tbuckley/cabot-search huggingface dataset:
Weekly selinexor, bortezomib, and dexamethasone (SVd) versus twice weekly bortezomib and dexamethasone (Vd) in patients with multiple myeloma (MM) after one to three prior therapies: Initial results of the phase III BOSTON study.
Authors: Meletios A. Dimopoulos, Sosana Delimpasi, Maryana Simonova, Ivan Spicka, Ludek Pour, Iryna Kryachok, Maria Gavriatopoulou, Halyna Pylypenko, Holger W Auner, Xavier Leleu, Vadim Doronin, Polina Kaplan, Roman Hajek, Benjamin Reuben, Tuphan Kanti Dolai, Dinesh Kumar Sinha, Melina Arazy, Paul G. Richardson, Nizar J. Bahlis, Sebastian Grosicki
Journal: Journal of Clinical Oncology (2020)

8501 Background: Selinexor is an oral, selective inhibitor of XPO1-mediated nuclear export, leading to the reactivation of tumor suppressor proteins. In a phase 1b/2 study, the combination of once weekly (QW) selinexor with bortezomib and dexamethasone (SVd) was well tolerated with anti-MM activity in patients (pts) with PI-sensitive and PI-refractory disease. While twice weekly (BIW) bortezomib in combination therapy is efficacious, prolonged use is limited due to peripheral neuropathy (PN, 50-60%). The BOSTON study was designed to determine if SVd improves progression free survival (PFS), overall response rates (ORR) and reduces the rate of PN vs Vd. Methods: BOSTON is a global, phase 3, randomized study of QW SVd vs BIW Vd after 1-3 prior anti-MM regimens. The primary endpoint is PFS. Secondary endpoints include ORR, overall survival (OS) and PN (rates and EORTC QLQ-CIPN20 outcomes). Randomization is stratified by treatment with prior PI therapies, number of prior anti-MM regimens (1 vs &gt; 1), and Revised International Staging System (R-ISS; Stage III vs I or II). Following confirmation of progressive disease, pts on Vd could cross over to either: 1) SVd for pts able to tolerate continued bortezomib or 2) selinexor and dexamethasone for pts with bortezomib intolerance. Results:402 pts were enrolled; 195 and 207 to SVd and Vd, respectively. Median age was 67 (range: 38-90). Most (59.6%) pts were &gt; 65 years and 57.1% were male. R-ISS stage at the time of MM diagnosis was III for 18.5% of pts. Baseline characteristics were balanced across the 2 arms. SVd significantly prolonged PFS vs Vd (median 13.93 vs 9.46 months, HR = 0.70, P = 0.0066). SVd was associated with a significantly higher ORR (76.4% vs 62.3%, P = 0.0012). Median OS was not reached on SVd vs 25 months on Vd (P = 0.28). Most frequent treatment-related adverse events (grade ≥3) for SVd vs Vd were thrombocytopenia (35.9% vs 15.2%), fatigue (11.3% vs 0.5%) and nausea (7.7% vs 0%). Clinically important differences were reported on the motor, autonomic and sensory scales on CIPN20. PN rates (grade ≥2) were significantly lower with SVd vs Vd (21.0% vs 34.3%, P = 0.0013). Conclusions: BOSTON is the first phase 3 study to evaluate the clinical benefit of SVd for relapsed/refractory MM. The study met the primary endpoint: once weekly SVd significantly improved PFS and ORR compared to twice weekly Vd. Rates of PN were significantly reduced with numerically fewer deaths on SVd vs Vd. Full dataset will be presented at the meeting. Clinical trial information: NCT03110562 .
Analysis of exhaled breath of lung cancer patients using infrared spectroscopy.
Authors: Tony J. Reiman, Robert Thompson, Farah Naz, James Charles Roger Michael, Erik Scheme, Angkoon Phinyomark, Luisa Galvis, Trisha Daigle-Maloney, Amanda Caissie, Joseph Ojah, Maged Salem, Holly Anne Campbell, Erin Brooks, Stephen Graham, Chris Purves, Gisia Beydaghyan, Mahmoud Abdelsalam
Journal: Journal of Clinical Oncology (2020)

