Lack of p38 activation in T cells increases IL-35 and protects against obesity by promoting thermogenesis.

Obesity is characterized by low-grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis is not well established. Here, we find that the p38 pathway is a key regulator of T cell-mediated adipose tissue (AT) inflammation and browning. Mice with T cells specifically lacking the p38 activators MKK3/6 are protected against diet-induced obesity, leading to an improved metabolic profile, increased browning, and enhanced thermogenesis. We identify IL-35 as a driver of adipocyte thermogenic program through the ATF2/UCP1/FGF21 pathway. IL-35 limits CD8+ T cell infiltration and inflammation in AT. Interestingly, we find that IL-35 levels are reduced in visceral fat from obese patients. Mechanistically, we demonstrate that p38 controls the expression of IL-35 in human and mouse Treg cells through mTOR pathway activation. Our findings highlight p38 signaling as a molecular orchestrator of AT T cell accumulation and function.

MCJ: A mitochondrial target for cardiac intervention in pulmonary hypertension.

Pulmonary hypertension (PH) can affect both pulmonary arterial tree and cardiac function, often leading to right heart failure and death. Despite the urgency, the lack of understanding has limited the development of effective cardiac therapeutic strategies. Our research reveals that MCJ modulates mitochondrial response to chronic hypoxia. MCJ levels elevate under hypoxic conditions, as in lungs of patients affected by COPD, mice exposed to hypoxia, and myocardium from pigs subjected to right ventricular (RV) overload. The absence of MCJ preserves RV function, safeguarding against both cardiac and lung remodeling induced by chronic hypoxia. Cardiac-specific silencing is enough to protect against cardiac dysfunction despite the adverse pulmonary remodeling. Mechanistically, the absence of MCJ triggers a protective preconditioning state mediated by the ROS/mTOR/HIF-1α axis. As a result, it preserves RV systolic function following hypoxia exposure. These discoveries provide a potential avenue to alleviate chronic hypoxia-induced PH, highlighting MCJ as a promising target against this condition.

18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Findings of Polymyalgia Rheumatica in Patients with Giant Cell Arteritis.

OBJECTIVE: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are often overlapping conditions. We studied whether 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is useful in identifying PMR in the setting of large vessel (LV) GCA. METHODS: LV-GCA patients diagnosed by PET-CT at a tertiary care center for a population of 450,000 people over a two-year period were reviewed. Scoring was performed based on potential significant FDG uptake at up to 16 sites in nine different extravascular areas (SCORE 16). Differences in extravascular sites of significant FDG uptake were evaluated between LV-GCA with a clinical diagnosis of PMR or not. RESULTS: Fifty-four patients were diagnosed with LV-GCA by 18F-FDG-PET-CT. Of them, 21 (38.8%) were clinically diagnosed with PMR. Significant extravascular FDG uptake was more frequently observed in those with a clinical diagnosis of PMR. In this sense, the SCORE 16 was higher in those with clinical PMR (5.10 ± 4.05 versus 1.73 ± 2.31 in those without a clinical diagnosis of PMR; p < 0.001). A SCORE 16 involving more than four sites of significant FDG uptake yielded a sensitivity of 52% and a specificity of 91% for establishing a clinical diagnosis of PMR associated with LV-GCA. The best areas of significant FDG uptake to clinically identify PMR in patients with LV-GCA were the shoulder, the greater trochanter, and the lumbar interspinous regions, with an area under the ROC curve of 0.810 (0.691-0.930). CONCLUSIONS: Significant extravascular 18F-FDG-PET-CT uptake may help establish a clinical diagnosis of PMR in patients with LV-GCA. These patients are more commonly diagnosed with PMR if they have significant FDG uptake in the shoulder, greater trochanter, and lumbar interspinous areas.

Positron Emission Computed Tomography Spectrum of Large Vessel Vasculitis in a Tertiary Center: Differences in 18F-fluorodeoxyglucose Uptake between Large Vessel Vasculitis with Predominant Cranial and Extracranial Giant Cell Arteritis Phenotypes.

