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INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 is a viral respiratory infection that can cause systemic disorders and lead to death, particularly in older people. Proton pump inhibitors (PPIs) increase the risk of enteric and lung infections. Considering the broad use of PPIs in older people, the potential role of PPIs in COVID-19 could be of dramatic significance. The objective of our study was to evaluate the link between PPIs and severe COVID-19 in older people. METHOD: We performed a retrospective cohort study, including all patients aged ≥65, hospitalised for a diagnosis of COVID-19. Epidemiological, clinical and biological data were extracted and we performed an Inverse Probability of Treatment Weighing method based on a propensity score. RESULTS: From March 2020 to February 2021, a total of 834 patients were included, with a median age of 83 and 52.8% were male. A total of 410 patients had a PPIs prescription, 358 (87.3%) were long-term PPIs-users and 52 (12.7%) were recent PPIs-users. Among PPIs-users, 163 (39.8%) patients developed severe COVID-19 versus 113 (26.7%) in PPIs-non users (odds ratio (OR) = 1.59 [1.18-2.14]; P < 0.05). Moreover, the double dose PPI-users had a higher risk of developing severe COVID-19 (OR = 3.36 [1.17-9.66]; P < 0.05) than the full dose PPI-users (OR = 2.15 [1.22-3.76]; P < 0.05) and the half dose PPI-users (OR = 1.64 [1.13-2.37]; P < 0.05). CONCLUSION: Our study reports evidence that the use of PPIs was associated with an increased risk of severe COVID-19 in older people.
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COVID-19 , Humanos , Masculino , Anciano , Femenino , Inhibidores de la Bomba de Protones/efectos adversos , Estudios Retrospectivos , SARS-CoV-2 , Puntaje de PropensiónRESUMEN
Exercise in long COVID is poorly studied. Nevertheless, exerciserehabilitation could improve cardiorespiratory, muscular and autonomic functions. We aimed to investigate improvement in physical and autonomic performances of long COVID patients (n = 38) after a 4-week exercise rehabilitation program (3 sessions/week) compared to two control groups composed of coronary artery disease (n = 38) and fibromyalgia patients (n = 38), two populations for whom exercise benefits are well known. Efficacy of exercise training was assessed by a cardiopulmonary exercise test, a handgrip force test, and a supine heart rate variability recording at rest before and after the rehabilitation program. Cardiorespiratory and muscular parameters were enhanced after exercise rehabilitation in the three groups (p < 0.001). No significant difference was observed for the autonomic variables. Through this comparative study with control groups, we confirm and reinforce the interest of caring for long COVID patients without post-exertional symptom exacerbation by exercise rehabilitation of both strength and endurance training, by personalizing the program to the patient and symptoms.
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COVID-19 , Enfermedad de la Arteria Coronaria , Fibromialgia , Humanos , Síndrome Post Agudo de COVID-19 , Fuerza de la Mano , Terapia por Ejercicio , Ejercicio Físico , Prueba de EsfuerzoRESUMEN
BACKGROUND AND OBJECTIVES: Autoantibodies (Abs) improve diagnosis and treatment decisions of idiopathic neurologic disorders. Recently, we identified Abs against Argonaute (AGO) proteins as potential autoimmunity biomarkers in neurologic disorders. In this study, we aim to reveal (1) the frequency of AGO1 Abs in sensory neuronopathy (SNN), (2) titers and IgG subclasses, and (3) their clinical pattern including response to treatment. METHODS: This retrospective multicentric case/control study screened 132 patients with SNN, 301 with non-SNN neuropathies, 274 with autoimmune diseases (AIDs), and 116 healthy controls (HCs) for AGO1 Abs through ELISA. Seropositive cases were also tested for IgG subclasses, titers, and conformation specificity. RESULTS: AGO1 Abs occurred in 44 patients, comprising significantly more of those with SNN (17/132 [12.9%]) than those with non-SNN neuropathies (11/301 [3.7%]; p = 0.001), those with AIDs (16/274 [5.8%]; p = 0.02), or HCs (0/116; p < 0.0001). Ab titers ranged from 1:100 to 1:100,000. IgG subclass was mainly IgG1, and 11/17 AGO1 Ab-positive SNN (65%) had a conformational epitope. AGO1 Ab-positive SNN was more severe than AGO1 Ab-negative SNN (e.g., SNN score: 12.2 vs 11.0, p = 0.004), and they more frequently and more efficiently responded to immunomodulatory treatments than AGO1 Ab-negative SNN (7/13 [54%] vs 6/37 [16%], p = 0.02). Regarding the type of treatments more precisely, this significant difference was confirmed for the use of IV immunoglobulins (IVIg) but not for steroids or second-line treatments. Multivariate logistic regression adjusted for potential confounders showed that AGO1 Ab positivity was the only predictor of response to treatment (OR 4.93, 1.10-22.24 95% CI, p = 0.03). DISCUSSION: Although AGO Abs are not specific for SNN, based on our retrospective data, they may identify a subset of cases with SNN with more severe features and a possibly better response to IVIg. The significance of AGO1 Abs in clinical practice needs to be explored on a larger series.
