tbuckley/cabot-search huggingface dataset:
Phase I expansion study of XMT-1536, a novel NaPi2b-targeting antibody-drug conjugate (ADC): Preliminary efficacy, safety, and biomarker results in patients with previously treated metastatic ovarian cancer (OC) or non-small cell lung cancer (NSCLC).
Authors: Debra L. Richardson, Minal A. Barve, James Fredric Strauss, Susanna Varkey Ulahannan, Kathleen N. Moore, Erika Paige Hamilton, Melissa Lynne Johnson, Kyriakos P. Papadopoulos, Corrine Zarwan, Charles K Anderson, Joseph Buscema, Deborah Blythe Doroshow, William Jeffery Edenfield, Ursula A. Matulonis, Timothy F. Burns, Dirk Huebner, Valerie Malyvanh Jansen, Rebecca Mosher, Donna Jarlenski, Anthony W. Tolcher
Journal: Journal of Clinical Oncology (2020)

3549 Background: XMT-1536 is a first-in-class ADC targeting the sodium-dependent phosphate transport protein NaPi2b, broadly expressed in NSCLC and ovarian cancer. XMT-1536 utilizes the Dolaflexin platform to deliver 10-12 DolaLock auristatin payload molecules per antibody. In the dose-escalation portion of the Phase I study (NCT03319628), XMT-1536 showed clinical activity at doses &gt;20mg/m 2 with confirmed responses and prolonged stable disease in heavily pretreated OC and NSCLC patients, without preselection for NaPi2b expression. XMT-1536 was generally well-tolerated without the severe toxicities observed with other ADC platforms such as neutropenia, peripheral neuropathy, or ocular toxicity (Tolcher et al., ASCO 2019; Richardson et al., SGO 2020). Here, we report on the expansion (EXP) cohort, which included patients with fewer prior lines of therapy, in the ongoing Phase I study. Methods: Doses administered intravenously every 4 weeks (q4w) of 36 and 43 mg/m 2 were evaluated in two cohorts (1) high grade serous ovarian, fallopian tube, or primary peritoneal cancer (OC) with up to 4 prior lines of therapy and (2) NSCLC adenocarcinoma; prior treatment with a platinum-based therapy, immune checkpoint inhibitor, and TKI, if indicated. Archival tumor tissue and tissue from a new tumor biopsy were required for retrospective evaluation of NaPi2b expression. Results: As of 10 February 2020, 23 patients (19 OC and 4 NSCLC) were enrolled in the EXP cohort: 16 dosed at 36 mg/m 2 and 7 dosed at 43 mg/m 2 . Adverse events were generally similar to those previously reported, including transient AST elevation, fatigue, nausea, and pyrexia. Clinical responses and stable diseases have been observed. Efficacy data (objective response rate) and initial correlation of NaPi2b score with clinical response will be reported. Available data from all patients with data cutoff in May 2020 will be included. Conclusions: Overall, XMT-1536 treatment demonstrated clinical activity in high grade serous ovarian cancer and NSCLC adenocarcinoma and was generally well-tolerated with no new safety signal trends identified in the EXP. Clinical efficacy and the relevance of NaPi2b expression for treatment with XMT-1536 will be presented. Clinical trial information: NCT03319628 .
门诊患者院前抗生素的使用情况
Authors: 田明庆, 方剑, 黄秀清
Journal: BMJ (2005)

随机抽查衢州市人民医院2002年3月至2004年3月以来的1637例呼吸科门诊患者的资料,分析院前抗生素的使用情况.结果,38.3%的患者院前使用过抗生素,其中13.9%的患者使用过2种或2种以上的抗生素,且不规则使用抗生素的比例达79.0%.院前抗生素的使用以头孢类、青霉素类较多.说明院前抗生素滥用现象严重,需加强全社会的教育及采取相应措施杜绝滥用抗生素。
Liver-directed therapy (LDT) and systemic chemotherapy for pancreatic adenocarcinoma with liver metastases (PCLM): Experience of 12 years.
Authors: Shreya Prasad Goyal, Jyothi Jose, Craig R. Greben, Igor Lobko, Gregory Michael Grimaldi, Maged Ghaly, Kevin P Daly, Wasif M. Saif
Journal: Journal of Clinical Oncology (2020)

