tbuckley/cabot-search huggingface dataset:
Pembrolizumab monotherapy for patients with advanced MSI-H colorectal cancer: Longer-term follow-up of the phase II, KEYNOTE-164 study.
Authors: Luis A. Diaz, Dung T. Le, Tae Won Kim, Eric Van Cutsem, Ravit Geva, Dirk Jaeger, Hiroki Hara, Matthew E. Burge, Bert H. O'Neil, Petr Kavan, Takayuki Yoshino, Rosine Guimbaud, Hiroya Taniguchi, Elena Elez, Salah-Eddin Al-Batran, Patrick M Boland, Yi Cui, Carlos Alberto Mayo, Patricia Marinello, Thierry Andre
Journal: Journal of Clinical Oncology (2020)

4032 Background: Pembrolizumab provides effective antitumor immunity and durable responses in patients (pts) with advanced, colorectal cancer (CRC) with microsatellite instability-high (MSI-H) tumors. We present data on antitumor immunity with pembrolizumab in pts from the phase 2, KEYNOTE-164 study who had approximately 3 years of follow-up, and in pts re-treated after disease progression. Methods: KEYNOTE-164 enrolled pts with metastatic MSI-H CRC, MSI-H status confirmed locally by IHC or PCR, and ≥2 (cohort A) or ≥1 (cohort B) prior lines of therapy (fluoropyrimidine, oxaliplatin, irinotecan, or anti VEGF/EGFR). Eligible pts received pembrolizumab 200 mg Q3W for 2y (35 administrations) or until progression, unacceptable toxicity, or withdrawal. Pts who stopped pembro due to a confirmed CR or after completing 2y of treatment and who progressed after stopping were eligible for re-treatment with up to 17 administrations in the second-course phase, at investigator discretion. Tumor response was assessed Q9W per RECIST v1.1 by independent review. The primary endpoint was ORR. Secondary endpoints included DOR, PFS, OS, and safety. The data cutoff date was Sep 9, 2019. Results: At data cutoff, the median follow-up was 31.4 mo (range, 0.2-47.8) for 61 pts in cohort A and 36.1 mo (0.1-39.3) for 63 pts in cohort B. ORR was 32.8% (3CR, 17PR; 95% CI% 21.3-46.0) for cohort A and 34.9% (8CR, 14PR; 95% CI 23.3-48.0) in cohort B. Median DOR was not reached (NR [range, 6.2-41.3+]) and not reached (range, 3.9+ to 37.1+), respectively. Fifteen pts in cohort A and 17 in cohort B had ongoing responses at data cutoff. Median PFS was 2.3 mo (95% CI 2.1-8.1) with 3-yr PFS rate of 31% in cohort A and was 4.1 mo (2.1-18.9) with 3-yr PFS rate of 34% in cohort B. Median OS was 31.4 mo (21.4-NR) with 3-yr OS rate of 49% in cohort A and was not reached (19.2-NR) with 3-yr OS rate of 52% in cohort B. Nine pts (6 in cohort A, 3 in cohort B) had a second course of treatment. The best response in second course was PR in 1 patient each in cohort A and B. Grade 3-4 drug-related adverse events occurred in 10 (16%) pts in cohort A and 8 (13%) pts in cohort B. No grade 5 drug-related events occurred. Conclusions: After approximately 3 y of follow-up, pembrolizumab continues to provide effective long-term antitumor immunity with durable responses, with small numbers of drug-related adverse events and no drug-related deaths in pts with advanced, MSI-H CRC. Clinical trial information: NCT02460198 .
Characteristics of electroencephalograph in cerebral infarction patients with subsequent vascular dementia
Authors: Fugang Luo, Zhihua Shen, Yueqi Huang, Xiaoying Zhang, Meifang Chen
Journal: BMJ (2018)

