tbuckley/cabot-search huggingface dataset:
Impact of the COVID-19 pandemic on the homeless: results from a retrospective closed cohort in France (March–May 2020)
Authors: Maya Husain, Anne Rachline, Anthony Cousien, Simon Rolland, Claire Rouzaud, Valentine Marie Ferre, Maria Vargas Gomez, Maï Le Teurnier, Marie Wicky-Thisse, Diane Descamps, Yazdan Yazdanpanah, Charlotte Charpentier, Armelle Pasquet-Cadre
Journal: Clinical Microbiology and Infection (2021)
Vertebral osteomyelitis in patients with Staphylococcus aureus bloodstream infection: Evaluation of risk factors for treatment failure
Authors: N Jung, A Ernst, I Joost, A Yagdiran, G Peyerl-Hoffmann, S Grau, M Breuninger, M Hellmich, D C Kubosch, J H Klingler, H Seifert, W V Kern, A J Kaasch, S Rieg
Journal: Journal of Infection (2021)
Residual ctDNA after treatment predicts early relapse in patients with early-stage NSCLC.
Authors: Davina Gale, Katrin Heider, Malcolm Perry, Giovanni Marsico, Andrea Ruiz-Valdepeñas, Viona Rundell, Jerome Wulff, Garima Sharma, Karen Howarth, David Gilligan, Susan Harden, Doris M. Rassl, Robert Rintoul, Nitzan Rosenfeld
Journal: Journal of Clinical Oncology (2021)

8517 Background: Liquid biopsies based on circulating tumor DNA (ctDNA) analysis are being investigated for detection of residual disease and recurrence. Conclusive evidence for utility of ctDNA in early-stage non-small cell lung cancer (NSCLC) is awaited. Due to low ctDNA levels in early-stage disease or post-treatment, effective methods require high analytical sensitivity to detect mutant allele fractions (MAF) below 0.01%. Methods: We analysed 363 plasma samples from 88 patients with NSCLC recruited to the LUng cancer CIrculating tumour DNA (LUCID) study, with disease stage I (49%), II (28%) and III (23%). 62% were adenocarcinomas. Plasma was collected before and after treatment, and at 3, 6 and 9 months after surgery (N = 69) or chemoradiotherapy (N = 19). Additional plasma was collected at disease relapse for 17 patients. Median follow-up was 3 years, and 40 patients progressed or died of any cause. We employed the RaDaR™ assay, a highly sensitive personalized assay using deep sequencing of up to 48 tumor-specific variants. Variants identified by tumor exome analysis were tested by deep sequencing of tumor tissue and buffy coat DNA to verify somatic mutations and exclude clonal hematopoiesis. The RaDaR assay demonstrated 90% sensitivity at 0.001% MAF in analytical validation studies. Results: ctDNA was detected in 26% of samples, at median MAF of 0.047% (range: 0.0007% to &gt; 2%), and prior to treatment in 87%, 77% and 24% for disease stage III, II and I respectively. For 62 patients, plasma was collected at a landmark timepoint, between 2 weeks and 4 months after initial treatment. ctDNA detection at the landmark timepoint was strongly predictive of clinical disease relapse, with Hazard Ratio of 20.7 (CI: 7.7-55.5, p-value &lt; 0.0001). All 11 cases with ctDNA detected at landmark had disease progression, a median of 121 days after detection, and these included all 8 patients that relapsed within 300 days of treatment. Across 27 patients whose disease progressed during the study, ctDNA was detected at any timepoint post-treatment in 17 cases, with a median lead time of 203 days, and up to 741 days prior to clinical progression. ctDNA was detected post-treatment, in 13 of the 15 patients that progressed and had ctDNA detected prior to treatment. Conclusions: Our results support an emerging paradigm shift, by demonstrating that liquid biopsies can reliably detect recurrence of NSCLC at a preclinical stage, many months before clinical progression, thereby offering the opportunity for earlier therapeutic intervention. Clinical trial information: NCT04153526.
High incidence of concurrent disease states detected during mobile lung cancer screening in an underserved population.
Authors: Daniel R. Carrizosa, Darcy L. Doege, Mellisa S Wheeler, Kia Dungan, Lauren Davis, Glenn Hickman, Brooke Weatherford, Stephanie White, John D. Doty, Kathryn Finch Mileham, Derek Raghavan
Journal: Journal of Clinical Oncology (2021)

