Update of the evidence based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis.

BACKGROUND: Uveitis in juvenile idiopathic arthritis (JIAU) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first line therapy, and disease modifying anti-rheumatic drugs (DMARDs) are commonly used. However, treatment has not been standardized. METHODS: Interdisciplinary guideline were developed with representatives from the German Ophthalmological Society, Society for Paediatric Rheumatology, Professional Association of Ophthalmologists, German Society for Rheumatology, parents' group, moderated by the Association of the Scientific Medical Societies in Germany. A systematic literature analysis in MEDLINE was performed, evidence and recommendations were graded, an algorithm for anti-inflammatory treatment and final statements were discussed in a consensus meeting (Nominal Group Technique), a preliminary draft was fine-tuned and discussed thereafter by all participants (Delphi procedure). RESULTS: Consensus was reached on recommendations, including a standardized treatment strategy according to uveitis severity in the individual patient. Thus, methotrexate shall be introduced for uveitis not responding to low-dose (≤ 2 applications/day) topical corticosteroids, and a TNFalpha antibody (preferably adalimumab) used, if uveitis inactivity is not achieved. In very severe active uveitis with uveitis-related deterioration of vision, systemic corticosteroids should be considered for bridging until DMARDs take effect. If TNFalpha antibodies fail to take effect or lose effect, another biological should be selected (tocilizumab, abatacept or rituximab). De-escalation of DMARDs should be preceded by a period of  ≥ 2 years of uveitis inactivity. CONCLUSIONS: An interdisciplinary, evidence-based treatment guideline for JIAU is presented.

High carriage rate of extended-spectrum beta-lactamase-producing Enterobacteriaceae among patients admitted for surgery in Tanzanian hospitals with a low rate of endogenous surgical site infections.

INTRODUCTION: Despite the high reported rates of surgical site infections (SSIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (EPE) in low-income countries, including Tanzania, the role of EPE carriage in subsequent occurrence of SSIs is not known. This study investigated the rates of EPE carriage among surgical patients at the time of admission and discharge, and linked EPE genotype with SSIs. METHODS: EPE were confirmed among isolates from rectal and wound/pus swabs using VITEK-2. Polymerase chain reaction and sequencing were performed to detect beta-lactamase genes. Multi-locus sequence typing was used to determine the genotypes of EPE isolates. RESULTS: Among 930 patients enrolled, EPE carriage was significantly higher on discharge than admission (36.4% vs 23.7%, P<0.001). Of 272 patients who tested negative on admission, 78 (28.7%) acquired EPE during hospitalization. History of hospital stay within the previous three months was an independent predictor of EPE acquisition [hazard ratio 2, 95% confidence interval (CI) 1.04-3.98, P=0.038]. Of the 536 patients who were successfully followed-up after surgery, 78 (14.6%, 95% CI 11.6-17.5) developed SSIs. Of 57 SSIs investigated, 33 (58%) were caused by enteric Gram-negative bacteria, of which 63.6% (21/33) were EPE. Escherichia coli sequence type (ST)131 pandemic clone and Klebsiella pneumoniae ST391 predominated among wound isolates. The blaCTX-M-15 gene was detected in 37 (97.3%) of 38 ESBL isolates. Male sex was an independent predictor of SSI (odds ratio 2.92, 95% CI 1.73-4.91, P<0.001). CONCLUSION: These findings warrant implementation of strict infection control measures, antimicrobial stewardship and exploration of the transmission dynamics of EPE in surgical wards.

High-resolution magnetic resonance imaging reveals nuclei of the human amygdala: manual segmentation to automatic atlas.

