Dose reduction is a feasible strategy in patients with plaque psoriasis who achieve sustained response with secukinumab: a retrospective, multicenter cohort study in daily practice setting.

BACKGROUND: Biological therapy dose modification is a common practice in the long-term treatment of plaque psoriasis. OBJECTIVE: The objective of the study was to determine prevalence, characteristics of patients, effectiveness, treatment survival of secukinumab dose reduction (SEC-DR) strategy and assess its safety and cost implications. METHODS: A retrospective, observational, multicenter cohort study was conducted in patients with plaque psoriasis treated with secukinumab and up to 2 years of follow-up. RESULTS: In 63/347 patients with an initial standard dose regimen, SEC-DR was tried at any moment in 18.2% of them after sustained response. In 51 patients, the interval between administrations was increased while in 12 patients, monthly dose was reduced to 150 mg. Successful SEC-DR was achieved in 77.8% of the patients, with sustained PASI response to the end of the study. Survival of secukinumab treatment and safety profile were not compromised by DR. The use of DR saved 33% of the cost, including failures in which standard treatment was resumed. LIMITATIONS: The proper of the study designed and the arbitrary definition of "DR success." CONCLUSION: Off-label SEC-DR strategy was used in patients with sustained response to standard dose regimen; this strategy showed long-term efficacy without compromising treatment survival or worsening the safety profile while also being cost saving.

Clearance of Neutrophils From ICH-Affected Brain by Macrophages Is Beneficial and Is Assisted by Lactoferrin and CD91.

BACKGROUND: Within hours after intracerebral hemorrhage (ICH) onset, masses of polymorphonuclear neutrophils (PMNs) infiltrate the ICH-affected brain. After degranulation involving controlled release of many toxic antimicrobial molecules, the PMNs undergo rapid apoptosis and then are removed by phagocytic microglia/macrophages (MΦ) through a process called efferocytosis. Effective removal of PMNs may limit secondary brain damage and inflammation; however, the molecular mechanisms governing these cleanup activities are not well understood. We propose that scavenger receptor CD91 on myeloid phagocytes especially in presence of CD91 ligand, LTF (lactoferrin, protein abundant in PMNs), plays an important role in clearance of dead apoptotic PMNs (ANs). METHODS: Mice/rats were subjected to an autologous blood injection model of ICH. Primary cultured microglia were used to assess phagocytosis of ANs. Immunohistochemistry was employed to assess CD91 expression and PMN infiltration. CD91 knockout mice selectively in myeloid phagocytes (Mac-CD91-KO) were used to establish the CD91/LTF function in phagocytosis and in reducing ICH-induced injury, as assessed using behavioral tests, hematoma resolution, and oxidative stress. RESULTS: Masses of PMNs are found in ICH-affected brain, and they contain LTF. MΦ at the outer border of hematoma are densely packed, expressing CD91 and phagocytosing ANs. Microglia deficient in CD91 demonstrate defective phagocytosis of ANs, and mice deficient in CD91 (Mac-CD91-KO) subjected to ICH injury have increased neurological dysfunction that is associated with impaired hematoma resolution (hemoglobin and iron clearance) and elevated oxidative stress. LTF that normally ameliorates ICH injury in CD91-proficient control mice shows reduced therapeutic effects in Mac-CD91-KO mice. CONCLUSIONS: Our study suggests that CD91 plays a beneficial role in improving ANs phagocytosis and ultimately post-ICH outcome and that the beneficial effect of LTF in ICH is in part dependent on presence of CD91 on MΦ.

Young Astrocytic Mitochondria Attenuate the Elevated Level of CCL11 in the Aged Mice, Contributing to Cognitive Function Improvement.

Aging drives cognitive decline, and mitochondrial dysfunction is a hallmark of age-induced neurodegeneration. Recently, we demonstrated that astrocytes secrete functional mitochondria (Mt), which help adjacent cells to resist damage and promote repair after neurological injuries. However, the relationship between age-dependent changes in astrocytic Mt function and cognitive decline remains poorly understood. Here, we established that aged astrocytes secret less functional Mt compared to young astrocytes. We found the aging factor C-C motif chemokine 11 (CCL11) is elevated in the hippocampus of aged mice, and that its level is reduced upon systemic administration of young Mt, in vivo. Aged mice receiving young Mt, but not aged Mt improved cognitive function and hippocampal integrity. Using a CCL11-induced aging-like model in vitro, we found that astrocytic Mt protect hippocampal neurons and enhance a regenerative environment through upregulating synaptogenesis-related gene expression and anti-oxidants that were suppressed by CCL11. Moreover, the inhibition of CCL11-specific receptor C-C chemokine receptor 3 (CCR3) boosted the expression of synaptogenesis-related genes in the cultured hippocampal neurons and restored the neurite outgrowth. This study suggests that young astrocytic Mt can preserve cognitive function in the CCL11-mediated aging brain by promoting neuronal survival and neuroplasticity in the hippocampus.

