tbuckley/cabot-search huggingface dataset:
Practice-changing use of the 21-gene oncotype DX breast recurrence score test in Latin American hospitals.
Authors: Henry Leonidas Gomez, Juan Enrique Bargallo-Rocha, Roberto Jorge Billinghurst, Aníbal Roberto Núñez de Pierro, Federico Andrés Coló, Lisandro Luis Benitez Gil, Carola Allemand, Ignacio Leonardo McLean, Mauricio Lema-Medina, Fernando Herazo-Maya, Francisco Jose Terrier, Raquel Gerson Cwilich, Mauricio León Rivera, Silvia Gabriela Falcon, Roberto Eduardo Castaño, Sergio Cordeiro Oliveira, Debbie M Jakubowski, Calvin Y. Chao
Journal: Journal of Clinical Oncology (2020)

e12539 Background: The 21-gene test is clinically validated to predict chemotherapy (CT) benefit in node-negative (N0) and node-positive (up to 3 axillary nodes, N+) HR+, HER2− early-stage breast cancer (ESBC). TAILORx showed no CT benefit overall in N0 patients with RS 0-25, but younger patients with RS 16-25 might have some. Clinical guidelines worldwide incorporate the 21-gene test; still, the impact of the test on treatment decisions is unclear in Latin America, where patients often present younger and with more advanced disease. We present a physician survey of the impact of Recurrence Score results on treatment decisions in clinical practice in Latin America. Methods: This multicenter, non-therapeutic, prospective survey enrolled consecutive patients who had 21-gene testing during routine care at 14 community and academic sites in Argentina, Colombia, Mexico, and Peru. Tests were paid for by patients. The physician survey captured patient and tumor characteristics and treatment decisions by physicians pre- and post-assay result. The survey included patients treated before and after TAILORx results reported in 6/2018. Overall net percent change in CT recommendation and 95% Clopper Pearson confidence intervals (CI) were estimated. The proportion with a change between pre-assay treatment recommendation and actual treatment received was calculated overall and by Recurrence Score groups per TAILORx. Results: Between 3/2015 and 12/2019, the survey was completed for 647 patients. 20% had N+ ESBC. Mean patient age was 54 y (24-85 y); 55% were postmenopausal. 17%/63%/20% had grade 1/2/3 tumors; 70%/30% had tumors ≤2/ &gt; 2 cm in size. Recurrence Score results were: 20% RS 0-10, 56% RS 11-25, and 24% RS 26-100. Overall, CT recommendations fell from 325 patients pre-assay to 199 patients post-assay, a 39% decrease (95% CI 33.4 to 44.3) (36% decrease in N0; 46% decrease in N+). The direction of change was consistent with Recurrence Score results. Among N0 patients, the decrease in CT recommendations was 28% (95% CI 18.9 to 39.5) before TAILORx reported and 36% (95% CI 28.4 to 43.7) after. Conclusions: This large survey of 21-gene test practice patterns was the first conducted in Latin America and showed the relevance of 21-gene testing in low- and medium-resource countries to minimize CT over- and underuse in ESBC. Our results showed substantial reductions in CT use overall. After TAILORx, CT use was further reduced, indicating the practice-changing potential of that study.
Disparities in receipt of complete diagnostic evaluation to confirm myelodysplastic syndromes.
Authors: Sudipto Mukherjee, Weichuan Dong, Abby Statler, Siran M. Koroukian
Journal: Journal of Clinical Oncology (2020)

