tbuckley/cabot-search huggingface dataset:
Molecular predictors of central nervous system (CNS) recurrence in diffuse large B-cell lymphoma (DLBCL).
Authors: Jozal Waroich, Adam J. Olszewski, Habibe Kurt, John Vatkevich, Ashlee Sturtevant, Nimesh Patel, Thomas Ollila
Journal: Journal of Clinical Oncology (2020)

e20082 Background: CNS recurrence is a devastating outcome after treatment of DLBCL. Clinical features poorly predict CNS recurrence risk or the need for prophylactic therapy. We examined whether specific mutational profiles in DLBCL may correlate with the risk of CNS recurrence. Methods: We evaluated DLBCL tumors from patients (pts) with either isolated CNS or systemic (without CNS) recurrence using a 592 gene next generation sequencing (NGS) assay (Illumina NextSeq platform, average coverage depth &gt; 750x; Caris Life Sciences). 3 common molecular subtypes of DLBCL were identified using a simplified classification: (1) MCD subtype ( MYD88 L265P or &gt; 2 other mutations in CD79B, PIM1, ETV6, BTG1, TBL1XR1, or PRDM1) , (2) subtype characterized by TP53 mutations (± complex karyotype with multiple structural variants), and (3) GCB subtype characterized by ≥2 mutations in BCL2, CREBBP, EZH2, KMT2D, TNFRSF14, GNA13, MEF2B, or PTEN. We compared prevalence of these subtypes between our groups and unselected DLBCL datasets by Chapuy et al. ( Nat Med; n = 135) and Reddy et al. ( Cell, 2018; n = 1001). We additionally examined clinicopathologic data, including cell of origin, MYC, BCL2 and/or BCL6 rearrangements, and complex karyotype. Results: The study included 26 cases of DLBCL with CNS-only recurrence (n = 13) or systemic-only recurrence (n = 13). We observed no significant difference between these groups in any clinicopathologic characteristics, and no significant difference for mutations in any specific gene (using Fisher’s exact test adjusted for multiple testing). The MCD subtype was more frequent among pts with CNS recurrence (46%) versus systemic recurrence (31%), and was statistically significantly enriched in our CNS recurrence group compared with the unselected DLBCL datasets by Reddy (18%, P= 0.017) or Chapuy (19%, P= 0.030). In contrast, we observed no difference in CNS or systemic recurrence for the TP53 subtype (23% in both groups) or the GCB subtype (15% in both groups), and these proportions were not significantly different compared with the unselected DLBCL datasets ( P&gt; 0.05). Conclusions: In-depth molecular classification of DLBCL using single nucleotide, structural chromosomal, and copy number variants is unfeasible in current clinical practice. Our data demonstrate that a clinically meaningful molecular signature predicting future CNS recurrence could be designed from standard NGS assays using a simplified classification. With further validation, this signature may prove useful for selecting pts for CNS-directed prophylaxis.
Application of internal iliac artery interruption in management of pelvic hemorrea caused by pelvic fracture or other conditions
Authors: Xue-jun Ran, Chang-qing Deng
Journal: BMJ (2009)

Total 59 cases of pelvic hemorrhea caused by pelvic fracture or other conditions were treated with internal iliac artery interruption from 1999 to 2007. Among them 33 case were treated with bilateral internal iliac artery ligation during exploratory celiotomy; 26 underwent bilateral internal iliac artery angiography through left femur artery puncture. In angiography the hemorrhage site was identified in 19 cases and high-selective embolization with gelatin sponge was followed; for 7 cases the hemorrhage site was not confirmed, the bilateral internal iliac artery embolization was used. In all 59 cases pelvic hemorrhage was stopped; the results indicate that internal iliac artery interruption is effective and save in management of pelvic organ hemorrhea caused by pelvic fracture or other conditions.

Key words: 
Hip fractures;  Shock;  hemorrhagic
Infectious disease rotation for general practice residency training
Authors: Jinghang Xu, Zhennan Qi, Aimei Dong, Chang Gao, Xiaoyuan Xu, Yiyi Shi, Min Meng, Chunhua Chi
Journal: BMJ (2020)

The ability of prevention, treatment and management of infectious diseases is a basic requirement for general practitioners. This article introduces our experience in the infectious disease rotation for general practice residency training, focusing on the rotation management at different stages of training to explore how to improve teaching quality and the ability of trainers in a short period of the rotation.


