Rituximab in relapsing and de novo MPO ANCA-associated vasculitis with severe renal involvement: a case series.

BACKGROUND: Antineutrophil cytoplasmic antibody associated vasculitis (AAV) is a group of diseases associated in most cases with the presence of anti-neutrophil cytoplasmic antibodies (ANCAs). Rituximab- based remission induction has been proven effective in ANCA associated vasculitis but scarce data exist in forms with severe renal involvement. In this case series, we report the outcomes in patients with de novo or recurrent MPO-AAV and severe renal involvement treated with rituximab without cyclophosphamide (CYC). METHODS: In this single centre retrospective study, we analysed patients with a clinical diagnosis of de novo or recurrent AAV who met the following criteria: detection of P-ANCA, creatinine clearance lower than 30 ml/min, induction of remission therapy with rituximab without concomitant CYC and a follow up period of at least 6 months. The primary outcomes were complete remission after induction therapy, renal function recovery and mortality after the induction treatment. RESULTS: Eight patients met the inclusion criteria. The M:F ratio was 1:7, the average age was 54 years old and the median follow up was 10 months (7-72); in 2 patients there was a MPA renal limited vasculitis. A renal biopsy was performed in 7 patients. The median BVAS score at rituximab induction was 14(range 6-21). Two patients required haemodialysis before the induction treatment. Four patients developed end stage renal disease (ESRD) that required haemodialysis. These data show a remission of the disease, associated with a stabilization of the kidney function in 50% of patients. In 3 patients who did not show a response, there was also no response to CYC. CONCLUSIONS: This study shows a partial efficacy of rituximab in renal function recovery and a low risk of infectious complications in patients with MPO vasculitis with severe renal involvement, in particular in the short term. The optimal treatment in this subgroup of patients still has to be established because data are lacking.

The efficacy of Italian guidelines in promoting oral health in children and adolescents.

AIM: The purpose of the study was to evaluate the efficacy of the guidelines on oral health published by the Italian Health Ministry. STUDY DESIGN: 1239 patients (582 girls and 657 boys) with a mean age of 4.46 (SD 2.81) years were evaluated before application of the guidelines by paediatricians (T0) for the presence of caries, gingivitis, diseases of the oral mucosa, and malocclusion. Only patients aged 6 months, 3 years, 6 years, and 9 years at T0 were taken into consideration. All patients were reevaluated after application of the ministerial guidelines (T1). METHODS: the study took place over a 3-year period. Enrolled patients referred to the outpatient clinics of three paediatricians of the Province of Genoa who strictly applied the ministerial guidelines. STATISTICS: Chi square test analysis was performed to evaluate a statistically significant decrease in the incidence of caries, gingivitis and diseases of the oral mucosa. RESULTS: After a 3-year follow-up collected data underlined a statistically significant decrease in the incidence of dental caries, gingivitis and oral mucosal diseases after implementation of the recommended ministerial guidelines. A statistically significant decrease of malocclusions was also evident in the elder patients (12 years old at T1). CONCLUSION: The accurate implementation of the Guidelines is supported. Only collaboration and increased synergy between paedodontists and paediatricians can fulfill the objectives which were the reason for publishing the "National guidelines for the promotion of oral health and the prevention of oral diseases in developmental age".

[Comparison of the training schemes of the specialization schools of the public health area: a rational basis for a proposal of a core curriculum for the university training programme contained in article 38 of Legislative Decree (D.Lgs) 81/2008]. / Confronto dei contenuti formativi delle scuole di specializzazione dell'Area di Sanità Pubblica: le basi razionali per una proposta di core curriculum per il percorso formativo universitario ex art. 38, D.Lgs 81/2008.

A document by the B. Ramazzini College of University Teachers of Occupational Medicine of the Italian Society of Occupational Health and Industrial Hygiene (S.I.M.L.I.I). The aim of this document was to compare the professional competence, training profile and core curricula of the three main specialization courses in the Public Health postgraduate medical area, i.e., Occupational Medicine, Hygiene and Preventive Medicine, and Forensic Medicine, such as contained in the Ministerial Decree (D.M) of 1 August 2005. We set out to identify, using clear and objective criteria, the knowledge and skills that specialists in Hygiene or Forensic Medicine must develop, in accordance with Art. 38 of the new Italian law on safety ahd health at work (D.Lgs 81/2008), in order to be authorized to perform occupational health activities as "Competent Physicians" (CP). The comparison revealed significant differences in structure and content among the three courses. In particular, compared to the course in Occupational Medicine, the courses in Hygiene and in Forensic Medicine both lack clinical training, including diagnostic and therapeutic skills, risk-oriented occupational health activities, biological monitoring, assessment of individual susceptibility, and clinical or instrumental procedures to prevent and detect occupational diseases. Furthermore, the specialization course in Hygiene lacks any training regarding the criteria and methods for assessing the individual worker's fitness for work, while the course in Forensic Medicine lacks any training in occupational risk assessment and management. From this comparison, a list was derived of the education and training debits that specialists in Hygiene or Forensic Medicine should cover (credits) in order to be authorized to perform CP activities as indicated by the new law. A core curriculum is proposed here, based on the corresponding credits, for use as a reference.

