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2.
Clin Exp Rheumatol ; 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39051160

RESUMEN

OBJECTIVES: We aimed to evaluate ixekizumab (IXE) effectiveness, drug survival and clinical response predictors in moderate-severe psoriatic arthritis (PsA) patients in different clinical scenarios. METHODS: This was a multicentre real-life observational study based on Gruppo Italiano Studio Early Arthritis (GISEA) registry of IXE treatment in PsA patients (January 2019-June 2023). Data were collected at baseline and every six months. RESULTS: 223 PsA outpatients were included. Statistically significant improvement was observed after 6 (T6), 12 (T12) and 24 (T24) months of therapy for tender and swollen joint count (TJC and SJC), Visual Analogue Scale (VAS)-pain and Disease Activity in PSoriatic Arthritis (DAPSA) score. DAPSA remission was reached at T12 in 22% and at T24 in 18.5% of patients. At baseline, higher fibromyalgia and combination therapy with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in females with respect to males and higher Psoriasis Area Severity Index (PASI) in males than in females were observed. Therapeutic effectiveness showed in males higher DAPSA and VAS-pain reduction, higher percentage of males in DAPSA remission/low disease activity (LDA) at T6, and higher ∆PASI at T6 and T12 than in female patients. At multivariate analysis, male sex was predictive for treatment response at T6 [p=0.02, odds ratio (OR) 2.49 (95% confidence interval 1.11-5.54)], while it lost significance at T12. CONCLUSIONS: IXE effectiveness was highlighted after 6 months at both joint and skin levels and lasted up to 24 months in different clinical scenarios, making IXE effective in the complexity of managing PsA in a real-life setting.

3.
Echocardiography ; 41(6): e15853, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38853623

RESUMEN

BACKGROUND: Systemic Sclerosis (SSc), an intricate autoimmune disease causing tissue fibrosis, introduces cardiovascular complexities, notably pulmonary hypertension (PH), affecting both survival and quality of life. This study centers on evaluating echocardiographic parameters and endothelial function using flow-mediated dilatation (FMD) in SSc patients, aiming to differentiate those with and without pulmonary arterial hypertension (PAH). The emphasis lies in early detection, given the heightened vulnerability of the right ventricle (RV) in the presence of PH. METHODS: Fifty-nine SSc patients and 48 healthy subjects participated, undergoing clinical examinations, echocardiography, FMD assessments, blood analyses, and right heart catheterization (RHC) according to the ESC/ERS guidelines for diagnosis and treatment of PH. RESULTS: SSc-PAH patients displayed lower FMD, higher frequency of TAPSE < 18 mm, RA area > 18 cm2, act RVOT < 105 ms and TRV > 280 cm/s compared to those without PAH and healthy controls. Resting resistivity index (RI) was higher in SSc patients, with no significant difference between those with and without PAH. Lower FMD% serves as a predictive marker for adverse cardiovascular outcomes in both SSc and SSc-PAH patients. Stratification by TRV levels and PAH presence reveals notable FMD% variations, emphasizing its potential utility. CONCLUSIONS: Early identification of endothelial dysfunction and impaired RV echocardiographic parameters, such as TAPSE and TRV, could aid in predicting right ventricular dysfunction and PAH in SSc patients.


Asunto(s)
Ecocardiografía , Esclerodermia Sistémica , Humanos , Femenino , Masculino , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/fisiopatología , Persona de Mediana Edad , Ecocardiografía/métodos , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/diagnóstico por imagen , Adulto
4.
Diagnostics (Basel) ; 14(4)2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38396477

