tbuckley/cabot-search huggingface dataset:
Test of an online tool to facilitate NCCN guideline-compliant access to cancer genetics care.
Authors: Kara J. Milliron, Amanda Cook, David Keren, Lynn A. McCain, Lee Schroeder, Bailey Hulswit, James Arthurs, Diane M Harper, Susan Ernst, Philip Zazove, Jasmine Parvaz, Sofia Merajver
Journal: Journal of Clinical Oncology (2020)

1542 Background: Minority populations experience inequities of access to cancer genetics. We developed and tested an online family history collection and interpretation tool, InheRET, to determine acceptability, validity and utility.Patients are mostly unable to recall accurate family history in clinic and providers have little time to collect the 3-generation pedigree. Thus, ~90% of high risk patients remain unidentified. We evaluated the impact InheRET has on facilitating National Comprehensive Cancer Network (NCCN) Guideline-compliant referrals for cancer genetic counseling. Methods: Patients from 3 clinics were consented online to participate. A user experience survey for patients and providers followed the health history questionnaire. Results: 628 patients were consented over a year, 555 (&gt;88%) completed the tool. 439 (79%) completed the post-questionnaire user experience. Review of Inheret's recommendations by a genetic counselor found 100% accuracy. Ease of Use: 84-87% of patients reported tool was easy to use. Understandability: 92-97% of patients reported tool was easy to understand. No significant differences were reported between those with high school (n=28, avg age 50.1 yrs) compared to those with advanced degrees (n=139, avg age 45.4 yrs); patients age 70+ experienced increased difficulties. Among primary care patients (n=135), 43 established patients were newly identified as meeting NCCN referral criteria. Healthcare providers found InheRET useful, did not require extra clinical time, and all wish to continue to use it. The patient provided data were more complete and encompassed more family members than with paper forms. Turn-around-times to receive the patient’s information were decreased from 4-6 weeks to ~ 72 hours. A patient scheduling backlog of 400 patients was cleared using InheRET. Previously, 40% of cancer genetics patients were lost to follow up, due to not completing their intake forms. This number was reduced to 6.5%. Conclusions: Patients find InheRET to be easy to use and understand and they complete this health history tool more frequently and in greater detail than by paper forms. InheRET provides accurate results, verified by in person interviews, in a timely fashion, saving clinical time, possibly enabling increase in earned clinical revenues (under analysis), and improving patient care overall. Importantly, the 43 primary care patients identified to be at increased risk were already established patients, who had not been previously identified as such by their healthcare providers as being at increased risk.
Abstract 14900: Impact of ICD Programming Changes to Avoid Inappropriate Shocks in the Young
Authors: Frank J Zimmerman, Aishwarya Bhan, Anne Freter, Ira Shetty, Lisa Russo, Janis Dennis, Frank T Zimmerman, Adarsh Bhan
Journal: Circulation (2015)

Introduction: ICD therapy in young pts has been shown to improve mortality but inappropriate ICD shocks (IAS) occur in up to 25% of young pts. Adult studies have shown that changing the VF detection rate (RATE) and/or duration to detection (DUR) results in fewer IAS without increasing mortality. The purpose of this study is to assess the impact of RATE and/or DUR changes to avoid IAS in young pts with ICDs. Methods: This two-part study initially consisted of a retrospective analysis of IAS in young pts with ICDs at our institution from 2007-2012. A total of 1200 intervals from EGMs recorded from 16 pts with IAS were analyzed and the risk for VF detection was calculated at various RATE and DUR. Analysis of true episodes of VT/VF in 8 pts was also performed. We found that changing the RATE from 200 bpm to 250 bpm resulted in a 49-85% reduction of risk for IAS. Based on this analysis, the RATE was increased to 220-250 bpm in our ICD pts from 2012-2015. The clinical rate of IAS was then compared before and after changing ICD programming to higher RATE. Results: 64 pts (ages 8y to 57y, mean 21y, 41 male) were included in this study. In the time period from 2007-2012, IAS occurred in 30% of pts (50% due to lead malfunction and 50% due to SVT). ICD programming was changed to VF RATE of 220-250 bpm with DUR of 18/24 in all ICD pts in 2012 and thereafter. There was a significant reduction of IAS with ICD program changes (30% vs 1.5%, p=0.001) with no change in appropriate shock rate (APS) or lead malfunction rate between the two time periods (see table). There were no episodes of syncope or death in those with APS before or after programming changes. Conclusions: The incidence of IAS in young pts can be reduced by changes in ICD programming. Increasing the RATE has a greater impact on reduction of risk for IAS compared to prolonging DUR and did not result in an increase in syncope or death. These findings may help to standardize programming of ICDs in young pts.
Phase Ib study of CPX-351 lower-intensity therapy (LIT) plus venetoclax as first-line treatment for patients with AML who are unfit for intensive chemotherapy (IC).
Authors: Tara L. Lin, Geoffrey L. Uy, Roland B. Walter, Heng Zou, Qi Wang, Stefan Faderl, Ronald Cheung, Vinod A. Pullarkat
Journal: Journal of Clinical Oncology (2020)

