tbuckley/cabot-search huggingface dataset:
AB1022 PANNICULITIS IN RHEUMATOLOGICAL PRACTICE: THE RESULTS OF LONG-TERM FOLLOW-UP
Authors: O. Egorova, B. Belov
Journal: Annals of the Rheumatic Diseases (2020)

Background: Panniculitis is a group of heterogeneous inflammatory diseases that occur with damage to the subcutaneous fat (SCF), musculoskeletal system, and often internal organs Objectives: to evaluate the course and outcome in patients with panniculitis Methods: the course of the disease was monitored in 193 patients treated at the V.A. Nasonova Research Institute of Rheumatology for 3-5 years (142 women, 51 men) aged 19 to 77 with the referral diagnosis of erythema nodosum (EN) and undifferentiated panniculitis and with the disease duration of 1 week to 13 years. In addition to general clinical study, serum concentrations of α-1 antitrypsin, amylase, lipase, ferritin, creatinephosphokinase were determined, computed tomography of the chest organs, immunological, ultrasound scanning of the skin and SCF of the node area, tuberculosis tests and pathomorphological study of skin biopsy from the node area were performed. Results: : as a result of laboratory and instrumental examination, the following diagnoses were made: EN associated with infection (72 people – group 1), lipodermatosclerosis (LDS) (40 –group 2), idiopathic lobular panniculitis (ILP) (32 – group 3), Löfgren’s syndrome (SL) (49 –group 4). During the follow-up period, 6 deaths occurred (3.1%): in a patient with LDS due to acute heart failure and in 5 patients with ILP due to the activity of the disease which led to the development of cardiopulmonary pathology and disseminated intravascular coagulation (DIC) syndrome. In group 1, during the observation period, UE recurred in 18 people (25%), the probable causes were: hypothermia (6), exacerbation of chronic tonsillitis (6), acute respiratory viral infections (ARVI) (4), stress (1), a rapid decrease in the dose of glucocorticoids (GC) (1), the cause is unknown (2). In group 2, recurrence occurred in 19 patients (47.5%) due to the lack of anti-inflammatory therapy (plaquenil) (10), trauma (4), stress (3), and weight lifting (2). There was no recurrence in 7 patients in this group, however, nodes would not disappear completely, which is obviously due to the absence of plaquenil. In group 3, recurrence was registered in 24 cases (75%) and it was associated with insufficient effect of the ongoing anti-inflammatory therapy (9), a decrease in blood glucose to minimal doses (6), hypothermia (6) and the absence/cancellation of anti-inflammatory therapy (3). In group 4, recurrence of nodes was registered in 14 cases (28.5%), possible causes: cancellation of GC (9) and cooling/ARVI(5). Conclusion: in the observed group of patients with panniculitis mortality was 3.1%. The main causes of recurrence in EN were viral-bacterial infections, and in case of ILP, LDS and SL it was insufficient effect/absence of anti-inflammatory therapy. Disclosure of Interests: None declared
AB0128 Usefulness of mri for the diagnosis of inflammatory sacroiliitis
Authors: R Ghozlan, M Dupuis, J Mani, S Marciano
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The diagnosis of sacroiliitis is usually performed on X-rays but frequently this method of imaging can be normal and the diagnosis of sacroiliitis can be missed, particularly in patients B27 negative. <h3>Objectives</h3> To determine which signs are the most accurate in the diagnosis of sacroiliitis with MRI. <h3>Methods</h3> 15 patients with inflammatory low back pain have been referred to us. The patients were divided in 2 groups. Group 1: 8 patients with normal X-rays; 6 were B27 negative and 2 were B27 positive: MRI showed abnormalities related to sacroiliitis. Group 2: 7 patients with normal X-rays; 6 were B27 positive and 1 was negative: MRI showed inflammatory signs. <h3>Results</h3> The examination showed bone narrow oedema, bone erosions, ligamentous contrast enhancement and fluid in the joint space. <h3>Conclusion</h3> This study confirms the excellent positive predictive value of MRI for an early diagnosis of active sacroiliitis, especially in B27 negative patients and/or with normal X-rays.
Abstract 16778: Effectiveness of Platelet Inhibition on Reducing High-Intensity Transient Signals to Cerebral Circulation During Tavi
Authors: Charalampos Kalantzis, Michael Vavouranakis, Maria Kariori, Vasilios Voudris, Konstantinos Toutouzas, Georgios Latsios, Elias Kosmas, Konstantinos Kalogeras, Carmen-Maria Moldovan, Evangelia Bei, Angel-Michail Kolokathis, Dimitrios Vrachatis, Gerasimos Siasos, Dimitrios Tousoulis, Manolis Vavuranakis
Journal: Circulation (2018)