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Enfermedades Autoinmunes , Inmunoglobulinas Intravenosas , Humanos , Estudios Retrospectivos , Autoanticuerpos , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina G , Enfermedades Autoinmunes/diagnósticoRESUMEN
PURPOSE: Venous thromboembolism (VTE) causes significant morbidity and mortality in patients with traumatic injuries, despite thromboprophylaxis. To decrease both thrombotic and bleeding risks, some authors suggest adjusting the thromboprophylactic doses of low-molecular-weight heparins (LMWH), in particular according to body weight at treatment initiation or to changes in anti-factor Xa level during treatment. Our objective was to estimate in trauma patients the efficacy and safety of such adjustments, compared with the conventional strategy of fixed-dose LMWH thromboprophylaxis. SOURCE: A systematic review and a meta-analysis were conducted to identify and assess randomised control trials and observational studies with prospective enrolment that included trauma patients and compared adjustment of LMWH thromboprophylaxis versus no adjustment. The primary and secondary endpoints were VTE and bleeding, respectively. The Odds Ratio (OR) and 95% Confidence Interval (95% CI) were calculated using the Mantel-Haenszel method. PRINCIPAL FINDINGS: Nine studies were included in the meta-analysis. No significant reduction in the risk of VTE was observed with adjusted doses of LMWH compared with fixed doses when considering only randomised control trials (OR 1.02 [95% CI, 0.09 to 11.6]) or all trials (OR 0.70 [95% CI, 0.34 to 1.42]). Similarly, there was no significant difference in bleeding risk (OR 1.36, 95% CI 0.59 to 3.10). CONCLUSION: This meta-analysis shows that, to date, there is no evidence to justify adjusting LMWH doses, in agreement with the recommendations of the American College of Chest Physicians.
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Heparina de Bajo-Peso-Molecular , Tromboembolia Venosa , Humanos , Heparina de Bajo-Peso-Molecular/efectos adversos , Tromboembolia Venosa/prevención & control , Anticoagulantes/efectos adversos , Estudios Prospectivos , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológicoRESUMEN
BACKGROUND: Sjögren's syndrome (SjS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands associated with sicca syndrome. TAFRO syndrome is a systemic inflammatory disease of unknown cause, characterized by Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis, Renal dysfunction and Organomegaly, first reported in 2010 in Japanese patients. Despite their rarity, both conditions have been concurrently reported in several patients during the recent years, hence questioning the existence of shared or related features. METHODS: A systematic review of the literature regarding SjS associated with TAFRO syndrome (SjS-TAFRO) was performed. The 2019 updated Masaki diagnostic criteria were used for TAFRO syndrome and SjS was considered when the diagnosis was mentioned by the authors, necessarily with either anti-Sjogren's Syndrome A (SSA) ± anti-Sjogren's Syndrome B (SSB) antibodies and/or histological evidence of focal lymphocytic sialadenitis. RESULTS: Ten cases of SjS-TAFRO have been reported in the literature to date. Compared to SjS patients without TAFRO syndrome, these 10 SjS-TAFRO had a lower female predominance (2.3:1 vs 9:1 women to man ratio) and a higher frequency of anti-SSA antibodies (90% vs 70%). All fulfilled the three major Masaki criteria i.e., anasarca, thrombocytopenia, and systemic inflammation. Seven of them (70%) had megakaryocyte hyperplasia or reticulin fibrosis in the bone marrow. Lymph node biopsy was performed in 8 out of 10 cases (80%) and results were consistent with Castleman disease in 6 (75%). Eight of them had developed renal failure (80%) within six months. Nine of them (90%) had organomegaly, with hepatosplenomegaly in 8 cases and splenomegaly alone in 1. CONCLUSION: This review brings new insights regarding TAFRO syndrome and suggests it could be a severe manifestation of SjS. The identification of shared abnormal signaling pathways could help in the therapeutic management of both diseases, which face an unmet therapeutic need.
