Helper T cell immunity in humans with inherited CD4 deficiency.

CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5-61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple's disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαß+CD4-CD8- T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4-CD8- αß T cells exhibit intact responses to HLA class II-restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei.

Update on Femtosecond Laser-Assisted Cataract Surgery: A Review.

The advent of femtosecond lasers has resulted in a new standard in cataract surgery, intended to overmatch the paradigm of conventional phacoemulsification. Femtosecond laser-assisted cataract surgery (FLACS) enables a higher level of reproducibility, precision, accuracy, and customization when performing several steps of cataract (or lens) surgery. Capsulotomy, corneal incisions, lens fragmentation, and arcuate incisions are the main procedures performed using FLACS. As the demand for better refractive outcomes and spectacle independence increases, the features of FLACS are highly relevant, especially when considering the implantation of premium intraocular lenses, such as toric, enhanced depth-of-focus, or multifocal lenses. The present article reviews the state of the art of femtosecond laser-assisted cataract (lens) surgery, contemplating the advantages and limitations of the two types of femtosecond laser pulses available (high and low energy) by evaluating their reported outcomes and complications.

Pupil versus 1st Purkinje capsulotomy centration with femtosecond laser: Long term outcomes with a sinusoidal trifocal lens.

PURPOSE: To assess the role of femtosecond laser-assisted capsulotomy centration in the long-term intraocular positioning of a multifocal intraocular lens. DESIGN: Prospective comparative study. METHODS: A total of 60 eyes of 30 patients underwent femtosecond laser-assisted Refractive Lens Exchange (RLE). For every patient, capsulotomy centration was randomly performed according to pupil centre (PC) in one eye and first Purkinje reflex (FPR) in the other. The intraocular lens (IOL) positioning, visual acuities, spherical equivalent, internal aberrometry and quality of vision were assessed and compared at 3 years' follow-up between groups (PC and FPR). RESULTS: Intraocular lens positioning showed a statistically significant difference between groups, with a closer centration to the visual axis in the FPR patients (p < 0.001). Internal aberrometry showed higher values in the PC capsulotomy centration group (p < 0.01). CONCLUSIONS: FPR centered capsulotomy is associated to a closer centration of the IOL to the visual axis.

Distinct phenotypes in a cohort of anti-CASPR2 associated neurological syndromes.

INTRODUCTION: Anti-contactin-associated protein-like 2 (CASPR2) is classically associated with limbic encephalitis (LE), Morvan syndrome and peripheral nerve hyperexcitability (PNH). Additional clinical features have been previously recognized. OBJECTIVE: To describe a cohort of patients with anti-CASPR2-associated neurological syndromes from a tertiary referral centre. METHODS: Retrospective analysis of patients with positive serum anti-CASPR2 antibodies in the period between 2014 and 2021. RESULTS: Nineteen patients were identified, 11 (57.9%) male, with a median age at symptom onset of 49.0 (31.3-63.0) years and a median time to diagnosis of 1.0 (0.0-1.8) years. The most common clinical syndromes were LE (7 cases, 36.8%), Morvan syndrome (4, 21.1%) and PNH (2, 10.5%). Six patients presented with atypical phenotypes (31.6%), comprising dysautonomia (orthostatic hypotension and Adie's Pupil), motor tics/stereotypies, obsessive-compulsive disorder, and brainstem involvement. The most common presenting symptoms were seizures (31.6%), PNH (21.1%) and cognitive dysfunction (15.8%). One LE patient had a disease duration of 2,5 years and was initially diagnosed with dementia. CSF was normal in most cases. Brain MRI showed temporal lobe hyperintensities in 4 LE cases (57.1%). All PNH cases had myokymic discharges of fasciculations in the electromyography. Two patients had associated thymoma and 1 had lung adenocarcinoma. Eight patients (42.1%) received treatment during the acute phase and 26.3% maintenance treatment. Approximately half of the treated cases improved or stabilised, with 4 (21.1%) deaths in the whole cohort. CONCLUSION: Anti-CASPR2-associated neurological disorders may present with isolated atypical phenotypes, a slowly progressive clinical course, and with normal CSF or imaging findings.