Introduction: Despite the established dual antiplatelet treatment, embolic cerebrovascular events remain a major concern peri-operatively and following Transcatheter Aortic valve Implantation (TAVI). High Residual Platelet Reactivity (RPR) may contribute to platelet aggregation, propagating thrombosis on implanted materials. Therefore, we evaluated whether high RPR may predispose to an increased number of cerebrovascular emboli during the procedure. Methods: Consecutive patients who underwent transfemoral TAVI with Evolut™ R bioprosthesis were prospectively studied. Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor was administered to all patients 24 hours prior to the procedure at loading dose. The number of detected High Intensity Transient Signals (HITS) was assessed using Rimed Digi-Lite™ Transcranial Doppler on both cerebral arteries during the following phases of the procedure; Phase 0: 30 minutes prior to procedure initiation, Phase I: between access site puncture and introduction of the delivery system, Phase II: during the implantation of the bioprosthesis, until the removal of the delivery system. Platelet inhibition was measured prior to the procedure and expressed in PRU, using the VerifyNow® assay and defined as high RPR if PRU≥208. Results: Out of 28 total patients (81±7 years, 18 males (64%)), 12 patients (81±9 years, 8 males (66.7%)) had PRU ≥208 (high RPR group), while 16 patients (81±5 years, 10 males (62.5%)) had PRU&lt;208 (low RPR group). All device implantations were performed without balloon pre-dilation. Among the high RPR group, a statistically significant higher number of HITS was recorded compared to the low RPR group (707±149 vs. 530±152, p: 0.004). This was mainly driven by the number of HITS detected during Phase II, compared to the rest procedure stages (247±84 vs. 165±28, p:0.004). A statistical significant correlation of PRU with the total number of HITS was found (r2: 0.25, p: 0.006). Conclusions: High RPR after dual antiplatelet loading resulted in larger burden of embolic HITS during TAVI. This may has implications for future strategies for cerebral embolic protection.
Motexafin gadolinium mobilizes zinc and inhibits thioredoxin reductase in human cancer cell lines
Authors: Darren Magda, Philip Lecane, Cheryl Lepp, Richard A. Miller
Journal: Cancer Research (2005)

4968  Increased intracellular zinc concentration has been reported to alter cellular metabolism and signaling pathways. Motexafin gadolinium (MGd, Xcytrin®) is an anti-cancer agent that selectively localizes in tumors and promotes redox stress by oxidizing intracellular reducing species. MGd induces transcription of metallothioneins (MT) and zinc transporter 1 (ZnT1). In the present study, we describe the effects of MGd on zinc ion homeostasis, thioredoxin reductase activity, and viability in cancer cell lines. Human lung (A549) and prostate (PC3) cancer and lymphoma (Ramos) cells were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum. Zinc acetate (0-100 μM) and MGd (0-10 μM) were added for 4-6 hr. Medium was exchanged and thioredoxin reductase activity was assessed by measuring the rate of lipoate reduction (Biaglow, Anal. Biochem. 281:77, 2000). In other experiments, cells were treated with MGd and zinc, and analyzed by flow cytometry using propidium iodide and the ion-specific fluorescent probe, FluoZin-3-AM™. Fold increase is expressed as (median fluorescent signal - control)/control. RNA from treated cultures was harvested and metallothionein and ZnT1 induction assessed by Northern blotting. Treatment with MGd and zinc led to synergistic increases in free intracellular zinc levels, MT and ZnT-1 induction, inhibition of lipoate reduction, and cytotoxicity. In PC3 cells, FluoZn-3 fluorescence was increased 1.1-fold (i.e., 110%) after 4 hr treatment with 50 μM MGd and 50 μM zinc, relative to treatment with zinc alone. In A549 cells, exposure to 50 μM MGd and 75 μM zinc led to a 1.2, 3.0, 4.0, and 1.1 -fold increase in FluoZn-3 fluorescence after 2, 4, 8, or 24 hr. In Ramos, treatment 50 μM MGd and 50 μM zinc led to 0.4, 1.6, 4.2, and 22-fold increase in FluoZn-3 fluorescence after 2, 4, 6, or 24 hr. MT and ZnT1 transcript levels were elevated within 4 hr after treatment with MGd, zinc, or the combination, and remained elevated for at least 24 hr. For example, in A549, MT transcript levels were increased 20, 6.8, and 34-fold by 50 μM MGd, 50 μM zinc, or the combined treatment after 4 hr. There was a 3.7 and 11-fold increase in propidium iodide permeable A549 and Ramos cells by 24 hr, relative to treatment with zinc alone. The rate of lipoate reduction in A549, PC3, and Ramos cell lines after 4-6 hr treatment with MGd and zinc, decreased to 51%, 62%, and 50% of levels observed following treatment with zinc alone. These observations support the characterization of MGd as a redox cycling agent that increases the intracellular availability of free zinc. This activity leads to inhibition of thioredoxin reductase and, ultimately, induction of cell death. The proposed mechanism of action supports the use of this agent alone or in combination chemotherapy. Moreover, the above findings lead us to suggest that thioredoxin reductase is a key target of intracellular free zinc released by oxidative stress.
Reduced-Dose Radiation Therapy for HPV-Associated Oropharyngeal Carcinoma (NRG Oncology HN002)
Authors: Sue S. Yom, Pedro Torres-Saavedra, Jimmy J. Caudell, John N. Waldron, Maura L. Gillison, Ping Xia, Minh T. Truong, Christina Kong, Richard Jordan, Rathan M. Subramaniam, Min Yao, Christine H. Chung, Jessica L. Geiger, Jason W. Chan, Brian O'Sullivan, Dukagjin M. Blakaj, Loren K. Mell, Wade L. Thorstad, Christopher U. Jones, Robyn N. Banerjee, Christopher Lominska, Quynh-Thu Le
Journal: Journal of Clinical Oncology (2021)

Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven.In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI).Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% (P = .04). For IMRT, 2-year PFS was 87.6% (P = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% v 52.4%; P < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% (P = .56).The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.
Possible Immortal Time Bias in Study of Antibiotic Treatment and Outcomes in Patients Hospitalized for Asthma
Authors: Thomas B. Newman
Journal: JAMA Internal Medicine (2021)

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Occult Bone Metastases From Hepatocellular Carcinoma Detected on 68Ga-PMSA PET/CT
Authors: Sharjeel Usmani, Rashid Rasheed, Fareeda Al Kandari, Najeeb Ahmed
Journal: Clinical Nuclear Medicine (2021)

68Ga-PSMA is an excellent radiotracer for both staging and detection of recurrence in prostate cancer, but it can also be useful in other solid tumors due to tumor-associated angiogenic factors and endothelial cell sprouting. We report a case of an 82-year-old man with hepatocellular carcinoma who presented with rising tumor marker but stable CT findings 6 months after transarterial chemoembolization. 68Ga-PSMA PET/CT showed high PSMA-expressing hyperneovascular hepatic lesions (primary tumor), additional multifocal hepatic lesions, and with unexpected multiple bone metastases. 68Ga-PSMA expression in hepatocellular carcinoma can influence patient management and potentially guide radionuclide legend therapy.
Predicting recurrence of respiratory failure in critically ill patients with COVID-19: A preliminary study
Authors: Yuichi Adachi, Takayuki Shiroyama, Yuta Yamaguchi, Teruaki Murakami, Haruhiko Hirata, Saori Amiya, Takayuki Niitsu, Yoshimi Noda, Reina Hara, Takatoshi Enomoto, Takayoshi Morita, Yasuhiro Kato, Akinori Uchiyama, Yoshito Takeda, Atsushi Kumanogoh
Journal: Journal of Infection (2021)
Abstract 14812: Mental Illness is Independently Associated With Major Morbidity and Mortality After Cardiac Surgery
Authors: Zachary M Tyerman, J H Mehaffey, Robert B Hawkins, W Z Chancellor, Nicholas R Teman, Leora Yarboro, Gorav Ailawadi
Journal: Circulation (2018)

Introduction: Serious Mental Illness (SMI), defined as a mental disorder causing functional impairment. Affecting 9.8 million Americans (4.0%), SMI correlates with earlier onset and more extensive ...
AB1005 BULLOUS LUPUS (BSLE) AS THE FIRST MANIFESTATION OF SYSTEMIC LUPUS ERYTHEMATOSUS IN THE PEDIATRIC POPULATION (PSLE): A DIAGNOSTIC CHALLENGE IN DAILY PRACTICE
Authors: F. Torres, M. Velasquez, L. Ramirez, L. Leon, M. Martinez
Journal: Annals of the Rheumatic Diseases (2020)

