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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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Abstract: Strategies to prevent thrombosis in antiphospholipid antibody (aPL)-positive patients are of the utmost importance. The risk of thrombosis in patients with aPLs varies, depending on additional venous thrombosis and cardiovascular risk factors, as well as associated comorbidities. Recurrent thrombosis despite treatment with vitamin K antagonists is relatively common in daily practice. In this context, the effectiveness of the new direct oral anticoagulants in antiphospholipid syndrome is debated, as well as that of low-dose aspirin for primary thromboprophylaxis. There is an urgent unmet need to recognize the subgroup of patients that may benefit from low-dose aspirin use. Here we also discuss different points of view on primary and secondary thrombosis preventions in aPL-positive patients, which were presented as a debate during the 2021 PANLAR Congress (Pan-American League of the Association of Rheumatology) and that was organized by GESAF (Argentine Society of Rheumatology APS Study Group). It is the intention of this article to provide a useful discussion to aid treatment decision-making in daily clinical practice., Competing Interests: J.A.G.-P. received personal consultant fees from AbbVie, Amgen, AstraZeneca, BMS, Galápagos, GSK, Janssen, Lilly, Novartis, Pfizer Sanofi, and Roche. G.J.P.-E. received speaker fees, consultant fees, and grants from Pfizer, Janssen, GSK, Sandoz, and Sanofi. The other authors have no conflicts of interest to declare. This research received no external funding., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The vertiginous advance for identifying the genomic sequence of SARS-CoV-2 allowed the development of a vaccine including mRNA-based vaccines, inactivated viruses, protein subunits, and adenoviral vaccines such as Sputnik. This study aims to report on autoimmune disease manifestations that occurred following COVID-19 Sputnik vaccination. Patients and Methods: A retrospective study was conducted on patients with new-onset autoimmune diseases induced by a post-COVID-19 vaccine between March 2021 and December 2022, in two referral hospitals in Mexico City and Argentina. The study evaluated patients who received the Sputnik vaccine and developed recent-onset autoimmune diseases. Results: Twenty-eight patients developed recent-onset autoimmune diseases after Sputnik vaccine. The median age was 56.9 ± 21.7 years, with 14 females and 14 males. The autoimmune diseases observed were neurological in 13 patients (46%), hematological autoimmune manifestations occurred in 12 patients (42%), with thrombotic disease observed in 10 patients (28%), and autoimmune hemolytic anemia in two patients (7.1%). Rheumatological disorders were present in two patients (7.1%), and endocrine disorders in one patient (3.5%). Principio del formulario Conclusion: Although the COVID-19 Sputnik vaccine is generally safe, it can lead to adverse effects. Thrombosis and Guillain-Barre were the most frequent manifestations observed in our group of patients.

