tbuckley/cabot-search huggingface dataset:
Relation between measurable residual disease and morphologic relapse in AML.
Authors: Lauren Shih, Megan Othus, Kelda Gardner, Carole Shaw, Anna B. Halpern, Pamela Sue Becker, Roland B. Walter, Elihu Estey, Mary-Elizabeth M. Percival
Journal: Journal of Clinical Oncology (2020)

7535 Background: Measurable residual disease (MRD) in AML portends a poor prognosis. The outcomes and treatments of MRD after an initial MRD negative complete remission (MRD- CR) are unclear. Methods: We retrospectively identified 432 patients ≥ 18 years of age treated for AML or high grade myeloid neoplasm (10-19% blasts in blood and/or marrow) at University of Washington/Seattle Cancer Care Alliance from 2008-2017 who achieved MRD- CR after initial treatment. Next disease recurrence was recorded, with patients either developing MRD ( &lt; 5% blasts via multiparameter flow cytometry; n = 44) or developing morphologic relapse (≥5% blasts; n = 100). The remaining patients remained in MRD- CR (n = 288, median follow up time 3.7 years). A landmark analysis at one year was performed to compare overall survival (OS). Results: Patients who developed MRD tended to be older (p = 0.009), but baseline characteristics were otherwise similar. Therapies for MRD included allogeneic transplant, low intensity chemotherapy, and high intensity chemotherapy; no significant associations were found between type MRD directed therapy and survival. Landmark OS at 1 year after MRD- CR was significantly different for patients without relapse at 1 year compared to those with MRD or morphologic relapse (median OS was 8.5 years for no relapse, 2.2 years for MRD, and 1.0 years for morphologic relapse). A multivariable Cox regression model among patients alive at 1 year showed patients without relapse had significantly improved OS compared to those with morphologic relapse [HR 0.18 (95% CI 0.1-0.31)]. Although there was a trend towards improved OS, we did not identify a significant difference between patients with MRD relapse compared to morphologic relapse [HR 0.54 (95% CI 0.27-1.11)]. There were no significant differences in patient characteristics for patients with MRD vs morphologic relapse matched by time of relapse (days 30-90, 90-150, 150-210). Conclusions: Following MRD- CR, development of either MRD or morphologic relapse were both associated with decreased OS. Notably, no significant differences in terms of survival were seen between patients who presented with MRD as opposed to morphologic relapse. No clear predictors were identified for MRD vs morphologic relapse. In this cohort, development of MRD carried a poor OS prognosis, similar to the prognosis of developing morphologic relapse. Future clinical trials should focus on MRD directed therapies, as no consensus exists about optimal treatment of MRD.
A pediatric and young adult phase I dose escalation study of BXQ-350 for solid and central nervous system tumors.
Authors: Mohamed Abdelbaki, Bhuvana Setty, Mariko Dawn DeWire, Timothy P. Cripe, Richard Curry
Journal: Journal of Clinical Oncology (2020)

