Early vocational rehabilitation and psychological support for trauma patients to improve return to work (the ROWTATE trial): study protocol for an individually randomised controlled multicentre pragmatic trial.

BACKGROUND: Moderately severe or major trauma (injury severity score (ISS) > 8) is common, often resulting in physical and psychological problems and leading to difficulties in returning to work. Vocational rehabilitation (VR) can improve return to work/education in some injuries (e.g. traumatic brain and spinal cord injury), but evidence is lacking for other moderately severe or major trauma. METHODS: ROWTATE is an individually randomised controlled multicentre pragmatic trial of early VR and psychological support in trauma patients. It includes an internal pilot, economic evaluation, a process evaluation and an implementation study. Participants will be screened for eligibility and recruited within 12 weeks of admission to eight major trauma centres in England. A total of 722 participants with ISS > 8 will be randomised 1:1 to VR and psychological support (where needed, following psychological screening) plus usual care or to usual care alone. The ROWTATE VR intervention will be provided within 2 weeks of study recruitment by occupational therapists and where needed, by clinical psychologists. It will be individually tailored and provided for ≤ 12 months, dependent on participant need. Baseline assessment will collect data on demographics, injury details, work/education status, cognitive impairment, anxiety, depression, post-traumatic distress, disability, recovery expectations, financial stress and health-related quality of life. Participants will be followed up by postal/telephone/online questionnaires at 3, 6 and 12 months post-randomisation. The primary objective is to establish whether the ROWTATE VR intervention plus usual care is more effective than usual care alone for improving participants' self-reported return to work/education for at least 80% of pre-injury hours at 12 months post-randomisation. Secondary outcomes include other work outcomes (e.g. hours of work/education, time to return to work/education, sickness absence), depression, anxiety, post-traumatic distress, work self-efficacy, financial stress, purpose in life, health-related quality of life and healthcare/personal resource use. The process evaluation and implementation study will be described elsewhere. DISCUSSION: This trial will provide robust evidence regarding a VR intervention for a major trauma population. Evidence of a clinically and cost-effective VR intervention will be important for commissioners and providers to enable adoption of VR services for this large and important group of patients within the NHS. TRIAL REGISTRATION: ISRCTN: 43115471. Registered 27/07/2021.

Mast cell-derived interleukin-4 mediates activation of dendritic cell during toll-like receptor 2-mediated inflammation.

Introduction: During an innate inflammation, immune cells form distinct pro- and anti-inflammatory regions around pathogen-containing core-regions. Mast cells are localized in an anti-inflammatory microenvironment during the resolution of an innate inflammation, suggesting antiinflammatory roles of these cells. Methods: High-content imaging was used to investigated mast cell-dependent changes in the regional distribution of immune cells during an inflammation, induced by the toll-like receptor (TLR)-2 agonist zymosan. Results: The distance between the zymosan-containing core-region and the anti-inflammatory region, described by M2-like macrophages, increased in mast cell-deficient mice. Absence of mast cells abolished dendritic cell (DC) activation, as determined by CD86-expression and localized the DCs in greater distance to zymosan particles. The CD86- DCs had a higher expression of the pro-inflammatory interleukins (IL)-1ß and IL-12/23p40 as compared to activated CD86+ DCs. IL-4 administration restored CD86 expression, cytokine expression profile and localization of the DCs in mast cell-deficient mice. The IL-4 effects were mast cell-specific, since IL-4 reduction by eosinophil depletion did not affect activation of DCs. Discussion: We found that mast cells induce DC activation selectively at the site of inflammation and thereby determine their localization within the inflammation. Overall, mast cells have antiinflammatory functions in this inflammation model and limit the size of the pro-inflammatory region surrounding the zymosan-containing core region.

Molecular Analysis of Peri-implant Soft Tissue Response to Different Abutment Materials in Humans. A Pilot Study.