6540 Background: Studies such as the National Lung Screening Trial (NLST; N Engl J Med 2011;365:395-409) have shown a survival benefit to low-dose Lung CT screening in high-risk smokers. Levine Cancer Institute (LCI) initiated the first mobile low dose computerized tomographic (LDCT) lung screening program for underserved populations in 2017. In addition to being able to intervene early in the natural history of lung cancer, the project has also shown a previously unreported high incidence of incidental diseases in this population. We characterize these findings in 1198 patients. Methods: From May 2017, subjects with criteria eligible for NLST screening were identified and underwent LDCT for lung cancer detection. Patients screened in the program were all uninsured or underinsured, mean age 60.8 years, 18% were African American, 3% Latin-x and 78% were rural with an overall 47.1 mean pack-year smoking history. These patients were screened using a novel mobile LDCT (J Clin Oncol 37, 2019 suppl; abstr 6567) created for this program. By December 2020, 1198 patients completed their first screening. All CT scans were reviewed by two separate radiologists and were reviewed for quality assurance by a separate expert multidisciplinary team. Results: Of the 1198 subjects, 84% (1006 subjects) were found by LDCT to have a least one incidental disease. More than half of the subjects (645, 53.8%) had coronary atherosclerosis. Of those, 25% (183) were described to have at least moderate disease with 8% (96) described as severe. Overall, 42% (504) were found to have emphysema and 25% (299) had vascular atherosclerotic disease; 1.8% (22) of those screened had a detected aortic aneurysm. In total, thirty separate disease findings were found (listed from fourth to tenth most common finding: degenerative spine changes [205], cholelithiasis [59], hiatal hernia [52], pericardial effusions [38], fatty liver [32], kidney stone [3]), and cardiomegaly [30]). 3.5% (42) were found to have an undiscovered breast, adrenal, liver or kidney mass that required further workup. Conclusions: The number of incidental findings in our mainly rural underserved subject group was very high (84%). 35.5% of patients in the National Lung Screening Trial died from heart disease or respiratory disease. These numbers have not been overtly discussed and our study confirms the number of concerning incidental diseases that can lead to morbidity or mortality. In this high-risk, underserved population of heavy smokers, the opportunity for positive impact on other disease states can be increased by a mobile lung cancer screening program by increasing access to care.
Pembrolizumab and all-trans retinoic acid combination treatment of advanced melanoma.
Authors: Martin McCarter, Richard P. Tobin, Dasha T. Cogswell, Victoria M. Vorwald, Dana Davis, Robert J. Van Gulick, Kasey L. Couts, Kimberly R. Jordan, Victoria Nuanes, Dexiang Gao, Theresa Michelle Medina, Karl D. Lewis, Rene Gonzalez, Ross W. McFarland, William A. Robinson
Journal: Journal of Clinical Oncology (2021)

9536 Background: Myeloid-derived suppressor cells (MDSCs) are potent suppressors of antitumor immunity and are commonly associated with poor outcomes in melanoma patients treated with immune checkpoint inhibitors. Inducing the differentiation of MDSCs using all-trans retinoic acid (ATRA) reduces MDSC frequency. This analysis seeks to assess the safety and efficacy of combining ATRA and pembrolizumab in advanced melanoma patients. Methods: This single arm, single institution, phase I/II study (NCT03200847) enrolled 24 patients diagnosed with stage IV melanoma. Eligible patients were over the age of 18 and had not been previously treated anti-PD-1 therapy. Treatment consisted of 200mg Q3W pembrolizumab plus the supplemental treatment of 150 mg/m2 ATRA orally for 3 days surrounding each of the first four infusions of pembrolizumab, with patients continuing pembrolizumab for up to two years until confirmed disease progression or unacceptable toxicity. The primary endpoints were safety and reduction in circulating MDSCs. Secondary endpoints were overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) according to RECIST v1.1. Results: At data cut off (Feb, 2021) 22 patients were evaluable for tumor response. Median follow-up was 1.0 years (0.3-2 years). In general, the combination of pembrolizumab and ATRA was well tolerated. The most common treatment-related adverse events (AEs) were grade 1 or 2, including headache (22 pts, 92%), fatigue (18 pts, 75%), rash (16 pts, 66%), and nausea (8 pts, 33%), most of which corresponded with the 3-day course of ATRA treatment. Ten patients had grade 3 or higher AEs with most being common ICI-related AEs. The ORR was 60% and DCR was 83%. Six-month PFS rate was 62%. Excluding patients diagnosed with uveal melanoma (n = 2) the ORR was 72%, DCR was 86%, and the six-month PFS rate was 68%. Paired analysis showed sustained decreases in absolute numbers ( p = 0.002) and percentage ( p = 0.007) of circulating MDSCs (CD3 - CD19 - CD56 - CD11b + CD33 + HLA-DR -/low ) 4-6 weeks after stopping ATRA. The study is ongoing and further data will be presented in the future. Conclusions: This study demonstrates that the combination of ATRA and pembrolizumab is well tolerated and suggests that reducing MDSCs with ATRA may enhance the efficacy of pembrolizumab. This strategy of targeting MDSCs in combination with pembrolizumab warrants further development. Research Funding: Merck. Clinical trial information: NCT03200847.
Detection of genes related to peritoneal metastasis of primary gastric cancer based on large-panel Next Generation Sequencing.
Authors: Si Tao, Xin Liu, Chunhui Jin, Rongrong Chen
Journal: Journal of Clinical Oncology (2021)