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Enfermedad de Castleman , Síndrome de Sjögren , Trombocitopenia , Anticuerpos Antinucleares , Enfermedad de Castleman/complicaciones , Enfermedad de Castleman/diagnóstico , Enfermedad de Castleman/tratamiento farmacológico , Edema/complicaciones , Edema/diagnóstico , Edema/tratamiento farmacológico , Femenino , Fibrosis , Humanos , Masculino , Reticulina , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Trombocitopenia/etiologíaRESUMEN
While being the main potential beneficiaries of therapeutic fasting's health benefits, the elderly are frequently thought of as being too fragile to fast. The main objective of our survey was to review the knowledge, practices, and acceptability of therapeutic fasting in subjects aged 65 years and over. From September 2020 to March 2021, an online questionnaire was sent to subjects aged 65 and over, using the mailing list of local organizations working in the field of aging. The mean age of the 290 respondents was 73.8 ± 6.5 years, 75.2% were women and 54.1% had higher education. Among the respondents, 51.7% had already fasted and 80.7% deemed therapeutic fasting interesting, 83.1% would be willing to fast if it was proven beneficial for their health, and 77.2% if it was proven to decrease the burden of chronic diseases. Subjects aged 65 to 74 years considered themselves as having the greatest physical and motivational abilities to perform therapeutic fasting. People aged 65 years, or more, are interested in therapeutic fasting and a large majority would be ready to fast if such practice was proven beneficial. These results pave the way for future clinical trials evaluating therapeutic fasting in elderly subjects.
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Ayuno , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Encuestas y CuestionariosRESUMEN
The antiphospholipid syndrome is an autoimmune disease characterized by thrombosis and pregnancy morbidity. The manifestations are caused by antibodies targeting cell membrane phospholipids and/or associated proteins. The triggers leading to these antibodies' production are unknown but recent work suggests cross-reactivity between the autoantigens and peptides produced by the intestinal microbiome. Work on how the autoantibodies could cause clinical manifestations implicates different mechanisms. Binding to surface proteins of different cell types can induce intracellular signaling leading to cell activation and tissue factor expression. Complement activation and neutrophil extracellular-traps are also involved, and recent evidence implicates endothelial protein C receptor-lysobisphosphatidic acid complex. Pregnancy is a high-risk situation for antiphospholipid syndrome patients due to the increased risk of thrombosis and obstetric complications. Epidemiological and clinical research on APS is hampered by heterogeneity in populations, testing and treatment strategies. About one in 10 to one in fifty APS pregnancies is complicated by thrombosis, despite treatment. Pregnant patients with prior thrombosis are prescribed therapeutic dose heparins and low dose aspirin. Without prior thrombosis a prophylactic dose is used. The most frequent obstetrical manifestation is recurrent early pregnancy loss. The association of APS antibodies with late pregnancy loss is stronger, however. Prevention of recurrence is achieved with aspirin and prophylactic dose heparin, although the evidence is of low certainty. The third obstetrical classifying manifestation comprises preterm delivery due to placenta-mediated complications and is treated in subsequent pregnancies with aspirin with or without prophylactic dose heparin, again based on low quality evidence. New therapies are under investigation.
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Bone marrow biopsies are largely used for the diagnosis and prognostic of various hematological diseases. Complications are rare but can be as serious as hemorrhage. However, little is known about management of patients deemed at high hemorrhagic risk like thrombocytopenic patients or patients receiving antithrombotic drugs. The aim of the study was to describe the management of patients regarding their laboratory profile and antithrombotic treatment prior to bone marrow biopsy and the short-term outcomes, notably hemorrhage. We conducted a retrospective observational study between February 2007 and March 2018. A standardized form was used to collect data from patients' records, blood tests results, management of antiplatelet and anticoagulant treatment before biopsy and complications including bleeding and thromboembolic events until 3 months after the biopsy. A total of 524 bone marrow biopsies were performed. No major bleeding events were reported. The incidence of clinically relevant non-major bleeding was 0.19% (CI 95% 0.00-1.20) and was linked to low platelets counts (p = 0.002) and not to abnormal coagulation profile or antithrombotic therapy, whether or not a bridging therapy has been used. Anticoagulants were temporarily stopped before biopsy in most cases without subsequent thrombotic complications. Our data suggest that thrombocytopenic patients have a non-negligible bleeding risk. Coagulation profiling seems irrelevant. We propose an algorithm to assist the management of those patients, notably when receiving antithrombotic drugs.
