tbuckley/cabot-search huggingface dataset:
Incidence of SARS-COV-2 infection incancer patients undergoing active treatment
Authors: C. M. Bravo, I. B. Lopez-Barajas, R. Q. Lopez, M. R. Lasarte, R. V. Roldan, J. A. Garcia, V. N. Perez, D. P. Martin, I. Z. Pedrinaci, E. M. Mora, N. J. Garcia, S. V. Cabra, I. De Urrutia Undabarrena, I. B. Mallofret, C. Q. Blanco, E. Perez-Ruiz
Journal: Clinical Cancer Research (2020)

Introduction and Objectives: Cancer patients are more susceptible to infections because of the active treatmentthat they need to treat their disease  A new coronavirus, called SARS-CoV-2, has caused a global pandemic wherecancer patients have an increased risk of morbidity and mortality associated with COVID-19  However, the incidencedata of COVID-19 in cancer patient with active treatment are not known, although the main oncology societiesrecommend a delay and/or stop in active cancer treatment during this pandemic  Whether this stop will have animpact on the future evolution of their disease is also not known  Therefore, a study of the incidence of COVID-19 inthis type of patient can help us to organize the protocols and the treatment in these high-risk patient group  Materials and Methods: We conducted a prospective clinical study of cancer patients within active treatment(chemotherapy, palliative hormonotherapy, radiotherapy, target therapies, or immunotherapy), analyzing the numberof COVID-19 diagnoses between February 26 and May 13 in two oncology services of the Andalusian community  Adescriptive analysis of 692 patients with active treatment was carried out  In addition, the cumulative incidence andthe differences between groups were calculated using the SPSS vs 18  Results: A total of 692 cancer patients undergoing active treatment at the Hospital Costa del Sol (Marbella) and atthe Hospital San Cecilio (Granada) were analyzed  Sixty four percent were men with a mean age of 60 years  Fortyone percent had a breast cancer diagnosis, 12 9% had lung cancer, and 14 5% had colorectal tumor  Fifty threepercent of them received treatment for stage IV disease, and up to 43% were delayed treatment due to pandemic The total number of infections was 9, a cumulative incidence of 1 3%, 95% CI (0 384-2 217), and 22% of them diedafter developing the infection  Advanced age (p = 0 011), an admission in the 3 months prior to the diagnosis ofCOVID-19 (p = 0 031), and active treatment with chemotherapy (p = 0 003) were the factors that were associated with an increased risk of developing COVID-19  Conclusions: The incidence of SARS-CoV-2 in cancer patients on active treatment is low but the mortality is high, as previously reported for these patients  Given that the incidence of COVID-19 in patients with treatment is low, wecannot conclude any role of treatment delay in the development of COVID-19 in these patients
Impact and utility of COLONTOWN, an online CRC patient and caregiver support group in clinical trial design.
Authors: Manju George, Jesse Joshua Smith, Eric David Miller, Paul Bernard Romesser, Nancy Seybold
Journal: Journal of Clinical Oncology (2021)

140 Background: Online cancer patient and caregiver support groups have burgeoned in the recent years; many provide critical emotional support and experiential wisdom to newly diagnosed patients. We outline below our experience engaging patients in clinical trial design working with COLONTOWN, a 5000+ member, online colorectal cancer (CRC) patient and caregiver support and educational community. Effective trial design is a complicated and lengthy process that requires input from multiple sources. Complex trial design can be particularly challenging, where opinions are mixed and a clear path forward may not be visible. Informed patient perspectives from support groups can be invaluable in such situations. Methods: Principal Investigators (PIs) for the oligometastatic CRC ERASure trial and the Janus rectal cancer trial worked with the lead author, a patient who is the Scientific Director of COLONTOWN. An interactive survey strategy was adopted and followed to solicit group feedback. COLONTOWN members (n = 70-120) were enthusiastic to participate and share the logic behind poll choices, and their personal experiences. Poll participation led to additional scientific discussion and improved community engagement around the survey questions. Poll data and highlights of the discussion were collected and passed on to study PIs in a de-identified manner. Results: Feedback from COLONTOWN helped PIs gauge patient enthusiasm for trial concepts and provide patient perspective and clarity to controversial questions in study design. This was particularly useful where data to support more than one option was available and the guidance from the NCI Task Force or cooperative group was split. The perspective from COLONTOWN was invaluable and used alongside NCI Task Force and cooperative group feedback to make decisions to move the trial concept forward. Conclusions: Support groups such as COLONTOWN are a versatile, valuable, underutilized and available resource that can be used to tap into patient perspectives during any clinical trial design process. Ideally, when utilized early, structured patient input can provide unique insights to PIs developing clinical trial concepts that could eliminate barriers and shorten the inception part of trial design. Increased awareness and knowledge of trial design support provided by such cancer communities could facilitate the development of patient-friendly trials to promote better accrual.
