tbuckley/cabot-search huggingface dataset:
First-in-human phase I study of anti-HER2 ADC MRG002 in patients with relapsed/refractory solid tumors.
Authors: Jin Li, Ye Guo, Junli Xue, Wei Peng, Xiaoxiao Ge, Wei Zhao, Congqi Dai, Liqiong Xue, Wenbo Tang, Chaohong Hu
Journal: Journal of Clinical Oncology (2020)

TPS1101 Background: MRG002 is an antibody drug conjugate (ADC) composed of a humanized anti-HER2 IgG1 monoclonal antibody conjugated to a microtubule disrupting agent monomethyl auristatin E (MMAE). MRG002 is presently being investigated in an ongoing phase I study for safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity in patients (pts) with solid tumors. Methods: MRG002 is evaluated as monotherapy for the treatment of pts with confirmed HER2 positive locally advanced or metastatic cancers, including breast cancer (BC), gastric cancer (GC), salivary gland cancer (SGC) and others. The primary objective is to determine the maximum tolerated dose (MTD) and a recommended phase II dose (RP2D). Secondary objectives include evaluation of PK, tumor response, and immunogenicity. In the dose escalation phase with “3+3” design, approximately 24 pts will be enrolled to identify MTD. The starting dose of MRG002 is 0.3 mg/kg, followed by 0.6, 1.2, 1.8, 2.2, 2.6, and 3.0 mg/kg. In the dose expansion phase, about 50 pts with HER2 positive advanced cancers will be enrolled to further evaluate the safety, antitumor activity, and PK at an appropriate confirmed dose. In this phase I study, each pt receives single agent MRG002 once every 3 weeks (Q3W) for a maximum of 8 treatment cycles. Pts with BC and GC should have HER2 positive advanced solid tumors per College of American Pathologists (CAP) guidelines. For other cancers, pts must have IHC status of 2+ or 3+, regardless of FISH results. Pts should have either failed or are ineligible for standard treatments. All pts must have at least 1 measurable lesion per RECIST 1.1. ECOG should be 0-1, and bone marrow, hepatic, renal, cardiac functions should be adequate. Observations include adverse events (AEs), dose-limiting toxicity (DLT), and antitumor activity, which is assessed every two treatment cycles. Further clinical trial details can be found on chinadrugtrials.org.cn (CTR20181778). Enrollment is ongoing since November 2018. Clinical trial information: CTR20181778 .
Clinical strategy of heart rhythm and rate control in patients with atrial fibrillation
Authors: Yanpeng Chu, Shandong Yu
Journal: BMJ (2016)

心房颤动(房颤)是最常见的持续性快速心律失常。心律控制和心率控制是治疗房颤的两大基本策略。房颤的心律控制包括药物和电复律及介入治疗。心律控制理论上比单纯心率控制更有优势，部分研究也表明心律控制在改善某些患者的预后方面优于心率控制，特别是心率快合并心律失常性心肌病的情况下。除了心律控制，在有些情况下，可以将心率控制作为长期治疗方案。对存在动脉栓塞危险的患者，应进行抗凝治疗。
Non-Hodgkin lymphoma: The Indian scene.
Authors: Ajay Gogia, Sukesh Nair, Atul Sharma, Lalit Kumar, Saumyaranjan Mallick, Ahitagni Biswas, Ritu Gupta
Journal: Journal of Clinical Oncology (2020)