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Médula Ósea , Fibrinolíticos , Anticoagulantes/efectos adversos , Biopsia/efectos adversos , Fibrinolíticos/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Systemic autoimmune and inflammatory diseases have a complex and only partially known pathophysiology with various abnormalities involving all the components of the immune system. Among these components, antibodies, and especially autoantibodies are key elements contributing to autoimmunity. The interaction of antibody fragment crystallisable (Fc) and several distinct receptors, namely Fc receptors (FcRs), have gained much attention during the recent years, with possible major therapeutic perspectives for the future. The aim of this review is to comprehensively describe the known roles for FcRs (activating and inhibitory FcγRs, neonatal FcR [FcRn], FcαRI, FcεRs, Ro52/tripartite motif containing 21 [Ro52/TRIM21], FcδR, and the novel Fc receptor-like [FcRL] family) in systemic autoimmune and inflammatory disorders, namely rheumatoid arthritis, Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, Crohn's disease, ulcerative colitis, immunoglobulin (Ig) A vasculitis, Behçet's disease, Kawasaki disease, IgG4-related disease, immune thrombocytopenia, autoimmune hemolytic anemia, antiphospholipid syndrome and heparin-induced thrombocytopenia.
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Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Síndrome de Sjögren , Autoanticuerpos , Autoinmunidad , Humanos , Recién Nacido , Receptores FcRESUMEN
Maintaining commensal diversity is essential to host homeostasis, because microbial species provide a range of metabolic products and continuously educate the host immune system. The mucosal immune system must actively gather information about the composition of the microbiota, while offering an appropriate response. In mammals, bacterial sensing leads to the production of specific immunoglobulins (Ig), which reach the intestinal lumen as secretory Ig (SIg). Recent work has shed more light on the mechanisms by which SIg can shape bacterial repertoires and contribute to regulating host metabolism. In parallel, bacterial metabolites modulate Ig production and secretion. Here, we present an overview of the current knowledge of the relationship between bacterial metabolites and host SIg, correlating the disruption of this balance with chronic inflammation in humans.
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Microbiota , Animales , Bacterias , Humanos , Inmunidad Mucosa , Inmunoglobulinas/metabolismo , Mucosa Intestinal , Intestinos , Mamíferos , SimbiosisRESUMEN
BACKGROUND: In cases of loss of response due to mechanistic failure under antitumor necrosis factor agents, it is recommended to switch to another class of biologics. Two different strategies were compared in patients with inflammatory bowel disease (IBD) who were treated with nonoptimized adalimumab (ADA) and experienced a loss of response despite therapeutic trough levels of adalimuma-either ADA dose optimization or switching to vedolizumab or ustekinumab. METHODS: Patients under maintenance therapy with ADA monotherapy (40 mg every 14 days) and who experienced a secondary loss of response with trough levelsâ >â 4.9 µg/mL were included prospectively in this nonrandomized study. The primary end point was the survival rate without therapeutic discontinuation after ADA dose optimization or switching to another class of biologics. RESULTS: Adalimumab was optimized (nâ =â 61 patients, 42 Crohn's disease, 19 ulcerative colitis) or swapped for vedolizumab (nâ =â 40, 20 ulcerative colitis) or ustekinumab (nâ =â 30, 30 Crohn's disease). At 24 months, 11 out of 70 patients (14.8%) in the swap group discontinued treatment compared with 36 out of 61 (59.6%) patients in the optimization group (Pâ <â 0.001). The median time without therapeutic discontinuation was significantly longer in the swap group (>24 months) than in the optimization group (13.3 months, Pâ <â 0.001). In the optimization group, treatment discontinuation was positively associated with baseline fecal calprotectin >500 µg/g (HR, 3.53; 95% CI, 1.16-10.72; Pâ =â 0.026) and inversely associated with variation of trough levels of adalimumab (>2 µg/mL from baseline to week 8 after optimization; HR, 0.51; 95% CI, 0.13-0.82; Pâ =â 0.03). In the swap group, no factor was associated with treatment discontinuation. CONCLUSION: In IBD patients under ADA maintenance therapy who experience a secondary loss of response and in whom trough levels are >4.9µg/mL, swapping to another class is better than optimizing ADA, which is, however, appropriate in a subgroup of patients.
