tbuckley/cabot-search huggingface dataset:
Mutation in homologous recombination to predict a better prognosis in endometrial cancer.
Authors: Luyang Zhao, Dai Yibo, Yuanjin Hu, Zhiqi Wang, Chengcheng Li, Guoqiang Wang, Jianliu Wang
Journal: Journal of Clinical Oncology (2020)

6082 Background: Endometrial cancers have been categorized into four genomic classes by The Cancer Genome Atlas Research Network (TCGA) with comprehensive genomic analysis. However, TCGA molecular subtypes are hard to utilize in clinic as the expensive cost and a simply version of POLE, TP53 genes cannot fully differentiate the four subtypes. Therefore, more convenient and reliable biomarkers need to be identified for clinical practice. Methods: Whole-exome sequencing and RNA sequencing data for 515 patients with endometrial carcinomas were downloaded from TCGA. Mutations in 48 genes of homologous recombination repair (HR) signaling were defined as HR mutation. Associations between HR mutation and survival and RNA expression were analyzed.Gene set enrichment analysis (GSEA) were used to invesgate the gene signaling. Results: HR mutation was associated with a prolonged disease specific survival (DSS) (HR, 0.39; 95% CI, 0.22-0.71; P = 0.002), progression-free survival (PFS) (HR, 0.46; 95% CI, 0.31-0.68; P &lt; 0.001) and overall survival (OS) (HR, 0.45; 95% CI, 0.28-0.72; P = 0.001) in endometrial cancers. HR mutation was related with clinical characteristics including histological types (P &lt; 0.05). In the multivariable cox proportional hazards regression model including FIGO 2008, histology types, tumor grade and TCGA subtypes, TP53 mutation, POLE mutation, the association between HR mutation and PFS was still significant (HR, 0.48; 95% CI, 0.27-0.86; P &lt; 0.05), which indicating the HR mutation is an independent prognostic factor for PFS. HR mutations were associated with a higher tumor mutation burden. GSEA suggested that HR mutation was involved with the increase of genes related to activated T cells, immune cytolytic activity, and IFN-γ release. In MSS endometrial cancers, HR mutation still showed a longer PFS (HR, 0.57; 95% CI, 0.34-0.98; P = 0.04), suggested HR mutation may help predict the effect of immunotherapy in MSS endometrial carcinoma. Conclusions: HR mutation was related with a favorable prognosis through increasing T cells signature. Identification of HR mutation by genomic profiling provides a potentially novel and convenient approach for endometrial cancer patients to predict the prognosis independent of TCGA four subtype classifications and provides an inspiration for screening patients who may benefit from ICBs in endometrial cancer in the future.
A case of adult hepatolenticular degeneration with cirrhosis ascites as initial manifestation
Authors: Ping Wang, Yijin Zhang, Xiao Liu
Journal: BMJ (2020)

现报道1例成年女性的肝豆状核变性患者的临床资料。患者首发表现为肝硬化腹水，因腹胀3周余就诊，包含基因检测结果ATP7B发生杂合突变，行青霉胺500 mg/d驱铜及护肝治疗后病情改善。临床医生需提高对该病的认识，争取早诊断、早治疗。
TGF-β1-Licensed Murine MSCs Show Superior Therapeutic Efficacy in Modulating Corneal Allograft Immune Rejection In Vivo
Authors: Kevin Lynch, Oliver Treacy, Xizhe Chen, Nick Murphy, Paul Lohan, Md Nahidul Islam, Ellen Donohoe, Matthew D. Griffin, Luke Watson, Steven McLoughlin, Grace O’Malley, Aideen E. Ryan, Thomas Ritter
Journal: Molecular Therapy (2020)

