The presence of high mobility group box-1 and soluble receptor for advanced glycation end-products in juvenile idiopathic arthritis and juvenile systemic lupus erythematosus

BACKGROUND: The involvement of high mobility group box-1 (HMGB1) in various inflammatory and autoimmune diseases has been documented but clinical trials on the contribution of this pro-inflammatory alarmin in children with juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE) are basically absent. To address the presence of HMGB1 and a soluble receptor for advanced glycation end products (sRAGE) in different subtypes of JIA and additionally in children with SLE, we enrolled a consecutive sample of children harvested peripheral blood as well as synovial fluids (SF) at diagnosis and correlated it with ordinary acute-phase reactants and clinical markers. ----- METHODS: Serum and synovial fluids levels of HMGB1 and sRAGE in total of 144 children (97 with JIA, 19 with SLE and 27 healthy controls) were determined by ELISA. ----- RESULTS: The children with JIA and those with SLE were characterised by significantly higher serum levels of HMGB1 and significantly lower sRAGE levels compared to the healthy controls. A positive correlation between serum HMGB1 and ESR, CRP, α2 globulin was found while serum sRAGE levels were inversely correlated with the same inflammatory markers in children with JIA. Additionally, high level of serum HMGB1 was related to hepatosplenomegaly or serositis in systemic onset JIA. ----- CONCLUSION: The inverse relationship of the HMGB1 and its soluble receptor RAGE in the blood and SF indicates that inflammation triggered by alarmins may play a role in pathogenesis of JIA as well as SLE. HMGB1 may serve as an inflammatory marker and a potential target of biological therapy in these patients. Further studies need to show whether the determination of HMGB1 levels in patients with JIA can be a useful guideline for detecting disease activity

Childhood-onset systemic lupus erythematosus in Croatia: demographic, clinical and laboratory features, and factors influencing time to diagnosis

OBJECTIVES Childhood-onset systemic lupus erythematosus (cSLE) presents with diverse clinical features and often with non-classical symptoms that may delay diagnosis and increase risk of morbidity and mortality. This paper aims to analyse incidence, and clinical and laboratory features of cSLE in Croatia between 1991 and 2010, and to identify factors influencing time to diagnosis. ----- RESULTS Medical records at three university-based tertiary care centres were analysed retrospectively for 81 children with cSLE (68 girls). Mean age at onset was 13.4±2.8 yr (interquartile range 3), and annual incidence varied from 1-15 per million at risk. The most frequent clinical and laboratory features were musculoskeletal symptoms (80%) and increased erythrocyte sedimentation rate (96%). The most frequent immunological laboratory findings were the presence of antibodies against histones (86%), double-stranded DNA (73%), and Sm protein (64%), as well as low levels of C3 complement (69%). Haematuria was present in 58% of children, proteinuria in 56%, and biopsy-confirmed lupus nephritis in 43%. Median time from symptom onset to diagnosis was 2 months (range 0-96). Time to diagnosis was inversely associated with ECLAM score (p<0.001), but it showed no association with age, gender, clinical features or distance from the nearest paediatric centre. ----- CONCLUSIONS This is the first large-scale, in-depth study of clinical and laboratory features of cSLE in Croatia. Among all demographic, laboratory and clinical features examined, ECLAM score alone was inversely associated with time to diagnosis. This highlights the need to improve detection of children with fewer symptoms early in the course of the disease, therefore serious consequences for prognosis could be avoided

Neopterin Kinetics after Cardiac Surgery with or without Cardiopulmonary Bypass

Cardiac surgery (CS) with cardiopulmonary bypass (CPB) induces systemic inflammatory response by activating plasma proteins and blood cells. Activated monocytes/macrophages produce inflammatory marker neopterin (NP). The aim was to explore the NP kinetics in first 24 hours after CS according to the CPB use. Significant difference between groups was found for NP levels 12 and 24 hrs after CS, being higher in on-pump group. Strong association was found between NP levels 12 hrs after CS and the length of ICU stay for on-pump group (r=0.744, p<0.001). Strong association was found between preoperative NP levels and the length of ICU stay for those on-pump patients with elevated preoperative NP (r=0.855, p=0.001; linear regression equation y=0.50x – 5.14, p<0.001). Preoperative NP levels higher than 10 nmol/L in on-pump group could predict prolonged ICU stay and outpoint patients at higher risk for developing postoperative complications and, therefore, help to determine the necessary therapeutic interventions

Risk factors for non-melanoma skin cancer development in renal transplant recipients: a 40 year retrospective study in Croatia

