tbuckley/cabot-search huggingface dataset:
Biomimetic Silk Fibroin Hydrogels Strengthened by Silica Nanoparticles Distributed Nanofibers Facilitate Bone Repair
Authors: Yuet Cheng, Gu Cheng, Congyong Xie, Chengcheng Yin, Xiangyang Dong, Zhi Li, Xue Zhou, Qun Wang, Hongbing Deng, Zubing Li
Journal: Advanced Healthcare Materials (2021)

Abstract Various materials are utilized as artificial substitutes for bone repair. In this study, a silk fibroin (SF) hydrogel reinforced by short silica nanoparticles (SiNPs)‐distributed‐silk fibroin nanofibers (SiNPs@NFs), which exhibits a superior osteoinductive property, is fabricated for treating bone defects. SF acts as the base part of the composite scaffold to mimic the extracellular matrix (ECM), which is the organic component of a native bone. The distribution of SiNPs clusters within the composite hydrogel partially mimics the distribution of mineral crystals within the ECM. Incorporation of SiNPs@NFs enhances the mechanical properties of the composite hydrogel. In addition, the composite hydrogel provides a biocompatible microenvironment for cell adhesion, proliferation, and osteogenic differentiation in vitro. In vivo studies confirm that the successful repair is achieved with the formation of a large amount of new bone in the large‐sized cranial defects that are treated with the composite hydrogel. In conclusion, the SiNPs@NFs‐reinforced‐hydrogel fabricated in this study has the potential for use in bone tissue engineering.
Reduction in COVID-19 Patients Requiring Mechanical Ventilation Following Implementation of a National COVID-19 Vaccination Program — Israel, December 2020–February 2021
Authors: Ehud Rinott, Ilan Youngster, Yair E. Lewis
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

The availability of COVID-19 vaccines represents an opportunity to mitigate the effects of the global pandemic.Achieving high vaccination coverage through intensive vaccination campaigns has the potential to substantially reduce COVID-19-associated morbidity and mortality.Clinical trials have demonstrated the efficacy of COVID-19 vaccines in preventing mild and severe COVID-19 in a controlled setting.However, clinical trials are not designed to assess the population impact of vaccination in a real-world setting (1,2).Israel initiated a national vaccination campaign using the Pfizer-BioNTech BNT162b2 (Pfizer-BioNTech) vaccine in December 2020, prioritizing persons aged >60 years, health care workers, and persons with underlying medical conditions.By February 2021, 2-dose vaccination coverage among persons aged ≥70 years was 84%.To assess the effect of COVID-19 vaccination on the occurrence of severe disease, an ecological study was conducted.Requiring mechanical ventilation was used as a proxy for severe COVID-19.The number of COVID-19 patients aged ≥70 years (who had the highest 2-dose vaccination coverage, 84.3%) requiring mechanical ventilation was compared with that of patients aged <50 years, who had the lowest 2-dose vaccination coverage (9.9%).Since implementation of the second dose of the vaccination campaign, the ratio of COVID-19 patients requiring mechanical ventilation aged ≥70 years to those aged <50 years has declined 67%, from 5.8:1 during October-December 2020 to 1.9:1 in February 2021.These findings provide preliminary evidence of the effectiveness of vaccines in preventing severe cases of COVID-19 at the national level in Israel.Receipt of COVID-19 vaccines by eligible persons can help limit spread of disease and potentially reduce the occurrence of severe disease.The first case of COVID-19 in Israel, a country with a population of approximately 9 million, was reported in February 2020.As of February 9, 2021, approximately 700,000 cases and 5,200 deaths had been reported (3).Nonpharmaceutical interventions have included three national stay-at-home orders, † multiple rounds of school closures, restrictions on commercial activity and travel, and a mask mandate, among others.The most recent * These authors contributed equally to this report.
IgE blockade with omalizumab reduces pruritus related to immune checkpoint inhibitors and anti-HER2 therapies
Authors: D.M. Barrios, G.S. Phillips, A.N. Geisler, S.R. Trelles, A. Markova, S.J. Noor, E.A. Quigley, H.C. Haliasos, A.P. Moy, A.M. Schram, J. Bromberg, S.A. Funt, M.H. Voss, A. Drilon, M.D. Hellmann, E.A. Comen, S. Narala, A.B. Patel, M. Wetzel, J.Y. Jung, D.Y.M. Leung, M.E. Lacouture
Journal: Annals of Oncology (2021)