Mesenchymal stromal cells (MSCs) are a promising therapeutic option for multiple immune diseases/disorders; however, efficacy of MSC treatments can vary significantly. We present a novel licensing strategy to improve the immunosuppressive capacity of MSCs. Licensing murine MSCs with transforming growth factor-β1 (TGF-β MSCs) significantly improved their ability to modulate both the phenotype and secretome of inflammatory bone marrow-derived macrophages and significantly increased the numbers of regulatory T lymphocytes following co-culture assays. These TGF-β MSC-expanded regulatory T lymphocytes also expressed significantly higher levels of PD-L1 and CD73, indicating enhanced suppressive potential. Detailed analysis of T lymphocyte co-cultures revealed modulation of secreted factors, most notably elevated prostaglandin E2 (PGE2). Furthermore, TGF-β MSCs could significantly prolong rejection-free survival (69.2% acceptance rate compared to 21.4% for unlicensed MSC-treated recipients) in a murine corneal allograft model. Mechanistic studies revealed that (1) therapeutic efficacy of TGF-β MSCs is Smad2/3-dependent, (2) the enhanced immunosuppressive capacity of TGF-β MSCs is contact-dependent, and (3) enhanced secretion of PGE2 (via prostaglandin EP4 [E-type prostanoid 4] receptor) by TGF-β MSCs is the predominant mediator of Treg expansion and T cell activation and is associated with corneal allograft survival. Collectively, we provide compelling evidence for the use of TGF-β1 licensing as an unconventional strategy for enhancing MSC immunosuppressive capacity.
Preoperative chemotherapy for advanced endometrial cancer-registry analysis of outcomes.
Authors: Samer Salamekh, Jingsheng Yan, Hong Zhu, Kevin V. Albuquerque
Journal: Journal of Clinical Oncology (2020)

6088 Background: Hysterectomy followed by risk-adjusted adjuvant treatment is the standard of care for staging and treatment of locally advanced endometrial cancer. Up-front surgery is difficult in some locally advanced cases with extensive local invasion since negative margins may not be achievable. Pre-operative systemic treatment may be used to shrink the tumor and facilitate resection, echoing the experience from ovarian cancer. There is limited data for this paradigm in endometrial cancer. Methods: The National Cancer Database (NCDB) was queried for cases with FIGO stage III/IV endometrial cancer (serous, clear cell, or endometrial histology) who underwent surgery and had known chemotherapy/radiation sequencing. Those who received pre-operative chemotherapy +/- post-operative chemotherapy (PreCT) were compared to those who received post-operative chemotherapy alone (PostCT). PreCT cases were considered to be initially borderline resectable or unresectable. Downstaging was determined by comparing clinical and pathologic T-stage. Univariable (UV) and multivariable (MV) analyses were performed, with statistically significant values reported. Results: 12,310 cases in PostCT and 1,059 cases in PreCT were included in the analysis. Pre-CT cases were more likely to have higher AJCC T-stage, clinically positive nodes, serous histology, higher grade, and positive surgical margins (28% compared to 16%). Overall survival (OS) was lower for PreCT compared to PostCT (HR = 2.18 UV; HR = 1.87 MV). 20% of patients who received PreCT were down-staged compared to 2% in PostCT group. Patients who were downstaged with PreCT were more likely to achieve negative margins (OR 0.36 UV) and had improved OS compared to those whose stage did not change (HR = 0.61 UV; HR = 0.37 MV). Positive margins portended worse OS for both PreCT (HR = 1.93 UV) and PostCT (HR = 2.63 UV). Negative margins in PreCT had improved OS compared to positive margins in PostCT (HR = 1.2 UV; 2.67 MV). Post-operative radiation benefited both PreCT (HR = 0.45 UV; HR = 0.34 MV) and PostCT groups (HR = 0.48 UV; HR 0.64 MV). Conclusions: Preoperative chemotherapy increased the number of patients who were downstaged and those who were downstaged were more likely to achieve a negative margin. Patients who achieved negative margins in PreCT had improved OS compared to those with positive margins in PostCT. Adjuvant radiation further improved OS in both cohorts. Pre-operative chemotherapy can be considered for patients with unresectable/borderline resectable locally advanced endometrial cancer.
Prognostication based on TNM staging for socioeconomically disadvantaged colorectal cancer patients.
Authors: Yan Lu, Aaron Gehr, Jolonda Bullock, Bassam Ghabach, Latha Sri Neerukonda, Kalyani Narra, Rohit P. Ojha
Journal: Journal of Clinical Oncology (2020)

