RESUMEN
Background and Objectives: Vision significantly contributes to postural control, balance, coordination, and body kinematics, thus deeply influencing everyday functionality. Sight-impaired subjects often show upper body anatomofunctional and kinetic chain alterations negatively impacting daily living efficiency and autonomy. The present study aimed to investigate and train, for the first time, upper body sensorimotor control in an Italian blind baseball team to boost global and segmental functionality while contemporarily prevent injuries. Materials and Methods: The whole team underwent a validated test battery using both quantitative traditional tools, such as goniometric active range of motion and muscular/functional tests, and an innovative biofeedback-based device, a Libra proprioceptive board. Consequently, a 6-week adapted training protocol was designed and leaded to improve sensorimotor control and, hence, counteract disability-related deficits and sport-specific overuse syndromes. Results: Statistically significant improvements were observed in all the investigated parameters. Noteworthy, an overall boost of global and segmental stability was detected through an orthostatic dynamic balance enhancement during the Y Balance test (p = 0.01) and trunk multiplanar control improvement on the Libra board (p = 0.01). Concurrently, the comparison of baseline vs. post-intervention outcomes revealed a consistent increase in upper body mobility (p < 0.05 for all the assessed districts), core recruitment (p = 0.01 for all the administered functional tests), and proprioceptive postural control (p = 0.01 for the Libra board validated test). Conclusions: Our findings suggest that a tailored sensorimotor training, conceived and led by an adapted physical activity kinesiologist, may effectively improve upper body functional prerequisites and global proprioceptive control, thus potentially promoting autonomy, quality of life, and physical activity/sport practice adherence in visually impaired individuals.
Asunto(s)
Béisbol , Humanos , Masculino , Adulto , Béisbol/lesiones , Béisbol/fisiología , Equilibrio Postural/fisiología , Personas con Daño Visual , Italia , Actividades Cotidianas , Femenino , Rango del Movimiento Articular , Fenómenos BiomecánicosRESUMEN
A 26-weeks pregnant woman presented with progressively worsening dyspnoea and poor general conditions. Using low-dose radiation multi-imaging techniques and thoracic biopsy a primary mediastinal large B cell was diagnosed. A multidisciplinary approach identified the correct hemodynamic management, the best therapeutic strategy and the timing for delivery.
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Linfoma de Células B Grandes Difuso , Neoplasias del Mediastino , Disnea/etiología , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/terapia , Neoplasias del Mediastino/diagnóstico por imagen , Neoplasias del Mediastino/terapia , Mediastino/patología , EmbarazoRESUMEN
There are five tumor necrosis factor alpha (TNF-α) inhibitors available for clinical use that have demonstrated efficacy as monotherapy or in combination with other anti-inflammatory or disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of immune-mediated diseases. These include the anti-TNF-α monoclonal antibodies infliximab, adalimumab, golimumab, and certolizumab pegol, and the fusion protein, etanercept. The use of pharmacogenetic testing has the potential to increase drug efficiency by identifying genetic factors responsible for a lack of response to, or toxicities from, TNF-α inhibitors, and could be used to individualize therapy. Several studies have reported associations between genetic polymorphisms and the response to etanercept, but most are small and insufficiently powered to detect effect, and markers tend to be more prognostic than predictive of therapeutic response. Limitations of pharmacogenetic studies include the use of single nucleotide polymorphisms (SNPs), genes in linkage with other loci, interaction of environmental factors, and cohort heterogeneity, all of which can complicate the relationship between genetic polymorphisms and treatment response. Further studies are needed for pharmacogenetics to become a routine part of daily clinical therapeutic practice.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Inmunoglobulina G/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genética , Artritis Reumatoide/sangre , Etanercept , Genotipo , Humanos , Linfotoxina-alfa/sangre , Polimorfismo de Nucleótido Simple , Resultado del TratamientoRESUMEN
Purpose of our study was to assess the prevalence of hypertension mediated organ damage (HMOD) in healthy subjects with high-normal Blood Pressure (BP) comparing them with subjects with BP values that are considered normal (<130/85 mmHg) or indicative of hypertension (≥140/90 mmHg). Seven hundred fifty-five otherwise healthy subjects were included. HMOD was evaluated as pulse wave velocity (PWV), left ventricular mass index (LVMI), and carotid intima-media thickness (IMT) and plaque. When subjects were classified according to BP levels we found that the high-normal BP group showed intermediate values of PWV and higher values of IMT. This corresponds to intermediate prevalence of arterial stiffness, while there were no differences for increased IMT or carotid plaque. No subjects showed left ventricular hypertrophy. At multivariable analysis, the odds of having arterial stiffness or carotid HMOD in the high-normal group resulted not different to the normal group. In conclusion, in our otherwise healthy population, high-normal BP values were not related to aortic, carotid or cardiac HMOD.