Immunoglobulin E (IgE) blockade with omalizumab has demonstrated clinical benefit in pruritus-associated dermatoses (e.g. atopic dermatitis, bullous pemphigoid, urticaria). In oncology, pruritus-associated cutaneous adverse events (paCAEs) are frequent with immune checkpoint inhibitors (CPIs) and targeted anti-human epidermal growth factor receptor 2 (HER2) therapies. Thus, we sought to evaluate the efficacy and safety of IgE blockade with omalizumab in cancer patients with refractory paCAEs related to CPIs and anti-HER2 agents.Patients included in this multicenter retrospective analysis received monthly subcutaneous injections of omalizumab for CPI or anti-HER2 therapy-related grade 2/3 pruritus that was refractory to topical corticosteroids plus at least one additional systemic intervention. To assess clinical response to omalizumab, we used the Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was defined as reduction in the severity of paCAEs to grade 1/0.A total of 34 patients (50% female, median age 67.5 years) received omalizumab for cancer therapy-related paCAEs (71% CPIs; 29% anti-HER2). All had solid tumors (29% breast, 29% genitourinary, 15% lung, 26% other), and most (n = 18, 64%) presented with an urticarial phenotype. In total 28 of 34 (82%) patients responded to omalizumab. The proportion of patients receiving oral corticosteroids as supportive treatment for management of paCAEs decreased with IgE blockade, from 50% to 9% (P < 0.001). Ten of 32 (31%) patients had interruption of oncologic therapy due to skin toxicity; four of six (67%) were successfully rechallenged following omalizumab. There were no reports of anaphylaxis or hypersensitivity reactions related to omalizumab.IgE blockade with omalizumab demonstrated clinical efficacy and was well tolerated in cancer patients with pruritus related to CPIs and anti-HER2 therapies.
The need for ethical guidance for the use of patient-reported outcomes in research and clinical practice
Authors: Samantha Cruz Rivera, Rebecca Mercieca-Bebber, Olalekan Lee Aiyegbusi, Jane Scott, Amanda Hunn, Conrad Fernandez, Jonathan Ives, Carolyn Ells, Gary Price, Heather Draper, Melanie J. Calvert
Journal: Nature Medicine (2021)
Efficacy of VEGFR-TKI plus immune checkpoint inhibitor (ICI) in metastatic renal cell carcinoma (mRCC) patients with favorable IMDC prognosis.
Authors: Chiara Ciccarese, Roberto Iacovelli, Emilio Bria, Giovanni Schinzari, Ernesto Rossi, Serena Astore, Maria Antonella Cannella, Tatiana D'Angelo, Carlo Maria Cicala, Maria Grazia Maratta, Giampaolo Tortora
Journal: Journal of Clinical Oncology (2021)

318 Background: Combinations of a PD-1/PD-L1 immune checkpoint inhibitor (ICI) with a VEGFR-TKI as front-line/treatment-naïve therapy significantly improve the outcome of metastatic renal cell carcinoma (mRCC) patients. The benefit of these combinations is well evident in IMDC intermediate- and poor-risk population, while it is unclear in the subgroup of mRCC patients with favorable prognosis. We performed a meta-analysis with the aim to evaluate whether the addition of ICIs to VEGFR-TKIs is able to improve the outcome compared to VEGFR-TKIs alone in mRCC patients with favorable IMDC prognosis. Methods: This meta-analysis searched MEDLINE/PubMed, the Cochrane Library and ASCO Meeting abstracts for phase II or III randomized clinical trials (RCTs) testing the combination of VEGFR-TKI+ICI in mRCC. Data extraction was conducted according to the PRISMA statement. The hazard ratios (HRs) for PFS and OS with the relative 95% CIs were extracted from each study. Summary HRs was calculated using random- or fixed-effects models, depending on the heterogeneity of the included studies. Results: Three RCTs were selected for the final analysis, with a total of 605 patients (306 treated with VEGFR-TKI+ICI combinations and 299 who received sunitinib in the control arms). The combination of VEGFR-TKI+ICI improved PFS compared to sunitinib, with a 30% reduction of the risk of progression (fixed-effect, HR=0.70; p = 0.003). However, VEGFR-TKI+ICI combinations did not significantly prolong OS (fixed-effect; HR = 0.94; 95% CI 0.62–1.43; p = 0.77). Conclusions: Our analysis demonstrates a PFS benefit without an OS advantage for VEGFR-TKI+ICI combinations as first-line therapy for mRCC patients with favourable prognosis according to IMDC. Longer follow-up is required to definitely confirm the best therapy for treatment-naïve mRCC patients with favorable prognosis. [Table: see text]
BET proteolysis targeted chimera-based therapy of novel models of Richter Transformation-diffuse large B-cell lymphoma
Authors: Warren Fiskus, Christopher P. Mill, Dimuthu Perera, Christine Birdwell, Qing Deng, Haopeng Yang, Bernardo H. Lara, Nitin Jain, Jan Burger, Alessandra Ferrajoli, John A. Davis, Dyana T. Saenz, Wendy Jin, Cristian Coarfa, Craig M. Crews, Michael R. Green, Joseph D. Khoury, Kapil N. Bhalla
Journal: Leukemia (2021)