7555 Background: A complete diagnostic evaluation (CDE), including bone marrow (BM) biopsy, cytogenic testing, FISH panel, and/or flow cytometry, is widely accepted as a prerequisite for histopathologic confirmation of MDS. Earlier reports have raised concerns regarding accuracy of MDS diagnosis in population registries that do not require confirmatory tests for disease reporting. We queried Medicare files to analyze the extent of use of, and factors associated with CDE for diagnosing MDS. Methods: The study population included Medicare patients with at least one inpatient or two outpatient claims for MDS within a 12-month period during the years 2012 and 2013. Variables included age, sex, race, morphologic MDS categories, cytopenias (isolated or any combination), transfusion burden, comorbididities, as well as county-level characteristics (income, educational attainment, rurality, and availability of internal medicine subspecialists). Classification and regression tree (CART) and multivariable logistic regression analysis were used to identify combinations of factors associated with receipt of CDE. Results: Our study population included 45,067 MDS patients, of whom only 68.6% received CDE that included BM biopsy and/or chromosomal studies. The percent of patients undergoing CDE was significantly lower among those 85 years of age or older (56.1%); women (63.7%); Blacks (64.2%); patients with isolated anemia (60.3%); and those who were transfusion independent (p &lt; 0.001 for all comparisons). On the other hand, CDE was significantly higher among patients with the category of MDS with excess blasts (89.4%); those presenting with pancytopenia (92.2%); and those with high transfusion burden (80%). There was little variation by comorbidity burden, county level characteristics, or availability of subspecialists. In CART analysis, 80% of patients presenting with any two or more cytopenias received CDE. In multivariable analysis, advanced age, female sex, Black race, higher comorbidity burden and availability of subspecialists were associated with a lower likelihood to receive CDE, while patients with MDS with excess blasts, and with any &gt; 2 cytopenias were more likely to receive CDE ( P&lt; .0001). Conclusions: Nearly one third (31%) of MDS patients in the Medicare database lack CDE especially BM biopsy. Disparities in CDE can be corrected through proper physician education and stringent registry reporting to avoid such high diagnostic inaccuracies, leading to potential missed treatment opportunities.
A trial of two-way referral system between community health service and medical center
Authors: Jian-jun Wang, Li-min Zhu
Journal: BMJ (2009)

The trial of two-way referral enrolled 26 patients with hypertension, including 20 cases of refractory hypertension, 3 new cases and 3 cases of secondary hypertension, the average length of follow-up was 22 d (10-35 d). The family physicians in Huaihaizhong Road Community Health Service Center communicated with specialists in the medical center (Ruijin hospital), appointments were made and medical information and other materials were sent in advance. When investigations and adjustment of medication were made, and the blood pressure was under control, patients were referred back to the community. This two-way referral system promoted the information exchanges between two side, doctors got prior knowledge about patients' condition and would spend more time with the patients; and patients' feeling of satisfaction and compliance of the treatment were increased. From our experiences, we suggest that the therapeutic regime made by the medical center should be feasible to the community, and more convenience should be given to the referred patients, so that the effectiveness and efficiency of the two-way referral can be further improved.

Key words: 
Community health service;  Two-way referral
Genomic characterization and outcome evaluation of kinome fusions in a large non-small cell lung cancer population.
Authors: Fengying Wu, Sisi Liu, Qiuxiang Ou, Hua Bao, Xue Wu, Yang Shao, Caicun Zhou
Journal: Journal of Clinical Oncology (2020)