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Hipertensión , Enfermedades Renales , Presión Sanguínea/fisiología , Arterias Carótidas/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Prevalencia , Análisis de la Onda del PulsoAsunto(s)
Adenocarcinoma/diagnóstico , Neoplasias Encefálicas/secundario , Eosinofilia/diagnóstico , Neoplasias Pulmonares/diagnóstico , Miocarditis/diagnóstico , Síndromes Paraneoplásicos/diagnóstico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/etiología , Biopsia , Neoplasias Encefálicas/tratamiento farmacológico , Cardiomegalia/diagnóstico por imagen , Cardiomegalia/etiología , Diagnóstico Diferencial , Disnea/etiología , Ecocardiografía , Electrocardiografía , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/etiología , Persona de Mediana Edad , Miocardio/patología , Síndromes Paraneoplásicos/etiología , Derrame Pericárdico/diagnóstico por imagen , Derrame Pericárdico/etiología , Derrame Pleural/diagnóstico por imagen , Derrame Pleural/etiología , Derrame Pleural/patología , Radiografía , Insuficiencia Respiratoria/etiología , Choque Cardiogénico/etiología , Fumar/efectos adversosRESUMEN
Treatment of overt form of hypertrophic cardiomyopathy (HCM) is often unsuccessful. Efforts are focused on a possible early identification in order to prevent or delaying the development of hypertrophy. Our aim was to find an echocardiographic marker able to distinguish mutation carriers without left ventricular hypertrophy (LVH) from healthy subjects. We evaluated 28 patients, members of eight families. Three types of mutation were recognized: MYBPC3 (five families), MYH7 (two families) and TNNT2 (one family). According to genetic (G) and phenotypic (Ph) features, patients were divided in three groups: Group A (10 patients), mutation carriers with LVH (G+/Ph+); Group B (9 patients), mutation carriers without LVH (G+/Ph-); Group C (9 patients), healthy subjects (G-/Ph-). Echocardiography examination was performed acquiring standard 2D, DTI and 2D-strain imaging. Global longitudinal strain (GLS) and global radial strain (GRS) at basal and mid-level were measured. GRS was significantly different between group B and C at basal level (32.18% ± 9.6 vs. 44.59% ± 12.67 respectively; p-value < 0.0001). In basal posterior and basal inferior segments this difference was particularly evident. ROC curves showed for both the involved segments good AUCs (0.931 and 0.861 for basal posterior and inferior GRS respectively) with the best predictive cut-off for basal posterior GRS at 43.65%, while it was 38.4% for basal inferior GRS. Conversely, GLS values were similar in the three group. 2D longitudinal strain is a valid technique to study HCM. Radial strain and particularly basal posterior and inferior segmental reduction could be able to identify mutation carriers in a pre-clinical phase of disease.
