tbuckley/cabot-search huggingface dataset:
Indirect comparison of TAK-788 vs real-world data outcomes in refractory non-small cell lung cancer (NSCLC) with <i>EGFR</i> exon 20 insertions.
Authors: Leora Horn, Huamao Mark Lin, Sukhmani Kaur Padda, Charu Aggarwal, Caroline Elizabeth McCoach, Yanyan Zhu, Yu Yin, Jianchang Lin, Shuanglian Li, Zhongling Feng, Joel W. Neal
Journal: Journal of Clinical Oncology (2020)

9580 Background: Currently approved epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are ineffective in patients (pts) with EGFR exon 20 insertion NSCLC. TAK-788 is an EGFR TKI with potent and selective preclinical inhibitory activity against EGFR exon 20 insertions, and has demonstrated preliminary efficacy in a single-arm phase 1/2 clinical trial (NCT02716116). We performed an indirect comparison of real-world outcomes with clinical trial data for this subset of pts to determine whether TAK-788 provides superior efficacy over standard treatment options. Methods: We compared efficacy in pts with refractory NSCLC with EGFR exon 20 insertions treated with TAK-788 160 mg qd (1–7 prior lines) from the ongoing clinical trial (data cut Mar 1, 2019) vs real-world data (RWD) in the second-line setting from the US Flatiron Health electronic health record–derived database (Jan 2011‒Jun 2018). This analysis was conducted using an unadjusted data set, as well as by applying propensity score modeling with inverse probability of treatment weighting (IPTW) to adjust for group differences in key baseline characteristics. Progression-free survival (PFS) and objective response rate (ORR) were compared between groups. Results: A total of 99 pts were included, n=28 TAK-788 and n=71 RWD; mean age 62/65 y; male 25%/46%; Asian 18%/10%; former smoker 39%/45%; brain metastases 43%/34%. In the RWD, there was no consistent regimen for second-line treatment (including 29.6% immuno-oncologic agents, 25.4% EGFR TKI, 10% docetaxel). Baseline characteristics were comparable after weighting. PFS and ORR showed statistically significant improvements with TAK-788 vs RWD (Table). Specifically, after weighting, median PFS for TAK-788 vs RWD is 7.3 vs 3.5 mo, and ORR is 43% vs 13%. Conclusions: Despite a more heavily pretreated pt population, the efficacy of TAK-788 in pts with refractory NSCLC with EGFR exon 20 insertions appears better than other second-line treatment options used in the real-world setting. Clinical trial information: NCT02716116 . [Table: see text]
Prevalence of overweight, obesity and related metabolic diseases among male public institution office workers in health check-up
Authors: Qingying Tan, Xiujing Wang, Jiaqi Yao, Jing Wang, Yun Ruan
Journal: BMJ (2014)

Objective
To investigate the prevalence of overweight, obesity and related metabolic diseases among male public institution office workers in health check-up.


Methods
Total 1 018 male public institution office workers aged 23-60 underwent annual health check-up at our hospital in 2012. The data including blood pressure, waist circumference, height, body weight, serum glucose, plasma lipids and serum uric acid were analyzed. According to body mass index (BMI), the subjects were classified as: underweight(BMI<18.5 kg/m2), normal weight(18.5 kg/m2≤BMI<24 kg/m2), overweight(24 kg/m2 ≤BMI<28 kg/m2)and obesity(BMI≥28 kg/m2).


Results
The prevalence of overweight, obesity, central obesity and metabolic syndrome (MS) were 40.9%(416/1 018), 7.9%(80/1 018), 53.0%(540/1 018), and 11.2%(114/1 018), respectively. There were significant differences in fasting blood glucose(FPG), TC, TG, uric acid(UA), systolic blood pressure( SBP) and diastolic blood pressure(DBP) levels among different groups (F=4.82, 12.09, 40.55, 6.19, 28.97 and 49.29, respectively, all P<0.01). The prevalence rate of hypertension in underweight, normal, overweight and obesity groups was 0, 11.8%, 27.4% and 37.5%, respectively; that of diabetes was 0, 1.6%, 5.5% and 10.0%, respectively; that of hyperlipidemia was 40.0%, 47.2%, 66.3% and 71.2%, respectively; that of hyperuricemia was 0, 5.0%, 13.5% and 13.8%, respectively, which showed that with the increasing of BMI , the prevalence rates of related metabolic diseases were increased(χ2=55.97, 9.65, 43.32 and 24.08, all P<0.01). And the co-morbidity rate with ≥3 diseases in 4 BMI groups were 0(0/20), 1.4%(7/502), 5.8%(24/416) and 13.8%(11/80), respectively (χ2=31.90, P<0.01).


