tbuckley/cabot-search huggingface dataset:
Ruxolitinib combined with etanercept induce a rapid response to corticosteroid‐refractory severe acute graft vs host disease after allogeneic stem cell transplantation: Results of a multi‐center prospective study
Authors: Yanmin Zhao, Hengwei Wu, Jimin Shi, Yi Luo, Xiaoqing Li, Jianping Lan, Wanmao Ni, Ying Lu, Lieguang Chen, Yamin Tan, Xiaoyu Lai, Jian Yu, He Huang
Journal: American Journal of Hematology (2020)

About half of patients with severe acute graft vs host disease (aGVHD) show resistance to treatment with first-line steroids. We enrolled 64 patients with grades III-IV SR-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-SCT), to assess the efficacy and safety of the combination therapy of ruxolitinib and etanercept. The overall response rate was 87.5% (95% CI, 79.7%-95.3%) at day 28 of the combination treatment, from which 73.4% reached complete response (CR). A marked reduction ≥75% in daily corticosteroid dosing was documented in 75.4% of patients at day 28. Delayed time from aGVHD to ruxolitinib (OR = 4.88, 95% CI, 0.98-23.56), stages 3-4 liver aGVHD (OR = 8.57, 95% CI, 0.96-46.59) and gut Enterobacteriaceae colonization (OR = 12.39, 95% CI, 1.71-59.77) were related to incomplete response. Grades 3/4 anemia, leukopenia, or thrombocytopenia and CMV-reactivation were found in 29.7%, 26.6%, 39.1%, and 50.0% of patients, respectively. So, 25 (39.1%) experienced complications of severe infection ≥3 grade, in which pulmonary infections were most frequent (15/64, 23.4%). The 2-year overall survival (OS) after the combination therapy was 61.2%. The 2-year incidence of non-relapse mortality and relapse of the underlying malignancy was 26.7% and 15.7%, respectively. Combined treatment with ruxolitinib and etanercept was very effective and relatively safe for severe aGVHD patients, while the various infection complications deserve more attention. This study was registered at the Chinese Clinical Trial Registry (ChiCTR1900024408).
A unique device enabling electrohydraulic lithotripsy with an ultraslim scope for difficult stones after endoscopic ultrasound-guided biliary drainage
Authors: Hassan Atalla, Hideyuki Shiomi, Takuya Ikegawa, Takashi Kobayashi, Arata Sakai, Atsuhiro Masuda, Yuzo Kodama
Journal: Endoscopy (2020)

Endoscopic ultrasound-guided biliary drainage (EUS-BD) is a well-established treatment option for benign biliary diseases after failure of conventional procedures [1]. A two-step approach of cholangioscopy-assisted management for a difficult biliary stone through an EUS-guided bilioenteric fistula has previously been reported [2]. Cholangioscopy-guided electrohydraulic lithotripsy (EHL) is currently considered one of the effective methods for stone removal, with clearance rates of 69 % and 97 % in single and multiple sessions, respectively [3]. Nevertheless, the high cost of digital cholangioscopy has limited its use in many centers [4]. Herein, we present a modified device that enabled EHL to be performed using a conventional ultraslim endoscope for a difficult biliary stone after EUS-BD.
AB0879 DOES BODY WEIGHT INFLUENCE THE KNEE INJURY AND OSTEOARTHRITIS OUTCOME SCORE IN PERSONS WITH SYMPTOMATIC KNEE OSTEOARTHRITIS?
Authors: A. Ben Tekaya, L. Rouached, A. Slimi, J. Galalou, E. Bahlouli, O. Saidane, S. Bouden, R. Tekaya, I. Mahmoud, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2020)

