tbuckley/cabot-search huggingface dataset:
AB1365 SKELETAL METASTASES OF DIGESTIVE ORIGIN IN RHEUMATOLOGY: A DESCRIPTIVE STUDY OF 18 CASES
Authors: R. Ben Chehida, S. Ben Jemaa, Z. Gassara, A. Feki, M. Ezzeddine, R. Akrout, M. H. Kallel, H. Fourati, S. Baklouti
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Digestive metastases to the bones represent an advanced stage of cancer, commonly originating from organs like the colon, stomach, pancreas, liver, or biliary system. Patients with these metastases often exhibit diverse symptoms, including localized or diffuse pain. Knowledge of their epidemiology and clinical characteristics is vital for effective patient management. <h3>Objectives:</h3> Describe the epidemioclinical features of patients admitted to Sfax Rheumatology Department with bone metastases of digestive origin. Outline complications and patient progression profiles <h3>Methods:</h3> A retrospective descriptive study in Rheumatology Department focused on patients hospitalized for digestive origin bone metastases. <h3>Results:</h3> Studying 18 cases of bone metastases from digestive primaries revealed an average age of 65.89 years (34-86), 83.3% males, and a 5:1 male-to-female ratio. Half were rural. Patient presentations included inflammatory or mixed back pain (38.88%), lumboradicular pain (27.77%), diffuse bone pain with systemic decline (22.22%), and incidentally discovered hypercalcemia (11.11%). Eighty-eight point nine percent had a revealing metastasis with symptoms lasting 1 to 35 months. Hospitalization durations ranged from 2 to 63 days, averaging 28.72 days. Primary cancers included colon (27.8%), gastric (22.2%), pancreatic (16.7%), biliary (11.1%), hepatic (11.1%), gastrointestinal (5.6%), and cholangiocarcinoma (5.6%). Forty-four point four percent had no other metastatic sites. Other sites included hepatic (27.8%), nodal (22.2%), pulmonary (16.7%), and peritoneal carcinomatosis (5.6%). Biopsy methods: bone alone (27.8%), primary tumor alone (22.2%), bone marrow (16.7%), both (5.6%). Complications during hospitalization: neurological (11.1%), hemodynamic (16.7%). Transfer rate: 16.7%. Mortality: 11.1%. Outcomes: clinical improvement (5.6%), discontinuation against medical advice (16.7%), and 50% lost to follow-up. <h3>Conclusion:</h3> Though not conventionally considered osteophilic, the increasing occurrence of bone metastases from digestive neoplasms, with male predominance, multi-site metastases, high complications, and diagnostic implications, suggests potential osteophilic characteristics <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1359 CCN6 GENE MUTATION INDUCES MITOCHONDRIAL DYSFUNCTION: THE CAUSE OF PROGRESSIVE PSEUDO-PSEUDORHEUMATOID DYSPLASIA (PPRD)
Authors: Y. Liu, Y. Li, D. Mou, X. Bai
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Progressive pseudo-pseudorheumatoid dysplasia (PPRD) is a rare autosomal recessive non-inflammatory joint disorder characterized by articular cartilage involvement, resulting in progressive joint stiffness and enlargement without inflammation [1]. The pathogenesis of PPRD remains elusive, although mutations in the cellular communication network factor 6 (CCN6) have been directly associated with this condition. <h3>Objectives:</h3> Revealing the molecular mechanism underlying PPRD triggered by CCN6 mutation. <h3>Methods:</h3> Exome sequencing was performed on a PPRD pedigree to identify potential mutations. A lentivirus-based expression vector containing the identified CCN6 mutation was constructed and utilized for chondrocyte infection to simulate the cellular pathology observed in PPRD. Co-immunoprecipitation, confocal imaging, Western blotting, and flow cytometry were employed to analyze changes in cellular function. <h3>Results:</h3> Both affected individuals within the pedigree, including the patient and her sister, were diagnosed with PPRD. Exome sequencing revealed that the most frequently reported CCN6 mutation site among published Chinese literature on PPRD was C223G. Subsequent cell transfection experiments demonstrated that wild-type CCN6 localized to chondrocyte mitochondria while CCN6 (C223G) remained cytoplasmic. Further investigation revealed impaired interaction between mutant