Clinical data of 65 patients with acute cerebral infarction (frontal or temporal or both lobes) treated in our hospital during 2015—2016 were retrospectively reviewed.The patients were followed up for 6 months, 34 cases were diagnosed as vascular dementia (VD) according to ICD-10 (VD group) and 31 cases were diagnosed as simple cerebral infarction (control group). The abnormal rate of electroencephalograph (EEG) at baseline in VD group was significantly higher than that in control group (χ2=5.44, P=0.02). Compared to control group, the powers of slow wave (θ wave and δ wave) at baseline, third month and sixth month in VD group were significantly increased (Fbetween groups=17.39, Finner groups=163.50, Finteraction=38.71; all P=0.00) and (Fbetween groups=5.10, Finner groups=119.04, Finteraction=6.54; P<0.05). Compared to baseline, the α wave and β wave were significantly decreased at third month and sixth month in VD (Finner groups=116.40, P=0.00) and (Finner groups=55.90, P<0.05). Compared to control group, the powers of θ wave (except in the frontal lobe at baseline and third month) and δ wave were significantly increased at all time points (P<0.05). Except the θ wave in occipital lobe, there were significant differences in slow wave at all time points between VD group and control group (P<0.05). The featured EEG with increased slow wave in many regions of cerebral infarction can be used for early diagnosis of VD in patients with cerebral infarction.


Key words: 
Vascular dementia; Cerebral infarction; Electroencephalograph
Standardized management of patients with coronary heart disease in Yuetan Community of Beijing
Authors: Wen-li Zhou, Jian-qin Dong, Xiu-mei Tong
Journal: BMJ (2009)

Five hundred and twenty two coronary heart disease (CHD) patients in Yuetan Community of Beijing during January 2005 to December 2007 were divided into two groups: 234 patients received standardized management and 288 patients received routine management as the control group.The quality of life and the effectiveness of general management were compared between two groups after one year.The grade of quality of life in standardized management group was higher than that in routine management group (P<0.05 or P<0.01).The former was better than the latter in alleviating chest distress and breath-hold, decreasing blood pressure, blood glucose and lipid, improving the electrocardiogram on the ST section and T wave (P<0.05 or P<0.01), and reducing the medical expenses (P<0.01).Standardized management is favorable in community management of patients with coronary heart disease.

Key words: 
Coronary Disease;  Disease Management
Correlation of depression and cognitive function in patients with chronic obstructive pulmonary disease
Authors: Chuan-qin Xu, Yuan-qiang He, Yu-long Zheng, Li-yang Zhou, Shu Liu
Journal: BMJ (2013)

Based upon the measure of depression as defined by Hamilton depression scale (HAMD) scores >17, 120 patients with chronic obstructive pulmonary disease (COPD) were classified into 2 groups: COPD patients with or without depression. According to the mini-mental state examination (MMSE), the cognitive functions of all patients were evaluated. Meanwhile, oxygen saturation and pulmonary function were measured by blood gas analyzer and spirometer respectively. Fifty-four COPD patients were complicated with depression. HAMD scores were significantly negatively correlated with oxygen saturation and pulmonary function (P<0.05). Multiple regression analysis revealed that gender, oxygen saturation and MMSE scores were risk factors of depression (P<0.05). MMSE scores decreased more obviously in the COPD patients with depression and were positively correlated with oxygen saturation (P<0.01). A negative correlation existed between MMSE scores and HAMD scores (r=-0.549, P<0.05).


Key words: 
Pulmonary disease, chronic obstructive; Depression
Factors related to death of thoracic trauma emergency in children
Authors: Tao Liu, Yu Sun, Jianji Guo, Mingwu Chen, Yongyong Wang, Lei Xian, Huamin Tang
Journal: BMJ (2017)

Objective
To investigate the factors related to death of thoracic trauma emergency in children.


Methods
Total 528 children and infants aged 0-14 years with thoracic injuries, including 317 boys and 211 girls, admitted in emergency department from January 2010 to January 2014 were included in the study. The factors related to emergency death were investigated by using conditional logistic analysis.


