous cell vaccine is made with the patient's own tumor cells processed in vitro, which may elicit a cytotoxic T-lymphocytic immune response against tumor cells antigens, resulting in tumor cell death. We performed a pilot study to evaluate the clinical relevance and general outcome of an autologous vaccine as a treatment in different types of cancer. Methods: A total of 31 patients (n=31) with advanced solid tumors and the lack of standard treatments were treated with an immunotherapy protocol consisting of 6 intradermal doses of the vaccine, given the first two doses at day 1 and 2, and the rest every two weeks. All patients signed an informed consent form. Response evaluation was assessed by PET/CT identified as metric (iRECIST) response and in some cases tumor markers where available. Results: Out of 31 patients treated, 2 patients suffered from pancreatic cancer, 2 from sarcoma, 1 from lung cancer, 13 from breast cancer, 2 from ovarian cancer, 1 from prostate cancer, 1 from cholangiocarcinoma, 4 from colorectal cancer, 1 from non-Hodgkin lymphoma, 1 from gastric cancer, 1 from laryngeal and hypopharyngeal cancer, 1 from fallopian tube cancer, 1 from peritoneal cancer. Side effects related to the therapy were rare including light redness in the area of injection and in one case inflammation of the tumor area. 26 patients were evaluated for metric response and 5 for tumor marker response assessment. For tumor marker follow up 9.6 % had a SD of &gt; 3 month and 6.5 % a PD. For metric follow up 12.9 % had a CR, 6.5 % a PR, 25.8 % a SD of &gt; 3 month and 38.7 % a PD. Conclusions: This study have confirmed an anti-tumor response in the majority of patients treated, with none to very low side effects and a good quality of life during the treatment. To obtain more detailed and significant data on the efficacy of this therapy, a further controlled clinical phase study should be performed.
社区卫生工作中遇到的问题及建议
Authors: 杜雪平
Journal: BMJ (2011)

社区卫生服务机构是基层医疗的主力军，全科医生是其中的核心力量，是社区医疗发展的关键。随着《国务院关于建立全科医生制度的指导意见》（《指导意见》）的发布，我觉得特别振奋，社区卫生服务的春天来了。中华医学会一直为从事社区卫生服务的医生提供了一个非常好的学术平台。相信随着《指导意见》的出台，我国的社区卫生服务一定会蓬勃发展。作为一名社区卫生工作者，我谈谈目前社区卫生机构遇到的问题。
两例口腔门诊病史采集失败所引起的反思
Authors: 胡群英, 张晓团, 周文平
Journal: BMJ (2009)

我在门诊遇到两例病史采集失败,并引发纠纷.通过一段时间的学习和反思,加上以往工作经验,写出与大家分享. 第1例是47岁女性,主因4+残冠要求修复就诊,给予4+死髓牙拔髓,开放处理,并告知已经拔除坏死牙神经,并神经管内放置灭菌药.次日患者复诊时主诉右半侧头痛,右侧面部及右下颌有蚁走样不适,闭眼困难.临床检查:面部皮肤颜色正常,皱眉、鼓气、闭眼功能正常,4+叩(±),颊舌侧牙龈黏膜和根尖x线片均未见异常.转上级医院检查仍未见异常.患者要求解除痛苦,并提出赔偿。
Clinical study of infant modified Snodgrass hypospadias correction
Authors: Bo Liu, Xia Wang, Xing Liu
Journal: BMJ (2018)

The clinical data of 100 children or infants with penile hypospadias corrected with modified Snodgrass procedure during January 2013 to April 2016 from Yongchuan Hospital of Chongqing Medical University were retrospectively analyzed, including 50 cases aged  1 years (control group). The cure rates of study group and control group were 98% and 90%, and there was no significant difference between two groups (P>0.05). There were also no significant differences in intraoperative blood loss, postoperative ambulation time, length of hospital stay, pain scores and quality of life scores between two groups (P>0.05). However, the incidence of major complications, including urethral fistula, urethral opening stenosis, penis malunion, penile curvature in study group was lower than that in control group (P<0.05). This study indicates that hypospadias correction during infancy may achieve better outcomes.


Key words: 
Hypospadias; Treatment outcome
A PK/PD mathematical model to forecast severe toxicities in pancreatic cancer patients treated with FOLFIRINOX regimen.
Authors: Laure Deyme, Marine Gilabert, Laurent Mineur, Clemence Toullec, Mohamed Gasmi, Joseph Ciccolini, Dominique Barbolosi, Florence Gattacceca
Journal: Journal of Clinical Oncology (2020)

