tbuckley/cabot-search huggingface dataset:
A phase I study of Aurora kinase A inhibitor LY3295668 erbumine as a single agent and in combination in patients with relapsed/refractory neuroblastoma.
Authors: Steven G. DuBois, Jill D. Kremer, Bram De Wilde, Chad Jacobsen, Isabelle Aerts, Yael P. Mosse, John M. Maris, Andrew Lithio, Andreas Gosberg, C.L. Banks, Courtney Tate, Michele Dowless, Xueqian Gong, Louis Stancato, Katherine M. Bell-McGuinn, Julie R. Park, Andrew DJ Pearson, Araz Marachelian
Journal: Journal of Clinical Oncology (2020)

TPS10561 Background: Aurora kinase A (AurA) has been implicated in high-risk neuroblastoma, including roles stabilizing and increasing expression of MYCN protein. AurA impacts the function of MYCN in mediating transcription in a cell cycle dependent manner, suggesting that neuroblastoma and other MYC/MYCN-driven tumors may be sensitive to AurA inhibition. LY3295668 is a selective AurA inhibitor. The lack of AurB inhibitory activity is hypothesized to minimize on-target hematologic toxicity associated with AurB inhibition. The molecule’s selectivity is intended to allow for continuous dosing at exposures associated with &gt; 90% target inhibition at trough. In an analysis of LY3295668 antiproliferative effects in 560 cancer cell lines, neuroblastoma was among the most sensitive histologies tested. This screen also separately evaluated genomic predictors of response to LY3295668, with MYC/ MYCN amplification identified as among the strongest predictors of sensitivity to this agent. LY3295668 is currently being evaluated in early phase adult trials. The current trial (J10-MC-JZHD) was uniquely designed to hasten time to first-in-child oncology development for a rare unmet need of relapsed/refractory neuroblastoma patients. Methods: Study J1O-MC-JZHD (NCT04106219) is a multicenter, dual collaboration (NANT and ITCC), randomized, open-label, Phase 1 study of oral LY3295668 in children with relapsed/refractory neuroblastoma. A rolling 6 design will be followed for dose escalation in both a monotherapy cohort and a combination cohort testing LY3295668 together with cyclophosphamide and topotecan. The starting monotherapy dose will be equivalent to 80% of the adult maximum tolerated dose. Key eligibility criteria include recurrent/refractory neuroblastoma not amenable to curative treatment, age 2-21 years, mandatory archival tissue submission, ability to swallow capsules, and adequate hematologic and organ function. LY3295668 is administered in capsule form orally BID continuously. Primary objectives include assessments of safety and tolerability of study drug to identify RP2D as monotherapy and combination, and assess antitumor activity. Secondary objectives include assessment of the pharmacokinetic profile as monotherapy and in combination, and assessment of the relationship between study drug exposure and efficacy. Following determination of the RP2Ds, an expansion phase will randomize patients to monotherapy or to the combination arm. Enrollment began 16 Dec 2019 and is ongoing. Clinical trial information: NCT04106219.
A single-institution and commercial laboratory database analysis of BRIP1-associated cancer risks.
Authors: Kristen Danielle Whitaker, Ryan Bernhisel, John Kidd, Elisha Hughes, Eric Thomas Rosenthal, Michael J. Hall
Journal: Journal of Clinical Oncology (2020)