e16768 Background: PCLM has a poor prognosis with a median survival of ≤6 months. Treatment options are limited as only few patients can undergo curative surgery, therefore locoregional therapies such as LDT offer an adjunct to systemic therapies. Combination of LDT and systemic therapies is a strategy to enhance the effect of radioembolization or chemotherapy alone, akin to the use of radiotherapy with chemotherapy. The purpose of this retrospective study was to evaluate the efficacy of incorporating trans-arterial radioembolization (TARE) with 90Y, trans-arterial chemoembolization (TACE), and radiofrequency ablation (RFA) with systemic chemotherapy in the treatment of PCLM. Methods: We retrospectively evaluated 42 patients, with data available on 39 patients, with PCLM who underwent LDT between February 2007 and March 2019. Patient outcomes were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 including disease response, median overall survival (mOS) from the time of diagnosis of metastatic disease, and mOS following receipt of LDT. Treatment-related adverse events were assessed using Common Terminology Criteria for Adverse Events (CTACE), Version 5.0. Results: Of 39 patients, 56% underwent TARE, 36% RFA, and 7.8% TACE. The selection of modality was based on institutional standards and at the discretion of the referring physician. The mOS was 5 months (range 4-5.5 months) from the application of LDT and the one-year mOS was 7.8 months (6.5-9.5 months). Overall and liver specific disease response assessed with follow-up imaging (range 4-12 weeks post therapy) was complete response in 2.5%, partial response in 59%, stable disease in 21%, and progression of disease in 18% of patients. The mean interval between the diagnosis and initial LDT was 6 months. All patients received single course of TARE for each diseased liver lobe. In 26% of patients who had bilobar liver disease, the combination treatments for both diseased lobes was defined a single course. The mean Y90 radiation dose delivered to the right lobe was 1.00 GBq and to the left lobe was 0.64 Gbq. Grade 3 toxicities included abdominal pain in 13%, hyperbilirubinemia in 7.7%, fever in 7.7%, abscess in 2.6%, and thrombocytopenia in 5.1% of patients. No treatment-related grade 4 or 5 toxicities were seen. Conclusions: LDT can be safely combined with systemic chemotherapy for the treatment of PCLM. Patient outcomes following this treatment strategy are promising but prospective evaluations are needed to validate these preliminary findings.
Bevacizumab for the treatment of brain radionecrosis in cancer patients.
Authors: Luis E. Raez, Alina Khan, Ana Botero, Gelenis Calzadilla Domingo, Paola Izquierdo, Ignacio Castellon, Jameshia Below
Journal: Journal of Clinical Oncology (2020)

e19352 Background: Brain radionecrosis (BRN) occurs as a result of radiation therapy for brain tumors or metastatic brain lesions. BRN is characterized by an increase in permeability and disruption of the blood-brain barrier (BBB). There are currently no standard treatment options for BRN. While the mechanism of BRN is unknown, it is hypothesized that there is an inflammatory reaction of the local tissue to radiation which results in a continuous process involving endothelial cell dysfunction. This leads to tissue hypoxia and increased vascular endothelial growth factor (VEGF) which in turn causes capillary leakage, progressive BBB dysfunction, and cerebral edema. Bevacizumab (BEV), a humanized monoclonal antibody with action against VEGF, has recently been used in some studies for the treatment BRN. BEV essentially blocks VEGF from reaching its targets on the endothelium, thus making it an ideal treatment modality for BRN. Methods: The primary purpose of this study is to assess the effectiveness and safety of BEV for the treatment of BRN. Fifteen patients (pts), 14 diagnosed with lung cancer and one with breast cancer, that had BRN and treated with BEV between January 2014 and November 2019 were identified from Memorial Cancer Institute's database. A retrospective chart review analyzing pts's age, sex, BEV dose, dosing frequency, number of treatments received, medication-related adverse effects, and clinical benefit was conducted. Brain imaging pre-treatment and after four cycles of therapy were compared to assess the efficacy of BEV. Pts who exhibited clinical benefit (complete response (CR), partial response (PR), or stable disease (SD)) received an additional four cycles of treatment. Results: The median age was 65 years (y) (49-78y) and 10/15 (67%) of pts were female. Clinical benefit was achieved in 13/15 (87%) of pts. The most frequent dosing regimen administered was 10 mg/kg every two weeks and the median number of cycles given was eight cycles (1-12). Treatment with BEV was well tolerated with eight pts (53%) experiencing BEV-related Grade 2 or less adverse effects (AE), including hypertension (27%), proteinuria (13%), thrombocytopenia (7%), and mild nose bleeds (7%). There were no Grades 3-5 AE. Conclusions: This study demonstrates that there is a clinical benefit when administering BEV for the treatment of BRN. BEV was well tolerated and has an acceptable safety profile.
Skeletal muscle index and adverse events during a bladder cancer treatment episode.
Authors: Steven Ngo, Leonidas Nikolaos Diamantopoulos, Reno Maldonado, Ryan Blair O'Malley, Grace Laidlaw, Florian J. Fintelmann, Sarah K Holt, John L. Gore, George R. Schade, Daniel W. Lin, Petros Grivas, Robert B. Montgomery, Andrew Caleb Hsieh, Heather H. Cheng, Todd Yezefski, Michael Thomas Schweizer, Evan Y. Yu, Jonathan L. Wright, Sarah P. Psutka
Journal: Journal of Clinical Oncology (2020)

