Evaluation of VITEK® 2 AST cards (AST-N376 and AST-N397) for susceptibility testing of challenging Gram negatives.

Due to the increasing diffusion of MDR/XDR Gram-negatives it is necessary to offer reliable antibiotic susceptibility testing (AST), which also include new drugs. Here we evaluated the performances of the VITEK®2 AST-N376 and the AST-N397 cards. A collection of 180 clinical Gram-negative bacteria, producing relevant resistance mechanisms, were tested using VITEK 2 and MERLIN, in parallel. Discrepancies between the 2 systems were solved by the reference broth microdilution method. The workflow timing of the VITEK®2 system was also assessed. Overall, the VITEK®2 cards proved to be reliable in determining AST for the molecules evaluated, even if compliance with ISO acceptance criteria for accuracy assessment was not reached for some combinations and showed a short hands-on time for panels preparation. In conclusion, VITEK®2 is a valid system that ensures accurate results for AST of the molecules evaluated in this study and speeds up the workflow in the laboratory of diagnostic microbiology.

Neurological manifestations of Kawasaki disease and multisystem inflammatory syndrome in children associated with COVID-19: A comparison of two different clinical entities.

Kawasaki disease (KD) is one of the most frequent idiopathic vasculitis in children, affecting medium- and small-sized vessels. Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 has recently emerged as a new systemic hyperinflammatory condition affecting children some weeks after an acute COVID-19 infection. KD and MIS-C share different aspects and differ in many others: patients affected by MIS-C are usually older, with prominent gastrointestinal manifestations, diffuse adenopathy, extensive conjunctivitis, myocardial damage, leukopenia, and thrombocytopenia at the laboratory exams. Both conditions can present neurological complications. The aim of this manuscript is to provide a narrative review of neurological involvement in KD and MIS-C. A comprehensive review literature has been performed, and the main clinical features have been analyzed, contributing to neurological differential diagnosis.

Rapid microbiological tests for bloodstream infections due to multidrug resistant Gram-negative bacteria: therapeutic implications.

BACKGROUND: Treating severe infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB) is one of the most important challenges for clinicians worldwide, partly because resistance may remain unrecognized until identification of the causative agent and/or antimicrobial susceptibility testing (AST). Recently, some novel rapid test for identification and/or AST of MDR-GNB from positive blood cultures or the blood of patients with bloodstream infections (BSIs) have become available. OBJECTIVES: The objective of this narrative review is to discuss the advantages and limitations of different rapid tests for identification and/or AST of MDR-GNB from positive blood cultures or the blood of patients with BSI, as well as the available evidence on their possible role to improve therapeutic decisions and antimicrobial stewardship. SOURCES: Inductive PubMed search for publications relevant to the topic. CONTENT: The present review is structured in the following way: (a) rapid tests on positive blood cultures; (b) rapid tests directly on whole blood; (c) therapeutic implications. IMPLICATIONS: Novel molecular and phenotypic rapid tests for identification and AST show the potential for favourably influencing patients' outcomes and results of antimicrobial stewardship interventions by reducing both the time to effective treatment and the misuse of antibiotics, although the interpretation about their impact on actual therapeutic decisions and patients' outcomes is still complex. Factors such as feasibility and personnel availability, as well as the detailed knowledge of the local microbiological epidemiology, need to be considered very carefully when implementing novel rapid tests in laboratory workflows and algorithms. Providing high-level, comparable evidence on the clinical impact of rapid identification and AST is becoming of paramount importance for MDR-GNB infections, since in the near future rapid identification of specific resistance mechanisms could be crucial for guiding rapid, effective, and targeted therapy against specific resistance mechanisms.

Variable performance of different commercial systems for testing carbapenem susceptibility of KPC carbapenemase-producing Escherichia coli.

