Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy: Reducing Variability in Practice through a Collaborative Telemedicine Initiative.

OBJECTIVE: This study aimed to assess the viability of implementing a tele-educational training program in neurocritical care for newborns diagnosed with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia (TH), with the goal of reducing practice variation. STUDY DESIGN: Prospective study including newborns with HIE treated with TH from 12 neonatal intensive care units in Brazil conducted from February 2021 to February 2022. An educational intervention consisting of 12 biweekly, 1-hour, live videoconferences was implemented during a 6-month period in all centers. Half of the centers had the assistance of a remote neuromonitoring team. The primary outcome was the rate of deviations from TH protocol, and it was evaluated during a 3-month period before and after the intervention. Logistic regression via generalized estimating equations was performed to compare the primary and secondary outcomes. Protocol deviations were defined as practices not in compliance with the TH protocol provided. A subanalysis evaluated the differences in protocol deviations and clinical variables between centers with and without neuromonitoring. RESULTS: Sixty-six (39.5%) newborns with HIE were treated with TH during the preintervention period, 69 (41.3%) during the intervention period and 32 (19.1%) after intervention. There was not a significant reduction in protocol deviations between the pre- and postintervention periods (37.8 vs. 25%, p = 0.23); however, a decrease in the rates of missing Sarnat examinations within 6 hours after birth was seen between the preintervention (n = 5, 7.6%) and postintervention (n = 2, 6.3%) periods (adjusted odds ratio [aOR]: 0.36 [0.25-0.52], p < 0.001). Centers with remote neuromonitoring support had significantly lower rates of seizures (27.6 vs. 57.5%; aOR: 0.26 [0.12-0.55], p < 0.001) and significant less seizure medication (27.6 vs. 68.7%; aOR: 0.17 [0.07-0.4], p < 0.001). CONCLUSION: This study shows that implementing a tele-educational program in neonatal neurocritical care is feasible and may decrease variability in the delivery of care to patients with HIE treated with TH. KEY POINTS: · Neurocritical care strategies vary widely in low- and middle-income countries.. · Heterogeneity of care may lead to suboptimal efficacy of neuroprotective strategies.. · Tele-education and international collaboration can decrease the variability of neurocritical care provided to infants with HIE..

Impact of different evaluation methods for diagnostic tasks in panoramic radiography / Impacto de diferentes métodos de evaluación durante el diagnóstico en la radiografía panorámica

Abstract The aim of this study was to evaluate the observers diagnostic performance in panoramic radiography using monitor, tablet, X-ray image view box, and against window daylight as a visualization method in different diagnostic tasks. Thirty panoramic radiography were assessed by three calibrated observers for each visualization method, in standardized light conditions, concerning dental caries, widened periodontal ligament space, and periapical bone defects from the four first molars; mucosal thickening and retention cysts in maxillary sinus; and stylo-hyoid ligament calcification and atheroma. A five-point confidence scale was used. The standard-reference was performed by two experienced observers. Diagnostic values using window light were significantly lower for caries and periapical bone defect and retention cyst, stylo-hyoid ligament calcification detection (p<0.05). For atheroma detection, X-ray image view box, tablet, and widow light had lower accuracy than the evaluation on the monitor (p<0.05). Observers diagnostic performances are worsened using window light as an evaluation method for panoramic radiography for dental, sinus, and calcification disorders, while the monitor was the most reliable method.

