Patients with Schizophrenia Undergoing Gastric Bypass Surgery: a Case Series Study.

PURPOSE: Obesity affects approximately 45-55% of persons with schizophrenia and is more difficult to manage in these individuals than in the general population, apart from being an additional factor for morbidity and premature mortality. Although bariatric surgery is considered the most effective long-term treatment for severe obesity, there are few reports on the outcomes of this procedure in persons with schizophrenia. This study aimed to evaluate weight loss and psychiatric symptoms in persons with obesity and schizophrenia after bariatric surgery. MATERIALS AND METHODS: Five persons with schizophrenia and moderate to severe obesity who underwent bariatric surgery were followed up for 2 years. Anthropometric data were collected, and psychiatric symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS), which assessed the pre- and postoperative occurrence and severity of symptoms of schizophrenia. RESULTS: The mean body mass index before surgery was 43.5 ± 5.2 kg/m2 and decreased to 28.1 ± 1.9 kg/m2 1 year postoperatively. The mean percentage of total postoperative weight loss was 30.7 ± 6.8% after 6 months, 34.7 ± 7.9% after 1 year, and 34.3 ± 5.5% after 2 years. Before surgery, all subjects were in remission based on the PANSS. Postoperative evaluations showed that the participants had no relapse of psychiatric symptoms (p > 0.05 for the three PANSS dimensions throughout the follow-up period). There were no considerable changes in their medication regimens. CONCLUSIONS: These findings suggest that bariatric surgery may be a viable treatment option for stable patients with schizophrenia if they have a preoperative assessment and close management and involvement by mental health professionals throughout the course of treatment.

Indirect and direct costs of treating patients with ankylosing spondylitis in the Brazilian public health system.

INTRODUCTION: Patients with ankylosing spondylitis require a team approach from multiple professionals, various treatment modalities for continuous periods of time, and can lead to the loss of labour capacity in a young population. So, it is necessary to measure its socio-economic impact. OBJECTIVES: To describe the use of public resources to treat AS in a tertiary hospital after the use of biological medications was approved for treating spondyloarthritis in the Health Public System, establishing approximate values for the direct and indirect costs of treating this illness in Brazil. MATERIAL AND METHODS: 93 patients selected from the ambulatory spondyloarthritis clinic at the Hospital de Clínicas of the Federal University of Paraná between September 2011 and September 2012 had their direct costs indirect treatment costs estimation. RESULTS: 70 patients (75.28%) were male and 23 (24.72%) female. The mean age was 43.95 years. The disease duration was calculated based on the age of diagnosis and the mean was 8.92 years (standard deviation: 7.32); 63.44% were using anti-tumour necrotic factor drugs. Comparing male and female patients the mean Bath Ankylosing Spondylitis Disease Activity Index was 4.64 and 5.49 while the mean Bath Ankylosing Spondylitis Functional Index was 5.03 and 6.35 respectively. CONCLUSIONS: The Brazilian public health system's spending related to ankylosing spondylitis has increased in recent years. An important part of these costs is due to the introduction of new, more expensive health technologies, as in the case of nuclear magnetic resonance and, mainly, the incorporation of anti-tumour necrotic factor therapy into the therapeutic arsenal. The mean annual direct and indirect cost to the Brazilian public health system to treat a patient with ankylosing spondylitis, according to our findings, is US$ 23,183.56.

Indirect and direct costs of treating patients with ankylosing spondylitis in the Brazilian public health system / Custos diretos e indiretos do tratamento de pacientes com espondilite anquilosante pelo sistema público de saúde brasileiro

