tbuckley/cabot-search huggingface dataset:
Peripheral neuropathy after breast cancer: An analysis of data from the Women’s Health Initiative Life and Longevity After Cancer cohort.
Authors: Mandana Kamgar, Hadeel Assad, Theresa A. Hastert, Eric McLaughlin, Kerryn Reding, Electra D. Paskett, Jennifer W. Bea, Aladdin H. Shadyab, Marian L. Neuhouser, Rami Nassir, Tracy E Crane, Kalyan Sreeram, Mark K. Greenwald, Michael S. Simon
Journal: Journal of Clinical Oncology (2020)

e24093 Background: There are over 3.8 million breast cancer survivors in the United States, and many experience long-term side effects from chemotherapy. Factors associated with peripheral neuropathy (PN), one troubling side effect, following breast cancer among women are unknown. Methods: We included 2,420 women enrolled in the Women’s Health Initiative and diagnosed prospectively with local or regional stage breast cancer and followed in the Life and Longevity After Cancer (LILAC) study. PN was assessed by response to the baseline LILAC questionnaire regarding the presence of “nerve problems, tingling sensations” after treatment. Data were collected on initial course of therapy (surgery, radiation, and chemotherapy) through Medicare linkage or the LILAC staging and treatment form. Chi-square and Wilcoxon rank-sum tests were used for univariate comparison of socio-demographics, clinical and diagnosis characteristics associated with the presence or absence of PN. Results: The sample included 1,913 women (79%) with local and 507 women (21%) with regional stage disease. Initial course of therapy included either surgery alone (21%), surgery and radiation (53%), or surgery and chemotherapy (+/- radiation) (26%). Seventeen percent of women reported experiencing PN days (30%), months (46%) or years (24%) following treatment. Three-quarters (74%) reported ongoing symptoms at the time of the LILAC survey. PN was reported by 33% of chemotherapy recipients, compared to 12% in the surgery alone group, and 11% in the group that received surgery and radiation (p&lt;0.0001). The prevalence of PN was higher among women receiving regimens containing paclitaxel (52%) and docetaxel (39%), compared to those receiving other chemotherapy (17%) (p&lt;0.0001). Conclusions: PN is an important complication of taxane-based chemotherapy. Further analysis will explore the relationship between socio-demographic, clinical and treatment on the development, timing of, and severity of PN after cancer directed therapy.
Endoscopic submucosal dissection for gastric duplication cyst with heterotopic pancreas
Authors: Gwang Ha Kim, Moon Won Lee, Bong Eun Lee, Do Youn Park
Journal: Endoscopy (2020)

A 63-year-old man presented with a gastric subepithelial tumor, incidentally detected on screening endoscopy. A subepithelial tumor, approximately 30 mm in size and with a positive cushion sign, was observed on the greater curvature of the gastric lower body ([Fig. 1]). Severe erythema and hemorrhagic spots were seen on its surface. On endoscopic ultrasonography, the lesion was anechoic, mainly confined to the submucosal layer, and had a small branch-shaped hypoechoic portion in the cystic wall ([Fig. 2]). Endoscopic submucosal dissection (ESD) was suggested in order to prevent bleeding ([Video 1]).
Interrogation of neoantigen-specific CD8 T cells in peripheral blood following PD-L1 blockade in patients with metastatic urothelial carcinoma (mUC).
Authors: Jeppe Sejerø Holm, Samuel Aaron Funt, Anne-Mette Bjerregaard, James L. Reading, Colleen Anne Maher, Ashley Marie Regazzi, Phillip Wong, Hikmat Al-Ahmadie, Nana Haahr Overgaard, Tripti Tamhane, Amalie Kai Bentzen, Alexandra Snyder, Taha Merghoub, Jedd D. Wolchok, Morten Nielsen, Jonathan E. Rosenberg, Dean F. Bajorin, Sine Reker Hadrup
Journal: Journal of Clinical Oncology (2020)