Resumen El objetivo de este estudio fue evaluar el desempeño diagnóstico de los observadores en la radiografía panorámica utilizando monitor, tablet, caja de visualización de imágenes de rayos X y contra la luz del día de la ventana como método de visualización en diferentes tareas de diagnóstico. Treinta radiografías panorámicas fueron evaluadas por tres observadores calibrados para cada método de visualización, en condiciones de luz estandarizadas, con respecto a caries dental, espacio del ligamento periodontal ensanchado y defectos óseos periapicales de los cuatro primeros molares; engrosamiento de la mucosa y quistes de retención en el seno maxilar; y calcificación y ateroma del ligamento estilohioideo. Se utilizó una escala de confianza de cinco puntos. La referencia estándar fue realizada por dos observadores experimentados. Los valores diagnósticos con luz de ventana fueron significativamente menores para caries y defecto óseo periapical y quiste de retención, detección de calcificación del ligamento estilohioideo (p <0.05). Para la detección de ateroma, la caja de visualización de imágenes de rayos X, el tablet y la luz de viuda tuvieron una precisión menor que la evaluación en el monitor (p <0.05). El rendimiento diagnóstico del observador empeora al utilizar la luz de la ventana como método de evaluación de la radiografía panorámica para los trastornos dentales, de los senos nasales y de la calcificación, mientras que el monitor fue el método más fiable.

Incidental finding of bullous concha by cone beam computed tomography / Hallazgo incidental de concha bullosa por tomografía computarizada de haz cónico

Abstract This study aimed to describe the imaging aspects of a concha bullosa discovered incidentally by means of cone-beam computed tomography (CBCT) imaging. A female patient underwent a CBCT exam, and a bilateral extensive pneumatization of the middle concha was verified, presenting a larger dimension of the right side and a deviated septum. The patient reported nasal obstruction and loss of smell. The CBCT for covering the maxillofacial region allowed the discovery of this incidental finding, allowing the patient to be referred for appropriate treatment.

Resumen Este estudio tuvo como objetivo describir los aspectos imaginológicos de una concha bullosa hallada incidentalmente por medio de imágenes de tomografía computarizada de haz cónico (TCHC). Una paciente de sexo femenino fue sometida a examen de TCHC y se verificó una neumatización extensa bilateral de la concha media, presentando una mayor dimensión del lado derecho, asi como desvío del tabique. El paciente refirió obstrucción nasal y pérdida del olfato. La TCHC de la región maxilofacial permitió localizar este hallazgo incidental, permitiendo derivar al paciente para el tratamiento adecuado.

Safety indicators of a novel multi supplement based on guarana, selenium, and L-carnitine: Evidence from human and red earthworm immune cells.

Neurodegenerative diseases are associated with chronic inflammatory states. There is evidence to support the design of novel supplements based on guarana (G) (Paullinia cupana), selenium (S), and L-carnitine (C), the use of which, potentially attenuates neuro oxi-inflammatory conditions. Therefore, this study analyzed the cytotoxic and redox effects of GSC on human leucocytes, the inflammatory activation of microglia BV-2 cells, and effect on mortality, oxidative metabolism, and the immune modulation of red earthworms (Eisenia fetida). The GSC concentrations tested in cell culture were in the range of 0.04-2.1 mg/mL. All the GSC-supplemented samples tested, reverted H2O2 oxidation in DNA molecules, suggesting its genoprotective potential. GSC did not induce mortality in leucocyte cultures. On the contrary, a reduction in the levels of oxidation of lipids, proteins, and cell apoptosis was observed, via downregulation of caspase 3 and 8 genes. GSC showed a dual effect on microglia, decreasing the cellular proliferation at lower concentrations (<0.24 mg/mL) and increasing the cellular proliferation mainly at concentrations > 1.0 mg/mL. GSC did not have a toxic effect on red earthworms, but induced an increase in amoebocyte cells and in brown body formation, indicating immune response activation. The results suggest that GSC could be safe for human consumption.

Does dose optimisation in digital panoramic radiography affect diagnostic performance?