Orthostatic hypotension as an unusual presentation of spinal calcium pyrophosphate deposition disease: case report and review of literature.

Calcium pyrophosphate crystal deposition disease (CPPD), also known as pseudogout, with spinal involvement, is associated with clinical manifestations of acute nerve compression or chronic spinal stenosis. Precipitation of crystals of calcium pyrophosphate dihydrate in connective tissues can lead to acute inflammatory arthritis, degenerative chronic arthropathies, and radiographic evidence of cartilage calcification. We present a case of an 87-year-old woman, with unstudied chronic polyarthralgia and symptomatic orthostatic hypotension. It were documented acute calcium pyrophosphate deposition wrist arthritis, and cervical CT and MRI was suggestive of spinal involvement of CPPD. Workup excluded other causes of OH. Surgical approach could be indicated to minimize the symptoms, but it was contra-indicated due to the patient's performance status, so histological diagnosis was not possible. Muscle atrophy played an important part in the rapid progression of this insidious chronic disease. Conservative and symptomatic treatment achieve scarce short-term clinical improvement. Spinal involvement of CPPD was thought to be rare but recent studies show a higher prevalence than expected. We call for attention to the extent of structural changes that may occur when not early diagnosed nor treated. High clinical suspicion is required and this is, to our knowledge, the first report of orthostatic hypotension as a presentation of CPPD.

Cataract Grade and Pupil: Comparison Between Conventional Phacoemulsification and Low-Energy Femtosecond Laser Assisted Cataract Surgery.

Purpose: This study presents a comparison of pupil changes according to cataract grade between low-energy femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification (CP) in the same patient. Patients and Methods: Data from surgical records from patients submitted to cataract surgery with CP in one eye and FLACS in the other were retrospectively reviewed. The inclusion criterion was both eyes of the same patient having the same cataract grade in accordance with Lens Opacity Classification System (LOCS) III. Total pupil variation (TPV) was measured after recorded images, with intraindividual comparison between techniques, according to cataract grade (≤3 and >3), age and cumulative dissipated energy (CDE). Results: The study included a total of 124 eyes of 62 patients (mean age 72.65 ± 7.64 years). Analysis showed a statistically significant difference in TPV between techniques in the grade ≤3 cataract group (0.08 ± 0.22 mm²; p=0.034), with less pupil narrowing with FLACS, but not in the grade >3 group (0.01 ± 0.23 mm²; p=0.849). Regarding CDE, a significant difference (p<0.001) was found between techniques in both softer and harder cataracts, with lower values for FLACS. Correlation between CDE and TPV was significant for CP (p=0.021) but not for FLACS (p=0.922). TPV was significantly lower in older patients (age >74 years) for both techniques (p<0.001). Conclusion: There was a statistically significant difference between techniques (although of mild clinical relevance), with less reduction of pupil area with FLACS in softer cataracts (grade ≤3), as compared to CP. Higher levels of CDE are associated with more pupil narrowing in CP.

Biological therapy in systemic lupus erythematosus, antiphospholipid syndrome, and Sjögren's syndrome: evidence- and practice-based guidance.

Systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and Sjögren's syndrome (SS) are heterogeneous autoimmune diseases. Severe manifestations and refractory/intolerance to conventional immunosuppressants demand other options, namely biological drugs, and small molecules. We aimed to define evidence and practice-based guidance for the off-label use of biologics in SLE, APS, and SS. Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice in autoimmune disease management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2021. Preliminary recommendations were drafted by working groups for each disease. A revision meeting with all experts anticipated the consensus meeting held in June 2021. All experts voted (agree, disagree, neither agree nor disagree) during two rounds, and recommendations with at least 75% agreement were approved. A total of 32 final recommendations (20 for SLE treatment, 5 for APS, and 7 for SS) were approved by the experts. These recommendations consider organ involvement, manifestations, severity, and response to previous treatments. In these three autoimmune diseases, most recommendations refer to rituximab, which aligns with the higher number of studies and clinical experience with this biological agent. Belimumab sequential treatment after rituximab may also be used in severe cases of SLE and SS. Second-line therapy with baricitinib, bortezomib, eculizumab, secukinumab, or tocilizumab can be considered in SLE-specific manifestations. These evidence and practice-based recommendations may support treatment decision and, ultimately, improve the outcome of patients living with SLE, APS, or SS.

