[IOL choice predictability, 1-year visual outcome, and complications after cataract surgery in children]. / Prédictibilité du choix de l'implant, résultats visuels à 1 an et complications de la chirurgie de cataracte chez l'enfant.

PURPOSE: To measure the refraction 1year after cataract surgery in children as a function of under-correction of the implant power and to evaluate the visual prognosis and possible therapeutic challenges. PATIENTS AND METHODS: We conducted a retrospective study of 28 children (38 affected eyes) who underwent unilateral or bilateral cataract surgery with primary intraocular lens implantation over a one-year period of time. The age at the time of surgery was between 1month and 17years. RESULTS: Ten patients had bilateral cataracts (35%) and 18 patients unilateral (65%). Ten patients were between 0 and 2years of age, 10 patients between 2 and 6years of age, and 8 patients were over 6years old. 72 % of the cataracts were idiopathic. The cataracts were mainly cortico-nuclear (37%). Monocular acuity averaged 0.7 LogMAR (2/10) between 2 and 6years, and 0.2 LogMAR (6.3/10) after 6years. The percentage of under-correction was 31% between 0 and 2years, 12.2% between 2 and 6years, and 2.3% after 6years, for a mean under-correction of 15.2%. The power of the chosen implant after under-correction was 25 diopters on average. One year after surgery, visual acuity averaged 0.2 LogMAR (6.3/10) between 2 and 6years old,and 0.1 LogMAR (8/10) after 6years. The spherical equivalent remained globally stable after surgery (the mean postoperative value was+1.25 diopters). The highest rate of revision surgery occurred in the 0-2year-olds (40%). The most common complication was cellular proliferation (up to 80% of the 0-2year-olds). Only one case of ocular hypertension was noted. DISCUSSION: It is necessary to apply an under-correction of the intraocular lens power, decreasing with the age of the child. The gain in visual acuity is modest, and the main complication is cellular proliferation.

The development of a simple questionnaire to screen patients with SLE for the presence of neuropsychiatric symptoms in routine clinical practice.

AIM: The creation of a physician-administered questionnaire to screen patients with Systemic Lupus Erythematosus (SLE) for the presence of symptoms suggestive of neuropsychiatric involvement (NPSLE). METHODS: The development of the questionnaire followed three phases. First, a list of manifestations was prepared based on the ACR case definitions for NPSLE. A first questionnaire was constructed including 119 items. To reduce their number, a Delphi analysis was carried out and a second questionnaire with 62 questions was developed. This questionnaire was administered to 139 patients with SLE (58 with NPSLE: 29 active, 29 inactive; and 81 without NPSLE: 39 active, 42 inactive). Questions relevant to the screening of patients were selected on the basis of the receiver operating characteristic (ROC) curve analysis. RESULTS: Twenty-seven questions concerning central nervous system and psychiatric manifestations were found to be relevant; the remaining could be eliminated without significantly affecting AUC. The area under the ROC curve (AUC) was 0.69 (95% CI 0.61-0.78). A score above 17 was considered as suggestive of the presence of NPSLE with a sensitivity of 92.9% (95% CI 85.1-97.3 %) and specificity of 25.4% (95% CI 14.7-39.00 %). CONCLUSIONS: This questionnaire could represent a 'core set' of questions that could help in clinical practice to identify patients with neuropsychiatric symptoms requiring further evaluation.

General and specific factors associated with severity of cognitive impairment in systemic lupus erythematosus.

OBJECTIVE: To determine factors affecting the severity of cognitive impairment in systemic lupus erythematosus (SLE) and to analyze its anatomic location. METHODS: Fifteen cognitive functions grouped into 8 domains were evaluated in 52 patients with SLE and 20 with rheumatoid arthritis. Patients were classified according to severity of impairment as normal, mild, or moderate/severe. Multivariate analysis was performed to identify the main factors affecting severity of cognitive deficits. The most likely anatomic site of damage according to neuropsychological performance was compared with the lesion's location on magnetic resonance imaging (MRI). RESULTS: In SLE patients, a stepwise regression analysis showed that the number of impaired functions (dependent variable) was associated with antiphospholipid antibody positivity (aPL+; P = 0.04), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI; P = 0.001), hypertension (P = 0.032), and was inversely related to educational level (P = 0.021). Including MRI, the number of impaired functions was associated with severity of MRI (P < 0.001), the SDI (P = 0.013), and the presence of Raynaud's phenomenon (P = 0.04). The contemporary presence of aPL+ and Raynaud's phenomenon resulted in a higher probability to develop moderate/severe cognitive deficits (P = 0.015). Two logistic multiple regression analyses identified hypertension (P < 0.05), the SDI (P < 0.01), and moderate/severe MRI findings as main predictors of moderate/severe impairment (dependent variable). The damage site hypothesized through neuropsychological testing corresponded with MRI findings in 71.7% of SLE patients K = 0.42, P = 0.005). CONCLUSION: Hypertension, aPL+, accumulated damage, and MRI lesions are the main factors affecting severity of cognitive impairment in SLE. The hypothesized sites of central nervous system involvement according to neuropsychological testing correlated with MRI findings in most patients.