e16774 Background: FOLFIRINOX regimen is the most efficient treatment in pancreatic adenocarcinoma. However, this triple-therapy causes significant and dose-limiting toxic effects leading to empirical dose-reduction, postponement of the forthcoming courses and sometimes treatment discontinuation. Dose-limiting toxicities with FOLFIRINOX are mostly oxaliplatin-induced peripheral neuropathy (OIPN) and irinotecan-induced diarrhoea (IID). The first aim of our study was to establish dose-concentration-toxicity relationships for these two main ordinal toxicities. Second, we aimed to perform in silico simulations to define the optimal FOLFIRINOX administration protocol (i.e., dosing, scheduling, sequencing) for a maximal benefit to risk ratio. Methods: We performed a retrospective pharmacometric analysis from clinical data collected in three French institutes. Patients had all confirmed diagnosis of PDAC treated with FOLFIRINOX as first line regimen. Demographic characteristics, toxicity data and dosage modifications were collected. Two mathematical models connecting dose – concentration – toxicity (PKPD Tox model) were developed using Monolix2019 to describe both OIPN and IID. Results: Data from 75 patients (36 females/39 males) treated with FOLFIRINOX regimen between 2015-2018 and representing 566 courses were collected. Median age was 65.4 years (range 29-78). The performance status at the start of treatment was 0-1 for 70% of patients. The most frequent location of the tumor was pancreatic head (50%). 91% of patients were subject to empirical dose reduction during their treatment. Oxaliplatin doses were decreased in 258 courses and stopped in 66 courses. Irinotecan doses were decreased in 257 courses and stopped in 33 courses. Overall, 130 IID and 198 OIPN events were observed. From these data, two different PKPD Tox models were developed. The individual concentrations of SN38 (active metabolite of irinotecan) and oxaliplatin were simulated with population PK models, either home-built or taken from the literature. Concentrations were translated into adequate exposure via an interface model developed by our group. Exposure was finally related to a pharmacodynamic model to predict probabilities assigned to each grade of IID or OIPN. Conclusions: These PKPD Tox models help to predict dose-limiting toxicities upon FOLFIRINOX and are useful to select the administration protocol of FOLFIRINOX minimizing the occurrence probabilities of treatment-related neuropathy and diarrhoea, while maintaining efficacy.
Early diagnosis and treatment for deep venous thromboembolism in patients with fracture
Authors: Jian-long Liu, Wei Jia
Journal: BMJ (2008)

Objective To explore the measures in early diagnosis and treatment for venous thromboembolism(VTE)in patients with fracture.Methods All the patients with fracture visiting Beijing Jishuitan Hospital in emergency during October 2004 to October 2007 were screened by Well's prediction rules,and anticoagulation and thrombolysis were instituted for those with established diagnosis of VTE by color Doppler ultrasonography and venography.Results Totally,1 508 patients at higg-risk of VTE were identified by D-dimer test.1 455 by color ultrasonography and 53 by venography.Diagnosis of VTE was established in 652 of them(43.2%),619(94.9%)received anticoagulant treatment,162(24.8%)received anticoagulant plus thrombolytie treatment and 25 (3.8%) received anticoagulation plus thrombectomy.In order to prevent fatal pulmonary embolism,vena cava filters(VCFs)were implanted in 146(22.4%)patients,and 33(5.1%)of them were contraindicated to anticoagulation.After treatment,412 cases were cured and 240 were improved,with no one failed.Conclusions Patients with fracture are at high-risk of VTE and should be screened by D-dimer test and color Doppler ultrasonography based on Well's evaluation,as well as by venography for confirming the diagnosis of VTF as appropriate.Anticoagulation and thrombolysis are still the treatment of choice,with thrombectomy and VCF implantation performed only if necessary.

Key words: 
Venous thrombosis; Ultrasonography; Thrombolytic therapy
Predictive role of Vulnerable Elders Survey-13 screen tool for elder cancer patients in final oncology treatment plan.
Authors: Fahad Almugbel, Narhari Timilshina, Naser AlQurini, Rana Jin, Arielle Berger, Lindy Romanovsky, Martine Puts, Allison Loucks, Shabbir M.H. Alibhai
Journal: Journal of Clinical Oncology (2020)