e17016 Background: While sarcopenia is associated with increased mortality in bladder cancer, there is limited data in patients treated with neoadjuvant chemotherapy (NAC) that associates skeletal muscle index (SMI) and adverse treatment-associated outcomes. Herein, we evaluate associations between baseline SMI and severe adverse events (SAEs) during NAC and post-radical cystectomy (RC) 90-day Clavien ≥3 complications. Methods: SMI (cross sectional area of skeletal muscle, cm 2 / height 2 , m 2 ) was measured on an axial computed tomography (CT) image at the level of the third lumbar vertebral body, within 60 days prior to NAC and RC. Patients were classified as being sarcopenic, according to sex-specific consensus definitions: Male: SMI &lt; 55, Female: SMI &lt; 39. Associations with SAEs during NAC and 90-day Clavien grade 3-5 complications were assessed with multivariable logistic regression. Results: CT scans of sufficient quality (2005-18) were available for 143 patients. There were no significant differences in clinicopathologic characteristics between the study cohort and patients without available imaging (N = 261). Median SMI for men and women was 52.1 and 40.9 cm 2 /m 2 ; 86 (60%) were sarcopenic. SAEs were observed in 92 patients (64%), resulting in hospitalization during NAC in 27 (19%), while 20 (14%) patients did not complete planned NAC due to SAEs. After adjusting for age, performance status, and clinical stage, SMI was not independently associated with NAC-associated SAEs. Postoperative complications occurred in 82 (57%) patients, including infectious complications (39; 27%), wound dehiscence (8; 6%), 90-day readmission (27; 19%). Wound healing complications including dehiscence, clinically significant hernia, urine leaks, or fistulae occurred in 33 (23%). While SMI was not independently associated with risk of complications overall (OR: 1.00, 95% CI: 0.96 - 1.03), it was associated with infectious complications (OR: 0.96, 95% CI: 0.92 - 0.99, p = 0.02), and wound dehiscence (OR: 0.93, 95% CI: 0.86 - 0.99, p = 0.02) with a trend towards significance for associations with any wound-healing complications (OR: 0.96, 95% CI: 0.91 - 1.00, p = 0.08). Conclusions: In the largest reported series of post-NAC patients with RC and detailed follow-up, pretreatment SMI was not associated with SAEs during NAC but was associated with serious infectious complications and wound dehiscence after RC. This data highlights the potential value in measuring SMI to identify patients at risk for select SAEs. Future studies should assess the benefit of prehabilitation before and during NAC.
Effects of CosA plus Prednisone in the treatment of primary sjogren syndrome combined with thrombocytopenia
Authors: Yan Wang, Shao-ting Wang, Hong Yang, Yan Zhang
Journal: BMJ (2009)

Thirty patients with confirmed primary sjogren syndrome and thrombocytopenia during January 2002 and December 2007 were investigated.All the participants received 0.5 mg·kg-1·d-1 Prednisone and 100 ms/d CosA for 1 year.Clinical symptoms and the levels of white blood eell.platelet count,erythrocyte sedimentation rate,liver function,immunoglobin,and rheumatoid factors were recored before and after the treatment.After one-year follow.up,platelet count was elevated(t=11.4179,P< 0.01).There was no significant change in erythrocyte sedimentation rate.The concentrations of immunoglobin and rheumatoid factors were significantly decreased at 1 year(t=5.4222,P<0.01;t= 9.2857.P<0.01).Prednisone plus CosA could effectively treat primary sjOgren syndrome combined with thrombocytopenia and result in fewer side effects.