CCN6-C223G and mitochondrial chaperone HSP60 compared to wild-type CCN6-HSP60 binding, leading to abnormal HSP60 function. This activation of mitochondrial unfolded protein response (mtUPR) disrupted cellular energy metabolism and resulted in altered gene expression within the nucleus. <h3>Conclusion:</h3> The identification of the CCN6-C223G mutation sheds light on its role in triggering mtUPR and subsequent aberrant chondrocyte function in PPRD patients. These findings provide valuable insights for potential drug development targeting this molecular pathway implicated in PPRD. <h3>REFERENCES:</h3> <b>[1]</b> Wynne-Davies R, Hall C, Ansell BM: Spondylo-epiphysial dysplasia tarda with progressive arthropathy. A "new" disorder of autosomal recessive inheritance. The Journal of bone and joint surgery British volume 1982, 64(4):442-445. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1398 SPINAL FRACTURE REVEALING HYPERPARATHYROIDISM: CLINICAL, PARACLINICAL CHARACTERISTICS AND ASSOCIATED FACTORS
Authors: R. Grassa, H. Saghi, N. Ben Chekaya, M. Ben Bahri, H. Farah Ahmed, S. Zrour, M. Touzi, N. Bergaoui, M. Jguirim, I. Bejia
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Hyperparathyroidism (HP) is a common endocrine disorder responsible for a generalized disturbance in phosphocalcic and bone metabolism. The clinical presentation is highly polymorphic, and the discovery can occur within the etiological assessment of a spinal fracture. <h3>Objectives:</h3> The objective is to study the clinical and paraclinical profile of spinal fractures originating from hyperparathyroidism and determine the associated factors. <h3>Methods:</h3> This is a retrospective descriptive and analytical study conducted at Fattouma Bourguiba University Hospital in Monastir during the period from January 2012 to December 2022. The epidemiological, clinical, and paraclinical profile of patients with a Spinal fracture linked to hyperparathyroidism was studied. <h3>Results:</h3> Among 119 patients, six patients had a spinal fracture of hyperparathyroid origin, with an average age of 62 years. Women were more affected than men (5F/1H), with 4 women in menopause. Spinal pain dominated the clinical picture in 66.6% of cases. Radiculalgia and cervico-brachial neuralgia represented each 16.6% of cases. Manifestations related to confirmed hypercalcemia in laboratory tests were found in 2 patients, accounting for 33.3% of cases. In laboratory findings, an inflammatory syndrome was found in 2 patients, hypercalcemia was observed in all patients with an average value of 2.91±0.47 mmol/l, elevated alkaline phosphatase (ALP) with an average of 277.67±249.8, and elevated serum parathyroid hormone (PTH) with an average value of 211 ng/L. Radiologically, spinal fracture was benign in all patients. Primary hyperparathyroidism was the most frequent cause, affecting 5 patients (83.3%). Secondary hyperparathyroidism was noted in 1 patient (16.67%). Hyperparathyroid origin of spinal fractures was associated with spinal pain existence (p=0.04), elevated calcium levels (p&lt;0.001), and elevated alkaline phosphatase (p&lt;0.001). No association was demonstrated with gender (p=0.6), vitamin D levels (p&gt;0.05), thyroid dysfunction (p=0.6), and menopause (p=0.2). <h3>Conclusion:</h3> Hyperparathyroidism is a significant factor contributing to bone fragility, highlighting the importance of assessing parathyroid function in patients with spinal fractures. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1141 THERAPEUTIC POTENTIAL OF INHIBITION OF JAK1 AND 2 BY RUXOLITINIB, OF ROCK2 BY BELUMOSUDIL, AND OF BTK BY IBRUTINIB IN SYSTEMIC SCLEROSIS
Authors: X. Hong, Y. Xiao, A. H. Györfi, L. Xu, L. Shen, R. Neelagar, V. Devakumar, T. Filla, T. Trinh-Minh, M. Liang, A. Rius Rigau, J. Distler, A. E. Matei
Journal: Annals of the Rheumatic Diseases (2024)
AB1376 OSTEOARTICULAR INVOLVEMENT IN MULTIPLE MYELOMA: PREVALENCE AND RISK FACTORS
Authors: M. Dhifallah, A. Feki, S. Ben Jemaa, H. Fourati, M. H. Kallel, R. Akrout, S. Baklouti