e21037 Background: Currently low-dose computed tomography is used for lung cancer (LC) screening, but is limited by radiation exposure, cost, and a high false detection rate (1,2). An accurate, accessible and affordable screening technology is needed to improve detection of LC in high risk individuals. Methods: We conducted an unblinded, prospective cohort study on the effectiveness of a novel technology utilizing infrared absorption measurements via cavity ringdown spectroscopy (IR-CRDS) to differentiate the expired breath of treatment-naïve LC patients from controls without known cancer. Breath samples were taken from 100 LC patients and 98 control subjects but, only 62 non-small cell lung cancer (NSCLC) and 96 control samples were analyzed. Patients on treatment were eligible but, the protocol was amended to exclude these due to signal ambiguities. Samples were also excluded due to missing data, unclear histologic subtypes, or if they were classified as small cell LC samples to prevent obscuring the NSCLC signal. A piecewise cubic spline interpolation was used for the spectra with missing values (3). After first- and second-derivative spectra were computed to increase the information density, a one-dimensional local binary pattern extracted features from the spectra (4). Meaningful spectra-based features were selected using a minimum redundancy maximum relevance algorithm (5). Finally, a classification model was built using a support vector machine classifier (3). Results: The table below characterizes each cohort. The discriminant analysis differentiated between NSCLC and control cases with a cross validation accuracy of 86.1% (89.6% sensitivity and 80.7% specificity) using 20 selected spectra-based features. Conclusions: IR absorption measurements can be used to accurately discriminate between NSCLC and control participants. We continue to build our database to support more robust machine learning models. To our knowledge, this is the first time IR-CRDS has been used to differentiate between NSCLC and control cases. [Table: see text]
Establishment of a primary cell culture of bone metastasis from urothelial carcinoma.
Authors: Chiara Spadazzi, Claudia Cocchi, Roberto Casadei, Francesca Brandolini, Federica Pieri, Alberto Bongiovanni, Federica Recine, Chiara Liverani, Alessandro De Vita, Giacomo Miserocchi, Sebastiano Calpona, Silvia Angela Debonis, Toni Ibrahim, Laura Mercatali
Journal: Journal of Clinical Oncology (2020)

e17030 Background: Urothelial carcinoma (UC) accounts for 90% of cases of bladder cancer. In advanced UC diagnosis, skeletal involvement is frequent. Here we report the establishment of a primary culture of bone metastasis (BM) from High Grade UC derived from 81 years-old patient with a previous diagnosis of papillary urothelial cancer in 2016. After 2 years, patient relapsed to bone and visceral sites and because of poor clinical condition, patient underwent palliative best supportive care. Methods: Patient-derived bone metastatic cell culture was obtained from a surgical specimen. Tumor cells were isolated by collagenase digestion. Cells were seeded on in vitro 2D plates or into 3D collagen scaffolds composed of bovine collagen type I. The establishment of tumor cell isolation was confirmed through the evaluation of cytomorphologic features and positive pan-citokeratin staining. Then, drug treatments was performed and cell survival was evaluated. The study was approved by Ethical Committee and patient signed an informed consent. Results: After a long-term culture, we were able to isolate from a 3D scaffold a tumor clone that successfully growth until passage 20. Stabilized cells generate spheroid-like aggregates, recreating acinar-structures typical of the primary papillary urothelial tumor. Next, we treated cells with: Gemcitabine (Gem), Carboplatin (Carbo), Docetaxel, Carbo+Gem and Bone targeted drugs (Zoledronic Acid and Denosumab). The most effective treatment was Gem+Carbo, in particular 24% of survival in 2D platform and 87% on 3D collagen scaffold. For all treatments, cells cultured on 3D scaffold were more resistant to drugs, mimicking more closely the in-vivo condition. Conclusions: We were able to isolate and establish a BM primary culture from UC using a 3D in-vitro collagen scaffold. This system can recreate microenvironmental conditions more similar to in-vivo ones and it promoted the isolation of tumor cell clones from stromal components of the heterogeneous primary culture. This cell line could be useful to investigate the molecular and genetic profile in order to identify promising molecular targets and to better understard the natural history of BM from UC.
Summary and Recommendations
Journal: Diabetes Care (1980)

