tbuckley/cabot-search huggingface dataset:
Age and gender specific lung cancer incidence and mortality in Hungary: Trends from 2011 through 2016.
Authors: Gabriella Galffy, Zoltan Kiss, Krisztina Bogos, Judit Moldvay, Nora Bittner, Aladar Vastag, ZSOFIA MARIA NAGY-ERDEI, Gyorgy Rokszin, Gyula Ostoros, Veronika Judit Dr Szabone Dr Muller, Veronika Sarosi, Zoltan Polanyi, Balazs Nagy, Krisztian Horvath, Zsolt Abonyi-Toth, Zoltan Voko, Lilla Tamási
Journal: Journal of Clinical Oncology (2020)

e21572 Background: No assessment was conducted describing the age and gender specific epidemiology of lung cancer (LC) prior to 2018 in Hungary, thus the objective of this study was to appraise the detailed epidemiology of lung cancer (ICD-10 C34) in Hungary based on a retrospective analysis of the National Health Insurance Fund database. Methods: This longitudinal study included patients aged ≥20 years with LC diagnosis (ICD-10 C34) between 1 st January 2011 and 31 th December 2016. Patients with different cancer-related codes 6 months before or 12 months after LC diagnosis or having any anti-cancer treatment different from lung cancer protocols were excluded. Results: In 2011, 4,522 new male lung cancer cases were registered in the NHIF database, while we found 4,176 incident patients in 2016. The number of female patients increased from 2,636 to 2,828 during the same period. The mean age at diagnosis was 64.51 years for men (SD±9.85) and 64.93 years for women (SD±11.19) in 2011, increasing steadily to 65.80 years (SD±9.41) and 65.99 years (SD±10.45), respectively. Lung cancer incidence and mortality increases with age, peaking in the 70–79 age group (375.0/100,000 person-years) among males, while at 60–69 age group for females (148.1/100,000 person-years). The male-to-female incidence rate ratio reached 2.46 to 3.01 (p &lt; 0.0001) among the 70–79 age group. We found 2-11% decrease in male incidence rate at most age groups, while a significant 1-3% increase was observed in older females ( &gt; 60) annually during the study period. Conclusions: This nationwide epidemiology study demonstrated that LC incidence and mortality in Hungary is decreasing in younger male and female population, however we found significant increase of incidence in older female population, similar to international trends. Incidence rates peaked in younger age-groups compared to Western countries, most likely due to higher smoking prevalence in these cohorts, while lower age LC incidence could be attributed to higher competing cardiovascular risk resulting in earlier mortality in smoking population.
EIT PACMAN Study preliminary results: OncoSignal pathway analysis identifies actionable cancer targets.
Authors: Patricia Martin, Sigi Neerken, Anja Van De Stolpe, Eveline den Biezen-Timmermans, Martijn Akse, Maud Ngocamus, Claudio Nicotra, Alexander M. Eggermont, Paul Van De Wiel, Christophe Massard, Fabien M. Calvo
Journal: Journal of Clinical Oncology (2020)