9620 Background: Lung cancer is the leading cause of cancer death worldwide. Kinase fusion represents an important type of somatic alterations which promote oncogenesis and serve as a diagnostic marker in lung cancer. This study aims to identify the landscape of kinase fusions in lung cancer and expand our understanding of druggable fusions, together providing valuable information for therapeutics decision making. Methods: We performed genomic profiling of tumor/plasma biopsies of a total of 18,839 Chinese lung cancer patients using next generation sequencing (NGS) by targeting 425 cancer-relevant genes. Patients’ clinical characteristics and treatment history were retrospectively studied. Results: A total of 1,048 patients (5.56%, 1,048/18,839) were identified with kinase fusions, including 815 adenocarcinomas (ADCs) and 34 squamous cell carcinomas (SCCs). Briefly, a total of 198 unique gene fusion events have been observed, including 37 recurrent fusions and 114 novel fusions which have previously not been documented. ADC patients with kinase fusions were relatively younger than SCC patients (median: 53 vs 61 years old, p&lt; 0.01). The most frequently observed fusion was EML4-ALK for both ADCs (50.0%) and SCCs (32.4%), followed by FGFR3-TACC3 (29.4%) in SCCs and KIF5B-RET (11.8%), CD74-ROS1 (9.2%), CCDC6-RET (3.9%) and SLC34A2-ROS1 (2.3%) in ADCs, retrospectively. A total of 14 recurrent fusions including FN1-ALK, MEMO1-ALK, CUX1-ALK, KIF13A-RET and PHF20-NTRK1 were also identified at low frequencies. Of note, EML4- or STRN- ALK fusion events mainly rearranged in the intron 19 of ALK, but the breakpoints of VCL-ALK were mostly located upstream of ALK exon 18. Meanwhile, CD74-, SLC34A2- and TPM3- ROS1 rearrangement mainly occurred in the ROS1 introns 31, 33 and 34. In addition, among patients with novel fusions, RORB- ALK and AFF2-RET may potentially function as oncogenic drivers in lung cancer and have demonstrated clinical benefit from crizotinib treatment. Conclusions: Our data have depicted a comprehensive overview of the landscape of kinase fusions in lung cancer, which helps recognize potentially druggable fusions and translate into therapeutic applications.
First-line CyborD treatment for graft ineligible multiple myeloma patients: Real-life efficacy and tolerability.
Authors: Dominic Duquette, Marie-Michelle Germain
Journal: Journal of Clinical Oncology (2020)

e20516 Background: CyborD is a regimen that was widely adopted in Canada around 2010 despite very little data supporting it’s use. The aim of the study is to describe the efficacy and tolerability of First line CyborD regimen for graft ineligible myeloma patients. Methods: This is a retrospective study at two centres in the CHU de Québec for patients with graft ineligible multiple myeloma patients treated with first line CyborD regimen between 2013 and 2018. The objectives are to describe the efficacy and tolerability of CyborD and to document PFS and OS. Results: 51 patients were included in this study with a median follow-up of 31 months. Partial response or better (≥ PR) was obtain in 84% of patients and 63% of patients achieved a very good response or better (≥ VGPR). A high rate of 26% of complete response (CR) was also obtained. A median PFS of 30 months was obtained while 75% of patients were still alive at that time. Estimated survival at 48 months was 63%. Severe toxicities (grade 3 or 4) were seen as anemia (20%), neutropenia (10%), bacterial infection (16%), diarrhea (12%) and renal toxicity (4%). Side effects related to dexamethasone in this fragile patient population reached 69% of patients but only 28% needed a dose reduction. Conclusions: First-line CyborD treatment was highly effective for graft ineligible multiple myeloma patients and this is a very well tolerated regimen. It compares favorably to RD regimen making it still an excellent first-line treatment for this elderly population. [Table: see text]
Secondary autoimmune hemolytic anemia in patients with tuberculosis: a report of 4 cases
Authors: Haiyan Xie
Journal: BMJ (2015)

Medical charts of tuberculotic patients with secondary autoimmune hemolytic anemia (AIHA) admitted to Peking Union Medical College Hospital(PUMCH)from 2006 to 2015 were retrospectively reviewed. Four cases with complete information of laboratory tests, imaging findings and bone marrow results were included. Therapy regimens and outcomes of survival were followed by phone call if needed. Ages at diagnosis of AIHA were 58-80 years old, hemoglobin levels were 31-73 g/L, Coomb tests were negative in all cases. Therapy of cortical steroid did not work, while anti-TB therapy (including isoniazid, rifampicin, ethambutol) significantly improved hemoglobin to normal level in three cases during six to nine months. One case died within one week, for progressive TB to central neurological system. As one of rare complications of TB, AIHA may be fatal. Early diagnosis and appropriately anti-TB therapy is helpful for good outcomes.


