tbuckley/cabot-search huggingface dataset:
Aggressive care at end-of-life in the Veteran’s Health Administration versus fee-for-service Medicare among patients with advanced lung cancer.
Authors: Carolyn J Presley, Kiranveer Kaur, Ling Han, Pamela R. Soulos, Weiwei Zhu, Emily Corneau, John R. O'Leary, Herta H. Chao, Tracy Shamas, Michal G. Rose, Karl Lorenz, Cari Levy, Vincent Mor, Cary Philip Gross
Journal: Journal of Clinical Oncology (2020)

12025 Background: The Veteran’s Health Administration (VHA) allows simultaneous receipt of cancer treatment and hospice care, termed concurrent care, while fee-for-service Medicare does not. Although many physicians who care for patients in the VHA also care for private sector patients, it is unclear whether there is a “spillover” relation between end of life (EOL) care in the VHA and Medicare systems at the regional level. We examined temporal trends, as well as regional-level associations between Medicare and VHA EOL practice for patients with advanced lung cancer. Methods: We conducted a retrospective study on VHA and SEER-Medicare (SM) decedents from 2006-2012 with stage IV non-small cell lung cancer (NSCLC) who received any lung cancer care. Aggressive care (AC) at EOL was defined as any of the following within 30 days of death– intensive care unit (ICU) admission, no-hospice care, cardiopulmonary resuscitation(CPR), mechanical ventilation (MV), &gt; 1 inpatient admission and receipt of chemotherapy. Descriptive statistics were used to compare outcomes. We also analyzed the association between Medicare hospital referral region (HRR) hospice admissions, Medicare HRR EOL spending, and VHA AC use adjusted for patient’s characteristics using a random intercept mixed effect logistic regression model after matching VHA facilities with Medicare facilities in a particular HRR. Results: AC use significantly decreased during the study period, from 46% to 31% among 18,371 Veterans and from 42% to 38% among 25,283 in the SM cohort, (t-test P &lt; .05). Hospice use significantly increased within both cohorts (p &lt; .001). The receipt of chemotherapy at EOL was similar for both cohorts throughout the study period. Veterans who received care in regions with higher hospice admissions among Medicare beneficiaries were significantly less likely to receive AC at EOL (adjusted Odds Ratio (aOR): 0.13 95%CI: 0.08-0.23, P &lt; .001) than veterans in regions with lower Medicare hospice use. Medicare HRR spending at the EOL was not associated with receipt of AC among Medicare beneficiaries (aOR): 1.004 95%CI: 1.00-1.009, P = 0.07). Conclusions: Perhaps due to availability of concurrent care, VHA patients received less aggressive care at EOL as compared to SM patients. At the regional level, greater hospice use among Medicare beneficiaries was significantly associated with reduced AC within the VHA.
Capturing the pathway logic of cell signaling for epithelial-mesenchymal transition in ovarian cancer cell lines.
Authors: Matthew Morris, Jeselle Clark, Cole Lyman, Jennifer Brown Broderick, Zachary B. Kramer, Gary Skuse, Gordon Broderick
Journal: Journal of Clinical Oncology (2020)