Key words: 
Sjogren's syndrome; Thrombocytopenia
Why not use the Easybreath snorkeling mask to prevent COVID-19 transmission during endoscopy procedures when FFP2 are lacking?
Authors: Jérôme Rivory, Éric Beaugendre, Claire Yvon, Fréderic Ploteau, Bertrand Condat, Florian Rostain, Mathieu Pioche
Journal: Endoscopy (2020)

Coronavirus 2019 disease (COVID-19) is spreading all over the world. Endoscopy unit personnel are especially exposed to respiratory secretions (in aerosol-generating procedures) and feces [1].
Detection of residual disease and recurrence in early-stage non-small cell lung cancer (NSCLC) patients using sensitive personalized ctDNA sequencing assays.
Authors: Katrin Heider, Davina Gillian Gale, Giovanni Marsico, Andrea Ruiz-Valdepeñas, Garima Sharma, Malcolm Perry, Robert Osborne, Karen Howarth, Viona Rundell, Jelena Belic, Jerome Wulff, Susan Harden, Doris M Rassl, Robert Rintoul, Nitzan Rosenfeld
Journal: Journal of Clinical Oncology (2020)

e15560 Background: Detection of residual circulating tumour DNA (ctDNA) in patient plasma following curative intervention for localized non-small cell lung cancer (NSCLC) could identify patients who are at higher risk of relapse. These patients may benefit from adjuvant treatment, even if they have no macroscopic disease identified by radiographic imaging, which is the current standard of care. Here we evaluate the performance of the Inivata personalized sequencing assays to detect ctDNA in a cohort of 90 patients with early-stage NSCLC undergoing treatment with curative intent. Methods: The Inivata assay uses a highly sensitive next-generation sequencing platform, to identify tumor-specific variants from exome sequencing of tumor tissue and to track up to 48 patient-specific mutations in plasma specimens by multiplex PCR and ultra-high-depth next-generation sequencing. Samples from 90 patients with Stage I-III NSCLC who underwent radical treatment with curative intent, either surgery or radiotherapy ± chemotherapy, were collected as part of the LUng cancer - CIrculating tumor DNA (LUCID) study. Results: 350 plasma samples from 90 patients were analyzed using the Inivata assay, including samples collected before and after treatment and at subsequent follow-up visits. ctDNA was detected in pre-treatment samples in 38% of 32 patients (12/32) with Stage I NSCLC and in 90% of 21 patients (19/21) with Stage II/III disease, at allele fractions ranging from 6 parts per million (ppm, equivalent to 0.0006%) to over 20,000 ppm (equivalent to 2%). In plasma samples collected post-treatment, ctDNA was detected in close to 50% of cases. Conclusions: These findings highlight the Inivata assay is a sensitive method for detection of residual ctDNA and recurrence in early stage NSCLC. Initial detection rates ranged from 38% in Stage I disease to 90% for patients with Stage II/III disease prior to treatment, including detection of ctDNA to levels as low as a few parts per million. ctDNA was detected in at least one post-treatment timepoint in close to 50% patients. Together with additional data to be presented from the full 90 patient cohort, this suggests a possible route to improving treatment and designs of adjuvant trials for early stage NSCLC by detection of residual disease post-treatment and monitoring for early detection of relapse.
妊娠期糖尿病的危险因素及其临床研究
Authors: 张连英, 袁彤, 傅珂, 何英杰, 杜静
Journal: BMJ (2005)

