tbuckley/cabot-search huggingface dataset:
Abstract 13607: Correlation in Hospital Survival Following Out-of-Hospital Cardiac Arrest With Variation in Post-Arrest Inpatient Intervention Rates in Michigan
Authors: Robert A Swor, James Paxton, David Berger, Joseph B Miller, Christine Brett, Nai-Wei Chen
Journal: Circulation (2021)

Introduction: Wide variations in rates of survival to hospital discharge exist for survivors of out-of-hospital cardiac arrest (OHCA). The potential influence of variation in post-OHCA hospital care has not been adequately explored. We hypothesized that variation of in hospital survival rates may be influenced by variation of in-hospital care in Michigan. Methods: We performed a secondary analysis of a statewide cardiac arrest database constructed from two probabilistically-linked cardiac arrest registries [Cardiac Arrest Registry to Enhance Survival (CARES) and Michigan Inpatient Database (MIDB)] from 2014 - 2017. A novel composite rank score was created to characterize post-arrest in-hospital care, incorporating four specific interventions: left heart catheterization within 24 hours (LHC), emergent mechanical circulatory support (EMCS), targeted temperature management (TTM), and do-not-resuscitate order placed within 72 hours of arrival (DNR). The highest score (1 of 38) was given to the hospital with highest procedure rate (LHC, TTM, LHC) and the lowest rate of early DNR. Spearman’s correlation coefficients assessed the relationship between the equal weight composite rank score and rate of hospital survivors. Results: We included 3,644 patients admitted to 38 hospitals who treated &gt;30 OHCA patients during the study period. Patient mean age was 62.4 years, and 59.3% were male. Survival, rank scores and correlation coefficients are listed below: We observed four-fold variation in survival for all patients and witnessed arrest, with a non-significant correlation with care provision. However, we identified a sixteen-fold variation in survival among unwitnessed arrests, which was significantly correlated with a higher rank of care provided. Conclusions: In Michigan, the greatest variation in survival was identified among unwitnessed arrests. This variation was robustly associated with a composite rank of in-hospital post-arrest interventions.
IL-12 nanochaperone-engineered CAR T cell for robust tumor-immunotherapy
Authors: Yingmei Luo, Ze Chen, Mingjian Sun, Baohong Li, Fan Pan, Aiqing Ma, Jianhong Liao, Ting Yin, Xiaofan Tang, Guojun Huang, Baozhen Zhang, Hong Pan, Mingbin Zheng, Lintao Cai
Journal: Biomaterials (2021)
Errors in Results, Figure 1, Table 1, and Article Information
Journal: JAMA Network Open (2021)

