tbuckley/cabot-search huggingface dataset:
AB0137 INVOLVEMENT OF SYNOVIAL INFLAMMATION AND NEUROPATHIC PAIN IN ARTHRALGIA OF RHEUMATIC DISEASES, ASSESSED BY ULTRASOUND AND PAIN DETECT
Authors: M. Harada, M. Ogasawara, S. Nojiri, Y. Mastuki-Muramoto, T. Kawamoto, K. Yamaji, N. Tamura
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> A typical common symptom of rheumatic diseases is arthralgia, a factor that reduces quality of life and the leading unresolved PRO of rheumatic diseases. The main causes of arthralgia are inflammatory pain due to synovial inflammation and non-inflammatory pain due to neuropathic pain (NeP), and elucidating the causes of arthralgia in rheumatic diseases is an important issue for improving PROs. <h3>Objectives:</h3> To investigate the involvement of synovial inflammation and NeP in arthralgia, which rheumatologists have difficulty determining. <h3>Methods:</h3> This study enrolled 195 patients with rheumatic diseases who had arthralgia that was difficult for their physicians to determine. Systematic ultrasound examination was used to assess synovial inflammation, and the Pain DETECT Questionnaire (PDQ) was used to further assess non-inflammatory pain, NeP. Multivariate logistic analysis was used to determine contributing factors to arthralgia. Spearman's rank correlation coefficient, single regression, and receiver operating characteristic (ROC) curve analysis were performed to examine associations among arthralgia, synovial inflammation, and NeP. <h3>Results:</h3> We studied 187 patients including 70 RA, 8 PMR, 8 SjS, 5 PsA, 4 MCTD, 3 SLE, 2 RS3PE, 2 UC, 1 FMF, 1 dermatomyositis, 1 gout, 1 APS, 1 GCA, 80 patients with undetermined arthritis and 8 patients excluded from this study due to NeP with carpal tunnel syndrome, spinal canal stenosis or cervical disc hernia. In both overall and RA patients, numerical rating scale (NRS) was significantly associated with NeP (p&lt;0.001), while synovial inflammation showed no association with NRS and NeP. In the analysis grouped by the intensity of synovial inflammation, patients with moderate to severe synovial inflammation (Mod/High group) had significantly more burning pain in pain quality of PDQ than those with no or mild synovial inflammation (Non/Low group). Only in the Non/Low group of RA, NRS was not associated with NeP. <h3>Conclusion:</h3> Unexplained arthralgia in rheumatic diseases is predominantly noninflammatory pain similar to NeP. Synovial inflammation in RA may cause burning pain, which may alter pain quality and affect the value of PDQ score and thus require careful interpretation when used PDQ in RA. <h3>REFERENCES:</h3> [1] Rutter-Locher, Zoe et al. "A systematic review and meta-analysis of questionnaires to screen for pain sensitisation and neuropathic like pain in inflammatory arthritis." <i>Seminars in arthritis and rheumatism</i> vol. 61 (2023): 152207. doi:10.1016/j.semarthrit.2023.152207. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB0151 COMPARISON OF LIPID PEROXIDATION INDICES IN FIBROMYALGIA AND MYOFASCIAL SYNDROME
Authors: D. Cepoi
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Numerous authors reported oxidative stress data in fibromyalgia (FM), however oxidative stress seems to be associated with other persistent pain syndromes as well. In our study we made an attempt to compare various lipid peroxidation indices in FM and myofascial syndrome (MFS). <h3>Objectives:</h3> To assess the oxidant system status in FM and MFS. <h3>Methods:</h3> A total number of 160 patients with chronic musculoskeletal pain were examined and assigned to fibromyalgia and myofascial syndrome groups accordingly. Early, intermediate and late lipid peroxides (u/l), serum malondyaldehide (MDA) (mkmol/l), serum total antioxidant activity (mmol/l), serum prooxidant activity (mkmol/l) were assessed in both groups with the following results. <h3>Results:</h3> An active peroxidation process was found in FM, and likewise in SMF, but with a lower expression. In both cases early and intermediate peroxidation predominates, but with a greater value in FM vs SMF: early lipid peroxides – 0,386±0,153 vs 0,324±0,086 (M±SD, p=0,002252); intermediate lipid peroxides 0,363±0,149 vs 0,214±0,053 (M±SD, p=0,000000); and late lipid peroxides 0,127±0,053 vs 0,098±0,027 (M±SD, p=0,000037). <h3>Conclusion:</h3> Both FM and MFS patients presented with signs of oxidative stress, slightly more expressed in FM than MFS. However, the FM group displayed a statistically significant lower anti-oxidant activity compared to MFS, suggesting that rather deficient anti-oxidant ability than excessive pro-oxidant activity cause the perpetuation of oxidative stress in FM patients. <h3>REFERENCES:</h3> [1] Cordero MD. Oxidative stress in Fibromyalgia: pathophysiology and clinical implications. Reumatol Clin 2011; 7: 281-283. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB0140 CHARACTERISTICS OF FIBROMYALGIA IN PATIENTS WITH CONCOMITANT IMMUNE-MEDIATED RHEUMATIC DISEASES