Conclusion
Obesity and overweight are correlated with metabolic disorders and the obese subjects are at high risk for cardiovascular diseases.


Key words: 
Obesity; Metabolic diseases; Body mass index
Effects of theophylline plus salmeterol/fluticasone propionate combination therapy on lung function and airway inflammation in patients with asthma
Authors: Qing He, Hanxiang Nie, Qiaoyu Yang, Min Liu, Yi Huang
Journal: BMJ (2014)

Objective
To explore the effects of theophylline plus salmeterol/fluticasone propionate combination product (SFC) on clinical control, lung function and airway inflammation in asthmatics.


Methods
A total of 146 asthmatics received 200 mg theophylline plus 50/250 μg SFC twice daily for 24 weeks. The level of asthma control was assessed by the asthma control test. Testing of lung function and inflammatory markers in induced sputum were performed. And 142 asthmatics received 50/250 μg SFC twice daily for 24 weeks as control.


Results
Asthma was completely controlled in 61 and 59 in the theophylline plus SFC and SFC groups respectively after a 24-week treatment period (P>0.05). Theophylline plus SFC improved the FEF25%-75% value, indicating small airway function, to a greater extent than SFC [(66.7±18.2)% & (56.6±17.4)%, P<0.01]. Percentage of eosinophil and concentration of eosinophil cationic protein in induced sputum were significantly lower in the theophylline plus SFC group than those in the SFC group [(4.1±2.3)% vs. (6.2±2.7)% & (63.9±39.4) vs. (90.3±46.2) μg/L respectively] (all P<0.01).


Conclusion
The therapy of theophylline plus SFC may provide greater improvements in small airway function and airway inflammation.


Key words: 
Asthma; Theophylline; Drug therapy, combination
Descriptive evaluation of frequent patient referrals to our cardio-oncology clinic: The Mayo experience.
Authors: Anza Zahid, Prema P. Peethambaram, Carrie A. Thompson, Minetta C. Liu, Kathryn Jean Ruddy, Sushil s. Luis, Malcolm s. Anastasius, Mohamed s. Badawy, Vaibhav s. Jain, Deanne s. Smith, Joerg Herrmann, Hector R. Villarraga
Journal: Journal of Clinical Oncology (2020)