Abstract Richter Transformation (RT) develops in CLL as an aggressive, therapy-resistant, diffuse large B cell lymphoma (RT-DLBCL), commonly clonally-related (CLR) to the concomitant CLL. Lack of available pre-clinical human models has hampered the development of novel therapies for RT-DLBCL. Here, we report the profiles of genetic alterations, chromatin accessibility and active enhancers, gene-expressions and anti-lymphoma drug-sensitivity of three newly established, patient-derived, xenograft (PDX) models of RT-DLBCLs, including CLR and clonally-unrelated (CLUR) to concomitant CLL. The CLR and CLUR RT-DLBCL cells display active enhancers, higher single-cell RNA-Seq-determined mRNA, and protein expressions of IRF4, TCF4, and BCL2, as well as increased sensitivity to BET protein inhibitors. CRISPR knockout of IRF4 attenuated c-Myc levels and increased sensitivity to a BET protein inhibitor. Co-treatment with BET inhibitor or BET-PROTAC and ibrutinib or venetoclax exerted synergistic in vitro lethality in the RT-DLBCL cells. Finally, as compared to each agent alone, combination therapy with BET-PROTAC and venetoclax significantly reduced lymphoma burden and improved survival of immune-depleted mice engrafted with CLR-RT-DLBCL. These findings highlight a novel, potentially effective therapy for RT-DLBCL.
Preliminary phase 1 results from an HIV vaccine candidate trial
Authors: Priya Venkatesan
Journal: The Lancet Microbe (2021)

Findings from a small US trial in 48 HIV-negative adults presented last week at the HIV Research for Prevention (HIVR4P) virtual conference showed that 97% of participants who received an HIV vaccine immunogen candidate developed VRC01-class IgG B cells, precursors to broadly neutralising VRC01-class antibodies. The results have been announced in a press release, but are not published or peer-reviewed yet.
Atezolizumab (atezo) monotherapy versus chemotherapy in previously untreated locally advanced or metastatic urothelial carcinoma (mUC): Clinical outcomes by PD-L1 status in cisplatin (cis)-ineligible pts from the phase III IMvigor130 study.
Authors: Matt D. Galsky, Aristotelis Bamias, Jose Angel Arranz Arija, Ian D. Davis, Maria De Santis, Eiji Kikuchi, Xavier Garcia del Muro, Se Hoon Park, Ugo De Giorgi, Boris Alekseev, Marina Mencinger, Kouji Izumi, Javier Puente, Jian-Ri Li, Almut Mecke, Sanjeev Mariathasan, Romain Banchereau, Xinhui Huang, Chooi Peng Lee, Enrique Grande
Journal: Journal of Clinical Oncology (2021)

434 Background: Atezo (anti–PD-L1) monotherapy is approved for cis-ineligible pts who have locally advanced or mUC with PD-L1–expressing immune cells on ≥ 5% of the tumor area (IC2/3 per VENTANA SP142 IHC assay). The IMvigor130 primary analysis demonstrated a significant PFS benefit with atezo + platinum/gemcitabine (plt/gem) (arm A) vs placebo (pbo) + plt/gem (arm C) as 1L treatment for mUC (Galsky Lancet 2020); at that time, interim OS data for arm A vs C were encouraging but immature. OS with atezo monotherapy (arm B) could not be formally tested, but favorable efficacy was seen in IC2/3 pts. In this exploratory analysis, we assess outcomes by PD-L1 status in cis-ineligible pts. Methods: Pts were randomized 1:1:1 to arms A, B or C (Galsky Lancet 2020). Evaluation of OS (co-primary EP) was performed via a hierarchical fixed sequence procedure: arm A vs C ITT pts; then, arm B vs C ITT and IC2/3 pts. No formal testing was performed in this exploratory subgroup analyses; OS and RECIST 1.1 ORR (per investigator [secondary EP]) were descriptively evaluated. Results: Efficacy data suggested OS and ORR benefit in atezo-treated cis-ineligible IC2/3 pts (Table). In the overall safety population, all-grade treatment-related AEs (TRAEs) had occurred in 60% and 96% of arm B and C pts, respectively; grade 3-4 TRAEs occurred in 15% and 81%, respectively. Biomarker data evaluating PD-L1 biology (assessed by SP142) and associated transcriptome analysis in arms B vs C will be presented. Conclusions: This exploratory analysis of IMvigor130 pts with 1L cis–ineligible IC2/3 mUC provides additional evidence for clinical benefit with single-agent atezo, a well-tolerated treatment with a distinct safety profile vs chemo. Analyses with longer OS follow-up are warranted. Clinical trial information: NCT02807636 . Research Sponsor: F. Hoffmann-La Roche Ltd[Table: see text]
Abstract 13570: Effect of Chronic Kidney Disease on Efficacy of Remote Pulmonary Hemodynamic Monitoring System in Reducing Hospital Encounters
Authors: Udit B Bhatnagar, Michelle Corothers, Susan Puumala, Orvar Jonsson
Journal: Circulation (2017)

