tbuckley/cabot-search huggingface dataset:
Loss of direct adrenergic innervation after peripheral nerve injury causes lymph node expansion through IFN-γ
Authors: Chien-Sin Chen, Jasmin Weber, Stephan Jonas Holtkamp, Louise Madeleine Ince, Alba de Juan, Chen Wang, Lydia Lutes, Coline Barnoud, Burak Kizil, Sophia Martina Hergenhan, Johanna Salvermoser, Manuel Lasch, Elisabeth Deindl, Barbara Schraml, Dirk Baumjohann, Christoph Scheiermann
Journal: The Journal of Experimental Medicine (2021)

Peripheral nerve injury can cause debilitating disease and immune cell–mediated destruction of the affected nerve. While the focus has been on the nerve-regenerative response, the effect of loss of innervation on lymph node function is unclear. Here, we show that the popliteal lymph node (popLN) receives direct neural input from the sciatic nerve and that sciatic denervation causes lymph node expansion. Loss of sympathetic, adrenergic tone induces the expression of IFN-γ in LN CD8 T cells, which is responsible for LN expansion. Surgery-induced IFN-γ expression and expansion can be rescued by β2 adrenergic receptor agonists but not sensory nerve agonists. These data demonstrate the mechanisms governing the pro-inflammatory effect of loss of direct adrenergic input on lymph node function.
Abstract 9779: Arm Versus Treadmill Exercise for Detection of Cardiac Ischemia
Authors: Anandita Agarwala, Divya Kapoor, Clarence Balke, Jiafu Ou, Hong Xian, Wade Martin
Journal: Circulation (2019)

Treadmill exercise testing (ETT) provides powerful prognostic and important clinical information on functional capacity and cardiovascular responses to the relevant physiologic stress of exercise. ...
Clinimetric Criteria for Patient-Reported Outcome Measures
Authors: Danilo Carrozzino, Chiara Patierno, Jenny Guidi, Carmen Berrocal Montiel, Jianxin Cao, Mary E. Charlson, Kaj Sparle Christensen, John Concato, Carlos De las Cuevas, Jose de Leon, Ajandek Eöry, Marcelo Pio Fleck, Toshi A. Furukawa, Ralph I. Horwitz, Andrew A. Nierenberg, Chiara Rafanelli, Hongxing Wang, Thomas N. Wise, Nicoletta Sonino, Giovanni A. Fava
Journal: Psychotherapy and Psychosomatics (2021)

Patient-reported outcome measures (PROMs) are self-rated scales and indices developed to improve the detection of the patients’ subjective experience. Given that a considerable number of PROMs are available, it is important to evaluate their validity and usefulness in a specific research or clinical setting. Published guidelines, based on psychometric criteria, do not fit in with the complexity of clinical challenges, because of their quest for homogeneity of components and inadequate attention to sensitivity. Psychometric theory has stifled the field and led to the routine use of scales widely accepted yet with a history of poor performance. Clinimetrics, the science of clinical measurements, may provide a more suitable conceptual and methodological framework. The aims of this paper are to outline the major limitations of the psychometric model and to provide criteria for clinimetric patient-reported outcome measures (CLIPROMs). The characteristics related to reliability, sensitivity, validity, and clinical utility of instruments are critically reviewed, with particular reference to the differences between clinimetric and psychometric approaches. Of note is the fact that PROMs, rating scales, and indices developed according to psychometric criteria may display relevant clinimetric properties. The present paper underpins the importance of the clini­metric methodology in choosing the appropriate PROMs. CLIPROM criteria may also guide the development of new indices and the validation of existing PROMs to be employed in clinical settings.
Reporting of Participant Race, Sex, and Socioeconomic Status in Randomized Clinical Trials in General Medical Journals, 2015 vs 2019
Authors: Mikhaila Alegria, Shawn Sud, Benjamin E. Steinberg, Nan Gai, Asad Siddiqui
Journal: JAMA Network Open (2021)