e14018 Background: Cancer survival rates are improving. Therefore, management of cardiovascular complications has now become a crucial clinical concern. Cardio-oncology is the sub-specialty that assists in the overall management of cancer patients in a multi-disciplinary manner. Mayo Clinic cardio-oncology practice was initiated to work closely with our oncology colleagues for early detection of cardiovascular complications in response to cancer-therapy. Majority of the patients visit our cardio-oncology clinic once, we thought it is important to study the group of patients that visited frequently due to cardiovascular complications. Aim: To evaluate the most common cardiovascular complication in patients with 2 or more visits to our cardio-oncology clinic. Methods: From 2012-2017, there were &gt; 2500 patients visits to our clinic, with 24 patients having 2 or more visits. Data including patients’ demographics, ethnicity, chemotherapeutic medications, primary cancer type, cardiovascular risk factors, echocardiography and clinical outcomes were collected. Cardiotoxicity was defined as the decrease in left ventricular ejection fraction (LVEF) of &gt; 10% to a value of &lt; 53%. Heart failure was diagnosed based on Framingham’s criteria or by a cardiologist. Results: There were 19 women (80%) and 5 men (20%). Median age at the time of diagnosis was 56 years [19-76]. The most common malignancy was breast cancer (70%), followed by B-cell lymphoma (12%) and acute myeloid leukemia (8%). Thirty percent had &gt; 2 risk factors for cardiovascular disease. 75% of the patients had an LVEF of &lt; 53, of these 67% developed heart failure with 58% preserved and 42% reduced ejection fraction. Those with heart failure had received a mean anthracycline dose of 305 ± 91.8mg/m 2 . With initiation of ACEI, B-Blockers, and diuretics (GDMT) 79% showed recovery of LVEF to ≥53 during the follow up. Conclusions: In our experience, most patients who were seen at least twice in the cardio-oncology clinic for heart failure had received a dose of &gt; 300mg/m 2 anthracycline. With GDMT over 75% of the patients recovered. Care in the cardio-oncology clinic plays a key role in optimizing these clinical outcomes.
Serum phospholipids fatty acids and breast cancer risk by pathological subtype: EpiGEICAM study.
Authors: Marina Pollan, Virginia Lope, Angel Guerrero-Zotano, Ana Casas, José Manuel Baena-Cañada, Begoña Bermejo, Beatriz Perez-Gomez, Pedro Sanchez-Rovira, Manuel Ramos Vazquez, Antonio Anton, Jose Angel Garcia-Saenz, Montserrat Munoz, Ana de Juan, Raquel Andres, Antonio Llombart Cussac, Blanca Hernando, Rosa María Franquesa, Rosalia Caballero, Miguel Martin, Feliciano Priego
Journal: Journal of Clinical Oncology (2020)

e13604 Background: The role of fatty acids (FA) in breast cancer (BC) etiology is unclear. Most studies are based on self-reported dietary intake, without considering their internal transformation. This analysis tries to assess whether serum levels of 26 phospholipid FA (PL-FAs) and markers of their endogenous metabolism are associated with BC risk, both globally and by pathological BC subtype. Methods: EpiGEICAM-01 is a Spanish multicenter matched case-control study. BC cases and healthy women completed a lifestyle and a food frequency questionnaire, and serum samples were collected. Serum PL-FAs percentages were measured by gas chromatography-mass spectrometry (GC–MS). Conditional and multinomial logistic regression models were used to quantify the association of PL-FAs tertiles with BC risk, overall and by pathologic BC subtypes [luminal, HER2+ and triple negative]. Models were adjusted for age and region (multinomial models), education level, body mass index (BMI), menopausal status, age at menarche and at first birth, hormone replacement therapy, alcohol consumption, last year physical activity, history of benign breast disease, family history of BC and caloric intake, and were corrected for multiple testing. Stratified analyses by BMI and menopausal status were also performed. Results: Questionnaires and serum samples were collected from 795 case-control pairs. Women with high serum levels of stearic acid [odds ratio (OR)T3vsT1= 0.44; 95% confidence interval (CI) = 0.30-0.66], linoleic acid (ORT3vsT1= 0.66; 95% CI = 0.49-0.90) and arachidonic to dihomo-γ-linolenic acids ratio (OR T3vsT1= 0.64 95%; CI = 0.48-0.84; differences were remarkable in overweight/obese women) presented lower BC risk. Participants with high concentrations of palmitoleic acid (ORT3vsT1= 1.65; 95% CI = 1.20-2.26), trans-ruminant palmitelaidic acid (ORT3vsT1= 1.51; 95% CI = 1.12-2.02; differences observed were noticeable both in postmenopausal and in overweight/obese women), trans-industrial elaidic acid (ORT3vsT1= 1.52; 95% CI = 1.14-2.03; markedly both in premenopausal and in non-obese women), and high oleic to stearic acids ratio (ORT3vsT1= 2.04; 95% CI = 1.45-2.87) showed higher risk. These associations were similar in all BC pathological subtypes. Conclusions: Our results, which should be confirmed in future studies, emphasize the importance of analyzing fatty acids individually, as well as the desaturase activity indices. A decrease in the dietary intake of trans-monounsaturated fatty acids could be a good strategy for BC prevention.
Care home reforms should prioritise quality of life
Authors: Eleanor G Stevens, Stephanie Clarke, Jean Harrington
Journal: BMJ (2020)

Points made by other respondents to Oliver’s article concerning the indeterminate position of care homes1 correspond with our ethnographic observations of stroke survivors living in care homes.2 We are struck by the frequent mismatch between expectations—for example, of NHS providers, local authorities, and families—and the reality of homes’ abilities to provide optimal care for stroke survivors.