OBJECTIVES: The aim was to evaluate different methods for testing carbapenem susceptibility of Escherichia coli producing KPC-type carbapenemase. METHODS: Susceptibility to imipenem, meropenem and ertapenem was assayed using the reference broth microdilution method and several commercial methods (Vitek2, MicroScan, Etest, MIC Test Strip) starting from the same bacterial suspension. Susceptibility to imipenem and meropenem was also tested by Sensititre and disc diffusion (Bio-Rad). Results were interpreted according to EUCAST clinical breakpoints. Essential agreement (EA), category agreement (CA) and error rates were calculated as described by the International Organization for Standardization (ISO) guidelines and also considering the new EUCAST definitions. Genotypic diversity of isolates was evaluated with a RAPD profiling protocol. RESULTS: Of 54 KPC-positive E. coli isolates, 5.6%, 7.4% and 0% were susceptible standard dosing regimen (S), 55.6%, 72.2% and 0% susceptible increased exposure (I), and 38.9%, 20.4% and 100.0% resistant (R) to imipenem, meropenem and ertapenem, respectively, using the reference broth microdilution method. CA lower than 90% were observed with all systems for imipenem and meropenem using both the ISO and the modified EUCAST criteria. With ertapenem, CA >90% was observed with all methods except Vitek2. RAPD profiling revealed a remarkable genotypic diversity of the isolates, supporting that results were not biased by an oligoclonal nature of the collection. CONCLUSIONS: Commercial methods can be unreliable for testing susceptibility to carbapenems of KPC-producing E. coli. Susceptibility should be confirmed by reference broth microdilution.

Diversity of the epidemiology of carbapenemase-producing Enterobacteriaceae in long-term acute care rehabilitation settings from an area of hyperendemicity, and evaluation of an intervention bundle.

BACKGROUND: Long-term acute care rehabilitation facilities (LTACRFs) are affected by carbapenem-resistant Enterobacteriaceae (CRE) in endemic areas. However, the contribution of different subpopulations of patients has not been investigated in these settings. AIM: To study the epidemiology of CRE in an LTACRF, and the effect of an infection control intervention. METHODS: A surveillance programme was implemented in a large Italian LTACRF. The intervention included screening for CRE carriage at admission and weekly (for negative patients), and enforcement of contact precautions plus cohorting (in wards and rehabilitation areas) for presumed and confirmed carriers. Prevalence and incidence of CRE colonization and the number of CRE bacteraemias were monitored over one year. FINDINGS: Overall, 1084 patients underwent screening (adherence 89.8%). At admission, 11.6% of patients were colonized, and 9.9% of those negative at admission subsequently became colonized. These percentages were significantly higher among patients with severe brain injuries (SBIs) who were exposed to a higher intensity of care (44.1% vs 8.6% and 63.5% vs 6.8%, respectively). The majority of CRE bacteraemias occurred in the SBI ward. The intervention was associated with a decline in the incidence of CRE colonization in the SBI ward (from 17.7 to 7.2 acquisitions/100 at-risk patient-weeks), but not in other wards. All CRE isolates were Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. CONCLUSIONS: A peculiar CRE epidemiology was observed in a LTACRF from Italy, with very high rates of carriage and cross-transmission in SBI patients. A simplified infection control bundle was effective at reducing the incidence of CRE colonization in the SBI ward.

A simple phenotypic method for screening of MCR-1-mediated colistin resistance.

