tbuckley/cabot-search huggingface dataset:
Landscape of germline mutations in 1144 patients (Pts) with gastrointestinal (GI) cancers.
Authors: Mohamed E. Salem, Lisa Amacker-North, Mariah Gleason, Aly Athens, William Mills Worrilow, Lindsay McNeely, Katherine Broyhill, Alberto Puccini, Edward S. Kim, Sara Elrefai
Journal: Journal of Clinical Oncology (2020)

e13660 Background: The efficacy of PARP inhibitors in germline BRCA-mutated pancreatic adenocarcinoma (PC) and immune checkpoint inhibitors in dMMR colorectal cancer (CRC) shows the importance of genetic testing. We aimed to characterize the frequency of pathogenic/likely pathogenic germline variants (PLPVs) in GI cancer pts. Methods: A retrospective review of pts referred to the Levine Cancer Institute Genetics Program was conducted. Genetic testing used a focused hereditary cancer 4-43 gene panel or pan-cancer 82-84 gene panel. Results: Out of 1144 GI cancer pts seen between 2010 and 2019, 869 underwent germline testing, and 199 (23%) pts had at least one PLPV in a hereditary cancer susceptibility gene, while 253 (29.3%) had a variant of uncertain significance. Of 630 CRC pts, 24% had a PLPV and 13% harbored a germline mutation in DNA MMR genes and were diagnosed with Lynch Syndrome, representing ~50% of all pts with a PLPV. Other germline PLPVs were found in APC, ATM, BRCA1, BRCA2, CHEK2, MUTYH, and PALB2. Of 163 PC pts, 16.6% had a PLPV in ATM, BRCA2, CDKN2A, and MEN1. Gastric cancer pts (17%) had germline PLPVs in APC, BRCA2, CDH1, MLH1, and MSH2; biliary cancer pts (17%) had germline PLPVs in PALB2, RAD50, and PTCH1; and GIST pts (60%) had PLPVs in SDHA or SDHB. Conclusions: Germline mutations were found in 23% of GI cancer pts, underlining the importance of multigene germline testing. Knowledge of inherited GI cancer risk helps determine the likelihood of benefit from possible specific targeted therapies. Genetic testing and counseling pose a challenge, but implications for pts with hereditary syndromes are highly significant. [Table: see text]
The prevalence of targetable genomic alterations is substantially high in rare tumors.
Authors: Shuhang Wang, Ning Li, Rongrong Chen, Yue Yu, Yuan Fang, Dejian Gu, Xin Yi, Huiyao Huang, Dawei Wu, Hong Fang, Ying Bai, Chao Sun, Anqi Qi, Qi Fan, Ying Zhou
Journal: Journal of Clinical Oncology (2020)

e13539 Background: Comprehensive Genomic Profiling may be informative for novel treatment strategies and to improve outcome for patients with rare solid tumors. This study aims to discover opportunities for use of targeted therapies currently in routine practice in patients with rare tumors. Methods: Solid tumors with an incidence lower than 2.5/100,000 per year was defined as rare tumors in China after comprehensive analysis based on epidemiology data and current availability of standardized treatment. Genomic data of rare tumors from the public database cBioPortal was compared with that of Chinese population for targetable genomic alterations (TGAs). TGAs was defined as mutations of ALK, ATM, BRAF, BRCA1, BRCA2, CDKN2A, EGFR, ERBB2, FGFR1,2,3, KIT, MET, NF1, NTRK1,2,3, PIK3CA, PTEN, RET, and ROS1 with level 1 to 4 of evidence according to OncoKB knowledge database. Results: Genomic data of 4901 patients covering 63 subtypes of rare tumor from cBioportal was obtained as the western cohort. Data of next generation sequencing (NGS) of 1312 patients from across China covering 67 subtypes was summarized as the Chinese cohort. Forty-one subtypes were overlapped between the two cohorts. The accumulative prevalence of TGAs was 20.40% (1000/4901) in cBioportal cohort, and 53.43% (701/1312) in Chinese cohort (p &lt; 0.001). Among those 41 overlapping subtypes, it was still significantly higher in Chinese cohort compared with cBioportal cohort (54.1%% vs. 26.1%, p &lt; 0.001). Generally, targetable mutations in BRAF, BRCA2, CDKN2A, EGFR, ERBB2, KIT, MET, NF1, ROS1 were ≥3 times more frequent in Chinese cohort compared with that of cBioportal cohort. Cancer of unknown primary tumor type, gastrointestinal stromal tumor, gallbladder cancer, intrahepatic cholangiocarcinoma, and sarcomatoid carcinoma of the lung were the top 5 tumor types with highest TGAs. Conclusions: The incidence of TGAs in rare tumors was substantially high worldwide and was even higher in Chinese rare tumor population. Comprehensive genomic profiling may offer novel treatment paradigms to address the limited options for patients with rare tumors.
Author Correction: Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation
Authors: Mayilaadumveettil Nishana, Caryn Ha, Javier Rodriguez-Hernaez, Ali Ranjbaran, Erica Chio, Elphege P. Nora, Sana B. Badri, Andreas Kloetgen, Benoit G. Bruneau, Aristotelis Tsirigos, Jane A. Skok
Journal: Genome biology (2020)

