tbuckley/cabot-search huggingface dataset:
A phase I/II study of REGN5093, a MET x MET bispecific antibody, in patients with MET-altered advanced non-small cell lung cancer (NSCLC).
Authors: Tracey Rowlands, Anita Boyapati, Siyu Li, Christopher Daly, Frank A. Seebach, Israel Lowy, Petra Rietschel
Journal: Journal of Clinical Oncology (2020)

TPS9628 Background: Mesenchymal-epithelial transition (MET) factor is a transmembrane tyrosine kinase receptor activated by hepatocyte growth factor (HGF). Aberrant activation of MET via gene amplification or gene mutations, as well as MET protein overexpression, has been reported in NSCLC and other cancer types and can promote tumorigenesis. REGN5093 is a human bispecific antibody that binds to two distinct epitopes of MET, blocking HGF binding and inducing internalization and degradation of MET. REGN5093 prevents MET-mediated signaling and inhibits growth of MET-driven tumor cells without inducing MET-driven biological responses (DaSilva et al, CCR, 2019; PMID: 31848185). Methods: This Phase I/II, first-in-human, multicenter study is investigating the safety, tolerability, pharmacokinetics (PK), and efficacy of REGN5093 in patients with MET-altered advanced NSCLC who have received all available approved therapies (NCT04077099). Key eligibility criteria include age ≥18 years, Eastern Cooperative Oncology Group performance status of ≤1, and documented presence of either MET exon 14 gene mutation and/or MET gene amplification and/or elevated MET protein expression. Patients are required to provide a biopsy during screening for assessment of MET biomarkers. Key exclusion criteria include prior MET-targeted biologic therapy (expansion cohorts only). Prior therapy with tyrosine kinase inhibitors are not exclusionary in any part of the study. For each patient, the study comprises a screening period of up to 28 days, followed by 3-week cycles of REGN5093 monotherapy. Study treatment will continue until confirmed disease progression or other protocol-defined reason for discontinuation. The study has two parts: dose escalation and dose expansion. Dose escalation will proceed via 4+3 design until a maximum-tolerated dose is reached or a recommended Phase II dose selected. The primary objective of the dose escalation part is to assess safety (incidence and severity of adverse events and Grade ≥3 laboratory abnormalities), tolerability (incidence of dose-limiting toxicities), and PK of REGN5093. During the expansion phase, patients will be allocated to cohorts according to the type(s) of documented biomarkers of MET-altered disease. Anti-tumor activity based on objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, determined by CT or MRI, will be the primary endpoint in the expansion cohorts. The study is currently open for enrollment. Clinical trial information: NCT04077099 .
Correlation of visual field with corneal changes in angle closure glaucoma
Authors: Shengrong Ni, Qinmei Wang
Journal: BMJ (2017)

Forty four patients(84 eyes)with primary chronic angle closure glaucoma, including 14 cases(26 eyes)with mild visual field defect, 22 cases(42 eyes)with moderate defect and 8 cases(16 eyes)with severe defect, treated in our hospital from January 2014 to January 2016 were enrolled in the study. The visual field defect (MD), corneal endothelial cell density (ECD) and central corneal thickness (CCT) were measured. The average CCT in mild, moderate and severe visual field defect groups was (531.4±27.1) μm, (521.2±31.4)μm and(513.3±28.2)μm, respectively (F=-3.24, P=0.04). The mean endothelial cell density in three groups was (2 635.0±320.3) cells/mm2, (2 619.2±161.4) cells/mm2 and(2 589.7±290.4)cells/mm2, respectively (F=0.22, P=0.80). The results indicate that with the aggravation of visual field defect in patients with chronic angle closure glaucoma, the central corneal thickness is significantly thinner, and the mean density of central corneal endothelial cells shows a downward trend. Close observation and active intervention are needed for chronic angle closure glaucoma with thin central corneal thickness.