(1) Objective:To assess the spectrum of PET-CT-related large vessel vasculitis (LVV) in a Spanish tertiary center and to determine whether FDG uptake by PET-CT differs between giant cell arteritis (GCA) with predominant cranial or extracranial phenotypes. (2) Methods: The spectrum of patients diagnosed with LVV by PET-CT in a tertiary referral hospital that cares for 450,000 people over a period of two years was reviewed. Moreover, differences in FDG uptake between LVV-GCA with predominantly cranial and extracranial phenotype were analyzed. (3) Results: Eighty patients were diagnosed with LVV by PET-CT. Most were due to systemic vasculitis (n = 64; 80%), especially GCA (n = 54; 67.5%). Other conditions included the presence of rheumatic diseases (n = 4; 3.2%), tumors (n = 9; 7.2%) and infections (n = 3; 2.4%). LVV-GCA patients with predominant extracranial GCA phenotype were younger (mean ± SD: 68.07 ± 9.91 vs. 75.46 ± 7.64 years; p = 0.017) and had a longer delay to the diagnosis (median [interquartile range] 12 [4-18] vs. 4 [3-8]; p = 0.006), but had polymyalgia rheumatica symptoms more frequently than those with predominantly cranial GCA phenotype (46.3% vs. 15.4%, p = 0.057). When FDG uptake was compared according to the two different disease patterns, no statistically significant differences were observed. However, patients with extracranial LVV-GCA showed a non-significantly higher frequency of vasculitic involvement of lower-extremity arteries. (4) Conclusions: Regardless of the predominant phenotype, LVV identified by PET-CT is more commonly due to GCA in the Spanish population. In these GCA patients, younger age, PMR, and a higher frequency of lower-extremity artery vasculitis suggest the presence of LVV.

Cardiac Progenitor Cell Exosomal miR-935 Protects against Oxidative Stress.

Oxidative stress-induced myocardial apoptosis and necrosis are critically involved in ischemic infarction, and several sources of extracellular vesicles appear to be enriched in therapeutic activities. The central objective was to identify and validate the differential exosome miRNA repertoire in human cardiac progenitor cells (CPC). CPC exosomes were first analyzed by LC-MS/MS and compared by RNAseq with exomes of human mesenchymal stromal cells and human fibroblasts to define their differential exosome miRNA repertoire (exo-miRSEL). Proteomics demonstrated a highly significant representation of cardiovascular development functions and angiogenesis in CPC exosomes, and RNAseq analysis yielded about 350 different miRNAs; among the exo-miRSEL population, miR-935 was confirmed as the miRNA most significantly up-regulated; interestingly, miR-935 was also found to be preferentially expressed in mouse primary cardiac Bmi1+high CPC, a population highly enriched in progenitors. Furthermore, it was found that transfection of an miR-935 antagomiR combined with oxidative stress treatment provoked a significant increment both in apoptotic and necrotic populations, whereas transfection of a miR-935 mimic did not modify the response. Conclusion. miR-935 is a highly differentially expressed miRNA in exo-miRSEL, and its expression reduction promotes oxidative stress-associated apoptosis. MiR-935, together with other exosomal miRNA members, could counteract oxidative stress-related apoptosis, at least in CPC surroundings.

Disruption of Proteostasis by Natural Products and Synthetic Compounds That Induce Pervasive Unfolding of Proteins: Therapeutic Implications.

Exposure of many cancer cells, including multiple myeloma cells, to cytotoxic concentrations of natural products celastrol and withaferin A or synthetic compounds of the IHSF series resulted in denaturation of a luciferase reporter protein. Proteomic analysis of detergent-insoluble extract fractions from HeLa-derived cells revealed that withaferin A, IHSF058 and IHSF115 caused denaturation of 915, 722 and 991 of 5132 detected cellular proteins, respectively, of which 440 were targeted by all three compounds. Western blots showed that important fractions of these proteins, in some cases approaching half of total protein amounts, unfolded. Relatively indiscriminate covalent modification of target proteins was observed; 1178 different proteins were modified by IHSF058. Further illustrating the depth of the induced proteostasis crisis, only 13% of these proteins detectably aggregated, and 79% of the proteins that aggregated were not targets of covalent modification. Numerous proteostasis network components were modified and/or found in aggregates. Proteostasis disruption caused by the study compounds may be more profound than that mediated by proteasome inhibitors. The compounds act by a different mechanism that may be less susceptible to resistance development. Multiple myeloma cells were particularly sensitive to the compounds. Development of an additional proteostasis-disrupting therapy of multiple myeloma is suggested.