应用75 g葡萄糖负荷试验结合葡萄糖耐量试验筛查妊娠期糖尿病,在280例孕妇中,诊断出糖尿病11例,发生率3.9%,糖耐量异常妊娠期糖尿病21例,发生率7.5%.单因素分析显示,妊娠前体重指数增高、血压高、年龄增大、糖尿病家族史与妊娠期糖尿病有关;多因素分析显示妊娠前体重指数增高是妊娠期糖尿病的独立危险因素。
Effect of anlotinib in advanced small cell lung cancer (SCLC) patients relapsed within three months after second-line treatment: A subgroup analysis from a randomized, double-blind phase II trial (ALTER 1202).
Authors: Jianhua Shi, Ying Cheng, Qiming Wang, Kai Li, Lin Wu, Baohui Han, Gongyan Chen, Jianxing He, Jie Wang, Haifeng Qin, Xiao-Ling Li
Journal: Journal of Clinical Oncology (2020)

9063 Background: Anlotinib had significantly improved progress-free survival (PFS) and overall survival (OS) of advanced small cell lung cancer (SCLC) patients received at least two lines chemotherapy in the ALTER 1202 trial. Here, we reported the effect of anlotinib in advance SCLC patients relapsed within 3 months after second-line treatment. Methods: The ALTER 1202 was a randomized, double-blind phase 2 trial including patients with advanced SCLC that received at least two previous lines of chemotherapy. Eligible patients were randomized in a 2:1 ratio to receive either anlotinib or placebo until tumor progression or unacceptable toxicity. The subgroup analysis assessed the effect of anlotinib in patients relapsed within 3 months after second-line treatment. The primary outcome was PFS. The secondary outcomes were OS, objective response rate (ORR), disease control rate (DCR) and safety. This trial was registered with ClinicalTrials.gov, number NCT03059797. Results: In the ALTER1202 trial, 67 patients in anlotinib group and 34 patients in placebo group relapsed within 3 months after second-line treatment. Among them, the median PFS was 3.98 months (95% confidence interval [CI], 2.79 to 4.24) with anlotinib versus 0.72 months (95% CI, 0.69 to 0.82) with placebo (hazard ratio [HR], 0.14; 95% CI, 0.08 to 0.26; P &lt; 0.0001). Meanwhile, anlotinib significantly prolonged OS compared with placebo (7.29 months [95% CI, 6.51 to 10.51] versus 4.37 months [95% CI, 2.33 to 6.47]; HR, 0.42 [95% CI, 0.23 to 0.74]; P = 0.0059) in patients relapsed within 3 months after second-line treatment. ORR was 4.48% (3 PR) for anlotinib and 2.94% (1 PR) for placebo (P = 0.708). DCR was 73.13% for anlotinib and 11.76% for placebo (P &lt; 0.0001). The most common adverse events were hypertension (38.81%), anorexia (28.36%), fatigue (22.39%) and Elevation of alanine aminotransferase (17.91%). Conclusions: Anlotinib improved PFS and OS in advanced SCLC patients relapsed within 3 months after second-line treatment and was well tolerated.
Neoadjuvant docetaxel + carboplatin versus epirubicin+cyclophosphamide followed by docetaxel in triple-negative, early-stage breast cancer (NeoCART): Results from a multicenter, randomized controlled, open-label, phase II trial.
Authors: Liulu Zhang, Zhiyong Wu, Ying Lin, jie li, Zhenzhen Liu, Yin Cao, Gangling Zhang, Hong-Fei Gao, Mei Yang, Ci-Qiu Yang, Teng Zhu, Min-Yi Cheng, Fei Ji, Jieqing Li, Kun Wang
Journal: Journal of Clinical Oncology (2020)