e18063 Background: Epithelial-to- mesenchymal transition (EMT) plays a key role not only in cancer invasiveness and progression but also in treatment resistance. Experimental models suggest that epithelial and mesenchymal phenotypes may represent steady states supported by the regulatory logic of intracellular signaling networks. Using known regulatory interactions between intracellular signaling molecules as a framework, we explored EMT in silico with the aim of identifying potentially novel means of inhibiting metastasis in ovarian cancer. Methods: A mathematical model connecting 27 genes involved in EMT through 153 regulatory interactions was assembled from the Mogrify, Reactome, String and Pathway Studio (PS) databases, the last of which used the MedScan natural language processing (NLP) engine to process over 8,000 full-text publications. Logic model parameters dictating the regulatory response dynamics of the EMT circuit were constrained to values that accurately predicted the proteomic profiles characterized as either epithelial or mesenchymal in 30 cell lines in the publicly available MaxQB database. Results: A total of 94,672 candidate models predicted the protein expression in stable epithelial and mesenchymal cells equally well, clustering into 24 classes of slightly different EMT transition kinetics. Discrete event simulations based on these models identified 7 unique combinations, involving the concurrent modulation of at least 3 gene products capable of effecting this transition successfully even in the presence of noise. Every combination required inactivation of ZEB2, along with 2 other manipulations. Inactivation of TP53, HOXA5, or IRF7 was required in 3 combinations, while inactivation of ICAM1 was required in 2 cases. Only BCL2 was required to be activated in any of these scenarios. Interestingly, BCL2 inhibition is now applied clinically in some hematologic cancers and proving effective in patient-derived cell lines for high-grade serous ovarian cancer when combined with MEK inhibition. Conclusions: This work suggests that EMT might at least in part be driven by normal regulatory interactions between specific proteins in a network of pathways, without the requirement for additional mutations or alterations in the underlying circuitry. Maintenance of ZEB2 or TP53 activation as well as BCL2 inhibition may thus represent promising avenues for future research in arresting EMT and associated chemo-resistance.
Safety and tolerability of intratumorally administered OH2, an oncolytic herpes simplex virus 2, in patients with advanced solid tumors: A phase I dose escalation clinical study.
Authors: Jing Huang, Bo Zhang, Jialin Tang, Qing Chang, Rui Zhang, Chengyun Geng, Dawei Wu, Ling Qi, Xiangyong Gu, Binlei Liu
Journal: Journal of Clinical Oncology (2020)

3139 Background: There have been limited reports concerning treatment outcomes of oncolytic viruses in solid tumors other than melanoma. OH2 is a genetically engineered oncolytic herpes simplex virus type 2 designed to selectively amplify in tumor cells and express GM-CSF to enhance tumor-specific immune responses. Methods: We conducted an open-label, single-center, phase 1 study. Eligible pts were 18-75 years of age; had histologically confirmed advanced solid tumor; had progressed after standard systemic treatments. Pts were required to have tumor(s) deemed safe to inject, with a longest diameter of at least 0.5cm. Other eligibility criteria included measurable lesion as per RECIST v1.1; ECOGPS score of 0-1 and adequate organ functions. A 3+3 dose-escalation strategy was used in the study and 3 dose levels (10 6 , 10 7 and 10 8 CCID50/mL) of OH2 were assessed. OH2 was administered intratumorally every 3 weeks for the first cycle and every 2 weeks.Treatment may continue afterwards in ptswith potential clinical benefit at the discretion of the investigators. The primary objective was the safety and tolerability of OH2 injection as defined by the dose limiting toxicities (DLTs) within the first 3 weeks of therapy, and the maximum tolerated dose (MTD). Secondary objectives included efficacy and immunogenicity of OH2. Results: 11 pts were enrolled between April 17, 2019 and November 4, 2019. The median follow-up duration was 8.36 months (95%CI: 5.64-11.08). OH2 was well-tolerated as no DLTs were reported and no MTD reached. Before the end of the DLT assessment period,1 pt withdrew consent, and 1 pt died of arrhythmia unrelated to OH2, with negative OH2 DNA copies in serum, urine and saliva samples. Most treatment-related adverse events (TRAEs) observed were of grade 1-2, except that 1 pt in the 10 8 CCID50/mL group developed grade 3 fever. The most common TRAEs were fever (n =5) and blood bilirubin level increase (n = 4). There were no grade 4 or 5 TRAEs. One pt(rectal cancer) had PR and 2 (appendix cancer and ovarian cancer) had SD as per RECIST v1.1. One patient (esophageal cancer) achieved iPR as per iRECIST criteria. The duration of follow-up for the 2 responders were 9.70 months and 8.36 months, respectively, and both had ongoing responses. Notably, regression of a non-injected lesion was observed in 1 patient. Conclusions: OH2 had a favorable safety profile with no DLTs and MTD. The dose expansion study in selected tumor types is currently underway. Clinical trial information: NCT03866525 .
Anti–Citrullinated Protein Antibody Specificities, Rheumatoid Factor Isotypes, and Incident Cardiovascular Events in Patients With Rheumatoid Arthritis
Authors: Helga Westerlind, Johan Rönnelid, Monika Hansson, Lars Alfredsson, Linda Mathsson‐Alm, Guy Serre, Martin Cornillet, Rikard Holmdahl, Per‐Johan Jakobsson, Karl Skriner, Lars Klareskog, Saedis Saevarsdottir, Johan Askling
Journal: Arthritis & Rheumatology (2020)