TPS7567 Background: CPX-351 (Vyxeos; daunorubicin and cytarabine liposome for injection) is approved by the FDA and EMA for the treatment of adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. In a phase 3 study in patients (pts) aged 60-75 y with newly diagnosed high-risk/secondary AML who were fit for IC, CPX-351 significantly improved median survival versus 7+3 cytarabine/daunorubicin and had a comparable safety profile. However, it may not be appropriate to administer CPX-351 at the label dosage in pts unfit for IC. Venetoclax, a BCL-2 inhibitor, has clinical efficacy in combination with low-dose cytarabine in AML pts unfit for IC, and preclinical data suggest a rationale for combining CPX-351 and venetoclax. This study thus evaluates CPX-351 LIT in combination with venetoclax in AML pts unfit for IC. Methods: This is an open-label, multicenter, 2-part, phase 1b study (NCT04038437) to determine the maximum tolerated dose (MTD) and evaluate the safety, efficacy, and pharmacokinetics of CPX-351 LIT plus venetoclax. Key eligibility criteria are shown in the Table. In the dose-escalation phase (3+3 design), up to 24 pts will receive CPX-351 (dose levels: 20, 40, 60, and 75 units/m 2 ) on Days 1 and 3 plus venetoclax 400 mg on Days 2-21 of each cycle to determine the MTD, with each dose escalation confirmed by a safety assessment committee. Pts who achieve complete or partial remission after 1 or 2 cycles may receive up to 4 similar cycles of CPX-351 plus venetoclax. In the expansion phase, an additional 20 pts will be treated at the MTD. All pts are assessed for response by morphology and minimal residual disease testing, and are monitored for safety (until 1 month after end of treatment) and survival (up to 1 year after start of treatment). The study is ongoing and actively enrolling pts. Clinical trial information: NCT04038437 . [Table: see text]
Clinical analysis of 56 patients with relapsing polychondritis
Authors: 史旭华, 苏金梅, 陈志科, 张奉春, 唐福林
Journal: BMJ (2006)

目的 研究复发性多软骨炎的临床特点,提高对本病的认识.方法 回顾性分析56例复发性多软骨炎患者的临床及辅助检查资料.结果 男女比例1.2:1,发病年龄(46±11)岁.确诊时间(21±35)个月,以耳软骨起病者(8±6)个月,呼吸道起病者(16±31)个月,关节起病者(29±37)个月.受累部位依次为呼吸道40例(71.4%)、耳软骨32例(57.1%)、关节软骨32例(57.1%)、眼部27例(48.2%)、鼻软骨25例(44.6%)、内耳13例(23.2%).病程初期被误诊为呼吸道感染17例(30.4%)、软骨膜炎9例(16.1%)、肺结核感染6例(10.7%)、类风湿关节炎5例(8.9%).呼吸道受累的患者中7例接受气管内支架治疗.4例从治疗开始症状一直未缓解者均为呼吸道受累者.结论 非耳、鼻部位起病的复发性多软骨炎易被误诊,呼吸道受累比例高且预后差。
Breast cancer grade and clinical benefit in patients with advanced breast cancer treated with an engineered whole tumor cell-targeted immunotherapy alone or in combination with checkpoint inhibition.
Authors: William Williams, Shaker R. Dakhil, Carmen Julia Calfa, Jarrod P. Holmes, Saveri Bhattacharya, Jason Jerome Lukas, Elizabeth Tan-Chiu, George Earl Peoples, Vivekananda Sunkari, Markus Lacher, Charles L. Wiseman
Journal: Journal of Clinical Oncology (2020)