PURPOSE: To evaluate the response of human peri-implant soft tissue (PIST) on different healing abutment materials 24 hours after positioning, by assessing the expression of genes related to the early connective tissue wound healing response. MATERIALS AND METHODS: Experimental abutments of 4 different materials (A): grade 4 titanium, (B) grade 5 titanium, (C) zirconia and (D) PEEK, were mounted on installed implants in 5 patients, four different abutments each. Before implant placement, a gingival biopsy (control-CT) was obtained using a 2 mm diameter punch (T0). After 24 hours (T24), PIST biopsies were collected using a specifically designed custom-made cutting device. Real-time PCR was performed to analyze the expression of the following genes: COL-I, COL-III, MMP-1, TIMP-1,TGF-b1, FN, ITGA4, ITGA5, ITGB1, RAC-1, COL-IV, aSMA, IL-6 and CXCL-1. RESULTS: Gene expression analysis showed some differences between CT and abutment of different materials, although no significant differences were detected comparing the experimental groups. COL-I was significantly down-regulated in groups A and C compared to CT. MMP-1 and TIMP-1 increased in all the experimental groups, although at a lower extent in group A. FN, RAC-1, COL-IV and aSMA were down-regulated, especially in group A, in which CXCL-1 and IL-6 showed the lowest expression. CONCLUSIONS: The results of grade 4 titanium and zirconia abutments seem to be promising, since a lower expression of genes related with inflammation, myofibroblasts activation and ECM remodeling was observed when compared with grade 5 titanium and PEEK, without triggering a pro-fibrotic response in the early phases of PIST repair.

Dairy Matrix Effects: Physicochemical Properties Underlying a Multifaceted Paradigm.

When food products are often considered only as a source of individual nutrients or a collection of nutrients, this overlooks the importance of interactions between nutrients, but also interactions between nutrients and other constituents of food, i.e., the product matrix. This product matrix, which can be defined as 'The components of the product, their interactions, their structural organization within the product and the resultant physicochemical properties of the product', plays a critical role in determining important product properties, such as product stability, sensory properties and nutritional and health outcomes. Such matrix effects can be defined as 'the functional outcome of specific component(s) as part of a specific product matrix'. In this article, dairy matrix effects are reviewed, with particular emphasis on the nutrition and health impact of dairy products. Such matrix effects are critical in explaining many effects of milk and dairy products on human nutrition and health that cannot be explained solely based on nutrient composition. Examples hereof include the low glycemic responses of milk and dairy products, the positive impact on dental health, the controlled amino acid absorption and the absence of CVD risk despite the presence of saturated fatty acids. Particularly, the changes occurring in the stomach, including, e.g., coagulation of casein micelles and creaming of aggregated fat globules, play a critical role in determining the kinetics of nutrient release and absorption.

Aplastic Anaemia in Pregnancy: A Case-Based Comprehensive Review of the Literature.

Aplastic anaemia (AA) is a rare and life-threatening haematologic disorder characterised by pancytopenia and bone marrow failure. Its occurrence during pregnancy is exceedingly rare, posing significant risks and management challenges for both the mother and the foetus. We present here the case of a 23-year-old female, six months pregnant, diagnosed with severe aplastic anaemia (AA), aiming to highlight the diagnostic challenges and management considerations of AA in pregnancy. Our case underscores the critical nature of considering aplastic anaemia in differential diagnosis for pregnant patients presenting with unexplained pancytopenia. Based on that, we performed a comprehensive literature review of the past 20 years of papers published in the English language identified through searches in PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase and the Cochrane Library, to provide an in-depth analysis of the current understanding of AA in pregnancy. We emphasise the necessity for cautious yet thorough investigation in such cases to avoid complications in both maternal and foetal health, focusing attention on the need for further research into safe and effective treatment protocols for managing AA in pregnancy, given the complexities introduced by the condition and its treatment on pregnancy outcomes.

Clonal Relapse Dynamics in Acute Myeloid Leukemia Following Allogeneic Hematopoietic Cell Transplantation.

Patients with acute myeloid leukemia (AML) who experience relapse following allogeneic hematopoietic cell transplantation (alloHCT) face unfavorable outcomes regardless of the chosen relapse treatment. Early detection of relapse at the molecular level by measurable residual disease (MRD) assessment enables timely intervention, which may prevent hematological recurrence of the disease. It remains unclear whether molecular MRD assessment can detect MRD before impending relapse and, if so, how long in advance. This study elucidates the molecular architecture and kinetics preceding AML relapse by utilizing error-corrected next-generation sequencing (NGS) in 74 AML patients relapsing after alloHCT evaluating 140 samples from peripheral blood collected 0.6 to 14 months before relapse. At least one MRD marker became detectable in 10%, 38%, and 64% of patients at 6, 3, and 1 months prior to relapse, respectively. By translating these proportions into monitoring intervals, 38% of relapses would have been detected through MRD monitoring every 3 months, while 64% of relapses would have been detected with monthly intervals. The relapse kinetics after alloHCT are influenced by the functional class of mutations and their stability during molecular progression. Notably, mutations in epigenetic modifier genes exhibited a higher prevalence of MRD positivity and greater stability before relapse, while mutations in signaling genes demonstrated a shorter lead-time to relapse. Both DTA and non-DTA mutations displayed similar relapse kinetics during the follow-up period after alloHCT. Our study sets a framework for MRD monitoring after alloHCT by NGS supporting monthly monitoring from peripheral blood using all variants that are known from diagnosis.