Key words: 
General practitioner; diseases; Standardized training of resident
Personalized treatment of immune checkpoint inhibitor-related severe hemophagocytic lymphohistiocytosis (HLH).
Authors: Michel Obeid, Berna C. Özdemir, Sofiya Latifyan, Olivier Michielin
Journal: Journal of Clinical Oncology (2020)

e15079 Background: HLH is a rare but potentially lethal immune related adverse event (irAE) with an incidence of 0.03-0.4 % in cancer patients undergoing immune checkpoint inhibition (ICI). Given the rarity of HLH there are currently no diagnostic or therapeutic guidelines and the majority of the reported cases have been treated with corticosteroids alone with very variable response rates. There is currently no established therapy for corticosteroid resistant HLH occurring in the context of immunotherapies. We investigated the treatment possibility of severe HLH according to the cytokine profile. Methods: We report the clinical presentation, the cytokine profile and the outcome of three melanoma patients with ICI-related HLH not responding to high dose corticosteroid therapy alone who were treated with additional anti-IL-6R at the Centre Hospitalier Universitaire Vaudoise. We collected the following data: treatment setting, ICIs received, duration of each treatment, HLH criteria, bone marrow biopsy, cytokine profile, response to corticosteroid and to anti-IL-6R therapy. Results: We identified a severe HLH in three metastatic melanoma patients treated with ipilimumab and nivolumab for 2 of them and 1 with pembrolizumab. HLH occurred in a median of 10 weeks after initiation of immunotherapy. The patients met at least five of the HLH-2004 criteria including high ferritin levels ( &gt; 100.000 ng/ml). High levels of interferon-gamma (IFNγ), IFNγ-induced chemokines, particularly CXCL9, CXCL10, CXCL13, IL-18 and IL-6 were found in all patients. For 2 of them we identified a highly infiltrated bone marrow by activated CD8+ T and NK cells. Median duration of corticosteroids therapy was 6.5 weeks. The evolution of the three patients was rapidly favorable in a median of 2.5 weeks after the addition of an anti-IL-6R therapy targeting the IFNγ/Th1 axis. Conclusions: HLH is a potentially life-threatening irAE necessitating emergency therapy. CXCL9 and Th1 cytokines are markedly elevated in patients with ICI-related HLH due to the activation of the IFNγ pathway. High CXCL9 and Th1 cytokines levels appear to be potential specific biomarkers for ICI-related HLH diagnosis. Blocking this axis by anti-IL-6 therapy seems a very promising strategy for severe ICI-related HLH allowing rapid resolution of symptoms and normalization of the abnormal laboratory results.
Plasma cell free PD-L1 RNA expression correlated with tissue PD-L1 immunohistochemical staining and tumor mutation burden in non-small cell lung cancer.
Authors: Paul R. Walker, Mark Bowling, Nitika Sharma, Praveen Namireddy, Teresa Parent, Cynthia R. Cherry, Chen-Hsiung Yeh
Journal: Journal of Clinical Oncology (2020)