Key words: 
Visual fields defect; Corneal endouthelial cell loss
Getting Value From Electronic Health Records: Research Needed to Improve Practice
Authors: Robert S. Rudin, Mark W. Friedberg, Paul Shekelle, Neel Shah, David W. Bates
Journal: Annals of Internal Medicine (2020)

Electronic health records (EHRs) are now widely adopted in the United States, but health systems have barely begun using them to deliver high-value care. More directed and rigorous research is needed to fulfill the promise of EHRs to not only store information but also support the delivery of better care. This article describes 4 potential benefits of EHR-based research: improving clinical decisions, supporting triage decisions, enabling collaboration among the care team (including patients), and increasing productivity via automation of tasks. Six recommendations are made for conducting and reporting research to catalyze value creation: develop interventions systematically by using user-centered design and a building-block approach; assess value in terms of cost, quality, outcomes, and work required of providers and patients; consider the time horizon for the intervention; test best practices for implementation in a range of real-world contexts; assess subtleties of behavior change tools used to improve high-value behaviors; and report the intervention in enough detail that it can be replicated, including context. Just as research played a critical role in developing early EHR prototypes and demonstrating their value to justify dissemination, research will continue to be essential in the next phase: expanding EHR-based interventions and maximizing their role in creating value.
Analysis of health checkup results for elders over 65 in a Shanghai community
Authors: Peng-fei Han
Journal: BMJ (2012)

A total of 1273 elders above 65 years old received health check-up in our community.Among them,63.3％ ( 806/1273 ) had a history of hypertension and 64.9％ ( 523/806 ) showed abnormal blood pressure.And 43.2％ (202/467) of those without a history of hypertension were firstly found to have abnormal blood pressure.Among 674 blood testers,19.6％ had an elevated level of fasting blood glucose.And 11.4％ of those without a history of diabetes had an elevated level of fasting blood glucose.Hyperuricemia (21.8％,n =147),hypercholesteremia ( 11.1％,n =75),hypertriglyceridemia (35.5％,n =239) and increased low density lipoprotein-cholesterol (LDL-C) (46.3％,n =312) were noted.The levels of total cholesterol and LDL-C were higher in females than those in males ( both P ＞ 0.05 ).The results suggested that general practitioners should pay more attention to the management of chronic diseases and the health education and screening of high-risk populations.

Key words: 
Physical examination; Chronic disease
Current status in studies on polymyositis and dematomyositis
Authors: 周佳鑫, 唐福林
Journal: BMJ (2006)

多发性肌炎(polymyositis,PM)和皮肌炎(dematomyositis,DM)均属特发性炎性肌病(idiopathic inflammatory myopathy,ⅡM).此外,ⅡM还包括包涵体肌炎(inclusion body myositis,IBM)[1].目前认为PM和DM属于自身免疫性疾病,IBM的免疫反应继发于骨骼肌细胞的退行性变[2].现主要介绍对PM和DM的一些认识。
Effects of GC4419 (avasopasem manganese) on chronic kidney disease in head and neck cancer patients treated with radiation and cisplatin.
Authors: Emily J. Steinbach, Varun Monga, Muhammad Furqan, Douglas Earl Laux, Diana Zepeda-Orozco, Jennifer G. Jetton, Deborah Saunders, Neal Dunlap, Amarinthia Curtis, Robert Fairbanks, Sarah Bell, Carryn M. Anderson, Robert Alan Beardsley, Jon Holmlund, Douglas Spitz, Bryan G. Allen
Journal: Journal of Clinical Oncology (2020)

