[Cost-effectiveness analysis of fracture liaison services in Catalonia]. / Análisis de coste-efectividad de las Unidades de Coordinación de Fracturas en Cataluña.

OBJECTIVE: To assess the cost-effectiveness of Fracture Liaison Service (FLS) compared to the standard of care for secondary prevention of fragility fractures form the perspective of the Catalan Health Service. METHODS: Cost-utility assessment through a Markov model that simulated disease progression of a patients' cohort candidates to initiate antiosteoporotic treatment after a fragility fracture. A time horizon of 10 years and a 6-month duration per cycle was established. Clinical, economics and quality of life parameters were obtained from the literature and derived from four Catalan FLS. The Catalan Health Service perspective was adopted, considering direct health costs expressed in 2022 euros. A 3% discount rate was applied on costs and outcomes. Uncertainty was assessed through multiple sensitivity analyses. RESULTS: Compared to the standard of care, FLS would promote antiosteoporotic initiation and persistence, reducing the incidence and mortality associated with subsequent fragility fractures. This incremental clinical benefit was estimated at 0.055 years and 0.112 quality-adjusted life years (QALYs) per patient. A higher cost (€1,073.79 per patient) was estimated, resulting into an incremental cost-utility ratio of €9,602.72 per QALYs gained. The sensitivity analyses performed were consistent, corroborating the robustness and conservative approach of the base-case. CONCLUSIONS: The introduction of FLS for the secondary prevention of FF would represent a cost-effective strategy from the Catalan Health Service perspective.

Outcomes After Vascular Surgery Procedures in Patients with COVID-19 Infection: A National Multicenter Cohort Study (COVID-VAS).

OBJECTIVES: To analyze the outcome of vascular procedures performed in patients with COVID-19 infection during the 2020 pandemic. METHODS: This is a multicenter, prospective observational cohort study. We analyzed data from 75 patients with COVID-19 infection undergoing vascular surgery procedures in 17 hospitals across Spain and Andorra between March and May 2020. The primary end point was 30-day mortality. Clinical Trials registry number NCT04333693. RESULTS: The mean age was 70.9 (45-94) and 58 (77.0%) patients were male. Around 70.7% had postoperative complications, 36.0% of patients experienced respiratory failure, 22.7% acute renal failure, and 22.7% acute respiratory distress syndrome (ARDS). All-cause 30-days mortality rate was 37.3%. Multivariate analysis identified age >65 years (P = 0.009), American Society of Anesthesiologists (ASA) classification IV (P = 0.004), preoperative lymphocyte count <0.6 (×109/L) (P = 0.001) and lactate dehydrogenase (LDH) >500 (UI/L) (P = 0.004), need for invasive ventilation (P = 0.043), postoperative acute renal failure (P = 0.001), ARDS (P = 0.003) and major amputation (P = 0.009) as independent variables associated with mortality. Preoperative coma (P = 0.001), quick Sepsis Related Organ Failure Assessment (qSOFA) score ≥2 (P = 0.043), lymphocytes <0.6 (×109/L) (P = 0.019) leucocytes >11.5 (×109/L) (P = 0.007) and serum ferritin >1800 mg/dL (P = 0.004), bilateral lung infiltrates on thorax computed tomography (P = 0.025), and postoperative acute renal failure (P = 0.009) increased the risk of postoperative ARDS. qSOFA score ≥2 was the only risk factor associated with postoperative sepsis (P = 0.041). CONCLUSIONS: Patients with COVID-19 infection undergoing vascular surgery procedures showed poor 30-days survival. Age >65 years, preoperative lymphocytes <0.6 (x109/L) and LDH >500 (UI/L), and postoperative acute renal failure, ARDS and need for major amputation were identified as prognostic factors of 30-days mortality.

Vertebral fractures are increased in rheumatoid arthritis despite recent therapeutic advances: a case-control study.