Black-box and surrogate optimization for tuning spiking neural models of striatum plasticity.

The basal ganglia (BG) is a brain structure that has long been proposed to play an essential role in action selection, and theoretical models of spiking neurons have tried to explain how the BG solves this problem. A recently proposed functional and biologically inspired network model of the striatum (an important nucleus of the BG) is based on spike-timing-dependent eligibility (STDE) and captured important experimental features of this nucleus. The model can recognize complex input patterns and consistently choose rewarded actions to respond to such sensory inputs. However, model tuning is challenging due to two main reasons. The first is the expert knowledge required, resulting in tedious and potentially biased trial-and-error procedures. The second is the computational cost of assessing model configurations (approximately 1.78 h per evaluation). This study addresses the model tuning problem through numerical optimization. Considering the cost of assessing solutions, the selected methods stand out due to their low requirements for solution evaluations and compatibility with high-performance computing. They are the SurrogateOpt solver of Matlab and the RBFOpt library, both based on radial basis function approximations, and DIRECT-GL, an enhanced version of the widespread black-box optimizer DIRECT. Besides, a parallel random search serves as a baseline reference of the outcome of opting for sophisticated methods. SurrogateOpt turns out to be the best option for tuning this kind of model. It outperforms, on average, the quality of the configuration found by an expert and works significantly faster and autonomously. RBFOpt and the random search share the second position, but their average results are below the option found by hand. Finally, DIRECT-GL follows this line becoming the worst-performing method.

Increased Expression of Interferon-Induced Transmembrane 3 (IFITM3) in Stroke and Other Inflammatory Conditions in the Brain.

Microglia, the resident innate immune cells of the brain, become more highly reactive with aging and diseased conditions. In collaboration with other cell types in brains, microglia can contribute both to worsened outcome following stroke or other neurodegenerative diseases and to the recovery process by changing their phenotype toward reparative microglia. Recently, IFITM3 (a member of the "interferon-inducible transmembrane" family) has been revealed as a molecular mediator between amyloid pathology and neuroinflammation. Expression of IFITM3 in glial cells, especially microglia following stroke, is not well described. Here, we present evidence that ischemic stroke causes an increase in IFITM3 expression along with increased microglial activation marker genes in aged brains. To further validate the induction of IFITM3 in post-stroke brains, primary microglia and microglial-like cells were exposed to a variety of inflammatory conditions, which significantly induced IFITM3 as well as other inflammatory markers. These findings suggest the critical role of IFITM3 in inducing inflammation. Our findings on the expression of IFITM3 in microglia and in aged brains following stroke could establish the basic foundations for the role of IFITM3 in a variety of neurodegenerative diseases, particularly those that are prevalent or enhanced in the aged brain.

Transplantation of astrocytic mitochondria modulates neuronal antioxidant defense and neuroplasticity and promotes functional recovery after intracerebral hemorrhage.

Astrocytes release functional mitochondria (Mt) that play regulatory and pro-survival functions upon entering adjacent cells. We recently demonstrated that these released Mt could enter microglia to promote their reparative/pro-phagocytic phenotype that assists in hematoma cleanup and neurological recovery after intracerebral hemorrhage (ICH). However, a relevance of astrocytic Mt transfer into neurons in protecting brain after ICH is unclear. Here, we found that ICH causes a robust increase in superoxide generation and elevated oxidative damage that coincides with loss of the mitochondrial enzyme manganese superoxide dismutase (Mn-SOD). The damaging effect of ICH was reversed by intravenous transplantation of astrocytic Mt that upon entering the brain (and neurons), restored Mn-SOD levels and reduced neurological deficits in male mice subjected to ICH. Using an in vitro ICH-like injury model in cultured neurons, we established that astrocytic Mt upon entering neurons prevented reactive oxygen species-induced oxidative stress and neuronal death by restoring neuronal Mn-SOD levels, while at the same time promoted neurite extension and upregulation of synaptogenesis-related gene expression. Furthermore, we found that Mt genome-encoded small peptide humanin (HN) that is normally abundant in Mt, could simulate Mt-transfer effect on neuronal Mn-SOD expression, oxidative stress, and neuroplasticity under ICH-like injury. This study demonstrates that adoptive astrocytic Mt transfer enhances neuronal Mn-SOD-mediated anti-oxidative defense and neuroplasticity in the brain, which potentiate functional recovery following ICH.SIGNIFICANCE STATEMENTMitochondrial dysfunction and antioxidant defense play essential role in brain damage after intracerebral hemorrhage (ICH). Astrocytes release functional mitochondria (Mt) that enter adjacent cells to help brain homeostatic function. Here, we show that systemic transplantation of astrocytic Mt restores ICH-impaired neuronal anti-oxidative defense, enhances neurite outgrowth, and improves stroke recovery after ICH. Our study suggests that systemic transplantation of astrocytic Mt could be considered as a novel and potentially promising strategy for ICH treatment.