In 2011, a syndrome entitled ASIA (Autoimmune/inflammatory Syndrome Induced by Adjuvants; Shoenfeld's syndrome) was first described. ASIA aimed to organize under a single umbrella, the existing evidence regarding certain environmental factors which possess immune stimulatory properties, in order to shed light on a common pathway of autoimmune pathogenesis. Such environmental immune stimulators, or adjuvants, include among others: aluminum salts as in vaccines, various medical implants, as well as various infectious agents. After the launch of the ASIA syndrome, the expansion and recognition of this syndrome by different researchers from different countries began. During the past decades, evidence had been accumulating that (auto)immune symptoms can be triggered by exposure to environmental immune stimulatory factors that act as an adjuvant in genetically susceptible individuals. A panoply of unexplained subjective and autonomic-related symptoms has been reported in patients with ASIA syndrome. The current review summarizes and updates accumulated knowledge from the past decades, describing new adjuvants- (e.g. polypropylene meshes) and vaccine- (e.g. HPV and COVID vaccines) induced ASIA. Furthermore, a direct association between inflammatory/autoimmune diseases with ASIA syndrome, will be discussed. Recent cases will strengthen some of the criteria depicted in ASIA syndrome such as clear improvement of symptoms by the removal of adjuvants (e.g. silicone breast implants) from the body of patients. Finally, we will introduce additional factors to be included in the criteria for ASIA syndrome such as: (1) dysregulated non-classical autoantibodies directed against G-protein coupled receptors (GPCRs) of the autonomic nervous system and (2)) small fiber neuropathy (SFN), both of which might explain, at least in part, the development of 'dysautonomia' reported in many ASIA patients., Competing Interests: Declaration of Competing Interest Dr. Cohen Tervaert appeared as expert witness in court for patients with adverse effect due to biomaterials. Dr. Shoenfeld appeared as expert witness in court for patients with adverse effect due to vaccines., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: HLA and NLRP3 play an important role in the development of various autoimmune and autoinflammatory diseases. Gout is an autoinflammatory disease associated with multiple genetic and environmental factors. The objective of the present study was to evaluate the interaction and association between genetic polymorphisms of HLA-B and the NLRP3 gene in Mexican patients with gout., Methods and Results: Eighty-one patients with gout were included and compared with 95 healthy subjects. The polymorphisms rs4349859, rs116488202, rs2734583 and rs3099844 (within the HLA-B region) and rs3806268 and rs10754558 of the NLRP3 gene were genotyped using TaqMan probes in a Rotor-Gene device. The interactions were determined using the multifactorial dimensionality reduction (MDR) method, while the associations were determined through logistic regression models. The MDR analysis revealed significant interactions between the rs116488202 and rs10754558 polymorphisms with an entropy value of 4.31% (p < 0.0001). Significant risk associations were observed with rs4349859 and rs116488202 polymorphisms (p < 0.01); however, no significant associations were observed with the polymorphisms of the NLRP3 gene., Conclusions: The results suggest that HLA-B polymorphisms and their interaction with NLRP3 may contribute to the genetic susceptibility of gout., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Cognitive impairment (CI) occurs at a high frequency in primary antiphospholipid syndrome (PAPS). Its psychosocial-related factors are of interest., Objective: We aimed to determine disability and perceived stress and their correlation with CI in PAPS., Methods: First study phase: a longitudinal study including patients with PAPS and paired controls for cardiovascular risk factors, age, and sex, determining CI with Montreal Cognitive Assessment (MoCA) and then repeating the measurement 1 year later. Second study phase: a cross-sectional analytical study by quantification of disability with the World Health Organization Disability Assessment Schedule (WHODAS 2.0) and perceived stress with the Perceived Stress Scale (PSS-14). Descriptive statistics and Spearman correlation coefficient were used., Results: Sixty-three patients with PAPS and 60 controls were studied. In PAPS, age (range, 48.0 ± 13.5 years), thrombotic artery events (TAE) (44.4%), and stroke/TIA (42.8%) were found. Disability was documented in the majority of WHODAS 2.0 domains and the total score for this was higher in participation and mobility, the stress level was normal, and 65.1% had CI. PAPS exhibited greater deterioration in the WHODAS 2.0 total score ( p .017) and the MoCA test ( p < .0001). Personal domains and the total WHODAS 2.0 score correlated inversely with MoCA. Life activities ( rho = -0.419) and self-care ( rho = -0.407) were those that correlated to the greatest degree. Stroke conferred risk for CI., Conclusions: Disability in PAPS and CI are interdependent. New treatment options and neurocognitive stimulation strategies are necessary to maintain functionality and prevent further cognitive dysfunction in PAPS patients.

To date, around 60% of the world population has been protected by vaccines against SARS-CoV-2, significantly reducing the devastating effect of the pandemic and restoring social economic activity through mass vaccination. Multiple studies have demonstrated the effectiveness and safety of vaccines against COVID-19 in healthy populations, in people with risk factors, in people with or without SARS-CoV-2 infection, and in immunocompromised people. According to the criteria for post-vaccine adverse events established by the World Health Organization, a minority of individuals may develop adverse events, including autoimmune syndromes. The exact mechanisms for the development of these autoimmune syndromes are under study, and to date, a cause-effect relationship has not been established. Many of these autoimmune syndromes meet sufficient criteria for the diagnosis of Adjuvant-Induced Autoimmune Syndrome (ASIA syndrome). The descriptions of these autoimmune syndromes open new perspectives to the knowledge of the complex relationship between the host, its immune system, with the new vaccines and the development of new-onset autoimmune syndromes. Fortunately, most of these autoimmune syndromes are easily controlled with steroids and other immunomodulatory medications and are short-lived. Rheumatologists must be alert to the development of these autoimmune syndromes, and investigate the relationship between autoimmune/inflammatory symptoms and vaccination time, and assess their therapeutic response., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Patients with autoimmune disease (AID) and coronavirus disease 2019 (COVID-19) could have higher mortality due to the co-morbidity and the use of immunosuppressive therapy., Objectives: To analyze the risk factors and outcomes of patients with AID and COVID-19 versus a control group., Methods: A prospective cohort study included patients with and without AID and COVID-19. Patients were paired by age and sex. Clinical, biochemical, immunological treatments, and outcomes (days of hospital stay, invasive mechanical ventilation [IMV], oxygen at discharge, and death) were collected., Results: We included 226 COVID-19 patients: 113 with AID (51.15 ± 14.3 years) and 113 controls (53.45 ± 13.3 years). The most frequent AIDs were Rheumatoid arthritis (26.5%), systemic lupus erythematosus (21%), and systemic sclerosis (14%). AID patients had lower lactate dehydrogenas, C-reactive protein, fibrinogen, IMV (P = 0.027), and oxygen levels at discharge (P ≤ 0.0001) and lower death rates (P ≤ 0.0001). Oxygen saturation (SaO2) ≤ 88% at hospitalization provided risk for IMV (RR [relative risk] 3.83, 95% confidence interval [95%CI] 1.1-13.6, P = 0.038). Higher creatinine and LDH levels were associated with death in the AID group. SaO2 ≤ 88% and CO-RADS ≥ 4 were risk factors for in-hospital mortality (RR 4.90, 95%CI 1.8-13.0, P = 0.001 and RR 7.60, 95%CI 1.4-39.7, P = 0.016, respectively). Anticoagulant therapy was protective (RR 0.36, 95%CI 0.1-0.9, P = 0.041)., Conclusions: Patients with AID had better outcomes with COVID-19 than controls. Anticoagulation was associated with a lower death in patients with AID.

