Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing.

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 × 103, 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 (nallele = 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.

The Hidden Side of Complement Regulator C4BP: Dissection and Evaluation of Its Immunomodulatory Activity.

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(ß-) isoform directly acting over inflammatory phagocytes. Here we show that incorporation of the ß-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(ß-) and lacking its complement regulatory activity, might represent a promising and novel alternative to treat autoimmune diseases.

Mastitis granulomatosa asociada a eritema nudoso: estudio de 42 casos / Granulomatous mastitis associated with erythema nodosum: A case series of 42 patients

Introducción:La mastitis granulomatosa (MG) se define por la presencia de inflamación granulomatosa en el tejido mamario. El eritema nudoso (EN) es una paniculitis inflamatoria reactiva caracterizada por nódulos subcutáneos dolorosos en las extremidades inferiores. La asociación entre MG y EN ha sido descrita, pero está poco estudiada. Nuestro objetivo fue analizar las características clínicas de las pacientes diagnosticadas de MG en nuestro centro y su asociación con EN.Métodos:Se revisaron retrospectivamente los casos diagnosticados histológicamente de MG entre 1995 y 2020.Resultados:Cuarenta y dos mujeres fueron diagnosticadas de MG. La edad media al diagnóstico fue de 41,619años y el 59,5% tenían ascendencia sudamericana. El EN se asoció con MG en el 11,9% de las pacientes. Las pacientes con EN fueron diagnosticadas precozmente respecto a aquellas con MG aislada (0,4meses frente a 6,81; p<0,05). La ulceración en la MG fue más prevalente en pacientes con EN asociado (60% vs 14,7%; p<0,05).Conclusión:El EN en pacientes con GM puede facilitar el diagnóstico precoz de esta rara condición que imita el cáncer de mama.(AU)

Background:Granulomatous mastitis (GM) is defined by the formation of granulomatous inflammation in breast tissue. Erythema nodosum (EN) is a reactive inflammatory panniculitis characterized by erythematous subcutaneous nodules in the lower limbs. The association of GM with EN has been rarely reported. Our aim was to retrospectively review our series of patients with GM to better characterize their features and their association with EN.Methods:Cases histologically diagnosed as granulomatous inflammation in breast tissue between 1995 and 2020 were retrospectively reviewed.Results:Forty-two women were diagnosed with GM. The average age at diagnosis was 41.619years, and 59.5% were of South-American ethnicity. EN was associated with GM in 11.9% of the patients. Patients with EN were diagnosed earlier than isolated GM (0.4months vs 6.81months; P<.05). Ulceration in the GM was more prevalent in patients with associated EN (60% vs 14.7%; P<.05).Conclusion:EN in patients with GM may reduce the evolution time and may help to diagnose this rare condition that mimics breast carcinoma. (AU)

[Granulomatous mastitis associated with erythema nodosum: A case series of 42 patients]. / Mastitis granulomatosa asociada a eritema nudoso: estudio de 42 casos.

BACKGROUND: Granulomatous mastitis (GM) is defined by the formation of granulomatous inflammation in breast tissue. Erythema nodosum (EN) is a reactive inflammatory panniculitis characterized by erythematous subcutaneous nodules in the lower limbs. The association of GM with EN has been rarely reported. Our aim was to retrospectively review our series of patients with GM to better characterize their features and their association with EN. METHODS: Cases histologically diagnosed as granulomatous inflammation in breast tissue between 1995 and 2020 were retrospectively reviewed. RESULTS: Forty-two women were diagnosed with GM. The average age at diagnosis was 41.619years, and 59.5% were of South-American ethnicity. EN was associated with GM in 11.9% of the patients. Patients with EN were diagnosed earlier than isolated GM (0.4months vs 6.81months; P<.05). Ulceration in the GM was more prevalent in patients with associated EN (60% vs 14.7%; P<.05). CONCLUSION: EN in patients with GM may reduce the evolution time and may help to diagnose this rare condition that mimics breast carcinoma.