Results
Among 528 cases, emergency death occurred in 34 cases with an emergency mortality rate of 6.44%.Single-factor analysis showed that emergency death was correlated with complication with other organ trauma, the time of first medical intervention, the time of arriving at first contact hospital, the rank of first contact hospital, hypoxemia and causes of injuries (all P 0.05). Logistic analysis showed that the time of first medical intervention>30 min (B=1.467, 95%CI: 0.412-0.975), complication with other organ trauma (B=2.342, 95%CI: 0.415-0.943), hypoxemia (B=2.915, 95%CI: 0.749-0.819), and first visiting to tertiary hospital (B=-1.861, 95%CI: 1.023-1.742) were influencing factors of emergency death.


Conclusion
The results indicate that to improve the success rate of emergency treatment of thoracic trauma in children, it is necessary to reduce the time of first medical intervention and to correct the hypoxemia promptly.


Key words: 
Thoracic injuries; Child; Emergency death
Survey on aspirin application for secondary prevention of coronary artery disease in Beijing communities
Authors: Zhiyi Ma, Liping Wu, Xueping Du, Ningling Sun
Journal: BMJ (2019)

Objective
To survey the status of aspirin application asantiplatelet therapy for secondary prevention of coronary artery disease (CAD) in Beijing communities.


Methods
A cross-sectional survey on status of aspirin use was conducted among 60 communities in Beijing from September 2014 to January 2015. Items of survey included the duration of aspirin application, aspirin dosage, application time, reasons for interruption and reasons for non-application.


Results
Total 61 000 questionnaires were delivered and 56 969 valid ones were retrieved with a recovery of 93.39%. The aspirin application rate was 78.22% (15 105/19 311) among patients with diagnosed CAD, while that was 81.42% (1 319/1 620) among patients with self-reported CAD (χ2=9.06, P<0.01). There was no effect of early cardiovascular disease family history on aspirin application among patients with diagnosed CAD (P=0.77). Among the patients with diagnosed CAD, the reasons of no aspirin application were: rejection with unknown reasons, worry about stomach side effects, clopidogrel application, not suitable subjectsand other antiplatelet drugs application.


Conclusions
The proportion of aspirin application is relatively high among coronary artery disease patients in Beijing communities. The results of survey provide the direction of patient education in the future.


Key words: 
Coronary artery disease; Aspirin; Community health center
Cancer risk and overall survival in APC I1307K carriers.
Authors: Stephen B. Gruber, Joseph D Bonner, Flavio Lejbkowicz, Stephanie Schmit, Hedy Rennert, Joel K Greenson, Mila Pinchev, Marilena Melas, Victor Moreno, Lynn P Tomsho, Gabriel Capella, Danielle Braun, Sidney A Smith, Kevin McDonnell, Gregory Idos, Gad Rennert
Journal: Journal of Clinical Oncology (2020)