e19036 Background: The TNM classification system is the global standard for staging solid tumors, but the ability of TNM to differentiate prognostic groups may vary between settings because of differences in case-mix and treatments. Little information is available about prognostication using TNM in safety-net health systems, which provide care for socioeconomically disadvantaged individuals and have limited resources. Therefore, we aimed to assess the ability of TNM to differentiate prognostic groups for colorectal cancer patients in an urban safety-net cancer center. Methods: We used institutional registry data from the JPS Oncology and Infusion Center (Fort Worth, TX), which is a Comprehensive Community Cancer Program. Our eligible population included adults who were diagnosed with first primary colorectal cancer between 2008 and 2017, had TNM pathologic stage I – IV, and received at least part of the first course treatment at JPS. Our outcome of interest was 5-year all-cause mortality and our exposure of interest was TNM pathologic stage. Patients were followed from cancer diagnosis until death, loss to follow up, or end of study (December 31, 2018), whichever occurred first. We used a pseudo-observation approach and generalized linear models with log link to estimate risk ratios (RR) and corresponding 95% confidence limits (CL) comparing 5-year mortality between TNM stages, where stage I was the reference category. Results: Our eligible population comprised 655 colorectal cancer survivors, of whom 85% were aged &lt; 65 years, 54% were male, 60% were racial/ethnic minorities, and 65% were uninsured at time of diagnosis. Stage IV patients had 4.4 times higher risk of 5-year mortality compared with stage I (RR = 4.4, 95% CL: 2.9, 6.6). Stage III patients had 2.1 times higher risk of 5-year mortality compared with stage I (RR = 2.1, 95% CL: 1.3, 3.2). Stage II patients had 1.4 times higher risk of 5-year mortality compared with stage I (RR = 1.4, 95% CL: 0.81, 2.3). Conclusions: Our findings suggest that TNM stages do not adequately differentiate colorectal cancer prognostic groups in a socioeconomically disadvantaged population. Stage IV is distinct, but stages I – III have limited differentiation and notable overlap. The use of TNM stages for colorectal cancer prognostication may be misleading for socioeconomically disadvantaged individuals. Factors beyond TNM should be considered for better prognostication in this population.
发热门诊急性发热患者468例临床分析
Authors: 雷京生
Journal: BMJ (2011)

观察并分析2009年4月至2010年4月我院发热门诊468例急性发热患者的临床资料. 1.临床资料:468例中,男性226例(48.3%),女性242例(51.7%).0～5岁者205例(43.8%),6～14岁者99例(21.1%),15～24岁者86例(18.4%),25～59岁者65例(13.9%),≥60岁者13例(2.8%).37.3～38.0℃者279例(59.6%),38.1～39.0℃者164例(35.0%),39.1℃以上者25例(5.4%)。
General practitioner-led multidisciplinary team model in management of elderly comorbidity patients in community
Authors: hui Wang, Fuying Zhao
Journal: BMJ (2019)

Patients with multiple diseases have a variety of medical needs, especially in elderly patients with senile syndrome. The conventional specialty care model is not suitable for patients with comorbidities and multidisciplinary intervention and management are required. The article introduces the concept and practice of a general practitioner (GP)-led multidisciplinary team in management of comorbidities in the community. Using one case of elderly patient with multiple diseases as example, the article shows how this model worked and how the patient benefited, and the related issues and reflections are also discussed in the article.


Key words: 
Comorbidity; Aged; General practitioner; Interdisciplinary team
Clinical features of primary Sjǒgren's syndrome involved in the extra-gland organs as initial manifestations
Authors: Xue-wu Zhang, Yuan An, Zhan-guo Li
Journal: BMJ (2008)

Objective To investigate clinical characteristic of primary Sjogren's syndrome(pSS) with initial manifestations in the extra-gland organs. Methods Clinical data, including symptoms, laboratory parameters and complications of 85 pSS patients with initial manifestations of extra-gland organs hospitalized at the People's Hospital of Peking University during 2003 to 2006 were collected and analyzed retrospectively, as compared to those of pSS with xerophthalmia or xerostomia as initial ones. Results Mean time interval from onset to diagnosis in these patients with initial manifestations involved in the extra-gland organs was 94.5 months, higher than that in those with xerophthalmia or xerostomia as initial ones. Arthritis was manifested initially in 38 of the 85 patients (44.7 percent), peripheral leukopenia in 16 (18.8 percent), thrombocytopenia in nine (10.6 percent) and abnormal liver function in 13 (15.3 percent), respectively. Percentage of serum positive autoantibedies was higher in the patients with initial manifestation of the extra-gland organs than that in those with xerophthalmia or xerostomia as initial ones. Conclusions Initial manifestation of primary Sjogren's syndrome varies, and some patients can be initially involved in their extra-gland organs, with more proportion of arthritis than of other symptoms, and xerophthalmia or xerestomia could appear in them during the course of disease. And, xerophthalmia or xerostomia would not appear even as pSS was diagnosed in some other pSS patients. More attention should be paid to these clinical characteristics mentioned above in practice to avoid misdiagnosis.