Francesco Menichetti, MD; Patrizia Popoli, MD; Maria Puopolo, MS; Stefania Spila Alegiani, MS; Giusy Tiseo, MD; Alessandro Bartoloni, MD; Giuseppe Vittorio De Socio, MD; Sauro Luchi, MD; Pierluigi Blanc, MD; Massimo Puoti, MD; Elena Toschi, MS; Marco Massari, MS; Lucia Palmisano, MS; Giuseppe Marano, MD; Margherita Chiamenti, MD; Laura Martinelli, MD; Silvia Franchi, MD; Carlo Pallotto, MD; Lorenzo Roberto Suardi, MD; Barbara Luciani Pasqua, MD; Marco Merli, MD; Plinio Fabiani, MD; Luca Bertolucci, MD; Beatrice Borchi, MD; Sara Modica, MD; Sara Moneta, MD; Giulia Marchetti, MD; Antonella d’Arminio Monforte, MD; Laura Stoppini, MD; Nadia Ferracchiato, MD; Stefania Piconi, MD; Claudio Fabbri, MD; Enrico Beccastrini, MD; Riccardo Saccardi, MD; Andrea Giacometti, MD; Sara Esperti, MD; Piera Pierotti, MD; Laura Bernini, MD; Claudia Bianco, MD; Sara Benedetti, MD; Alessandra Lanzi, MD; Paolo Bonfanti, MD; Marco Massari, MD; Spartaco Sani, MD; Annalisa Saracino, MD; Antonella Castagna, MD; Luigia Trabace, PhD; Maria Lanza, MD; Daniele Focosi, MD; Alessandro Mazzoni, MD; Mauro Pistello, MD; Marco Falcone, MD; TSUNAMI Study group; Roberto Palazzolo; Salvatore Casari; Alessandro Occhionero; Tiziana Grazzini; Dina Leonarda Silvestri; Mariacarla Iorio; Andrea Tosti; Daniela Francisci; Cecilia Becattini; Matteo Pirro; Mauro Marchesi; Sabrina Bastianelli; Sara Pierucci; Chiara Busti; Antonella Mencacci; Silvia Bozza; Barbara Camilloni; Valentina Annoni; Chiara Bellotto; Adriano Cioppi; Giorgia Querci; Giacomo Ciusa; Michela Tassara; Anna Danise; Silvia Chigiotti; Giovanna Morelli; Micaela Meini; Valentina Galfo; Simone Ferranti; Enrico Tagliaferri; Riccardo Iapoce; Chiara Barbieri; Arianna Forniti; Claudio Caroselli; Stefano Verdenelli; Fabio Monzani; Paola Mazzetti; Giovanna Moscato; Francesco Barchiesi; Mauro Andreotti; Fausto Baldanti; Andrea Binelli; Maria R Capobianchi; Roberto Da Cas; Daniela Di Sevo; Paola Fazi; Cinzia Gasparrini; Ilaria Ippoliti; Alessandra Mancino; Francesca Menniti Ippolito; Francesca Paoloni; Paola Ruggeri; Arianna Rughini; Emanuela Salvi; Valeria Sargentini; Maria P Trotta; Marco Vignetti
FDA Approval Summary: Sotorasib for <i>KRAS G12C</i>-Mutated Metastatic NSCLC
Authors: Erica C. Nakajima, Nicole Drezner, Xiaoxue Li, Pallavi S. Mishra-Kalyani, Yajun Liu, Hong Zhao, Youwei Bi, Jiang Liu, Atiqur Rahman, Emily Wearne, Idara Ojofeitimi, Lauren Tesh Hotaki, Dianne Spillman, Richard Pazdur, Julia A. Beaver, Harpreet Singh
Journal: Clinical Cancer Research (2021)

On May 28, 2021, the FDA granted accelerated approval to sotorasib (Lumakras, Amgen) for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with a Kirsten rat sarcoma proto-oncogene (KRAS) G12C mutation who have received at least one prior systemic therapy. The approval was based on CodeBreaK 100 (Study 20170543), a dose-escalation and dose-expansion trial in patients with an advanced, KRAS G12C-mutated, solid tumor. The overall response rate (ORR) observed in patients with KRAS G12C-mutated NSCLC treated with sotorasib (n = 124) was 36% [95% confidence interval (CI), 28-45]. The median duration of response was 10.0 months (95% CI, 6.9-not estimable). The most common adverse reactions (≥20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. This is the first approval of a targeted therapy for KRAS G12C-mutated NSCLC. Because of pharmacokinetic data and ORRs of patient cohorts who took sotorasib at lower doses in the dose-escalation portion of CodeBreaK 100, a dose comparison study is being conducted as a post-marketing requirement.
Influence of liver stiffness heterogeneity on staging fibrosis in patients with nonalcoholic fatty liver disease
Authors: Nobuyoshi Kawamura, Kento Imajo, Kyle J. Kalutkiewicz, Koki Nagai, Michihiro Iwaki, Takashi Kobayashi, Asako Nogami, Yasushi Honda, Takaomi Kessoku, Yuji Ogawa, Takuma Higurashi, Kunihiro Hosono, Hirokazu Takahashi, Masato Yoneda, Satoru Saito, Shinichi Aishima, Hidenori Toyoda, Hideki Hayashi, Yoshio Sumida, Richard L. Ehman, Atsushi Nakajima
Journal: Hepatology (2021)

