tbuckley/cabot-search huggingface dataset:
Prognostic impact of <scp> <i>KMT2A‐AFF1</i> </scp> ‐positivity in 926 <scp> <i>BCR‐ABL1</i> </scp> ‐negative B‐lineage acute lymphoblastic leukemia patients treated in <scp>GIMEMA</scp> clinical trials since 1996
Authors: Alfonso Piciocchi, Monica Messina, Loredana Elia, Antonella Vitale, Stefano Soddu, Anna Maria Testi, Sabina Chiaretti, Marco Mancini, Francesco Albano, Antonio Spadano, Mauro Krampera, Massimiliano Bonifacio, Roberto Cairoli, Calogero Vetro, Florinda Colella, Felicetto Ferrara, Giuseppe Cimino, Renato Bassan, Paola Fazi, Marco Vignetti
Journal: American Journal of Hematology (2021)

Prognostic impact of KMT2A-AFF1-positivity in 926 BCR-ABL1-negative B-lineage acute lymphoblastic leukemia
10-Year Follow-Up After Revascularization in Elderly Patients With Complex Coronary Artery Disease
Authors: Masafumi Ono, Patrick W. Serruys, Hironori Hara, Hideyuki Kawashima, Chao Gao, Rutao Wang, Kuniaki Takahashi, Neil O’Leary, Joanna J. Wykrzykowska, Faisal Sharif, Jan J. Piek, Scot Garg, Michael J. Mack, David R. Holmes, Marie-Claude Morice, Stuart J. Head, Arie Pieter Kappetein, Daniel J.F.M. Thuijs, Thilo Noack, Piroze M. Davierwala, Friedrich W. Mohr, David J. Cohen, Yoshinobu Onuma
Journal: Journal of the American College of Cardiology (2021)
Taking regulatory T cells into medicine
Authors: Shimon Sakaguchi
Journal: The Journal of Experimental Medicine (2021)

Regulatory T cells (Tregs) are indispensable for the establishment and maintenance of immunological self-tolerance. Their genetic anomalies or variations in function are causative of various monogenic and polygenic autoimmune diseases. Treg-based reestablishment of self-tolerance is envisioned to cure autoimmune diseases in the clinic.
Covid-19: Local councils initiate surge vaccination to tackle B.1.617.2 variant
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Covid-19: Local councils initiate surge vaccination to tackle B.1.617.2 variant Gareth IacobucciLocal public health teams in areas with high case numbers of the B.1.617.2 variant first detected in India are boosting efforts to vaccinate their populations and targeting younger adults to try to limit the spread of infection.The actions come amid growing concerns about the rise in infections of B.1.617.2, with early data from Public Health England 1 suggesting that one dose of both AstraZeneca and Pfizer vaccine is only 33% effective against the variant.National guidance from the Joint Committee on Vaccination and Immunisation continues to advise vaccinating adults according to risk profile and age-with people aged 30 being offered the vaccine this week.But some local authorities have taken matters into their own hands and are offering any adult aged 18 or over a vaccination.10 Mobile vaccination services and testing up and running this week in North Tyneside.https://my.northtyneside.gov.uk/news/28321/mobile-vaccinationservices-and-testing-and-running-week-north-tyneside.
POS1099 EFFICACY OF INTRA-ARTICULAR CORTICOSTEROID INJECTIONS IN KNEE OSTEOARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: A. Najm, A. Alunno, C. Weill, J. Gwinnutt, F. Berenbaum
Journal: Annals of the Rheumatic Diseases (2021)