SAT0511 CYTOKINES, CHEMOKINES AND INFLAMMATORY BIOMARKERS IN NEUROSARCOIDOSIS
Authors: K. E. Byg, Z. Illes, T. Sejbaek, A. Kindt, T. Ellingsen, H. Nielsen
Journal: Annals of the Rheumatic Diseases (2020)

Background: Sarcoidosis is characterized by granulomatous inflammation, which in rare cases can affect the central nervous system, neurosarcoidosis (NS). Objectives: The aim of this study was to estimate levels of cytokines, chemokines, and vascular biomarkers in patients with NS. Methods: In this observational, cross-sectional study, cerebrospinal fluid (CSF) and plasma were collected from biopsy-proven sarcoidosis patients with clinical suspicion of NS. They were categorized into either a NS group (n=14) or a non-NS group (n=5) depending on fulfilment of NS criteria. The results were compared to a healthy control group (HC, n=11). Samples were analysed with Electrochemiluminescence, Mesoscale®. Results: The level of INF γ was significantly higher in NS group compared to non-NS group in CSF (median 11.3 pg/mL vs. 3.3 pg/mL) and in plasma (median 21.6 pg/mL vs. 4.5 pg/mL) In CSF and not in plasma, the level differs significantly in NS group compared to non-NS group, IL12/IL23p40 (median 54.05 pg/mL vs. 3.61 pg/mL), IL16 (median 8.7 pg/mL vs. 4.3 pg/mL), IL17A (median 1.37 pg/mL vs. 0.19 pg/mL), TNF β (median 0.37 pg/mL vs. 0.02 pg/mL), IL8 (median 55.4 pg/mL vs. 37.8 pg/mL), CCL11 (median 36.1 pg/mL vs. 16.4 pg/mL, CCL26 (median 6.7 pg/mL vs. 3.7 pg/mL), CXCL10 (median 4981 pg/mL vs. 771 pg/mL), CCL13 (median 24.5 pg/mL vs. 10.0 pg/mL), CCL22 (median 129.8 pg/mL vs. 22.6 pg/mL), CCL3 (median 54.1 pg/mL vs. 20.7 pg/mL), CCL17 (median 54.0 pg/mL vs. 6.9 pg/mL), ICAM1 (median 13901 pg/mL vs. 7327 pg/ml), and VCAM1 (median 18594 pg/mL vs. 12132 pg/mL) A cut-off level for each cytokine was set at 20% above the maximum values of both non-NS group and HC. Using this, the ratio of patients in NS group over were: -INF γ, 57% had level over 6.2 pg/mL in CSF, and 50% had level over 21.6 pg/mL in plasma. -IL12/IL23p40, 71% had level over 16.7 pg/mL in CFS. -CXCL10, 79% had level over 1614 pg/mL in CFS. -CCL22, 79% had level over 49.8 pg/mL in CFS. Conclusion: In NS patients, INF γ was elevated in both CSF and plasma, and multiple cytokines, chemokinves and vascular biomarkers were elevated in CSF. Disclosure of Interests: Keld-Erik Byg: None declared, Zsolt Illes: None declared, Tobias Sejbaek Grant/research support from: Biogen, grants, outside the submitted work. , Consultant of: Personal fees from Novartis, outside the submitted work. , Astrid Kindt: None declared, Torkell Ellingsen: None declared, Helle Nielsen: None declared
SAT0009 Cervical spine involvement in ankylosing spondylitis
Authors: A El Maghraoui, R Bensabbah, R Bahiri, A Bezza, N Guedira, N Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To study cervical spine involvement in ankylosing spondylitis (AS) and evaluate correlations with disease symptomatic and structural severity. <h3>Methods</h3> Prospective evaluation of AS during one year. Clinical, biological, and radiological data were collected. The risk of CS involvement was estimated using Kaplan-Maier?s method. <h3>Results</h3> 61 patients were enrolled: 38 males (62.2%) and 23 females of mean age 35.1 yrs (11) [range 17–66]. The mean disease duration was 10.6 yrs (7) [0.5–30]. Forty three patients (70.4%) had history of neck pain. Radiological involvement was present in 33 cases (54%). The concordance between clinical and radiological presentation was statistically significant (k = 0.49; p &lt; 1–6). The risk of the cervical spine involvement with regard to disease duration showed