Authors: T. Hügle, J. Mettler, P. Ming Azevedo
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Fibromyalgia is a complex chronic syndrome characterized by widespread pain, fatigue, sleep impairment, and dysfunction of the autonomic nervous system. Its prevalence is higher in patients suffering from immune-mediated rheumatic diseases (IMRD), ranging from 10-30%. Concomitant fibromyalgia, also referred to as secondary fibromyalgia, significantly impacts pain perception, quality of life, and the response to treatment in patients with IMRD. <h3>Objectives:</h3> To Compare Fibromyalgia Features in Patients With and Without Concomitant IMRD. <h3>Methods:</h3> A comprehensive clinical and laboratory assessment was performed on 318 patients with chronic musculoskeletal pain syndromes during a rheumatology-led two-week multimodal inpatient program. This program included psychiatric evaluation and sleep analysis by actigraphy. Fibromyalgia was diagnosed in 152 patients using the ACR2010 and/or FiRST criteria. Among these, 56 out of 318 patients suffered from a confirmed IMRD (Figure 1) according to their respective classification criteria. Univariate analysis was conducted to compare fibromyalgia patients with and without concomitant IMRD. <h3>Results:</h3> In this cohort, 25 out of 56 (45%) patients with IMRD fulfilled the ACR2010 or FiRST criteria for fibromyalgia. The presence of IMRD was associated with the use of DMARDs, cortisone, biologics, or NSAIDs, as well as with peripheral inflammatory pain, enthesopathy, and CRP levels &gt;10 mg/L. Higher rates of hypermobility (Beighton score) as well as sleep problems or pain in childhood or adolescence were found in the fibromyalgia/IMRD group (see Table 1). Conversely, patients with both fibromyalgia and IMRD had lower levels of kinesiophobia and and a tendency towards lower FiRST scores compared to fibromyalgia patients without concomitant IMRD. <h3>Conclusion:</h3> Generally, fibromyalgia features are similar in patients with or without concurrent IMRD. However, IMRD patients with fibromyalgia tend to experience more peripheral inflammatory and enthesiopathic pain, and they exhibit less kinesiophobia. The presence of hypermobility, as well as pain or sleep problems that have persisted since childhood, may have influenced the diagnosis of IMRD in this cohort. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Thomas Hügle Roche, Novartis, GSK, BMS, Janssen, Galapagos, Atreon, Vtuls, Johanna Mettler: None declared, Pedro Ming Azevedo: None declared.
AB1452 HOW CANCER LOCATION AND TIMING DIFFER BETWEEN INFLAMATORY MYOPATHY AND IGA VASCULITIS
Authors: A. Hocevar, K. Perdan-Pirkmajer, Z. Rotar
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Patients with inflammatory myopathies (IM), especially dermatomyositis, are at increased risk of cancer. In addition, cancer is associated with approximately 5% of systemic vasculitides, including IgA vasculitis. In adults with IgAV, malignancy represents one of the possible triggers of vasculitis. <h3>Objectives:</h3> We aimed to investigate differences in cancer type/location and their temporal occurrence in well-defined and prospectively followed groups of IM and IgAV patients. <h3>Methods:</h3> Adults diagnosed with MI or IgAV between January 2010 and November 2022 and followed up in our outpatient clinic were included. Episodes of cancer that developed in the 3 years before or after the diagnosis of IM or IgAV were recorded. Episodes of non-melanoma skin cancer were excluded from the analysis. Cancer episodes were divided into 3 groups: 1) cancer diagnosed in the 3 years before the diagnosis of IM or IgAV; 2) cancer diagnosed at the same time as IM or IgAV; 3) cancer diagnosed in the 3 years of follow-up. <h3>Results:</h3> In a cohort of 158 IM patients (110 (69.6%) women; median age at IM diagnosis 63.6 (52.6-72.2) years), we found 28 different cancers in 27 patients (17.1%; 12 (55.6%) women; median age at IM diagnosis 64.8 (60.0-71.9) years). In the group of 305 patients with IgAV (124 (40.7%) women; median (IQR) age at