Clinical characterization of a cohort of patients treated for systemic lupus erythematosus in Colombia: A retrospective study.

INTRODUCTION: Systemic lupus erythematosus is an autoimmune disease associated with serious complications and high costs. The aim was to describe the clinical characteristics and health care resource utilization of a Colombian systemic lupus erythematosus outpatient cohort. METHODS: This was a retrospective descriptive study. Clinical records and claims data for systemic lupus erythematosus patients from ten specialized care centers in Colombia were reviewed for up to 12 months. Baseline clinical variables, Systemic Lupus Erythematosus Disease Activity Index, drug use, and direct costs were measured. Descriptive statistics were analyzed using SPSS. RESULTS: A total of 413 patients were included; 361 (87.4%) were female, and the mean age was 42 ± 14 years. The mean disease evolution was 8.9 ± 6.0 years; 174 patients (42.1%) had a systemic manifestation at baseline, mostly lupus nephritis (105; 25.4%). A total of 334 patients (80.9%) had at least one comorbidity, mainly antiphospholipid syndrome (90; 21.8%) and hypertension (76; 18.4%). The baseline Systemic Lupus Erythematosus Disease Activity Index score was 0 in 215 patients (52.0%), 1-5 in 154 (37.3%), 6-10 in 41 (9.9%) and 11+ in 3 (0.7%). All patients received pharmacological therapy, and the most common treatment was corticosteroids (293; 70.9%), followed by antimalarials (chloroquine 52.5%, hydroxychloroquine 31.0%), immunosuppressants (azathioprine 45.3%, methotrexate 21.5%, mycophenolate mofetil 20.1%, cyclosporine 8.0%, cyclophosphamide 6.8%, leflunomide 4.8%) and biologicals (10.9%). The mean annual costs were USD1954 per patient/year, USD1555 for antirheumatic drugs (USD10,487 for those with biologicals), USD86 for medical visits, USD235 for drug infusions and USD199 for laboratory tests. CONCLUSIONS: Systemic lupus erythematosus generates an important economic and morbidity burden for the Colombian health system. Systemic lupus erythematosus outpatient attention costs in the observation year were mainly determined by drug therapy (especially biologics), medical visits and laboratory tests. New studies addressing the rate of exacerbations, long-term follow-up or costs related to hospital care are recommended.

Análisis epidemiológico multicéntrico de las fracturas de cadera en Uruguay: importancia y planificación de un registro nacional / Multicenter epidemiological analysis of hip fractures in Uruguay: importance and planning of a national register / Análise epidemiológica multicêntrica de fraturas de quadril no Uruguai: importância e planejamento de um registro nacional

Introducción: La incidencia de fracturas de cadera presenta un aumento dramático desde la mediana edad, constituyendo un problema de salud prevalente en adultos mayores. Se realizó una revisión bibliográfica de los registros internacionales de fracturas de cadera y un estudio epidemiológico multicéntrico para conocer la incidencia, los costos y la mortalidad de esta patología en nuestro país. Material y métodos: Se realizó una búsqueda, revisión y análisis de todos los registros internacionales de fracturas de cadera existentes en el mundo. Posteriormente, se llevó a cabo un análisis descriptivo observacional retrospectivo y multicéntrico en 4 instituciones de pacientes mayores de 50 años intervenidos quirúrgicamente con osteosíntesis por fractura de cadera en el año 2019. En los datos anonimizados se evaluaron edad, sexo, tipo de fractura, incidencia y costos. Se incluyeron y asociaron, además, datos estadísticos y económicos del Registro del Fondo Nacional de Recursos. Se utilizó el software estadístico SPSS para establecer asociaciones univariadas, bivariadas y multivariadas. Para comparar las proporciones se empleó el test estadístico de chi cuadrado. Resultados: Se resume la revisión de registros en una tabla. El análisis multicéntrico contó con 646 pacientes con fracturas de cadera. Destacamos la alta prevalencia de esta patología en pacientes mayores de 79 años (63,1%) y en el sexo femenino (77,6%), en concordancia con los registros internacionales, con asociación significativa entre ambas variables (p < 0,0001). A diferencia de otros registros, y quizás dato erróneo, la fractura más frecuente fue la del cuello de fémur (43%). El tiempo entre la fractura y la cirugía y los días de internación fueron de 2,6 y 7,2 días, respectivamente, en la institución de asistencia más efectiva. Nuestro cálculo mostró una incidencia de fractura de cadera en Uruguay que oscila entre 235 y 391 en 100.000 habitantes mayores de 50 años. El costo calculado de la serie evaluada fue de unos U$S 2.855.320 y, en general, esta patología provoca un gasto para nuestro país que se aproxima a U$S 20.000.000 por año. Conclusión: La fractura de cadera presenta una elevada incidencia, costos y morbimortalidad en la población de adultos mayores, comparable con datos internacionales. Es necesario contar con un Registro Nacional de Fracturas de Cadera que permita conocer datos estadísticos certeros para poder establecer políticas adecuadas de prevención, tratamiento y control de gastos.