that 19.6% of patients had radiological involvement after 5 years of disease duration, 29.9% after 10 years, 45.1% after 15 years and 70.0% after 20 years. Comparison between patients with and without cervical spine radiological involvement showed no difference in age of onset or sex. There was statistical difference in symptomatic severity parameters (Schöber, chest expansion, BASMI, BASFI, BASDAI, BASG) and structural severity parameters (lumbar syndesmophytes score, BASRI). There was a significant correlation between cervical spine radiological scores (facet joint score and BASRI) and age, disease duration, and symptomatic severity indexes (chest expansion, Schober, BASMI, BASFI) and disease activity index (BASDAI). <h3>Conclusion</h3> Cervical spine involvement increases with age and disease duration in AS. Its severity is correlated to symptomatic and structural severity indexes of the disease.
Noninvasive monitoring of fibre fermentation in healthy volunteers by analyzing breath volatile metabolites: lessons from the FiberTAG intervention study
Authors: Audrey M. Neyrinck, Julie Rodriguez, Zhengxiao Zhang, Benjamin Seethaler, Florence Mailleux, Joeri Vercammen, Laure B. Bindels, Patrice D. Cani, Julie-Anne Nazare, Véronique Maquet, Martine Laville, Stephan C. Bischoff, Jens Walter, Nathalie M. Delzenne
Journal: Gut Microbes (2021)

The fermentation of dietary fibre (DF) leads to the production of bioactive metabolites, the most volatile ones being excreted in the breath. The aim of this study was to analyze the profile of exhaled breath volatile metabolites (BVM) and gastrointestinal symptoms in healthy volunteers after a single ingestion of maltodextrin (placebo) versus chitin-glucan (CG), an insoluble DF previously shown to be fermented into short-chain fatty acids (SCFA) by the human microbiota in vitro. Maltodextrin (4.5 g at day 0) or CG (4.5 g at day 2) were added to a standardized breakfast in fasting healthy volunteers (n = 15). BVM were measured using selected ion flow tube mass spectrometry (SIFT-MS) throughout the day. A single ingestion of 4.5 g CG did not induce significant gastrointestinal discomfort. Untargeted metabolomics analysis of breath highlighted that 13 MS-fragments (among 408 obtained from ionizations of breath) discriminated CG versus maltodextrin acute intake in the posprandial state. The targeted analysis revealed that CG increased exhaled butyrate and 5 other BVM – including the microbial metabolites 2,3-butanedione and 3-hydroxybutanone – with a peak observed 6 h after CG intake. Correlation analyses with fecal microbiota (Illumina 16S rRNA sequencing) spotlighted Mitsuokella as a potential genus responsible for the presence of butyric acid, triethylamine and 3-hydroxybutanone in the breath. In conclusion, measuring BMV in the breath reveals the microbial signature of the fermentation of DF after a single ingestion. This protocol allows to analyze the time-course of released bioactive metabolites that could be proposed as new biomarkers of DF fermentation, potentially linked to their biological properties.Trial registration: Clinical Trials NCT03494491. Registered 11 April 2018 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03494491
Antibody–drug conjugates in solid tumors: a look into novel targets
Authors: Carmen Criscitiello, Stefania Morganti, Giuseppe Curigliano
Journal: Journal of Hematology & Oncology (2021)