Sarcopenia in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

(1) Background: We estimated the prevalence and clinical outcomes of sarcopenia among breast cancer patients. (2) Methods: A systematic literature search was carried out for the period between July 2023 and October 2023. Studies with breast cancer patients evaluated for sarcopenia in relation to overall survival (OS), progression-free survival (PFS), relapse of disease (DFS), pathological complete response (pCR), or toxicity to chemotherapy were included. (3) Results: Out of 359 screened studies, 16 were eligible for meta-analysis, including 6130 patients, of whom 5284 with non-MBC. Sarcopenia was evaluated with the computed tomography (CT) scan skeletal muscle index and, in two studies, with the dual-energy x-ray absorptiometry (DEXA) appendicular lean mass index. Using different classifications and cut-off points, overall, there were 2007 sarcopenic patients (33%), of whom 1901 (95%) presented with non-MBC. Sarcopenia was associated with a 33% and 29% higher risk of mortality and progression/relapse of disease, respectively. Sarcopenic patients were more likely to develop grade 3-4 toxicity (OR 3.58, 95% CI 2.11-6.06, p < 0.0001). In the neoadjuvant setting, a higher rate of pCR was observed among sarcopenic patients (49%) (OR 2.74, 95% CI 0.92-8.22). (4) Conclusions: Our meta-analysis confirms the correlation between sarcopenia and negative outcomes, especially in terms of higher toxicity.

Widening the Prostacyclin Paradigm: Tissue Fibroblasts Are a Critical Site of Production and Antithrombotic Protection.

BACKGROUND: Prostacyclin is a fundamental signaling pathway traditionally associated with the cardiovascular system and protection against thrombosis but which also has regulatory functions in fibrosis, proliferation, and immunity. Prevailing dogma states that prostacyclin is principally derived from vascular endothelium, although it is known that other cells can also synthesize it. However, the role of nonendothelial sources in prostacyclin production has not been systematically evaluated resulting in an underappreciation of their importance relative to better characterized endothelial sources. METHODS: To address this, we have used novel endothelial cell-specific and fibroblast-specific COX (cyclo-oxygenase) and prostacyclin synthase knockout mice and cells freshly isolated from mouse and human lung tissue. We have assessed prostacyclin release by immunoassay and thrombosis in vivo using an FeCl3-induced carotid artery injury model. RESULTS: We found that in arteries, endothelial cells are the main source of prostacyclin but that in the lung, and other tissues, prostacyclin production occurs largely independently of endothelial and vascular smooth muscle cells. Instead, in mouse and human lung, prostacyclin production was strongly associated with fibroblasts. By comparison, microvascular endothelial cells from the lung showed weak prostacyclin synthetic capacity compared with those isolated from large arteries. Prostacyclin derived from fibroblasts and other nonendothelial sources was seen to contribute to antithrombotic protection. CONCLUSIONS: These observations define a new paradigm in prostacyclin biology in which fibroblast/nonendothelial-derived prostacyclin works in parallel with endothelium-derived prostanoids to control thrombotic risk and potentially a broad range of other biology. Although generation of prostacyclin by fibroblasts has been shown previously, the scale and systemic activity was unappreciated. As such, this represents a basic change in our understanding and may provide new insight into how diseases of the lung result in cardiovascular risk.

Sweat gland development requires an eccrine dermal niche and couples two epidermal programs.