Middle horizontal lines represent medians; boxes, the interquartile range; and error bars, 1.5 times the interquartile ranges beyond the 25th and
POS1442 THE SUBGROUP OF ACPA-NEGATIVE RHEUMATOID ARTHRITIS PATIENTS ACHIEVING SUSTAINED DMARD-FREE REMISSION IS CHARACTERIZED BY A DIFFERENT RESPONSE IN SEROLOGICAL MARKERS WITHIN THE FIRST YEAR OF DMARD-INITIATION
Authors: M. Verstappen, A. Van der Helm - van Mil
Journal: Annals of the Rheumatic Diseases (2021)

Background: Whilst ~40% of ACPA-negative RA-patients achieve sustained DMARD-free remission (SDFR; the sustained absence of synovitis after DMARD-cessation), the biological pathways involved in SDFR-development are incompletely understood. Previously, high baseline levels of MMP-3, SAA and CRP were found in ACPA-negative RA-patients achieving SDFR. Differences in biomarker levels might reflect distinct underlying biological pathways leading towards disease resolution in this subgroup of ACPA-negative RA-patients. Subsequently, the course of specific biomarkers after treatment-initiation could attain more insight in the understanding of SDFR-development in ACPA-negative RA. Objectives: We explored whether the response of specific biomarkers after treatment-initiation could increase the understanding of SDFR-development in ACPA-negative RA. Methods: One-hundred-thirty-one consecutive ACPA-negative RA-patients were studied on SDFR-development during (median) 7.2-years follow-up. Twelve biomarkers (SAA/CRP/MMP-1/MMP-3/resistin/leptin/IL-6/TNF-R1/YKL-40/EGF/VEGF/VCAM-1) were measured at diagnosis and 1-, and 2-years after DMARD-initiation and compared between patients achieving and not achieving SDFR. To extend on previous findings on baseline levels, correlations between baseline levels and change in levels within year-1 were determined using spearman’s rho (ρ). Results: RA-patients that achieved SDFR (n=63) were characterized by a stronger decline in MMP-1, MMP-3, SAA and CRP in the first 12-months after DMARD-start, compared to RA-patients not achieving SDFR. MMP-1 and MMP-3 declined 1.30-times (95%CI; 1.08-1.57) and 1.44-times (95%CI; 1.00-2.06) stronger in SDFR-patients. In SAA and CRP, this decline was 2.12-times (95%CI; 1.08-4.14) and 2.24-times (95%CI; 1.16-4.35) stronger. Baseline levels of MMP-3, SAA and CRP and strongly correlated with decline in 12-months; ρ -0.6991, ρ -0.9205 respectively ρ -0.9008. RA-patients with high baseline levels characterized the subgroup with the strongest decline in biomarker levels in the first year after DMARD-initiation. Conclusion: The subgroup ACPA-negative RA-patients achieving SDFR are characterized by higher baseline levels and a stronger serological response of MMP-3, SAA and CRP after DMARD-initiation. Because MMP-3 and SAA are expressed by fibroblast-like synoviocytes, these cells may differ in RA-patients achieving disease resolution; molecular studies on synovial tissue could be a next step. Disclosure of Interests: None declared
Oxygen Toxicity in Critically Ill Adults
Authors: Chad H. Hochberg, Matthew W. Semler, Roy G. Brower
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Oxygen supplementation is one of the most common interventions in critically ill patients. Despite over a century of data suggesting both beneficial and detrimental effects of supplemental oxygen, optimal arterial oxygenation targets in adult patients remain unclear. Laboratory animal studies have consistently showed that exposure to a high FiO2 causes respiratory failure and early death. Human autopsy studies from the 1960s purported to provide histologic evidence of pulmonary oxygen toxicity in the form of diffuse alveolar damage. However, concomitant ventilator-induced lung injury and/or other causes of acute lung injury may explain these findings. Although some observational studies in general populations of critically adults showed higher mortality in association with higher oxygen exposures, this finding has not been consistent. For some specific populations, such as those with cardiac arrest, studies have suggested harm from targeting supraphysiologic PaO2 levels. More recently, randomized clinical trials of arterial oxygenation targets in narrower physiologic ranges were conducted in critically ill adult patients. Although two smaller trials came to opposite conclusions, the two largest of these trials showed no differences in clinical outcomes in study groups that received conservative versus liberal oxygen targets, suggesting that either strategy is reasonable. It is possible that some strategies are of benefit in some subpopulations, and this remains an important ongoing area of research. Because of the ubiquity of oxygen supplementation in critically ill adults, even small treatment effects could have a large impact on a global scale.
Natural history and prognostic significance of iron deficiency and anaemia in ambulatory patients with chronic heart failure
Authors: Fraser J. Graham, Gabriele Masini, Pierpaolo Pellicori, John G.F. Cleland, Nicola Greenlaw, Jocelyn Friday, Syed Kazmi, Andrew L. Clark
Journal: European Journal of Heart Failure (2021)