Prevalence and risk factors of vertebral fractures in postmenopausal RA women were assessed in 323 patients and compared with 660 age-matched women. Of patients, 24.15% had at least one vertebral fracture vs.16.06% of controls. Age, glucocorticoids and falls were the main fracture risks. Vertebral fractures were associated with disease severity. INTRODUCTION: There is little quality data on the updated prevalence of fractures in rheumatoid arthritis (RA) that may have changed due to advances in the therapeutic strategy in recent years. This study was aimed at analysing the prevalence and risk factors of vertebral fractures in postmenopausal women with RA and comparing it with that of the general population. METHODS: We included 323 postmenopausal women diagnosed with RA from 19 Spanish Rheumatology Departments, randomly selected and recruited in 2018. Lateral radiographs of the thoracic and lumbar spine were obtained to evaluate morphometric vertebral fractures and the spinal deformity index. We analysed subject characteristics, factors related to RA, and fracture risk factors. The control group consisted of 660 age-matched Spanish postmenopausal women from the population-based Camargo cohort. RESULTS: Seventy-eight (24.15%) RA patients had at least one vertebral fracture. RA patients had increased fracture risk compared with controls (106 of 660, 16.06%) (p = 0.02). Logistic regression analysis showed that age (OR 2.17; 95% CI 1.27-4.00), glucocorticoids (OR 3.83; 95% CI 1.32-14.09) and falls (OR 3.57; 95% CI 1.91-6.86) were the independent predictors of vertebral fractures in RA patients. The subgroup with vertebral fractures had higher disease activity (DAS28: 3.15 vs. 2.78, p = 0.038) and disability (HAQ: 0.96 vs. 0.63, p = 0.049), as compared with those without vertebral fractures. CONCLUSION: The risk of vertebral fracture in RA is still high in recent years, when compared with the general population. The key determinants of fracture risk are age, glucocorticoids and falls. Patients with vertebral fractures have a more severe RA.

Absence of Relationship between Mitochondrial DNA Haplogroups and Cisplatin-Induced Hearing Loss.

BACKGROUND: Many drugs used for cancer chemotherapy produce reactive oxygen species, thus leading to various complications including nephrotoxicity, cardiotoxicity, and ototoxicity. OBJECTIVE: We have provided a haplogroup analysis of a cohort of cancer patients treated with chemotherapy and compared factors associated with associated hearing loss. STUDY DESIGN AND METHODS: This observational cohort study includes a pure-tone audiometry of the patients who underwent chemotherapeutic treatment. Medical history, presence of risk factors for hearing loss, toxic habits, and association with haplogroups have been determined. RESULTS: 40% of patients developed hearing loss after administration of cisplatin, which was bilateral and symmetrical and of high frequencies. The most frequent haplogroup was H with a slight overexpression of groups V and K and a low frequency of groups J and T. No association of the haplogroup types with the hearing loss has been found; however age was revealed as an important determining factor. CONCLUSIONS: Ototoxicity caused by cisplatin is manifested as bilateral, symmetrical, and predominantly high frequency hearing loss. Although we did not find a strong correlation of haplogroups with ototoxicity, our results revealed the existence of a risk group of elderly patients over 60, which are more susceptible to hearing loss induced by cisplatin, than young adults, regardless of preexisting hearing loss.

Comparison of total, free and bioavailable 25-OH vitamin D determinations to evaluate its biological activity in healthy adults: the LabOscat study.

Determination of different forms of 25-OHD (total, free and bioavailable) in healthy young women does not offer additional advantages over standard 25-OHDT for evaluating vitamin D deficiency. In these subjects 25-OHDT values <15 ng/ml would be more appropriate for defining this deficiency. INTRODUCTION: Determination of 25-OH vitamin D serum levels (25-OHD) constitutes the method of choice for evaluating vitamin D deficiency. However, vitamin D-binding protein (DBP) may modulate its bioavailability thereby affecting correct evaluation of 25-OHD status. We analysed the impact of the determination of 25-OHD (total, free and bioavailable) on the evaluation its biologic activity (estimated by serum PTH determination) in healthy young women. METHODS: 173 premenopausal women (aged 35-45 yrs.) were included. We analysed serum values of total 25-OHD (25-OHDT), DBP, albumin, PTH and bone formation (PINP,OC) and resorption (NTx,CTx) markers. Free(25-OHDF) and bioavailable (25-OHDB) serum 25-OHD levels were estimated by DBP and albumin determinations and also directly by ELISA (25-OHDF-2). We analysed threshold PTH values for the different forms of 25-OHD and the correlations and differences according to 25-OHDT levels <20 ng/ml. RESULTS: 62% of subjects had 25-OHD values <20 ng/ml and also had significantly lower 25-OHDF and 25-OHDB values, with no significant differences in bone markers and PTH values. The PTH threshold value was similar for all forms of 25-OHD (∼70 pg/ml). Women with PTH values >70 had lower 25-OHDT (15.4 ± 1.4 vs. 18.3 ± 2.7, p < 0.05) and 25OHDB values (1.7 ± 0.2 vs. 2.2 ± 0.09, p < 0.05). The different forms of 25OHD were significantly intercorrelated, with marginal correlations between PTH and 25-OHDT (r = -0.136, p = 0.082). CONCLUSIONS: Determination of different forms of 25-OHD in healthy young women does not offer additional advantages over standard 25-OHDT for evaluating vitamin D deficiency. In these subjects 25-OHDT values <15 ng/ml would be more appropriate for defining this deficiency.