Gestational diabetes is defined as glucose intolerance recognized during pregnancy. Research is necessary to achieve more accurate diagnosis, precise definition of outcome criteria and assessment of their significance, correlation of outcomes with maternal variables, and more effective therapies to control glucose levels. Until such information is available, the following guidelines are proposed. All pregnant women should be screened for glucose intolerance between the 24th and 28th weeks of pregnancy. The diagnosis should be based on O'Sullivan's oral glucose tolerance procedure. Management should include high risk pregnancy surveillance and nutritional counseling. Some centers advocate insulin administration if dietary management does not consistently maintain the fasting plasma glucose below 105 mg/dl and the 2-h postprandial glucose below 120 mg/dl. However, the point at which insulin therapy should be instituted remains to be established. All agree that close control of plasma glucose is importance in reducing fetal and perinatal morbidity and mortality.
Identification of risk factors associated with pelvic lymph node metastasis in patients with stage IB1 cervical cancer.
Authors: Ping Jiang, Jing Cai, Xiaoqi He, Hongbo Wang, Weihong Dong, Yuan Zhang, Juergen Dunst, Kay C Willborn, Bangxing Huang, Zehua Wang
Journal: Journal of Clinical Oncology (2020)

e18005 Background: Evaluation the distribution of nodal metastases in the stage IB1 cervical cancer and the risk factors associated with pelvic lymph node metastasis (LNM) at each anatomic location. Methods: 728 patients with stage IB1 cervical cancer who underwent radical hysterectomies and systemic pelvic lymphadenectomies from January 2008 to December 2017 were retrospectively studied. All removed pelvic lymph nodes were pathologically examined, and the risk factors for LNM at the obturator, internal iliac, external iliac, and common iliac regions were evaluated by univariate and multivariate logistic regression analyses. Results: 20,134 lymph nodes were analysed with the average number of 27.80 (± SD 9.43) lymph nodes per patient. Nodal metastases were present in 266 (14.6%) patients. The obturator was the most common site for nodal metastasis (42.5%) followed by the internal iliac nodes (20.3%) and the external iliac nodes (19.9%), while the common iliac (9.8%) and parametrial (7.5%) nodes were the least likely to be involved. Tumor size more than 2 cm, histologically proven lymphovascular space involvement (LVSI) and parametrial invasion correlated independently significantly with the higher risk of the lymphatic metastasis. Obesity (BMI≥25) was independently significantly negatively correlated with the risk of lymphatic metastases. All the positive common iliac nodes were found in patients with tumors greater than 2 cm. The multivariate analysis showed that tumor size greater than 3 cm was associated with a 16.6-fold increase in the risk for common iliac LNM. Interestingly, tumor size was not an independent risk factor for pelvic LNM in the lower regions, i.e., the obturator, internal iliac and external iliac areas, where LVSI was the most significant predictor for LNM. In addition, parametrial invasion was related to external and internal iliac LNM; deep stromal invasion and age less than 50 years were associated with obturator LNM. Conclusions: The incidence of lymph node metastasis in patients with stage IB1 cervical cancer is low but prognostically relevant. The data offer the opportunity for tailored individual treatment in selected patients with small tumors and obesity.
Chtonic diseases and theMOS 36 item short from health survey score in community residents older than 60
Authors: Chun-hui Liu
Journal: BMJ (2008)

：This study was toinvestigate the relationship between chronic diseases and quality of life among communityresidents beyond 60.From September 2005 to November 2005,1731 residents aged 60-89 weresurveyed with a general information form and the the MOS 36 item short from health survey(SF-36).The results showed that the subjects with no chronic diseases seemed to havehigher scores,while SF-36 values dropped to some extent when the number of diseasesincreased.In comparison with diabetic or hypertensive subjects,those with heart diseasehad lower SF-36 scores for all items,except for general conditions and physicalcapability.
Clinical significance of U1-nuclear ribonucleoprotein antibodies in Chinese patients with systemic sclerosis
Authors: Meng-tao Li, Dong Xu, Yong Hou, Qian Wang, Zhao-jun Hu, Ning Song, Feng-chun Zhang, Yan Zhao, Xiao-feng Zeng
Journal: BMJ (2011)