IgAV diagnosis 63.5 (45.6-75.8) years), we recorded 24 different cancers in 22 patients (7.2%; 5 (22.7%) women; median (IQR) age at diagnosis of IgAV 73.7 (64.9-79.2) years). The temporal relationship between cancer diagnosis and IM or IgAV is presented in Table 1. Figure 1 shows the site of cancer diagnosed in patients with IM or IgAV. In contrast to IgAV, where prostatic, kidney and bladder cancers together accounted for 55% of all cancers, these cancers accounted for only 14% of IM cancers. IM patients had a more aggressive cancer course, resulting in 11 out of 27 deaths during follow-up (40.7%), while 4 out of 22 IgAV patients (18.2%) died of cancer progression during follow-up. <b>Table 1.</b> Temporal association between cancer diagnosis and diagnosis of IM or IgAV <h3>Conclusion:</h3> While most IgAV patients were diagnosed with cancer in the three years before the diagnosis of vasculitis, the timing of cancer onset was more uniform in IM patients. The two groups compared also differed in terms of the location of the cancer and its aggressiveness/prognosis. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB0180 FROM SYNOVIUM TO ALVEOLI: INTERROGATING DIFFUSE INTERSTITIAL PNEUMONIA IN RHEUMATOID ARTHRITIS AND ITS SYNERGY WITH ANTI-CCP ANTIBODIES
Authors: H. Elhani, L. Taoubane, H. Toufik, N. El Ouardi, A. Majjad, A. Bezza
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA). Previous studies have suggested pathophysiological links between ILD and the presence of anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies). The main aim of our study was to evaluate the prevalence and features of RA-associated ILD (RA-ILD) and to explore a possible association between the presence of anti-CCP antibodies and the development of ILD. <h3>Objectives:</h3> Examine the relationship between anti-CCP antibodies and diffuse interstitial pneumonia in rheumatoid arthritis, aiming to enhance strategies for early detection and effective management. <h3>Methods:</h3> We conducted a prospective study that included 180 patients diagnosed with RA according to the ACR/EULAR 2010 criteria, from January 2022 to January 2023. Screening for RA-ILD and characterization of the ILD pattern were performed using high-resolution computed tomography, which was centrally interpreted by expert radiologists and pulmonologists. <h3>Results:</h3> Of the 180 RA patients, 87.9% were female, with a median age of 56 years (interquartile range: 31 to 89 years). The median duration of RA was 8 years (interquartile range: 1 to 32 years). Erosive lesions were observed in 58% of patients on standard radiographs, anti-CCP antibodies were positive in 72% of cases, and rheumatoid factor (RF) was present in 62.9% of patients. The mean DAS28-CRP score was 4.48 ± 1.24. About 91% of patients had received at least one csDMARDs treatment, and nearly 59.8% were on biologic therapies. Moreover, 90.7% of patients had been treated with glucocorticoids. RA-ILD was present in 24.7% of patients, with a distribution of usual interstitial pneumonia (UIP) in 54% of cases, non-specific interstitial pneumonia (NSIP) in 43.18% of cases, and organized pneumonia (OP) in one patient. Factors associated with the presence of RA-ILD were male gender (p &lt; 0.001) and a significant correlation with the presence of anti-CCP antibodies (p = 0.004). <h3>Conclusion:</h3> Interstitial lung disease associated with rheumatoid arthritis requires special attention from rheumatologists due to its high prevalence, often asymptomatic nature, and tendency to progress to fibrosis. This study contributes to a better understanding of the relationship between RA and ILD, emphasizing the importance of early detection and management of this potentially severe complication. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB0160 THE USE OF IL-6 INHIBITORS IN PATIENTS WITH POLYMYALGIA RHEUMATICA RECEIVING GLUCOCORTICOID THERAPY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: O. Martins, V. Antunes, O. Udoma-Udofa