e15049 Background: Programmed death ligand-1 (PD-L1) protein expression by immunohistochemical staining (IHC) correlates with response to immune checkpoint inhibitor (ICI) therapies in non-small cell lung cancer (NSCLC). Tumor mutational burden (TMB) is another immune biomarker of ICI response in NSCLC. Clinical studies indicate tissue PD-L1 protein expression and TMB are independent yet complementary. Both are limited by tissue acquisition and potential heterogeneity. Plasma cell free PD-L1 RNA (cfRNA) levels and tissue protein PD-L1 expression and TMB was analyzed and correlated in patients with advanced NSCLC. Methods: Patients with advanced NSCLC underwent complementary plasma and tissue next generation sequencing (NGS) with immune biomarkers prior to treatment. Plasma PD-L1 cfRNA was assessed by the Circulogene proprietary direct-on-specimen enrichment technology NGS platform. Correlating tissue testing was performed by the Caris Molecular Intelligence platform with the anti-PD-L1 22C3 IHC antibody and TMB measuring the total number of non-synonymous somatic mutations per megabase. Results: 107 patients with advanced NSCLC were evaluated with simultaneous plasma and tissue NGS testing. 17% (95% confidence interval [CI] 10-24%) patients plasma PD-L1 positive. 48.5% (CI 38-57%) tissue IHC PD-L1 positive. 7 of 18 plasma PD-L1 positive patients were tissue PD-L1 negative. 48% (CI 39-58%) total patients TMB ≥ 10 mutations per megabase (TMB high). Correlating TMB high in 72% (CI 50-94%) of plasma PD-L1 positive and 56% (CI 42-69%) of tissue PD-L1 positive patients. TMB high in 49% (CI 37-59%) plasma PD-L1 negative and 50% (CI 35-65%) tissue PD-L1 negative patients. Conclusions: Although less frequent than tissue PD-L1 protein expression, plasma PD-L1 cfRNA expression correlated with a higher association of tissue TMB high findings than tissue PD-L1 positive patients. There was not any TMB high difference between plasma PD-L1 negative and tissue PD-L1 negative patients. Over one-third of plasma PD-L1 positive patients were tissue PD-L1 negative. Clinical correlation with immune checkpoint inhibitor therapies is ongoing.
Sputum supernatant as an alternative source for liquid biopsy in patients with advanced lung cancer.
Authors: Ting Guo, Chengping Hu, Ling Qin, Huaping Yang, Qihua Gu, Liming Cao, Pengbo Deng, Han Han-Zhang, Bing Li, Junyi Ye, Lu Zhang, Zhiqiu Chen
Journal: Journal of Clinical Oncology (2020)

e21617 Background: With the advancements in the development of targeted therapy, the detection of actionable genes has become routine practice in diagnosing lung cancer. Plasma-based mutation profiling is widely used in clinical settings. Profiling using other body fluids is actively explored. In this study, we investigated the potential of induced sputum obtained from non-small cell lung cancer (NSCLC) patients for mutation profiling. Methods: We performed targeted sequencing on matched FFPE, plasma and induced sputum samples of 41 treatment-naïve advanced NSCLC using a panel consisting of 168 lung cancer-related genes. 10ml of whole blood and 8 ml of induced sputum were obtained from each patient. Induced sputum samples were fractionated into supernatant (sup) and precipitates (ppt). The cohort had a median age of 65 with a majority (32/41) diagnosed with lung adenocarcinoma. 7 of them were diagnosed with squamous cell carcinoma and the remaining 2 patients were diagnosed with neuroendocrine tumor. All patients had advanced disease (stage III or IV). Results: First, we investigated the optimal sputum fraction for mutation profiling by comparing the detection rates and maximum allelic fraction (maxAF) between sputum sup and ppt samples using matched tissue and plasma as references. The detection rate was defined as any mutation detected from the panel used; while maxAF was defined as the highest mutation allelic fraction among all mutations detected. Tissue, plasma, sputum sup and ppt achieved a rate of detection of 100%, 76.9%, 72.4% and 65.7% respectively, revealing comparable detection rates between plasma and sputum sup (p = 0.89). Sup had a significantly higher average maxAF than plasma (p = 0.03) and ppt samples (p &lt; 0.01). Using driver mutations detected from tissue samples as references, sup, ppt and plasma samples achieved a sensitivity of 63.2%, 50% and 67.8%, respectively. Next, we investigated whether induced sputum obtained from smokers would be more informative than non-smokers. Our analysis revealed that sup from smokers had a significantly higher average AF than sup from non-smokers (p &lt; 0.001). Furthermore, there was a statistical significant difference in average AF between sup and ppt obtained from smoker (p &lt; 0.001) but such difference was non-existent in non-smokers (p = 0.46). Conclusions: Our study demonstrated that sputum sup demonstrates a comparable performance as plasma samples and is as a better sampling source than its ppt. Induced sputum from advanced stage NSCLC patients is an alternative media for mutation profiling.
高频电切除上消化道息肉59例
Authors: 付强, 焦红霞, 张清红, 朱琳, 雷大勇
Journal: BMJ (2006)