1592 Background: The germline variant APC I1307K is one of the most commonly identified pathogenic variants on germline genetic testing panels. The purpose of the Molecular Epidemiology of Colorectal Cancer study was to quantify the risk of colorectal cancer among carriers, characterize the clinical, pathologic, and molecular features of colorectal cancers arising in patients with APC I1307K, and to describe the overall and disease-specific survival of carriers with colorectal cancer. Here, the final results of the Molecular Epidemiology of Colorectal Cancer Study are reported with respect to APC I1307K. Methods: We consented 6,006 incident, pathologically confirmed cases of colorectal adenocarcinoma and 5,023 age, sex, and ethnicity matched controls without colorectal cancer between March 31, 1998 and July 1, 2017 within a geographically defined area of Northern Israel. Comprehensive, in-person epidemiologic interviews were conducted for cases and controls, with uniform histopathologic review, detailed molecular analysis, medical record review and clinical follow-up for up to 21 years. Results: The demographic and clinical features of incident colorectal cancer cases matched the population distribution of colorectal cancer in Israel. APC I1307K was identified in 429 (7.1%) of cases and 201 (4.0%) of controls. The estimated relative risk of colorectal cancer among carriers was 1.89 (95% confidence interval, 1.59 - 2.24), p &lt; 0.0001. The prevalence and odds ratios differed by ethnic group. Homozygous carriers were at especially high risk, with an odds ratio of 3.90 (95% confidence interval 1.11–13.71). APC I1307K carriers were significantly less likely to have microsatellite instable tumors (p = 0.04). Overall survival of APC I1307K carriers was not significantly different than survival of non-carriers, after adjustment for age, stage, sex, ethnicity, and microsatellite instability. Conclusions: APC I1307K is an actionable germline mutation that confers meaningful lifetime risk of colorectal cancer in heterozygous and homozygous carriers. APC I1307K is not an independent prognostic factor for overall survival or disease specific survival and is not associated with the MSI phenotype. Cumulative lifetime risk estimates inform genetic counseling and provide data for policies regarding the timing and frequency of screening and other preventive strategies.
The efficacy and safety profile of anlotinib with etoposide plus cisplatin/carboplatin in treatment-naive extensive-stage small cell lung cancer(SCLC) patients: Results from a phase II single-arm trial.
Authors: Pengbo Deng, Huaping Yang, Cen Chen, Chengping Hu, Liming Cao, Qihua Gu, Jian An, Bin Li, Yongjun Tang, Jie Meng, Juntao Feng
Journal: Journal of Clinical Oncology (2020)

9066 Background: Combination of etoposide and cisplatin/carboplatin is the most commonly used initial chemoptherapy regiment in extensive-stage small cell lung cancer. A meta-analysis released that, there is no significant difference was observed in Objective response rate(ORR), progression-free survival (PFS), or overall survival(OS) in patients(pts) receiving cisplatin-base versus carboplatin-based regimens. We performed a single-arm phase II trial to determine if maintain of single-agent anlotinib, an oral VEGFR, FGFR, PDGFR and c-Kit tyrosine kinase inhibitor, after 4-6 cycles of anlotinib + etoposide + cisplatin/carboplatin would improve PFS and ORR. Methods: SCLC pts (18~70 yrs, extensive-stage SCLC, no prior systematic chemo/ICI therapy) received anlotinib( 12mg QD from day 1 to 14 of a 21-day cycle) +etoposide( 100mg/m 2 , d1~3 of 21-day cycle)+ cisplatin( 75-80mg/m 2 ,Q3W)/ carboplatin( AUC = 5~6,Q3W) for 4~6 cycles, and anlotinib maintenance. The dual-primary endpoint were PFS and ORR. Results: Between Oct.2018 to Dec.2019, 27 pts enrolled and included in the efficacy and safety analysis: age: median 62 (range:44-71); male 93%; cisplatin/ carboplatin/ both 11%/78%/11%; 37%(10/27) of pts required chemotherapy dose modification only, and the other 30% (8/27) of pts required anlotinib+ chemotherapy dose modification.The median PFS was 9.61 months ( 95%Cl:7.80-11.42). ORR was 77.78% (21/27), disease control rate (DCR) was 96.30% (26/27).Toxicities≥grade 3 included: neutropenia 22%, leukopenia 11%, hand-foot syndrome 15%, nausea 4%, mucositis 4%, edema 4%, anorexia 4%, xerostomia 4% and fatigue 4%; there were no grade 5 toxicities. Conclusions: Combined treatment with anlotinib plus etoposide and cisplatin/carboplatin for treatment-naive extensive-stage SCLC was well tolerated with promising PFS and ORR to date but showed no new risk for AEs. Based on these encouraging results, phase III trial of anlotinib plus etoposide and cisplatin/carboplatin for treatment-naive SCLC has been warranted.
Survival trend of chronic lymphocytic leukemia and prognostic factors in the United States: An analysis of the National Cancer Database.
Authors: Ning Dong, Hayder Saeed, Sameh Gaballa, Bijal D. Shah, Anna Coghill, Leidy Lismeri Isenalumhe, Bello Celeste, Javier Pinilla-Ibarz, Julio C. Chavez
Journal: Journal of Clinical Oncology (2020)