To investigate the relationship between anti-citrullinated protein antibodies (ACPAs), specific ACPA subspecificities, rheumatoid factor (RF) isotypes, and incident cardiovascular (CV) events in patients with rheumatoid arthritis (RA).Serum samples from Swedish patients with new-onset RA (diagnosed within 1 year of symptom onset between 1996 and 2009) were centrally typed for anti-cyclic citrullinated peptide 2 (anti-CCP2) antibodies, 20 ACPA subspecificities, and RF isotypes. Patients were followed up longitudinally in nationwide registers to monitor the occurrence of acute coronary syndrome (ACS), stroke, CV-related death, and major adverse CV events (MACE). The association between each serologic marker and CV outcome, and the impact of adjustment for the Disease Activity Score in 28 joints (DAS28), smoking status, and income at baseline, were assessed using Cox proportional hazards models. In addition, associations of serologic markers with all-cause mortality were explored.In total, 2,814 patients with RA were included in the study. The median follow-up was 13 years, during which the CV end points of ACS, stroke, or CV-related death were reported to occur in 375 patients. Occurrence and/or levels of anti-CCP2 were associated with risk of incident ACS (hazard ratio [HR] 1.46, 95% confidence interval [95% CI] 1.03-2.06), stroke (HR 1.47, 95% CI 1.03-2.10), CV-related death (P = 0.024 for association with anti-CCP2 levels), and MACE (HR 1.34, 95% CI 1.06-1.70). Similarly, an association with the number of ACPA subspecificities was observed; however, this could not be attributed to any individual or group of ACPA subspecificities. Presence of IgM-RF was associated with all CV end points except ACS, and IgA-RF was exclusively associated with CV-related death. Adjustment for smoking status, income, and DAS28 scores decreased most of the HRs, whereas IgA-RF remained associated with CV-related death (HR 1.61, 95% CI 1.05-2.48). All of the assessed serologic makers were associated with all-cause mortality.RF isotypes and ACPAs are associated with future CV events in patients with RA. ACPA levels and number of subspecificities seem more important than the occurrence of particular subspecificities, and these associations were not explained by a history of ever smoking.
胸腔引流管放置不当致膈疝及胸壁疝一例
Authors: 姜波, 于炳强
Journal: BMJ (2011)

患者女性,45岁.2009年10月13日因车祸致胸痛、胸闷憋气1 h,急诊入当地镇医院.经胸部X线片检查证实为右侧多发性肋骨骨折、右侧血气胸,立即行胸腔闭式引流术.引流管放置的位置在右侧腋中线第9肋间,第1次置胸腔引流管后水封瓶水柱波动不明显,未引流出血液及气体,患者症状无改善.随即拔除引流管,于同一肋间该切口后侧约2 cm再次置管,当即有血液及气体溢出,水封瓶水柱波动良好,患者胸闷、憋气明显减轻.经镇痛、协助咳痰、预防感染等治疗,7 d后胸腔引流管未再明显引流出液体及气体,拔出引流管,住院9 d痊愈出院。
A phase II study of anlotinib with cediranib as a second-line treatment for patients with advanced biliary tract cancers (aBTCs).
Authors: Ruihua Zhao, Hong Zong, Shuiling Jin, Qian Zhong, Miao Jiang, Ming Jin, Rui Li, Guozhong Jiang
Journal: Journal of Clinical Oncology (2020)

