CD16 promotes Escherichia coli sepsis through an FcR gamma inhibitory pathway that prevents phagocytosis and facilitates inflammation.

Sepsis, a leading cause of death worldwide, involves proinflammatory responses and inefficient bacterial clearance. Phagocytic cells play a crucial part in the prevention of sepsis by clearing bacteria through host innate receptors. Here we show that the FcRgamma adaptor, an immunoreceptor tyrosine-based activation motif (ITAM)-bearing signal transduction subunit of the Fc receptor family, has a deleterious effect on sepsis. FcRgamma(-/-) mice show increased survival during peritonitis, owing to markedly increased E. coli phagocytosis and killing and to lower production of the proinflammatory cytokine tumor necrosis factor (TNF)-alpha. The FcRgamma-associated receptor that inhibits E. coli phagocytosis is FcgammaRIII (also called CD16), and its absence protects mice from sepsis. FcgammaRIII binds E. coli, and this interaction induces FcRgamma phosphorylation, recruitment of the tyrosine phosphatase SHP-1 and phosphatidylinositide-3 kinase (PI3K) dephosphorylation. Decreased PI3K activity inhibits E. coli phagocytosis and increases TNF-alpha production through Toll-like receptor 4. We identified the phagocytic receptor negatively regulated by FcRgamma on macrophages as the class A scavenger receptor MARCO. E. coli-FcgammaRIII interaction induces the recruitment of SHP-1 to MARCO, thereby inhibiting E. coli phagocytosis. Thus, by binding FcgammaRIII, E. coli triggers an inhibitory FcRgamma pathway that both impairs MARCO-mediated bacterial clearance and activates TNF-alpha secretion.

Telemedicine medical evaluation of low-risk patients with dengue during an outbreak may be an option in reducing the need for on-site physicians.

OBJECTIVE: To analyze the effectiveness of telemedicine consultations during an outbreak in reducing the need for face-to-face consultations at a field hospital for patients with dengue. METHODS: We performed a retrospective unicentric study between April and May 2015 with 4626 patients (≥15 years old) who spontaneously sought care at an emergency field hospital (Sao Paulo/Brazil). A nurse initially assessed all patients with dengue through rapid diagnostic testing, automated complete blood count, and risk stratification. During overcrowded situations, a video-based telemedicine consultation was provided as an option to all low-to-moderate risk patients who tested positive. The management was carried out according to current dengue guidelines. The primary end point was a referral to immediate face-to-face medical evaluation. RESULTS: Of all patients suspected of dengue infection, 2003 presented positive testing, 1978 were classified as low-moderate risk, and 267 patients with dengue were evaluated by telemedicine. The mean age was 38.17 ± 13.7 years (54.6% female). Oral medications were recommended in 169 (63.3%), intravenous hydration or symptomatic drugs in 96 (36%), 252 (94.4%) were discharged after telemedicine assessment, and only 15 (5.6%) were referred to immediate face-to-face medical evaluation. No adverse events were recorded. CONCLUSION: Telemedicine medical assessment of low-to-moderate risk patients with dengue previously screened by nursing triage is effective in replacing the face-to-face evaluation in a field hospital. Telemedicine may be reinforced in epidemiological outbreak scenarios as a cost-effective strategy for the initial assessment of acute patients.

B lymphocytes undergo apoptosis because of FcgammaRIIb stress response to infection: a novel mechanism of cell death in sepsis.

Sepsis is predominantly characterized by proinflammatory signs in its initial phase, but can be also associated with immune suppression that can be a consequence of apoptotic cell death. The role of Fc receptors (FcRs) is poorly understood in this disease, and it was recently shown that, in addition to the promotion of opposite inflammatory responses, they are implicated in apoptosis. Using a model of peritonitis in mice that do not express activating FcRs, we tested the hypothesis that FcgammaRIIb, the only known immunoglobulin G receptor capable of inducing apoptosis, would participate in the induction of this kind of cell death during serious infection. The blocking of this receptor by a monoclonal antibody significantly decreased the number of apoptotic splenic B cells, demonstrating its involvement in apoptosis. FcgammaRIIb-mediated apoptosis was neither the result of increased TNFalpha levels nor was it associated with IL-10 production. Finally, the decreased apoptosis after mice treatment with FcgammaRIIb-blocking antibody was not sufficient to increase its survival. Thus, we conclude that although apoptosis is a multifactorial phenomenon in sepsis, one of these factors is the inhibitory immunoglobulin G receptor FcgammaRIIb. FcgammaRIIb stress response to infection is a novel mechanism that contributes to the comprehension of apoptosis in sepsis.