Asunto(s)
Cardiomiopatía Hipertrófica/diagnóstico por imagen , Ecocardiografía , Función Ventricular Izquierda , Adolescente , Adulto , Anciano , Miosinas Cardíacas/genética , Cardiomiopatía Hipertrófica/genética , Cardiomiopatía Hipertrófica/fisiopatología , Proteínas Portadoras/genética , Estudios de Casos y Controles , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Mutación , Cadenas Pesadas de Miosina/genética , Fenotipo , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Troponina T/genética , Adulto JovenRESUMEN
Cilostazol is a selective inhibitor of phosphodiesterase-III with antiplatelet, antithrombotic and vasodilating properties. The aim of our study was to evaluate the effect of the drug on vasculopathy and Raynaud's phenomenon (RP), in a series of patients with systemic sclerosis (SSc), before and after cilostazol treatment. Twenty-one consecutive SSc patients with moderate or severe RP were enrolled in an open-label study. Cilostazol was administered at the dose of 100 mg twice a day, for 12 months. Evaluations included: daily RP attack diary documenting the frequency and duration of RP episodes, Health Assessment Questionnaire-Disability Index, scleroderma visual analogue scales (VAS), flow-mediated dilation and immunological status, including endothelin 1 and interleukin 6 plasma levels. Thirteen patients completed the study. RP duration and daily number episodes recorded over a 3-week period significantly decreased after cilostazol treatment (p = 0.0049 and p = 0.0067, respectively). VAS score indicated a significant amelioration of the patients' perception of RP (p = 0.0117), and both baseline and post-ischemic brachial artery diameters were significantly increased after cilostazol treatment, as compared with basal values (p = 0.0119 and p = 0.0076, respectively). None of the patients developed digital ulcers during the study. A significant clinical improvement of RP was recorded in SSc patients undergoing cilostazol treatment. Study results indicate a potential role of cilostazol as oral maintenance therapy in SSc patients with RP.
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Enfermedad de Raynaud/terapia , Esclerodermia Sistémica/complicaciones , Tetrazoles/administración & dosificación , Vasodilatadores/administración & dosificación , Adulto , Anciano , Cilostazol , Estudios Controlados Antes y Después , Humanos , Persona de Mediana Edad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Systemic Lupus Erythematosus (SLE) is characterized by abnormal autoantibody production and clearance. Infections are among the most important causes of morbidity and mortality in SLE patients; they have an increased frequency of severe bacterial and viral infections possibly due to inherited genetic and immunologic defects and to immunosuppressive therapies. In addition, infectious agents can switch on lupus disease expression and activity. Among the strategies to reduce the risk of infection, vaccination can be considered the most reliable option. Most vaccines are effective and safe in SLE patients, although in certain cases immunogenicity may be sub-optimal and vaccination can trigger a flare. Although these issues are currently unresolved, the risk benefit balance is in favor for vaccination to reduce the risk of infection in SLE patients. In the present review we discuss the preventive strategies currently recommended to reduce bacterial and viral infections in SLE.
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Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/prevención & control , Lupus Eritematoso Sistémico/complicaciones , Vacunas/administración & dosificación , Vacunas/inmunología , Virosis/epidemiología , Virosis/prevención & control , HumanosRESUMEN
INTRODUCTION: TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying antirheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases such as rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriasis and/or psoriatic arthritis, and may be administered off-label to treat disseminated granuloma annulare systemic lupus erythematosus and systemic sclerosis. There are several TNF-α inhibitors available for clinical use including infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. AREAS COVERED: infliximab and adalimumab can induce the development of anti-infliximab (anti-IFX) and anti-adalimumab (anti-ADA) monoclonal antibodies (mAbs). In this review, we discuss the impact of anti-IFX and anti-ADA mAbs upon efficacy and safety of these biological agents. EXPERT OPINION: IgG/IgE neutralizing antibodies against infliximab and adalimumab decrease the possibility of achieving a minimal disease activity state or clinical remission, decrease drug survival, increase the need for doctors to prescribe a higher drug dosage and, finally, favor the occurrence of adverse events. Concomitant administration of DMARDs such as methotrexate or leflunomide prevents the development of neutralizing Abs against infliximab and adalimumab.
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Adalimumab/inmunología , Antirreumáticos/inmunología , Infliximab/inmunología , Adalimumab/administración & dosificación , Adalimumab/efectos adversos , Anticuerpos Monoclonales/inmunología , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Relación Dosis-Respuesta a Droga , Humanos , Hipersensibilidad Tardía/inmunología , Enfermedades del Sistema Inmune/tratamiento farmacológico , Enfermedades del Sistema Inmune/inmunología , Inmunoglobulina E/inmunología , Inmunoglobulina G/inmunología , Infliximab/administración & dosificación , Infliximab/efectos adversos , Receptores del Factor de Necrosis Tumoral/antagonistas & inhibidoresRESUMEN
INTRODUCTION: TNF-α is a pro-inflammatory cytokine known to a have a key role in the pathogenesis of chronic immune-mediated diseases. TNF-α inhibitors can be administered either as monotherapy or in combination with other anti-inflammatory or disease-modifying anti-rheumatic drugs (DMARDs) to treat chronic immune-mediated diseases. AREAS COVERED: Patients receiving TNF-α inhibitors are at high risk of infections. Based on our experience, in this paper, we discuss the risk of infections associated with the administration of TNF-α inhibitors and the strategies for mitigating against the development of these serious adverse events. EXPERT OPINION: Infliximab more so than etanercept appears to be responsible for the increased risk of infections. Re-activation of latent tuberculosis (LTB) infection and the overall risk of opportunistic infections should be considered before beginning TNF-α inhibitor therapy. A careful medical history, Mantoux test and chest-x-ray should always be performed before prescribing TNF-α inhibitors. Particular attention should be paid to risk factors for Pneumocystis jirovecii infection. Hepatitis B and C virological follow-up should be considered during TNF-α inhibitor treatment. Finally, patients who are at high risk of herpes zoster (HZ) reactivation would benefit from a second vaccination in adulthood when receiving TNF-α inhibitors.
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Factores Inmunológicos/efectos adversos , Infecciones/etiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Etanercept/administración & dosificación , Etanercept/efectos adversos , Humanos , Enfermedades del Sistema Inmune/tratamiento farmacológico , Factores Inmunológicos/administración & dosificación , Infecciones/epidemiología , Infliximab/administración & dosificación , Infliximab/efectos adversos , Factores de RiesgoRESUMEN
We report the description of a cardiac mass occupying almost the entire right atrium in a young man who developed paroxysmal supraventricular tachycardia during endovascular treatment of intracranial arteriovenous fistulas. The mass was detected at echocardiographic examination, its tissue characteristics were defined with cardiac magnetic resonance and it was successfully surgically removed. The histopathological findings were consistent with a mixed type cavernous-capillary hemangioma of the heart. The intriguing co-existence of cardiac hemangioma and cerebral arteriovenous fistulas, to the best of our knowledge, has not been previously reported in English Literature.
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Fístula Arteriovenosa/cirugía , Hemangioma/etiología , Taquicardia Supraventricular/etiología , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/patología , Hemangioma/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Taquicardia Supraventricular/diagnóstico por imagen , UltrasonografíaRESUMEN
We report the case of a 61-year-old woman referred to our center for cardiac evaluation after a syncope, with echocardiographic findings of a papillary fibroelastoma on the edge of the non-coronary aortic cusp. The three-dimensional transesophageal approach provided a unique understanding of the size and shape of the mass and it favorably directed the surgeon towards treatment with conservative surgery.