ABSTRACT Introduction: Patients with Ankylosing Spondylitis (AS) require a team approach from multiple professionals, various treatment modalities for continuous periods of time, and can lead to the loss of labour capacity in a young population. So, it is necessary to measure its socio-economic impact. Objectives: To describe the use of public resources to treat AS in a tertiary hospital after the use of biological medications was approved for treating spondyloarthritis in the Health Public System, establishing approximate values for the direct and indirect costs of treating this illness in Brazil. Material and methods: 93 patients selected from the ambulatory spondyloarthritis clinic at the Hospital de Clínicas of the Federal University of Paraná between September 2011 and September 2012 had their direct costs indirect treatment costs estimation. Results: 70 patients (75.28%) were male and 23 (24.72%) female. The mean age was 43.95 years. The disease duration was calculated based on the age of diagnosis and the mean was 8.92 years (standard deviation: 7.32); 63.44% were using anti-TNF drugs. Comparing male and female patients the mean BASDAI was 4.64 and 5.49 while the mean BASFI was 5.03 and 6.35 respectively. Conclusions: The Brazilian public health system's spending related to ankylosing spondylitis has increased in recent years. An important part of these costs is due to the introduction of new, more expensive health technologies, as in the case of nuclear magnetic resonance and, mainly, the incorporation of anti-TNF therapy into the therapeutic arsenal. The mean annual direct and indirect cost to the Brazilian public health system to treat a patient with ankylosing spondylitis, according to our findings, is US$ 23,183.56.

RESUMO Introdução: Os pacientes com espondilite anquilosante (EA) exigem uma abordagem de equipe com vários profissionais e várias modalidades de tratamento, continuamente; além disso, a doença pode levar à perda da capacidade de trabalho em uma população jovem, de modo que é necessário medir o seu impacto socioeconômico. Objetivos: Descrever o uso de recursos públicos para o tratamento da EA em um hospital terciário após o uso dos fármacos biológicos ter sido aprovado para o tratamento das espondiloartrites pelo Sistema Público de Saúde e estabelecer valores aproximados para os custos diretos e indiretos do tratamento dessa doença no Brasil. Material e métodos: Foram estimados os custos de tratamento diretos e indiretos de 93 pacientes com EA do ambulatório de espondiloartrite do Hospital de Clínicas da Universidade Federal do Paraná, entre setembro de 2011 e setembro 2012. Resultados: Dos pacientes, 70 (75,28%) eram do sexo masculino e 23 (24,72%) do feminino. A idade média foi de 43,95 anos. A duração da doença foi calculada com base na idade do diagnóstico e a média foi de 8,92 anos (desvio padrão: 7,32); 63,44% dos indivíduos usavam fármacos anti-TNF. Na comparação dos pacientes dos sexos masculino e feminino, a média no Bath Ankylosing Spondylitis Disease Activity Index (Basdai) foi de 4,64 e 5,49, enquanto a média no Bath Ankylosing Spondylitis Functional Index (Basfi) foi de 5,03 e 6,35, respectivamente. Conclusões: Os gastos do sistema público de saúde brasileiro relacionados com a espondilite anquilosante aumentaram nos últimos anos. Uma parte importante desses custos deve-se à introdução das novas tecnologias de saúde, mais dispendiosas, como no caso da ressonância nuclear magnética e, principalmente, da incorporação da terapia anti-TNF ao arsenal terapêutico. O custo médio anual direto e indireto do sistema público de saúde brasileiro para tratar de um paciente com espondilite anquilosante, de acordo com os resultados deste estudo, é de US$ 23.183,56.

Reduced levels of cytosolic DNA sensor AIM2 are associated with impaired cytokine responses in healthy elderly.