Biologic therapy in large and small vessels vasculitis, and Behçet's disease: Evidence- and practice-based guidance.

OBJECTIVE: Vasculitis are a very heterogenous group of systemic autoimmune diseases, affecting large vessels (LVV), small vessels or presenting as a multisystemic variable vessel vasculitis. We aimed to define evidence and practice-based recommendations for the use of biologics in large and small vessels vasculitis, and Behçet's disease (BD). METHODS: Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice on autoimmune diseases management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2022. Preliminary recommendations were drafted by working groups for each disease and voted in two rounds, in June and September 2021. Recommendations with at least 75% agreement were approved. RESULTS: A total of 32 final recommendations (10 for LVV treatment, 7 for small vessels vasculitis and 15 for BD) were approved by the experts and several biologic drugs were considered with different supporting evidence. Among LVV treatment options, tocilizumab presents the higher level of supporting evidence. Rituximab is recommended for treatment of severe/refractory cryoglobulinemic vasculitis. Infliximab and adalimumab are most recommended in treatment of severe/refractory BD manifestations. Other biologic drugs can be considered is specific presentations. CONCLUSION: These evidence and practice-based recommendations are a contribute to treatment decision and may, ultimately, improve the outcome of patients living with these conditions.

Different relationships between epilepsy syndromes and autoimmune diseases.

OBJECTIVE: Our objective was to study the relationship between epilepsy and autoimmune diseases in two different types of epilepsy: idiopathic generalized epilepsies (IGEs) and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). The contribution of the human leukocyte antigen (HLA) system to this relationship was analyzed. METHODS: Adult patients with IGEs and MTLE-HS at a tertiary epilepsy center were consecutively enrolled between January 2016 and December 2020. RESULTS: A total of 664 patients, 422 with IGEs and 242 with MTLE-HS, were included. Patients with IGEs were 15 years younger, on average, than patients with MTLE-HS (p < .001). The frequency of autoimmune diseases was 5.5% (n = 23) and 4.5% (n = 11) in patients with IGEs and MTLE-HS, respectively (p = .716). The mean age of autoimmune disease onset was 20 ± 15.6 years in patients with IGEs and 36.7 ± 16.5 years in patients with MTLE-HS (p < .05). Clinical manifestations of autoimmune diseases preceded epilepsy onset in 30.4% of patients with IGEs (i.e., in early childhood); in the other patients, epilepsy appeared before autoimmune disease onset. In all but one patient with MTLE-HS and autoimmune diseases, the autoimmune diseases appeared after epilepsy onset from adolescence onward. SIGNIFICANCE: Our study indicates two relationship patterns: a bidirectional association between IGEs and autoimmune diseases and a unidirectional relationship between MTLE-HS and autoimmune diseases. The involvement of genetic susceptibility factors (such as the HLA system), autoinflammatory mechanisms, female sex, and antiseizure medications in these relationships are discussed.

Host-derived mannose glycans trigger a pathogenic γδ T cell/IL-17a axis in autoimmunity.

Autoimmune diseases are life-threatening disorders that cause increasing disability over time. Systemic lupus erythematosus (SLE) and other autoimmune diseases arise when immune stimuli override mechanisms of self-tolerance. Accumulating evidence has demonstrated that protein glycosylation is substantially altered in autoimmune disease development, but the mechanisms by which glycans trigger these autoreactive immune responses are still largely unclear. In this study, we found that presence of microbial-associated mannose structures at the surface of the kidney triggers the recognition of DC-SIGN-expressing γδ T cells, inducing a pathogenic interleukin-17a (IL-17a)-mediated autoimmune response. Mice lacking Mgat5, which have a higher abundance of mannose structures in the kidney, displayed increased γδ T cell infiltration into the kidney that was associated with spontaneous development of lupus in older mice. N-acetylglucosamine supplementation, which promoted biosynthesis of tolerogenic branched N-glycans in the kidney, was found to inhibit γδ T cell infiltration and control disease development. Together, this work reveals a mannose-γδ T cell-IL-17a axis in SLE immunopathogenesis and highlights glycometabolic reprogramming as a therapeutic strategy for autoimmune disease treatment.

