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Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the presence of autoantibodies against factor VIII (FVIII). As with other autoimmune diseases, its etiology is complex and its genetic basis is unknown. The aim of this study was to identify the immunogenetic background that predisposes individuals to AHA. HLA and KIR gene clusters, as well as KLRK1 , were sequenced using next-generation sequencing in 49 AHA patients. Associations between candidate genes involved in innate and adaptive immune responses and AHA were addressed by comparing the alleles, genotypes, haplotypes, and gene frequencies in the AHA cohort with those in the donors' samples or Spanish population cohort. Two genes of the HLA cluster, as well as rs1049174 in KLRK1 , which tags the natural killer (NK) cytotoxic activity haplotype, were found to be linked to AHA. Specifically, A*03:01 ( p = 0.024; odds ratio (OR) = 0.26[0.06-0.85]) and DRB1*13:03 ( p = 6.8 × 10 3 , OR = 7.56[1.64-51.40]), as well as rs1049174 ( p = 0.012), were significantly associated with AHA. In addition, two AHA patients were found to carry one copy each of the low-frequency allele DQB1*03:09 ( n allele = 2, 2.04%), which was completely absent in the donors. To the best of our knowledge, this is the first time that the involvement of these specific alleles in the predisposition to AHA has been proposed. Further molecular and functional studies will be needed to unravel their specific contributions. We believe our findings expand the current knowledge on the genetic factors involved in susceptibility to AHA, which will contribute to improving the diagnosis and prognosis of AHA patients.

Objectives : To analyze the characteristics and the predictive factors of the use of rituximab and belimumab in daily practice in patients from the inception cohort Registro Español de Lupus (RELES). Material and methods : The study included 518 patients. We considered patients treated with biologics who received at least one dose of rituximab or belimumab, and possible indications of those manifestations registered at the same time or in the previous 2 months of the start of the therapy. Results : In our cohort, 37 (7%) patients received at least one biological treatment. Rituximab was prescribed in 26 patients and belimumab in 11. Rituximab was mainly prescribed for hemolytic anemia or thrombocytopenia (11 patients, 42%), lupus nephritis and neuropsychiatric lupus (5 patients each, 19%). Belimumab was mostly used for arthritis (8 patients, 73%). In the univariate analysis, the predictive factors at diagnosis for the use of biologic therapy were younger age ( p = 0.022), a higher SLEDAI ( p = 0.001) and the presence of psychosis ( p = 0.011), organic mental syndrome (SOCA) ( p = 0.006), hemolytic anemia ( p = 0.001), or thrombocytopenia ( p = 0.01). In the multivariant model, only younger age, psychosis, and hemolytic anemia were independent predictors of the use of biologics. Conclusions : Rituximab is usually given to patients with hematological, neuropsychiatric and renal involvement and belimumab for arthritis. Psychosis, hemolytic anemia and age at the diagnosis of lupus were independent predictive factors of the use of biological agents. Their global effects are beneficial, with a significant reduction in SLE activity and a low rate of side effects.

C4b-binding protein (C4BP) is a well-known regulator of the complement system that holds additional and important activities unrelated to complement inhibition. Recently, we have described a novel immunomodulatory activity in the minor C4BP(β-) isoform directly acting over inflammatory phagocytes. Here we show that incorporation of the β-chain to the C4BP α-chain oligomer interferes with this immunomodulatory activity of C4BP. Moreover, an oligomeric form including only the complement control protein 6 (CCP6) domain of the C4BP α-chain (PRP6-HO7) is sufficient to "reprogram" monocyte-derived DCs (Mo-DCs) from a pro-inflammatory and immunogenic phenotype to an anti-inflammatory and tolerogenic state. PRP6-HO7 lacks complement regulatory activity but retains full immunomodulatory activity over inflammatory Mo-DCs induced by TLRs, characterized by downregulation of relevant surface markers such as CD83, HLA-DR, co-stimulatory molecules such as CD86, CD80 and CD40, and pro-inflammatory cytokines such as IL-12 and TNF-α. Furthermore, PRP6-HO7-treated Mo-DCs shows increased endocytosis, significantly reduced CCR7 expression and CCL21-mediated chemotaxis, and prevents T cell alloproliferation. Finally, PRP6-HO7 shows also full immunomodulatory activity over Mo-DCs isolated from lupus nephritis patients with active disease, even without further pro-inflammatory stimulation. Therefore PRP6-HO7, retaining the immunomodulatory activity of C4BP(β-) and lacking its complement regulatory activity, might represent a promising and novel alternative to treat autoimmune diseases., Competing Interests: IS, AL and JA are co-inventors on pending or issued patents involving compounds and methods for immunomodulation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Serrano, Luque, Mitjavila, Blom, Rodríguez de Córdoba, Vega, Torras and Aran.)

