tbuckley/cabot-search huggingface dataset:
Patient trial matching using pseudo-siamese network.
Authors: Cao Xiao, Junyi Gao, Lucas Glass, Jimeng Sun
Journal: Journal of Clinical Oncology (2020)

e14050 Background: Clinical trials suffer from insufficient patient (pt) recruitment. The availability of electronic health records (EHR) and trial eligibility criteria (EC) is promising for data driven pt-trial matching. The objective is to find qualified pt given patients' EHR and trial EC in unstructured text EC. Pseudo-Siamese network is a novel subfield within information retrieval and has shown great success in the cross-modal information retrieval problems such as semantic image-text retrieval (e.g., match images with text descriptions). The objective is to find the match between pts and clinical trials using Pseudo-Siamese network based cross-modal retrieval. Our model addresses the following challenges: (1) How to match unstructured EC text with structured EHR where EC often encode more general disease concepts and EHR represent pt conditions using more specific medical codes. (2) How to capture pts' evolving health conditions. (3) How to explicitly handle the difference for inclusion and exclusion criteria. Methods: Our matching model addresses these challenges as follows: (1) we augment the medical codes in pts’ records with their textual descriptions and hierarchical taxonomies, such that concepts can be embedded in finer and more coarse levels for better concept alignment across pt data and ECs. (2) We include an attentive dynamic memory network that extracts the best matching and more recent pt EHR to match with ECs. (3) We introduce a composite loss term to maximize the similarity between pt records and inclusion criteria while minimizes the similarity between pt records and exclusion criteria. Results: We evaluated our model on a pt-trial match dataset on the ECs collected from 590 clinical trials from ClinicalTrials.gov. We also extract 83,371 pt claims data from IQVIA database collected (2002-2018), where each pt is eligible for at least one trial. We compared our model with leading pt-trial matching models. Our model significantly outperforms the best baseline model by 24.3% relatively higher accuracy score. We also tested these models in 34 oncology trials in 25 cancers. Results will be reported. Conclusions: Pseudo-Siamese network successfully solved the cross-modal information retrieval problems. We therefore propose a new pt-trial matching model based on Pseudo-Siamese network model. Experiments on real-world datasets demonstrated that our model significantly outperforms existing works in pt-trial matching for oncology trials.
小梁切除术后滤过量的早期物理干预
Authors: 荣世松, 孟海林, 梁远波, 王宁利
Journal: BMJ (2012)

小梁切除术是治疗青光眼的重要手段.对术后早期(术后1或3个月内)滤过量及眼压的把握是其关键环节,而早期物理干预(包括眼球按摩、激光断线、缝线拆除等)的作用不可替代.缝线拆除及激光断线技术允许术者术中紧密地关闭巩膜瓣限制滤过量,可减少术后短期强滤过相关的并发症.眼球按摩可进一步调控眼压,但在3个月后效果减弱。
PCR-based comprehensive genomic profiling (PCR-CGP): Feasibility from &gt;20,000 tumor tissue specimens (TTS) and predicted impact on actionable biomarker identification versus hybrid capture (H)-CGP and plasma (P)-CGP.
Authors: Dan Rhodes, Daniel H Hovelson, Jennifer Marie Suga, Daniel M. Anderson, Elizabeth Claire Dees, Han A. Koh, Mark E. Burkard, Jamil Khatri, Malek M. Safa, Marc Ryan Matrana, Eddy Shih-Hsin Yang, Alex R. Menter, Benjamin Marshall Parsons, Jennifer Nadine Slim, Jayson Falkner, Travis Reeder, Hana Vakil, Kat Kwiatkowski, Bryan Johnson, Scott A. Tomlins
Journal: Journal of Clinical Oncology (2020)