12071 Background: Nephrotoxicity is a major complication of platinum-based chemotherapy and ranges in incidence from 31-68%. The effects of platinum-based chemotherapeutics on long-term renal outcomes (chronic kidney disease, CKD) profoundly affect morbidity and mortality. Concurrent chemoradiotherapy (CRT) including cisplatin is standard for locally advanced squamous cell head and neck cancer (HNC) but is accompanied by the risk of CKD. In a randomized, multi-center, placebo-controlled Phase 2b trial ( NCT02508389 ) of GC4419 (avasopasem manganese) in HNC patients receiving CRT, avasopasem reduced the duration, incidence, and severity of severe oral mucositis (Anderson et al, JCO 2019). Avasopasem did not appear to alter the safety profile of CRT in that trial, including incidence of adverse events of kidney injury or azotemia. Methods: Pre- and post-treatment markers of kidney function including blood urea nitrogen (BUN), serum creatinine (sCr), and estimated glomerular filtration rate (eGFR) were retrospectively evaluated for a subset of 52 of the trial patients who received 3 cycles x 100 mg/m 2 cisplatin plus placebo or 30 or 90 mg of avasopasem intravenously prior to RT, and 7 comparator patients who received the same CRT outside the study. Kidney function was evaluated between 3- and 24-months post-completion of cisplatin-radiation therapy by two-way analysis of variance (ANOVA) as defined by the Kidney Disease Improving Global Outcomes (KDIGO) CKD staging. Results: Baseline patient characteristics were skewed towards a male population but were balanced across all treatment arms with regards to baseline kidney function (comparator + placebo, n = 19; 30 mg GC4419, n = 18; 90 mg GC4419, n = 15). Treatment with 90 mg GC4419 demonstrated normal BUN values (10-20 mg/dL) at 3, 6, and 18 months and normal sCr values (0.6-1.2 mg/dL) between 3 and 24 months as compared to the placebo arm + comparator group, which exhibited statistically elevated BUN and sCr (p &lt; 0.05). Treatment with 90 mg GC4419 also demonstrated significantly higher eGFR between 3 and 24 months post-chemoradiation (p &lt; 0.05) compared to the placebo arm + comparator group. 90 mg GC4419 treatment significantly reduced the incidence of CKD compared to the placebo arm and comparator group, as determined by fold change in sCr values and eGFR measurements &lt; 60 mL/min (stage G3a/b, G4, or G5 CKD). Conclusions: Avasopasem has the potential to reduce the incidence and severity of CKD in patients receiving cisplatin therapy. Clinical trial information: NCT02508389 .
Clinical analysis of acute primary Vogt-Koyanagl-Harada syndrome
Authors: Jie Zhang, Xiaomei Meng
Journal: BMJ (2016)

The clinical characteristics, therapeutic effects and complications of 32 incipient patients with acute Vogt-Koyanagi-Harada (VKH) syndrome admitted in Wuxi Second Hospital during October 2010 to September 2013 were retrospectively analyzed. There were 15 males and 17 females with a mean age of (41.3±14.1) years (22-71 years), the time from the disease onset to treatment ranged from 3 to 20 days. Among 32 cases, 30(94%) had premonitory symptoms. The multifocal bullous neurosensory detachment, optic disk hyperemia and edema in posterior pole of fundus were found in all cases, and exudative retinal detachment was found in 4 cases (6 eyes). The results of optical coherence tomography (OCT) showed the macula neurosensory detachment, thick retinal neuroepithelial layer and wavy RPE layer in all patients. Fundus fluorescein angiography (FFA) showed that scattered hyperfluorescence dots and cystic fluorescein reservoir was observed in early phase and later period respectively. Patients received intravenous methylprednisolone with the onset dose of 80 mg per day for 3-7 days and oral administration followed, which would gradually decrease later; the average treatment duration was (52.9±14.6) weeks. The visual acuity of 40 eyes (22 cases) was recovered to more than 0.8, and no blindness occurred after the treatment. During the treatment hair loss, depigmentation of skin and hair were found in 12 cases (38%), and 2 cases showed short-term elevated intraocular pressure. These symptoms disappeared after drug therapy ceased. And no recurrence was found during the follow-up of 6 months. However, sunset glow fundus was found in 13 patients (26 eyes). The study shows that the diagnosis of VKH syndrome is based on the typical signs of the fundus presented on OCT and FFA. Early and systemic administration of glucocorticoids is important treatment for patients with VHK syndrome, which could decrease systemic and local complications effectively.


