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Background:Systemic diseases most frequently associated with uveitis are spondyloarthritis (SpA). Differences in the presentation of uveitis have been described in each type of SpA, however, this information is contradictory and scarce in the literature. The differentiation of these associated inflammatory processes has important therapeutic and prognostic implications and may condition the treatment of the underlying disease in Ophthalmology/Rheumatology Ocular Inflammation Interdisciplinary Units.Objectives:The aim of the study is to analyze the characteristics of non-infectious ocular inflammation in the different types of spondyloarthritis in a multidisciplinary ocular inflammation practice.Methods:Descriptive observational study including data from patients with a non-infectious inflammatory ocular process secondary to SpA evaluated in a multidisciplinary ocular inflammation consultation from January 2012 to January 2024. Demographic, ocular involvement, sequelae, and therapy data are comparatively analyzed. Quantitative variables were described as median and interquartile range (IQR) or mean and standard deviation (SD), and frequencies were used for the qualitative variables. Comparative analysis was performed using the IBM SPSS 21.0 program and the comparison of proportions using the chi-square test. P-values <0.05 were considered statistically significant.Results:From our “Inflammatory ocular process Registry” at La Paz University Hospital with a total of 564 patients included, we collected data from 147 patients with SpA (26%). Table 1 shows clinical characteristics in the global sample and in the different types of spondyloarthritis. In the comparative analysis, according to the type of spondyloarthritis, significant differences were found in the percentage of positive HLAB27 (p<0.01); being more frequent in ankylosing spondylitis (AS) and axial spondyloarthritis (AxSpA) than in the rest of the groups. The age of onset was significantly higher in AS and psoriatic arthritis (PsA) than in others (p<0.01). Regarding the ocular involvement, significant differences were found (p<0.01) in the pattern and course. Recurrent acute anterior uveitis (RAAU) pattern and the recurrent acute course were predominant in AS, axSpA and PsA. Bilateral acute anterior uveitis (BAAU) pattern and chronic forms were more frequent in peripheral spondyloarthritis (pSpA) and inflammatory bowel disease associated with spondyloarthritis (IbdSpA). Concerning the ophthalmological examination, significant differences (p<0.05) were found in the presence of keratic precipitates (more frequent in AS, axSpA and PsA), vitritis (higher proportion in PsA) and cataract (more frequent in AS, IbdSpA and PsA). No differences were found in sex, location/laterality of the uveitis (anterior and unilateral involvement are predominant in all cases), neither in complications such as visual impairment, synechiae, cystic macular edema, glaucoma, retinal vasculitis, epiretinian membrane or papilitis. Regarding therapy, there were significant differences (p<0.05) in the use of systemic corticosteroids; most commonly used in pSpA and PsA. The use of disease-modifying anti-rheumatic drugs (DMARDs) was also more frequent in pSpA and PsA without reaching statistical significance (p=0.056). There were no significant differences in the use of biological therapy.Conclusion:This study reveals differences in the inflammatory ocular involvement regarding the type of spondyloarthritis. Bilateral and chronic forms of uveitis were more frequently observed in IbdSpA o pSpA. Additionally, the use of systemic steroids and DMARDs was most common in pSpA and PsA.Table 1.REFERENCES:NIL.Acknowledgements:To the Ophthalmology/Rheumatology Ocular Inflammation Interdisciplinary Unit of La Paz University Hospital.Disclosure of Interests:None declared.