e20063 Background: There is a lack of data available regarding the distribution of Non-Hodgkin lymphoma (NHL) subtype, according to a recent WHO- 2016 classification and outcome of diffuse large B cell lymphoma (DLBCL) on the basis of cell of origin (COO) from developing country in Rituximab era. Methods: This is an ambispective study of newly diagnosed patients with NHL, treated in the Department of Medical Oncology, AIIMS, New Delhi. A total of 775 cases of adult ( &gt; 18 years) lymphoma were registered over a period of 5 years (January 2014 to December 2018). Outcome of DLBCL patients who have received uniform RCHOP protocol separately analysed. The patients were classified as germinal center B-cell like (GCB) or activated B-cell (ABC) type using the Hans classification Results: NHL constituted 622 (80.26%) and Hodgkin's lymphoma 153 (19.74%) of the cases. B- cell constituted 553 (88.9%) among all NHL and rest 69 (11.1%) cases were T cell in origin.. Diffuse large B cell lymphoma (DLBCL) was the most common NHL 417(67%) followed by follicular lymphoma 60 (9.64%), mantle cell lymphoma 35 (5.62%), PTCL-NOS 25 (4.01%), ALCL 16 (2.57%),marginal zone lymphoma 14 (2.25%), T-LBL 13(2.1%) and the rest of the cases were rare NHL( &lt; 1% cases each) for e.g. SLL, NK-T, BL, SLVL, AITL etc. Among the 417 cases of DLBCL, 262 (62.8%) cases received rituximab along with CHOP regimen. The median age of RCHOP treated patients was 47.6 years with male female ratio of 2.3:1. B symptoms were seen in 39% patients and bulky disease in 33%. ECOG performance status of 0-2 was present in 67% and 51% presented with advanced disease. GCB was seen in 42% and 44% were ABC. Low risk IPI was seen in 48 % and 40% were intermediate risk IPI. The overall response rate (ORR) was 82 % with a complete response rate (CR) of 75.6 %. Presence of bulky disease and non-radiotherapy treatment protocols were associated with inferior CR rate. After a median follow up of 30 months, the 3-year event free (EFS) survival and overall survival (OS) were 78 % and 88 % respectively. Low albumin ( &lt; 4 gm/dl) and age &gt; 60 years were associated with inferior EFS whereas high IPI risk score was associated with inferior OS. Pre-phase was used in 20% of cases. Grade III/ IV anaemia, neutropenia and thrombocytopenia were seen in 5%, 13% and 2% of patients respectively. Febrile neutropenia was seen in 7 % of patients and there were 3 treatment related death. Rituximab infusion related toxicity was seen in 7 patients. Conclusions: DLBCL is the most common NHL ( GC-42%, ABC-44%). The distribution according to COO dose not impact on CR rate and EFS and OS . RCHOP is well tolerated in our patients and results are comparable with the western data.
A retrospective analysis of cost and survival outcomes based on consolidation regimens in primary central nervous system lymphoma.
Authors: Savannah Gelhard, Amiee Maxwell, Howard Colman, Adam Louis Cohen, Joe Sammy Mendez
Journal: Journal of Clinical Oncology (2020)

e14544 Background: Treatment for Primary Central Nervous System Lymphoma (PCNSL) includes induction therapy consisting of polychemotherapy including high-dose methotrexate followed by consolidation therapy. There are various induction and consolidation regimens with wide variability in their treatment duration, inpatient vs outpatient administration, and the number of chemotherapeutic agents utilized. We performed a comparative cost and efficacy analysis of three consolidation techniques in an effort to provide insight into the cost-benefit of these treatment regimens. Methods: Patients treated for newly diagnosed PCNSL at our institution after July 1, 2012 were retrospectively reviewed. Patients who completed one of the following regimens and received consolidation therapy at our institution were included: rituximab/methotrexate/vincristine/procarbazine (R-MVP), rituximab/methotrexate/temozolomide (R-MT), or rituximab/methotrexate (R-M) for induction followed by consolidation with etoposide/cytarabine (EA), high-dose cytarabine (HIDAC), or high-dose chemotherapy with autologous stem cell rescue (HDC-ASCR). Cost to health system was derived from a Value Driven Outcomes tool and filtered to compare major costs of treatment. Survival was calculated from the date of diagnosis and last date of known survival. Results: Twenty-two patients met eligibility criteria and received the following four treatment regimens: R-MT+EA (12), R-MT+ HDC-ASCR (3), R-M+ HDC-ASCR (1), and R-MVP+HIDAC (6). Patients receiving HDC-ASCR (4) had a trend towards a more favorable overall survival (p = 0.0880) compared to the other two consolidation therapies with no recurrence or death in those patients treated with HDC-ASCR. Comparative cost analysis of facility and pharmacy costs of the three consolidation techniques found that HDC-ASCR was 40 times the cost of the cheapest treatment, HIDAC. Conclusions: This small retrospective review provides evidence that HDC-ASCR may be a superior consolidation strategy but with a profound increase in financial cost. To our knowledge this is the first study completed in the U.S. comparing treatment outcomes and cost in PCNSL. Based on our results, it is clear that a larger and prospective review could potentially shed light on selecting a standard of care based on cost-benefit analysis.
Survival for oropharyngeal and oral cavity cancer patients based on time to recurrence and HPV status.
Authors: Jeffrey Means, Douglas Stram, Jed Abraham Katzel
Journal: Journal of Clinical Oncology (2020)