Introduction: The incidence of hip fractures dramatically increases from middle age on, posing a prevalent health problem in elderly people. A literature review of the international hip fracture registers, as well as a multicenter, epidemiological study were carried out in order to assess the incidence, costs, and mortality of this pathology in our country. Material and methods: All international hip fracture registers in the world were searched, reviewed and analyzed. An observational, retrospective, multicenter descriptive analysis was then carried out in 4 health-care centers for patents over 50 years of age who underwent surgery with osteosynthesis due to hip fracture in 2019. Age, sex, type of fracture, incidence and costs were assessed from the anonymized data. Statistical and economic data from the National Resources Fund Register were also included and associated. The SPSS statistical software was used to establish univariate, bivariate, and multivariate associations. The chi-squared statistical test was used to compare proportions. Results: Review of the registers is summarized in a table. The multicenter analysis included 646 patients with hip fractures. Worth of note is the high prevalence of this pathology in patients over 79 years of age (63.1%) and females (77.6%), in line with the international registers, and a significant association between both variables (p < 0.0001). Unlike other registers, and probably due to inaccurate data, the most frequent fracture was that of femoral neck (43%). The time from fracture to surgery and inpatient days were 2.6 and 7.2 days, respectively, in the most effective health care center. Our calculation showed a hip fracture incidence in Uruguay between 235 and 391 per 100,000 inhabitants over 50 years of age. The estimated cost of the assessed series was about U$S 2,855,320, and in general this pathology generates an annual expense of about U$S 20,000,000 for our country. Conclusion: Hip fractures have high incidence, costs and mortality and morbidity in the elderly population comparable with international data. It is necessary to have a National Hip Fracture Register that provides accurate statistical data in order to establish adequate prevention, treatment and cost control policies.

Introdução: A incidência de fraturas de quadril apresenta um aumento dramático a partir da meia-idade, constituindo um problema de saúde prevalente em idosos. Uma revisão bibliográfica dos Registros Internacionais de Fratura de Quadril e um estudo epidemiológico multicêntrico foram realizados para determinar a incidência, os custos e a mortalidade dessa patologia em nosso país. Material e métodos: Foi realizada uma busca, revisão e análise de todos os Registros Internacionais de fraturas de quadril existentes no mundo. Posteriormente, foi realizada uma análise observacional descritiva retrospectiva e multicêntrica, em 4 Instituições, de pacientes maiores de 50 anos, submetidos à cirurgia com osteossíntese, para fratura de quadril em 2019. Nos dados anônimos foram avaliados idade e sexo, tipo de fratura , incidência e custos. Dados estatísticos e econômicos do Registro do Fundo Nacional de Recursos também foram incluídos e associados. O software estatístico SPSS foi usado para estabelecer associações univariadas, bivariadas e multivariadas. O teste estatístico do qui quadrado foi usado para comparar as proporções. Resultados: a revisão dos registros é resumida em uma tabela. A análise multicêntrica incluiu 646 pacientes com fraturas de quadril. Destaca-se a alta prevalência dessa patologia em pacientes maiores de 79 anos (63,1%) e no sexo feminino (77,6%), de acordo com registros internacionais, com associação significativa entre as duas variáveis ​​(p <0,0001). Ao contrário de outros registros, e talvez dados errôneos, a fratura mais frequente foi a do colo do fêmur (43%). O tempo decorrido entre a fratura e a cirurgia e os dias de internação foram de 2,6 e 7,2 dias, respectivamente, na instituição assistencial mais efetiva. Nosso cálculo mostrou uma incidência de fratura de quadril no Uruguai, variando entre 235 e 391 em 100.000 habitantes com mais de 50 anos de idade. O custo calculado da série avaliada foi em torno de US $ 2.855.320 e, em geral, essa patologia acarreta um gasto para o nosso país que é próximo a US $ 20.000.000 por ano. Conclusão: A fratura de quadril tem alta incidência, custo e morbimortalidade na população idosa, comparável a dados internacionais. É necessário um Cadastro Nacional de Fraturas de Quadril, que permita conhecer dados estatísticos precisos, para estabelecer políticas adequadas de prevenção, tratamento e controle de custos.

