Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 37
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
4.
Front Immunol ; 10: 376, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30891041

RESUMO

Background: Is it well-known that one of the major drawbacks of Lupus Anticoagulant (LA) test is their sensitivity to anticoagulant therapy, due to the coagulation based principle. In this study we aimed to assess the reproducibility of LA testing and to evaluate the performance of solid assay phosphatidylserine/prothrombin (aPS/PT) antibodies. Methods: We included 60 patients that fulfilled the following inclusion criteria: (I) diagnosis of thrombotic antiphospholipid syndrome (APS); (II) patients with thrombosis and (a) inconstant previous LA positivity and/or (b) positivity for antiphospholipid antibodies (aPL) at low-medium titers [defined as levels of anti-ß2Glycoprotein-I or anticardiolipin (IgG/IgM) 10-30 GPL/MPL] with no previous evidence of LA positivity. aPL testing was performed blindly in 4 centers undertaking periodic external quality assessment. Results: The 60 patients enrolled were distributed as follows: 43 (71.7%) with thrombotic APS, 7 (11.7%) with thrombosis and inconstant LA positivity and 10 (16.7%) with low-medium aPL titers. Categorical agreement for LA among the centers ranged from 0.41 to 0.60 (Cohen's kappa coefficient; moderate agreement). The correlation determined at the 4 sites for aPS/PT was strong, both quantitatively (Spearman rho 0.84) and when dichotomized (Cohen's kappa coefficients = 0.81 to 1.0). Discordant (as defined by lack of agreement in ≥3 laboratories) or inconclusive LA results were observed in 27/60 (45%) cases; when limiting the analysis to those receiving vitamin K antagonist (VKA), the level of discordant LA results was as high as 75%(15/20). Conversely, aPS/PT testing showed an overall agreement of 83% (up to 90% in patients receiving VKA), providing an overall increase in test reproducibility of +28% when compared to LA, becoming even more evident (+65%) when analyzing patients on VKA. In patients treated with VKA, we observed a good correlation for aPS/PT IgG testing (Cohen's kappa coefficients = 0.81-1; Spearman rho 0.86). Conclusion: Despite the progress in the standardization of aPL testing, we observed up to 45% of overall discrepant results for LA, even higher in patients on VKA. The introduction of aPS/PT testing might represent a further diagnostic tool, especially when LA testing is not available or the results are uncertain.

6.
Autoimmun Rev ; 17(11): 1138-1149, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30217550

RESUMO

Rheumatoid Arthritis (RA) is a complex systemic autoimmune disease in which various cell types are involved. Among them, neutrophils have been recognized as important players in the onset and the progression of RA. The pathogenic role of neutrophils in RA lies in the alteration of several processes, including increased cell survival and migratory capacity, abnormal inflammatory activity, elevated oxidative stress and an exacerbated release of neutrophil extracellular traps. Through these mechanisms, neutrophils can activate other immune cells, thus perpetuating inflammation and leading to the destruction of the cartilage and bone of the affected joint. Given the considerable contribution of neutrophils to the pathophysiology of RA, several studies have attempted to clarify the effects of various therapeutic agents on this subtype of leukocyte. To date, recent studies have envisaged the role of new molecules on the pathogenic profile of neutrophils in RA, which could represent novel targets in future therapies. In this review, we aim to review the pathogenic role of neutrophils in RA, the effect of conventional treatments and biologic therapies, and the new, potential targets of neutrophil-derived molecules for the treatment of RA.