Background: Overweight is a major risk factor for the development and progression of knee osteoarthritis (OA). Weight loss for patients with knee OA has been associated with improvement in self-reported pain and function and is recommended by EULAR as part of the therapeutic management. Objectives: The aim of the study was to evaluate the relation between overweight and functional impairment in adults with knee OA. Methods: It was a prospective study conducted in a rheumatologic department over a 4 months period. Patients with symptomatic knee OA based on the ACR criteria, were included. A screening of body mass index (BMI) was carried out for all patients. It was categorized following the WHO classification into: normal (&lt;25 kg/m2), overweight (25 to &lt;30), obese (up to 30). Pain level was evaluated using the Visual Analogue Scale (VAS). Function was assessed by the short form of the Knee injury and Osteoarthritis Outcome Score (KOOS-PS) (KOOS-PS scores to 0 representing no difficulty and 100 representing extreme difficulty). The patients’ knee radiographies were graded according to Kellgren Lawrence criteria (KL). The patients were allocated in two groups; as grade I-II KL (Group 1) and grade III-IV KL (Group 2). Results: We included 143 patients with a mean age of 65.17± 10.7 years and 88.1% of women. Patients were from low socio-economic class in 30.8% of cases. Mean disease duration of the KOA was 5.4 years [3months-20 years] and mean BMI was 31.8±5.6kg/m 2 . Patients were with normal weight in 16.1%, overweight in 19.6% and obese in 64.3%. Knee OA was bilateral in 85.3% and other OA sites were associated in 37.8% of patients. Mean VAS pain of knee OA was 6.6±1.5 and KOOS-PS was 48.8±16.5/100. Concerning the radiographic damage; we found grade I-II (KL) in 22.6% and grade III-IV (KL) in 77.4%. High BMI (BMI≥25 kg/m 2 was not significantly associated with worse KOOS score (p=0.9), more pain (p=0.5) or an increasing severity of radiological knee osteoarthritis (p=0.14). Moreover, the level BMI was not associated with the presence of other OA sites (p=0.9) or a bilateral KOA (p=0.07). Conclusion: These data, from a subset of participants with symptomatic radiographic knee OA, demonstrate no correlation between obesity and pain, functional impairment and radiographic severity. Acknowledgments: none Disclosure of Interests: None declared
Quality and Safety in Healthcare, Part LXXII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2020)

Abstract Healthcare credentialing is the methodology used by an organization to obtain and validate a practitioner’s credentials, typically to participate in patient care. Privileging is the process by which the designated individuals in the healthcare organization evaluate the credentials, as well as the performance of the individual to determine that the provider is worthy to have certain privileges in the institution to contribute to the care of patients. The healthcare institution must have appropriate processes to ensure that providers continue to give excellent care in order to maintain privileges. There must also be procedures in place for remediation and revocation of privileges when necessary, as well as an appeals procedure. In addition, there should be provisions for privileging of temporary workers and for privileging in emergency situations.
Changes in colistin resistance and mcr-1 abundance in Escherichia coli of animal and human origins following the ban of colistin-positive additives in China: an epidemiological comparative study
Authors: Yang Wang, Chunyan Xu, Rong Zhang, Yiqiang Chen, Yingbo Shen, Fupin Hu, Dejun Liu, Jiayue Lu, Yan Guo, Xi Xia, Junyao Jiang, Xueyang Wang, Yulin Fu, Lu Yang, Jiayi Wang, Juan Li, Chang Cai, Dandan Yin, Jie Che, Run Fan, Yongqiang Wang, Yan Qing, Yi Li, Kang Liao, Hui Chen, Mingxiang Zou, Liang Liang, Jin Tang, Zhangqi Shen, Shaolin Wang, Xiaorong Yang, Congming Wu, Shixin Xu, Timothy R Walsh, Jianzhong Shen
Journal: The Lancet Infectious Diseases (2020)
Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients
Authors: Mehul S. Suthar, Matthew G. Zimmerman, Robert C. Kauffman, Grace Mantus, Susanne L. Linderman, William H. Hudson, Abigail Vanderheiden, Lindsay Nyhoff, Carl W. Davis, Oluwaseyi Adekunle, Maurizio Affer, Melanie Sherman, Stacian Reynolds, Hans P. Verkerke, David N. Alter, Jeannette Guarner, Janetta Bryksin, Michael C. Horwath, Connie M. Arthur, Natia Saakadze, Geoffrey H. Smith, Srilatha Edupuganti, Erin M. Scherer, Kieffer Hellmeister, Andrew Cheng, Juliet A. Morales, Andrew S. Neish, Sean R. Stowell, Filipp Frank, Eric Ortlund, Evan J. Anderson, Vineet D. Menachery, Nadine Rouphael, Aneesh K. Mehta, David S. Stephens, Rafi Ahmed, John D. Roback, Jens Wrammert
Journal: Cell Reports Medicine (2020)

SARS-CoV-2, the virus responsible for COVID-19, is causing a devastating worldwide pandemic, and there is a pressing need to understand the development, specificity, and neutralizing potency of humoral immune responses during acute infection. We report a cross-sectional study of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in a cohort of 44 hospitalized COVID-19 patients. RBD-specific IgG responses are detectable in all patients 6 days after PCR confirmation. Isotype switching to IgG occurs rapidly, primarily to IgG1 and IgG3. Using a clinical SARS-CoV-2 isolate, neutralizing antibody titers are detectable in all patients by 6 days after PCR confirmation and correlate with RBD-specific binding IgG titers. The RBD-specific binding data were further validated in a clinical setting with 231 PCR-confirmed COVID-19 patient samples. These findings have implications for understanding protective immunity against SARS-CoV-2, therapeutic use of immune plasma, and development of much-needed vaccines.
A novel kinetic model to describe the ultra-fast triggered release of thermosensitive liposomal drug delivery systems
Authors: Tao Lu, Timo L.M. ten Hagen
Journal: Journal of Controlled Release (2020)