RESUMEN

BACKGROUND AND OBJECTIVES: oral alterations in Systemic Sclerosis (SSc) patients are widespread and include microstomia, periodontitis, telangiectasias, mandibular resorption, bone lesions, and xerostomia. This cross-sectional study aims to evaluate the differences between SSc patients (cases) and healthy subjects (controls) regarding oral manifestations, quality of life (QoL), and microcirculation alterations. METHODS: plaque index (PCR), periodontal index (PSR), DMFT, salivary flow rate, and buccal opening were measured by expert clinicians. S-HAQ test, the Self-Rating Anxiety State (SAS), the Self-Rating Depression Scale (SDS), and the WHOQOL-BREF test were administered to patients to evaluate their QoL. Microvascular alterations were assessed by oral videocapillaroscopy, performed on gingival and labial mucosa. A statistical analysis was conducted to find significant differences between healthy people and SSc patients. RESULTS: 59 patients were enrolled in this study. Standard salivary flow is significantly more frequent in controls, while xerostomia, reduced flow, microstomia, lip retraction, and periodontitis are significantly more frequent in the cases. Gingival capillaroscopy showed differences concerning loop visibility, thickening of the gum, tortuosity of gingival loops, and reduced gingival density. Labial capillaroscopy demonstrates that visibility of the labial loops, the labial ectasias, and the tortuosity of the loops are significantly associated with the presence of scleroderma. Hand and facial deformities, hypomobility of the tongue, cheeks, lips, microstomia, and xerostomia significantly compromised the quality of life of SSc patients, which was significantly worse among them. Moreover, oral videocapillaroscopy could be a proper diagnostic method to detect oral microcirculation alterations. SSc patients often present ectasias, rarefaction of the reticulum, microhemorrhages, and megacapillaries, which negatively impact their oral health. CONCLUSIONS: periodontitis, reduced salivary flow, and microstomia could be considered SSc oral manifestations. Joint deformities, facial appearance, and comorbidities significantly reduce the QoL of SSc patients compared to healthy subjects. Oral videocapillaroscopy could be an innovative and reliable technique to detect oral microcirculation anomalies.

5.
Vascul Pharmacol ; 154: 107252, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38061409

RESUMEN

AIM: Endothelial dysfunction represents a key feature of the pathological process underlying micro and macro-vascular damage in Systemic Sclerosis (SSc). This study aims to improve knowledge of the physiopathology of vascular damage in SSc through the assessment of the endothelial dysfunction by Flow Mediated Dilation (FMD) and serum levels of circulating endothelial dysfunction markers and the correlation of macrovascular damage with clinical findings and microvascular capillaroscopic patterns. METHODS: 57 SSc patients and 37 healthy subjects were recruited. All included subjects underwent radial artery FMD test and Nailfold Video-Capillaroscopy; serum levels of Vascular Endothelial Growth Factor (VEGF), Vascular Cell Adhesion Molecule-1 (VCAM-1) and angiopoietin-2 were evaluated. RESULTS: Compared to healthy subjects, in SSc patients lower FMD and higher time needed to obtain the maximal FMD responsewere observed, whereas serum levels of VEGF, VCAM-1, and angiopoietin-2 were significantly higher. The impairment of FMD values was associated with disease duration, pulmonary arterial hypertension, and digital ulcers and correlates with greater microvascular damage evaluated by Nailfold Video-Capillaroscopy… An inverse relationship between VEGF, angiopoietin-2, VCAM-1 levels and FMD was observed, but only VEGF and angiopoietin-2 were significantly higher in patients with digital ulcers and pulmonary arterial hypertension. CONCLUSIONS: FMD ultrasound test and circulating levels of endothelial dysfuncion markers could be useful as biomarkers of vasculopathy and could be a helpful tool in the overall assessment of vascular injury in Systemic Sclerosis patients.


Asunto(s)
Hipertensión Arterial Pulmonar , Esclerodermia Sistémica , Úlcera Cutánea , Humanos , Angioscopía Microscópica , Factor A de Crecimiento Endotelial Vascular , Angiopoyetina 2 , Dilatación , Molécula 1 de Adhesión Celular Vascular , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/patología
6.
Int J Mol Sci ; 24(6)2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36982443

RESUMEN

A growing body of evidence on the importance of vitamin D in immune modulation has increased the interest in its possible impact on the course of rheumatological diseases. The scope of our study is to assess if the presence of different statuses of vitamin D could interfere in the clinical subsets, in methotrexate monotherapy discontinuation, and biological drug (b-DMARDs) survival in psoriatic arthritis patients (PsA). We conducted a retrospective study on PsA patients and split them into three groups based on their vitamin D status: the group with 25(OH)D ≤ 20 ng/mL, the group with levels of 25(OH)D between 20 and 30 ng/mL, and the group with serum levels of 25(OH)D ≥ 30 ng/mL. All patients were required to fulfill the CASPAR criteria for psoriatic arthritis and to have the evaluation of vitamin D serum levels at baseline visit and at clinical follow-up visits. The exclusion criteria were ages less than 18 years old, the presence of HLA B27, and satisfaction of rheumatoid arthritis classification criteria (during the study time). Statistical significance was set at p ≤ 0.05. Furthermore, 570 patients with PsA were screened and 233 were recruited. A level of 25(OH)D ≤ 20 ng/mL was present in 39% of patients; levels of 25(OH)D between 20 and 30 ng/mL presented in 25% of patients; 65% of patients with sacroiliitis presented 25 (OH)D ≤ 20 ng/mL. Methotrexate monotherapy discontinuation for failure was higher in the group with 25 (OH)D ≤ 20 ng/mL (survival time: 92 ± 10.3 weeks vs. 141.9 ± 24.1 weeks vs. 160.1 ± 23.6 weeks; p = 0.02) with higher discontinuation risk (HR = 2.168, 95% CI 1.334, 3.522; p = 0.002) than those with 25(OH)D between 20 and 30 ng/mL and those with 25(OH)D ≥ 30 ng/mL. Significantly shorter survival of first b-DMARDs was assessed in the group with 25 (OH)D ≤ 20 ng/mL versus the other groups (133.6 ± 11 weeks vs. 204.8 ± 35.8 weeks vs. 298.9 ± 35.4; p = 0.028) (discontinuation risk 2.129, 95% CI 1.186, 3.821; p = 0.011). This study highlights significant differences in clinical presentation, in particular sacroiliac involvement and on drug survival (methotrexate and b-DMARDs) in PsA patients with vitamin D deficiency. Further prospective studies, including a larger sample of patients, are needed to validate these data and to assess if the supplementation of vitamin D could improve the b-DMARDs response in PsA patients.


Asunto(s)
Antirreumáticos , Artritis Psoriásica , Sacroileítis , Deficiencia de Vitamina D , Humanos , Adolescente , Vitamina D/uso terapéutico , Estudios Retrospectivos , Sacroileítis/tratamiento farmacológico , Sacroileítis/complicaciones , Metotrexato/uso terapéutico , Estudios Prospectivos , Deficiencia de Vitamina D/complicaciones , Vitaminas/uso terapéutico , Antirreumáticos/uso terapéutico
7.
Postgrad Med J ; 99(1175): 976-984, 2023 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-36841226

RESUMEN

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation and synovitis which evolve into joint destruction and deformity. Bone abnormalities are represented by marginal bone erosions and iuxta-articular and generalized osteoporosis. Overactivation of osteoclasts along with dysregulation of osteoblasts are the key events. Bone resorption is mediated by the receptor activator of nuclear factor (NF)-κB (RANK) ligand (RANK-L), responsible for the differentiation, proliferation, and activation of osteoclasts. RANK-L binds its receptor RANK, localized on the surface of preosteoclasts and mature osteoclasts promoting osteoclastogenesis. High levels of RANK-L were demonstrated in active RA patients. Denosumab, a fully human monoclonal antibody, binds RANK-L and suppresses the RANK-RANK-L signaling pathway leading to the inhibition of osteoclastogenesis. A retrospective analysis of published studies such as clinical trials evidenced the efficacy of denosumab in preventing bone erosion progression in RA patients. Key messages Key questions to answer in future include the following: Could denosumab be associated with other biologic therapies in RA patients? Could denosumab block the progression of bone damage in RA? Could denosumab be used for the prevention of bone erosion in RA?