The amygdala is composed of multiple nuclei with unique functions and connections in the limbic system and to the rest of the brain. However, standard in vivo neuroimaging tools to automatically delineate the amygdala into its multiple nuclei are still rare. By scanning postmortem specimens at high resolution (100-150µm) at 7T field strength (n = 10), we were able to visualize and label nine amygdala nuclei (anterior amygdaloid, cortico-amygdaloid transition area; basal, lateral, accessory basal, central, cortical medial, paralaminar nuclei). We created an atlas from these labels using a recently developed atlas building algorithm based on Bayesian inference. This atlas, which will be released as part of FreeSurfer, can be used to automatically segment nine amygdala nuclei from a standard resolution structural MR image. We applied this atlas to two publicly available datasets (ADNI and ABIDE) with standard resolution T1 data, used individual volumetric data of the amygdala nuclei as the measure and found that our atlas i) discriminates between Alzheimer's disease participants and age-matched control participants with 84% accuracy (AUC=0.915), and ii) discriminates between individuals with autism and age-, sex- and IQ-matched neurotypically developed control participants with 59.5% accuracy (AUC=0.59). For both datasets, the new ex vivo atlas significantly outperformed (all p < .05) estimations of the whole amygdala derived from the segmentation in FreeSurfer 5.1 (ADNI: 75%, ABIDE: 54% accuracy), as well as classification based on whole amygdala volume (using the sum of all amygdala nuclei volumes; ADNI: 81%, ABIDE: 55% accuracy). This new atlas and the segmentation tools that utilize it will provide neuroimaging researchers with the ability to explore the function and connectivity of the human amygdala nuclei with unprecedented detail in healthy adults as well as those with neurodevelopmental and neurodegenerative disorders.

Analysis of non-typeable Haemophilus influenzae in invasive disease reveals lack of the capsule locus.

Among invasive Haemophilus influenzae, unencapsulated strains have largely surpassed the previously predominant serotype b (Hib) because of Hib vaccination. Isolates without the genomic capsule (cap) locus are designated non-typeable H. influenzae (NTHi). They are different from capsule-deficient variants that show deletion of the capsule transport gene bexA within the cap locus. The frequency of capsule-deficient variants in invasive disease is unknown. We analysed 783 unencapsulated invasive isolates collected over 5 years in Germany and found no single capsule-deficient isolate. Invasive unencapsulated strains in Germany were exclusively NTHi. A negative serotyping result by slide agglutination was therefore highly predictive for NTHi.

[Pediatric general practitioners and tertiary care structures for pain therapy. A qualitative study on the need for networking]. / Niedergelassene Pädiater und tertiäre Versorgungsstrukturen der Schmerztherapie. Eine qualitative Studie zum Bedarf an Vernetzung.

BACKGROUND: Despite the urgency of the problem of chronic pediatric pain and the importance of early interventions, many children experience intermittent episodes of pain over a long period of time. One aim of this study was to investigate the need of structured diagnostic tools and therapies of chronic pediatric pain in pediatric general practices. Another aim was to describe the aims, services and challenges of a network between pediatric practices and a tertiary pediatric pain centre, from the perspective of general pediatric practitioners. MATERIAL AND METHODS: A qualitative research design was selected and 20 general pediatric practitioners were interviewed using a semistructured interview guide. Interviews were analyzed by use of qualitative content analysis according to Mayring. RESULTS: Generally, the idea of a network between pediatric practices and the German Pediatric Pain Centre was rated positively by pediatric general practitioners. From the results of the analysis three categories were identified: (i) expectations from the network (ii) desire for cooperation in the network and (iii) recommendations for improved patient care. CONCLUSION: A network with a centre for tertiary care was preferred by the general pediatric practitioners. To optimize the care of children with chronic pain further education for general pediatric practitioners as well as structured diagnostic tools and therapies of frequent pediatric chronic pain diseases are warranted.

Anesthetic management in pediatric patients with epidermolysis bullosa: a single center experience.

BACKGROUND: Anesthesia in children with dystrophic epidermolysis bullosa (EB) presents a significant challenge as many children have a difficult airway and are at risk for additional blistering. In this retrospective study we compared deep sedation/ analgesia and general anesthesia for safety and efficiency. Procedure, type of anesthesia, airway management, complications, time for induction and awakening, length of stay in recovery room, length of procedure were noted and compared, qualitatively and with statistic tests as appropriate. METHODS: Fourteen children underwent 148 procedures: 79 under general anesthesia, 67 under sedation. RESULTS: Several complications - including intubation difficulties and the need for change of airway management - were observed in the general anesthesia group, none in the sedated group. Induction time was 36 min vs. 17 min (P<0.001), mean time to recovery 23 min vs. 6 min (P<0.001). Surgical duration did not differ between groups. CONCLUSIONS: In children with dystrophic EB deep sedation/ analgesia can be safely performed and is less time consuming than traditional management.

Cognitive function in patients with epidermolysis bullosa: social adjustment and emotional problems.