e24020 Background: The Vulnerable Elders Survey (VES-13) is one of several tools that can identify older patients who are vulnerable (if the score is ≥ 3 out of 10) and more likely to benefit from Comprehensive Geriatric Assessment (CGA) prior to cancer treatment. The optimal cutpoint of the VES-13 to identify those whose final oncologic treatment plan would change after CGA is unclear. We hypothesized that patients with high positive scores (7-10) will have a higher likelihood of a change in the final oncologic treatment plan compared to low positive patients (score 3-6). Methods: Retrospective review of a customized database of all patients seen for pre-treatment assessment (solid tumor and lymphoma) in the geriatric oncology clinic at the Princess Margaret Cancer Centre from June 2015 to June 2019. Various VES-13 score cutpoints were compared with the final treatment plan to identify those individuals whose treatment was modified after CGA. Area under the curve was calculated and subgroups of patients treated locally or systemically were also examined to determine if performance varied by type of patient. Results: 386 patients with mean age 81, 58% males were included. Gastrointestinal cancer was the most common site 31% and 60% were planned to receive curative treatment. The final treatment plan was modified in 50% with VES-13 scores 7-10, 46.7% with scores 3-6 and 26.8 % for scores &lt; 3 (P = 0.002; Table). The optimal VES-13 cutoff was between 3-6 (C-statistics 0.57-0.59).The VES-13 performed similarly in those considering local treatment (surgery with/without radiation) vs. chemotherapy. Modified final treatment for local therapy with VES-13 scores &lt; 3 was 11.4 % compared to 42.9% with scores ≥ 3 was 42.9% (p-value &lt; 0.001), whereas for systemic therapy it was 32.4% and 62.5%, respectively (p-value = 0.002). Conclusions: Although high positive VES-13 scores (7-10) had slightly higher likelihood of having the final oncologic treatment plan modified, there was no strong advantage compared to the conventional cutpoint of 3 or higher. The VES-13 performed similarly in predicting treatment change after CGA for local and systemic treatment plans. Further studies are required to identify the optimal frailty screening tool and cutpoint. [Table: see text]
Intracranial anti-tumor activity of lazertinib in patients with advanced NSCLC who progressed after prior EGFR TKI therapy: Data from a phase I/II study.
Authors: Sang-We Kim, Myung-Ju Ahn, Ji-Youn Han, Ki Hyeong Lee, Eun Kyung Cho, Yun-Gyoo Lee, Dong-Wan Kim, Joo-Hang Kim, Jong-Seok Lee, Gyeong-Won Lee, Byoung Yong Shim, Jin-Soo Kim, Sang Hoon Chun, Sung Sook Lee, Young Joo Min, Sang Won Shin, Young Joo Lee, Dae Ho Lee, Hana Lee, Byoung Chul Cho
Journal: Journal of Clinical Oncology (2020)

9571 Background: Lazertinib (YH25448) is a highly mutant-selective, irreversible 3 rd -generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets the activating EGFR mutations (Del19 and L858R), as well as the T790M mutation, while sparing wild type. Brain metastasis (BM) are common in patients (pts) with advanced NSCLC. Lazertinib showed a high blood-brain barrier penetration profile in preclinical studies. We report intracranial response data in pts with advanced NSCLC from a Phase I/II study of lazertinib (NCT03046992). Methods: Pts with advanced NSCLC, who had progressed after prior EGFR-TKI therapy, were enrolled in an open-label, multicenter, phase I/II study with dose-escalation, dose-expansion and dose-extension phases. Brain MRI was done in all pts at baseline. Pts with asymptomatic BM were eligible for enrollment. Intracranial anti-tumor activity of lazertinib was analysed in pts with BM present on baseline brain scan. Pre-defined intracranial endpoints included objective intracranial response rate (OIRR) and intracranial progression-free survival (IPFS) by independent central review (ICR). The brain metastasis full analysis population included pts with measurable and/or non-measurable BM lesion present on baseline brain scan; the brain metastasis population evaluable for response included only pts with measurable BM lesion. Results: As of 30 Sep 2019, a total of 181 pts received at least one dose of lazertinib 20-320 mg across 7 dose levels. Of those, 64 pts (56% female, median age 63, 86% T790M mutation positive by central testing) were included in the brain metastasis full analysis population; Intracranial disease control rate (IDCR) was 90.6% (58/64; 95% CI 83.5, 97.8) and median IPFS was not reached (95% CI 14.0, NR). In the brain metastasis population evaluable for response, a total of 22 pts were included; OIRR and IDCR were 54.5% (12/22; 95% CI 33.7, 75.4) and 90.9% (20/22; 95% CI 78.9, 100), respectively. In 13 pts (7.2%) out of 181 pts, brain was the first site of disease progression by existing and/or new lesions. Conclusions: Lazertinib demonstrated clinically meaningful activity against BM, aligned with preclinical data. Clinical trial information: NCT03046992 .
癫痫持续状态的初步诊治
Authors: 刘凤君, 吴逊
Journal: BMJ (2007)

癫痫持续状态是综合医院急诊室常见的急症之一,作为全科医生应对癫痫持续状态的基本诊治原则有较详细的了解.大多数癫痫发作不超过2～3 min,发作超过5 min就有很大的机会进展到癫痫持续状态,因此早期处理至关重要。
The relationship between electrocardiogram and infarction-related artery in 69 cases of acute inferior myocardial infarction
Authors: Li-ming Geng
Journal: BMJ (2009)

The results of electrocardiogram and coronary angiography were compared in 69 patients with acute inferior myocardial infarction(right ventricle, later wall). The sensitivity and specificity of ST segment elevation Ⅲ> Ⅱ in diagnosis of right coronary artery (RCA) as the infarction related artery (IRA) were 92.00% and 84. 21% respectively;those for ST segment depression avL > Ⅰ were 90. 00% and 89. 5% respectively. Therefore if ST-elevation Ⅲ > Ⅱ , ST-depression avL > Ⅰ and no depression on STV1 and V2 in acute inferior myocardial infarction may highly indicate that RAC be the IRA;on the contrary, the LCX be the IRA.

Key words: 
Myocardial infarction; Electrocardiography