tbuckley/cabot-search huggingface dataset:
The role of Systemic Inflammation Score (SIS) in BRAF(V600) mutant metastatic colorectal cancer (mCRC).
Authors: Nieves Martinez Lago, Marta Covela Rúa, Elena Brozos, Ana Fernandez Montes, Juan de La Camara Gomez, Carlos Méndez Méndez, Mónica Jorge Fernández, Antia Cousillas Castiñeira
Journal: Journal of Clinical Oncology (2020)

e16051 Background: Multiple studies have reported prognostic association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLT) and albumin levels in patients (pts) with colorectal cancer. However, it is unknown the prognostic impact in patients with BRAF(V600) mutant metastatic colorectal cancer (mCRC). Methods: Observational, retrospective, multicentric study pts with BRAF V600mt mCRC treated at 9 university Spanish hospitals in NW Spain, belonging to GITuD Group. Demographic, clinic, pathological characteristics, overall survival (OS) and progression free survival (PFS) data were retrospectively collected and analyzed. We calculated a Systemic Inflammation Score (SIS) summing the number of risk factors that each patient had: albumin levels &lt;3.6 g/dL, Hemoglobin levels &lt;12.5, Neutrophil to Lymphocyte ratio (NLR) &gt;3 and Platelet to lymphocyte ratio (PLR) &gt;175. Results: We recorded data from 71 pts between November 2010 to June 2018. Median age was 62.0 years (range 31-83y), 54.9% female, 73.2% ECOG PS0-1, 49.3% right-sided, 37.3% high grade, 70.4% synchronous presentation, 64.8% primary tumor resection. Median OS was 11.9 months (m) (95% CI, 9.7-14.0 (m)). Pts with higher NLR (&gt;3) had a significantly lower OS: 7.8 vs 13.7 (m) HR 1.934 (95% CI 1.2-3.3) p = 0.014, which was also true for pts with low Hb (&lt;12.5g/dL): OS 9.0 vs 13.0 (m) (HR 1.767,95% CI 1.1-3.0 p = 0.035) and low albumin (&lt;3.6 g/dL): OS 4.9 vs 12.5 (m) (HR 2.142; 95% CI 1.1-4.5, p = 0.040). Pts. with higher PLR (&gt;175) was associated with a non-significant trend worse OS: 5.7 vs 13.5 (m) (HR 1.555; 95% CI 0.9-2.7, p = 0.102). SIS was associated with a worse prognosis: median OS 0/1/2/3/4 factors were 16.7 vs. 11.0 vs. 11.4 vs. 4.8 vs. 4.0 (m) (p = 0.006). Pts with SIS = 0 had significantly higher OS: 16.7 vs 9.0 (m) (HR 0.357; 95% CI 0.3-0.9; p = 0.027). First-line PFS was 4.4 (m) (95% CI, 3.2-5.7 months). First line PFS according type of treatment: Bev+Triplet-CT/Bev+Doublet-CT/antiEGFR+Doublet-CT/Doublet-CT: 8.0 vs 4.8 vs 2.9 vs 2.1 (m) (p = 0.091). BEV based CT was associated with a prolonged first line PFS: median 5.2 vs. 2.3 (m) (HR 0.562; 95% CI, 0.3-0.9; p = 0.033). BEV based CT was associated with prolonged first-line PFS in SIS Score 1-4: 4.8 vs. 2.3 (m) (HR 0.426; 95% CI 0.2-0.8; p = 0.009). Nevertheless, we don’t identify differences in first-line PFS in SIS Score 0: 7.0 vs 2.1 (m) (HR 0.803; 95% CI 0.3-2.5; p = 0.700). Conclusions: SIS identifies a population with a worse prognosis and subsidiary of improvement in First-line PFS with BEV based CT.
血小板计数常可提供诊断线索
Authors: 陈绍潞
Journal: BMJ (2010)