OBJECTIVES: To compare the overall diagnostic performance of digital panoramic radiographs obtained with low-dose protocols and to estimate the absorbed dose in the head and neck. MATERIALS AND METHODS: Forty-eight panoramic radiographs were obtained from eight imaging phantoms using six exposure protocols of progressively lower tube voltages (kVp) and currents (mA), as follows: (1) 70 kVp and 12.5 mA, (2) 66 kVp and 10 mA, (3) 66 kVp and 8 mA, (4) 66 kVp and 5 mA, (5) 66 kVp and 4 mA and (6) 66 kVp and 3.2 mA. Five oral radiologists independently evaluated the images and reported all detectable radiographic findings. Intra-examiner reproducibility was assessed by re-evaluation of 25% of the images. The data were analysed using the McNemar and weighted Kappa tests. Absorbed doses of the six protocols were obtained from thermoluminescent dosimeters placed inside a Rando phantom and compared using one-way ANOVA with post hoc Tukey (α = 0.05). RESULTS: The overall diagnostic performance of panoramic radiographs obtained with low-dose protocols did not differ from that of panoramic radiographs obtained with the highest dose (p > 0.05). Moreover, substantial agreement was observed between all protocols. Protocol 1 resulted in the highest absorbed dose and protocols 4, 5 and 6 in the lowest absorbed doses, with the difference being significant (p ≤ 0.05). CONCLUSION: Although digital panoramic radiography is considered a relatively low-dose examination, the radiation dose can be further reduced without negatively affecting its overall diagnostic performance. CLINICAL RELEVANCE: Considering the risks associated with X-rays, digital panoramic radiographs can be obtained at even lower exposure levels.

Impact of micro-computed tomography reconstruction protocols on bone microarchitecture analysis.

OBJECTIVE: The aim of this study was to assess the influence of reconstruction protocols of micro-computed tomography (micro-CT) images on analyses of bone microarchitecture. STUDY DESIGN: Micro-CT images of the maxillae of 5 Wistar rats were reconstructed with different protocols by varying the levels of the following tools: smoothing filter (SF; 2-6); ring artifact correction (RAC; 5-15); and beam hardening correction (BHC; 15%-60%). A control protocol (P0; without any correction tool) and a standard protocol (SP; according to the manufacturer's recommendation: SF = 2; RAC = 5; BHC = 45%) were also obtained. For each protocol, 8 bone microarchitecture parameters were calculated (bone volume/total volume [BV/TV], bone surface/total volume [BS/TV], trabecular number [Tb.N], trabecular thickness [Tb.Th], trabecular separation [Tb.Sp], degree of anisotropy [DA], connectivity density [Conn.D], and total porosity [Po-tot]) by using CTAn software. Test protocols were compared with the SP by using 1-way analysis of variance and the Dunnet post hoc test (α = 0.05). RESULTS: An inverse relationship was observed between BHC tool levels and all microarchitecture parameters except BV/TV and Tb.Th. The combination of BHC and SF significantly influenced all microarchitecture parameters except for DA, for which all protocols were similar to the SP (P > .05). CONCLUSIONS: Calculation of bone microarchitecture parameters is influenced by the applied levels of artifact correction tools, mainly BHC and SF. It is necessary to standardize such tool levels for correct data interpretation.

Single Hepatocellular Carcinoma approached by curative-intent treatment: A propensity score analysis comparing radiofrequency ablation and liver resection.

INTRODUCTION: Patients with a single small Hepatocellular Carcinoma (HCC) may be definitively treated by Radiofrequency ablation (RFA) with a very low rate of peri-operative morbidity. However, results are still controversial comparing RFA to Liver Resection (LR). METHODS: All consecutive patients treated by RFA or LR for a single untreated small HCC on liver cirrhosis between January 2006-December 2016 were enrolled. Patients were matched 1:1 basing on: age, MELD-score, platelet count, nodule's diameter, HCV status, α-fetoprotein level, and Albumin-Bilirubin score. First analysis compered LR to RFA. Second analysis compared Laparoscopic LR (LLR) to RFA. RESULTS: Of 484 patients with single small HCC, 91 patients were selected for each group after a 1:1 propensity score matching (PS-M). The 5-years OS was 70% and 60% respectively for LR and RFA group (P = 0.666). The 5-year RFS was 36% and 21% respectively for LR and RFA group (P < 0.001). Patients treated by LR had a significantly longer hospital stay and higher complications rate. Comparing 50 cases of LLR and 50 of RFA, the 5-years OS was 79% and 56% respectively for LLR and RFA group (P = 0.22). The 5-year RFS was 54% and 19% respectively for LR and RFA group (P < 0.001). Post-operative complications were not significantly different. CONCLUSIONS: LLR confers similar peri-operative complications rate compared to RFA. LLR should be considered as a first-line approach for the treatment of a single small HCC as it combines the effectiveness of open LR and the safety profile of RFA.