e15606 Background: Precision medicine refers to tailoring of treatment to each individual patient, although identifying tumor driving signaling pathways (SP) that are functionally active is still a challenge. OncoSignal pathway tests quantitatively measure activity of SP such as estrogen receptor (ER), androgen receptor (AR), PI3K, MAPK, Hedgehog (HH), TGF-β, Notch on fresh frozen and formalin-fixed paraffin-embedded (FFPE) tissue samples. OncoSignal pathway analysis aimed at assessing clinically actionable SP and retrospectively predicting targeted drug response on a series of patients’ (pts) samples from the MOSCATO trial run at Gustave Roussy. Methods: OncoSignal pathway analysis (ER, AR, PI3K, MAPK, HH, Notch, TGF-β) was performed blinded by Molecular Pathway Dx (Philips, Eindhoven) on metastatic tumor tissue samples from breast cancer (BC), prostate (PC), and high grade serous ovarian cancers (OC). Using Affymetrix expression array data from public GEO datasets, SP activity was analyzed in healthy prostate, breast, and ovarian tissue to define abnormal SP activity thresholds for tumor tissue pathway analysis. For each individual sample, SP alterations were considered tumor driving SP if sample SP activity exceeded the 95 th percentile of SP activity within healthy tissue. Results by OncoSignal were also combined with clinical characteristics and molecular alterations identified in the MOSCATO trial. Results: Identified tumor driving SP were ER, AR, MAPK-AP1, HH, PI3K pathway in BC (n = 5), AR in PC (n = 30); AP1, Notch, TGFβ in OC (n = 17). OncoSignal identified clinically actionable tumor driving pathways in all BC samples (median tumor cellularity [MTC]: 40%, range 15-80%); 30/31 PC samples (MTC: 62%, range 25-90%), 16/17 OC samples (MTC 62%, range 15-80%). Actionable mutations were previously identified in 4/5 BC; 13/31 PC; 6/17 OC. Seven pts with BC and PC were treated with targeted therapy. OncoSignal pathway analysis correctly predicted response/resistance in 4 of these pts (57%). Conclusions: OncoSignal pathway analysis correctly identified SP activity alterations and predicted targeted drug response in this series of patients. OncoSignal will be further validated prospectively in precision medicine studies at Gustave Roussy in which patients are stratified for targeted treatment by mutation analysis.
Real-world outcomes of pembrolizumab plus carboplatin plus paclitaxel or nab-paclitaxel in non-small cell lung cancer (NSCLC).
Authors: Ashley Tabah, David Huggar, Jonathan Kish, Bela Bapat, Djibril Liassou, Ajeet Gajra, Talia Miller, Ronda Copher, Manali I. Patel
Journal: Journal of Clinical Oncology (2020)

e21717 Background: Pem+carbo+pac or nab-pac are approved first-line (1L) treatments for metastatic squamous NSCLC since 10/30/2018. Difference in real-world outcomes of these triplet combinations are unknown. Methods: Providers from community oncology practices in the USA reviewed the charts of consecutive NSCLC patients initiating 1L treatment with either pem+carbo+pac (“pac”) or pem+carbor+nab-pac (“nab-pac”) from 06/01/18-12/31/18; data were collected 11/22/2019-12/23/2019. Patient characteristics, treatment patterns, grade 3/4 toxicities, disease response, date of progression/death were retrospectively abstracted into an electronic case report form (eCRF). Univariate statistics were used to compare demographics, clinical characteristics and treatment patterns between cohorts. Overall survival (OS) from 1L was calculated using the Kaplan-Meier method. A Cox proportional hazards model was used to compare the risk of death between the two cohorts adjusted for multiple variables. Results: eCRFs were completed for 254 patients: nab-pac = 115, pac = 139. Median follow-up was 13.1 mos in both cohorts. No differences in demographics/clinical characteristics were noted (table). Median duration of therapy was 3.9 mos (nab-pac) and 3.8 mos (pac) (p = 0.58). Objective response rate: nab-pac = 69.6%, pac = 69.8% (p = 0.96). Receipt of maintenance therapy: nab-pac = 44.4%, pac = 48.9% (p = 0.47) . Median time to progression was 6.4 mos for nab-pac (n = 32) and 3.5 mos for pac (n = 29) (p = 0.10). 13.9% of nab-pac and 7.9% of pac patients had grade 3/4 toxicities (p = 0.16). At data cut-off, 18 nab-pac (15.7%) and 30 pac (21.6%) patients were deceased. Median OS from initiation of 1L was not reached. 12-month OS: nab-pac = 87.8% (95% CI: 81.8-93.8), pac = 79.3% (95% CI: 72.5-86.2). Adjusting for sex, age, race, PD-1 expression level, charlson comorbidity index (CCI) and ECOG-PS patients treated with nab-pac had a 40% reduction in mortality risk (HR = 0.55, 95% CI: 0.30-1.01, p = 0.05). Conclusions: No significant differences in demographics and clinical characteristics between patients treated with nab-pac or pac were observed. Median duration of treatment was equivalent with a marginally longer 12-month survival rate, and a lower adjusted mortality risk, among patients treated with nab-pac. [Table: see text]
免调码技术在提高自我血糖监测准确性方面的作用
Authors: 姚军, 高妍
Journal: BMJ (2008)