阅读血常规报告,我们一般都重视白细胞及其分类和血红蛋白数值的高低,但血小板计数异常也常可给诊断提供重要线索. 对无明显血红蛋白降低及无白细胞异常的患儿,如发现血小板计数明显降低,有出血倾向时,应考虑血小板减少性紫癜,其中以免疫性血小板减少性紫癜最常见,患者常近期曾有感染.由于血小板被免疫抗体破坏过多,骨髓代偿性产生新的血小板,新生血小板体积较大,可在血常规报告中有反映。
Application of IMDC criteria across first-line (1L) and second-line (2L) therapies in metastatic renal-cell carcinoma (mRCC): New and updated benchmarks of clinical outcomes.
Authors: Shaan Dudani, Chun Loo Gan, Connor Wells, Ziad Bakouny, Nazli Dizman, Sumanta K. Pal, Lori Wood, Christian K. Kollmannsberger, Bernadett Szabados, Thomas Powles, Benoit Beuselinck, Frede Donskov, Aaron Richard Hansen, Georg A. Bjarnason, Christina M. Canil, Sandy Srinivas, Neeraj Agarwal, Elizabeth Chien Hern Liow, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2020)

5063 Background: In patients with mRCC, the International mRCC Database Consortium (IMDC) criteria have been validated as a prognostic tool in patients treated with targeted therapy in the 1-4L settings and with 2L Nivolumab (Nivo). However, it is unknown whether the IMDC criteria can be used to risk stratify in recently approved 1L IO combination therapies, including Ipilimumab + Nivolumab (IOIO) and Axitinib + Pembrolizumab/Avelumab (IOVE). We sought to assess the ability of the IMDC criteria to risk stratify with the use of novel 1L IO combinations and provide updated benchmarks for older 1L and 2L treatments. Methods: Patients with mRCC starting systemic therapy between 2010-2019 were identified through the IMDC. IMDC risk score was calculated at the time of starting the line of therapy of interest. The primary endpoint was overall survival (OS) from time of initiating the treatment of interest. Results: From a total of 6596 unique patients, 5043 treated in the 1L setting and 2498 treated in the 2L setting were included in the analysis. Across the entire cohort, median age was 61, 73% were male, 16% had sarcomatoid features, 79% underwent nephrectomy and 88% had clear-cell histology. IMDC risk groups for 1L and 2L treatment were 17%, 57%, 27% and 10%, 60%, 30% for favourable-, intermediate- and poor-risk disease, respectively. IMDC criteria appropriately risk stratified into 3 prognostic groups in 1L IOIO and 1L IOVE combinations, in addition to older treatments: 1L VEGF TT, 2L VEGF TT, 2L Nivo and 2L Everolimus. Results are displayed in Table. Due to the novelty of 1L IO combinations, median follow up time was shorter and thus landmark OS values are presented. Conclusions: IMDC criteria may be used to risk stratify in recently approved 1L IO combination therapies in addition to older 1L and 2L treatments. These data provide contemporary benchmarks for OS that may be used for patient counseling and trial design. [Table: see text]
The neuropeptide VIP confers anticipatory mucosal immunity by regulating ILC3 activity (vol 78, pg 567, 2019)
Authors: Cyril Seillet, Kylie Luong, Julie Tellier, Nicolas Jacquelot, Rui Dong Shen, Peter Hickey, Verena C Wimmer, Lachlan Whitehead, Kelly Rogers, Gordon K Smyth, Alexandra L Garnham, Matthew E Ritchie, Gabrielle T Belz
Journal: Nature Immunology (2020)
Alternatives to Invasive Ventilation in the COVID-19 Pandemic
Authors: Bhakti K. Patel, John P. Kress, Jesse B. Hall
Journal: JAMA (2020)

Bruno L. Ferreyro, MD; Federico Angriman, MD, MPH; Laveena Munshi, MD, MSc; Lorenzo Del Sorbo, MD; Niall D. Ferguson, MD, MSc; Bram Rochwerg, MD, MSc; Michelle J. Ryu, MLIS; Refik Saskin, MSc; Hannah Wunsch, MD, MSc; Bruno R. da Costa, MSc, PhD; Damon C. Scales, MD, PhD
Clinical perspectives of "schism" between treatment and prevention
Authors: 曾昭耆
Journal: BMJ (2006)

弥合裂痕(healing the schism)这个词,始见于美国流行病学家卡尔·怀特1991年出版的一本书名.他在该书中系统分析了公共卫生和临床医学从统一到分离的过程,分离的后果和重新结合起来的必要性.在此,主要从临床角度做一些相关的讨论。
心搏骤停的院前急救--脑复苏和脑保护
Authors: 冯庚
Journal: BMJ (2005)