Background: Pregnancy in patients with systemic lupus erythematosus is considered a high risk one since it is associated with a higher rate of maternal-fetal complications compared with the pregnancies in healthy women., Objectives: The aim of this study was to describe the maternal-fetal outcomes in a cohort of Mexican patients with systemic lupus erythematosus and to identify risk factors associated with adverse maternal and fetal outcomes., Patients and Methods: A cohort of pregnant lupus patients was analyzed. Maternal-fetal complications were described, and clinical, biochemical, and immunological variables associated with obstetric adverse outcomes were studied. Descriptive statistics, comparison of variables using appropriate tests, and finally logistic regression analysis were performed to identify potential risk factors for adverse maternal and fetal outcomes., Results: A total of 351 pregnancies were included in a 10-year period. The most frequently observed maternal adverse outcomes were lupus flare (35%) and preeclampsia (14.5%). Active lupus before pregnancy (hazards ratio [HR], 3.7; 95% confidence interval [CI], 1.1-12.5; p = 0.003) was a predictor for these complications, whereas the use of antimalarial drugs (HR, 0.4; 95% CI, 0.2-0.7; p = 0.007) was a protective factor. The most frequent fetal adverse outcomes were preterm birth (38.1%), miscarriages (10%), and low birth weight babies (28%), and very low birth weight newborns (11%). Proteinuria in early pregnancy (HR, 7.1; 95% CI, 1.01-50.3; p = 0.04) and preeclampsia (HR, 9.3; 95% CI, 1.7-49.7; p = 0.009) were risk factors associated with these complications., Conclusions: Variables related to systemic lupus erythematosus activity predict an adverse maternal outcome, whereas proteinuria in early pregnancy and preeclampsia are associated with an adverse fetal outcome., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Consequences of organ damage in primary antiphospholipid syndrome (PAPS) are diverse, our aim was to determine organ damage over time and the correlation of organ damage accrual with health-related quality of life (HRQoL) in PAPS., Methods: First phase: retrospective cohort applying Damage Index for Antiphospholipid Syndrome (DIAPS) at 1, 5, 10, 20 years, or longer since diagnosis. Second phase: cross-sectional study, assessing HRQoL by the Medical Outcomes Study Short Form 36 (SF-36), and organ damage accrual. Descriptive statistics and Spearman correlation coefficient were used., Results: Sixty-seven patients were included, mean follow-up:15 years. Deep vein thrombosis prevailed (71.6%), pulmonary embolism (35.8%) and stroke (32.8%). Organ damage was found in 98.5%, with a cumulative DIAPS value of 3, with greater involvement in the neuropsychiatric and peripheral vascular domains. Regarding HRQoL, deterioration in the physical component summary (PCS) was found in 89.6%. Organ damage accrual correlated inversely and significantly with all the SF-36 domains, mainly with the total score and PCS. Body pain and PCS correlated the most (rho = -0.503, rho = -0.475)., Conclusions: Organ damage accrual impaired HRQoL in PAPS. Secondary thromboprophylxis through adequate systemic management and control of cardiovascular risk factors are necessary to prevent further impairment.

Background: Autoimmune/inflammatory syndrome induced by adjuvants has been associated with different substances used for cosmetic purposes; for example, silicone, methylmethacrylate, autoimmune disorders and cancer., Discussion: A 40-year-old man with a prior history of methylmethacrylate injection in the buttocks for aesthetic purposes 8 years ago, presented with deep venous thrombosis in the left leg 6 months ago, accompanied with inflammation, hardening, changes in colour, ulceration in the buttocks, arthritis, myalgias and fever. Weak and moderate lupus anticoagulant and low levels of anticardiolipin antibodies were present. Thoracoabdominal tomography showed hepatosplenomegaly and a pulmonary nodule, the biopsy of which showed chronic granulomatous inflammation. After a month, a new chest tomography showed multiple nodular pulmonary lesions. The new pulmonary biopsy showed a diffuse large B-cell non-Hodgkin's lymphoma which was treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab for four cycles, with good response of the autoimmune/inflammatory syndrome, but partial response of the diffuse large B-cell non-Hodgkin's lymphoma., Conclusion: We describe the first case of seronegative antiphospholipid syndrome and lymphoma associated with methylmethacrylate in a patient with autoimmune/inflammatory syndrome.