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Polymyalgia rheumatica (PMR), a common inflammatory rheumatic disease in the elderly, causes fatigue, morning stiffness, and neck, shoulder, and hip girdle pain. The pathophysiology is hypothesized to be associated with abnormal production of interleukin-6 (IL-6). Current recommended treatment consists of low or intermediate-dose glucocorticoids, although relapses are common, and the adverse effects of long-term therapy may discourage their use. In this context, IL-6 inhibitors might serve as an alternative option for these patients. While these inhibitors have been extensively researched for their potential use in managing giant cell arteritis, a condition commonly associated with PMR, the efficacy of these inhibitors in patients with PMR symptoms alone remains uncertain. <h3>Objectives:</h3> To evaluate the efficacy and safety of IL-6 inhibitors (tocilizumab, sarilumab) plus glucocorticoid therapy compared to glucocorticoid therapy alone in the management of symptoms of PMR. <h3>Methods:</h3> PubMed, Embase, and Cochrane were systematically searched for randomized controlled trials. The primary outcome was Short Form-36 (SF-36): Physical Component Score after treatment. Secondary outcomes were overall adverse events rate; discontinuation due to adverse event; and evaluator global assessment by Visual Analogue Scale (VAS). Statistical analyses were performed using R language 4.3.1. Odds ratio (OR) was used for binary outcomes and mean difference (MD) with standard deviation (SD) for continuous outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using I<sup>2</sup> statistics. <h3>Results:</h3> 4 RCTs with 358 patients (IL-6i 188 <i>vs.</i> placebo 170) were included. Patients treated with IL-6 inhibitors demonstrated a significantly higher SF-36: Physical Component Score compared to placebo (MD 4.75; 95% CI 0.67 to 8.83; p = 0.02). There was no significant difference in adverse events rate (OR 1.69; 95% CI 0.81 to 3.53; p = 0.16) or discontinuation due to adverse event (OR 0.80; 95% CI 0.24 to 2.70; p = 0.723). Also, results from evaluator global assessment by VAS did not differ between groups (MD -6.51; 95% CI -12.92 to -0.09). <h3>Conclusion:</h3> The use of IL-6 inhibitors was associated with an improvement in SF-36: Physical Component Score, and did not increase overall adverse events in patients under treatment. Further studies evaluating a wider variety of outcomes may demonstrate more benefits of their use in the management of polymyalgia rheumatica. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB0182 ‘RIGHT PERSON, RIGHT TIME, RIGHT PLACE’ UTILISING AN ADVANCED CLINICAL PRIORITISATION MODEL TO STREAMLINE INFLAMMATORY ARTHRITIS REFERRALS
Authors: B. Lynch, J. Malone, G. Fitzgerald
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Traditionally, rheumatology referral prioritisation depended solely on information contained in referral letters. Often, referrals lacked sufficient information to enable a decision about disease activity. This led to patients not being seen within appropriate timeframes, reduced clinic efficiency and reduced capacity. A standardised system of prioritisation called Advanced Clinical Prioritisation (ACP) was introduced for the Inflammatory Arthritis (IA) Waiting Lists (WL). <h3>Objectives:</h3> To align patients with the most appropriate care pathway thus increasing clinic efficiency and optimising capacity for specialist services versus traditional methods of prioritisation. <h3>Methods:</h3> A standardised assessment proforma was designed, containing recognised symptoms of IA. Clinical Specialist Physiotherapists (CSP) contacted all patients referred to IA clinics between November 2022 and November 2023 in a virtual clinic setting to complete this ACP assessment. High-scoring patients were fast-tracked to a consultant-led clinic. Lower-scoring patients were directed to a CSP-led clinic with consultant support. <h3>Results:</h3> A total of 414 phone calls were made to 364 patients. 61% (n=221) patients were deemed appropriate for the Consultant-led IA clinic, (n=151 from the urgent, n=70 from the soon WL). Additionally, 28% (n=102; 57 from the urgent, 45 from the soon WL) were directed to the CSP clinic and 11% (n=41; 29 from the urgent, 12 from the soon WL) were discharged directly from the ACP clinic (Figure 1). Of the 196 patients booked in the Consultant-led IA clinic in this timeframe, 52% (n=102) were diagnosed with an IA (Figure 2). 40% (n=78) did not have an IA diagnoses, with a Did Not Attend (DNA) rate of 8% (n=16). In the CSP-led clinic a total of 72 patients were booked. Of this cohort 18% (n=12) were diagnosed with IA, 82% (n=54) did not have an inflammatory diagnosis. There was a 9% (n=6) DNA rate. Had the traditional prioritisation system of urgent and soon been used, this method would have gleaned 43% (n=83) IA diagnoses from the urgent WL, and 32% (n=31) from the soon WL. <h3>Conclusion:</h3> Utilising an ACP method to streamline referrals for IA to appropriate clinics is an effective method, providing a standardised pathway of care by aligning patients with the most appropriate clinic. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1471 MACHINE-LEARNING BASED MODELS ASSIST THE IDENTIFICATION OF PULMONARY EMBOLISM IN AUTOIMMUNE DISEASES-A RETROSPECTIVE, MULTICENTER STUDY