An amendment to this paper has been published and can be accessed via the original article.
The effects of combined modality therapy on stage II-III primary gastric signet ring cell carcinoma.
Authors: Yang Li, Yantao Tian, Zhikai Zhu
Journal: Journal of Clinical Oncology (2020)

e16530 Background: To date, there is no well-defined standard of care for gastric signet ring cell carcinoma (GSRC). Clinical guidelines support that combined modality therapy (CMT) on localized gastric cancer, but this may not be appropriate for GSRC as it was generally found to be chemo-resistant. We conducted a population-based study to examine the effects of therapeutic strategies on survival outcomes by using the Surveillance, Epidemiology, and End Results (SEER) data. Methods: Analyses included primary GSRC patients with stage II-III who survived more than 6 months, and were diagnosed between 2006 and 2016 from SEER data.CMT were categorized as gastrectomy group, adjuvant CT group (gastrectomy with adjuvant chemotherapy), neoadjuvant RT group (gastrectomy with neoadjuvant radiotherapy combined adjuvant chemotherapy), and adjuvant CRT group (gastrectomy with chemoradiotherapy). Survival analyses were conducted by Kaplan-Meier method and multivariate Cox proportional hazards models, adjusted for age, gender, race, marital status, histology, AJCC stage, tumor location, and lymph nodes removed. Models were stratified by gender, AJCC stage, lymph nodes removed and tumor location. Results: Of the 1,717 cases of stage II-III primary GSRC, the mean age was 66.9 (SD: 11.0) years, over a half were male (52.8%), and the majority were white (66.0%). A total of 39.9% received adjuvant CRT. The five-year overall survival (OS) rate was 34.6% for this treatment, and 29.6% for adjuvant CT group, 25.4% for adjuvant CRT group, only 23.8% for the gastrectomy group. The median OS of patients treated with adjuvant CRT was significantly longer than that of the gastrectomy group (33 vs 24 months, aHR = 0.71, 95%CI = 0.60,0.84). Although the crude model showed a significant association between adjuvant CT and total survival (cHR = 0.81, 95%CI = 0.68,0.96), the effect measure turned null in the multivariable and sub-group analysis. Independent prognostic factors were adjuvant CRT, ≥60 years old, AJCC stage, and &gt; 20 lymoh nodes removed. Conclusions: In this study, GSRC patients with stage II-III experienced improved overall survival after receiving adjuvant CRT, which provides several treatment implications. Future clinical trials considering adjuvant CRT will be needed to verify the conclusion derived from this study.
上呼吸道感染并发急性非特异性心包炎、出血性心包填塞一例
Authors: 刘芳, 曾爱平, 吕孙成, 丁翊
Journal: BMJ (2006)