Background: Knee osteoarthritis (OA) is a frequent degenerative disease representing an important health and economic burden. Symptomatic medical treatments available include intra-articular (IA) injections of corticosteroids (GC) but their efficacy is debated. In addition, safety signals regarding cartilage damage with IA GC have been highlighted in a few studies. Objectives: To perform a meta-analysis of studies assessing IA GC efficacy and safety in knee OA. Methods: A systematic literature review and a meta-analysis of randomized controlled trials (RCTs) assessing the effect of GC IA injections versus other interventions (IA Hyaluronic Acid, IA placebo, IA NSAID, oral NSAID or physiotherapy) in knee OA was performed. The effect of the interventions on pain and function were extracted from the single studies and pooled and are presented as short term (&lt;6weeks), medium term (6-24 weeks) and long term (&gt;24 weeks) follow-up period. Standardized mean differences (SMD) are reported. Results: Of 520 studies screened, 23 were included in the SLR and 14 subsequently included in the MA. While IA GC showed a superior effect compared to control on both pain (SMD -0.61 (95% CI -1,25, 0.03)) and function (SMD -1.02 (95% CI -2.14, 0.10)) in short term follow-up; long term follow-up analysis favored controls (IA HA, IA NSAID, physiotherapy) for both pain (SMD 0.68 (95% CI -0.11, 1.47)) and function (SMD 0.88 (95% CI -0.36, 2.12) outcomes (Figure 1). No difference was found between interventions in the medium term. Safety data were reported in 18/23 studies (n= 1936/2314 patients); and side effects were reported as follows: arthralgia (69 IA GC patients, 146 IA HA patients, and 20 saline patients); site injection pain (7 in the IA GC group, 2 in the IA saline group, 14 in the IA HA group); 16 post injection knee swelling without signs of septic arthritis in the IA GC group and 24 in the IA HA group. In one study assessing cartilage effects of GCs, the rate of cartilage loss was greater in the GC group with a reduction of cartilage thickness at 2 year compared to placebo group. No difference was observed in the progression of cartilage denudation or bone marrow lesion. On the contrary, another study showed no effect of injections on the cartilage structure. Conclusion: We demonstrate in this work that IA GC injections reduce pain and improve function in the early phase (≤6 weeks) of treatment. In the long term (≥24 weeks), other intervention such as IA HA injections or physiotherapy seem to be more efficient, but this effect was largely driven by single studies with large effect sizes and the comparators were heterogeneous. Figure 1. Knee pain outcome at short term (≤6weeks) (A), medium term (&gt;6 &amp; &lt;24 weeks) (B), and long term (≥24 weeks) (C) follow up. Disclosure of Interests: None declared.
Middle Ear “Adenoma”: a Neuroendocrine Tumor with Predominant L Cell Differentiation
Authors: Sylvia L. Asa, Knarik Arkun, Arthur S. Tischler, Adnan Qamar, Fang-Ming Deng, Bayardo Perez-Ordonez, Ilan Weinreb, Justin A. Bishop, Bruce M. Wenig, Ozgur Mete
Journal: Endocrine Pathology (2021)
Clinical Study of Single‐Stranded Oligonucleotide RO7062931 in Healthy Volunteers and Patients With Chronic Hepatitis B
Authors: Edward Gane, Man‐Fung Yuen, Dong Joon Kim, Henry Lik‐Yuen Chan, Bernadette Surujbally, Vedran Pavlovic, Sudip Das, Miriam Triyatni, Remi Kazma, Joseph F. Grippo, Simon Buatois, Annabelle Lemenuel‐Diot, Ben‐Fillippo Krippendorff, Henrik Mueller, Yuchen Zhang, Hyung Joon Kim, Apinya Leerapun, Tien Huey Lim, Young‐Suk Lim, Tawesak Tanwandee, Won Kim, Wendy Cheng, Tsung‐Hui Hu, Cynthia Wat
Journal: Hepatology (2021)

