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BACKGROUND A clinically meaningful impairment of bone mass secondary to malabsorption is frequent in untreated celiac disease. In adult patients, a rigorous gluten-free diet (GFD) significantly improves, but does not always normalize, bone mineral density (BMD). The reason for this marginal response is unclear. Accordingly, we evaluated the role of both local and systemic factors for bone loss in celiac patients on long-term GFD. STUDY In a prospective cohort, 22 patients with low lumbar and/or femoral BMD and 22 with normal BMD underwent bone and mineral metabolism evaluation: we tested calcium, phosphate, parathyroid hormone, and vitamin D; telopeptide of type I collagen, a bone resorption index; propeptide of type I procollagen, a bone neoformation index; receptor antagonist of NF-kB ligand, an osteoclast-stimulating factor; osteoprotegerin (OPG), a decoy receptor for RANKL. Sunlight exposure and physical exercise were measured. RESULTS Patients with bone loss showed prevalently osteopenia, severe osteoporosis was rare. In comparison with normal BMD patients, they showed higher serum OPG, telopeptide, and lower serum propeptide, suggesting an increased bone turnover. Lumbar T-score was negatively correlated with OPG, telopeptide and RANKL and positively with propeptide. Propeptide was negatively correlated with OPG and telopeptide. OPG was positively correlated with telopeptide. CONCLUSIONS The persistent activation of inflammation should be considered the main pathophysiological mechanism for bone defect in celiac disease patients with bone loss on long-term GFD. High levels of OPG, an attempt at protective mechanism, and low levels of propeptide of type I procollagen, reflecting an insufficient matrix production, characterize this subgroup of patients.

Research Question Infections and/or inflammation processes of male genital tract are highly prevalent and often associated with risk of infertility. These conditions represent a possible cause of leukocytospermia, which is still under debate. Leukocytes are key-factors to reactive oxygen species (ROS) production and the increase of ROS in semen fluid is associated with the worsening of semen parameters. At present, there are not appropriate andrological tests to identify asymptomatic inflammatory conditions when the amount of leukocytes is in the normal range. Design We studied the innate immunity profile of myeloperoxidase and lactoferrin (MPO/LAC) proteins expressed in the semen fluid of 39 men evaluated for couple infertility, in the absence of leukocytospermia. Results The presence of both MPO and LAC proteins was associated with a decrease of sperm concentration and of progressive/total motility, whereas the increase of MPO-/LAC + indicated a worse sperm morphology. It is worth to report the predictive potential of MPO+/LAC + pattern (above 4.36 %) as a biological marker to distinguish normozoospermic from pathological patients. Conclusion Our findings indicate MPO/LAC analysis as a potential diagnostic tool to identify asymptomatic conditions eventually related to male infertility, even when the number of leukocytes in semen fluid is below 1 million/mL.

BackgroundHydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin.MethodsNew user cohort studies were conducted including 16 severe adverse events (SAEs). Rheumatoid arthritis patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine and followed up over 30 days. Self-controlled case series (SCCS) were conducted to further establish safety in wider populations. Separately, SAEs associated with hydroxychloroquine- azithromycin (compared to hydroxychloroquine-amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, Netherlands, Spain, UK, and USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (CalHRs) according to drug use. Estimates were pooled where I2ResultsOverall, 956,374 and 310,350 users of hydroxychloroquine and sulfasalazine, and 323,122 and 351,956 users of hydroxychloroquine-azithromycin and hydroxychloroquine-amoxicillin were included. No excess risk of SAEs was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. SCCS confirmed these findings. However, when azithromycin was added to hydroxychloroquine, we observed an increased risk of 30-day cardiovascular mortality (CalHR2.19 [1.22- 3.94]), chest pain/angina (CalHR 1.15 [95% CI 1.05-1.26]), and heart failure (CalHR 1.22 [95% CI 1.02- 1.45])ConclusionsShort-term hydroxychloroquine treatment is safe, but addition of azithromycin may induce heart failure and cardiovascular mortality, potentially due to synergistic effects on QT length. We call for caution if such combination is to be used in the management of Covid-19.Trial registration numberRegistered with EU PAS; Reference number EUPAS34497 (http://www.encepp.eu/encepp/viewResource.htm?id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine.Funding sourcesThis research received partial support from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) and Senior Research Fellowship (DPA), US National Institutes of Health, Janssen Research & Development, IQVIA, and by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea [grant number: HI16C0992]. Personal funding included Versus Arthritis [21605] (JL), MRC-DTP [MR/K501256/1] (JL), MRC and FAME (APU). The European Health Data & Evidence Network has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. No funders had a direct role in this study. The views and opinions expressed are those of the authors and do not necessarily reflect those of the Clinician Scientist Award programme, NIHR, NHS or the Department of Health, England.

Introduction Obstructive sleep apnea (OSA) is a recognized risk factor for ischemic stroke; however, there is a paucity of studies devoted to modifying stroke risk factors in patients with OSA. We aimed to evaluate the prevalence and treatment of stroke risk factors in newly diagnosed OSA patients. Methods We evaluated consecutive patients with an OSA diagnosis made within 12 months and CHADS2 score of >2, consistent with high risk for atrial fibrillation. The patients completed polysomnography, sleep questionnaires, and systematic assessments for demographic variables, vascular risk factors, and medication use. Participants also completed up to four weeks of ambulatory cardiac monitoring. A six-month follow-up visit screened for new hospitalizations associated to vascular events and use of new anticoagulants or antiplatelet therapy. Results The sample consisted of 87 patients, mean age 59±8 years, 53% women, and 69% of Hispanic/Latino background. The mean BMI was 35±9. Hypertension was seen in 57% and diabetes mellitus in 33% of the sample. The mean apnea-hypopnea index was 41±27 events/hour. Atrial fibrillation was detected in 3% of the sample through prolonged monitoring. At six-month follow-up, 9% of the sample was hospitalized due to stroke, transient ischemic attack, or coronary artery disease, while 13% reported use of anticoagulants and 38% antiplatelet therapy. Conclusion In this high risk sample of OSA patients, there was a high prevalence of cerebrovascular events and use of medical treatment for secondary stroke prevention. Future studies evaluating the treatment of vascular risk factors in OSA can provide strategies to minimize stroke occurrence. Support Boehringer Ingelheim

