Anti-TNF-α therapy reduces retinol-binding protein 4 serum levels in non-diabetic patients with psoriasis: a 6-month prospective study.

BACKGROUND: Retinol-binding protein-4 (RBP4), an adipokine considered as an emerging cardiometabolic risk factor, is increased in patients with moderate-to-severe psoriasis. OBJECTIVE: In this study, we aimed to establish the effect of anti-TNF-α therapy on RBP4 levels in patients with moderate-to-severe psoriasis. We also assessed if RBP4 levels correlate with metabolic syndrome features and disease severity in these patients. METHODS: Prospective study on a series of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with adalimumab. Patients with kidney disease, hypertension or body mass index ≥ 35 kg/m(2) were excluded. Metabolic and clinical evaluation was performed at the onset of treatment (time 0) and at month 6. RESULTS: Twenty-nine patients were assessed. Statistically significant reduction (P = 0.0001) of RBP4 levels was observed after 6 months of therapy (RBP4 at time 0: 55.7 ± 21.4 µg/mL, vs. 35.6 ± 29.9 µg/mL at month 6). No significant correlation between basal RBP4 levels and metabolic syndrome features or disease severity was found. Nevertheless, although RBP4 levels did not correlate with insulin resistance, a negative and significant correlation between RBP4 levels obtained after 6 months of adalimumab therapy and other metabolic syndrome features such as abdominal perimeter and body mass index were observed. At that time, a negative and significant correlation between RBP4 levels and disease activity scores and ultrasensitive CRP levels was also disclosed. CONCLUSION: Our results support an influence of the anti-TNF-α blockade on RBP4 serum levels. This finding is of potential relevance due to increased risk of cardiovascular disease in patients with psoriasis.

Relationship of leptin with adiposity and inflammation and resistin with disease severity in psoriatic patients undergoing anti-TNF-alpha therapy.

BACKGROUND: Altered secretion patterns of proinflammatory adipokines may influence the increased risk of cardiovascular mortality observed in patients with chronic inflammatory diseases. OBJECTIVE: To determine whether two adipokines, leptin and resistin, correlate with metabolic syndrome features and disease severity in psoriatic patients who underwent anti-TNF-α therapy. METHODS: Prospective study of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α- adalimumab. Patients with kidney disease, hypertension or body mass index ≥35 Kg/m(2) were excluded. Metabolic and clinical evaluation was performed at the onset of anti-TNF-α treatment and at month 6. RESULTS: Twenty-nine patients were assessed. A correlation between adiposity and leptin was observed (waist circumference and leptin levels after 6 months of therapy: r = 0.43; P = 0.030). Leptin concentration also correlated with blood pressure before adalimumab onset (systolic: r = 0.48; P = 0.013 and diastolic blood pressure: r = 0.50; P = 0.010 ). A marginally significant negative correlation between insulin sensitivity (QUICKI) and leptin levels was also observed. CRP levels correlated with leptin prior to the onset of adalimumab (r = 0.45; P = 0.020) and with resistin both before (r = 0.45; P = 0.020) and after 6 months of therapy (r = 0.55; P = 0.004). A positive association between parameters of disease activity such as BSA (r = 0.60; P = 0.001) and PASI (r = 0.63; P = 0.001) prior to the onset of adalimumab therapy and resistin concentrations was also disclosed. No significant changes in leptin and resistin concentrations following the 6-month treatment with adalimumab were seen. CONCLUSION: In patients with moderate-to-severe psoriasis leptin correlates with metabolic syndrome features and inflammation whereas resistin correlate with inflammation and disease severity.

Anti-TNF-α therapy improves insulin sensitivity in non-diabetic patients with psoriasis: a 6-month prospective study.