e16712 Background: Gemcitabine combined with cisplatin (GP) is currently used as a standard first-line chemotherapy regimen for aBTCs, However, the median overall survival (mOS) is only about 11.7 months, and there is no standard treatment option for patients who failed GP therapy. In this study, we aimed to investigate the efficacy and safety of anlotinib with cediranib as a second-line treatment for patients with aBTCs. Methods: A monocenter single-arm phase II study was conducted at the First Affiliated Hospital of Zhengzhou University. Patients with measurable aBTCs and progressed on GP were enrolled in this study. Patients received cediranib 200mg, on day1 + anlotinib 12mg on day1-14, Q3W until disease progression, intolerance of toxicity, investigator/patient decision to withdraw or other reasons specified in the protocol. Response (RECIST1.1) was assessed every 8 weeks. Plasma, stool and tumor tissues were collected for exploratory analyses. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and drug safety. Results: We planned to include 20 patients. So far 9 patients were enrolled in this study, 66.7% (6/9) were men, 33.3% were women. The median age was 56y (43y-61y). The primary sites of the tumor were intrahepatic biliary (66.7%, 6/9) and gallbladder (33.3%, 3/9). At data cutoff (Dec 14, 2019), the median duration of follow-up was 2.5mos (range, 1.2 to 4) and all of the patients were still under treatment. 8 patients have undergone at least one efficacy evaluation, of which 2 (25%) PR, 5 SD (62.5%), DCR was 87.5% ((7/8). An SD patient had a long-term intermittent fever, which considered to be tumor fever, the body temperature returned to normal after 1 cycle of treatment. 1 patient was considered to be undefined because, at the first evaluation, the liver lesions were reduced however the lymph nodes in the retroperitoneum were enlarged. The median PFS and OS not yet reached. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 11.1% (1/9) of patients. TRAEs led to discontinuation in 1 patient (grade 3 hypertension). TRAEs led to dose reduction of anlotinib in 2 patients. No TRAEs were fatal. Conclusions: The primary result showed that the combination of anlotinib and cediranib was well tolerated and demonstrates encouraging efficacy than historical control in second-line treatment for aBTC. Updated data, including safety, efficacy, and biomarkers will be presented. Clinical trial information: ChiCTR1900022003 .
Morphologic Variants of Pancreatic Neuroendocrine Tumors: Clinicopathologic Analysis and Prognostic Stratification
Authors: Yue Xue, Michelle D. Reid, Burcin Pehlivanoglu, Rebecca C. Obeng, Hongmei Jiang, Bahar Memis, Shu K. Lui, Juan Sarmiento, David Kooby, Shishir K. Maithel, Bassel El-Rayes, Olca Basturk, Volkan Adsay
Journal: Endocrine Pathology (2020)
Storytelling as a means of improving community and decreasing burnout in a large academic cancer center.
Authors: Sherise C. Rogers, Don M. Benson, Eric H. Kraut, Tamanna Zohra Haque, Luay Mousa, Jeffery Fowler, Janet Dettorre
Journal: Journal of Clinical Oncology (2020)