心肺复苏的最佳结果是恢复患者脑皮质的高级活动,进而使其能够正常生活和工作,脑功能的恢复是复苏成败的关键和终极目标.自70年代以来医学界已把心肺复苏(CPR)发展为心肺脑复苏(CPCR),因此,现代心肺复苏实际上指心肺脑复苏.目前心脏复跳之后患者脑皮质功能的恢复仍然是难题,Safar教授报道没有使用监护器的院内患者心肺复苏成功后最终生存而且没有脑损伤者不足10%.传统观念认为,大脑耐受循环完全停止的时间极限是4～5 min,但近年来有基础研究提示,经积极治疗脑缺血20 min后仍可获得功能以及组织学恢复,但这只是在实验室得出的结果,目前在院前急救中尚未见到常温下心搏骤停超过10 min而脑复苏成功病例.20%～50%的心肺复苏成功患者会遗留不同程度的脑损害,院前急救时脑复苏研究任重而道远。
High flow oxygen for dyspnea in hospitalized patients with cancer: A 4x4 crossover randomized clinical trial.
Authors: David Hui, Farley Hernandez, Saji Thomas, Zhanni Lu, Ahmed F. Elsayem, Dave Balachandran, Lara Bashoura, Eduardo Bruera
Journal: Journal of Clinical Oncology (2020)

12077 Background: Dyspnea is common in hospitalized cancer patients and highly distressing. High flow oxygen (HFOx) is administered for oxygenation in this setting; however, its effect on dyspnea has not been well examined, particularly among non-hypoxemic patients. In this phase II trial, we assessed the effect of HFOx, high flow air (HFAir), low flow oxygen (LFOx) and low flow air (LFAir) on dyspnea. We hypothesized that HFO and HFA can alleviate dyspnea. Methods: This double-blind, 4x4 crossover clinical trial enrolled hospitalized patients with cancer who were dyspneic (NRS ≥3 at rest) and non-hypoxemic (SpO2&gt;90% on room air). Patients were randomized to 10 minutes of HFOx, HFAir, LFOx and LFAir in different orders. The flow rate was titrated between 20-60 L/min in the high flow groups and 2 L/min in the low flow groups. The primary outcome was dyspnea 0-10 numeric rating scale (NRS) “now”, where 0=none and 10=worst. Secondary outcomes included modified Borg scale dyspnea intensity and unpleasantness, adverse effects, and overall preference. We compared among the interventions with a linear mixed model adjusting for time, treatment effect, period effect and carryover effect. Results: 17 patients completed 55 interventions in a random order. Mean age 51, 58% female, mean baseline dyspnea NRS 6.3 (SD 1.7). The absolute change of dyspnea NRS between 0 and 10 minutes was -1.8 (SD 1.7) for HFOx, -1.8 (2.0) for HFAir, -0.5 (0.8) for LFOx and -0.6 (1.2) for LFAir. In mixed model analysis, HFOx group provided greater dyspnea relief than LFOx (mean difference [95% CI] -0.80 [-1.45, -0.15], P=0.02) and LFAir (-1.24 [-1.90, -0.57], P&lt;0.001). HFAir also provided a significantly greater dyspnea relief than LFOx (-0.95 [-1.61, -0.30], P=0.005) and LFAir (-1.39 [-2.05, -0.73], P&lt;0.001). No difference was found between HFOx and HFAir nor between LFOx and LFAir. There was no significant carryover effect. Dyspnea Borg scale intensity and unpleasantness showed similar changes. Oxygen saturation increased in the HFOx group (97.2% to 99.7%) and LFOx group (95.5% to 98.2%) but not HFAir nor LFAir groups. HFOx was well tolerated. At the end of the study, 7 (54%), 4 (31%), 1 (8%) and 1 (8%) patients blindly preferred HFOx, HFAir, LFOx and LFAir, respectively. Conclusions: For the first time, we found that HFOx and HFAir provided a rapid and clinically significant reduction of dyspnea at rest in hospitalized cancer patients even when they were non-hypoxemic, supporting a role for high flow devices to provide palliation beyond oxygenation. Larger studies are needed to confirm these findings. Clinical trial information: NCT02932332 .
A qualitative study of barriers and facilitators to enrollment of adolescents and young adults onto cancer clinical trials at NCI community oncology research program (NCORP) sites.
Authors: Elizabeth Siembida, Holli Ann Loomans-Kropp, Irene Tami-Maury, Lillian Sung, Brad H. Pollock, David Robert Freyer, Michael Roth
Journal: Journal of Clinical Oncology (2020)

