tbuckley/cabot-search huggingface dataset:
Using a clinicopathologic and gene expression model to identify melanoma patients at high risk for disease relapse.
Authors: Alexander M. Eggermont, Domenico Bellomo, Félicia Tjien-Fooh, Renske Wever, Enrica Quattrocchi, Sindhuja Sominidi Damodaran, Martin Van Vliet, Jvalini Dwarkasing, Alexander Meves
Journal: Journal of Clinical Oncology (2020)

10068 Background: The identification of early stage melanoma patients at high risk for relapse is still difficult. Roughly 50% of melanoma deaths occur in patients who were initially diagnosed with nonmetastatic melanoma. Therefore, a strong clinical need has emerged for diagnostic tools that can identify melanoma patients at high risk for relapse. Here, we assessed the performance of a recently developed model (Bellomo et al., JCO Precis Oncol. 2020: in press), combining clinicopathologic and gene expression variables (CP-GEP), in identifying melanoma patients that have a high risk for disease relapse. Methods: We assessed the prognostic performance of the CP-GEP model in a cohort of 837 consecutive melanoma patients from Mayo Clinic who had a sentinel lymph node biopsy (SLNb) performed within 90 days of their diagnosis. The CP-GEP model combines Breslow thickness and patient age, with the expression of 8 genes in the primary tumor, to stratify patients according to their risk of relapse: CP-GEP High Risk or CP-GEP Low Risk. The main clinical endpoint of this study was five-year relapse free survival (RFS). Results: Patients were stratified based on SLNb status and CP-GEP classification. 76% of the patients were SLNb negative and had an RFS of 79% versus 52% for SLNb positive patients; HR, 3.21; P &lt; 0.0001. 60% of the patients were identified as CP-GEP High Risk and had an RFS of 62% versus 87% for CP-GEP Low Risk patients; HR, 4.12; P &lt; 0.0001. Within the SLNb negative group (637 patients of which 65% stage I), 51% of patients were classified as CP-GEP High Risk. Here, RFS was 70% for CP-GEP High Risk patients versus 89% for CP-GEP Low Risk patients; HR, 3.61; P &lt; 0.0001. The prognosis of these CP-GEP High Risk patients is similar to stage IIC/IIIA patients with reported RFS ranging from 63% to 77%. This confirms the heterogeneity in prognosis among patients with stage I/II melanoma disease. Conclusions: The CP-GEP model can be successfully used to stratify patients based on their risk for relapse. In particular, it can be used to identify SLNb negative patients with a high risk for disease relapse who may benefit from therapeutic interventions. Independent validation studies are ongoing to validate the CP-GEP model in various patient populations. [Table: see text]
Epidemiological and clinical features of 4430 cases of measles in Shenzhen Municipality
Authors: Yi-wen Hu, Hui-ming Liu, Ya-hong Zhou, Fei-jian Ao, Zhi-chao Liu
Journal: BMJ (2010)

Since the attenuated live vaccine against measles was developed,the epidemic of measles has been controlled effectively,however,there is a trend of gradual increase of measles cases in recent years.The epidemiological and clinical features of 4430 measles patients in Shenzhen Municipality in last 10 years were reviewed.The data showed that the epidemic season was postponed with the peak of June to September;the prevalent age groups were infants and adults,the number of severe cases increased;and the positive rate of serological antibody in infants with measles was the lowest.