 The covid-19 pandemic has sharply underlined how care homes and the NHS interact or are avoidant during a crisis. Crises notwithstanding, …
癫痫治疗对儿童认知功能影响的研究进展
Authors: 陈虹, 陈瑛
Journal: BMJ (2012)

儿童期是神经系统发育渐趋成熟的时期,也是癫痫的高发阶段.认知功能的损害是癫痫治疗中十分关注的问题.癫痫治疗包括传统和新型抗癫痫药物、手术、迷走神经刺激术、高压氧等多种方法,治疗中需考虑利弊及谨慎选择适应证。
社区常见抑郁的识别与处理
Authors: 甘一方, 姜民慧
Journal: BMJ (2011)

甘一方:本次主要讨论社区常见抑郁的识别与处理.在社区,是否见到过抑郁患者?怎样判断是不是抑郁? 学员:遇到过很多,像愁眉苦脸、自残,中年人觉得活着无望、很自责,还有失眠、吃的很少、自认为有病,考虑可能是抑郁症,希望他们到专科就诊。
Trifluridine/tipiracil plus bevacizumab in patients with untreated metastatic colorectal cancer ineligible for intensive therapy: the randomized TASCO1 study
Authors: E. Van Cutsem, I. Danielewicz, M.P. Saunders, P. Pfeiffer, G. Argilés, C. Borg, R. Glynne-Jones, C.J.A. Punt, A.J. Van de Wouw, M. Fedyanin, D. Stroyakovskiy, H. Kroening, P. Garcia-Alfonso, H. Wasan, A. Falcone, A. Kanehisa, A. Egorov, P. Aubel, N. Amellal, V. Moiseenko
Journal: Annals of Oncology (2020)

We designed an open-label, noncomparative phase II study to assess the safety and efficacy of first-line treatment with trifluridine/tipiracil plus bevacizumab (TT-B) and capecitabine plus bevacizumab (C-B) in untreated patients with unresectable metastatic colorectal cancer (mCRC) who were not candidates for combination with cytotoxic chemotherapies.From 29 April 2016 to 29 March 2017, 153 patients were randomly assigned (1:1) to either TT-B (N = 77) or C-B (N = 76). The primary end point was progression-free survival (PFS). The primary PFS analysis was performed after 100 events (radiological progression or death) were observed. Secondary end points included overall survival (OS), quality of life (QoL; QLQ-C30 and QLQ-CR29 questionnaires), and safety.Median (range) duration of treatment was 7.8 (6.0-9.7) months and 6.2 (4.1-9.1) months in the TT-B and C-B groups, respectively. Median (range) PFS was 9.2 (7.6-11.6) and 7.8 (5.5-10.1) months, respectively. Median (range) OS was 18 (15.2 to NA) and 16.2 (12.5 to NA) months, respectively. QoL questionnaires showed no relevant changes over time for either treatment. Therapies were well tolerated. Patients receiving TT-B had more grade ≥3 neutropenia (47% versus 5% with C-B). Patients receiving C-B had more grade ≥3 hand-foot syndrome (12% versus 0% with TT-B) and grade ≥3 diarrhea (8% versus 1% with TT-B), consistent with the known safety profiles of these agents.TT-B treatment showed promising clinical activity in untreated patients with unresectable mCRC ineligible for intensive therapy, with an acceptable safety profile and no clinically relevant changes in QoL.NCT02743221 (ClinicalTrials.gov).
Taxane resistance in prostate cancer is mediated by decreased drug-target engagement
Authors: Ada Gjyrezi, Fang Xie, Olga Voznesensky, Prateek Khanna, Carla Calagua, Yang Bai, Justin Kung, Jim Wu, Eva Corey, Bruce Montgomery, Sandrine Mace, Diego A Gianolio, Glenn J Bubley, Steven P Balk, Paraskevi Giannakakou, Rupal S Bhatt
Journal: Journal of Clinical Investigation (2020)