Assuntos
Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Inflamação/imunologia , Inflamação/patologia , Neutrófilos/imunologia , Animais , Humanos
7.
Oncotarget ; 9(48): 28799-28804, 2018 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-29989000

RESUMO

Minimal change disease (MCD) accounts for 15% of adult nephrotic syndrome (NS) cases. Adult-MCD patients may have more severe clinical features than pediatric patients. In children, Rituximab (RTX) has been used since 2006 to treat frequently relapsing NS. In adults, data about the efficacy of RTX for MCD are limited. We report our experience on the use of RTX in adult biopsy-proven MCD. Our series includes 6 adult patients (2 males and 4 females), age 45-73 years, treated with RTX (4 weekly doses of 375 mg/m2). Proteinuria decreased from 11,2 (23-4.8) g/24 hours to 0.6 (0-2) g/24 hours after 6 months, and to 0.4 (0-1, 4) g/24 h in the 4 pts with the longer follow-up. Creatinine decreased from 1.95 (0.5-5) mg/dl to 0.88 (0.6-1.3) mg/l. Five patients achieved a complete renal remission, while in 1 pt proteinuria decreased by 75%. RTX successfully depleted CD19 lymphocytes in 100% of pts for at least 6 months. No clinically relevant adverse events have been observed. This case series shows a remarkable efficacy of RTX in treatment of MCD. RTX can be an attractive alternative both in recurrent forms and in induction-therapy of MCD. RTX may be preferentially used in patients at a high risk of development of the adverse effects of corticosteroids and should be considered as an alternative option in patients with recurrent NS. Additional data are needed to inform clinical practice on how best to use RTX in this patient population, so that definitive randomized trials can be planned.

8.
PLoS One ; 13(5): e0197436, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29763469

RESUMO

Bloodstream infection (BSI) and associated sepsis represent a major source of mortality in industrialized countries. Prompt treatment with targeted antibiotics affects both the financial impact and the clinical outcome of BSI: every hour gained in initiating the correct antimicrobial therapy significantly increases the probability of patient survival. However, the current standard-of-care, which depends on blood culture-based diagnosis, are often unable to provide such a fast response. Fast and sensitive molecular techniques for the detection of sepsis-related pathogens from primary blood samples are strongly needed. The aim of this study was to assess the usefulness of the IRIDICA BAC BSI Assay, a PCR/ESI-MS-based technology for the early diagnosis of bloodstream infections from primary blood samples in critical patients. This evaluation has been performed by comparison with the traditional culture-based methods. The study was performed on a total of 300 prospective whole blood specimens obtained from patients suspected of sepsis, admitted to enrolling ER units from The Greater Romagna Area. The overall concordance between the two techniques was of 86%, with a calculated sensitivity of 76% and an assay specificity of 90%. The clinical significance of discrepant results was evaluated reviewing the patients' clinical records and the results of additional relevant microbiological tests. The data here obtained support the ability of the IRIDICA BAC BSI Assay to identify a broad range of bacteria directly from primary whole blood samples, within eight hours. This might allow a timely administration of a suitable treatment.


Assuntos
Reação em Cadeia da Polimerase/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Bacteriemia/sangue , Bacteriemia/diagnóstico , Estado Terminal , Feminino , Humanos , Masculino , Estudos Prospectivos , Sepse/sangue , Sepse/diagnóstico
9.
Adv Exp Med Biol ; 1031: 497-509, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29214588

RESUMO

The immune system is delegated to defend the body from attacks from outside or inside. Many diseases can affect immune system reducing its ability to defend self or inducing an abnormal response against external or internal antigens. Rare diseases affecting immune system present some issue in common with other rare diseases and some peculiarities due to the huge variability in the disease's expression. However, a correct estimation of the epidemiology of rare disorders is necessary for evaluating the prognosis and the responses to new therapies, for planning proper public health services, and finally to establish fair and sustainable prices for innovative medicines. Due to the enormous number of different rare immunological diseases, in this chapter we are going to analyse some of them that can be considered paradigmatic of the various expressions of disease.