BACKGROUND: Children with Epidermolysis bullosa (EB) suffer from an intractable, burdensome skin disease that may result in cognitive as well as social and emotional problems. PATIENTS: To assess cognitive problems in patients with EB, we investigated 20 affected children and adolescents, 6-17 years of age (mean: 10.8 years; SD: 3.4 years), and 24 healthy controls (6-15 years, mean: 10.9 years; SD: 3.0 years) for cognitive abilities. Additionally, parents were asked to assess social and emotional problems of their children. METHODS: Patients and controls were assessed using the Wechsler Intelligence Scales. Parents completed Achenbach's Child Behaviour Checklist (CBCL), a parent-report measure on emotional and behavioural symptoms in children. RESULTS: The mean scores of the young patients tested with WISC-R and WAIS-R showed no significant left shift if compared to healthy controls. Analyzing the subtypes of EB, however, considerable cognitive deficits were associated with recessive dystrophic EB (RDEB), severe generalized. Less social competence and more social and emotional problems were reported for the entire patient group. CONCLUSIONS: Functional rehabilitation is required to increase not only the physical but the cognitive development of the severely affected children with RDEB. Children and adolescents with all subtypes of EB require therapeutic support regarding their social and emotional life.

Evidence-based, interdisciplinary guidelines for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis.

Uveitis in juvenile idiopathic arthritis (JIA) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first-choice therapy, and immunosuppression is commonly used. However, treatment has not been standardized. Representatives from the German Ophthalmological Society, Society for Childhood and Adolescent Rheumatology, and the German Society for Rheumatology reached consensus on a standardized treatment strategy according to disease severity in the individual patient. The recommendations were based on a systematic literature analysis in MEDLINE and consensus expert meetings. Evidence and recommendations were graded, and an algorithm for anti-inflammatory treatment and final statements confirmed in a Delphi method. An interdisciplinary, evidence-based treatment guideline for JIA uveitis is presented.

[Evidence and consensus based treatment guidelines 2010 for juvenile idiopathic arthritis by the German Society of Paediatric Rheumatology]. / Interdisziplinäre S2-Therapieleitlinie der Juvenilen Idiopathischen Arthritis (2. Auflage).

BACKGROUND: Treatment of Juvenile Idiopathic Arthritis (JIA) has improved quality of life in children and adolescents with JIA. Standardisation of care offers the chance to improve the quality of care of those patients. New studies have been published after completion of our last treatment guideline (2007). An updated consensus process is mandatory. METHODS: A systematic literature analysis in PUBMED (key words: juvenile idiopathic (rheumatoid) arthritis, therapy; limits: humans, published in the last 3 years, all child 0-18 years, clinical trial) revealed 17 relevant studies. Studies relating to diagnosis of JIA, Uveitis, vaccination, transition were excluded. Representatives nominated by scientific societies and organisations were invited to consensus conferences which were hosted by a professional moderator. The following societies were invited: Berufsverband der Kinder- und Jugendärzte (BVKJ), Deutsche Gesellschaft für Kinder- und Jugendmedizin (DGKJ), Deutsche Gesellschaft für Rheumatologie (DGRh), Deutsche Ophthalmologische Gesellschaft (DOG), Deutsche Rheuma-Liga Bundesverband, Verein zur Förderung und Unterstützung rheumatologisch erkrankter Kinder und deren Eltern, Vereinigung für Kinderorthopädie, Zentraler Verband der Physiotherapeuten und Krankengymnasten (ZVK). Consensus conferences were each attended by more than 95% of the nominated representatives. Consensus statements were confirmed by nominal group technique and Delphi method. RESULTS AND CONCLUSION: Updated consensus statements regarding drug therapy, symptomatic and surgical management of JIA were compiled and judged strictly by the criteria of Evidence-Based Medicine (EBM).

Results of the German ESPED-recording of new patients with juvenile dermatomyositis (JDM).

In a nation-wide registration project 38 incident cases of juvenile dermatomyositis were collected in Germany over a 2-year-period. Diagnostic methods as well as the primary treatment for these patients were recorded. Detailed information was available for 25 of these patients. Diagnostic as well as therapeutic decisions varied widely. Steroids were used in almost all of the 25 patients either as oral or as parenteral pulse therapy, additional immunosuppressive drugs were used in 52%. We plan to establish national consensus recommendations for diagnostic and therapeutic standards in JDM. Due to the rarity of JDM clinical trials will have to be performed on an international basis.

Evaluation of the VITEK 2 AST-N111 card for detection of extended-spectrum beta-lactamases (ESBLs) in Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca compared to ESBL Etests and combination disk methods.