Introduction: Severe lung injury is triggered by both the SARS-CoV-2 infection and the subsequent host-immune response in some COVID-19 patients. Methods: We conducted a randomized, single-center, open-label, phase II trial with the aim to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) vs. SoC alone, in hospitalized patients with severe COVID-19. The primary outcome was time to clinical stability within 56 days after randomization. Results: From April 1 to May 2, 2020, 55 patients were prospectively included for subsequent randomization; 27 were assigned to the experimental group and 28 to the control group. The experimental treatment was not associated with a difference in time to clinical stability (hazard ratio 0.73 [95% CI 0.39-1.37]) nor most secondary outcomes. Median methylprednisolone cumulative doses were significantly lower (360 mg [IQR 360-842] vs. 870 mg [IQR 364-1451]; p = 0.007), and administered for a shorter time (median of 4.00 days [3.00-17.5] vs. 18.5 days [3.00-53.2]; p = 0.011) in the experimental group than in the control group. Although not statistically significant, those receiving the experimental therapy showed a numerically lower all-cause mortality than those receiving SoC, especially at day 10 [2 (7.41%) vs. 5 (17.9%); OR 0.39 (95% CI 0.05-2.1); p = 0.282]. The total number of non-serious adverse events was 42 in each the two groups. Those receiving experimental treatment had a numerically higher rate of non-serious infectious adverse events [16 (38%) vs. 10 (24%)] and serious infectious adverse events [7 (35%) vs. 3 (23%)] than those receiving SoC. Conclusions: The combined use of methylprednisolone pulses plus tacrolimus, in addition to the SoC, did not significantly improve the time to clinical stability or other secondary outcomes compared with the SoC alone in severe COVID-19. Although not statistically significant, patients receiving the experimental therapy had numerically lower all-cause mortality than those receiving SoC, supporting recent non-randomized studies with calcineurin inhibitors. It is noteworthy that the present trial had a limited sample size and several other limitations. Therefore, further RCTs should be done to assess the efficacy and safety of tacrolimus to tackle the inflammatory stages of COVID-19. Clinical Trial Registration: Identifier [NCT04341038/EudraCT: 2020-001445-39]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Solanich, Antolí, Rocamora-Blanch, Padullés, Fanlo-Maresma, Iriarte, Mitjavila, Capdevila, Riera-Mestre, Bas, Vicens-Zygmunt, Niubó, Calvo, Bolivar, Rigo-Bonnin, Mensa-Vilaró, Arregui, Tebe, Videla, Hereu and Corbella.)

Introduction: Some COVID-19 patients evolve to severe lung injury and systemic hyperinflammatory syndrome triggered by both the coronavirus infection and the subsequent host-immune response. Accordingly, the use of immunomodulatory agents has been suggested but still remains controversial. Our working hypothesis is that methylprednisolone pulses and tacrolimus may be an effective and safety drug combination for treating severe COVID-19 patients., Methods: and analysis: TACROVID is a randomized, open-label, single-center, phase II trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) versus SoC alone, in patients at advanced stage of COVID-19 disease with lung injury and systemic hyperinflammatory response. Patients are randomly assigned (1:1) to one of two arms (42 patients in each group). The primary aim is to assess the time to clinical stability after initiating randomization. Clinical stability is defined as body temperature ≤37.5 °C, and PaO2/FiO2 > 400 and/or SatO2/FiO2 > 300, and respiratory rate ≤24 rpm; for 48 consecutive hours., Discussion: Methylprednisolone and tacrolimus might be beneficial to treat those COVID-19 patients progressing into severe pulmonary failure and systemic hyperinflammatory syndrome. The rationale for its use is the fast effect of methylprednisolone pulses and the ability of tacrolimus to inhibit both the CoV-2 replication and the secondary cytokine storm. Interestingly, both drugs are low-cost and can be manufactured on a large scale; thus, if effective and safe, a large number of patients could be treated in developed and developing countries., Trial Registration Number: NCT04341038 / EudraCT: 2020-001445-39., Competing Interests: Authors declare no conflicts of interest., (© 2021 The Authors.)