3075 Background: Proliferation of CD8 T cells can be detected in the blood of cancer patients (pts) following a single dose of immune checkpoint blockade (ICB) and tends to be more robust in responding pts. Furthermore, tumor mutational burden (TMB) is seen to predict outcome to ICB across cancers. Mutation-derived neoepitopes presented on the tumor cell surface is believed to be recognized by T cells and are thus critical for tumor clearance. However, the capacity to mount a neoantigen T cell response and the kinetics in relation to ICB remain poorly understood. Methods: 24 pts with mUC were treated with atezolizumab (anti-PD-L1) 1200mg q3w on IMVigor 210 at MSKCC and included in here. Pt-specific neoepitopes were predicted based on whole-exome and RNA sequencing of pre-treatment archival tumors using the MuPeXI platform. Using DNA-barcode labelled pMHC multimers, we investigated CD8 T cell recognition of mutation-derived neoepitopes by screening pt PBMC samples pre- and post-treatment with atezolizumab (n = 85 PBMC samples). The kinetics of neoepitope-specific CD8 T cells were assessed for association with durable clinical benefit (DCB; defined as progression free survival &gt; 6 mo). Results: Neoepitope peptide libraries of between 200-587 peptides were generated per pt (mean = 260 peptides per pt). 31 out of a combined 56 possible pt HLA types across the cohort were utilized for T cell analyses (mean four HLAs per pt). MHC multimer-based screening of pt PBMCs revealed detection of neoepitope-specific CD8 T cells in 22 of 24 pts pre-treatment (range one to 14 neoepitope responses) and 21 of 22 pts post-treatment (up to 273 weeks after trial start; one to 19 neoepitope responses). There were large inter- and intra-patient variations of neoepitope-specific CD8 T cell responses during treatment with the largest increases occurring at the 3-wk, post-treatment initiation timepoint. We observed that pts with DCB tend to raise a broader neoantigen T cell response than patients without DCB. 38% of pts without DCB and 67% of pts with DCB exhibited an increase in neoepitope-specific CD8 T cell responses within 3 wks of treatment initiation. Conclusions: Using high-throughput screening, pt-specific neoepitope reactive CD8 T cells could be detected pre- and post-treatment in pts with mUC treated with atezolizumab. Phenotypic characterization of neoepitope reactive CD8 T cells is ongoing. These data may help elucidate the dynamics and characteristics of the T cells of highest relevance to the ICB-induced, anti-tumor immune response.
Machine learning radiomics signature on magnetic resonance imaging associated with phenotypes and disease-free survival in patients with breast cancer (RBC-01): A registry-based, multicenter cohort study.
Authors: Herui Yao, Yunfang Yu, Yujie Tan, Qiugen Hu, Jie Ouyang, Yongjian Chen, Yang Gu, Anlin Li, Zifan He, Yaping Yang, Kai Chen, Jiafan Ma, Chenchen Li, Mudi Ma, Xiaohong Li, Haitao Zhong, Qiyun Ou, Zhuo Wu, Fengxi Su, Erwei Song
Journal: Journal of Clinical Oncology (2020)

3563 Background: The early stage breast cancer patients can vary in disease-free survival (DFS), innovative predictors evaluate the prognostic capacity are urgently needed. We aimed to develop and independently validate a radiomics signature based on MRI associated with phenotypes and DFS in patients with breast cancer and to establish a radiomics nomogram that incorporates the radiomics signature and clinicopathological findings using computational algorithms. Methods: In this multicenter, retrospective, cohort study, we analyzed preoperative contrast–enhanced MRI data from the prospective cohort study (n = 123) of patients who had been treated with neoadjuvant chemotherapy in phase 3 trials and independent cohort (n = 438) at the Sun Yat-sen Memorial Hospital as training cohort to develop the radiomic signature, and validated it in validation cohort (Foshan cohort, n = 121; Dongguan cohort, n = 89) between November 17, 2011, and September 21, 2019, and validated in TGCA cohort (n = 84). Machine-learning algorithm to identify robust imaging subtypes and evaluated their clinical and biologic relevance. A nomogram combining the radiomic signature and clinicopathological findings to predict individual survival based on Cox regression model. The primary endpoint was disease-free survival (DFS). This study is registered with ClinicalTrials.gov, number NCT04003558, and Chinese Clinical Trail Registry, number ChiCTR1900024020. Results: A total of 855 breast cancer patients were included. Radiomics signature was generated to classify patients into high-risk and low-risk groups in the Guangzhou training cohort. Patients with low-risk scores in the training cohort had higher DFS (hazard ratio [HR] 0.55, 95% CI 0.31 to 0.99; P= 0.045) than patients with high-risk scores, and validated in in validation cohort (HR 0.14, 95% CI 0.03 to 0.62; P= 0.003). The nomogram combined radiomics score with clinicopathological factors could accurately predict DFS benefits in training cohort (C-index = 0.83; AUC, 1, 2, 3-year were 0.80, 0.85, 0.82, respectively) and validated in validation cohorts. Conclusions: The radiomics signature are significantly associated with the DFS in patients with breast cancer. Combining the radiomics nomogram improved individualized DFS pretiction. Clinical trial information: NCT04003558 .
X versus XELOX versus PF in definitive concurrent chemoradiotherapy (DCRT) for local advanced squamous esophageal cancer (ESCC): Update from a multicenter, open-label, randomized III trial, CRTCOESC trial.
Authors: Ruinuo Jia, Tanyou Shan, Lixin Wan, Anping Zheng, Shuang Hui, Zhiqiao Xu, Feng Wang, Guobao Zheng, Ping Lu, Guifang Zhang, Yingjuan Zheng, Yanhui Cui, Xiaoyong Luo, Weiguo Zhang, Wanying Li, Ruonan Li, Fuyou Zhou, Shegan Gao
Journal: Journal of Clinical Oncology (2020)

