tbuckley/cabot-search huggingface dataset:
Phase II trial of bicalutamide in combination with palbociclib for the treatment of androgen receptor (+) metastatic breast cancer.
Authors: Ayca Gucalp, Leigh Ann Boyle, Tina Alano, Artavazd Arumov, Mrinal M. Gounder, Sujata Patil, Kimberly Feigin, Marcia Edelweiss, Gabriella D'Andrea, Jacqueline Bromberg, Shari Beth Goldfarb, Louise Ligresti, Serena Tsan-Lai Wong, Tiffany A. Traina
Journal: Journal of Clinical Oncology (2020)

1017 Background: Genome-wide transcriptional analysis has identified a unique subset of androgen receptor (AR) +, estrogen receptor (ER)/progesterone receptor (PR)- breast cancer (BC). The functional role of AR was confirmed initially in preclinical models demonstrating that androgen-driven growth could be abrogated by antiandrogen therapy. TBCRC011 established the safety and efficacy of inhibiting AR with bicalutamide (B) in patients (pts) with AR+/ER/PR- metastatic BC (MBC) with a median progression free survival (PFS) of 12 weeks (wks) (95% CI, 11–22 wks). In preclinical data, palbociclib (P) has been shown to reduce growth of AR+/ER/PR- MDA-MB-453 BC cells. It has been shown that AR+ triple negative BC (TNBC) expresses a luminal profile and has intact Rb protein, the target of P activity. We conducted this Phase I/II trial of the AR inhibitor B in combination with the CDK4/6 inhibitor P in pts with AR+/ER/PR/HER2- BC (NCT02605486) to test the hypothesis that androgen blockade, paired with CDK4/6 inhibition would have increased efficacy in pts with androgen-dependent BC. Methods: Postmenopausal pts with AR+ TN MBC defined as IHC ≥ 1% nuclear staining (DAKO, Clone AR441 (5/2016-11/2016) then Ventana AR SP107 (11/2016-6/2018), ECOG ≤2, measurable/non-measurable disease were eligible for enrollment. Any number of prior regimens was permitted. Pts received B 150 mg daily and P 125 mg daily 3 wks on 1 wk off. Pts were evaluated for toxicity every 2-4 wks and for response every 8-12 wks. Primary endpoint: 6 month (mo) PFS. Secondary endpoints: clinical benefit rate, toxicity, correlative studies to better characterize AR+ TNBC. A Simon 2-stage minimax design that discriminates between 6 mo PFS rates of 20% and 40% was used. If ≥ 11/33 pts were PF at 6 mo then B+P would warrant further study. Results: As of 1.1.20 33 pts were enrolled on study with median (med) age 67 (42-79), performance status 0 (0-1). Number of pts with visceral metastases: 20, measurable disease: 22. AR% 1-9: 3, 10-50: 6; 51-100: 24. Med prior lines for MBC: 3 (0-9). Best response: (31 evaluable pts): 11 pts PF at 6mo: 10 SD &gt; 6mo, 1 PR. Med wks on study: 14 (2-101). Toxicity &gt; 10% grade &gt;3 related: Number of pts with leukopenia: 21, neutropenia: 21, lymphocytopenia: 6, thrombocytopenia: 3. One pt with febrile neutropenia. One death due to disease progression within 30 days off study. Conclusions: In this selected subset of pts with AR+ TN MBC, this study met its prespecified endpoint with 11 pts PF at 6 mo on B 150 mg + P 125 mg. B+P has been well tolerated with no unexpected toxicity observed. Clinical trial information: NCT02605486 .
Evidence for Limited Early Spread of COVID-19 Within the United States, January–February 2020
Authors: Michelle A. Jorden, Sarah L. Rudman, Elsa Villarino, Stacey Hoferka, Megan T. Patel, Kelley Bemis, Cristal R. Simmons, Megan Jespersen, Jenna Iberg Johnson, Elizabeth Mytty, Katherine D. Arends, Justin J. Henderson, Robert W. Mathes, Charlene X. Weng, Jeffrey Duchin, Jennifer Lenahan, Natasha Close, Trevor Bedford, Michael Boeckh, Helen Y. Chu, Janet A. Englund, Michael Famulare, Deborah A. Nickerson, Mark J. Rieder, Jay Shendure, Lea M. Starita, Gregory L. Armstrong, Jay C. Butler, Michael A. Coletta, Aaron Kite-Powell, Julu Bhatnagar, Sarah Reagan-Steiner, Suxiang Tong, Brendan Flannery, Jill M. Ferdinands, Jessie R. Chung
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