Personalized medicine. Closing the gap between knowledge and clinical practice.

Personalized medicine encompasses a broad and evolving field informed by a patient distinctive information and biomarker profile. Although terminology is evolving and some semantic interpretations exist (e.g., personalized, individualized, precision), in a broad sense personalized medicine can be coined as: "To practice medicine as it once used to be in the past using the current biotechnological tools." A humanized approach to personalized medicine would offer the possibility of exploiting systems biology and its concept of P5 medicine, where predictive factors for developing a disease should be examined within populations in order to establish preventive measures on at-risk individuals, for whom healthcare should be personalized and participatory. Herein, the process of personalized medicine is presented together with the options that can be offered in health care systems with limited resources for diseases like rheumatoid arthritis and type 1 diabetes.

Simultaneous assessment of rotavirus-specific memory B cells and serological memory after B cell depletion therapy with rituximab.

The mechanisms that contribute to the maintenance of serological memory are still unclear. Rotavirus (RV) memory B cells (mBc) are enriched in IgM(+) and CD27- subpopulations, which are associated with autoimmune diseases pathogenesis. In patients with autoimmune diseases treated with Rituximab (RTX), some autoantibodies (auto-Abs) decrease after treatment, but other auto-Abs and pathogen-specific IgG Abs remain unchanged. Thus, maintenance of autoimmune and pathogen-specific serological memory may depend on the type of antigen and/or Ab isotype evaluated. Antigen-specific mBc and antigen-specific Abs of different isotypes have not been simultaneously assessed in patients after RTX treatment. To study the relationship between mBc subpopulations and serological memory we characterized total, RV- and tetanus toxoid (TT)-specific mBc by flow cytometry in patients with autoimmune diseases before and after treatment with RTX. We also measured total, RV- and TT-Abs, and some auto-Abs by kinetic nephelometry, ELISA, and EliA tests, respectively. Minor differences were observed between the relative frequencies of RV-mBc in healthy controls and patients with autoimmune disease. After RTX treatment, naïve Bc and total, RV- and TT-specific mBc [IgM(+), switched (IgA(+)/IgG(+)), IgM(+) only, IgD(+) only, and CD27- (IgA(+)/IgG(+)/IgM(+))] were significantly diminished. An important decrease in total plasma IgM and minor decreases in total IgG and IgA levels were also observed. IgM rheumatoid factor, IgG anti-CCP, and IgG anti-dsDNA were significantly diminished. In contrast, RV-IgA, RV-IgG and RV-IgG1, and TT-IgG titers remained stable. In conclusion, in patients with autoimmunity, serological memory against RV and TT seem to be maintained by long-lived plasma cells, unaffected by RTX, and an important proportion of total IgM and serological memory against some auto-antigens seem to be maintained by short-lived plasma cells, dependent on mBc precursors depleted by RTX.

Prevalence and clinical features of multiple sclerosis in Latin America.