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Productos Biológicos , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Adalimumab/uso terapéutico , Productos Biológicos/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Resultado del Tratamiento , Ustekinumab/uso terapéuticoRESUMEN
Sjögren's syndrome (SjS) is a frequent systemic autoimmune disease responsible for a major decrease in patients' quality of life, potentially leading to life-threatening conditions while facing an unmet therapeutic need. Hence, we assessed the immunogenicity, efficacy, and tolerance of IFN-Kinoid (IFN-K), an anti-IFNα vaccination strategy, in a well-known mouse model of systemic autoimmunity with SjS-like features: MRL/MpJ-Faslpr/lpr (MRL/lpr) mice. Two cohorts (with ISA51 or SWE01 as adjuvants) of 26 female MRL/lpr were divided in parallel groups, "controls" (not treated, PBS and Keyhole Limpet Hemocyanin [KLH] groups) or "IFN-K" and followed up for 122 days. Eight-week-old mice received intra-muscular injections (days 0, 7, 28, 56 and 84) of PBS, KLH or IFN-K, emulsified in the appropriate adjuvant, and blood samples were serially collected. At sacrifice, surviving mice were euthanized and their organs were harvested for histopathological analysis (focus score in salivary/lacrimal glands) and IFN signature evaluation. SjS-like features were monitored. IFN-K induced a disease-modifying polyclonal anti-IFNα antibody response in all treated mice with high IFNα neutralization capacities, type 1 IFN signature's reduction and disease features' (ocular and oral sicca syndrome, neuropathy, focus score, glandular production of BAFF) improvement, as reflected by the decrease in Murine Sjögren's Syndrome Disease Activity Index (MuSSDAI) modelled on EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). No adverse effects were observed. We herein report on the strong efficacy of an innovative anti-IFNα vaccination strategy in a mouse model of SjS, paving the way for further clinical development (a phase IIb trial has just been completed in systemic lupus erythematosus with promising results).
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Interferón-alfa/antagonistas & inhibidores , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/terapia , Animales , Anticuerpos Neutralizantes/sangre , Autoanticuerpos/sangre , Autoinmunidad , Linfocitos B/inmunología , Modelos Animales de Enfermedad , Femenino , Perfilación de la Expresión Génica , Hemocianinas/administración & dosificación , Hemocianinas/inmunología , Humanos , Inmunoconjugados/administración & dosificación , Inmunoconjugados/inmunología , Inmunoterapia Activa , Interferón-alfa/administración & dosificación , Interferón-alfa/inmunología , Interferones/biosíntesis , Interferones/genética , Aparato Lagrimal/inmunología , Aparato Lagrimal/patología , Ratones , Ratones Endogámicos MRL lpr , Glándulas Salivales/inmunología , Glándulas Salivales/patología , Síndrome de Sjögren/genéticaRESUMEN
Secretory immunoglobulin A (SIgA) can travel to and from the lumen and transport antigen to subepithelial cells. However, IgM can also multimerize into functional secretory component-bound immunoglobulin. While it is already known that both SIgA and SIgM undergo transcytosis to be secreted at the mucosal surface, only SIgA has been shown to perform retrotranscytosis through microfold cells (M cells) of the Peyer's patch. Here, we investigate whether SIgM could also be taken up by M cells via retrotranscytosis. This transport involves FcµR binding at the apical membrane of M cells. We then demonstrate that SIgM can be exploited by SIgM-p24 (HIV-capsid protein) complexes during immunization in the nasal- or gut-associated lymphoid tissue (NALT or GALT), conferring efficient immune responses against p24. Our data demonstrate a mucosal function of SIgM, which could play a role in the regulation of mucosal immunity.