Abstract Antibody–drug conjugates (ADCs) are a relatively new class of anticancer agents designed to merge the selectivity of monoclonal antibodies with cell killing properties of chemotherapy. They are commonly described as the “Trojan Horses” of therapeutic armamentarium, because of their capability of directly conveying cytotoxic drug (payloads) into the tumor space, thus transforming chemotherapy into a targeted agent. Three novel ADCs have been recently approved, i.e., trastuzumab deruxtecan, sacituzumab govitecan and enfortumab vedotin, respectively, targeting HER2, Trop2 and Nectin4. Thanks to progressive advances in engineering technologies these drugs rely on, the spectrum of diseases sensitive to these drugs as well as their indications are in continuous expansion. Several novel ADCs are under evaluation, exploring new potential targets along with innovative payloads. This review aims at providing a summary of the technology behind these compounds and at presenting the latest ADCs approved in solid tumors, as well as at describing novel targets for ADCs under investigation and new strategies to optimize their efficacy in solid tumors.
Abstract 16387: Non-Muscle Myosin Light Chain Kinase Activity Mediates Hyper-Proliferation and Anti-Apoptosis in Human Pulmonary Artery Endothelial Cells Leading to Pulmonary Arterial Hypertension
Authors: Mariam Anis, Yulia Epshtein, Jeffrey R Jacobson, Dustin R Fraidenburg
Journal: Circulation (2018)

Introduction: Endothelial cell hyper-proliferation and inhibition of apoptosis contribute to the pathobiology of pulmonary arterial hypertension (PAH). Bone morphogenetic protein receptor II (BMPR2...
Chemoradiation-induced molecular alterations and associated outcomes in patients with rectal cancer.
Authors: Mohamed E. Salem, Hsih-Te Yang, James Thomas Symanowski, Alberto Puccini, Carol J. Farhangfar, Sherif El-Refai, David King, Edward S. Kim
Journal: Journal of Clinical Oncology (2021)

104 Background: Molecular changes and associated acquired resistance of rectal tumors following chemoradiotherapy (CRT) have not been well studied. We aimed to examine CRT-induced molecular changes and prognostic associations in rectal cancer patients (pts) undergoing preoperative CRT followed by surgery. Methods: A paired analysis using pre-CRT biopsies and the corresponding post-CRT resected tissues of rectal cancer patients undergoing preoperative CRT followed by surgery was performed. Pre- and post-CRT tumor samples underwent next-generation sequencing (NGS) by Tempus xT assay, which detects a panel of 596 gene mutations, including single nucleotide variants, insertions/deletions, copy number amplifications, and gene rearrangements. The cancer driver gene was detected based on positional clustering of gained mutations using OncodriveCLUST. The paired t-test was used to examine differences in tumor mutational burden (TMB) and microsatellite instability (MSI) between pre- and post-CRT samples. Results: In total, 61pts of median age 61yrs—75% white, 18% black, and 57% male—with localized rectal cancer were studied. NGS testing was performed in 57 pt tumor samples; 43 pts had pre-CRT samples, 48 pts had post-CRT samples, and 34 pts had paired samples. The most frequent genetic alterations seen in the 43 pre-CRT tumor samples were APC (37.2%), ARID1B (30.2%), KMT2C (30.2%), ZFXH3 (25.6%), FLT4 (20.9%), MLLT3 (20.9%), and TP53 (20.9%), whereas in the 48 post-CRT tumor samples, the most frequent mutations were APC (54.2%), TP53 (35.4%), KRAS (27.1%), MKI67 (25.0%), KMT2C (18.8%), APOB (14.6%), and CEBPA (12.5%). Comparing the pre- and post-CRT samples, no significant differences in TMB (median: 5.0 mut/MB vs. 3.3 mut/MB, p=0.922) or MSI status by NGS (p=0.069) were observed. Among the 34 pts with paired samples, 26.5% (9/34) relapsed, and 17.6% (6/34) died. When examining tumor mutation changes between pre- and post-CRT