Key words: 
Measles; Epidemiologic factors
Superior therapy response predictions for patients with glioblastoma (GBM) using Cellworks Singula: MyCare-009-03.
Authors: Patrick Y. Wen, Drew Watson, Shweta Kapoor, Aftab Alam, Aktar Alam, Deepak Anil Lala, Diwyanshu Sahu, Ashish Agrawal, Kabya Basu, Naga Ganesh, Anusha Pampana, Himanshu Grover, Nirjhar Mundkur, Chandan Kumar, Subrat Mohapatra, Rahul K Raman, Preethi Elangovan, Mamatha Patil, Shivgonda Birajdar, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2020)

2519 Background: Despite using cytogenetic and molecular-risk stratification and precision medicine, the current overall outcome of GBM patients remains relatively poor. Therapy selection is often based on information considering only a single aberration and ignoring other patient-specific omics data which could potentially enable more effective treatment selection. The Cellworks Singula™ report predicts response for physician prescribed therapies (PPT) using the novel Cellworks Omics Biology Model (CBM) to simulate downstream molecular effects of cell signaling, drugs, and radiation on patient-specific in silico diseased cells. We test the hypothesis that Singula is a superior predictor of progression-free survival (PFS) and overall survival (OS) compared to PPT. Methods: Singula’s ability to predict response was evaluated in an independent, randomly selected, retrospective cohort of 109 GBM patients aged 17 to 83 years treated with PPT. Patient omics data was available from TCGA. Singula uses PubMed to generate protein interaction network activated and inactivated disease pathways. We simulated PPT for each patient and calculated the quantitative drug effect on a composite GBM disease inhibition score based on specific phenotypes while blinded to clinical response. Univariate and multivariate proportional hazards (PH) regression analyses were performed to determine if Singula provides predictive information for PFS and OS, respectively, above and beyond age and PPT. Results: In univariate analyses, Singula was a significant predictor of both PFS (HR = 4.130, p &lt; 0.000) and OS (HR = 2.418, p &lt; 0.0001). In multivariate PH regression analyses, Singula (HR = 4.033, p &lt; 0.0001) remained an independent predictor of PFS after adjustment for PPT (p = 0.1453) and patient age (p = 0.4273). Singula (HR = 1.852, p = 0.0070) was also a significant independent predictor of OS after adjustment for PPT (p = 0.4127) and patient age (p = 0.0003). Results indicate that Singula is a superior predictor of both PFS and OS compared to PPT. Singula provided alternative therapy selections for 29 of 52 disease progressors detected by Cellworks. Conclusions: Singula is a superior predictor of PFS and OS in GBM patients compared to PPT. Singula can identify non-responders to PPT and provide alternative therapy selections.
ER-/PgR+ breast cancer is a separate entity characterized by distinct phenotype: Comprehensive reevaluation of cases from Polish and Hungarian centers.
Authors: Elzbieta Senkus-Konefka, Michał Kunc, Rafał Pęksa, Aleksandra Łacko, Barbara Radecka, Marcin Braun, Joanna Pikiel, Maria Litwiniuk, Katarzyna Pogoda, Gabor Cserni, Ewa Iżycka-Świeszewska, Anna Szwajkosz, Wojciech Biernat
Journal: Journal of Clinical Oncology (2020)