Assessing pulp stones by cone-beam computed tomography.

OBJECTIVES: The aim of this study was to evaluate the occurrence of pulp stones by cone-beam computed tomography (CBCT) and to correlate their prevalence with patient's gender, location of tooth (right or left of maxillary or mandibular arch), group of teeth, and restorations. MATERIALS AND METHODS: CBCT images of 382 patients randomly selected from the database of the University Oral Radiology Department were retrospectively examined. A total of 2833 tooth images obtained using the i-CAT 3D Imaging System were evaluated. Image analysis was performed with the i-CAT software, and all teeth were evaluated in sagittal, axial, and coronal views. All the measurements were subjected to chi square test, odds ratio, and Fisher's exact tests (p < 0.05). RESULTS: The prevalence of pulp stones was similar between patient's genders and tooth locations. Pulp stones were detected in 31.9% of patients and 9.5% of teeth. Maxillary and mandibular molars were the groups of teeth with the highest frequency of pulp stones. The presence of restorations increased the chance of occurrence of pulp stones by 2.1 times in all teeth examined (p < 0.0001) and by 4.7 times in maxillary teeth (p < 0.0001). CONCLUSIONS: Pulp stones had a high prevalence with molar teeth showing the highest prevalence. The presence of restorations increased the chance of occurrence of these calcifications, specifically in maxillary teeth. CLINICAL RELEVANCE: CBCT provides accurate anatomical details in three dimensions, offering the possibility to view an individual tooth in axial, sagittal, and coronal views. This study performed an investigation of the occurrence of pulp stones by CBCT.

7th International Immunoglobulin Conference: Immunomodulation.

Immunomodulation uses synthetic, natural and recombinant preparations to modify the immune response to a desired level, typically to treat specific autoimmune diseases, as will be discussed in this section. Rheumatoid arthritis (RA) is a common systemic autoimmune disease, affecting 1% of the population worldwide. Currently, a first-line disease-modifying therapy for RA is methotrexate; however, more than 40 monoclonal antibodies are in use or under investigation for the treatment of RA. This panoply of biological disease-modifying agents means that clinicians can make use of drugs with different mechanisms of action should one type become ineffective. In autoimmune pemphigus conditions, identification of pathogenic autoantibodies against intercellular cadherin desmoglein 1 and/or 3 antigens is one of the criteria for appropriate diagnosis. In pemphigoid conditions, autoantibodies are directed against bullous pemphigoid antigens BP230 and BP180, and in both types of immunobullous disease intravenous immunoglobulin (IVIg), as adjuvant therapy in combination with a cytotoxic drug, is effective in reducing autoantibody levels, disease severity and background steroid use. Further studies are required to establish the role of monoclonal antibodies in the treatment of autoimmune bullous disease. IVIg may also be effective in another at-risk population with autoimmune disease, namely secondary recurrent miscarriage (RM). However, the mechanism of action of IVIg in secondary RM is largely unknown, although levels of natural killer cell biomarkers, particularly CD56(+) , have been shown to decline after IVIg treatment. Data from meta-analyses of heterogeneous placebo-controlled trials indicate that IVIg may be effective in secondary RM, but most trials to date have used immunomodulatory doses lower than those considered to be efficient in autoimmune disease. The results of a recently completed study may help to address this question.

7th International Immunoglobulin Conference: Immunomodulation.