Bilensectomy: Safety and Visual Outcomes in Angle-Supported, Iris-Fixated, and Posterior Chamber Phakic Intraocular Lenses.

PURPOSE: To report the visual and refractive outcomes, intraoperative and postoperative complications, and main causes of bilensectomy in the different types of phakic intraocular lenses (pIOLs). METHODS: This was a retrospective multicenter study that included 234 eyes of 185 patients that underwent bilensectomy. Patients were divided into three groups depending on the pIOL that was explanted (angle-supported, iris-fixated, or posterior chamber). The main reasons leading to the indication for bilensectomy, time elapsed between pIOL implantation and bilensectomy, intraoperative and postoperative complications, uncorrected and corrected distance visual acuity (UDVA and CDVA), and endothelial cell density loss 1 year after bilensectomy were evaluated. RESULTS: There was a statistically significant improvement in UDVA and CDVA after bilensectomy in all groups. Cataract development was the main reason for bilensectomy, followed by significant endothelial cell density loss. Time between pIOL implantation and bilensectomy was significantly greater in eyes with an anterior chamber pIOL. CONCLUSIONS: Bilensectomy outcomes in general are good. Iris-fixated lenses, particularly hyperopic, are more prone to intraoperative complications and endothelial cell loss than the other pIOLs models. The results show that bilensectomy is a safe and effective procedure with a relatively low rate of intraoperative and postoperative complications and acceptable refractive predictability. [J Refract Surg. 2023;39(3):128-134.].

Pupil Status with Low-Energy Femtosecond Laser-Assisted Cataract Surgery versus Conventional Phacoemulsification: An Intraindividual Comparative Study.

Purpose: To compare the pupil changes in low-energy femtosecond laser-assisted cataract surgery (FLACS) with conventional phacoemulsification (CP) intraindividually. Patients and Methods: A retrospective review of registered surgical data from patients that undergone uncomplicated cataract surgery in a single centre, with randomly assigned femtosecond laser-assisted cataract surgery (FLACS) to one eye and conventional phacoemulsification (CP) to the other, was performed. The recorded pupil images were evaluated at pre and post laser treatment (after suction release) and at several surgical timepoints for both techniques (FLACS and CP). Pupil areas were calculated and compared in the same eye undergone FLACS (pre vs post laser treatment), between eyes (CP vs FLACS) in the same patient and between groups. Subgroups were built regarding age and ocular comorbidity. Results: This study involved a total of 164 eyes of 82 patients (55 female, 27 male). No statistical differences regarding the total duration of surgery (p=0.805) between FLACS and CP. Pupil measurements between pre and post laser treatment in the FLACS group showed no statistically significant differences (p=0.107). The mean change in pupil area from the beginning until the end of surgery (total variation) was 6.59±2.08 mm2 in the FLACS group and 6.67±2.13 mm2 in the CP group, associated to less narrowing of pupil area with FLACS, although not statistically significant (p=0.080). Comorbidity group analysis revealed less, but not significant, pupil narrowing with the FLACS technique (p=0.071). No statistically significant differences between FLACS and CP concerning age subgroups were registered. Conclusion: This study shows no significant pupil changes, namely myosis, after low-energy FLACS pre-treatment. Comparison between techniques showed less pupil variation in FLACS as compared to CP, more markedly in eyes with comorbidities (particularly with shallow anterior chamber), although non-statistically significant.

Clinical associations and prognostic implications of 6-minute walk test in rheumatoid arthritis.

