tbuckley/cabot-search huggingface dataset:
Liquid biopsy testing: Impact on treatment assignment and survival in a community-based oncology practice—A real-world experience.
Authors: Khalil Choucair, Bassam Ibrahim Mattar, Quoc Van Truong, Travis Lee Koeneke, Phu Van Truong, Christopher Dakhil, Michael W. Cannon, Seth Joel Page, Jeremy Michael Deutsch, Eric A. Carlson, Dennis Frederic Moore, Nassim H. Nabbout, K. James Kallail, Shaker R. Dakhil, Pavan S. Reddy
Journal: Journal of Clinical Oncology (2021)

3027 Background: Liquid biopsy is a promising, rapid and minimally invasive genetic test examining circulating tumor DNA. It offers a significant potential in selecting signal-matched therapeutic options. Methods: A retrospective chart review was conducted on adult patients with advanced solid cancer whose tumors were tested with the Guardant 360® (Guardant Health) assay between December 2018 and 2019. A follow-up analysis (censor date: 01/06/2021) was carried to assess the actual impact of testing results on treatment assignment and survival. Results: A total of 178 patients underwent testing. Mean age at diagnosis was 65 years. Median (m) Karnofsky Performance Scale was 90% and the majority of patients (89.9%) had ≥ stage III-B disease. Lung (LCa; 50.56%), breast (BCa; 17.42%) and colorectal (CRCa; 7.87%) cancers were the most common cancer types. A positive test was reported in 140/178 patients (78.7%); of those, 105/140 (75%) had an actionable mutation, either with an FDA-approved target-matched therapy (n = 32/105; 30.5%) or with a therapy outside current FDA indication (n = 73/105; 69.5%). In patients with no actionable mutation (n = 35/140; 25%), 85.7% (n = 30/35) had a signal-based clinical trial opportunity. The actual overall signal-based matching rate was 17.8% (24/135; vs. 82.2% no-match rate). Within candidates for FDA-approved treatment, 50% (16/32) received targeted therapy while only 6.9% (5/73) were treated with targeted agents outside current FDA indication: mean matching score (number of matched drugs/number of actionable mutations) was 0.6 (range: 0.33-2) and 0.8 (range: 0.17-2), respectively. Only 10% (3/30) were referred to signal-based clinical trials. Survival analysis of LCa, BCa and CRCa patients with actionable mutations who actually received any therapy (n = 66) revealed post-testing survival advantage for target-matched therapy (n = 22) compared to unmatched therapy (n = 44): overall survival (OS) was longer in the matched cohort (mOS: 13.3 months; 95% CI: 11.8-14.8 vs. 10.7 months; 95% CI: 9-12.4 in unmatched) but did not reach statistical significance ( P = 0.09). Progression free survival (PFS) was significantly longer in patients who received matched therapy (mPFS: 11.3 months; 95% CI: 9.9-12.7 vs. mPFS: 6.8 months; 95% CI: 5.1-8.5 in unmatched; P &lt; 0.05). Conclusions: Implementation of liquid biopsy testing is feasible in community practice and impacts therapeutic choices in patients with advanced malignancies. Receipt of liquid biopsy-generated signal-matched precision therapies conferred added survival benefit compared to unmatched therapy. Larger sample size studies are needed to validate these findings.
Cecilia Elizabeth Thomas
Authors: Roger Thomas, Rhys Thomas, Roland Salmon
Journal: BMJ (2021)

Cecilia Elizabeth Thomas (nee Mullen and known as “Celia”) spent her whole professional career in Cardiff. She was brought up in Birmingham, where she attended Bishop Walsh (RC) Comprehensive School. At medical school she met and married Roger Thomas, a fellow student in her year. She subsequently did vocational training for general practice, became a partner in the practice where she had been a trainee, and worked there for 40 years.