3574 Background: Tissue-based h-CGP is increasingly utilized for treatment selection in patients with advanced solid tumors but has high tumor surface area [TSA] requirements (≥25mm 2 for leading commercial tests). P-CGP is recommended when tissue is insufficient for H-CGP. Here we assessed the feasibility and clinical impact on actionable biomarker identification of PCR-CGP. Methods: We performed a post-hoc, non-prespecified analysis on 21,743 consecutive subjects with advanced solid tumors who sent TTS for PCR-CGP from 5/17-12/19 as part of an ongoing observational trial at &gt; 20 U.S. health systems (NCT03061305). PCR-CGP was performed using StrataNGS, a single-site laboratory developed test assessing all CGP biomarker classes (including microsatellite instability (MSI) status and tumor mutation burden [TMB]). We predicted actionable biomarker identification rates for PCR-CGP, H-CGP and P-CGP if applied to all U.S. patients with advanced solid tumors through incorporating population incidence, biomarker frequencies, test TSA and tumor content requirements (or cfDNA detection rates), and performance characteristics. Actionable biomarkers were the 30 in 11 tumor types from the MolDX p-CGP local coverage determination (L38043), pan-tumor NTRK fusions and MSI, and TMB in lung cancer. Results: Among TTS from 21,734 patients with advanced cancer, 20,493 (94.3%) met TSA requirements for PCR-CGP (≥2mm 2 ) vs. 9,281 (42.7%) for H-CGP. PCR-CGP reported results for 98.0% and 95.0% of patients with large (≥25mm 2 TSA) and small (2-24mm 2 ) TS, respectively, in a median of 7 business days. Compared to 1,882 orthogonal actionable biomarker results, PCR-CGP accuracy was 96.6% and 96.5% in large and small TTS, respectively. Actionable biomarker frequency was highly correlated in PCR-CGP tested large vs. small TTS (r 2 = 0.99), as well as in this PCR-CGP cohort vs. a MSKCC institutional pan-cancer H-CGP cohort (r 2 = 0.92). If applied to all U.S. patients with advanced solid tumors, PCR-CGP has significantly greater predicted actionable biomarker identification rate (88.5%) compared to P-CGP (77.0%, N-1 chi-squared test, p &lt; 0.0001) or H-CGP (54.3%, p &lt; 0.0001). Conclusions: Half of TTS submitted for PCR-CGP did not meet H-CGP tissue requirements. PCR-CGP is feasible for the vast majority of patients and is predicted to expand the actionable biomarker evaluable proportion of patients with advanced solid tumors compared to H-CGP or P-CGP. Clinical trial information: NCT03061305 .
Effects of extravascular lung water on severity of illness and survival of patients with acute respiratory distress syndrome
Authors: Xiao-yan Wu, Zhi-qing Zhuang, Qi-hong Chen, Nian-fang Lu, Hua Lin
Journal: BMJ (2013)

Objective
To evaluate the relationship between the extravascular lung water (EVLW) and other markers of lung injury and determine whether or not EVLW predicts survival in patients with acute respiratory distress syndrome (ARDS) and examine if indexing EVLW with predicted body weight (EVLWp) strengthens its discriminative power.


Methods
EVLW and other markers of lung injury [including: PaO2/FiO2 (P/F), oxygenation index (OI) = mean pressure (Pm) ×FiO2×100/PaO2, static compliance (Cst) and lung injury score (LIS)] were measured prospectively for 3 days in 27 patients with early ARDS between January 2011 and December 2011 at intensive care units (ICU) of Subei People's Hospital. The relationship between indexing EVLW with actual body weight (EVLWa), EVLWp and other markers of lung injury, the 28-day mortality were evaluated.


Results
Acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), fluid balance in first 3 days, days of mechanical ventilation and ICU stay were significantly higher on admission in nonsurvivors compared with survivors (P 0.05). ROC curve analysis indicated that EVLWp (0.759, P 0.05) discriminated between survivors and nonsurvivors. Three-day average EVLWp ≥12.5 ml/kg predicted the 28-day mortality with 62.5% specificity and 80% sensitivity.


Conclusion
Increased extravascular lung water is a feature of early ARDS and predicts survival. EVLWp, instead of EVLWa, improves the predictive value of extravascular lung water for survival and it is correlated with markers of disease severity.


Key words: 
Pulmonary edema; Respiratory distress syndrome, adult; Prognosis
Relationship between care burden and social support among family caregivers of disabled elders in Beijing urban area
Authors: Wei Xu, Chenguang Qian, Xinmei Liu, Shuang Shao
Journal: BMJ (2015)

Objective
To explore the relationship between care burden and social support among family caregivers of disabled elders in Beijing urban area.


Methods
A cross-sectional survey based on convenience sampling was conducted among 744 family caregivers in Dongcheng District in Beijing urban area. All subjects were interviewed by the Zarit Burden Interview (ZBI), Social Support Rating Scale (SSRS) and general social and demographical material lists. And then we analyzed the correlation between social support and care burden.


Results
The mean scores of ZBT and SSRS were (40.3±15.2) and (31.1±6.9) respectively. And a negative correlation existed between the level of caregiver burden and total social support. The care burden of disability elders was negatively associated with objective support, subjective support and social support availability (P<0.05).