Key words: 
Uveitis; Uveomenigo-encephalitic syndrome
Effect of neoadjuvant chemotherapy on health-related quality of life in patients with muscle invasive bladder cancer: Results from JCOG0209, a randomized phase III study.
Authors: Naotaka Nishiyama, Hiroshi Kitamura, Shiro Hinotsu, Taiji Tsukamoto, Taro Shibata, Junki Mizusawa, Takashi Kobayashi, Makito Miyake, Takahiro Kojima, Hiroyuki Nishiyama
Journal: Journal of Clinical Oncology (2020)

e17006 Background: Although neoadjuvant chemotherapy (NAC) provides survival benefits in muscle-invasive bladder cancer (MIBC), the impact of NAC on health-related quality of life (HRQoL) has not been investigated by a randomized trial. The purpose of this study is to compare HRQoL in patients with MIBC who received NAC followed by radical cystectomy (RC) or RC alone based on patient-reported outcome data. Methods: Patients were randomized to receive 2 cycles of neoadjuvant methotrexate, doxorubicin, vinblastine, and cisplatin (MVAC) followed by RC or RC alone. HRQoL was measured using the Functional Assessment of Cancer Therapy – Bladder (FACT-BL, version 4) questionnaire before the protocol treatments, after NAC, after RC, and one year after registration. Results: A total of 99 patients were analyzed. No statistically significant differences in postoperative HRQoL were found between the arms. In the NAC arm, the scores after NAC were significantly lower than the baseline scores in physical well-being, functional well-being, FACT-General total, weight loss, diarrhea, appetite, body appearance, embarrassment by ostomy appliance, and total FACT-BL. However, there was no difference in scores for these domains, except for embarrassment by ostomy appliance, between the two arms after RC and one year after registration. Conclusions: Although HRQoL declined during NAC, no negative effect of NAC on HRQoL was apparent after RC. These data support the view that NAC can be considered as a standard of care for patients with MIBC regarding HRQoL. Clinical trial information: C000000093.
乙型肝炎病毒血清学标志物临床意义解读
Authors: 何卫平, 赵军
Journal: BMJ (2010)

乙型肝炎病毒(HBV)感染后可演变为急慢性肝炎、肝硬化、肝衰竭和原发性肝癌等多种临床形式,是严重危害人类健康的全球性公共卫生问题.我国是乙型肝炎的高发区,大约10%的人感染和携带HBV,对HBV感染及时准确地监测有利于乙型肝炎的防治.目前HBV感染的血清学标志物仍是临床实验室诊断最主要的检测指标之一.正确理解HBV感染血清学标志物的临床意义,对乙型肝炎的临床诊断、治疗疗效及预后的观察均有重要的意义。
Relationship between arterial elasticity and tobacco exposure in urban and rural residents of north China
Authors: Jiang Xie, Xian Wang, Da-yi Hu, Ya-li Luo, Jin-wen Wang
Journal: BMJ (2009)

Objective To study tobacco exposure in urban and rural residents of north China with serum cotinine as its indicator and explore its destructive effects on their arterial elasticity.Methods In total, 897 volunteers who visited Beijing Army General Hospital in Beijing and Julu County Hospital in Hebei for regular physical check-ups were recruited for this study.Blood specimen was collected from them for cotinine determination.Serum level of cotinine more than 1 ng/ml was conformed as exposure to tobacco.Brachial-ankle pulse wave velocity (baPWV) was measured using an automatic device.Results Two hundred and eighty-nine of 897 participants (32.2%) were obviously exposed to tobacco, with prevalence of tobacco exposure more in rural Julu than in urban east Beijing (34.8% vs.25.0%, P=0.006).baPWV in exposed participants was significantly higher than that in non-exposed ones (1429 cm/s vs.1393 cm/s, P=0.017) adjusted for covariates.Among non-exposed participants, baPWV in residents of urban east Beijing was significantly higher than that in those of rural Julu (1447 cm/s vs.1380 cm/s, P=0.001).But, there was no significant difference in baPWV between the residents of two areas with severe and mild tobacco exposure.Conclusions Worse arterial elasticity can be determined by serum cotinine determination.Effects of tobacco exposure on arterial elasticity in residents of poor areas in north China were more than those in urban residents.