Iron deficiency (ID) and anaemia are common in heart failure; less is known about changes over time.We investigated prevalence, incidence and resolution of ID and anaemia in 906 patients with chronic heart failure (median age 73 (65-79) years, 70% men, 51% with heart failure with reduced ejection fraction) 1 year apart. ID was defined as serum iron ≤13 µmol/L and anaemia as haemoglobin <13.0 g/dL for men or <12.0 g/dL for women. FAIR-HF criteria for ID were also considered. At baseline, 10% had anaemia without ID, 23% had ID without anaemia, 20% had both, and 47% had neither. Percentages changed little over 1 year, but 157 (30%) patients had new-onset ID, 104 (16%) new-onset anaemia, whilst ID resolved in 173 (44%) and anaemia in 63 (23%). Compared to those who remained iron replete (iron >13 µmol/L), mortality was higher in those with persistent or incident ID at 1 year [hazard ratio (HR) 1.81 (1.23-2.67), and HR 1.40 (0.91-2.14), respectively] in multivariable models (P = 0.02). Compared to persistent ID, resolution of ID was associated with a lower mortality [HR 0.61 (0.44-0.86); P = 0.004]. Changes in ID defined by FAIR-HF criteria were not similarly associated with mortality. Anaemia was associated with a poor outcome even if it resolved.The prevalence and incidence of ID and anaemia are high in chronic heart failure but so is the rate of resolution. Persistent or incident ID, defined by a serum iron ≤13 µmol/L, is associated with higher mortality and resolution of ID with lower mortality.
Trade-off Between Bleeding and Thrombotic Risk in Patients With Academic Research Consortium for High Bleeding Risk
Authors: Hironori Hara, Masafumi Ono, Hideyuki Kawashima, Yoshinobu Onuma, Patrick W. Serruys
Journal: JAMA Cardiology (2021)

Urban et al 1 recently developed the Academic Research Consortium for high bleeding risk (ARC-HBR) trade-off model.The new scores provide the predicted 1-year risk of nonperiprocedural major bleeding (Bleeding Ac ademic Research Consortium [BARC] types 3-5 bleeding) and thrombotic events (myocardial infarction [MI] and/or definite or probable stent thrombosis [ST]) after coronary stenting in patients with HBR.In the development and validation cohorts, the C statistics were 0.68 and 0.74 for major bleeding and 0.68 and 0.74 for thrombotic events, respectively; C statistics in validation cohorts typically are lower than those observed in the development cohort.To support individual optimal antiplatelet therapy, bleeding and thrombotic risk scores should achieve helpful discrimination (C statistics, ≥0.60) in contemporary treatment strategies. 2 We applied the scores to the GLOBAL LEADERS trial population. 3 Methods | The GLOBAL LEADERS trial investigated aspirinfree antiplatelet treatment (experimental arm, 1 month of dual antiplatelet therapy [DAPT] followed by 11 months of ticagrelor monotherapy vs reference arm, 12 months of DAPT) in an all-comers population.All patients provided informed consent.The trial was approved by the institutional review board at each center and followed the ethical principles of the Declaration of Helsinki (Supplement 1).Patients were enrolled between July 2013 to November 2015 and had an outpatient clinic visit at 30 days and 3, 6, 12, 18, and 24 months after the index procedure.Data were analyzed during January 2021.The ARC-HBR trade-off model was externally validated in patients with ARC-HBR in the GLOBAL LEADERS trial.Multiple imputation (20 times) of missing values was conducted based on the correlation between all potential predictors and clinical outcomes to make efficient use of the available data without introducing bias under the missing-at-random assumption. 4 The discriminative abilities for BARC types 3 to 5 bleeding and MI and/or ST between 3 to 365 days were assessed using the Harrell C statistic (C index).Agreement between observed and predicted rates was assessed by calibration plot. 4 The discriminative abilities of the PARIS and PRECISE-DAPT scores were also assessed.Analyses were performed using R, version 3.6.0(R Foundation for Statistical Computing).
POS1377 SOME PARAMETERS OF ENDOTHELIAL FUNCTION IN PATIENTS WITH IDIOPATHIC AVASCLAR NECROSIS
Authors: K. Gudkevich, N. Martusevitch, E. Dashkevich
Journal: Annals of the Rheumatic Diseases (2021)