Asunto(s)
Artritis Reumatoide , Conservadores de la Densidad Ósea , Humanos , Denosumab/uso terapéutico , Estudios Retrospectivos , Conservadores de la Densidad Ósea/uso terapéutico , Ligando RANK/metabolismo , Ligando RANK/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico
8.
Int J Rheum Dis ; 26(8): 1590-1593, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36814395

RESUMEN

Ozone therapy is a minimally invasive technique now widely used for the treatment of pain due to herniated discs. In literature there are conflicting results concerning its real effectiveness and few data about its possible complications. In this case report we present a case of spondylodiscitis, septic arthritis and gluteal abscess following the execution of 4 sessions of ozone therapy. Given the impossibility of isolating the etiological agent, an empirical antibiotic therapy with an overall duration of 6 weeks was set up, initially with daptomycin and ceftriazone, to which was added after 2 days metronidazole, administered intravenously; after 20 days the cephalosporin was replaced with oral amoxicillin/clavulanate. Neridronate was added to treat bone edema and to avoid bone erosion. The patient showed improvement of both clinical conditions and inflammation indexes, and was discharged after 4 weeks without further complications at follow-up. Few cases are reported in the literature about spondylodiscitis secondary to ozone treatment, and just 1 case is described about the use of neridronate as additive drug to antibiotic treatment in spondylodiscitis to avoid bone disruption and surgery complications.


Asunto(s)
Discitis , Dolor de la Región Lumbar , Ozono , Sacroileítis , Humanos , Discitis/diagnóstico , Discitis/tratamiento farmacológico , Discitis/etiología , Absceso/diagnóstico , Absceso/tratamiento farmacológico , Absceso/etiología , Antibacterianos/uso terapéutico , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/tratamiento farmacológico , Dolor de la Región Lumbar/etiología , Ozono/efectos adversos , Vértebras Lumbares/diagnóstico por imagen
9.
Rev. colomb. reumatol ; 29(4)oct.-dic. 2022.
Artículo en Inglés | LILACS | ID: biblio-1536201

RESUMEN

Turner's syndrome (TS) is one of the most common sex chromosome disorders caused by numeric or structural abnormalities of the X chromosome. A case of TS and Systemic Sclerosis (SSc) is reported, along with a summary of all associated TS/autoimmune diseases described in English literature from 1948 to 2020, using a search in MEDLINE (Pubmed). A 32-year-old woman affected by TS was seen due to inflammatory arthralgia in small joints and dysphagia, as well as a two-year history of Raynaud's phenomenon and puffy hands. Biohumoural laboratory tests and severity scales revealed changes that allowed us to diagnose SSc. This case report emphasises the role played by sex hormones and chromosomal abnormalities in the pathogenesis of autoimmune disorders, and to our knowledge, this is the only case described in literature of a TS patient who developed SSc.


El síndrome de Turner (TS) es uno de los trastornos cromosómicos sexuales más comunes causados por anomalías numéricas o estructurales del cromosoma X. En este documento informamos de un caso de TS y esclerosis sistémica (SSc) y resumimos toda la asociación de TS/enfermedades autoinmunes descrita en la literatura inglesa de 1948 a 2020, encontrada buscando en MEDLINE (PubMed). Una mujer de 32 arios afectada por TS acudió a nuestra observación debido a la artralgia inflamatoria en pequenas articulaciones y disfagia y 2 anos de historia del fenómeno de Raynaud y las manos hinchadas. El laboratorio biohumoral y las pruebas instrumentales revelaron alteraciones que nos permitieron diagnosticar SSc. Nuestro informe de caso hace hincapié en el papel desempefíado por las hormonas sexuales y las anomalías cromosómicas en la patogénesis del trastorno autoinmune; y hasta nuestro conocimiento, este es el único caso descrito en la literatura de un paciente TS que desarrolló SSc.