4531 Background: PF (5-fluorouracil plus cisplatin) is the standard regimen for local advanced ESCC with DCRT. CRTCOESC aims to evaluate the effect and safety of X (capecitabine) regimen versus XELOX (capecitabine plus oxaliplatin) and PF in Chinese local advanced ESCC with DCRT by randomized, open-label, multicenter designed. Methods: Patients with ESCC (T2-4N0-2M0) were randomized to 3 groups as X (capecitabine 625mg/m 2 , bid d1-5, 6 weeks), XELOX (oxaliplatin: 65mg/m 2 , d1, 8, 22, 29; capecitabine: 625mg/m 2 , bid d1-5; 6 weeks), or PF (cisplatin: 75mg/m 2 d1, 29, 5-Fu: 750mg/m 2 CIV24h d1-4, d29-32), Intensity Modulated Radiation Therapy (IMRT) was delivered by 50Gy/2Gy currently. In addition, quadratic randomize were done within all groups to decide whether 2 cycles chemotherapy adding or not after DCRT. 2-year OS and Grade 3-5 AEs were the primary endpoints, 2-year PFS and short-term efficacy (STE) as rates of CR and ORR (CR+PR+SD) (confirmed by gastroscopy biopsy at 16 weeks) were the secondary endpoints. Results: 244 pts successfully were accrued from 13 centers during 2014.10-2020.1. 209 pts were finished DCRT and 193 were evaluated STE at 16 weeks. 192 and 147 pts were followed up for 1- and 2- years respectively. There were no differences between 3 groups on patients’ baseline characters including age, gender, ECGO score, clinical stage, pathology grade and smoking. In X, XELOX and PF groups, the 2-year OS were 63.8% (30/46), 61.5% (32/52) and 62.5% (30/49) ( P = 0.973), the median OS were 39.7 (6.567), 40 (5.195) and 34 (5.736) (months, P = 0.703); the incidences of AEs (grade 3-5) were 26.5% (18/68), 33.8% (25/74) and 49.3% (33/67) ( P = 0.0193); the 2-year PFS were 54.3% (25/46), 53.8% (28/52) and 51% (25/49) ( P = 0.939), the median PFS were 29.06 (6.124), 17.4 (8.745) and 24.833 (6.777) (months, P = 0.811); the CR rate were 43.8% (28/64), 41.4% (29/70), and 42.4% (25/59) ( P = 0.964), and the ORR were 85.6%, 88.6%, and 96.6% ( P = 0.119), respectively. There were no differences on OS, PFS and rates of CR and ORR between 3 groups but the incidence of AEs in X group was the lowest significantly. Subgroup analysis results shown adding 2 cycles chemotherapy after CRT had both OS and PFS advantages but lacked statistically significance. Conclusions: Compared with PF, DCRT with X or XELOX shown lower incidence of AEs and similar OS, PFS and STE. X regimen carried out the lowest AEs incidence. Adding 2 cycles chemotherapy after DCRT seemly had advantages on OS and PFS. Clinical trial information: NCT02025036 .
浅谈全科医生在家庭病床及出诊中医疗风险的防范
Authors: 吴南屏
Journal: BMJ (2006)