e20012 Background: The management of chronic lymphocytic leukemia (CLL) has evolved in the past decade, mainly due to the introduction of novel agents. The outcome of CLL in the general US population and the prognostic factors have not been studied. National Cancer Database (NCDB) includes about 70% of all malignancies in the US and provides a resource to address those questions. Methods: The most recent release of NCDB included CLL cases diagnosed in years 2004-2016. The following variables were included in Cox proportional hazard model for multivariate analysis: age, gender, race, ethnicity, comorbidity score, year of diagnosis, insurance, education, income, facility type, facility volume of CLL and distance to facility. Results: A total of 91309 CLL patients were identified. Median age of diagnosis was 70 years (IQR 61-79). Among the patients, 60.4% were male, 89.4% of patients were White, 7.7% were African American (AA) and 5.8% of patients had either Medicaid or no insurance. At the initial diagnosis, 31.5% of patients were started on treatment and the rest were under active surveillance. Transplant was performed in 0.18% of patients. The OS has improved in years 2010-2016 compared to 2004-2009 with median OS of 90.3 months (95% CI 87.3, .) and 83.6 months (95% CI 82.1-85.0), respectively and 5-year survival rate of 64.2% and 59.9%, respectively (p &lt; 0.0001). Among the 1348 facilities, 16% saw less than 2 CLL patients per year. In the multivariate analysis, the following factors were associated with worse OS: older age, more comorbidities, AA, male gender, East South Central or South Atlantic area, no insurance or Medicaid, lower quartiles of education, and being treated in facilities with lower CLL-patient volume. Conclusions: CLL survival has improved in the past decade. Socioeconomic factors seem to impact survival and with the introduction of newer more expensive therapies, this discrepancy in survival might increase. Furthermore, CLL is a relatively rare malignancy and patients treated at lower-volume facilities had inferior survival. Special attention paid to patients with risk factors might improve outcome. [Table: see text]
TTOM in action: Refining the variational approach to cognition and culture
Authors: Samuel P. L. Veissière, Axel Constant, Maxwell J. D. Ramstead, Karl J. Friston, Laurence J. Kirmayer
Journal: Behavioral and Brain Sciences (2020)

Abstract The target article “Thinking Through Other Minds” (TTOM) offered an account of the distinctively human capacity to acquire cultural knowledge, norms, and practices. To this end, we leveraged recent ideas from theoretical neurobiology to understand the human mind in social and cultural contexts. Our aim was both synthetic – building an integrative model adequate to account for key features of cultural learning and adaptation; and prescriptive – showing how the tools developed to explain brain dynamics can be applied to the emergence of social and cultural ecologies of mind. In this reply to commentators, we address key issues, including: (1) refining the concept of culture to show how TTOM and the free-energy principle (FEP) can capture essential elements of human adaptation and functioning; (2) addressing cognition as an embodied, enactive, affective process involving cultural affordances; (3) clarifying the significance of the FEP formalism related to entropy minimization, Bayesian inference, Markov blankets, and enactivist views; (4) developing empirical tests and applications of the TTOM model; (5) incorporating cultural diversity and context at the level of intra-cultural variation, individual differences, and the transition to digital niches; and (6) considering some implications for psychiatry. The commentators’ critiques and suggestions point to useful refinements and applications of the model. In ongoing collaborations, we are exploring how to augment the theory with affective valence, take into account individual differences and historicity, and apply the model to specific domains including epistemic bias.
Clinical studies on efficacy of trisequens in adjusting menstrual cycle and menopausal symptoms during perimenopause
Authors: 孙爱军, 孔桂英, 张忠兰, 迟闺珠, 魏杨, 赖爱鸾, 高晓秋, 戴兆亨, 王凤英, 林守清
Journal: BMJ (2005)