2541 Background: BXQ-350 is a novel agent composed of the multifunctional, lysosomal activator protein Saposin C (SapC) and dioleoyl- phosphatidylserine (DOPS) and has demonstrated antitumor effects in both in vitro and in vivo preclinical models. Many tumors, including high-grade glioma and diffuse intrinsic pontine glioma (DIPG), and cells of tumor vasculature have aberrantly exposed phosphatidylserine (PS)-rich domains on the cell surface. BXQ-350 is an anti-tumor agent in development from Bexion Pharmaceuticals, Inc. that selectively targets tumor cell PS, particularly those translocated to the outer leaflet of the plasma membrane in tumor cells. BXQ-350 activates and participates in various cellular processes, including apoptosis and necrosis, and may also exhibit novel mechanisms leading to cell death that require further investigation. Methods: Nine refractory solid (2) and central nervous system (7) tumor patients (5F:4M, age 4-23 years of age) were enrolled in a 2-site dose escalation phase I first-in-pediatric trial ( NCT03967093 ) which completed in 2019. All patients received at least one dose of BXQ-350 which was administered as an intravenous infusion. Dosing began at 1.8 mg/kg and escalated to the highest planned dose level of 3.2mg/kg. Results: There were no BXQ-350-related serious adverse events, dose limiting toxicities, or withdrawals. The highest planned dose of 3.2 mg/kg was achieved safely but a maximum tolerated dose was not established. One osteosarcoma patient had progressive disease prior to completing cycle one of treatment and was removed from trial. Eight patients (DIPG-3, HGG-1, GBM-1, Pineoblasotoma-1, Ependymoma-1, Osteosarcoma-1) completed at least one cycle, with one DIPG patient completing cycle five. Conclusions: BXQ-350 was well tolerated with no significant dose-limiting toxicities at the highest planed dose level. A pediatric phase I trial in newly diagnosed patients is planned for 2 nd quarter 2020. Clinical trial information: NCT03967093 .
Application of percutaneous transthoracic automated biopsy instrument in diagnosis for pulmonary lesions
Authors: Zhen-shun Cheng, Jiong Yang, Yu-hui Lin, Yan-qing Ye, Shi-qing Zou, Yi-bing Yang, Wei-ming Liu, Kai-song Wu, Chun-xian Du, Qi-yong Xu
Journal: BMJ (2008)

Objective To study clinical application of Bard automated disposable instrument for percutaneous transtheracic biopsy guided by CT in diagnosis of pulmonary lesions. Methods Percutaneons transthoracic biopsy was performed with CT-guided Bard automated disposable instrument for 95 patients with pulmonary lesions but without established diagnosis by clinical and imaging procedures in order to obtain pathological diagnosis. Results Tissue specimens were obtained from all the 95 patients by Bard automated disposable instrument for percutaneous transthoracis biopsy, with a hundred percent of success. After the procedure, 68 of 95 were pathologically diagnosed as lung cancer (including adenocarcinoma in 44,squamous carcinoma in 19, alveolar cell carcinoma in three and small cell carcinoma in two), 10 as chronic inflammatory lesions, eight as tuberculosis, two as inflammatory pseudotumor, one as metastatic cancer, two as fungal infection, and four without an established diagnosis, with an overall diagnosis rate of 95.8%.Pneumothorax occurred in eight and mild haemoptysis in six of 95 patients, respectively, by the procedure.Conclusion Percutaneons transthoracic biopsy with Bard automated disposable instrument is an effective diagnostic procedure for patients with pulmonary lesions but their diagnoses were not established by routine examinations.

Key words: 
Biopsy, needle;  Lung diseases;  Biopsy
Utilization of basic public health service among hypertensive and diabetic patients in communities
Authors: Huijuan Zuo, Jinwen Wang, Xiaorong Chen, Jianglian Su, Lei Hou, Hai Xu, Jixiang Ma
Journal: BMJ (2018)

Objective
To survey the utilization of basic public health service among hypertensive and diabetic patients in communities.


Methods
A survey on the utilization of basic public health service was conducted between October 2014 and November 2014, 1 511 patients with hypertension and 1 508 patients with type 2 diabetes aged ≥35 years were randomly selected for the survey from 18 communities in 2 cities and 4 townships of Shandong and Jiangsu provinces in China.


Results
The survey showed that 87.0% (1 314/1 511) of hypertensive patients and 88.5% (1 334/1 508) of diabetic patients visited community health services within the year, and the blood pressure/blood glucose elevation were found in community health services in 68.5% (1 035/1 511) of the hypertensive patients and 53.3% (804/1 508) of the diabetic patients, respectively. The proportion of participants in community health education was higher in rural areas than that in urban areas [hypertension 73.2% (556/760) vs. 60.3% (453/751), χ2=48.48, P 0.05]. The control rates of hypertension and diabetes were 39.8% (602/1 511) and 39.6% (597/1 508), respectively. 82.5% (1 247/1 511) hypertensive patients and 75.6% (1 140/1 508) diabetic patients selected community clinics for treatment and disease management, and satisfaction rate with primary health care in community clinics were 82.1%(1 077/1 312) and 82.5% (1 101/1 334) respectively.


