The prognostic value of neutrophile/lymphocyte ratio and serum chemerin to predict maternal-fetal complications in pregnant systemic lupus erythematosus patients.

BACKGROUND: Pregnancy in SLE continues to be a challenge. The neutrophil-to-lymphocyte ratio (NLR) and chemerin are predictors of preeclampsia in the general population; however, their role as predictors of maternal-fetal complications in pregnant SLE patients has not been analyzed. OBJECTIVE: To investigate the prognostic value of NLR and serum chemerin, to predict maternal-fetal complications in pregnant SLE patients, and compare both biomarkers among three study groups. METHODS: Design: Analytical cross-sectional study of cases and controls with the following study groups: systemic lupus erythematosus (SLE), preeclampsia, and healthy. NLR and chemerin serum were determined between 20 and 25 weeks of gestation. Patients were evaluated every 4-6 weeks until pregnancy resolution. Maternal and fetal outcomes were registered. We employed Receiver Operating Characteristic (ROC) curves to validate prognostic values. RESULTS: Seventy pregnant patients were included: 20 with SLE, 20 with preeclampsia, and 30 healthy pregnant women; NLR values were 4 (2.3-5.6) in SLE, 6 (4.6-9.2) in preeclampsia, and 2.8 (2.1-2.9) in the group of healthy women (p = .0001). Chemerin levels were: 26 (15.3-56.2) in SLE, 96 (37.3-146.2) in preeclampsia, and 24.6 ng/mL (15.3-47.4) in the healthy group (p = .007) Maternal complications were observed in 11 (55%), 20 (100%), and 8 (26%) per group, respectively. Thrombocytopenia was the most frequent complication in all pregnant women, followed by hypertensive disorders. Fetal complications were registered in 12 (60%), 16 (80%), and 2 (6.7%), respectively. Congenital malformations and prematurity were the most frequent fetal complications. NLR had good diagnostic accuracy in predicting maternal-fetal complications (AUROC 0.715) p = .015, CI 95% 0.56-0.86, cut-off point level: 2.9, sensitivity 61%, specificity 78%, positive predictive value (PPV) 65%, negative predictive value (NPV) 75%. Regarding chemerin, a cut-off point level >43 ng/mL had a sensitivity of 75%, specificity of 72% AUROC 0.75, p = .001, CI 95% 0.61-0.89, PPV 51.7% NPV 87.8%, meaning that 51.7% of patients with chemerin levels >43 ng/mL have or will have preeclampsia. CONCLUSION: The NLR may help predict maternal-fetal complications in SLE pregnancy, constituting a marker of subclinical inflammation. Chemerin levels may be associated with preeclampsia. These biomarkers could improve the care of SLE patients with timely intervention of potential complications during pregnancy.

Effectiveness of Saccharomyces boulardii and Metronidazole for Small Intestinal Bacterial Overgrowth in Systemic Sclerosis.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) affects up to 60% of patients with systemic sclerosis (SSc), and it improves with antibiotics. The addition of probiotics could lead to better results. AIMS: To evaluate the efficacy and safety of Saccharomyces boulardii (SB) versus metronidazole (M) versus M + SB for 2 months, to reduce gastrointestinal symptoms and SIBO assessed with hydrogen breath test in SSc. METHODS: An open pilot clinical trial performed in forty patients with SIBO and SSc (ACR-EULAR 2013) who signed informed consent. Three groups were assigned: M, SB, and M + SB, for 2 months. Hydrogen was measured in parts per million with a hydrogen breath test to evaluate SIBO. The National Institutes of Health Patient-Reported Outcomes Measurement Information System (NIH-PROMIS) questionnaire was applied to quantify gastrointestinal symptoms with a raw score of eight symptoms. This study is registered in ClinicalTrials.gov with the following ID: NCT03692299. RESULTS: Baseline characteristics were similar between groups. The average age was 53.2 ± 9.3 years, and the evolution of SSc was 13.5 (1-34) years. After 2 months of treatment, SIBO was eradicated in 55% of the M + SB group: 33% of SB, and 25% of M. The SB and M + SB groups had decreased diarrhea, abdominal pain, and gas/bloating/flatulence, but M remained unchanged. Reductions in expired hydrogen at 45 to 60 min were as follows: M + SB 48% and 44%, M 18% and 20%, and SB 53% and 60% at the first and second months, respectively (p < 0.01). Adverse effects were epigastric burning and constipation in M (53%) and M + SB (36%), and flatulence/diarrhea in SB (22%). CONCLUSIONS: Metronidazole treatment is partially effective in SIBO, but S. boulardii in monotherapy or in combination improves the gastrointestinal outcomes in SSc.