On the Use of a Multimodal Optimizer for Fitting Neuron Models. Application to the Cerebellar Granule Cell.

This article extends a recent methodological workflow for creating realistic and computationally efficient neuron models whilst capturing essential aspects of single-neuron dynamics. We overcome the intrinsic limitations of the extant optimization methods by proposing an alternative optimization component based on multimodal algorithms. This approach can natively explore a diverse population of neuron model configurations. In contrast to methods that focus on a single global optimum, the multimodal method allows directly obtaining a set of promising solutions for a single but complex multi-feature objective function. The final sparse population of candidate solutions has to be analyzed and evaluated according to the biological plausibility and their objective to the target features by the expert. In order to illustrate the value of this approach, we base our proposal on the optimization of cerebellar granule cell (GrC) models that replicate the essential properties of the biological cell. Our results show the emerging variability of plausible sets of values that this type of neuron can adopt underlying complex spiking characteristics. Also, the set of selected cerebellar GrC models captured spiking dynamics closer to the reference model than the single model obtained with off-the-shelf parameter optimization algorithms used in our previous article. The method hereby proposed represents a valuable strategy for adjusting a varied population of realistic and simplified neuron models. It can be applied to other kinds of neuron models and biological contexts.

On Robot Compliance: A Cerebellar Control Approach.

The work presented here is a novel biological approach for the compliant control of a robotic arm in real time (RT). We integrate a spiking cerebellar network at the core of a feedback control loop performing torque-driven control. The spiking cerebellar controller provides torque commands allowing for accurate and coordinated arm movements. To compute these output motor commands, the spiking cerebellar controller receives the robot's sensorial signals, the robot's goal behavior, and an instructive signal. These input signals are translated into a set of evolving spiking patterns representing univocally a specific system state at every point of time. Spike-timing-dependent plasticity (STDP) is then supported, allowing for building adaptive control. The spiking cerebellar controller continuously adapts the torque commands provided to the robot from experience as STDP is deployed. Adaptive torque commands, in turn, help the spiking cerebellar controller to cope with built-in elastic elements within the robot's actuators mimicking human muscles (inherently elastic). We propose a natural integration of a bioinspired control scheme, based on the cerebellum, with a compliant robot. We prove that our compliant approach outperforms the accuracy of the default factory-installed position control in a set of tasks used for addressing cerebellar motor behavior: controlling six degrees of freedom (DoF) in smooth movements, fast ballistic movements, and unstructured scenario compliant movements.

European Registry on Helicobacter pylori management (Hp-EuReg): patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients.

OBJECTIVE: The best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care. DESIGN: International multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed. RESULTS: 30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%-90%). CONCLUSION: Management of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness.

How Variable Is the Volar Subcutaneous Tissue of the Digits on B-Mode and Color Doppler Ultrasound in Non-Psoriatic Individuals and Could It Be Included in a Dactylitis Score?