Assuntos
Doenças do Sistema Imunitário/imunologia , Sistema Imunitário/imunologia , Doenças Raras/imunologia , Humanos , Sistema Imunitário/fisiopatologia , Doenças do Sistema Imunitário/diagnóstico , Doenças do Sistema Imunitário/epidemiologia , Doenças do Sistema Imunitário/terapia , Prognóstico , Doenças Raras/diagnóstico , Doenças Raras/epidemiologia , Doenças Raras/terapia , Fatores de Risco
10.
Oncotarget ; 8(32): 52072-52077, 2017 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-28881714

RESUMO

BACKGROUND: ANCA associated vasculitides (AAV) often present with a chronic relapsing course. Relapse leads to increased immunosuppressive exposure and consequent toxicity. While two randomized controlled trials have shown rituximab (RTX) to be the most effective induction treatment in patients with relapsing disease, the optimal treatment duration and RTX dose remain debated. Whether to administer a maintenance dose to every patient, at a fixed time interval or on the basis of B cell count and ANCA titre or only when disease manifestations do occur is still debated as well. METHODS: 11 patients (5 with granulomatosis with polyangiitis, 4 with microscopic polyangiitis-MPA-, and 2 with eosinophilic granulomatosis with polyangiitis -EGPA-) intolerant or refractory to conventional therapies including cyclophosphamide were enrolled. All patients received the so called "improved 4+2" RTX scheme as a rescue therapy. Following RTX administration, immunosuppressive drugs were rapidly tapered and no immunosuppressive maintenance therapy had been given. RESULTS: After a mean follow-up of 85 months since the "4+2" RTX protocol: four out of 11 patients (37%, 1 EGPA and 3 MPA, all MPO-positive) remained in remission after one cycle of "4+2" RTX infusion protocol with no relapse for a median 66 months [60-108]). Seven relapsing patients were re-treated once with RTX (again as monotherapy with the same protocol) after a median of 54 months (24-96). Following re-treatment, they again showed complete remission over a median of 32 months (12-96) of observation. CONCLUSION: In one of the longest-term observation (85 months) studies, sustained clinical remission without immunosuppressive maintenance therapy (and a negligible dose of prednisone since the 5thmonth) was obtained by the "4 + 2" RTX infusion protocol in patients with ANCA-associated vasculitis intolerant or refractory to conventional therapy.

11.
Am J Nephrol ; 46(2): 108-113, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28700988

RESUMO

BACKGROUND: A beneficial effect of rituximab (RTX) on focal segmental glomerulosclerosis (FSGS) in pediatric patients or in transplant recipients has been reported in isolated cases. However, the use of RTX in adult patients with idiopathic FSGS needs further investigation. METHODS: Eight patients who had biopsy-proven FSGS (63.9 ± 14.0, range 40-81 years, 4 women, 4 men) with major risk factors precluding corticosteroids or conventional immunosuppression were treated with a high dose of RTX (8 weekly doses of 375 mg/m2) and prospectively followed up for at least 2 years (29.1 ± 8.8 months, range 24-42 months). RESULTS: RTX failed to improve proteinuria in 7 out of 8 patients, who had persistent nephrotic proteinuria. In one case, a rapidly deteriorating renal function was also observed. Only one patient showed an improvement in renal function and a remarkable reduction in proteinuria. There were no differences in clinical or laboratory characteristics or in the CD20 B lymphocyte count after RTX between the responder and the 7 nonresponder patients. CONCLUSIONS: Only a minority (1 of 8) in our series of adult patients with FSGS showed positive effects of high doses of RTX. Future studies are warranted to investigate more promising therapeutic options in the management of FSGS.