[Respiratory risk among students in an industrialized area of Sardinia: role of smoking and air pollution]. / Rischio respiratorio in studenti di un'area industrializzata della Sardegna: fumo di tabacco e inquinamento ambientale.

Among 273 students (age 11-16 years) living in two small towns located respectively 2 (Portoscuso) and 15 kilometres (S. Antioco) far from the industrial area of Portovesme, the respiratory risk associated to cigarette smoking and environmental pollution was evaluated by the ISAAC questionnaire and standardized spirometry. The prevalence of parent's smoking was high in both groups (66.3% and 59.4%). Smoking during pregnancy was reported by 15% of mothers, without significant differences between the two schools. The prevalence of smokers among students was similar comparing the two groups (7% vs 6%). The prevalence of asthma in the whole population was significantly associated to skin positivity to common allergens, to the familiarity for asthma and to the environmental tobacco smoking, particularly if maternal. Spirometric values were significantly lower among students living in Portoscuso than among those of the S. Antioco school, with an evident interaction between the residential factor and the tobacco smoking, active and/or passive, in reducing the forced end- expiratory flows. Our results support the significant role of tobacco smoking, active and passive, particularly if derived from maternal smoking during pregnancy, in increasing the prevalence of respiratory disorders and lowering lung function in children. Living in Portoscuso, because of higher environmental exposure to airborne pollutants of industrial origin, has been shown as a relevant factor further lowering the lung function among the studied sample.

[Environmental exposure to inorganic lead and neurobehavioural tests among adolescents living in the Sulcis-Iglesiente, Sardinia]. / Esposizione ambientale a piombo e test neuro- comportamentali in adolescenti del Sulcis-Iglesiente.

In several recent studies blood lead levels below 100 microg/L have been associated with reduced neurocognitive capacities and neurobehavioural performances in children, with no clear evidence of the lowest "safe" level not associated to adverse effects on the CNS. We analyzed blood lead concentration and the results of 5 neurocognitive tests, two derived from the Swedish Performance Evaluating System (SPES) and three from the Wechsler Intelligence Scale for Children-Revised (WISC-R), in 139 Sardinian adolescents living in Portoscuso, a town 2 Km far from a lead smelter, and in 72 age-matched students living in S. Antioco, a town about 15 Km far from the same smelter. The blood lead concentrations were lower than 100 microg/l in almost subjects, but, in average, significantly higher particularly among males, in the Portoscuso group compared to controls. The regression coefficients derived from the multivariate stepwise analysis, adjusted for the student's age and gender and for the educational and socio-economic level of parents, showed that reduced performances in neurocognitive test were significantly associated to increasing blood lead concentrations. According to previous our surveys in the same area and to the recent scientific literature on this topic, the present study suggests the need to further low the blood lead levels, considered by the U.S. CDC in 1991 as potentially "safe" for the children's CNS, to a threshold possibly < 50 microg/L.

Anemia and Immunosuppressive Regimen in Renal Transplanted Patients: Single-Center Retrospective Study.

We compared retrospectively the level of hemoglobin and the percentage of patients with anemia among 59 kidney transplant recipients receiving everolimus, cyclosporine, and corticosteroids and 128 treated with cyclosporine, mycophenolic acid, and corticosteroids. We also compared age at the time of transplantation, sex and ferritine, serum creatinine, creatinine clearance, folic acid, cyanocobalamine levels, use od recombinant erythropoietin, mean corpuscolar volume at the last ambulatory control. Statistical analysis included Student t test, χ(2) test, and logistic regression. The analysis was performed using SPSS software. We observed no difference in terms of hemoglobin levels in patients treated with everolimus (12.9 ± 1.6 vs 12.7 ± 1.5 g/dL). Anemia (defined as hemoglobin <13 g/dL in men and <12 g/dL in women, or need to use erythropoietin) was found in 49% and 45% of patients in the 2 groups respectively (P = .6). The other parameters evaluated were similar except for the mean corpuscular volume, which was significantly lower in the everolimus group. In the multivariate analysis only serum creatinine and estimated glomerular filtration rate influenced the level of hemoglobin. We observed no differences in terms of development of anemia in renal transplanted patients treated with everolimus-based regimen.