High incidence of clinical fragility fractures in postmenopausal women with rheumatoid arthritis. A case-control study.

OBJECTIVES: To estimate the incidence of clinical fragility fractures in postmenopausal women with rheumatoid arthritis (RA) and analyze risk factors for fracture. METHODS: Incidence of clinical fragility fractures in 330 postmenopausal women with RA was compared to that of a control population of 660 age-matched postmenopausal Spanish women. Clinical fractures during the previous five years were recorded. We analyzed associations with risk factors for fracture in both populations and with disease-related variables in RA patients. RESULTS: Median age of RA patients was 64 years; median RA duration was eight years. Sixty-nine percent were in remission or on low activity. Eighty-five percent had received glucocorticoids (GCs); 85 %, methotrexate; and 40 %, ≥1 biologic DMARD. Fifty-four patients and 47 controls had ≥1 major osteoporotic fracture (MOF). Incidence of MOFs was 3.55 per 100 patient-year in patients and 0.72 in controls (HR: 2.6). Risk factors for MOFs in RA patients were age, previous fracture, parental hip fracture, years since menopause, BMD, erosions, disease activity and disability, and cumulative dose of GCs. Previous fracture in RA patients was a strong risk for MOFs (HR: 10.37). CONCLUSION: Of every 100 postmenopausal Spanish women with RA, 3-4 have a MOF per year. This is more than double that of the general population. A previous fracture poses a high risk for a new fracture. Other classic risk factors for fracture, RA disease activity and disability, and the cumulative dose of GCs are associated with fracture development.

Importance of family planning in patients with immune-mediated inflammatory diseases: A multidisciplinary approach.

BACKGROUND AND OBJECTIVES: Family planning in women with immune-mediated inflammatory diseases is a challenge for healthcare teams, highlighting the need for standardized available evidence to provide patients with objective and agreed information. This study reflects the work performed by a multidisciplinary team in reviewing available scientific evidence, and the strategy agreed for family planning, pregnancy, postpartum, and breastfeeding in patients with immune-mediated inflammatory diseases. METHODS: A literature search was conducted, information was structured across the different stages (preconception, pregnancy, postpartum and breastfeeding), and an on-site meeting was convened, in which patients and healthcare providers participated. RESULTS: Specific materials, which are included in this work, were developed to guide clinical decisions to be agreed upon by patients and healthcare providers. CONCLUSION: These materials meet the need for validated and updated information on the approach and use of indicated drugs for professionals responsible for the management of immune-mediated inflammatory diseases.

Multidisciplinary models for pregnancy care in patients with rheumatic diseases: Clinical experiences and experts opinion.

OBJECTIVES: To describe different models of multidisciplinary pregnancy care for patients with inflammatory and autoimmune rheumatic diseases, and the steps to follow concerning their implementation. METHODS: A qualitative study was conducted including: (1) a comprehensive literature search in PUBMED focused on multidisciplinary care models; (2) structured interviews with seven rheumatologists from multidisciplinary pregnancy clinics for patients with inflammatory and autoimmune rheumatic diseases. Data were collected related to the hospitals, medical departments, populations cared for, and multidisciplinary care models (type, material, and human resources, professional requirements, objectives, referral criteria, agendas, protocols, responsibilities, decision-making, research and educational activities, multidisciplinary clinical sessions, initiation/start, planning, advantages/disadvantages, and barriers/facilitators for implementation); (3) a nominal meeting group in which the results of searches and interviews were analyzed and the recommendations for the implementation of the multidisciplinary care models defined. RESULTS: We analyzed seven models of multidisciplinary care in pregnancy, implemented 3-10 years ago, which can all be summarized by two different subtypes: parallel (patients are assessed the same day in the involved medical services) and preferential (patients are assessed on different days in the involved medical services) circuits. The implementation of a specific model results rather from an adaptation to the hospital's and professionals' circumstances. Correct planning and good harmony among professionals are key points to implementing a model. CONCLUSION: Different multidisciplinary care models have been implemented for patients with inflammatory and autoimmune rheumatic diseases during pregnancy. They pretend to improve care, system efficiency, and collaboration among specialists and should be carefully implemented.

Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells.