Assuntos
Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Proteinúria/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/urina , Humanos , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/patologia , Síndrome Nefrótica/urina , Estudos Prospectivos , Proteinúria/patologia , Proteinúria/urina , Resultado do Tratamento
12.
BMJ Open ; 7(6): e015243, 2017 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-28637732

RESUMO

OBJECTIVES: We aim to evaluate the safety of performing percutaneous native kidney biopsy (PKB) as an outpatient procedure (implying an observation period of 6 hours) compared with the traditional inpatient policy. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Group I, in whom PKB was performed in the outpatient department (2012-2016) and followed by 6 hours' observation period and then by regular outpatient visits and group II, in whom PKB was performed and followed by at least 1 day hospital admission. Group II included retrospectively retrieved patients who underwent PKB in our Institution between January 2000 and November 2012 as an inpatient procedure. All biopsies were performed by a single nephrologist following a structured protocol. RESULTS: 462 biopsies were reviewed, 210 (45.5%) of patients were women and the mean age was 54.7±17.9 years. One hundred and twenty-nine (27.9%) of these biopsies were performed in outpatients. A total of 36 (7.8%) of patients developed a complication, and of those, 9 (1.9%) suffered for a major complication (arteriovenous fistula (six cases, 1.2%), ischaemic stroke (2; 0.4%), thromboembolic pulmonary embolism (1; 0.2%)) and 27 (5.8%) for minor(macroscopic haematuria (12 cases, 2.6%), haematomas on sonography not requiring intervention (15 cases, 3.2%)). When comparing the complication rate between groups I and II, no statical difference was observed. When analysing together both groups, after multivariate analysis, serum creatinine >3 mg/dL (OR 2.03, 95% CI 1.18 to 6.81) and known severe hypertension (OR 2.01, 95% CI 1.2 to 4.7) were found to be independent risk factors for minor and major complications, respectively. Conversely, we found no association of risk with the number of biopsy passes, gender, age, diagnosis, presence of haematuria before the kidney biopsy nor the degree of proteinuria. CONCLUSIONS: Outpatient biopsy could be a valuable, safe and perhaps cost-effective method of obtaining diagnostic renal tissue in the majority of patients.


Assuntos
Assistência Ambulatorial , Biópsia/efeitos adversos , Hematoma/etiologia , Rim/patologia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Fístula Arteriovenosa/etiologia , Creatinina/sangue , Feminino , Hematúria/etiologia , Hospitalização , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Ambulatório Hospitalar , Embolia Pulmonar/etiologia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia
13.
Gynecol Endocrinol ; 33(12): 918-922, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28609197

RESUMO

17α-Hydroxylase deficiency is an uncommon type of congenital adrenal hyperplasia (CAH) caused by mutations in the CYP17A1 gene encoding both 17α-hydroxylase and 17,20-lyase, essential for sex steroids production. Main clinical features include lack of pubertal development, hypertension, and hypokalemia. We report the first case of a 46,XX female homozygote for the p.Glu331del mutation in the CYP17A1 gene showing an atypical clinical presentation. She was evaluated the first time for primary amenorrhea and delayed puberty in the presence of low levels of androgens, 17ß-estradiol, serum cortisol, and high levels of progesterone and gonadotropins. After puberty, the patient did not show hypocortisolism and/or hypertension. She started estrogen therapy for pubertal induction, followed by ethinylestradiol/gestodene with clinical and biochemical stability during the follow-up period. At the age of 40 years, she developed hypokalemia and clinical signs of hypocortisolism. Oral corticosteroid treatment was started showing a prompt clinical improvement. Modeling analysis predicted the main outcome of the E331 deletion to impair cytochrome b5 binding, according to a major effect on the enzyme's lyase activity. These data broaden the molecular and clinical spectrum of CAH caused by 17α-hydroxylase deficiency and adds to current genotype-phenotype correlations.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Esteroide 17-alfa-Hidroxilase/genética , Adolescente , Feminino , Humanos
14.
Oncotarget ; 8(25): 41764-41777, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28454112