Rationale for T cell inhibition by cyclosporin A in major autoimmune diseases.

T cells exert a fundamental role in different autoimmune chronic inflammatory diseases. The low-affinity autoreactive T cell clones provide the first amplification loop after the antigen (AgX) presentation, and if not counterregulated by the T regulatory cells (Treg), they maintain the inflammation and predispose to organ damage. Interrupting the T cell amplification loop through calcineurin antagonists leads to maintenance of the whole process under the autoimmune threshold.

Relationship between the tumor necrosis factor receptor II (TNF-RII) gene polymorphism and sTNF-RII plasma levels in healthy controls and in rheumatoid arthritis.

OBJECTIVE: To assess the relationship between tumor necrosis factor receptor II (TNF-RII) gene polymorphisms and sTNFRII plasma levels in healthy blood donors (HBDs) and in rheumatoid arthritis (RA) patients. 113 HBDs and 49 RA patients were genotyped for the T/G polymorphism in exon 6 of the TNF-RII gene. In the same cases, sTNF-RII plasma levels were determined by an enzyme-linked immunosorbent assay (ELISA) procedure. sTNF-RII levels were higher in RA patients than in HBDs (p < 0.0001). No difference in sTNF-RII levels arose between RA patients on low oral doses of glucocorticoids versus those not taking glucocorticoids. In healthy controls, we observed lower levels of the sTNF-RII in carriers of the TT genotype compared to TG/GG genotype (p = 0.04). In RA there was the same behaviour between TT and TG/GG carriers, even though the difference was not statistically significant. When analyzing the correlation between sTNF-RII plasma levels and disease activity parameters, significant correlations were seen with disease activity score (r = 0.40, p = 0.01), swollen joint count (r = 0.38, p = 0.01), and tender joint count (r = 0.42, p = 0.01), but not with erythrocyte sedimentation rate (r = 0.22, p = ns) nor with C-reactive protein (r = 0.14, p = NS). The correlation remained significant only in the RA subgroup carrying the TT genotype. Healthy donors carrying the TT genotype showed lower sTNF-RII plasma levels than carriers of the TG/GG genotypes, while in RA patients we observed only a trend.

[Analysis of the kinetic of expression of tristetraprolin and HuR by rheumatoid arthritis patients peripheral blood mononuclear cells stimulated with lipopolysaccharide]. / Analisi della cinetica di espressione della tristetraprolina e della HuR in cellule mononucleate di pazienti con artrite reumatoide dopo stimolazione con Lipopolisaccaride.

OBJECTIVE: Given the role of TNF-alpha in Rheumatoid Arthritis (RA) we decided to define the characteristics of the TNF-alpha synthesis by peripheral blood mononuclear cells (PBMNCs) obtained from active-aggressive RA patients giving a particular attention to the modulation of the expression of two fundamental proteins in TNF-alpha mRNA stability regulation, Tristetraprolin (TTP) and HuR. METHODS: 11 RA patients with active disease were enrolled in the study before their entry in 2 double blind protocols: Infliximab versus MTX and Etanercept versus MTX. 9 healthy blood donors were taken as controls. PBMNCs obtained by Ficoll centrifugation and plastic adherence were stimulated with lipopolysaccharide (LPS) and TNF-alpha was measured in the supernatant during 8 hours by ELISA. At each time point the cells were harvested and analysed for TNF-alpha, TTP and HuR mRNA expression by semi-quantitative PCR. RESULTS: MNCs TNF-alpha secretion after LPS stimulation did not differ significantly between RA and control subjects, even if a tendency towards a more prompt response was observed in the patients. More importantly only the DMARDs responsive patients (DAS < 3.7 at the 6th month, with a minimal reduction of 1.2 points) disclosed precociously (at the first month) a significant change in the profile of TNF-alpha secretion and maintained it until the 6th month. The "normalization" of the synthetic behaviour was accompanied by the resetting in the regulation of the expression of the TTP, that appeared significantly different in the patients before and after therapy. CONCLUSIONS: Independently from the type of therapy, responsive patients demonstrate a rapid change in the cellular biology at the systemic level that might drive the resolution of the inflammatory process at the synovial level.