[Twinkling artifact in kidney stone disease]. / Arlecchino e la calcolosi urinaria.

BACKGROUND: Ultrasonography artifacts are false representations of the image caused by the interaction between the ultrasound and the tissues. The ability to identify artifacts is an important source of information that can help the clinician in performing a correct diagnosis. The twinkling artifact (called 'Effetto Arlecchino' by the Italians) consists of a series of colored pixels that appear inside, around and often along the shadow cone of the calculi. METHODS: We evaluated the clinical effectiveness of this artifact in the diagnosis of kidney stone disease. In 107 ultrasonography cases of hyperechogenic formations with clinical features of kidney stones, we used the color box to evoke the twinkling artifact. Of the 107 cases, 102 cases (95%) presented this artifact, while five cases did not. Moreover, this artifact was present in all urethral and bladder stones and in 62/67 kidney stone cases. CONCLUSIONS: In our experience, we found that the twinkling artifact is often positive in urinary stone disease, and the ability to identify it adds useful information to the diagnosis of urinary kidney stone disease.

[Neurobehavioural testing in lead smelter workers]. / Test neurocomportamentali in lavoratori esposti a piombo inorganico.

Several recent meta-analyses, although some inconsistencies between studies, provide evidence for subtle deficits in neurobehavioural tests being associated with average blood levels (PbB) between 350 and 600 microg/l and for significant correlations between impairments in some test results and increasing indices present andlor cumulative exposure to inorganic lead. In this study we assessed the relationship between blood lead level (PbB) and results of some neurobehavioural tests derived from the SPES battery and from the WAIS-R among a sample of 94 lead smelter workers (median PbB: 302 microg/l; range: 60-690 microg/l). The stepwise multiple regression analysis shows that, even after adjusting for age, education level, score in the vocabulary test and for alcohol and cigarette consumption, the rise of PbB above 300 microg/l was significantly associated with the rise in the number of errors and in the response time of the Symbol Digit test. No significant relationship between PbB and results of the other tests was observed after adjusting for the main confounding factors. Despite the small size of this study and the few number of neurobehavioural tests applied, our results are suggestive for suble potential neurotoxic effects of inorganic lead even at the present exposure levels found in the studied sample of smelter workers and support the ACGIH BEI and the SCOEL recommendation for a biological limit of 300 microg/l of PbB.

[Study on mortality by specific cause among workers at a lead and zinc foundry in Sardinia]. / Studio di mortalità per cause specifiche in lavoratori di una fonderia di piombo e zinco della Sardegna.

The mortality of 918 Sardinian lead-smelter workers followed between 1972 and 2001 is reported. The assessment of individual exposure to inorganic lead was based on several environmental and blood lead measurements available, for each department and task, between 1985 and 2001. The mortality for all cancers was within the expected numbers (SMR 1.01, n 108). Even if not statistically significant, the mortality for gastric cancer (SMR 1.22, n 4), for lung cancer (SMR 1.21, n 18) and for lymphomas and leukaemias (SMR 1.82, n 6) was higher than that expected from the regional rates during the follow-up. Only for the lung cancer mortality a statistically significant upward trend with increasing categories of lead exposure was observed (SMR 1.96, 95% CI 1.02-3.68 for the highest exposure group). Our study, even if of small size, suggests an association between occupational exposure to inorganic lead and lung cancer risk.

[Lead: indicators of dose and effects on heme]. / Piombo: indicatori di dose e di effetto sull'eme.

In the present study the role of the traditional biomarkers of exposure and effect on haeme system during lead exposure was analysed: the opportunity of introducing new biomarkers such as lead and delta-aminolevulinic acid in plasma was also evaluated, especially by considering the current levels of exposure. The population in study was constituted by 371 males owning to different production fields and selected by five national units. The results suggest caution in the use of lead in plasma as a biomarker of lead exposure in the biological monitoring procedures, mainly in reason of its great variability affecting in particular the sampling time and the pre-analytical treatment of the sample. The other biomarkers were well correlated between them and with the exposure biomarkers for lead in blood >300 microg/L, suggesting the BEI to which the protection of workers exposed to lead would be guaranteed (instead the actual of 600 microg/L).