Eccrine sweat glands are indispensable for human thermoregulation and, similar to other mammalian skin appendages, form from multipotent epidermal progenitors. Limited understanding of how epidermal progenitors specialize to form these vital organs has precluded therapeutic efforts toward their regeneration. Herein, we applied single-nucleus transcriptomics to compare the expression content of wild-type, eccrine-forming mouse skin to that of mice harboring a skin-specific disruption of Engrailed 1 (En1), a transcription factor that promotes eccrine gland formation in humans and mice. We identify two concurrent but disproportionate epidermal transcriptomes in the early eccrine anlagen: one that is shared with hair follicles and one that is En1 dependent and eccrine specific. We demonstrate that eccrine development requires the induction of a dermal niche proximal to each developing gland in humans and mice. Our study defines the signatures of eccrine identity and uncovers the eccrine dermal niche, setting the stage for targeted regeneration and comprehensive skin repair.

Describing the readiness for interprofessional education among university students attending healthcare programs: insights from a monocentric cross-sectional study.

BACKGROUND AND AIM: Readiness for interprofessional education (IPE) was recognized by international authorities as a key approach for educating students attending healthcare programs. Thus far, there are no descriptions of readiness for IPE in the Albanian context. For this reason, this study aimed to describe readiness for IPE, assessed by measuring "teamwork and collaboration" and "positive professional identity, roles, and responsibilities" among students attending healthcare programs in an Italian-speaking university based in Albania, and describe the correlations between readiness for IPE and the characteristics of the respondents. METHODS: This study had a descriptive observational design, a cross-sectional data collection, and a convenience sampling procedure performed in a single centre. The study was accomplished between April 2020 and June 2021, involving 688 students, 38.2% of the entire population of students attending healthcare programs in the context of the investigation. RESULTS: The teamwork and collaboration mean score was 4.40 (standard deviation = 0.56), and no differences were found between programs (p-value=0.159). The positive professional identity, roles, and responsibilities mean score was 4.33 (standard deviation = 0.64) with no differences between programs (p-value=0.340). Females attending nursing or midwifery reported higher positive professional identity, roles, and responsibilities scores (p-value=0.020), and females in dentistry reported higher teamwork and collaboration scores than males (p-value=0.045). CONCLUSIONS: Future research should evaluate readiness for IPE longitudinally to ascertain its trajectories over time and analyze any potential individual- or organizational-level variables that may impact IPE and sex-related differences regarding factors influencing IPE.

Early mortality in German patients with lung cancer: risk factors associated with 30-and 60-day mortality.

Despite therapeutic advances, early mortality in lung cancer is still prevalent. In this study, we aimed to assess risk factors for 30- and 60-day mortality in German lung cancer patients. In this retrospective cross-sectional analysis, we used data of lung cancer patients treated at LMU Hospital Munich between 2015 and 2019. We categorized patients into 30-day mortality, 60 day-mortality, and longer survival. We used Student's t-test and ANOVA to compare means and Chi2-test to compare frequencies. We used logistic regression analysis to identify factors associated with a risk for early mortality. Of the 2454 lung cancer patients, 2.0% (n = 50) died within 30 and 1.7% (n = 41) within 30 to 60 days of diagnosis. Older age and advanced stage at diagnosis were significantly associated with early mortality in the univariate and the multivariate analysis. Patients in the 30-day mortality group significantly more often did not receive tumor-directed therapy. They were also more likely to die in an acute care setting compared to the 60-day mortality group. The group of patients who died unexpectedly (12.0%) was dominantly female, with a high proportion of patients with unintentional weight loss at the time of diagnosis. Our results suggest that in the treatment of patients with lung cancer there is a need for a greater focus on older patients. Moreover, physicians should pay special attention to females with recent weight loss and patients with a comorbidity of diabetes mellitus or renal impairment. Engaging a case manager focused on detecting patients with the above characteristics could help improve overall care.

Cophylogeny Reconstruction Allowing for Multiple Associations Through Approximate Bayesian Computation.