Dyspnea is the most common symptom among hospitalized patients with heart failure (HF) but besides dyspnea questionnaires (which reflect the subjective patient sensation and are not fully validated in HF) there are no measurable physiological variables providing objective assessment of dyspnea in a setting of acute HF patients. Studies performed in respiratory patients suggest that the measurement of electromyographic (EMG) activity of the respiratory muscles with surface electrodes correlates well with dyspnea. Our aim was to test the hypothesis that respiratory muscles EMG activity is a potential marker of dyspnea severity in acute HF patients. Prospective and descriptive pilot study carried out in 25 adult patients admitted for acute HF. Measurements were carried out with a cardio-respiratory portable polygraph including EMG surface electrodes for measuring the activity of main (diaphragm) and accessory (scalene and pectoralis minor) respiratory muscles. Dyspnea sensation was assessed by means of the Likert 5 questionnaire. Data were recorded during 3 min of spontaneous breathing and after breathing at maximum effort for several cycles for normalizing data. An index to quantify the activity of each respiratory muscle was computed. This assessment was carried out within the first 24 h of admission, and at day 2 and 5. Dyspnea score decreased along the three measured days. Diaphragm and scalene EMG index showed a positive and significant direct relationship with dyspnea score (p<0.001 and p = 0.003 respectively) whereas pectoralis minor muscle did not. In our pilot study, diaphragm and scalene EMG activity was associated with increasing severity of dyspnea. Surface respiratory EMG could be a useful objective tool to improve assessment of dyspnea in acute HF patients.

Background Hypophosphatasia (HPP) is a rare and underdiagnosed condition characterized by deficient bone and teeth mineralization. The aim of this study was first, to evaluate the diagnostic utility of employing alkaline phosphatase (ALP) threshold levels to identify adults with variants in ALPL among individuals with persistently low ALP levels and second, to determine the value of also including its substrates (serum pyridoxal-5′-phosphate—PLP—and urinary phosphoetanolamine-PEA) for this purpose in order to create a biochemical algorithm that could facilitate the diagnostic work-up of HPP. Results The study population comprised 77 subjects with persistent hypophosphatasaemia. They were divided into two groups according to the presence (+GT) or absence (−GT) of pathogenic ALPL variants: 40 +GT and 37 −GT. Diagnostic utility measures were calculated for different ALP thresholds and Receiver Operating Characteristic (ROC) curves were employed to determine PLP and PEA optimal cut-off levels to predict the presence of variants. The optimal threshold for ALP was 25 IU/L; for PLP, 180 nmol/L and for PEA, 30 µmol/g creatinine. Biochemical predictive models were assessed using binary logistic regression analysis and bootstrapping machine learning technique and results were then validated. For ALP < 25 UI/L (model 1), the area under curve (AUC) and the 95% confidence intervals (CI) was 0.68 (95% CI 0.63–0.72) and it improved to 0.87 (95% CI 0.8–0.9), when PEA or PLP threshold levels were added (models 2 and 3), reaching 0.94 (0.91–0.97) when both substrates were included (model 4). The internal validation showed that the addition of serum PLP threshold levels to the model just including ALP improved significantly sensitivity (S) and negative predictive value (NPV) − 100%, respectively- with an accuracy (AC) of 93% in comparison to the inclusion of urinary PEA (S: 71%; NPV 75% and AC: 79%) and similar diagnostic utility measures as those observed in model 3 were detected when both substrates were added. Conclusions In this study, we propose a biochemical predictive model based on the threshold levels of the main biochemical markers of HPP (ALP < 25 IU/L and PLP > 180 nmol/L) that when combined, seem to be very useful to identify individuals with ALPL variants.