e19050 Background: Cancer clinical trials (CCTs) contribute to improving patient survival and quality of life; however, adolescents and young adults (AYAs, 15-39 years old), are underrepresented in CCTs, especially in the community setting. We aimed to identify barriers and facilitators to AYA CCT enrollment in the NCORP. Methods: We conducted 43 one-on-one semi-structured qualitative interviews with key stakeholders involved in the enrollment of AYAs across a diverse group of NCORP primary (n = 5) and affiliate (n = 10) sites. Interviews were conducted remotely by 3 trained interviewers using the Zoom platform. Stakeholders were recruited from high and low AYA enrolling sites (AYA/total site enrollments &gt; 10% and &lt; 3%, respectively). Stakeholders were overall NCORP Site PIs (n = 5), lead NCORP administrators (n = 4), clinical research associates (n = 11), medical and pediatric oncologists involved in the enrollment of AYAs (n = 7), regulatory research associates (n = 5), nurse navigators (n = 6), and patient advocates (n = 5). Interviews were audiotaped and transcribed. Thematic analysis was conducted to identify themes and relate them back to our primary research questions regarding barriers and facilitators to AYA CCT enrollment. Results: Stakeholder views on enrollment barriers centered on 5 main themes: (1) lack of site-level prioritization or discussion of AYA enrollment; (2) limited number of clinical trials for AYAs available nationally, with few trials opened locally; (3) insufficient resources and research staff; (4) concerns about the cost effectiveness of opening AYA trials due to low numbers of eligible patients; and (5) patient misconceptions about CCTs. Stakeholder views on enrollment facilitators centered on 3 main themes: (1) presence of an AYA program focused on increasing enrollment; (2) having a designated site AYA “champion”; and (3) having site leadership identify AYA enrollment as a priority. Stakeholders agreed that incentivizing AYA enrollments via increased reimbursement and/or study credits could potentially lead to increased enrollment. Conclusions: In addition to identifying multiple shared barriers to AYA CCT enrollment, our study also identified possible interventions for enrollment improvement, including designation of AYA “champions”, increased reimbursement for AYA enrollments, and improving AYA’s understanding of CCTs. Further studies are needed to assess the impact of interventions aimed at increasing AYA enrollment across the NCORP.
Dietary intake and eating patterns of young children with type 1 diabetes achieving glycemic targets
Authors: Seckold Rowen, Howley Peter, King Bruce R, Bell Kirstine, Smith Angela, Smart Carmel E, 张志巍, 赵映璇
Journal: BMJ (2019)

背景
相比常规糖尿病饮食指南推荐量，患1型糖尿病（T1D）的幼儿摄入饱和脂肪更多、水果和蔬菜更少。该年龄段儿童的常见特点之一是饮食时间和摄入量不确定，这影响着父母对其餐时血糖的管理方案。本小型研究旨在评估门诊T1D幼儿中血糖达标者的膳食摄入量和饮食习惯，探讨饮食模式与糖化血红蛋白（HbA1c）的关系。


方法
采用回顾性横断面研究方法，对澳大利亚一家儿童糖尿病服务中心7.0岁以下的T1D患儿（n=24）进行研究。收集患儿的基线资料、HbA1c、3天食物称重记录和进餐时间管理调查表。


结果
纳入符合条件的儿童22例（男性55%），平均年龄（4.9±1.3）岁（均数±标准差），HbA1c（47±10）mmol/mol（6.4%±0.9%），体质指数Z评分（0.8±0.9），糖尿病患病时间（1.7±1.1）年。结果显示，95%患儿在餐前注射胰岛素。主要营养摄入分布（能量摄入比例）：碳水化合物（48%±4%）、蛋白质（16%±2%）和脂肪（33%±5%），其中包括饱和脂肪（15%±3%）。大部分患儿没有达到蔬菜和瘦肉/蛋白质的摄入量建议（分别为0%和28%)。HbA1c与每日总碳水化合物、蛋白质或脂肪摄入量无相关性（P>0.05)。放牧模式（grazing pattern）（编者注：放牧模式指饮食的摄入量和膳食模式不受限制）下的儿童HbA1c水平明显高于正常膳食的儿童（平均61 mmol/mol比43 mmol/mol) (7.7%比6.1%)，P=0.01。