3033 Background: SV-BR-1 is a breast cancer cell line derived from a grade II (moderately differentiated) tumor. SV-BR-1 was transfected with the CSF2 gene (encoding GM-CSF) to form SV-BR-1-GM. SV-BR-1-GM expresses HLA class I &amp; II antigens and has functional antigen-presenting cell activity, directly stimulating CD4+ T cells in an HLA-DR restricted fashion. The SV-BR-1-GM regimen consists of low-dose cyclophosphamide (300 mg/m 2 ) to reduce immune suppression, intradermal inoculation with irradiated SV-BR-1-GM (20x10 6 cells divided into 4 sites) and interferon-α2b (10,000 IU into each inoculation site ~2 &amp; 4 days later) to boost the response. Here, we evaluate the impact of tumor grade on clinical benefit following treatment with the SV-BR-1-GM regimen. Methods: Patients with advanced breast cancer were treated with either the SV-BR-1-GM regimen alone or with the SV-BR-1-GM regimen with pembrolizumab. For the SV-BR-1-GM regimen alone, cycles were administered every 2 weeks x 3 and then monthly, while combination with pembrolizumab (200 mg IV 1-5 days following SV-BR-1-GM inoculation) administered cycles every 3 weeks. Tumor restaging was every 6-12 weeks. Results: 33 patients were enrolled. The treatment was generally safe with inoculation site pruritis, erythema and induration the most common adverse events. 23 patients had grade III (poorly differentiated) tumors, 9 had grade II tumors and one had a grade I (well differentiated) tumor. None of the patients with grade III tumors exhibited clinical benefit. 7 patients with grade I/II tumors received the SV-BR-1-GM regimen alone, 2 received the SV-BR-1-GM regimen with pembrolizumab and 1 received both regimens. As noted in the Table, 7 patients experienced clinical benefit including all 3 patients treated in combination with pembrolizumab. This included 6 patients with stable disease and one with a partial response. Conclusions: The SV-BR-1-GM regimen with or without pembrolizumab appears safe and able to induce clinical benefit even in very heavily pre-treated patients with low or intermediate grade advanced breast cancer. Clinical trial information: NCT03328026 . [Table: see text]
老年肠道血管畸形内镜下特点分析
Authors: 邹莉萍, 于皆平
Journal: BMJ (2007)

回顾性分析肠道血管畸形老年患者43例的内镜下特点,结果示43例中39例为血管扩张型,4例为动静脉畸形.累及肠腔情况为盲肠受累者14例(33%)、直肠受累8例(19%)、横结肠6例(14%)、降结肠5例(11%)、乙状结肠4例(9%)、升结肠3例(7%)、结肠脾曲2例(5%)、回肠末端1例(2%).提示肠道血管畸形是造成老年患者不明原因出血的一种原因,病变大多在结肠部位.肠镜检查已成为诊断肠道血管畸形的首选方法,且可在肠镜下直接治疗。
Estimating clinical competence of general practitioner by DxR Clinician software
Authors: Feika Li, Yajie Zhao, Peijing Cui, Fang Wu
Journal: BMJ (2015)

Clinical competence was estimated for grades 2011—2013 general practitioners (GPs) trained by the DxR Clinician software. Clinical cases were solved on computer. And the abilities of diagnosis, thinking and handling were assessed. The average score of all GPs was 61.68±10.69. The average score of diagnostic ability was the highest at 71.82±15.47 (weighted score of 25.1). The average score of thinking ability was 62.36±10.40 (weighted score of 28.1). And the average score of handling ability was the least at 42.27±18.22(weighted score of 8.5). Significant differences in average scores existed between grades 2011 and 2013 (P<0.05). Significant differences in score of clinical thinking ability existed between grades 2011, 2012 and 2013 (P<0.01) respectively. None of them passed the part of handling. The longer period of training, the higher scores the residents obtained. Since the ability of clinical handling fared the worst, targeted training should be strengthened.