Conclusions
High percentage of community clinic choice and visit was found, and most of the patients got the recommendation about health life style. But difference existed between the practice of self-monitoring of blood pressure and fasting blood glucose and control of blood pressure and blood glucose and plan of chronic disease prevention and control.


Key words: 
Hypertension; Diabetes inellitus, type 2; Public health care; Disease management
Positive rate of HBsAg among high school graduates in 1998——2008 in Karamy areas Chin
Authors: Li-xia Gao, Yuan-kui Yang, Fu-gang Wang, Feng-lei Xu, Mulageer
Journal: BMJ (2009)

In 1998--2008 in Karamy, the HBsAg in serum in 32 569 cases was detected by ELISA.The total positive rate of HBsAg was 6.27%, with the males being higher than the females.The positive rate of Kazaks and Uyger was higher than the Han nationality.For 11 years in Karamy the positive rate of HBsAg was getting decreased year by year.

Key words: 
Hepatitis B surface antigens;  Retrospective studies
Clinical features of 1880 patients with AIDS
Authors: Shi-cheng Gao, Xi-en Gui, Tie-long Chen
Journal: BMJ (2010)

Clinical data of 1880 newly diagnosed and hospitalized AIDS cases in adults and adolescents were analyzed retrospectively. Most of them were infected by sexual transmission. Their most common symptoms at onset were fever, cough and weight loss, accounting for 91.4% ( 1719) , 72.2% (1357 ) and 64. 8% ( 1218) of the total cases, respectively. Their common opportunistic infections included oral candidiasis, pneumosystis jiroveci pneumonia (PCP) , recurrent bacterial pneumonia and tuberculosis,accounting for 52.4% (985), 33.4% (628), 28.4% (534) and 26. 3% (494) of the total cases, respectively. Therefore, for those with manifestations of compromised immune system, such as oral candidiasis, PCP, recurrent bacterial pneumonia or tuberculosis, serum HIV antibody should be tested timely.

Key words: 
Acquired immunodeficiency syndrome;  Disease attributes
Diagnosis and treatment of allergic bronchopulmonary aspergillosis: clinical features of eight cases and literature reviews
Authors: Song Liu
Journal: BMJ (2009)

Objective To study clinical features, diagnosis and treatment of allergic bronchopulmonary aspergillosis (ABPA) . Methods Clinical data and auxiliary examinations of eight patients with ABPA were analyzed, as well as relevant literatures were reviewed. Results All patients had symptom of cough, expectoration, out of breath and wheezing tale, seven of them with history of asthma, and all of them had increased peripheral blood eosinophil (EOS) count, serum levels of total immunoglobulin E (IgE) and lgE specific for Aspergillus fumigatus and showed positive prick test specific for Aspergillas fumigatus. Six of them showed infiltration shadows and six of them showed bronchiectasis in their chest CT images. Lung function test indicated obstructive ventilation dysfunction or mixed ventilation dysfunction with reversible airflow obstruction after administration of bronchodilator. Conclusions Diagnosis for ABPA should be made by integration of clinical features, increased blood eosinophil count and serum level of IgE, and result of prick test specific for Aspergillus fumigatus. Corticosteroid is a mainstay therapy for ABPA, ancillary with anti-fungi therapy. Patients with ABPA should be followed-up to prevent its recurrence. 