Patient doses and occupational exposure in a hybrid operating room.

PURPOSE: This study aimed to characterize the radiation exposure to patients and workers in a new vascular hybrid operating room during X-ray-guided procedures. METHODS: During one year, data from 260 interventions performed in a hybrid operating room equipped with a Siemens Artis Zeego angiography system were monitored. The patient doses were analysed using the following parameters: radiation time, kerma-area product, patient entrance reference point dose and peak skin dose. Staff radiation exposure and ambient dose equivalent were also measured using direct reading dosimeters and thermoluminescent dosimeters. RESULTS: The radiation time, kerma-area product, patient entrance reference point dose and peak skin dose were, on average, 19:15min, 67Gy·cm2, 0.41Gy and 0.23Gy, respectively. Although the contribution of the acquisition mode was smaller than 5% in terms of the radiation time, this mode accounted for more than 60% of the effective dose per patient. All of the worker dose measurements remained below the limits established by law. CONCLUSIONS: The working conditions in the hybrid operating room HOR are safe in terms of patient and staff radiation protection. Nevertheless, doses are highly dependent on the workload; thus, further research is necessary to evaluate any possible radiological deviation of the daily working conditions in the HOR.

Influence of the IL17A locus in giant cell arteritis susceptibility.

OBJECTIVE: Different lines of evidence have highlighted the role of IL-17A in the inflammatory process occurring in giant cell arteritis (GCA). The aim of the present study was to assess whether the IL17A locus influences GCA susceptibility and its clinical subphenotypes. METHODS: We carried out a large meta-analysis including a total of 1266 biopsy-proven GCA patients and 3779 healthy controls from four European populations (Spain, Italy, Germany and Norway). Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were selected by tagging and genotyped using TaqMan assays. Allelic combination and dependency tests were also performed. RESULTS: In the pooled analysis, two of the five analysed polymorphisms showed evidence of association with GCA (rs2275913: PMH=1.85E-03, OR=1.17 (1.06-1.29); rs7747909: PMH=8.49E-03, OR=1.15 (1.04-1.27)). A clear trend of association was also found for the rs4711998 variant (PMH=0.059, OR=1.11 (1.00-1.23)). An independent effect of rs2275913 and rs4711998 was evident by conditional regression analysis. In addition, the haplotype harbouring the risk alleles better explained the observed association than the polymorphisms independently (likelihood p value <10(-05)). CONCLUSIONS: Polymorphisms within the IL17A locus show a novel association with GCA. This finding supports the relevant role of the Th17 cells in this vasculitis pathophysiology.

Role of calcifying nanoparticle in the development of hyperplasia and vascular calcification in an animal model.

OBJECTIVE: Calcifying nanoparticles (NPs) have been detected recently in calcified human arterial specimens and are involved in the process of calcification. This study was designed to test the hypothesis that human-derived NPs could worsen the response to arterial endothelial injury and induce vascular calcification. METHODS: The right carotid artery of 24 New Zealand rabbits was injured with an angioplasty balloon. Animals were perfused intravenously with saline (100 mL) during the experiment and divided into three groups: group-A, control; group-B, exposed to NPs (2 mL) obtained from calcified aortic valves; and group-C, exposed to NPs (2 mL) and treated postoperatively with atorvastatin (2.5 mg/kg/24 h). At 30 days, both carotid arteries were removed and examined histologically. Blood measurements were monitored during the study. RESULTS: The intimal hyperplasia area was significantly larger in the injured right carotid artery compared with the left unoperated carotid artery in all groups. There was no significant variation in medial area between groups. Morphometrically, the intima/media ratio (IMR) was significantly higher in damaged carotids compared with controls. A significant increase of IMR was found in group-B (1.81 ± 0.41) compared with group-A (0.38 ± 0.59; p = .004) or group-C (0.89 ± 0.79; p = .035). Differences between groups C and A were not significant (p = .064). Calcifications were observed in six animals, all of which had been exposed to NPs (4 in group-B, 2 in group-C, p = .027). Plasma levels of cholesterol and triglycerides remained stable. CONCLUSIONS: This research confirms the ability of systemic inoculation of human-derived NPs to accelerate hyperplasia and stimulate calcification in localized areas of arteries previously submitted to endothelial damage, while it was harmless in healthy arteries. Atorvastatin was demonstrated to slow down this process.