586 Background: Taxane- and anthracycline-based neoadjuvant regimens have become a standard treatment for triple-negative breast cancer (TNBC). Previous studies have shown that adding carboplatin to neoadjuvant chemotherapy regimens significantly improved pCR rate in TNBC patients. The NeoCART study was designed to compare the efficacy and safety of docetaxel plus carboplatin with standard neoadjuvant chemotherapy in TNBC. Methods: NeoCART was designed as a multicenter, randomized controlled, open-label, phase 2 trial. The patients enrolled were at least 18 years old with previously untreated stage II-III (T1cN1-2 or T2-4N0-2) invasive TNBC who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. All eligible patients were randomly assigned, in a 1:1 ratio, to the experimental arm (docetaxel (75 mg/m2) plus carboplatin (AUC 6) for six cycles) or the standard treatment arm (epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 four cycles, followed by docetaxel 100 mg/m2 for four cycles). The primary end point was the pCR rate (ypT0/is and ypN0). Secondary endpoints included event-free survival, frequency of breast-conserving surgery, and safety. Results: Between September 1, 2016, and December 31, 2019, 88 patients from 6 participating centers were included and randomized (44 patients to the DCb arm and 44 to the EC-D arm). In the primary end point analysis, 27 patients (61.4%, 95% CI 47.0 - 75.8) in the DCb group achieved a pCR compared with 17 patients (38·6%, 95% CI 24.3 - 53.0) in the EC-D group (odds ratio 2.52, 95% CI 2.4 - 43.1; p = 0.033). In different stage disease, the pCR rates of the DCb and the EC-D groups were 73.3% (22/30) vs 48.4% (15/31) in stage II (p = 0.046), and 35.7% (5/14) vs 15.4% (2/13) in stage III (p = 0.384). In patients with axillary lymph node involvement, the pCR rates were 45.8% (11/24) vs 30.8% (8/26) (p = 0.273); and 80.0% (16/20) vs 50.0% (9/18) with lymph node negative disease (p = 0.052). The frequency of breast-conserving surgery in the DCb and EC-D groups was 36.4% and 37.2%, respectively (p = 0·935). The grade 3/4 adverse events include anemia (4.5%), thrombocytopenia (2.3%), neutropenia (2.3%) and ALT/AST increased (2.3%) in the DCb group. Conclusions: Compared with the standard neoadjuvant regimen, docetaxel combined with carboplatin showed a higher pCR rate in TNBC. The higher pCR rate was more significant in patients with earlier disease stage and negative lymph node. Clinical trial information: NCT03154749 .
Characteristics of difficult-to-treat rheumatoid arthritis: results of an international survey
Authors: Roodenrijs Nadia Mt, de Hair Maria J H, van der Goes Marlies C, Jacobs Johannes Wg, Welsing Paco Mj, van der Heijde Désirée, Aletaha Daniel, Dougados Maxime, Hyrich Kimme L, McInnes Iain B, Mueller-Ladner Ulf, Senolt Ladislav, Szekanecz Zoltan, van Laar Jacob M, Nagy György, 黄艳荣, 张卓莉
Journal: BMJ (2019)

目的
尽管按照目前欧洲抗风湿联盟（EULAR）的推荐对类风湿关节炎（rheumatoid arthritis，RA）患者进行治疗，难治性RA患者的临床症状却仍然没有得到完全控制，目前EULAR指南主要关注的是RA的早期治疗和药物治疗。本研究的目的在于分析难治性RA患者的临床特点，以及在患者管理中需要探索然而现有EULAR指南并未涉及的问题。


方法
对多个国家的风湿科医生进行问卷调查，分析难治性RA的临床特点。问卷包括多选题以及开放性问题，从开放性问题的回答中发现需要进一步阐明的问题以及现有EULAR指南需要增加的内容。


结果
410名受访者完成了调查问卷，关于难治性RA的特点：50%受访者认为基于28个关节评估的疾病活动评分（disease activity score assessing 28 joints,DAS28)>3.2或存在疾病活动的征象；42%受访者认为疲劳是其特点；48%认为至少两种传统合成改变病情抗风湿药（DMARDs）以及使用至少两种生物制剂或靶向合成DMARDs治疗失败；89%认为糖皮质激素不能减量到5 mg/天或泼尼松不能减量到10 mg/天或同等剂量的其他激素。另外，现有EULAR指南中应增加合并症和关节外表现的干预以及多种药物联合治疗等重要内容。


结论
目前风湿科医生对难治性RA的定义有很大争议。难治性RA患者的很多重要问题目前EULAR指南中均没有涉及。
Encultured minds, not error reduction minds
Authors: Robert Mirski, Mark H. Bickhard, David Eck, Arkadiusz Gut
Journal: Behavioral and Brain Sciences (2020)

Abstract There are serious theoretical problems with the free-energy principle model, which are shown in the current article. We discuss the proposed model's inability to account for culturally emergent normativities, and point out the foundational issues that we claim this inability stems from.