近年来,糖尿病发病率在我国呈迅速上升趋势.自我血糖监测(self monitoring of blood glucose,SMBG)作为糖尿病控制的重要辅助手段,是糖尿病综合治疗方法中的一个重要组成部分,检测方法的准确性以及如何提高准确性已经越来越受到临床医生和糖尿病保健机构的重视。
Strengthen the training of general practitioner to promote the construction of Healthy China
Authors: Yuying Zheng, Zuoqin Yan, Zhigang Pan, Shanzhu Zhu
Journal: BMJ (2017)

Department of General Medicine in Zhongshan Hospital, Fudan University was founded in 1994, which was the only unit established in a tertiary hospital in the country at that time, engaged in clinical practice, teaching and research of general practice. Zhongshan Hospital won the second prize of National Teaching Achievement in 2014 for Exploration and innovation of training system of general practitioners in China , which contributed to development of standardized training system of general practitioners suitable to China's national conditions. This article summarizes the experience in training general physician, development of disciplines and enhancing influence of Zhongshan Hospital over years, hopefully it will be of reference value for medical educators.


Key words: 
General physician; Training
Endoscopic findings and clinical implication of heterotopic gastric mucosa in upper esophagus
Authors: Ya Jiang
Journal: BMJ (2019)

Heterotopic gastric mucosa in upper esophagus (HGMUE) is a rare clinical condition, which is often associated with congenital agenesis. The diagnosis of HGMUE mainly depends on endoscopic and pathological examinations. The detection rate is increasing with the development of endoscopic techniques, however, there is no consensus on the duration of follow-up and therapeutic strategies for HGMUE and its clinical implication need to be further studied.


Key words: 
Esophagus; Heterotopic gastric mucosa; Endoscopy
Training needs and assessment of pilot training program for assistant general practioner (3+ 2 mode) in Shanghai: questionnaire survey and in-depth interview
Authors: Jie Gu, Xuan Lu, Zhi-gang Pan, Ying-min Chen, Kun Zhu, Xiu-ling Ying, Yue-lin Xie, Jian-ye Qin, Jing Yuan
Journal: BMJ (2013)

Objective
To survey  training needs and assessment of a pilop training program for assistant general practioner (3+ 2 mode) in Shanghai.


Methods
A qustionnaire survey and in-depth interview were conducted among 30 trainees of  pilot assistant general practitioner training program of 3+ 2 mode in Jiading District of Shanghai from September to October 2012.


Results
Thirty trainees aged (22.6±0.7)y (5 males and 25 females) received  questionnaire survey. All trainees were in favor of  3+ 2 mode, of whom 50.0% (15/30) showed  willing. In  intension of attending 3+ 2 mode, 40.0% (12/30) expressed   and no one showed unwilling or   In  intension of recommending colleagues to attend 3+ 2 mode, 46.7% (14/30) were completely willing and 6.7%(2/30)were unwilling. The basic theory of family medicine was  most needed for trainging contents and 63.3% showed  need;  other item was  least needed and 41.1% showed  need. In overall assessment of 3+ 2 mode, 26.7% (8/30) showed  satisfied, 50.0% (15/30) showed  and 23.3% (7/30) showed so-so. The highest proportion (46.7%, 14/30) scored  ablities of mentors as  satisfied and  lowest proportion (26.7%, 8/30) thought  trainging contents was very satistied. Five trainees received in-depth interview, their main points included the training content should meet  needs of routine work of village clinics, the study of basic theory of family medicine lacks of practice, teachers did not have enough knowledge about general practice and income was low during training. There were different views on  choice of 3+ 2 mode or diploma-upgrading courses among intervewees.


Conclusions
The trainees have positive attitudes and strong willingness for 3+ 2 mode. But it should be improved in training content, training method, teacher training and supporting policies.