Primary adrenal failure comprises an insufficient production of mineralocorticoids and glucocorticoids in the adrenal cortex. A rare manifestation of antiphospholipid syndrome (APS) is adrenal failure. The majority of patients with adrenal involvement in APS develop an irreversible cortisol deficiency and atrophy of the adrenal glands. Adrenal incidentalomas are adrenal masses larger than 1 cm that are discovered in the course of diagnostic evaluation or treatment for another medical condition. Its prevalence is calculated in 1.5-9% of individuals. We describe an exceptional case of a 23-year-old male patient with APS with persistent high levels of antiphospholipid antibodies (aPL) from the time of diagnosis, who developed Addison's disease as a manifestation of APS with atrophy of the adrenal glands, in whom an adrenal incidentaloma was developed later and was corroborated as an aldosterone-producing adenoma. Currently, the patient is asymptomatic and without manifestations of tumor recurrence. The protumoral effect of elevated and persistent aPL is discussed.

Introduction: Several factors have been associated with the development of preeclampsia in women with systemic lupus erythematosus (SLE)., Objective: To identify risk factors associated with preeclampsia in patients with SLE and its impact on fetal outcomes., Patients and Methods: We studied a prospective cohort of pregnancies in women with SLE from January 2009 to December 2018. Demographic, clinical, serological and drug use characteristics were compared between patients who developed preeclampsia and those who did not, as well as the main neonatal outcomes. An adjusted logistic regression analysis was performed to identify factors potentially associated with preeclampsia., Results: We studied 316 pregnancies of 20 or more weeks of gestation. A total of 46 pregnancies (14.5%) were complicated by preeclampsia. A higher frequency of active disease before pregnancy (24.4% vs 11.3%, P = .01) and history of lupus nephritis (56.5% vs 30.1%, P < .001) were found in those patients who developed preeclampsia compared to those who did not. Preeclampsia was associated with a higher rate of prematurity, births of very low birth weight, stillbirth, and neonatal death. The multivariate analysis showed that the activity of the disease before (relative risk [RR] 2.7, 95% CI 1.04-7.4, P = .04) and during pregnancy (RR 3.0, 95% CI 1.0-9.1, P = .04) was associated with the development of preeclampsia. The use of antimalarial drugs during pregnancy was associated with a lower risk of preeclampsia (RR 0.21, 95% CI 0.08-0.53, P < .001)., Conclusions: Our study suggests that the use of antimalarial drugs during pregnancy reduces the risk of preeclampsia in lupus pregnancies., (© 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

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.

Background:  In microsurgical reconstruction, vascular obstruction occurs in approximately 20% of patients. Close monitoring is central to their care. Clinical/Doppler detection of vascular obstruction could be enhanced by thermography., Methods:  A diagnostic test design included consecutive cases of hospitalized patients, ≥18 years old, who underwent surgery with free flaps. Two researchers separately evaluated patients with clinical/Doppler methods and thermographic camera hourly for 24 hours, every 2 hours for the next 24 hours, and then every 3 hours until discharge. The gold standard was visualization of thrombus or vascular obstruction during surgical reintervention. Sensitivity, specificity, positive/negative predictive value (PPV/NPV), and a delta temperature receiver operating characteristic (ROC) curve were calculated., Results:  A total of 2,364 tests were performed with a thermographic camera in 40 patients (31 females, 9 males) aged 50.12 ± 9.7 years. There were 28 deep inferior epigastric perforator, 5 anterolateral thigh, 3 radial, 2 scapular, 1 fibular, and 1 anteromedial thigh flaps included. Six (15%) had postoperative vascular obstruction (5 venous and 1 arterial). One flap developed partial necrosis and one total necrosis (overall survival 97.5%). ROC curve (area 0.97) showed the best results at ≥ 1.8°C of difference to the surrounding skin. Considering two consecutive positive evaluations, the sensitivity was 93%, specificity 96%, PPV 57%, and NPV 99%. The thermal imaging camera allows to identify the obstruction between 2 and 12 hours before the clinical method., Conclusion:  Utilizing a thermographic camera can reduce detection time of vascular obstruction by several hours in microvascular free flaps that include the cutaneous island. This method proves useful for early diagnosis of postoperative vascular obstruction., Competing Interests: The authors have no commercial associations or financial disclosures that might pose a conflict of interest with any of the information presented in this article., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose of Review: To provide an update about the impact of infections in autoimmune rheumatic diseases (ARDs), from the analysis of the role of infections in pregnant women without ARDs, to the identification of maternal-fetal infections and their role in the maternal-fetal outcome of women with ARDs., Recent Findings: Recent studies indicate that patients with ARDs and pregnancy are also susceptible to presenting infections of varying degrees, including serious infections, which contribute to the morbidity and mortality observed in pregnancy and postpartum of these patients.Any type of infectious agent will interact with a hormonal, immunological and metabolic environments modified by ARD, treatments, and by the changes inherent in pregnancy. Therefore, infections in the pregnancy of patients with ARDs should be considered as a risk factor for an unfavorable maternal-fetal outcome., Summary: The recognition of infections in the pregnancy of ARDs as a risk factor is the first step to prevent, identify, and treat them in a timely manner, and thus contribute to the favorable course of pregnancy in these patients. Patients with ARDs and major organ involvement, use of high doses of steroids, immunosuppressant and biological therapies, adolescence, and obesity are populations susceptible to developing infections.