Thermosensitive liposomes, as one of the stimuli-responsive drug delivery systems, receive growing attention, due to their ability to generate rapid and massive drug release in the heated area, and marginal release of contents in non-heated parts of the body. This typical triggered release behavior cannot be fitted adequately by most of the current mathematical kinetic models. The aim of this study was to establish the proper kinetic equation to describe the rapid release of drugs from trigger-sensitive drug delivery systems. We summarized all commonly used kinetic models mentioned in the literature and fitted the release data with these models, finding that only the Korsmeyer-Peppas and the Weibull models show acceptable fitting results. To better describe the release from thermosensitive liposomes with a size below 100 nm, we took Laplace pressure as a release-driving force and proposed a new equation that demonstrates improved fitting in liposomes ranging down to a size of 70 nm. Our new kinetic model shows desirable fitting, not only at the optimal temperature but also of releases within the whole release-temperature range, providing a useful kinetic model to describe release profiles of smaller nano-sized stimuli-responsive drug delivery systems.
Serial Assessment of Urinary Incontinence in Breast Cancer Survivors Undergoing (Neo)Adjuvant Therapy
Authors: Christopher P. Chung, Carolyn Behrendt, Louise Wong, Sarah Flores, Joanne E. Mortimer
Journal: Journal of the National Comprehensive Cancer Network (2020)

Background: Among breast cancer survivors, urinary incontinence (UI) is often attributed to cancer therapy. We prospectively assessed urinary symptoms before and after (neo)adjuvant treatment of early-stage breast cancer. Methods: With consent, women with stage I–III breast cancer completed the Urogenital Distress Inventory and the Incontinence Impact Questionnaire before and 3 months after initiating (neo)adjuvant therapy. Patients with UI were at least slightly bothered by urinary symptoms. If UI was present pretreatment, it was considered prevalent; if UI was new or worse at 3 months posttreatment, it was considered incident; if prevalent UI was no worse at 3 months posttreatment, it was considered stable. Ordinal logistic regression models identified characteristics associated with the level of prevalent UI and with the degree of UI impact on quality of life (QoL). Results: On pretreatment surveys, participants (N=203; age 54.5 ± 11.4 years) reported 79.8% prevalence of UI, including overactive bladder (29.1%), stress incontinence (10.8%), or both (39.9%). The level of prevalent UI increased with body mass index (BMI; P &lt;.05). Of 163 participants assessed at both time points, incident UI developed in 12 of 32 patients without prevalent UI and 27 of 131 patients with prevalent UI. Regardless of whether UI was prevalent (n=162), incident (n=39), or stable (n=94) at QoL assessment, the impact of UI increased ( P &lt;.01) with the number and severity of UI symptoms, subjective urinary retention, and BMI. Adjusted for those characteristics, incident UI had less impact on QoL ( P &lt;.05) than did prevalent or stable UI. Conclusions: We found that UI is highly prevalent at breast cancer diagnosis and that new or worsened UI is common after (neo)adjuvant therapy. Because UI often impairs QoL, appropriate treatment strategies are needed.
A Combination of Human Broadly Neutralizing Antibodies against Hepatitis B Virus HBsAg with Distinct Epitopes Suppresses Escape Mutations
Authors: Qiao Wang, Eleftherios Michailidis, Yingpu Yu, Zijun Wang, Arlene M. Hurley, Deena A. Oren, Christian T. Mayer, Anna Gazumyan, Zhenmi Liu, Yunjiao Zhou, Till Schoofs, Kai-hui Yao, Jan P. Nieke, Jianbo Wu, Qingling Jiang, Chenhui Zou, Mohanmmad Kabbani, Corrine Quirk, Thiago Oliveira, Kalsang Chhosphel, Qianqian Zhang, William M. Schneider, Cyprien Jahan, Tianlei Ying, Jill Horowitz, Marina Caskey, Mila Jankovic, Davide F. Robbiani, Yumei Wen, Ype P. de Jong, Charles M. Rice, Michel C. Nussenzweig
Journal: Cell Host & Microbe (2020)
Monocyte mimics improve mesenchymal stem cell-derived extracellular vesicle homing in a mouse MI/RI model
Authors: Ning Zhang, Yanan Song, Zheyong Huang, Jing Chen, Haipeng Tan, Hongbo Yang, Mengkang Fan, Qiyu Li, Qiaozi Wang, Jinfeng Gao, Zhiqing Pang, Juying Qian, Junbo Ge
Journal: Biomaterials (2020)