Key words: 
Physician assistants; General practioner; Training; Needs assessment
Development of home-based rehabilitation mode for stroke patients based on Lean Six Sigma theory
Authors: Yan Qin, Yongxiang Zhou, Yunqing Zhou, Yikai Mi, Xingna Zhang, Jianping Wu
Journal: BMJ (2017)

The community rehabilitation model for stroke patients was developed based on the experiences of Quyang Community Health Service Center in Shanghai under the guidance of Lean Six Sigma. The validity of the process and results were evaluated by a expert group according to validity theory. The developed Manual of Home-based Rehabilitation mode for Stroke Patients in Community had good validity, which may provide guidance for stroke patients rehabilitation in the community, and also provide reference for clinical application.


Key words: 
stroke; rehabilitation; community health service; Lean Six Sigma
BT5528-100 phase I/II study of the safety, pharmacokinetics, and preliminary clinical activity of BT5528 in patients with advanced malignancies associated with EphA2 expression.
Authors: Johanna C. Bendell, Judy Sing-Zan Wang, Babar Bashir, Debra L. Richardson, Gavin Bennett, Carly Campbell, Meliessa G. Hennessy, Phil Jeffrey, Julius Kirui, Lisa Mahnke, Geoffrey Shapiro
Journal: Journal of Clinical Oncology (2020)

TPS3655 Background: BT5528 is a Bicycle Toxin Conjugate (BTC), comprising a bicyclic peptide targeting the tumor antigen EphA2, linked to a cytotoxin (monomethyl auristatin E [MMAE]) via a tumor microenvironment cleavable linker. Bicycles are a novel class of chemically synthesized constrained peptides, developed by Bicycle Therapeutics. EphA2 is reported to be overexpressed in a range of solid tumors, contributes to oncogenesis, tumor-associated angiogenesis and metastasis. Intracellular EphA2 signaling converges on pathways that are integral to cell growth, proliferation, migration and invasion. Increased EphA2 expression has been identified as a resistance mechanism to EGFR Tyrosine Kinase Inhibitor based therapy. BT5528 mechanism of action is dependent on tumor penetration, target binding and release of MMAE toxin payload. BTCs offer advantages over antibody-toxin conjugates exhibiting rapid penetration of dense tumors and decreased extra-tumor exposure. BT5528 exhibited a favorable preclinical profile supporting the initiation of a first-in-human study to investigate safety and efficacy of BT5528 in indications with evidence of EphA2 expression including non-small-cell lung cancer (NSCLC), ovarian cancer, triple-negative breast cancer (TNBC), gastric/upper gastrointestinal (GI), pancreatic and urothelial cancers. Methods: BT5528-100 (NCT04180371) is a Ph I/II study to evaluate safety and tolerability of weekly BT5528 alone and in combination with Q4W nivolumab. Each dose escalation utilizes a 3+3 design which converts to a Bayesian design to determine MTD or MAD and RP2D for BT5528 with and without nivolumab. Eligible patients must have advanced solid tumors associated with EphA2 expression which have recurred after exhausting standard treatment options. Patients must have available tumor tissue and acceptable hematologic and organ function, with exclusions for uncontrolled brain metastases, thromboembolic events, bleeding disorders, uncontrolled hypertension, CYP3A4 inhibitors/inducers or, for the nivolumab cohorts, autoimmune disease. On-study tumor and blood samples will be collected for biomarker evaluations including tumor EphA2 expression, ADA, and candidate response biomarkers for BT5528 alone and combination with nivolumab. Pharmacokinetic data will be reported for C1D1 and D15 for BT5528 and MMAE. The expansion phase will enroll specific tumor types to evaluate clinical activity of BT5528. Enrollment is ongoing. Clinical trial information: NCT04180371 .
继发性骨质疏松症诊疗指南(讨论稿)
Authors: 中华医学会骨质疏松和骨矿盐疾病分会
Journal: BMJ (2006)

