Hereditary angioedema (HAE) in children and adolescents : a consensus on therapeutic strategies

Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.Conclusion Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis

Limited T Cell Receptor Diversity of HCV-specific T Cell Responses Is Associated with CTL Escape

Escape mutations are believed to be important contributors to immune evasion by rapidly evolving viruses such as hepatitis C virus (HCV). We show that the majority of HCV-specific cytotoxic T lymphocyte (CTL) responses directed against viral epitopes that escaped immune recognition in HCV-infected chimpanzees displayed a reduced CDR3 amino acid diversity when compared with responses in which no CTL epitope variation was detected during chronic infection or with those associated with protective immunity. Decreased T cell receptor (TCR) CDR3 amino acid diversity in chronic infection could be detected long before the appearance of viral escape mutations in the plasma. In both chronic and resolved infection, identical T cell receptor clonotypes were present in liver and peripheral blood. These findings provide a deeper understanding of the evolution of CTL epitope variations in chronic viral infections and highlight the importance of the generation and maintenance of a diverse TCR repertoire directed against individual epitopes

Loss of CCR7 Expression on CD56brightCD56^{bright} NK Cells Is Associated with a CD56dimCD16+CD56^{dim}CD16^{+} NK Cell-Like Phenotype and Correlates with HIV Viral Load

NK cells are pivotal sentinels of the innate immune system and distinct subpopulations in peripheral blood have been described. A number of studies addressed HIV-induced alterations of NK cell phenotype and functionality mainly focusing on $CD56^{dim}CD16^{+}$ and $CD56^{-} CD16^{+}$ NK cells. However, the impact of HIV-infection on $CD56^{bright}$ NK cells is less well understood. Here we report a rise of $CD56^{bright}$ NK cells in HIV-infected individuals, which lack CCR7-expression and strongly correlate with HIV viral load. $CCR7^{−} CD56^{bright}$ NK cells were characterized by increased cytolytic potential, higher activation states and a more differentiated phenotype. These cells thus acquired a number of features of $CD56^{dim}CD16^{+}$ NK cells. Furthermore, $CD56^{bright}$ NK cells from HIV patients exhibited higher degranulation levels compared to uninfected individuals. Thus, chronic HIV-infection is associated with a phenotypic and functional shift of $CD56^{bright}$ NK cells, which provides a novel aspect of HIV-associated pathogenesis within the NK cell compartment

Delegation ärztlicher Leistungen an rheumatologische Fachassistenten: Effekte auf Depression und Angst bei Patienten mit rheumatoider Arthritis

Background: At least 1 comorbidity occurs in 80% of patients with rheumatoid arthritis (RA). In addition to cardiovascular comorbidities psychological comorbid conditions are common. The prevalence of depression and anxiety is higher in patients than in the general population. Screening for comorbidities is crucial. A shortage of outpatient specialist care barely allows resources for this. The implementation of team-based care holds the potential to improve the standard of care while simultaneously working against the shortage of care. Objective: The aim of the study was to examine the effects of care on the course of depression and anxiety in patients with seropositive RA and active disease. Material and methods: A multicenter pragmatic randomized controlled trial was conducted over the course of 1 year with 224 patients. After baseline, five more visits followed. In the intervention group (IG), three were initially carried out by qualified rheumatological assistants. Depression, anxiety and patient satisfaction with outpatient care were looked at in detail. Results: In the IG the anxiety symptoms significantly improved over 12 months (p = 0.036). The proportions of patients with anxiety also significantly changed in the IG (p < 0.001), while there was no change in the control group between baseline and month 12. The values of the depression scale did not differ significantly (p = 0.866). In terms of the information dimension of the satisfaction questionnaire, patients in the IG felt significantly better informed after 6 months (p = 0.013) and 12 months (p = 0.003). Conclusion: A positive effect of team-based care on the course of depression and anxiety in patients with seropositive RA and active disease could be shown.Hintergrund: Bei 80 % der Patienten mit einer rheumatoiden Arthritis (RA) tritt mindestens eine Komorbidität auf. Neben kardiovaskulären Komorbiditäten sind psychische Erkrankungen häufig. Die Prävalenz von Depression und Angst ist bei Betroffenen höher als in der Allgemeinbevölkerung. Ein Screening auf Komorbidität ist hoch relevant. Die Unterversorgung im fachärztlichen Bereich lässt dies kaum zu. Die Implementierung einer Visite durch die rheumatologische Fachassistenz (RFA) bietet Potenzial, die Versorgung zu verbessern und der Unterversorgung zu begegnen. Fragestellung: Ziel ist, Auswirkungen einer teambasierten Versorgung auf den Verlauf von Depression und Angst bei Patienten mit einer seropositiven RA im Krankheitsschub zu untersuchen. Material und Methoden: Es handelt sich um eine multizentrische, pragmatische, randomisierte, kontrollierte Studie über 1 Jahr mit 224 Patienten. Nach Baseline folgen 5 Visiten. In der Interventionsgruppe (IG) fanden 3 zunächst bei der RFA statt. Depression, Angst und Behandlungszufriedenheit werden genauer betrachtet. Ergebnisse: In der IG hat sich die ängstliche Symptomatik über 12 Monate signifikant verbessert (p = 0,036). Auch die Anteile der Patienten mit Ängstlichkeit verändern sich signifikant in der Interventionsgruppe (p < 0,001), während es in der Kontrollgruppe im Vergleich zwischen Baseline und Monat 12 zu keiner Veränderung kam. Die Werte der Depressionsskala unterschieden sich nicht signifikant (p = 0,866). Bei der Dimension „Information“ des Zufriedenheitsfragebogens haben sich die Patienten in der IG nach 6 (p = 0,013) und 12 Monaten (p = 0,003) signifikant besser informiert gefühlt. Diskussion: Ein positiver Effekt der teambasierten Versorgung auf den Verlauf von Depression und Angst bei Patienten mit einer seropositiven RA im Krankheitsschub konnte gezeigt werden