From January 21 through February 23, 2020, public health agencies detected 14 U.S. cases of coronavirus disease 2019 (COVID-19), all related to travel from China (1,2). The first nontravel-related U.S. case was confirmed on February 26 in a California resident who had become ill on February 13 (3). Two days later, on February 28, a second nontravel-related case was confirmed in the state of Washington (4,5). Examination of four lines of evidence provides insight into the timing of introduction and early transmission of SARS-CoV-2, the virus that causes COVID-19, into the United States before the detection of these two cases. First, syndromic surveillance based on emergency department records from counties affected early by the pandemic did not show an increase in visits for COVID-19-like illness before February 28. Second, retrospective SARS-CoV-2 testing of approximately 11,000 respiratory specimens from several U.S. locations beginning January 1 identified no positive results before February 20. Third, analysis of viral RNA sequences from early cases suggested that a single lineage of virus imported directly or indirectly from China began circulating in the United States between January 18 and February 9, followed by several SARS-CoV-2 importations from Europe. Finally, the occurrence of three cases, one in a California resident who died on February 6, a second in another resident of the same county who died February 17, and a third in an unidentified passenger or crew member aboard a Pacific cruise ship that left San Francisco on February 11, confirms cryptic circulation of the virus by early February. These data indicate that sustained, community transmission had begun before detection of the first two nontravel-related U.S. cases, likely resulting from the importation of a single lineage of virus from China in late January or early February, followed by several importations from Europe. The widespread emergence of COVID-19 throughout the United States after February highlights the importance of robust public health systems to respond rapidly to emerging infectious threats.
Retrospective analysis of an alternative immuno-score in clinical management of patients with pT2 urothelial carcinoma.
Authors: Piergiuseppe Colombo, Paolo Andrea Zucali, Camilla De Carlo, Laura Giordano, Rodolfo Hurle, Massimo Lazzeri, Grazia Maria Elefante, Federica D'Antonio, Federica Regis, Giorgio Ferruccio Guazzoni, Armando Santoro, Massimo Roncalli
Journal: Journal of Clinical Oncology (2020)

e17038 Background: Within the mapping of the genome through the TCGA collaborative project, the urothelial carcinoma (UC) has recently revealed major intrinsic molecular subtypes, Basal, Luminal and Neural muscle-invasive UC. Here we propose a fast and standardized immuno-phenotypical score classification (Piescore), as a surrogate, which may discriminate Luminal, Basal or Neural UC and may correlate with histological and clinical variables in a mono-institutional cohort of patients treated with trans-urethral resection (TURB) and radical cystectomy (RC). Methods: This is a retrospective study of TURB specimens that harbored foci of HG pT2 (MIBC) UC from 116 pts who underwent RC. All the samples were assessed for immunohistochemical pattern, using relevant gene-expression-based markers for Basal type (CD44, CK5/6) and Luminal type (CK20 and pPARg). Piescore, investigated in both superficial and muscle-invasive component of the tumors, divided Basal and Luminal UC-types when at least 3 of the 4 markers were consistent with a specific phenotype, Mixed if two luminal and two basal markers were present simultaneously, and Neural when all four markers were negative. Results: Overall in muscle-invasive component, Piescore identified Basal phenotypes in 49 pts (42,2%), Luminal in 38 pts (32,7%), and Mixed in 9 pts (7,8%). No expression was identified in 20 pts (17,2%): 7 cases with morphological neuroendocrine differentiation and 13 cases with classical urothelial histology, all consistent with Neural phenotype. In 26,7% of cases (31/116 pts) we observed an immuno-phenotypical switch from superficial to deep component: 16 of 31 (51,6%) switched to Basal, 10 (32,2%) switched to Neural, and 5 cases (16,2%) to Mixed phenotype. No cases switched to Luminal. No cases have lost Basal phenotype from superficial to deep component, with the exception of one (switched to Neural). No statistically significant differences in terms of staging, DFS, and OS were observed in the different phenotypes. The presence of phenotypical switch did not affect angioinvasion, staging, DFS, and OS compared to non-switched cases. Conclusions: Piescore immunophenotyping (CD44, CK5/6, CK20 and pPARg) could be a simple surrogate able to stratify UC-TURB patients between Luminal vs Basal type. To our knowledge, preliminary results using the Piescore identify for the first time a phenotypical switch (to basal, Mixed or Neural) between superficial and deeper side of the same tumor, although this phenomenon did not show any prognostic implication.
Prospective observational trial of low-dose skin electron therapy in mycosis fungoides using rotational technique.
Authors: Neil Newman, Austin Noah Kirschner, Chirayu Patel
Journal: Journal of Clinical Oncology (2020)