Authors: L. Dong
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with a high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRD). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with are scarce. <h3>Objectives:</h3> To investigate the potential value of PE prediction in AIIRD patients with different machine learning models. <h3>Methods:</h3> In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariate logistic regression and LASSO were used to select the clinical features for the further training with machine learning (ML) methods, including RF, SVM, NN, LR GBDT, CART and C5.0. The performances of these models were subsequently validated using a multi-center validation cohort. <h3>Results:</h3> In training cohort, 24 and 13 clinical features were selected by univariate LR and LASSO strategies, respectively. All five ML models (<b>RF</b>, <b>SVM</b>, <b>NN</b>, <b>LR</b>, and <b>GBDT</b>) showed promising performances, with an AUC of 0.962–1 in the training cohort, and 0.969–0.999 in the validation cohort. <b>CART</b> and <b>C5.0</b> trees achieved AUCs of 0.850 and 0.932 respectively in the training cohort, respectively. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort, and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone (Figure 1). <h3>Conclusion:</h3> ML-based models prove to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB0177 EUPHORBIA FACTOR L2 ALLEVIATED GOUTY INFLAMMATION BY SPECIFICALLY SUPPRESSING BOTH THE PRIMING AND ACTIVATION PROCEDURE IN NLRP3 INFLAMMASOME
Authors: Y. Li, Y. Zhuang, Y. Chen, G. Wang, Z. Tang, Y. Zhong, Y. Zhang, L. Wu, X. Ji, Q. Zhang, B. Pan, Y. Luo
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Euphorbia L. is a traditionally used herb and contains many newly identified compounds with novel chemical structures. EFL2, a diterpenoid derived from Euphorbia seeds, is reported to alleviate acute lung injury and arthritis by exerting anti-inflammatory effects [1,2]. However, its inhibitory activity on the NLRP3 inflammasome and its direct regulatory target are still unknown. <h3>Objectives:</h3> In this study, we aimed to test the therapeutic benefit and mechanisms of EFL2 in NLRP3 inflammasome-mediated murine gouty models and identified the potential molecular mechanism. <h3>Methods:</h3> An air pouch and acute gouty murine model was used to evaluate EFL2's antiarthritic effect. The inhibitory effect of this compound on inflammatory cell infiltration was determined by flow cytometry in vivo. Cytokine levels were measured using ELISA. The mechanism by which EFL2 activates the NLRP3 inflammasome signalling pathway was evaluated by Western blotting, coimmunoprecipitation, immunofluorescence staining and transmission electron microscopy. Discovery Studio was used to visualize the interaction between the binding target and EFL2, followed by drug affinity responsive target stability and cellular thermal shift assays. <h3>Results:</h3> In vitro, EFL2 specifically reduced NLRP3 inflammasome-mediated IL-1β production in bone marrow-derived macrophages. It also significantly alleviated MSU crystal-induced arthritis and inflammatory cell infiltration in the air pouch in mice in an NLRP3 inflammasome-dependent manner. Mechanistically, EFL2 robustly downregulated NF-κB p65 phosphorylation and subsequent NLRP3 inflammasome expression by binding to glucocorticoid receptors. Moreover, EFL2 could specifically suppress the lysosome damage-mediated NLRP3 inflammasome activation process. <h3>Conclusion:</h3> Overall, EFL2 is able to suppress both the priming and activation of the NLRP3 inflammasome and has therapeutic potential as a candidate for NLRP3 inflammasome-mediated diseases. <h3>REFERENCES:</h3> [1] Zhang, Q. et al. Euphorbia factor L2 alleviates lipopolysaccharide-induced acute lung injury and inflammation in mice through the suppression of NF-κB activation. Biochem Pharmacol 155, 444-454, doi:10.1016/j.bcp.2018.07.025 (2018). [2] Tang, J. et al. Euphorbia Factor L2 ameliorates the Progression of K/BxN Serum-Induced Arthritis by Blocking TLR7 Mediated IRAK4/IKKβ/IRF5 and NF-kB Signaling Pathways. Front Pharmacol 12, 773592, doi:10.3389/fphar.2021.773592 (2021). <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>