Asunto(s)
Humanos , Femenino , Adulto , Síndrome de Turner , Enfermedades Reumáticas , Enfermedades Musculoesqueléticas , Enfermedades Urogenitales Femeninas , Enfermedades Urogenitales Femeninas y Complicaciones del Embarazo , Varicocele
10.
Int J Med Sci ; 19(5): 867-877, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35693738

RESUMEN

Objectives: IL-17 modulates the synthesis of several molecules involved in the pathogenesis of Systemic Sclerosis (SSc). Vitamin D (1,25(OH)2D3) shows anti-fibrotic properties and it is able to affect the IL-17 production in several experimental conditions. The aim of this study is to assess the production of IL-17A and pro-fibrotic cytokines in peripheral blood mononuclear cells (PBMCs) from subjects with SSc in basal conditions and after treatment with 1,25(OH)2D3 and IL-17A neutralizing antibodies. Methods: The production of IL-17A and pro-fibrotic cytokines (TGFß, CTGF and FGF2) in PBMCs obtained from 51 SSc patients and 31 healthy subjects was assessed both in basal conditions and in presence of anti-IL17A antibodies and several concentrations of 1,25(OH)2D3. The association of cytokines production with clinical disease characteristics and the in vitro effect of 1,25(OH)2D3 and IL-17A inhibition were assessed. Results: PBMCs from SSc subjects produced higher amount IL-17A, TGFß, CTGF and FGF2 compared to healthy controls. IL17, TGFß, CTGF and FGF2 levels were higher in SSc patients with interstitial lung disease and digital ulcers, whereas IL-17A production was lower in patients with PAH. IL- 17A inhibition reduced the production of FGF2, whereas enhanced the synthesis of TGFß and CTGF. 1,25(OH)2D3 decreased the production of IL17A and pro-fibrotic cytokines in a dose- dependent manner. Conclusions: IL-17A is involved in the regulation of fibrogenesis in SSc, and could represent an intriguing potential therapeutic target, even if its role remains controversial. 1,25(OH)2D3 inhibits both IL-17A and pro-fibrotic cytokines, confirming its potential anti-fibrotic effect.


Asunto(s)
Interleucina-17 , Esclerodermia Sistémica , Colecalciferol , Citocinas/farmacología , Factor 2 de Crecimiento de Fibroblastos , Fibrosis , Humanos , Leucocitos Mononucleares , Esclerodermia Sistémica/tratamiento farmacológico , Esclerodermia Sistémica/patología , Factor de Crecimiento Transformador beta
11.
Int J Mol Sci ; 23(10)2022 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-35628614

RESUMEN

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a wide variability of clinical manifestations due to the potential involvement of several tissues and internal organs, with a relapsing and remitting course. Dysregulation of innate and adaptive immune systems, due to genetic, hormonal and environmental factors, may be responsible for a broad spectrum of clinical manifestations, affecting quality of life, morbidity and mortality. Bone involvement represents one of the most common cause of morbidity and disability in SLE. Particularly, an increased incidence of osteoporosis, avascular necrosis of bone and osteomyelitis has been observed in SLE patients compared to the general population. Moreover, due to the improvement in diagnosis and therapy, the survival of SLE patient has improved, increasing long-term morbidities, including osteoporosis and related fractures. This review aims to highlight bone manifestations in SLE patients, deepening underlying etiopathogenetic mechanisms, diagnostic tools and available treatment.


Asunto(s)
Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Osteoporosis , Enfermedades Autoinmunes/diagnóstico , Humanos , Lupus Eritematoso Sistémico/genética , Osteoporosis/etiología , Calidad de Vida
12.
Curr Rheumatol Rev ; 18(4): 286-297, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35184707

RESUMEN

Previous research has shown conflicting reports about the effect of systemic sclerosis (SSc) on bone metabolism, especially considering bone mineral density (BMD), bone microarchitecture, and risk of fracture. The objective of this review is to analyze data from previous articles to investigate the differences in BMD and fracture risk between SSc and non-SSc populations and to discuss potential underlying mechanisms. The main factors investigated have been BMD (mean and standard deviation), t-scores and z-scores at the lumbar spine, femoral neck, and total hip measured by dual-energy X-ray absorptiometry (DEXA), bone remodeling markers, fracture prevalence, and incidence, trabecular bone score (TBS), musculoskeletal involvement with particular correlation to SSc skin subtype and extent, disease duration, serological pattern, and vitamin D levels. Since microvascular alterations evaluated through nailfold videocapillaroscopy (NVC) of SSc patients have recently been correlated with decreased BMD and bone microarchitecture, the vascular impairment in SSc has been proposed as a remarkable contributing element in bone remodeling, and the role of hypoxia has been investigated.


Asunto(s)
Enfermedades Óseas , Esclerodermia Sistémica , Humanos , Densidad Ósea , Absorciometría de Fotón , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico por imagen , Esclerodermia Sistémica/metabolismo , Vitamina D , Vértebras Lumbares/metabolismo , Vértebras Lumbares/patología
14.
Vaccines (Basel) ; 9(7)2021 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-34358147

RESUMEN

An increased risk of developing severe infections has been evidenced in rheumatic disease (RD) patients, and anti-COVID-19 vaccination is strictly recommended for RD patients. However, up to now, no data are available on safety, immunogenicity and efficacy of COVID-19 vaccinations in RD patients. The possible development of adverse events (AEs), including the flare-up of underlying RD, represents a matter of growing importance. The aim of our study is to assess, in RD patients, the safety profile of different types of approved vaccines and the possible influence of immunosuppressive therapies and clinical or demographic characteristics of RD patients on development of AEs. Participants (n = 185; 30.7%) received anti-COVID-19 vaccinations, 137 with autoimmune/chronic inflammatory RD (Au/cIn-RD) and 48 with nonautoimmune/chronic inflammatory RD (no-Au/cIn-RD). AEs were recorded in 42% of patients after the first dose of vaccine, and in 26% of patients after the second dose. The most common reported AEs after anti-COVID 19 vaccines were site injection pain (17%), headache (12%), fever (12%), myalgia (10%) and fatigue (10%). Relapses of the underlying Au/c-In-RD were recorded in 2.2% of patients after the first dose of vaccine. In Au/c-In-RD the risk of developing AEs after the first dose of vaccine was lower in older patients (OR = 0.95; p = 0.001), and in the group of patients with complete control of RD (OR: 0.2; p = 0.010). A lower percentage of AEs was observed in patients with complete control of their Au/cIn-RD (29%) compared to those with low (57%) or moderate-high disease activity (63%) (p = 0.002 and p = 0.006 respectively). In this study all types of COVID-19 vaccines in use in Italy seemed safe in RD patients. The results of this study might provide reassuring information for Au/cIn RD patients and clinicians and could strengthen the data on vaccine safety to guide the use of COVID-19 vaccines in Au/cIn-RD on immunosuppressive agents.

15.
Clin Exp Immunol ; 206(2): 153-160, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34358345

RESUMEN

Body fat has regulatory functions through producing cytokines and adipokines whose role in the pathogenesis of systemic sclerosis (SSc) is currently emerging. Changes in body mass, either over- or underweight, entail a dysregulation of the cytokine/adipokine network that may impact upon SSc disease activity. We evaluated serum levels of adipokines and cytokines in SSc patients and correlated them to clinical features and body mass index (BMI) categories. The study included 89 SSc patients and 26 healthy donors (HD). Serum levels of adiponectin, leptin, resistin, visfatin, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-10 and IL-17A were measured by multiplex immunoassay and correlated to BMI and disease-specific features. Student's t-test or analysis of variance (ANOVA) were used for comparisons between groups. Spearman's or Pearson's tests were used for correlation analysis. Serum levels of TNF-α, IL-2, leptin and resistin were significantly higher in SSc than in HD. Leptin levels were significantly higher in interstitial lung disease (ILD)- and pulmonary arterial hypertension (PAH)-SSc subgroups. The highest levels of IL-17A, IL-2, IL-10, leptin and visfatin were detected in SSc patients with obesity (p < 0.01). Conversely, underweight SSc patients showed the highest TNF-α levels (p < 0.05). Adipokines, IL-2, IL-10 and IL-17A were found to be increased in SSc patients with obesity, but whether or not they play a role in the pathogenesis of the disease remains to be investigated. Intriguingly, underweight patients had the highest TNF-α levels, suggesting a potential role of TNF-α in inducing the cachexia observed in long-lasting disease.