Conclusions
There is a close relationship between care burden and social support among family caregivers of disabled elders. The more objective support, subjective support and social support availability the caregivers acquire, the less burden they bear.


Key words: 
Aged; Family caregivers; Care burden; Social support
Large scale clinico-genomic analyses among patients with BRAF-mutated non-small cell lung cancers (NSCLC) identified by nationwide genomic screening project (LC-SCRUM-Japan).
Authors: Tetsuya Sakai, Shingo Matsumoto, Taku Nakagawa, Kadoaki Ohashi, Hidetoshi Itani, Masato Shingyoji, Atsushi Nakamura, Ryo Toyozawa, Masahide Mori, Takeshi Tuda, Yuichiro Ohe, Tomohiro Sakamoto, Terufumi Kato, Takaya Ikeda, Yoshitaka Zenke, Hibiki Udagawa, Keisuke Kirita, Kiyotaka Yoh, Seiji Niho, Koichi Goto
Journal: Journal of Clinical Oncology (2020)

9590 Background: BRAF mutations are functionally classified into three groups, comprisingV600-mutant kinase-activating monomers (class I), kinase-activating dimers (class II), kinase-inactivating heterodimers (class III). The difference of clinical outcomes and concomitant genetic alterations among the three classes in non-small cell lung cancers (NSCLC) are unclear. Methods: We have prospectively analyzed NSCLC patients (pts) for cancer-related genes by a next-generation sequencing system, Oncomine™ Comprehensive Assay, in a large-scale genome screening project in Japan (LC-SCRUM-Japan). The clinical characteristics and outcomes of pts with BRAF-mutated non-squamous (non-sq) NSCLC were comparatively evaluated among the three classes of BRAF mutations. Results: A total of 5166 non-sq NSCLC pts were enrolled into the LC-SCRUM-Japan from 2015 to 2019. BRAF mutations were detected in 176 pts (3%). Among the 176 pts, 153 (87%) were classified into the three classes according to the mutation variants, including 65 (42%) into class I, 52 (34%) into class II and 36 (24%) into class III. The remaining 23 were not classified into any of the three classes. Compared with class I, class II or class III was significantly associated with smoking (P = 0.02 and &lt; 0.01, respectively). Concomitant RAS mutations were significantly more frequent in class II and class III than in class I (P &lt; 0.01 and = 0.04, respectively). The frequency of concomitant STK11 mutations was significantly higher in class III than in others (P &lt; 0.01, respectively). There was no significant difference in the frequency of other oncogene and tumor suppressor gene mutations among the three classes. In the 1 st -line platinum-containing chemotherapies for advanced or recurrent cases, median progression-free survival (mPFS) of class III pts was shorter than class I or class II pts (4.2, 11.5 and 4.8 months, I vs III; P &lt; 0.01, II vs III; P = 0.06). In the treatment with 2 nd -4 th line PD-1/PD-L1 inhibitors, mPFS was not significantly different among the three classes. Overall survival of class III pts was significantly shorter than class I pts (11.9 vs 35.2 months, P = 0.03). Conclusions: Concomitant gene mutations and clinical features are largely different among the BRAF mutation classes. Especially in class III, concomitant RAS and STK11 mutations are more frequent and clinical outcomes were significantly less favorable. These results suggest the need of novel therapeutic strategy based on the mutation class for BRAF-mutated lung cancers.
Abstract 12001: Cardiac Troponin T and N-terminal Pro-B-type Natriuretic Peptide for Detection of Myocardial Ischemia Among Patients With Suspected Stable Angina
Authors: Peder L Myhre, Helge Rosjo, Sebastian I Sarvari, Heikki J Ukkonen, Frank E Rademakers, Jan E Engvall, Tor-Arne Hagve, Eike C Nagel, Rosa Sicari, Jose Zamorano, Mark J Monaghan, Jan d’Hooge, Thor Edvardsen, Torbjoern Omland
Journal: Circulation (2019)

Introduction: Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have both been associated with myocardial ischemia, but it remains unclear whether this is directly...
Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer
Authors: Neal D. Shore, Fred Saad, Michael S. Cookson, Daniel J. George, Daniel R. Saltzstein, Ronald Tutrone, Hideyuki Akaza, Alberto Bossi, David F. van Veenhuyzen, Bryan Selby, Xiaolin Fan, Vicky Kang, Jackie Walling, Bertrand Tombal
Journal: New England Journal of Medicine (2020)