RO7062931 is an N-acetylgalactosamine (GalNAc)-conjugated single-stranded locked nucleic acid oligonucleotide complementary to HBV RNA. GalNAc conjugation targets the liver through the asialoglycoprotein receptor (ASGPR). This two-part phase 1 study evaluated the safety, pharmacokinetics, and pharmacodynamics of RO7062931 in healthy volunteers and patients with chronic hepatitis B (CHB) who were virologically suppressed.Part 1 was a single ascending dose study in healthy volunteers randomized to receive a single RO7062931 dose (0.1-4.0 mg/kg), or placebo. Part 2 was a multiple ascending dose study in patients with CHB randomized to receive RO7062931 at 0.5, 1.5, or 3.0 mg/kg or placebo every month for a total of 2 doses (Part 2a) or RO7062931 at 3.0 mg/kg every 2 weeks, 3.0 mg/kg every week (QW), or 4.0 mg/kg QW or placebo for a total of 3-5 doses (Part 2b). Sixty healthy volunteers and 59 patients received RO7062931 or placebo. The majority of adverse events (AEs) reported were mild in intensity. Common AEs included self-limiting injection site reactions and influenza-like illness. Supradose-proportional increases in RO7062931 plasma exposure and urinary excretion occurred at doses ≥3.0 mg/kg. In patients with CHB, RO7062931 resulted in dose-dependent and time-dependent reduction in HBsAg versus placebo. The greatest HBsAg declines from baseline were achieved with the 3.0 mg/kg QW dose regimen (mean nadir ~0.5 log10 IU/mL) independent of HBeAg status.RO7062931 is safe and well tolerated at doses up to 4.0 mg/kg QW. Supradose-proportional exposure at doses of 3.0-4.0 mg/kg was indicative of partial saturation of the ASGPR-mediated liver uptake system. Dose-dependent declines in HBsAg demonstrated target engagement with RO7062931.
AB0209 SERIOUS INFECTIOUS COMPLICATIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH BIOLOGICS
Authors: E. Aronova, G. Gridneva, A. Kudryavtseva, G. Lukina
Journal: Annals of the Rheumatic Diseases (2021)

Objectives: To study infectious complications of therapy with biologics, analyze the frequency of withdrawal of bDMARDs due to infectious complications. Methods: The ambispective analysis included data on 505 cases of prescribing biologics with different mechanism of action in 188 patients with rheumatoid arthritis (160 women, 28 men). Results: Patients in the study group received from 2 to 5 bDMARDs, mediana (25% -75%) 2 (2-3). Biologics were discontinued 326 times, of which due to the development of serious adverse reactions - 70 times, of which due to the development of infectious complications - 16 times (5% of all cases of discontinuations, 29% of all serious adverse reactions). During treatment with the first bDMARD, infectious complications that required discontinuation of the drug developed in 5.3% of cases (N = 10), with the second bDMARD - in 5.2% of cases (N = 4), no statistical differences were found between these groups. On the background of treatment with the third bDMARD, infectious complications led to the withdrawal of treatment in 14.3% of cases (N = 1), in the fourth - 0%, and in the fifth - 33.4% of cases (N = 1). There was no correlation between the number of sequentially prescribed biologics and the incidence of infectious complications. Most often, serious infections developed during treatment with drugs of the TNF-α inhibitor group (infliximab, etanercept, adalimumab, golimumab, certolizumab pegol) and tofacitinib. Out of 16 cases of infectious complications, 5 were associated with tuberculosis infection. Conclusion: Infectious complications make up a significant proportion (29%) of all serious adverse reactions leading to the discontinuations of biologics in patients with rheumatoid arthritis. The frequency of discontinuation of bDMARDs due to infectious complications was about 5% and did not change during treatment with both the first and second biologics. It is necessary to remain alert about tuberculosis infection and examine patients before prescribing and during treatment with bDMARDs. Disclosure of Interests: None declared
Chips for Biomaterials and Biomaterials for Chips: Recent Advances at the Interface between Microfabrication and Biomaterials Research
Authors: Alexander P. M. Guttenplan, Zeinab Tahmasebi Birgani, Stefan Giselbrecht, Roman K. Truckenmüller, Pamela Habibović
Journal: Advanced Healthcare Materials (2021)