Key words: 
Tobacco;  Cotinine;  Brachial-ankle pulse wave velocity
Clinical features and outcomes of neuroblastomas in adults.
Authors: Dawood Findakly, Eric Nguyen, Jue Wang
Journal: Journal of Clinical Oncology (2020)

e14546 Background: Neuroblastomas (NBs) are a spectrum of primitive tumors that include Esthesioneuroblastoma (ENB), and both neuroblastoma (NB) and ganglioneuroblastoma (GNB). NB and GNB are prevalent in children and rare in adults with a paucity of data on their therapy and outcomes. This review is to investigate the clinicopathologic features, treatment, and outcomes of NBs in adults. In addition, we highlight genomic findings of a 63-year-old man treated at our institution and discuss ALK-inhibition as a novel treatment strategy for ALK-driven adult-onset NB. Methods: PubMed literature search for NB adults (19+ years) for the period 2000 – 2020 pooled with a case from our institution. Results: Of the 163 included cases, 105 were ENB, 40 were NB, and 18 were GNB. Male:female ratio (1.50:1, 1.29:1, and 1.83:1 respectively). Mean age at diagnosis (49.8, 39.3, and 38.8 respectively). Most common primary site was sinonasal (60%) in ENB, retroperitoneal (20%) in NB, and adrenal (22%) in GNB. Metastasis found in 31.4%, 42.0%, and 16.7% with a mortality rate of 45%, 53%, and 33% respectively. Most common treatment modality overall was surgery with radiation in ENB (35%), Surgery with chemotherapy in NB (28%) and surgery alone in GNB (50%). Most common treatment modality in metastatic cases was surgery with chemoradiation in ENB (50%), surgery with chemotherapy in NB (36%), and surgery alone in GNB (33%). In our patient, ALK gene (R1275Q) gain of function mutation found both in molecular profiling and genomic circulating DNA analysis. Conclusions: Metastatic NB in adults is associated with very high mortality. Their rarity, heterogeneity of clinical behaviors, diverse treatment regimens, and variable outcomes make them even more challenging. The findings of this study would improve our understanding and develop multidisciplinary management strategies for this rare malignancy in adults. Moreover, further research focusing on the potential novel treatment with ALK-targeted inhibitors may hold promise to improve survival outcomes in adult-onset ALK-positive NB. [Table: see text]
Neoadjuvant chemotherapy in locally advanced breast cancer: Clinicopathological characteristics and correlation with pathological complete response.
Authors: Priyanshu Choudhary, Ajay Gogia, Svs Deo, Sandeep Mathur, Dayanand Sharma
Journal: Journal of Clinical Oncology (2020)

e12658 Background: The data regarding incidence, response rates to neoadjuvant chemotherapy (NACT) and factors affecting pathological complete response (pCR) rate in locally advanced breast cancer (LABC) patients are lacking from India. Methods: This ambispective study was carried out at B.R.A., I.R.C.H, AIIMS, New Delhi, in between period of January 2013 to December 2019. We screened 1500 cases of breast cancer who presented to our institute and found 600 cases to be LABC,425 patients were started on NACT, 284 had undergone surgery and were included in our analysis. Results: The median age of diagnosis was 46 years (range 24-72years). Fifty four percent cases were postmenopausal, 54% had a left sided cancer,45 % right sided cancer,1 % had bilateral breast cancer. The median duration of symptoms was 5 months. The clinical stage according to AJCC staging system was Stage IIB – 11%(32), IIIA -21 % (58), IIIB- 60%(169) and IIIC- 8%(24) .Sixty five percent(186) cases presented with clinical skin involvement and 80% (228) patients has clinical node positivity.In our cohort 52% (148) cases were hormone positive (ER/PR positive), 42 %(119) cases were HER2/neu positive, 30%(84) were triple negative breast cancer (TNBC), 23 % (67) were positive for ER/PR and HER2/neu. Ninety percent of the cases were able to receive the planned neoadjuvant treatment before surgery. Post NACT 83% cases had a modified radical mastectomy (MRM) and 17% were able to undergo breast conserving surgery (BCS).Overall pCR was achieved in 59(21%) cases, 17% in hormone positive cases, 25% in HER2/neu positive cases (30% in cases receiving HER2/neu directed therapy vs 20% in cases who didn’t receive HER2 /neu directed therapy) and 27% in TNBC cases. During the study period 54 cases (19%) had relapsed,8 cases (3%) had a local relapse and a 46 cases (16%) had a systemic relapse. Grade ¾ toxicity occurred in 25 % cases, the most common were diarrhea, neutropenia, CINV, oral mucositis and thrombocytopenia and other rare toxicities (DVT, hand foot syndrome,myalgia). Febrile neutropenia was recorded in 2.5 % cases. There were 2 induction deaths. Stage II, absence of ER/PR expression showed statistically significant correlation with path CR rates. Conclusions: Locally advanced breast cancer constitutes around 40% cases at our institute. Post NACT pCR was achieved in 21% of cases, HER2/neu positive cases and TNBC showed higher pCR rates. The factors affecting pCR rate were absence of ER/PR expression and stage II disease.
基底动脉尖综合征二例磁共振影像分析
Authors: 刘晓林, 刘志钦, 戈明媚, 王秋良
Journal: BMJ (2009)