e18544 Background: It is unknown whether patients with recurrent oral cavity (OC) or oropharyngeal squamous cell carcinoma (OPSCC) have improved survival if the recurrence occurs beyond one year. We analyzed a cohort of recurrent OC/OPSCC patients to study survival outcomes stratified by time to recurrence and human papillomavirus (HPV) status. Methods: From a cohort of 3201 OC/OPSCC patients initially diagnosed between 1/1/2008 and 6/30/2019, 235 recurrent cases were identified. Time from the end of treatment until first recurrence was ascertained by chart review. HPV status was determined by HPV testing or based on anatomical site. Overall survival (OS) rates and median OS time after diagnosis of recurrence was evaluated across the time-to-recurrence and HPV groups using the Kaplan-Meier method. Differences in the survival curves tested for using the log-rank test. Results: 130 (56%) of the recurrent tumors recurred &lt;1 year after end of treatment, and 104 (44%) ≥1 year. Patients with HPV-related tumors that recurred beyond one year had the best survival, with two-year OS at 0.62 (95% CI: 0.42-0.76), while patients with non-HPV related tumors that recurred &lt;1 year had the worst survival, two-year OS of 0.38 (95% CI: 0.28-0.48). HPV-related tumors that recurred &lt;1 year had roughly similar survival (two-year OS of 0.45, 95% CI: 0.30-0.59) to non-HPV-related tumors that recurred &lt; 1 year (two-year OS of 0.51, 95% CI: 0.38-0.62). The log-rank test for difference in survival across time-to-recurrence and HPV groups was significant at p=0.03. Conclusions: In our cohort, patients with HPV-related head and neck cancer with recurrence ≥1 year had improved survival compared to all other recurrent head and neck cancer patients. In addition, our findings suggest that patients with HPV-related head and neck squamous cell carcinoma who recur prior to 12 months have long-term survival similar to patients with HPV-unrelated cancers. This has important implications for clinicians treating patients with recurrent head and neck cancer and may help guide the design of future clinical trials. [Table: see text]
A phase Ib trial of enzalutamide with venetoclax in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Dharmesh Gopalakrishnan, Jason Kirk, John Davis, Saby George, Ellis Glenn Levine, Jan Hendrik Beumer, Leonard Joseph Appleman, Dean Tang, Gurkamal S. Chatta
Journal: Journal of Clinical Oncology (2020)