消化道息肉在临床上很常见,它可引起消化道出血、腹痛、腹泻,更重要的是引起癌变,常被视为癌前期病变,故一旦发现,主张应予摘除.目前内镜下息肉摘除术取代了70年代以前的外科手术治疗,高频电圈套器摘除为常用方法.我院2001年3月至2003年12月对59例患者的胃、十二指肠息肉进行了内镜下高频电凝切除术。
肺巨大炎性假瘤误诊肺癌一例
Authors: 董成功, 栾春法, 初文霞
Journal: BMJ (2006)

患者男,48岁.1个月前患者自觉乏力、刺激性干咳,近1周咳嗽、咳痰加重,痰中带血,发热4 d,体温39℃,服退热药效果不明显.于2004年7月来我院就诊.查体:右肺语颤增强,叩诊实音;右肺上方呼吸音消失,下方呼吸音低.血常规:白细胞16.83×109/L;结核菌素试验(-).胸部X线片:右肺上叶高密度阴影.胸部CT:右肺尖巨大软组织肿块,边缘不规则,内缘及右纵隔分界不清;肿块最大截面积约8.5 cm×7.0 cm,腔静脉后及主动脉窗内见多发肿大淋巴结,最大约2.5 cm,双肺门阴影不大,各叶段支气管通畅;诊断:右肺上叶癌伴纵隔淋巴结转移.行支气管镜检查,刷片细胞病理结果找到可疑肿瘤细胞.
Abstract 12497: Regulation of Mitochondrial Biogenesis and Oxidative Phosphorylation by miR-1825 Promotes Proliferation and Survival of Quiescent Adult Cardiomyocytes
Authors: Raghav Pandey, Jeffrey S Crocker, Benajmin Weller, Rafeeq P Ahmed
Journal: Circulation (2015)

Background: Generation of reactive oxygen species (ROS) by mitochondrial oxidative phosphorylation is known to induce DNA Damage Response (DDR) pathway resulting in cell cycle arrest and apoptosis in a number of cell types including Adult Cardiomyocytes (ACMs). In our recent studies, we have identified miR-1825 to be the most robust ACM proliferation inducing miR. Here we hypothesize that miR-1825 promotes proliferation by regulating mitochondrial biogenesis and ROS production. Methods and Results: ACMs isolated from 10 week old male rats were transfected with hsa-miR-1825 and cel-miR-67 (control). EdU was added (5μM) each day for 6 days and cells were used for immuno-staining, RNA and protein analysis. In addition to EdU, TnI, and DAPI staining, Dihydro-rhodamine 123 was used as a marker for mitochondrial ROS production, VDAC immuno-staining was used to detect mitochondrial number. We identified 25% less mitochondrial ROS production in ACMs transfected with miR-1825. Moreover, when ACMs were administered H2O2 (10μM), along with miR-1825 a significant decrease in apoptosis was detected (TUNEL+ ACM 0.53±0.10 fold less than control). In addition to reduction of mitochondrial ROS, miR-1825 transfected ACMs also showed a significant reduction in total ROS. VDAC immuno-staining showed over 85% decrease in mitochondrial number in miR-1825 transfected ACMs compared to control. Our whole transcriptome micro-array analysis of ACMs transfected with miR-1825 identified down regulation of genes involved in oxidative phosphorylation and TCA cycle; while cell-cycle genes like Cyclin-D and Cyclin-B were up regulated. Our RNA sequencing data and in-silico analysis reveal miR-1825 regulates mitochondrial biogenesis indirectly through up-regulating miR-199a expression and by subsequent down regulation of miR-199a target SIRTUIN1 which is a known inhibitor of PGC-1α and mitochondrial biogenesis. Conclusion: We identified that the increase in proliferation of ACMs observed with miR-1825 is through miR-199a mediated inhibition of PGC-1α expression which inhibits mitochondrial biogenesis and ROS production. This is a novel mechanism and has translational potential for inducing proliferation of ACM post myocardial infarction.
Bern procedure in duodenum-preservingpancreatic head resection
Authors: Dong-sheng Zhang, Jiang Yu, Xiang-yang Bu, Zeng-yin Chen
Journal: BMJ (2009)

Eight patients with chronic pancreatitis or benign pancreatic head tumors were investigate to evaluate the use of Bern procedure in duodenum-preserving pancreatic head resection.Our data indicated no periopemtive deaths and serious complications.During median follow-up of 10 monks(range,6 to 14 monks),all patients reported impmvod clinical symptoms,and those with chronic pancreatitis had weight increased by 7.9 kg(range,4 to 18 kg).Pancreatic exocfine function wag improved,although the endocrine function showed no change.The Bern procedure might be a relatively safe and effective procedure for the treatment of chronic pancreatitis or benign pancreatic head tumors.