The clinical associations and prognostic implications of the 6-minute walk test (6MWT) distance in patients with rheumatoid arthritis (RA) is yet to be explored. To identify the clinical features and prognostic implications associated with the 6MWT in patients with RA. Cohort study including 387 RA patients who underwent 6MWT. Regression models (linear and logistic) were built to identify independent predictors of shorter 6MWT distance. Cox proportional models were used to study the association of 6MWT distance with cardiovascular outcomes. Patients were subdivided according to 6MWT tertiles: 126 patients walked > 405 m, 129 walked 345-405 m, and 132 walked < 345 m. Older age (> 55 years), elevated waist circumference, NT-pro BNP > 125 pg/mL, anemia, C-reactive protein ≥ 3 mg/dL, and troponin T ≥ 14 pg/mL were independent predictors of walking shorter distances. Patients walking less than 345 m had higher risk of a subsequent cardiovascular hospitalization or cardiovascular death compared with patients walking 345 m or more (adjusted HR: 2.98, 95%CI: 1.37-6.51, p = 0.006). Older age, abdominal obesity, anemia, cardiac dysfunction, and inflammation were associated with walking shorter distances in patients with RA. Walking less than 345 m in the 6MWT was associated with a poor cardiovascular prognosis. The 6MWT is simple, reproducible, and inexpensive, easily performed in routine practice, and provides important information regarding the patients´ status and outcomes, enabling the monitorization of the therapeutic optimization of the various domains of the RA.

Sjögren's syndrome and pregnancy: a Portuguese case-control study.

Introduction: Pregnancy in patients with autoimmune disorders is associated with an increased risk of adverse outcomes. Sjögren's syndrome (SS) is one of the most common among autoimmune diseases. Presently data regarding the impact of SS on obstetric outcomes are scarce and inconclusive. This study aims to evaluate the impact of SS on maternal-fetal and neonatal outcomes compared with pregnancy outcomes in the general population. Material and methods: A retrospective case-control study included 26 pregnancies in SS patients and a healthy control group (CG), followed in a Portuguese tertiary center, between 2015 and 2020. Baseline maternal data were collected, and maternal-fetal and neonatal outcomes were evaluated. Statistical analysis used SPSS 25.0, and a p-value of 0.05 was considered statistically significant. Results: All pregnancies occurred after the diagnosis of SS, with a mean exposure time between diagnosis and pregnancy of 4.92 ±2.78 years. In the SS group, the incidence of ANA, anti-Ro/SSA, and anti-La/SSB antibodies positivity was 80.8%, 61.5%, and 46.2%, respectively. Hydroxychloroquine (HCQ) was used in 57.7%.Miscarriage was significantly higher in the SS group (19.2% vs. 1.8%, p < 0.01). There was a higher prevalence of fetal growth restriction (OR 11.16, 95% CI: 0.96-129.26). Preterm delivery (9.5% vs. 5.6%, p = 0.503) and mean birth weight (2998.16 g vs. 3155.79 g, p = 0.178) did not differ significantly between the groups. In the SS group, admission to the neonatal intensive care unit (NICU) rate was increased (OR 71.67, 95% CI: 3.78-1357.16). Three pregnancies were complicated by congenital heart block (CHB) (14.3% vs. 0%, p = 0.015). In all cases, the diagnosis was performed during second trimester of pregnancy, and betamethasone was administered. Conclusions: Women with SS had a significantly higher incidence of miscarriage, admission to NICU, and CHB than controls. Congenital heart block was the most critical condition that affects the offspring of mothers with SS. Successful pregnancy in the study group was possible with prenatal monitoring and a multidisciplinary approach.

Campylobacter jejuni Pericarditis: A Case Report.

Campylobacter jejuni is one of the most common causes of enteritis. In rare cases, extraintestinal infection can occur, with a handful of cases of cardiac involvement, of which the pathophysiological mechanism is unclear. We report a case of pericarditis in a patient with X-linked agammaglobulinemia presenting with chronic diarrhea and chest pain who evolved to cardiac tamponade, requiring a pericardial window and a long course of broad-spectrum antibiotics. To the best of our knowledge, this is the third case of pericarditis caused by Campylobacter jejuni reported in the literature, the second in a patient with X-linked agammaglobulinemia. Despite its rarity, this case serves as a reminder of Campylobacter as a potential cause of cardiac inflammation for clinicians treating pericarditis/myocarditis, especially in patients with a history of diarrhea or immunosuppression.