1538 Background: BRIP1/ FANCJ participates in DNA replication and repair via interactions with BRCA1 and possibly MLH1. Previous studies have reported that pathogenic variants (PV) in BRIP1 are associated with an ~2-fold increase in risk for ovarian cancer (OC) and triple-negative breast cancer (TNBC). Although multigene panel testing for hereditary cancer (CA) has identified BRIP1 PV and uncertain variants (VUS) in patients with diverse CAs including breast (BC), colorectal (CRC) and melanoma (Mel), association with these CA types has not been established. Methods: We examined BRIP1 risks in two independent populations: Fox Chase Cancer Center (FCCC) and Myriad Genetics (MGL). At FCCC, pedigrees of BRIP1 PV ( N= 10) and VUS families ( N= 47) were reviewed. The MGL population included patients referred for testing by multigene panel (9/2013-12/2019) ( N= 586,740). Multivariable logistic regression analysis estimated BRIP1 CA risks as odds ratios (ORs) and 95% confidence intervals (CIs). Models were adjusted for age, sex, ancestry, personal CA history (PHX), and family CA history. Results: In the FCCC cohort, BRIP1 PV carriers ( N= 12) reported PHX of early-onset ( &lt; 50) BC, CRC, and bladder CA. BRIP1 VUS were also identified among several patients with striking PHX and negative panel testing: BC &lt; 40 ( N= 3), bilateral BC ( N= 4), TNBC ( N= 2), CRC &lt; 40 ( N= 3), and a patient with 3 CAs &lt; 40 (CRC, BC, and Mel). All FCCC families with a BRIP1 PV and select VUS families ( N= 6) are seen in the Table. In the MGL population, 0.3% (1,678/586,740) carried a BRIP1 PV. Logistic regression analyses found that female BRIP1 PV carriers have significantly increased risk for OC (OR 2.40, 95% CI 1.93-2.98) and TNBC (OR 1.93, 95% CI 1.52-2.46). Data were insufficient for testing risk of bladder or prostate CA. Findings did not support associations of BRIP1 with CRC, melanoma, endometrial, pancreatic or gastric CA. Conclusions: BRIP1 PV and VUS may be identified in patients with diverse CA histories. These results confirm studies showing that BRIP1 PV are associated with an ~2-fold increased risk of OC and TNBC, but do not support increased risks of CRC, melanoma or endometrial CA in BRIP1 PV carriers. [Table: see text]
Reply to the comment on “What are the barriers faced by underrepresented minorities applying to dermatology? A qualitative cross-sectional study of applicants applying to a large dermatology residency program”
Authors: Rebecca Vasquez, Haneol Jeong, Stephanie Florez-Pollack, Laura H. Rubinos, Simon C. Lee, Amit G. Pandya
Journal: Journal of the American Academy of Dermatology (2020)

To the Editor: We were pleased to read the response to our letter by Jones et al1 and agree that dermatology residency programs can take further action to reduce barriers for underrepresented minorities, such as diversity mentorship programs and a more systematic and holistic approach to recruiting underrepresented minority students. We also agree with their comments pointing out biases against underrepresented minorities with the current system, which uses standardized test scores to triage applicants.
Survey on smoking status and risk factors in residents
Authors: Xiao-yu He, Jia-ying Sun, Shuo Liu, Ling-ling Wang, Ming-jing Zhao, Xiao-ge Wang
Journal: BMJ (2012)

A survey on smoking status and risk factors was conducted among 3373 residents in two districts of Shen yang city during November 2008 and September 2009 ; the pulmonary function tests were also performed for all subjects.A logistical regression model was used to evaluate the risk factors of smoking,and the knowledge about diseases caused by smoking was evaluated by chi-square test.The overall smoking rate was 50.7％ ( 1710/3373 ) ; 86.8％ (1458/1680) for males a(un)14.9％ (252/1693)for females.The risk factors of smoking ( P ＜ 0.05 ) in order of OR value were as follows:drinking,work environment and underlying diseases ; the protective factors were:female,educational level,overweight ( BMI ≥ 24) and old age.The survey on knowledge of smoking-related disease was conducted in 2478 residents including 815 smokers and 1663 non-smokers. The awareness levels about whether smoking can cause COPD,asthma,birth defects,malignant tumor,abortion,growth retardation,fetal death and myocardial infarction were significantly different between smokers and non-smokers.