Key words: 
Clinical competence; General practitioner
阑尾重复畸形一例
Authors: 刘会光
Journal: BMJ (2005)

1.临床资料:患者男,18岁.转移性右下腹痛18 h入院.查体:体温39.5℃,右下腹压痛、反跳痛.实验室检查:血白细胞13×109/L.临床诊断:急性化脓性阑尾炎.行阑尾切除术.病理检查:巨检:阑尾1条,长 7 cm,外径 3 cm,浆膜面覆有脓苔.距阑尾末端约1.5 cm 处见2个独立肠腔,其中大者直径1.1 cm,小者直径 0.4 cm.近阑尾中段见两个肠腔逐渐相通成为一个扁圆形肠腔,直径约2 cm.镜检:阑尾末端肠壁各层可见大量的中性粒细胞、嗜酸性粒细胞浸润,浆膜面为渗出的纤维和中性粒细胞组成的薄膜覆盖.在阑尾末端可见2个小腔隙,在同一浆膜内各自均有完整的平滑肌围绕.阑尾中段见有两个管腔外层平滑肌相移行,在距阑尾根部1 cm 处完全融合成一个阑尾腔.病理诊断:①急性化脓性阑尾炎,阑尾周围化脓性炎;②阑尾重复畸形。
意识障碍的现代概念
Authors: 冯庚
Journal: BMJ (2005)

意识(consciousness)是人脑对于客观物质世界的反映,是感觉、思维等各种心理过程的总和.人类的意识活动由两方面的内容组成,第一是觉醒状态,它属于脑皮质下的一种初级生理功能,相对属于低级功能,其作用是使人保持清醒,清醒状态是在脑皮质下激活系统的作用下实现的,与睡眠状态交替循环出现.第二是意识内容的存在,属于脑皮质的高级功能,表现为人类的思维、情感、认知、记忆以及视觉、技巧性运动、对外界刺激的反应能力等.意识活动的两项内容缺一不可,否则人将不可能实现正常的意识活动。
恶性胸膜间皮瘤并气胸和胸水嗜酸粒细胞增多一例
Authors: 周一平, 陈小可, 李明, 夏利萍
Journal: BMJ (2005)

患者男,65岁,因右胸痛3个月于2004年3月13日入院.3个月前无诱因出现右胸刺痛,未作诊治好转,近1周加重,持续性钝痛,伴活动后气促咳嗽,咳少量白黏痰,无发热、咯血、盗汗.入院体检:体温36.5℃,呼吸20次/min,消瘦,唇无紫绀,浅表淋巴结无肿大,气管居中,右下肺叩浊、呼吸音消失.心界不大,心率76次/min,律齐,肝脾未及,下肢不肿。
Prevalence and significance of clonal hematopoiesis of indeterminate prognosis (CHIP) in multiple myeloma.
Authors: Leslie Jane Padrnos, Betsy LaPlant, Shaji Kumar, Kimbery Henderson, Angela Dispenzieri, Terra L. Lasho, Mrinal Patnaik, A. Keith Stewart
Journal: Journal of Clinical Oncology (2020)