e16026 Background: Peritoneum is a common site of recurrence and metastasis of gastric cancer. The traditional clinical methods have poor sensitivity for the diagnosis of peritoneal metastasis, and there is no effective marker for predicting peritoneal metastasis of gastric cancer. In this study, the genetic profiles of primary tumors in gastric cancer patients with and without peritoneal metastasis, as well as the genetic alterations before and after metastasis in the same patient were analyzed to explore the genetic alterations associated with peritoneal metastasis. Methods: 232 patients with stage Ⅳ gastric cancer were divided into PM group and non-PM group according to whether there was peritoneal metastasis, DNA based Next Generation Sequencing (NGS) with a 1021 gene panel was performed on their samples. Clinical information was obtained synchronously from physicians and surgeons. Results: There was no significant difference in baseline clinical characteristics between patients in PM and non-PM groups. Molecular analysis revealed that in the PM group, the incidence of CDH1, CDH23, HDAC1, IDH1, KRAS, MED12, RHOA, NOTCH2, TGFBR1 mutations was significantly higher in PM group than that in non-PM group, and these mutated genes were mostly located in wnt/β- catenin and MAPK signaling pathway. On the contrary, the incidence of ERBB2 and CCNE1 amplification was significantly higher in non-PM group than in the other group. Further analysis of samples before and after peritoneal metastasis of 13 patients did not find significant differences in genetic alterations. Conclusions: Compared with other sites, the primary tumor of gastric cancer patients with peritoneal metastasis seems to have its unique molecular characteristics, and large-panel NGS can help us identify this part of patients. Future research may need to clarify whether more radical treatment strategies are needed for these patients.
Health-related quality of life for glioblastoma short and long-term survivors receiving treatment with TTfields.
Authors: Joshua David Palmer, Po-Ya Chuang, Gordon Chavez, Bruce CM Wang, Christina Proescholdt
Journal: Journal of Clinical Oncology (2021)

2055 Background: The aim of this study was to administer the first large-scale, international survey eliciting real-world patient-reported quality-of-life (QoL) for patients with newly diagnosed and long-term glioblastoma (GBM) currently receiving treatment with TTFields. Methods: A survey was designed and mailed to 2,815 patients actively using TTFields for treatment of GBM in the United States (US, n = 2,182) and Europe (EU, n = 633). The survey included 1) demographic information, 2) patient-reported clinical information and 3) EuroQol’s EQ-5D-5L and EQ visual analogue scale (EQ-VAS) surveys. Univariate and multivariate analyses were performed on five dimensions (mobility, self-care, usual activity, pain/discomfort, anxiety/depression) of the EQ-5D-5L and EQ-VAS to understand the impact of patient demographics and clinical characteristics on QOL. Results: A total of 1,106 patients were included (39.3% response rate) with 782 and 324 responses in the US and EU, respectively. The median time from diagnosis was 14 mos (range, 0-301 mos) and ≥24 mos in 28.4% of patients. Patients were mostly male (62.3%) with a mean age of 58.5 (SD = 12.5) and 69.3% had stable disease. Mean EQ-VAS was 68.2 for all patients and was significantly higher for those with &gt; 15 months since diagnosis compared to &lt; 15 months since diagnosis (p = 0.008). There were significantly fewer problems reported on self-care ( p = 0.04) and usual activity ( p = 0.007) in patients with a longer time since diagnosis in the univariate analysis. In the multivariate analysis, patients with a longer time since diagnosis reported significantly better EQ-VAS ( p = 0.04). The effect size in the multivariate analysis for time since diagnosis on EQ-VAS was higher in the progressed subgroup ( p = 0.17) compared to the broader sample (0.08). The EQ-VAS and all five dimensions including mobility, self-care, usual activity, pain/discomfort, and anxiety/depression were improved for stable patients compared to progressed patients in the univariate and multivariate analyses. However, when stratified by progression status, progressed patients with longer time from diagnosis had significantly fewer reported problems with mobility ( p = 0.04), self-care ( p = 0.004) and usual activity ( p = 0.008), and significantly better self-rated health status ( p = 0.02). Conclusions: GBM survivors receiving TTFields reported significantly improved health status over time since diagnosis. Long-term survival with TTFields does not have a detriment in patient reported quality of life, in fact with longer time from diagnosis QOL significantly improves. This is true for patients with stable and progressed disease. Future prospective clinical trials are needed to further study the impact of our treatment and tumor progression on patient QOL.
Rapid, simplified whole blood-based multiparameter assay to quantify and phenotype SARS-CoV-2-specific T-cells
Authors: Catherine Riou, Georgia Schäfer, Elsa du Bruyn, Rene T. Goliath, Cari Stek, Huihui Mou, Deli Hung, Katalin A. Wilkinson, Robert J. Wilkinson
Journal: European Respiratory Journal (2021)