一、概述 继发性骨质疏松症是由于疾病、药物、器官移植等原因所致的骨量减少、骨微结构破坏、骨脆性增加和易于骨折的代谢性骨病.引起继发性骨质疏松症的病因很多,临床上以内分泌代谢疾病、结缔组织疾病、肾脏疾病、消化道疾病和药物所致者多见。
Maintenance oral etoposide (VP-16) after high-dose chemotherapy (HDCT) for patients with relapsed metastatic germ-cell tumors (mGCT).
Authors: Bilal Anouti, Reem Akel, Sandra K. Althouse, Rafat Abonour, Mohammad Issam Abu Zaid, Nasser H. Hanna, Lawrence H. Einhorn, Nabil Adra
Journal: Journal of Clinical Oncology (2020)

5051 Background: HDCT and peripheral-blood stem-cell transplant (PBSCT) can cure up to 60% of patients with relapsed mGCT. Maintenance daily oral VP-16 after salvage therapy has been shown effective in inducing remissions (J Clin Oncol 1995;13:1167-9). We evaluate the role of maintenance VP-16 post HDCT+PBSCT compared to observation. Methods: The prospectively maintained Indiana University testicular cancer database was interrogated. Patients with relapsed non-seminoma who completed HDCT+PBSCT and achieved serologic remission and hematologic recovery were evaluated. Outcomes of patients who received maintenance VP16 (N = 141) were compared to patients who were observed (N = 252). In this retrospective study, Kaplan-Meier method was used to analyze progression free survival (PFS) and overall survival (OS). Univariable and multivariable cox regression models were used to determine variables associated with PFS. Results: 2-year PFS in the maintenance VP-16 versus observation group was 55% vs. 44% (p = 0.008). 2-year OS was 61% vs. 52% (p = 0.01). A multivariable analysis was performed including the factors: primary tumor site (testis vs. mediastinum), IGCCCG risk, platinum refractory, HDCT line of therapy (2 nd vs. ≥3 rd ), tumor marker amplitude at HDCT initiation, and receipt of maintenance VP-16 post HDCT vs. observation. Maintenance VP-16 was confirmed as an independent predictor of improved PFS with HR 0.48 [95% CI, 0.35-0.66] (p &lt; 0.001). Conclusions: Maintenance oral VP-16 post HDCT+PBSCT improved PFS and OS. In a multivariable model including known adverse prognostic factors, maintenance VP-16 was an independent predictor of improved PFS. [Table: see text]
Moderate to vigorous physical activity effect on chemotherapy-induced peripheral neuropathy.
Authors: Grace Kanzawa-Lee, John C. Krauss, Robert Ploutz-Snyder, Janet Larson, Ken Resnicow, Athena Lievense, Lauren Kavanagh, Ellen M. Lavoie Smith
Journal: Journal of Clinical Oncology (2020)