She combined being an excellent …
The association between bacteria colonizing the upper respiratory tract and lower respiratory tract infection in young children: a systematic review and meta-analysis
Authors: Shantelle Claassen-Weitz, Katherine Y.L. Lim, Christopher Mullally, Heather J. Zar, Mark P. Nicol
Journal: Clinical Microbiology and Infection (2021)

BackgroundBacteria colonizing the upper respiratory tract (URT) of young children play a key role in the pathogenesis of lower respiratory tract infection (LRTI).ObjectivesTo systematically review the literature on the association between bacteria colonizing the URT and LRTI among young children.Data sourcesMEDLINE, Academic Search Premier, Africa-Wide Information and CINAHL, Scopus and Web of Science.Study eligibility criteriaStudies published between 1923 and 2020, investigating URT bacteria from LRTI cases and controls.ParticipantsChildren under 5 years with and without acute LRTI.MethodsThree reviewers independently screened titles, abstracts and full texts. Meta-analysis was done using Mantel–Haenszel fixed- or random-effects models.ResultsMost eligible studies (41/50) tested nasopharyngeal specimens when investigating URT bacteria. Most studies were of cross-sectional design (44/50). Twenty-four studies were performed in children in lower- or lower-middle-income countries (LMICs). There was higher prevalence of Haemophilus influenzae (pooled OR 1.60; 95% CI 1.23–2.07) and Klebsiella spp. (pooled OR 2.04; 95% CI 1.17–3.55) from URT specimens of cases versus controls. We observed a positive association between the detection of Streptococcus pneumoniae from URT specimens and LRTI after excluding studies where there was more antibiotic treatment prior to sampling in cases vs. controls (pooled OR 1.41; 95% CI 1.04–1.90). High density colonization with S. pneumoniae (>6.9 log10 copies/mL) was associated with an increased risk for LRTI. The associations between both Streptococcus and Haemophilus URT detection and LRTI were supported, at genus level, by 16S rRNA sequencing. Evidence for the role of Moraxella catarrhalis and Staphylococcus aureus was inconclusive.ConclusionsDetection of H. influenzae or Klebsiella spp. in the URT was associated with LRTI, while evidence for association with S. pneumoniae was less conclusive. Longitudinal studies assessing URT microbial communities, together with environmental and host factors are needed to better understand pathogenesis of childhood LRTI.
Combining mannose receptor mediated nanovaccines and gene regulated PD-L1 blockade for boosting cancer immunotherapy
Authors: Jie Chen, Huapan Fang, Yingying Hu, Jiayan Wu, Sijia Zhang, Yuanji Feng, Lin Lin, Huayu Tian, Xuesi Chen
Journal: Bioactive Materials (2021)

Tumor nanovaccines have potential applications in the prevention and treatment of malignant tumors. However, it remains a longstanding challenge in exploiting efficient nanocarriers for inducing potent specifically cellular immune responses. Toward this objective, we herein explore an intensive tumor immunotherapeutic strategy by combining mannosylated nanovaccines and gene regulated PD-L1 blockade for immune stimulation and killing activity. Here, we fabricate a mannose modified PLL-RT (Man-PLL-RT) mediated nanovaccines with dendritic cells (DCs) targeting capacity. Man-PLL-RT is capable of co-encapsulating with antigen (ovalbumin, OVA) and adjuvant (unmethylated cytosine-phosphate-guanine, CpG) by electrostatic interaction. This positively charged Man-PLL-RT/OVA/CpG nanovaccines can facilitate the endocytosis, maturation and cross presentation in DCs. However, the nanovaccines arouse limited inhibition of tumor growth, which is mainly due to the immunosuppressed microenvironment of tumors. Combining tumor nanovaccines with gene regulated PD-L1 blockade leads to an obvious tumor remission in B16F10 melanoma bearing mice. The collaborative strategy provides essential insights to boost the benefits of tumor vaccines by regulating the checkpoint blockade with gene therapy.
Optimizing the Start Time of Biologics in Polyarticular Juvenile Idiopathic Arthritis: A Comparative Effectiveness Study of Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans
Authors: Yukiko Kimura, Laura E. Schanberg, George A. Tomlinson, Mary Ellen Riordan, Anne C. Dennos, Vincent Del Gaizo, Katherine L. Murphy, Pamela F. Weiss, Marc D. Natter, Brian M. Feldman, Sarah Ringold
Journal: Arthritis & Rheumatology (2021)

