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OBJECTIVES: The gastrointestinal tract (GIT) is frequently involved in systemic sclerosis (SSc) and is responsible for alteration of quality of life. Many complications can occur, including chronic intestinal pseudo-obstruction, digestive haemorrhage and small-intestinal bacterial overgrowth. Since early development of organ failure is associated with poor prognosis, we need to identify risk factors associated with severe GIT involvement to prevent severe forms of the disease. METHODS: We conducted an observational prospective study, which included 90 SSc patients from December 2019 to September 2021. We collected questionnaires about digestive manifestations and quality of life, blood and stool samples, and performed imaging. At inclusion and throughout the study we assessed the occurrence of malnutrition and severe GIT disorders. We performed statistical analysis to highlight eventual risk factors associated with digestive manifestations, including hierarchical cluster analysis. RESULTS: A majority of our patients had gastro-oesophageal manifestations (93.3%), followed by intestinal manifestations (67.8%) and anorectal manifestations (18.9%). We found a correlation between anorectal disorders and cardiac disease, and between gastro-oesophageal involvement and impaired pulmonary function tests. Smoking was significantly associated with occurrence of severe GIT disorders. Malnutrition was frequent and associated with more cardiac and pulmonary disease. Cluster analysis identified three groups of patients, including one cluster with cardiac and digestive involvement. CONCLUSIONS: GIT manifestations are frequent and severe in SSc. Smoking appears to be associated with severe disease. Anorectal manifestations may be associated with cardiac disease, but we need more studies to validate these results.
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Gastroenteropatias , Qualidade de Vida , Escleroderma Sistêmico , Humanos , Feminino , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Estudos Prospectivos , Masculino , Pessoa de Meia-Idade , Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , Gastroenteropatias/diagnóstico , Prognóstico , França/epidemiologia , Fatores de Risco , Idoso , Análise por Conglomerados , Adulto , Índice de Gravidade de Doença , Fumar/efeitos adversos , Fumar/epidemiologia , Desnutrição/epidemiologia , Desnutrição/diagnósticoRESUMO
INTRODUCTION: Chronic histiocytic intervillositis (CHI) is a rare inflammatory placental disease characterized by diffuse infiltration of monocytes into the intervillous space and is associated with adverse pregnancy outcomes. No treatment is currently validated and although in some small reports, steroids with hydroxychloroquine have been described. There are no data for other therapies in refractory cases. PATIENTS AND METHODS: We here report four cases of patients with a history of CHI treated with immunoglobulins during a subsequent pregnancy. The four patients with recurrent CHI had failed to previous immunomodulatory therapies with steroids and hydroxychloroquine. All patients had at least four pregnancy losses with histopathological confirmation of CHI for at least one pregnancy loss. The usual pregnancy-loss etiology screening and immunological screening were negative for all the patients. RESULTS: For three patients, intravenous immunoglobulins were initiated at the ßHCG positivity at 1 g/kg every 15 days until delivery. In one case with combined therapy since the beginning of the pregnancy, intravenous immunoglobulins were introduced at 20 WG because of severe growth restriction. Two patients had live births at 36 WG and one patient at 39 WG. One patient, who presented early first-trimester hypertension and severe placental lesions, failed to intravenous immunoglobulins and had a pregnancy loss at 15 WG. CONCLUSION: This is the first report demonstrating the potential benefit of intravenous immunoglobulins in recurrent chronic intervillositis. Larger studies are needed to confirm this potential benefit for patients presenting severe cases of recurrent CHI.
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Imunoglobulinas Intravenosas , Doenças Placentárias , Humanos , Feminino , Gravidez , Imunoglobulinas Intravenosas/uso terapêutico , Adulto , Doenças Placentárias/tratamento farmacológico , Doenças Placentárias/patologia , Doença Crônica , Vilosidades Coriônicas/patologia , Recidiva , Placenta/patologia , Resultado da GravidezRESUMO
STUDY QUESTION: What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester? SUMMARY ANSWER: In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages. WHAT IS KNOWN ALREADY: Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL. STUDY DESIGN, SIZE, DURATION: The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals. PARTICIPANTS/MATERIALS, SETTING, METHODS: Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth. MAIN RESULTS AND THE ROLE OF CHANCE: One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01). LIMITATIONS, REASONS FOR CAUTION: Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered. WIDER IMPLICATIONS OF THE FINDINGS: Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system. STUDY FUNDING/COMPETING INTEREST(S): The research received no specific funding, and the authors declare no competing interests. TRIAL REGISTRATION NUMBER: clinicaltrial.gov NCT05557201.
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OBJECTIVES: Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease associated with somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutations. We aimed to evaluate the efficacy and safety of targeted therapies. METHODS: Multicentre retrospective study including patients with genetically proven VEXAS syndrome who had received at least one targeted therapy. Complete response (CR) was defined by a clinical remission, C-reactive protein (CRP) ≤10 mg/L and a ≤10 mg/day of prednisone-equivalent therapy, and partial response (PR) was defined by a clinical remission and a 50% reduction in CRP levels and glucocorticoid dose. RESULTS: 110 patients (median age 71 (68-79) years) who received 194 targeted therapies were included: 78 (40%) received Janus kinase (JAK) inhibitors (JAKi), 51 (26%) interleukin (IL)-6 inhibitors, 33 (17%) IL-1 inhibitors, 20 (10%) tumour necrosis factor (TNFα) blockers and 12 (6%) other targeted therapies. At 3 months, the overall response (CR and PR) rate was 24% with JAKi, 32% with IL-6 inhibitors, 9% with anti-IL-1 and 0% with TNFα blockers or other targeted therapies. At 6 months, the overall response rate was 30% with JAKi and 26% with IL-6 inhibitors. Survival without treatment discontinuation was significantly longer with JAKi than with the other targeted therapies. Among patients who discontinued treatment, causes were primary failure, secondary failure, serious adverse event or death in 43%, 14%, 19% and 19%, respectively, with JAKi and 46%, 11%, 31% and 9%, respectively, with IL-6 inhibitors. CONCLUSIONS: This study shows the benefit of JAKi and IL-6 inhibitors, whereas other therapies have lower efficacy. These results need to be confirmed in prospective trials.
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The role of the immune system is to defend the host and preserve the functionality in response to stress. This function is not limited to infection or injury as it also plays a role in the response to overnutrition. Indeed, low-grade chronic activation of the immune system associated with overnutrition may be deleterious, contributing importantly to diabetes and long-term complications, such as cardiovascular disorders. Increasing evidence shows that adipose tissue participates in the obesity-related inflammatory response and that interleukins are one of the key players, either as a pro-inflammatory response to the metabolic dysregulation or to restore homeostasis. The crosstalk between adipocytes and immune cells through some important interleukins and their role in metabolic disruption is the topic of this review.
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Resistência à Insulina , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Humanos , Inflamação/metabolismo , Interleucinas/metabolismoRESUMO
Acute attacks could occur during the convalescent phase of COVID-19 illness, more commonly in patients with a history of frequent attacks. However it is unclear whether the acute attacks during the convalescent phase are specifically triggered by COVID-19 or not.
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Angioedemas Hereditários , COVID-19/metabolismo , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioedemas Hereditários/sangue , Angioedemas Hereditários/epidemiologia , Angioedemas Hereditários/terapia , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2RESUMO
Objective: Adipokines could be a link between metabolic syndrome (MS) and infertility. While the association between circulating adipokines and fertility has been extensively studied in females, this relationship in males was less investigated, although some adipokines are detectable in seminal plasma (SP). The aim of this study was to determine adipokine levels in blood and SP and to assess the relationships between adipokines, MS and semen parameters in men from infertile couples. Design: Male partners of infertile couples referred to four medical French centers were enrolled in years 2013-2016. Methods: Subjects (n = 160) aged 18-45 years were assessed for anthropometric, biochemical, sperm, and circulating hormonal parameters. Leptin, adiponectin, resistin, chemerin, visfatin, and IL-6 were measured in serum and SP. Results: Infertility duration was higher in men with than without MS. Adipokine concentrations were higher in blood than in SP, except for IL-6 and visfatin. The most striking result was the significant correlation observed between seminal IL-6 and spermatozoid concentration, progressive motility, and sperm vitality. Moreover, while men with MS exhibited an expected lower adiponectinemia, they displayed 2.1-fold higher adiponectin levels in SP than men without MS. Finally, logistic regression analysis showed that BMI, infertility duration, and adiponectin serum/SP ratio were independently associated with MS. Conclusions: These results suggest an involvement of seminal adipokines to modulate fertility in men with MS and that seminal IL-6 could play a beneficial role on sperm functionality. Further mechanistic studies are necessary to investigate the precise roles of these adipokines in male reproduction.
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Adipocinas/metabolismo , Infertilidade Masculina/metabolismo , Infertilidade Masculina/fisiopatologia , Adipocinas/sangue , Adolescente , Adulto , Quimiocinas/sangue , Quimiocinas/metabolismo , Feminino , Humanos , Interleucina-6/sangue , Interleucina-6/metabolismo , Leptina/sangue , Leptina/metabolismo , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/sangue , Nicotinamida Fosforribosiltransferase/metabolismo , Reprodução/fisiologia , Sêmen/metabolismo , Sêmen/fisiologia , Contagem de Espermatozoides , Motilidade dos Espermatozoides/fisiologia , Espermatozoides/metabolismo , Espermatozoides/fisiologia , Adulto JovemRESUMO
Adipokines are secreted by adipose tissue and could be the link between obesity and infertility. Different studies investigated the involvement of adipokines in reproductive functions but only a few have looked into the male part. This review assesses adipokine functions on male reproductive parameters. Adiponectin seems to have a positive effect on sperm parameters, whereas other adipokines such as resistin or chemerin would have a rather deleterious effect on spermatogenesis. Semen parameters seem to be impacted when resistin and chemerin are increased: indeed, there is a decrease of sperm motility. Sperm morphology is improved when adiponectin is increased. The most studied adipokine, leptin, has a dual effect with a positive effect on sperm at physiological levels and a negative one for high seminal concentrations. Many semen parameters and fertility itself are disturbed according to semen adipokine levels, even if it is not the only interfering element. Taken together, adipokines are found in human and animal semen and most of them or their receptors are expressed in male genital tract. Although the pathophysiological role of adipokines in semen is not clearly elucidated, the adipokines could influence sperm functionality and could be potential biomarkers of male fertility.
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Adipocinas/análise , Biomarcadores/análise , Infertilidade Masculina/diagnóstico , Fase Pré-Analítica/normas , Sêmen/química , Adipocinas/metabolismo , Biomarcadores/metabolismo , Calibragem , Ensaio de Imunoadsorção Enzimática , Humanos , Infertilidade Masculina/metabolismo , Interleucina-6/análise , Interleucina-6/metabolismo , Masculino , Fase Pré-Analítica/métodos , Valor Preditivo dos Testes , Kit de Reagentes para Diagnóstico/normas , Reprodutibilidade dos Testes , Sêmen/metabolismo , Análise do Sêmen/normas , Preservação do Sêmen/normasRESUMO
Infertility, which increased worldwide over the past few decades, has recently been linked to obesity prevalence. Adipokines, produced by adipose tissue, could be the link between obesity and infertility. The association between circulating adipokines and female infertility has been extensively studied in the last ten years. However, the male aspect has been less investigated, although some adipokines are present in seminal plasma. We have attempted to analyze published studies that measured seminal plasma adipokines and their relationships with semen parameters. Apart from leptin, other seminal adipokines have rarely been studied. Indeed, leptin seems to have a differential role depending on its concentration in the seminal plasma. Thus, it could have a beneficial effect at lower concentrations but a deleterious effect at higher seminal levels. Although some studies are currently available, the roles of leptin and other adipokines in seminal plasma on sperm parameters and their consequences on male fertility remain to be clarified.