BACKGROUND: Digital subcutaneous tissue (SCT) changes are involved in dactylitis, a hallmark feature of psoriatic arthritis (PsA). There are no studies on the ultrasound (US) characteristics of the digital SCT in the general population. OBJECTIVES: To investigate the variability in US-measured thickness (TH) and color Doppler (CD)-detected blood flow of the SCT of the volar aspects of the fingers in a non-psoriatic population and to investigate the impact of the scanning method and demographics and clinical features on these measurements. METHODS: SCT TH and semiquantitative (SQD) and quantitative (QD) Doppler signals were measured in the bilateral second finger at the proximal and middle phalanges in 81 non-psoriatic volunteers [49 female, 32 men; 18-78 years]. Two scanning methods with and without (thick gel layer interposition) probe-skin contact were used. Demographics and clinical features were collected. RESULTS: There was high variability of SCT TH and Doppler measurements between individuals. All US measurements obtained without probe-skin contact were significantly greater than their corresponding measurements obtained with the probe contacting the skin (p < 0.001). SCT TH was positively related to dominant hand, age, masculine gender, weight, height, body mass index, and alcohol consumption while Doppler measurements were positively related to age and non-dominant hand. CONCLUSIONS: US-measured SCT thickness and Doppler-detected SCT blood flow of the volar aspect of the fingers seem to be highly variable in the non-psoriatic population as well as highly dependent on the US scanning method. This variability is of utmost importance for assessing dactylitis in PsA.

A Basal Ganglia Computational Model to Explain the Paradoxical Sensorial Improvement in the Presence of Huntington's Disease.

The basal ganglia (BG) represent a critical center of the nervous system for sensorial discrimination. Although it is known that Huntington's disease (HD) affects this brain area, it still remains unclear how HD patients achieve paradoxical improvement in sensorial discrimination tasks. This paper presents a computational model of the BG including the main nuclei and the typical firing properties of their neurons. The BG model has been embedded within an auditory signal detection task. We have emulated the effect that the altered levels of dopamine and the degree of HD affectation have in information processing at different layers of the BG, and how these aspects shape transient and steady states differently throughout the selection task. By extracting the independent components of the BG activity at different populations, it is evidenced that early and medium stages of HD affectation may enhance transient activity in the striatum and the substantia nigra pars reticulata. These results represent a possible explanation for the paradoxical improvement that HD patients present in discrimination task performance. Thus, this paper provides a novel understanding on how the fast dynamics of the BG network at different layers interact and enable transient states to emerge throughout the successive neuron populations.

Newmark displacement data for low to moderate magnitude events in the Betic Cordillera.

Land-use decisions in relation to seismic-induced landslide hazard are usually made through the preparation of hazard maps. The rigid-block method is probably the most used for this purpose. Under this method, Newmark displacement is computed for each slope unit and this displacement is used as a guide for establishing categories of hazard. At present, most relations used for computing Newmark displacement are established from moderate-to-high magnitude earthquakes (Mw ≥ 6.5). This data article provides Newmark displacements computed from accelerograms recorded in the Betic Cordillera for low-to-moderate magnitude earthquakes (Mw = 3.5-6.3). Records come from the Spanish Strong Ground Motion database (Instituto Geográfico Nacional). Newmark displacements were computed focusing on yield accelerations frequently recorded in such scenarios (0.02, 0.03, 0.04, 0.05, 0.06, 0.08 and 0.10), although higher accelerations were also considered (0.125, 0.15, 0.20, 0.25 and 0.30 g's). These data are useful for the study of the hazard in seismic scenarios of low-to-moderate magnitude, very frequent in practice. These data have been used in the study by Delgado et al. [1].

Optimization of Efficient Neuron Models With Realistic Firing Dynamics. The Case of the Cerebellar Granule Cell.

Biologically relevant large-scale computational models currently represent one of the main methods in neuroscience for studying information processing primitives of brain areas. However, biologically realistic neuron models tend to be computationally heavy and thus prevent these models from being part of brain-area models including thousands or even millions of neurons. The cerebellar input layer represents a canonical example of large scale networks. In particular, the cerebellar granule cells, the most numerous cells in the whole mammalian brain, have been proposed as playing a pivotal role in the creation of somato-sensorial information representations. Enhanced burst frequency (spiking resonance) in the granule cells has been proposed as facilitating the input signal transmission at the theta-frequency band (4-12 Hz), but the functional role of this cell feature in the operation of the granular layer remains largely unclear. This study aims to develop a methodological pipeline for creating neuron models that maintain biological realism and computational efficiency whilst capturing essential aspects of single-neuron processing. Therefore, we selected a light computational neuron model template (the adaptive-exponential integrate-and-fire model), whose parameters were progressively refined using an automatic parameter tuning with evolutionary algorithms (EAs). The resulting point-neuron models are suitable for reproducing the main firing properties of a realistic granule cell from electrophysiological measurements, including the spiking resonance at the theta-frequency band, repetitive firing according to a specified intensity-frequency (I-F) curve and delayed firing under current-pulse stimulation. Interestingly, the proposed model also reproduced some other emergent properties (namely, silent at rest, rheobase and negligible adaptation under depolarizing currents) even though these properties were not set in the EA as a target in the fitness function (FF), proving that these features are compatible even in computationally simple models. The proposed methodology represents a valuable tool for adjusting AdEx models according to a FF defined in the spiking regime and based on biological data. These models are appropriate for future research of the functional implication of bursting resonance at the theta band in large-scale granular layer network models.