8542 Background: Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the presence of leukemia-associated somatic mutations in clonally expanded hematopoietic stem cells with a VAF of ≥2%. CHIP has been associated with myeloid malignancies and increased all cause mortality largely from atherovascular disease. The prevalence and impact of CHIP in patients with myeloma (MM) is yet to be defined. Aims: Evaluate the prevalence and significance of CHIP in 101 lenalidomide exposed patients with multiple myeloma. Methods: 101 MM patients, the majority exposed to &gt; 2 years of lenalidomide (Len), with stored mononuclear blood samples were identified for Next Generation Sequencing (NGS) using a panel encompassing 42 gene mutations associated with CHIP. Electronic medical records were reviewed and outcomes of secondary malignancy, macrocytosis, thrombosis and mortality were extracted. Results: Thirty of 101patients were found to have CHIP with the most frequent mutations: DNMT3A (12%), TET2 (5%), and TP53 (4%). One third of patients with CHIP had &gt; 1 mutation (37%). At 68 months median follow up over a quarter of patients experienced thrombosis (31%) and 13% developed subsequent malignancy/premalignant condition including myelodysplastic syndrome (3%). There was no significant difference in age, gender, duration of Len prior to NGS testing, thrombosis complication, or survival in those with versus without a CHIP mutation. At last F/U 30% had died, 25% remained on therapy, 27% were on maintenance therapy and 11% were on observation alone. Conclusions: CHIP mutations are common in plasma cell neoplasms, with 30% of patients in this study retrospectively found to have CHIP mutations by NGS testing. CHIP mutations have been associated with cardiovascular events and malignancy development, however no associations were identified in this small study. Limitations to this study include small sample size, retrospective nature and duration of follow up. Further study of this very common finding in MM patients regarding timing of development and subsequent impact of these mutations could help risk stratify and inform therapy selection. [Table: see text]
Tumor response to a mastermind inhibitor protein.
Authors: Agamemnon A. Epenetos, Marianna Prokopi, Costas Pitsillides, Konstantinos Kapnisis, Mahendra Deonarain, Christina Kousparou, Andreas Anayiotos
Journal: Journal of Clinical Oncology (2020)

e17601 Background: Notch signalling is implicated in tumorigenesis prompting scientists to research and develop anti-Notch therapeutics. Drugging the Notch pathway has been a challenge due to severe G-I toxicity seen by many small-molecule inhibitors. Mastermind is a key nuclear factor that mediates Notch activity. We generated a novel protein drug, Syntana-4, that inhibits the Notch pathway at the Mastermind transcriptional level. Syntana-4 consists of the cell penetrating domain of Antennapedia, fused to a truncated peptide from Mastermind-like (MAML) that behaves in a dominant-negative fashion inhibiting Notch. Syntana-4 translocates into the cell nucleus, suppressing Notch activity and inducing apoptosis in Notch-driven cancer cells. Methods: We have conducted pharmacokinetics (PK), pharmacodynamics (PD) and toxicology studies, in combination with innovative imaging including in vivo flow cytometry and whole-body fluorescence reflectance imaging to define the behaviour of Syntana-4, determine its mode of action and establish a safety and efficacy profile in an orthotopic model of breast cancer in SCID mice based on the implantation of MDA-MB-231 cells into mammary fat pads. Samples of blood and tissues were examined for toxicity, apoptosis and immunogenicity. Results: We found that Syntana-4 was well-tolerated by normal cells and organs and was not immunogenic. Also, it was shown that free, non-internalized drug was rapidly cleared from the circulation. Whole body imaging showed that the drug in tissues was cleared within 24 hrs. Assessment of tumor growth demonstrated a reduction in tumor growth as evidenced by an overall increase of less than 50% in the intensity of fluorescence signal in the treated group compared to a 3-fold increase in signal and thus tumour size in untreated group by day 14. Conclusions: Syntana-4, a Mastermind inhibitor, was found to be well-tolerated and non-immunogenic in healthy animals. This drug targets the oncogenic Notch mechanism and can be applied across tumours with genetic defects in Notch signalling including breast, prostate, etc. We have demonstrated the utility of an innovative molecular imaging system emulating a clinical ‘phase I/II’ study in an orthotopic cancer model in order to measure the biodistribution, PK, PD, mode of action, toxicity and efficacy of a first-in-class biological therapy prior to entering the clinic. This innovative approach could be useful for accurate selection of lead drug candidates prior to entering clinical development.
Correlation of pathologic tumor grade with survival in oral cavity squamous cell carcinoma.
Authors: Eric Anderson, Michael Luu, Diana J. Lu, Anthony Tuan Nguyen, Jon Mallen-St. Clair, Kevin Scher, Alain C. Mita, Allen S. Ho, Zachary Stephan Zumsteg
Journal: Journal of Clinical Oncology (2020)