Background:Apremilast is a non-biologic systemic agent approved for the treatment of plaque psoriasis, oral ulcers of Behcet’s disease and PsA with proven efficacy in clinical trials [1,2]. However, more real-world evidence of apremilast use and effectiveness is needed to identify the patient profile most likely to benefit from this treatment [3].Objectives:To evaluate the persistence of apremilast treatment in patients with PsA naïve to biological treatments in routine clinical practice and assess its effectiveness. Baseline clinical characteristics on patients who started apremilast were also evaluated.Methods:Observational, prospective, multicenter (20 centers) study including consecutive adult patients with PsA naïve to biological therapies who had started treatment with apremilast during the previous 5 to 7 months and were followed-up during 12 months. Variables recorded were persistence of treatment with apremilast at 6 months (6mo) and number of swelling joints, presence of enthesitis and dactylitis, and disease activity, measured by the Disease Activity in Psoriatic Arthritis (DAPSA) score and Physician Global Assessment (PGA) of psoriasis, collected at baseline (BL) (i.e., apremilast treatment start) and 6mo; comorbidities were retrospectively collected at BL. Categorical and quantitative variables were compared using McNemar’s and Wilcoxon test, respectively. Data sets analyzed included all assessable patients.Results:Of the 60 patients recruited at the time of this interim analysis, 54 (90.0%) [mean (SD) age 53.4 (13.9) years] were assessable; 41 (75.9%) of these continued treatment with apremilast at 6mo. At BL, 34 (63.0%) patients had at least one comorbidity, the most frequent being cardiovascular disease (n=15, 27.8%), including hypertension (n=8, 14.8%), metabolic/endocrine disease (n=18, 33.3%), including obesity (n=8, 14.8%) and dyslipidemia (n=10, 18.5%). Psychiatric disease (i.e., depression) (n=5, 9.3%) and neoplasia (n=8, 14.8%) were also observed. The number of swelling joints decreased from median (Q1, Q3) 4.0 (2.0, 7.0) at BL to 1.5 (0.0, 4.0) at 6mo (p=0.0012). Patients with dactylitis and enthesitis decreased from 19 (35.2%) and 16 (29.6%) at BL to 10 (18.5%) and 9 (16.7%) at 6mo (p=0.0225 and p=0.0391), respectively. The distribution of patients in the different disease activity categories according to DAPSA scale changed between BL and 6mo, indicating a favorable disease evolution (Figure 1 next page). According to PGA, at BL (n=53), disease activity was categorized as mild in 18.0%, as moderate in 72.0%, and as severe in 10% of patients and, at 6mo (n=54), as mild in 70.6%, as moderate in 25.5%, and as severe in 3.9% of patients. Fifteen (27.8%) patients interrupted treatment permanently (n=13, 24.1%) or temporarily (n=2, 3.7%), due to no/partial response (n=8, 14.8%), tolerability issues leading to adverse events (n=3, 5.6%), patient decision (n=2, 3.7%), and other reasons (n=2, 3.7%) after a mean (SD) treatment of 3.05 (2.20) months.Conclusion:Forty-one (75.9%) patients with PsA naïve to biological therapies were treated with apremilast during ≥6 months. After treatment, the number of swelling joints, and dactylitis and enthesitis decreased and changes in disease activity according to DAPSA and PGA pointed to a favorable disease evolution. Apremilast treatment provides a clinical benefit to patients with PsA treated in clinical practice.References:[1]Gossec L, Smolen JS, Ramiro S, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis. 2016 Feb 10;75(3):499 LP-510[2]Torres T and Puig L. Apremilast: A novel oral treatment for psoriasis and psoriatic arthritis. Am J clin Dermatol. 2018 Feb;19(1):23-32[3]Coates LC, Kavanaugh A, Mease PJ et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015. Treatment Recommendations for Psoriatic Arthritis. Arthritis Rheumatol. 2016;68(5):1060– 71.Disclosure of Interests:Jordi Gratacos-Masmitja Speakers bureau: MSD, Pfizer, AbbVie, Janssen Cilag, Novartis, Celgene y Lilly., Consultant of: MSD, Pfizer, AbbVie, Janssen Cilag, Novartis, Celgene y Lilly., José Luis Álvarez Vega Speakers bureau: Abbvie, Amgen, MSD, Lilly, Roche, Esteve, UCB, Menarini, Pfizer, GSK, BMS, Janssen, Novartis, Gebro., Consultant of: Abbvie, Amgen, MSD, Lilly, Roche, Esteve, UCB, Menarini, Pfizer, GSK, BMS, Janssen, Novartis, Gebro., Grant/research support from: Abbvie, Amgen, MSD, Lilly, Roche, Esteve, UCB, Menarini, Pfizer, GSK, BMS, Janssen, Novartis, Gebro., Emma Beltrán Speakers bureau: Abbvie, Bristol, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Consultant of: Abbvie, Bristol, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, ANA URRUTICOECHEA-ARANA: None declared., C. Fito-Manteca: None declared., Francisco Maceiras: None declared., Joaquin Maria Belzunegui Otano Speakers bureau: Lilly, Amgen, Novartis, Abbvie, Janssen., J. Fernández-Melón Speakers bureau: Amgen SL, Eugenio Chamizo Carmona: None declared., Abad Hernández Speakers bureau: MSD, Abbvie, Pfizer, Kern, Novartis, Biogen, Sandoz, Amgen, Sanofi, Lilly, Roche and Janssen-Cilag, Consultant of: MSD, Abbvie, Pfizer, Kern, Novartis, Biogen, Sandoz, Amgen, Sanofi, Lilly, Roche and Janssen-Cilag, Grant/research support from: MSD, Abbvie, Pfizer, Kern, Novartis, Biogen, Sandoz, Amgen, Sanofi, Lilly, Roche and Janssen-Cilag, Inmaculada Ros Consultant of: Amgen, Grant/research support from: MSD, Roche, Novartis, lilly, Pfizer, Amgen, Eva Pascual Shareholder of: Amgen, Employee of: Amgen, Juan Carlos Torre Speakers bureau: Amgen, Lilly, Novartis, Janssen, Pfizer, Consultant of: Amgen, Lilly, Novartis, Janssen, Pfizer, Grant/research support from: Amgen, Lilly, Novartis, Janssen, Pfizer.