Abstract Background and Aims Despite that hepatic fibrosis often affects the liver globally, spatial distribution can be heterogeneous. This study aimed to investigate the effect of liver stiffness (LS) heterogeneity on concordance between MR elastography (MRE)‐based fibrosis staging and biopsy staging in patients with NAFLD. Approach and Results We retrospectively evaluated data from 155 NAFLD patients who underwent liver biopsy and 3 Tesla MRE and undertook a retrospective validation study of 169 NAFLD patients at three hepatology centers. Heterogeneity of stiffness was assessed by measuring the range between minimum and maximum MRE‐based LS measurement (LSM). Variability of LSM was defined as the stiffness range divided by the maximum stiffness value. The cohort was divided into two groups (homogenous or heterogeneous), according to whether variability was below or above the average for the training cohort. Based on histopathology and receiver operating characteristic (ROC) analysis, optimum LSM thresholds were determined for MRE‐based fibrosis staging of stage 4 (4.43, kPa; AUROC, 0.89) and stage ≥3 (3.93, kPa; AUROC, 0.89). In total, 53 had LSM above the threshold for stage 4. Within this group, 30 had a biopsy stage of &lt;4. In 86.7% of these discordant cases, variability of LSM was classified as heterogeneous. In MRE‐based LSM stage ≥3, 88.9% of discordant cases were classified as heterogeneous. Results of the validation cohort were similar to those of the training cohort. Conclusions Discordance between biopsy‐ and MRE‐based fibrosis staging is associated with heterogeneity in LSM, as depicted with MRE.
When I use a word . . . . The Precautionary Principle: a definition
Authors: Jeffrey K Aronson
Journal: BMJ (2021)

Many definitions of the Precautionary Principle omit two important ideas: that it applies only when the benefit to harm balance of a proposed intervention is unfavourable or uncertain and that the onus to prove that it is <i>not</i> unfavourable is on those who would advocate use of the intervention. The following proposed definition for healthcare interventions incorporates these two ideas: "The principle that if a healthcare intervention, pharmacological or non-pharmacological, may cause harm to the individual, the public, or the environment, the benefit to harm balance being unfavourable or uncertain, precautionary measures should be taken, and the burden of proving that the intervention is <i>not</i> harmful falls on those proposing that it be implemented."
重度银屑病患者采用细胞疗法的前景如何?
Journal: British Journal of Dermatology (2021)

银屑病是一种免疫介导的皮肤病, 近年来我们在治疗银屑病方面取得了重大进展, 其中最值得注意的是使用靶向免疫系统成分的“生物”疗法。然而, 这些药物不能治愈这种疾病, 并且有少数重度银屑病患者对目前提供的所有治疗方案均无反应。细胞疗法已成功用于其他免疫介导疾病, 如多发性硬化、克罗恩病和关节炎。该疗法需要从患者 (自体) 或供者 (异体) 体内分离细胞, 进行制备, 然后将其注射到患者体内。
A Failure to Disseminate Transformative Science — HIV Treatment as Prevention, 10 Years On
Authors: Jacob Bor, Dorina Onoya, Bruce Richman, Kenneth H. Mayer
Journal: New England Journal of Medicine (2021)