e18557 Background: Pathologic tumor grade is a well-established prognostic risk factor that impacts staging and standard-of-care treatment decisions across multiple cancer types. However, the significance of tumor grade in cancers of the head and neck is less certain. Even in oral cavity squamous cell carcinoma (OCSCC), the head and neck cancer subsite with largest body of literature regarding the predictive value of tumor grade is, the prognostic significance of tumor grade remains controversial. Thus, we sought to better elucidate the prognostic importance of tumor grade in OCSCC. Methods: Patients with OCSCC diagnosed from 2004-2015 and undergoing primary surgery with or without adjuvant treatment in the National Cancer Data Base (NCDB) were identified. Overall survival (OS) was estimated using the Kaplan-Meier method with and without propensity score matching (PSM). Univariate and multivariable survival analyses were performed using Cox regression. Analyses were adjusted for multiple clinicopathologic factors, including age, sex, comorbidity status, year of diagnosis, pathologic staging, margin status, number of lymph nodes (LN) examined/positive, extranodal extension (ENE), lymphovascular invasion (LVI), adjuvant radiation, and concomitant chemotherapy. Results: Median follow-up was 40.7 months. Of 13,941 patients with OCSCC, 2,883 had low-grade tumors, 8,716 had intermediate-grade tumors, and 2,342 had high-grade tumors. Higher tumor grade was strongly associated with decreased survival. Specifically, five year OS was 62.7%, 52.8%, and 42.5% in low-grade (LG), intermediate-grade (IG), and high-grade (HG) OCSCC, respectively (p-value &lt; 0.001). In PSM cohorts, OCSCC patients with high-grade had significantly worse 5 year OS (47.7% vs. 57.7%, p &lt; 0.001) in comparison to those with LG OCSCC. Similarly, patients with IG tumors has worse 5-year OS (55.6% vs. 60.3%, p = 0.001) than patients with LG tumors in PSM cohorts. In multivariable analysis, both HG (HR 1.38, 95% CI 1.25-1.52, p &lt; 0.001) and IG (HR 1.17, 95% CI 1.08-1.26, p &lt; 0.001) OCSCC was associated with worse survival than what was observed in LG tumors. The magnitude of the independent effect of tumor grade in multivariable analysis was greater than or equal to what was observed with other well-established prognostic factors like margin positivity (HR 1.34), ENE (HR 1.35), and LVI (HR 1.18). Conclusions: Pathologic tumor grade is a strong predictor of survival among patients with OCSCC. Tumor grade should be considered when making therapeutic recommendations for OCSCC.
Clinical analysis of 61 cases of imported malaria
Authors: Ji-xiang Zhang, Xiao-hua Duan, Cheng-ze Zheng, Jin Cheng
Journal: BMJ (2011)

Clinical data of 61 cases of imported malaria were analyzed retrospectively.Patients with malaria were divided into three groups,asymptomatic tertian (vivax) malaria,symptomatic tertian malaria and pernicious (falciparum) malaria.Only mild hepatic damage occurred in some patients with asymptomatic tertian malaria,compared with other groups Symptomatic tertian malaria and pernicious malaria were misdiagnosed in 6 of 20 and three of six,respectively before hospitalization,and 16 of 20 and four of six patients complicated with thrombocytopenia,respectively,and both of them had increased serum level of C-reactive protein (CRP).Platelet count negatively correlated with their serum level of CRP significantly in patients with symptomatic tertian malaria (r =-0.555,P ＜ 0.05).Routine anti-malaria therapy was used in imported malaria,blackwater fever occurred in two patients and acute renal failure occurred in one with falciparum malaria.It is suggested plasmodium exam ination in peripheral blood should be performed in all persons returned from countries prevalent with malaria,thrombocytopenia is an indicator of acute malaria,and more severe complications usually tend to occur in falciparum malaria.

Key words: 
Malaria; Thrombocytopenia