tbuckley/cabot-search huggingface dataset:
Fracture risk and survival outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) sequentially treated with abiraterone acetate (AA) and radium-223 (RA223).
Authors: Orazio Caffo, Viviana Frantellizzi, Marcello Tucci, Luca Galli, Fabio Monari, Sergio Baldari, Cristina Masini, Roberto Bortolus, Gaetano Facchini, Pierpaolo Alongi, Clizia Zichi, Elisa Biasco, Stefano Fanti, Salvatore Pignata, Angelina Filice, Eugenio Borsatti, Sabrina Rossetti, Massimiliano Spada, Enrico Cortesi, Giuseppe De Vincentis
Journal: Journal of Clinical Oncology (2020)

e17593 Background: The increased incidence of bone fractures found in pts who received the AA-RA223 combination compared to those treated with AA alone in the ERA223 trial led to restrictive recommendations by the European Medicines Agency which limited the use of RA223 to pts who have received at least two previous treatments for mCRPC or who cannot receive any other treatment. Moreover, clinicians started to debate the risk of RA223-related fractures associated with the sequential administration of AA and RA223. The aim of this retrospective study was to assess the safety of administering RA223 to pts who have progressed during AA treatment mainly in terms of the rate of skeletal fractures. Methods: We retrospectively reviewed the records of mCRPC pts who received RA223 after progressing during an AA treatment line in everyday clinical practice in ten Italian Hospitals. Results: We reviewed data of a consecutive series of 94 mCRPC pts. Most of the pts (85.1%) received RA223 as second- or third-line treatment and had a Soloway score 2 or 3 (90%). RA223 treatment was well-tolerated: there were only four cases of grade 3 anemia, two case of grade 3 leukopenia, and one case of grade 3 neutropenia. The overall fracture rate of 2.1%: one fracture was recorded during the course of RA223 treatment, and one was recorded one month after its end. The fractures both occurred at metastatic sites in pts who were not treated with antiresorptive agents. Median overall survival (OS) from RA223 start was more than 14 mos and the pts who received Ra223 in second line (which is not allowed today in Europe) had the same median OS as those who received this agent in later lines. Conclusions: The findings of this study showed that the treatment with RA223 as subsequent treatment line after AA was active and safe with a very low risk of a fracture. The OS outcomes indicated that the administration of RA223 in early treatment lines is not detrimental, even after AA. Thus the present observational report makes a valuable contribution to the current debate concerning the risks and benefits of including RA223 in the therapeutic algorithm.
Population-adjusted indirect treatment comparison (PAITC) of maintenance PARP inhibitor (PARPi) with or without bevacizumab versus bevacizumab in women with newly diagnosed ovarian cancer (OC).
Authors: Robert Hettle, Charles McCrea, Chee Khoon Lee, Richard Davidson
Journal: Journal of Clinical Oncology (2020)

6052 Background: In patients (pts) with newly diagnosed OC, bevacizumab (B), PARPi, and PARPi + B have shown benefit as maintenance treatment options after platinum chemotherapy response. Phase III trials have demonstrated longer median progression-free survival (PFS) with PARPi + B (PAOLA-1, olaparib [O]; NCT02477644) vs placebo (P) + B and with PARPi alone (PRIMA, niraparib [N]; NCT02655016) vs P. As there are no randomized head-to-head trials comparing PARPi + B vs PARPi, or PARPi vs B, we performed indirect treatment comparison across these regimens. Methods: Unanchored PAITC was performed with individual pt data (IPD) from a PAOLA-1 subset comprising pts with stage IV disease, stage III with residual disease after primary surgery, inoperable stage III disease, or any patient who received neoadjuvant chemotherapy. Propensity weights were used to match the baseline (BL) characteristics of the PRIMA population. PRIMA dataset was reconstructed using published PFS curves. Both datasets were pooled; treatment efficacy was assessed by weighted Cox regression and Kaplan–Meier methods. PAITC was performed in all pts (biomarker unselected) and the homologous recombination repair deficiency positive (HRD+; cut-off 42) subgroup. Results: 595/806 (266/387 HRD+) PAOLA-1 pts were included. After matching, the effective sample size (ESS) for PAOLA-1 was 532 (242 HRD+; weights 0.241–2.37). Weighted BL data were balanced across cohorts. Conclusions: In biomarker-unselected and HRD+ pts, PAITC suggests that adding O to B significantly improved PFS vs. N or B alone. In biomarker-unselected pts, PAITC results show no significant difference in PFS between N and B. In HRD+, improved efficacy with N appears to translate into improved PFS vs. B alone, although follow-up was &lt;2 years (14 vs 22 months, respectively). Results are hypothesis generating and could guide randomized trial design. Clinical trial information: NCT02477644 and NCT02655016. [Table: see text]
Clinical value of combined examination of transient and steady-state flash visual evoked potential
Authors: Feng-lan Zhang, Ying Sun
Journal: BMJ (2010)