Objectives The purpose of the study was to evaluate the mucosal immune response in women affected by primary human papillomavirus (HPV) infection, in comparison with HPV-negative women with no previous history of HPV. Methods A case-control study comparing the activity of myeloperoxidase (MPO) and lactoferrin (LF) between 19 HPV-positive and 19 HPV-negative women matched for age. Plasmatic and cervicovaginal levels of polymorphonuclear neutrophils (PMN) exhibiting MPO and LF receptors were measured using cytofluorimetric analysis and expressed as mean of percentages. Results Cervicovaginal levels of MPO-/LF- PMN were lower among HPV-negative women, with a mean rate of 18.81% (SD, 21.38), as opposed to a mean rate of 35.56% (SD, 21.02) (P = 0.020) in HPV-positive women. A similar significant difference was not proven in plasma. The mean rates of plasmatic levels of MPO-/LF- PMN were 36.21% (SD, 16.87) and 36.93% (SD, 10.54) (P = 0.875) in cases and controls, respectively. All patients were evaluated 1 year later, and only 6 cases became negative. Conclusions The presence of MPO-/LF- PMN has been considered as a marker of lower rate of apoptosis of HPV-infected cells. This could explain why HPV-positive women are less capable to deal with a primary infection.

Background/Aims: Patients with type 1 diabetes mellitus (T1DM), autoimmune thyroiditis (ATD), and celiac disease (CD) are at increased risk for developing other autoimmune diseases. We evaluated zinc transporter 8 (ZnT8) prevalence in patients with ATD and/or CD in order to define the usefulness of ZnT8 autoantibodies for prediabetes screening. Methods: Eighty-one young patients with ATD and/or CD were included in the study; 32 subjects with clinical onset of T1DM were enrolled as a control group. GAD65, IA-2, and ZnT8 antibodies were measured. An intravenous glucose tolerance test, C-peptide, glycosylated hemoglobin levels, and genomic analysis of HLA-DQA1* and -DQB1* were also considered in patients positive for autoantibodies. Results: The ZnT8 prevalence was higher in T1DM patients than in patients with other autoimmune diseases (p < 0.001); positive ZnT8 detection was found in 2 ATD (p = 0.004) and 3 ATD + CD (p = 0.04) patients. Positive ZnT8 was associated with GAD65 (p = 0.01) but not with IA-2 positivity. No correlation between ZnT8 detection and the number of T1DM-susceptible HLA-DQ heterodimers was found. Pathological C-peptide levels and insulin response were found in subjects with islet autoimmunity and genetic susceptibility. Conclusion: ZnT8 autoantibodies detection in ATD and/or CD patients is low, and routine ZnT8 screening is not justified. ZnT8 evaluation may be recommended in subjects with autoimmune diseases as a marker for predicting compromised insulin secretion.

Background Some cardiovascular risk factors (CVRF) have been related to poorer responses to biological therapy 1 . We aimed to evaluate the potential link between the MDA response and the presence of CVRF in patients treated with traditional and/or biological DMARDs. Objectives The objective has been to evaluate the potential association beetween classic CVRF and the probability of reaching an MDA response in PsA patients. Methods Cross-sectional study carried out at 25 rheumatology outpatient clinics in patients who fulfilled the Classification for Psoriatic Arthritis (CASPAR) criteria with at least one year disease duration, and treated with biological or conventional synthetic (cs) DMARDs according to routine clinical practice in Spain. Patients were considered in MDA if they met at least 5/7 of the MDA criteria 2 . The relationship between MDA and CVRF was evaluated by uni and multivariate analyses. Results 227 patients were included, 133 (58.6%) were in MDA state (52% on anti-TNFα monotherapy, 24% on csDMARD monotherapy, 24% on anti-TNFα in combination with csDMARD). Among the classic CVRF, tobacco (crude OR: 0.54), sedentary lifestyle (crude OR: 1.95), hyperuricemia (crude OR: 2.01) and obesity (crude OR: 1.54) were related to the likelihood of MDA in the univariate model (p Conclusions Contrary to what has been found in other studies, in this cross-sectional multicenter study we could not find any relationship between traditional CVRF (except for sedentary lifestyle) and MDA. In any case, patients with psoriatic disease should be encouraged to maintain healthy lifestyle habits. References Ogdie A, Eder L. Improving cardiovascular health and metabolic comorbidities in patients with psoriatic arthritis. Int J Clin Rheumatol 2015; 10(6):451–459. Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis 2010; 69(1):48–53. Acknowledgements This study was funded by Pfizer. Disclosure of Interest None declared

INTRODUCTION Completion thyroidectomy plays an important role in the management of patients with thyroid cancer. The aim of this study is to determine the indications for and timing of a second surgery, as well as surgical complications. MATERIAL AND METHODS Operative reports, as well as the hospital and outpatient records of 686 consecutive patients, who had undergone surgery for differentiated thyroid cancer, were reviewed. Among these, 68 (9,9%) patient records of a completion thyroidectomy for cancer were analyzed. RESULTS The mean time interval between the first and second operation was 3.6 months (range: 1-9). Post-operative complications occurred in 9 patients (12,9%). Among three patients with inferior laryngeal nerve palsy (4,4%) one had definitive palsy (1.4%). Hypoparathyroidism occurred in 6 patients (8,8%) being permanent in one of them (1.4%). No significant difference either for definitive inferior laryngeal nerve lesions (p = 0.9) or for definitive hypocalcemia (p = 1) was found between the groups of patients who had a completion thyroidectomy and those who had a one-step total thyroidectomy for cancer. CONCLUSIONS Correct indications for re-operation, total lobectomy as a primary surgical procedure as well as lateral access to the residual thyroid gland could all reduce the high risks of complications related to this kind of surgery.

Background An IgG response to allergens has been well characterized, however few studies have investigated IgG and IgG4 production in normal subjects. Objective The aim of this study was to find reference values for six common inhalant allergens in a population of healthy children. Methods One hundred and six females and 107 males, from one to 12 years old, were studied assessing the serum levels of specific total IgG and IgG4 for six allergens. Results A homogeneous behaviour was not observed, among allergens or among patient subgroups. Some allergens increased, while others decreased from pre-school to elementary school age. In females, this decrease was less evident, while increases were more evident. Differences were found between seasonal and perennial allergens, the latter showing higher values. We also observed differences between temporal trends of IgG and IgG 4 in some patient groups. Percentiles of distributions have been provided as reference values, for all subgroups that were significantly different. Conclusion Defining an individual profile would be useful for characterising the specific humoral response.