Background: Avascular necrosis (AN) is a disease, which is the result of blood flow disturbance and necrosis of the bone tissue. It affects predominantly men of working age and steadily progresses to secondary osteoarthritis. AN is a multifactorial disease. In the context of vascular hypothesis it is of particular interest to evaluate homocysteine and its metabolism in patients with AN. Objectives: The aim of the present study was to evaluate some parameters of endothelial function in patients with AN of the femoral head or femoral condyles in order to determine possible treatment and prevention options. Methods: We included 53 patients with AN of the femoral head or femoral condyles into the study. The patients were aged 49 (35-62) years, 58,49% (n=31) were male. The inclusion criteria was diagnosis of AN confirmed by X-Ray, CT or MRI. The exclusion criteria were: traumatic AN, Legg-Calve-Pertes disease, connective tissue systemic diseases. We recruited 51 patients into the control group. The groups were comparable by age and gender. In order to analyse engothelial function in the groups we investigated the following serum parameters: homocysteine, vitamin B12, folate. In order to analyse the data obtained we used non-parametric statistics. Results: We determined a higher level of homocysteine in patients with AN (12,15 (7,55-14,60) vs. 8,18 (6,57-10,70) mcmol/l in the control group, p=0,04). Also we observed almost equal levels of vitamin B12 in patients with AN an in the control group (531,95 (340,80-793,55) vs. 532,75 (417,60-669,7) pg/ml, p=0,99). The level of folate was lower in the study group (5,66 (3,83-6,83) vs. 6,99 (5,02-10,38) ng/ml, p=0,01). Conclusion: The data obtained show that homocysteine level in patients with AN is higher. This can be a consequence of folate deficiency, which takes part in homocysteine metabolism. Therefore, homocysteine metabolism disturbances can lead to endothelial dysfunction, which results in cardiovascular events in the heart, brain, kidneys [1] as well as in the bone, according to the study results. Folate supplement is the possible way of AN treatment and prevention. References: [1]Nowroozpoor A, Gutterman D, Safdar B. Is microvascular dysfunction a systemic disorder with common biomarkers found in the heart, brain, and kidneys? - A scoping review. Microvasc Res. 2021 Mar;134:104123. doi: 10.1016/j.mvr.2020.104123. Epub 2020 Dec 15. PMID: 33333140. Disclosure of Interests: None declared
AB0504 TOPOGRAPHY OF 18F-FDG PET/CT INFLAMMATORY SITES IN SPONDYLOARTHRITIS IN COMPARISON TO POLYMYALGIA RHEUMATICA AND TO PATIENTS WITHOUT INFLAMMATORY RHEUMATIC DISEASE
Authors: N. Giraud, M. Sondag, M. Chouk, F. Verhoeven, D. Wendling, C. Prati
Journal: Annals of the Rheumatic Diseases (2021)