RESUMO

Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis involving kidneys, joints, skin, and peripheral nerves. While many autoimmune, lymphoproliferative, and neoplastic disorders have been associated with this disorder, hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients. Therefore, clinical research has focused on anti-viral drugs and, more recently, on the new, highly potent Direct-acting Antiviral Agents (DAAs). These drugs assure sustained virologic response (SVR) rates >90%. Nevertheless, data on their efficacy in patients with HCV-associated cryoglobulinemic vasculitis are disappointing, possibly due to the inability of the drugs to suppress the immune-mediated process once it has been triggered.Despite the potential risk of exacerbation of the infection, immunosuppression has traditionally been regarded as the first-line intervention in cryoglobulinemic vasculitis, especially if renal involvement is severe. Biologic agents have raised hopes for more manageable therapeutic approaches, and Rituximab (RTX), an anti CD20 monoclonal antibody, is the most widely used biologic drug. It has proved to be safer than conventional immunosuppressants, thus substantially changing the natural history of HCV-associated cryoglobulinemic vasculitis by providing long-term remission, especially with intensive regimens.The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with DAAs.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , Crioglobulinemia/tratamento farmacológico , Hepacivirus/patogenicidade , Hepatite C/complicações , Vasculite/tratamento farmacológico , Estudos de Coortes , Hepatite C/tratamento farmacológico , Hepatite C/patologia , Humanos , Imunossupressão , Prognóstico
15.
Clin Mol Allergy ; 14: 6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27429595

RESUMO

Antiphospholipid syndrome (APS) is an autoimmune condition characterized by the presence of antiphospholipid antibodies (aPL) in subjects presenting with thrombosis and/or pregnancy loss. The currently used classification criteria were updated in the international consensus held in Sidney in 2005. Vascular events seem to result of local procoagulative alterations upon triggers influence (the so called "second-hit theory"), while placental thrombosis and complement activation seem to lead to pregnancy morbidity. The laboratory tests suggested by the current classification criteria include lupus anticoagulant, a functional coagulation assay, and anticardiolipin and anti-ß2-glycoprotein-I antibodies, generally detected by solid phase enzyme-linked immunosorbent assay. The real challenge for treating physicians is understanding what is the actual weight of aPL in provoking clinical manifestations in each case. As thrombosis has a multi-factorial cause, each patient needs a risk-stratified approach. In this review we discuss the role of thrombotic risk assessment in primary and secondary prevention of venous and arterial thromboembolic disease in patients with APS, focusing on new antibody specificities, available risk scoring models and new coagulation assays.

16.
Am J Nephrol ; 43(4): 251-60, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27161362

RESUMO

BACKGROUND: In a prospective, single-center open study, we evaluated the very long-term effects of rituximab (RTX) administered to patients with severe mixed cryoglobulinemia (MC). METHODS: RTX was administered to 31 patients with MC (type II in 29 cases and type III in 2) with diffuse membranoproliferative glomerulonephritis (16 cases), peripheral neuropathy (26) and large skin ulcers (7). All but 4 patients had serum anti-hepatitis C virus antibodies. RTX was administered at a dose of 375 mg/m2, according to a '4 + 2' protocol (days 1, 8, 15 and 22 plus 1 dose 1 and 2 months later). No other immunosuppressive drugs were added. Response was evaluated over a very long-term follow-up (mean 72.47 months, range 30-148). RESULTS: Complete remission of pretreatment active manifestations was observed in all cases of purpuric lesions and non-healing vasculitic ulcers, and in 80% of the peripheral neuropathies. Cryoglobulinemic nephropathy significantly improved during follow-up, starting from the 2nd month after RTX (serum creatinine from 2.1 ± 1.7 to 1.5 ± 1.6 mg/dl, p ≤ 0.05; 24-hour proteinuria from 2.3 ± 2.1 to 0.9 ± 1.9 g/24 h, p ≤ 0.05). Improvement of cryoglobulinemic serological hallmarks, such as cryocrit and low complement C4, were observed. No clinically relevant side effects were recorded. Re-induction with RTX was carried out in 9 relapsed patients after a mean of 31.1 months (12-54), again with beneficial effects. The survival rate was 75% at 6 years and the probability of remaining symptom-free for 10 years without any therapy was of about 60% after a single '4 + 2' infusion cycle, while the probability of living symptom-free 5 years after relapsing was 80% if given the same treatment. CONCLUSION: In this open, prospective study, RTX appeared to be very effective and safe in the treatment of the most severe cases of MC.