患者男,76岁,因咽痛5 d,加重伴发热1 d于2004年10月31日入院.既往有高血压病史20余年,冠心病史3年.入院查体:咽部充血,右侧扁桃体Ⅱ度.诊断考虑为上呼吸道感染,予青霉素抗感染治疗,1周后仍有低热,并出现咳嗽、乏力、胸闷、气短.2004年11月5日心脏彩色多普勒检查:心包腔少量积液.3 d后胸部CT示:两侧胸腔积液,左侧叶间积液,心包大量积液.次日在彩色多普勒监测下行心包穿刺置管术,抽出不凝血性心包积液约150 ml,后置管引流,持续心包引流每日引流出血性液体200～300 ml。
Neighborhood disparities in timeliness of treatment for early stage lung cancer patients.
Authors: Chelsea A Obrochta, Joseph Gibbons, Atsushi Nara, James Don Murphy, Caroline A. Thompson
Journal: Journal of Clinical Oncology (2020)

e19017 Background: Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer-related death in the United States, accounting for approximately 25% of all cancer deaths. The National Comprehensive Cancer Network (NCCN) provides evidence-based cancer treatment recommendations. Evidence suggests that a patient’s receipt of guideline-concordant treatment (GCT) increases survival, especially for screen-detected, earlier stage cancers. Neighborhoods are key determinants of health and the neighborhood social and built environments can influence cancer treatment and outcomes. Minority segregated neighborhoods often have limited health resource availability. The objective of this study is to estimate the relationship between neighborhood segregation on racial and ethnic disparities in timely receipt of GCT in early-stage lung cancer patients in California. Methods: We studied 22,903 patients diagnosed with stage I/II non-small cell lung cancer (2006-2015) in the California Cancer Registry. The primary outcome of the study is receipt of GCT according to the 2016 NCCN guidelines defined as the administration of proper initial and adjuvant treatment(s) according to cancer site and stage, and measured using surgery type, chemotherapy type, and radiation type. The secondary outcome was timely receipt of care as defined as the initiation of surgery, radiation, or chemotherapy within 45 days of diagnosis for initial treatment and the initiation of chemotherapy +/- radiation within 6 months of initial surgery for N1 patients for adjuvant treatment. Multivariable hierarchical logistic regression will be used to estimate the effect of neighborhood segregation on timely receipt of GCT, adjusting for individual- and neighborhood-level covariates, and stratified by patient race/ethnicity. Results: Overall, 81.39% of patients received GCT; 57.63% of them within 45 days of diagnosis. Under-treatment and treatment delay were more frequent in patients who were black or Hispanic, had public insurance, and were of lower socioeconomic status. We hypothesize that increased neighborhood segregation will decrease a patient’s likelihood of adherence to GCT and timely GCT. Conclusions: This research is vital to improving our understanding of cancer-related health disparities and promoting health in vulnerable neighborhoods. With rising numbers of early stage lung cancers due to screening smokers, administration of timely proper treatment is critical.
Differential diagnosis between functional and organic palpitation and chest tightness
Authors: Erdong Chen
Journal: BMJ (2018)

心悸、胸闷这两种症状是心血管门诊的常见主诉，部分患者由功能性临床情况引起，仔细询问症状可以帮助鉴别不同病因。文章对上述两种症状的问诊、鉴别及可能病因进行了详细分析，适当的辅助检查手段可以帮助明确诊断。对功能性心悸、胸闷的患者，应以对症治疗、心理疏导为主，部分患者可能需转至精神专科就诊。
Ophthalmic immune-related adverse events following anti-CTLA-4 or PD-1 therapy recorded in the American Academy of Ophthalmology IRIS Registry.
Authors: Michel M. Sun, Scott P. Kelly, Apoorva Lakshmi Mylavarapu, Anne L. Coleman, Gary N. Holland, Fei Yu, Sukhminder Singh, Stephen Hsu, Flora Lum, Lynn K. Gordon
Journal: Journal of Clinical Oncology (2020)