Phylogenetic tree reconciliation is extensively employed for the examination of coevolution between host and symbiont species. An important concern is the requirement for dependable cost values when selecting event-based parsimonious reconciliation. Although certain approaches deduce event probabilities unique to each pair of host and symbiont trees, which can subsequently be converted into cost values, a significant limitation lies in their inability to model the invasion of diverse host species by the same symbiont species (termed as a spread event), which is believed to occur in symbiotic relationships. Invasions lead to the observation of multiple associations between symbionts and their hosts (indicating that a symbiont is no longer exclusive to a single host), which are incompatible with the existing methods of coevolution. Here, we present a method called AmoCoala (an enhanced version of the tool Coala) that provides a more realistic estimation of cophylogeny event probabilities for a given pair of host and symbiont trees, even in the presence of spread events. We expand the classical 4-event coevolutionary model to include 2 additional outcomes, vertical and horizontal spreads, that lead to multiple associations. In the initial step, we estimate the probabilities of spread events using heuristic frequencies. Subsequently, in the second step, we employ an approximate Bayesian computation approach to infer the probabilities of the remaining 4 classical events (cospeciation, duplication, host switch, and loss) based on these values. By incorporating spread events, our reconciliation model enables a more accurate consideration of multiple associations. This improvement enhances the precision of estimated cost sets, paving the way to a more reliable reconciliation of host and symbiont trees. To validate our method, we conducted experiments on synthetic datasets and demonstrated its efficacy using real-world examples. Our results showcase that AmoCoala produces biologically plausible reconciliation scenarios, further emphasizing its effectiveness.

STARGATE-X: a Python package for statistical analysis on the REACTOME network.

Many important aspects of biological knowledge at the molecular level can be represented by pathways. Through their analysis, we gain mechanistic insights and interpret lists of interesting genes from experiments (usually omics and functional genomic experiments). As a result, pathways play a central role in the development of bioinformatics methods and tools for computing predictions from known molecular-level mechanisms. Qualitative as well as quantitative knowledge about pathways can be effectively represented through biochemical networks linking the biochemical reactions and the compounds (e.g., proteins) occurring in the considered pathways. So, repositories providing biochemical networks for known pathways play a central role in bioinformatics and in systems biology. Here we focus on Reactome, a free, comprehensive, and widely used repository for biochemical networks and pathways. In this paper, we: (1) introduce a tool StARGate-X (STatistical Analysis of the Reactome multi-GrAph Through nEtworkX) to carry out an automated analysis of the connectivity properties of Reactome biochemical reaction network and of its biological hierarchy (i.e., cell compartments, namely, the closed parts within the cytosol, usually surrounded by a membrane); the code is freely available at https://github.com/marinoandrea/stargate-x; (2) show the effectiveness of our tool by providing an analysis of the Reactome network, in terms of centrality measures, with respect to in- and out-degree. As an example of usage of StARGate-X, we provide a detailed automated analysis of the Reactome network, in terms of centrality measures. We focus both on the subgraphs induced by single compartments and on the graph whose nodes are the strongly connected components. To the best of our knowledge, this is the first freely available tool that enables automatic analysis of the large biochemical network within Reactome through easy-to-use APIs (Application Programming Interfaces).

Translation, validation and psychometric properties of the Albanian version of the Nurses Professional Competence Scale Short form.

BACKGROUND AND AIM: The primary aim of this study was the translation and psychometric validation of the Albanian Nurse Professional Competence Scale Short Form (A-NPCS-SF) for further application in Albanian healthcare settings. METHODS: The multiphase design used to develop the A-NPCS-SF comprised (1) cultural and linguistic validation, (2) content and face validity, and (3) construct validity. RESULTS: The A-NPCS-SF showed adequate content validity. Confirmatory factor analysis supported the six-factor structure of the A-NPCS-SF to explain the data obtained from the nurses. CONCLUSIONS: The A-NPCS-SF showed evidence of validity and reliability in measuring four professional competencies. Having an appropriate scale in Albanian for professional competence self-assessment by nurses constitutes an essential step in measuring these competencies.  (www.actabiomedica.it).

Pretreated EGFRdel19/BRAFV600E Lung Adenocarcinoma With Leptomeningeal Disease Achieving Long-Lasting Disease Control on Osimertinib, Dabrafenib, and Trametinib: A Case Report.

Oncogene-addicted NSCLC inevitably becomes resistant to targeted therapy by developing acquired resistance through on- or off-target mechanisms, potentially detectable by liquid biopsy. We present the first reported case of a patient with pretreated EGFRdel19/BRAFV600E lung adenocarcinoma and symptomatic leptomeningeal metastasis obtaining durable clinical benefit on osimertinib, dabrafenib, and trametinib treatment.

ADPGK-AS1 long noncoding RNA switches macrophage metabolic and phenotypic state to promote lung cancer growth.