TPS5599 Background: Androgen receptor (AR) signaling plays an important role in prostate cancer (PCa) cell survival and proliferation. Xenograft and PDX models demonstrate that untreated PCa harbors AR −/lo stem cells not critically dependent on androgens for survival. 1 Furthermore, castration and enzalutamide (enza) leads to expansion of both AR −/lo and AR +/hi resistant clones in xenograft tumors, resulting in two distinct CRPC-propagating populations. 2 However, most current CRPC treatments are directed towards AR +/hi cells. RNAseq revealed that BCL-2 is highly up-regulated in AR −/lo tumors post-castration and in AR +/hi CRPC tumors post-enza. 2 Strikingly, BCL-2, but not BCL-X L and MCL-1, was selectively up-regulated in these xenograft tumors. These results were subsequently validated in patient CRPC datasets. 2,3 Venetoclax (ven), a potent and selective BCL-2 inhibitor, inhibits enza resistance in AR +/hi CRPC and tumor growth in AR −/lo xenograft models. 2 A recent phase I trial of ven combined with tamoxifen showed promising activity in ER + and BCL2 + metastatic breast cancer. 4 We hypothesize that co-targeting AR −/lo and AR +/hi PCa clones with ven and enza will prevent the emergence of enza resistance in human mCRPC. Methods: This is a phase Ib, single-center, single-arm trial of enza (160mg/d) with ven in patients with mCRPC that has progressed on previous therapies which may include anti-androgens. Three dose-levels of ven (400mg, 600mg and 800mg/d q28d) will be evaluated using a 3+3 study design. Fifteen to 18 patients will be enrolled in this phase to assess dose-limiting toxicities, maximum tolerated dose, and recommended phase II dose. Aims of correlative studies include (1) assessing the pharmacokinetic interaction between enza and ven, (2) identification of potentially predictive blood and tissue biomarkers (including pre- and post-treatment CTC levels, expression of BCL2, AR, ARv7 in pre-and post-treatment biopsies and CTCs), (3) measurement of pre- and post-treatment BCL2 expression in peripheral blood mononuclear cells as a surrogate for ven activity, and (4) the development of 3D organoid models from CTCs and biopsies. The trial is open with 3 patients enrolled to dose-level 1, and 2 patients currently at dose-level 2. Correlative studies are ongoing. References: (1) Qin J, et al. Cell Stem Cell. 10(5): 556-69, 2012 (2) Li Q, et al. Nat Commun. 9(1): 3600, 2018 (3) Rajan P, et al. Eur Urol. 66 (1):32-9, 2014 (4) Lok SW, et al. Cancer Discov. 9(3):354-69, 2019. Clinical trial information: NCT03751436 .
Tail-phase safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in HIV-uninfected adults: a secondary analysis of the HPTN 077 trial
Authors: Raphael J Landovitz, Sue Li, Joseph J Eron, Beatriz Grinsztejn, Halima Dawood, Albert Y Liu, Manya Magnus, Mina C Hosseinipour, Ravindre Panchia, Leslie Cottle, Gordon Chau, Paul Richardson, Mark A Marzinke, Susan H Eshleman, Ryan Kofron, Adeola Adeyeye, David Burns, Alex R Rinehart, David Margolis, Myron S Cohen, Marybeth McCauley, Craig W Hendrix
Journal: The Lancet HIV (2020)
克罗恩病与肠结核的临床病理鉴别诊断
Authors: 马红梅, 汪福良, 陶海莉
Journal: BMJ (2007)

对两所大型省级医院近5年来确诊的45例克罗恩病与43例肠结核病例进行回顾分析.结果 显示两者临床表现相似.内镜下卵石样、节段性改变仅见于克罗恩病,与肠结核有明显差别;病理学检查裂隙样溃疡、肠系膜淋巴结增生在克罗恩病多见,干酪性肉芽肿仅见于肠结核病.提示临床病理学检查对二者鉴别诊断具有参考意义。
Clinical analysis of 16 cases with SAPHO syndrome
Authors: Feng-chun Zhang
Journal: BMJ (2012)

The clinical data of 16 patients with synovitis,acne,pustulosis,hypemstosis,osteitis (SAPHO) syndrome were retrospectively analyzed.There were 7 men and 9 women with a mean age of (38 ± 11) years at onset and middle-aged females predominated.The most common clinical manifestations were palmoplantar pustulosis and osteoarticular disease involving anterior chest wall,spondylarthrilides and shoulder joint.ECT was the sensitive imaging examination for SAPHO syndrome.Combined treatment can alleviate symptoms of the disease.