Background: Patients with chronic kidney disease (CKD) are prone to heart failure (HF) exacerbations and have difficult to manage volume status. Objective: To study real world data regarding the ef...
Correspondence on ‘SARS-CoV-2 antibody response after COVID-19 in patients with rheumatic disease’
Authors: Shanoj K C, Sakir Ahmed, Veena Shenoy, Aparna R Menon, Sanjo Saijan, Sageer AS Babu, Padmanabha Shenoy
Journal: Annals of the Rheumatic Diseases (2021)

We read with great interest the article published by D’Silva et al .1 The authors reported three patients with inadequate antibody response to SARS-CoV-2 infection, two of whom received rituximab (RTX). Presence of antispike or antinucleocapsid IgG antibodies is strongly associated with reduced reinfection rates following the COVID-19.2 RTX is an anti-CD 20 monoclonal antibody that depletes B cells. Both T cell-dependent and T cell-independent immune responses against various infections agents are drastically reduced up to 6 months following RTX infusion.3 4 Here we report the antibody response to SARS-CoV-2 infection in five patients with autoimmune rheumatic disease on RTX therapy.

In our centre 224 patients with autoimmune rheumatic diseases had RT-PCR proven COVID-19 infection between March 2020 and December 2020. Of these, five patients had received RTX therapy within 18 months. …
Mitigating ethnic disparities in covid-19 and beyond: census linkage can help tackle the data deficit
Authors: Laurence Gruer, Raj S Bhopal
Journal: BMJ (2021)

We disagree with Razai and colleagues on the comparative lack of data on ethnicity in the United Kingdom. 1 Few countries have produced more data than the UK, in part through inclusion of ethnicity and country of birth in its national censuses since 1991. 2 The Scottish Health and Ethnicity Linkage Study linked the 2001 Scotland census to death records and NHS databases.It has published 28 papers on many outcomes for up to 15 ethnic groups. 3 This includes an analysis of infection related hospital admission or death and bloodborne viral infections. 4 Showing complex ethnic differences across 18 specific infection categories, the study contextualises the disproportionate effects of covid-19 on ethnic minorities.
Clinical-pathological characterization and outcomes of metastatic urothelial cancer in Latin America: Retrospective and translational multicenter database (LACOG 1518).
Authors: Vinicius Carrera Souza, Murilo Luz, Diogo Assed Bastos, Marcelo Roberto Pereira Freitas, Breno Dauster Pereira E Silva, Fernando Sabino M. Monteiro, Roni Fernandes, Manuel Caitano, Karine Trindade, Lucas Nogueira, Daniel Herchenhorn, Juan Sade, Fernando Nunes Galvão de Oliveira, Andre P. Fay, Gustavo Werutsky, Fernando C. Maluf, Vanessa Carvalho Fabricio, Rosemarie Gidekel, Patricia Pacheco, Andrey Soares
Journal: Journal of Clinical Oncology (2021)