e12554 Background: ER negative (-)/PgR positive (+) breast cancer (BC) is very uncommon and questioned by many experts. We comprehensively reevaluated ER-/PgR+ BCs in the large cohort from Polish and Hungarian centers. Methods: FFPE blocks from 105 ER-/PgR+ tumors (45 breast biopsies and 64 post-operative samples from tumors not exposed to systemic therapy) were collected from 10 Polish and 3 Hungarian centers. In 60 cases available original slides with ER/PgR staining underwent reevaluation by 3 pathologists (MK, RP, WB) for ER and PgR expression by ASCO/CAP criteria. Subsequently, all samples were stained with 3 antibodies against ER (Dako monoclonal (MC) mouse anti-ERα, clone 1D5; Dako MC rabbit anti-ERα, clone EP1; VENTANA Roche MC rabbit anti-ERα, clone SP1), and PgR (Dako MC mouse anti-PgR, clone 636). If available, &gt; 1 tissue block was used (av. 2.04 blocks/case, range 1-6). In 5 cases ESR1/PGR/ERBB2/MKi67 mRNA was measured by the Xpert® Breast Cancer STRAT4 (Cepheid, Sunnyvale, CA, USA). Results: 13 cases were excluded from immunohistochemical steps of the study due to insufficient amount of tissue and 8 - due to misdiagnosis after ER/PgR reevaluation of original slides. After re-staining, 42 cases (41.5%) retained the original phenotype, in 34 (33.67%) the ER status was corrected to ER+, and 16 (15.84%) tumors were ER/PgR-double-negative. The general agreement between anti-ER clones was moderate (Fleiss’ κ = 0.54). There were 56 ER- and 16 ER+ cases across all three assays. Five cases showed ER positivity with 2 antibodies (either SP1/EP1 or SP1/1D5), 5 tumors reacted exclusively with SP1 clone, and 2 - with 1D5 clone. Xpert Breast Cancer STRAT4 confirmed the ER-/PgR+ phenotype in 4 of 5 analyzed cases. The confirmed ER-/PgR+ BCs were characterized by lower percentage of PgR+ cells (median 5%) than BCs reclassified to ER+ (median 70%) (p = 0.022) and higher Ki67 expression than ER+ cases (median 54.5% vs 25%, respectively; p = 0.003). 39 (92.85%) ER-/PgR+ BCs presented with grade 3. Besides “conventional” high-grade cancers, we identified two distinct morphologies of ER-/PgR+ BC: resembling apocrine carcinoma (n = 5, 11.9%) and carcinoma with central acellular zone (n = 4, 9.5%). Conclusions: ER-/PgR+ BCs confirmed in the current study were defined by high-grade histology, high proliferation index and low percentage of PgR+ cells. We postulate ER-/PgR+ BC is a real albeit rare entity, and its diagnosis should be made cautiously, utilizing retesting with an alternative tissue block and anti-ER antibody.
经阴道三维超声在子宫血管瘤诊断中的价值
Authors: 石华, 张王国, 胡佳琪, 郝力丹, 陈瑾
Journal: BMJ (2011)

一、临床资料例1 患者女,25岁,于2010年10月24日因“发现宫腔占位性病变2年余”来诊,入院诊断:右侧宫角处肌层内混合回声区,血管瘤可能性大.初潮年龄12岁,经期7d,周期26 d,末次月经2010年10月16日,有阴道不规则出血症状,孕3产0.体检:子宫前位,活动度可,宫底部偏右侧包块性质待查,有3次孕40余天自然流产+清宫术病史.末次妊娠2008年2月,于2008年4月行清宫术,其后一直未孕. 关键词：血管瘤
Phase II study of apatinib combined with temozolomide in advanced melanoma patients after failure of anti-PD-1 therapy.
Authors: Li Zhou, Chuanliang Cui, Lu Si, Zhihong Chi, Xinan Sheng, BIN LIAN, Xuan Wang, Bixia Tang, Lili Mao, Xieqiao Yan, Xue Bai, Jun Guo
Journal: Journal of Clinical Oncology (2020)