Injectable luteinizing hormone-releasing hormone agonists (e.g., leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect. The efficacy and safety of relugolix, an oral gonadotropin-releasing hormone antagonist, as compared with those of leuprolide are not known.In this phase 3 trial, we randomly assigned patients with advanced prostate cancer, in a 2:1 ratio, to receive relugolix (120 mg orally once daily) or leuprolide (injections every 3 months) for 48 weeks. The primary end point was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary end points included noninferiority with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 15. Testosterone recovery was evaluated in a subgroup of patients.A total of 622 patients received relugolix and 308 received leuprolide. Of men who received relugolix, 96.7% (95% confidence interval [CI], 94.9 to 97.9) maintained castration through 48 weeks, as compared with 88.8% (95% CI, 84.6 to 91.8) of men receiving leuprolide. The difference of 7.9 percentage points (95% CI, 4.1 to 11.8) showed noninferiority and superiority of relugolix (P<0.001 for superiority). All other key secondary end points showed superiority of relugolix over leuprolide (P<0.001). The percentage of patients with castrate levels of testosterone on day 4 was 56.0% with relugolix and 0% with leuprolide. In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone levels 90 days after treatment discontinuation were 288.4 ng per deciliter in the relugolix group and 58.6 ng per deciliter in the leuprolide group. Among all the patients, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group (hazard ratio, 0.46; 95% CI, 0.24 to 0.88).In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095.).
Balixafortide (a CXCR4 antagonist) plus eribulin in HER2 negative metastatic breast cancer: Dose-response analysis of efficacy from phase I single-arm trial.
Authors: Peter A. Kaufman, Sonia Pernas Simon, Miguel Martin, Marta Gil-Martin, Patricia Gomez Pardo, Sara Lopez-Tarruella, Luis Manso, Eva Ciruelos, Jose Alejandro Perez-Fidalgo, Cristina Hernando, Foluso Olabisi Ademuyiwa, Katherine N. Weilbaecher, Ingrid A. Mayer, Timothy J. Pluard, Maria Martinez Garcia, Linda T. Vahdat, Francois Philippe Ringeisen, Alexandra Bobirca, Javier Cortes
Journal: Journal of Clinical Oncology (2020)

e15209 Background: Balixafortide (B) is a potent, selective antagonist of the chemokine receptor CXCR4. High CXCR4 levels correlate with aggressive metastatic phenotypes and poor prognosis in metastatic breast cancer (MBC). Efficacy and safety data were published recently from the Phase 1 trial investigating B + eribulin (E) in patients with HER2 negative MBC 1 . We report the final efficacy analyses from this trial, including assessment of dose-response. Methods: In this single-arm, dose escalation trial, patients (pts) received E + increasing doses of B using a 3+3 design in 3 parts: Part I (cohorts received low E doses); Part II (dose-escalation cohort for B [1−5.5mg/kg] + 1.4mg/m 2 E); Expanded Cohort (EC; 5.5mg/kg B + 1.4mg/m 2 E) to confirm safety and efficacy. Results: At entry, all 56 women (age range 33−82 years) were HER2-negative (IHC and/or FISH), CXCR4 positive. The majority were Caucasian. Most pts were heavily pre-treated in the metastatic setting (line of chemotherapy on study: 29% 2 nd line, 50% 3 rd line, 21% 4 th line). 75% were hormone receptor positive and 23% had triple negative breast cancer. Conclusions: A consistent dose response effect for B + E was suggested in heavily pretreated pts with HER2 negative MBC across all efficacy endpoints. A comparison of these efficacy results, and particularly response data, with single agent data for E in similar populations 2, 3 showed that pts in the EC had a more profound benefit observed consistently throughout all efficacy endpoints. Further data and analysis will be forthcoming for presentation. 1. 3 patients from Part II also included in EC because they received the B dose selected for EC (5.5mg/kg). 2. Part I was an initial safety run-in with lower E doses, and so is not included in the table. 1. Pernas S et al. Lancet Oncol. 2018; 19: 812−24 2. Cortes J et al. Lancet. 2011; 377: 914−923 3. Kaufman PA et al. J Clin Oncol. 2015; 33: 594−601. Clinical trial information: NCT01837095 . [Table: see text]
A pilot study of Bruton’s tyrosine kinase inhibitor ibrutinib alone and in combination with PD-1 inhibitor nivolumab in patients with metastatic solid tumors.
Authors: Brooke Benner, Dionisia Marie Quiroga, Logan Good, Steven Sun, Himanshu Savardekar, Megan Christina Duggan, Bhavana Konda, Claire F. Verschraegen, Kari Lynn Kendra, Manisha H. Shah, Robert Rupert, Paul Monk, Hiral A. Shah, Anne M. Noonan, Kristin Leigh Bixel, John L. Hays, Gregory Behbehani, Maciej Pietrzak, William Edgar Carson, Robert Wesolowski
Journal: Journal of Clinical Oncology (2020)