Objective: To analyze the utility of neutrophil-to-lymphocyte ratio (NLR) plus C-reactive protein (CRP) to differentiate between infection and active disease in patients with SLE., Methods: A cross-sectional study of a cohort of patients with SLE was carried out. Blood samples from four groups (patients without infection or active disease, patients with infection, patients with active disease, and patients with both infection and active disease) before therapeutic interventions were analyzed. We excluded patients with current malignancy, pregnancy, ischemic heart disease or use of antimicrobials during previous 7 days. Hematological cell count, CRP and cultures were obtained. We constructed receiver operating characteristic curves; sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated., Results: Forty patients were included. NLR cut-off ≥6.3 had sensitivity 70%, specificity 85%, PPV 83% and NPV 74% to detect patients with non-viral infections. A CRP cut-off ≥7.5 mg/L had sensitivity 90%, specificity 75%, PPV 78% and NPV 88% to detect infections regardless of SLE activity. Combination of CRP plus NLR improves the specificity to 90% and PPV to 88%. Excluding the group with both infection and active disease, CRP plus NLR expands specificity to 95% and NPV to 90%., Conclusion: In our experience, levels of CRP, particularly CRP plus NLR, were useful in differentiating patients with SLE from those with suspected non-viral infection regardless of the activity of the disease.

There are national and international clinical practice guidelines for systemic lupus erythematosus treatment. Nonetheless, most of them are not designed for the Mexican population or are devoted only to the treatment of certain disease manifestations, like lupus nephritis, or are designed for some physiological state like pregnancy. The Mexican College of Rheumatology aimed to create clinical practice guidelines that included the majority of the manifestations of systemic lupus erythematosus, and also incorporated guidelines in controversial situations like vaccination and the perioperative period. The present document introduces the «Clinical Practice Guidelines for the Treatment of Systemic Lupus Erythematosus» proposed by the Mexican College of Rheumatology, which could be useful mostly for non-rheumatologist physicians who need to treat patients with systemic lupus erythematosus without having the appropriate training in the field of rheumatology. In these guidelines, the reader will find recommendations on the management of general, articular, kidney, cardiovascular, pulmonary, neurological, hematologic and gastrointestinal manifestations, and recommendations on vaccination and treatment management during the perioperative period., (Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Antiphospholipid syndrome (APS) patients have high cardiovascular risk. Speckle-tracking echocardiography (STE) detects myocardial function. To evaluate the myocardial function in primary APS (PAPS) patients using two-dimensional echocardiography (2-D) obtaining values of left ventricle global longitudinal strain (GLS) by STE. Patients with PAPS, > 16 years, both genders, without signs and symptoms of heart disease were recruited and matched with healthy controls by age and gender. Demographic, clinical data, and cardiovascular risk factors were recorded. Images from the two-, three-, and four-chamber views were recorded and analyzed with STE and values of GLS. Descriptive and analytic statistics were applied. Thirty-eight PAPS patients and 21 controls were included. Age 46.7 ± 10, disease evolution 13.06 ± 6.69 years. Obesity and dyslipidemia were more frequent in PAPS patients in comparison with controls. Even though the proportion of obesity was greater in PAPS patients than in the control group, we did not find significant differences, neither in patients with/without metabolic syndrome. Regarding patients with and without obesity with lower GLS values, there were no differences either. Average GLS was lower in PAPS than in controls. Segments and myocardial regions showed lower values of myocardial deformation in PAPS patients than controls, including apical segments suggesting underlying heart disease. GLS is reduced in PAPS compared with healthy subjects. STE is a suitable method to detect cardiac affection in patients without apparent cardiac involvement. Studies with this technique to monitor progression of heart disease in PAPS are necessary.