OBJECTIVES: To evaluate a novel method, the colistin-MAC test, for phenotypic screening of acquired colistin resistance mediated by transferable mcr-1 resistance determinants, based on colistin MIC reduction in the presence of dipicolinic acid (DPA). METHODS: The colistin-MAC test consists in a broth microdilution method, in which colistin MIC is tested in the absence or presence of DPA (900 µg/mL). Overall, 74 colistin-resistant strains of Enterobacteriaceae (65 Escherichia coli and nine other species), including 61 strains carrying mcr-1-like genes and 13 strains negative for mcr genes, were evaluated with the colistin-MAC test. The presence of mcr-1-like and mcr-2-like genes was assessed by real-time PCR and end-point PCR. For 20 strains, whole-genome sequencing data were also available. RESULTS: A ≥8-fold reduction of colistin MIC in the presence of DPA was observed with 59 mcr-1-positive strains, including 53 E. coli of clinical origin, three E. coli transconjugants carrying MCR-1-encoding plasmids, one Enterobacter cloacae complex and two Citrobacter spp. Colistin MICs were unchanged, increased or at most reduced by twofold with the 13 mcr-negative colistin-resistant strains (nine E. coli and four Klebsiella pneumoniae), but also with two mcr-1-like-positive K. pneumoniae strains. CONCLUSIONS: The colistin-MAC test could be a simple phenotypic test for presumptive identification of mcr-1-positive strains among isolates of colistin-resistant E. coli, based on a ≥8-fold reduction of colistin MIC in the presence of DPA. Evaluation of the test with a larger number of strains, species and mcr-type resistance determinants would be of interest.

Colistin resistance superimposed to endemic carbapenem-resistant Klebsiella pneumoniae: a rapidly evolving problem in Italy, November 2013 to April 2014.

Consecutive non-replicate clinical isolates (n=191) of carbapenem non-susceptible Enterobacteriaceae were collected from 21 hospital laboratories across Italy from November 2013 to April 2014 as part of the European Survey on Carbapenemase-producing Enterobacteriaceae (EuSCAPE) project. Klebsiella pneumonia carbapenemase-producing K. pneumoniae (KPC-KP) represented 178 (93%) isolates with 76 (43%) respectively resistant to colistin, a key drug for treating carbapenamase-producing Enterobacteriaceae. KPC-KP colistin-resistant isolates were detected in all participating laboratories. This underscores a concerning evolution of colistin resistance in a setting of high KPC-KP endemicity.

Sodium thiosulfate for the treatment of calcinosis secondary to juvenile dermatomyositis.

We report the successful use of sodium thiosulfate in a patient with juvenile dermatomyositis complicated by ulcerative skin disease and progressive calcinosis. This therapy may have a role in improving calcinosis, even if more studies are necessary to determine the safety and efficacy of this treatment in juvenile dermatomyositis-related calcinosis.

Epidemic diffusion of KPC carbapenemase-producing Klebsiella pneumoniae in Italy: results of the first countrywide survey, 15 May to 30 June 2011.

Carbapenem-resistant Enterobacteriaceae (CRE) are emerging as a public health problem in various settings. In Italy, a rapid and remarkable increase of carbapenem-non-susceptible Klebsiella pneumoniae has been reported since 2010. Here we report on the results of a countrywide cross-sectional survey, carried out from 15 May to 30 June 2011 to investigate the diffusion of CRE in Italy and to characterise the most prevalent resistance mechanisms and their dissemination patterns. CRE were reported from most (23 of 25) participating laboratories, with an overall proportion of 3.5% and 0.3% among consecutive non-duplicate clinical isolates of Enterobacteriaceae from inpatients (n=7,154) and outpatients (n=6,595), respectively. K. pneumoniae was the most frequent species (proportion of carbapenem-non-susceptible isolates: 11.9%), while a minority of CRE of other species were detected. Carbapenemase production was detected in the majority (85%) of CRE. KPC-type enzymes were by far the most common (89.5% of carbapenemase producers), followed by VIM-1 (9.2%) and OXA-48 (1.3%). KPC-producing K. pneumoniae (KPC-KP) were detected in most centres and contributed majorly to the epidemic dissemination of CRE recently observed in our country. Dissemination of KPC-KP was mostly sustained by strains of clonal complex 258 (ST-258 producing KPC-2 or KPC-3, and ST-512 producing KPC-3), while a minority belonged to ST-101.

Assessment of the Phoenix™ automated system and EUCAST breakpoints for antimicrobial susceptibility testing against isolates expressing clinically relevant resistance mechanisms.