Objective The optimal time to start biologics in polyarticular juvenile idiopathic arthritis (JIA) remains uncertain. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed 3 consensus treatment plans (CTPs) for untreated polyarticular JIA to compare strategies for starting biologics. Methods Start Time Optimization of Biologics in Polyarticular JIA (STOP‐JIA) was a prospective, observational, CARRA Registry study comparing the effectiveness of 3 CTPs: 1) the step‐up plan (initial nonbiologic disease‐modifying antirheumatic drug [DMARD] monotherapy, adding a biologic if needed, 2) the early combination plan (DMARD and biologic started together), and 3) the biologic first plan (biologic monotherapy). The primary outcome measure was clinically inactive disease according to the provisional American College of Rheumatology (ACR) criteria, without glucocorticoids, at 12 months. Secondary outcome measures included Patient‐Reported Outcomes Measurement Information System (PROMIS) pain interference and mobility scores, inactive disease as defined by the clinical Juvenile Arthritis Disease Activity Score in 10 joints (JADAS‐10), and the ACR Pediatric 70 criteria (Pedi 70). Results Of 400 patients enrolled, 257 (64%) began the step‐up plan, 100 (25%) the early combination plan, and 43 (11%) the biologic first plan. After propensity score weighting and multiple imputation, clinically inactive disease according to the ACR criteria was achieved in 37% of those on the early combination plan, 32% on the step‐up plan, and 24% on the biologic first plan ( P = 0.17). Inactive disease according to the clinical JADAS‐10 (score ≤2.5) was also achieved in more patients on the early combination plan than the step‐up plan (59% versus 43%; P = 0.03), as was ACR Pedi 70 (81% versus 62%; P = 0.008), but generalizability was limited by missing data. PROMIS measures improved in all groups, but without significant differences. Twenty serious adverse events were reported (mostly infections). Conclusion Achievement of clinically inactive disease without glucocorticoids did not significantly differ between groups at 12 months. While there was a significantly higher likelihood of early combination therapy achieving inactive disease according to the clinical JADAS‐10 and ACR Pedi 70, these results require further exploration.
A pilot study of individualized exercise prescription to improve physical activity in cancer survivors.
Authors: Priyanka Avinash Pophali, Urshila Durani, John Shin, Melissa C. Larson, Adam Shultz, Julie Becker, Melissa Bowman, Carrie A. Thompson, Elizabeth Jane Cathcart-Rake
Journal: Journal of Clinical Oncology (2021)

e24030 Background: Physical activity (PA) in cancer survivors improves quality of life (QOL), functioning, fatigue, and reduces the risk of treatment complications, cancer recurrence and death. However, the optimal intervention for increasing PA is not established. Most prospective studies have shown a 6-12-week program to be an effective intervention but this is often not feasible. Therefore, we piloted a one-time individualized exercise prescription in our cardiac rehabilitation center to improve PA in cancer survivors. Methods: We prospectively enrolled cancer survivors who had completed curative intent treatment, with no evidence of active disease in this pilot study. Survivors who consented underwent a consultation with an exercise physiologist for needs assessment followed by a supervised exercise session with a tailored exercise prescription. Survivors also filled out surveys assessing their PA and QOL at baseline (bl), 3, 6 and 12 months after intervention. Clinical information was collected via chart review. We estimated longitudinal PA score and change in PA using mixed models incorporating scores from all available time points using SAS (v 9.4). Results: Between May 2018 and January 2020, 50 participants (26 lymphoma and 24 solid tumor survivors) completed the intervention. 20% participants were on maintenance therapy during the study. Clinical characteristics of 42 evaluable participants are summarized in Table. The survey response rate was 82%, 58%, 58%, 46% at bl, 3, 6 and 12 months respectively. The level of PA improved with time [mean (SE) PA score: 58.5 (4.3) bl, 63.9 (4.8) at 3, 57.6 (4.8) at 6, 62.6 (5.3) at 12 months]. The change in PA from baseline to follow-up time-points [bl vs 3m p=0.41; bl vs 6m p=0.88; bl vs 12m p=0.55] or between the lymphoma and solid tumor survivors was not statistically significant and limited by sample size. No significant trend in QOL was seen. Conclusions: Individualized exercise prescription using the cardiac rehabilitation program may be a feasible, widely applicable tool to implement a PA intervention among cancer survivors. The trend towards improvement in PA in this novel one-time intervention provides intriguing evidence and deserves future study in larger sample sizes to understand if it can improve and create sustainable PA change comparable to longer term exercise interventions.[Table: see text]
Association of Rideshare Use With Alcohol-Associated Motor Vehicle Crash Trauma
Authors: Christopher R. Conner, Hunter M. Ray, Ryan M. McCormack, Jacqueline S. Dickey, Samantha L. Parker, Xu Zhang, Roberto M. Vera, John A. Harvin, Ryan S. Kitagawa
Journal: JAMA Surgery (2021)