e22077 Background: Low dose total skin electron therapy (TSET) utilizing 12 Gy in 12 fractions has been shown to provide a durable treatment response for dermal lesions caused by mycosis fungoides secondary to cutaneous T cell lymphoma (CTCL). We sought to prospectively assess the durability of response and quality of life (QOL) for patients receiving low dose TSET using the rotational technique technique. Methods: We prospectively enrolled patients with CTCL on an IRB approved study from 2016 to 2019 who had pathologically confirmed CTCL from stage IB-III. Patients completed a baseline validated Skindex-29 survey encompassing 29 questions assessing QOL. Physicians graded the appearance of the skin using the modified severity-weighted assessment tool (mSWAT) at baseline. Patients received 12 Gy in 12 Fractions on consecutive dates and patients were treated with a dual field rotational technique. The mSWAT was reassessed on ensuing follow-up visits along with the Skindex. The primary outcome was overall response rate with the secondary outcomes being time to treatment response, duration of clinical benefit (time to requiring an additional intervention), as well as improvements in Skindex questionnaire items. Results: We enrolled 20 patients and recorded an overall response rate (ORR) of 90% with four complete responses. The time to treatment response was 9.7 weeks. While the baseline mSWAT was 55.6 it declined to a median mSWAT of 2.2 at last follow-up (p &lt; 0.001) with there being a median decline of nearly 97% in the scores. The median duration of clinical benefit was 15.7 months. There was a precipitous decline in the Skindex total score and every subdomain when comparing each follow-up visit (p = 0.004) with post-hoc analysis demonstrating the decline between the baseline visit and first follow-up as the primary driver of the decline (p &lt; 0.0001). Conclusions: This prospective study demonstrates the subjective and objective clinical benefits of utilizing low dose TSE with a dual beam rotational technique. This control rates and QOL will continue to be observed for ongoing feasibility as a treatment modality.
阻塞性睡眠呼吸暂停低通气综合征者血清M2-乙酰胆碱能受体自身抗体水平的初步研究
Authors: 陈娟, 丁可, 叶静, 陆玫, 刘淼冰, 张麟
Journal: BMJ (2008)

近年来研究发现,心力衰竭(心衰)患者血清中的抗心脏M2-乙酰胆碱能受体的自身抗体参与了心衰的发生和发展[1-3],本研究是要了解阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者血清中是否存在M2-乙酰胆碱能受体的自身抗体以及抗体的分布情况,旨在探讨该抗体在OSAHS发生、发展中可能的病理生理作用。
由病例分析看多发性肌炎和皮肌炎的诊断和治疗
Authors: 孙凌云
Journal: BMJ (2006)

多发性肌炎(polymyositis, PM)和皮肌炎(dermatomyositis, DM)是以横纹肌炎症为主的自身免疫病,以对称性四肢近端肌无力和进行性肌萎缩为特征,也可累及呼吸肌、腰肌、吞咽肌等,其他多个系统器官可受到侵犯,伴有皮疹的PM称为DM.PM和DM患者肿瘤发生率高于一般人群。
Interventions of pregnancies with borderline gestational glucose intolerance: a randomized controlled trial
Authors: Zheng Hu, Hao-ping Zhu, Jun Xu
Journal: BMJ (2013)

Objective
To explore the effectiveness of dietary treatment in reducing macrosomia risks for pregnancies with borderline gestational glucose intolerance (BGGI).


Methods
From July 2009 to June 2011, a total of 1046 pregnant women with BGGI were randomized into group A (intervention, n=525) and group B (non-intervention, n=521). Another 521 pregnancies with normal glucose screening were assigned into group C (normal control). Randomization was applied following stratification according to age, body mass index (BMI), prior Cesarean section (C-section) and multiparity, etc. Women in group A underwent the examinations of fasting plasma glucose (FPG), 2 h-post prandial glucose and HbA1c once every 2 weeks. Their newborn outcomes were collected for analysis.