Aim To determine the prevalence of non-melanoma skin cancer (NMSC) and disease-specific risk factors in renal transplant recipients (RTRs). Methods This retrospective cohort study enrolled 1232 RTRs (736 men) treated in University Hospital Center Zagreb over 40 years. The effect of sex, age at transplantation, geographic residence, dialysis vintage, and the type of immunosuppressive therapy on NMSC occurrence was investigated. Results The prevalence of NMSC was 6.81%. Overall, 60.7% of patients developed basal cell carcinoma (BCC) and 30.9% of patients developed cutaneous squamous cell carcinoma (cSCC). Only 8.3% developed both tumors. The BCC:cSCC ratio was 1.76:1. The risk for NMSC was 50% higher in men. Patients older than 50 years at transplantation were at greater risk for NMSC development. Residence in an area with higher ultraviolaet radiation (UV) exposure and dialysis vintage before transplantation did not influence NMSC development. Cyclosporine and azathioprine treatment conferred a greater risk for NMSC than tacrolimus or mycophenolate mofetil treatment. Conclusion RTRs are at high risk for NMSC development. Sex, age at transplantation, and type of immunosuppressive therapy play a role in tumor development

Termografija skrotuma u procjeni ishoda operacije varikokele: prikaz slučaja

Scrotal thermography is a diagnostic method for varicocele. In short, there are five diagnostic thermographic criteria for varicocele, i.e., pattern of scrotal thermographic image indicative of varicocele, temperature at pampiniform plexus ≥34 C°, temperature difference between left and right pampiniform plexus ≥0.5 C°, enhancement of image during Valsalva maneuver, and temperature at pampiniform plexus ≥ temperature at ipsilateral thigh. Three or more positive signs are indicative of varicocele. The aim of this report is to present the use of digital thermography as a diagnostic method to evaluate the outcome of varicocele repair. We present a case of a student diagnosed with varicocele grade III, and assessed preoperatively and followed up postoperatively by scrotal thermography. According to thermographic indicators, our patient was positive for varicocele diagnosis before surgical treatment. Three months after varicocele repair, the patient did not show positive thermographic indicators of varicocele while physical examination and color Doppler ultrasound were equivocal. This case report suggests that infrared digital thermography of scrotum could be very valuable for monitoring patients in the period after surgery for varicocele, however, it should be confirmed in a larger number of patients.Termografija skrotuma je metoda dijagnostike varikokele. Postoji pet termografskih dijagnostičkih kriterija za dijagnozu varikokele: termografski prikaz karakterističan za varikokelu, temperatura pampiniformnog pleksusa ≥34 C°, razlika temperature između lijevog i desnog pampiniformnog pleksusa ≥0,5 C°, indikativna promjena slike prilikom Valsalvina manevra i temperatura pampiniformnog pleksusa koja je ≥ temperaturi ipsilateralne natkoljenice. Tri ili više pozitivnih znakova predstavlja pozitivan nalaz u slučaju dijagnostike varikokele. Cilj ovoga rada je prikazati primjenu termografije skrotuma kao dijagnostičke metode u procjeni ishoda operacije varikokele. Prikazat ćemo slučaj studenta koji je imao dijagnozu varikokele III. stupnja te je prijeoperacijski dijagnosticiran, a poslijeoperacijski praćen termografijom skrotuma. Prema termografskim kriterijima ovaj bolesnik je prijeoperacijski imao varikokelu. Tri mjeseca nakon operacije bolesnik nije imao pozitivne termografske znakove za varikokelu, međutim, klinički pregled i obojeni doppler nisu bilo tako uvjerljivi. Ovaj prikaz slučaja pokazuje mogućnost primjene termografije skrotuma u praćenju bolesnika nakon operacije varikokele, no ovo svakako treba potvrditi na većem broju ispitanika

Mehanizmi nastanka koštanog fenotipa u generaliziranom limfoproliferativnom poremećaju u miša [ Mechanism of development of bone phenotype in murine generalised lymphoproliferative disorder ]

Mice with mutation in the Fas-ligand gene develop generalised lymphoproliferative disorder (gld mice), characterised by accumulation of double negative (DN) T cells (CD4–CD8–), as well as higher bone mineral density and more trabecular bone. To evaluate the role of immune system in the development of bone phenotype of gld mice, we parabiotically joined the wild-type (C57BL/6, B6) with gld mice. The mice were sacrificed weekly for four weeks. Additionally, the mice were separated after four weeks and sacrificed two weeks after separation. Lymphoproliferative disorder was suppressed in gld mice during the first week and the suppression was evident even after the animals were separated. The proportion of DN T cells in the lymphoid tissues of B6 increased during parabiosis, suggesting that the immune phenotype of B6 mice became similar to that of gld mice. At the same time, the bone phenotype of B6 animals shifted towards the gld bone phenotype. The number of osteoclast precursors in the cell culture of B6 bone marrow decreased at one and four weeks, while the number of osteoblast precursors increased at four weeks after parabiosis. The alterations of B6 bone marrow during parabiosis were paralleled by increased expression of cytokine osteoprotegerin in the bone, both at the gene and the protein levels, suggesting that osteoprotegerin was the link between the bone and immune phenotype. Simultaneous transfer of both immune and bone phenotype from gld to B6 mice point to the immune component of gld bone phenotype. On the other hand, lack of changes in the bone marrow of gld mice during parabiosis indicated that Fas-ligand has a direct role in the formation of bone phenotype of gld mice