Key words: 
Acquired hyperostosis syndrome; Diagnosis; Therapy
改良超滤在10 kg以下婴幼儿体外循环心脏手术中的应用
Authors: 刘英军, 柳尧林, 肖剑光
Journal: BMJ (2006)

改良超滤是近几年为减少因体外循环导致的婴幼儿全身水分增加及组织水肿而采用的一项新技术,莱州市人民医院自2000年起在10kg以下婴幼儿心内直视手术体外循环中应用改良超滤,收到良好效果,报告如下。
Cardiotoxicity after chemoradiation for locally advanced esophageal cancer: Contributions of substructure and whole heart dose-volume parameters to risk prediction.
Authors: Guoxin Cai, Jinming Yu, Xue Meng
Journal: Journal of Clinical Oncology (2020)

e16576 Background: To investigate the predictive value of substructure and whole heart dosimetric parameters for cardiotoxicity and overall survival (OS) in patients with esophageal cancer receiving concurrent chemoradiation (cCRT). Methods: We retrospectively reviewed the records of 125 patients with stage Ⅲ middle and lower thoracic esophageal cancer treated with cCRT from 2011 to 2015. The primary endpoint was grade ≥ 2 cardiac events and the second endpoint was OS. Dose-volume histogram parameters for whole heart, left atrium (LA), left ventricle (LV), right atrium (RA), right ventricle (RV), right coronary artery (RCA), left anterior descending (LAD), left circumflex (LCX), and pericardium were extracted. Automated multivariable logistic regression model selection using the MATLAB-based Dose Response Explorer System was performed. Models were evaluated by Spearman correlation coefficient (Rs) and ROC area. Cox regressions analysis was performed to evaluate the association between covariates and OS. Results: Median follow-up was 32 months. The prescribed dose was 60 Gy. Forty patients (32.0%) developed 44 grade ≥ 2 cardiac events, at a median of 14.5 months to first event. The most frequently observed cardiac events were pericardial effusion or pericarditis (n = 13), arrhythmia (n = 12), acute coronary syndrome (ACS, n = 10), and congestive heart failure (CHF, n = 5). Variables included in the models most frequently selected by bootstrap were age, WHO/International Society of Hypertension (ISH) risk score and mean LA dose (Rs = 0.36, AUC = 0.796, p &lt; 0.001) for all cardiac events; age, WHO/ISH risk score and pericardium volume receiving ≥ 20 Gy (Rs = 0.33, AUC = 0.771, p &lt; 0.001) for pericardial events; age, mean LA dose and RA volume receiving ≥ 5 Gy (Rs = 0.31, AUC = 0.754, p &lt; 0.001) for arrhythmic events; and WHO/ISH risk score, mean LA dose and LCX volume receiving ≥ 30 Gy (Rs = 0.37, AUC = 0.812, p &lt; 0.001) for ACS/CHF events. On multivariable analysis, disease progression, Eastern Cooperative Oncology Group (ECOG) performance status, mean LA dose, and gross tumor volume were significant predictors of OS. Conclusions: Whether for whole cardiac, pericardial, arrhythmic or ischemic events, models including corresponding substructure dose outperformed those with whole heart dose in risk prediction. High cardiac substructure dose was associated with a worse OS.
Serum soluble Fas levels in malignant melanoma patients and its clinical significance
Authors: Jing Liu, Yong-chen Wang
Journal: BMJ (2009)

Serum soluble Fas (sFas) levels were detected by enzyme-link immunosorbent assay (ELISA) in 19 cases of malignant melanoma and 21 healthy subjects. There were statistically significant differences in serum sFas levels between malignant melanoma patients and healthy subjects (median 28.47μg/L, 4. 67 μg/L; U=5. 376, P <0. 01 ). No correlation was observed between serum sFas levels and gender or age of the patients. There was a significant difference in serum sFas levels either between groups with different TNM stages or between groups with and without distant metastasis (Ustage=3. 220,Udistant metastasis = 3. 240, P < 0. 01 ). Our results show that serum sFas levels were correlated with the progression of malignant melanoma, and it indicates that serum sFas may sever as an indicator for the progression of malignant melanoma.