Motor vehicle crashes (MVCs) are an important public health concern. Recent trends suggest that introducing rideshare services has decreased the incidence of MVCs. However, detailed analyses linking rideshare volume, convictions for impaired driving, and nonfatal MVC traumas remain inconclusive.To determine if there is an association between rideshare use and MVC traumas and convictions for impaired driving in Houston, Texas.This multicenter cohort study was conducted between January 2007 and November 2019 with hospital data from the Red Duke Trauma Institute within the Memorial Hermann Hospital-Texas Medical Center and Ben Taub General Hospital. Rideshare data from Uber and Google covered trips taken within Houston, Texas, from February 2014 (the date of deployment of Uber to Houston) to December 2018. Impaired driving convictions included all indictments made by the Harris County, Texas, District Attorney's office from January 2007 to December 2018. All adults with MVC traumas evaluated at both centers in the study population (individuals >16 years with a mechanism of injury classified under "motor vehicle collision") were included. Impaired driving incidents were included only if the final legal outcome was conviction.The primary study outcomes were the incident rate ratios for hourly MVC traumas and daily impaired driving convictions.A total of 23 491 MVC traumas (involving patients with a mean [SD] age of 37.9 [17.8] years and 14 603 male individuals [62.1%]), 93 742 impaired driving convictions, and more than 24 million Uber rides were analyzed. Following the introduction of Uber in February 2014, MVC traumas decreased by 23.8% (from a mean [SD] of 0.26 [0.04] to 0.21 [0.06] trauma incidents per hour) during peak trauma periods (Friday and Saturday nights). The incident rate ratio of MVC traumas following Uber deployment was 0.33 (95% CI, 0.17-0.67) per 1000 indexed rides (P = .002). Furthermore, rideshare use was associated with a significant, geographically linked reduction in impaired driving convictions between January 2014 to December 2019 (incidence rate ratio, 0.76 [95% CI, 0.73-0.78]; P < .001).In this study, introducing rideshare services in the Houston metropolitan area was associated with significant reductions in MVC traumas and impaired driving convictions. Increased use of rideshares may be an effective means of reducing impaired driving and decreasing rate of MVC traumas.
IMMU-07. “STROKE MIMICS” ARE NOT BENIGN IN IMMUNOCOMPROMISED CHILDREN
Authors: Jasia Mahdi, Alicia Bach, Alyssa Smith, Stuart Tomko, Melanie Fields, Jennifer Griffith, Stephanie Morris, Rejean Guerriero, Michael Noetzel, Kristin Guilliams, Shannon Agner
Journal: Neuro-Oncology (2021)

Abstract Objective To determine the clinical variances between strokes and stroke mimics in a pediatric immunocompromised population that consists of children with central nervous system (CNS) and non-CNS malignancies and a history of solid organ transplantation. Methods We performed a retrospective cohort analysis of stroke alert activations in patients with high-grade gliomas, low-grade gliomas, atypical teratoid rhabdoid tumors, rare CNS tumors, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, osteosarcoma, and solid organ transplants at St. Louis Children’s Hospital between February 2013 and September 2019. We categorized final diagnoses as strokes or stroke mimics. We classified diagnoses as a neurologic emergency if the diagnosis necessitated changes in management. Results Out of 217 stroke alerts, 31 alerts occurred for 28 patients meeting inclusion criteria. All final diagnoses constituted neurologic emergencies, including: stroke (39%), chemotherapy-related neurotoxicity (29%), tumor progression (19%), and seizures/posterior reversible encephalopathy syndrome (13%). Patients meeting inclusion criteria with strokes and stroke mimics presented similarly, with the exception of altered mental status, which was more prevalent in patients with strokes than stroke mimics (p = 0.03). One child received hyperacute thrombectomy for stroke. Only 58% of children with stroke mimics had complete resolution of their presenting neurologic symptoms. Children with strokes and stroke mimics had similar mortality incidences of 33% and 37%, respectively. Conclusions Although all acute neurologic changes in immunocompromised children are not strokes, stroke mimics in this population are neither benign nor self-limited and carry long-term neurologic morbidity and mortality. This study highlights the utility of an acute stroke evaluation infrastructure and the need for acute and long-term neurology involvement in the care of these patients.
Photothermal scaffolds/surfaces for regulation of cell behaviors
Authors: Yangcui Qu, Kunyan Lu, Yanjun Zheng, Chaobo Huang, Guannan Wang, Yanxia Zhang, Qian Yu
Journal: Bioactive Materials (2021)