The Subsystems Approach to Genome Annotation and its Use in the Project to Annotate 1000 Genomes

The release of the 1000(th) complete microbial genome will occur in the next two to three years. In anticipation of this milestone, the Fellowship for Interpretation of Genomes (FIG) launched the Project to Annotate 1000 Genomes. The project is built around the principle that the key to improved accuracy in high-throughput annotation technology is to have experts annotate single subsystems over the complete collection of genomes, rather than having an annotation expert attempt to annotate all of the genes in a single genome. Using the subsystems approach, all of the genes implementing the subsystem are analyzed by an expert in that subsystem. An annotation environment was created where populated subsystems are curated and projected to new genomes. A portable notion of a populated subsystem was defined, and tools developed for exchanging and curating these objects. Tools were also developed to resolve conflicts between populated subsystems. The SEED is the first annotation environment that supports this model of annotation. Here, we describe the subsystem approach, and offer the first release of our growing library of populated subsystems. The initial release of data includes 180 177 distinct proteins with 2133 distinct functional roles. This data comes from 173 subsystems and 383 different organisms

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Work participation in patients with axial spondyloarthritis: high prevalence of negative workplace experiences and long-term work impairment

Introduction Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that typically affects people in their second and third decades of life, which are important years for establishing a professional career. We aim to study outcomes of work participation (WP) and their associations with demographic and clinical confounders, in addition to prevalence of negative workplace experiences in axSpA.Methods In total, 770 patients with axSpA participated in the multicentre, observational ATTENTUS–axSpA survey in Germany. Demographic information, clinical parameters and patient-related outcomes (including disease activity and function) with a focus on WP were prospectively recorded.Results A high prevalence of negative workplace experiences was reported among the 770 patients analysed. Overall, 23.4% of patients were not employed and 6.5% received disability pensions. Current work cessation was prevalent in 120 patients, and 28 of those were out of work for 10 years or longer. Of the 590 currently employed patients, 31.9% reported absenteeism and 35.9% reported presenteeism for &gt;1 month within the past year. Multivariate logistic regression identified low disease activity (Bath Ankylosing Spondylitis Disease Activity Index), better physical function (Bath Ankylosing Spondylitis Functional Index) and better global functioning (Assessment of SpondylAarthritis International Society–Health Index) as the main predictors for unimpaired WP (n=242). Importantly, biological treatment, disease duration, age, sex, education level and body mass index were not reliable predictors.Discussion Despite improvements in pharmacological treatment options, we still observed substantially impaired WP in patients with axSpA. These data emphasise the high unmet need for targeted strategies to provide improved medical and social care