Meningococcal disease (MD) remains an important infectious cause of life threatening infection in both industrialized and resource poor countries. Genetic factors influence both occurrence and severity of presentation, but the genes responsible are largely unknown. We performed a genome-wide association study (GWAS) examining 5,440,063 SNPs in 422 Spanish MD patients and 910 controls. We then performed a meta-analysis of the Spanish GWAS with GWAS data from the United Kingdom (combined cohorts: 897 cases and 5,613 controls; 4,898,259 SNPs). The meta-analysis identified strong evidence of association (P-value ≤ 5 × 10−8) in 20 variants located at the CFH gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR) = 0.62, 95% confidence interval (C.I.) = 0.52–0.73; P-value = 9.62 × 10−9). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR = 0.64, 95% C.I.) = 0.55–0.76, P-value = 3.25 × 10−8). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of CFH with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease.

The combination of Low Intensity Laser Therapy and Photodynamic Therapy constitutes a minimal invasive and highly selective alternative for the treatment of skin tumors. Photodynamic effectiveness, specially the absence of recurrence, highly depends on the type of tumor, as well as on several parameters such as those related with the optical source. Therefore it is important to have predictive tools to provide an appropriate treatment planning. This work proposes the use of a complex predictive model that includes a three-dimensional meshing of the considered tumor geometry and the optical propagation therein by a three-dimensional Monte Carlo method. The proposed tool is applied to three different types of skin tumors, squamous cell carcinoma, nodular and infiltrative basal cell carcinomas. The estimated volume of treatment, depending on the tumor type and source parameters, allows an appropriate treatment planning in order to avoid undesirable tumor recurrence.

Objectives: To determine the predictive factors of clinical response to infliximab in patients with refractory psoriatic polyarthritis. Methods: A multicentre open study which included 69 patients with psoriatic polyarthritis refractory to methotrexate (15 mg/week at least for 8 weeks). Patients were treated with infliximab 5 mg/kg every 8 weeks in addition to their stable doses of methotrexate. A major clinical response was defined by the ACR50 at week 38. Logistic regression analysis was performed to analyse which of the following measures at the start of treatment were associated with an ACR50 response: demographic and clinical characteristics, duration of disease, tender and swollen joint counts, involvement of large joints (knee or hip, or both), erythrocyte sedimentation rate, C reactive protein (CRP), Health Assessment Questionnaire disability index, axial involvement, and the presence of erosions at baseline. Results: In an intention to treat analysis 30/69 (44%) patients achieved an ACR50 response. In the univariate analysis both the presence of large joint involvement and severe disability were associated with a poor clinical response. In a multivariate logistic regression analysis high CRP values were independently associated with a good therapeutic response (odds ratio (OR) = 18.7; 95% confidence interval (CI) 1.8 to 181.6; p = 0.011). In contrast, large joint involvement and severe disability were associated with a poor response, which reached significance for large joint involvement (OR = 29.3; 95% CI 3.2 to 266.3; p = 0.003). Conclusion: A lower disability and, in particular, the absence of large joint involvement and higher CRP serum levels at the start of infliximab treatment are factors that seem to influence the probability of achieving a good therapeutic response in patients with psoriatic arthritis.

To analyse the relative role of HLA-DR antigens in the susceptibility to, and clinical expression of psoriatic arthritis (PsA).A retrospective cohort study of 120 patients with PsA who were assessed according to a standard protocol. Patients were classified in accordance with the predominant pattern observed in the last 5 years of disease evolution: polyarthritis (n = 33), oligoarthritis (n = 45), and spondylitis (n = 42). HLA-Cw gene typing was done by the polymerase chain reaction (PCR) sequence-specific oligonucleotide probes (PCR-SSOP) method, while HLA-DR and B27 typing were performed by serological methods. The distribution of HLA-DR and Cw antigens was also analysed in 50 patients with psoriasis alone. One hundred and seventy subjects from our general population served as controls.No definite association was found between HLA-DR alleles and the risk of psoriasis or PsA. HLA-DR4 was found to be under-represented in arthritic patients [probability (p) = 0.03]. HLA-DR7 showed association with oligoarthritis [odds ratio (OR) 6, 95% confidence interval (CI): 2-16, corrected probability (Pc) = 0.01], whereas HLA-DR8 appeared to be related to the risk of polyarthritis (OR 9.5, 95% CI: 2-42, Pc = 0.02). HLA-Cw*0602 conferred risk for psoriasis (Pc0.00001), but not for PsA. As expected, HLA-B27 appeared to be over-represented in patients with spondylitis (p = 0.03).This is the first report that associates HLA-DR8 with psoriatic polyarthritis. Although HLA-DR antigens have a marginal role in PsA or psoriasis susceptibility, they may be relevant to the modulation of the clinical expression of PsA. These HLA data add support to the classification of PsA into three disease subsets.

Objectives: To analyze the clinical features of uveitis in psoriatic arthritis (PsA) and to investigate the factors predicting its appearance. Patients and Methods: Retrospective cohort study (1991-2000) of 71 patients diagnosed with PsA according to the criteria of Moll and Wright. All patients were studied according to a standard protocol. The group was divided into 3 articular categories: axial, oligoarticular, and polyarticular. Human leukocyte antigen (HLA)-Cw typing was performed by the polymerase chain reaction–sequence specific oligonucleotide probes (PCR-SSOP) method in 65 patients and in 177 healthy donors. HLA-DR typing was done by serologic methods in the 71 patients and in 82 healthy donors from the same racial and geographic origin. The HLA-B27 allele also was tested among the study population. All subjects with possible inflammatory ocular disease received a complete ophthalmologic examination at the Ophthalmology Department of our hospital. Only patients with uveitis were analyzed. Univariate and multivariate analyses were applied. Results: Thirteen patients had uveitis (18% of this series), 4 (31%) had an insidious onset, and the remaining had acute-onset uveitis. Five cases (39%) had bilateral-simultaneous uveitis. Ten (77%) presented with anterior uveitis only, 2 with anterior and posterior pole involvement, and only 1 case with isolated posterior pole involvement. Four patients needed oral corticosteroids; 2 of them also used immunosuppresive drugs. None of our patients developed sequelae or complications. In univariate analysis, uveitis was associated with inflammatory back pain ( P =.02), sacroiliac pain ( P =.001), syndesmophytes ( P =.001), bilateral sacroileitis ( P =.0001), HLA-DR13 ( P =.002), and HLA-B27 ( P =.026). In multivariate analysis, the predictive factors for uveitis were bilateral sacroileitis (OR 17, 95% CI: 3.7-76, P =.0002), HLA-DR13 (OR 24, 95% CI: 3.78-150, P =.0056), and syndesmophytes (OR 9.7, 95% CI: 0.97-97, P =.05). Conclusions: Insidious onset, bilaterality, posterior pole involvement, and chronicity are common in PsA patients with uveitis. In this study, extensive axial involvement (bilateral sacroileitis and syndesmophytes), and the HLA-DR13 antigen were the best predictors for the appearance of uveitis. Semin Arthritis Rheum 31:264-270. Copyright 2002, Elsevier Science (USA). All rights reserved.

The aim of this study was to analyse retrospectively the prevalence and the clinical features of clinically asymptomatic axial involvement in patients with psoriasis and axial radiological features of spondyloarthropathy (PsSpA). We performed a cross-sectional study based on the clinical records of 70 patients, 44 men and 26 women, with a mean age of 48.7+/-14.2 years. PsSpA was defined by the presence of radiographic sacroiliitis (SI) greater than or equal to grade 2, and/or any other typical radiological sign of spondylitis in patients with psoriasis. When the radiological signs were present in the absence of inflammatory back pain and/or buttock pain, patients were grouped as having asymptomatic axial disease. HLA-B27 was determined by serological methods in the 70 patients and in 82 healthy controls from our general population. Fourteen patients (20%), 11 with radiological SI, two with facet joint erosion-fusion and one with aseptic discitis, showed no evidence of symptomatic spinal disease. Twenty-nine patients (41%) showed cervical spine disease (CSD), but only 17 of them (58.6%) had pain and rigidity at this level, whereas 12 (41.4%) did not show clinical symptoms. CSD was associated with duration of arthritis (P = 0.043) and peripheral erosions (P = 0.037). HLA-B27 correlated well with bilateral SI (P = 0.002) and PsSpA (P0.0004, RR 6.4), but showed no association with unilateral SI nor with syndesmophytes or asymptomatic disease. Univariate analysis demonstrated associations between symptomatic disease and longer duration of arthritis (P = 0.041) and higher IgM values (P = 0.05). There is a high prevalence of asymptomatic involvement in patients with PsSpA The significance of these asymptomatic changes is not known, but they probably represent a common characteristic of spondyloarthropathies rather than a specific feature associated with psoriasis.

Recent findings, such as the presence of diseased cortical microvasculature in Alzheimer’s dementia (DAT)Z and the reduced cerebral blood flow in those at risk for DAT: suggest that brain hypoperfusion may be pathogenic in the etiology of this disease. To assess this possibility in an animal model of cerebral hypoperfusion, we permanently ligated both common carotid arteries in the early middle-aged (-10 months old) Sprague Dawley rats? In Wistar rats, this procedure (2-VO) chronically (and perhaps permanently) reduces cortical and hippocampal blood flow by approximately 30%.’ Using this model, we do not observe the behavioral and neuropathologic sequelae that are characteristic after transient ischemia in the rat. Surgery is performed with the rats under barbiturate plus ketamine anesthesia. Ketamine may prevent the immediate neurodegenerative consequences of the relatively severe reduction in blood flow resulting from the carotid ligation procedure in the early postligation period. 2-VO progressively impairs the ability of the rats to perform the Morris water maze. This task requires that the rat escape to a submerged platform in a circular pool of water. The rats use extra-maze cues to guide their navigation to the platformcontaining area. As shown in FIGURE 1(upper panel), the Morris maze impairment appears as early as 7 days post surgery and persists over time despite repeated training. It is unlikely that this early-appearing deficit reflects impaired learning or memory mechanisms. A more plausible explanation is that the spatial ability of the rats is compromised by 2-VO and that this deficit is exacerbated by the moderately stressful water maze task. In support of this hypothesis, we have shown that 2-VO rats demonstrate a greater plasma corticosterone elevation to water immersion than do sham-operated animals: As well, presurgical training attenuates the deficit, indicating that if the animals are allowed to adapt to the stress of water immersion prior to 2-VO surgery, they are capable of normal performance. It should be noted that spatial disorientation and “getting lost” are characteristics of DAT and are also anxiogenic and thus self-fueling. In rats that have been pre-trained to perform the radial arm maze task, 2-VO causes a strikingly late-emerging increase in errors. Rats will effectively forage for food located on the arms of this maze, shunning arms that are never baited with food (unbaited-arm entries, a measure of long-term, habit memory) and avoiding

Background Biological therapies have greatly improved the management of psoriatic arthritis (PsA). Minimal disease activity (MDA) has become the optimal target in the treatment of PsA, waiting for a standardized definition of remission. Knowing the proportion of PsA patients in the MDA state could inform on the quality of management of these patients. Objectives To determine the prevalence of MDA (Coates et al.) in patients with PsA in Spain as well as its potential predictors. To evaluate the association between MDA and the impact of disease, as evaluated by the PsA Impact of Disease questionnaire (PsAID). Methods This was a non-interventional, cross-sectional, multicenter study, which aimed to evaluate the prevalence of MDA in a Spanish population with PsA. The study was carried out at 25 rheumatology outpatient clinics between May/2014 and Feb/2015. A total of 238 adult patients diagnosed with PsA (CASPAR criteria) with at least one year disease duration and treated with biological and non-biological DMARDS were included. Finally, 227 were considered evaluable. Clinical, demographic, treatment data, physical function (HAQ) and quality of life (PsAID) were obtained. According to the latter, the patient acceptable symptoms state (PASS) has been defined as a PsAID value Results Overall, 133 out of 227 (58.6%) subjects achieved MDA at study entry. Seventy-seven (37.9%) and 137 (64.4%) patients reached joint and skin remission, respectively. However, a fair relationship between MDA and joint remission (k=0.390) and a slight relationship between MDA and skin remission (k=0.178) were observed. Patients in MDA state had better functional capacity by HAQ (0.35 ± 0.47) vs non-MDA patients (0.79 ± 0.63), p Conclusions MDA was achieved by nearly 60% of patients in this study reflecting clinical practice in agreement with results from earlier studies. These patients had better functional state and most of them reached an acceptable symptoms state according to the PsAID. Our results of predictors to achive MDA should be confirmed in further prospective studies. References Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis. 2010 Jan;69(1):48–53. Perrotta FM, Marchesoni A, Lubrano E. Minimal Disease Activity and Remission in Psoriatic Arthritis Patients Treated with Anti-TNF-alpha Drugs. J Rheumatol. 2015 Dec 15. pii: jrheum.150805. Haddad A, Thavaneswaran A, Ruiz-Arruza I, Pellett F, Chandran V, Cook RJ et al. Minimal disease activity and anti-tumor necrosis factor therapy in psoriatic arthritis. Arthritis Care Res (Hoboken) 2015;67(6):842–847. Acknowledgement This work has been funded by Pfizer Disclosure of Interest None declared

To analyse the factors predicting erosive-deforming arthropathy in patients with psoriatic arthritis (PsA).A prospective cohort study was undertaken with 71 patients diagnosed as having PsA (44 men and 27 women, mean age 47 (SD 12) years). At the recruitment period patients had disease without evidence of radiological damage. Patients were studied and followed up according to a standard protocol from January 1991 to June 2001. Erosive and deforming disease was defined by the presence of erosions, joint space narrowing, subluxation, and/or ankylosis of peripheral joints. Univariate and multivariate analyses were performed to evaluate factors predicting erosive and deforming disease.At the end of the study 32 of 71 (45%) patients had developed erosive and deforming disease. Among them, 18 of 32 (56%) had a polyarticular onset, two of 32 (6%) showed a distal interphalangeal joint disease onset, six of 32 (19%) presented with oligoarthritis, and six of 32 (19%) presented with axial disease as the form of disease onset (p=0.001). Mean time to detect erosions or joint space narrowing was 20 (SD 4) months. Men showed fewer erosions than women (p=0.05). Patients who carried the HLA-B27 antigen showed less erosive disease than patients who lacked it (p=0.05). Patients with erosive and deforming disease had poorer functional performance than those without it as measured with the Health Assessment Questionnaire (HAQ) and the American College of Rheumatology (ACR) criteria (p0.05 with both measurements). In multivariate analysis, only a polyarticular onset remained as an indicator of erosive and deforming disease (odds ratio (OR) 37, 95% confidence interval (95% CI) 3.6 to 88, p=0.025).A polyarticular onset (five or more swollen joints) of PsA was the unique independent risk factor which predicted the appearance of erosive and deforming disease over time. These data may be useful for clinicians treating patients with PsA, as it may guide treatment towards a more aggressive and earlier intervention.

This paper describes a process for achieving oil spill detection in satellite images acquired after tanker accidents. These images have been treated with image processing techniques, such us image equalization, image binarization and morphological operations, to obtain the residue segmentation. Once the oil slick is segmented and localized in the image, an active contour is generated around it and fitted to it. The active contour provides useful information about the shape and localization of the oil spill, even providing an estimation of the deformation and the displacement that it could suffer over the time. This information could allow the evolution of residues dumped at sea to be tracked. The validity of this process is demonstrated using several ENVISAT-ASAR images acquired over several regions (Spanish, Philippine and Korean coasts), in which a tanker accident has occurred and as a consequence oil spillage has taken place.

In this paper we introduced an alternative view of text mining and we review several alternative views proposed by different authors. We propose a classification of text mining techniques into two main groups: techniques based on inductive inference, that we call text data mining (TDM, comprising most of the existing proposals in the literature), and techniques based on deductive or abductive inference, that we call text knowledge mining (TKM). To our knowledge, the TKM view of text mining is new though, as we shall show, several existing techniques could be considered in this group. We discuss about the possibilities and challenges of TKM techniques. We also discuss about the application of existing theories in possible future research in this field.

Cervical spondylitis has been reported in 35%-75% of patients with psoriatic arthritis (PsA), and this likely represents the highest frequency of cervical involvement among the spondyloarthropathies. Although 2 patterns of cervical spondylitis have been recognized in PsA, this may reflect a lack of a satisfactory definition of cervical spondylitis in PsA. In a retrospective cross-sectional study, we analyzed the clinical records of 100 consecutive patients recruited at a single university hospital who were diagnosed as having psoriatic spondyloarthropathy on the basis of radiographic sacroiliitis. All patients were involved in a clinicoradiologic study of the cervical column to evaluate the frequency and the predictors of this involvement. Forty-one patients showed radiographic signs of cervical involvement and 24 of them (58.5%) complained of cervical pain and stiffness, whereas 17 (41.5%) had radiologic disease with no symptoms. Arthritis duration (odds ratio, 1.08; 95% confidence interval, 0.99-1.19; p < 0.05) and peripheral erosive disease (odds ratio, 2.5; 95% confidence interval, 1.91-6.92; p < 0.05) were found to be associated with cervical spondylitis development. This study showed a high frequency of cervical spondylitis among patients with psoriatic spondyloarthropathy, confirming previous reports. Although none of our patients developed neurologic sequelae, this report also showed that clinical symptoms of cervical pain and stiffness are not a universal predictor of involvement of the cervical spine, and therefore, patients with PsA with longer disease duration and erosive disease should be screened radiologically to detect those cervical lesions (i.e., atlantoaxial subluxation) with potential catastrophic complications.

La reconstrucción mamaria tras mastectomía se realiza primordialmente para proporcionar calidad de vida a la paciente. Este estudio se desarrolló para valorar la satisfacción y calidad de vida de las pacientes reconstruidas mediante colgajo D.I.E.P. (Deep Inferior Epigastric Perforator) y evaluar el resultado estético de la reconstrucción. Treinta y tres pacientes, de 51 reconstrucciones mamarias con colgajo DIEP realizadas entre enero de 2000 y noviembre de 2004 fueron preguntadas acerca de aspectos generales relativos a la cirugía, imagen corporal y sensación subjetiva. El resultado de imagen corporal fue evaluado por dos observadores externos, un cirujano plástico y una enfermera, además de por la propia paciente. Para valorar la reconstrucción mamaria, se utilizó una escala de 4 puntos. La satisfacción general de nuestro estudio fue más elevada que la observada en estudios precedentes. Hemos conseguido una valoración alta en simetría, dentro de los parámetros objetivos y en integridad corporal entre los subjetivos. Hemos encontrado una correlación alta entre las respuestas de los observadores comparada con las respuestas de las propias pacientes. Por último, hemos visto una fuerte correlación entre integridad corporal y satisfacción general

This work explains an industrial application of neural networks for use in a robotic pick-up process. The neural network has to obtain the pose of a piece in order for it to be picked up by a robot arm. Compared with other methods, the use of neural networks permits obtaining a quick estimation of this pose. This work evaluates different configurations of neural networks in order to estimate the most adequate one to solve this application problem.

El objetivo de este trabajo es analizar el comportamiento metatarsal durante la marcha en rampa ascendente y descendente en individuos sanos mediante la utilización del sistema de plantillas podométricas Pdm 240. Hemos estudiado los parámetros temporales de la marcha y las presiones que se registran en el retropié, el antepié, y, dentro de éste, en cada una de las cabezas metatarsales, durante el ciclo y sus fases, mientras caminan en un tapiz rodante a 3,5 Km/h con una pendiente del 15%. De forma global se comprueba que durante el ciclo de la marcha, el retropié soporta mayor pico de presión en inclinación descendente, mientras que el antepié lo hace en pendiente positiva. Si se analiza cada metatarsiano por separado se observa que los valores de presión más altos se registran en rampa ascendente. La localización de estos picos de presión difiere según las fases del apoyo: en rampa ascendente se observan en la fase de apoyo medio y en pendiente negativa se reparten entre esa misma fase (M1, M4 y M5) y la de contacto de antepié (M2 y M3). Durante el ciclo, M1 registra mayor porcentaje de presión en inclinación positiva, y M5 lo hace en rampa descendente. The aim of this paper is to study the behaviour of the metatarsals in healthy individuals while walking uphill and downhill through the use of the podometric insole system Pdm 240. We have studied the walking temporal patterns and the pressures registered on the hindfoot and the forefoot, and, within the latter, on each of its metatarsal heads, during the stride and its phases, while the individuals walked on a treadmill at 3.5 Km/h on a 15% gradient. We found that the hindfoot bears more pressure while walking downhill whereas the forefoot bears it walking uphill. If we analyse each metatarsal separately we will see that the highest pressure values are registered when walking uphill. The location of these peaks varies according to the different phases within stance: while walking uphill, they are observed on the midstance phase, and while walking downhill, on that same phase (M1, M4 and M5) and on the forefoot contact phase (M2 and M3). During stance, M1 bears a bigger share of the pressure on a positive gradient, whereas M5 bear it on a negative gradient.

This study analyzed gender-related differences in a cohort of patients with psoriatic spondyloarthropathy (SpA) We performed a retrospective cross-sectional study of 100 patients (mean age 48 +/- 14 years; 63 men, 37 women), diagnosed as having psoriatic SpA on the basis of ESSG criteria. All patients were studied according to a standard protocol, and HLA-B27 and Cw status were analyzed in the study population and their frequencies compared to that of 177 healthy blood donors. The clinical features of PsSpA were compared between men and women by univariate analyses. Twenty-three patients showed isolated axial disease (M:F ratio 3.6:1), 36 had polyaxial disease (M:F ratio 1:1), and 41 showed oligoaxial pattern (M:F ratio 1.7:1). HLA-B27 was correlated with male sex (P=0.002) and isolated axial disease (P=0.016). Univariate analysis showed female sex to be correlated with lower complement levels (P < 0.05), erosive disease (P = 0.05), higher swelling joint count (P = 0.002), and higher scores on the Health Assessment Questionnaire-Specific for SpA (P < 0.05). The HLA-B27 antigen seems to be a defined genetic risk factor only in men with psoriatic SpA. The extent of the spondylitic process is quite similar between the two, although women show poorer functional performance and more aggressive peripheral disease.

Background Infliximab, a chimeric anti-TNF-alpha antibody has been used successfully for the treatment of rheumatoid arthritis in combination with methotrexate. Open studies with a few number of patients suggested that infliximab as monotherapy is also effective in active spondyloarthropathies. Objectives To evaluate the efficacy of infliximab as monotherapy in patients with refractory and active spondyloarthropathy. Methods Thirty-eight week, open, multicentric and prospective trial, in 42 patients with spondyloarthropathy, according the ESSG and/or Amor criteria. All patients have disease duration of more than one year and persistent disease activity despite use of different drugs (NSAIDs, sulfasalazine, methotrexate or pamidronate). Infliximab is administered at a dose of 5 mg/kg, at 0, 2, 6, 14, 22 and 30 weeks. Clinical assessment was performed at these weeks at a week 38. Different clinical disease activity measures are performed, including BASDAI and patient global assessment of disease status. Disability is measured by BASFI and HAQ-Sp. ESR and CRP is used as laboratory parameters of inflammation. Results Preliminary results at week 0, 2 and 6 in 10 patients (3F/7M): 8 AS patients and 2 undifferentiated spondyloarthropathy; mean age: 36 ± 7 yr, mean disease duration: 14 ± 6 yr are presented in this Table 1. In all patients a significant improvement in clinical, functional and laboratory parameters were observed. This improvement was seen at week 2 (after the first dose) and is maintained at week 6. Conclusion Preliminary results of this open study show that infliximab provides a quick and significant clinical improvement in refractory spondyloarthropathies.

Squamous cell carcinoma (SCC) antigen (Ag) present and expressed in normal epithelium and epithelial tissues is used primarily as tumor marker of SCC of the uterine cervix. In this review, we considered factors interfering in vitro with the collection of samples and assay procedures, benign and malignant nongynecological diseases which may be the cause of elevated serum levels of SCC Ag. Contamination with skin or saliva strongly influences SCC Ag levels. SCC Ag is elevated in several benign lesions, including pulmonary (tuberculosis, adult respiratory distress syndrome, pulmonary infiltration with eosinophilia, sarcoidosis, bronchogenic cyst) and skin (eczema, pemphigus, erythroderma epidermitis, psoriasis) diseases. Elevations are observed in SCC malignancies of the head and neck, esophagus, skin, lung, urothelium, anal canal and vulva.

Since the extension of concepts like carrying capacity, non-market resources, sustainability has taken a wide place in the scientific debate among scholars of planning, of estimating and of environmental economics, the practices on equity planning and evaluation have assumed a new importance; at the same time, the interest in their operational issues is increasing.