The 11q23.3 genomic region-rs964184-is associated with cardiovascular disease in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory disease associated with high risk of cardiovascular (CV) events. Recently, the rs964184 polymorphism has been associated with coronary artery disease in nonrheumatic Caucasian individuals. 2160 Spanish RA patients were genotyped for the rs964184 polymorphism. Sex, age at diagnosis and traditional CV risk factors (diabetes mellitus, dyslipidemia and smoking habit) were associated with increased risk of CV events. Interestingly, RA patients carrying the rs964184 GG genotype had significantly higher risk of CV events than those with CC genotype [hazard ratio (HR) = 2.91, 95% confidence interval (CI): 1.36-6.26, P = 0.006] after adjusting the results for sex, age at diagnosis and traditional CV risk factors. Our results indicate that rs964184 polymorphism is associated with CV disease in RA.

A case-control study suggests that the CCR6 locus is not involved in the susceptibility to giant cell arteritis.

OBJECTIVES: Polymorphisms of the CC chemokine receptor 6 (CCR6) gene have been recently reported to be associated with a number of autoimmune diseases. We aimed to investigate the possible influence of CCR6 rs3093024 gene variant in the susceptibility to and clinical expression of GCA. METHODS: The CCR6 polymorphism rs3093024 was genotyped in a total of 463 Spanish patients diagnosed with biopsy-proven GCA and 920 healthy controls using a TaqMan® allelic discrimination assay. PLINK software was used for the statistical analyses. RESULTS: No significant association between this CCR6 variant and GCA was observed (p=0.42, OR=0.94, CI95% 0.79-1.10). Similarly, when patients were stratified according to the specific clinical features of GCA such as polymyalgia rheumatica, visual ischaemic manifestations or irreversible occlusive disease, no statistical significant difference was detected either between the case subgroups and the control set or between GCA patients with and without the specific features of the disease. CONCLUSIONS: Our results suggest that the CCR6 rs3093024 polymorphism may not play a relevant role in the GCA pathophysiology.

Single-nucleotide polymorphisms at the 9p21.3 genomic region not associated with the risk of cardiovascular disease in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic polygenic inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular disease (CVD). In this study, we evaluated the potential association of 9p21.3 single-nucleotide polymorphisms (SNPs) - previously linked to coronary artery disease - and CVD risk in 2001 Spanish RA patients genotyped for 9p21.3 SNPs using TaqMan™ assays. Carotid intima media thickness (cIMT) and presence of carotid plaques were also analyzed. Cox regression model did not disclose significant differences between patients who experienced CVD and those who did not. Neither association was found between cIMT or carotid plaques and SNPs allele distribution. In conclusion, results do not support a role of rs10116277 or rs1537375 SNPs in CVD risk in Spanish RA patients.

Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis.

OBJECTIVE: The methionine sulfoxide reductase A (MSRA) gene is related to oxidative stress that has been involved in the susceptibility to rheumatoid arthritis (RA) in genome-wide pathway analysis and replication studies. The aim of the present study was to determine whether the MSRA gene is implicated in susceptibility to cardiovascular (CV) disease in RA patients. METHODS: A total of 1302 patients fulfilling the 1987 American College of Rheumatism classification criteria for RA were genotyped for the MSRA rs10903323 (G/A) polymorphism. Two hundred and thirty-three (17.9%) patients experienced CV events. Human leucocyte antigen (HLA)-DRB1 genotyping was performed using molecular-based methods. Multiple logistic regression models were constructed with adjustments for gender, age at RA diagnosis, follow-up, rheumatoid shared epitope, and traditional CV risk as potential confounders. RESULTS: There were no statistically significant differences in the allele or genotype frequencies for the MSRA rs10903323 polymorphism between RA patients who experienced CV events and those who did not. However, an adjusted logistic regression model disclosed that the minor allele G yielded a marginally significant increased risk of CV events in this series of patients with RA [p = 0.05, odds ratio (OR) 1.68, 95% confidence interval (CI) 1.00-2.85]. When the logistic regression model was adjusted for anti-cyclic citrullinated peptide (anti-CCP) antibody status instead of for shared epitope, an increased risk of having ischaemic heart disease was found in patients carrying the minor allele G (p = 0.04, OR 2.00, 95% CI 1.03-3.88). CONCLUSION: The MSRA rs10903323 gene polymorphism may be implicated in the increased risk to develop CV events, in particular ischaemic heart disease, observed in RA patients.

Influence of MHCIITA rs3087456 and rs4774 polymorphisms in the susceptibility to cardiovascular disease of patients with rheumatoid arthritis.