e15124 Background: The detailed study of ophthalmic immune-related adverse events (OirAEs) is of integral importance in the evolving field of cancer immunotherapy to inform management and treatment guidelines. This study seeks to quantify the differences in incidence and recurrence rates of OirAEs by immune checkpoint inhibitor (ICI) status in a longitudinal big-data registry in patients who are seen in ophthalmic clinics. Methods: This retrospective registry study examined patients newly diagnosed with OirAEs between January 1, 2013 and December 31, 2017 in the American Academy of Ophthalmology’s IRIS Registry. The primary exposure of interest was prior initiation of ICIs. Incidence of OirAEs within 1 year following initiation of ICIs, including anti–PD-1 or anti-CTLA-4 therapy was determined. Incidence rate ratios (IRR) were derived by comparing incidence of OirAEs after ICIs versus rates of non-drug related ocular complications in the entire registry population. Rates of OirAEs in patients with a past history of ocular inflammation or other specific ophthalmic condition prior to initiation of ICIs were further examined. Results: A total of 3,123 patients were identified to have received anti-CTLA-4, anti-PD-1, or anti-PD-L1 therapy, 111 of whom developed an OirAE (3.6%). All OirAE patients had a documented initial pre-drug cancer ICD code, when available, of malignant metastatic melanoma or choroidal melanoma, with the exception of one patient. Incidence rates for anterior uveitis, the most common OirAE, were found to be 3,736 per 100,000 among all ICIs. Rates of all analyzed OirAEs among patients on ICI therapy were elevated compared to baseline ocular complication rates (IRR = 3.5 - 43.0). Time to development of OirAE was drug dependent, with anti-CTLA-4 monotherapy demonstrating rapid onset of OirAE, with most cases within 20 days of starting drug administration. Patients with a prior history of uveitis or other ocular inflammation demonstrated extremely high recurrence rates of OirAEs after initiating ICIs (51.1% for intermediate/posterior/panuveitis, 38.9% for anterior uveitis). Conclusions: Patients initiating ICI therapy are at risk of a number of ocular complications. Rates of OirAEs following ICI therapy are as high as 50% in specific patient populations, including those with a previous history of any uveitis or autoimmune ocular disease. Early coordination with ophthalmic subspecialist care, possibly before ICI is initiated, is critical for optimal care of these high risk populations.
Efficacy and safety of human recombinant endostatin plus pemetrexed and cisplatin in the treatment of advanced non-small cell lung cancer
Authors: Yan-zhi Peng
Journal: BMJ (2013)

To explore the efficacy and safety of human recombinant endostatin (rh-endostatin) plus pemetrexed and cisplatin in the treatment of advanced non-small cell lung cancer (NSCLC). A total of 79 patients with advanced NSCLC were randomly divided into control group (n=39, pemetrexed plus cisplatin) and study group (n=40, rh-endostatin plus pemetrexed and cisplatin). The short-term relative risks of the test group (19/40, 47.5%) was significantly higher than that in the control group (10/39, 25.6%). And the clinical benefit rate the test group (33/40, 82.5%) was higher than that of the control group (23/39, 59.0%, P<0.05). The predominant adverse effects were bone marrow suppression and digestive reactions. And the incidence rate was not significantly different between two groups.


Key words: 
Carcinoma, non-small cell lung; Drug therapy, combination
Correlation between five-year overall survival by PREDICT and 21 gene recurrence score (RS) in a Mexican private institution.
Authors: Geovani Amador García, Omar Serrano Villamayor, Raul Alejandro Andrade Moreno, Elina Alexandra Rodríguez Meléndez, José Fabián Martínez-Herrera, Alain Sánchez Rodríguez, Eduardo Reyes, Guillermo Olivares, Alberto Villalobos, Alvaro Aguayo, Fernando Perez-Zincer, Christian Patricio Camacho Limas, Jesus Miguel Lazaro, Juan Alberto Serrano, Raquel Gerson Cwilich
Journal: Journal of Clinical Oncology (2020)