Background: Cutaneous manifestations are observed in 59–85% of patients with SLE but less than 5% developed BSLE. In the GLADEL cohort, the prevalence is 0.41%. BSLE literature in children is scarce Objectives: to describe the clinical characteristics of the patients with BSLE Methods: series of cases between 2010-2019 of two reference centers. The cases met Camisa and Grimwood criteria for BSLE Results: 5 cases had bullous lesions that resolved with residual hypopigmentation. One case had focal seizure and other patient had arthritis with leukopenia and thrombocytopenia. 2 patients had proteinuria &lt;500 mg/24 hours. There were no cases of lupus nephritis. The median SLEDAI-2K score was 12 (IR: 8-17). All had ANAs in titers greater than 1:160 and four had anti-DNA (+). 5 patients had anti-RNP and 4 had anti-Sm. One case had anti-Ro/anti-La. All presented low C3 and 80% had low C4. 80% had ESR ≥20 mm/hour and CRP greater than 0.5 mg/dl in 60%. All presented clinical response with glucocorticoids and dapsone; one patient had methemoglobinemia that improved. At 3 months, the blisters did not recur in 4 patients except one case that presented relapse due to inadherence. Histologically, the most common finding was subepidermal blisters with neutrophils in the papilar dermis. DIF showed linear deposits of Igs and complement in 4 cases and granular deposits in one case; IgG/IgM were in 5 of the samples. IgA was positive in 60% and C3 in 80% Conclusion: In this series, BSLE was associated with neuropsychiatric, joint and haematological involvement in 40% of patients, without lupus nephritis. Such abnormalities had a parallel course to skin involvement, without recurrences. BSLE tends to have a single-phase behavior and in children unlike adults, severe renal involvement is uncommon References: [1]Pons-Estel GJ, et al. Lupus 2018; 27(10): 1753-1754 Disclosure of Interests: None declared
Is antiangiogenic therapy necessary for patients with metastatic colorectal cancer (mCRC) and mutation in the <i>BRAF</i> gene? Results of the systematic review and meta-analysis.
Authors: Mikhail Fedyanin, Elizaveta Polyanskaya, Kheda Elsnukaeva, Alexey Tryakin, Ilya Pokataev, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2021)

88 Background: There are no direct prospective randomized studies supporting the need for antiangiogenic drugs in the treatment of patients with the m BRAF mCRC. However, subgroup analysis of different studies showed conflicting results. Therefore, we performed systemic review and meta-analysis to compare efficacy anti-angiogenic targeted therapy with chemotherapy and chemotherapy alone in patients with m BRAF mCRC in terms of progression free survival (PFS), and overall survival (OS). Methods: We performed a search of all prospective randomized phase III studies in PubMed, ASCO and ESMO congresses for all years before September, 2020, compared chemotherapy (CT) plus bevacizumab or aflibercept or ramucirumab and CT alone at the first-line or second-lines with information of the BRAF status. Primary outcome was hazard ratio (HR) for PFS and 95% confidence interval (CI); secondary–HR for OS and 95%CI. Fixed effects were used for analysis. Meta-analysis was conducted by "Review Manager" Ver. 5.3. Results: We identified 4 trials (AVF2107g, AGITG MAX, VELOUR and RAISE), which included 120 patients with mBRAF (anti-angiogenic plus CT–65 (54%) and CT alone–55 (46%). According to results of the meta-analysis there was a tendency for significant improvement in PFS (HR 0.64, 95% CI 0.4-1.02; p = 0.06; I 2 = 0%, p for heterogeneity 0.7; 53trials) and significant improvement in OS (HR 0.51, 95% CI 0.32-0.82; p = 0.005; I 2 = 0%, p for heterogeneity 0.52; 4 trials) in group of ani-angiogenic therapy. Conclusions: Addition of anti-angiogenic therapy to chemotherapy showed improvement in the PFS and OS in pts with m BRAF compared with chemotherapy alone. A prospective randomized trial is needed to determine the optimal regimen of systemic therapy for pts with m BRAF mCRC.
NLRP3 inflammasome as a key driver of vascular disease
Authors: Masafumi Takahashi
Journal: Cardiovascular Research (2021)