Unbiased logic-tree data for earthquake-induced landslide hazard maps for low-to-moderate magnitude events.

Land-use planning in regard of earthquake-triggered landslides is usually implemented by means of the production of hazard maps. The well-known Newmark rigid block methodology is the most frequent used approach for this purpose. In this method, slope stability is evaluated by the estimation of the Newmark displacement, which is used to set different categories of hazard. This methodology presents limitations due to the difficulty of incorporating the variability of the used variables. For that reason, the logic-tree approach has been used in order to incorporate the epistemic uncertainties and compute probabilistic seismic-landslide hazard maps. However, the used weights in the logic-tree are usually set for each branch based on an expert judgement or subjective criteria. This article provide data obtained from the use of logic-tree methodology; this dataset is useful for deriving the unbiased weights to use in such methodology and in moderate-to-low magnitude scenarios. The data presented here are related to the article entitled "Obtaining suitable logic-tree weights for probabilistic earthquake-induced landslide hazard analyses" (Rodríguez-Peces et al., 2020) [1].

Assessment of Collateral Circulation Using Perfusion CT in Middle Cerebral Artery Thrombectomy-Treated Patients.

INTRODUCTION: The prognostic value of leptomeningeal collateral circulation in thrombectomy-treated patients remains unclear. We evaluated the construct validity of assessing leptomeningeal collateral circulation using a new regional perfusion CT source image-based approach, the Perfusion Acquisition for THrombectomy Scale (PATHS). We also compared the prognostic value of PATHS with a further 6 scales based on various techniques: CT-angiography, perfusion CT, and digital subtraction angiography. Additionally, we studied the relationship between the scores for the different scales. PATIENTS AND METHODS: We performed a retrospective study of consecutive patients with stroke and M1/terminal carotid occlusion treated with thrombectomy in our center. Leptomeningeal collateral circulation was prospectively evaluated using 7 scales: Tan and Miteff (CT Angiography); Calleja, Cao, American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology, and PATHS (perfusion); and Christoforidis (Digital Subtraction Angiography). Correlations were studied using the Spearman method. RESULTS: The study population comprised 108 patients. All scales predicted the modified Rankin Scale at 3 months (P ≤ .02) and all but 1 (Christoforidis) correlated with 24-hour brain infarct volume (P ≤ .02). These correlations were higher with PATHS (rho = -0.47, P < .001 for 3-month modified Rankin Scale; rho = -0.35, P < .001 for follow-up infarct volume). The multivariate analysis showed PATHS to be an independent predictor of modified Rankin Scale at 3 months less than equal to 2. A crosscorrelation analysis revealed a better correlation between scales that used the same techniques. CONCLUSIONS: PATHS can be used to assess leptomeningeal collateral circulation. PATHS had better prognostic value than other scales; therefore, it might be considered for assessment of leptomeningeal collateral circulation in candidates for thrombectomy. The moderate correlation between scales suggests that scores are not interchangeable.

The Mitochondria-Derived Peptide Humanin Improves Recovery from Intracerebral Hemorrhage: Implication of Mitochondria Transfer and Microglia Phenotype Change.

Astrocytes are an integral component of the neurovascular unit where they act as homeostatic regulators, especially after brain injuries, such as stroke. One process by which astrocytes modulate homeostasis is the release of functional mitochondria (Mt) that are taken up by other cells to improve their function. However, the mechanisms underlying the beneficial effect of Mt transfer are unclear and likely multifactorial. Using a cell culture system, we established that astrocytes release both intact Mt and humanin (HN), a small bioactive peptide normally transcribed from the Mt genome. Further experiments revealed that astrocyte-secreted Mt enter microglia, where they induce HN expression. Similar to the effect of HN alone, incorporation of Mt by microglia (1) upregulated expression of the transcription factor peroxisome proliferator-activated receptor gamma and its target genes (including mitochondrial superoxide dismutase), (2) enhanced phagocytic activity toward red blood cells (an in vitro model of hematoma clearance after intracerebral hemorrhage [ICH]), and (3) reduced proinflammatory responses. ICH induction in male mice caused profound HN loss in the affected hemisphere. Intravenously administered HN penetrated perihematoma brain tissue, reduced neurological deficits, and improved hematoma clearance, a function that normally requires microglia/macrophages. This study suggests that astrocytic Mt-derived HN could act as a beneficial secretory factor, including when transported within Mt to microglia, where it promotes a phagocytic/reparative phenotype. These findings also indicate that restoring HN levels in the injured brain could represent a translational target for ICH. These favorable biological responses to HN warrant studies on HN as therapeutic target for ICH.SIGNIFICANCE STATEMENT Astrocytes are critical for maintaining brain homeostasis. Here, we demonstrate that astrocytes secrete mitochondria (Mt) and the Mt-genome-encoded, small bioactive peptide humanin (HN). Mt incorporate into microglia, and both Mt and HN promote a "reparative" microglia phenotype characterized by enhanced phagocytosis and reduced proinflammatory responses. Treatment with HN improved outcomes in an animal model of intracerebral hemorrhage, suggesting that this process could have biological relevance to stroke pathogenesis.