Rheumatoid arthritis (RA) is a debilitating autoimmune disease that is usually treated aggressively to slow the rate of joint destruction. The therapeutic strategy used at the French centre, described here, is to use the non-biological disease-modifying drug, methotrexate, as first-line therapy and to add biological agents as second-line treatment. The two other autoimmune diseases discussed in this session were immunobullous skin diseases, and secondary recurrent miscarriage (RM). In the former conditions, low levels of pathogenic autoantibodies can be achieved with adjuvant intravenous immunoglobulin (IVIg) therapy, usually in combination with an immunosuppressant. Secondary RM has an autoimmune basis, as shown by high tumour necrosis factor (TNF)-α levels and specific human leucocyte antigen (HLA) polymorphisms. Although the mechanism is not yet known, IVIg may also be an effective treatment, despite the generally low doses used in published studies.

Resistance or sensitivity of Wilms' tumor to anti-FZD7 antibody highlights the Wnt pathway as a possible therapeutic target.

Wilms' tumor (WT), the most frequent renal solid tumor in children, has been linked to aberrant Wnt signaling. Herein, we demonstrate that different WTs can be grouped according to either sensitivity or resistance to an antibody (Ab) specific to frizzled7 (FZD7), a Wnt receptor. In the FZD7-sensitive WT phenotype, the Ab induced cell death of the FZD7(+) fraction, which in turn depleted primary WT cultures of their clonogenic and sphere-forming cells and decreased in vivo proliferation and survival on xenografting to the chick chorio-allantoic-membrane. In contrast, FZD7-resistant WT in which no cell death was induced showed a different intra-cellular route of the Ab-FZD7 complex compared with sensitive tumors and accumulation of ß-catenin. This coincided with a low sFRP1 and DKK1 (Wnt inhibitors) expression pattern, restored epigenetically with de-methylating agents, and lack of ß-catenin or WTX mutations. The addition of exogenous DKK1 and sFRP1 to the tumor cells enabled the sensitization of FZD7-resistant WT to the FZD7 Ab. Finally, although extremely difficult to achieve because of dynamic cellular localization of FZD7, sorting of FZD7(+) cells from resistant WT, showed them to be highly clonogenic/proliferative, overexpressing WT 'stemness' genes, emphasizing the importance of targeting this fraction. FZD7 Ab therapy alone or in combination with Wnt pathway antagonists may have a significant role in the treatment of WT via targeting of a tumor progenitor population.

The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide.

OBJECTIVE: To update the follow-up of the Euro-Lupus Nephritis Trial (ELNT), a randomised prospective trial comparing low-dose (LD) and high-dose (HD) intravenous (IV) cyclophosphamide (CY) followed by azathioprine (AZA) as treatment for proliferative lupus nephritis. PATIENTS AND METHODS: Data for survival and kidney function were prospectively collected during a 10-year period for the 90 patients randomised in the ELNT, except in 6 lost to follow-up. RESULTS: Death, sustained doubling of serum creatinine and end-stage renal disease rates did not differ between the LD and HD group (5/44 (11%) vs 2/46 (4%), 6/44 (14%) vs 5/46 (11%) and 2/44 (5%) vs 4/46 (9%), respectively) nor did mean serum creatinine, 24 h proteinuria and damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. After 10 years of follow-up, the positive predictive value for a good outcome of an early drop in proteinuria in response to initial immunosuppressive therapy was confirmed. CONCLUSION: The data confirm that a LD IVCY regimen followed by AZA-the "Euro-Lupus regimen"-achieves good clinical results in the very long term.

6th International Immunoglobulin Symposium: poster presentations.