11018 Background: Burnout is highly experienced amongst physicians who care for patients with cancer. Workplace isolation is a risk factor for burnout. The field of oncology is growing at a rapid pace and many cancer centers are expanding to meet the demands of patient care and research. Prior assessments revealed that our hematology and oncology fellows were experiencing feelings of isolation and disconnection, which was likely reflected from our greater academic community. Methods: The traditional art of storytelling has been used to offer guidance, teaching, new perspective taking and understanding of self. The concept of “My Story”, an interactive storytelling lecture series was developed to address the following objectives at a large academic cancer center: 1) Promote connection and decrease isolation amongst the cancer sub-specialties 2) Increase fellow-faculty interaction for mentorship, 3) provide an outlet to discuss sensitive topics such as burnout, grief, unexpected patient outcomes, medical errors, work- life balance, career transitions, personal struggles, and bias. A faculty member was identified to tell their unique story for a special lecture. Fellows and faculty members from hematology, oncology, radiation-oncology, neuro-oncology, gynecology-oncology, and surgical oncology were invited. All audience members were encouraged to ask questions and engage in discussion. A survey was distributed after the inaugural event for evaluation. Results: A total of 56 people attended the inaugural event. There were 14 fellows, 9 faculty members and 33 others, which included basic scientists and advance practice providers. 17 individuals completed our post survey, which included 6 faculty members, 4 fellows, 1 nurse practitioner, 1 student and 5 others. On a scale from 1-10 (mean scores reported), participants rated the experience 7.5 for enjoyment, 6.6 for sense of connection with the group, 6.0 for inspiring them to make new connections with others and 6.8 when asked if they left with new tools to assist with personal challenge. Conclusions: A lecture series that invites multidisciplinary cancer physicians and surgeons to discuss personal career and life challenges can be beneficial to addressing burnout, decreasing isolation and improving connection and community at a large academic cancer center.
Stability of eosinophilic inflammation in COPD bronchial biopsies
Authors: Andrew Higham, Sophie Leow-Dyke, Natalie Jackson, Dave Singh
Journal: European Respiratory Journal (2020)

Blood eosinophil counts (BEC) predict the response to inhaled corticosteroids (ICS) in COPD patients with increased exacerbation risk [1, 2]. Studies have shown an association between BEC and both sputum and lung tissue eosinophil counts in COPD patients [3, 4], supporting BEC as a biomarker that reflects the degree of eosinophilic lung inflammation. While the long-term stability of BEC in COPD patients has been studied [5–7], the stability of eosinophilic airway inflammation in COPD patients is less clear. Good stability of COPD sputum eosinophil counts up to 3 months has been reported [8, 9], but similar analysis using submucosal eosinophil counts (SMEC) are lacking. Eosinophilic airway inflammation shows greater regional and temporal variability in COPD patients with higher numbers of submucosal eosinophils <https://bit.ly/3cApnTd>
Alliance A071701: Genomically guided treatment trial in brain metastases.
Authors: Priscilla Kaliopi Brastianos, Erin Twohy, Carey K. Anders, A. John Iafrate, Peter A. Kaufman, Justine Vanessa Cohen, Rebecca Suk Heist, Elizabeth Robins Gerstner, Timothy J. Kaufmann, Susan Geyer, Laura Hoffman, Priya Kumthekar, Frederick G. Barker, Scott L. Carter, Paul D. Brown, Evanthia Galanis
Journal: Journal of Clinical Oncology (2020)

TPS2573 Background: Brain metastases, most commonly derived from melanoma, lung and breast cancers, are the most common brain tumor, with approximately 200,000 cases diagnosed annually in the United States. Median survival is on the order of months. For patients with clinically symptomatic brain metastases, approximately half succumb due to intracranial progression. In preclinical work, we demonstrated that brain metastases and primary tumors are often genetically distinct with frequent alterations in the CDK and PI3K pathway (Brastianos, Carter et al. Cancer Discovery 2015). Methods: We are currently accruing to a prospective multi-arm phase II study of CDK, PI3K/mTOR, and NTRK/ROS1 inhibitors in patients with brain metastases harboring alterations associated with sensitivity to these inhibitors (abemaciclib, paxalisib and entrectinib), respectively. Patients with new, recurrent or progressive brain metastases are eligible for this trial. Previously obtained tissue from brain metastases and extracranial sites (primary or extracranial metastases) are screened for the presence of these alterations, and if present in both tumor sites, patients will receive the appropriate corresponding targeted treatment. Screening is carried out with the SNaPshot NGS assay, which is a fully validated clinical test designed and developed at the MGH Center for Integrated Diagnostics. The primary endpoint of response rate (RR) in the central nervous system as per RANO criteria will be evaluated separately for each inhibitor, stratified by histology within each arm. There will be 21 evaluable patients assigned to each of the CDK and PI3K inhibitor and tumor type cohorts (breast, lung and other) and 10 patients assigned to the NTRK/ROS1 inhibitor cohort (lung) for a total of 136 evaluable patients. Although current systemic therapy for brain metastases is often ineffective, we hypothesize that targeted therapies will demonstrate efficacy in patients harboring the appropriate mutations. This study represents a novel individualized therapeutic approach in brain metastases, a disease with a critical need for effective therapy. Support: U10CA180821, U10CA180882, https://acknowledgments.alliancefound.org ; Genentech, Kazia Therapeutics Limited, Eli Lilly; Clinical trial information: NCT03994796 .
The next-generation RET inhibitor TPX-0046 is active in drug-resistant and naïve RET-driven cancer models.
Authors: Alexander E. Drilon, Dayong Zhai, Evan Rogers, Wei Deng, Xin Zhang, Jane Ung, Dong Lee, Laura Rodon, Armin Graber, Zachary Franklin Zimmerman, Brion W Murray, Vivek Subbiah
Journal: Journal of Clinical Oncology (2020)