Clinical trials evaluating cardiac progenitor cells (CPC) demonstrated feasibility and safety, but no clear functional benefits. Therefore a deeper understanding of CPC biology is warranted to inform strategies capable to enhance their therapeutic potential. Here we have defined, using a label-free proteomic approach, the differential cytoplasmic and nuclear compartments of human CPC (hCPC). Global analysis of cytoplasmic repertoire in hCPC suggested an important hypoxia response capacity and active collagen metabolism. In addition, comparative analysis of the nuclear protein compartment identified a significant regulation of a small number of proteins in hCPC versus human mesenchymal stem cells (hMSC). Two proteins significantly upregulated in the hCPC nuclear compartment, IL1A and IMP3, showed also a parallel increase in mRNA expression in hCPC versus hMSC, and were studied further. IL1A, subjected to an important post-transcriptional regulation, was demonstrated to act as a dual-function cytokine with a plausible role in apoptosis regulation. The knockdown of the mRNA binding protein (IMP3) did not negatively impact hCPC viability, but reduced their proliferation and migration capacity. Analysis of a panel of putative candidate genes identified HMGA2 and PTPRF as IMP3 targets in hCPC. Therefore, they are potentially involved in hCPC proliferation/migration regulation.

Telangiectasia hemorrágica hereditaria durante el embarazo: Reporte de caso / Hereditary hemorrhagic telangiectasia during pregnancy: Case report

Resumen ANTECEDENTES: La telangiectasia hemorrágica hereditaria, o síndrome de Rendu-Osler-Weber, es una enfermedad vascular, hereditaria y autosómica caracterizada por telangiectasias mucocutáneas y malformaciones arteriovenosas en el pulmón, el cerebro e hígado. La prevalencia estimada es de 1.5 a 2 personas afectadas por cada 10,000 habitantes. El 90% de los casos se debe a una mutación en el gen endoglina y en el de la cinasa 1 similar al receptor de activina (ACVRL1). En la mujer embarazada, la telangiectasia hemorrágica hereditaria es de alto riesgo, sobre todo durante el segundo y tercer trimestre. OBJETIVO: Reportar un caso de telangiectasia hemorrágica hereditaria y exponer las complicaciones que pueden registrarse durante el embarazo. CASO CLÍNICO: Paciente de 23 años, con antecedente heredofamiliar de madre con diagnóstico de telangiectasia hemorrágica hereditaria (síndrome de Osler-Weber-Rendu) que falleció a los 38 años. Antecedente personal patológico de telangiectasia hemorrágica hereditaria, con diagnóstico a los 12 años luego de múltiples episodios de epistaxis. Recibió tratamiento con transfusiones sanguíneas en múltiples ocasiones y 200 mg de sulfato ferroso cada 24 horas. CONCLUSIÓN: La telangiectasia hemorrágica hereditaria condiciona, en la mujer embarazada, la aparición de complicaciones que pueden poner en riesgo la vida de la madre y el feto. Las mujeres con antecedente conocido deben valorarse antes de la concepción con el propósito de conocer el estado de la enfermedad.

Abstract BACKGROUND: Hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber syndrome, is an autosomal inherited vascular disease characterized by mucocutaneous telangiectasias and arteriovenous malformations in the lung, brain and liver. The estimated prevalence is 1.5 to 2 affected persons per 10,000 population. Ninety percent of cases are due to a mutation in the endoglin gene and in the activin receptor-like kinase 1 gene (ACVRL1). In pregnant women, hereditary hemorrhagic telangiectasia is high risk, especially during the second and third trimester. OBJECTIVE: To report a case of hereditary hemorrhagic telangiectasia and to expose the complications that can occur during pregnancy. CLINICAL CASE: 23-year-old patient, with hereditary family history of mother diagnosed with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) who died at 38 years of age. Personal pathological history of hereditary hemorrhagic telangiectasia, diagnosed at the age of 12 years after multiple episodes of epistaxis. She was treated with multiple blood transfusions and 200 mg of ferrous sulfate every 24 hours. CONCLUSION: Hereditary hemorrhagic telangiectasia conditions, in pregnant women, the appearance of complications that can put the life of the mother and fetus at risk. Women with a known history should be evaluated before conception in order to know the status of the disease.

p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1.