Interview with Dr. Jacob Bor on barriers to disseminating information about HIV treatment as a strategy for preventing virus transmission. (13:26)Download HIV treatment leading to viral suppression prevents transmission. Despite widespread awareness of the therapeutic benefits of HIV treatment, there are large global disparities in knowledge about the efficacy of treatment as prevention.
Efficacy and Safety Associated With Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma
Authors: Alexandre A. Jácome, Ana Carolina G. Castro, João Paulo S. Vasconcelos, Maria Helena C. R. Silva, Marco Antônio O. Lessa, Eduardo D. Moraes, Aline C. Andrade, Frederico M. T. Lima, João Paulo F. Farias, Roberto A. Gil, Gabriel Prolla, Bernardo Garicochea
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Immune checkpoint inhibitors (ICIs) have yielded conflicting results in hepatocellular carcinoma (HCC). The overall effect of ICIs compared with standard therapies in unresectable HCC requires more research. <h3>Objective</h3> To estimate the efficacy and safety associated with ICIs compared with standard therapies in patients with unresectable HCC. <h3>Data Sources</h3> PubMed, Cochrane Library, Web of Science, Latin American and Caribbean Health Sciences Literature, and American Society of Clinical Oncology and European Society of Medical Oncology meeting proceedings were systematically searched. Reference lists from studies selected by electronic searching were manually searched to identify additional relevant studies. The search included literature published or presented from February 2010 to February 2020. <h3>Study Selection</h3> From December 2019 to February 2020, independent reviewers evaluated each database, scanning the title, abstract, and keywords of every record retrieved. Full articles were further assessed if the information given suggested that the study was a randomized clinical trial (RCT) comparing ICIs vs standard therapies in the treatment of unresectable HCC. <h3>Data Extraction and Synthesis</h3> The full text of the resulting studies and extracted data were reviewed independently according to PRISMA guidelines. Summary hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were calculated by a random-effects model. The likelihood of ICIs being associated with overall response rate (ORR) and treatment-related adverse events (TRAEs) was expressed by odds ratios (ORs) using a random-effects model. <h3>Main Outcomes and Measures</h3> The main outcomes were OS, PFS, ORR, and TRAEs. <h3>Results</h3> Of 1836 studies yielded by the search, 3 were retained, totaling 1657 patients (985 treated with ICIs vs 672 receiving standard treatment). Two studies evaluated ICIs as monotherapy, and 1 study investigated the combination of ICIs with bevacizumab. Compared with standard therapies (sorafenib in first-line therapy or placebo in second-line therapy), ICIs were associated with significantly improved OS (HR, 0.75; 95% CI, 0.62-0.92;<i>P</i> = .006), PFS (HR, 0.74; 95% CI, 0.56-0.97;<i>P</i> = .03), and ORR (OR, 2.82; 95% CI 2.02-3.93;<i>P</i> &lt; .001). The probability of grade 3 or 4 TRAEs was lower with ICIs than with sorafenib (OR, 0.44; 95% CI, 0.20-0.96;<i>P</i> = .04). <h3>Conclusions and Relevance</h3> This meta-analysis found superior efficacy and safety associated with ICIs compared with standard therapies and highlights the survival benefit associated with the combination of antiangiogenic therapy with ICIs in first-line systemic therapy of unresectable HCC.
First report of CART treatment in AL amyloidosis and relapsed/refractory multiple myeloma
Authors: Aina Oliver-Caldes, Raquel Jiménez, Marta Español-Rego, Maria Teresa Cibeira, Valentín Ortiz-Maldonado, Luis F Quintana, Paola Castillo, Francesca Guijarro, Natalia Tovar, Mercedes Montoro, Daniel Benitez-Ribas, Alex Bataller, E Azucena González-Navarro, Joan Cid, Miquel Lozano, Lorena Perez-Amill, Beatriz Martin-Antonio, Mari-Pau Mena, David F Moreno, Luis Gerardo Rodríguez-Lobato, Josep Maria Campistol, Gonzalo Calvo, Joan Bladé, Laura Rosiñol, Manel Juan, Mariona Pascal, Alvaro Urbano-Ispizua, Carlos Fernández de Larrea
Journal: Journal for ImmunoTherapy of Cancer (2021)

Multiple myeloma (MM) remains incurable despite the number of novel therapies that have become available in recent years. Occasionally, a patient with MM will develop an amyloid light-chain (AL) amyloidosis with organ dysfunction. Chimeric antigen receptor T-cell (CART) therapy has become a promising approach in treating hematological malignancies. Our institution has developed a second-generation B-cell maturation antigen (BCMA)–CART which is currently being tested in a clinical trial for relapsed/refractory MM. We present the first reported case, to our knowledge, of a patient with AL amyloidosis and renal involvement in the course of an MM, successfully treated with CART therapy targeting BCMA. The patient received a fractioned dose of 3×10 6 /kg BCMA–CARTs after lymphodepletion. At 3 months from infusion, the patient had already obtained a deep hematological response with negative measurable residual disease by flow cytometry in the bone marrow. After 12 months, the patient remains in hematological stringent complete remission and has achieved an organ renal response with a decrease of 70% of proteinuria. This case suggests that concomitant AL amyloidosis in the setting of MM can benefit from CART therapy, even in patients in which predominant symptoms at the time of treating are caused by AL amyloidosis.
Synergistic T cell signaling by 41BB and CD28 is optimally achieved by membrane proximal positioning within parallel chimeric antigen receptors
Authors: Tamara Muliaditan, Leena Halim, Lynsey M. Whilding, Benjamin Draper, Daniela Y. Achkova, Fahima Kausar, Maya Glover, Natasha Bechman, Appitha Arulappu, Jenifer Sanchez, Katie R. Flaherty, Jana Obajdin, Kristiana Grigoriadis, Pierre Antoine, Daniel Larcombe-Young, Caroline M. Hull, Richard Buus, Peter Gordon, Anita Grigoriadis, David M. Davies, Anna Schurich, John Maher
Journal: Cell Reports Medicine (2021)
Re: Anthony Emmanuel, Abi Kanthabalan, Cameron Alexander, et al. Expedited Radical Orchidectomy for Testicular Cancer: Compromising Fertility Outcomes Without Oncological Benefit? Eur Urol. 2020;80:766–7
Authors: Akshat M. Patel, Jeffrey M. Howard, Aditya Bagrodia
Journal: European Urology (2021)
ORF8/ORF8a: a difference between SARS-CoV-2 and SARS-CoV
Authors: Milad Zandi
Journal: European Respiratory Journal (2021)

<h3>Abstract</h3> Lipid-based particles are used worldwide in clinical trials as carriers of hydrophobic paclitaxel (PTXL) for cancer chemotherapy, albeit with little improvement over the standard-of-care. Improving efficacy requires an understanding of intramembrane interactions between PTXL and lipids to enhance PTXL solubilization and suppress PTXL phase separation into crystals. We studied the solubility of PTXL in cationic liposomes (CLs) composed of positively charged 2,3-dioleyloxypropyltrimethylammonium chloride (DOTAP) and neutral 1,2-dioleoyl-<i>sn</i>-glycero-3-phosphatidylcholine (DOPC) as a function of PTXL membrane content and its relation to efficacy. Time-dependent kinetic phase diagrams were generated from observations of PTXL crystal formation by differential-interference-contrast microscopy. Furthermore, a new Synchrotron small-angle x-ray scattering in situ methodology applied to DOTAP/DOPC/PTXL membranes condensed with DNA enabled us to detect the time-dependent depletion of PTXL from membranes by measurements of variations in the membrane interlayer and DNA interaxial spacings. Our results revealed three regimes with distinct time scales for PTXL membrane solubility: hours for &gt; 3 mol% PTXL (low), days for ≈ 3 mol% PTXL (moderate), and ≥ 20 days for &lt; 3 mol% PTXL (long-term). Cell viability experiments on human cancer cell lines using CL<sub>PTXL</sub> nanoparticles (NPs) in the distinct CL<sub>PTXL</sub> solubility regimes reveal an unexpected nonmonotonic dependence of efficacy on PTXL content in NPs delivered at short time scales (hours) after liposome hydration, where we see two distinct high-efficacy regimes at low (&lt; 2 mol%) and high (9 mol%) drug loading. These newly identified high-efficacy regimes flank the membrane solubility limit (≈ 3 mol%, where efficacy declines), which has been the focus of most previous physicochemical studies (and clinical trials) of PTXL-loaded CLs. At longer times scales (days), CL<sub>PTXL</sub> NPs with ≥ 3 mol% PTXL lose efficacy while formulations with 1–2 mol% PTXL maintain high efficacy. Our findings underscore the importance of understanding the relationship of the kinetic phase behavior and physicochemical properties of CL<sub>PTXL</sub> NPs to efficacy.
Association of Cognitive Decline With Anesthesia and Surgery in Older Patients
Authors: Kotaro Kida, Tomohiko Sato, Tsunehisa Tsubokawa
Journal: JAMA (2021)