Spondyloarthritis (SpA) are a heterogeneous group of chronic inflammatory joint diseases that includes several clinical subgroups. SpA can affect women in the reproductive stage so pregnancy can influence the course of the disease and SpA can affect the maternal-fetal outcome. The treatment of SpA has changed dramatically in recent years and the use of targeted drugs is part of therapeutic armamentarium. The use of targeted drugs during pregnancy is controversial because the information available on safety during this period is still limited. Several cytokines have an important role in the normal development of pregnancy or other cytokines may play a role in certain maternal-fetal complications. Potentially targeted drugs can affect the function of these cytokines during pregnancy. The aim of this study is to review the interrelationship between SpA during pregnancy and lactation, the role of some cytokines during normal pregnancy and the development of maternal-fetal complications as well as to review recent information on targeted drugs during pregnancy and breastfeeding in these patients in order to maximize their use in these critical periods of life., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Hyperammonemia results from hepatic inability to remove nitrogenous products generated by protein metabolism of intestinal microbiota, which leads to hepatic encephalopathy (HE) in chronic liver disease (CLD). In ammonium neurotoxicity, oxidative stress (OxS) plays a pathogenic role. Our objective was to evaluate if intestinal mannitol is as effective and safe as conventional treatment for diminishing hyperammonemia, OxS, and HE in patients with CLD., Material and Methods: We included 30 patients with HE classified by "Haven Criteria for Hepatic Encephalopathy". They were randomized into two groups: 1) Mannitol Group (MG) with mannitol 20% administered into the intestine by an enema, 2) conventional group (CG) with lactulose 40 g enema both substances were diluted in 800 mL of double distilled solution every 6 h; all patients received neomycin. We evaluated ammonia concentration, plasma oxidative stress, HE severity, intestinal discomfort and adverse effects., Results: Hyperammonemia (171 ± 104 vs 79 ± 49 μmol ammonia/L, p < 0.01), and oxidative stress (MDA 29 vs 27%, formazan 15 vs 11%, carbonyls 16 vs 9% and dityrosines 10 vs 5%) were reduced in MG and CG respectively. The HE severity decreased by two degrees compared to baseline values in both groups. Intestinal discomfort and electrolyte plasma alterations were less frequent (p < 0.05) in MG than CG., Conclusions: Intestinal mannitol is as effective and safe as conventional treatment for reducing hyperammonemia, oxidative stress, and hepatic encephalopathy of CLD patients in the emergency room. Likewise, mannitol is better tolerated than conventional treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Key Message: We have elucidated the Andigena origin of the potato Ry adg gene on chromosome XI of CIP breeding lines and developed two marker assays to facilitate its introgression in potato by marker-assisted selection. Potato virus Y (PVY) is causing yield and quality losses forcing farmers to renew periodically their seeds from clean stocks. Two loci for extreme resistance to PVY, one on chromosome XI and the other on XII, have been identified and used in breeding. The latter corresponds to a well-known source of resistance (Solanum stoloniferum), whereas the one on chromosome XI was reported from S. stoloniferum and S. tuberosum group Andigena as well. To elucidate its taxonomic origin in our breeding lines, we analyzed the nucleotide sequences of tightly linked markers (M45, M6) and screened 251 landraces of S. tuberosum group Andigena for the presence of this gene. Our results indicate that the PVY resistance allele on chromosome XI in our breeding lines originated from S. tuberosum group Andigena. We have developed two marker assays to accelerate the introgression of Ry adg gene into breeding lines by marker-assisted selection (MAS). First, we have multiplexed RYSC3, M6 and M45 DNA markers flanking the Ry adg gene and validated it on potato varieties with known presence/absence of the Ry adg gene and a progeny of 6,521 individuals. Secondly, we developed an allele-dosage assay particularly useful to identify multiplex Ry adg progenitors. The assay based on high-resolution melting analysis at the M6 marker confirmed Ry adg plex level as nulliplex, simplex and duplex progenitors and few triplex progenies. These marker assays have been validated and can be used to facilitate MAS in potato breeding.

Metabolic syndrome (MetS) is a cluster of metabolic and cardiovascular (CV) risk factors including obesity and visceral adiposity, insulin resistance, dyslipidemia and hypertension contributing to CV mortality. The interface between the metabolic and immune systems has been of great interest recently. These interactions are regulated through genetics, nutritional status, and the intestinal microbiome. Alterations in the immune-metabolic cross-talk contribute to the development of autoimmune diseases. Adipokines exert a variety of metabolic activities contributing to the ethiopathogenesis of MetS and are involved in the regulation of both inflammatory processes and autoimmunity occurring in rheumatic diseases. Patients with autoinflammatory disease such as gout and those with autoimmune rheumatic diseases (ARD), such as systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, ankylosing spondylitis and vasculitis among others, have increased prevalence of MetS. Despite recent advances in treatment of ARD, incidence of CVD remains high. MetS and altered secretion patterns of proinflammatory adipokines could be the link between CVDs and ARD. In addition, in ARD the activation of proinflammatory signalling pathways results in the induction of several biological markers of chronic inflammation contributing to CVD. In the present paper, we review recent evidences of the interactions between MetS and ARD, as well as novel therapeutic targets., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose of Review: To provide an update about the interactions between infections and autoimmune diseases (AIDs), from the molecular perspective to the clinical spectrum and the differentiation between infection and disease activity., Recent Findings: Any kind of infection may modify the innate and adaptive immune response through the following mechanisms: molecular mimicry, superantigens, epitope spreading and B-cell activation. The consequence is the overproduction of antibodies shared with those found in AIDs. Viral infections, especially HIV and hepatitis C virus, can stimulate the production of antiphospholipid antibodies and confer an increased risk to develop antiphospholipid syndrome., Summary: The identification of risk factors to develop infections in patients with AIDs is remarkable to prevent them. These factors are the use of steroids and immunosuppressants, the involvement of a major organ (lungs, brain and kidney) and severe activity. Biomarkers to differentiate infection from disease activity are scarce, but the combination of procalcitonine and C-reactive protein seems to have higher specificity and sensibility to identify infections in patients with AIDs. Finally, the clinical judgment is the hallmark to differentiate between infections and disease activity.

Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) includes the following conditions: siliconosis, Gulf War syndrome, macrophagic myofasciitis syndrome, and post-vaccination phenomena. Afterward, other syndromes have been recognized, such as in ASIA by mineral oil (ASIA-MO). These conditions are triggered by adjuvants and they are the result of the interplay of genetic and environmental factors. ASIA-MO is defined as the infiltration of oily type modeling substances for cosmetic purposes. It has been reported in many countries and used surreptitiously. Pathogenesis of ASIA-MO is not clear, but is characterized by chronic granulomatous inflammation, like the pristane model in mice, with increase of proinflammatory cytokines: type I interferons (IFNα and IFNß), systemic lupus erythematosus (SLE), and erosive arthritis. In humans, an increase of interleukin 1 (IL-1) has been found. Clinical spectrum of ASIA-MO is heterogeneous, varying from mild to severe and being local and systemic. The systemic manifestations can be non-specific and specific, meeting criteria for any autoimmune disease (AID), i.e., SLE, rheumatoid arthritis, and systemic sclerosis, among others. The areas of the body where the mineral oil is mostly applied include the following: buttocks (38-72%), breasts (12-16%), lower extremities (18-22%), and face (6-10%). The penis augmentation is also common. Treatment is focused on local and systemic manifestations and requires medical and surgical management representing a challenge for the physician.

The objective of the study is to analyze the efficacy and safety of splenectomy in the management of refractory autoimmune thrombocytopenia (AT)/autoimmune hemolytic anemia (AIHA) associated or not with systemic lupus erythematosus. Thirty-four patients after splenectomy due to severe AT and/or AIHA were divided into group 1 (G1) 18 SLE/APS patients: 9 AT/SLE patients, 6 SLE/antiphospholipid syndrome (APS), and 3 primary APS. Group 2 (G2): 16 patients without SLE/APS: 2 Fisher-Evans syndrome and 14 AIHA. Surgery approach when (1) platelets ≤ 50,000/ml despite 2 weeks on medical therapy, (2) medically dependent, and (3) medically intolerant or after two hemolytic crises in AIHA patients. Splenectomy response: (1) complete (CR): ≥ 150,000 platelets/ml, (2) partial: 50,000-149,000/ml, or (3) none: ≤ 50,000/ml. CR for AIHA: hemoglobin ≥9 g/dl., Statistical Analysis: descriptive statistics and chi-square test. The mean age was 34.6 years; mean follow-up: 28.5 months. Open splenectomy in 15/34 vs laparoscopy in 19/34 (p = NS). CR in 15/34, G1: 4/18, G2: 11/16, (p = 0.006). Complications in 6/34, 5 from G2 vs 1 from G1 (p = 0.05). Relapse in 7/18 patients in G1 and 3/16 in G2 (p = 0.05). Open and laparoscopic splenectomies in SLE and AT patients are as effective as in those without SLE; however, patients with SLE and APS had more relapses.

Purpose: Antinuclear autoantibodies (ANA) targeting the dense fine speckled antigen DFS70, also known as lens epithelium-derived growth factor p75 (LEDGF/p75), are attracting attention due to their low frequency in systemic rheumatic diseases but increased frequency in clinical laboratory referrals and healthy individuals (HI). These ANA specifically recognize the stress protein DFS70/LEDGFp75, implicated in cancer, HIV-AIDS, and inflammation. While their frequency has been investigated in various ethnic populations, there is little information on their frequency among Hispanics/Latinos. In this study, we determined the frequency of anti-DFS70/LEDGFp75 autoantibodies in Mexican Hispanics using multiple detection platforms., Methods: The frequency of anti-DFS70/LEDGFp75 antibodies was determined in 171 individuals, including 71 dermatomyositis (DM) patients, 47 rheumatoid arthritis (RA) patients, 30 obesity (OB) patients, and 23 HI. Antibody detection was achieved using four complementary assay platforms: indirect immunofluorescence, Western blotting, ELISA, and chemiluminescent immunoassay., Results: We detected relatively low frequencies of anti-DFS70/LEDGFp75 antibodies in patients with DM (1.4%), RA (4.3%), and OB (6.6%), and elevated frequency (17.4%) in HI. A strong concordance between the different antibody detection platforms was observed., Conclusions: The low frequency of anti-DFS70/LEDGFp75 antibodies in Mexican patients with rheumatic diseases, but relatively higher frequency in HI, is consistent with previous observations with non-Hispanic populations, suggesting that geographic differences or ethnicity do not influence the frequency of these autoantibodies. Our results also highlight the importance of confirmatory assays for the accurate detection of these autoantibodies. Future studies with larger cohorts of healthy Hispanics/Latinos are needed to confirm if their anti-DFS70/LEDGFp75 antibody frequencies are significantly higher than in non-Hispanics., Competing Interests: Compliance with ethical standards Funding CAC received funding from the National Institutes of Health (NIH) through grant 5P20MD006988. MVDM received funding from the University of Guadalajara through grants UDG-CA-703 (Immunology and Rheumatology) and UDG-CA-701 (Aging, Immunometabolism, and Oxidative Stress). Conflict of interest Dr. Ignacio Garcia De La Torre is an employee of Immuno-Mex (Guadalajara, Mexico), a company that distributes reagents and equipment for clinical and diagnostic laboratories. Dr. Michael Mahler and Mr. Roger Albesa are employees of Inova Diagnostics (San Diego, USA), a company that specializes on the development of autoimmune technologies and diagnostic markers used in clinical laboratories and hospitals. For the remaining authors none were declared. Research involving human subjects and animals All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The studies with human subjects presented in this article were approved by the Institutional Review Boards of the University of Guadalajara and Loma Linda University. This article does not contain any studies with animals performed by any of the authors. Informed consent Informed consent was obtained from all individual participants included in this 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.