Background: Spondyloarthritis (SpA) is a common inflammatory rheumatism, characterized by axial and/or peripheral enthesitis. The positron emission tomography (PET/CT) allows the detection of inflammation. Objectives: Our objective was to study the rhizomelic fixation with 18F-FDG (18-Fluorine deoxyglucose) PET/CT in SpA, compared to a Polymyalgia Rheumatica (PMR) group and to a control without rheumatological manifestations Methods: Monocentric and retrospective study, including patients who have benefited from PET/CT. 2 groups of patients, with SpA on the one hand, and PMR on the other hand, fulfilling standard diagnostic criteria. A third group of controls (CN) benefiting from PET/CT in the context of assessment of a neoplasia. The rhizomelic fixations were evaluated according to the average of semi-quantitative scores. This in different rhizomelic sites, articular (gleno-humeral, coxo-femoral) and extra-articular (sub acromial (BSAD), trochanteric bursitis). Results: 147 patients were included: 44 SpA, 50 PMR, and 53 CN. The rhizomelic fixations were significantly lower in SpA compared to PMR: on the pelvic girdle [0.31(0.7) vs 1.15(1.04), p=1.2*10-10], the scapular girdle [0.15(0.44) vs. 1.35(1.2), p=7.09*10-15], the hip joints [0.27(0.62) vs 1.16(1.16), p=1.6*10-5], glenohumeral joints [0.18(0.49) vs. 1.71(1.04), p=4.75*10-12], the trochanteric bursae [0.36(0.77) vs 1.14(0.91), p=3.54*10-6], BSADs [0.11(0.38) vs. 0.98(1.24),p=4.63*10-5], or overall rhizomelic fixation. [0.23(0.59) vs. 1.26(1.14), p= 4.47*10-24]. The fixation was also significantly lower for SpA compared to CN, in trochanters [0.36(0.77) vs 0.58(0.68),p=3.54*10-6], at the glenohumeral joints [0.18(0.49) vs 0.58(0.66),p=3.27*10-5], pelvic girdle [0.31(0.7) vs. 0.49(0.67),p=0.0028] and scapular girdle [0.15(0.44) vs. 0.41(0.66), p=7.09*10-15] and on the global overall rhizomelic fixation [0.23(0.59) vs. 0.49(0.67), p=1.22*10-6]. Conclusion: Our study is the first to study the rhizomelic fixations with 18f-FDG in SpA, compared to another rheumatism inflammatory and controls. We found a lower fixation in SpA compared to PMR, confirming the major and specific rhizomelic fixation of PMR. We found a lower fixing of SpA compared to CN, without anatomical, articular or extra-articular systematization. SpA seems to be a condition with low uptake on 18f-FDG PET/CT, particularly at the rhizomelic level, compared to PMR and controls. Disclosure of Interests: None declared.
Follow-up study of pulmonary function among COVID-19 survivors 1 year after recovery
Authors: Xiquan Yan, Huxiang Huang, Changfeng Wang, Zhaoxia Jin, Zhongwei Zhang, Jiangming He, Siqing Yin, Maiying Fan, Juanshu Huang, Fang Chen, Yong Zeng, Xiaotong Han, Yimin Zhu
Journal: Journal of Infection (2021)
Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis
Authors: Ruilin Tian, Anthony Abarientos, Jason Hong, Sayed Hadi Hashemi, Rui Yan, Nina Dräger, Kun Leng, Mike A. Nalls, Andrew B. Singleton, Ke Xu, Faraz Faghri, Martin Kampmann
Journal: Nature Neuroscience (2021)
AB0407 CARDIOVASCULAR BURDEN IN SYSTEMIC SCLEROSIS: QRISK3 VERSUS FRAMINGHAM FOR RISK ESTIMATION
Authors: M. Di Battista, S. Barsotti, A. Della Rossa, M. Mosca
Journal: Annals of the Rheumatic Diseases (2021)