结论
T1D患儿饱和脂肪摄入量过多、蔬菜摄入量不足的饮食质量问题值得关注。我们的研究结果表明，血糖达标的患儿多在餐前给予胰岛素，并遵循规律的饮食模式。
Hepatic failure in malignancy: A nationwide analysis.
Authors: Binav Baral, Ishaan Vohra, Bashar Attar, Vatsala Katiyar, Prasanth Lingamaneni, Krishna Rekha Moturi, Shristi Upadhyay Banskota, Sindhu Janarthanam Malapati, Sunny R K Singh, Muhammad Zain Farooq, Sheeba Habeeb Ba Aqeel, Shweta Gupta
Journal: Journal of Clinical Oncology (2020)

e19257 Background: Hepatic failure (HeF) accounts for 6% of all liver-related mortality and 7% liver transplants (LT) in the US. Epidemiologically, while viral hepatitis, acetaminophen and drug injuries are common; malignancy-related HeF remains relatively unexplored. Methods: We performed a retrospective study using nationwide inpatient database (NIS) 2016, which is the largest US inpatient database. HeF admissions were identified as primary diagnosis (through ICD-10 codes) and stratified into two major groups with and without cancer. The cancer group was subdivided into solid (excluding hepato-cellular cancer (HCC)) and non-solid malignancies. Primary outcome was inpatient mortality while secondary outcomes included Length of stay (LOS), Total charge (TCHG), LT and respiratory failure requiring ventilation (MV). Results: 71,000 inpatients met inclusion criteria for HeF, of which 7,715(10.87%) had an underlying malignancy. 39.4%( n = 3,045) had solid malignancies (excluding HCC), 8.4%( n = 650) had non-solid malignancies and 56%( n = 4,020) had HCC. Mean LOS was 5.4 days (95% CI 5.4-5.6, p = 0.23) and mean TCHG was 63,240$(95% CI 57,258$-69,222$, p = 0.03). African Americans (61.2 % vs 53.6%, p = 0.001) and males (12.05% vs 8.71%, p = 0.001) were preponderant in the cancer group. Inpatient mortality was higher in the cancer group (15.3% vs 5.5% p = 0.000), among which solid cancer (20.39%) predominated over non-solids (13.85%) and HCC (11.71%). LT was higher in cancer group (3.7 % vs 2%), whereas no difference in MV was found. Multivariable analysis results are summarized in the table below. Conclusions: HeF patients with underlying malignancy have higher mortality, LOS, TCHG and LT rates. Furthermore, high median income, large center admissions, HCC and Charlson index &lt; = 3 among others were associated with higher odds of undergoing LT in HeF. This study sheds light on the epidemiology and impact of HeF in cancers, as well as disparities in LT among GI cancer patients with HeF. [Table: see text]
A novel approach for 21-genes testing associated with prognosis in Chinese patients with ER-positive/HER2-negative breast cancer: A real-world study.
Authors: Yinduo Zeng, Qian Li, Jiannan Wu, Heran Deng, Ying Wang, Wenjing Wu, Jianli Zhao, Xiao-Xiao Dinglin, Tao Qin, Qiang Liu, Fengxi Su, Weijuan Jia, Herui Yao
Journal: Journal of Clinical Oncology (2020)