OBJECTIVE: Psoriasis is a chronic inflammatory disease associated with increased risk of cardiovascular death. Several studies have shown a beneficial effect of anti-TNF-α therapy on the mechanisms associated with accelerated atherogenesis in patients with inflammatory arthritis, including an improvement of insulin sensitivity. In this study, we aimed to determine for the first time whether the anti-TNF-α monoclonal antibody adalimumab may improve insulin sensitivity in non-diabetic patients with psoriasis. METHODS: Prospective study on a series of consecutive non-diabetic patients with moderate to severe psoriasis seen at the Dermatology Division of Hospital Universitario Marques de Valdecilla (Northern Spain) who completed 6 months of therapy with adalimumab (80 mg at week 0 followed by 40 mg every other week, starting 1 week after the initial dose). Patients with chronic kidney disease, hypertension or body mass index ≥ 35 kg/m(2) were excluded. Metabolic and clinical evaluation including assessment of insulin sensitivity using the Quantitative Insulin Sensitivity Check Index (QUICKI) was performed at the onset of the treatment (time 0) and at month 6. RESULTS: Twenty-nine patients (52% women; 38.6 ± 10.7 years) with moderate to severe psoriasis [body surface area (BSA) 37.9 ± 16.3%], Psoriasis Area and Severity Index [(PASI) 18.9 ± 7.8] were assessed. Statistically significant improvement (P=0.008) of insulin sensitivity was observed after 6 months of adalimumab therapy (QUICKI at time 0: 0.35 ± 0.04 vs. 0.37 ± 0.04 at month 6). Significant improvement of erythrocyte sedimentation rate, ultrasensitive C-reactive protein, BSA, PASI, Nail Psoriasis Severity Index, physician global assessment and psoriatic arthritis screening and evaluation questionnaire was also observed at month 6 (P < 0.05 for each variable). CONCLUSION: Our results support a beneficial effect of the anti-TNF-α blockade on the mechanisms associated with accelerated atherogenesis in patients with psoriasis.

Gelsolin levels are decreased in ankylosing spondylitis patients undergoing anti-TNF-alpha therapy.

OBJECTIVES: To determine whether circulating gelsolin (GSN) levels in patients with ankylosing spondylitis (AS) undergoing TNF-α antagonist-infliximab-therapy are altered compared with controls and to establish whether disease activity, systemic inflammation and metabolic syndrome are potential determinants of circulating GSN levels in these patients. METHODS: We assessed GSN serum concentrations in a series of 30 non-diabetic AS patients without cardiovascular (CV) disease undergoing TNF-α antagonist-infliximab therapy and 48 matched controls. GSN levels were measured immediately before and after an infliximab infusion. Correlations of GSN serum levels with disease activity, systemic inflammation and metabolic syndrome were assessed. Potential changes in GSN concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed. RESULTS: Although at the time of the study AS patients undergoing anti-TNF-α therapy had adequate control of the disease (mean BASDAI 2.94), they showed lower GSN serum levels than healthy controls (mean±SD: 38660.42±23624.6 ng/ml versus 68975.43±31246.79 ng/ml; p<0.0001). When AS patients were stratified according to sex, we observed that GSN levels were significantly lower in men than in women (p=0.032). However, no differences in GSN levels according to the specific clinical features of the disease were seen. No association was found between GSN concentration and adipokines or biomarkers of endothelial cell activation. However, correlation between basal GSN levels and insulin resistance was observed. A single infliximab infusion did not lead to significant changes in GSN levels. CONCLUSIONS: GSN concentration is reduced in AS patients undergoing periodical anti-TNF-α therapy and low disease activity. Potential association with some metabolic syndrome features seems to exist.

Correlation between two biomarkers of atherosclerosis, osteopontin and angiopoietin-2, in non-diabetic ankylosing spondylitis patients undergoing TNF-α antagonist therapy.

OBJECTIVES: To determine whether circulating osteopontin (OPN) levels in patients with ankylosing spondylitis (AS) undergoing TNF-α antagonist-infliximab-therapy are increased compared with controls and to establish whether disease activity, systemic inflammation, metabolic syndrome, adipokines and biomarkers of atherosclerosis are potential determinants of circulating OPN levels in these patients. METHODS: We assessed OPN serum concentrations in a series of 30 non-diabetic AS patients without cardiovascular disease undergoing TNF-α antagonist-infliximab therapy and 48 matched controls. OPN levels were measured immediately before and after an infliximab infusion, at time 0 and at time 120 minutes respectively. Correlations of OPN serum levels with clinical features, disease activity, systemic inflammation, metabolic syndrome and several biomarkers of atherosclerosis were assessed. Potential changes in OPN concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed. RESULTS: At the time of the study AS patients undergoing anti-TNF-α therapy had low disease activity (mean BASDAI 2.94) and they showed similar OPN serum levels to healthy controls. No differences in OPN levels according to the specific clinical features of the disease were seen. Also, no correlation between OPN concentration and insulin resistance and adipokines was observed. However, a positive correlation between OPN and angiopoietin-2 (Angpt-2) serum levels was found (r=0.397; p=0.04). In addition, a single infliximab infusion led to a marginal statistically significant reduction in OPN levels (24112.19±14608.73 pg/ml at time 0 versus 21806.62±11390.83 pg/ml at time 120'; p=0.05). CONCLUSIONS: OPN and Angpt-2 serum levels are correlated in non-diabetic AS patients undergoing TNF-α antagonist therapy.