Asunto(s)
Adipoquinas/inmunología , Índice de Masa Corporal , Citocinas/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Esclerodermia Sistémica/inmunología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
16.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-34360745

RESUMEN

A review of the available literature was performed in order to summarize the existing evidence between osteoblast dysfunction and clinical features in non-hereditary sclerosing bone diseases. It has been known that proliferation and migration of osteoblasts are concerted by soluble factors such as fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF), bone morphogenetic protein (BMP) but also by signal transduction cascades such as Wnt signaling pathway. Protein kinases play also a leading role in triggering the activation of osteoblasts in this group of diseases. Post-zygotic changes in mitogen-activated protein kinase (MAPK) have been shown to be associated with sporadic cases of Melorheostosis. Serum levels of FGF and PDGF have been shown to be increased in myelofibrosis, although studies focusing on Sphingosine-1-phosphate receptor was shown to be strongly expressed in Paget disease of the bone, which may partially explain the osteoblastic hyperactivity during this condition. Pathophysiological mechanisms of osteoblasts in osteoblastic metastases have been studied much more thoroughly than in rare sclerosing syndromes: striking cellular mechanisms such as osteomimicry or complex intercellular signaling alterations have been described. Further research is needed to describe pathological mechanisms by which rare sclerosing non hereditary diseases lead to osteoblast dysfunction.


Asunto(s)
Sistema de Señalización de MAP Quinasas , Melorreostosis/metabolismo , Osteoblastos/metabolismo , Animales , Proteínas Morfogenéticas Óseas/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Humanos , Melorreostosis/patología , Osteoblastos/patología , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo
17.
Arthritis Res Ther ; 23(1): 180, 2021 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-34229744

RESUMEN

BACKGROUND: Glucocorticoids (GC) modulate several regulators involved in the pathogenesis of bone changes in rheumatoid arthritis (RA). Trabecular bone score (TBS) allows the indirect assessment of bone quality. The aim of this study was to investigate the effects of GC on TBS and serum levels of bone turnover regulators in patients with recent-onset RA. MATERIALS AND METHODS: Forty-seven subjects with recent-onset RA (< 6 months) were classified in two groups, low (lGC) and high (hGC) glucocorticoids, according to glucocorticoid dose regimens. Bone mineral density (BMD), TBS, and circulating Dickkopf-1 (Dkk1), sclerostin, osteoprotegerin (OPG), and RANK-L were evaluated at baseline and 6 and 12 months. RESULTS: BMD significantly declined after 12 months with no significant difference between the lGC and hGC group, whereas TBS decreased in the hGC group only. Circulating OPG decreased during the follow-up period, the reduction being significantly greater in hGC group; conversely, sclerostin and RANK-L serum increased, in a significantly greater extent in the hGC group. TBS inversely correlated with sclerostin, RANK-L, and Dkk1 circulating levels whereas directly correlated with OPG circulating levels. GC cumulative dose showed an inverse relationship with BMD in both the hGC and lGC groups; TBS values showed an inverse relationship with GC cumulative dose in the hGC group only. GC cumulative dose was associated to higher sclerostin and lower OPG serum levels. TBS did not correlate with disease activity whereas BMD was inversely related to disease activity. CONCLUSIONS: In early RA, GC exposure contributes to the reduction of BMD and affects bone quality depending on dose regimens. TBS could be a useful tool to evaluate the negative effect of GC on bone microarchitecture. TRIAL REGISTRATION: This study was ancillary to a parallel-group observational prospective study which was approved by the medical local ethics committee (protocol number DDG 334/19-06-2019).