OBJECTIVE: Human aging is associated with remodeling of the immune system. While most studies on immunosenescence have focused on adaptive immunity, the effects of aging on innate immunity are not well understood. Here, we investigated whether aging affects cytokine responses to a wide range of well-defined pattern recognition receptor (PRR) ligands, such as ligands for Toll-like receptors (TLRs), C-type lectin receptors (CLRs), NOD-like receptors (NLRs), retinoic-acid-inducible gene-I like receptors (RLRs) and the cytosolic DNA sensor absent in melanoma 2 (AIM2). METHOD: Blood was collected from 16 young (20-39 years) and 18 elderly (60-84 years) healthy participants. Pro-inflammatory cytokine (TNF-α, IL-1ß, IL-6, and IL-8) production in a whole blood assay (WBA) after stimulation with TLR ligands (Pam3csk4, poly(I:C), LPS, CpG), CLR ligand (ß-glucan), NLR ligand (MDP), RLR ligands (5'ppp-dsDNA and poly(I:C)/lyovec) and the AIM2 ligand (poly(dA:dT) was assessed by ELISA. TLR2 and TLR4 expression by leukocytes and monocytes was determined by flow-cytometry. Expression of AIM2 by peripheral blood mononuclear cells (PBMC) was assessed by qRT-PCR and Western blot. RESULT: Cytokine responses to Pam3csk4, poly(I:C) and CpG, ß-glucan, MDP, 5'ppp-dsDNA and poly(I:C)/lyovec were comparable between young and old participants. We observed a higher IL-8 response following stimulation of elderly blood samples with the TLR4 ligand LPS, which was associated with higher proportions of TLR4 expressing monocytes. Interestingly, stimulation of whole blood cells with the AIM2 ligand poly(dA:dT) resulted in significantly lower cytokine responses in old participants. Moreover, these lower cytokine responses were associated with lower AIM2 protein expression and activation in PBMC of old participants. CONCLUSION: Our findings reveal an age-dependent reduction of AIM2 expression and activation which may explain reduced cytokine responses to the cytosolic DNA mimic poly(dA:dT) in healthy elderly individuals. Reduced AIM2-mediated sensing with age may contribute to increased vulnerability to bacterial or viral infections in the elderly.

Aging-dependent decline of IL-10 producing B cells coincides with production of antinuclear antibodies but not rheumatoid factors.

Aging is associated with development of autoimmunity. Loss of B cell tolerance in the elderly is suggested by an increased prevalence of anti-nuclear antibodies (ANAs) and rheumatoid factors (RFs). Accumulating evidence indicates that B cells also impact autoimmunity via secretion of cytokines. So far, few studies have directly assessed the effect of aging on the latter B cell function. Here, we determined if and how human aging influences the production of cytokines by B cells. In a cross-sectional study, we found that absolute numbers of circulating B cells were similar in 31 young (ages 19-39) and 73 old (age ≥ 60) individuals. Numbers of transitional B cells (CD19(+)CD27(-)CD38(High)CD24(High)) were decreased in old individuals, whereas numbers of naive and memory B cell subsets were comparable in young and old individuals. Short-term in vitro stimulation of whole blood samples revealed that numbers of B cells capable of producing TNF-α were similar in young and old individuals. In contrast, B cells capable of IL-10 production were decreased in old subjects. This decline of IL-10(+) B cells was observed in old individuals that were ANA positive, and in those that were negative for both ANAs and RFs. However, IL-10(+) B cells were remarkably well retained in the circulation of old subjects that were RF positive. Thus, pro-inflammatory TNF-α(+) B cells are retained in the elderly, whereas IL-10(+) B cells generally decline. In addition, our findings indicate that IL-10(+) B cells may differentially impact the development of ANAs and RFs in the elderly.

Low-affinity TCR engagement drives IL-2-dependent post-thymic maintenance of naive CD4+ T cells in aged humans.

Insight into the maintenance of naive T cells is essential to understand defective immune responses in the context of aging and other immune compromised states. In humans, naive CD4+ T cells, in contrast to CD8+ T cells, are remarkably well retained with aging. Here, we show that low-affinity TCR engagement is the main driving force behind the emergence and accumulation of naive-like CD4+ T cells with enhanced sensitivity to IL-2 in aged humans. In vitro, we show that these CD45RA(+) CD25(dim) CD4(+) T cells can develop from conventional naive CD25(-) CD4+ T cells upon CD3 cross-linking alone, in the absence of costimulation, rather than via stimulation by the homeostatic cytokines IL-2, IL-7, or IL-15. In vivo, TCR engagement likely occurs in secondary lymphoid organs as these cells were detected in lymph nodes and spleen where they showed signs of recent activation. CD45RA(+) CD25(dim) CD4+ T cells expressed a broad TCRVß repertoire and could readily differentiate into functional T helper cells. Strikingly, no expansion of CD45RA(+) CD25(dim) CD8+ T cells was detected with aging, thereby implying that maintenance of naive CD4+ T cells is uniquely regulated. Our data provide novel insight into the homeostasis of naive T cells and may guide the development of therapies to preserve or restore immunity in the elderly.