Key words: 
Sjogren's syndrome;  Symptoms and signs;  Xerostomia;  Arthritis
Are symptoms distinguishable in ovarian cancer? A nested case control study of insurance claims.
Authors: Denise Manon Langabeer, Trudy Krause, Cecilia M Ganduglia Cazaban, Michael D Swartz, David S Lopez, Diane C. Bodurka
Journal: Journal of Clinical Oncology (2020)

6063 Background: Over 60% of ovarian cancer cases are diagnosed with Stage III and IV disease. The US healthcare system does not support a standard screening method for ovarian cancer. Our goal was to determine whether certain symptoms based on ICD-9 categories are distinguishable among women diagnosed with ovarian cancer and women without ovarian cancer. Methods: Women diagnosed with ovarian cancer were randomly matched 1:1 to women without cancer to support a nested case-control analysis of health insurance claims between 2008 through 2013 from a commercial payer. The following eligibility criteria were applied: 1) 24 years of age or older; 2) continuously enrolled in healthcare plan for a minimum period of 6 months; 3) experienced more than 1 symptom over the observation period; and 4) an observation period of a minimum of 6 months. Symptoms were based on 47 ICD-9 diagnosis codes and categorized specific to pain, abdominal and pelvic, digestive, and bladder. The analysis was based on 1,578 women (789 cases; 789 controls). Results: Overall, 90% (n = 1,421) of the women experienced abdominal and pelvic symptoms, and 92% (n = 725) of the women with ovarian cancer visited their physician for this complaint 6-70 months prior to diagnosis, OR 1.66 (CI 1.14 to 2.41; p = .008). Pain was reported as a complaint by cases at nearly 60% (n = 464) and controls at 48% (n = 376); OR 1.75 (CI 1.39 to 2.19; p &lt; .001). Symptoms for bladder and digestive combined represented 68% of complaints for both cases (n = 507) and controls (n = 555), p = .024 and p = .298, respectively. Of the 1,578 women, 77% (cases = 621; controls = 595) experienced more than one category of symptoms. Both cases (n = 206) and controls (n = 153) complained of abdomen and pelvic symptoms along with pain; OR 1.54 (CI 1.19 to 1.99; p = .001). A second combination included abdomen and pelvic symptoms with pain and digestive symptoms in 14% of women (cases n = 99; controls n = 67); OR 1.58 (CI 1.13 to 2.22; p = .008). Sixty percent (n = 473) of women with ovarian cancer experienced the majority of associated pre-diagnosed symptoms analyzed for the study. Conclusions: Certain recurring symptoms associated with abdomen and pelvic as well as pain appear to indicate an association with ovarian cancer, signifying that symptom awareness remains relevant to this disease that is diagnosed at a late stage and currently does not have routine screening methods to support early detection.
Data to decisions: The impact of online education on immunotherapy in advanced renal cell carcinoma.
Authors: Kinjal Parikh, Katie Lucero, Charlotte Warren, Emily Sherene Van Laar, Ann Carothers, Haleh Kadkhoda, Brian I. Rini
Journal: Journal of Clinical Oncology (2020)