Key words: 
Tuberculosis; Anemia, hemolytic, autoimmune
Focus on long-term effects of obese children addescents
Authors: 季成叶
Journal: BMJ (2004)

人们对青少儿肥胖的危害近年有了全新认识:肥胖是导致成人高血压、高血脂、糖尿病、冠心病和脑卒中等代谢综合征的独立危险因素;防治成人期代谢综合征的早龄化趋势是今后工作的重点;强调尽早、尽快采取综合防治措施,消除肥胖对青少儿健康的长期和深远危害[1].青少儿肥胖的危害具体如下。
Destructive damage of bile duct induced by transcatheter arterial embolization for hepatic hemangiomas: Report of 2 cases and literature review
Authors: Xin-yue Wan, Tao Deng
Journal: BMJ (2013)

Two cases of hepatic cavernous hemangioma underwent transcatheter arterial embolization and the bile duct damage occurred after operation. Chemical cholecystitis developed in one case, gallbladder necrosis in another and hilar bile duct stricture occurred in both cases. Thirty reported cases of destructive damage of bile duct induced by transcatheter arterial embolization were found from searching PubMed databases and CNKI net. The main complications included acute cholecystitis, hepatonecrosis, biliary cirrhosis and bile duct damage. The literature review indicates that thanscatheter arterial embolization may cause severe bile duct damage and should be chosen and operated with caution.


Key words: 
Hemangioma, cavernous; Liver
Results from Melanoma Antigen Redirected Vaccine Stimulated Autologous Lymphocytes (MARVSmALo): A pilot study.
Authors: Joy M. Fulbright, Gary C. Doolittle, Cliona M. Rooney, Siddhartha Ganguly, Sunil H. Abhyankar, Margaret Gilbert, Olga Dakhova, Mina Al-Sabbagh, Huimin Zhang, G. Douglas Myers, Natalia Lapteva
Journal: Journal of Clinical Oncology (2020)

e15026 Background: Despite improvements in treatment with targeted agents and immunotherapeutics metastatic melanoma still has a guarded prognosis. Many melanoma cells upregulate the disialoganglioside GD2. Early GD2 chimeric antigen receptor (CAR) T-cell studies in neuroblastoma demonstrated no toxicity but limited ability to expand in vivo. Strategies to expand these GD2.CAR T cells might improve efficacy while retaining safety. This pilot study aimed to evaluate the safety and efficacy of first generation 14g2a.zeta chimeric antigen receptor ( GD2.CAR ) transduced, activated T cells enriched for vaccine specific cytotoxic T-Lymphocytes (tvs-CTL). Methods: Patients with metastatic melanoma in which standard therapy had failed were eligible if they had recovered from effects of prior therapy, did not have rapidly progressive disease, were free of melanoma involving the CNS and did not have a contraindication to receiving Hepatitis B, Polio or DTAP vaccine. Patients received each of these vaccines prior to cell harvest, 4 days before and 28 days after autologous T cell infusion. Patient 1 was treated with 2 x 10 8 cell dose and patients 2 and 3 were treated with 4x10 8 cell dose. We used QPCR to measure transgene copy number in patients before and after infusion. Interferon-gamma enzyme linked immunospot (ELISPOT) assay was used to measure the frequencies of tetanus, pertussis, diphtheria, poliovirus and tumor antigens-specific T cells in peripheral blood. Results: GD2.CAR-tvs-CTL were manufactured and infused in 3 patients. Overall the infusions were safe. Seven low grade adverse events possibly related to study participation were reported. The first 2 patients did not demonstrate robust in vivo expansion of GD2.CAR-tvs-CTLs by QPCR and had rapid disease progression. In patient 3 a significant expansion of GD2.CAR-tvs-CTLs, i.e. 18,250 copies/ug genomic DNA was observed on day 7 and cells persisted at 159 copies/ug DNA for up to 12 months (latest measured time point). High pertussis-specific responses were also observed by INF-gamma ELISPOT in this patient starting from day 14 after the vaccination through month 12. Conclusions: We have demonstrated that GD2.CAR T cells expanded and persisted in melanoma patient for up to 12 months. The use of vaccination before blood procurement for T cell manufacture and boosting virus-specific T cell after CAR T cell infusion is a safe strategy and may have helped induced higher transgene levels in one of three patients. Clinical trial information: NCT02482532 .
Retrospective analysis about effects of initiating insulin therapy on islet function patients with latent autoimmune diabetes in adults
Authors: Ma Yan, Feng Kai, Li Wei, Ping Fan, Zhao Dong, Li Yuxiu
Journal: BMJ (2016)

Objective
To investigate the effects of initiating oral-medication and insulin-treatment to residual islet function in adult patients with latent autoimmune diabetes in adults(LADA).