Background: Cardiovascular (CV) diseases, namely myocardial infarction and stroke, are not among the most known and frequent complications of systemic sclerosis (SSc), but there is growing evidence that SSc patients have a higher prevalence of CV diseases than the general population [1]. Objectives: To compare two algorithms for CV risk estimation in a cohort of patients with SSc, finding any correlation with clinical characteristics of the disease. Methods: SSc patients without previous myocardial infarction or stroke were enrolled. Traditional CV risk factors, SSc-specific characteristics and ongoing therapies were assessed. Framingham and QRISK3 algorithms were then used to estimate the risk of develop a CV disease over the next 10 years. Results: Fifty-six SSc patients were enrolled. Framingham reported a median risk score of 9.6% (IQR 8.5), classifying 24 (42.9%) subjects at high risk, with a two-fold increase of the mean relative risk in comparison to general population. QRISK3 showed a median risk score of 15.8% (IQR 19.4), with 36 (64.3%) patients considered at high-risk. Both algorithms revealed a significant role of some traditional risk factors and a noteworthy potential protective role of endothelin receptor antagonists (p=0.003). QRISK3 was also significantly influenced by some SSc-specific characteristics, as limited cutaneous subset (p=0.01), interstitial lung disease (p=0.04) and non-ischemic heart involvement (p=0.03), with the first two that maintain statistically significance in the multivariate analysis (p=0.02 for both). Conclusion: QRISK3 classifies more SSc patients at high-risk to develop CV diseases than Framingham, and it seems to be influenced by some SSc-specific characteristics. If its predictive accuracy were prospectively verified, the use of QRISK3 as a tool in the early detection of SSc patients at high CV risk should be recommended. References: [1]Ngian GS, Sahhar J, Proudman SM, Stevens W, Wicks IP, Van Doornum S. Prevalence of coronary heart disease and cardiovascular risk factors in a national cross-sectional cohort study of systemic sclerosis. Ann Rheum Dis. 2012;71:1980-3. Disclosure of Interests: None declared
AB0352 ANTICARDIOLIPIN ANTIBODIES AND ACTIVITY OF GIANT CELL ARTERITIS
Authors: A. Hočevar, R. Jese, J. Kramarič, S. Cucnik, M. Tomsic, Z. Rotar
Journal: Annals of the Rheumatic Diseases (2021)

Background: Anticardiolipin antibodies (aCL) can be detected in newly diagnosed GCA as reactive antibodies to endothelial lesions. Their prognostic role, as a marker of disease activity, has not been extensively studied in GCA. Objectives: Our aim was to determine whether aCL IgG might represent laboratory marker of active GCA. Methods: We included patients with new clinical diagnosis of GCA supported by histology or imaging between September 2011 and July 2019, who completed at least a 48-week follow-up at our secondary/tertiary rheumatology center. Follow up visits with predetermined clinical and laboratory tests, including aCL IgG, were performed 12, 24, 48, and 96 weeks after diagnosis. GCA relapse was defined as worsening or new disease activity after initial remission. Other reasons for the disease-related symptoms, elevated inflammatory markers (C reactive protein or erythrocyte sedimentation rate) had to be excluded. aCL IgG were determined in the patients’ sera samples at baseline and at follow up visits, using an in-house solid phase enzyme-linked immunosorbent assay 1 . A value above the 99 th percentile of the healthy control population was taken as significant. Results: During the observation period we identified 288 newly diagnosed GCA patients. Two hundred and twelve GCA patients (66.5% females, median (IQR) age 73.9 (67.0–78.7) years) fulfilled the study inclusion criterion, among them 145 patients completed the 96-week follow up visit. At baseline, 129/212 (60.8%) GCA patients had positive aCL IgG. During in total 781 follow up visits, we recorded 77 (9.9%) episodes of active/relapsing GCA (clinical, laboratory or combined in 4 (5.2%), 48 (62.3%), 25 (32.5%) episodes, respectively). aCL IgG were present at 155/781 (19.8%) measurements (at 24/77 episodes of relapsing/active and 131/573 episodes of quiescent GCA). The correlation between active/relapsing GCA and aCL IgG positivity was only weekly positive (r coefficient=0.094; p= 0.015). Conclusion: The role of aCL IgG as a biomarker for GCA activity seems to be rather limited. References: [1]Božič B, et al. Int Arch Allerg Immunol. 1997; 112:19-26. doi.org/ 10.1159/000237426 Disclosure of Interests: None declared