The study intended to evaluate the combined examination of transient flash visual evoked potential (T-FVEP) and steady-state flash visual evoked potential (SS-FVEP) in diagnosis of optic neuropathy and macular disease. T-FVEP and SS-FVEP were examined in 22 cases (29 eyes) with optic neuropathy, 8 cases (9 eyes) with macular disease and 32 cases (32 eyes) of controls. The positive rates of T-FVEP and SS-FVEP in diagnosis of optic neuropathy were 83% and 100% respectively; that of combined examination was 100%. The positive rates of T-FVEP and SS-FVEP in diagnosis of macular disease were 5/9 and 7/9, and that of combined examination was 8/9. The positive rates of combined examination of T-FVEP and SS-FVEP in diagnosis of optic neuropathy and macular disease are higher than that of T-FVEP and SS-FVEP alone, and should be used routinely in the diagnosis of visual pathway disease.

Key words: 
Evoked potentials,visual;  Diagnostic tests,routine
Efficacy of Savolitinib vs Sunitinib in Patients With<i>MET</i>-Driven Papillary Renal Cell Carcinoma
Authors: Toni K. Choueiri, Daniel Y. C. Heng, Jae Lyun Lee, Mathilde Cancel, Remy B. Verheijen, Anders Mellemgaard, Lone H. Ottesen, Melanie M. Frigault, Anne L’Hernault, Zsolt Szijgyarto, Sabina Signoretti, Laurence Albiges
Journal: JAMA Oncology (2020)

Papillary renal cell carcinoma (PRCC) is the most common type of non-clear cell RCC. Because some cases of PRCC are MET-driven, MET inhibition could be a targeted treatment approach. In previous studies, savolitinib (AZD6094, HMPL-504, volitinib), a highly selective MET-tyrosine kinase inhibitor, demonstrated antitumor activity in this patient group.
Family rehabilitation enhances functional recovery of patients with post-stroke hemiplegia
Authors: Fang-ying Wei, Xiao-an Jing, Min Liu
Journal: BMJ (2011)

Two hundred and forty patients with post-stroke hemiplegia, discharged from October 2009 to January 2010, were randomly divided into two groups. One hundred twenty patients received home-based rehabilitation training, another 120 patients received conventional treatment and non-specific home rehabilitation. Brunnstrom rating and Barthel index ( BI) evaluation of motor function and activities of daily living (ADL) were performed in both groups before and after training program; Hamilton anxiety scale (HAMA) , Hospital Anxiety and Depression Scale (HAD) Assessment of anxiety and depression were also performed. Results showed that the lower limb function and ADL ability in home rehabilitation group were significantly increased, the anxiety and depression were significantly improved after home rehabilitation training ( P   0. 05 ).

Key words: 
Rehabilitation nursing;  Cerebrovascular accident
Epidemiology and mortality of metastatic castration-resistant prostate cancer (mCRPC) in a managed care population in the United States.
Authors: Katrine Wallace, Adrienne Landsteiner, Scott Bunner, Nicole Engel-Nitz, Amy Luckenbaugh
Journal: Journal of Clinical Oncology (2020)

e13592 Background: To date, there has been a paucity of information in the literature describing the epidemiology of mCRPC within the prostate cancer population. We present a real-world data study describing characteristics and mortality of patients with mCRPC within an administrative claims database of an insured population within the United States. Methods: In an administrative claims database of ≈18,000,000 covered lives, adult male patients were included if they had ≥1 claim for prostate cancer (ICD-9: 185 or 233.4; ICD-10: C61 or D075), underwent pharmacologic or surgical castration, and had a code for metastatic disease during the identification period (January 1, 2008–March 31, 2018). The index date was the first metastatic claim; 6 months of continuous enrollment (CE) prior to (baseline period) and after (follow-up period) the index date was required. Patients with metastatic claims in the baseline period were excluded. Patients were followed until the earliest of: death (unless prior to the 6-month CE), end of study period, or disenrollment. A claims-based algorithm was employed to identify locally advanced and distant mCRPC patients in the prostate cancer study population. Mortality data were sourced from the Social Security Administration Medicare data, and a claims algorithm. Results: 343,089 patients were identified with a claim for prostate cancer; of those, 3690 mCRPC cases (1.1%) were identified using the claims-based algorithm and met the study inclusion criteria. Median age was 75 years. Insurance type included commercial plans (27%) and Medicare (73%). Castration type included pharmacologic (99%) and surgical (1%). First claims for metastases were most commonly in the bone (65%) or lymph nodes (15%), with 20% in other sites. The study population averaged a Charlson comorbidity index score of 3.05 at baseline, with 16% of patients receiving a score of ≥5. The most common baseline comorbidities were hypertension (67%), urinary disease (58%), dyslipidemia (52%), and cardiac disease (45%). Median follow-up time among the mCRPC group was 538 days, during which 1834 deaths occurred; 50% of the population experienced mortality during the study period. Conclusions: This study provides valuable insights into the epidemiology, clinical characteristics, prevalence rate, and mortality of patients with mCRPC. Given the high mortality proportion of this disease, the development of novel therapies to prolong life in patients with mCRPC is warranted.
小肠肌源性肠梗阻一例
Authors: 刘华军, 吕红权
Journal: BMJ (2009)

患者男,66岁.因反复腹痛伴腹胀、呕吐3年曾先后3次在本院住院治疗.第1次为2006年7月29日至8月3日,入院时腹部X线透视(腹透)检查示左侧上、中腹部多个气液平面,肠管充气、扩张,右侧上中腹部一气液平面,长约8 cm。
Incidence trends of squamous cell carcinoma of the head and neck (SCCHN) in the aging population: A SEER based analysis from 2000-2016.
Authors: Melissa Taylor, Mihir Patel, Jeffrey M. Switchenko, Mark William McDonald, Conor Ernst Steuer, Jonathan Jay Beitler, Dong Moon Shin, Nabil F. Saba
Journal: Journal of Clinical Oncology (2020)

e18522 Background: SCCHN is more prevalent in the elderly. As the United States population ages, it is increasingly important to evaluate the change in the incidence of SCCHN in this population. Methods: This was a retrospective study using data from a population-based cancer registry (Surveillance, Epidemiology, and End Results) to identify patients ≥65 years old with the diagnosis of SCCHN between the years 2000-2016. The subgroups of oral cavity (OCC)and oropharynx cancer (OPC) were also analyzed independently. The incidence per year was calculated and joinpoint detection was used to identity significant changes in incidence trends. Annual percent change (APC) was detected to determine if the incidence trend was statistically significant. The study population was further stratified by sex. Results: For all sites, a joinpoint was found in 2003 with a statistically significant decrease in APC in incidence for males from 2000-2003 of -2.45%. For OCC, there was a joinpoint in 2005 with a statistically significant increase in APC in incidence for male patients of 1.41%. For (OPC), no joinpoint was found, but there was a statistically significant increase in APC in incidence for males of 3.41%. For females no joinpoint was found, but for OCC there was a statistically significant decrease in APC in incidence of -0.40%. Conclusions: In patients ≥ 65 years old the trend in incidence rate for all SCCHN sites stratified by sex has decreased between 2000-2016. However, for males the annual percent change in incidence has increased for OCC from 2005-2016 and for OPC from 2000-2016. [Table: see text]
Real-world clinical analysis and overall survival-related biomarker of breast cancer (BC) patients under 35 years old.
Authors: Jinpu Yu, Yang Li, Xuesong Li, Beibei Yang, Shuaibing Wang, Su Lu, Yehui Shi, Chunfang Hao, Geng Zhang, Xiaohong Wang, Jie Ma, Hong Liu, Xiaoliang Shi, Huidong Qiao, Zhenzhen Liu
Journal: Journal of Clinical Oncology (2020)

e12569 Background: Breast cancer (BC) is one of the most common malignant tumors among women in the world. Although under 7% of all BC cases, young BC is more difficult to diagnose and can be aggressive and less likely to respond to treatment. Exploring and identifying potential biomarkers for the diagnosis and prognosis of younger BC patients is necessary. Methods: A total of 1,202 BC patients under 35 years old (YD) were enrolled. Deep sequencing targeting 450 cancer genes was performed in a laboratory accredited by College of American Pathologists (CAP) and certified by Clinical Laboratory Improvement Amendments (CLIA) for genomic alteration identification. Statistical analysis was performed by Fisher’s exact test. Results: Of 1,202 young BC patients, 3 were under 20 YD, 85 were 20-25 YD, 371 were 26-30 YD, and 747 were 31-35 YD. Based on pathological, there were 899 infiltrative duct carcinomas, 10 infiltrative lobular carcinomas, and 292 BCs with unclear pathological type. According to molecular features, 587 HR+/HER2- (group I), 118 HR+/HER2+ (group II), 75 HR-/HER2+ (group III) and 193 HR-/HER2- (group IV) were included. Chemotherapy, radiotherapy, endocrine therapy and targeted therapy were received and 1074 patients were followed up. The median overall survival (OS) was 76 (5-156) months. There was no significant difference in OS between different treatments. The median OS was 81 (range 5-156) months, 67 (range 10-153) months, 76 (range 14-146) months, and 78 (range 13-151) months for group I, II, III, and IV, respectively. The significantly lower OS was observed in group II ( P=0.044). Although group II and group III had similar proportion of targeted treatment (43.22% vs 43.24%, respectively), the OS rate was different (67 vs 76 months, P=0.064). Samples from 46 young BC patients were performed on deep sequencing targeting 450 cancer genes. The most common mutations were TP53 (56%), GATA3 (29%), ERBB2 (27%), CDK12 (20%), and FGFR1 (20%). Different from previous studies, only 4.35% (2/46) of BRCA1/2 mutations were detected in this cohort. The mutation frequency of GATA3 in group II was significantly lower than that in group III (0% vs 71.43%, P=0.017). Conclusions: The most common pathological type of young BC was infiltrative duct carcinoma. The OS of HR+/HER2+ patients were significantly lower than that of others. Our results showed that GATA3 could be a potential biomarker for OS prediction for BC with HER2+, which help to further guide targeted therapy in young BC patients.
Early life stress and schizophrenia: a retrospective case-control study
Authors: Shilin Cao, Guoqiang Tian, Shenglin Liang, Haichao Jiang, Jianguang Gan, Chao Qian
Journal: BMJ (2014)

A total of 105 patients with first-episode schizophrenia (male=51, female=54) and 99 normal controls (male=51, female=48) were included into this retrospective case-control study.Childhood trauma questionnaire-28 item short form (CTQ-SF) was used to assess the experience of childhood abuse.The result of binary logistic regression showed that emotional abuse(β=0.630, P<0.05)and emotional neglect(β=0.270, P<0.05)were included into the final model of predicting schizophrenia.It indicates that patients with first-episode schizophrenia experienced more early life stress than controls.Particularly emotional abuse and emotional neglect may play important roles in the onset of schizophrenia.


Key words: 
Early life stress; Schizoprenia
大型多功能呼吸机无创通气治疗急性肺水肿
Authors: 卓越, 涂尚贵, 李永顺, 金宁双
Journal: BMJ (2006)

研究常规呼吸机模拟双相气道正压通气呼吸机治疗急性肺水肿的临床价值.将117例急性肺水肿患者分为无创通气治疗组(58例)和对照组(59例),观察治疗前、后1 h两组的血气分析及相关的症状、体征及病情缓解分值并进行统计学配对比较处理.治疗前各匹配组分析P＞0.05,说明两组基础病情具有可比性;治疗后1 h动脉血氧饱和度、血氧分压、呼吸频率、心率及缓解积分各组比较P＜0.01.表明治疗组较对照组的心肺功能改善更明显,由此表明本方法有极高的临床应用价值,是急诊抢救急性肺水肿的新方法.
HER family ligand traps (Hermodulins) inhibit tumor cell proliferation in vitro and growth of subcutaneous tumors in nude mice
Authors: Pei Jin, Malgorzata Beryt, Jeffrey Higaki, Ying Feng, Peter Lindley, Daniel Maneval, H. Shepard
Journal: Cancer Research (2008)

4078  Resistance to single targeted anti-HER agents has been attributed to multiple HER co-activation that occurs through receptor dimerization. We constructed and purified novel molecules comprising HER1/EGFR and HER3 ligand binding domains tethered to a human IgG1 Fc region. By design, these Hermodulins bind the majority of HER ligands and provide a therapeutic anti-cancer strategy similar to clinically-proven molecules developed for both TNF-alpha and VEGF-related diseases. RB200, a prototypic Hermodulin, was evaluated for activity against a spectrum of cell lines derived from human malignancies. Effects on monolayer cell growth in the presence of serum were measured using a 5-day crystal violet-based assay. Dose-dependent RB200 inhibition of cell growth was demonstrated in most cell lines including cells derived from human lung (NCI-H1437), epidermoid (A431), and breast (MDA-MB-468) cancers. Anti-proliferative effects appeared to be more pronounced in cells that express both wild type HER1/EGFR and elevated levels of amphiregulin. Synergistic growth inhibition in vitro was also demonstrated when RB200 was combined with small molecule tyrosine kinase inhibitors (TKIs) and conventional cytotoxic chemotherapies. Nude mice bearing established subcutaneous human NSCLC tumors, derived from the H1437 tumor cell line, were used to evaluate in vivo activity of RB200. Mice (N=10/group) were treated with RB200, PBS or cetuximab. Tumor sizes were measured via external calipers. These studies showed ~70% inhibition of tumor growth at 10 mg/kg vs. PBS control. Greater anti-tumor effects were observed when RB200 was combined with the TKI, erlotinib. These results support continued development of Hermodulins as novel ligand traps for anti-cancer therapy.
A data-driven framework for selecting and validating digital health metrics: use-case in neurological sensorimotor impairments
Authors: Christoph M. Kanzler, Mike D. Rinderknecht, Anne Schwarz, Ilse Lamers, Cynthia Gagnon, Jeremia P. O. Held, Peter Feys, Andreas R. Luft, Roger Gassert, Olivier Lambercy
Journal: npj Digital Medicine (2020)

Abstract Digital health metrics promise to advance the understanding of impaired body functions, for example in neurological disorders. However, their clinical integration is challenged by an insufficient validation of the many existing and often abstract metrics. Here, we propose a data-driven framework to select and validate a clinically relevant core set of digital health metrics extracted from a technology-aided assessment. As an exemplary use-case, the framework is applied to the Virtual Peg Insertion Test (VPIT), a technology-aided assessment of upper limb sensorimotor impairments. The framework builds on a use-case-specific pathophysiological motivation of metrics, models demographic confounds, and evaluates the most important clinimetric properties (discriminant validity, structural validity, reliability, measurement error, learning effects). Applied to 77 metrics of the VPIT collected from 120 neurologically intact and 89 affected individuals, the framework allowed selecting 10 clinically relevant core metrics. These assessed the severity of multiple sensorimotor impairments in a valid, reliable, and informative manner. These metrics provided added clinical value by detecting impairments in neurological subjects that did not show any deficits according to conventional scales, and by covering sensorimotor impairments of the arm and hand with a single assessment. The proposed framework provides a transparent, step-by-step selection procedure based on clinically relevant evidence. This creates an interesting alternative to established selection algorithms that optimize mathematical loss functions and are not always intuitive to retrace. This could help addressing the insufficient clinical integration of digital health metrics. For the VPIT, it allowed establishing validated core metrics, paving the way for their integration into neurorehabilitation trials.
Novel immunotherapy combinations for betel-nuts related HNSCC: One institutional experience in Taiwan.
Authors: Jo-Pai Chen, Wei-Chen Lu, Ruey-Long Hong, Sung-Hsin Kuo
Journal: Journal of Clinical Oncology (2020)

e18502 Background: The treatment of HNSCC in Taiwan is still very challenging. Betel nut chewing might contribute to (1)strong invasion; (2)easy recurrence; (3)poor response to traditional therapies. In our retrospective analysis for 75 patients receiving front-line EPF, patients, with rapid progression within 3 months after previous CCRT, had significantly worse survival with only 2.6 months; however, the survival increased significantly to 7.5 months in the same population if under later-line immunotherapy. Methods: From 2016 to early 2020, 46 R/M HNSCC patients receiving immunotherapy-containing regimens in Yun-lin Branch of National Taiwan University Hospital were reviewed. Results: These patients consisted of 2 HPV and 44 non-HPV; 24 pembrolizumab and 22 nivolumab; 18 with afatinib(11 pembrolizumab &amp; 7 nivolumab); 7 with bevacizumab; 9 with chemotherapy. The objective response rate was 48%(22/46) and clinical benefit was 80%(37/46). 20 patients were still under use(8 afatinib with pembrolizumab; 4 afatinib with nivolumab). 1 patient under afatinib and pembrolizumab had hyperprogression but then got pCR after bevacizumab &amp; strong CT. 1 patient had rapid skin metastasis over previous radiation fields after pembrolizumab, bevacizumab, and CT. 5 patients under afatinib &amp; pembrolizumab developed autoimmune cholestasis(3 also with pneumonitis). Afatinib with nivolumab had similar efficacy but less toxicity. 18 patients receiving afatinib combined with anti-PD1(11 failing EPF, 14 with pleural/pericardial/skin metastases, 13 rapid progression within 3 months after CCRT) had 67% response rate(12/18) and 89% clinical benefit(16/18). 11 patients under afatinib &amp; anti-PD1, who had failed EPF, had the response rate in 55%(6/11). 7 patients under front-line afatinib &amp; anti-PD1 had the response rate in 86%(6/7). Post-progression use of anti-PD1 with other treatments were seen in 12 patients(esp. 1 with nivolumab &amp; ipilimumab; 3 with Avastin, taxane, cisplatin). 7 patients got benefits and had longer survivals. Conclusions: Novel immunotherapy-containing combinations are of clinical significance in refractory betel-nuts related HNSCC in Taiwan. Afatinib has several immuno-modulatory effects in high risk patients(pleural/pericardial/skin metastases failing EPF, rapid progression within 3 months after definite CCRT). Afatinib with anti-PD1 may be a good option to avoid hyperprogression for more immunotherapy efficacy. Adding on CTLA4 blockage to previous afatinib/anti-PD1 after progression seemed potential for further studies.