EUCAST breakpoint criteria are being adopted by automatic antimicrobial susceptibility testing systems. The accuracy of the Phoenix Automated System in combination with 2012 EUCAST breakpoints against recent clinical isolates was evaluated. A total of 697 isolates (349 Enterobacteriaceae, 113 Pseudomonas spp., 25 Acinetobacter baumannii, 11 Stenotrophomonas maltophilia, 95 Staphylococcus aureus, 6 coagulase negative staphylococci, 77 enterococci and 21 Streptococcus pneumoniae) with defined resistance phenotypes and well-characterized resistance mechanisms recovered in Spain (n = 343) and Italy (n = 354) were tested. Comparator antimicrobial susceptibility testing data were obtained following CLSI guidelines. Experimental agreement (EA), defined as MIC agreement ±1 log(2) dilution, category agreement (CA) and relative discrepancies (minor (mD), major (MD) and very major discrepancies (VMD)) were determined. The overall EA and CA for all organism-antimicrobial agent combinations (n = 6.294) were 97.3% and 95.2%, respectively. mD, MD and VMD were 4.7%, 1.3% and 2.7%, all of them in agreement with the ISO (ISO20776-2:2007) acceptance criteria for assessment of susceptibility testing devices. VMD were mainly observed in amoxicillin-clavulanate and cefuroxime in Enterobacteriaceae and gentamicin in Pseudomonas aeruginosa, whereas MD were mainly observed in amoxicillin-clavulante in Enterobacteriaceae. mD were mainly observed in Enterobacteriaceae but distributed in different antimicrobials. For S. aureus and enterococci relative discrepancies were low. The Phoenix system showed accuracy assessment in accordance with the ISO standards when using EUCAST breakpoints. Inclusion of EUCAST criteria in automatic antimicrobial susceptibility testing systems will facilitate the implementation of EUCAST breakpoints in clinical microbiology laboratories.

Rapid detection of intestinal carriage of Klebsiella pneumoniae producing KPC carbapenemase during an outbreak.

Two different approaches are described for rapid detection of intestinal carriage of Klebsiella pneumoniae producing KPC-type carbapenemase (KPC-KP), based on PCR amplification of DNA extracts from rectal swabs (K-PCR), and on direct plating of rectal swabs on to MacConkey agar with a meropenem disc and a meropenem plus 3-aminophenylboronic acid disc (direct KPC screening test, DKST). K-PCR and DKST were tested with a total of 101 samples from 65 patients, during an outbreak. Although less sensitive, DKST could detect high-level carriage, which appears to be common among infected and colonised patients, while being very cheap and easy to perform, and requiring only basic facilities.

Epidemiological characterization and distribution of carbapenem-resistant Acinetobacter baumannii clinical isolates in Italy.

This study was aimed at tracing the molecular characteristics of carbapenem-resistant Acinetobacter baumannii (CRAB) clinical isolates in Italy with both pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Two hundred and two CRAB isolates were collected during 2004-2009, in two different surveillance periods, from 22 Italian hospitals that were representative for both distribution and infection. PFGE was performed, and the MLST scheme used was based on the gene sequence as published on the MLST Pasteur website http://www.pasteur.fr/mlst. Representatives of the major European clones I (RUH 875) and II (RUH 134) were used as controls. The two groups of isolates were characterized for their carbapenem resistance genes: 154 of 202 carried bla(OXA-58) alone, 21 of 202 also carried bla(OXA-23) , and 27 of 202 carried bla(OXA-23) alone. No isolates were positive for bla(OXA-24) . Genotype analysis of all isolates identified four distinct patterns by PFGE, which correlated with four distinct sequence types (STs) by MLST. The distribution of these four clusters in Italy confirmed the propensity of A. baumannii for nosocomial cross-transmission in a vast geographical area. We observed that clones A and B had similarities with European clone II and I respectively. By MLST, clone A was ST2, like European clone II, and clone B was ST1, like European clone I. PFGE and MLST showed the same discriminatory power and reproducibility. In addition, the two methods were concordant in defining CRAB Italian clones and in correlating them with the two pan-European clones.