e12528 Background: We previously reported a Chinese version of 21-genes Recurrence Score (RS) provides reduction chemotherapy prescription in patients with ER-Positive/HER2-Negative node negative breast cancer, while Oncotype Dx was hardly to be reached. However, the impact on clinical outcome was not mentioned. Herein, we explored whether this 21-genes recurrence score (RS) impacted on prognosis in patients with this molecular subtype of breast cancer. Methods: From Jan 2013 to Aug 2018, 378 patients with ER-Positive/HER2-Negative early stage breast cancer were enrolled. All patients received a Chinese version of 21-genes RS test, which is a new method using RNA extracted from formalin-fixed paraffin-embedded tissue performed by SurExam Campany, Guangzhou, China. . The RS score for each patient was calculated based on expression level of 21-genes used in a prosperctively defined algorithm and calculate a recurrence score range from 0 to 100 and divided three risk groups according to TAILORs study.Distant metastases-free survival (DMFS) were correlated with the 21-genes RS by Kaplan-Meier (log-rank method), and Cox regression. Multivariable logistic regression was performed to determine factors correlated with RS testing and receipt of a high-risk RS. Results: Median patient age was 46 years (18 to 77 years). The Chinese version of 21-gene RS was generated for 378 patients: 61 (16.1%) low risk ( &lt; 11), 241 (63.8%) intermediate risk (11 to 25), and 76 (20.1%) high risk (≥ 26). At a median follow-up of 40 months, the 4-year-rate of estimated DMFS was 100%, 98.7% and 92.9% in low risk, intermediate risk and high risk groups. Meanwhile, there was no difference in RFS among three risk groups. For all patients, 21-gene RS was associated with DMFS ( P = .021). In multivariable Cox regression models, 21-gene RS was independently prognostic factor of DMFS (hazard ratio, 5.375; 95% CI, 1.00 to 28.84; P = .05). Tumor size (&gt;2cm vs ≤2cm, OR = 2.31, P = .005), high grade ( OR = 2.15, P = .013), ki67 index ( &gt; 14% vs ≤14%, OR = 4.24, P = .002), progesterone receptor expression ( &lt; 20% vs ≥20%, OR = 5.07, P &lt; .001) were predictor of high risk of RS. Conclusions: The Chinese version of 21-genes RS is independently prognostic factor for DMFS patients with ER–positive/HER2-negative node negative breast cancer. Future study was needed to explore the impact of 21 gene RS on long-term prognosis.
Clinical trial in progress: Pivotal study of VB-111 combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).
Authors: Rebecca Christian Arend, Bradley J. Monk, Robert Allen Burger, Thomas J. Herzog, Jonathan A. Ledermann, Kathleen N. Moore, Angeles Alvarez Secord, Roni Shapira, Krishnansu Sujata Tewari, Marilyn Huang, Amnon Amit, Tamar Rachmilewitz Minei, Dror Harats, Richard T. Penson
Journal: Journal of Clinical Oncology (2020)

TPS6097 Background: Ofranergene obadenovec (VB-111) is a targeted anti-cancer gene therapy with a dual mechanism: a broad antiangiogenic effect and induction of a tumor directed viral immune response. In a phase II trial in platinum resistant ovarian cancer VB-111 in combination with weekly paclitaxel showed a CA-125 response rate (RR) of 58% and median overall survival (OS) of 498 days compared to 172.5 days in the sub-therapeutic dose (p = 0.028). The combination treatment was well tolerated. Favorable outcomes were associated with induction of an immunotherapeutic effect of tumor infiltration with CD-8 T cells. Based on these observations, a phase III randomized controlled trial, VB-111-701/GOG-3018 (OVAL) was initiated in collaboration with the GOG Foundation, Inc. Methods: The OVAL study, NCT03398655, is an international, randomized, double-blind, placebo-controlled, phase III study. Patients with recurrent platinum-resistant epithelial ovarian cancer, who have measurable disease (RECIST 1.1) and were previously treated with up to 5 lines are randomized 1:1 to receive VB-111 (1x10 13 VPs) with weekly paclitaxel (80mg/m 2 ), or weekly paclitaxel with placebo. Randomization is stratified by number of prior treatment lines, prior antiangiogenic therapy and platinum refractory disease status. Treatment beyond asymptomatic RECIST progression may continue until progression is confirmed by follow up imaging. The primary endpoints are OS, safety and tolerability. Secondary endpoints include progression free survival, and objective RR by CA-125 (per GCIG criteria) and RECIST 1.1. The sample size calculation of 400 patients (event driven) provides 92% power to detect a difference in survival at the two-sided 5% significance level using the logrank test. A pre-planned interim analysis will take place in Q1 2020 to assess whether the CA-125 RR per GCIG criteria in the treatment arm is sufficiently larger than in the control arm and is comparable to the positive results of the phase II study. Study enrolment is ongoing and over 80 patients were enrolled in the US and Israel. Enrollment expansion to Europe is planned in 2020. Clinical trial information: NCT03398655.