Rapid tests to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell responses are urgently needed to decipher protective immunity and aid monitoring vaccine-induced immunity.
Abstract 11653: Ischemic Heart Disease and Change in Left Ventricular Ejection Fraction Over Time Among Patients With Heart Failure
Authors: Jay M Patel, Paul A Heidenreich
Journal: Circulation (2018)

Background: Patients who are diagnosed with heart failure (HF) are characterized by left ventricular ejection fraction (LVEF) at the time of diagnosis into preserved LVEF (LVEF > 50%) or reduced LV...
Glycoproteogenomics: Setting the Course for Next-generation Cancer Neoantigen Discovery for Cancer Vaccines
Authors: José Alexandre Ferreira, Marta Relvas-Santos, Andreia Peixoto, André M.N. Silva, Lúcio Lara Santos
Journal: Genomics Proteomics & Bioinformatics (2021)

Molecular-assisted precision oncology gained tremendous ground with high-throughput next-generation sequencing (NGS), supported by robust bioinformatics. The quest for genomics-based cancer medicine set the foundations for improved patient stratification, while unveiling a wide array of neoantigens for immunotherapy. Upfront pre-clinical and clinical studies have successfully used tumor-specific peptides in vaccines with minimal off-target effects. However, the low mutational burden presented by many lesions challenges the generalization of these solutions, requiring the diversification of neoantigen sources. Oncoproteogenomics utilizing customized databases for protein annotation by mass spectrometry (MS) is a powerful tool toward this end. Expanding the concept toward exploring proteoforms originated from post-translational modifications (PTMs) will be decisive to improve molecular subtyping and provide potentially targetable functional nodes with increased cancer specificity. Walking through the path of systems biology, we highlight that alterations in protein glycosylation at the cell surface not only have functional impact on cancer progression and dissemination but also originate unique molecular fingerprints for targeted therapeutics. Moreover, we discuss the outstanding challenges required to accommodate glycoproteomics in oncoproteogenomics platforms. We envisage that such rationale may flag a rather neglected research field, generating novel paradigms for precision oncology and immunotherapy.
Further Evidence Supporting the Use of Prophylactic Anticoagulation in Hospitalized Patients With COVID-19
Authors: Andrew B. Dicks, Ido Weinberg
Journal: JAMA Network Open (2021)

Valerie M. Vaughn, MD, MSc; Monica Yost, MPH; Chelsea Abshire, MPH; Scott A. Flanders, MD; David Paje, MD, MPH; Paul Grant, MD; Scott Kaatz, DO, MSc; Tae Kim, MHSA; Geoffrey D. Barnes, MD, MSc
Patients with early-stage (T1-2N0) adenosquamous lung cancer have worse long-term survival compared to patients with early-stage lung adenocarcinoma or squamous cell histology.
Authors: Larisa Shagabayeva, Patel B. Heer, Chi-Fu Jeffrey Yang, Michael Lanuti
Journal: Journal of Clinical Oncology (2021)