随着医疗模式的转变,全科医生正承担着日益增多的家庭病床及出诊任务.然而随着医疗保险制度的改革和医疗事故处理办法的出台,全科医生在家庭病床及出诊中正面临着更大的压力和风险,如何防患于未然,成为广大基层全科医生面临的问题.其中涉及患者、家庭、社会各方面因素,有躯体的,也有心理的,同时也和医生的医疗水平、医德素质、处理人际关系技巧有很大关系.下面就此进行探讨。
老年高血压治疗注意事项
Authors: 朱宁
Journal: BMJ (2012)

老年高血压患者降压治疗中血压目标值和血压对老年人寿命、生活质量、认知功能以及跌倒的影响等都需要考虑.2008年及2011年我国和美国先后发表了有关老年高血压治疗的专家共识.本文结合共识讨论对老年高血压患者治疗的注意事项。
主动免疫治疗不明原因的反复自然流产
Authors: 包洪初, 郝翠芳, 曲庆兰
Journal: BMJ (2006)

2002年6月起在本中心就诊行免疫治疗成功并获分娩的患者36例,均为不明原因的反复自然流产者,将这些临床资料与同期在我院分娩的正常孕妇的资料做比较,重点比较产科并发症和新生儿情况.发现不明原因反复自然流产组孕妇胎膜早破、胎盘粘连、胎膜残留发生率均显著增高; 不明原因反复自然流产组新生儿出生孕周及新生儿平均体重有降低趋势,两组差异无统计学意义。
Risk factors of new-onset diabetes among senior public officials in Chengdu
Authors: Hui Jiang, Han Wang, Xiuqiong Yu, Lin Cai, Yuanbiao Guo, Gang Feng, Xiaomei Wang, Yuan Luo, Yuanhang Huang, Cong Zhao
Journal: BMJ (2018)

The consecutive data of 822 senior public officials in Chengdu undergoing health checkup from 2011 to 2016 were retrospectively reviewed. Among them, 56 new cases of diabetes was diagnosed with a cumulative incidence of 6.81%. Fifty six age- and sex-matched healthy subjects served as controls, the risk factors of new-onset diabetes were analyzed with multivariate logistic regression. The results showed that BMI (OR=1.82, 95%CI: 1.27-2.59, P=0.00) and fasting plasma glucose (OR=13.63, 95%CI: 2.71-68.43, P=0.00) were independent risk factors of new-onset diabetes in senior public officials.


Key words: 
Personal health services; New-onset diabetes; Risk factors
Pharmacokinetics/pharmacodynamics of liposomal cytarabine (VYXEOS) in AML patients: Influence of cytidine deaminase genetic polymorphisms.
Authors: Mélanie Donnette, Geoffroy Venton, Laure Farnault, Bertrand Pourroy, Regis Costello, Bruno Lacarelle, L'Houcine Ouafik, Joseph Ciccolini, Raphaëlle Fanciullino
Journal: Journal of Clinical Oncology (2020)