samples (table), the most common gained mutations were seen in APC (29.4% ), MKI67 (26.5% ), KTM2C (17.6%), and TP53 (17.67%); and most common losses were in ARID1B (26.5%), ZFHX3 (26.5%), FLT4 (21.0%) and GATA6 (21.0%). Of the gained mutations, OncodriveCLUST analysis showed that MKI67 potentially carries a driver mutation (pG866V) at exon 12 (p = 0.045), which exclusively existed in the two relapsed pts. Conclusions: Our data suggest that CRT did not alter MSI status nor the level of TMB. However, CRT did result in gained molecular alterations that could be responsible for treatment resistance and predict relapse. Gained MKI67 mutation may be a prognostic biomarker for relapse after CRT. Further prospective studies are needed to validate these findings. [Table: see text]
Polymorphisms of pluripotency transcription factors for predicting cetuximab efficacy in metastatic colorectal cancer: Data from FIRE-3 and TRIBE trials.
Authors: Hiroyuki Arai, Joshua Millstein, Fotios Loupakis, Sebastian Stintzing, Jingyuan Wang, Francesca Battaglin, Natsuko Kawanishi, Shivani Soni, Zhang Wu, Chiara Cremolini, Volker Heinemann, Alfredo Falcone, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2021)

98 Background: Cancer stem cells are subpopulation of cancer cells characterized by the self-renewal ability, and primarily maintained by a network of pluripotency transcription factors (PTFs). Despite their chemo-resistant phenotype, recent clinical trials data show cetuximab (Cet) is more beneficial for a subset of metastatic colorectal cancer (mCRC) categorized in a mesenchymal/stem-like subtype based on transcriptomic classifications. We investigated whether single nucleotide polymorphisms (SNPs) in PTF encoding genes have predictive values for the efficacy of Cet in mCRC patients. Methods: Genomic and clinical data from three independent cohorts of patient treated with first-line chemotherapy ( n = 451, in total) were tested: Cet cohort (FOLFIRI+Cet arm in FIRE-3 trial, n = 129); bevacizumab (Bev) cohort 1 (FOLFIRI+Bev arm in FIRE-3 trial, n = 107) and Bev cohort 2 (FOLFIRI+Bev arm in TRIBE trial, n = 215), as controls. Genomic DNA extracted from blood samples was genotyped using an OncoArray (Illumina, Inc., San Diego, CA, USA). Eight SNPs in PTF encoding genes ( NANOG rs11055786, NANOG rs11055767, NANOGP8 rs2168958, NANOGP8 rs9944179, POU5F1 rs3130501, POU5F1 rs3130932, SOX2 rs11915160, and MYC rs3891248) were tested for association with progression-free survival (PFS) and overall survival (OS), using Cox proportional hazards model. Results: In the Cet cohort, three SNPs were significantly associated with PFS in univariate analysis: NANOG rs11055767 (C/C vs any A allele, hazard ratio [HR] = 0.62, 95% confidence interval [CI] = 0.42–0.94, log-rank p = 0.02), NANOGP8 rs2168958 (A/A vs any C allele, HR = 2.12, 95% CI = 1.36–3.29, log-rank p &lt; 0.01), and NANOGP8 rs9944179 (G/G vs any A allele, HR = 3.68, 95% CI = 1.46–9.31, log-rank p &lt; 0.01). Multivariate analysis confirmed the significance in NANOGP8 rs2168958 and NANOGP8 rs9944179. Furthermore, two SNPs were significantly associated with OS in multivariate analysis: POU5F1 rs313051 (G/G vs any A allele, HR = 0.46, 95% CI = 0.22–0.99, adjusted p = 0.04) and POU5F1 rs3130932 (A/A vs any C allele, HR = 0.46, 95% CI = 0.22–0.93, adjusted p = 0.03). Both in the Bev cohorts 1 and 2, no significant associations between the SNPs and clinical outcomes were observed. Conclusions: The current findings suggest that polymorphisms in the PTF genes could be predictive markers for Cet in patients with mCRC. Further studies are warranted to validate the predictive utility.