Validation of a diagnostic score for the diagnosis of autoinflammatory diseases in adults.

Most autoinflammatory disorders typically come out in the pediatric population, although a limited number of patients may experience disease onset during adulthood. To date, a late disease onset has been described only in familial Mediterranean fever, caused by mutations in the MEFV gene, and in tumor necrosis factor receptor-associated periodic syndrome, caused by mutations in the TNFRSF1A gene. The relative rarity and lack of information on adult-onset autoinflammatory diseases make it likely that mutations will be found in an even smaller percentage of cases. With the aim of improving the genetic diagnosis in adults with suspected autoinflammatory disorders, we recently identified a set of variables related to the probability of detecting gene mutations in MEFV and TNFRSF1A and, in addition, we have also proposed a diagnostic score for identifying those patients at high risk of carrying mutations in these genes. In the present study we evaluated the preliminary score sensitivity and specificity on a wider number of patients in order to validate the goodness of fit of the model. Two hundred and nineteen consecutive patients with a clinical history of periodic fever attacks were screened for mutations in MEFV and TNFRSF1A genes; detailed information about family/personal history and clinical manifestations were also collected. For the validation of the score we considered data both from the 110 patients used to build the preliminary diagnostic score and from the additional 219 patients enrolled in the present study, for a total number of 329 patients. Early age at disease onset, positive family history for recurrent fever episodes, thoracic pain, abdominal pain and skin rash, which are the variables that had previously been shown to be significantly associated with a positive genetic test result (12), were used for validation. On univariate analysis the associations with a positive genetic test were: age at onset (odds ratio [OR] 0.43, p=0.003), positive family history for recurrent fever episodes (OR 5.81, p<0.001), thoracic pain (OR 3.17, p<0.001), abdominal pain (OR 3.80, p<0.001) and skin rash (OR 1.58, p=0.103). The diagnostic score was calculated using the linear combination of the estimated coefficients of the logistic multivariate model (cut-off equals to 0.24) revealing good sensitivity (0.778) and good specificity (0.718). In conclusion, our score may serve in the diagnostic evaluation of adult patients presenting with recurrent fever episodes suspected of having an autoinflammatory disorder, helping identify the few subjects among them who may be carriers of mutations in MEFV and TNFRSF1A genes.

Evolution and spread of a multidrug-resistant Proteus mirabilis clone with chromosomal AmpC-type cephalosporinases in Europe.

Proteus mirabilis isolates obtained in 1999 to 2008 from three European countries were analyzed; all carried chromosomal AmpC-type cephalosporinase bla(CMY) genes from a Citrobacter freundii origin (bla(CMY-2)-like genes). Isolates from Poland harbored several bla(CMY) genes (bla(CMY-4), bla(CMY-12), bla(CMY-14), bla(CMY-15), and bla(CMY-38) and the new gene bla(CMY-45)), while isolates from Italy and Greece harbored bla(CMY-16) only. Earlier isolates with bla(CMY-4) or bla(CMY-12), recovered in France from Greek and Algerian patients, were also studied. All isolates showed striking similarities. Their bla(CMY) genes resided within ISEcp1 transposition modules, named Tn6093, characterized by a 110-bp distance between ISEcp1 and bla(CMY), and identical fragments of both C. freundii DNA and a ColE1-type plasmid backbone. Moreover, these modules were inserted into the same chromosomal site, within the pepQ gene. Since ColE1 plasmids carrying ISEcp1 with similar C. freundii DNA fragments (Tn6114) had been identified earlier, it is likely that a similar molecule had mediated at some stage this DNA transfer between C. freundii and P. mirabilis. In addition, isolates with bla(CMY-12), bla(CMY-15), and bla(CMY-38) genes harbored a second bla(CMY) copy within a shorter ISEcp1 module (Tn6113), always inserted downstream of the ppiD gene. Sequence analysis of all mobile bla(CMY-2)-like genes indicated that those integrated in the P. mirabilis chromosome form a distinct cluster that may have evolved by the stepwise accumulation of mutations. All of these observations, coupled to strain typing data, suggest that the bla(CMY) genes studied here may have originated from a single ISEcp1-mediated mobilization-transfer-integration process, followed by the spread and evolution of a P. mirabilis clone over time and a large geographic area.