A Campylobacter jejuni é uma das causas mais comuns de enterite. A infeção extraintestinal pode ocorrer raramente, estando reportados alguns casos de atingimento cardíaco, de mecanismo fisiopatológico incerto. Reportamos um caso de pericardite num doente com agamaglobulinemia ligada ao X, que se apresentou como diarreia crónica e dor torácica, evoluindo para tamponamento cardíaco com necessidade de confeção de janela pericárdica e tratamento prolongado com antibióticos de largo espectro. Este é, tanto quanto é do nosso conhecimento, o terceiro caso de pericardite por Campylobacter jejuni reportado na literatura, o segundo em doente com agamaglobulinemia ligada ao X. Apesar da sua raridade, este caso serve para reforçar a importância do género Campylobacter como causa de inflamação cardíaca para médicos que tratem pericardite/miocardite, especialmente em doentes com história de diarreia ou imunossupressão.

Sex differences in circulating proteins of patients with rheumatoid arthritis: A cohort study.

OBJECTIVES: Differences in proteomic profiles between men and women may provide insights into the biological pathways that contribute to known sex differences in rheumatoid arthritis (RA). Studies focusing on sex differences in circulating proteins in RA patients are scarce. Our objective was to investigate the sex differences in circulating proteins of RA patients. METHODS: Cohort study enrolling 399 RA patients. Ninety-four circulating protein-biomarkers (92CVDIIOlink®  + troponin-T + C-reactive protein) were measured. Clinical, demographic, and echocardiographic characteristics were compared between men and women. Sex differences in biomarker expression were assessed using regression modeling. RESULTS: In all, 306 (76.7%) patients were women. Compared with men, women had less visceral fat, smoked less, had diabetes and chronic obstructive pulmonary disease less frequently, and expressed more fatigue, anxiety, and depression. The association with cardiovascular outcomes did not differ between sexes. After adjusting for potential confounders, women expressed higher levels of circulating proteins related to adipokine signaling and vascular function (eg, leptin and vascular endothelial growth factor), whereas men expressed higher levels of circulating proteins related to extracellular matrix organization and inflammation (eg, matrix metalloproteinase-2 and C-reactive protein). These results were not found in patients without RA. CONCLUSION: Sex differences in circulating proteins reflect distinct pathways implicated in the pathogenesis of RA, including inflammation, adiposity, angiogenesis, and extracellular matrix organization. These findings may help further investigations into factors underlying sex-based differences and allow future studies focused on sex-specific personalized treatment approaches in RA. CLINICALTRIALS: gov ID: NCT03960515.

Systemic Lupus Erythematosus and Pregnancy: a Portuguese Case-Control Study.

Pregnancy in systemic lupus erythematosus (SLE) patients is associated with an increased risk of adverse outcomes. During pregnancy, SLE patients have a higher rate of miscarriage, stillbirth, preterm delivery, fetal growth restriction, or hypertensive disorders of pregnancy. To date, only a few case-control studies were published with the purpose to evaluate the magnitude of risk associated with pregnancy in lupus patients. The aim of our study was to evaluate the maternal and fetal outcomes in a cohort of Portuguese SLE patients and to compare it with a group of healthy pregnant women. We conducted a retrospective case-control study that included all pregnant women with SLE managed at a Portuguese tertiary center, between 2010 and 2019. Pregnancy outcomes were compared between SLE patients and a group of matched healthy pregnant women. Baseline maternal data was collected, and maternal-fetal and neonatal outcomes were evaluated. One hundred twenty-four SLE pregnancies were included. Of the patients, 95.2% were in remission at conception. In 13.7% of cases, a lupus flare was diagnosed during gestation and in 17.9% in the postpartum period. The live birth rate was 84.6%, and the incidence of adverse outcomes was 40.3% (OR 2.64, 95% CI 1.67-4.18). Considering only patients in remission at conception, the presence of adverse outcomes remained significantly higher (36.8% vs. 20.3%, P < 0.01). Miscarriage rate was 15.3% (OR 5.85, 95% CI 2.57-13.34) and preterm delivery occurred in 12.4% of the patients (OR 1.72, 95% CI 0.83-3.57). Preeclampsia prevalence was higher in SLE patients (OR 3.92, 95% CI 1.32-11.57). In the SLE group, the newborn admission to an intensive care unit rate was increased (OR 4.99, 95% CI 1.47-16.90). No neonatal or maternal deaths were reported. In our study, pregnancy with SLE was associated with an increased incidence of adverse outcomes, even in a population of SLE patients with well-controlled disease.