Quantifying Distribution of Flow Cytometric TCR-Vß Usage with Economic Statistics.

Measuring changes of the T cell receptor (TCR) repertoire is important to many fields of medicine. Flow cytometry is a popular technique to study the TCR repertoire, as it quickly provides insight into the TCR-Vß usage among well-defined populations of T cells. However, the interpretation of the flow cytometric data remains difficult, and subtle TCR repertoire changes may go undetected. Here, we introduce a novel means for analyzing the flow cytometric data on TCR-Vß usage. By applying economic statistics, we calculated the Gini-TCR skewing index from the flow cytometric TCR-Vß analysis. The Gini-TCR skewing index, which is a direct measure of TCR-Vß distribution among T cells, allowed us to track subtle changes of the TCR repertoire among distinct populations of T cells. Application of the Gini-TCR skewing index to the flow cytometric TCR-Vß analysis will greatly help to gain better understanding of the TCR repertoire in health and disease.

Aging disturbs the balance between effector and regulatory CD4+ T cells.

Healthy aging requires an optimal balance between pro-inflammatory and anti-inflammatory immune responses. Although CD4+ T cells play an essential role in many immune responses, few studies have directly assessed the effect of aging on the balance between effector T (Teff) cells and regulatory T (Treg) cells. Here, we determined if and how aging affects the ratio between Treg and Teff cells. Percentages of both naive Treg (nTreg; CD45RA+CD25(int)FOXP3(low)) and memory Treg (memTreg; CD45RA-CD25(high)FOXP3(high)) cells were determined by flow cytometry in peripheral blood samples of healthy individuals of various ages (20-84 years). Circulating Th1, Th2 and Th17 effector cells were identified by intracellular staining for IFN-γ, IL-4 and IL-17, respectively, upon in vitro stimulation with PMA and calcium ionophore. Whereas proportions of nTreg cells declined with age, memTreg cells increased. Both Th1 and Th2 cells were largely maintained in the circulation of aged humans, whereas Th17 cells were decreased. Similar to memTreg cells, the 3 Teff subsets resided primarily in the memory CD4+ T cell compartment. Overall, Treg/Teff ratios were increased in the memory CD4+ T cell compartment of aged individuals when compared to that of young individuals. Finally, the relative increase of memTreg cells in elderly individuals was associated with poor responses to influenza vaccination. Taken together, our findings imply that aging disturbs the balance between Treg cells and Teff cells.

IL-8 but not other biomarkers of endothelial damage is associated with disease activity in patients with ankylosing spondylitis without treatment with anti-TNF agents.

The objective of the study was to investigate the association between IL-8 and other biomarkers of endothelial dysfunction (MCP-1, V-CAM, I-CAM) and the disease activity scores in a sample of 54 patients with ankylosing spondylitis (AS) without use of biological agents. Fifty-four AS patients without treatment with anti-TNFs agents between 18 and 80 years old, who met modified New York criteria and at the same time the axial ASAS criteria, were evaluated using an epidemiological questionnaire that included among others clinical data, BASDAI, BASFI, ASQoL, ASDAS and plasma levels of CRP, ESR, MCP-1, IL-8, ICAM-1 and VCAM-1. IL-8 varied in proportion to disease activity rates (BASDAI and ASDAS) p < 0.05, being strongly correlated with the disease activity. The levels of adhesion molecules I-CAM and VCAM, as described in other studies, were positively correlated with predisposing factors for cardiovascular disease. IL-8 has shown to be strongly correlated with clinical markers of disease activity and inflammatory activity and may be an additional variable to the overall assessment of the activity of the AS.