e22043 Background: Immunotherapy is first-line therapy in advanced melanoma. Because of different subtypes and gene alterations, the efficacy of immunotherapy in Asians, mostly comprised of acral and mucosal melanoma, is lower than Caucasians. There are no standard treatment strategies after immunotherapy failure. Chemotherapy and anti-angiogenesis combination showed emerging evidence of activity in mucosal and acral melanoma. This study was to evaluate the efficacy of apatinib combined with temozolomide in advanced immunotherapy refractory melanoma patients (pts). Methods: This prospective, single-arm, phase II study recruited unresectable or metastatic melanoma pts after failure of anti-PD-1 therapy. Other treatment including targeted therapy, chemotherapy, and clinical trials were allowed. Primary endpoint was progression-free survival (PFS), and secondary endpoints were objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). According to the dose recommended from previous phase I study, pts were given apatinib 500 mg every day and temozolomide 300mg day 1-5, 28 days for one cycle. Results: 31 pts were enrolled between Feb 2018 and Dec 2018, with 8 males, average age 55 yrs (range 24 – 69 yrs). 13 pts (41.9%) were from mucosal primaries, 9 (29.0%) acral, 5 (16.1%) cutaneous (non-acral), and 4 (12.9%) unknown primaries. One had BRAF mutation, 1 CKIT, and 3 NRAS mutations. 9 pts (29.0%) were classified as IIIc/M1a, 9 (29.0%) M1b, and 13 (41.9%) M1c. 18 pts (58.1%) had elevated lactate dehydrogenase level. All pts progressed after anti-PD-1 therapy. In addition, 29.0% pts received dacarbazine based chemotherapy, 29.0% paclitaxel or albumin-bound paclitaxel, and 3.2% had dabrafenib with trametinib. Up to Dec 2019, 30 pts can be evaluated for efficacy. Median follow-up time was 10.2 mos (2.0-23.1 mos). There were 5 confirmed PRs and 20 SDs. ORR was 16.7%, DCR 83.3%, and median PFS was 5.0 mos (95%CI 1.9-8.1 mos). Median overall survival was 10.1 mos (95%CI 4.7-15.5 mos). Common AEs were hypertension (51.6%), proteinuria (41.9%), elevated transaminase (25.8%), thrombocytopenia (16.1%), and hand-foot syndrome (16.1%). Most were grade 1-2. Grade 3-4 AEs included proteinuria (12.9%), hypertension (6.4%), and thrombocytopenia (6.4%); 10 pts required a dose reduction, and 1 had to discontinue. No treatment-related deaths were observed. Conclusions: In pts progressed after anti-PD-1 therapy, apatinib in combination with temozolomide demonstrated promising efficacy and favorable safety profile. Clinical trial information: NCT03422445.
Efficacy and its related factors of phenobarbital treatment for epilepsy management in rural China
Authors: Xiaowei Wang, Xiaojuan Ru, Jianzhong Wu, Zhen Hong, Di Li, Shichuo Li, Wenzhi Wang
Journal: BMJ (2016)

Objective
To analyze efficacy and its influencing factors of phenobarbital treatment for epilepsy management in rural China.


Methods
Total 3 315 patients with convulsive epilepsy from rural areas of 24 counties were enrolled in this joint epilepsy management program. All patients received phenobarbital monotherapy for 1 year during November 2011 to November 2013. The efficacy and potential influencing factors including sex, age, duration of epilepsy, number of seizures in the 12 months before management(≥2), previous treatment, daily dose of phenobarbital, taking other antiepileptic drugs and compliance of patients were studied with multivariate analysis.


Results
Among 3 315 patients, 38.9% were seizure-free during the entire management period. The rates of seizure-free in 15 to 39 y age group(35.2%, 495/1 405)and in patients receiving irregular treatment previously(34.6%, 625/1 808)were lower. The rates of seizure-free were higher in patients taking phenobarbital 60-90 mg everyday(49.4%, 988/2 000)and those with good compliance(42.3%, 1 160/2 744). Patients taking other antiepileptic drugs in 12 months had lower seizure-free rate(31.0%, 45/145). Univariate analysis showed that gender of patients was not related to seizure-free rate (P>0.1). Multivariate analysis showed that the longer duration of epilepsy(OR=0.015, 95%CI: 1.008-1.021, P<0.001), more seizures in the 12 months(OR=0.005, 95%CI: 1.002-1.007, P=0.002)and the irregular treatment before management were the risk factors for low seizure-free rate (P<0.05). Patients received formal treatment or untreated had a lower risk of seizure compare with the irregular treatment(OR=0.737, 95%CI: 0.611-0.889, P=0.001; OR=0.566, 95%CI: 0.469-0.683, P<0.001). Patients with good compliance and with a daily dose of 60-89 mg phenobarbital(OR=0.107, 95%CI: 0.013-0.905, P=0.040)were associated with high seizure-free rate; in contrast the poor compliance was a risk factor for not being seizure-free(OR=2.038, 95%CI: 1.634-2.541, P<0.001).