基底动脉尖综合征(top of basilar artery syndrome,TOBS)是特殊类型的脑梗死,是基底动脉尖端部位血液循环障碍引起的一组临床综合征,临床表现多样,起病凶险,病死率高[1].磁共振成像(MRI)能帮助临床早期诊断、评估预后。
Real-world study of the treatments following trastuzumab-emtansine for HER2-positive metastatic breast cancer: A multicentral cohort study (WJOG12519B).
Authors: Sasagu Kurozumi, Takamichi Yokoe, Kazuki Nozawa, Yukinori Ozaki, Tetsuyo Maeda, Shu Yazaki, Mai Onishi, Akihiro Fujimoto, Sayuka Nakayama, Yuko Tsuboguchi, Tsutomu Iwasa, Hitomi Sakai, Misato Ogata, Mitsuo Terada, Meiko Nishimura, Takuma Onoe, Jun Masuda, Michiko Kurikawa, Mototsugu Shimokawa, Toshimi Takano
Journal: Journal of Clinical Oncology (2020)

e13019 Background: Since trastuzumab emtansine (T-DM1) was established as a standard treatment option, the treatment strategy of metastatic HER2-positive breast cancer has markedly changed. However, clinical evidence regarding the treatments beyond T-DM1 is insufficient. In this study, we attempted to describe real-world selection and efficacy of treatments following T-DM1 for metastatic HER2-positive breast cancer. Methods: This multi-center retrospective cohort study was conducted in 17 hospitals in Japan. Consecutive patients with metastatic HER2-positive breast cancer who had received T-DM1 and started post-T-DM1 treatments between January 2014 and December 2018 were enrolled. Patients treated with investigational drugs were excluded. The primary endpoint was objective response rate (ORR) of post-T-DM1 treatments. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). Results: In this study, 325 patients were eligible, of which 182 (56.0%) cases were estrogen receptor-positive and 61 (18.8%) had brain metastases. T-DM1 had been used as the first to 11th (median third) line treatment for metastatic disease. The types of post-T-DM1 treatment were as follows: 1) chemotherapy concomitant with trastuzumab and pertuzumab (n = 102; 31.4%), 2) chemotherapy concomitant with trastuzumab only (n = 78; 24.0%), 3) lapatinib with capecitabine (n = 63; 19.4%), and 4) others (n = 82; 25.2%). ORR of post-T-DM1 treatments was 22.8% (95% confidence interval [CI]: 18.1 to 28.0) and DCR was 66.6% (95% CI: 60.8 to 72.0), calculated with 290 eligible cases with the target lesion. Median PFS was 6.1 months (95%CI: 5.3 to 6.7), median TTF was 5.1 months (95%CI: 4.4 to 5.6), and median OS was 23.7 months (95%CI: 20.7 to 27.4). Conclusions: This real-world study showed that post-T-DM1 treatments had modest anti-tumor activity. Development of more effective treatments beyond T-DM1 is needed for metastatic HER2-positive breast cancer. Clinical trial information: UMIN000037747 .