Objective To investigate clinical relevance of U1-nuclear ribonucleoprotein antibody (anti-U1 RNP) in Chinese patients with systemic sclerosis (SSc). Methods In total, 131 Chinese patients with SSc were prospectively and consecutively recruited into Scleroderma Trials and Research Group sponsored by European League Against Rheumatism (EUSTAR) from clinical database of Peking Union Medical College Hospital ( PUMCH). Their clinical features, visceral lesions and laboratory findings including detection of anti- U1 RNP were recorded. Relevance between existing anti-U1 RNP and clinical characteristics and other laboratory indicators of SSc was analyzed statistically. Results Eighty-seven of the 131 patients presented as diffused SSc (dSSc) , 36 limited SSc ( lSSc) and eight SSc/systemic lupus erythematosus (SLE) overlap syndrome, with positive rate of anti-U, RNP of 28. 2 (37/131) percent in patients with SSc. Positive rate of anti-U1 RNP in dSSc was similar to that in lSSc groups [28. 7% (25/87) and 25. 0% ( 9/36 ) , respectively, P = 0. 673]. But significantly higher prevalence of pulmonary arterial hypertension and cardiac involvement, and less white blood cell and platelets counts were observed in the patients with positive anti-U1 RNP than in those with negative anti-U1 RNP (all P   0. 05 ) . Detection rate of anti-DNA topoisomerase I ( Scl-70 antibody) was higher in SSc patients with negative anti-U, RNP. Conclusions U1 RNP antibody is a common antibody in Chinese patients with SSc, and detection for it combined with other autoantibodies will be helpful for diagnosing of SSc and predicting development of pulmonary arterial hypertension, cardiac and hematological involvements in them.

Key words: 
Scleroderma, systemic;  Autoantibodies;  Diagnosis
肺部白色念珠菌感染40例分析
Authors: 王建英
Journal: BMJ (2004)

回顾2001年3月～2003年2月收治的肺部白色念珠菌感染40例. 1.临床资料:40例中男25例,女15例,年龄50～88岁,平均68岁,其中＞70岁24例(占60%).有基础疾病的38例(占95%);使用抗生素治疗的36例(占90%),大多为联合用药;低蛋白血症22例(占28%),全身使用糖皮质激素15例(占38%),放疗及应用细胞毒药物8例(占20%),鼻饲、胃肠减压6例(占15%).所有病例均有咳嗽、咳痰、气促,拉丝样痰3例(占8%);肺部均可闻湿啰音,半数有干鸣音;发热22例(占55%),口腔痛10例(占25%).X线表现形态不一,血象无特征改变.以连续3次痰液或深部支气管分泌物培养出白色念珠菌而确定诊断.
Airborne Spread of SARS-CoV-2 and a Potential Role for Air Disinfection
Authors: Edward A. Nardell, Ruvandhi R. Nathavitharana
Journal: JAMA (2020)

In the context of potential aerosol spread of SARS-CoV-2 infection, this Viewpoint argues for use of upper-room germicidal UV (GUV) fixtures as a means to disinfect circulating air and prevent spread of COVID-19 and other infections in health care settings.
Systematic analysis of chemotherapy agents for home-based administration.
Authors: George Xiangyun Ye, Adam Binder, Nathan Handley, Maria Piddoubny, Gloria Espinosa, Justine Chung, Judith Alberto
Journal: Journal of Clinical Oncology (2020)

e14012 Background: Improvement in supportive care medications, feasibility of outpatient management, and regulatory changes have led to a dramatic shift in the primary location of chemotherapy delivery from the inpatient setting to outpatient infusion centers. Over the last decade, centers in Europe and Canada have taken the next logical step – home based chemotherapy infusion. To our knowledge there is no systematic large scale initiative that has transitioned chemotherapy to the home in the United States. In order to implement a home based chemotherapy infusion program, we systematically scored anti-neoplastic agents for ease of administration. Methods: We reviewed all anti-neoplastic agents administered at our infusion center. Characteristics of each medication that could be a barrier to home infusion were identified. These included route and duration of administration, vesicant status, emetogenic potential, and duration of stability at room temperature. Scoring was determined by a multi-disciplinary team of pharmacists and oncologists (see Table). Higher scores indicated greater potential for home administration. Results: We reviewed 100 medications. The highest possible score was 8; the lowest possible score was -4. Agents ranged with scores from 8 (fulvestrant) to -1 (dactinomycin), with a median score of 4. The mode score was 3 (24 medications). The largest factor lowering the ease of administration score was stability at room temperature; score of -2 and -1 in 19 and 18 medications respectively. Conclusions: It is feasible to administer the majority of our chemotherapeutic agents in the home setting. The biggest barrier to administration at home is stability of medications at room temperature. This issue can be addressed by transporting and storing the medication in a refrigerated container. Expectedly, injectable drugs and medications with short infusion times that are stable at room temperature would be the easiest to administer in the home. Further analysis in ongoing to assess the financial feasibility and establishment of our home based program. [Table: see text]
Extrapolation of indications and drug interchangeability as barriers to use trastuzumab-dkst biosimilar in Brazil.
Authors: Heloisa Magda Resende, Paola Cardoso, Pedro Marassi, Maristela Seoanes Precivale, Alexandre Alcantara, Ana Carolina Cardoso, Lara Lopes Facó, Leandro Ladislau Alves, Vivienne Carduz Castilho
Journal: Journal of Clinical Oncology (2020)