Impacto del cambio de técnica de biopsia en tasa de detección de cáncer prostático: estudio prospectivo en 456 pacientes / Impact of changes in biopsy technique in detection rate of prostate cancer: a prospective study in 456 patients

El propósito de este estudio es comparar dos métodos para realizar una biopsia de próstata en dos grupos similares de pacientes. En el grupo A se hicieron 8-12 cores y en el grupo B de 13 a 18 cores. Pacientes y método: Un estudio prospectivo fue planeado para comparar los resultados de la biopsia de próstata realizado por los mismos dos operadores, y por el mismo patólogo (HV) en 456 biopsias consecutivas divididas en dos grupos comparables de pacientes a lo largo de cuatro años, con las mismas indicaciones para la biopsia .Resultados: Desde enero 2005 hasta junio 2009 456 biopsias se realizaron en la Conac V región. En el grupo A se obtuvo una tasa de detección del cáncer de 24,8 por ciento, por el otro lado en el Grupo B 38,1 por ciento, lo que fue estadísticamente significativo con p = 0,003. La detección de cáncer en general para toda la serie, fue 34,77 por ciento. Las complicaciones fueron mayores en el grupo B con 4 casos de sepsis que requirieron hospitalización en comparación con 1 caso en el grupo A, no hubo mortalidad en la serie. Conclusiones: En este trabajo dos grupos de pacientes comparables con indicaciones idénticas sometidos a biopsia de próstata, diferentes sólo en el número de pinchazos –cores obtenidos. El grupo donde se obtuvieron 13 a 18 muestras tuvo un porcentaje significativamente mayor de cáncer de próstata, pero con aumento de las complicaciones. Recomendamos que no perder la oportunidad de llegar a por lo menos 13 muestras en pacientes con sospecha de cáncer de próstata.

The purpose of this study is to compare two methods for prostate biopsy in two similar groups of patients. PATIENTS AND METHOD A prospective study was planned to compare the results of the prostate biopsy performed by the same two operators and by the same pathologist (HV) in 456 consecutive biopsies divided in two comparable groups of patients over the course of four years with the same indications for biopsy . In group A 8-12 cores were made and in group B 13 to 18 cores. RESULTS: From January 2005 to June 2009 456 biopsies were performed at Conac V region. In group A a cancer detection rate of 24.8 percent was obtained, on the other side in Group B 38.1 percent, which was statistically significant with p = 0.003.Overall cancer detection for the entire series, was 34.77 percent . Complications were higher in group B with 4 cases of sepsis that required hospitalization versus 1 case in group A, there was no mortality in the series. CONCLUSIONS: In this work two groups of comparable patients with identical indications underwent prostate biopsy, different only in the number of punctures –cores obtained. The Group where 13-18 samples were obtained had a significantly higher percentage of prostate cancers but with increased complications. We recommend not to miss the opportunity to get to at least 13 samples from patients with suspected prostate cancer.

No evidence of association between functional polymorphisms located within IL6R and IL6ST genes and Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is the most common type of primary small-sized blood vessel vasculitis in children and an uncommon condition in adults. Interleukin (IL)-6 is a proinflammatory cytokine whose effect is controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/gp130) is the signal-transducing subunit of the IL-6R. Two hundred and eighty five Spanish HSP patients and 877 sex and ethnically matched controls were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional polymorphisms. No significant differences in the genotype and allele frequencies between HSP patients and controls were observed. Moreover, there were no differences between HSP patients according to the age at disease onset, presence of nephritis or gastrointestinal manifestations. Our results do not confirm association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with HSP.