Regulation of cell behaviors and even cell fates is of great significance in diverse biomedical applications such as cancer treatment, cell-based therapy, and tissue engineering. During the past decades, diverse methods have been developed to regulate cell behaviors such as applying external stimuli, delivering exogenous molecules into cell interior and changing the physicochemical properties of the substrates where cells adhere. Photothermal scaffolds/surfaces refer to a kind of materials embedded or coated with photothermal agents that can absorb light with proper wavelength (usually in near infrared region) and convert light energy to heat; the generated heat shows great potential for regulation of cell behaviors in different ways. In the current review, we summarize the recent research progress, especially over the past decade, of using photothermal scaffolds/surfaces to regulate cell behaviors, which could be further categorized into three types: (i) killing the tumor cells via hyperthermia or thermal ablation, (ii) engineering cells by intracellular delivery of exogenous molecules via photothermal poration of cell membranes, and (iii) releasing a single cell or an intact cell sheet via modulation of surface physicochemical properties in response to heat. In the end, challenges and perspectives in these areas are commented.
Outcomes with venetoclax in myelodysplastic syndromes: A systematic review.
Authors: Razwana Khanam, Moazzam Shahzad, Pranali Santhoshini Pachika, Zahoor Ahmed, Fatima Ali, Adeel Masood, Zunairah Shah, Asmi Chattaraj, Sibgha Gull Chaudhary, Ramesh Balusu, Nausheen Ahmed, Sharad Khurana, Faiz Anwer, Sunil H. Abhyankar, Joseph P McGuirk, Muhammad Umair Mushtaq
Journal: Journal of Clinical Oncology (2021)

e19035 Background: Myelodysplastic syndromes (MDS) are clonal hemopoietic disorders causing cytopenia(s) and increased risk of transformation to acute myeloid leukemia (AML). Venetoclax is a B-cell lymphoma-2 (BCL-2) inhibitor that induces apoptosis in malignant cells. The FDA has approved venetoclax for the treatment of newly diagnosed adult AML patients unfit for intensive chemotherapy and its utility in MDS is being explored. We present a systematic review aimed to evaluate outcomes with venetoclax in MDS patients. Methods: We performed a literature search on 3 databases (Pubmed, Cochrane, and Clinicaltrials.gov) following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We screened 62 studies using the Mesh terms ‘myelodysplastic syndrome’ and ‘venetoclax’. After excluding review, duplicate and non-relevant articles, 8 studies were included in the analysis. Quality evaluation was done using the NIH quality assessment tool. Pooled analysis was done using the ‘meta’ package (Schwarzer et al, R programming language) and proportions with 95% confidence intervals (CI) were computed. The Inter-study heterogeneity among the studies was assessed using the Q statistic proposed by Cochrane and the I2 index introduced by Higgins and Thompson. Results: We identified 313 patients from 8 studies (1 prospective, 3 retrospective, 2 ex-vivo, 2 clinical trials). Venetoclax was used in combination with hypomethylating agents (HMA) in 6 studies and with other agents in 2 studies. Most patients were pre-treated. Complete response (CR) with or without hematological recovery (CRi) was reported in 45% of patients (95% CI 0.26-0.66, I 2 = 90%, n = 292). Stable disease (SD) was seen in 18% patients (95% CI 0.08-0.37, I 2 = 85%, n = 223). Overall response rate (ORR) was 51% (95% CI 0.31-0.70, I 2 = 89%, n = 122). Hematopoietic stem cell transplant (HCT) was performed in 22% patients (95% CI 0.09-0.44, I 2 = 75%, n = 122). Twenty percent patients (95% CI 0.15-0.28, I 2 = 0%, n = 149) died. Common adverse events seen with venetoclax were cytopenias, gastrointestinal side effects and infections, often requiring drug interruption or dose. Conclusions: Despite heterogeneity of available literature, venetoclax seems to be a promising agent in treatment of MDS patients. Prospective clinical trial data is needed to ascertain safety and efficacy of venetoclax in MDS and impact on overall survival, in particular, in patients proceeding to HCT.[Table: see text]
Cerebrovascular Disease after Allogeneic Hematopoietic Stem Cell Transplantation: Incidence, Manifestations, Risk and Clinical Outcome
Authors: Yao-Chung Liu, Ting-An Lin, Po-Shen Ko, Hao-Yuan Wang, Sheng-Hsuan Chien, Chia-Jen Liu, Tzeon-Jye Chiou, Liang-Tsai Hsiao, Jyh-Pyng Gau, Jin-Hwang Liu
Journal: Blood (2017)