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Osteoarticular (OA) involvement represents the most common extra-hematologic manifestation of multiple myeloma (MM). <h3>Objectives:</h3> This study aims to describe the OA manifestations during MM and identify its risk factors. <h3>Methods:</h3> We conducted a retrospective study including 126 multiple myeloma cases treated in our department over a 30-year period (1993–2023). Sociodemographic, clinical, and biological data were gathered. OA involvement was assessed through radiographic and/or magnetic resonance imaging (MRI) data. <h3>Results:</h3> The study included 126 patients with a mean age of 65.23±11.63 years [36–92], comprising 65 males and 61 females. Bone pain was present in 92.1% (n=116) with an average duration of 4 months. Mean erythrocyte sedimentation rate and C-reactive protein levels were 99.08 mm [3–190] and 27.74mg/l [0–196], respectively. Hemoglobin was below 10g/dl in 51.2% of cases, averaging 9.902±2.22 g/dl [5–13.9]. Calcium levels exceeded 2.75 mmol/l in 20% of cases, averaging 2.49 ± 0.33 mmol/l. Mean creatinine level was 88.28 μmol/l [36–587]. Plasmocyte rates, observed in sternal puncture or bone marrow biopsy, averaged 43.93% [5–80], with 31.7% exceeding 60%. Radiological osteolysis was found in 76.2% (n=96) of patients, with multiple lesions in 91 cases. Commonly affected bones were the skull (37.12%), pelvis (16.8%), and spine (12%). Diffuse osteosclerosis was identified in only two patients. Pathological fractures were present in 59.5% (n=75), including 15 peripheral fractures and 70 vertebral fractures, with 43.2% affecting the lumbar region (n=54) and 36.8% the dorsal region (n=46). Durie and Salmon prognostic classification distributed patients as follows: Stage IA (3.2%), Stage IIA (4%), Stage IIB (0.8%), Stage IIIA (72.2%), and Stage IIIB (18.3%). Plasmocyte rates in bone marrow were significantly higher in patients with multiple osteolytic lesions (36.4 vs 52.32%, p=0.016). Male gender was associated with higher onset of bone pain (OR=9.643, 95% CI [1.183–78.57], p=0.017). Stage III of the Durie and Salmon classification was associated with radiological osteolysis (Chi2=5.703, p=0.05). <h3>Conclusion:</h3> Articular involvement in multiple myeloma is polymorphic, ranging from bone pain to multiple pathological fractures. Evaluation of prognostic markers, such as plasmocyte rates and the Durie and Salmon prognostic classification, helps identify patients at risk of developing osteoarticular complications. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS1469-HPR INVESTIGATING PHYSICAL INACTIVITY AND ASSOCIATED HEALTH PARAMETERS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: F. Sari, G. G. Pala, D. Oskay, A. Tufan
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic lupus erythematosus (SLE) is a chronic, autoimmune, and inflammatory rheumatic disease that causes tissue damage through autoantibodies and immune complexes. In the disease, constitutional complaints are seen together with skin, hematological, renal, musculoskeletal, and pulmonary involvements. There is considerable evidence of a significant prevalence of physical inactivity in patients with SLE [1, 2]. Physical inactivity, which is highly prevalent in patients with SLE, is an independent risk factor for cardiovascular events and causes many complications [1, 3]. <h3>Objectives:</h3> This study aimed to investigate the effect of objective measurement and physical activity level on peripheral muscle strength, exercise capacity, pain, dyspnea, fatigue, anxiety, and depression in patients with SLE. <h3>Methods:</h3> The present cross-sectional study analyzed 41 patients with SLE. Clinical and demographic characteristics of patients were recorded. Functional exercise capacity, peripheral muscle strength, dyspnea, pain, fatigue, anxiety, and depression were assessed. The physical activity level was assessed by a wearable activity tracker. <h3>Results:</h3> The number of steps measured by the activity tracker was 4384.43±1558.21 steps per day in patients with SLE. Patients with physical activity levels below 5,000 steps exhibited elevated levels of fatigue, along with diminished functional exercise capacity and knee muscle strength, in comparison to those who were above the 5,000-step threshold. Physical activity levels correlated with functional exercise capacity (6MWT), physiological parameters (maximum heart rate, Δ heart rate, Δ dyspnea, QFM fatigue, Δ QFM fatigue), and knee extension muscle strength. The functional exercise capacity and knee extension were identified as significantly and dependently associated with physical activity levels in SLE patients. <h3>Conclusion:</h3> Physical activity level is associated with functional exercise capacity and knee muscle strength in patients with SLE. <h3>REFERENCES:</h3> [1] O'Dwyer T, Durcan L, Wilson F. Exercise and physical activity in systemic lupus erythematosus: A systematic review with meta-analyses. <i>Semin Arthritis Rheum</i> 2017; 47(2): 204-215. [2] Ayán C, Martín V. Systemic lupus erythematosus and exercise. <i>Lupus</i> 2007; 16(1): 5-9. [3] Sari F, Bayram S, Oskay D, Tufan A. Comparison of Exercise Capacity, Physical Activity Level and Peripheral Muscle Strength in Systemic Lupus Erythematosus Patients with Healthy Individuals. <i>Aktuelle Rheumatologie</i> 2023; DOI: 10.1055/a-2106-7129. <h3>Acknowledgements:</h3> Thank you to all our patients in this study <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1121 THE PROGNOSTIC VALUE OF THE RATIO OF NEUTROPHILS TO LYMPHOCYTES AND THE PLATELET-TO-LYMPHOCYTE RATIO IN PATIENTS WITH SLE
Authors: B. Mayssa, H. Tounsi, S. Wafa, W. Garbouj, M. Lajmi, I. Ghachem, M. Y. Kaabar, S. Dghais, R. Amri
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with diverse clinical manifestations. <h3>Objectives:</h3> This study aimed to determine the impact of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) on the prognosis of SLE. <h3>Methods:</h3> A retrospective and descriptive study, was conducted within the internal medicine department of Taher Maamouri Hospital, between 2015 and 2023. All patients fulfilled American College of Rheumatology ACR/ EULAR classification criteria for SLE. NLR and PLR were calculated for each observation at the initial consultation. The correlation between these biomarkers and LES manifestations was analyzed. <h3>Results:</h3> Data from seventy-five patients were analysed. The female to male ratio was 4, 66. The median age was 37 years, with extremes ranging from 16 to 75 years. Neutropenia, lymphopenia and thrombocytopenia were present in 3%, 41% and 44% of cases respectively. The median NLR and median PLR were 2.88 and 148 respectively. NLR&gt;2 and PLR&gt;140 accounted for 82% and 56% respectively. In univariate analysis, high NLR and PLR were significantly associated with elevated C-reactive protein (CRP). Patients with lupus nephritis had higher PLR levels, and proteinuria&gt;2g/24 hours correlated with PLR&gt;140 (<b><i>P</i></b>=<b>0.046</b>). elevated PLR was significantly associated with severe disease flare-ups (<b><i>P</i></b>=<b>0.016</b>) and intensive care hospitalizations(ICH) (<b><i>P</i></b>=<b>0.007</b>). The two biomarkers found were not significantly associated with antinuclear antibody (ANA) levels, neurological impairment or severe infectious complications. <h3>Conclusion:</h3> Elevation of PRL and NRL appears to be useful in assessing the activity and severity of SLE. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1124 PRELIMINARY ANALYSIS OF THE RATIOS BETWEEN ADVANCED-GLYCATION END PRODUCTS (AGEs) AND THEIR SOLUBLE RECEPTOR (sRAGE) AS BIOMARKERS IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: I. Carrión-Barberà, L. Tío, C. Pérez-García, A. Ribes, A. Toloba, V. Abad, L. Polino, A. Pros, T. C. Salman-Monte, J. Monfort, L. Triginer
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> It has been postulated that the axis of advanced glycation end-products (AGEs) and their soluble receptor (sRAGE) could play a relevant role as inducers in the chronic inflammatory pathway in various conditions; among them, in systemic lupus erythematosus (SLE). However, some authors<sup>1</sup> defend that the ratio AGEs to RAGE could be a better and universal biomarker than them individually. <h3>Objectives:</h3> As the ratios between AGEs and sRAGE have not been studied in SLE, the aim of this project is to perform an exploratory analysis of their associations with SLE characteristics. <h3>Methods:</h3> Multiple demographic and clinical characteristics of the 122 SLE patients who signed the informed consent were recorded. Skin AGE concentrations were measured