8550 Background: Survival outcomes for patients with adenosquamous carcinoma of the lung are not well understood by virtue of reduced prevalence. The objective of this study is to compare the long-term survival among patients with adenocarcinoma, squamous cell carcinoma and adenosquamous carcinoma of the lung. Methods: Overall survival of all patients with adenosquamous carcinoma, squamous cell carcinoma, and adenocarcinoma who received guideline-concordant treatment for T1-2N0M0 from 2004-2017 in the National Cancer Data Base was assessed using Kaplan-Meier analysis, multivariable Cox proportional hazard analysis, and propensity score-matched analysis. Results: Among patients who met study criteria (N = 88,983), there were 2,469 (2.77%) patients with adenosquamous, 60,148 (67.59%) with adenocarcinoma and 26,366 (29.63%) with squamous cell carcinoma histology. In patients who had T1-T2 N0 M0 disease, adenosquamous carcinoma was associated with significantly worse 5-year overall survival (58.9% [95%CI:56.6%-61.1%]) when compared with adenocarcinoma (72.4% [95% CI:72.0%-72.8%]) and squamous cell carcinoma (62.6% [95% CI:61.9%-63.3%]). In multivariable Cox proportional hazards analysis, adenocarcinoma (HR 0.81 [95% CI:0.76-0.87], p &lt; 0.001) and squamous cell carcinoma (HR 0.86 [95% CI:0.80-0.92], p &lt; 0.001) continued to be associated with significantly better survival when compared to adenosquamous carcinoma histology. A propensity score-matched analysis of 1,854 adenocarcinoma and 1,854 adenosquamous patients who were well matched by 17 common prognostic covariates (including tumor size and comorbidities) found that adenosquamous histology (57.2% [95% CI:54.7%-59.6%]) was associated with worse survival when compared to adenocarcinoma (63.0% [95% CI:60.6%-65.4%]). An additional propensity score-matched analysis of 1,852 squamous cell carcinoma and 1,852 adenosquamous patients matched by the same covariates demonstrated that adenosquamous carcinoma (57.1% [95%CI:54.6%-59.6%]) was associated with worse survival when compared with squamous cell carcinoma (64.0% [95% CI:61.5%-66.4%]). Conclusions: Early stage adenosquamous carcinoma of the lung is associated with worse overall survival compared to its individual histologic components of adenocarcinoma or squamous cell carcinoma. These observations in both the unmatched and propensity matched patient cohorts invoke consideration of multimodality therapy for these early tumors.
Abstract 90: Proportion of Citizens Who Are Unwilling to Perform Mouth-to-Mouth Rescue Breathing After Attending Basic Cpr Training Course and Its Characteristics
Authors: Harumi Hirose, Ken Nagao, Kimio Kikusima, Kazuhiro Watanabe
Journal: Circulation (2010)

Background: SOS-KANTO showed that bystander chest compression-only resuscitation (CCR) was the preferable approach to resuscitation for patients with out-of-hospital cardiac arrest, but few clinica...
Patient-reported barriers to online meetings: The case of a myeloma support group in western Kenya in the era of COVID-19.
Authors: Mercy Oduor, Kelvin Manyega, Therese Lotodo, Austin Okuku, Diana Namaemba, Lorraine Oyolo, John Oguda, Terry A. Vik
Journal: Journal of Clinical Oncology (2021)

e24036 Background: Multiple myeloma is a chronic progressive disease that calls for extended survivorship support post-diagnosis. Pre- COVID-19, the AMPATH Multiple Myeloma Program had created support groups for myeloma survivors and their caregivers that regularly met for health education, emotional support, and social opportunities. With the enforcement COVID-19 prevention and control protocols physical support group meetings became impossible. The program shifted to the online platform to sustain peer to peer support for myeloma patients and caregivers. We aim to describe challenges faced with online patient support group meetings as this has not been well documented in a resource-constrained setting. Methods: Myeloma patients and caregivers at Moi Teaching and Referral Hospital were contacted and a meeting date and time agreed. Participants were briefed on how to download and operate the zoom application in preparation for online meetings. A meeting link was shared with the expected attendees and a reminder sent two days before a meeting. Support group meetings were held for different groups among them myeloma survivors and caregivers. The meeting sessions were led by healthcare professionals – hematology consultants, social workers, nutritionist and psychosocial counsellors. Peer-to-peer sessions were also held. Results: Six online meeting sessions were held between June 2020 and December 2020. A total of 199 participants were expected to join the six different meetings but a low meeting turn-out of 25.6% was experienced. Participants were later contacted to unravel the reasons for a low turn-out. A total of 129 participants were contacted of which 88 responded. Out of the 88 respondents, 29% reported a tight work schedule, 25% short time meeting alerts, 20% did not have access to smartphones, and 8% had poor internet connectivity and another 8% reported no internet data bundles to connect to the internet. Conclusions: Low attendance of online meetings was observed. Participants cited scheduling and internet access as major obstacles to attending online support group meetings. Improved access to the internet through smartphones, reliable internet connection, and affordable data are needed in underserved communities to fully unlock the benefits of virtual platforms namely cost savings and effective information sharing.