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Proteínas Reguladoras de la Apoptosis/metabolismo , Intestinos/fisiología , Proteínas de la Membrana/metabolismo , Transcitosis/fisiología , Animales , Proteínas Reguladoras de la Apoptosis/fisiología , Femenino , Inmunidad Mucosa/fisiología , Inmunoglobulina A Secretora/metabolismo , Inmunoglobulina M/inmunología , Mucosa Intestinal/metabolismo , Intestinos/inmunología , Intestinos/metabolismo , Proteínas de la Membrana/fisiología , Ratones , Ratones Endogámicos BALB C , Ganglios Linfáticos Agregados/citología , Transcitosis/genéticaRESUMEN
While the diagnosis of adult-onset Still's disease (AOSD) involves the exclusion of differential diagnoses, the characteristics and value of 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography coupled with CT (PET/CT) in the management of AOSD remain poorly known. Our retrospective study included patients from four centers, fulfilling Yamaguchi or Fautrel criteria, who underwent a PET/CT during an active AOSD. Thirty-five patients were included. At the time of PET/CT, the Yamaguchi criteria were met in 23 of 29 evaluable cases. PET/CT showed bone marrow (74.3%), lymph node (74.3%), and splenic (48.6%) FDG uptake. Despite arthralgia or arthritis in most patients, joints were rarely the sites of 18F-FDG accumulation. The spatial distribution of 18F-FDG uptake was nonspecific, and its intensity could be similar to malignant disease. Lymph node or bone marrow biopsy was performed after PET/CT in 20 patients (57.1%). The intensity of bone marrow; splenic and lymph node hypermetabolism appeared to be correlated with disease activity. Abnormal PET/CT in the cervical lymph nodes and age ≥ 60 years seemed to be predictive factors for monocyclic evolution. The clinical value of PET/CT is not in direct diagnosis; but as an aid in excluding differential diagnoses by searching for their scintigraphic features and guiding biopsy.
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BACKGROUND: Anti-drug antibodies develop mostly during the induction therapy with anti-tumour necrosis factor (TNF) drugs and can be revealed by means of a drug-tolerant assay. AIM: To investigate whether the early detection of anti-drug antibodies during the induction therapy was predictive of treatment discontinuation. METHODS: In a prospective study, consecutive patients with inflammatory bowel disease (IBD), who should start an anti-TNF, were enrolled and followed regularly during 24 months or less in case of non- or loss of response (LOR) or adverse events requiring treatment discontinuation. Anti-TNF levels and anti-drug antibodies were measured at week 2 for adalimumab (ADA) and weeks 2 and 6 for infliximab (IFX) using a drug-tolerant assay. RESULTS: One hundred and eight patients were enrolled (54 under ADA). At week 2, antibodies to ADA and to IFX were detected in 76% and 67% of patients. Time to treatment discontinuation was significantly shorter (P < 0.001) in patients with antibodies to ADA ≥2.0 µg/mL-eq (6.0 vs 24 months, HR = 18.51, 95% CI [4.35-78.71]) or with antibodies to IFX ≥4.0 µg/mL-eq (5.5 vs >24 months, HR = 13.89, 95% CI [4.08-47.31]) at week 2 compared to patients without positive antibodies. Antibodies to ADA and to IFX were predictive of treatment failure within 24 months with a sensitivity of 79% and 62%, and specificities and positive predictive values of 100%. In multivariate analysis, antibodies to ADA or to IFX at week 2 were the only factors associated with treatment discontinuation. CONCLUSIONS: The prevalence of antibodies to anti-TNF is high when detected early using a drug-tolerant assay, and their appearance predicts further treatment discontinuation.
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Enfermedades Inflamatorias del Intestino , Factor de Necrosis Tumoral alfa , Adalimumab/uso terapéutico , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Eosinophils have widespread procoagulant effects. Eosinophilic cardiovascular toxicity mostly consists of endomyocardial damage or eosinophilic vasculitis, while reported cases of venous thrombosis (VT) are scarce. We aimed to report on the clinical features and treatment outcomes of patients with unexplained VT and eosinophilia, and to identify predictors of relapse. This retrospective, multicenter, observational study included patients aged over 15 years with VT, concomitant blood eosinophilia ≥ 1G/L and without any other moderate-to-strong contributing factors for VT. Fifty-four patients were included. VT was the initial manifestation of eosinophil-related disease in 29 (54%) patients and included pulmonary embolism (52%), deep venous thrombosis (37%), hepatic (11%) and portal vein (9%) thromboses. The median [IQR] absolute eosinophil count at VT onset was 3.3G/L [1.6-7.4]. Underlying eosinophil-related diseases included FIP1L1-PDGFRA-associated chronic myeloid neoplasm (n = 4), Eosinophilic Granulomatosis with Polyangiitis (n = 9), lymphocytic (n = 1) and idiopathic (n = 29) variants of hypereosinophilic syndrome. After a median [IQR] follow-up of 24 [10-62] months, 7 (13%) patients had a recurrence of VT. In multivariate analysis, persistent eosinophilia was the sole variable associated with a shorter time to VT relapse (HR 7.48; CI95% [1.94-29.47]; p = 0.015). Long-term normalization of eosinophil count could prevent the recurrence of VT in a subset of patients with unexplained VT and eosinophilia ≥ 1G/L.
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Síndrome de Churg-Strauss/terapia , Eosinofilia/terapia , Síndrome Hipereosinofílico/terapia , Leucemia/terapia , Trombosis de la Vena/terapia , Adulto , Anciano , Síndrome de Churg-Strauss/epidemiología , Síndrome de Churg-Strauss/patología , Eosinofilia/complicaciones , Eosinofilia/epidemiología , Eosinofilia/patología , Eosinófilos/patología , Femenino , Humanos , Síndrome Hipereosinofílico/epidemiología , Síndrome Hipereosinofílico/genética , Síndrome Hipereosinofílico/patología , Leucemia/epidemiología , Leucemia/genética , Leucemia/patología , Masculino , Persona de Mediana Edad , Vena Porta/patología , Embolia Pulmonar/epidemiología , Embolia Pulmonar/patología , Embolia Pulmonar/terapia , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento , Trombosis de la Vena/epidemiología , Trombosis de la Vena/genética , Trombosis de la Vena/patología , Factores de Escisión y Poliadenilación de ARNm/genéticaRESUMEN
Immune effector responses against Plasmodium falciparum include antibody-mediated activation of innate immune cells, which can induce Fc effector functions, including antibody-dependent cellular cytotoxicity, and the secretion of cytokines and chemokines. These effector functions are regulated by the composition of immunoglobulin G (IgG) Fc N-linked glycans. However, a role for antibody-mediated natural killer (NK) cells activation or Fc N-linked glycans in pregnant women with malaria has not yet been established. Herein, we studied the capacity of IgG antibodies from pregnant women, with placental malaria or non-placental malaria, to induce NK cell activation in response to placental malaria-associated antigens DBL2 and DBL3. Antibody-mediated NK cell activation was observed in pregnant women with malaria, but no differences were associated with susceptibility to placental malaria. Elevated anti-inflammatory glycosylation patterns of IgG antibodies were observed in pregnant women with or without malaria infection, which were not seen in healthy non-pregnant controls. This suggests that pregnancy-associated anti-inflammatory Fc N-linked glycans may dampen the antibody-mediated activation of NK cells in pregnant women with malaria infection. Overall, although anti-inflammatory glycans and antibody-dependent NK cell activation were detected in pregnant women with malaria, a definitive role for these antibody features in protecting against placental malaria remains to be proven.
Asunto(s)
Anticuerpos Antiprotozoarios/inmunología , Células Asesinas Naturales/inmunología , Malaria Falciparum/inmunología , Complicaciones Parasitarias del Embarazo/inmunología , Adulto , Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Antígenos de Protozoos/inmunología , Eritrocitos/inmunología , Eritrocitos/parasitología , Femenino , Glicosilación , Humanos , Fragmentos Fc de Inmunoglobulinas/inmunología , Inmunoglobulina G/inmunología , Células Asesinas Naturales/parasitología , Malaria Falciparum/parasitología , Placenta/inmunología , Placenta/parasitología , Plasmodium falciparum/inmunología , Embarazo , Complicaciones Parasitarias del Embarazo/parasitología , Mujeres Embarazadas , Adulto JovenRESUMEN
A 67-year-old man was referred to our department for the onset of cutaneous lesions following venepunctures. His recent medical history included brief flu-like syndrome, persistent cough, dyspnoea, dry mouth, blurred vision and weight loss. The extensive clinical, biological and radiological check-up showed signs consistent with systemic sarcoidosis: right uveitis, hypercalcemia, renal failure, inflammatory syndrome, elevated levels of ACE, alveolitis with elevated CD4+/CD8+ T cell ratio, hilar and mediastinal lymphadenopathy, bilateral pulmonary infiltrates, mild bronchial obstruction and lowered diffusing capacity of the lungs for carbon monoxide. Multiple biopsy samples (bronchus, accessory salivary glands and one of the skin lesions) eventually confirmed the diagnosis. Corticosteroids resulted in skin lesions resolution in a few days and overall clinical, biological and lung function improvement. The infiltration of scars by granulomatous tissue is well recognised in sarcoidosis but its onset in venepuncture sites is a very rare but easily recognisable condition, which can be helpful for quick diagnosis purpose.