Key words: 
Aspergillosis fumigatus;  Hypersensitivity;  Asthma
Safety and activity of Combined AVElumab with Axitinib in unresectable or metastatic Thymomas B3 and Thymic carcinomas: The CAVEATT study.
Authors: Fabio Conforti, Laura Pala, Chiara Catania, Paolo Andrea Zucali, Paolo Della Vigna, Sara Pirola, Sara Stucchi, Elisabetta Pennacchioli, Paola Queirolo, Giuseppe Giaccone, Tommaso Martino De Pas
Journal: Journal of Clinical Oncology (2020)

e21114 Background: Patients (pts) with advanced B3 thymoma (B3T) and thymic carcinoma (TC) resistant to chemotherapy have limited treatment options. Treatment with Anti-PD1 showed not negligible toxicity and limited activity, and anti-VEGFR drugs obtained limited and short lasting antitumor responses. No data on combined anti-PD1/PD-L1 with antiangiogenic drugs are available in B3T/TC. We report preliminary results on safety and activity of avelumab combined with axitinib in this pts population. Methods: The CAVEATT is a single arm, multicentric, phase II trial in immunotherapy-naive pts with advanced B3T or TC, progressing after at least one line of platinum based chemotherapy. Prior therapy with antiangiogenic drugs is allowed. Pts received Avelumab 10 mg/kg iv every 2 weeks and Axitinib 5 mg twice a day until progression or toxicity. The primary objective of the study is overall response rate (ORR) by RECIST 1.1; secondary endpoints include ORR by irRC and ITMIG, and QoL by EORTC QLQ-C30. An interim futility analysis is planned after the enrollment of the first 18 patients. If at least 5 out of 18 patients will obtain a PR, the accrual will continue to reach the total number of 33 pts, according with a Simon’s minimax design. Tumor and blood samples are collected at baseline and whenever feasible at disease progression, to identify predictive biomarkers of response and mechanisms of resistance to treatment. Results: 1 pt with B3T and 12 with TC were enrolled from April 2019 to January 2020. Median age was 59 years (range 33-77). 8 pts received ≥2 previous line of therapies, and 6 pts were pretreated with an antiangiogenic drug. The median follow-up was 5.1 months. 10 pts were evaluable for response. The proportions of patients who achieved a partial response (PR) or a stable disease (SD) were respectively 40% (95% CI 17%–69%) and 60% (95% CI 30%–83%). The median PFS was 7.9 months (95% CI 2.5–NA) 12 pts were evaluable for toxicity. Treatment-related adverse events (AE) of grade 1 or 2 occurred in 7 (58%) pts, and the most common was diarrhea (3 pts). Grade ≥3 AEs occurred in 2 (17%) pts: 1 had G3 hyperthension and 1 G3 hand foot syndrome, both leading to axitinib drug reduction. No immune-related AEs (irAEs) were observed. No patient stopped treatment for toxicity, 5 pts stopped for progressive disease, and 8 pts are still on treatment. Conclusions: Preliminary results suggest promising antitumor activity and a good toxicity profile of the combination of axitinib and avelumab in pts with advanced B3T and TC. Accrual is ongoing to reach the target of 33 pts Clinical trial information: 2017-004048-38 .
New York City COVID-19 resident physician exposure during exponential phase of pandemic
Authors: Mark P. Breazzano, Junchao Shen, Aliaa H. Abdelhakim, Lora R. Dagi Glass, Jason D. Horowitz, Sharon X. Xie, C. Gustavo de Moraes, Alice Chen-Plotkin, Royce W.S. Chen
Journal: Journal of Clinical Investigation (2020)