OBJECTIVES: MHCIITA is a major regulator of MHC expression that has been reported to be involved in the susceptibility to rheumatoid arthritis (RA) and myocardial infarction. In this study we investigated the potential association of two MHCIITA gene polymorphisms with cardiovascular (CV) risk in patients with RA. METHODS: 1302 patients fulfilling the 1987 ACR classification criteria for RA were genotyped for the MHCIITA rs3087456 and rs4774 gene polymorphisms to determine the influence of MHCIITA variants in the development of CV events. The potential influence of these polymorphisms in the development of subclinical atherosclerosis was also analysed in a subgroup of patients with no history of CV events by the assessment of two surrogate markers of atherosclerosis; brachial and carotid ultrasonography to determine endothelial function and carotid artery intima-media thickness, respectively. RESULTS: No statistically significant differences in the allele or genotype frequencies for each individual MHCIITA gene polymorphism between RA patients who experienced CV events, or not, were found. This was also the case when each polymorphism was assessed according to results obtained from surrogate markers of atherosclerosis. Also, in assessing the combined influence of both MHCIITA gene polymorphisms in the risk of CV disease after adjustment for gender, age at time of disease diagnosis, follow-up time, traditional CV risk factors, and shared epitope status, patients with CV events only showed a marginally decreased frequency of the MHCIITA rs3087456-rs4774 G-G allele combination (p=0.08; odds ratio: 0.63 [95% confidence interval: 0.37-1.05]). CONCLUSIONS: Our data do not support an influence of MHCIITA rs3087456 and rs4774 polymorphisms in the increased risk of CV events of patients with RA.

Percutaneous treatment of liver failure and acute mesenteric ischaemia.

INTRODUCTION: Synchronous embolism to the superior mesenteric artery (SMA) and coeliac axis (CA) is a rare disease. REPORT: A 67-year-old man with atrial fibrillation developed acute liver failure due to an embolic occlusion of the CA and SMA, with a severe coagulation disorder. He was successfully managed with percutaneous stent placement and an exploratory laparotomy was not needed. He remains symptom-free 1 year after the procedure, and duplex follow-up showed stent patency. CONCLUSION: Endovascular techniques in patients with liver failure, no signs of peritonism, early diagnosis and high operative risk seem feasible and should be used if possible, as first-line option.

Lack of association of IL6R rs2228145 and IL6ST/gp130 rs2228044 gene polymorphisms with cardiovascular disease in patients with rheumatoid arthritis.

Interleukin-6 (IL-6) is a key mediator of inflammation in rheumatoid arthritis (RA) and its actions may be controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/ gp130) is the signal transducing subunit of the IL-6R. We assessed the influence of the IL6R and the IL6ST/gp130 genes in the risk of cardiovascular (CV) disease in RA. For this purpose, 1250 Spanish patients with RA were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional gene polymorphisms. Patients were stratified according to the presence or absence of CV events. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using two surrogate markers of atherosclerosis (flow-mediated endothelium-dependent vasodilatation and carotid intima-media thickness). No significant differences in the genotype and allele frequencies for both gene polymorphisms between patients with and without CV events were observed. It was also the case when values of surrogate markers of atherosclerosis were compared according to IL6R and IL6ST genotype frequencies. In conclusion, our results do not confirm an association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with CV disease in RA.

The stromal gene encoding the CD274 antigen as a genetic modifier controlling survival of mice with γ-radiation-induced T-cell lymphoblastic lymphomas.

Using an inter-specific subcongenic strain, Nested Recombinant Haplotype 3 (NRH3), generated between two mouse strains showing extreme differences in γ-radiation-induced thymic lymphoma susceptibility (SEG/Pas and C57BL/6J), we have identified a critical region on chromosome 19 that regulates survival of mice suffering from T-cell lymphoblastic lymphomas. Mapped on this region, the gene encoding the Cd274 ligand is able to trigger an inhibitory effect that modulates T-cell receptor (TCR) signalling and affects thymocyte maturation. Interestingly, this gene shows differential expression between thymic stromal cells from both strains in early response to a single sublethal γ-ray dose, but is inhibited in T-cell lymphoblastic lymphomas. Furthermore, we have identified several polymorphisms in the complementary DNA sequence of this gene that affect the affinity for its Cd279 receptor and are able to induce a differential rate of thymocyte apoptosis. Taken together, our data are consistent with Cd274 acting as a genetic modifier that influences the survival of γ-radiation-induced T-cell lymphoma-bearing mice. The data similarly support the idea of a co-evolution of tumour cells and associated stromal cells to generate a favourable microenvironment for T-cell lymphoma growth.