Methylprednisolone Pulses Plus Tacrolimus in Addition to Standard of Care vs. Standard of Care Alone in Patients With Severe COVID-19. A Randomized Controlled Trial.

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].

Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness.

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.

Comparative study between two European inception cohorts of patients with early systemic lupus erythematosus.

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.

The value of repeat biopsy in lupus nephritis flares.

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%.

Enteric-coated mycophenolate sodium versus azathioprine in patients with active systemic lupus erythematosus: a randomised clinical trial.

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.

Efficacy of anakinra in an adult patient with recurrent pericarditis and cardiac tamponade as initial manifestations of tumor necrosis factor receptor-associated periodic syndrome due to the R92Q TNFRSF1A variant.

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.

Shrinking lung syndrome in systemic lupus erythematosus: A case series and review of the literature.

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.

Patterns of drug therapy in newly diagnosed Spanish patients with systemic lupus erythematosus.

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.

Nefritis lúpica mesangial proliferativa: descripción de una cohorte de 27 pacientes / Proliferative mesangial lupus nephritis: description of a cohort of 27 patients

Fundamento y objetivo: Describir nuestra cohorte de pacientes con nefritis lúpica mesangial proliferativa y su seguimiento a largo plazo, con especial atención a los factores de mal pronóstico.Pacientes y método: Se evaluaron 27 pacientes de forma retrospectiva y controlados en el Servicio de Medicina Interna del Hospital Universitario de Bellvitge entre 1974 y 2010. Se realizó un control al año, a los 3 y a los 5 años de la biopsia. Resultados: Había 22 mujeres (81,5%), con una edad media (DE) en el momento del diagnóstico de la nefritis de 34,83 (13,45) años. Al año de la biopsia 21 pacientes habían alcanzado la remisión parcial o completa (80,77%) y a los 5 años de control 21 pacientes (77,77%) estaban en remisión. Cuatro pacientes sufrieron transformación a otra clase histológica. Recidivaron 7 pacientes (29,63%). En estos 36 años de seguimiento fallecieron 7 pacientes, 3 de ellos por causas relacionadas con el lupus eritematoso sistémico. Conclusiones: El factor pronóstico más claramente relacionado con una mala respuesta es el inicio de la nefritis por encima de los 45 años, por lo que se debería valorar el uso de inmunodepresores de entrada asociados a glucocorticoides en estos pacientes (AU)

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 (AU)

Nefritis lúpica mesangial proliferativa: descripción de una cohorte de 27 pacientes / Proliferative mesangial lupus nephritis: description of a cohort of 27 patients

Fundamento y objetivo: Describir nuestra cohorte de pacientes con nefritis lúpica mesangial proliferativa y su seguimiento a largo plazo, con especial atención a los factores de mal pronóstico.Pacientes y método: Se evaluaron 27 pacientes de forma retrospectiva y controlados en el Servicio de Medicina Interna del Hospital Universitario de Bellvitge entre 1974 y 2010. Se realizó un control al año, a los 3 y a los 5 años de la biopsia. Resultados: Había 22 mujeres (81,5%), con una edad media (DE) en el momento del diagnóstico de la nefritis de 34,83 (13,45) años. Al año de la biopsia 21 pacientes habían alcanzado la remisión parcial o completa (80,77%) y a los 5 años de control 21 pacientes (77,77%) estaban en remisión. Cuatro pacientes sufrieron transformación a otra clase histológica. Recidivaron 7 pacientes (29,63%). En estos 36 años de seguimiento fallecieron 7 pacientes, 3 de ellos por causas relacionadas con el lupus eritematoso sistémico. Conclusiones:El factor pronóstico más claramente relacionado con una mala respuesta es el inicio de la nefritis por encima de los 45 años, por lo que se debería valorar el uso de inmunodepresores de entrada asociados a glucocorticoides en estos paciente (AU)

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 (AU)

[Proliferative mesangial lupus nephritis: description of a cohort of 27 patients]. / Nefritis lúpica mesangial proliferativa: descripción de una cohorte de 27 pacientes.

