tbuckley/cabot-search huggingface dataset:
Identification of paclitaxel resistance through a new statistical approach based on a random forest of perfect trees classifcation.
Authors: Jean-Michel Nguyen, Philippe Juin, Daniel Antonioli, Alexandre Moreau-Gaudry, Mario Campone, Pascal Jézéquel
Journal: Journal of Clinical Oncology (2020)

e13513 Background: Predictors of paclitaxel sensitivity in breast cancer published ten years ago, are still pending. The authors showed that paclitaxel pathological complete response (pCR) was in one hand, encountered in aggressive breast tumor with immune response and in another hand, paclitaxel resistance in less aggressive tumor. We have developed a new analysis paradigm, mixing neurons into nodes of trees classification and news class of statistical information based on free-error trees classification. We proposed to reanalyze the Bauer et al’s dataset using this novel approach. Methods: GES22513 dataset including 14 duplicated observations and 54675 anonymized probes was analyzed. A random forest of one million trees whose nodes were composed of neurons including 15 probes, was developped. We selected probes for which a free-error classification was obtained and ranked them according to the inverse of the probability of being a confounding factor and to the inverse of the probability of interacting with another probe. We compared the sets of probes which were necessary to obtain an error-free classification between those associated with a decrease and those associated with an increase of the probability of pCR. Results: Our 15 best ranked predictors were free-error classification for all observations. This includes gene expression of TLCD2, BRCC3, CHI3L2 and PROX1. Their over-expressions were associated with an increase in the probability of pCR, and gene expression of APH1B, ARFGEF1, ARID2, BPGM, CAMK2N1, CCNY, PARM1, PHKA1, PSMD9, SUDS3 (two probes) whose over-expressions are associated with a decrease in the probability of pCR. Ten out of these probes were concordant with Bauer et al’s conclusion. Four probes ( BPGM, PHKA1, CCNY and ARFGEF1) are in contradiction with it. The limited biological information were available for TLCD2. The statistical analysis also showed that TLCD2, BBRCC3, CHI3L2 and PROX1 were altogether positively modulated by eight genes/probes ( CKS1B, ADIG, NCR3, RIN3, NIPAL1, 234422_at, DCLRE1C, SLC17A4). At the opposite, the modulation of genes associated with a decrease in the probability of pCR, was rather heterogeneous and involves many more genes. Conclusions: This preliminary work shows that our statistical approach allows a perfect classification of tumors with and without pCR. Also, it proves that the selected probes/genes are respectively associated with aggressiveness/basal and less aggressiveness/luminal phenotypes. These results need to be validated on an independent cohort.
Sustained Minimal Residual Disease Negativity Predicted in Chronic Lymphocytic Leukemia Patients Treated with Venetoclax Combination Therapy for 2 Years: an Integrated Mechanistic Analysis of Multiple Phase I and II Studies
Authors: Sathej Gopalakrishnan, Brenda Chyla, Sven Mensing, Rajeev Menon, Rod Humerickhouse, Walid Awni, Ahmed Hamed Salem, Kevin J. Freise
Journal: Blood (2017)
A population-based study of chronic neutrophilic leukemia in the United States: 2004 to 2015.
Authors: Gordon Ruan, Caleb Smith, Courtney N. Day, William S. Harmsen, Darci Zblewski, Hassan Alkhateeb, Aref Al-Kali, Mark Robert Litzow, William J. Hogan, Natasha Szuber, Naseema Gangat, Mrinal Patnaik, Animesh Dev Pardanani, Michelle A. Elliott, Ayalew Tefferi, Ronald S. Go, Mithun Vinod Shah
Journal: Journal of Clinical Oncology (2020)