Concentración de la hidroxiprolina en la orina de jóvenes tras un programa de estiramientos estáticos y facilitación neuromuscular proprioceptiva / Concentration of hydroxyproline in urine of the young undergoing a static stretching program and proprioceptive neuromuscular facilitation

Introducción. La flexibilidad está en los debates sobre la actividad física y su prescripción. Es necesario identificar la forma de entrenamiento que aumente el catabolismo del colágeno locomotor generando la adaptación en los tejidos, llegando a la fase plástica del estiramiento. Objetivo. Comparar el nivel de hidroxiprolina (HP) entre jóvenes sedentarios sometidos a 2 tipos de estiramientos: a) estáticos pasivos (EP); y b) facilitación neuromuscular propioceptiva (FNP). Material y método. La muestra es de 30 sujetos distribuidos de forma aleatoria en: grupo FNP (GF, n = 15; edad: 22 ± 3 años; IMC: 24,12 ± 3,69), grupo EP (GA, n = 15; edad: 23 ± 4 años; IMC: 25 ± 4,33) y grupo control (GC, n = 15; edad: 24 ± 4 años; IMC: 23, 91 ± 3,09). El estiramiento (EP) se realizó con mantenimiento durante 6 segundos, mientras que el estiramiento por FNP se realizó por el método mantener y relajar. La intensidad de cada intervención fue controlada mediante la Escala de estrés percibido en la flexibilidad (PERFLEX). Resultados. Respecto al intra-grupo en GF (Δ = 3,55mg/24 horas; p = 0,0001) y GA (Δ = 3,47mg/24 horas; p = 0,002) y entre los grupos, entre GF y GC (Δ = 2,43mg/24 horas; p = 0,018) y entre GA y GC (Δ = 2,83mg/24 horas; p = 0,005), favorable a los dos grupos de entrenamiento. Podría estar relacionado que ambas metodologías obtuvieran resultados similares, aumentando el nivel de HP, lo que hace posible concluir que los resultados de este estudio no nos permiten afirmar cuál de los dos métodos es el más adecuado por tener menor riesgo de lesiones en lo que respecta a su prescripción(AU)

Introduction. Flexibility has been increasingly incorporated into discussions about physical activity and its prescription, creating the need for identifying the form of flexibility training that will increase catabolism of collagen in the locomotor system, thus forcing the conjunctive tissue to adapt and achieve the plastic phase of stretching. Objective. This study has aimed to compare hydroxyproline (HP) levels among sedentary young people submitted to two types of stretchings: static stretching (SS) and proprioceptive neuromuscular facilitation (PNF). Material and methods. The sample was randomly divided into PNF group (PG; n=15; age=22±3 years; BMI=24, 12±3.69); static stretching group (SG; n=15; age=23±4 years; BMI= 25±4.33) and control group (CG; n=15; age: 24±4 years; BMI: 23.91±3.09). Static stretching was done by passive straining during six seconds and PNF was done according to the hold-relax method. The intensity of each intervention was controlled with the Scale of Perceived Exertion in the Flexibility – PERFLEX. Results. The study found satisfactory results: intra-group, in PG (Δ = 3.55mg/24h; p = 0.0001) and in SG (Δ= 3.47mg/24h; p=0.002) and inter-groups, between PG and CG (Δ = 2.43mg/24h; p = 0.018) and between SG and CG (Δ = 2.83mg/24h; p = 0.005), both favorable to the training groups. It was possible to infer that both forms of training obtained satisfactory results, increasing the level of HP, which leads to the conclusion that the results of this study do not allow us to state that one of these forms of training is more adequate than the other in regards to the prescription of which one would entail the lowest risk of injuries(AU)

Evaluation of the in vitro effect of a Lantana camara extract on the labeling of blood constituents of rats with technetium-99m.