The VITEK 2 AST-N111 card was evaluated for detection of extended-spectrum beta-lactamases (ESBLs) by testing 51 ESBL positive and 50 ESBL negative isolates of E. coli, K. pneumoniae, and K. oxytoca. The occurrence of beta-lactamase genes was confirmed by PCR and sequencing. The advanced expert system (AES) of the VITEK 2 system achieved sensitivity and specificity values of 100% and 96.0%, respectively. The ESBL test of the VITEK 2 AST-N111 card showed a sensitivity of 92.1% and a specificity of 90.0%. Contradictory results obtained with the two VITEK 2 tools could be clarified by combination disk tests in nine of 11 isolates. The combined use of AES and ESBL tests of the AST-N111 card in association with combination disk tests in case of contradictory results seems to be a reliable method for ESBL detection.

Real-time impedance analysis of host cell response to meningococcal infection.

Measuring cell proliferation and cell death during bacterial infection involves performing end-point assays that represent the response at a single time point. A new technology from Roche Applied Science and ACEA Biosciences allows continuous monitoring of cells in real-time using specialized cell culture microplates containing micro-electrodes. The xCELLigence system enables continuous measurement and quantification of cell adhesion, proliferation, spreading, cell death and detachment, thus creating a picture of cell function during bacterial infection. Furthermore, lag and log phases can be determined to estimate optimal times to infect cells. In this study we used this system to provide valuable insights into cell function in response to several virulence factors of the meningitis causing pathogen Neisseria meningitidis, including the lipopolysaccharide (LPS), the polysaccharide capsule and the outer membrane protein Opc. We observed that prolonged time of infection with pathogenic Neisseria strains led to morphological changes including cell rounding and loss of cell-cell contact, thus resulting in changed electrical impedance as monitored in real-time. Furthermore, cell function in response to 14 strains of apathogenic Neisseria spp. (N. lactamica and N. mucosa) was analyzed. In contrast, infection with apathogenic N. lactamica isolates did not change electrical impedance monitored for 48 h. Together our data show that this system can be used as a rapid monitoring tool for cellular function in response to bacterial infection and combines high data acquisition rates with ease of handling.

[Methotrexate in the therapy of juvenile idiopathic arthritis]. / Methotrexat bei der Therapie der juvenilen idiopathischen Arthritis.

Treatment with low-dose methotrexate (MTX) is an important element in the therapy of juvenile idiopathic arthritis (JIA). It could be demonstrated in placebo-controlled trials that MTX is a safe and effective drug which is generally well tolerated by children and adolescents. MTX is usually used at a dose of 10-15 mg/m(2)/week, whereby oral administration is preferred for children. Side effects occur mainly in the form of gastro-intestinal discomfort such as nausea and vomiting or raised transaminases, which can be effectively treated with folic-acid supplementation.There are no general recommendations to date regarding in particular duration and discontinuation of MTX treatment or combination treatment with other disease-modifying antirheumatic drugs or biologics. These unresolved questions are the subject of current trials in which biomarkers have an increasingly important role.

Banding pattern indicative of echinococcosis in a commercial cysticercosis Western blot.

OBJECTIVE: A commercial cysticercosis Western blot was evaluated for serological cross-reactivity of sera from patients with alveolar (AE) and cystic echinococcosis (CE). METHODS: A total of 161 sera were examined, including 31 sera from AE-patients, 11 sera from CE- patients, 9 sera from patients with other parasitic diseases and 109 sera from patients with unrelated medical conditions. All AE- and CE-sera were also examined by the echinococcosis Western blot. RESULTS: More sera from patients with AE than with CE showed cross-reactivity in the form of ladder-like patterns ("Mikado aspect") and untypical bands at 6-8 kDa (71% and 77.4% versus 27.3% and 45.5%, respectively). In contrast, triplets of bands in the area above 50 kDa and between 24 and 39-42 kDa were more frequent in CE than in AE sera. The fuzzy band at 50-55 kDa typical for cysticercosis was absent in all AE and CE sera. CONCLUSIONS: Atypical banding patterns in the cysticercosis Western blot should raise the suspicion of a meta?cestode infection different from Taenia solium, i.e. Echinococcus multilocularis or E. granulosus, especially when the Mikado aspect and an altered 6-8 kDa band is visible in the absence of a fuzzy 50-55 kDa band.