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Fibroma/diagnóstico , Neoplasias Cardíacas/diagnóstico , Síncope/etiología , Válvula Aórtica/patología , Ecocardiografía Transesofágica/métodos , Femenino , Fibroma/patología , Fibroma/cirugía , Neoplasias Cardíacas/patología , Neoplasias Cardíacas/cirugía , Enfermedades de las Válvulas Cardíacas/diagnóstico , Enfermedades de las Válvulas Cardíacas/patología , Enfermedades de las Válvulas Cardíacas/cirugía , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Diabetes insipidus is a disease in which large volumes of dilute urine (polyuria) are excreted due to vasopressin (AVP) deficiency [central diabetes insipidus (CDI)] or to AVP resistance (nephrogenic diabetes insipidus). In the majority of patients, the occurrence of CDI is related to the destruction or degeneration of neurons of the hypothalamic supraoptic and paraventricular nuclei. The most common and well recognized causes include local inflammatory or autoimmune diseases, vascular disorders, Langerhans cell histiocytosis (LCH), sarcoidosis, tumors such as germinoma/craniopharyngioma or metastases, traumatic brain injuries, intracranial surgery, and midline cerebral and cranial malformations. Here we have the opportunity to describe an unusual case of female patient who developed autoimmune CDI following ureaplasma urealyticum infection and to review the literature on this uncommon feature. Moreover, we also discussed the potential mechanisms by which ureaplasma urealyticum might favor the development of autoimmune CDI.
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Artritis Reactiva/inmunología , Enfermedades Autoinmunes/microbiología , Diabetes Insípida Neurogénica/microbiología , Infecciones por Ureaplasma/inmunología , Ureaplasma urealyticum , Artritis Reactiva/microbiología , Autoanticuerpos , Enfermedades Autoinmunes/etiología , Diabetes Insípida Neurogénica/etiología , Diabetes Insípida Neurogénica/inmunología , Femenino , Humanos , Persona de Mediana Edad , Neurofisinas/inmunología , Precursores de Proteínas/inmunología , Infecciones por Ureaplasma/complicaciones , Vasopresinas/inmunologíaRESUMEN
INTRODUCTION: Systemic sclerosis (SSc) is a rare connective tissue disease characterized by chronic inflammation and fibrosis of the skin, vascular abnormalities and variable involvement of organs. Patients with limited SSc typically develop pulmonary arterial hypertension (PAH). TNF-α, VEGF, platelet-derived growth factor and endothelin-1 play a key role in the development of PAH. AREAS COVERED: This paper addresses the efficacy and safety of current drugs used for the treatment of PAH. EXPERT OPINION: Bosentan, ambrisentan, sildenafil, tadalafil, iloprost, epoprostenol and treprostinil were associated with hemodynamic improvements in PAH patients. Ambrisentan has a better safety profile compared with bosentan, regarding the risk of increase in hepatic transaminases. Flushing, dyspepsia and diarrhea were the most frequent adverse events in patients treated with sildenafil, while headache, myalgia and flushing were the adverse events in those receiving tadalafil. Inhaled iloprost is also effective, but it requires multiple daily nebulizations up to 15 min each and may induce cough, flushing, jaw pain and headache. Epoprostenol is considered the most effective approved therapy for severe PAH in WHO functional class III and class IV. TNF-α inhibitors reduce the systemic inflammation in patients with chronic immune-mediated diseases and improve the endothelial function, decreasing the risk of PAH progression.
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Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Esclerodermia Sistémica/complicaciones , Hipertensión Pulmonar Primaria Familiar , HumanosRESUMEN
Systemic sclerosis (SSc) is a rare connective tissue disease characterized by chronic inflammation and fibrosis of the skin, vascular abnormalities and variable involvement of organs. TNF-α has a central role in initial host response to infections and in the pathogenesis of various systemic immune-mediated diseases. Serum levels of TNF-α are elevated in patients with SSc and favor the development of pulmonary fibrosis and pulmonary arterial hypertension. Inflammatory arthritis can occur in patients with SSc. Infliximab and etanercept may improve the inflammatory arthritis and disability in SSc. TNF-α inhibitors reduce the systemic inflammation, improve the endothelial function decreasing the risk of pulmonary arterial hypertension progression and of acute cardiovascular and/or cerebrovascular events. Physicians need to be aware of the potential risks of tuberculosis reactivation and opportunistic infections. Randomized controlled trials with TNF-α inhibitors in patients with SSc are needed to confirm the potential role of these agents in the treatment of SSc.