Stem cell-derived extracellular vesicles (EVs) have been demonstrated to be effective in heart repair and regeneration post infarction. However, the poor homing efficiency and low yields of these therapeutics remain the major obstacles before they can be used in the clinic. To improve the delivery efficiency of EVs to ischemia-injured myocardium, we modified mesenchymal stem cell (MSC)-derived EVs with monocyte mimics through the method of membrane fusion. Monocyte mimic-bioinspired MSC-EVs (Mon-Exos) exhibited enhanced targeting efficiency to injured myocardium by mimicking the recruitment feature of monocytes after MI/RI, thus contributing to these exclusive adhesive molecules on monocyte mimics, particularly the Mac1/LFA1-ICAM-1 interaction. Through this strategy, Mon-Exos were shown to promote endothelial maturation during angiogenesis and modulate macrophage subpopulations after MI/RI, consistent with MSC-Exos biofunctions, and eventually improve therapeutic outcomes in cardiac function and pathohistology changes after treatments in a mouse MI/RI model. Ultimately, this strategy might provide us with a better way to assess the effects of stem cell EVs and offer additional techniques to help clinicians better manage regenerative therapeutics for ischemic heart diseases.
Clarification Regarding Noninferiority and a Discussion of Model Selection and Treatment Effects in Observational Research—Reply
Authors: Shayan Cheraghlou, George O. Agogo, Michael Girardi
Journal: JAMA Dermatology (2020)

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Screening for Unhealthy Drug Use in Adults and Adolescents
Authors: Jill Jin
Journal: JAMA (2020)

Carrie D. Patnode, PhD, MPH; Leslie A. Perdue, MPH; Megan Rushkin, MPH; Tracy Dana, MLS; Ian Blazina, MPH; Christina Bougatsos, MPH; Sara Grusing, BA; Elizabeth A. O’Connor, PhD; Rongwei Fu, PhD; Roger Chou, MD
THU0078 EXPRESSION PROFILE ANALYSIS OF LONG NONCODING RNAS INDUCED BY IL-1ß IN RHEUMATOID ARTHRITIS FIBROBLAST-LIKE SYNOVIOCYTES
Authors: J. M. Kim, H. J. Kang, S. J. Jung, B. W. Song, H. J. Jeong, C. N. Son, S. H. Kim, K. Hur
Journal: Annals of the Rheumatic Diseases (2020)

Background: Long noncoding RNAs (lncRNAs) have recently emerged as important biological regulators and the aberrant expression of lncRNAs has been reported in various diseases including cancer, cardiovascular disease, and diabetes mellitus. However, the role of lncRNAs in the pathogenesis of rheumatoid arthritis (RA) remains unknown. Objectives: Thus, we studied lncRNAs influenced by IL-1, which is one of the key mediators in the pathogenesis of RA, and also investigated whether regulation of NF-κB activation, which is known to be induced by IL-1, could lead to the changes of expression of those lncRNAs. Methods: Fibroblast-like synoviocytes (FLS) were obtained from the knee joints of the patients with RA. The next-generation sequencing (NGS) data were analyzed to identify differentially expressed lncRNAs between unstimulated RA FLS and IL-1-stimulated RA FLS. The expression levels of the top 5 candidates in NGS data were validated by RT-qPCR using extended number of unstimulated RA FLS and IL-1-stimulated RA FLS. IMD-0560, an inhibitor of IκB kinase (IKK) was used for the regulation of NF-κB activation. Activation and inhibition of NF-κB were confirmed by Western blotting. Changed expressions of the lncRNAs were identified by RT-qPCR. Results: NGS analysis revealed up-regulated 30 lncRNAs and down-regulated 15 lncRNAs in IL-1-treated RA FLS compared with unstimulated RA FLS. Top 5 lncRNAs were selected among 30 lncRNAs up-regulated by IL-1 in RA FLS based on fold-change with P-value cutoff. The up-regulated lncRNAs including NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 were validated by RT-qPCR. IMD-0560 inhibited phosphorylation of IκBα induced by IL-1 in RA FLS. Overexpression of lncRNAs induced by IL-1 was also inhibited by IMD-0560 in RA FLS. Conclusion: Our study revealed that IL-1 increased the expression of NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 in RA FLS. In addition, the expression of these lncRNAs was regulated by inhibition of NF-κB activation. Thus, our data suggest that the lncRNAs might be involved in the pathogenesis of RA through NF-κB signaling pathway. References: [1]Long noncoding RNAs and human disease. Trends Cell Biol. 2011 Jun;21(6):354-61. [2]A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013 Aug 16;341(6147):789-92. [3]Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Res Ther. 2016 Oct 6;18(1):227. Disclosure of Interests: None declared
High impact of COVID-19 in long-term care facilities, suggestion for monitoring in the EU/EEA, May 2020
Authors: Kostas Danis, Laure Fonteneau, Scarlett Georges, Côme Daniau, Sibylle Bernard-Stoecklin, Lisa Domegan, Joan O’Donnell, Siri Helene Hauge, Sara Dequeker, Eline Vandael, Johan Van der Heyden, Françoise Renard, Natalia Bustos Sierra, Enrico Ricchizzi, Birgitta Schweickert, Nicole Schmidt, Muna Abu Sin, Tim Eckmanns, José-Artur Paiva, Elke Schneider
Journal: Eurosurveillance (2020)