e19538 Background: Chronic neutrophilic leukemia (CNL) is a rare and aggressive myeloproliferative neoplasm with poor survival. No standard of care exists. Case reports describe allogeneic stem cell transplantation (ASCT) as the only curative therapy. Using the National Cancer Database (NCDB), we studied prognostic factors and survival outcomes of CNL. Methods: Patients diagnosed in 2004-2015 were included. 9963/3 was the ICD-O-3 code. Overall survival (OS) was analyzed using the Kaplan-Meier method. Hazard ratios (HR) with confidence intervals (CI) were calculated using Cox proportional hazards model. Variables significant in univariate analysis were included in a multivariate analysis. Data on incidence was obtained from the Surveillance, Epidemiology, and End Results Program (SEER) 21 Registries (2004-2015). The analysis was done with SEER*Stat software. Incidence was age-adjusted to the U.S. 2000 standard population. Results: A total of 121 CNL patients were in NCDB. The median age at diagnosis was 70 years (range 21-90); 74 (61%) were males and 107 (88%) were ≥ 50 years. The median follow up time was 5.8 years (interquartile range [IQR] 2.9-7.4). 32 (26%) had a Charlson Deyo score (CDS) &gt; 1. 80 (70%) had government insurance, while 34 (30%) had private insurance. Median OS was 2.2 years (IQR 0.8-6.7). OS was 70% at 1 year, 29% at 5 years, and 11% at 10 years. The year of diagnosis was not associated with improved OS (HR: 0.95 (95% CI: 0.88-1.02), p =0.14). 71 (59%) patients received chemotherapy. The median time to chemotherapy from the day of diagnosis was 15 days (IQR 7-35). The OS of those who received chemotherapy was 71% at 1 year and 27% at 5 years versus 69% and 32% at 1- and 5- years for those who did not ( p= 0.38). 2 patients received ASCT (age 52 and 61 years) as initial therapy and both were alive at 5 years. Factors predicting inferior OS on univariate analysis were age ≥ 50 years at diagnosis ( p= 0.005), male ( p&lt; 0.001), CDS &gt; 1 ( p= 0.038), and government insurance ( p= 0.004). The table shows the multivariate (MV) analysis. The overall incidence of CNL was 0.1 cases/1,000,000 individuals and did not change significantly from 2004-2015. The incidences by male, female, White, Black, and American Indian/Alaska Native were also 0.1 cases/1,000,000 individuals. Conclusions: OS and incidence of CNL have not changed over the years. Age ≥ 50 years, male gender, and use of government insurance predicted inferior OS. [Table: see text]
How to effectively prevent and cure ischemic stroke/transient ischemic attack for general practitioners
Authors: Yuhui Chen
Journal: BMJ (2016)

缺血性脑卒中(IS)和短暂性脑缺血发作(TIA)是社区常见疾病，其高发病率、高患病率、高死亡率和高致残率严重影响了人们的健康状况。近几年来，在IS/TIA一级预防、二级预防及急性期治疗方面均取得了很多进展。本文对IS/TIA的防治进展作简要介绍，重点突出全科医生在上述患者处置中的策略。
Dissecting aortic aneurysm 'disseminated intravascular coagulation
Authors: 梁晓春, 林兰
Journal: BMJ (1977)

《糖尿病中西医结合诊疗规范(2010》(《规范》)是中国中西医结合学会内分泌专业委员会主任委员林兰教授牵头,由中国中医科学院广安门医院、北京协和医院、北京大学第一医院、黑龙江中西医结合研究所、江苏省中医院、中国中医科学院眼科医院、上海中医药大学附属龙华医院等中西医结合糖尿病专家共同完成的.《规范》分为12个部分,包括糖尿病及其常见的慢性并发症[1],对于从事中西医结合防治糖尿病的临床工作者,具有很好的指导性和操作性.下面就其中糖尿病部分的关键内容进行解读。
Actionable policy barriers for receiving standard of care treatment among unresected stage III non-small cell lung cancer (NSCLC) patients in the United States.
Authors: Zhiyuan Zheng, Charles B. Simone, Stephen G. Chun, Xuesong Han, Helmneh M. Sineshaw, Jingxuan Zhao, Brian S. Seal, Candice Yong, Doris Makari, Ramesh Rengan
Journal: Journal of Clinical Oncology (2020)

2069 Background: Recent data suggests that a significant number of good performance, unresectable stage III non-small cell lung cancer (NSCLC) patients do not receive standard-of-care treatment, i.e. concurrent chemoradiotherapy (cCRT) followed by durvalumab, despite being eligible. However, little is known about actionable policy barriers to delivery of cCRT to this patient population. Methods: The National Cancer Database (2004-2016) was used to identify unresected stage III NSCLC patients aged 18-79 years with Charlson comorbidity score ≤ 1. cCRT was defined as the initiations of chemotherapy (CT) and radiation therapy (RT) that were ≤14 days (n = 53,444) apart. The remaining treatment groups included sequential CRT (sCRT; n = 16,666), CT only (n = 15,416), RT only (n = 11,579), and no first course treatment (n = 16,691). Multinomial logistic regressions were used to examine the likelihoods of receiving different treatment modalities, controlling for patient demographics, Charlson comorbidity score, health insurance, facility type, social deprivation index (SDI, a comprehensive socio-economic measure; higher SDI indicates lower socioeconomic status [SES]), driving time to facility, diagnosis year, and region. Results: Of the total 113,796 patients assessed (median age 66 years), most were male (55.7%), non-Hispanic white (81.7%), and with SDI score ≥50 (51.3%). 29.5% had Charlson comorbidity score = 1 while the rest had 0. In adjusted analyses (predicted margins), 47.0% patients received cCRT (sCRT: 14.6%; CT only: 13.5%; RT only: 10.2%; no treatment: 14.7%). Compared to the privately insured, Medicaid, Medicare, and uninsured patients were more likely to receive RT only (relative risk ratios [95%CI]: 1.93 [1.77-2.11]; 1.51 [1.41-1.61]; 1.80 [1.61-2.01], respectively) and no treatment (1.84 [1.71-1.99]; 1.54 [1.45-1.63]; 2.19 [2.01-2.40], respectively) rather than cCRT (all p &lt; .001). Moreover, higher SDI was associated with higher likelihood of receiving RT only (highest vs lowest SDI scores: 1.42 [1.33-1.52]), or no treatment (1.46 [1.38-1.55]) rather than cCRT (all p &lt; .001). Longer driving time was associated with higher likelihood of receiving CT only ( &gt; 120 mins vs &lt; 30 mins: 1.24 [1.10-1.39]), or no treatment (1.33 [1.18-1.50]) rather than cCRT (all p &lt; .001). Conclusions: Health policies should focus on patients who are not privately insured and live in neighborhoods with low SES. Moreover, helping their transportation needs may also improve the likelihood of receiving cCRT.
T-cell inflamed gene expression to predict prognosis and response to immune checkpoint inhibitors.
Authors: Yao Yu, Jingjiao Ma, Jie Chen, Ning He, Xiaohong Xu, Lingyu Wang, Rongbo Lin
Journal: Journal of Clinical Oncology (2020)

e15264 Background: To prove that T-cell-inflamed gene-expression profile (GEP) can predict prognosis and response to immune checkpoint inhibitors (ICIs) in the real-world study. Methods: 36 patients admitted from January 2018 to December 2018 were enrolled, including 15 patients with advanced NSCLC, 12 with advanced bladder cancer and 9 with advanced liver cancer. All patients were treated with nivolumab or pembrolizumab and provided informed written consent for analysis. Tumor total RNA was isolated from pretreatment FFPE samples and RNA-seq was performed on the Illumina NovaSeq 6000 system. GEP was calculated as a weighted sum of normalized expression values for 18 genes, as described in the article written by Ayer M, et al. in 2017. The data cutoff date was July 30, 2019. Primary end points were objective response rate (ORR) and disease control rate (DCR). Secondary end point was progression-free survival (PFS) assessed per RECIST v1.1. 95% CIs and P values for ORR and DCR were evaluated by the binomial exact method. Correlation between GEP and ORR, DCR and PFS was assessed by Wilcoxon rank sum test and Cox regression model, respectively. Survival curves were estimated by Kaplan-Meier methods. Cut-off value of GEP was confirmed by the Youden Index. The comparisons of DCR and PFS were performed by Fisher’s exact test and log-rank test, respectively. Results: ORR was 30.6% (95% CI, 16.3%-48.1%) and DCR was 50.0% (95% CI, 32.9%-67.1%). Median PFS was 3.9 months (95% CI, 0.8-NR). We found that GEP was higher in patients who achieved DCR and had longer PFS. And then GEP was significantly associated with DCR (p = 0.019) and PFS (p = 0.005), but not significantly with ORR (p = 0.42). Based on Youden Index, cut-off value of GEP was confirmed as -0.368, with 94.4% of sensitivity and 66.7% of specificity. According to cut-off value, 23 patients were evaluated as GEP-H. GEP-H group had higher DCR and longer PFS (DCR: 73.9% vs 7.69%, p = 0.0003; mPFS: 7.0m vs 2.1m, p = 0.00049). Conclusions: GEP can predict prognosis and response to ICIs in multiple cancers in our real-world study. Interpretation of these data may be limited by small sample sizes. Further studies are being conducted.
社区精神卫生服务中误诊、误治病例分析
Authors: 韦程瀚
Journal: BMJ (2009)

在农村特别是边远地区,绝大多数患者看病都是在基层医院或社区卫生服务中心,因此,能否识别日常就诊患者是否存在精神症状,对避免造成误诊误治十分重要.现介绍工作中遇到的3例误诊、误治病例供学习讨论,以期引起全科医师及基层医院医师的关注和重视.同时,建议进一步加强社区全科医师和基层医院医师精神卫生专业知识的学习培训,提高精神卫生服务意识和对精神科疾病的识别能力,不断完善社区精神卫生服务功能,更好地为社区患者服务。
Clinical progress of wound management in venous leg ulcers
Authors: Han Wang, Qihong Ni, Ting Zhang, Haiyan Ding, Xin Qian, Can Lu
Journal: BMJ (2019)

Venous leg ulcer (VLU) is a disease of venous hypertension leading to open skin lesions of lower extremities, which is the terminal stage of chronic venous insufficiency. Considering the high prevalence and recurrence rate, VLU restrain daily activities, impair mental health and even contribute to social isolation of patients. Currently, surgery and compression therapy are wildly used to relieve symptoms and eliminate the etiological factors, however, ulcers remain unhealed even after these treatments in many cases. In this article, we review the clinical progress of treatment for VLU, including the debridement, antibiotics, ulcer dressing, negative pressure wound therapy and skin graft, to provide reference on the therapeutic strategy for different ulcer conditions.


Key words: 
Varicose ulcer; Wound healing
A pilot study of tofacitinib for refractory Behçet’s syndrome
Authors: Jinjing Liu, Yunxia Hou, Luxi Sun, Chaoran Li, Lu Li, Yan Zhao, Xiaofeng Zeng, Fengchun Zhang, Wenjie Zheng
Journal: Annals of the Rheumatic Diseases (2020)

Behcet’s syndrome (BS) is a chronic inflammatory disease characterised by recurrent oral and genital ulcers, frequently complicated with uveitis gastrointestinal, neurological, major vessel and cardiac involvement. For severe and (or) refractory BS, tumour necrosis factor alpha (TNF-α) inhibitors are indicated beyond glucocorticoids (GCs) and immunosuppressants,1 which are still responded inadequately in a small portion of refractory patients. Tofacitinib, a JAK1/3 inhibitor targeting T cell signalling, was approved for autoinflammatory diseases including rheumatoid arthritis, psoriatic arthritis and ulcerative colitis (UC).2 Given T cells are implicated in BS,3 tofacitinib could be a promising approach for BS.

In this study, we explored the efficacy and safety of tofacitinib in refractory BS. We enrolled seven male and six female patients with BS fulfilling the 2013 International Criteria for BS,4 presented with active vascular/cardiac (n=5), gastrointestinal (n=6) and articular (n=2) involvements between May 2018 and January 2020 (table 1), with a mean age of 42.2±15.5 years and a median disease duration of 102 (IQR 72–240) months. At enrolment, all patients had active disease (Behcet's Disease Current …
Roles of IL-8 and eotaxin in airway inflammation and lung function injury of chronic obstruction pulmonary disease
Authors: Xia Zhu, Zeng-lian Tian
Journal: BMJ (2011)

The clinical data of 25 patients with acute exacerbations of chronic obstruction pulmonary disease (AECOPD) admitted from March 2009 to October 2010 were analyzed. The sputum samples were collected and the levels of inflammatory cell, interleukin-8 (IL-8) and eotaxin in sputum were determined. The lung function was measured. Twenty healthy subjects served as controls. The counts of neutrophils and eosinophils, and the levels of IL-8 and eotaxin in sputum of AECOPD were higher than those of health subjects. There was a positive correlation between the levels of IL-8 and the counts of neutrophils (P < 0. 01), and between the levels of eotaxin and the counts of eosinophils in sputum ( P < 0.01). The levels of IL-8 and eotaxin were negatively correlated with the lung function (FEV1% ).

Key words: 
Interleukin-8;  Chemotactic factors,eosinophil
Efficacy and safety of bevacizumab biosimilar FKB238 versus originator bevacizumab: Results from a phase III trial in patients with non-squamous non-small cell lung cancer (NS-NSCLC).
Authors: Konstantinos N. Syrigos, Dongyue Fu, Stephanie Jones, Zahid Bashir
Journal: Journal of Clinical Oncology (2020)

e21728 Background: Bevacizumab (bev) is a recombinant humanized monoclonal antibody that binds selectively to VEGF-A and prevents it from interacting with its receptors, thereby inhibiting formation of new tumor vasculature to block tumor growth. FKB238, a bev biosimilar, has similar pharmacokinetic and safety profiles to originator bev (o-bev). This phase 3 trial (NCT02810457) compared the efficacy and safety of FKB238 with o-bev in patients with advanced/recurrent non-squamous non-small cell lung cancer (NS-NSCLC). Methods: This global, multicenter, double-blind, parallel, randomized, comparative clinical trial enrolled and randomized 731 patients with advanced/recurrent NS-NSCLC to receive 15 mg/kg intravenous (IV) infusion of either FKB238 (N = 364) or o-bev (N = 367). All patients received IV infusions of paclitaxel (200 mg/m 2 ) and carboplatin (AUC 6.0) immediately prior to investigational drugs for 4-6 cycles. FKB238 and o-bev were administered on day 1 of each 21-day cycle until objective progressive disease or other discontinuation criteria were met. Results: The objective response rate (ORR) based on blinded independent central review assessment for the intent-to-treat population was 51.6% and 53.7% for patients in the FKB238 and o-bev arms, respectively. The FKB238/o-bev ORR ratio was 0.96 (90% CI: 0.86 to 1.08) and the 90% CI fell within the pre-specified equivalence margin. The estimated proportion of patients alive and progression free at 12 months was 25.0% in the FKB238 arm vs 25.3% in the o-bev arm (HR of 0.97, 95% CI 0.82-1.16). The estimated median progression-free survival was 7.72 months in the FKB238 arm and 7.62 months in the o-bev arm. TEAEs were reported for 94.2% (FKB238) and 95.1% (o-bev) of patients. TEAEs ≥ grade 3 were reported for 53.6% (FKB238) and 55.5% (o-bev) of patients. SAEs were reported for 25.1% and 26.0% of patients treated with FKB238 and o-bev, respectively. Conclusions: There were no meaningful differences in efficacy and safety between FKB238 or o-bev in patients with NS-NSCLC. ORR efficacy equivalence was demonstrated, and the safety profiles of both drugs were similar. Clinical trial information: NCT02810457.
Percutaneous endoscopic gastrostomy improves nutritional status and reduces complications in patients with enteral nutrition support
Authors: Fusheng Gao, Bin Liu
Journal: BMJ (2016)

Objective
To evaluate the effect of percutaneous endoscopic gastrostomy (PEG) on the nutritional status and complication rate in patients with enteral nutrition support.


Methods
Sixty five patients receiving PEG from January 2008 to December 2014 were enrolled in the study. The nutritional status was examined and the incidence of complications was documented before and after PEG.


Results
The serum albumin, body mass index (BMI) and arm muscle circumference were (29.2±3.2)g/L, (18.0±1.0)kg/m2, (21.1±1.9)cm and (32.9±3.0)g/L, (18.8±1.6)kg/m2, (23.0±3.0)cm before and 1 month after PEG, respectively (t=-6.798, -3.202 and -3.957, all P<0.05). Compared to those before PEG, the serum albumin, BMI and arm muscle circumference at 3 and 6 months after PEG were increased to (35.4±4.9)g/L, (19.7±1.4)kg/m2, (24.9±2.2)cm (t=-7.845, -7.202, -10.432, all P<0.05) and (37.9±3.7)g/L, (20.7±1.6)kg/m2, (26.9±3.7)cm (t=-14.046, -10.686, -9.827, all P<0.05), respectively. Compared to those with nasal feeding, the incidence of aspiration pneumonia was decreased from 62% (40/65) to 18% (10/57) and the incidence of reflux esophagitis was decreased from 51% (33/65) to 19% (11/57) 6 months after PEG, respectively (χ2=24.3 and 13.5, all P<0.01).


Conclusion
PEG can improve nutritional status and reduce the incidence of aspiration pneumonia and reflux esophagitis for patients with enteral nutrition support.


Key words: 
Gastroscopes; Percutaneous endoscopic gastrostomy; Nutritional status
Characteristics and survival of secondary male breast cancer: SEER database analysis.
Authors: John Khoury, Siddhartha Yadav, Tara Rangarajan, Dana Zakalik
Journal: Journal of Clinical Oncology (2020)

e13690 Background: Male breast cancer (MBC) is rare accounting for less than 0.5% of all cancer diagnoses in men. We used the term secondary male breast cancer (sMBC) to refer to ipsilateral and contralateral recurrences in addition to new primary MBC. Given its low incidence, data regarding the risk of developing sMBC and its characteristics are scarce. Methods: Multiple Primary Standardized Incidence Ratios (MP-SIR) session was conducted from the SEER*Stat software. We included all patients diagnosed with stage I,II and III MBC between 1990 to 2015 from the Surveillance Epidemiology and End Results (SEER) 18 registry. The standardized incidence ratio (SIR) was calculated as an estimate of the risk of a second primary malignancy based on the incidence in the general population. Descriptive statistics and Kaplan-Meier analysis were performed using SPSS software. Results: Among all 2321 men diagnosed with a first primary MBC during the study period, 28 patients had a subsequent diagnosis of MBC. The risk of sMBC was significantly elevated with SIR of 33.12 (95% CI, 22.18 – 47.56). The median latency period between the initial and subsequent diagnoses was 5.9 years. 82.1% of the patients were White, 14.3% Black and 3.6% Asian/Pacific Islander. Majority of the cases constituting 85.7% of sMBC were diagnosed in the contralateral breast. 67.8% of the sMBC remained hormone receptors status positive similar to the initial status of the primary diagnosis. 42.9% of the sMBC patients were diagnosed with stage I, 17.9% with stage II, 3.6% with stage III, 17.9% with stage IV and 17.9% of unknown stage. The median overall survival for sMBC was 96 months (95% CI, 11.3-180.6). We also found an increased risk of developing liver cancer (SIR: 2.16), prostate cancer (SIR: 1.29), thyroid cancer (SIR: 3.08) and acute myeloid leukemia (SIR: 2.4) in individuals after a diagnosis of MBC. Conclusions: Men diagnosed with breast cancer are at increased risk of sMBC in addition to other malignancies which require careful monitoring after completing initial treatment. Contralateral mammogram screening or prophylactic contralateral mastectomy can be considered based on patient’s preferences and values.
Early ileostomy closure is safe and feasible during adjuvant chemotherapy after total mesorectal excision surgery for rectal cancer.
Authors: Xiaodong Gu, Minwei Zhou, Zihao Wang, Zhenyang Li, Yi Yang, Yiwen Zang, Yiming Zhou, Jianbin Xiang, Zongyou Chen
Journal: Journal of Clinical Oncology (2020)

4111 Background: The aim of this study was to evaluate the comparative clinical and oncological outcomes of temporary ileostomy closure during or after adjuvant chemotherapy in patients with total mesorectal excision (TME) for rectal cancer. Methods: This randomized controlled trial investigated 87 patients (51 males, 36 females) with rectal cancer undergoing TME surgery with temporary ileostomy from January 2016 to December 2018. Patients were randomized divided into 2 groups: early group (43 patients, mean age: 60.35) who underwent stoma closure during adjuvant chemotherapy (3 months after primary surgery) and late group (44 patients, mean age 61.80) who underwent stoma closure after adjuvant chemotherapy (6 months after primary surgery). Both clinical and oncological outcomes were analyzed. Results: No significant differences were observed in operative time, blood loss, postoperative hospital stay, postoperative complications or hospital costs in ileostomy closure between the 2 groups. Stoma-quality of life (QOL) of patients in early group was significantly better than late group (52.02±5.68 vs 46.91±5.68, P &lt;0.05). No significant difference in overall survival (P = 0.702) or progression-free survival (P = 0.638) was observed between the 2 groups. Conclusions: Ileostomy closure during adjuvant chemotherapy was clinically safe, and interruption of chemotherapy due to ileostomy closure did not change oncologic outcomes. Early ileostomy closure can improve QOL in those patients. Clinical trial information: NCT02665026 .