Asunto(s)
Artritis Reumatoide , Fracturas Osteoporóticas , Absorciometría de Fotón , Artritis Reumatoide/tratamiento farmacológico , Densidad Ósea , Remodelación Ósea , Hueso Esponjoso , Glucocorticoides/uso terapéutico , Humanos , Vértebras Lumbares , Estudios Prospectivos
19.
Postgrad Med ; 133(6): 688-693, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34176427

RESUMEN

BACKGROUND: Limited data on myoglobin and infectious diseases are available. In this study, we evaluate the potential role of myoglobin in predicting poor outcome in patients with Sars-Cov2 pneumonia. METHODS: One hundred and twenty-one Sars-Cov 2 patients with an average age of 69.9 ± 13.2 years, and symptoms duration of 8.8 ± 7.9 days were enrolled in the study. At the admission, the serum levels of myoglobin, erythrocyte sedimentation rate, C reactive protein (CRP), procalcitonin, ferritin, creatine phosphokinase, creatinine, fibrinogen, d-dimers, lactic dehydrogenase, troponin (Tn-I), creatine kinase myocardial band (CK-MB), complement fractions C3 and C4, immunoglobulins, interleukin 6 were evaluated. We also assessed the patients' complete clinical history and performed a thorough physical examination including age, disease history, and medications. RESULTS: Twenty-four (20%) patients died, and 18 (15%) patients required intensive care. The mean time between symptoms onset and death was 12.4 days ± 9.1. Univariate analysis of the patients' data highlighted some independent risk factors for mortality in COVID-19, including higher neutrophils rate (HR: 1.171), lower lymphocyte rate (HR: 0.798), high CK-MB serum levels (HR: 1.6), high Tn-I serum levels (HR: 1.03), high myoglobin serum levels (HR: 1.014), Alzheimer (HR 5.8), and higher CRP values (HR: 1.011). Cox regression analysis model revealed that higher serum values of myoglobin (HR 1.003; 95%CI: 1.001-1.006; p = 0.01), and CRP (HR 1.012; 95% CI: 1.001-1.023; p = 0.035) could be predictors of mortality in COVID-19 patients. The value of the myoglobin level for predicting 28 days-mortality using ROC curve was 121.8 ng/dL. Lower survival rate was observed in patients with serum levels of myoglobin>121.8 ng/dL (84% vs 20% respectively, p = 0.0001). CONCLUSION: Our results suggest that higher serum levels of myoglobin could be a considerable and effective predictor of poor outcomes in COVID-19 patients; a careful follow-up in these patients is strongly suggested. The possibility of enhancing these findings in other cohorts of COVID-19 patients could validate the clinical value of myoglobin as a biomarker for worse prognosis in COVID-19.


Asunto(s)
COVID-19 , Cuidados Críticos , Mioglobina/sangre , Medición de Riesgo/métodos , Anciano , Biomarcadores/sangre , COVID-19/sangre , COVID-19/mortalidad , COVID-19/fisiopatología , COVID-19/terapia , Comorbilidad , Cuidados Críticos/métodos , Cuidados Críticos/estadística & datos numéricos , Femenino , Mortalidad Hospitalaria , Humanos , Italia/epidemiología , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2/aislamiento & purificación
20.
J Med Invest ; 68(1.2): 6-14, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33994482

RESUMEN

Nailfold video-capillaroscopy (NVC) is a useful diagnostic tool, used to early detect abnormalities in micro-circulation, providing a qualitative description of microvascular anomalies in Raynaud's phenomenon. NVC role in the diagnosis of Systemic Sclerosis is well known. In other rheumatic conditions such as connective tissue diseases, vasculitis, and arthritis, the NVC anomalies are often included in a scleroderma like pattern. The use of NVC in non-rheumatic diseases (NRD), with remarkable microvascular damage, as diabetes, is not standardized yet, although several research studies are carrying on. The aim of this article is to provide a resume of published results in order to lay the groundwork for the employment of NVC both in the diagnosis and follow up of microvascular complication in NRD. Furthermore, we mention NVC findings in pathologies without well recognize microvascular damages in their pathogenesis : micro-vessels abnormalities may suggest a different point of view. J. Med. Invest. 68 : 6-14, February, 2021.


Asunto(s)
Enfermedad de Raynaud , Enfermedades Reumáticas , Esclerodermia Sistémica , Humanos , Angioscopía Microscópica , Uñas/diagnóstico por imagen , Enfermedad de Raynaud/diagnóstico , Enfermedades Reumáticas/diagnóstico , Esclerodermia Sistémica/diagnóstico
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