Abstract Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) is an intracellular innate immune receptor that recognizes a diverse range of stimuli derived from pathogens, damaged or dead cells, and irritants. NLRP3 activation causes the assembly of a large multiprotein complex termed the NLRP3 inflammasome, and leads to the secretion of bioactive interleukin (IL)-1β and IL-18 as well as the induction of inflammatory cell death termed pyroptosis. Accumulating evidence indicates that NLRP3 inflammasome plays a key role in the pathogenesis of sterile inflammatory diseases, including atherosclerosis and other vascular diseases. Indeed, the results of the Canakinumab Anti-inflammatory Thrombosis Outcome Study trial demonstrated that IL-1β-mediated inflammation plays an important role in atherothrombotic events and suggested that NLRP3 inflammasome is a key driver of atherosclerosis. In this review, we will summarize the current state of knowledge regarding the role of NLRP3 inflammasome in vascular diseases, in particular in atherosclerosis, vascular injury, aortic aneurysm, and Kawasaki disease vasculitis, and discuss NLRP3 inflammasome as a therapeutic target for these disorders.
Abstract 463: The Orphan G Protein-Coupled Receptor C5B is Regulated by Hyperglycemia and Activates Pro-Inflammatory Signaling in <i>Endothelial Cells</i> Via the Tyrosine Kinase Fyn
Authors: Greta Freundt, Jan Thorge Nitz, Norbert Frey, Hans-Jörg Hippe
Journal: Circulation Research (2017)

Background: Atherosclerosis is driven by an inflammatory process of the vascular wall in which endothelial cells (EC) are decisively involved. The orphan G protein-coupled receptor GPRC5B activates inflammatory pathways in adipocytes and regulates the glucose and lipid metabolism in Drosophila melanogaster . Hypothesis: We hypothesize that GPRC5B is involved in inflammatory signaling of EC, particularly in hyperglycemia. Methods &amp; Results: Stimulation of mouse brain endothelial cells (bEnd.3) and primary human umbilical vein endothelial cells (HUVEC) with high glucose concentration (25 mM), Tumor Necrosis Factor α (TNFα 0,1 μg/ml) or Lipopolysaccharides (LPS 1 μg/ml), respectively, leads to a significant upregulation of GPRC5B mRNA and protein level compared to unstimulated cells (mRNA / protein: gluc +254% / +86%, p&lt;0.001; TNFα +203% / +124%, p&lt;0.001; LPS +195%, p&lt;0.05, n=6). Similar results are obtained in HUVECs after stimulation with high glucose and cytokines. Overexpression of GPRC5B in EC induced a significant increase in Interleukin 6 (IL6), Intercellular Adhesion Molecule 1 (ICAM1) and Vascular Cell Adhesion Molecule 1 (VCAM1) mRNA and protein expression. Furthermore, activation of NFκB (luciferase reporter assay) and phosphorylation of extracellular signal–regulated kinases 1/2 (Erk 1/2) were significantly increased compared to controls (mRNA: IL6 +42%, p&lt;0.01; ICAM1 +37%, p&lt;0.01; VCAM1 +40%, p&lt;0.001, n=8. Protein: ICAM1 +48%, p&lt;0.05; VCAM1 +52%, p&lt;0.05; pErk 1/2 +67%, p&lt;0.01, n=5. NFκB: +165%, p&lt;0.001, n=18). Conversely, the siRNA-mediated GPRC5B knockdown resulted in diminished expression of IL6 and VCAM1 as well as decreased NFκB activity compared to controls (IL6 -55%, p&lt;0.05, n=3, NFκB -36%, p&lt;0.05, n=6) . The knockdown results were confirmed in HUVECs. Co-immunoprecipitations in EC revealed the tyrosine kinase Fyn as interaction partner of GPRC5B. Conclusion: Our data suggest that GPRC5B is not only regulated by glucose and pro-inflammatory cytokines but also activates pro-inflammatory and pro-atherogenic pathways in mouse and human endothelial cells. Therefore, GPRC5B might play an important role in hyperglycemia-accelerated vascular inflammation and pathogenesis of atherosclerosis.
David Oliver: Should we allow filming in covid filled hospitals?
Authors: David Oliver
Journal: BMJ (2021)

Simon Stevens, NHS chief executive, has publicly condemned undercover filming on camera phones inside NHS hospitals.1 Footage has been posted online in a twisted attempt to show that covid-19 pressures are exaggerated, fake news.2 Stevens, normally calm and unruffled, was visibly angry about the impact on NHS staff doing difficult jobs and the spread of disinformation. Many healthcare workers, whose morale is suffering at the hands of people who think covid is a hoax, were encouraged to hear him speak out so strongly. Since then the Times has published a story about organised groups of secret filmers claiming the pandemic to be a “hoax,”3 and Facebook has taken down one of their sites.4

In parallel, I’ve seen growing calls in social media to “let the cameras onto the …