3111 Background: Myeloid-derived suppressor cells (MDSC) are expanded in cancer and promote immune suppression. We have shown that ibrutinib inhibits migration and immunosuppressive function of MDSC. Moreover, the combination of ibrutinib and a PD-L1 inhibitor has been found to have synergistic anti-tumor effects in a multiple solid tumor mouse models. Therefore, we conducted a pilot study testing the combination of ibrutinib and nivolumab in patients with metastatic solid tumors. Methods: Sixteen patients with advanced solid tumors were recruited to this trial. Ibrutinib was dosed as an oral single agent, starting 7 days prior to cycle 1 of nivolumab and given until cycle 1, day 8 of nivolumab. Nivolumab was administered intravenously on days 1 and 15 on 28-day cycles. Patients had blood samples collected prior to initiation of ibrutinib, day 1 of cycle 1, day 8 of cycle 1, day 1 of cycle 2, and at the time of disease progression. From these specimens, we measured circulating MDSC levels, other circulating immune subsets, T cell proliferation, and cytokines/chemokines levels. Circulating MDSC levels were measured by mass spectrometry. T cell function was evaluated by CFSE to monitor proliferating cells by dye dilution and cytokine/chemokine levels were measured with a U-PLEX assay. Data were analyzed using two-tailed, paired Student's t-tests to assess statistical significance. Results: An increase in circulating MDSC (22% to 28%; SD 9.158) levels was observed following 7 days of single-agent ibrutinib compared to baseline. However, in combination therapy, MDSC levels decreased (19%; SD 13.17) prior to cycle 2. Despite increasing levels of circulating MDSC, T cell function improved throughout the study. Furthermore, plasma levels of chemokines associated with MDSC recruitment and migration significantly decreased with ibrutinib treatment (IL-12, CCL2, CCL3, and CCL4). Of the 16 patients, four achieved a partial response and four achieved stable disease. Median progression free survival was 3.5 months and median overall survival was 11.5 months. Conclusions: The combination of ibrutinib and nivolumab was well tolerated, demonstrated early signs of immune modulation, and showed preliminary signs of promising clinical activity in patients with metastatic solid tumors. Clinical trial information: NCT03525925 .
Breast cancer recurrence rate in patients treated for early breast cancer.
Authors: Cecilia Munguti, Miriam Claire Mutebi, Mukuhi Ng'ang'a, Ronald Wasike
Journal: Journal of Clinical Oncology (2020)

e12508 Background: Recurrence rates for early breast cancer vary in different studies from 7% to 18%. Recurrent breast cancer is associated with poorer outcome and higher mortality rates. The recurrence rate in the Kenyan population remains unknown despite high prevalence of known risk factors. Methods: Single institution retrospective study of all women (18 -75 years) treated for early breast cancer at a single center private tertiary unit from 2009 to 2017. Results: 239 patient records were reviewed. The mean age at diagnosis was 51 (SD13.1). 98% of women presented with a palpable breast lesion. The molecular sub-type’s prevalence was: ER/PR+ (76%), triple negative (12.1%), HER2+ (2.9%). The overall recurrence rate was 7.2%, 66% recurrences were loco-regional, while 27% were metastatic disease, with 61% of the recurrences being detected initially on clinical/ self-breast examination. 77% of the recurrences were in women with ER/PR+ molecular sub-types. Recurrences in women with DCIS (2/27) were invasive breast cancers. There were no identified risk factors on uni-variate and multivariate regression analysis which conferred a risk of breast cancer recurrence. Discussion: The mean age at diagnosis in this group is younger than the western average (65 - 75 years). Majority of the women presented with symptoms – a presentation that differs from that of countries with a national breast cancer screening program. The molecular distribution of breast cancers is comparable to western populations. Conclusions: Recurrence rate for early breast cancer in this series is 7.2%, which is comparable with documented western data, with majority of the recurrences being detected initially on clinical/self-breast examination.
Ondansetron Use in Pregnancy and Congenital Malformations
Authors: Alicia Saban, Philippe Deruelle, Thomas Boisrame
Journal: JAMA (2020)

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