e19517 Background: Vyxeos is a liposomal formulation of daunorubicin and cytarabine recently approved for treating adults with newly-diagnosed sAML subtypes therapy-related (t-AML) or AML with myelodysplasia-related changes (AML-MRC). The objective of this pilot study was to evaluate the influence of cytidine deaminase, the enzyme responsible for cytarabine detoxification step in the liver, on drug exposition and clinical outcome. Methods: In this proof-of-concept study, 9 adult patients were treated with Vyxeos. CDA status (i.e., determination of Poor Metabolizer or Extensive Metabolizer phenotypes) was evaluated before treatment by measuring residual CDA activity in serum. Pharmacokinetic sampling was performed 90min before infusion stops, then from T4H to T168H after the end of the infusion. Total cytarabine, encapsulated cytarabine and released cytarabine were discriminated and assayed using a validated LC-MS/MS method. Results: Nine Vyxeos patients (3M, 6F, 66 ±13 years) were included in this pilot study. Aplasia duration was significantly longer in AML-MRC patients than in AML-t (38 ±5.5 days VS. 28 ±3 days, respectively (p &lt; 0.05)). All AML-t had complete response after induction phase (VS. 60% in AML-MRC, p &gt; 0.05). Similar cytarabine exposure was measured in both population. Surprisingly, 8 out of 9 patients (i.e., 88%) were identified as CDA PM (CDA &lt; 2UI/mg). Marked differences in pharmacokinetics were observed between PM and EM patients. Total, encapsulated and released cytarabine AUC’s were 2.77, 1.42, and1.46 mg/ml*h in PM patients. In EM patient, total, encapsulated and released cytarabine AUC’s were 0.97, 0.76 and 0.17 mg/ml*h. When available, microscopy analysis confirmed the presence of liposomes in patients bone marrow. Conclusions: Differences in clinical outcome between AML-t and AML-MRC patient are not supported by differences in exposure levels upon Vyxeos administration. Surprisingly, we found that CDA status has a strong impact on cytarabine pharmacokinetics since PM patients treated with Vyxeos present a +185% increase in cytarabine levels as compared with EM patient. This suggests that upfront CDA testing could help to predict clinical outcome.
An open-label, first-in-human, phase I trial of the safety and efficacy of daily PCLX-001.
Authors: Randeep S. Sangha, Laurie Helen Sehn, John Kuruvilla, Michael Weickert, John Robert Mackey, Luc G. Berthiaume
Journal: Journal of Clinical Oncology (2020)

TPS3656 Background: Myristoylation regulates numerous membrane-bound signal transduction pathways important in cancer biology. This modification is catalyzed by N-myristoyltransferases 1 and 2 (NMT1 and NMT2). PCLX-001 is an oral small molecule with high affinity for both NMT proteins (IC50 of 5nM and 8nM, respectively) with high bioavailability and drug-like pharmacokinetic properties. In ex vivo sensitivity screening cell lines of hematologic cancer origin were exquisitely sensitive to PCLX-001, although high sensitivities and cell killing were also seen in some solid tumor lines derived from lung, pancreas, breast, colon, and bladder carcinomas. PCLX-001 demonstrated strong preclinical single-agent antitumor activity and tolerability in vivo in subcutaneous tumor xenograft models derived from lymphoma cell lines, lung cancer cell lines, a breast cancer cell line, as well as in a patient derived xenograft model from a patient with refractory DLBCL. The primary objective of this study is to determine the MTD and/or recommended phase II dose, safety, tolerability, and pharmacokinetics of PCLX-001 as a single agent, in patients with refractory lymphomas and advanced solid tumors. The secondary objective of the study is to evaluate the preliminary single agent anti-tumor activity of PCLX-001 in the patient populations studied. Methods: This is a multicenter, open-label, phase I dose-escalation study of oral PCLX-001 comprised of two parts (dose escalation and dose expansion). Eligible patients will have: histologically-confirmed advanced solid tumor or B-cell lymphomas who have failed prior therapy and/or are not eligible for therapies; ages ≥ 18 years; adequate organ function; life expectancy of at least 12 weeks; and measurable disease. Part A (dose-escalation) patients will be accrued in cohorts of 3 to 6 patients to each dose level, starting at 20 mg daily on a 28 day cycle. Dose escalation will follow a modified Fibonacci design such that the magnitude of escalation decreases as the dose level nears the human equivalent dose of the highest non-severely toxic dose in dogs and then escalate at 1.4 times the previous dose. Dose escalation and determination of the maximum tolerated dose will be based on the occurrence of dose limiting toxicities in cycle 1. Part B will have two single agent expansion cohorts (n = 20 each) in advanced solid malignancies and relapsed/refractory B-cell lymphoma, to determine the preliminary clinical activity of PCLX-001 to determine the recommended phase II dose. The first patient on study is planned for Q3 2020.
Role of clinical pharmacists in standardized residency training of general practice
Authors: Zhiqiang He, Mei Feng
Journal: BMJ (2018)

This article introduces the background and current status of the involvement of clinical pharmacists in residency training of general practice in Shanxi Dayi Hospital, and also describes their role in general practice team building, clinical medication guidance and teaching practice, to provide reference for the continuous improvement of training management.