Results
Women of three groups were similar in age, parity, initial BMI and initial FPG. Dietary treatment for group A improved glucose-related indices and women's pregnancy weight gain (P<0.01). Also, in comparison with group B, the intervention of group A reduced risk of macrosomia (9.14% vs. 13.82%, P=0.02), prior C-section rate (43.87% vs. 56.07%, P<0.01) and postpartum hemorrhage (3.81% vs. 7.10%, P=0.02). However these indices were no better than group C. Dietary treatment did not increase the risk of fetal growth restriction, neonatal hypoglycemia and hyperbilirubinemia.


Conclusion
As a simple noninvasive therapeutic measure for improved glucose tolerance, BGGI may reduce the risk of risk of macrosomia and prior C-section rate.


Key words: 
Diabetes, gestational; Fetal, macrosomia; Pregnancy outcome; Randomized controlled trials
Distance from a comprehensive cancer center: A poor proxy for serous endometrial cancer outcomes?
Authors: Patrick Blackburn, Jennifer Gordon, Naixin Zhang, Laura Becca Daily, Todd D. Tillmanns
Journal: Journal of Clinical Oncology (2020)

e19084 Background: To compare the relationship between outcomes in serous endometrial cancer patients based on distance from a tertiary referral center in the Southern US. Methods: A retrospective cohort study among all women diagnosed with serous endometrial cancer between 2009 to 2018 was completed at a tertiary referral center in a low socioeconomic Southern US city with a predominately African American population. The primary exposure variable was the distance traveled by the patient to the treatment center. This distance was calculated using Google Maps from the patients’ home addresses to the cancer center. Abstracted data from each patient included patient demographics of home address, BMI at time of first visit, race, transportation method to the cancer center, and presence of primary care provider (PCP). Clinical variables of stage at diagnosis and pathology, treatment, and outcomes were included. Chi square analysis and log-rank analysis were completed. Data was analyzed by SPSS software. Results: In total, 202 patients were living a median distance of 31.4miles (range of 0.9mi to 194mi) from the cancer center. Of this cohort, the median age at time of diagnosis was 67 years old with a median BMI of 31.4kg/m 2 . The most common stage at diagnosis was stage 1A (26.7%). Using log rank analysis, there was no difference in overall survival when compared based on age, race, BMI and access to transportation. 92% (n=185) of the cohort had immediate access to a transportation method via personal car or family car, the remaining patients relied on other methods of transport. The total distance from treatment center was significant when compared with stage at diagnosis (p=0.011) portending greater stage at diagnosis with further distance. However, this did not correlate to progression free or overall survival (p = 0.83) in the cohort. Patients with a PCP were likely to be diagnosed at an earlier stage (Stage IA or Stage IB) compared to those without a PCP with a p=0.003, mean of 0.93, 95% CI (0.89 – 0.97). Conclusions: Living closer to a cancer center and having a PCP were associated with earlier stage at diagnosis in patients with serous endometrial cancer. Distance from the cancer center did not affect overall survival when adequate transportation methods were available.
马兜铃酸肾病66例临床分析
Authors: 孙勇, 赵红
Journal: BMJ (2008)

含马兜铃酸的中草药引发急性、慢性肾损害的临床报道已较多.现总结2001年1月至2007年6月在本科住院的66例马兜铃酸肾病患者的资料,对其成因、临床表现及可能的预防性措施进行了归纳。
Compatibility of topical agents with tumor treating fields (TTFields) for treatment of associated skin events in glioblastoma (GBM).
Authors: Moshe Giladi, Mario E. Lacouture, Uri Weinberg, Zeev Bomzon, Yoram Palti
Journal: Journal of Clinical Oncology (2020)