Key words: 
Smoking;  Factor analysis, statistical
Medical resource utilization among multiple myeloma (MM) patients who were triple-exposed to a proteasome inhibitor, an immunomodulatory agent, and daratumumab.
Authors: Maneesha Mehra, Concetta Crivera, Satish Valluri, Sandhya Nair, Martin Vogel, Tonia Nesheiwat, Ravi C. Potluri, Sundar Jagannath, Nina Shah
Journal: Journal of Clinical Oncology (2020)

e20539 Background: MM patients undergo several lines of treatment (LOT), mainly involving ≥1 proteasome inhibitor (PI), immunomodulatory (IMiD), and novel agents such as daratumumab (dara). Research is underway to address the need of patients previously exposed to a PI, an IMiD, and dara (triple-exposed). This retrospective cohort analysis assessed costs and healthcare resource (HR) utilization in triple-exposed patients. Methods: A pooled cohort of patients from Optum’s Humedica Electronic Health Records and Clinformatics claims data with an index MM diagnosis between 2008-2018 and who 1) had ≥12 months of activity/insurance coverage prior to index MM diagnosis, 2) did not have any other cancer during this period, 3) were aged ≥18 years at index diagnosis, 4) were triple exposed and 5) had ≥1 LOT subsequent to triple-exposure were studied. Costs per LOT after triple-exposure, broken down into cost categories, were analyzed in patients from Optum claims data (N = 94), while HR utilization (hospitalization, ER/outpatient visits, lab tests and MM drugs) was analyzed in the pooled cohort (N = 517). Descriptive statistics are reported. Results: 53% of patients were male; mean follow-up was 8.9 months (272 days). At LOT1 following triple-exposure, mean age was 68 yrs, mean time from index MM diagnosis was 37 months, and median prior LOTs were 4. 50% were penta-exposed (2 PIs + 2 IMiDs + dara) following triple exposure. 42% received a pomalidomide-containing regimen in LOT1 after triple-exposure. 56% of patients had ≥2 LOTs after triple-exposure; 28% had ≥3. Mean duration of LOT1, LOT2, and LOT3 in claims data patients was 132, 102 and 101 days, respectively, with associated mean cost per LOT of $165,453, $131,759, and $116,915. Over the follow-up, patients had a mean of 1.75 hospitalizations, 0.92 ER visits, 32.1 outpatient/office visits and 28.8 lab tests; post triple-exposure mean cost per patient per month was $38,214 (Table). Conclusions: Substantial MM drug costs, inpatient stays and frequent outpatient visits contribute to high cost per month of post triple-exposure treatment, underscoring the need for effective MM treatments with durable response. [Table: see text]
Osimertinib in non-small cell lung cancer (NSCLC) with atypical EGFR activating mutations: A retrospective multicenter study.
Authors: Jingran Ji, Jacqueline V Aredo, Andrew Piper-Vallillo, Laura Huppert, Julia K Rotow, Hatim Husain, Susan L Stewart, Rosemary Cobb, Heather A. Wakelee, Collin Michael Blakely, Melisa L. Wong, Matthew A. Gubens, Justin Chen, Geoffrey R. Oxnard, Caroline Elizabeth McCoach, Zofia Piotrowska, Joel W. Neal, Jonathan W. Riess
Journal: Journal of Clinical Oncology (2020)