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.

Patient registries of acute coronary syndrome: assessing or biasing the clinical real world data?

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.

Predicting in-hospital mortality with coronary bypass surgery using hospital discharge data: comparison with a prospective observational study.

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.

Predicción de la mortalidad hospitalaria en la cirugía de derivación aortocoronaria mediante datos administrativos: comparación con un estudio observacional prospectivo / Predicting In-Hospital Mortality With Coronary Bypass Surgery Using Hospital Discharge Data: Comparison With a Prospective Observational Study

Introducción y objetivos. Este estudio pretende evaluarla validez del Conjunto Mínimo Básico de Datos(CMBD) al alta hospitalaria para predecir la mortalidadhospitalaria en cirugía coronaria, utilizando como referencia los datos de un estudio observacional prospectivo.Métodos. Entre noviembre de 2001 y noviembre de2003 se recogieron prospectivamente los datos de lospacientes sometidos a una primera intervención de derivación aortocoronaria en cinco hospitales catalanes. Se obtuvieron del CMBD los registros del mismo período ylos mismos centros con código de procedimiento 36.1. Seanalizó la concordancia de la información procedente deambas fuentes y se construyeron modelos predictivos demortalidad hospitalaria mediante regresión logística. Sevalidó el modelo derivado de datos administrativos aplicándolo a los datos procedentes del estudio observacional y a los datos del CMBD del período 2004-2006 mediante los índices de discriminación y calibración.Resultados. El 4,1% de los casos incluidos en el estudioprospectivo no se localizaron en el CMBD. La concordanciaentre la información procedente de ambas fuentesfue variable (kappa, 0,16-0,79) y globalmente baja. La capacidad de discriminación del modelo administrativo fuecomparable a la del modelo del estudio observacional (c= 0,80 frente a c = 0,79), pero al validarlo con los datos prospectivos y los datos del CMBD 2004-2006, la capacidad de discriminación disminuyó (c = 0,76 y c = 0,65) y la calibración empeoró (p < 0,001).Conclusiones. El CMBD es insuficiente para una adecuadavaloración del riesgo de mortalidad hospitalaria encirugía coronaria. Sin embargo, los resultados indican que hay potencial de mejora en su uso como instrumentopredictivo

Introduction and objectives. The aim was todetermine the usefulness of the hospital dischargeMinimum Basic Data Set (MBDS) for predicting in-hospitalmortality with coronary bypass surgery by using data froma prospective observational study as a reference.Methods. The observational study involved collectingdata on all patients undergoing first coronary bypasssurgery at five hospitals in Catalonia, Spain betweenNovember 2001 and November 2003. In addition, datacovering the same period and hospitals were obtainedfrom the MBDS for procedure code 36.1. We investigatedthe concordance between the information from the twodata sources and logistic regression was used to derivepredictive models for in-hospital mortality. The modelderived using MBDS data was validated using data fromthe prospective observational study and MBDS data forthe years 2004-2006. Model validity was evaluated usingdiscrimination and calibration indices.Results. Some 4.1% of cases in the observationalstudy could not be found in the MBDS. The concordancebetween the two data sources was highly variable andgenerally low (kappa values ranged from 0.16 to 0.79).The discriminative ability of the MBDS model wasequivalent to that of the observational study model(c=0.80 vs. c=0.79), but when the validity of the formerwas tested using prospective data and MBDS data for2004-2006, the discrimination c-index decreased to 0.76and 0.65, respectively, and the calibration worsenedsignificantly (P<.001).Conclusions. The risk of in-hospital mortality followingcoronary surgery cannot be accurately evaluated usingMBDS data. However, our results indicate that their useas a predictive tool could be improved