Abstract In recent years, the use of microfabrication techniques has allowed biomaterials studies which were originally carried out at larger length scales to be miniaturized as so‐called “on‐chip” experiments. These miniaturized experiments have a range of advantages which have led to an increase in their popularity. A range of biomaterial shapes and compositions are synthesized or manufactured on chip. Moreover, chips are developed to investigate specific aspects of interactions between biomaterials and biological systems. Finally, biomaterials are used in microfabricated devices to replicate the physiological microenvironment in studies using so‐called “organ‐on‐chip,” “tissue‐on‐chip” or “disease‐on‐chip” models, which can reduce the use of animal models with their inherent high cost and ethical issues, and due to the possible use of human cells can increase the translation of research from lab to clinic. This review gives an overview of recent developments at the interface between microfabrication and biomaterials science, and indicates potential future directions that the field may take. In particular, a trend toward increased scale and automation is apparent, allowing both industrial production of micron‐scale biomaterials and high‐throughput screening of the interaction of diverse materials libraries with cells and bioengineered tissues and organs.
Evidence for lack of transmission by close contact and surface touch in a restaurant outbreak of COVID-19
Authors: Nan Zhang, Xuguang Chen, Wei Jia, Tianyi Jin, Shenglan Xiao, Wenzhao Chen, Jian Hang, Cuiyun Ou, Hao Lei, Hua Qian, Boni Su, Jiansen Li, Dongmei Liu, Weirong Zhang, Peng Xue, Jiaping Liu, Louise B. Weschler, Jingchao Xie, Yuguo Li, Min Kang
Journal: Journal of Infection (2021)

Coronavirus disease 2019 (COVID-19) is primarily a respiratory disease that has become a global pandemic. Close contact plays an important role in infection spread, while fomite may also be a possible transmission route. Research during the COVID-19 pandemic has identified long-range airborne transmission as one of the important transmission routes although lack solid evidence.
Management of belantamab mafodotin-associated corneal events in patients with relapsed or refractory multiple myeloma (RRMM)
Authors: Sagar Lonial, Ajay K. Nooka, Praneetha Thulasi, Ashraf Z. Badros, Bennie H. Jeng, Natalie S. Callander, Heather A. Potter, Douglas Sborov, Brian E. Zaugg, Rakesh Popat, Simona Degli Esposti, Julie Byrne, Joanna Opalinska, January Baron, Trisha Piontek, Ira Gupta, Reza Dana, Asim V. Farooq, Kathryn Colby, Andrzej Jakubowiak
Journal: Blood Cancer Journal (2021)

Abstract Belantamab mafodotin (belamaf) demonstrated deep and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) in DREAMM-2 (NCT03525678). Corneal events, specifically keratopathy (including superficial punctate keratopathy and/or microcyst-like epithelial changes (MECs), eye examination findings with/without symptoms), were common, consistent with reports from other antibody–drug conjugates. Given the novel nature of corneal events in RRMM management, guidelines are required for their prompt identification and appropriate management. Eye examination findings from DREAMM-2 and insights from hematology/oncology investigators and ophthalmologists, including corneal specialists, were collated and used to develop corneal event management guidelines. The following recommendations were formulated: close collaboration among hematologist/oncologists and eye care professionals is needed, in part, to provide optimal care in relation to the belamaf benefit–risk profile. Patients receiving belamaf should undergo eye examinations before and during every treatment cycle and promptly upon worsening of symptoms. Severity of corneal events should be determined based on corneal examination findings and changes in best-corrected visual acuity. Treatment decisions, including dose modifications, should be based on the most severe finding present. These guidelines are recommended for the assessment and management of belamaf-associated ocular events to help mitigate ocular risk and enable patients to continue to experience a clinical benefit with belamaf.
A novel PI3K inhibitor XH30 suppresses orthotopic glioblastoma and brain metastasis in mice models
Authors: Ming Ji, Dongjie Wang, Songwen Lin, Chunyang Wang, Ling Li, Zhihui Zhang, Jing Jin, Deyu Wu, Yi Dong, Heng Xu, Duo Lu, Xiaoguang Chen
Journal: Acta Pharmaceutica Sinica B (2021)