Background: Obstetric antiphospholipid syndrome (Obs-APS) is one of the most commonly identified causes of recurrent pregnancy loss and its accurate diagnosis is a requirement for optimal treatment. Some patients do not fulfill the revised Sapporo classification criteria, the original APS classification criteria, and are considered to be non-criteria Obs-APS. In these patients with non-criteria, there is controversy about their inclusion within the spectrum of APS and eventually their treatment as having Obs-APS. A subset of patients may also have clinical characteristics of Obs-APS even though lupus anticoagulant (LA), anticardiolipin antibodies, and anti-β2-glycoprotein I (aβ2GPI) antibodies are consistently negative. These patients are recognized as seronegative Obs-APS. We reviewed evidence of non-criteria Obs-APS and discuss a case of a woman with a diagnosis of active systemic lupus erythematosus (SLE) and non-criteria Obs-APS with four consecutive pregnancy losses. After an accurate diagnosis the patient received prenatal counseling and benefited from the optimal treatment of Obs-APS that led to a successful pregnancy. The applicability of this successful experience about outcomes in women with non-criteria, or seronegative, Obs-APS is also evaluated.

The aim of this study was to estimate the impact of the haematological manifestations of systemic lupus erythematosus (SLE) on mortality in hospitalized patients. For that purpose a case-control study of hospitalized patients in a medical referral centre from January 2009 to December 2014 was performed. For analysis, patients hospitalized for any haematological activity of SLE ( n = 103) were compared with patients hospitalized for other manifestations of SLE activity or complications of treatment ( n = 206). Taking as a variable outcome hospital death, an analysis of potential associated factors was performed. The most common haematological manifestation was thrombocytopenia (63.1%), followed by haemolytic anaemia (30%) and neutropenia (25.2%). In the group of haematological manifestations, 17 (16.5%) deaths were observed compared to 10 (4.8%) deaths in the control group ( P < 0.001). The causes of death were similar in both groups. In the analysis of the variables, it was found that only haematological manifestations were associated with intra-hospital death (odds ratio 3.87, 95% confidence interval 1.8-88, P < 0.001). Our study suggests that apparently any manifestation of haematological activity of SLE is associated with poor prognosis and contributes to increased hospital mortality.

Objective: To evaluate the clinical outcome after aPL (antiphospholipid antibodies) disappearance in primary APS patients., Methods: From a cohort of 70 patients with primary APS, we selected patients with positive aPL determinations at onset and ≥2 subsequent negative aPL determinations during the last 5years. To corroborate the immunologic profile, we determined IgG/IgM aCL antibodies, IgG/IgM antiβ2GPl, anti-annexin A5 antibodies and lupus anticoagulant (LA). All patients continued treatment with oral anticoagulants. Clinical data and aPL determinations at onset/after disappearance were obtained., Statistical Analysis: descriptive statistics and Kaplan-Meier analysis., Results: We found 24 patients with persistently negative aPL, including the last immunologic profile, 17 females, 7 males, mean age 51.7, disease evolution 16.3years, mean of 4 aPL previous positive determinations. aCL was positive at onset in 87.5%, 29% had double aPL positivity at onset (aCL/LA). Deep venous thrombosis (DVT) and ischemic stroke in 33% and pulmonary embolism in 12.5% were the most frequent manifestations at onset. INR range: 2-3. Time with aPL positive 109.4±80.7months. After 60months of follow-up since aPL disappearance, 45.8% of patients presented thrombosis recurrence, DVT in 9 patients, ischemic stroke in 1, pulmonary artery hypertension in 1. Other non-thrombotic APS manifestations were chronic ulcers in lower extremities and severe thrombocytopenia., Conclusions: This study suggest, that in primary APS, persistent negative aPL profile is not an indication to interrupt oral anticoagulant therapy. However, there is a subset of patients that remained asymptomatic. Other studies are necessary in order to elucidate this controversy., (Copyright © 2017 Elsevier B.V. All rights reserved.)