e24126 Background: TTFields are low intensity, intermediate frequency, alternating electric fields applied continuously using 2 pairs of skin-affixed transducer arrays. TTFields are FDA-approved in GBM and mesothelioma. The most common TTFields-related adverse event (AE) is mild-to-moderate dermatitis (beneath arrays), via long-term irritant exposure and local hyperhidrosis and occlusion exacerbation. Skin reaction mitigation strategies may improve quality-of-life (QoL) and ensure usage, as maximal survival benefits have been correlated with duration of use. Not all skin care products are TTFields compatible and may increase electrical impedance and lead to beneath array temperature increases. The aim of this in vivo study was to investigate the effects of 62 commercially available skin care products on electrical impedance during TTFields treatment. Methods: TTFields (200 kHz; optimal GBM frequency) were applied to rats using transducer arrays made of the same ceramic disks and hydrogels used in patients with GBM. To test electrical impedance effects, skin care products were applied to the skin immediately before array placement. The change in impedance relative to naïve skin was measured using the Optune device. Sixty-two commercially available products from 8 groups (adhesive removers, antibiotics, antiperspirants, antiseptics, cleansers, moisturizers, skin barriers, and topical corticosteroids) were evaluated. Results: Most lotions, soaps, foams, and solutions had minimal effect on electrical impedance, while petrolatum-based ointments significantly increased electrical impedance. Conclusions: TTFields compatible skin care products that did not affect electrical impedance were identified from each of the 8 groups and could be considered for further evaluation. All petrolatum-based ointments that were tested led to an increase in electrical impedance and are thus not recommended. Local application of TTFields compatible skin care products should be prospectively investigated in the clinical setting for their potential role in minimizing TTFields–related skin AEs. The randomized, double-blind PROTECT (PROphylactic skin Toxicity thErapy with Clindamycin and triamcinolone in GBM patients Treated with TTFields) study, should help establish which products best reduce skin AEs in patients with GBM and assess impact on QoL.
Multi-analyte liquid biopsies based treatment in advanced refractory cancers.
Authors: Sewanti Limaye, Darshana Patil, Dadasaheb B Akolkar, Timothy Crook, Anantbhushan Ranade, Amit Bhatt, Vineet Datta, Stefan Schuster, Cynthe Sims, Navin Srivastava, Pradip Fulmali, Pradip Devhare, Sanket Patil, Sachin Apurwa, Ajay Srinivasan, Rajan Datar
Journal: Journal of Clinical Oncology (2020)

e15623 Background: Tumor tissue profiling following invasive biopsies is presently the standard approach for indication-based therapy management in solid organ cancers. However, challenges in biopsy are traditionally described due to proximity to vital organs, or patients’ co-morbidities or unwillingness for an invasive procedure. Liquid biopsies for evaluation of cancers are also largely restricted to single gene testing for selection of targeted therapy agents. We developed a comprehensive liquid biopsy based multi-analyte (molecular and functional) investigation of the cancer (eLBx: Encyclopedic Liquid Biopsy) for selection and management of individualised treatments in a cohort of advanced refractory cancers. Methods: We obtained 20 mL blood from 65 patients with solid organ cancers where the disease had progressed following failure of at least two lines of systemic therapies and where biopsy to obtain tumor tissue for molecular profiling of tumor was unviable. Cell free tumor DNA (ctDNA) was interrogated for mutations, while exosomal mRNA was profiled for gene expression. Viable circulating tumor associated cells (C-TACs) were tested in vitro for chemoresistance and used to determine expression of cell surface signalling receptors by immunocytochemistry (ICC). The findings were integrated to generate patient-specific treatment regimens. In patients who received treatment, response was determined radiologically. Results: Fifty-one patients received eLBx-guided personalized treatments with combinations of cytotoxic, targeted and endocrine agents. No two patients received the same treatment regimen. Forty-three patients were evaluable for treatment response per protocol among whom Partial Response (PR) was observed in 14 patients yielding an Objective Response Rate (ORR) of 32.6%. Additionally, 23 patients showed Stable Disease thus yielding an overall Disease Control rate of 86.1%. Median Progression Free Survival (PFS) was 108 days. There were no Grade IV therapy related Adverse Events or therapy related deaths. Conclusions: The ability to make informed treatment choices from a convenient blood draw implies a reduced dependence on invasive biopsies for disease management. We demonstrate successful management of advanced refractory solid tumor malignancies using an integrational non-invasive multi-analyte liquid biopsy approach. Clinical trial information: CTRI/2019/02/017548.
Evaluation on internal service quality, employee satisfaction and behavior of the community health service in Beijing
Authors: Yue-song Pan, Qi Chen, Jun-li Wang, Na Wang, Wan-nian Liang
Journal: BMJ (2009)

All 220 employees from 97 community health services in Beijing were surveyed as to evaluating the internal service quality, employee satisfaction and work behavior.Both in internal service quality and employee satisfaction degrees, the community health service employees had a low scores as comparing with their salaries, benefits and workloads.And 28.2% employees had once the idea of resigning.

Key words: 
Community health services;  Questionnaires