e12543 Background: In México the 5-year overall survival of Early Breast Cancer (EBC) reaches to 82-97%. Oncotype Dx evaluates the expression of 21 genes associated with recurrence and classifies patients into risk groups. PREDICT (https://breast.predict.nhs.uk/tool) is an online tool which assesses 5 and 10 year overall survival in breast cancer patients who receive adjuvant chemotherapy, adjuvant hormonal therapy and trastuzumab therapy for HER2(+) patients. Methods: Retrospective review of medical records of early stage breast cancer patients with (HR+) and HER2 (-) treated at our institution. Clinicopathological characteristics and (RS) were collected. 5-year overall survival was calculated with the PREDICT online tool. Both scores were compared and the correlation was estimated with Spearman’s Rho and global agreement with intraclass correlation coefficient (CCI), statistical software: STATA SE ver11.0 (StataCorp LLC Texas,USA). Results: From January 2008 to December 2018, 136 patients with EBC (IA-IIB), HR(+) HER2(-), N0-1 were included. The Median age at diagnosis was 55.03 years (30-80). Stage IA patients accounted for 68.38% of the population. Patients were classified into risks according to the original description of Oncotype. 72 patients (53%) were classified as low risk (LR), 49 (36%) at intermediate risk (IR) and 15 (11%) patients at high risk (HR). When reclassifying the risk categories using the cut-off values in TAILORx trial, the population distribution was modified, with a notable increase in the population in IR with 86 (63.2%) patients in this group, 28 patients in the LR group ( 20.5%) and 22 patients (16.1%) in HR. We decided to use TAILORx cut-off values for the aim of this work. Mean overall survival established by the 21 gene RS was 98% for the overall population. The mean overall survival calculated by PREDICT was 93%. Spearman’s correlation coefficient was 0.16 (Spearman’s Rho = 0.16 p = 0.065) with intraclass correlation coefficient (ICC) = 0.04 (IC 95% -0.15 – 0.22, p = 0.33). Conclusions: The results do not show a clear correlation between the tests. Lack of such correlation may be due to a low number of patients. In our population PREDICT couldn't replace the RS test for therapeutic decision making.
Analysis for clinical value of 64-slice spiral CT coronary angiography in diagnosing coronary heart disease
Authors: Jian Wang, Tian-hao Wang, Qin Li, Yi Zhou, Meng-su Zeng, Qi Zhao, Shan-zhu Zhu
Journal: BMJ (2009)

Objecfive To explore clinical value of 64-slice spiral CT coronary angiography in diagnosing coronary atherosclerotic heart disease. as compared to that with selective coronary angiography.Methods One hundred and thirteen patients who underwent both 64-slice spiral CT coronary angiography as well as selective coronary angiography at an interval of no more than one month at Zhongshan Hospital.Shanghm in 2006 were selected for the study and their imaging reports were analyzed and compared.Results Images of 910 segments of coronary arteries were collected and assessed.Sensitivity,specificity and likelihood ratio for negative test result of 64-slice spiral CT coronary angiography in diagnosis of coronary atherosclerotic heart disease were 73.8 percent.97.0 percent and 24.4,respectively,with an overall agreement of 93.2 percent,positive predictive value of 82.7 percent and negative predictive value of 95.0 percenL Conclusions Sixty-four-slice spiral CT coronary angiography has hish specificity,negative predictive value and positive likelihood ratio,with high accuracy,in diagnosing coronary atherosclemtic heart disease.

Key words: 
Coronary disease; Tomography,spiral computed; Diagnostic imaging
Awareness of knowledge about iron deficiency anemia in patients with it
Authors: Shao-ling Wu
Journal: BMJ (2010)