TPS497 Background: There is lack of high-quality and comprehensive data on advanced urothelial cancer in Latin America. Pathological and clinical outcomes information of this cancer can help the scientific community to understand the current standard of treatment and identify possible gaps for optimal care. Very few translational studies were performed in advanced urothelial cancer in developing countries describing the prevalence of key biomarkers for targeted agents and immunotherapy. Methods: LACOG 1518 is a large multi-institutional retrospective study that will collect information about sociodemographic data, treatment and outcome of patients diagnosed with recurrent/ metastatic urothelial cancer in Latin America between January 2016 and December 2019. Socio-demographic characteristics, clinical-pathological features, treatment patterns and outcomes will be extracted from medical charts. Tumor tissue will be collected for fibroblast growth factor receptor (FGFR) gene mutation or fusion test in a central laboratory. A biorepository will be built for future translational research including PD-L1 test and next generation sequencing. Primary endpoint consists on characterize demographic, socioeconomic factors, medical and oncological history of patients diagnosed with recurrent/metastatic urothelial cancer. This study aim to describe treatment sequence, duration, best response and progression time in each line of therapy as well as survival at 1 and 2 years. Translational research endpoints are biomarkers prevalence and association with treatment responses and outcomes.
Mental Health Resource Use Among Patients Undergoing Curative Intent Treatment for Bladder Cancer
Authors: Michael J Raphael, Rebecca Griffiths, Yingwei Peng, Sumit Gupta, D Robert Siemens, Claudio N Soares, Christopher M Booth
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Patients with bladder cancer may experience mental health distress. Mental health-care service (MHS) use can quantify the magnitude of the problem. Methods The Ontario Cancer Registry was used to identify all patients with bladder cancer treated with curative-intent cystectomy or radiotherapy in Ontario, Canada (2004-2013). Population-level databases were used to identify MHS use (visits to general practitioner, psychiatrist, emergency department, or hospitalization). Generalized estimating equations were used to compare rates of MHS use. Baseline, peritreatment, and posttreatment MHS use were defined as visits from 2 years to 3 months before, 3 months before to 3 months after, and from 3 months after to 2 years after start of treatment, respectively. Results From 2004 to 2013, 4296 patients underwent cystectomy (n = 3332) or curative-intent radiotherapy (n = 964). Compared with baseline, the rate of MHS use was higher in the peritreatment (adjusted rate ratio [aRR] = 1.64, 95% confidence interval [CI] = 1.48 to 1.82) and posttreatment periods (aRR = 1.45, 95% CI =1.30 to 1.63). By 2 years posttreatment, 24.6% (95% CI = 23.4% to 25.9%) of all patients had MHS use. Patients with baseline MHS use had substantially higher MHS use in the peritreatment (aRR = 5.77, 95% CI = 4.86 to 6.86) and posttreatment periods (aRR = 4.58, 95% CI = 3.78 to 5.55). Female patients had higher use MHS use overall, but males had a higher incremental increase in the posttreatment period compared with baseline (2-sided Pinteraction = .02). Male patients had a statistically significant increase in MHS use following surgery or radiotherapy, whereas female patients only had an increase following surgery. Conclusions MHS use is common among patients undergoing treatment for bladder cancer, particularly in the peritreatment period. Screening for mental health concerns in this population is warranted.
5P Anti-GD2 chimeric antigen receptor &amp; TRAIL modified mesenchymal progenitors as novel strategy against Ewing’s sarcoma
Authors: G. Golinelli, G. Grisendi, M. Dall'Ora, G. Casari, M. Prapa, C. Spano, R. Talami, F. Banchelli, M. Dominici
Journal: Annals of Oncology (2021)
Exploratory gene-by-gene analysis of olaparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): PROfound.
Authors: Johann S. De Bono, Nobuaki Matsubara, Nicolas Penel, Niven Mehra, Michael Paul Kolinsky, Emmanuelle Bompas, Susan Feyerabend, Gwenaelle Gravis, Jae Young Joung, Kazuo Nishimura, Craig Gedye, Joaquin Mateo, Fred Saad, Karim Fizazi, Neal Shore, Jinyu Kang, Chintu Desai, Joseph E. Burgents, Elizabeth Harrington, Maha H. A. Hussain
Journal: Journal of Clinical Oncology (2021)

126 Background: The Phase 3 PROfound trial (NCT02987543) met its primary endpoint and key secondary endpoints, including improved overall survival (OS) for olaparib in men with mCRPC with alterations in BRCA1, BRCA2, or ATM (Cohort A). We report gene-by-gene analysis of olaparib antitumor activity among the 15 prespecified homologous recombination repair (HRR) genes. Methods: Pts were randomized to olaparib (300 mg bid; n=256) or physician’s choice of enzalutamide or abiraterone (control; n=131). Exploratory analyses in pts with alterations in BRCA1 and/or BRCA2 (BRCA, regardless of co-occurring alterations with other HRR genes) or in single genes were conducted. Results: Evidence of olaparib antitumor activity was observed in subgroups with &gt;10 pts (table). Data for pts with alterations in only BRCA1, BRCA2, PPP2R2A, RAD51B, RAD54L, PALB2, BRIP1, CHEK1, BARD1, and RAD51D will be reported (no FANCL or RAD51C enrolled). Conclusions: Small subgroups limit interpretation for some genes. Olaparib antitumor activity is greatest in pts with BRCA alterations, with a spectrum of clinical sensitivity to olaparib as defined by rPFS and OS across the broader population with alterations in other HRR genes. Clinical trial information: NCT02987543. [Table: see text]