Key words: 
Clinical pharmacist; Standardized training; General practitioners
A phase II study on the efficacy and toxicity of cabozantinib in recurrent/metastatic salivary gland cancer patients.
Authors: Wim van Boxtel, Maike Uijen, Chantal Driessen, Sjoert Pegge, Stefan M. Willems, Marianne Jonker, Tim Dijkema, Ilse van Engen - van Grunsven, Carla M.L.- Van Herpen
Journal: Journal of Clinical Oncology (2020)

6529 A phase II study on the efficacy and toxicity of cabozantinib in recurrent/metastatic salivary gland cancer patients. Background: Because c-MET and VEGFR are often overexpressed in salivary gland cancer (SGC), this study evaluated the efficacy and safety of cabozantinib in recurrent/metastatic (R/M) SGC pts. Methods: A single center, single arm, phase II study was conducted. Immunohistochemical c-MET positive (H-score ≥10) R/M SGC pts were included in 3 cohorts: adenoid cystic carcinoma (ACC), salivary duct carcinoma (SDC), and other SGCs. Objective growth or complaints due to the disease were required before inclusion in the ACC and other SGC cohort. No prior systemic treatments were required. Pts started 60 mg cabozantinib tablets OD. Primary endpoint was the objective response rate (ORR). A Simon two-stage design was used. In case of ≥1 objective response in the first 9 pts/cohort, 8 additional pts would be included in the cohort. Results: In total 25 pts were included from Sep. 2018 until premature closure due to severe toxicity in Nov. 2019. Median age was 56 years (range 49-72), prior treatments included: primary tumor resection ( n=19), radiotherapy ≥50Gy ( n=24), systemic therapy ( n=10; adjuvant in 2 pts, palliative in 8 pts). Six pts had grade 3 ( n=4), grade 4 ( n=1), or grade 5 ( n=1) wound/fistula complications, occurring at a median of 7.2 mths on cabozantinib (range 2.1-12.8). This resulted in a severe wound complication rate of 32% in 19 pts on treatment for ≥2 mths. Remarkably, 4 out of 6 pts developed this complication in the area exposed to high-dose Rx; 2/4 had a pre-existing fistula in this area. Median interval between Rx and start of cabozantinib was 71.3 mths (range 10.6-94.7). Other grade ≥3 adverse events in &gt;1 pt were: hypertension (5 pts), diarrhoea (2 pts) and dehydration (2 pts). Current median follow-up is 6.8 mths. The ORR was 6% (1/17 pts) in the ACC cohort, 20% (1/5 pts) in the SDC cohort, and 0% (0/3 pts) in other SGC pts; median PFS is 12.6 mths (95% CI 6.8 – 18.4 mths), 9.0 mths (insufficient events for 95% CI), and 6.9 mths (95% CI 0 – 15.2 mths), respectively. Median OS is not reached in any cohort. Conclusions: This phase II study on cabozantinib in R/M SGC pts demonstrated severe wound and fistula complications in 32% of pts on treatment for ≥2 mths, mostly (4/6 pts) within the radiotherapy field. Because of this toxicity the study was closed prematurely. Furthermore, cabozantinib showed minimal clinical activity in SGC pts. Research funding: Ipsen Pharmaceuticals Clinical trial information: NCT03729297 .
Diagnosis and treatment of childhood bronchiolitis obliterans
Authors: Yu-qi Zhao, Yong-ju Zhang, Jie Zhanc
Journal: BMJ (2011)

Clinical data of 28 cases of childhood bronchiolitis obliterans treated from September 2008 to November 2010 were retrospectively analysis.Pulmonary high-resolution CT (HRCT) showed that bronchial wall thicken was seen in all 28 patients,the mosaic pattern in 26 cases,patchy shadows in 18 cases,bronchiectasis with typical signet ring sign in 2 cases,atelectasis in 2 cases without pleural effusion.Pulmonary function tests and flexible bronchofiberscopy were performed in 6 cases,which showed the inflammation in bronchial tunica intima and obstruction of small airway.Blood routine,blood sedimentation,c-reaction protein,TORCH,hepatic function,renal function and immune function were normal.Patients received comprehensive treatment with methylprednisolone,clarithromycin and montelukast.The clinical conditions of 28 cases were improved with varying degrees after treatment and no significant side effects were observed.

Key words: 
Bronchiolitis; obliterans ; Diagnosis; Therapy