Key words: 
Panereatitis,chmmc; Panereaticojejunostomy
Impact of treatment on prognosis of inflammatory myopathy-associated cardiomyopathy
Authors: Yingxian Liu, Wei Chen, Xue Lin, Qian Wang, Zhuang Tian, Xiaowei Yan, Quan Fang, Shuyang Zhang, Ligang Fang
Journal: BMJ (2019)

Objective
To observe the treatment of inflammatory myopathy-associatied cardiomyopathy and its impact on prognosis of disease.


Methods
In this single-center retrospective study, 29 cases of inflammatory myopathy-associated cardiomyopathy were collected in Peking Union Medical College Hospital from 1999 to 2016. The clinical data and adverse events during follow up were documented. Among 29 patients there were 11 cases of polymyositis, 8 cases of dermatomyositis, 8 cases of overlap syndrome and 2 cases of nonspecific myositis.All the patients started with sufficiene prednisone (1-2 mg·kg-1·d-1). 7 cases received intravenous immune globulin, while 12 cases were prescribed with steroid pulse therapy, 16 cases with methotrexate, 15 cases with cyclophosphamide, 6 cases with cyclosporine A, while 11 cases with combination of immune suppressors (methotrexate plus cyclophosphamide or cyclosporine A). After a median follow up of 4.8 years (2 month to 15 years), 14 cases died including 9 of cardiac death. Patients with cardiac deaths had lower usage percentages of intravenous gamma globulin (0 vs. 7/20, P=0.05) and steroid pulse therapy (1/9 vs. 11/20, P=0.043) than controls. Comparing with controls, patients in the group of adverse events were more prone to choose methotrexate alone rather than combination of immune suppressors (all-cause death: 1/14 vs. 8/15, P=0.014; cardiac death: 0 vs. 9/20, P=0.027). Kaplan-Meier survival analysis showed significant difference of survival rates between patients with combination of immune suppressors and controls (Log Rank χ2=6.001, HR=7.58, P=0.014), as well as between patients with β receptor blockers and controls (Log Rank χ2=4.589, HR=2.95, P=0.032).


Conclusions
We recommend a management strategy that emphasize both primary disease controlling and cardiac remodeling improvement in patients with inflammatory myopathy-associated cardiomyopathy. On the basis of sufficient glucocorticoids, intravenous gamma globulin, steroid pulse therapy, combination of methotrexate plus other immune suppressants, and β receptor blockers were worthy to be considered.


Key words: 
Inflammatory myopathy; Cardiomyopathy; Heart failure; Treatment; Prognosis
外伤性脾破裂脾切除术后再出血行介入治疗一例
Authors: 刘浩, 赵燕
Journal: BMJ (2010)

患者男性,49岁.因从8 m高处坠落摔伤头、胸、腹部疼痛、胸闷2h于2009年9月29日来院就诊.既往乙型肝炎病毒表面抗原(HBsAg)、e抗原(HBeAg)、核心抗体(HBcAb)阳性6年.入院体检:血压87/45 mm Hg(1 mm Hg=0.133 kPa),脉搏122次/min.神志清楚,面色苍白.左侧胸壁握雪感,挤压试验阳性,左侧呼吸音低,闻及湿哕音.心率122次/min,律齐.上腹大片皮肤擦伤,全腹压痛,反跳痛,移动性浊音阳性,肠鸣音8次/min.CT检查示:左侧多发肋骨骨折并液气胸,左胸、颈、腹部皮下积气,符合脾破裂并腹水表现,左额部硬膜下积液.外周血白细胞计数24.9×109/L,红细胞3.73×1012/L,血红蛋白107 g/L。
Houssay综合征一例
Authors: 孙丽萍, 刘海霞, 王秀军
Journal: BMJ (2006)