Conclusion
Regular medication of phenobarbital with good compliance is effective for convulsive epilepsy management in rural China.


Key words: 
Epilepsy; Disease management; Phenobarbital; Influencing factors
Skill-based engagement with a rich landscape of affordances as an alternative to thinking through other minds
Authors: Julian Kiverstein, Erik Rietveld
Journal: Behavioral and Brain Sciences (2020)

Abstract Veissière and colleagues make a valiant attempt at reconciling an internalist account of implicit cultural learning with an externalist account that understands social behaviour in terms of its environment-involving dynamics. However, unfortunately the author's attempt to forge a middle way between internalism and externalism fails. We argue their failure stems from the overly individualistic understanding of the perception of cultural affordances they propose.
Correlation of apolipoprotein levels with the severity of hyperlipidemic acute pancreatitis
Authors: Zijin Liu, Ziyu Liu
Journal: BMJ (2019)

Objective
To explore the correlation of apolipoprotein levels with the severity of hyperlipidemic acute pancreatitis.


Methods
Clinical date of 169 patients with hyperlipidemic acute pancreatitis (AP) admitted in our hospital from September 2012 to December 2018 were retrospectively analyzed. Apolipoprotein (Apo) AⅠ, Apo B, Apo B/Apo AⅠ ratio were compared among hyperlipidemic AP patients with different severity. Pearson correlation analysis was conducted to explore the correlation of Apo AⅠ, Apo B, Apo B/Apo AⅠ with Atlanta classification, CTSI score, APACHE-Ⅱscore, RANSON score and C-reaction protein level. The optimal cut-off point of apolipoproteins for predict the severe hyperlipidemic AP was determined by ROC curve. The local and systemic complications of pancreatitis patients with different Apo levels were compared with chi-square test.


Results
There were no significant differences in general conditions among patients with severe AP (SAP), median-severe AP (MSAP) and mild AP (MAP). The Apo AⅠ levels of SAP [ (0.89±0.36) g/L] were lower than those of MSAP [(1.07±0.40)g/L, t=2.07, P=0.04] and MAP [(1.14±0.70) g/L, t=2.55, P=0.01]. Apo AⅠ was negatively correlated with Atlanta classification (r=-0.24, P 8 [70.59%(36/51) vs. 55.08%(65/118), χ2=3.56, P=0.04] in patients with Apo AⅠ≤0.8 g/L were higher than those in patients with Apo AⅠ>0.8 g/L.


Conclusion
Apolipoprotein AⅠ level is negatively correlated with Atlanta classification and Apo AⅠ level can be used to predict severity of hyperlipidemic acute pancreatitis.


Key words: 
Pancreatitis; Hyperlipidemia; Apolipoproteins; APACHEⅡ; C-reactive protein
平顶山市社区医生糖尿病防治知识水平的调查
Authors: 王俊宏, 李进, 崔晓磊, 侯卫东, 刘艳晓, 刘惠双, 张志宇, 田勇, 丁红霞, 禹远远
Journal: BMJ (2011)

糖尿病是临床常见疾病,随着生活水平的提高、人口老化及生活方式改变患病率呈增长趋势.社区医生掌握糖尿病的防治知识,对在社区开展糖尿病的防治工作尤为重要.本研究于2008年7月至2009年11月,对平顶山市31家社区卫生服务中心医生的糖尿病防治知识情况进行问卷调查,结果如下。
Association between pigmented pretibial patches and diabetic microangiopathy
Authors: Jie-yu Liu, Miao-yan Zheng, Bao-cheng Chang, Ju-hong Yang, Chun-yan Shan, Hang Guo, Yan Kong
Journal: BMJ (2013)

Objective
To investigate the association of pigmented pretibial patches (PPP) with diabetic microangiopathy in type 2 diabetic (T2DM) patients.