by skin autofluorescence and serum AGEs and sRAGE were measured through ELISA according to the manufacturer instructions. The relationship between the different serum AGEs (pentosidine, CML and CEL) and sRAGE was analyzed using both an OLS regression model and a GML as all the ratios followed a non-normal distribution. All were adjusted for confounders based on previous bivariate analysis. <h3>Results:</h3> Figures 1 and 2 show the statistically significant associations between each of the ratios and SLE characteristics. We found a lower pentosidine/sRAGE ratio in patients on bDMARDs (Figure 1a) and a higher one in anti-Ro52+ patients (Figure 1b). Higher ratios of CEL/sRAGE (Figure 1c-e) and CML/sRAGE (Figure 2a-d) were associated with higher markers of activity and damage, while higher skin AGEs/sRAGE ratio were associated with male sex (Figure 2d) and lower one with shorter disease duration (Figure 2e). <h3>Conclusion:</h3> Most of these associations, although preliminary and not intended for drawing conclusions, support our hypothesis that the different ratios between AGEs and sRAGE could also have implications, and maybe used as biomarkers, related to patients phenotypes, response to treatment, activity and prognosis. However, these observations should be further explored. <h3>REFERENCES:</h3> [1] Prasad K, Dhar I, Caspar-Bell G. Role of advanced glycation end products and its receptors in the pathogenesis of cigarette smoke-induced cardiovascular disease. Int J Angiol. 2014;24(2):75–80. <h3>Acknowledgements:</h3> This work was supported by the Instituto de Salud Carlos III (ISCIII) and the European Union (Grant number "PI18/00059"), by the Fundación Española de Reumatología through the Ayuda a la Intensificación de la Actividad Investigadora awarded in 2021 and by a Jordi Gras scholarship awarded by the Hospital del Mar Research Institute from 2019 to 2021. We would also want to thank Dr. Isaac Alarcón Valero for his statistical support. <h3>Disclosure of Interests:</h3> <b>None declared.</b>
AB1119 REPRESSION OF ID3 AGGRAVATES LUPUS PHENOTYPES IN MURINE MODELS VIA ABERRANT B CELL DIFFERENTIATION
Authors: Y. Park, D. S. Kim, M. L. Cho, S. K. Kwok
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Id3 is a member of the inhibitor of DNA binding (Id) family which is a helix-loop-helix protein acting as a transcriptional regulator. Previous studies have reported that Id3 plays an important role in development and function of regulatory T cells in lupus. However, its role in B cells remains unclarified. <h3>Objectives:</h3> To investigate a role Id3 in B cells and lupus pathogenesis. <h3>Methods:</h3> To investigate a role of Id3 in B cells, we generated C57BL/6 mice with a CD19Cre-mediated B cell-specific depletion of Id3 as well as mice (Id3-/-) with conventional knockout of Id3. In these mice, we evaluated presentation of lupus-mimicking phenotypes and changes of immune cell populations. Additionally, we assessed influences of B cell-specific Id3 depletion in lupus-induced mice by R848. <h3>Results:</h3> In Id3-/- mice, proportions of effector T cells such as Th1, Th2, and Th17 cells were elevated whereas those of regulatory T cells were lower than in control mice. Furthermore, proportions of plasma cells were significantly elevated in Id3-/- mice. These mice presented with increased inflammation in kidney tissues, resembling lupus nephritis. Elevated proportion of plasma cells was replicated in mice with B cell-specific Id3 depletion. Induction using R848 resulted in exacerbated lupus-like manifestations including increased proteinuria and higher serum immunoglobulin levels in B cell-specific Id3-depleted mice than in control mice. In an in vitro study, CD19+ B cells from Id3-/- mice were more differentiated into plasma cells than those from control mice whereas there were no significant differences in other B cell subsets. <h3>Conclusion:</h3> Genetic suppression of Id3 in murine models exacerbated lupus-like phenotypes with aberrant B cell differentiation. These findings may imply a potential role of Id3 in the pathogenesis of lupus. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant number: 2022R1I1A1A01068210). <h3>Disclosure of Interests:</h3> <b>None declared.</b>