Objectives: To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS)., Methods: From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality., Results: A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up., Conclusions: In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To compare the main characteristics of two inception cohorts (Italian [ITC] and Spanish [SPC]) cohorts of patients with systemic lupus erythematosus (SLE) at the time of diagnosis and at one year of follow-up., Methods: Demographic, clinical and immunological characteristics, and treatments at SLE diagnosis and at 12 months of follow-up of ITC and SPC were compared., Results: One hundred and sixty-four patients in the ITC and 231 patients in the SPC were compared. the patients from ITC were younger at SLE diagnosis (41.1±15.0 years vs. 46.4±15.6 years; p<0.001) and had a higher prevalence of arthritis (62.8% vs. 45.5%; p=0.001), serositis (25.6% vs. 16.0%; p=0.026), neurological involvement (7.9% vs. 1.7%; p=0.006), and immunological abnormalities (anti-dsDNA, anti-Sm, antiphospholipid antibodies) (93.9% vs. 77.8%; p<0.001). Conversely, photosensitivity (29.5% in ITC vs. 45.9% in SPC; p=0.001) and oral ulcers (12.4% vs. 30.3%; p<0.001) were more frequent at onset of SLE in the Spanish patients. At the first 12 months of follow-up, these differences were maintained. At SLE onset, more Italian patients received glucocorticoids (85.4% vs. 50.2%; p<0.001) and immunosuppressive agents. At 12 months of follow-up, more Spanish patients were treated with antimalarials (75.6% in ITC vs. 90.0% in SPC; p<0.001). Conversely, the use of glucocorticoids was lower in SPC (89.0% in ITC vs. 57.1% in SPC; p<0.001)., Conclusions: These cohorts presented different profiles in terms of pattern of organ/system involvement and disease treatment, possibly as a consequence of patient selection or different disease management approaches between Italy and Spain.