During the first weeks of postnatal heart development, cardiomyocytes undergo a major adaptive metabolic shift from glycolytic energy production to fatty acid oxidation. This metabolic change is contemporaneous to the up-regulation and activation of the p38γ and p38δ stress-activated protein kinases in the heart. We demonstrate that p38γ/δ contribute to the early postnatal cardiac metabolic switch through inhibitory phosphorylation of glycogen synthase 1 (GYS1) and glycogen metabolism inactivation. Premature induction of p38γ/δ activation in cardiomyocytes of newborn mice results in an early GYS1 phosphorylation and inhibition of cardiac glycogen production, triggering an early metabolic shift that induces a deficit in cardiomyocyte fuel supply, leading to whole-body metabolic deregulation and maladaptive cardiac pathogenesis. Notably, the adverse effects of forced premature cardiac p38γ/δ activation in neonate mice are prevented by maternal diet supplementation of fatty acids during pregnancy and lactation. These results suggest that diet interventions have a potential for treating human cardiac genetic diseases that affect heart metabolism.

Early renal and vascular damage within the normoalbuminuria condition.

OBJECTIVE: A continuous association between albuminuria and cardiorenal risk exists further below moderately increased albuminuria ranges. If only based in albumin to creatinine ratio (ACR) higher than 30 mg/g, a significant percentage of individuals may be out of the scope for therapeutic management. Despite epidemiological outcomes, the identification of biochemical changes linked to early albuminuria is underexplored, and normoalbuminuric individuals are usually considered at no risk in clinical practice. Here, we aimed to identify early molecular alterations behind albuminuria development. METHODS: Hypertensive patients under renin-angiotensin system (RAS) suppression were classified as control, (ACR < 10 mg/g) or high-normal (ACR = 10-30 mg/g). Urinary protein alterations were quantified and confirmed by untargeted and targeted mass spectrometry. Coordinated protein responses with biological significance in albuminuria development were investigated. Immunohistochemistry assays were performed in human kidney and arterial tissue to in situ evaluate the associated damage. RESULTS: A total of 2663 identified proteins reflect inflammation, immune response, ion transport and lipids metabolism (P value ≤ 0.01). A1AT, VTDB and KNG1 varied in high-normal individuals (P value < 0.05), correlated with ACR and associated with the high-normal condition (odds ratio of 20.76, 6.00 and 7.04 were found, respectively (P value < 0.001)). After 12 months, protein variations persist and aggravate in progressors to moderately increased albuminuria. At tissue level, differential protein expression was found in kidney from individuals with moderately increased albuminuria and atherosclerotic aortas for the three proteins, confirming their capacity to reflect subclinical organ damage. CONCLUSION: Early renal and vascular damage is molecularly evidenced within the normoalbuminuria condition.

Proteomic and Biological Analysis of an In Vitro Human Endothelial System in Response to Drug Anaphylaxis.

Anaphylaxis is a life-threatening systemic hypersensitivity reaction. During anaphylaxis, mediator release by effector cells causes endothelial barrier breakdown, increasing vascular permeability and leakage of fluids, which may lead to tissue edema. Although endothelial cells (ECs) are key players in this context, scant attention has been paid to the molecular analysis of the vascular system, and further analyses of this cell type are necessary, especially in humans. The protein expression pattern of human microvascular ECs was analyzed in response to sera from anaphylactic patients (EC-anaphylaxis) and sera from non-allergic subjects (EC-control) after 2 hours of contact. Firstly, a differential quantitative proteomic analysis of the protein extracts was performed by mass spectrometry using an isobaric labeling method. Second, the coordinated behavior of the identified proteins was analyzed using systems biology analysis (SBA). The proteome of the EC-anaphylaxis system showed 7,707 proteins, of which 1,069 were found to be significantly altered between the EC-control and EC-anaphylaxis groups (p-value < 0.05). Among them, a subproteome of 47 proteins presented a high rate of change (|ΔZq| ≥ 3). This panel offers an endothelial snapshot of the anaphylactic reaction. Those proteins with the highest individual changes in abundance were hemoglobin subunits and structural support proteins. The interacting network analysis of this altered subproteome revealed that the coagulation and complement systems are the main biological processes altered in the EC-anaphylactic system. The comprehensive SBA resulted in 5,512 functional subcategories (biological processes), 57 of which were significantly altered between EC-control and EC-anaphylaxis. The complement system, once again, was observed as the main process altered in the EC system created with serum from anaphylactic patients. Findings of the current study further our understanding of the underlying pathophysiological mechanisms operating in anaphylactic reactions. New target proteins and relevant signaling pathways operating in the in vitro endothelial-serum system have been identified. Interestingly, our results offer a protein overview of the micro-EC-anaphylaxis environment. The relevance of the coagulation, fibrinolytic, contact and complement systems in human anaphylaxis is described. Additionally, the untargeted high-throughput analysis used here is a novel approach that reveals new pathways in the study of the endothelial niche in anaphylaxis.