Method
One thousand one hundred and thirty four T2DM patients admitted from February 2011 to February 2012 were enrolled in the study. The association of PPP with diabetic microangiopathy, serum C-reactive protein and IL-18 levels and other disease parameters was analyzed with logistic regression method.


Results
The overall prevalence of PPP was 32.1% (364/1134) with 37.7% (203/539) for males and 27.1% (161/595) for females. The prevalence of diabetic retinopathy, diabetic nephropathy and diabetic neuropathy in patients with or without PPP were 64.0%(233/364), 54.9%(200/364), 52.7%(192/364) and 21.7%(167/770), 19.5%(150/770), 17.3%(133/770) respectively; the prevalence of all three microvascular complications in patients with PPP was significantly higher than that in patients without PPP [31.0%(113/364) vs. 7.8%(60/770), P<0.05]. Logistic analysis indicated that the levels of glycosylated hemoglobin, duration of diabetes≥10 years and C-reactive protein≥3 g/L were associated with prevalence of PPP.


Conclusions
PPP is a common sign in diabetic patients and may be used as a indicator for diabetic microvascular complications. The prevalence of PPP is also associated with the levels of blood glucose, C-reactive protein and course duration of the disease.


Key words: 
Hyperpigmentation; Diabetes mellitus, type 2; Diabetic angiopathies
A multicenter chart review study of patients with metastatic pancreatic ductal adenocarcinoma receiving liposomal irinotecan after gemcitabine-based therapy.
Authors: Kenneth H. Yu, Andrew Eugene Hendifar, Olatunji B. Alese, Amber Draper, Maen Abdelrahim, Ethan Burns, Gazala Naaz Khan, Paul Cockrum, Rachel Bhak, Maral DerSarkissian, Catherine Nguyen, Mei Sheng Duh, Nathan Bahary
Journal: Journal of Clinical Oncology (2020)

e16733 Background: Real-world data allows healthcare decision-makers to assess and manage therapeutic and economic options for patients, including those who would and would not have met eligibility criteria for randomized control trials (RCT) and are instead managed under usual care. This retrospective multi-academic center chart review study describes real-world characteristics and outcomes of US patients receiving liposomal irinotecan for the management of metastatic pancreatic ductal adenocarcinoma (mPDAC). Methods: Patients with mPDAC treated with liposomal irinotecan were eligible. Initiation of liposomal irinotecan defined index date; covariates assessed included clinical characteristics and treatment patterns; real-world overall survival (rwOS) was assessed via Kaplan-Meier methodology. The target enrollment is 300 patients. The study centers included were Memorial Sloan Kettering Cancer Center, Cedars-Sinai Medical Center, Emory Winship Cancer Institute, Houston Methodist Cancer Center, Henry Ford Cancer Institute, and University of Pittsburgh Medical Center. Results: Data on 26 patients were available for initial analyses. Mean age was 68 years; 58% were female and 65% Caucasian. 54% of patients had stage IV disease at first diagnosis, and 17%, 65%, and 17% had index ECOG score of 0, 1, and 2, respectively. Common genetic mutations include KRAS (40%) and TP53 (40%). Prior to liposomal irinotecan, treatments received for metastatic disease include gemcitabine+nab-paclitaxel (77%) and fluorouracil (5-FU)/leucovorin (LV)+irinotecan+oxaliplatin (19%). Patients had received 0 (12%), 1 (23%), and ≥2 (65%) lines of therapy in the metastatic setting prior to liposomal irinotecan. Mean duration of liposomal irinotecan use was 3.0 months; liposomal irinotecan was mostly received with 5-FU (23%) or 5-FU/LV (69%). Median rwOS was 4.9 months (95% CI: 3.0, 6.3). Conclusions: Real-world data of the first 26 patients in this study show patients treated with liposomal irinotecan are older, sicker, and have had more lines of therapy than previously reported in RCT data.