Despite widespread use of taxanes, mechanisms of action and resistance in vivo remain to be established, and there is no way of predicting who will respond to therapy. This study examined prostate cancer (PCa) xenografts and patient samples to identify in vivo mechanisms of taxane action and resistance. Docetaxel drug-target engagement was assessed by confocal anti-tubulin immunofluorescence to quantify microtubule bundling in interphase cells and aberrant mitoses. Tumor biopsies from metastatic PCa patients obtained 2 to 5 days after their first dose of docetaxel or cabazitaxel were processed to assess microtubule bundling, which correlated with clinical response. Microtubule bundling was evident in PCa xenografts 2 to 3 days after docetaxel treatment but was decreased or lost with acquired resistance. Biopsies after treatment with leuprolide plus docetaxel showed extensive microtubule bundling as did biopsies obtained 2 to 3 days after initiation of docetaxel or cabazitaxel in 2 patients with castration-resistant PCa with clinical responses. In contrast, microtubule bundling in biopsies 2 to 3 days after the first dose of docetaxel was markedly lower in 4 nonresponding patients. These findings indicate that taxanes target both mitotic and interphase cells in vivo and that resistance is through mechanisms that impair drug-target engagement. Moreover, the findings suggest that microtubule bundling after initial taxane treatment may be a predictive biomarker for clinical response.
One-year real-world clinical effectiveness, safety, and laboratory safety of dupilumab in Japanese adult patients with atopic dermatitis: A single-center retrospective study
Authors: Hideaki Uchida, Masahiro Kamata, Aika Kato, Itsumi Mizukawa, Ayu Watanabe, Ai Agematsu, Mayumi Nagata, Saki Fukaya, Kotaro Hayashi, Atsuko Fukuyasu, Takamitsu Tanaka, Takeko Ishikawa, Takamitsu Ohnishi, Yayoi Tada
Journal: Journal of the American Academy of Dermatology (2020)
Consensus molecular subtype (CMS) as a novel integral biomarker in colorectal cancer: A phase II trial of bintrafusp alfa in CMS4 metastatic CRC.
Authors: Amir Mehrvarz Sarshekeh, Michael Lam, Isabel R. Zorrilla, Emma Brey Holliday, Prajnan Das, Bryan K. Kee, Michael J. Overman, Christine Megerdichian Parseghian, John Paul Y.C. Shen, Alda Tam, Edwin Roger Parra Cuentas, Liren Zhang, Xuemei Wang, Dzifa Yawa Duose, Rajyalakshmi Luthra, Neelima Reddy, Dipen M. Maru, Scott Kopetz, Van K. Morris
Journal: Journal of Clinical Oncology (2020)

4084 Background: Consensus Molecular Subtype 4 (CMS4) colorectal cancer (CRC) features increased TGFβ signaling, which may account for de novo resistance to immunotherapy for patients (pts) with microsatellite stable mCRC. To date, no prior trial has incorporated CMS status as an integral biomarker. Bintrafusp alfa (M7824) is a dual PD-L1 antibody/TGFβ trap with acceptable safety. Methods: Primary tumors from pts with metastatic CRC underwent CMS testing in a CLIA setting. In this Simon two-stage phase II trial (Ho: p &lt; .05; Ha: p≥.25) for CMS4 mCRC, pts received bintrafusp alfa 1200mg IV every 14 days. RT (8Gy/day x 3 days) to a single metastatic lesion with abscopal intent was administered between doses 2 and 3. The primary objective was to estimate response rate (RR) per iRECIST. Correlative studies including RNA sequencing were performed on pre- and on-treatment biopsies. Results: 53 of 137 tested pts (39%) between June 2018-December 2019 had CMS4 mCRC. 13 of 15 treated pts received the agent with RT. All pts were evaluable for toxicity, and 13 for response. Median number of doses was 3 (IQR, 2-4). There was one grade 3 immune-related adverse event (colitis) requiring study discontinuation. There were 2 pts with stable disease and 11 with progressive disease as best response (RR 0%, 95% CI 0-22%). Enrollment was stopped after first stage for futility. Median PFS and OS were 1.6 months and 5.0 months, respectively. In paired samples, treatment with bintrafusp alfa resulted in an increase in the expression of IFNγ signature in nonirradiated metastatic lesions ( p&lt; .001, q&lt; .001). Updated results will be presented. Conclusions: This is the first reported clinical trial to utilize CMS status as an integral biomarker for pts with metastatic CRC and capitalizes on treating CRC subpopulations with targeted agents based upon validated RNA-based signatures. Although the efficacy for bintrafusp alfa and RT is low, changes in IFNγ signature provides a potential signal for refining therapeutic strategies based upon TGFβ enrichment in pts with mCRC. Clinical trial information: NCT03436563 .
痛悔和教训
Authors: 孔鲁英
Journal: BMJ (2011)