BACKGROUNDFrom March 2, 2020, to April 12, 2020, New York City (NYC) experienced exponential growth of the COVID-19 pandemic due to novel coronavirus (SARS-CoV-2). Little is known regarding how physicians have been affected. We aimed to characterize the COVID-19 impact on NYC resident physicians.METHODSIRB-exempt and expedited cross-sectional analysis through survey to NYC residency program directors April 3-12, 2020, encompassing events from March 2, 2020, to April 12, 2020.RESULTSFrom an estimated 340 residency programs around NYC, recruitment yielded 91 responses, representing 24 specialties and 2306 residents. In 45.1% of programs, at least 1 resident with confirmed COVID-19 was reported. One hundred one resident physicians were confirmed COVID-19-positive, with an additional 163 residents presumed positive for COVID-19 based on symptoms but awaiting or unable to obtain testing. Two COVID-19-positive residents were hospitalized, with 1 in intensive care. Among specialties with more than 100 residents represented, negative binomial regression indicated that infection risk differed by specialty (P = 0.039). In 80% of programs, quarantining a resident was reported. Ninety of 91 programs reported reuse or extended mask use, and 43 programs reported that personal protective equipment (PPE) was suboptimal. Sixty-five programs (74.7%) redeployed residents elsewhere to support COVID-19 efforts.CONCLUSIONMany resident physicians around NYC have been affected by COVID-19 through direct infection, quarantine, or redeployment. Lack of access to testing and concern regarding suboptimal PPE are common among residency programs. Infection risk may differ by specialty.FUNDINGNational Eye Institute Core Grant P30EY019007; Research to Prevent Blindness Unrestricted Grant; Parker Family Chair; University of Pennsylvania.
Safety and activity of autologous T cells with enhanced NY-ESO-1–specific T-cell receptor (GSK3377794) in HLA-a*02<sup>+</sup> previously-treated and -untreated patients with advanced metastatic/unresectable synovial sarcoma: A master protocol study design (IGNYTE-ESO).
Authors: Sandra P. D'Angelo, Jean-Yves Blay, Warren Allen Chow, George D. Demetri, Fiona Thistlethwaite, Shiraj Sen, Albiruni Ryan Abdul Razak, John B. A. G. Haanen, Jonathan Christopher Noujaim, Melissa Lynne Johnson, Theodore Willis Laetsch, Victoria L. Chiou, Laura Pearce, Thomas H. Faitg, Ran Ji, Laura A. Johnson, Aiman M. Shalabi, Katherine Anne Thornton, Crystal Mackall, Brian Andrew Van Tine
Journal: Journal of Clinical Oncology (2020)

TPS11571 Background: T cells modified to target NY-ESO-1 have shown encouraging activity in HLA-A*02 + patients with NY-ESO-1–positive synovial sarcoma. NY-ESO-1 is a cancer/testis antigen that is expressed across multiple tumor types and highly expressed in synovial sarcoma. NY-ESO-1 TCR T (GSK3377794) are autologous polyclonal T cells transduced by a self-inactivating lentiviral vector to express an affinity-enhanced TCR able to recognize NY-ESO-1 epitope in complex with HLA-A*02. Ongoing trials are evaluating GSK3377794 in multiple solid tumors and multiple myeloma. Methods: This study (NCT03967223) uses a Master Protocol design that allows investigation of GSK3377794 in multiple tumor types under the same protocol in separate substudies. The first two are single-arm substudies in patients with advanced metastatic or unresectable synovial sarcoma: treatment-naïve (1 st line [1L], substudy 1; n = 10 planned) and progressing after anthracycline-based chemotherapy (2L+, substudy 2; n = 55 planned). Patients must be aged ≥10 years, have adequate organ function, ECOG performance status 0–1, measurable disease, and no central nervous system metastases. Excluded prior treatments include gene therapy with an integrating vector or NY-ESO-1–specific T cells, vaccine or targeting antibody, or allogeneic stem cell transplant. Patients will undergo leukapheresis and manufacture of GSK3377794; lymphodepletion then GSK3377794 infusion, followed by safety and disease assessments; and long-term follow-up for 15 years (under a separate protocol). The primary objective of substudy 2 is overall response rate per RECIST v1.1 by central independent review. Secondary objectives include time to response, duration of response, disease control rate, progression-free survival, overall survival, plus safety and tolerability. Exploratory objectives include assessment of the correlation of T-cell persistence with safety, clinical responses, and infused T-cell phenotype. Evaluation of quality of life and daily functioning of patients will also be assessed. Enrollment began in December 2019. These data are presented on behalf of the original authors with their permission. A similar presentation (P453) was presented at the SITC Annual Meeting, National Harbor, MD, USA, Nov 6–10, 2019. Funding: GlaxoSmithKline (208467) Clinical trial information: NCT03967223 .
NRG Oncology/Alliance LU005: A phase II/III randomized clinical trial of chemoradiation versus chemoradiation plus atezolizumab in limited stage small cell lung cancer.
Authors: Helen J. Ross, Chen Hu, Kristin Ann Higgins, Salma K. Jabbour, David E. Kozono, Taofeek Kunle Owonikoko, Benjamin Movsas, Timothy Solberg, Canhua Xiao, Terence Marques Williams, James William Welsh, Jeffry Simko, Xiaofei F. Wang, Nisha Anjali Mohindra, Charles Hsu, Tom Stinchcombe, Jeffrey Bradley
Journal: Journal of Clinical Oncology (2020)