Objective To investigate awareness of knowledge about iron deficiency anemia (IDA)in patients with it.Methods Patients diagnosed as IDA at their initial visits to Affiliated Hospital of Qingdao University Medical School were randomly selected for the study during January 2008 to January 2009 with self-designed questionnaire to investigate their awareness of knowledge about IDA.Results Among 199 patients with IDA investigated, their awareness was lower in general, five percent about its etiologies, 34.2 percent about its clinical manifestations, 18.1 percent about its hazard to health, and two percent about food abundant of iron.For preventive measures of IDA, 50.7 percent (101/199) of them knew that daily diet should be diversified and 43.7 percent (87/199) knew that meals should be prepared with ferric cooking pot.Awareness of knowledge about other preventive measures of IDA was lower in them.No significant difference in awareness of IDA-related knowledge between them at varied ages was found, except for knowledge about etiology and hazard of IDA.Awareness of etiology of IDA differed between them at varied ages (P ＜0.05), and about 75.3 percent (64/85)of patients with IDA aged 30 -45 years were caused by chronic blood loss.There was no significant difference in awareness of IDA-related knowledge between patients with IDA caused by varied etiologies (P ＞ 0.05).Conclusions In general, awareness of IDA-related knowledge was lower in patients with IDA.It is necessary to strengthen its popularization, with varied focuses in preventive measures for IDA patients with different etiologies.

Key words: 
Anemia, iron deficiency;  Questionnaire;  Understanding rate
Advances in precision therapy with venetoclax in multiple myeloma with t(11;14) and high BCL2 expression: A systematic review.
Authors: Zahoor Ahmed, Shaha Nabeel, Arafat Ali Farooqui, Hassan Imtiaz, Aqsa Ashraf, Umer Farooq, Mohammad Ammad Ud Din, Ahsan Wahab, Saif ur Rehman, Faiz Anwer
Journal: Journal of Clinical Oncology (2020)

e20535 Background: In multiple myeloma (MM), translocation t(11;14) has shown higher expression of B Cell Lymphoma 2 protein (BCL2)- a target for Venetoclax (VEN). This review highlights the role of precision therapy with VEN in t(11;14) MM. Methods: A systematic search of PubMed, Cochrane, Web of Science and Clinicaltrials.gov was performed for use of VEN in MM from inception to 1/2/20. 5 out of 183 studies were finalized (N = 512). Results: Out of 500 relapsed refractory (R/R) MM patients, 97 had t(11;14) and 168 had high BCL2. VEN as monotherapy had encouraging responses in t(11;14) MM patients with high BCL2:BCL2L1 (Kumar 2017). VEN when combined with proteasome inhibitors (PIs) achieved promising results. VEN achieved superior results with carfilzomib and dexamethasone (d) (ORR 100%) in t(11;14) MM patients (Costa 2018) as compared to bortezomib (B) and d (ORR 94%) (Moreau 2017). With high BCL2, VEN-Bd achieved ORR of 84% (CR 35%, VGPR 73%) versus placebo (ORR 83%; VGPR 33%) (Bellini 2019). Conclusions: Venetoclax achieved superior responses in RRMM pts with t(11;14) and high BCL2 expression. Further studies are warranted. [Table: see text]
Survey on follow-up status in patients with chronic liver diseases
Authors: Di Zhang, Guang-bin Zhao, Su-ping Yuan, Yu-ni Zhang, Xiao-juan He
Journal: BMJ (2012)

A questionnaire and telephone survey was conducted on 246 patients with chronic liver diseases in the Outpatient Clinic from August 2010 to May 2011.The distribution of diseases and the causes of losing follow-up were analyzed. Most subjects in this survey (182/246,74.0％ ) were patients with chronic viral hepatitis( HBV or HCV)and cirrhosis; and their follow-up status was better than others (X2 =12.382,P ＜ 0.05). There were no differences in gender( X2 =10.137,P ＞ 0.05),but significant differences in age ( X2 =31.783,P ＜ 0.05 ) and educational levels ( X2 =32.803,P ＜ 0.05 ) between patients with chronic viral hepatitis and cirrhosis and patients with other liver diseases.The main causes of losing follow-up were neglect of disease by patients (38.3％) and lack of good communication between doctors and patients ( 18.3％ ).It is important to reinforce the understanding and awareness of chronic liver diseases for patients.

Key words: 
Liver diseases; Follow-up studies