Background Currently, the use of standards of care (SoC) could be the first step to achieve optimal care in patients with spondyloarthritis (SpA). Objectives The aim of this project (2e) was to develop evidence-based and user-focused SoC for SpA. Methods A RAND-modified Delphi method was applied. First, a systematic literature review of national and international documents covering SOC for SpA was conducted. This included consensus, clinical guidelines and care management documents. Social leagues and health professionals were contacted. All the information retrieved was evaluated by two expert methodologists and, subsequently, adapted and classified according to the three categories of SOC: structure, process and outcomes. A group of 23 experts on SpA was selected and a consensus meeting was held where these SOC were discussed. Afterwards, a first questionnaire round was sent to the experts panel and the SOC were modified according to the results of this round. Finally, a second questionnaire round with the final set of SOC was sent to 167 rheumatologists all around Spain to assess their agreement grade about every SoC. Results A total of 38 SoC were set (12 for structure, 20 for process and 6 for outcomes). A selection with the SoC that got highest priority is shown in the table. In general, standards of process achieved high priority whereas standards of result got the lowest grade of agreement. Image/graph Conclusions The implementation in clinical practice of this set of SoC could help assess and improve the quality of care for patients with SpA. Disclosure of Interest None Declared

The complement receptor type 1 (CR1) levels on erythrocyte membranes from 23 patients with PsA was determined by using ELISA. Six patients had an axial form, the rest had peripheral arthritis (10 polyarthritis and seven oligoarthritis). A significant decrease in levels of this receptor was found in patients with polyarthritis compared with healthy controls. Non-significant differences were found when comparing the other two groups of patients with the controls, although the mean values of CR1 were lower in the patients' group. We also found an inverse correlation between CR1 levels and articular index, but not with ESR, CRP or disease duration. No differences in the CR1 density were obtained for HLA-B27 positive and HLA-B27 negative patients.

In their initial work, Moll and Wright recognised five patterns of psoriatic arthritis (PsA)—namely, distal joint disease, oligoarthritis, polyarthritis, arthritis mutilans, and spondylitis.1 Although psoriatic spondyloarthropathy was recognised as a specific pattern of PsA, it has become clear that the presence of isolated spondyloarthropathy (SpA) in PsA is unusual, and in most cases, it occurs with peripheral arthritis.2,3 We undertook the present work to analyse the clinical features of our patients with psoriatic SpA and to compare the different subgroups included within the psoriatic SpA spectrum. One hundred patients with psoriatic SpA, defined in accordance with the European Spondyloarthropathy Study Group (ESSG) criteria,4 were consecutively recruited and their clinical records were analysed in this retrospective cross sectional study. All patients were evaluated according to a standard protocol, and their functional ability was assessed using the Health Assessment Questionnaire-Specific for SpA (HAQ-S).5 We included patients with isolated axial involvement, as well as those with axial plus peripheral disease. The study group was divided according to the articular patterns seen during …

We carried out a prospective study of the clinical, laboratory and radiological features of 180 patients with psoriatic arthritis. We initially classified our patients into five groups as described in the publications of Moll and Wright. Thirty-seven per cent had oligoarthritis, 36% polyarthritis, 23% spondarthritis (sacroiliitis and/or spondylitis) and 4% had the mutilans form. The distal joint arthritis type did not exist as an entity and the distal interphalangeal (DIP) joints were affected in all groups. The spondarthritis form includes patients with exclusively axial manifestations and also those who in addition have peripheral arthritis (oligoarthritis, polyarthritis, DIP arthritis). Only 53% of our patients had nail involvement. We found an increase of IgA levels in patients with axial disease. This suggests a relationship between ankylosing spondylitis and psoriatic spondylitis. The HLA-B17/Cw6 association increased in the oligoarticular form. The increase of antigen B17 correlated with the spondarthritic and oligoarthritis forms whereas Cw6 was more important in the oligoarthritis form. An increase of the HLA-B27/Cw1 association and the spondarthritic form was also found. Moreover, we detected a greater incidence of the HLA-B27 antigen in patients with bilateral sacroiliitis (85%) than in patients with unilateral sacroiliitis (22%). Our work revealed that PA is not a harmless disease; 57% of our patients had erosive arthritis while 19% had ARA class III or IV functional impairment.

The behavior of tumor-associated trypsin inhibitor (TATI) as a marker for gynecological cancer was studied in a control population and in patients with different benign and malignant diseases. When a cut-off level of 21.4 micrograms/l was used the specificity was 100% in patients with benign diseases. The sensitivity in patients with malignant tumors was low for cervical and corpus cancer, 13% and 14%, respectively, whereas it was 33% in all the ovarian malignant tumors, reaching 60% in the mucinous type. There was a clear correlation between TATI level and stage.

HLA-A, B, and C antigens were studied in 104 Spanish patients with psoriatic arthritis. Different clinical features were evaluated and the patients divided into disease subsets. HLA-B17, B27, B16, and Cw6 were the most common haplotypes in the total group. The HLA-B17/Cw6 haplotype was increased in patients with oligoarthritis. The increase of antigen B17 correlated with oligoarthritis and spondarthritis, whereas Cw6 was more significant in oligoarthritis. The prevalence of the B27/Cw1 haplotype was greater in association with spondarthritis and was probably related to the B27.5 subtype linked to Cw1. A significant negative association between the B44/Cw5 haplotype and psoriatic arthritis was found. The existence of several haplotypic factors in the different subsets is discussed. Lack of one or more HLA factors is thought to be responsible for the different clinical forms of psoriatic arthritis.

Direct and empirical evidence indicates that intravenous administration of DMSO can arrest or reverse cerebral and extracerebral ischemia following experimental or clinical injury. When the delivery of oxygen and nutrients to the tissue is deficient or unavailable (as in ischemia), cell damage or death with all its attending pathological consequences becomes an end-point. In the brain, this equates to build-up of intracranial pressure, impairment of neural transmission to vital centers, and loss of function or death. We have reviewed a number of studies that show the usefulness of DMSO in preventing significant pathology from developing in various experimental injury models and in clinical subjects. We have proposed that the action of DMSO in biochemical, morphological, and functional subsystems is not specific but rather interactive. Figure 5 illustrates this point. Any one effect by DMSO on these subsystems that does not affect the others seems highly unlikely. How DMSO or similar drugs affect these systems, could provide important clues in clarifying the pathogenesis of ischemia and in reducing its severity. We conclude from the available evidence that ischemic injury is a dynamic process constantly promoting biochemical, vascular, and morphological changes and that DMSO is able to intervene at various levels of this pathochemical cascade. DMSO may do this by its ability to normalize tissue perfusion when this is lacking or impaired. We speculate that this effect by DMSO is predominantly on the PG-TX and platelet systems, since these appear to be the most important candidates implicated in vessel occlusion and spasm. It is further concluded from the available and theoretical evidence presented here, that clinical trials using DMSO in cerebral and extracerebral organ ischemia should be designed in order to evaluate the efficacy of this compound to other antithrombogenic therapies. It is reasonable to assume that DMSO may provide a primary approach to the treatment of cerebral, myocardial, renal, and platelet-induced ischemic disorders.