e24151 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common intractable side effect of oxaliplatin treatment that presents with numbness, tingling, and nerve pain in both hands and feet; and sometimes, weakness and impaired balance and quality of life. Moderate-vigorous (MV) physical activity (PA) may reduce CIPN by improving blood circulation, chemotherapy distribution, inflammation, oxidative stress, and neuroplasticity. This dose-response analysis aimed to explore the effect of different MVPA and total PA doses on CIPN severity among oxaliplatin-receiving gastrointestinal cancer survivors. Methods: The original pilot RCT tested an 8-week home-based brisk walking intervention versus PA education alone to reduce CIPN. This analysis focuses on the intervention group ( n = 29), which received MVPA motivational supports (e.g., a Fitbit Charge 2, walking plan, motivational interviewing). Participants completed self-report CIPN severity surveys at baseline (2 nd oxaliplatin infusion) and 8 weeks. Fitbit-classified minutes of weekly MV and daily total (light-vigorous) PA were averaged over the 8 weeks. MVPA was dichotomized: met 225 weekly MVPA minutes ( n = 17) or not ( n = 19). Linear regression was used to analyze the effect of MVPA/total PA changes and effects on 8-week CIPN severity, controlling for oxaliplatin dose received and baseline CIPN levels. Results: Increases over the 8 weeks were observed in patients’ MVPA (mean difference [ MD] = 17.39 min/week; 95% CI 1.38, 33.40; p = .03) and total PA ( MD = 7.80 min/week; 95% CI 2.31, 13.29; p = .01). Total PA had no effect on the outcomes. However, averaging at least 225 MVPA minutes per week led to less severe sensory CIPN ( MD = -7.28; 95% CI -13.53, -1.03; p = .03), particularly tingling in the hands ( MD = -26.35; 95% CI -44.03, -8.68; p = .01). The models accounted for 37% and 44% of the variance in sensory CIPN ( p = .02) and tingling at 8 weeks ( p = .01), respectively. Conclusions: This pilot study provides preliminary evidence that increasing weekly MVPA, specifically, may lead to reduced CIPN severity among gastrointestinal cancer survivors receiving oxaliplatin. A larger study that utilizes stronger MVPA measurement and biomarker evaluation is needed. Clinical trial information: NCT03515356 .
The neural phenotype in invasive urothelial carcinoma patients: Alternative score detection and prognostic implication.
Authors: Paolo Andrea Zucali, Piergiuseppe Colombo, Camilla De Carlo, Laura Giordano, Rodolfo Hurle, Massimo Lazzeri, Grazia Maria Elefante, Federica D'Antonio, Federica Regis, Matteo Perrino, Fabio De Vincenzo, Giorgio Ferruccio Guazzoni, Massimo Roncalli, Armando Santoro
Journal: Journal of Clinical Oncology (2020)

e17037 Background: Recent molecular subtyping studies (NGS) identified a subset (5-15%) of muscle invasive urothelial carcinoma (MIBC) with transcriptomic patterns consistent with neuroendocrine (NE) differentiation in the absence of NE histology (NE-like), representing a potentially high risk subgroup of carcinoma which may require a different treatment strategy. We recently set an alternative immuno-phenotypical score (Piescore), to discriminate Luminal from Basal from Neural carcinoma. Aim of this study was to test the ability of Piescore in identifying NE-like cases in a mono-institutional cohort of patients treated with trans-urethral resection and radical cystectomy (RC) and to correlate them with clinical outcomes. Methods: Transurethral resection specimens harbored foci of HG pT2 (MIBC) UC from 116 pts who subsequently underwent RC have been submitted for immunohistochemical analysis, using relevant gene-expression-based markers for Basal type (CD44, CK5/6) and Luminal type (CK20 and pPARg). Piescore divided Basal and Luminal types when at least 3 of the 4 markers were consistent with a specific phenotype; Mixed if two luminal and two basal markers were present simultaneously; NE-like when all four markers were negative. Results: Overall, the Piescore identified Basal phenotypes in 49 patients (42,2%), Luminal in 38 (32,7%), and Mixed in 9 (7,8%). No expression was identified in 20 patients (17,2%): 7 cases with morphological NE differentiation and 13 cases with classical urothelial histology, all consistent with NE-like phenotype. Interestingly, in 10/13 patients the NE-like phenotype was only documented in the muscle invasive component of the tumor whereas in the non-invasive component they retained Luminal phenotype in 9 cases and Basal in one. With a median follow up of 188 months, the pathological stage of disease (pT2 versus ≥pT3 and/or N+) and the tumor vascular invasion (absent versus present) resulted prognostic (Stage: 5-years DFS rate 65% versus 30%, p = 0.038; 5-years OS rate 69% versus 32%, p = 0.017) (vascular invasion: 5-years DFS rate 47% versus 24%, p = 0.020; 5-years OS rate 54% versus 21%, p &lt; 0.001) in all population. No statistically significant differences in terms of pathological stage of disease, vascular invasion, DFS, and OS were observed in NE-like cases compared with non-NE-like cases. Conclusions: The NE-like urothelial carcinoma identified by Piescore immunophenotyping (CD44, CK5/6, CK20 and pPARg) did not show any statistically significant association with worse prognosis.