e17076 Background: Cytokine therapy was initially the only immunotherapy for patients with advanced renal cell carcinoma (RCC). The advent of targeted therapies ushered in a new area of precision medicine in the treatment paradigm. Recently, immunotherapy in the form of immune checkpoint inhibitors has shown improved outcomes as compared to targeted therapies and has become a mainstay in treatment. As immunotherapy use moves into earlier stages of disease and combination therapies are explored, education remains essential to optimize patient outcomes. Through the partnership between Medscape Oncology and the Society for Immunotherapy of Cancer, educational activities were designed to increase the knowledge and competence among oncologists surrounding the role of immunotherapy in patients with advanced RCC and uncover remaining educational needs. Methods: The 2 educational activities included a 30-minute online, video discussion with 2 faculty presenters and synchronized slides and a text-based online activity with 2 patient cases and interactive questions. Educational effectiveness was assessed with repeated paired pre/post assessment where learners served as their own controls. The first activity launched September 19, 2018, the second activity launched December 19, 2018, and the data were collected and are reported through December 27, 2019. Results: A total of 9474 learners participated from September 2018-December 2019 including 1029 oncologists. Participation in education resulted in significant improvements for oncologist who answered all pre/post questions for an activity during the study period (n = 302). Improvements in knowledge and competency were observed in the following areas: Knowledge regarding the latest clinical trial data on the use of cancer immunotherapies for the treatment of RCC (49% vs. 74%, p &lt; .001). Knowledge regarding the immune checkpoint inhibitor regimens on the care of patients with RCC (49% vs. 70%, p &lt; .001). Competence related to choosing the most appropriate regimen for patients with mRCC across the continuum of care (54% vs. 76%, p &lt; .001). Conclusions: Participation in online, video- and case-based CME-certified educational activities resulted in statistically significant gains in oncologist knowledge and competency surrounding the use of immunotherapy in advanced RCC. These results demonstrate the value and benefit of multi-modal and sequential activities on improving knowledge and competence outcomes for oncologists caring for patients with advanced renal cell carcinoma.
Association of phthalates with nasal patency and small airway dysfunction in first‐grade elementary school children
Authors: Mi‐Ae Kim, Dong Keon Yon, Hye Mi Jee, Ju Hee Kim, Jisoo Park, Seung Won Lee, Myongsoon Sung, Youn Ho Sheen, Man Young Han
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
A pilot trial of multiple-TSA-specific adoptive immune cell (MAIC) as adjuvant therapy in gastrointestinal cancer.
Authors: Wei Shi, Jin Song, Xiaohong Cui, Yan Wang, Boyuan Mei, Shucheng Ren, Haiwen Wang, Huan Chen, Li Li, Henghui Zhang, Hao Zhang, Jilin Lu
Journal: Journal of Clinical Oncology (2020)

e15013 Background: Given the heterogeneity of tumors, more tumor antigens need to be covered for better efficacy in oncologic immunotherapy. We conducted a pilot clinical trial to evaluate the safety and efficacy of adoptive immune cell therapy targeting multiple tumor specific antigens in individual patients. Methods: A total of 10 patients bearing resectable gastrointestinal tumor are going to be recruited in the study. The tumor-specific antigens of each patient were identified by RNA sequencing of the surgical tumor tissue. And then the antigenic peptides were synthesized and adapted to produce the multiple-TSA-specific adoptive immune cells (MAIC), including dendritic cell (DC) and cytotoxic T lymphocyte (CTL). 1 st dose of MAICs injected during the 2 nd or 3 rd week after surgery; three doses of MAICs administered at 3-week intervals. Results: Currently, 4 patients have been enrolled, as shown in Table. The first enrolled patient, P01, underwent adjuvant MAIC therapy and have no progression nearly 9 months. P02, P03 and P04 developed new lesions about 3 months after the 1 st surgery. After the 2 nd surgery, tumor antigens were modified and MAIC targeting new antigens were given for adjuvant therapy. Up to now, there were no death events with survival months from 6.57 to 9.10. Safety evaluation showed that no irAE occurred in 4 patients. Intriguingly, antigenic drift was observed in patient P02.The top 3 antigens were shift from GPC3, AFP and GAGE10 to MAGEA1, GPC3 and CTAG2. And the mutation profile of tumors revealed totally different tumor clones with no shared SNV mutation between two surgery lesions at all. Through TCR sequencing, we found new T cell clones introduced by MAICs persisted in peripheral blood (sum ratio variated from 6.47% to 9.68%). Among them, specific T cell clones were identified targeting four antigens, including GPC3, AFP, TERT and MAGEA1. Among them, TERT-specific T cell clones shew highest expansion ratio, from 0.63±0.17% in PBMC to 7.85±3.10% in CTL. Conclusions: Treatment with MAICs have be proved safety in resectable gastrointestinal cancer. And all together four-antigen-specific T cell clones elevated apparently in peripheral blood after the 1st infusion of MAIC, reflecting the advantage of MAIC at renewable antigenic targets. [Table: see text]
针刺足三里穴治疗单纯性呃逆29例
Authors: 温安东, 马建春
Journal: BMJ (2004)

我们以针刺足三里,治疗因一过性胃肠功能障碍引起的单纯性呃逆患者29例,疗效满意. 1.临床资料:本组男11例,女18例,12～64岁,病程2 h～2 d,均为单纯性呃逆.我们取足三里穴常规消毒,直刺 2寸,强刺激1～2 min,边捻转提插边询问患者局部针感,然后留针5 min,让患者注意针感.一次未止者1 h后再针,可连针2～3次.一般针单侧足三里,对呃逆较频者可针双侧.