Mixed Cryoglobulinaemia Vasculitis Treated with Obinutuzumab in a Patient Allergic to Rituximab.

Cryoglobulinaemia is defined as the presence of cryoglobulins in the serum, which are immunoglobulins that reversibly precipitate and form a gel when the temperature is <37ºC. Autoimmune diseases such as Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis could be associated with mixed cryoglobulinaemia vasculitis (MCV). The treatment of MCV generally consists of glucocorticoids, cytotoxic agents such as cyclophosphamide, plasmapheresis or anti-CD20 monoclonal antibodies including rituximab. Here, we present a case of a 60-year-old woman who developed type II MCV in the context of overlap autoimmune disease and who has been treated with a new anti-CD20 agent, obinutuzumab. LEARNING POINTS: Mixed cryoglobulinaemia can occur in the context of autoimmune diseases such as Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis.The treatment generally consists of glucocorticoids, cytotoxic agents such as cyclophosphamide, plasmapheresis or anti-CD20 monoclonal antibodies including rituximab.New generations of humanized anti-CD20 monoclonal antibodies such as obinutuzumab have been developed to increase complement-dependent cytotoxicity and/or antibody-dependent cellular cytotoxicity, while limiting immunogenicity. These new optimized B-cell depletion strategies could be very interesting and useful in autoimmune disease treatment.

Circulating Biomarkers and Cardiac Structure and Function in Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) increases the risk for abnormalities of the cardiac structure and function, which may lead to heart failure (HF). Studying the association between circulating biomarkers and echocardiographic parameters is important to screen patients with RA with a higher risk of cardiac dysfunction. Aim: To study the association between circulating biomarkers and echocardiographic parameters in patients with RA. Methods: Echocardiography was performed in 355 patients with RA from RA Porto cohort and the associations between echocardiographic characteristics and 94 circulating biomarkers were assessed. These associations were also assessed in the Metabolic Road to Diastolic Heart Failure (MEDIA-DHF) [392 patients with HF with preserved ejection fraction (HFpEF)] and the Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) (1,672 healthy population) cohorts. Results: In the RA Porto cohort, mean age was 58 ± 13 years, 23% were males and mean RA duration was 12 ± 10 years. After adjustment and multiple testing correction, left ventricular mass index (LVMi), left atrial volume index (LAVi), and E/e' were independently associated with biomarkers reflecting inflammation [i.e., bone morphogenetic protein 9 (BMP9), pentraxin-related protein 3 (PTX3), tumor necrosis factor receptor superfamily member 11a (TNFRSF11A)], extracellular matrix remodeling [i.e., placental growth factor (PGF)], congestion [i.e., N-terminal pro-brain natriuretic peptide (NT-proBNP), adrenomedullin (ADM)], and myocardial injury (e.g., troponin). Greater LVMi [hazard ratio (HR) (95% CI) per 1 g/m2 = 1.03 (1.02-1.04), p < 0.001], LAVi [HR (95% CI) per 1 ml/m2 = 1.03 (1.01-1.06), p < 0.001], and E/e' [HR (95% CI) per 1 = 1.08 (1.04-1.13), p < 0.001] were associated with higher rates of cardiovascular events. These associations were externally replicated in patients with HFpEF and asymptomatic individuals. Conclusion: Circulating biomarkers reflecting inflammation, extracellular matrix remodeling, congestion, and myocardial injury were associated with underlying alterations of cardiac structure and function. Biomarkers might be used for the screening of cardiac alterations in patients with RA.