Objective: To compare the efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS) versus azathioprine (AZA) in patients with active systemic lupus erythematosus (SLE) disease., Methods: A multicentre, 24-month, superiority, open-label, randomised controlled trial (NCT01112215) was conducted with 240 patients (120 per arm) receiving either EC-MPS (target dose: 1440 mg/day) or AZA (target dose: 2 mg/kg/day) in addition to prednisone and/or antimalarials. The primary endpoint was the proportion of patients achieving clinical remission, assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and British Isles Lupus Assessment Group (BILAG), at 3 and 24 months. Secondary endpoints included time to clinical remission, BILAG A and B flare rates, time to flare, corticosteroid reduction and adverse events (AEs)., Results: Proportion of patients achieving clinical remission (clinical SLEDAI=0) was higher in the EC-MPS group at 3 (32.5% vs 19.2%; treatment difference, 13.3 (CI 2.3 to 24), p=0.034) and 24 months (71.2% vs 48.3%; treatment difference, 22.9 (CI 10.4 to 34.4), p<0.001). EC-MPS was superior with respect to time to clinical remission (HR 1.43; 95% CI 1.07 to 1.91; p=0.017). BILAG A/B and B flares occurred more frequently in the AZA group (71.7% vs 50%, p=0.001 and 21.67% vs 8.3%, p=0.004, respectively). EC-MPS was superior with respect to time to first BILAG A/B (HR 1.81; 95% CI 1.3 to 2.56; p=0.0004) and BILAG A flare (HR 2.84; 95% CI 1.37 to 5.89; p=0.003). AEs were similar in both groups except for leucopenia that occurred more frequently with AZA., Conclusions: EC-MPS was superior to AZA in treating SLE and preventing further relapses., Trial Registration Number: NCT01112215; Results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Whether a repeat renal biopsy is helpful during lupus nephritis (LN) flares remains debatable. In order to analyze the clinical utility of repeat renal biopsy in this complex situation, we retrospectively reviewed our series of 54 LN patients who had one or more repeat biopsies performed only on clinical indications. Additionally, we reviewed 686 well-documented similar cases previously reported (PubMed 1990-2015).The analysis of all patients reviewed showed that histological transformations are common during a LN flare, ranging from 40% to 76% of cases. However, the prevalence of transformations and the clinical value of repeat biopsy vary when they are analyzed according to proliferative or nonproliferative lesions.The great majority of patients with class II (78% in our series and 77.5% in the literature review) progressed to a higher grade of nephritis (classes III, IV, or V), resulting in worse renal prognosis. The frequency of pathological conversion in class V is lower (33% and 43%, respectively) but equally clinically relevant, since almost all cases switched to a proliferative class. Therefore, repeat biopsy is highly advisable in patients with nonproliferative LN at baseline biopsy, because these patients have a reasonable likelihood of switch to a proliferative LN that may require more aggressive immunosuppression.In contrast, the majority of patients (82% and 73%) with proliferative classes in the reference biopsy (III, IV or mixed III/IV + V), remained into proliferative classes on repeat biopsy. Although rebiopsy in this group does not seem as necessary, it is still advisable since it will allow us to identify the 18% to 20% of patients that switch to a nonproliferative class. In addition, consistent with the reported clinical experience, repeat biopsy might also be helpful to identify selected cases with clear progression of proliferative lesions despite the initial treatment, for whom it is advisable to intensify inmunosuppression. Thus, our experience and the literature data support that repeat biopsy also brings more advantges than threats in this group.The results of the repeat biopsy led to a change in the immunosuppresive treatment in more than half of the patients on average, intensifying it in the majority of the cases, but also reducing it in 5% to 30%.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a dominantly inherited autoinflammatory disease caused by TNFRSF1A mutations. Patients with TRAPS suffer from recurrent, long episodes with fever, arthralgia/arthritis, migratory myalgias, abdominal pain, serositis, conjunctivitis and migratory erythematous skin rash. More than 70 different TNFRSF1A mutations have been reported to date, and as consequence of its genetic heterogeneity, TRAPS shows a variable phenotypic expression. Among TNFRSF1A variants, the low-penetrance p.Arg92Gln variant represents the most commonly detected, and is typically associated with mild and short episodes, with a higher tendency to spontaneous resolution, and less familial association than the structural TNFRSF1A mutations. Pericardial involvement is rare but a well-known clinical feature of TRAPS, with a significant increased rate in those adult patients in whom the onset of the disease occurred during adulthood. Moreover, idiopathic recurrent acute pericarditis has also been occasionally described as a clinical presentation of TRAPS. However, cardiac tamponade is an unusual initial manifestation of the disease. Herein, we present a brief review based on the description of the exceptional case of a 35-year-old female patient who presented with recurrent pericardial effusions and cardiac tamponade. TNFRSF1A analyses showed a heterozygous genotype for the low-penetrance p.Arg92Gln variant. Due to disease severity, the patient was treated with the anti-interleukin-1 drug anakinra, showing a prompt resolution of her clinical manifestations., (© 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Introduction: Patient registries are useful tools for assessing rare diseases. Our objective is to present the Spanish registry of patients with systemic lupus erythematosus (Registro español de pacientes con lupus eritematoso sistémico, RELES)., Patients and Methods: RELES was started in 2008 as an observational, prospective, multicentre cohort registry that included patients from the time they were diagnosed. The registry's objective is to analyse the incidence and noninflammatory complications of systemic lupus erythematosus (SLE). The departments of internal medicine of 38 Spanish hospitals participate in this registry., Results: A total of 298 patients with a mean age of 40.8±15.7 years were included, 88.9% of whom were women and 85.6% of whom were white. In the first visit, there was a predominance of joint manifestations (74.5%). One hundred and seventy-seven patients (59.4%) were positive for anti-native DNA. In these patients, there was a higher rate of lupus nephritis (26.7% vs. 14%, p=.009; relative risk [RR], 1.33), haemolytic anaemia (13.6% vs. 4.1%, p=.07; RR, 1.46) and lymphopenia (55.4% vs. 43.8%, p=.05; RR, 1.21). The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) score was 9.64 points (interquartile range, 4-13). The patients treated with antimalarial drugs before the diagnosis of SLE had a median SLEDAI score in the first visit of 5, compared with 8 for those who were not treated with these drugs (p=.02)., Conclusions: RELES constitutes the first Spanish patient cohort with SLE recorded from the time of the diagnosis. The presence of anti-DNA has been related to severe manifestations such as nephritis and haemolytic anaemia. Treatment with antimalarial drugs before the diagnosis was associated with less active disease at the initial presentation., (Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Aim: To study the influence of prednisone dose during the first month after systemic lupus erythematosus (SLE) diagnosis (prednisone-1) on glucocorticoid burden during the subsequent 11 months (prednisone-2-12)., Methods: 223 patients from the Registro Español de Lupus Eritematoso Sistémico inception cohort were studied. The cumulative dose of prednisone-1 and prednisone-2-12 were calculated and recoded into a four-level categorical variable: no prednisone, low dose (up to 7.5 mg/day), medium dose (up to 30 mg/day) and high dose (over 30 mg/day). The association between the cumulative prednisone-1 and prednisone-2-12 doses was tested. We analysed whether the four-level prednisone-1 categorical variable was an independent predictor of an average dose >7.5 mg/day of prednisone-2-12. Adjusting variables included age, immunosuppressives, antimalarials, methyl-prednisolone pulses, lupus nephritis and baseline SLE Disease Activity Index (SLEDAI)., Results: Within the first month, 113 patients (51%) did not receive any prednisone, 24 patients (11%) received average low doses, 46 patients (21%) received medium doses and 40 patients (18%) received high doses. There was a strong association between prednisone-1 and prednisone-2-12 dose categories (p<0.001). The cumulative prednisone-1 dose was directly associated with the cumulative prednisone-2-12 dose (p<0.001). Compared with patients on no prednisone, patients taking medium (adjusted OR 5.27, 95% CI 2.18 to 12.73) or high-dose prednisone-1 (adjusted OR 10.5, 95% CI 3.8 to 29.17) were more likely to receive prednisone-2-12 doses of >7.5 mg/day, while patients receiving low-dose prednisone-1 were not (adjusted OR 1.4, 95% CI 0. 0.38 to 5.2). If the analysis was restricted to the 158 patients with a baseline SLEDAI of ≥6, the model did not change., Conclusion: The dose of prednisone during the first month after the diagnosis of SLE is an independent predictor of prednisone burden during the following 11 months.

Shrinking lung syndrome (SLS) is a rare and less known complication mainly associated with systemic lupus erythematosus (SLE). In this study, we analyze the clinical features, investigation findings, approaches to management, and outcome in a case series of 9 adult patients with SLE and SLS diagnosed during a 35-year period in 3 referral tertiary care hospitals in Spain. Additionally, we reviewed 80 additional cases previously reported (PubMed 1965-2015). These 80 cases, together with our 9 patients, form the basis of the present analysis.The overall SLS prevalence in our SLE population was 1.1% (9/829). SLS may complicate SLE at any time over its course, and it usually occurs in patients without previous or concomitant major organ involvement. More than half of the patients had inactive lupus according to SELENA-systemic lupus erythematosus disease activity index (SLEDAI) scores. Typically, it presents with progressive exertional dyspnea of variable severity, accompanied by pleuritic chest pain in 76% of the cases.An important diagnostic delay is common. The diagnostic tools that showed better yield for SLS detection are the imaging techniques (chest x-ray and high-resolution computed tomography) along with pulmonary and diaphragmatic function tests. Evaluation of diaphragm dome motion by M-mode ultrasonography and phrenic nerve conduction studies are less useful.There are no standardized guidelines for the treatment of SLS in SLE. The majority of patients were treated with medium or high doses of glucocorticoids. Several immunosuppressive agents have been used in conjunction with steroids either if the patient fails to improve or since the beginning of the treatment. Theophylline and beta-agonists, alone or in combination with glucocorticoids, have been suggested with the intent to increase diaphragmatic strength.The overall long-term prognosis was good. The great majority of patients had significant clinical improvement and stabilization, or mild to moderate improvement on pulmonary function tests. The mortality rate was very low.

Objectives: This is the first Spanish multicentric inception lupus cohort, formed by SLE patients attending Spanish Internal Medicine Services since January 2009. We aimed to analyse drug therapy during the first year of follow-up according to disease severity., Methods: 223 patients who had at least one year of follow-up were enrolled upon diagnosis of SLE. Therapy with prednisone, pulse methyl-prednisolone, hydroxychloroquine, immunosuppressives and calcium/vitamin D was analysed., Results: Prednisone was given to 65% patients, at a mean (SD) daily dose of 11 (10) mg/d. 38% patients received average doses >7.5 mg/d during the first year. Patients with nephritis and with a SLEDAI ≥6 were treated with higher doses of prednisone. 81% of patients were treated with hydroxychloroquine, with higher frequency among those with a SLEDAI ≥6 (88% vs. 68%, p<0.001). The use of immunosuppressive drugs and methyl-prednisolone pulses was higher in patients with a baseline SLEDAI ≥6, however, differences were no longer significant when patients with lupus nephritis were excluded. The use of calcium/vitamin D increased with the dose of prednisone, however, 43% of patients on medium-high doses of prednisone did not take any calcium or vitamin D., Conclusions: This study gives a real-world view of the current therapeutic approach to early lupus in Spain. The generalised use of hydroxychloroquine is well consolidated. There is still a tendency to use prednisone at medium to high doses. Pulse methyl-prednisolone and immunosuppressive drugs were used in more severe cases, but not as steroid sparing agents. Vitamin D use was suboptimal.

Background and Objective: To describe our cohort of 27 biopsy-proven patients and their long-term follow-up, with special attention to prognostic factors., Patients and Methods: Twenty seven patients were retrospectively collected. They were controlled in the Internal Medicine Department of the Bellvitge's Hospital (Spain) between 1974 and 2010. Evaluation was performed at one, 3 and 5 year follow-up., Results: There were 22 women (81.5%). Mean age at onset of nephritis was 34.83 years (SD 13.45). Partial or complete remission was achieved by 21 patients (80.77%) in the one-year follow-up, 22 patients (84.61%) in the third-year follow-up and 21 patients (77.77%) in the fifth-year follow-up. A change in the histology class was diagnosed in 4 patients. Seven patients suffered flares of nephritis. Seven patients died in the long term follow-up, 3 out of this 7 died because of systemic erythematosus lupus., Conclusion: Nephritis onset beyond 45 years old is the factor mostly related with a poor prognosis. That is the reason why we recommend co-therapy with immunosuppressors from the beginning in such patients., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Background: The risk of selection bias in registries and its consequences are relatively unexplored. We sought to assess selection bias in a recent registry about acute coronary syndrome and to explore the way of conducting and reporting patient registries of acute coronary syndrome., Methods and Results: We analyzed data from patients of a national acute coronary syndrome registry undergoing an audit about the comprehensiveness of the recruitment/inclusion. Patients initially included by hospital investigators (n=3265) were compared to eligible nonincluded (missed) patients (n=1439). We assessed, for 25 exposure variables, the deviation of the in-hospital mortality relative risks calculated in the initial sample from the actual relative risks. Missed patients were of higher risk and received less recommended therapies than the included patients. In-hospital mortality was almost 3 times higher in the missed population (9.34% [95% CI, 7.84 to 10.85] versus 3.9% [95% CI, 2.89 to 4.92]). Initial relative risks diverged from the actual relative risks more than expected by chance (P<0.05) in 21 variables, being higher than 10% in 17 variables. This deviation persisted on a smaller degree on multivariable analysis. Additionally, we reviewed a sample of 129 patient registries focused on acute coronary syndrome published in thirteen journals, collecting information on good registry performance items. Only in 38 (29.4%) and 48 (37.2%) registries was any audit of recruitment/inclusion and data abstraction, respectively, mentioned. Only 4 (3.1%) authors acknowledged potential selection bias because of incomplete recruitment., Conclusions: Irregular inclusion can introduce substantial systematic bias in registries. This problem has not been explicitly addressed in a substantial number of them.

Introduction and Objectives: The aim was to determine the usefulness of the hospital discharge Minimum Basic Data Set (MBDS) for predicting in-hospital mortality with coronary bypass surgery by using data from a prospective observational study as a reference., Methods: The observational study involved collecting data on all patients undergoing first coronary bypass surgery at five hospitals in Catalonia, Spain between November 2001 and November 2003. In addition, data covering the same period and hospitals were obtained from the MBDS for procedure code 36.1. We investigated the concordance between the information from the two data sources and logistic regression was used to derive predictive models for in-hospital mortality. The model derived using MBDS data was validated using data from the prospective observational study and MBDS data for the years 2004-2006. Model validity was evaluated using discrimination and calibration indices., Results: Some 4.1% of cases in the observational study could not be found in the MBDS. The concordance between the two data sources was highly variable and generally low (kappa values ranged from 0.16 to 0.79). The discriminative ability of the MBDS model was equivalent to that of the observational study model (c=0.80 vs. c=0.79), but when the validity of the former was tested using prospective data and MBDS data for 2004-2006, the discrimination c-index decreased to 0.76 and 0.65, respectively, and the calibration worsened significantly (P< .001)., Conclusions: The risk of in-hospital mortality following coronary surgery cannot be accurately evaluated using MBDS data. However, our results indicate that their use as a predictive tool could be improved.

Objective: To evaluate the utility of systemic lupus erythematosus (SLE) initial clinical manifestations and the SLE Disease Activity Index (SLEDAI) for identifying patients who will have a remission., Methods: We studied 100 SLE patients (85 females, 15 males) and identified all patients who had remission (defined as at least one continuous year during which lack of disease activity permitted withdrawal of all treatment to suppress general lupus activity of a particular clinical manifestation). Changes in laboratory parameters without clinical activity, thus not requiring treatment, did not invalidate remission. We did not include any patient who had never required treatment. We evaluated the SLEDAI values and the main SLE manifestations at the time of diagnosis of SLE, and also every 3 months during the first year of disease., Results: Twenty-four of the 100 SLE patients achieved remission that occurred a mean of 64 months after the diagnosis. They remained in remission for a mean of 55 months. There were no statistical differences in SLEDAI values and the initial manifestations (including renal and cerebral) between patients who reached remission and those who did not. The patients who have a higher SLEDAI score take longer to achieve remission., Conclusion: SLE patients with severe initial clinical manifestations and higher SLEDAI values may achieve clinical remission.

Objective: Systemic lupus erythematosus (SLE) predominantly affects young patients. SLE starting in later life has a clinical presentation different than in younger patients. We have used the SLE Disease Activity Index (SLEDAI) to explore the relationship between age of onset and disease activity., Methods: We selected all patients controlled in our hospital at the moment of clinical diagnosis of SLE (100 patients; 85 females and 15 males). They were classified in two groups: those with early onset (>50 y) and those with late onset (>50 y) based on their age at the moment of clinical diagnosis of SLE., Results: In 12 patients the onset of SLE was >50 y (10 females and two males; mean age 59 y). The early onset patients had significantly higher SLEDAI values at the presentation and during the first year of disease with respect to elderly patients. Antibodies to DNA and hypocomplementemia were detected more often in younger patients., Conclusion: Our results confirm using SLEDAI, that the lupus of the elderly patients is a distinct clinical subgroup with a milder course of disease.

Introduction: Behçet disease is a systemic form of vasculitis which presents with neurological symptoms with a frequency varying between 16 and 40%. Involvement of the parenchyma has been found to worsen the prognosis in patients with neuroBehçet (NB)., Objective: To review the clinical features and course of patients with NB involving the parenchyma of the central nervous system (CNS)., Clinical Cases: Seven patients with Behçet disease and neurological localizing signs were seen in our hospital between 1989 and 1996. The initial diagnosis was of ischemic ictus in five of the seven patients. Both neuroimaging studies and investigation of the cerebrospinal fluid were always pathological in all cases. Vascular studies (arteriography and echo-Doppler of the supra-aortic trunks) were normal. One patient died. Four patients had serious sequelae following treatment., Conclusion: NB should be included in the different diagnosis of ictus. Involvement of the parenchyma of the CNS was accompanied by lymphocytic meningitis, perhaps also leading to a worse functional prognosis.

Objective: To define prognostic factors at the moment of the diagnosis in lupus nephritis, and to assess the contribution of renal histologic data., Patients and Methods: Sixty-two patients with systemic lupus erythematosus (SLE) and histologic evidence of nephritis were studied for renal outcome. Correlations between clinical or biological and histological data were carried out as an indicator of the utility of the renal biopsy., Results: There were no significant differences in creatinine between the different histologic classes at the moment of the diagnosis, although the WHO classification correlated well with proteinuria and immunologic activity. There was a strong correlation between clinical and histological activity as measured by the activity index in proliferative glomerulonephritis, mainly with creatinine and proteinuria, but not with haematuria or immunological activity. Young age at the time of renal biopsy, proliferative classes III and IV, and the chronicity index were associated with a poorer renal prognosis., Conclusions: High immunologic activity, mainly elevated anti-DNA titers and decreased levels of CH100, is highly suggestive of proliferative glomerulonephritis. Proliferative classes III and IV and high chronicity indexes are associated with a worse prognosis in lupus nephritis.

We present three cases of patients with systemic lupus erythematosus (SLE) and osteonecrosis or avascular necrosis (AV). Although, the pathogenesis of osteonecrosis is controversial and multifactorial, the glucocorticoids therapy is the most important factor contributing to the lesion. We report the clinical presentation of the three patients. We comment the characteristics of AV, the diagnosis and the treatment of this uncommon complication in SLE patients.

A loss in bone mass was reported in premenopausal systemic lupus erythematosus (SLE) women, but this problem has not been studied in SLE males. We evaluated bone mineral density (BMD) in SLE males and the relationship between prolactin (PRL) and testosterone with BMD. We also studied the controversial effect of steroid therapy on BMD in these patients. We measured BMD in the lumbar spine and at the hip in 20 SLE men (mean age 37 y) and in the controls (n = 40). We measured PRL and testosterone in serum and saliva. The mean dose of prednisone at the time of study was 11.6 mg; and cumulative dose was 17.6 g. No significative decrease in BMD was detected in SLE males vs controls; either in the lumbar spine (1.00 +/- 0.1 vs 1.05 +/- 0.1 g/cm2) or in the femoral neck (0.84 +/- 0.1 vs 0.87 +/- 0.1 g/cm2). No patient or control had osteoporosis or fractures. We did not find any relationship between BMD and cumulative dose and baseline dose of corticosteroids. The mean values of PRL and testosterone (serum and salivary) were in the normal range. We did not find any correlation between BMD, PRL and androgens. This study did not show a loss in bone mass in SLE men on corticosteroid therapy.

Objective: To verify the possible relationship between the presence of antiphospholipid antibodies (APLA) and the presence of epileptic seizures in patients with systemic lupus erythematosus (SLE)., Methods: A total of 168 patients with SLE were studied. Fifteen patients had antecedents of epilepsy which were non attributable to a cause other than SLE. Epilepsy was diagnosed on clinical and electroencephalographic grounds. Antibodies to cardiolipin (CLa) and lupus anticoagulant (LA) were measured., Results: Epileptic seizures were generalized in 13 and partial in two patients. The lupus anticoagulant was positive in 40% of patients with epilepsy compared to 32% in the control group; CLa IgG in 53.5% compared to 65.6%, and CLa IgM in 40% compared to 35.2%. Differences were never statistically significant. Neither when patients with moderate/high CLa levels were studied. Seven patients (40%) had some of the classical manifestations of antiphospholipid syndrome., Conclusions: No association was found between positive APLA and epilepsy in patients with SLE.

The prevalence of infection with VZV in 145 patients with SLE was investigated, with a mean follow-up of 7.6 years; its relationship with different variables, particularly with therapy of the underlying disease, was analyzed. Twenty episodes of VZV infection in 19 patients were diagnosed (13.1%). In no case was the therapeutic regime changed nor was worsening of SLE observed. There was neither dissemination of herpes nor superinfection. An increase in the number of VZV infections was observed in patients with SLE under corticosteroid therapy (p = 0.04) and particularly when drug administration was on a daily basis (p = 0.00006). Cytotoxic agents also favored the infection (p = 0.0014). VZV infection is of a benign nature in SLE and its emergence is favored by immunosuppressive agents. The risk is lower if corticosteroid administration is on alternate days. There is no need to decrease therapy for SLE.

Objective: To evaluate bone mineral density (BMD) in premenopausal patients with systemic lupus erythematosus (SLE)., Methods: We measured BMD by dual energy x ray absorptiometry at lumbar vertebrae L2-4 and at the right femoral neck in 74 premenopausal white patients (mean age 30.8 years) with SLE who were receiving glucocorticoid therapy, and in a control group., Results: The mean cumulative dose of prednisone was 32.5 (SD 28) g. The mean dose at the time of absorptiometry was 13.7 (6.9) mg. BMD was significantly reduced at the spine and at the femoral neck in SLE patients when compared with the control group: L2-4 = 0.943 (0.1) g/cm2 v 1.038 (0.1) g/cm2 (p < 0.001); femoral neck = 0.766 (0.09) g/cm2 v 0.864 (0.1) g/cm2 (p < 0.001). Nine patients (12.1%), but none of the control group, had a BMD less than the reference range., Conclusion: BMD in premenopausal patients with SLE was less than that in a control group and less than the reference range of values defining the presence of osteoporosis in 12.1%. We did not find a relationship between BMD and either cumulative or baseline dose of corticosteroid therapy.

Because doctors are reluctant to diagnose systemic lupus erythematosus (SLE) in elderly patients, the initial diagnosis in this age group is usually tardy. Furthermore, the presenting manifestations in these patients are commonly atypical. We describe a 72-year-old woman in whom chronic ascites with antiphospholipid antibodies was the initial predominant manifestation of subsequently fatal SLE. Only 13 cases of chronic lupus ascites have been reported in the English and French literature. Our patient represents the first case reported in an elderly person.

We analyzed the effects of interleukin 2 (IL 2) and IL 4 isolated and in association on the specific response of human B cells triggered by trinitrophenylated polyacrylamide beads (TNP-PAA). IL 2 induced an increase (more than 10 times) in the number of hapten-binding cells [detected by a rosette-forming cell (RFC) assay] as well as the generation of antibody-producing cells [detected by a plaque-forming cell (PFC) assay]. IL 4 induced an isolated RFC response without PFC response. We verified that the IL 4 (as well as 12)-induced RFC were hapten specific and mediated through membrane IgM. Density fractionation experiments showed that IL 4-induced RFC were equally distributed between high-density and intermediate-density B cells. IL 2 appeared to drive more B cells into the intermediate density fraction. IL 2-induced PFC belonged to the RFC population and were intermediate-size B cells. IL 2 drove more RFC into an activated stage and it induced the differentiation of a number of them into antibody-producing cells. The evaluation of the proportion of RFC able to incorporate thymidine showed that both IL induced a substantial proliferation of antigen-activated B cells. However, IL 4 inhibited the IL 2-dependent PFC without affecting the number of RFC nor the proportion of proliferating RFC induced by this IL. These results directly demonstrate that human IL 4 triggers the expansion of antigen-activated B cells and selectively inhibits the IL 2-induced differentiation.