Asunto(s)
Antirreumáticos/uso terapéutico , Inmunosupresores/uso terapéutico , Esclerodermia Sistémica/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Neutralizantes/biosíntesis , Antirreumáticos/efectos adversos , Antirreumáticos/farmacología , Artritis/etiología , Artritis/prevención & control , Certolizumab Pegol , Evaluación de Medicamentos , Quimioterapia Combinada , Endotelio Vascular/fisiopatología , Etanercept , Predicción , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/prevención & control , Fragmentos Fab de Inmunoglobulinas/efectos adversos , Fragmentos Fab de Inmunoglobulinas/farmacología , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Inmunoglobulina G/efectos adversos , Inmunoglobulina G/farmacología , Inmunoglobulina G/uso terapéutico , Inmunosupresores/efectos adversos , Inmunosupresores/farmacología , Infliximab , Tuberculosis Latente/complicaciones , Tuberculosis Latente/fisiopatología , Infecciones Oportunistas/etiología , Infecciones Oportunistas/prevención & control , Polietilenglicoles/efectos adversos , Polietilenglicoles/farmacología , Polietilenglicoles/uso terapéutico , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/prevención & control , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/inmunología , Factor de Necrosis Tumoral alfa/fisiologíaRESUMEN
INTRODUCTION: During the last decade, many new biological immune modulators have entered the market as new therapeutic principles. Biologics, including TNF-α inhibitors, are the new frontier in the treatment of immune-mediated or inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, ankylosing spondylitis, systemic sclerosis, disseminated granuloma annulare, psoriasis and/or psoriatic arthritis. TNF-α inhibitors have demonstrated efficacy and are well tolerated in large, randomized, controlled clinical trials. However, a substantial proportion of patients do not respond to these agents and potential adverse drug reactions may be associated with its use. AREAS COVERED: Pharmacogenetics has the potential of increasing drug efficiency by identifying genetic factors responsible for lack of response or toxicities to TNF-α inhibitors. In this review, we analyze the influence of several polymorphisms upon the efficacy and safety of TNF-α inhibitors. EXPERT OPINION: Several polymorphisms have been proven to influence the response to etanercept. Among them, single nucleotide polymorphisms (SNPs) -308 G/G, -857 C/T, +489 GG and GA, HLA-DRB1-encoding SE (allele *0404 and allele *0101) favor the response to etanercept, whereas SNP -308 A/A and TNFR1A AA decrease the response. Large clinical studies are needed to confirm the relevance of these associations in order to tailor treatment and to decrease unnecessary toxicity.
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Antiinflamatorios/uso terapéutico , Inmunoglobulina G/uso terapéutico , Farmacogenética , Polimorfismo de Nucleótido Simple , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genética , Animales , Etanercept , Humanos , Selección de Paciente , Fenotipo , Medicina de PrecisiónRESUMEN
Systemic lupus erythematosus (SLE) is a chronic immune-mediated inflammatory multisystem disease. The onset of viral and bacterial infections may favor the exacerbation of the disease, amplify autoimmune processes and contribute to mortality and morbidity. The prevention of influenza and Streptococcus pneumoniae infections with vaccination should receive particular attention in SLE patients considering their elevated incidence, their high attack rate in epidemic periods, their potentially severe complications as well as the immunocompromised state of the host. The use of non-adjuvanted vaccine preparations should be preferred in order to avoid the onset of the "Autoimmune (auto-inflammatory) Syndrome Induced by Adjuvants" or "ASIA". In this review, we report that influenza and pneumococcal vaccinations in SLE patients are: 1) recommended to reduce the risk of development of these infections; 2) strongly suggested in elderly subjects and in those receiving high dose immunosuppressive treatments; 3) efficacious, even if specific immune responses may be lower than in the general population, as generally the humoral response fulfills the criteria for vaccine immunogenicity; and 4) safe in inactive disease although may favor a transient increase in autoantibody levels and rarely disease flares.