我是一名校医,也算是全科医生,从事医疗工作20多年来,也一直是我的近亲们的家庭医生.由于我在异地,他们生病后总是先给我打电话,根据他们讲诉的症状,我会指导他们是去药店买药服用,还是去当地市立医院做检查。
Cost and efficacy of low-dose pembrolizumab in the treatment of non-small cell lung cancer patients in Asia.
Authors: Jia Li Low, Kenneth Sooi, Yiqing Huang, Gloria HJ Chan, Yvonne Ang, Wan Qin Chong, Hon Lyn Tan, Natalie Ngoi, Joan Choo, Matilda Lee, Vaishnavi Muthu, Yugarajah Asokumaran, Robert John Walsh, Rachel Su Jen Wong, Zhi Yao Chan, Ross A. Soo, Raghav Sundar, Wei-Peng Yong
Journal: Journal of Clinical Oncology (2020)

e19385 Background: Pembrolizumab has dramatically improved the survival of patients with non-small cell lung cancer (NSCLC) and is considered the standard of care for first line treatment of NSCLC who do not harbour oncogenic drivers. The fixed dose of 200mg was approved by the US Food and Drug Administration. The dose of 200mg was based on pharmacokinetic analysis. Studies have demonstrated equivalent efficacy with weight-based dosing 2mg/kg. An average Asian weighs 50-60kg. We aimed to look at the efficacy of pembrolizumab at a low fixed dose compared to the standard dosing. Methods: A review of all consecutive patients receiving pembrolizumab for advanced NSCLC from January 2016 to December 2019 in a large, high-volume academic medical centre, the National University Hospital, Singapore was conducted. Data fields collected include patient’s demographics, treatment doses and clinical characteristics. Time on treatment and overall survival were analysed using the Kaplan Meier method. Results: In total, 92 ECOG 0-2 patients with advanced NSCLC were treated with pembrolizumab. Median age was 69 years (Range, 29-92). Most were males (76%) and Chinese race (68%). Of the 92 patients, 46 (50%) and 46 (50%) received 100mg (Pem100) and 200mg (Pem200) of pembrolizumab respectively. Pembrolizumab was prescribed as first line in 73 (79%) and second line in 19 patients (21%). The average dose of pembrolizumab received in the low dose group was 1.87mg/kg (Range, 1.24mg/kg – 2.70mg/kg). 88 patients were included in the survival analysis. 4 were excluded due to the presence of an oncogenic driver. Patients were followed up for a median of 13.2 months. There was no difference in progression free survival between Pem100 and Pem200 for first-line single agent and when combined with chemotherapy (PFS: NR versus 5.3months, HR 2.17, 95% CI 0.76-6.16, p = 0.15 and NR vs 16.9 months, HR 2.89, 95% CI 0.35-25.16, p = 0.33 respectively). For patients who received pembrolizumab in the first line setting, the response rate was 56% vs 20% (p = 0.07), 67% vs 52% (p = 0.69) for Pem100 and Pem200 as a single agent and when combined with chemotherapy respectively. The median number of cycles received was 8.9 (Range, 1-60 cycles), translating to estimated cost savings of SGD 45 395 (~ USD 32 664) per patient who received Pem100. Conclusions: A lower fixed dose of pembrolizumab at 100mg showed no difference in progression free survival and response rate in an Asian cohort with significant cost savings. A further randomised controlled trial in an Asian population should be carried out.