TPS9082 Background: Limited stage small cell lung cancer (LS-SCLC) is treated with standard of care platinum/etoposide (EP) and thoracic radiation therapy (TRT) with curative intent, however the majority of patients are not cured and median overall survival is approximately 30 months. Addition of atezolizumab to chemotherapy in extensive stage SCLC has improved progression free and overall survival in a non-curative setting leading to hope that addition of an immune checkpoint inhibitor to standard chemoradiotherapy could benefit LS-SCLC patients. LU005 is a randomized phase II/III trial of standard concurrent chemoradiation with or without atezolizumab for patients with LS-SCLC. Methods: Patients are randomly assigned in a 1:1 ratio to standard EP chemotherapy with concurrent TRT (45 Gy BID or 66 Gy QD) with or without atezolizumab beginning concurrently with TRT, and continued every 3 weeks for up to 12 months. Eligible patients have LS-SCLC, PS 0-2, adequate organ function, no concerning comorbidities (including no active autoimmune disease) and are eligible for TRT. Patients are randomized prior to their second cycle of EP and thoracic radiation begins with the second overall cycle of chemotherapy (first cycle of study therapy) in both treatment arms. Prophylactic cranial radiation (PCI) is recommended for patients who respond to treatment. The phase II/III primary endpoints are progression free (PFS) and overall survival (OS) respectively. Secondary endpoints include objective response rates, local and distant disease control, and quality of life/patient reported outcomes assessment. Translational science component includes blood and tissue based immune related assays. This study activated in May 2019. 50 of 506 planned patients have been accrued as of 2/1/2020. Supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U23CA180803 (IROC) from the National Cancer Institute (NCI) and Genentech. *Authors Ross and Higgins are co-first authors and contributed equally to this work. Clinical trial information: NCT03811002.
Association between chronotropic incompetence and metabolic equivalents in type 2 diabetic mellitus patients complicated with metabolic syndrome
Authors: Min Gao, Wei Chen, Zun-ke Gong, Liang Han
Journal: BMJ (2013)

Objective
To investigate the association between chronotropic incompetence (CI) and motor ability in type 2 diabetic mellitus (T2DM) patients complicated with metabolic syndrome (MS).


Methods
One hundred and twenty patients with T2DM were enrolled in the study, including 66 cases with MS (MS group) and 54 without MS (non-MS group). The electrocardiographic exercise test was performed, the CI indexes including ratio of heart rate (rHR), heart rate reserve (HRR) were measured and the max metabolic equivalents (maxMETs) were calculated.


Result
The rHR (0.77±0.04 vs. 0.81±0.06, t=3.41, P<0.05), HRR (0.62±0.05 vs. 0.70±0.07, t=5.96, P<0.05) and maxMETs (8.8±1.1 vs. 9.7±1.2, t=0.16, P<0.05) in patients of MS group all lower than those in non-MS group. The maxMETs were positively correlated with rHR (r=0.81,P<0.05) and HRR (r=0.78,P<0.05).


Conclusion
The results indicate that CI as well as maxMETs and rating of perceived exertion can be used as monitoring index in type 2 diabetic patients complicated with metabolic syndrome.


Key words: 
Type 2 diabetes mellitus; Metabolic syndrome; Electrocardiographic exercise testing; Chronotropic incompetence; Metabolic equivalents