Cardiovascular Risk Stratification Based on Oxidative Stress for Early Detection of Pathology.

Aims: Current cardiovascular (CV) risk prediction algorithms are able to quantify the individual risk of CV disease. However, CV risk in young adults is underestimated due to the high dependency of age in biomarker-based algorithms. Because oxidative stress is associated with CV disease, we sought to examine CV risk stratification in young adults based on oxidative stress to approach the discovery of new markers for early detection of pathology. Results: Young adults were stratified into (i) healthy controls, (ii) subjects with CV risk factors, and (iii) patients with a reported CV event. Plasma samples were analyzed using FASILOX, a novel approach to interrogate the dynamic thiol redox proteome. We also analyzed irreversible oxidation by targeted searches using the Uniprot database. Irreversible oxidation of cysteine (Cys) residues was greater in patients with reported CV events than in healthy subjects. These results also indicate that oxidation is progressive. Moreover, we found that glutathione reductase and glutaredoxin 1 proteins are differentially expressed between groups and are proteins involved in antioxidant response, which is in line with the impaired redox homeostasis in CV disease. Innovation: This study, for the first time, describes the oxidative stress (reversible and irreversible Cys oxidation) implication in human plasma according to CV risk stratification. Conclusion: The identification of redox targets and the quantification of protein and oxidative changes might help to better understand the role of oxidative stress in CV disease, and aid stratification for CV events beyond traditional prognostic and diagnostic markers. Antioxid. Redox Signal. 35, 602-617.

Prediction of low birth weight with hypoglycemia in glucose tolerance test.

OBJECTIVE: Determine the value of the combination of fasting glucose less than the 10th percentile (FG < p10) during 75 gram oral glucose tolerance test (75g OGTT) with maternal characteristics to predict low birth weight (LBW) established by Intergrowth-21st tables. METHODS: Prospective cohort study of pregnant women who was underwent 75g OGTT between 24 and 28.6 weeks. The 10th percentile fasting glucose of the population was determined at 65 mg/dL and women with risk factors that could modify fetal weight, including those related to intrauterine growth restriction, were excluded. Two groups were formed: group FG < p10 and group with normal fasting glucose. The main finding was the diagnosis of LBW. The association between FG < p10, maternal characteristics and LBW was established by multivariate logistic regression. The predictive performance of the models constructed was evaluated by receiver operating characteristic (ROC) curve and area under the curve (AUC) analysis. RESULTS: 349 women were eligible for study, of whom 66 (18.91%) had FG < p10; neonates in this group had lower birth weights (2947.28 g and 3138.26 g, p = 0.001), higher frequencies of LBW (25% and 6.81%, p < 0.001) and of weights < 2500 g in term births (8.6% and 2.3%, p = 0.034). The basal prediction model consisted of nulliparity by achieving an AUC of 60%, while the addition of FG < p10 resulted in the significant improvement of the previous model (AUC 72%, DeLong: p = 0.005). CONCLUSIONS: In pregnant women without factors that could modify fetal weight, the predictive model created by combining FG < p10 during 75g OGTT with nulliparity was significantly associated with increased risk of LBW. REGISTRATION: ClinicalTrials.gov: NCT04144595.

Importance of family planning in patients with immune-mediated inflammatory diseases: a multidisciplinary approach. / Importancia de la planificación familiar en pacientes con enfermedades inflamatorias inmunomediadas: un abordaje multidisciplinar.

