tbuckley/cabot-search huggingface dataset:
Symptoms (Sx) in English (E) and Spanish (S) speaking children with cancer.
Authors: Donna S. Zhukovsky, Robert J. Wells, Rhonda J. Robert, Gary B. Chisholm, J. Lynn Palmer, Marlene Z. Cohen, Cathy L. Rozmus, Julio Allo, Eduardo Bruera
Journal: Journal of Clinical Oncology (2012)

9096 Background: Sx in children receiving treatment for cancer are poorly described and often reported by proxies. Study aims were to 1. Characterize sx of pediatric oncology outpatients 2. Evaluate the agreement between patient (pt) and proxy reports 3. Report the association between pt assessed sx and treatments prescribed by physicians (MD). Methods: The pediatric Memorial Symptom Assessment Scale (pMSAS) is a validated tool that evaluates frequency, intensity and distress of 8 sx (version 7-12) or 30 sx (version 10-18) for pts of corresponding ages. Higher scores indicate greater sx burden. pMSAS was translated into S versions. Pt eligibility included ages 7-18, E or S speaking, advanced cancer, pediatric assent/parent consent and E or S speaking family caregiver (CG) with IRB approved consent for self participation. Pts and CG were administered age appropriate pMSAS in E or S independently just prior to MD visit and consenting MDs, the corresponding pMSAS after the visit. Subscale scores included total pMSAS score (TOTAL), psychological, physical and global distress index for older group (OG) and TOTAL for younger group (YG). Statistical analysis included Spearman correlation coefficients and weighted kappas. Results: E and S results were similar and combined. 60 children [age mean +SD 12 +.5, 62% male, 35 S] and their CG completed the pMSAS. 14 MD completed pMSAS for 20 pts. 9 pts (15%) had no sx and 38 (63%), ≥2. The most common sx for ages 7-10 were tired (N=12, 40%) and itch (N=9, 30%) and for ages 11-18, pain (15/30, 50%) and energy (13/29, 45%). Subscale score agreement varied by proxy type and subscale. For TOTAL, highest correlation was 0.6 (p&lt;.001) for YG and 0.7 (p&lt;.001) for OG. For individual sx, agreement between patient and proxy was highly variable (Table). Of symptomatic patients, 6% (3/51) received sx recommendations. Conclusions: Sx in children with cancer are common and undertreated. CG and MD ratings are often not congruent with pt reports which may explain the apparent under treatment of sx. [Table: see text]
A Wearable Sensor Using Structured Silver‐Particle Reinforced PDMS for Radial Arterial Pulse Wave Monitoring
Authors: Yu Fu, Shuai Zhao, Liangqi Wang, Rong Zhu
Journal: Advanced Healthcare Materials (2019)

Abstract Human pulse signals contain important and useful physiological information for the auxiliary diagnosis of cardiovascular disease. Here, a wearable pulse sensor based on piezo‐thermic transduction is reported using a structured silver‐particle reinforced polydimethylsiloxane (PDMS) membrane, for monitoring radial arterial pulse waves. The structured silver‐particle reinforced PDMS membrane is optimally designed to meet the specific requirements on sensitivity, linearity, and effective preload measuring range for pulse detection by adjusting the air gap volume fraction and silver particle volume fraction of the structured material. The sensor is endowed with high sensitivity, good linearity in preload measuring range, allowing to detect the subtle pulse waveforms of subjects at different ages under different contact pressures, such as superficial (Fu), medium (Zhong) and deep (Chen). The developed pulse device provides a promising approach for homecare pulse monitoring.
Association of Genetic and Environmental Factors With Autism in a 5-Country Cohort
Authors: Dan Bai, Benjamin Hon Kei Yip, Gayle C. Windham, Andre Sourander, Richard Francis, Rinat Yoffe, Emma Glasson, Behrang Mahjani, Auli Suominen, Helen Leonard, Mika Gissler, Joseph D. Buxbaum, Kingsley Wong, Diana Schendel, Arad Kodesh, Michaeline Breshnahan, Stephen Z. Levine, Erik T. Parner, Stefan N. Hansen, Christina Hultman, Abraham Reichenberg, Sven Sandin
Journal: JAMA Psychiatry (2019)

The origins and development of autism spectrum disorder (ASD) remain unresolved. No individual-level study has provided estimates of additive genetic, maternal, and environmental effects in ASD across several countries.To estimate the additive genetic, maternal, and environmental effects in ASD.Population-based, multinational cohort study including full birth cohorts of children from Denmark, Finland, Sweden, Israel, and Western Australia born between January 1, 1998, and December 31, 2011, and followed up to age 16 years. Data were analyzed from September 23, 2016 through February 4, 2018.Across 5 countries, models were fitted to estimate variance components describing the total variance in risk for ASD occurrence owing to additive genetics, maternal, and shared and nonshared environmental effects.The analytic sample included 2 001 631 individuals, of whom 1 027 546 (51.3%) were male. Among the entire sample, 22 156 were diagnosed with ASD. The median (95% CI) ASD heritability was 80.8% (73.2%-85.5%) for country-specific point estimates, ranging from 50.9% (25.1%-75.6%) (Finland) to 86.8% (69.8%-100.0%) (Israel). For the Nordic countries combined, heritability estimates ranged from 81.2% (73.9%-85.3%) to 82.7% (79.1%-86.0%). Maternal effect was estimated to range from 0.4% to 1.6%. Estimates of genetic, maternal, and environmental effects for autistic disorder were similar with ASD.Based on population data from 5 countries, the heritability of ASD was estimated to be approximately 80%, indicating that the variation in ASD occurrence in the population is mostly owing to inherited genetic influences, with no support for contribution from maternal effects. The results suggest possible modest differences in the sources of ASD risk between countries.
A prospective study investigating the impact of definitive chemoradiation in locoregionally advanced squamous cell carcinoma of the skin.
Authors: Michelle K. Nottage, Alessandra Bastian Francesconi, Kathleen Emilie Mary Houston, Charles Lin, Lizbeth M. Kenny, Brett Gordon Maxwell Hughes
Journal: Journal of Clinical Oncology (2012)

8538 Background: Our state, Queensland, Australia, has the highest rate of cutaneous squamous cell cancer (SCC) in the world. Spread to regional lymph nodes or more distant sites occurs in 5-10%. A proportion of patients can not undergo surgical resection but complete response rates with radiotherapy alone are low. This led to the hypothesis that combined chemoradiation (CRT) may be of benefit. We decided to document the outcomes of concurrent chemoradiation by means of a prospective trial. Methods: This was a single arm, phase II study with planned sample size 30 patients. The primary endpoint was complete response rate (CRR), estimate 60%. Patients with locally/regionally advanced (non-metastatic) cutaneous SCC deemed unresectable or unsuitable for surgery by consensus of the multidisciplinary Head and Neck Cancer Clinic, with measurable disease, aged over 18, performance status 0-2, received definitive radiotherapy (XRT) (70Gy in 35#) and concurrent weekly platinum based chemotherapy (CT) (cisplatin 40mg/m2 or carboplatin AUC 2). Results: 14 patients were enrolled (Feb 2008-June 2011), median age 66 (48-84), 64% ECOG PS 0, 64% stage IV, 57% nodal disease only. Cisplatin/carboplatin was administered in 64%/36% respectively. 42% received all planned CT while 58% had 1 or 2 weeks omitted. 2 patients had dose reductions. XRT was completed as planned in 93%. The CRR was 57% (8/14) at analysis in December 2011 (median follow-up 13.5m). 2 further patients with partial response (PR) achieved CR after undergoing salvage surgery. Six (43%) patients had a PR; 4(29%) did not receive surgery and later progressed. Median overall survival was not reached, with 3 year survival 54%. The most frequent toxicities were dermatitis, mucositis, thrombocytopenia, nausea, anaemia, dysphagia. 28% had grade 3/4 toxicity, mainly cytopenias, infection, dehydration and nausea. Conclusions: This is the only prospective series of CRT for cutaneous squamous cell cancer. A high complete response rate was documented in patients with loco-regionally advanced disease and multiple co-morbidities, with acceptable toxicity, making this a reasonable alternative for patients unable to undergo surgery.
High Court upholds tribunal decision that surgeon was fit to practise despite lying to patient
Authors: Clare Dyer
Journal: BMJ (2019)

A High Court judge has refused to quash the decision of a medical practitioners tribunal that a consultant surgeon was fit to practise, even though he had lied to a patient about a screw that had been misplaced during a lumbar spinal fusion operation.1

The tribunal decided that the spinal surgeon Andrew Hilton had acted from a positive motive when he told the lie and that, though his action amounted to misconduct, his fitness to practise was not impaired in November 2018, when the case was heard. The tribunal also decided not to exercise the option to issue a warning to Hilton.

The General Medical Council has been reluctant to appeal …
Mixed response to immunotherapy in lung cancer.
Authors: Candice Baldeo, Tasneem Kaleem, Ricardo Paz-Fumagalli, John A. Copland, Michael E. Menefee
Journal: Journal of Clinical Oncology (2019)

122 Background: Mixed response (MR) to systemic therapy is common and associated with a poor prognosis. MR often represents a therapeutic dilemma resulting in the discontinuation of a therapy to which a portion of the tumor is still sensitive, due to the emergence of resistance in other metastatic deposits. We hypothesize that discordant responses in patients receiving immunotherapy may be associated with genomic variation within discordant tumors. Methods: We defined MR with the following criteria: 1) At least one tumor has increased in size while another tumor has decreased; 2) One or more tumors have remained stable while another has increased; 3) One or more tumors have remained stable while another has decreased. 4) A new tumor has developed while other tumors have decreased or remained stable. Between 2012 and 2017, we identified 112 patients with a MR. Two patients with metastatic lung cancer, treated with nivolumab underwent paired, simultaneous sampling of discordant tumors. Results: Both patients treated with nivolumab demonstrated genomic heterogeneity between discordant tumors on next-generation sequencing, including one patient with SCLC. Conclusions: MR remains a common and challenging therapeutic quandary. Genomic heterogeneity and differences in TMB of metastatic tumors demonstrating a MR, may be factors that contribute to this phenomenon. Further characterization of genomic discrepancies in MR may provide insights into mechanisms of emerging resistance, as well as, more rational and effective combinatorial therapies.[Table: see text]
A phase Ib/II trial of lenvatinib plus pembrolizumab in non-small cell lung cancer.
Authors: Marcia S. Brose, Nicholas J. Vogelzang, Christopher DiSimone, Sharad K. Jain, Donald A. Richards, Carlos A. Encarnacion, Drew W. Rasco, Robert Charles Shumaker, Corina E. Dutcus, Daniel E. Stepan, Matthew Guo, Emmett V. Schmidt, Matthew H. Taylor
Journal: Journal of Clinical Oncology (2019)

16 Background: Lenvatinib (LEN) is a multikinase inhibitor of VEGFR 1−3, FGFR 1−4, PDGFRα, RET, and KIT. Pembrolizumab (PEM), an anti-PD-1 antibody, is an approved monotherapy for previously treated patients (pts) with PD-L1 (+) (tumor proportion score ≥1%) metastatic non-small cell lung cancer (mNSCLC; objective response rate [ORR] 18%). We report interim results of an ongoing phase 1b/2 trial of LEN + PEM in pts with solid tumors, focusing on the mNSCLC cohort. Methods: In this multicenter, open-label study (NCT02501096), pts with measurable, confirmed mNSCLC, ECOG PS ≤1, ≤ 2 prior systemic therapies (phase 2 only) received oral LEN (20 mg/day) and PEM (200 mg Q3W, IV). Pts were not preselected by PD-L1 status. The phase 2 primary end point was ORR at 24 weeks (ORR WK24 ) by investigator-assessed immune-related RECIST (irRECIST). Secondary end points included ORR, progression-free survival (PFS) and duration of response (DOR). Results: At data cutoff (March 1, 2018), 21 pts were enrolled: 9 (43%) PD-L1(+), 5 (24%) PD-L1(-), and 7 (33%) not tested. Pts were treatment-naïve (14%); or had 1 (33%), 2 (48%), or ≥3 (5%) prior lines of systemic therapy. ORR WK24 was 33.3% (95% CI, 14.6–57.0); other efficacy outcomes are summarized in the table. Grade 3 and 4 treatment-related adverse events (TRAEs) occurred in 48% and 5% (increased aspartate aminotransferase) of pts. There was 1 fatal TRAE (exsanguination; “possibly related” to study treatment). The most common grade 3 TRAEs were hypertension (24%), fatigue (14%), diarrhea (14%), proteinuria (10%), and arthralgia (10%). Conclusions: LEN + PEM showed promising clinical activity and a manageable safety profile in previously treated pts with mNSCLC who were not preselected for PD-L1 status. Further study is warranted.[Table: see text]
Impaired Autonomic Nervous System-Microbiome Circuit in Hypertension
Authors: Jasenka Zubcevic, Elaine M. Richards, Tao Yang, Seungbum Kim, Colin Sumners, Carl J. Pepine, Mohan K. Raizada
Journal: Circulation Research (2019)