9570 Background: Osimertinib (osi) is a 3 rd generation EGFR tyrosine kinase inhibitor (TKI) approved for first line (1L) treatment of metastatic NSCLC harboring EGFR Exon 19 del and L858R (representing &gt; 80% of EGFR activating mutations) or in NSCLC with EGFR T790M (the most common resistance mutation to 1 st or 2 nd generation TKI). However, it has not been well-studied in EGFR-mutant NSCLC harboring less common EGFR activating mutations such as G719X, L861Q, S768I, and exon 20 insertion (ins), among others. Methods: We conducted a multi-institution, retrospective study approved on institutional IRB protocols in a series of patients (pts.) with metastatic NSCLC treated with osi who harbored at least one atypical EGFR mutation, excluding those with concurrent L858R, Exon 19 del, or T790M. Kaplan-Meier analyses were generated with SPSS, v25 (IBM Corp., USA). Response was assessed by RECIST 1.1 in evaluable pts. Time on osi was employed as a surrogate endpoint for clinical benefit in this retrospective analysis. Results: Fifty-one NSCLC pts with uncommon EGFR mutations were identified among six US institutions. Pt characteristics: 72.5% women, median age 65 yo (44-83 yo), 82.3% ECOG PS 0-1, 43.1% never smoker, 100% lung adenocarcinoma, 58.8% Caucasian, 25.5% Asian, 3.9% Black, 2.0% Hispanic, and 9.8% Other. The most frequent mutations were L861Q (35.3%, N = 18), G719X (27.5%, N = 14), and Exon 20 ins (15.7%, N = 8). Osi was used in the 1L setting in 39.2% (N = 20). Median time on osi was 7.1 months (mo.) in the overall cohort (95% CI, 5.4 to 8.8 mo.) and 8.9 mo. (95% CI, 7.0 to 10.8 mo.) in pts receiving 1L osi. Patients harboring G719X (N = 4) and L861Q (N = 10) mutations had a median time on 1L osimertinib of 5.8 mo. and 19.3 mo., respectively. One patient’s tumor had an EGFR exon 19 ins and was on 1L osi with a partial response for 16.8 months. Two patients with Exon 20 ins were on 1L osi for 9.3 mo. and 8 mo., respectively. Conclusions: In this largest known clinically annotated dataset of patients with atypical EGFR-mutations treated with osi, activity was noted, though 1L clinical benefit on osi appears lower in this multicenter US cohort than in E19del or L858R. These results are comparable to the recently published prospective phase II trial ( Cho et al, 2019) conducted in Korea. Patients with L861Q and Exon 19 insertion appeared to benefit the most from osi in this time on treatment retrospective analysis. More detailed analysis of this cohort is planned and further prospective studies are warranted to determine clinical benefit of osi amongst diverse atypical EGFR-mutations.
Changes in lymphocyte/monocyte ratio, prognostic marker to predict overall survival in patients with advanced cancer treated with immune checkpoint inhibitor.
Authors: Sandip H. Patel, Mingjia Li, Songzhu Zhao, Lai Wei, Jarred Thomas Burkart, Marium Husain, Kai He, Erin Marie Bertino, Peter G. Shields, David Paul Carbone, Claire F. Verschraegen, Gregory Alan Otterson, Kari Lynn Kendra, Daniel Spakowicz, Carolyn J Presley, Dwight Hall Owen
Journal: Journal of Clinical Oncology (2020)

3047 Background: Immunosuppressive factors within the tumor microenvironment (TME) pose a barrier to response to treatment with immune checkpoint inhibitors (ICI). Monocytes alter the TME to promote cancer progression through local immune suppression and angiogenesis. Peripheral blood lymphocyte-to-monocyte ratio (LMR) may reflect the interaction between host immunity, represented by lymphocytes, and the tumor microenvironment, represented by monocytes. A low LMR in the peripheral blood may serve as a surrogate biomarker and has been associated with poor prognosis in various cancers; however, its role has not been well defined in the era of treatment with ICI. Methods: We retrospectively evaluated 1034 patients with advanced cancer treated with ICI from 2011 to 2017. We calculated LMR as ratio of absolute lymphocyte/monocyte counts at baseline and median of 21 days after first cycle of ICI (on-treatment LMR) and considered low if &lt; 2. Overall survival (OS) was calculated from the initiation of ICI to date of death or censored at last follow-up. Median OS with 95% confidence intervals (CI) was estimated using the Kaplan-Meier method. Log rank test was used for group comparison. Results: 536 pts (52%) with LMR &lt; 2 at baseline had shorted median OS compared to 498 (48%) with LMR≥2 (median OS 8.4 months vs 17.8 months, p &lt; 0.001). Of 1034 pts with baseline LMR, 837 had follow up LMR evaluable. In patients with baseline and on-treatment LMR, those with baseline LMR &lt; 2, who had on treatment LMR ≥2, had OS of 16.8 months (95% CI 10.3-23.5) compared to median OS 8.0 months (95% CI 6-9.4) for patients with on treatment LMR &lt; 2 after first cycle of ICI, p &lt; 0.001. Patients with baseline LMR≥2, who had on treatment LMR ≥ 2, had median OS of 23 months (95% CI 19.7-28.9), but median OS was 9.4 months (95% CI 7.1-11.1) for patients with on-treatment LMR &lt; 2 after first cycle of ICI, p &lt; 0.001. Conclusions: We observed a statistically significant association between not only baseline LMR but also change in LMR from baseline after first cycle of ICI and overall survival in cancer patients treated with ICI. The role of LMR at baseline and on-treatment LMR should be evaluated in further studies incorporating known additional prognostic factors for ICI therapy. [Table: see text]
Cabozantinib in combination with atezolizumab in urothelial carcinoma previously treated with platinum-containing chemotherapy: Results from cohort 2 of the COSMIC-021 study.
Authors: Sumanta K. Pal, Neeraj Agarwal, Yohann Loriot, Cristina Suarez Rodriguez, Parminder Singh, Ulka N. Vaishampayan, Elizabeth Mcilvaine, Dominic Curran, Daniel Castellano, Andrea Necchi
Journal: Journal of Clinical Oncology (2020)