Multiple sclerosis (MS) in Latin America (LA) is considered to have a low to medium prevalence. However, accurate information on MS in LA is scarce. The aim of this study was to compare clinical characteristics among LA patients through a systematic review of the literature. A systematic search (Spanish, Portuguese and English) was done for all clinical studies of MS in humans (MEDLINE, PubMed, Scielo, BIREME, EMBASE and LILACS) up to May 2011 being focused on a well-defined Latin American population (peer-reviewed journal) following the MOOSE guidelines. The search strategy included combinations of different Mesh terms (two independent researchers). Classification of each article by using the Oxford Centre for Evidence-based Medicine - Levels of Evidence was done. The total number of patients per country for each specific characteristic was compiled. Chi-square test was used to compare the characteristics in the studies retrieved per country. There were 38 articles fulfilling the inclusion criteria, accounting for 4524 patients. Relapsing-remitting form was the most frequent in LA patients and the main initial symptom was motor, followed by optic neuritis and sensorial. A mild expanded disability status scale was the most prevalent in all LA countries. Factors accounting for differences in distribution and clinical course across LA countries include genetics, environment, diagnostic techniques, socioeconomic structure and medical facilities.

Primary biliary cirrhosis and the nuclear pore complex.

Experimental models of autoimmune diseases have led to the conclusion that an immune response to nuclear antigens is a sentinel marker for loss of tolerance and potential tissue damage. Various proteins are targets of antinuclear antibodies in a variety of autoimmune diseases, ranging from systemic rheumatologic disorders to diseases affecting specific organs such as the liver. Autoantibodies against specific nuclear constituents have also been used as probes to understand the structure and the function of the targeted components and their relevance to disease pathogenesis. Approximately a quarter of patients with primary biliary cirrhosis (PBC) have antibodies targeting proteins of the nuclear pore complex (NPC), a multi-protein structure that mediates molecular transport across the nuclear envelope. Autoantibodies against the integral membrane glycoprotein gp210 and nucleoporin p62 appear to be highly specific for PBC, an autoimmune disease characterized by progressive destruction of intrahepatic biliary epithelial cells. This review discusses the diagnostic and clinical relevance of anti-NPC antibodies in PBC and the possibility that this autoimmune response may arise as a result of molecular mimicry.

IgM predominance in autoimmune disease: genetics and gender.

The role of specific immunoglobulin isotypes in human autoimmune disease has long attracted attention. Indeed, the presence of a polyclonal gammopathy is well known in a variety of systemic autoimmune diseases and is likely the result of chronic inflammation. However, in specific clinical situations, patients manifest isolated and elevated IgM levels, but normal IgG and IgA. The pathophysiology of this elevation and the clinical significance have been elusive. However, the relationships between specific genes and hyper-IgM are now very well defined, as it has been documented in primary hyper IgM syndromes. In this review we present data on clinical diseases with characteristic IgM abnormalities, including primary and secondary hyper IgM syndromes, autoimmune hemolytic anemia, cryoglobulinemia, primary biliary cirrhosis and multiple sclerosis and place the data in the perspective of the normal maturation of the immune response, including somatic mutation and genetic rearrangement.

A TGF-beta mediated regulatory mechanism modulates the T cell immune response to rotavirus in adults but not in children.

Children with acute RV-gastroenteritis (GE) had low or undetectable levels of circulating IFN-gamma(+), IL-13(+), IL-2(+), IL-10(+) or IL-17(+) RV-T cells. IFN-gamma(+) T cells and low frequencies of IL-10(+) and IL-2(+) CD4(+) T cells were found in adults with RV-GE during acute and convalescence phases, respectively. Circulating single IFN-gamma(+)>double IFN-gamma(+)/IL-2(+)>single IL-2(+)RV-CD4(+)T cells were observed in healthy adults. In this group, frequencies of IFN-gamma(+) RV-T cells increased after removing CD25(+)cells, blocking TGF-beta with its natural inhibitor, LAP, or inhibiting TGF-betaRI signalling pathway with ALK5i. The frequencies of IFN-gamma(+) RV-T cells were also incremented in PBMC depleted of CD25(+)cells and treated with ALK5i, suggesting that TGFbeta inhibition may be independent of Treg cells. The ALK5i effect was observed in adults but not in children with RV-GE, who had normal numbers of TGF-beta+ Treg cells. Thus, a TGF-beta-mediated regulatory mechanism that modulates RV-T cells in adults is not evident in children.

