Abstract Objective To present a pooled analysis of the efficacy of rituximab from European cohorts diagnosed with biopsy-proven lupus nephropathy (LN) who were treated with rituximab. Methods ...Consecutive patients with biopsy-proven LN treated with rituximab in European reference centers were included. Complete response (CR) was defined as normal serum creatinine with inactive urinary sediment and 24-hour urinary albumin < 0.5 g, and partial response (PR) as a > 50% improvement in all renal parameters that were abnormal at baseline, with no deterioration in any parameter. Results 164 patients were included (145 women and 19 men, with a mean age of 32.3 years). Rituximab was administered in combination with corticosteroids (162 patients, 99%) and immunosuppressive agents in 124 (76%) patients (cyclophosphamide in 58 and mycophenolate in 55). At 6– and 12-months, respectively, response rates were 27% and 30% for CR, 40% and 37% for PR and 33% for no response. Significant improvement in 24-h proteinuria (4.41 g. baseline vs 1.31 g. post-therapy, p = 0.006), serum albumin (28.55 g. baseline to 36.46 g. post-therapy, p < 0.001) and protein/creatinine ratio (from 421.94 g/mmol baseline to 234.98 post-therapy, p < 0.001) at 12 months was observed. A better response (CR + PR) was found in patients with type III LN in comparison with those with type IV and type V (p = 0.007 and 0.03, respectively). Nephrotic syndrome and renal failure at the time of rituximab administration predicted a worse response (no achievement of CR at 12 months) (p < 0.001 and p = 0.024, respectively). Conclusion Rituximab is currently being used to treat refractory systemic autoimmune diseases. Rituximab may be an effective option for patients with lupus nephritis, especially those refractory to standard treatment or who experience a new flare after intensive immunosuppressive treatment.
To analyze the effects of a short course of methyl-prednisolone pulses (MP) during the second week of disease (week-2) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia.
...Comparative observational study using data collected from routine care at Hospital Universitario Cruces, Barakaldo, Bizkaia, Spain in patients with COVID-19 pneumonia. We compared patients who received week-2-MP (125-250 mg/d x3) with those who did not, with the end-points time to death and time to death or endotracheal intubation.
We included 242 patients with COVID-19 pneumonia and elevated inflammatory markers at admission. Sixty-one patients (25%) received week-2-MP. Twenty-two patients (9%) died and 31 (12.8%) suffered death or intubation. The adjusted HRs for death and death or intubation for patients in the week-2-MP group were 0.35 (95%CI 0.11 to 1.06, p = 0.064) and 0.33 (95%CI 0.13 to 0.84, p = 0.020), respectively. These differences were specifically seen in the subcohort of patients with a SpO2/FiO2 at day 7 lower than 353 (adjusted HR 0.31, 95% CI 0.08 to 1.12, p = 0.073 and HR 0.34, 95%CI 0.12 to 0.94, p = 0.038, respectively) but not in patients with higher SpO2/FiO2. Patients receiving out-of-week-2-MP, non-pulse glucocorticoids or no glucocorticoids had an increased adjusted risk for both outcomes compared with week-2-MP group: HR 5.04 (95% CI 0.91-27.86), HR 10.09 (95% CI 2.14-47.50), HR 4.14 (95% CI 0.81-21.23), respectively, for death; HR 7.38 (95% CI 1.86-29.29), HR 13.71 (95% CI 3.76-50.07), HR 3.58 (95% CI 0.89-14.32), respectively, for death or intubation. These differences were significant only in the subgroup with low SpO2/FiO2.
Week-2-MP are effective in improving the prognosis of patients with COVID-19 pneumonia with features of inflammatory activity and respiratory deterioration entering the second week of disease. The recognition of this high-risk population should prompt early use of MP at this point.
Infections commonly complicate the course of systemic lupus erythematosus (SLE). Our aim is to investigate the clinical predictors of major infections in patients with SLE.
A nested case-control ...study design was used within the prospective Lupus-Cruces cohort. The endpoints of the study were major infections. Cases were defined as patients with a major infection. Two controls (SLE patients without major infections), matched for time of follow-up until the event and age at diagnosis, were selected for each case. Univariate analysis and logistic regression models were used for the analysis of data.
Two hundred and forty-nine patients (83 cases, 166 controls) were selected. Eighty-three episodes of major infections were analyzed; E. coli, S. aureus, M. tuberculosis and S. pneumoniae being the most frequent isolates. Univariate analysis identified several variables related with infection: lung and renal involvement, at or previous to the study point; leukopenia at the study point; antiphospholipid antibody-positivity and treatment with prednisone within 3 months previous to the study point, and the dose of prednisone received. Treatment with antimalarials, on the other hand, showed a strong inverse association with major infections. Logistic regression models identified treatment with antimalarials (odds ratio (OR) = 0.06, 95% confidence interval (CI) = 0.02 to 0.18), prednisone dose (OR = 1.12, 95% CI = 1.04 to 1.19) and lung involvement (OR = 4.41, 95% CI = 1.06 to 18.36) as significant and independent predictors of major infections. No significant interactions among these three variables were found. Further adjustment for potential confounders related with antimalarial treatment did not change the results.