Ultrasound salivary gland involvement in Sjogren's syndrome vs. other connective tissue diseases: is it autoantibody and gland dependent?

This study aims to investigate ultrasound (US) findings on salivary glands (SG) in patients with Sjögren syndrome (SS) vs. other connective tissue diseases (CTDs) and to assess the relationship of SGUS abnormalities with autoantibody profile in both groups. We enrolled 81 patients, 45 diagnosed with SS (39 with primary SS, 6 with secondary SS) and 36 diagnosed with other CTDs. All patients underwent a prospective evaluation of sicca symptoms, a Schirmer's test, and a B-mode US assessment of the parotid and submandibular glands, all blinded to the diagnosis. Each SG was semi-quantitatively scored 0-3; a grade ≥ 2 was considered pathological. SGUS involvement was classified as normal or pathological at the patient level and for each pair at the gland level. In addition, a total SGUS score of 0-12 and a parotid/submandibular score of 0-6 were calculated for each patient. Autoimmunity laboratory data were also obtained. All SGUS scores were higher in SS patients than in those with CTD (p < 0.001) and significantly more SS patients showed a pathological global (p < 0.001), parotid (p < 0.001), or submandibular (p = 0.001) US score compared with CTD patients. In SS patients, the presence of autoantibodies was significantly associated with pathological SGUS and higher scores, particularly at the parotid level, while in CTD patients, xerostomia and a pathological Schirmer's test were associated with pathological US and higher scores at the submandibular level (p < 0.05). SGUS showed a different grade of abnormality, site involvement, and associated autoantibody profile in SS patients as compared with other CTD. KEY POINTS: • Patients with SS and other CTDs showed different grades of SGUS abnormality. • Patients with SS and other CTDs showed different gland involvement and associated autoantibody profiles. • Anti-Ro60 and anti-Ro52 Ro60 positivity were associated with the severity of parotid involvement in SS patients.

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Can ultrasound-detected subclinical synovitis be an indicator of flare recurrence in juvenile idiopathic arthritis remission patients on tapered TNFi?

OBJECTIVES: Subclinical synovitis is often detected by musculoskeletal ultrasound (MSUS) in juvenile idiopathic arthritis (JIA) patients in clinical remission. The main objective of this prospective, observational, longitudinal, multicentre study was to evaluate the predictive value of MSUS-detected subclinical synovitis in relation to flares at 12 months following TNFi tapering in a JIA population in stable clinical remission. METHODS: We included 56 JIA patients in stable remission undergoing TNFi therapy tapered at baseline and in some cases at 6 months. We performed baseline and 6-month MSUS assessment on B-mode (BM) and power Doppler (PD) mode of 22 joints and 8 tendons. RESULTS: Eighteen patients (32.1%) experienced a flare during the 12-month study period. BM synovitis was frequent (83.9%) but PD synovitis was scarcely found (8.9%). There were no significant differences in MSUS findings between patients who experienced a flare and those who remained in remission. Only 5 patients had positive for PD synovitis, in joints with BM synovitis grades 2 or 3, and none experienced a flare. Concomitant methotrexate (MTX) was more frequent in patients who were successfully tapered (71.1% vs. 27.8%; p=0.002) and patients older than 12 experienced a greater number of flares and earlier onset. CONCLUSIONS: Subclinical synovitis, as detected by MSUS, proved not to be a predictor of flares. Those patients on a TNFi-tapered concomitant methotrexate regimen experienced the fewest flares although flare risk increased with age.