Glioblastoma is carcinogenesis of glial cells in central nervous system and has the highest incidence among primary brain tumors. Brain metastasis, such as breast cancer and lung cancer, also leads to high mortality. The available medicines are limited due to blood-brain barrier. Abnormal activation of phosphatidylinositol 3-kinases (PI3K) signaling pathway is prevalent in glioblastoma and metastatic tumors. Here, we characterized a 2-amino-4-methylquinazoline derivative XH30 as a potent PI3K inhibitor with excellent anti-tumor activity against human glioblastoma. XH30 significantly repressed the proliferation of various brain cancer cells and decreased the phosphorylation of key proteins of PI3K signaling pathway, induced cell cycle arrest in G1 phase as well. Additionally, XH30 inhibited the migration of glioma cells and blocked the activation of PI3K pathway by interleukin-17A (IL-17A), which increased the migration of U87MG. Oral administration of XH30 significantly suppressed the tumor growth in both subcutaneous and orthotopic tumor models. XH30 also repressed tumor growth in brain metastasis models of lung cancers. Moreover, XH30 reduced IL-17A and its receptor IL-17RA in vivo. These results indicate that XH30 might be a potential therapeutic drug candidate for glioblastoma migration and brain metastasis.
Cytosolic replication in epithelial cells fuels intestinal expansion and chronic fecal shedding of Salmonella Typhimurium
Authors: Audrey Chong, Kendal G. Cooper, Laszlo Kari, Olof R. Nilsson, Chad Hillman, Brittany A. Fleming, Qinlu Wang, Vinod Nair, Olivia Steele-Mortimer
Journal: Cell Host & Microbe (2021)
Errors in the Discussion and Funding/Support Sections
Authors: Ezra Golberstein
Journal: JAMA Pediatrics (2020)

Summer Rosenstock, PhD, MHS; Allison Ingalls, MPH; Reese Foy Cuddy, MPH; Nicole Neault, MPH; Shea Littlepage, MSPH; Lisa Cohoe; Leonela Nelson, BS; Kimberlyn Shephard-Yazzie; Shaneyka Yazzie; Anna Alikhani, MPH; Raymond Reid, MD; Anne Kenney, MPH; Allison Barlow, PhD, MPH, MA
POS0021 INTERMETATARSAL BURSITIS, A NOVEL FEATURE OF JUXTA-ARTICULAR INFLAMMATION IN EARLY RHEUMATOID ARTHRITIS: RESULTS FROM A LONGITUDINAL MRI-STUDY
Authors: B. Van Dijk, Y. Dakkak, X. Matthijssen, E. Niemantsverdriet, M. Reijnierse, A. Van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2021)