Key words: 
Melanoma;  Soluble Fas
Oral oncolytic education and adherence monitoring in poor, rural and minority patients.
Authors: Tiffany Menhorn, Amy Zarick-Jones, Moises Harari Turquie, Shenthol Sasankan, Neda Hashemi-Sadraei, Zoneddy R. Dayao, Richard C. Lauer, Bernard Tawfik, Harmony Bowles, Nick Crozier
Journal: Journal of Clinical Oncology (2020)

e19212 Background: Oral oncolytics therapy use has been exponentially growing over the last several years necessitating education and monitoring. Pharmacy driven interventions have been shown to increase side effects detection, mitigation and ensure adherence. The University of New Mexico Comprehensive Cancer Center (UNMCCC) treats a unique population composed of poor (poverty rate 19.7%), rural (22.6%) and minority (Native Americans and Hispanics constitute 10.4% and 48% of the population respectively). Methods: New patients starting oral oncolytics were enrolled from May 2019 to January 2020 with an initial 30-minute educational visit with a pharmacist. UNMCCC initiated a pharmacy driven process of tracking patients via phone calls to monitor compliance, early presence of adverse events and issues surrounding the administration of oral oncolytics. Phone calls were conducted monthly for three months and then spaced out depending on patient and drug characteristics. Late education occurred when the initial education was performed after the patient started chemotherapy. Late first follow-ups occurred when the follow-up date was greater thirty-eight days after the start of chemotherapy. Results: A total of 196 patients started on oral chemotherapy of which 70% (139) received education following prescription, 17% (35) received late education and 11% (22) missed education. Newly started actively monitored patients significantly increased to 196 patients by the ninth month of the program. A total of 296 follow ups calls were performed within the first three months, 41% (111) were considered late follow-up. The first, second and third call were missed in 18% (49), 14% (40) and 16% (45) of patients. Conclusions: The UNMCCC cares for poor, rural and minority based patients and was able to reach the majority of patients in a timely manner for education and adherence monitoring. Our efforts were significantly hampered by the increasing number of active patients needing monitoring as the program progressed which will require further resources including, a close collaboration between physicians and pharmacists to provide a service that was previously absent and process changes which we are addressing as our next steps.
Effects of nutritional education on knowledge, attitude and practice among hospitalized elderly patients
Authors: Peng Liu, Bo-shi Wang, Jing L
Journal: BMJ (2011)

One hundred and twenty elderly inpatients (average aged 78) were randomly sampled from the Department of Geriatrics, Peking University People's Hospital for a questionnaire survey on the knowledge, attitude and practice (KAP) before and after receiving nutritional education. The results showed that the average score for nutrition knowledge of the subjects was 46 ± 21 and 85 ± 18 before and after nutrition education respectively (P ＜0. 01 ); the progress for patients aged over 80 was more remarkable:nutrition knowledge score increased to 83 ± 18 from 41 ±21 on the admission ( P ＜0. 01 ). Before nutritional education, the rates of treatment diet implementation, ordinary diet implementation and hospital repast were 48.9%, 57.7% and 50. 8%, respectively, which reached to 93. 6%, 100. 0% and 95.0% after nutritional education (P ＜0. 01 ). The results indicate that the nutrition education is an effective approach to improve nutritional KAP among elderly inpatients. We propose to implement nutrition education in elderly inpatients as a routine clinical treatment measures.

Key words: 
Health education;  Health knowledge,attitudes,practice
避孕方法选择的原则
Authors: 范光升
Journal: BMJ (2010)

随着科学技术的发展、社会的进步,人们对生殖健康的需求也逐渐增加.近年来,我国妇女生殖健康状况不断改善,但仍面临许多问题,如不安全性行为引起的非意愿妊娠、性行为的提前、未婚性行为的增加,以及由此导致的人工流产、不孕症、生殖道感染.要改善这一现状,需要对育龄男女提供生命周期各阶段的优质生殖健康服务,提供最广泛的信息及技术服务。