Malnutrition is an independent risk factor for mortality in Mexican patients with systemic sclerosis: a cohort study.

Factors for mortality in systemic sclerosis (SSc) vary in different cohorts around the world. Case-control study nested in a cohort. We included patients ≥16 years of age with SSc (ACR/EULAR 2013), from 2005 to 2015. Demographic and clinical variables and causes of mortality were recorded. We calculated Crude Mortality Rate (CMR), Standardized Mortality Ratio (SMR), and Kaplan-Meier survival analysis was performed. A Cox proportional hazard (HR) regression analysis of the potential risk factors associated with mortality was also performed. A total of 220 patients with SSc were included. During follow-up, 28 deaths occurred. The sum of total time contributed by all subjects was 1074 years-person, the CMR was 12.72%, the overall SMR was 4.5, in women 3.7, and in men 4.7. The survival rate at 5 and 10 years was 83 and 70%, respectively. The causes of death were definitively attributed to SSc in 21.4% of the cases, probably in 28.7%, unrelated in 35.6%, and unknown in 14.3%. The direct cause of death of the patients was infection in 25% of cases, cardiovascular disease in 14%, lung involvement in 14%, pulmonary embolism in 11%, and neoplasia in 11%. The Cox regression analysis showed that the factors associated with mortality were: male gender (HR 5.84, CI 95% 1.31-26, p = 0.013), severe Medsger's score for general symptoms (HR 5.12, CI 95% 1.74-14.97, p = 0.021) and severe malnutrition (HR 3.77, CI 95% 1.23-11.06, p = 0.008). Infections, cardiovascular disease, and lung involvement were the leading cause of death. Male gender and severe general affection and malnutrition were associated with a poorer prognosis of SSc.

The Systemic Sclerosis Questionnaire (SySQ): Validation of the translation of the original German version into Spanish and its relationship to the disease and to quality of life. / Cuestionario de funcionalidad para esclerosis sistémica (SySQ): validación en español del original en alemán y su relación con la enfermedad y la calidad de vida.

OBJECTIVE: Translation, transculturation and validity of the self-administered questionnaire for functionality (Systemic Sclerosis Questionnaires [SySQ]) for use in Spanish patients with systemic sclerosis and its relationship to the severity of the disease and to quality of life. PATIENTS AND METHODS: We conducted an observational analytical study to perform a cross-cultural validation of the self-administered questionnaire on functionality in scleroderma. The validity of the form and content was evaluated by an expert panel. The method included: a) adaptation into Spanish of the construct for translation and back translation, and transculturation; b) internal consistency with the SySQ (Cronbach's alpha), and c) reproducibility was assessed taking into account all occasions in which the test was performed with Cohen's kappa. Additionally, we calculated the Spearman correlation coefficient with the Medsger severity scale, Health Assessment Questionnaire score and SF-36 score. RESULTS: We included 70 patients with systemic sclerosis: age 17-78 (51±12) years, 65 (93%) were women, diffuse/limited subtype 64/36%, disease duration of 0.5-40 years. Optimal internal consistency for all categories of the final version of SySQ (Cronbach's α of 0.961) and intraobserver reliability in 2 tests over a 2-week interval (Cohen's kappa coefficient 0.618) and optimal interobserver reliability in 2 tests on the same day (Cohen's kappa coefficient 0.911). Moderate correlation between functionality by SySQ and by Health Assessment Questionnaire (r=0.573, P<.0001). Inverse correlation between SySQ and quality of life mental health domain SF-36 (r=-0.435, P<.001) and physical domain SF-36 (r=-0.638, P<.001). Medsger severity scale (tendon, heart, lung, vascular) also showed significant correlation with SySQ. CONCLUSIONS: SySQ in this validated Spanish version is a suitable instrument to measure functional status in patients with systemic sclerosis. Reduced functionality is related to greater tendon and peripheral vascular involvement and to a poorer quality of life.