The posters presented at the 6th International Immunoglobulin Symposium covered a wide range of fields and included both basic science and clinical research. From the abstracts accepted for poster presentation, 12 abstracts were selected for oral presentations in three parallel sessions on immunodeficiencies, autoimmunity and basic research. The immunodeficiency presentations dealt with novel, rare class-switch recombination (CSR) deficiencies, attenuation of adverse events following IVIg treatment, association of immunoglobulin (Ig)G trough levels and protection against acute infection in patients with X-linked agammaglobulinaemia (XLA) and common variable immunodeficiency (CVID), and the reduction of class-switched memory B cells in patients with specific antibody deficiency (SAD). The impact of intravenous immunoglobulin on fetal alloimmune thrombocytopenia, pregnancy and postpartum-related relapses in multiple sclerosis and refractory myositis, as well as experiences with subcutaneous immunoglobulin in patients with multi-focal motor neuropathy, were the topics presented in the autoimmunity session. The interaction of dendritic cell (DC)-SIGN and alpha2,6-sialylated IgG Fc and its impact on human DCs, the enrichment of sialylated IgG in plasma-derived IgG, as wells as prion surveillance and monitoring of anti-measles titres in immunoglobulin products, were covered in the basic science session. In summary, the presentations illustrated the breadth of immunoglobulin therapy usage and highlighted the progress that is being made in diverse areas of basic and clinical research, extending our understanding of the mechanisms of immunoglobulin action and contributing to improved patient care.

Risk factors for Sjögren's syndrome: a case-control study.

OBJECTIVE: The aim of this study was to investigate potential risk factors for Sjögren's syndrome (SS) by means of a multi-centre case-control study, focusing in particular on familial and environmental risk factors. 140 female SS patients and 109 female controls with orthopaedic problems were consecutively enrolled in seven university hospitals in Italy. METHODS: Information regarding the patient's lifestyle, her medical, menstrual and pregnancy history, and any family history of autoimmune diseases (AD) was obtained through a detailed structured questionnaire. The odds ratio (OR) and 95% confidence interval (95%CI) were calculated using unconditional logistic regression, adjusting for age and family size. The probability of first-degree relatives developing an autoimmune disease was also investigated. RESULTS: A positive family history of AD was significantly associated with SS. Subjects with a first-degree relative (FDR) with AD showed a seven-fold increase in the risk for SS compared to controls (OR=7.4, 95%CI 2.8-20.1); the strength of this association increased with the number of relatives affected. Similarly, the FDR of SS patients had a higher risk of AD in comparison to subjects without FDR affected by SS. Women with one or more pregnancies had an increased risk of SS (OR=2.1, 95%CI 1.0-4.3). CONCLUSION: This study suggests that a family history of AD is associated with SS.

Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium--the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Two single-nucleotide polymorphisms in the 5' and 3' ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus.

OBJECTIVE: To test the association of osteopontin (OPN) polymorphisms with systemic lupus erythematosus (SLE). METHODS: The coding 5' and 3' flanking regions of the OPN gene were scanned for polymorphisms by denaturing high-performance liquid chromatography. A case-control association study was performed in 394 Italian SLE patients and 479 matched controls. OPN serum levels were determined by enzyme-linked immunosorbent assay in 40 patients and 124 controls, and the mean levels were compared between the different OPN genotypes. RESULTS: Among the 13 detected single-nucleotide polymorphisms (SNPs), alleles -156G (frequency 0.714 versus 0.651; P = 0.006, corrected P [P(corr)] = 0.036) and +1239C (0.377 versus 0.297; P = 0.00094, P(corr) = 0.0056) were significantly increased in the SLE patients compared with the controls. The presence of the associated allele in single or double dose conferred an odds ratio (OR) of 2.35 (95% confidence interval [95% CI] 1.38-4.02) for SNP -156 and an OR of 1.57 (95% CI 1.16-2.13) for SNP +1239. These effects were independent of each other, i.e., not a consequence of linkage disequilibrium between the 2 alleles. The risk associated with a double dose of susceptibility alleles at both SNPs was 3.8-fold higher (95% CI 2.0-7.4) relative to the complete absence of susceptibility alleles. With regard to individual clinical and immunologic features, a significant association was seen between lymphadenopathy and -156 genotypes (overall P = 0.0011, P(corr) = 0.046). A significantly increased OPN serum level was detected in healthy individuals carrying +1239C (P = 0.002), which is indicative of an association between the SLE susceptibility allele and OPN levels. CONCLUSION: These data suggest the independent effect of a promoter (-156) and a 3'-untranslated region (+1239) SNP in SLE susceptibility. We can speculate that these sequence variants (or others in perfect linkage disequilibrium) create a predisposition to high production of OPN, and that this in turn may confer susceptibility to SLE.