Assuntos
Crioglobulinemia/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Rituximab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
17.
Clin Exp Rheumatol ; 34(3 Suppl 97): S12-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26842656

RESUMO

OBJECTIVES: A low C4 level is one of the hallmarks of mixed cryoglobulinaemia (MC). However, several reports suggest that other factors may be involved in C4 depletion. The C4 gene is located in a multiallelic CNV locus in the human MHC region. We studied the C4 gene copy number (GCN) and both C4A and C4B isotypes, as well as the presence of the hypofunctional C4A6 allotype (rs41315824) and C4A0 allotype (rs367709216) in 41 MC patients, 16 SLE patients and 78 healthy controls. METHODS: GCN of the C4 gene were evaluated by real time PCR. C4A6 allotype (p.Arg458Trp) and ins 2-bp mutation in exon 29 were screened by primer extension. Correlation with clinical signs of the disease (cutaneous ulcers, peripheral neuropathy, GN, purpura, hepatitis) have been performed by cluster analysis, (K-means algorithm). RESULTS: C4 GCN analysis showed that fewer MC patients had more than 2 copies of the C4A gene as well as a lower C4A gene-copy index (1.90 ± 0.54 vs. 2.21 ± 0.78) as compared to healthy controls. SNP rs41315824 analysis showed a significant increase in the frequency of the p.Arg458Trp (C4A6) variant in cryoglobulinaemic patients. Lastly, cluster analysis allowed us to identify two separate clusters of patients. The cluster that included patients with three or less C4 gene copies was found to have a greater prevalence of the most severe complications such as glomerulonephritis, neuropathy and severe cutaneous ulcers. CONCLUSIONS: These data suggest there may be a relationship between polymorphisms of the C4 gene and clinical presentation.


Assuntos
Complemento C4/genética , Crioglobulinemia/imunologia , Idoso , Idoso de 80 Anos ou mais , Crioglobulinemia/genética , Feminino , Dosagem de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
18.
J Med Case Rep ; 9: 274, 2015 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-26607201

RESUMO

INTRODUCTION: Pulmonary embolism remains one of the leading causes of cardiovascular mortality. The standard treatment for pulmonary embolism is anticoagulant therapy using low molecular weight heparin, fondaparinux and a vitamin K antagonist, but a recent clinical trial showed that rivaroxaban, an oral factor Xa inhibitor, was as effective as standard therapy for the initial and long-term treatment of pulmonary embolism and had less bleeding complications. CASE PRESENTATION: The present report describes the case of an 80-year-old white man with an intermediate to low early mortality risk of pulmonary embolism. He was successfully treated with rivaroxaban (administered orally as monotherapy), demonstrating rapid benefit without any adverse events. CONCLUSION: Rivaroxaban, particularly in the acute phase of pulmonary embolism, may be considered an effective and safe therapeutic choice even in elderly patients, a population less represented in clinical trials.


Assuntos
Anticoagulantes/administração & dosagem , Dispneia/etiologia , Embolia Pulmonar/tratamento farmacológico , Rivaroxabana/administração & dosagem , Administração Oral , Idoso de 80 Anos ou mais , Humanos , Masculino , Embolia Pulmonar/complicações , Embolia Pulmonar/fisiopatologia , Medição de Risco , Resultado do Tratamento
19.
Autoimmun Rev ; 14(12): 1123-30, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26244817