目的 观察雌孕激素复方制剂(诺康律)用于控制月经周期与缓解绝经相关症状的临床疗效与副作用.方法采取开放、多中心、自身对照临床研究方法,观察对象为有绝经相关症状或同时有月经紊乱的绝经过渡期或绝经早期妇女.共入组153例,完成观察146例.所用的雌孕激素复方制剂诺康律,含17β-雌二醇与醋酸炔诺酮两种成分,连续治疗3个周期.分别在治疗前、治疗1、2、3个月时采用Greene评分进行绝经相关症状评分.结果治疗后心理症状、躯体症状和血管舒缩症状等评分指标均有显著降低,症状总分从治疗前19±9降低至1个月时的10±7,2个月时的6±6,3个月时的5±10.在用药1个月、2个月和3个月时,95.4%、96.7%和98.6%的人出现规律性月经;不规则出血发生率分别为3.3%、2.7%和0.7%;闭经者分别为1.3%、0.7%和0.7%.副作用中,治疗前乳房胀发生率9.6%(14例),治疗1个月时38.2%(58例),2个月时36.7%(55例),3个月时21.9%(32例).治疗1个月时消化道反应5例(3.3%),2个月时2例(1.3%),3个月时1例(0.7%).无其他严重副作用发生,用药依从性较好,退出率低(4.6%).结论序贯联合应用雌孕激素能够显著缓解绝经相关症状,调整月经周期.不良反应少,依从性好。
PD-L1, brain metastases, and survival among patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors.
Authors: James Feisal, Pragathi Balakrishna, Aleena Itani, Caleb King, Pawan Acharya, Sara Vesely, Raid Aljumaily
Journal: Journal of Clinical Oncology (2020)

e21655 Background: PD-L1 expression is predictive of response to treatment with PD-1/PD-L1 immune checkpoint inhibitors (ICI) among patients with metastatic non-small cell lung cancer (mNSCLC). Brain metastases (BM) are common in patients with mNSCLC and carry significant morbidity. While the use of ICI has significantly improved survival for mNSCLC, it is unclear if patients with brain metastases have the same survival benefit. Methods: In this retrospective study, we reviewed data from all patients treated at our center with mNSCLC who had PD-L1 testing from 2015-2019. Patients with another active malignancy were excluded. Descriptive statistics were calculated using proportions and means using SAS v9.4. We examined the relationship between PD-L1 level ( &lt; 50% vs ≥50%) and BM at diagnosis among patients with mNSCLC using chi-square analysis. We then compared overall survival (OS) and progression free survival (PFS) among mNSCLC patients with and without BM at diagnosis treated with ICI using Kaplan-Meier plots followed by log rank tests. Results: 141 mNSCLC patients with PD-L1 results were identified. 71 (50.4%) were female. Mean age was 63. 71 (50.4%) were current smokers, 53 (37.6%) were former smokers. Histology included 111 (78.7%) adenocarcinoma, 19 (13.5%) squamous cell carcinoma, and 11 (7.8%) other or mixed types. 19 (13.5%) had KRAS mutation, 13 (9.2%) had EGFR mutation, 1 had ALK rearrangement, 3 had ROS1 rearrangement, and 2 had BRAF mutations. 86 (61.0%) were PD-L1 high (≥50%). 57 (40.4%) had BM at diagnosis. Patients with high PD-L1 had a higher rate of BM at diagnosis (47.3% vs 36.0%), but this trend was not statistically significant (p = 0.18). There were significantly more current smokers among those with BM at diagnosis than those without BM (p = 0.01). Among patients treated with first line ICI (n = 78), median OS was 26.5 months for those without BM and 12.2 months for those with BM at diagnosis, although this difference was not significant (p = 0.11). Median PFS was 8.9 months for patients without BM and 8.6 for those with BM (p = 0.58). Conclusions: While a higher proportion of patients with high PD-L1 had BM at the time of metastatic diagnosis, this trend was not significant. Among patients treated with ICI, survival for those with or without BM at the time of diagnosis was not significantly different. Our observations may be limited by the number of patients.