The risk of major infections in patients with SLE is mostly influenced by treatment. Prednisone treatment, even at moderate doses, increases the risk, whilst antimalarials have a protective effect.
The purpose of this observational study was to analyze the rates, characteristics and associated risk factors of severe infections in patients with systemic autoimmune diseases (SAD) who were treated ...off-label with biological agents in daily practice.
The BIOGEAS registry is an ongoing Spanish prospective cohort study investigating the long-term safety and efficacy of the off-label use of biological agents in adult patients with severe, refractory SAD. Severe infections were defined according to previous studies as those that required intravenous treatment or that led to hospitalization or death. Patients contributed person-years of follow-up for the period in which they were treated with biological agents.
A total of 344 patients with SAD treated with biological agents off-label were included in the Registry until July 2010. The first biological therapies included rituximab in 264 (77%) patients, infliximab in 37 (11%), etanercept in 21 (6%), adalimumab in 19 (5%), and 'other' agents in 3 (1%). Forty-five severe infections occurred in 37 patients after a mean follow-up of 26.76 months. These infections resulted in four deaths. The crude rate of severe infections was 90.9 events/1000 person-years (112.5 for rituximab, 76.9 for infliximab, 66.9 for adalimumab and 30.5 for etanercept respectively). In patients treated with more than two courses of rituximab, the crude rate of severe infection was 226.4 events/1000 person-years. A pathogen was identified in 24 (53%) severe infections. The most common sites of severe infection were the lower respiratory tract (39%), bacteremia/sepsis (20%) and the urinary tract (16%). There were no significant differences relating to gender, SAD, agent, other previous therapies, number of previous immunosuppressive agents received or other therapies administered concomitantly. Cox regression analysis showed that age (P = 0.015) was independently associated with an increased risk of severe infection. Survival curves showed a lower survival rate in patients with severe infections (log-rank and Breslow tests < 0.001).
The rates of severe infections in SAD patients with severe, refractory disease treated depended on the biological agent used, with the highest rates being observed for rituximab and the lowest for etanercept. The rate of infection was especially high in patients receiving three or more courses of rituximab. In patients with severe infections, survival was significantly reduced. Older age was the only significant predictive factor of severe infection.
Fluctuations in the titers of anticardiolipin antibodies (aCL) have been reported in systemic lupus erythematosus (SLE) patients, but their relation with thrombosis is not completely understood. ...Prospective inception cohort of 237 patients with SLE (American College of Rheumatology criteria). Positivity for antiphospholipid antibodies (aPL) was defined according to Sapporo criteria. aCL was defined as persistently positive when more than two-thirds of the determinations were positive during follow-up. Patients were classified into four groups: A positive lupus anticoagulant (LA), B (negative LA and persistently positive aCL), C (negative LA and transiently positive aCL) and D (negative LA and aCL). Of these 237 patients, 211 (89%) patients were women. Median age at diagnosis and follow-up were 32 (2—78) and 10 (1—31) years, respectively; 33 (13.9%), 23 (9.7%), 42 (17.7%) and 139 (58.6%) patients were classified in groups A, B, C and D, respectively. Thirty (12.6%) and 23 (9.7%) patients suffered arterial and venous thrombotic events, respectively. Adjusted risk for arterial thrombosis was increased in groups A odds ratio (OR) 15.69, 95% confidential interval (CI) 4.79—51.42, P < 0.001 and B (OR 7.63, 95% CI 2.00—29.08, P = 0.003), but not in group C when compared with group D. Adjusted risk of venous thrombosis was increased in group A (OR 4.24, 95% CI 1.36—13.20, P = 0.013), but not in groups B or C when compared with group D. Risk of thrombosis is not increased in SLE patients with negative LA and transiently positive aCL, even fulfilling Sapporo laboratory criteria, when compared with aPL-negative SLE patients. Lupus (2007) 16, 810—816.
Ocular toxoplasmosis causes abnormalities in the vitreous that are responsible for several types of well-known complications including retinal detachment and epiretinal membranes. We report on a ...patient who developed toxoplasmic panuveitis with a full-thickness macular hole (MH) and was successfully treated with vitreoretinal surgery. A 35-year-old Hispanic female presented with a 2-week history of loss of visual acuity and metamorphopsia in her right eye. Funduscopy revealed a typical toxoplasmosis lesion and a MH, which was confirmed by optical coherence tomography. After 8 weeks of medical treatment with sulfamethoxazole (800 mg)/trimethoprim (160 mg) and steroids, the intraocular inflammation was considered inactive. Pars plana vitrectomy with inner limiting membrane peeling and injection of 24 % sulphur hexafluoride gas were performed to treat the MH, without success. Repeat pars plana vitrectomy was then performed with injection of 14 % perfluoropropane (C
3
F
8
). Closure of the MH was achieved after this second procedure. Vitreoretinal surgery may be safe and effective for treating MHs secondary to toxoplasmosis lesions, a very uncommon complication of this disease.