Factors influencing polyautoimmunity in systemic lupus erythematosus.

OBJECTIVE: Since characterization of the extent to which particular combinations of autoimmune diseases (ADs) occur in excess of that expected by chance may offer new insights into possible common pathophysiological mechanisms, polyautoimmunity (i.e., ADs co-occurring within patients) in systemic lupus erythematosus (SLE) and its associated factors were investigated. METHODS: This was a cross-sectional study in which 335 consecutive patients with SLE and the history of 22 ADs were investigated. A multivariate analysis was performed. A systematic literature review was done and results were grouped by hierarchical cluster procedure analysis. RESULTS: There were 136 (41%) SLE patients presenting with at least one other AD. A total of 191 ADs were observed, of which the most frequent were autoimmune thyroid disease (AITD), antiphospholipid syndrome (APS) and Sjögren's syndrome (SS), registered in 60 (18%), 48 (14%) and 47 (14%) cases, respectively. Out of a total number of 1515 SLE patients with polyautoimmunity (1379 reported previously and 136 informed here) there were 77 (5.1%) cases with multiple autoimmune syndrome (i.e., two or more ADs in addition to SLE). Female gender, articular involvement, familial autoimmunity, anti-Ro positivity and patient's origin were risk factors for polyautoimmunity while the presence of anti-RNP antibodies was protective. Four clusters of ADs were found. The most hierarchical one was composed of AITD, APS, SS, and systemic sclerosis. CONCLUSION: Polyautoimmunity is frequent in SLE, and it is influenced by clinical and immunological features. These findings support that clinically different autoimmune phenotypes might share common susceptibility variants.

Successful treatment of relapsing autoimmune pancreatitis in primary Sjögren's syndrome with rituximab: report of a case and review of the literature.

Autoimmune pancreatitis (AIP) is a rare disorder often associated with multiple autoimmune diseases like rheumatoid arthritis, inflammatory bowel disease and Sjögren's syndrome (SS). Although knowledge of AIP has grown over the last few years, little is certain about its cause and pathogenesis. Positive immunologic markers like antinuclear antibodies (ANA) or elevated serum levels of IgG4, systemic autoimmune disease association and positive response to oral steroid therapy strongly supports the idea of autoimmune mechanisms involved in the pathogenesis of AIP. We describe the first case reported on the literature of a patient with primary SS who developed relapsing AIP to steroids but responded successfully to Rituximab (RTX) therapy. New theories about the role of B-cells activity in SS and other autoimmune diseases has encourage the use of RTX, proving tolerance and efficacy especially in extra-glandular manifestations.

HLA class II association with autoimmune hepatitis in Latin America: a meta-analysis.

BACKGROUND: Autoimmune hepatitis (AIH) is a chronic liver disease to which different Human Leukocyte Antigens (HLA) have been associated, according to the ethnic/geographical group affected, age of presentation, prognosis, and serologic profile. OBJECTIVE: To identify common HLA class II alleles contributing to susceptibility to AIH in Latin American population. METHODS: The present study was held through a systematic review of the literature, followed by a meta-analysis of 694 cases and 1769 controls of all case-control studies that supplied enough information for odd ratio and 95% confidence interval calculation conducted to date in Latin America. RESULTS: The serological group DQ2 was found to be risk factor for AIH, while DR5 and DQ3 were found to be protective factors in this population. At the allelic level, DQB1*02, DQB1*0603, DRB1*0405, and DRB1*1301, were found to be risk factors, while DRB1*1302 and DQB1*0301 alleles were protective factors. The physicochemical similarities and differences of critical amino acids encoding the peptide binding groove at pockets P1, P4, and P6 of these HLA molecules, elucidates their influence in the development of disease. CONCLUSION: The current study strengthens the HLA component of AIH in Latin America and its relationship to other populations around the world.