ヒト鼻上皮細胞(HNEC)のciclesonide(CIC)の代謝に関係するエステラーゼ
Authors: Wingertzahn Ma, Sato H, Nave R, Nonaka T, Mochizuki T, Takahama S, Kondo S
Journal: Journal of Allergy and Clinical Immunology (2006)
Changes in treatment and outcomes of stage II/III rectal cancer patients treated with trimodality therapy (TT) between 2006-2016: An NCDB analysis.
Authors: Hagen F. Kennecke, Henry T. Bahnson, Bruce Lin, Jennifer Kaplan, Huong Pham, Andrew Suen, Val Simianu
Journal: Journal of Clinical Oncology (2021)

32 Background: Trimodality therapy (TT) remains standard for stage 2/3 rectal cancer and emerging evidence supports better outcomes with total neoadjuvant therapy (TNT) than similar therapy given post-operatively (Post-op). Real-world practice patterns and sequence of TT have significant implications on rectal cancer quality of care, outcomes and clinical trial design, and are not well described. Methods: The National Cancer Database was used to identify patients with clinical (c) stage 2/3 rectal adenocarcinoma diagnosed between 2006-2016, while pathologic (p) stage 2/3 was used when c stage was missing. Patients were included if they received Chemo/Radiation (C/RT), single or multiagent (SA or MA) chemotherapy (CT) and surgery. TNT was defined as receipt of pre-op C/RT and MA CT and no post-op therapy. Survival analyses were performed using Kaplan-Meier (KM) estimates and Cox univariate and multivariate hazard ratios (HRs) adjusted for TNT group, sex, race, year of diagnosis, stage, facility type, and age of diagnosis. Five-year KM survival proportions were limited to years 2006-2012, while Cox HRs were estimated from 2006 to 2015. Results: Of 32,467 patients who received TT, 8883 (27%) received TNT and 23,584 were classified no-TNT. TNT and no-TNT cohorts were numerically similar in age, race and gender. A significantly higher proportion of pStages 0-2 patients were observed in the TNT vs the no-TNT cohorts (61% vs. 48%, p &lt; .001). In analysis of annual treatment patterns of the whole cohort, a gradual reduction in Post-op C/RT was observed between 2006 (28%) and 2016 (8%, p &lt; .001), while use of TNT and MA CT did not increase. A migration to lower pStages 0/1/2/3 was seen between 2006 (1/10/31/57%, respectively) and 2016 (3/22/29/45%) (2016) (p &lt; .001). Five-year OS analysis showed superior OS for Pre-op vs Post-op C/RT (74 vs 69%, HR = .81, p &lt; .001), and MA CT vs. SA CT (76 vs 71%, HR = 0.79, p &lt; .001) but inferior 5-y OS for the TNT vs. no-TNT cohorts (74 vs 78%, HR = 1.17, p &lt; .001). Conclusions: Between 2006-16, a minority of patients treated with TT for stage 2/3 rectal cancer received TNT which did not increase over time. Significant annual shifts from Post-op C/RT to Pre-op C/RT, and migration to lower pStages were seen during this time period. Pre-op C/RT and MA CT were associated with improved OS, while TNT patients experienced inferior OS vs. the no-TNT cohort, possibly related to confounding factors in this observational cohort; multivariate sub-group analysis to be presented. Emerging evidence in support of TNT may further change treatment patterns and outcomes. [Table: see text]