Blood constituents labeled with technetium-99m (99mTc) have been used in nuclear medicine procedures and drugs are capable to interfere on this labeling. Lantana camara (lantana) has medicinal properties and it has been used in folk medicine. The aim is to verify the effect of a lantana extract on the labeling of blood constituents with 99mTc. Blood of rats was incubated with extract, stannous chloride and 99mTc, as sodium pertechnetate. Plasma (P) and blood cells (BC) were isolated, also precipitated with trichloroacetic acid and soluble (SF) and insoluble fractions (IF) were separated. The % of radioactivity (%ATI) in these samples was calculated. Samples of labeled BC were washed and the %ATI maintained (%ATI-M) in the BC was determined. The results showed that lantana extract decreased significantly (p < 0.05) in the IF-P from 70.24 +/- 2.59 to 11.95 +/- 3.07. This effect was not observed in the BC and IF-BC. The BC-%ATI-M was significantly (p < 0.05) decreased in all concentrations tested when the BC was washed. This fact was not observed in the control. Substances present on the extract should have redoxi action decreasing the concentration of the stannous ion and this condition could justify the effect on the IF-P. The results about the BC-%ATI-M should indicate a possible effect on the transport of ions through the erythrocyte membrane.

Juvenile psoriatic arthritis and acquired sensorineural hearing loss in a teenager: is there an association?

Autoimmune inner ear disease is a cause of sensorineural hearing loss, first described in 1979 by McCabe. The occurrence during rheumatic diseases is already documented in adults, but to our knowledge, this evidence is still lacking in children. A 13-yr-old girl affected by juvenile psoriatic arthritis, treated with etanercept, developed a bilateral and asymmetric sensorineural deafness. The patient significantly improved after steroid administration. Once ruled out the principal causes of sensorineural hearing loss, we also considered the hypothesis of an anti-TNF side effect. However, the clinical presentation, the efficacy on steroid treatment and the presence of inner ear auto-antibodies prompt us to consider autoimmune-SNHL as the most plausible diagnosis. The young age of our patient seems to suggest a genetic susceptibility to autoimmunity and supports the concept of associated autoimmune diseases.

Bone status over 1 yr of etanercept treatment in juvenile idiopathic arthritis.

OBJECTIVE: To evaluate bone mineral status over 1 yr of etanercept treatment in juvenile idiopathic arthritis (JIA). METHODS: Twenty children (13 female, 7 male) aged 5.2-11.4 yr, with active polyarticular JIA were prospectively enrolled to receive etanercept (0.4 mg/kg, twice weekly). Responders were defined according to the American College of Rheumatology Pediatric 50 definition of improvement. Broadband ultrasound attenuation (BUA) by bone was determined at the left calcaneus to assess bone status at baseline and at 1-yr follow-up. RESULTS: After 12 months of treatment, 15 (75%) patients were considered as responders. At baseline, responders and non-responders did not differ with regard to age, disease duration, core-set variables or BUA and Z-score values (patient's value--age specific normal value/normal group's s.d.). At 6-month and 1-yr follow-up in the whole group, BUA and Z-score values were not significantly different compared with baseline. At 1-yr follow-up, but not at 6 months, all 15 responders, differently from non-responders, showed a significant increase in both BUA and Z-score values: BUA at 1 yr 55.2 +/- 3.3 vs baseline 43.5 +/- 3.2 dB/MHz, P<0.001; Z score at 1 yr -0.3 +/- 0.2 vs baseline 1.5 +/- 0.4, P<0.002. CONCLUSION: For the first time in childhood rheumatic disease this pilot prospective study, although in a small group, shows evidence that 1 yr of etanercept therapy by controlling the underlying disease activity induces a sustained benefit on JIA bone loss. Prospective studies in larger patient samples are needed to confirm these data.