5013 Background: Cabozantinib (C), an inhibitor of MET, AXL, and VEGFR, has been shown to promote an immune-permissive environment and has shown promising clinical activity in combination with immune checkpoint inhibitors (ICIs) in solid tumors including renal cell carcinoma and urothelial carcinoma (UC). ICI monotherapy is approved for patients (pts) with locally advanced or metastatic UC with disease progression after platinum-containing chemotherapy. COSMIC-021, a multi-center phase 1b study, is evaluating the combination of C with atezolizumab (A) in various solid tumors (NCT03170960). We report results from Cohort 2 in UC pts with prior platinum-containing chemotherapy. Methods: Eligible pts had ECOG PS 0-1 and had progressed on or after a platinum-containing chemotherapy (including pts with disease recurrences &lt; 12 months after the end of perioperative chemotherapy). Pts received C 40 mg PO QD and A 1200 mg IV Q3W. CT/MRI scans were performed Q6W for first year and Q12W thereafter. The primary endpoint is objective response rate (ORR) per RECIST v1.1 by investigator. Other endpoints include safety, duration of response (DOR), PFS, and OS. Results: As of Dec 20, 2019, 30 pts with advanced UC were enrolled with a median follow-up of 16.5 mo (range 12, 21). Median age was 66 yrs (range 44, 84), 73% were male, and 60% had ECOG PS 1. Primary tumor sites were bladder (80%), renal pelvis (10%), and ureter (10%); the most frequent metastatic sites included lung (40%) and liver (27%). Fourteen pts (47%) had received ≥2 prior systemic anticancer therapies. The most common treatment-related AEs (TRAEs) of any grade were asthenia (37%), diarrhea (27%), decreased appetite (23%), increased transaminases (23%), and mucosal inflammation (20%). Grade 3/4 TRAEs occurred in 57% of pts, with no grade 5 TRAEs. Confirmed ORR per RECIST v1.1 was 27% (8 of 30 pts), including 2 pts with CR. DCR (CR+PR+SD) was 64%. Median DOR was not reached, with the longest DOR ongoing at 14.3+ mos. Median PFS was 5.4 mo (range 0.0+, 17.3+). Conclusions: C in combination with A demonstrated encouraging clinical activity in pts with advanced UC with an acceptable safety profile. Additional cohorts of pts with advanced UC are being explored in the study. Clinical trial information: NCT03170960 .
Strengthen prevention and control for tuberculosis
Authors: 端木宏谨
Journal: BMJ (2006)

结核病俗称痨病,是由结核分枝杆菌引起的传染性疾病,1882年Koch发现结核杆菌为结核病的病原菌,1896年命名为结核分枝杆菌.感染结核分枝杆菌后约有十分之一的人在一生中有发生结核病的危险,人体许多脏器可以发生结核病,以肺结核病最常见。
股骨头坏死的影像学表现
Authors: 刘霞, 屈辉
Journal: BMJ (2006)