Hypertension affects an estimated 103 million Americans, yet gaps in knowledge continue to limit its successful management. Rapidly emerging evidence is linking gut dysbiosis to many disorders and diseases including hypertension. The evolution of the -omics techniques has allowed determination of the abundance and potential function of gut bacterial species by next-generation bacterial sequencing, whereas metabolomics techniques report shifts in bacterial metabolites in the systemic circulation of hypertensive patients and rodent models of hypertension. The gut microbiome and host have evolved to exist in balance and cooperation, and there is extensive crosstalk between the 2 to maintain this balance, including during regulation of blood pressure. However, an understanding of the mechanisms of dysfunctional host-microbiome interactions in hypertension is still lacking. Here, we synthesize some of our recent data with published reports and present concepts and a rationale for our emerging hypothesis of a dysfunctional gut-brain axis in hypertension. Hopefully, this new information will improve the understanding of hypertension and help to address some of these knowledge gaps.
Concordance and discordance in myeloma bone marrow studies.
Authors: Vincent Louie Mendiola, Meghana Kesireddy, Bagi RP Jana
Journal: Journal of Clinical Oncology (2019)

e19508 Background: Multiple myeloma (MM) diagnostic costs, including bone marrow (BM) studies: (flow (F), aspirate (manual differential) (A) and biopsy (Bx)) are increasing. BM studies already have underlying discordance issues that may lead to repetitive studies. Thus, elucidation of characteristics associated with concordant/discordant BM studies in identifying plasma cell percentage (PC%) of ≥10, a key MM diagnostic criteria, arises. Methods: A retrospective chart review (total of152 patients diagnosed with MM and managed at UTMB through 1/2016-1/2018) was completed. 56 subjects met inclusion, PC ≥10% in any BM study, and exclusion criteria. Subjects were grouped into BMA vs BMBx and BMF vs BMBx groups and subdivided into MM subtypes for exploratory review. Two-sample Independent t-test (CI 95%) and descriptive statistics were used for comparison of variables. Two-sided p value ≤ 0.05 was considered significant. Results: Sensitivities in identifying BM PC≥10% were as follows: BMA (66.1%), BMF (39.3%) and BMBx (96.4%) (Gold standard: BMA+BMF+BMBx (100%)). Concordance rates were at 60.7% between BMA and BMBx and 35.7% between BMF and BMBx. Larger BMBx spicule size (mean(cm) = 1.3(1.1-1.48) x 0.27(0.22- 0.31) x 0.21(0.19-0.22), p = 0.037) and higher B2 microglobulin (B2m) levels (mean(mcg/mL) = 11.92 (8.04- 15.79), p = 0.003) were associated with BMA and BMBx concordance in typical/secretory MM types but not in oligo-secretory and non-secretory subtypes of MM, nor is associated with BMF and BMB concordance or discordance. Meanwhile, # of BM acquisition attempts, tool types (hand trochar vs drill) for BM acquisition, LDH and CRP levels had no significant associations with concordance or discordance in any BM study groups. Conclusions: BMF is the least sensitive in identifying PC≥10% likely due to PC damage during flow cytometry, and it may be prudent to just perform BMA with BMBx to save on costs. The associations between larger spicule sizes and higher B2m levels to BMA and BMBx concordance are likely due to an increase in the chance of identifying monoclonal PCs in bigger samples, and greater monoclonal PC tumor burden, respectively, and may have predictability benefits.
Phase 2 study of parsaclisib (INCB050465) for relapsed or refractory diffuse large b-cell lymphoma (DLBCL) (CITADEL-202).
Authors: Morton Coleman, David Belada, René-Olivier Casasnovas, Rémy Gressin, Hui-Peng Lee, Amitkumar Mehta, Javier Munoz, Gregor Verhoef, Claudia Corrado, Douglas James DeMarini, Wanying Zhao, Xuejun Chen, Keith Fay
Journal: Journal of Clinical Oncology (2019)