e13010 Background: Brazil has a complex health-care system which comprises 76% of population in the public unified health system (SUS) and only 24% in private system. Even with most of the population in the public system low resources has been allocated SUS by the government compared with that in private system. Breast cancer (BC) is the more frequent malignant neoplasm in Brazilian women, including HER2 overexpression, and the most are treated in SUS. Although, the HER2 blockage benefits in overall survival have been demonstrated since 2005, the adjuvant and neoadjuvant HER2 blockage was included in SUS protocols only 2013 while the metastatic only 2018. Brazil and development countries have limited accesses to biological drugs and target therapies due to the high cost. The biosimilar technology would improve the patient access to these drugs, health-care savings with efficacy and safety. In 2017, Brazil has approved the first biosimilar in oncology, the anti-HER2 monoclonal antibody trastuzumab-dkst. Our aim is understanding the reasons that hampered the Brazilian oncologists changing practice about biosimilars. Methods: We submitted an on-line survey with 12 questions to 144 Brazilian oncologists which are registered in Brazilian Clinical Oncology Society from North, Northeast, Center east, Center west and Southeast regions in Brazil. The questions were about the anti-HER2 biosimilars knowledge, the manufacturing process, the costs, the biosimilars-based clinical trial, the drug efficacy and safety. Results: We observed that all responders have 9 years experienced oncologist with mean of care 15 patient with HER2 BC per month. In total, 95% of oncologist knows biosimilar definition and 96% assume prescribe biosimilars without doubts. However, 81% oncologists would prescribe biosimilars to all patients, 82% would interchanges and 63% would extrapolate the indication. Conclusions: This survey was conducted to understand the Brazilian oncologist knowledge about biosimilar. We demonstrated a high knowledge of biosimilar definition, however with high percentage indicated adherence barriers. The pharmacovigilance, clinical trials that support biosimilar approval and extrapolation concepts are the main aspects to be addressed. The opportunity of patient access with biosimilars is real and it is the oncologist’s duty to engage in medical education programs. This study could highlight a crucial need for greater strategies to educate physicians, to disseminate biosimilars and provide more informed decision making.
新生儿呼吸窘迫综合征防治进展
Authors: 郝小清, 武荣
Journal: BMJ (2012)

呼吸窘迫综合征是早产儿常见疾病,其处理措施涉及产前及产后多方面,包括产前的预防处理、产前和产后肺表面活性物质的应用、呼吸机的使用以及慢性肺损伤的防治等方面；治疗的目的也从最初的挽救患儿生命扩大到防治肺损伤、脑损伤等并发症,提高患儿的生存质量。
Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances
Authors: Wenzhang Wang, Fanpeng Zhao, Xiaopin Ma, George Perry, Xiongwei Zhu
Journal: Molecular Neurodegeneration (2020)

Abstract Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by impaired cognitive function due to progressive loss of neurons in the brain. Under the microscope, neuronal accumulation of abnormal tau proteins and amyloid plaques are two pathological hallmarks in affected brain regions. Although the detailed mechanism of the pathogenesis of AD is still elusive, a large body of evidence suggests that damaged mitochondria likely play fundamental roles in the pathogenesis of AD. It is believed that a healthy pool of mitochondria not only supports neuronal activity by providing enough energy supply and other related mitochondrial functions to neurons, but also guards neurons by minimizing mitochondrial related oxidative damage. In this regard, exploration of the multitude of mitochondrial mechanisms altered in the pathogenesis of AD constitutes novel promising therapeutic targets for the disease. In this review, we will summarize recent progress that underscores the essential role of mitochondria dysfunction in the pathogenesis of AD and discuss mechanisms underlying mitochondrial dysfunction with a focus on the loss of mitochondrial structural and functional integrity in AD including mitochondrial biogenesis and dynamics, axonal transport, ER-mitochondria interaction, mitophagy and mitochondrial proteostasis.