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Benralizumab's anti-eosinophil efficacy may be decreased by impaired NK cell activity
Authors: Sophie M. Poznanski, Ana Portillo, Manali Mukherjee, Anurag Bhalla, Kiho Son, Ali A. Ashkar, Nader Khalidi, Parameswaran Nair
Journal: European Respiratory Journal (2021)

<b>Although likely to be exceedingly rare, impaired ADCC due to NK cell dysfunction needs to be considered as one of the reasons, along with the development of anti-drug neutralising antibodies, for impaired anti-eosinophil activity of benralizumab</b> https://bit.ly/3nxeFVg
Incidence and Outcomes Associated With <i>Clostridioides difficile</i> Infection in Solid Organ Transplant Recipients
Authors: Seyed M. Hosseini-Moghaddam, Bin Luo, Sarah E. Bota, Shahid Husain, Michael S. Silverman, Nick Daneman, Kevin A. Brown, J. Michael Paterson
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Little is known about the incidence and outcomes of<i>Clostridioides difficile</i>infection (CDI) in solid organ transplant (SOT) recipients. <h3>Objective</h3> To estimate the CDI incidence and outcomes in SOT recipients. <h3>Design, Setting, and Participants</h3> A population-based cohort study was conducted using administrative health care data for all Ontario, Canada, residents who received organ allografts from April 1, 2003, to December 31, 2017; March 31, 2020, was the end of the study period. <h3>Main Outcomes and Measures</h3> The primary outcome was hospital admission with CDI diagnosis. The secondary outcomes included all-cause death, intensive care unit admission, acute kidney injury requiring dialysis, and fulminant CDI comprising any of the following: toxic megacolon, ileus, perforation, or colectomy. The association between short- vs long-term mortality (ie, death occurring within or after 90 days post-CDI) and the following variables was evaluated: age, sex, Deyo-Charlson Comorbidity Index, SOT type, early- vs late-onset CDI, fulminant CDI, intensive care unit admission, and acute kidney injury requiring acute dialysis. <h3>Results</h3> Overall, 10 724 SOT recipients (6901 [64.4%] men; median age, 54 [IQR, 44-62] years) were eligible. Kidney transplant was the most common SOT type (6453 [60.2%]). The median follow-up time was 5.0 (IQR, 2.3-8.8) years, resulting in 61 987 person-years of follow-up. A total of 726 patients (6.8%) were hospitalized with CDI. The 1-year CDI incidence significantly increased in annual cohorts (ie, from 23.1; 95% CI, 12.8-41.8 per 1000 person-years in 2004 to 46.7; 95% CI, 35.0-62.3 per 1000 person-years in 2017;<i>P</i> = .001).<i>Clostridioides difficile</i>was associated with a 16.8% rate (n = 122) of 90-day mortality. In patients who underwent kidney transplant, CDI was typically late-onset (median interval, 2.2; IQR, 0.4-6.0 years) compared with recipients of other organs. Acute kidney injury requiring dialysis was significantly associated with short-term (adjusted odds ratio [aOR], 1.86; 95% CI, 1.07-3.26) and long-term (adjusted hazard ratio [aHR], 1.89; 95% CI, 1.29-2.78) mortality, and late-onset CDI was also significantly associated with a greater risk of short-term (aOR, 4.26; 95% CI, 2.51-7.22) and long-term (aHR, 2.49; 95% CI, 1.78-3.49) mortality. <h3>Conclusions and Relevance</h3> In this study, increasing CDI trends in annual cohorts of SOT recipients were observed. Posttransplant CDI was associated with mortality, and late-onset CDI was associated with a greater risk of death than early-onset CDI. These findings suggest that preventive strategies should not be limited to the initial months following transplantation. Comprehensive therapeutic approaches targeting acute kidney injury risk factors in SOT recipients may reduce short- and long-term post-CDI mortality.