[Neuropsychological tests, MRI and SPECT in the evaluation of CNS involvement in SLE]. / Test neuropsicologici, RMN e SPECT nella valutazione del danno cerebrale nel LES.

OBJECTIVE: To assess the agreement between presence and location of central nervous system (CNS) structural damage and neuropsychological performance. METHODS: 21 unselected SLE patients underwent a 3 hours-long battery of neuropsychological tests sampling 15 cognitive functions. A neuropsychologist hypothesized for each SLE patient the most likely site of possible involvement, according to the neuropsychological performance. Patients underwent MRI scans within 6 months (3 months before or after) from neuropsychological tests and SPECT. RESULTS: 14 of the 21 SLE patients (66.6%) were impaired in at least 1 function; among these, 7 patients (33.3%) were mildly impaired and 7 (33.3%) had more than 3 functions impaired. 10 patients (48%) had abnormal MRI scan. Negative and positive agreements between neuropsychological performance and MRI scan were detected in 15 patients (71%; ?2 with Yates' correction 6.09, p 0.007, measure K for concordance 0.44, p 0.03). All the 6 negative agreements had no records of major neurologic or psychiatric events; among the 9 positive agreements, 6 presented previous major neurologic events and 2 minor neuropsychiatric symptoms. Among the subjects with disagreement, 1 was unimpaired with positive MRI and without neuropsychiatric symptoms, 5 were mildly impaired with negative MRI. CONCLUSIONS: A detailed neuropsychological evaluation along with MRI arose as a valid method to exclude or to identify, localize and clinically interpret CNS involvement in SLE. Disagreement between MRI and neuropsychological tests was detected mainly for mild cognitive impairment that might be the expression of functional (inflammatory or ischemic) processes.

Analysis of improvements, full responses, remission and toxicity in rheumatoid patients treated with step-up combination therapy (methotrexate, cyclosporin A, sulphasalazine) or monotherapy for three years.

OBJECTIVE: To evaluate two monotherapies followed by step-up combination therapy with two or three complementary drugs in active rheumatoid arthritis (RA) in comparison with sulphasalazine (SSZ) alone. METHODS: One hundred and twenty-six consecutive patients with early active RA were enrolled in this open controlled clinical trial. The primary end-point was 50% improvement according to the ACR criteria (ACR50) at 6, 12 or 18 months. The secondary end-points were a full response (Magnusson criteria) and/or remission (ACR criteria) at 3 yr. Methotrexate (MTX) (group 1), cyclosporin A (CsA) (group 2) or SSZ (group 3) was used first. After 6 months, a combination of two drugs (CsA and MTX) was employed in groups 1 and 2. SSZ was added after 12 months if improvement was less than ACR50 with the combination. Group 3 continued with SSZ alone. RESULTS: After 6 months, 57% of patients in group 1, 31% of group 2 (MTX vs CsA, P=0.002) and 33% of group 3 (MTX vs SSZ, P=0.01) had reached ACR50 improvement according to intention-to-treat analysis. At month 12 after starting a drug combination, 67% of group 1 and 76% of group 2 had reached ACR50 compared with 24% of group 3. At the 18-month follow-up, 90% of group 1 and 88% of group 2 but only 24% of group 3 had reached ACR50. After 18 months, 62% of group 1, 60% of group 2 and 48% of group 3 showed side-effects and three, five and eight patients in the three groups respectively had dropped out of the study. At the 3-yr follow-up, 9% of the patients in groups 1 and 2 and 7% of group 3 were in remission according to the ACR criteria; according to the Magnusson criteria, 40% showed a full response in groups 1 and 2 but only 21% did so in group 3. CONCLUSION: MTX appears to be the fastest-acting agent. A step-up approach with MTX plus CsA plus SSZ led to a 50% improvement according to the ACR criteria in most patients. After 3 yr, 40% of patients receiving combination therapy and 21% of patients receiving monotherapy showed a full response, while 9 and 7% respectively attained remission.