Residents in long-term care facilities (LTCF) are a vulnerable population group. Coronavirus disease (COVID-19)-related deaths in LTCF residents represent 30-60% of all COVID-19 deaths in many European countries. This situation demands that countries implement local and national testing, infection prevention and control, and monitoring programmes for COVID-19 in LTCF in order to identify clusters early, decrease the spread within and between facilities and reduce the size and severity of outbreaks.
Novel Variant Ig Domain (vIgD) Proteins Generated Via Directed Evolution of Igsf Domains Have Therapeutic Efficacy in Animal Models of Graft Versus Host Disease
Authors: Steven D Levin, Lawrence S. Evans, Erika Rickel, Martin F. Wolfson, Stacey R. Dillon, Michael G. Kornacker, Ryan Swanson, Stanford L. Peng
Journal: Blood (2017)
Liposomal delivery of antibiotic loaded nucleic acid nanogels with enhanced drug loading and synergistic anti-inflammatory activity against S. aureus intracellular infections
Authors: Sybil Obuobi, Kjersti Julin, Elizabeth G.A. Fredheim, Mona Johannessen, Nataša Škalko-Basnet
Journal: Journal of Controlled Release (2020)

The persistence of Staphylococcus aureus has been accredited to its ability to escape immune response via host cell invasion. Despite the efficacy of many antibiotics against S. aureus, the high extracellular concentrations of conventional antibiotics required for bactericidal activity is limited by their low cellular accumulation and poor intracellular retention. While nanocarriers have received tremendous attention for antibiotic delivery against persistent pathogens, they suffer daunting challenges such as low drug loading, poor retention and untimely release of hydrophilic cargos. Here, a hybrid system (Van_DNL) is fabricated wherein nucleic acid nanogels are caged within a liposomal vesicle for antibiotic delivery. The central principle of this approach relies on exploiting non-covalent electrostatic interactions between cationic cargos and polyanionic DNA to immobilize antibiotics and enable precise temporal release against intracellular S. aureus. In vitro characterization of Van_DNL revealed a stable homogenous formulation with circular morphology and enhanced vancomycin loading efficiency. The hybrid system significantly sustained the release of vancomycin over 24 h compared to liposomal or nanogel controls. Under enzymatic conditions relevant to S. aureus infections, lipase triggered release of vancomycin was observed from the hybrid. While using Van_DNL to treat S. aureus infected macrophages, a dose dependent reduction in intracellular bacterial load was observed over 24 h and exposure to Van_DNL for 48 h caused negligible cellular toxicity. Pre-treatment of macrophages with the antimicrobial hybrid resulted in a strong anti-inflammatory activity in synergy with vancomycin following endotoxin stimulation. Conceptually, these findings highlight these hybrids as a unique and universal platform for synergistic antimicrobial and anti-inflammatory therapy against persistent infections.
Covid-19: Risk of second wave is very real, say researchers
Authors: Jacqui Wise
Journal: BMJ (2020)

Lockdown measures may have averted 3.1 million deaths from covid-19 across 11 European countries, including 470 000 in the UK, a new modelling study indicates.1 However, the researchers warn that European countries are very far from achieving herd immunity, as less than 4% of their populations were infected with SARS-CoV-2 up to 4 May, when lockdowns started to be lifted. The estimated proportion of the total population infected varies between the countries from less than 1% in Norway, Germany, and Austria to 8% in Belgium (box 1). Box 1 ### Covid-19 infection rate in 11 European countries Percentage of total population infected (95% credible interval) up to 4 MayRETURN TO TEXT