Asunto(s)
Vacunas contra la Influenza/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/inmunología , Vacunas Neumococicas/uso terapéutico , Humanos , Huésped Inmunocomprometido , Vacunas contra la Influenza/efectos adversos , Vacunas contra la Influenza/inmunología , Gripe Humana/epidemiología , Gripe Humana/inmunología , Gripe Humana/prevención & control , Lupus Eritematoso Sistémico/tratamiento farmacológico , Vacunas Neumococicas/efectos adversos , Vacunas Neumococicas/inmunología , Guías de Práctica Clínica como AsuntoRESUMEN
The tumor necrosis factor-α (TNF-α) gene has been proposed as a major candidate gene in psoriatic arthritis (PsA). TNF-α is a therapeutic target for patients responding poorly to conventional treatments. We investigated the role of single-nucleotide polymorphisms (SNPs) at positions -238, -308, and +489 of the TNF-α gene in the genetic susceptibility to PsA, in the severity of the disease, and, finally, in the response to TNF-α inhibitors (adalimumab, etanercept, or infliximab). Fifty-seven Caucasian PsA patients and 155 healthy matched controls were studied. The SNP +489 variant allele A was significantly associated with PsA susceptibility (P=0.0136) and severity of clinical (Psoriasis Area and Severity Index score, American College of Rheumatology criteria, Disease Activity Score 28, and Disability Index Health Assessment Questionnaire) and laboratory (C-reactive protein and erythrocyte sedimentation rate) parameters (P-values ranging from 0.016 to 2.908 × 10(-12)). The difference in severity was accounted for by the differences between the AA and GA genotypes with respect to the GG genotype. The SNP +489A allele shows a trend of association with the response to PsA treatment with etanercept. These findings suggest a role of the SNP +489A allele in the susceptibility and severity of PsA.
Asunto(s)
Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genética , Adalimumab , Adulto , Alelos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Estudios de Casos y Controles , Etanercept , Femenino , Genotipo , Humanos , Inmunoglobulina G/uso terapéutico , Infliximab , Masculino , Persona de Mediana Edad , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
INTRODUCTION: TNF-α inhibitors have demonstrated efficacy in large, randomized controlled clinical trials either as monotherapy or in combination with other anti-inflammatory or disease-modifying antirheumatic drugs in the treatment of chronic inflammatory immune-mediated diseases. Etanercept is a fusion protein that acts as a 'decoy receptor' for TNF-α. AREAS COVERED: This paper evaluates the efficacy and safety of etanercept in patients with chronic inflammatory immune-mediated diseases. EXPERT OPINION: Etanercept was first approved for the treatment of rheumatoid arthritis (RA) and subsequently of chronic plaque psoriasis, psoriatic arthritis, ankylosing spondylitis and juvenile RA. Etanercept as other TNF-α inhibitors, particularly infliximab, may be administered off-label to treat other chronic inflammatory immune-mediated diseases such as systemic sclerosis, Behcet disease, systemic lupus erythematosus, polymyositis, dermatomyositis and mixed connective tissue disease. Early etanercept treatment prevents joint damage and helps to avoid long-term disability in arthritis. Etanercept administered at a dose of 50 mg once weekly is effective in inducing an earlier remission of RA, and etanercept 50 mg twice weekly may favor a more rapid improvement of psoriasis and psoriatic arthritis. Etanercept and adalimumab may exert beneficial effects on lipid profile and improve endothelial dysfunction. Appropriate screening tests for latent tuberculosis, hepatitis B virus and hepatitis C virus should be performed before starting etanercept. TNF-α inhibitors including etanercept are contraindicated in patients with demyelinating diseases.