Long term effectiveness of intravenous immunoglobulin in Churg-Strauss syndrome.

OBJECTIVE: To study the long term effectiveness of intravenous immunoglobulin and plasmapheresis associated with prednisone and cyclophosphamide in Churg-Strauss syndrome. SUBJECTS: and methods: We studied 18 subjects with new onset Churg-Strauss syndrome. All received the "standard" treatment based on prednisone (1 mg/kg/day for 1 month and then slowly tapered) and cyclophosphamide (2 mg/kg/day for 6 months in severe cases). In nine patients, synchronised cycles with plasmapheresis and intravenous immunoglobulin (2 g/kg) were repeated monthly for 6 months and every other month for a further three cycles. Clinical (disease activity monitored by Birmingham vasculitis activity score (BVAS) and damage index (modified Rankin score)) and functional (C reactive protein, blood eosinophil count, and electromyogram-electoneurogram) parameters were collected during treatment and the 3 year follow up period. RESULTS: After 12 months, all patients in the treatment group and four (44%) in the control group were in remission. At the end of the 3 year follow up period, we documented significant differences in BVAS (p<0.01), global damage (p<0.02), modified Rankin score (p<0.04), and the daily maintenance prednisone dose (p<0.002) between the two groups. We found a tendency towards lower frequency of relapse and incidence of osteoporosis in the treatment group. CONCLUSION: Complete clinical and functional recovery with a long term stable remission and a low incidence of side effects can be achieved by intravenous immunoglobulin associated with plasmapheresis in patients with Churg-Strauss syndrome.

Familial autoimmunity as a risk factor for systemic lupus erythematosus and vice versa: a case-control study.

The objective of this multicentric case-control study was to investigate if a history of autoimmune disease (AD) in first-degree relatives (FDR) is a risk factor for systemic lupus erythematosus (SLE) and to evaluate the risk of AD among FDR of SLE patients. Cases were Italian SLE patients consecutively enrolled. Controls were orthopaedic inpatients without any autoimmune diseases. The strength of the association between family history of AD and SLE was measured as an odds ratio (OR) calculated from the coefficient of an unconditional regression model. To calculate the risk of AD among FDR of SLE patients, the extended generalized estimating equation technique was used. In total, 154 SLE cases and 140 controls were enrolled. A family history of AD was reported by 22.7% of SLE patients and by 5.7% of the controls. The risk of SLE increased with the number of FDR with AD (one FDR affected, OR = 4.1; two or more, OR = 11.3). The probability of having AD was higher among FDR of SLE cases in comparison to FDR of controls (RR = 4.6; 95%CI 1.9-11.1). A female SLE patient conferred an increased risk of AD to her FDR; this risk is doubled in females (OR 10.3; 95% CI 3.1-34.4).

Heterogeneity of the humoral anti-HCV/E2 response in persistently infected patients as demonstrated by divergent patterns of inhibition of the binding of anti-HCV/E2 human monoclonal antibodies.

A complete understanding of the molecular features of humoral immune response could be of pivotal importance in the management of persistent viruses as HCV. In this study, 24 HCV-positive samples, characterized by classical virological parameters, are evaluated using a new assay for the quantitation of antibody subpopulations directed against discrete epitopes on surface glycoprotein E2, a key viral protein. The results, besides confirming the usefulness of this new approach, highlight the extreme heterogeneity of anti-HCV/E2 response as far as single epitopes are concerned. The specific epitopes under study are also demonstrated to be widely shared among different genotypes.