Clinical, biochemical, and radiological characterization of the calcinosis in a cohort of Mexican patients with systemic sclerosis.

Calcinosis is a frequent complication of systemic sclerosis (SSc) that is usually located in extremities but may occur across the board. The aim of our study was to identify and quantify the distribution of calcinosis in a cohort of Mexican patients with SSc and its association with clinical features and autoantibodies. A cohort of patients with SSc (2013 ACR/EULAR criteria), classified in diffuse cutaneous (dcSSc) and limited cutaneous (lcSSc) (Le Roy criteria), was studied. For their analysis, patients were allocated into those with and without calcinosis (clinical and/or radiological). The evaluation included the modified Rodnan scale for skin and Medsger disease severity scale (DSS). Calcium, phosphorus, vitamin D, and parathyroid hormone (PTH) and antinuclear antibodies and extractable nuclear antigens were determined in serum. A total of 109 patients were included, 41 (37 %) with and 68 (63 %) without calcinosis. Calcinosis was more frequent in patients with dcSSc (55 vs 27 %). In total, we identified 354 sites with calcinosis and mean per patient of 12.0 ± 9.1; the most common sites affected were the hands (83 %), proximal upper extremity (27 %), and proximal lower extremity (22 %). Patients with calcinosis had a higher score of Rodnan scale, Mesdger DSS, and frequency of anti-nucleolar and anti-Scl-70 antibodies compared to those without calcinosis. Abnormal PTH elevation was found in 35 % of patients with calcinosis and 23 % without it. The prevalence of calcinosis is high in Mexican patients with SSc, especially in diffuse variety, and is associated with increased severity of disease.

Severe manifestations of autoimmune syndrome induced by adjuvants (Shoenfeld's syndrome).

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) encompassing conditions linked to previous exposure to an adjuvant substance. The clinical picture is very heterogeneous, from mild to severe manifestations, including death. However, the systematic analysis of severe ASIA cases has not been performed. The aim of this study was to systematically review the literature on severe ASIA cases. A systematic review of the literature was performed investigating severe ASIA cases. All publications were identified through PubMed, EMBASE, MEDLINE and Cochrane. Articles published from 2011 to 2016 were included. Severe ASIA was arbitrarily defined as follows: major organ involvement, life-threatening conditions, intensive treatment, disability, hospitalization and outcome (survival and death). Cases described before 2011 were excluded. From 2011 to 2016, we identified 4479 ASIA cases, of them 305 fulfilled arbitrary criteria of severe ASIA including our case presentation and 11 deaths. The majority of severe ASIA cases were related to HPV vaccine, silicone, influenza vaccine and mineral oil injections. The interval from exposition to severe manifestation was from 2 days to 23 years. (1) This is the first study that analyzes all cases published on ASIA with severe manifestations. (2) The current HPV vaccine is both effective and generally safe. However, it should be noted that severe autoimmune side effects have been reported in several studies. Severe ASIA may be observed after influenza vaccines, and other vaccines. (3) Efforts should be made to discover the connection between adjuvants, autoimmunity and autoimmune diseases, because there is an increase in cases severe and life-threatening of ASIA.