Methods
Fifty nice inpatients and 11 outpatients of LADA were enrolled from the Peking Union Medical College Hospital from January 1981 to October 2014, including 34 cases with initiating insulin therapy and 36 cases with initiating oral medication. Patients were followed up at least twice and with a 6-month interval. The age, body mass index (BMI), diagnosis time, fasting C peptide (FCP), 2-hour postprandial C peptide (2 hCP), glycosylated hemoglobin (HbA1c) were compared between two groups.


Results
The age of disease onset in insulin-treatment group was significantly lower than that in oral-medication group (t=2.049, P=0.045). The proportion of patients complicated with other autoimmune diseases in oral-medication group were higher than that in insulin-treatment group [24%(8/34) vs. 47%(17/36), χ2=4.275, P=0.039]. The FCP and 2 hCP in insulin-treatment group were significantly higher than those in oral-medication group [FCP: 0.25(0.00-0.80) vs. 0.00(0.00-0.60) μg/L, Z=3.498, P=0.030, 2 hCP: 0.42(0.02-1.20) vs. 0.14(0.02-0.19) μg/L, Z=3.235, P=0.001] on 6 month after treatment; however, there were no significant differences on 6-12 months, 13-36 months or 37-60 months after treatment between two groups. No antibody negative conversion was detected in 10 inpatients, who were reexamined with glutamic acid decarboxylase antibody (GADA) more than twice. The detection rate of diabetes retinopathy was 4%(1/26) in insulin-treatment group and 28%(8/29) in oral-medication group (χ2=6.179, P=0.013).


Conclusion
Initiating insulin therapy at first diagnosis of LADA can protect the residual islet function, and may reduce the rate of diabetic retinopathy.


Key words: 
Diabetes mellitus, autoimmune, adults; Insulin; Antibodies, antiglutamate decarboxylase; Diabetes complications
Impact of olaparib vs physician’s choice of new hormonal agent (pcNHA) on burden of pain in metastatic castration-resistant prostate cancer (mCRPC): PROfound.
Authors: Fred Saad, Guilhem Roubaud, Giuseppe Procopio, Neal D. Shore, Karim Fizazi, Antoine Thiery-Vuillemin, Gabriel dos Anjos, Gwenaelle Gravis, Jae Young Joung, Nobuaki Matsubara, Daniel Castellano, Maha H. A. Hussain, Arnold Degboe, Christopher Gresty, Jinyu Kang, Joseph E Burgents, Johann S. De Bono
Journal: Journal of Clinical Oncology (2020)

5538 Background: In the Phase III PROfound study (NCT02987543) olaparib significantly improved radiographic progression-free survival (primary endpoint) vs pcNHA (enzalutamide or abiraterone) in patients (pts) with mCRPC and homologous recombination repair (HRR) gene alterations. In pts with alterations in BRCA1, BRCA2 and/or ATM (cohort A), time to pain progression was also significantly improved by olaparib vs pcNHA. We report additional pain analyses evaluated in the overall study population (cohort A and B). Methods: Pts were randomized to olaparib tablets (300 mg bid; n=256) or pcNHA (n=131). Pts completed the Brief Pain Inventory-Short Form (BPI–SF) questionnaire (electronic administration) every 4 weeks up to 6 months after progression or treatment crossover. Responses were analysed to determine time to progression to worst pain, pain severity and first opiate use for cancer-related pain (Kaplan-Meier), and also pain interference in daily activity (mixed model for repeated measures). Results: 85% and 76% of olaparib pts were free of pain progression (worst pain item) compared with 75% and 51% in the pcNHA arm, respectively at 6 and 12 months. The proportion of pts without pain progression (overall pain severity) also favoured olaparib (Table). Median time to first opiate use was significantly prolonged in olaparib arm compared with pcNHA arm; 18 months for olaparib vs 9 months for pcNHA (Table). BPI-SF pain interference scores were also more favourable for olaparib than pcNHA; difference in overall adjusted mean change from baseline score −0.75 (95% CI: −1.14, −0.36) P=0.0002. Further pain burden results for cohort A will also be presented. Conclusions: Olaparib reduced the burden of pain and time to first opiate use in pts with mCRPC and HRR gene alterations vs pcNHA, demonstrating a clinical and symptomatic patient benefit. Clinical trial information: NCT02987543 . [Table: see text]
社区产后访视对促进母婴健康作用的调查
Authors: 彭淑梅, 曾静, 陈以荣
Journal: BMJ (2006)