BACKGROUND AND OBJECTIVES: Family planning in women with immune-mediated inflammatory diseases is a challenge for healthcare teams, highlighting the need for standardized available evidence to provide patients with objective and agreed information. This study reflects the work performed by a multidisciplinary team in reviewing available scientific evidence, and the strategy agreed for family planning, pregnancy, postpartum, and breastfeeding in patients with immune-mediated inflammatory diseases. METHODS: A literature search was conducted, information was structured across the different stages (preconception, pregnancy, postpartum and breastfeeding), and an on-site meeting was convened, in which patients and healthcare providers participated. RESULTS: Specific materials, which are included in this work, were developed to guide clinical decisions to be agreed upon by patients and healthcare providers. CONCLUSION: These materials meet the need for validated and updated information on the approach and use of indicated drugs for professionals responsible for the management of immune-mediated inflammatory diseases.

Pregnancy control in patients with systemic lupus erythematosus/antiphospholipid syndrome. Part 2: Pregnancy follow-up. / Control del embarazo en pacientes con lupus eritematoso sistémico/síndrome antifosfolípido. parte 2: seguimiento del embarazo.

OBJECTIVE: In order to agree on the fundamental aspects related to the management of pregnancy in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), the Spanish Societies of Gynaecology and Obstetrics, Internal Medicine and Rheumatology set up a working group for the preparation of three consensus documents. METHODS: Each of the Scientific Societies involved proposed five representatives based on their experience in the field of pregnancy control in patients with autoimmune diseases. The recommendations were developed following the Delphi methodology. RESULTS: This second document contains the recommendations regarding the management of pregnancy in women with SLE and APS, including complications such as lupus activity, congenital heart block, thrombotic and obstetric manifestations of APS and placental vascular disease. CONCLUSIONS: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with SLE/APS during pregnancy.

Pregnancy Control in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome. Part 1: Infertility, Ovarian Preservation and Preconception Assessment. Consensus Document of the Spanish Society of Gynaecology and Obstetrics (SEGO), the Spanish Society of Internal Medicine (SEMI) and the Spanish Society of Rheumatology (SER). / Control del embarazo en pacientes con lupus eritematoso sistémico y síndrome antifosfolípido. Parte 1: Infertilidad, preservación ovárica y valoración preconcepcional. Documento de consenso de la Sociedad Española de Ginecología y Obstetricia (SEGO), Sociedad Española de Medicina Interna (SEMI) y Sociedad Española de Reumatología (SER).

OBJECTIVE: Pregnancy and puerperium are considered a risk situation in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Therefore, specialized assessment is essential both preconception and during pregnancy and the puerperium. Likewise, it is very important that different specialists in autoimmune diseases and high-risk pregnancies participate in the follow-up of these patients in a coordinated manner. The Spanish Society of Gynaecology and Obstetrics, the Spanish Society of Internal Medicine, and the Spanish Society of Rheumatology have set up a working group for the preparation of three consensus documents. METHODS: The stages of the work were: distribution of work in three groups corresponding to the three periods related to pregnancy (preconception, during pregnancy and childbirth and puerperium), identification of key areas, exhaustive review of the literature and formulation of recommendations. RESULTS: This first document includes the 48 recommendations that address aspects related to infertility, the need for and treatments for gonadal preservation and preconception assessment. CONCLUSIONS: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with SLE/APS during pregnancy.

Pregnancy control in Patients with Systemic Lupus Erythematosus/Antiphospholipid Syndrome. Part 3: Childbirth. Puerperium. Breastfeeding Contraception. Newborn. / Control del embarazo en pacientes con lupus eritematoso sistémico/síndrome antifosfolípido. Parte 3. Parto. Puerperio. Lactancia. Anticoncepción. Recién nacido.

OBJECTIVE: In order to agree on the fundamental aspects related to the management of pregnancy in patients with systemic lupus erythematosus and antiphospholipid syndrome, the Spanish Societies of Gynaecology and Obstetrics, Internal Medicine and Rheumatology have set up a working group for the preparation of three consensus documents. METHODS: Each of the Scientific Societies involved proposed five representatives based on their experience in the field of pregnancy control in patients with autoimmune diseases. The recommendations were developed following the Delphi methodology. RESULTS: This third document contains the recommendations regarding the management of delivery, puerperium and lactation, including medication use during these periods and the care of the newborn. In addition, a section on contraception is included. CONCLUSIONS: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with systemic lupus erythematosus/antiphospholipid syndrome during pregnancy.