Purpose: To describe a case of sarcoid uveitis subsequent to anti-TNFα therapy and review previously reported cases.
Methods: Review of the clinical records of the authors' patient and of the ...literature using the PubMed database.
Results: A 30-year-old woman presented with intermediate uveitis with snowballs in both eyes. She was on treatment with etanercept due to psoriatic arthritis. An ultrasound-guided biopsy of a mediastinal adenopathy showed non-necrotizing granulomas compatible with sarcoidosis. The clinical picture resolved after etanercept was withdrawn and treatment with immunosuppressants. In a literature search the authors identified six other cases of sarcoid uveitis induced by anti-TNFα therapy. The types of uveitis were anterior uveitis, posterior uveitis, or panuveitis. Management consisted of withdrawal of anti-TNFα therapy and administration of immunosuppressive agents in 5 cases.
Conclusions: Sarcoid uveitis induced by TNFα antagonists is a rare complication. Appropriate management consists of withdrawing the TNFα antagonist and giving immunosuppressants.
Recently, different genetic variants located within the IL2/IL21 genetic region as well as within both IL2RA and IL2RB loci have been associated to multiple autoimmune disorders. We aimed to ...investigate for the first time the potential influence of the IL2/IL21, IL2RA and IL2RB most associated polymorphisms with autoimmunity on the endogenous non-anterior uveitis genetic predisposition.
A total of 196 patients with endogenous non-anterior uveitis and 760 healthy controls, all of them from Caucasian population, were included in the current study. The IL2/IL21 (rs2069762, rs6822844 and rs907715), IL2RA (2104286, rs11594656 and rs12722495) and IL2RB (rs743777) genetic variants were genotyped using TaqMan® allelic discrimination assays.
A statistically significant difference was found for the rs6822844 (IL2/IL21 region) minor allele frequency in the group of uveitis patients compared with controls (P(-value)=0.02, OR=0.64 CI 95%=0.43-0.94) although the significance was lost after multiple testing correction. Furthermore, no evidence of association with uveitis was detected for the analyzed genetic variants of the IL2RA or IL2RB loci.
Our results indicate that analyzed IL2/IL21, IL2RA and IL2RB polymorphisms do not seem to play a significant role on the non-anterior uveitis genetic predisposition although further studies are needed in order to clear up the influence of these loci on the non-anterior uveitis susceptibility.
Purpose: To describe the clinical characteristics and to assess visual prognosis of patients with syphilis-associated uveitis in northern Spain.
Methods: Retrospective review of clinical records in ...eight general uveitis referral centers.
Results: Since the year 2000, 50 patients have been diagnosed: 31 men and 19 women; median age was 41 (19-76) years. A total of 34% were co-infected with HIV and 24% presented systemic manifestations of syphilis. Median initial visual acuity and vision at last visit in 93 affected eyes was 20/50 (20/20-20/2000) and 20/22 (20/20-20/2000), respectively (p < .0001). The most frequent manifestation was papillitis (33.3%). Fifty percent of eyes with macular edema on admission presented worsening of visual acuity at last visit, whereas frequency of worsening in eyes without edema was 7.1% (p = 0.009).
Conclusions: In our series, patients with syphilitic uveitis were more usually middle-aged men and were frequently co-infected with HIV. Although most patients showed posterior segment involvement, visual prognosis was good.
Present role of homocysteine in clinical medicine Aguirre Errasti, Ciriaco; Egurbide Arberas, M Victoria; Martínez Berriotxoa, Agustín
Medicina clínica,
2009-Oct-03, Letnik:
133, Številka:
12
Journal Article
Recenzirano
There has been a great interest in the last decades about the clinical significance of elevated total plasma homocysteine (tHcy), and especially its possible association with an increased ...cardiovascular risk. Measurement of tHcy is clearly indicated when homocystinuria is suspected in young or adult patients (in the presence of a severe, atypical or progressive myopia with ectopia lentis and/or venous thromboembolism and/or severe, premature or atypical atherosclerotic vascular disease) and in the evaluation of vitamin B12 and/or folic acid deficiencies. The current evidence does not support either the screening measurement of tHcy or the treatment with vitamin B12 and/or folic acid supplementation in patients with cardiovascular disease. It is important to remember that it remains to be proved whether the long-term administration of folic acid at pharmacological doses is safe.
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