Background Hypophosphatasia (HPP) is an inborn error of metabolism characterized by low levels of serum alkaline phosphatase (ALP). Scarce evidence exists about features that should signal the potential association between hypophosphatasaemia and HPP in adults. The aim of this study is to estimate the prevalence of ALPL variants in subjects with persistent hypophosphatasaemia and determine the associated clinical and laboratory features. For this cross-sectional study, laboratory records of 386,353 subjects were screened by measurement of ALP activity. A total of 85 (0.18%) subjects with persistent hypophosphatasaemia (≥2 serum alkaline phosphatase–ALP–measurements ≤35 IU/L and none > 45 IU/L) were included (secondary causes previously discarded). ALPL genetic testing and a systematized questionnaire to retrieve demographic, clinical and laboratory data were performed. Descriptive analysis and logistic regression models were employed to identify the clinical and laboratory characteristics associated with ALPL variants. Results Forty subjects ( 47%) had a variant(s) in ALPL . With regard to clinical characteristics, the presence of an ALPL variant was significantly associated only with musculoskeletal pain (OR: 7.6; 95% IC: 1.9–30.9). Nevertheless, a trend to present more dental abnormalities (OR: 3.6; 95% IC: 0.9–13.4) was observed. Metatarsal stress fractures were also more frequent (4 vs 0; p  < 0.05) in this group. Regarding laboratory features, median ALP levels were lower in subjects with ALPL variants (26 vs 29 IU/L; p  < 0.005). Interestingly, the threshold of ALP levels < 25 IU/L showed a specificity, positive predictive value and positive likelihood ratio of 97.8, 94.4% and 19.8 to detect a positive ALPL test, respectively. Conclusions In subjects with persistent hypophosphatasaemia –secondary causes excluded– one out of two presented ALPL variants. Musculoskeletal pain and ALP levels < 25 IU/L are associated with this variant(s). In this scenario, ALP levels < 25 IU/L seem to be very useful to identify individuals with the presence of an ALPL variant.

BackgroundVitamin D plays an essential paper in the regulation of the bone metabolism. Its role in the modulation of the autoimmune system is better known every day as well as its involvement in the pathogenesis of the autoimmune diseases. Some studies have shown a possible implication of the vitamin D in the development of lung diseases, as the interstitial lung diseases (ILD) through the inhibition of the fibroblasts' profibrotic phenotype. Likewise, it's been described a possible association between serum calcidiol levels and a decreased pulmonary function.ObjectivesAnalyze the prevalence of vitamin D insufficiency. Evaluate a possible relationship between calcidiol levels and lung respiratory tests. Asses the prevalence of low bone mineral density (BMD) and its correlation with risk factors.MethodsRetrospective study of a cohort of patients with ILD referred from the pulmonary consultation. We analyzed demographic and analytics aspects, dual-energy x-ray absorptiometry (DXA), spinal column radiographies, and lung respiratory tests. The statistical study was performed with SPSS.Results44 patients were recruited, 68% women with median age 66 years. 45.5% presented an idiopathic ILD (Usual Interstitial Pneumonia (UIP), Nonspecific IP and Cryptogenic Organizing Pneumonia) and 40.1% sarcoidosis. The 20% left was composed by patients with ANCA-Vasculitis (2), Extrinsic Allergic Alveolitis (6) and ILD related to connective tissue diseases (3 Rheumatoid Arthritis). 79.5% had received corticosteroids with a median dose of 5 grams.The prevalence of vitamin D insufficiency (<30ng/dl) was 81.3%, 42.9% presented calcidiol levels under 20 ng/dl and 6.80% <10ng/dl. The creatinine clearance rate, age and ESR were correlated with calcidiol levels. Upon the studied factors, we found no statistically association between vitamin D levels and lung respiratory tests and neither with the DLCO. By contrast, we did find an indirect association between FVC and trochanteric BMD which was removed by adjustment for sex, age and smoking status.About the bone density measures, 33.3% presented a normal BMD, 47.6% osteopenia and 19% osteoporosis. BMD was related to the renal function in total hip, wards triangle, trochanter and intertrochanteric region. We established an inverse association between BMD and ESR too. In the subgroup analysis, we found a younger population in the sarcoidosis group with a greater BMD in total hip, trochanter and intertrochanteric region as well as a smaller FRAX index. There were no statistically significant differences in the prevalence of osteoporosis or osteopenia and the subtype of pneumopathy, middle levels of calcidiol and the other bone metabolism parameters.ConclusionsIn our patients with ILD, we found a high prevalence of vitamin D insufficiency. Nonetheless, there was no association between calcidiol levels and a worse obstructive pattern as it has been described in other chronic lung diseases. It is especially interesting the indirect correlation established between BMD and ESR, concluding the own disease activity can play a determinant role in the regulation of the bone metabolism.Disclosure of InterestNone declared

In temperate latitudes sheep have a seasonal reproductive behaviour, which imposes strong constraints on husbandry in terms of work organization and availability of animal products. During the last 50 years, researchers have focused on understanding the mechanisms driving small ruminants’ reproduction cycles and finding ways to control them. This characteristic is inherited from their wild ancestor. However, the history of its evolution over the 10 millennia that separates present day European sheep from their Near Eastern ancestors’ remains to be written. This perspective echoes archaeologists’ current attempts at reconstructing ancient pastoral societies’ socio-economical organization. Information related to birth seasonality may be retrieved directly from archaeological sheep teeth. The methodology consists of reconstructing the seasonal cycle record in sheep molars, through sequential analysis of the stable oxygen isotope composition (δ 18O) of enamel. Because the timing of tooth development is fixed within a species, inter-individual variability in this parameter reflects birth seasonality. A review of the data obtained from 10 European archaeological sites dated from the 6th to the 3rd millennia BC is provided. The results demonstrate a restricted breeding season for sheep: births occurred over a period of 3 to 4 months, from late winter to early summer at latitudes 43°N to 48°N, while a later onset was observed at a higher latitude (59°N). All conclusions concurred with currently held expectations based on present day sheep physiology, which, aside from the historical significance, contributes to the reinforcing of the methodological basis of the approach. Further study in this area will permit regional variability attributable to technical choices, within global schemes, to be fully reported.

Background: Information about health-related quality of life (HRQoL) in heart failure (HF) in older adults is scarce. Methods: We aimed to describe the HRQoL of the SENECOR study cohort, a single-center, randomized trial comparing the effects of multidisciplinary intervention by a geriatrician and a cardiologist (intervention group) to that of a cardiologist alone (control group) in older patients with a recent HF hospitalization. Results: HRQoL was assessed by the short version of the disease-specific Kansas Cardiomyopathy Questionnaire (KCCQ-12) in 141 patients at baseline and was impaired (KCCQ-12 < 75) in almost half of the cohort. Women comprised 50% of the population, the mean age was 82.2 years, and two-thirds of patients had preserved ejection fraction. Comorbidities were highly prevalent. Patients with impaired HRQoL had a worse NYHA functional class, a lower NT-proBNP, a lower Barthel index, and a higher Clinical Frailty Scale. One-year all-cause mortality was 22.7%, significantly lower in the group with good-to-excellent HRQoL (14.5% vs. 30.6%; hazard ratio 0.28; 95% confidence interval 0.10–0.78; p = 0.014). In the group with better HRQoL, all-cause hospitalization was lower, and there was a trend towards lower HF hospitalization. Conclusions: The KCCQ-12 questionnaire can provide inexpensive prognostic information even in older patients with HF. (Funded by grant Primitivo de la Vega, Fundación MAPFRE. ClinicalTrials number, NCT03555318).

Current paleodietary studies about the Naviform and Talayotic groups that took place in Minorca (Balearic Islands) during the Late Bronze Age–Early Iron Age (ca.1600–850/800 BC) have suggested a mixed and variable diet, largely depending on terrestrial sources of vegetables and meat. This study explores the nutritional pattern of the individuals buried in the Cova des Pas site (Minorca Island, Spain), a cave used as a collective sepulcher and the most exceptional and major human assemblage found in the Balearic Islands during this period. Carbon (δ 13 C) and nitrogen (δ 15 N) stable isotopic signatures were measured on extracted bone collagen from 49 individuals. Further, faunal remains from the Son Mercer de Baix site, the closest contemporaneous village to the collective sepulcher, were also analyzed to provide a baseline corpus of data to interpret human isotopic data. The results indicate a human diet based mainly on C 3 plants with an important consumption of animal protein. The δ 15 N values of infants up to 4 years were high, indicating the enriched isotopic signature of breast milk, and weaning is assumed to occur around this age. Differences between sexes and the age subcategories were not statistically significant, assuming that the different groups of society had the same access to food. The data obtained in this isotopic study provides insight into the palaeodietary pattern of the human groups dated to the Late Bronze Age–Early Iron Age ages in the island of Minorca, contributing to the present debate on the emergence and development of complex societies on the Balearic archipelago.

BackgroundAntisynthetase syndrome (AS) is an uncommon connective tissue disease characterised by the presence of antibodies to anti-aminoacyl t-RNA synthetase (anti-ARS) along with features of interstitial lung disease (ILD), myositis, arthritis and Mecanic’s hands.ObjectivesTo analyse the most common demographic, clinical, radiological, spirometry and capillaroscopic findings in a cohort of patients with AS. As a secondary objective, the association between capillaroscopic findings and diffusion lung capacity for carbon monoxide (DLCO) and the radiologic pattern in the high-resolution computed tomography of the chest (HRCT) was evaluated.MethodsA ten-year (2007–2017) retrospective analysis of patients diagnosed with AS followed in a multidisciplinary consultation with a pulmonologist and a rheumatologist. The nailfolds from 2nd to 5th fingers in both hands were examined in all subjects by using videocapillaroscopy (Mediscope-Optilia).ResultsTwenty patients were included, 15 (75%) females and 50% (10/20) non-smokers. Mean age at the clinical debut was 47,5±16 years. Throughout their evolution, 90% of patients (18/20) presented Interstitial Lund Disease (ILD); 70% (14/20), arthritis and 75% (15/20), myositis. Furthermore, 40% (8/20) associated fever, 45%; (9/20), Raynaud’s Phenomenon and 55% (11/20), Mechanic’s hands. Three patients only had ILD and Raynaud’s Phenomenon at presentation. In the immunologic assessment, 73,7% (14/19) were positive for anti – Jo-1 antibodies and 26,3%, for anti PL-12. As non-anti-ARS antibodies, 6 had positivity for rheumatoid factor; 3, for ACPA and 5, for antiRo-52 antibodies. Of those 18 diagnosed of ILD, spirometry tests at baseline were available for 13. It was remarkable that 69,23% (9/13) of patients presented a diminished value of DLCO (low in 23% (3/13), moderate in 46% (6/13) and normal in the rest of subjects. The most common ILD pattern was non-specific interstitial pneumonia (55%, 10/18) followed by usual interstitial pneumonia (33,3%, 6/18) and organising pneumonia (11,1%, 2/18). Nailfold capillaroscopy was performed in 16 patients: Scleroderma pattern was observed in 5 (all of them associating Raynaud’s phenomenon) and 6 patients showed microangiopathic changes. The most frequent capillaroscopic findings were neoangiogenesis (93,8%) and microhaemorragias68,8 followed by avascular areas (37,5%) and megacapillaries (31%). An association between capillaroscopic findings and reduction of DLCO or the radiologic pattern was not observed, possibly influenced by the number of patients included. One subject associated Sjögren Syndrome, another one cutaneous Lupus and another patient, morphea. All of the patients included, received steroids and inmunosupressants. Azathioprine was the most frequently used (18/20), followed by Methotrexate (7/20), Rituximab (5/20), Mycophenolate (4/20), Cyclophosphamide (3/20) and Abatacept (1/20).ConclusionsIn our cohort with AS, the most common clinical manifestation was ILD, and an important part of the patients showed a decreased DLCO. Capillaroscopy was pathogenic in most of them and could be useful for the diagnosis of AS, specially in those patients presenting solely with ILD at the clinical debut, although its pronostic value is still unknown. Multidisciplinary consultations are useful in the management of these truly challenging patients.Disclosure of InterestNone declared

Esperanza was a multicenter national health program developed to facilitate an early diagnosis of patients with Spondyloarthritis (SpA) in Spain. To compare the clinical evolution of patients with axial SpA (axSpA) and peripheral SpA (pSpA) included in this program. Patients from the Esperanza cohort fulfilling ASAS criteria for axSpA or pSpA and completed the 6-year follow-up were included. Patients were classified according to the predominant symptom. In case of having axSpA and pSpA, they were classified as axSpA. Clinical features, disease activity and treatment aspects at baseline and 6-year visit were evaluated. From 775 patients recruited at baseline, 6-year follow-up data from 178 (83.5%) fulfilling ASAS criteria at the final visit were available: 133 (74.7%) for axSpA and 45 for pSpA (25.3%). 118 (66.3%) were males (50.6% with axSpA and 62.2%, pSpA, p=0.4). Patients with axSpA had more frequently positive HLA-B27 (90.5%) vs. (9.5%), p<0.001. Follow-up clinical features are shown in Table 1. At the final visit, both axSpA and pSpA presented an improvement in clinical symptoms, disease activity (CRP, BASDAI, ASDAS and VAS-pt) and quality of life (ASQoL). A worsening of mobility (BASMI) was observed in both groups. The prevalence of uveitis, psoriasis and inflammatory bowel disease (IBD) at baseline was 10.7%, 18% and 5.6%, respectively. At the 6-year visit, the cumulative prevalence (CP) was 14% for uveitis (16.5% in axSpA and 6.7% in pSpA), 22.5% for psoriasis (12.8% in axSpA and 51.1% in pSpA) and 7.9% for IBD (5.3% in axSpA and 15.6% in pSpA). Most of the patients were prescribed NSAIDS at baseline and more patients maintained this treatment at the 6-year visit in axSpA compared with pSpA (96.9% vs 87.5%, p=0.02). At the final visit, a higher percentage with pSpA received csDMARDs in comparison with axSpA (81% vs. 35.7%, p<0.001). Sixty (44.4%) patients received biologic therapy at the final visit and no differences were observed in their prescription: 43% in axSpA and 48.6% in pSpA(p=0.6). The early diagnosis of recent-onset SpA achieves a significant improvement in clinical features, disease activity and quality of life in patients with axSpA and pSpA after 6 years of follow-up. Although previous publications revealed a low radiographic progression in this cohort1, the worsening of BASMI must aware clinicians of possible evolutive structural damage. [1]Fernández-Carballido et al. RMD Open. 2020 Sep;6(2):e001345 [Display omitted] The Spanish Foundation of Rheumatology received funding from Pfizer (formerly Wyeth) to develop the Esperanza Program. Later, the Program has been supported by restricted grants from the Instituto de Salud Carlos III and Fondos FEDER (FIS PI13/02034 and PI17/01840) and AbbVie. Carolina Tornero: None declared, Victoria Navarro-Compán: None declared, Beatriz Joven-Ibáñez: None declared, RAQUEL ALMODOVAR: None declared, Xavier Juanola-Roura: None declared, Cristina Fernández-Carballido: None declared, Juan Carlos Quevedo-Abeledo: None declared, Jose Rosas: None declared, Azucena Hernández: None declared, Carlos A. Montilla-Morales: None declared, Jose Ramón Maneiro: None declared, A. Juan-Mas: None declared, Jose Antonio Pinto Tasende: None declared, Mireia Moreno: None declared, Jesus Sanz: None declared, Teresa Ruiz Jimeno: None declared, Manuel Moreno: None declared, María Lourdes Ladehesa Pineda: None declared, Eugenio de Miguel Speakers bureau: AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi., Paid instructor for: Janssen, Novartis, Roche, Consultant of: AbbVie, Novartis, Pfizer, Galapagos, Grant/research support from: Abbvie, Novartis, Pfizer.