e19038 Background: Parsaclisib, a potent, highly selective, next-generation PI3Kδ inhibitor, showed preliminary efficacy as monotherapy for relapsed or refractory non-Hodgkin lymphoma, including DLBCL (Abstract 410, ASH 2017), in a phase 1/2 study. This phase 2 study further assessed parsaclisib in patients (pts) with relapsed or refractory DLBCL (NCT02998476). Methods: Pts enrolled into 2 groups (A, Bruton tyrosine kinase [BTK] inhibitor naïve; B, BTK inhibitor experienced) and received oral parsaclisib 20 mg QD for 8 wks, then 20 mg QW. In a planned interim futility analysis conducted in the first 40 pts treated in Group A, if ≤13 (≤32.5%) responded by IRC assessment, Group A was to be terminated. Results: At data cutoff (22 Jun 2018), 60 pts (Group A, n = 55; Group B, n = 5) were treated (median age, 71 y [range, 36—94]; men, 63.3%; ≥3 prior systemic therapies, 60%). At the planned interim analysis in Group A, ORR (by PET) was 25% (10/40 pts; 5 CMR, 5 PMR); the futility boundary was crossed. At data cutoff, ORR in Group A was 25.5% (14/55 pts; 8 CMR, 6 PMR); median PFS was 2.2 mo (95% CI: 2.0‒4.1); median DOR was 4.5 mo (95% CI: 2.1‒5.1). ORs were observed in germinal center B-cell (GCB) and non-GCB subtypes. ORR in Group B was 20% (1/5 pts; 1 CMR). The most common non-hematologic treatment-emergent adverse events (TEAEs) occurring in &gt; 10% of all pts (all grade [Gr]; Gr 3/4) were rash events (21.7%; 1.7%), colitis/diarrhea events (16.7%; 5%), nausea (16.7%; 0%), cough (15%; 0%), and pyrexia (15%; 8.3%). Gr 3/4 AST and ALT elevations occurred in 5% and 1.7% of pts, respectively; Gr 3/4 neutropenia and anemia occurred in 5% of pts each. The most frequent ( &gt; 5%) serious TEAEs were pyrexia (8.3%), general physical health deterioration (6.7%), and hypercalcemia (6.7%). TEAEs led to therapy discontinuation in 7 pts (2 treatment-related), dose interruption in 20 pts (10 treatment-related), and dose reduction in 3 pts (all treatment-related). Median duration of therapy was 57.5 d (range, 11–318). Conclusions: Parsaclisib monotherapy using a QD followed by QW dosing regimen was well tolerated with no new safety signals reported. Further evaluation of parsaclisib in all subtypes of DLBCL is ongoing in a combination study Clinical trial information: NCT02998476.
MRI-based maps differentiating tumor from nontumor tissues for improved clinical management of brain tumor patients.
Authors: Yael Mardor, David Guez, David Last, Dianne Daniels, Yuval Grober, Ouzi Nissim, Chen Hoffmann, Dvora Nass, Alisa Talianski, Roberto Spiegelmann, Zvi R Cohen, Leor Zach
Journal: Journal of Clinical Oncology (2013)

e13002 Background: We have recently demonstrated delayed contrast extravasation MRI for calculating maps providing clear, high resolution depiction of tumor/non-tumor tissues. &gt;100 brain tumor patients have been recruited in 3 clinical studies. In all cases increased tumor volumes (TVs) on our maps were followed by progression while stable/decreased TVs did not require treatment changes. Following histological validation the maps are being used for clinical decisions. Methods: Our maps were applied for improved patient management in 23 patients post treatment in which consensus regarding tumor progression vs. treatment effects (TEs) has not been reached. In all cases increased enhancement was shown on T1-MRI and rCBV was low/inconclusive. Results: In 5 GBM patients 1-3 months post surgery our maps showed significant TVs, therefore 2 were started on Avastin and 3 were re-operated. One of the latter showed increased enhancement on T1-MRI after the second operation. The maps showed no TV consistent with later clinical improvement. Two GBM patients 3-4.5 months post chemoRT showed increased TEs and stable TVs consistent with pseudoprogression. Adjuvant TMZ was continued followed by decreased lesion volumes. 2 patients (GBM/AA) showed increased TVs 5 months/years post chemoRT and were referred to Avastin/surgery. One patient was scanned 2 wks post chemoRT with clinical deterioration and rescanned 3 wks later when stabilized showing significantly increased TVs with no change on standard MRI. The patient was re-operated. Brain mets patients were recruited 1-21 months post SRS. Four showed significant TVs and were referred to treatment (surgery, WBRT, Xeloda). Two were followed for 3-6 months and upon increase in TV were referred to surgery. In 6 patients 73-100% of the enhancing lesion consisted of TEs thus are currently stable under FU. In 3 the lesion has resolved within 2-4 months. Active tumor was confirmed histologically in all above resected lesions. Conclusions: Following validation of our easily interpreted color code maps patients are now referred from 4 major Israeli hospitals with a question of progression vs TEs. Our data suggests that the maps may be used for improved patient management when standard MRI is inconclusive.
Prognostic and Predictive Value of Blood Eosinophil Count, Fractional Exhaled Nitric Oxide, and Their Combination in Severe Asthma: A <i>Post Hoc</i> Analysis
Authors: Rahul Shrimanker, Oliver Keene, Gareth Hynes, Sally Wenzel, Steven Yancey, Ian D. Pavord
Journal: American Journal of Respiratory and Critical Care Medicine (2019)