Background: Rheumatoid arthritis (RA) is characterised by inflammation of the synovial lining. In addition to synovitis, the tendon sheaths of small hand and foot joints are also frequently inflamed. This results in tenosynovitis, which is often missed at clinical evaluation in early RA but visible on imaging, such as MRI. A third anatomical structure surrounded by a synovial lining is formed by the intermetatarsal bursae in the forefeet. Inflammation of these bursae (intermetatarsal bursitis; IMB) was recently identified at MRI-studies and shown to be specific for early RA.[1] This suggests that IMB is also a feature of early RA. Objectives: We hypothesised that if IMB is indeed an RA-feature, then (1) at diagnosis its presence associates with other measures of local inflammation (synovitis, tenosynovitis and osteitis) and (2) it responds to DMARD therapy similarly as these other local inflammatory measures. These hypotheses were tested in a comprehensive MRI-study. Methods: 157 consecutive early RA patients underwent unilateral contrast-enhanced 1.5T MRI of the forefoot at diagnosis. MRIs were evaluated for presence of IMB and for synovitis, tenosynovitis and osteitis in line with the RA MRI scoring system (summed as RAMRIS-inflammation). MRIs at 4, 12 and 24 months were evaluated for presence and size of IMB-lesions in patients who had IMB at baseline and received early DMARD-therapy. Logistic regression was used for analyses at patient-level; generalised estimating equations were used for bursa-level analyses. Stratification for ACPA was performed. Results: 69% of RA patients had ≥1 IMB. In multivariable analyses on bursa-level, presence of IMB was independently associated with local presence of synovitis and tenosynovitis (OR 1.69 (95%CI 1.12–2.57) and 2.83 (1.80–4.44), respectively), but not with osteitis. On patient-level, presence of IMB was most strongly associated with tenosynovitis (OR 2.92 (1.62–5.24)). During treatment with DMARDs, the average size of IMB-lesions decreased (Figure 1). This decrease was associated with decrease in RAMRIS-inflammation scores; most strongly with a decrease in synovitis but not in osteitis. Within ACPA-positive and ACPA-negative RA similar results were obtained. Conclusion: IMB particularly accompanies inflammation of the synovial lining of joints and tendon-sheaths, both regarding simultaneous occurrence at diagnosis and simultaneous treatment-response. These findings suggest that IMB represents juxta-articular synovial inflammation and indeed is a hallmark of early RA. References: [1]Dakkak YJ et al. Increased frequency of intermetatarsal and submetatarsal bursitis in early rheumatoid arthritis: a large case-controlled MRI study. Arthritis Res Ther 22, 277 (2020). Disclosure of Interests: None declared.
Abstract 451: Beta Blocker Use in Asymptomatic Patients with Sepsis and Elevated Troponin is Associated with Lower Risk of Mortality
Authors: Hanumantha R Jogu, Parag A Chevli, Abhishek Bose, Amit Vasireddy, Sreeja Sompalli, Guru Anirudh Reddy Gopireddy, Abhishek Dutta, Obiora Maludum, Pradeep Yarra, Aysha Amjad, Suma Menon, Padageshwar R Sunkara, Waqas T Qureshi
Journal: Circulation Research (2017)

Background: In septic patients with elevated Troponin (e-Tn) levels, beta-blockers (BB) are usually avoided to prevent chronotropic incompetence. We examined the unclear association of BB at discharge with mortality in patients with sepsis and e-Tn levels. Methods: We assessed 936 consecutive patients with e-Tn levels and sepsis on admission. Those with septic shock were excluded. BB use was determined by their presence at the time of discharge. Cox proportional hazard models adjusted for demographics and clinical covariates examined the association of BB use with all-cause mortality. Results: 417 (44.6%) were on BB therapy with mean peak Tn level of 1.0 ± 0.09 ng/ml. Over a median follow-up of 5 years, 108 (36.5%) versus 236 (40.3%) deaths were reported in the BB versus the non-BB group respectively. On adjusting the Cox model for demographics, peak Tn, baseline cardiovascular disease risk factors, use of anticoagulants, antiplatelet and statins during hospitalization and discharge, BB use associated with a lower risk of mortality (HR 0.72; 95% CI 0.58-0.90, p = 0.004). In addition, BB use had a significant interaction with ischemic EKG changes (interaction p = 0.049) leading to a lower risk of mortality among patients without ischemic EKG changes (HR 0.66; 0.51-0.84, p = 0.0008 vs. HR 1.33; 0.75-2.36, p = 0.32, Figure 1). Conclusions: In septic patients with e-Tn levels, use of BB on discharge led to a lower risk of mortality and the protective effect was more pronounced in patients without ischemic EKG changes. Future research should focus on its protective mechanism and its use in septic patients with e-Tn in a randomized trial.