骨坏死(osteonecrosis)是指骨的活性成分(骨细胞、骨髓造血细胞及脂肪细胞)死亡的病理过程[1].骨坏死最易发生于股骨头,2003年4月至6月的严重急性呼吸综合征(SARS)患者在使用大量激素治疗后,很多患者和医护人员发生骨坏死,其中在我院检查的456例患者中有136例发生骨坏死,发生率为30%[2]。
Magseed localisation for loco-regional breast and lymph node recurrences: Placement prior to chemotherapy to allow focused removal of the initially diseased tissue.
Authors: Carol Benn, Dominic van Loggerenberg, Vernon Adrian robert Shaw
Journal: Journal of Clinical Oncology (2020)

e12610 Background: Multi-disciplinary meeting decisions may suggest chemotherapy prior to surgery. Prior to chemotherapy, localisation of the diseased tissue is important to ensure accurate retrieval. Magseed is induced to become a magnet when used in conjunction with a detector. The aim of this study was to assess the accuracy of placement, retrieval, and localisation of a Magseed into a radiologically suspicious loco-regional recurrence in patients requiring chemotherapy. Methods: Patients with loco-regional recurrence that had been assessed in the multidisciplinary meeting as requiring chemotherapy, as well as being potential candidates for surgery post-chemotherapy, were referred for placement of a Magseed prior to commencing chemotherapy or during treatment. The seed was placed by a senior radiologist in the unit. Ten patients have currently completed chemotherapy and surgery. Two patients had more than one Magseed placed. Giving a total seed placement number of 14 seeds. Results: Seed localisation with the Sentimag probe was successful in all cases at 100% localisation, however the retrieval rate was less at 93% due to a case where a lymph node underwent fibrosis. The maximum number of days between the seed placement and surgery was 249 days. Conclusions: Magseed is successful and accurate in localising and retrieving loco-regional recurrences in patients requiring surgery post chemotherapy. Retrieval is possible due to high recordings on the sensor in all cases. Magseed thus provides the treating clinician with an alternative to conventional radiological markers with the added benefit of a single placement to retrieval methodology.
Predictive value of CT signs in the diagnosis of benign and malignant thyroid nodules
Authors: Jian Zhou, Xufeng Lai, Zhijiang Han
Journal: BMJ (2018)

Objective
To investigate the predictive value of multiple CT signs in the diagnosis of benign and malignant thyroid nodules.


Methods
The CT data of 1 009 nodules with diameter >1.0 cm confirmed by histology from 931 patients was retrospectively analyzed, including 548 benign nodules from 484 patients and 461 malignant nodules from 447 patients. According to the inspection time, all nodules were divided into model group (2009—2014) and test group (2015—2016). The distribution of nodules with irregular shape, bite cake syndrome, micro calcification, enhanced range reduction/blur, cystic and high enhancement were evaluated in two groups. Univariate and multivariate logistic regression analysis were performed to evaluate the predicting value of multiple CT sighs for benign and malignant thyroid nodules in two groups.


Results
The numbers of benign and malignant nodules were 252 and 233 in model group, and were 296 and 228 in test group. The univariate logistic analysis of the model group and the test group showed that irregular shape, bite cake syndrome, micro calcification, enhanced range reduction/blur were more common in malignant nodules. OR values were 4.172 and 6.327, 3.927 and 3.493, 5.354 and 6.674, 11.814 and 5.082, 8.680 and 14.562, respectively. The areas under the predicted probability curve were 0.946 and 0.936, respectively. The micro calcification was an independent predictive factor in the multivariate logistic regression analysis in the model group but not in the test group.


Conclusion
Irregular shape, bite cake syndrome and enhanced blur/range reduction are the CT signs of the stable malignant nodules, cystic and high enhancement are the CT signs of stable and benign nodules. Combination of multiple CT signs could improve the accuracy of diagnosis for Benign and Malignant Thyroid Nodules.


Key words: 
Thyroid neoplasms; Goiter, nodular; Caleifieation; Cicatrix, hypertrophic