RESUMO

BACKGROUND: B cells (BC) play a critical role in systemic lupus erythematosus (SLE). BC depletion therapy still remains an attractive option, despite the disappointing results of randomized controlled trials (RTCs). METHODS: Twelve patients with SLE [3 males, mean age 43.8 yrs (25-55)] with severe multiorgan involvement all including kidney (3 patients with Class IV, 4 with Class III/V and 5 with Class V, according to the International Society of Nephrology/Renal Pathology Society glomerulonephritis classification), skin lesions [10], severe polyarthralgias with arthritis [10], polyserositis [2], and lymphadenopathy [5] have been prospectively treated with an intensified B cell depletion therapy (IBCDT) protocol due to their resistance or intolerance to previous therapy (six cases) or as a front line immunosuppressive treatment in 6 women with unsatisfactory therapeutic compliance or as a specific request of a short-time immunosuppression for gestational perspectives. PROTOCOL: Rituximab (RTX) 375 mg/sm on days 1, 8, 15, 22, and 2 more doses after 1 and 2 months, associated with 2 IV administrations of 10mg/kg of cyclophosphamide and 3 methylprednisolone pulses (15mg/kg) followed by oral prednisone (0.8 mg/kg/day, rapidly tapered to 5mg/day by the end of the 3rd month after RTX). No further immunosuppressive maintenance therapy has been given. RESULTS: Patients had been followed-up for a mean of 44.5 (24-93)months. Significant decreases (p<0.05) were found in the levels of ESR (baseline mean value: 55.0mm; 3 months: 36; end of follow-up: 13), anti-dsDNA antibodies (baseline: 185 U; 3 months: 107; end of follow-up: 15), and proteinuria (baseline: 4.9 g/24h; 3 months: 0.97; end of follow-up: 0.22). C4 values (baseline 11 mg/dl) significantly increased (p<0.05) after 3 months (22 mg/dl) and at the end of the follow-up (20mg/dl). Of the 12 patients, 9 (75%) have remained well after one cycle of IBCDT, with no flare (mean 51.6 months [25-93]). Three patients relapsed after 36, 41, and 72 months, respectively. Following re-treatment, they again showed complete remission over 18-48 months of observation. CONCLUSIONS: A promising role of RTX in an intensified protocol of induction therapy can be envisaged in patients for whom avoiding immunosuppressive maintenance therapy and sparing steroids are particularly appealing. Moreover, our data confirm in one of the longest follow-up available, the opportunity to reconsider the regimens of BL depletion in the treatment of the most severe or refractory forms of SLE despite the disappointing results of RCTs.


Assuntos
Linfócitos B/imunologia , Nefrite Lúpica/imunologia , Ensaios Clínicos como Assunto , Humanos , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Depleção Linfocítica , Estudos Observacionais como Assunto
20.
Int J Biol Markers ; 30(2): e262-6, 2015 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-25838055

RESUMO

BACKGROUND: Salivary and serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have previously been studied in oral cancer with conflicting results. METHODS: We designed a controlled study to assess the correlation between pretreatment salivary and serum levels of IL-6 and IL-8, and all-cause survival and cancer recurrence in oral cancer patients. RESULTS: Fifty-two oral cancer patients and 52 healthy control cases were selected. In univariate analysis, salivary IL-6 and IL-8 seemed to be more expressed in cases (p<0.001 and p = 0.010, respectively). Multivariate analysis showed that higher pretreatment saliva IL-6 levels were significantly associated with better survival (hazard ratio [HR] = 8.62; 95% confidence interval [95% CI], 1.21-62.50; p = 0.031). CONCLUSIONS: To date, this is the largest prospective controlled study that has analyzed the pretreatment salivary and serum levels of IL-6 and IL-8 in oral cancer patients, suggesting salivary IL-6 as a possible prognostic biomarker. But further validation in a larger sample is still necessary.


Assuntos
Interleucinas/metabolismo , Neoplasias Bucais/metabolismo , Neoplasias de Células Escamosas/metabolismo , Idoso , Biomarcadores Tumorais/análise , Estudos de Coortes , Feminino , Humanos , Masculino , Neoplasias Bucais/mortalidade , Recidiva Local de Neoplasia , Neoplasias de Células Escamosas/mortalidade , Estudos Prospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA