Biochemical phenotyping of paroxysmal nocturnal hemoglobinuria reveals solute carriers and ß-oxidation deficiencies.

INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal disease of hematopoietic cells with a variable clinical spectrum characterized by intravascular hemolysis, high risk of thrombosis, and cytopenias. To understand the biochemical shifts underlying PNH, this study aimed to search for the dysfunctional pathways involved in PNH physiopathology by comparing the systemic metabolic profiles of affected patients to healthy controls and the metabolomic profiles before and after the administration of eculizumab in PNH patients undergoing treatment. METHODS: Plasma metabolic profiles, comprising 186 specific annotated metabolites, were quantified using targeted quantitative electrospray ionization tandem mass spectrometry in 23 PNH patients and 166 population-based controls. In addition, samples from 12 PNH patients on regular eculizumab maintenance therapy collected before and 24 hours after eculizumab infusion were also analyzed. RESULTS: In the PNH group, levels of the long-chain acylcarnitines metabolites were significantly higher as compared to the controls, while levels of histidine, taurine, glutamate, glutamine, aspartate and phosphatidylcholines were significantly lower in the PNH group. These differences suggest altered acylcarnitine balance, reduction in the amino acids participating in the glycogenesis pathway and impaired glutaminolysis. In 12 PNH patients who were receiving regular eculizumab therapy, the concentrations of acylcarnitine C6:1, the C14:1/C6 ratio (reflecting the impaired action of the medium-chain acyl-Co A dehydrogenase), and the C4/C6 ratio (reflecting the impaired action of short-chain acyl-Co A dehydrogenase) were significantly reduced immediately before eculizumab infusion, revealing impairments in the Acyl CoA metabolism, and reached levels similar to those in the healthy controls 24 hours after infusion. CONCLUSIONS: We demonstrated significant differences in the metabolomes of the PNH patients compared to healthy controls. Eculizumab infusion seemed to improve deficiencies in the acyl CoA metabolism and may have a role in the mitochondrial oxidative process of long and medium-chain fatty acids, reducing oxidative stress, and inflammation.

Long-Term Follow-Up of Ruxolitinib in the Treatment of Steroid-Refractory Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) remains a major barrier to successful hematopoietic stem cell transplantation (HSCT). In cases refractory to first-line therapy with steroids, there is no standard of care for second-line therapy. As such, ruxolitinib is a promising drug in this scenario. We retrospectively analyzed the efficacy and safety of ruxolitinib in treating steroid-refractory cGVHD in 35 patients from 2 transplantation centers, with the longest follow-up described to date. The evaluated patients had a median of 3 organs affected (range, 1 to 7 organs), with most (64%) having moderate cGVHD. The median number of previous therapy lines was 2 (range, 1 to 6). The overall response rate was 89% (complete response, 26%) after a median of 4 weeks of therapy. The median follow-up was 43 months (range, 11 to 59 monts). At follow-up, of the 27 patients still alive, 18 (67%) were free of any immunosuppression, and 6 (22%) were receiving ruxolitinib as their sole immunosuppressive drug. Failure-free survival was 77.1% at 6 months, 68.6% at 12 months, 54% at 24 months, and 51.4% at 36 months. The median overall survival was not reached. Toxicities were mostly hematologic and resolved after dosage reduction in most cases. Overall, our data, which represent the cohort of patients with cGVHD treated with ruxolitinib with the longest follow-up to date, support the use of this drug as a safe and effective option for refractory cGVHD.

Exposure to Traumatic Events and Development of Psychotic Symptoms in a Prison Population: A Network Analysis Approach.

Previous studies consistently observed an association between exposure to traumatic events and psychotic symptoms. However, little is known about the differential impact of distinct traumatic events and the role of general symptoms in mediating this relationship. Thus, our study aimed to explore the differential association of several traumatic events to the psychotic symptoms in a sample of prisoners and whether this association is mediated by general symptoms. The total sample from the Survey of Psychiatric Morbidity Among Prisoners in England and Wales (N = 3039; 75.4% male) was used. Participants completed a list of traumatic events experienced before reclusion, the Psychosis Screening Questionnaire, Clinical Review Schedule-Revised. Network analysis was used to estimate the network of interactions between traumatic events and general and psychotic symptoms. Shortest paths analysis was performed to identify the different development trajectories. Results suggested that memory problems, compulsions, and irritability might be key mediating symptoms for most traumatic events. However, sexual abuse showed alternative mediators that might be specific of this traumatic event. Finally, the traumatic events, suffered from violence at work, separation/divorce and been homeless showed direct associations with specific psychotic symptoms.

The impact of pretransplant malnutrition on allogeneic hematopoietic stem cell transplantation outcomes.

BACKGROUND: Malnutrition is a common finding in allogeneic hematopoietic stem cell transplantation (alloHSCT) patients, and there is some evidence that malnutrition might negatively affect the transplant outcomes. METHOD: We performed a retrospective study with 148 patients aged 18-75 years, who underwent alloHSCT between 2011 and 2017. Patients were classified according to the body mass index (BMI) and the Subjective Global Assessment (SGA). The SGA was assessed on the day of hospitalization for the transplant, and classifies patients into three groups: A (well-nourished), B (moderately malnourished) and C (severely malnourished). RESULTS: The SGA classified 49 (33%) patients as well-nourished, 54 (37%) as moderately malnourished, and 45 (30%) as severely malnourished. SGA-C was also associated with severe acute graft versus host disease (aGVHD) with a cumulative incidence (CI) of 31% vs. a CI of 14% for combined well-nourished or moderately malnourished group (SGA-A or -B, P = 0.017). In multivariate analysis, SGA-C compared to SGA-A or -B, remained as an independent risk factor for aGVHD (hazard ratio - HR 1.68, 95% confidence interval - 95% CI 1.02-2.74), and nonrelapse mortality (NRM - HR 3.63, 95% CI 1.76-7.46), worse progression free survival (HR 2.12, 95% CI 1.25-3.60), and worse overall survival (HR 3.27, 95% CI 1.90-5.64). CONCLUSION: Malnutrition increases the risk of aGVHD and NRM and has a negative impact on survival.

Management of infections in rheumatic patients receiving biological therapies. The Portuguese Society of Rheumatology recommendations.

INTRODUCTION: Infections are a major cause of morbidity and mortality in systemic inflammatory rheumatic diseases and the management of infectious complications in patients under biological therapies deserves particular attention. OBJECTIVE: Develop evidence-based recommendations for the management of infections in rheumatic patients receiving biological therapies. METHODS: A search in PubMed (until 10 November 2014) and EMBASE (until 20 December 2014) databases was performed. Patients with systemic inflammatory rheumatic diseases treated with approved biologics in whom infections occurred were included. Search results were submitted to title and abstract selection, followed by detailed review of suitable studies. Information regarding presentation of the infectious complication, its diagnosis, treatment, and outcome, as well as maintenance or discontinuation of the biological agent was extracted and subsequently pooled according to the type of infection considered. Results of literature review were presented and critically reviewed in a dedicated meeting by a multidisciplinary panel. Recommendations were then formulated using the Delphi method. Finally, the level of agreement among rheumatologists was voted using an online survey. RESULTS: Fifteen recommendations were issued. Nine general recommendations concerned the assessment of infectious risk before and while on biologics, the procedures in case of suspected infection and the management of biologics during infectious complications. Six specific recommendations were developed for respiratory, urinary, gastrointestinal, skin, osteoarticular and disseminated infections. CONCLUSION: These fifteen recommendations are intended to help rheumatologists in the management of infections in patients on biological therapy. They integrate an extensive literature review, expert opinion and inputs from Portuguese rheumatologists.

Abuso sexual na infância: um estudo de validade de instrumentos projetivos / Child sexual abuse: a study for validation of projetive instruments

O presente trabalho teve como objetivo verificar se os instrumentos Desenho da Figura Humana e Teste de Apercepção Infantil - Animal são sensíveis à identificação do abuso sexual, se eles conseguem diferenciar o grupo de crianças que sofreram abuso sexual do grupo de crianças que não sofreram. Participaram do estudo 30 crianças de ambos os sexos, com idade de 6 a 10 anos, divididas em dois grupos distintos. Um grupo de 15 crianças que apresentavam histórico de abuso sexual e outro de 15 crianças que não. O DFH foi aplicado e avaliado segundo o sistema de avaliação de Koppitz, e o CAT-A foi aplicado de acordo com as instruções de Bellak. Os resultados mostraram que os dois instrumentos foram sensíveis e conseguiram discriminar o grupo de pesquisa do outro grupo e detectar situações de abuso sexual no grupo de pesquisa(AU)

Inventário SF-36: avaliação da qualidade de vida dos alunos do curso de Psicologia do Centro Unisal - U. E. de Lorena (SP) / Inventory SF-36: Quality of life evaluation of psychology students from Unisal - University Salesiana of Lorena (SP)

Este artigo busca narrar um estudo realizado com o Inventário de Qualidade de Vida SF-36, no qual oito aspectos distintos são avaliados: capacidade funcional, aspectos físicos, aspectos emocionais, intensidade da dor, estudo geral da saúde, vitalidade, aspectos sociais e saúde mental. O estudo foi realizado com alunos do curso de psicologia do Centro Unisal de Lorena (SP) buscando observar aspectos significativos da qualidade de vida desses alunos e se durante o processo da formação acadêmica houve melhora nessa qualidade. Dados, reflexões e conclusões significativas foram detectadas, tornando-se importantes para a realização de um trabalho de prevenção e de intervenção na vida dos alunos, uma vez que os mesmos serão profissionais promotores da saúde mental das pessoas(AU)

Estudo da toxicomania por meio do Questionamento Desiderativo / Study of toxicomania through Questionamento Desiderativo

Este trabalho tem como objetivo compreender a toxicomania em relação a organização psíquica do sujeito, suas defesas e a relação que estabelece com seu desenvolvimento interno e externo. A questão que se propõe é o entendimento da toxicomania como uma necessidade do uso do objeto-droga para a manutenção de um funcionamento psíquico; de outra maneira, o indivíduo não daria conta da apreensão da realidade. Foi utilizando o Questionário Desiderativo para avaliar a estrutura psíquica e traços comuns na personalidade dos toxicômanos. Os sujeitos foram sete pacientes, de 18 a 36 anos, sexo masculino, internos de uma casa de recuperação para dependentes químicos. Foi possível verificar falhas no funcionamento mental desses pacientes, independente de sua estrutura psíquica(AU)