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Background:Osteoporosis (OP) is a systemic disorder of bone metabolism characterized by reduced bone mass and micro-architectural deterioration. Lower total body mineral density (BMD) has been found in patients with inflammatory bowel disease (IBD) which may increase osteoporosis and pathological bone fractures risk (FR) due to several mechanisms.Objectives:To assess the prevalence of osteoporosis and proportion of treated patients in an IBD cohort and to evaluate the association of demographic, clinical and analytical features with fracture risk (based on FRAX® model) and BMD.Methods:Monocentric retrospective study in a tertiary hospital. All patients included had IBD and were referred from Gastroenterology to the Rheumatology Department over 10 years (January 2013 – June 2023). Demographic, clinical and analytical data and BMD by dual-energy X-ray absorptiometry (DXA, total hip, femoral neck and lumbar spine) were collected at the time of the first visit in the Rheumatology outpatient center (V1); for patients over 40 years old, major (MFR) and hip (HFR) fracture risk was assessed with DXA based on FRAX® (validated for Portuguese population) and proportion of patients with indication of therapy for OP was calculated (according to Portuguese recommendations). Correlations between continuous variables were evaluated by Spearman rank test and Pearson’s correlation coefficient and Mann-Whitney U test was used in the comparison analysis between groups (significance level at p<0.05).Results:Two hundred forty-four patients were included, mostly female (57.4%), with a mean age at V1 of 46.65 (±13.46) years (Table 1). One hundred eighty-four (75.4%) patients had Crohn’s disease (CD) and 60 (24.6%) had ulcerative colitis (UC). Regarding IBD treatment, azathioprine (41.0%) and infliximab (28.3%) were the most frequently used drugs; 12 patients (4.9%) were taking glucocorticoids at V1 and 185 (75.8%) had been previously treated with glucocorticoids. Of all patients, 33 (14.1%) had DXA T score ≤ -2.5 (compatible with osteoporosis), 10 (4.1%) had previous fragility fractures. One hundred ninety-two (78.7%) patients exhibited low levels of 25-hydroxy vitamin D (<30ng/mL), 155 (63.5%) showed elevated serum concentrations of beta-carboxy-terminal type-1 collagen crosslinks (beta-CTX); 17 (6.9%) were taking calcium and/or vitamin D supplements.Concerning to individuals ≥40 years old (n=148, 60.7%), serum levels of total proteins and albumin correlated negatively with HFR (r=-0.194, p=0.035) and MFR (r=-0.187, p=0.026), respectively. Erythrocyte sedimentation rate (ESR) correlated positively with MFR (r=0.175; p=0.045), ferritin correlated positively with MFR (r=0.214; p=0.017) and HFR (r=0.206; p=0.022); beta-CTX correlated positively with MFR (r=0.221; p=0.010). Other relevant correlations and differences are presented in Table 2. Of interest, serum levels of 25(HO)VitD correlated negatively with beta-CTX (r=-0.255; p=0.004). Fifteen patients (10.1%) had an indication for osteoporosis treatment (no differences between genders, p=0.848); only 3 were undergoing treatment with bisphosphonates. Across patients under 40 years old (n=96, 39.3%), serum levels of hemoglobin (Hb) correlated positively with total hip BMD (r=0.294; p=0.05) and with femoral neck BMD (r=0.221; p=0.042), serum levels of ESR correlated negatively with total hip BMD (r=-0.251; p=0.020), beta-CTX correlated positively with total hip (r=0.217; p=0.043) and femoral neck (r=0.238; p= 0.027) BMD and osteocalcin correlated positively with femoral neck BMD (r=0.221; p=0.041).No other statistically significant correlations were observed.Conclusion:This study shows a higher prevalence of OP in comparison with the general Portuguese population and an important number of untreated patients with high FR. It also reveals significant associations between clinical/analytical variables and FR (over 40 years old) and BMD (under 40 years old) in IBD patients: inflammatory state (positive correlation of FR with ESR and ferritin; negative correlation of BMD with ESR; positive correlation of BMD with Hb) and nutritional status (albumin correlated negatively with FR).REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Anti-tumor necrosis factor-α (anti-TNF) therapy is often part of the treatment strategy for rheumatic diseases (RD) and inflammatory bowel disease (IBD). An association between anti-TNF agents and the development of lupus erythematosus (LE)-like syndrome has been established and some patients may have a definitive diagnosis of systemic lupus erythematosus (SLE), requiring appropriate treatment. To date, no studies have been conducted to analyze follow-up between rheumatic and IBD patients who have developed LE-like syndrome induced by anti-TNF agents.Objectives:To assess clinical and serological markers of LE-like syndrome induced by anti-TNF therapy, and to characterize its development, in patients with RD and IBD receiving treatment with anti-TNF.Methods:In this monocentric descriptive study, with a minimum 6-month follow-up and conducted at a tertiary university hospital (Rheumatology Department), we reviewed the clinical and serological parameters of 8 patients with RD and 11 patients with IBD, all diagnosed with LE-like syndrome induced by anti-TNF therapy. Statistical analysis, using student’s t test, was performed to compare differences in anti-double-stranded DNA (anti-dsDNA) levels between patients with positive and negative anti-histone antibodies (anti-H).Results:Nineteen patients were included, mostly female (n=14). The mean age at the diagnosis of LE-like syndrome was 45.42 (±16.77) years. Ten IBD and 2 RD patients received infliximab. At the time of symptoms onset, anti-TNF agent was discontinued. Fifteen (78.9%) patients developed polyarthritis and 3 (15.8%) polyarthralgias. Three (15.8%) patients had constitutional symptoms (such as fatigue or fever), 2 (10.5%) patients developed skin rash, 2 (10.5%) patients had cytopenia (1 with anemia and 1 with anemia and leukopenia; both in RD group), 2 (10.5%) patients developed serositis (pleural effusion) and 1 (5.3%) patient had vasculitis-like skin lesions in the hands; 1 (5.3%) patient developed venous thrombosis associated with antiphospholipid antibodies positivity. At the time of LE-like syndrome diagnosis, all patients (n=100, 19%) tested positive for antinuclear antibodies (ANA), and almost all patients (n=14, 73.7%) tested positive (≥100 international units/L) for anti-dsDNA. Except for 4 (21.1%) patients (3 in IBD group and 1 in RD group) who had low complement (C3c/C4), complement levels were mostly normal. The relevant data are detailed in Table 1. Of note, positive anti-H were accompanied by low serum levels of anti-dsDNA antibodies, p<0.001 (Table 2).Seven (36.8%), all IBD patients, needed immunosuppressive therapy (methotrexate, azathioprine or hydroxychloroquine) to resolve their LE-like syndrome symptoms (in 3 patients, anti-dsDNA were negative only after at least 1 year of treatment) and continued to receive immunosuppressants during follow-up. In 11 (57.9%) cases, including all RD patients, discontinuation of anti-TNF therapy (and sometimes using low dose of glucocorticoids) was sufficient for symptoms resolution and antibody negativity. Five patients (26.3%) switched to another anti-TNF without experiencing relapse of symptoms.Conclusion:Studies show that SLE-like syndrome frequency has been increasing and recognition of the condition is very important as anti-TNF therapy is commonly used. This study, although limited by its descriptive nature and small sample size, revealed differences between the RD and IBD groups regarding the specific anti-TNF agents used and the necessity of immunosuppressive therapy, more prevalent in the IBD group. On the other hand, most patients improved after discontinuing therapy and those who tolerated the switch to another anti-TNF-α agent had no SLE recurrence. Of interest, positive anti-H was associated with absence or low levels of anti-dsDNA, suggesting that this clinical entity is an independent disease and different from classical drug-induced lupus with positive anti-histone antibodies. Further studies are required to establish definite differences between IBD and RD groups and determine the impact of definitive SLE diagnosis secondary to anti-TNF therapy.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

The aim of the present study was to analyze studies that cultivate microalgae in a consortium using effluent as a nutrient source, and later use the biomass to produce other biocompounds. The production of microalgal biomass, which is associated with the remediation of effluent, production of biofuels, and by-products of high added value (such as bioethanol, biomethane, biodiesel, biofertilizers, and biochar), has been highlighted among the types of sustainable refineries. Further, consortium cultures, with interactions between microalgae and bacteria, fungi, and protozoa at the cellular level, can generate mutual relationships in the conversion and use of nutrients. Large-scale microalgae cultivation enables the mitigation of the presence of inorganic carbon in the atmosphere through microalgal cellular respiration. To assess the economic and environmental sustainability of the promotion of technologies that use microalgae, the relationships between the bioeconomy and renewable energy must be established. The present study sought to demonstrate the relationship between the factors associated with the cultivation of microalgae using effluents and the use of microalgal biomass in the production of biocomposites. Furthermore, whether these factors could favor the reduction of costs related to the production processes and boost the biorefinery industry were also investigated.

Musculoskeletal symptoms represent the most common extraintestinal manifestations of inflammatory bowel disease (IBD) and a major cause of impaired quality of life in these patients. Spondyloarthritis (SpA) is classically associated with IBD, but other rheumatic manifestations may occur. To characterize musculoskeletal symptoms and rheumatic diseases in an IBD cohort. Retrospective monocentric descriptive study including all the patients with IBD consecutively reffered from Gastroenterology to the Rheumatology Department between January of 2013 and December 2020 in a tertiary university hospital. Demographic and clinical data and musculoskeletal symptoms were collected at the time of the first visit in the Rheumatology outpatient center and the rheumatic diseases diagnosed during the entire follow-up were registered. A total of 234 patients were included, 136 (58.1%) females, 20 (8.5%) smokers. At the first Rheumatology consultation the mean age was 43.6 (±13.7) years and the mean IBD duration was 11.7 (±9.7) years. Concerning IBD: 172 (73.5%) had Crohn's disease and 62 (26.5%) had ulcerative colitis; azathioprine (39.7%), infliximab (28.2%) and mesalazine (26.5%) were the most frequently used drugs; eleven patients (4.7%) were taking glucocorticoids and 106 (45.3%) had already been treated with glucocorticoids. Regarding musculoskeletal symptoms: 76 (32.5%) patients had peripheral symptoms and 98 (41.9%) had axial symptoms (Table 1). Twenty-six (11.1%) patients had radiographic sacroiliitis, 14 (6.0%) had sacroiliitis in computed tomography and 9 (3.8%) in magnetic resonance. Forty-four (18.8%) patients fulfilled Assessment of SpondyloArthritis international Society (ASAS) criteria for axial SpA and 5 (2.1%) for peripheral SpA. Also of note, 16 (6.8%) patients had a previous diagnosis of psoriasis and 5 (2.1%) had uveitis in the past. Concerning other rheumatic diagnosis, we observed: osteoarthritis in 64 (27.3%), osteoporosis in 16 (6.9%), diffuse idiopathic skeletal hyperostosis in 6 (2.6%), systemic lupus erythematosus in 4 (1.7%), rotator cuff tendinopathy in 2 (0.9%), rheumatoid arthritis, gout, calcium pyrophosphate deposition disease, fibromyalgia, drug-induced lupus, osteitis condensans ilii, Dupuytren's contracture and avascular necrosis of the femoral head in 1 (0.4%), each. Our results demonstrate a high prevalence of musculoskeletal symptoms and rheumatic diseases in patients with IBD. These diagnoses are not limited to the group of SpA and osteoporosis, emphasizing the importance of rheumatologists being alert to other rheumatic diagnoses in patients with IBD. None declared Table 1Characterization of peripheral and axial musculoskeletal symptoms in patients with Inflammatory Bowel Disease.N (%)Peripheral symptomsNo158 (67.5%)Arthritis / “inflammatory” joint pain24 (10.3%)“Mixed” rhythm joint pain15 (6.4%)“Mechanical” joint pain29 (12.4%)Enthesopathy8 (3.4%)Axial symptomsNo136 (58.1%)“Inflammatory” back pain46 (19.7%)“Mixed” rhythm back pain35 (14.9%)“Mechanical” back pain17 (7.3%)Total234 (100%)

Background and aims Predicting the treatment outcomes of biological therapies is an unmet need in Crohn's Disease. In this study, we explored the potential of serum neutrophil‐related biomarkers to predict infliximab therapeutic results and disease progression in Crohn's Disease patients, over a 2‐year period, in a real‐world setting. Methods The study included 100 asymptomatic Crohn's Disease patients in the IFX maintenance phase from the prospective, observational, multicenter DIRECT study. Patients were categorized according to a composite outcome reflecting progression that included surgery, hospitalizations, new fistulae, abscess or stricture, and drug treatment escalation. Serum neutrophil elastase, lipocalin‐2, lactoferrin, and resistin (non‐neutrophil control) were analyzed via multiplex magnetic bead assays at multiple touchpoints. Fecal calprotectin was assessed by ELISA. Results Over up to 2 years of follow‐up, serum biomarkers did not differentiate between the composite outcome groups, whereas fecal calprotectin was significantly higher in patients with worse outcomes. During the infliximab maintenance phase, there was a significant, sustained reduction of neutrophil elastase (p < 0.001), lipocalin‐2 (p < 0.001), and lactoferrin (p < 0.001), but not of resistin, despite stable neutrophil levels. Correlations between NE and NGAL levels were strong (Pearson correlations 0.75–0.85); all other correlations were of small magnitude. Conclusion Our real‐world data do not support using serum neutrophil elastase, lipocalin‐2, or lactoferrin concentrations as predictors of treatment outcomes or disease evolution in infliximab ‐treated Crohn's Disease patients. On the other hand, the sustained decrease in biomarkers over time suggests that neutrophil stabilization might be an additional infliximab mechanism of action.

Background: The advent of Remicade® biosimilars, Remsima®, Inflectra® and, more recently, Flixabi®, has brought along the potential to decrease the costs associated with this therapy, therefore increasing its access to a larger group of patients. However, and in order to assure a soft transition, one must make sure the assays and algorithms previously developed and optimized for Remicade perform equally well with its biosimilars. This study aimed to: (a) validate the utilization of Remicade-optimized therapeutic drug monitoring assays for the quantification of Flixabi; and (b) determine the existence of Remicade, Remsima and Flixabi cross-immunogenicity. Methods: Healthy donors’ sera spiked with Remicade, Remsima and Flixabi were quantified using three different Remicade-quantification assays, and the reactivity of anti-Remicade and anti-Remsima sera to Remicade and to its biosimilars was assessed. Results: The results show that all tested Remicade-infliximab-optimized assays measure Flixabi as accurately as they measure Remicade and Remsima: the intraclass correlation coefficients between theoretical and measured concentrations varied from 0.920 to 0.990. Moreover, the interassay agreement values for the same compounds were high (intraclass correlation coefficients varied from 0.936 to 0.995). Finally, the anti-Remicade and anti-Remsima sera reacted to the different drugs in a similar fashion. Conclusions: The tested assays can be used to monitor Flixabi levels. Moreover, Remicade, Remsima and Flixabi were shown to have a high cross-immunogenicity, which supports their high similarity but prevents their switching in nonresponders with antidrug antibodies.

We describe 5 cases of anti-tumor necrosis factor-alpha (anti-TNF-α) induced psoriasiform eruptions with severe scalp involvement inducing inflammatory alopecia and review the literature on this subject. All our 5 patients were provided topical therapy, with good results in only 1 case. The remaining 4 were provided systemic therapy (methotrexate ± cyclosporine): 3 concomitantly suspended the anti-TNF-α treatment (2 are currently clear/almost clear but 1 has so far only observed mild improvement) and 1 switched anti-TNF-α (recurrent flare-ups of the disease continue). So far, no patient has developed scarring alopecia. To our knowledge, a total of 15 cases of anti-TNF-α induced psoriatic alopecia have been described. Anti-TNF-α was discontinued in 9 of the 15 patients and systemic therapy was provided to 9 of the 15 patients. Nonetheless, 2 patients developed scarring alopecia. We conclude that in anti-TNF-α induced psoriasiform eruptions some patients may respond to topical treatment, however in cases of severe scalp involvement anti-TNF-α suspension and systemic treatment should be considered in order to avoid scarring alopecia.

BackgroundThe inflammatory bowel disease (IBD) increases the risk for metabolic bone disease due to several factors, including steroid use, increased cytokine production and malabsorption.ObjectivesDetermine prevalence of osteopenia/osteoporosis (OP) in IBD patients, characterizing their bone metabolism profile.We also intend evaluate correlation between bone mineral density (BMD) and T-score with bone biomarkers (BBM), 25(OH)D3 levels and use of steroids.MethodsCross-sectional study was conducted in adult IBD patients from a University Hospital in the North of Portugal. Patients who exhibited a controlled IBD were evaluated consecutively by a rheumatologist from June 2013 to December 2014. Age,IBD duration and treatment data were collected. Lumbar spine (LS) and total hip (TH) BMD were analyzed using osteo-densitometer LUNAR Expert 1320. We determined phosphorus, calcium, parathormone (PTH), 25(OH)D3 and BBM (beta-CTx,osteocalcin) levels in the serum. Descriptive statistics was used to report sample's demographic and clinical characteristics. Pearson's correlation was used to evaluate correlation between BMD and T-score with BBM and 25(OH)D3 levels;student t-test was used to evaluate relation with history of use of high-dose steroids. Statistical significance level was set at p<0.05.ResultsTotal of 57patients were included, with a mean age of 44 years-old (±11.84), the majority females (n=36). Thirty-seven (64.9%) had CD and 20 (35.1%) UC. Mean duration of IBD was 11.95 (±7.71) years. Twenty-six (45.6%) were under biological therapy due to IBD (25 infliximab; 1 adalimumab). Other therapies in use were azathioprine, sulphasalazine and mesalazine. Only 3 patients were under steroids (<10mg/d prednisolone) but 17 patients had a past history of high-dose steroids use. Osteopenia prevalence ranged from 21% (n=12) (TH) to 24.6% (n=14) (LS).The prevalence of OP ranged from 5.3% (n=3) (TH) to 7% (n=4) (LS). Eleven (19.3%) patients had 25 (OH)D3 levels between 20-30ng/mL and 36 (63.2%) had <20ng/mL. Eight (14%) patients had PTH levels >65pg/mL, of which 3 had hipophosphatemia. Seven (12.3%) patients exhibited high bone turn-over (beta-CTx≥0.28ng/mL and osteocalcin≥31.2ng/mL). Additionally, 25 patients presented with beta-CTx≥0.28ng/mL. Beta-CTx was correlated with LS and TH T-scores (r=-0.348 and r=-0.303, respectively; p<0.05) and BMD values (r=-0.340 and r=-0.297, respectively; p<0.05). Similarly, osteocalcin was correlated significantly with LS and TH T-scores (r=-0.454 and r=-0.443, respectively; p<0.01) and BMD values (r=-0.472 and r=-0.459, respectively; p<0.01).BMD values and T-score on LS and TH weren't correlated with the disease duration, 25(OH)D3 levels or acute phase reactants.We found that the use of high-doses steroids has a significant effect on BMD and T-score of the TH (p<0.05 for both) but not on the LS (p=0.065 and p=0.093, respectively).ConclusionsHigh prevalence of osteopenia/osteoporosis and lower serum 25(OH)D3 levels were observed, in both CD and UC patients. The early recognition of problem and more appropriate preventive and treatment strategies are essential.Disclosure of InterestNone declared