Long noncoding RNAs (lncRNAs) influence the transcription of gene networks in many cell types, but their role in tumor-associated macrophages (TAMs) is still largely unknown. We found that the lncRNA ADPGK-AS1 was substantially upregulated in artificially induced M2-like human macrophages, macrophages exposed to lung cancer cells in vitro, and TAMs from human lung cancer tissue. ADPGK-AS1 is partly located within mitochondria and binds to the mitochondrial ribosomal protein MRPL35. Overexpression of ADPGK-AS1 in macrophages upregulates the tricarboxylic acid cycle and promotes mitochondrial fission, suggesting a phenotypic switch toward an M2-like, tumor-promoting cytokine release profile. Macrophage-specific knockdown of ADPGK-AS1 induces a metabolic and phenotypic switch (as judged by cytokine profile and production of reactive oxygen species) to a pro-inflammatory tumor-suppressive M1-like state, inhibiting lung tumor growth in vitro in tumor cell-macrophage cocultures, ex vivo in human tumor precision-cut lung slices, and in vivo in mice. Silencing ADPGK-AS1 in TAMs may thus offer a novel therapeutic strategy for lung cancer.

An Observational Cross-Sectional Study on the Correlation between Professional Competencies and Self-Efficacy in Albanian Registered Nurses.

(1) Background: The assessment and application of registered nurses' professional skills are essential to providing quality and safe care. Self-efficacy can positively affect the professional competence of registered nurses. This study analysed professional competence and its association with self-efficacy among registered nurses. (2) Methods: A cross-sectional observational study was conducted. The sampling was conventional. The data collection took place through the Albanian version of the Nurse Professional Competence Scale Short Form (A-NPCS-SF), which was used to assess their professional skills, and the Albanian version of the Nursing Profession Self-Efficacy Scale (A-NPSES), which was used to assess their self-efficacy. The study was based on a convenience sample of 985 registered nurses from the 12 Albanian provinces. (3) Results: The Cronbach alpha value for the A-NPCS-SF scale was 0.947, while for the A-NPSES scale, it was 0.875, proving both scales to be reliable. Self-efficacy does not play an essential role in the development of the professional competence of registered nurses since our survey found only one dimension correlates with these two elements. (4) Conclusions: The results of our analysis have instead highlighted the importance of a close relationship between job satisfaction and the development of professional skills.

Synovial and serum B-cell signature of autoantibody-negative rheumatoid arthritis versus autoantibody-positive rheumatoid arthritis and psoriatic arthritis.

OBJECTIVES: Autoantibody-negative rheumatoid arthritis (RA) differs from autoantibody-positive RA in several clinical aspects, possibly underpinned by pathogenetic differences. At present, the role of adaptive immune responses in autoantibody-negative RA remains unclear. Here, we investigated the synovial and serum immunophenotype indicative of B-lymphocyte involvement across the spectrum of autoantibody-positive and -negative chronic arthritides. METHODS: Ultrasound-guided synovial biopsies were retrieved from 131 patients: 43 autoantibody-positive RA, 35 autoantibody-negative RA, 25 polyarticular psoriatic arthritis (PsA), 28 oligoarticular PsA. Samples were analysed for the degree of histological inflammation, B-lymphocyte infiltration and the distribution of different pathotypes (lympho-myeloid, myeloid, pauci-immune). Serum levels of the B-cell chemoattractant CXCL13 were compared among groups. RESULTS: Synovitis scores and CD68+ sublining macrophage infiltration were comparable irrespective of clinical diagnosis and disease subtype. In contrast, the degree of B-lymphocyte infiltration and the frequency of lympho-myeloid synovitis in autoantibody-negative RA were lower than those of autoantibody-positive RA (mean [SD] 1.8 [1] vs 2.4 [0.6], p = 0.03 and 38.2% vs 62.9%, p = 0.07, respectively), and similar to polyarticular PsA. Oligoarticular PsA had the lowest B-cell scores. Serum CXCL13 was associated with lympho-myeloid synovitis and followed a similar gradient, with the highest levels in autoantibody-positive RA, intermediate and comparable levels in autoantibody-negative RA and polyarticular PsA, and low levels in oligoarticular PsA. CONCLUSIONS: The synovial and serum immunophenotype indicative of B-lymphocyte involvement in autoantibody-negative RA differs from autoantibody-positive RA and more closely resembles that observed in polyarticular PsA. The pathobiological stratification of chronic inflammatory arthritides beyond clinical diagnosis may fuel personalised treatment strategies.