患者男,73岁.19年前确诊为2型糖尿病,用格列本脲(优降糖)、苯乙双胍(降糖灵)各3片/d控制血糖,空腹血糖7～10 mmol/L.8年前因感冒出现发热、恶心、呕吐,空腹血糖高达16.7 mmol/L,尿酮体(+++),收住内分泌科,诊断为糖尿病酮症酸中毒,经胰岛素治疗后病情好转而出院.出院后应用格列齐特(达美康)160 mg/d治疗,测空腹血糖8～10 mmol/L。
心脏康复的中心作用
Authors: 励建安
Journal: BMJ (2007)

心脏康复是指综合采用主动积极的身体、心理、行为和社会活动的训练与再训练,帮助患者缓解症状,改善心血管功能,在生理、心理、社会、职业和娱乐等方面达到理想状态,提高生存质量.同时强调积极干预心脏病危险因素,阻止或延缓疾病的发展过程,减轻残疾和减少再次发作的危险。
The development of pain medicine in China
Authors: 樊碧发
Journal: BMJ (2008)

疼痛是个常议常新的话题.正如国际著名疼痛医学专家Melzack和Wall教授曾经指出的那样,疼痛是医学和生物学中最富有挑战性的问题之一.免除疼痛是患者的基本权利,也是医生的神圣职责.随着近十几年来疼痛科学的迅猛发展,疼痛的理念已经取得了很大的进步,疼痛已成为人体继呼吸、脉搏、血压、体温之后的第五大生命体征.从全球范围讲,疼痛科学已提到了一个前所未有的高度,相应的疼痛学科也迅速成为当今医学热点学科之一。
Novel synthetic immune modulators for the activation of tumor antigen-specific T cells.
Authors: Di Zhang, Lihua Shi, Susan Tam, Man-Cheong Fung
Journal: Journal of Clinical Oncology (2020)

e15203 Background: Although checkpoint inhibitor immunotherapy and adoptive T-cell therapy revolutionized cancer treatments, such approaches suffer either from lack of target specificity for checkpoint inhibitors or inability to target intracellular tumor-related antigens from CAR-T therapy. Here, we report the development of novel Tavo Immune Modulator (TIM) biologics molecules which can specifically recognize tumor antigen-specific T cells through an engineered pMHC complex with peptides derived from intracellular tumor-related antigens. These molecules can selectively activate such T cells through engineered T cell co-stimulatory modulators for enhanced tumor cell killing. Methods: NY-ESO-1 and MAGE-A10 TIM molecules were constructed as fusions of HLA-A*02:01 MHC complexed with either NY-ESO-1 (157-165) or MAGE-A10 (254-262) epitope peptides at the N-termini and various T cell costimulatory modulators at the C-termini of IgG heavy and light chains. TIM molecules were expressed in Expi293 cells and purified by Protein A affinity chromatography. Specific binding of TIM with cancer specific T cells was evaluated by immunostaining. The activation and proliferation of tumor specific CD8+ T cells were confirmed in T cell activation and recall assays. Results: Both NY-ESO-1 and MAGE-A10 specific TIM molecules were generated which recognized corresponding tumor specific T cells. NY-ESO-1 TIM engineered with IL2 could activate NY-ESO-1 specific CD8+ T cell exclusively. Engineering additional T cell costimulatory factors along with IL2 on NY-ESO-1 TIM molecule could further boost T cell proliferation and activation in T cell recall assays. Besides NY-ESO-1, combinations of T cell costimulatory factors with MAGE-A10 TIM molecules enhanced specific T cell activation. Additional in vitro and in vivo studies are ongoing to demonstrate efficacy of such novel TIM molecules in eliminating different types of NY-ESO-1 and MAGE-A10 which are over-expressed on tumor cells. Conclusions: This study demonstrates the utility of NY-ESO-1 and MAGE-A10 TIM molecules in the selective recognition and activation of tumor antigen-specific T cells. Such novel biologics molecules may provide target specificity in tumor treatment, and potential targeting of intracellular tumor-related antigens presented as peptides in MHC complexes on cell surfaces. Selective activation of tumor-specific T cells may provide a unique method for the treatment of various solid tumors and warrants further investigation.