3616 Background: RET fusions/mutations drive oncogenesis in lung and thyroid cancers, and several other malignancies. Selective RET inhibitors (selpercatinib/pralsetinib) are active in patients with these cancers; unfortunately, resistance often occurs. On-target resistance includes the acquisition of solvent front mutations (SFMs i.e. RET G810 substitutions). TPX-0046 is a structurally differentiated RET inhibitor that is potent against a range of RET fusions and mutations including SFMs. Methods: The rationally-designed, compact, macrocyclic RET/SRC inhibitor TPX-0046 was characterized in RET-driven in vitro and in vivo tumor models. Results: In enzymatic assays, TPX-0046 showed low nanomolar potency against wild-type RET and 18 RET mutations/fusions. It was potent against SRC and spared VEGFR2/KDR. TPX-0046 inhibited RET phosphorylation (IC 50 &lt; 10 nM) in tumor cell lines (LC2/ad, CCDC6-RET; TT, RET C634W) and Ba/F3 engineered RET models (WT, G810R). In cell proliferation assays, TPX-0046 inhibited KIF5B-RET Ba/F3, LC2/ad, and TT cells with IC 50 values ~1 nM. Ba/F3 RET engineered cells with SFMs (e.g. G810C/R/S) were potently inhibited by TPX-0046 (mean proliferation IC 50 1–17 nM). TPX-0046 demonstrated marked in vivo anti-tumor efficacy in RET-driven cell-derived and patient-derived xenograft tumor models. In a Ba/F3 KIF5B-RET xenograft model, a single dose of 5 mg/kg TPX-0046 inhibited &gt; 80% of RET phosphorylation (corresponding mean free plasma concentration: 51 nM). At 5 mg/kg BID, tumor regression was observed in RET-dependent xenograft models, including those that harbor RET SFMs: TT, CTG-0838 PDX (NSCLC, KIF5B-RET), CR1520 PDX (CRC, NCOA4-RET), Ba/F3 KIF5B-RET, and Ba/F3 KIF5B-RET G810R. Conclusions: TPX-0046 is a unique next-generation RET inhibitor that possesses potent in vitro and in vivo activity against a diverse range of RET alterations, including SFM-mediated resistance. A phase 1/2 trial for RET inhibitor-resistant and naïve RET-driven cancers is on-going (NCT04161391).
Plasma brain natriuretic peptide test in patieuts with hyperthyroidism
Authors: Zong-yi Wu, De-shui Pang, Bin Hou
Journal: BMJ (2008)

Twenty-two patients with hyperthyroid caxdiopathy(HTC),38 patients with hyperthyroid (HT),and 10 healthy controls were tested for plasma levels of brain natriuretic peptide(BNP).The findings showed that BNP level in HTC group(433±141)μg/L was significantly higher than that in HT group(110±38)μg/L and healthy control group(10±3)μg/L(both P<0.01);HT group vs healthy control group,P<0.01).After 3 months'treatment for HT,BNP decreased significantly.The patients with higher BNP levels had an increased incidence of HTC.Plasma BNP test might be useful in predicting the prognosis and the treatment efficacy in patients with HT.

Key words: 
Natriuretic peptide,brain; Hyperthyroidism