Cuestionario de funcionalidad para esclerosis sistémica (SySQ): validación en español del original en alemán y su relación con la enfermedad y la calidad de vida / The Systemic Sclerosis Questionnaire (SySQ): validation of the translation of the original German version into Spanish and its relationship to the disease and to quality of life

OBJETIVO: Traducción, transculturización y validez del cuestionario autoadministrado para funcionalidad (Systemic Sclerosis Questionnaire [SySQ]) en esclerosis sistémica al idioma español y su relación con la enfermedad y la calidad de vida. PACIENTES Y MÉTODOS: Estudio observacional analítico. Validación realizada por panel de expertos, en apariencia y contenido. La metodología incluyó: a) adaptación al español del constructo por traducción, retrotraducción, y transculturización; b) consistencia interna para todas y cada una de las categorías del SySQ (alfa de Cronbach), y c) la reproducibilidad se evaluó tomando en cuenta todas las ocasiones en que se realizó la prueba con kappa de Cohen. Adicionalmente calculamos el coeficiente de correlación de Spearman con: 1) escala de severidad de Medsger; 2) Health Assessment Questionnaire, y 3) prueba SF-36. RESULTADOS: Se incluyeron 70 pacientes con esclerosis sistémica, edad 17-78 (51+/-12) años, 65 (93%) mujeres, subtipo difuso/limitado 64/36%, evolución de la enfermedad 0,5-40 años. Observamos consistencia interna óptima de la versión final del SySQ (alfa de Cronbach 0,961) y buena reproducibilidad intraobservador entre pruebas con intervalo de 2 semanas (kappa de Cohen 0,618) y óptima interobservador el mismo día (kappa de Cohen 0,911). Moderada correlación entre los cuestionarios de funcionalidad SySQ y de discapacidad de Health Assessment Questionnaire (r=0,573; p < 0,0001). Correlación inversa entre SySQ y calidad de vida en dominio mental del SF-36 (r=-0,435; p < 0,001) y en dominio físico del SF-36 (r=-0,680; p < 0,001). La escala de severidad de la enfermedad de Medsger (tendón, corazón, pulmón, vascular) también mostró correlación significativa con SySQ. CONCLUSIONES: Esta versión en español del cuestionario autoadministrado SySQ es un instrumento válido para evaluar el estado funcional de pacientes con esclerosis sistémica. La menor funcionalidad está relacionada con una mayor afección a tendón y vascular periférico y con una menor calidad de vida

OBJECTIVE: Translation, transculturation and validity of the self-administered questionnaire for functionality (Systemic Sclerosis Questionnaires [SySQ]) for use in Spanish patients with systemic sclerosis and its relationship to the severity of the disease and to quality of life. PATIENTS AND METHODS: We conducted an observational analytical study to perform a cross-cultural validation of the self-administered questionnaire on functionality in scleroderma. The validity of the form and content was evaluated by an expert panel. The method included: a) adaptation into Spanish of the construct for translation and back translation, and transculturation; b) internal consistency with the SySQ (Cronbach's alpha), and c) reproducibility was assessed taking into account all occasions in which the test was performed with Cohen's kappa. Additionally, we calculated the Spearman correlation coefficient with the Medsger severity scale, Health Assessment Questionnaire score and SF-36 score. RESULTS: We included 70 patients with systemic sclerosis: age 17-78 (51+/-12) years, 65 (93%) were women, diffuse/limited subtype 64/36%, disease duration of 0.5-40 years. Optimal internal consistency for all categories of the final version of SySQ (Cronbach's alfa of 0.961) and intraobserver reliability in 2 tests over a 2-week interval (Cohen's kappa coefficient 0.618) and optimal interobserver reliability in 2 tests on the same day (Cohen's kappa coefficient 0.911). Moderate correlation between functionality by SySQ and by Health Assessment Questionnaire (r=0.573, P<.0001). Inverse correlation between SySQ and quality of life mental health domain SF-36 (r=-0.435, P<.001) and physical domain SF-36 (r=-0.638, P<.001). Medsger severity scale (tendon, heart, lung, vascular) also showed significant correlation with SySQ. CONCLUSIONS: SySQ in this validated Spanish version is a suitable instrument to measure functional status in patients with systemic sclerosis. Reduced functionality is related to greater tendon and peripheral vascular involvement and to a poorer quality of life