为了解社区产后访视对母婴健康的影响,于产后42d对访视组(90例)和非访视组(95例)的产妇进行产褥期卫生、母乳喂养、脐部护理、预防接种等知识获知程度、母婴患病情况、母乳喂养率的调查,并对其出生后42d的婴儿进行身高和体重测量.结果表明,访视组纯母乳喂养率为86.7%,非访视组纯母乳喂养率为62.1%;访视组产妇对相关健康知识的知晓率高于非访视组;访视组产妇及婴儿的患病率明显低于非访视组;访视组42 d婴儿的身高、体重均显著超过非访视组。
A phase I/II clinical trial of autologous CMV-specific T cells in glioblastoma (GBM) patients to reveal a lack of immune effector function.
Authors: Shiao-Pei S. Weathers, Marta Penas-Prado, Pinaki Prosad Banerjee, Mustafa Bdiwi, Hila Shaim, Abdullah Alsuliman, Mayra Shanley, James Long, John Frederick De Groot, Barbara Jane O'Brien, Nazanin Majd, Rebecca A. Harrison, Carlos Kamiya-Matsuoka, Gregory N. Fuller, Linda Chi, Ganesh Rao, Frederick F. Lang, Elizabeth J. Shpall, Katayoun Rezvani, Amy B. Heimberger
Journal: Journal of Clinical Oncology (2020)

2515 Background: Cytomegalovirus (CMV) antigens are present in &gt; 90% of GBMs but not in normal brain making it an attractive immunological target. Methods: Highly functional autologous polyclonal CMV pp65 specific T cells were expanded under GMP-compliant conditions from GBM patients and administered after 3 weeks of lymphodepleting dose-dense temozolomide (ddTMZ, 100 mg/m 2 ). The phase I component used a 3+3 design ascending through four dose levels (5 x 10 6 cells to 1 x 10 8 cells). Treatment was repeated every 6 weeks for a total of 4 cycles. Dose expansion was conducted in recurrent GBM patients undergoing resection and in newly diagnosed GBM patients following concurrent chemoradiation. In vivo persistence and effector function of the adoptively transferred CMV-specific T cells was determined by dextramer staining and multiparameter flow cytometry in serially-sampled peripheral blood and in the tumor microenvironment. Results: 65 patients were screened, 25 underwent leukapheresis, and 20 completed at least 1 cycle. Median age 48 (27-69), 35% were MGMT methylated, and 10% were IDH mutated. No dose limiting toxicities (DLTs) observed. Complete radiographic response was observed in 1 patient, partial responses in 2, stable disease in 9, and progressive disease in 8. The median PFS time was 1.3 months (95% CI: 0-8.3 months) and the median OS time was 12 months (95% CI: 6 months to not reached). Repeated infusions of CMV-TC were associated with significant increase in circulating CMV+ CD8+ T cells, but cytokine production reflective of effector activity (CD107a, TNFα, IFNγ, IL2) was suppressed in these cells including directly from the GBM microenvironment. Conclusions: Adoptive infusion of CMV-specific T cells after lymphodepleting ddTMZ was well-tolerated. However, effector function of the adoptively transferred T cells was attenuated indicating further modulation of the T cell is required to prevent its dysfunction prior to proceeding to large scale clinical studies. Clinical trial information: NCT02661282 .