The role of pneumonia scores in the emergency room in patients infected by 2009 H1N1 infection.

Despite the severity of pneumonia in patients with pandemic influenza A infection (H1N1), no validated risk scores associated with H1N1 pneumonia were tested. In this prospective observational study, we analyzed data of consecutive patients in our emergency room, hospitalized because of pneumonia between July and August 2009 in a public hospital in Brazil. The following pneumonia scoring systems were applied: the SMART-COP rule; the Pneumonia Severity Index; and the CURB-65 rule. Of 105 patients with pneumonia, 53 had H1N1 infection. Among them, only 9.5% that had a low risk according to SMART-COP were admitted to ICU, compared with 36.8% of those with the Pneumonia Severity Index score of 1-2 and 49% of those with CURB-65 score of 0-1. The SMART-COP had an accuracy of 83% to predict ICU admission. The SMART-COP rule presented the best performance to indicate ICU admission in patients with H1N1 pneumonia.

Expressão dos receptores FC de imunoglobulina A em fagócitos do sangue de pacientes com bacteremia / Expression of immunoglobulin a FC receptors on blood phagocytes of patients with gram-negative bacteremia

Expressão aumentada do receptor Fc de IgA (CD89) e da cadeia g associada, avaliadas respectivamente por citometria de fluxo e por “immunobloting”, foram encontradas em fagócitos do sangue de pacientes com bacteremia por germes gram-negativos, em comparação com controles e pacientes com bacteremia por gram-positivos. A Mr do CD89 avaliada por SDS-PAGE estava diminuída, com núcleo protéico de 32kDa, sugerindo alteração de glicosilação. O aumento da expressão do CD89 correlacionou-se com aumento dos níveis séricos de IL-6. A cadeia g estava fosforilada nos neutrófilos, sugerindo participação do CD89 na sepsis por gram-negativos.

The expression and function of FcaRI (CD89) were analyzed on blood monocytes and neutrophils of patients with gram-positive and gram-negative bacteremia. Eighteen patients with gram-positive bacteremia, sixteen patients with gram-negative bacteremia and twenty healthy individuals were studied. CD89 expression were analyzed by flow cytometry using specific stained antibodies. Analysis of the surface iodinated CD89 molecules by SDS-PAGE and of the CD89 g-associated chain by immunoblotting also were performed. A marked increase in expression of the a and g subunits of the FcaRI were found on both types of cells in patients with gram-negative bacteremia, but not in patients with gram-positive bacteremia. This increase was independent of serum IgA levels. FcaRI Mr was lower on cells from gram negative patients than on cells from controls (50-65 kDa vs 55-75 kDa) despite of similar 32 kDa backbone, indicating altered glycosylation. Increased levels of FcaRI on blood phagocytes correlated with enhanced serum IL-6 levels, but not with IFN-g or TNF-a levels. The CD89 g-associated chain was phosphorylated on neutrophils, suggesting an engagement of CD89 during gram negative sepsis.

Serviço Integrado de Neurogeriatria. Ambulatório da Memória - Análise dos resultados iniciais / Neurogeriatric Integrated Service. Memory Clinic - description of the initial results

Demência é o declínio da capacidade intelectual e adequação social em grau suficiente para afetar as atividades de vida diária. A demência pode ter várias etiologias, sendo algumas reversíveis. O Ambulatório da Memória do Serviço Integrado de Neurogeriatria da Real e Benemérita Sociedade Portuguesa de Beneficência - Hospital São Joaquim - propõe um modelo de atendimento multidisciplinar para o diagnóstico e tratamento das síndromes demenciais, com os seguintes resultados preliminares: dos 104 pacientes, 10 (9,6 por cento) não apresentavam deterioração intelectual. Dos 94 demais, 27 (28,7 por cento) tinham afecções potencialmentereversíveis: 18 casos de doença psiquiátrica; dois de doenças metabólicas; três de intoxicações exógenas e 4 casos de hidrocefalia. Foram 67 casos (71,2 por cento) de perda cognitiva causada por lesão estrutural, dos quais 42 pacientes (62,5 por cento) tinham doença de Alzheimer, que, atualmente possui tratamento específico. A proposta de uma equipe multidisciplinar, bem estruturada, pode beneficiar estes pacientes e seus familiares

Aspectos gerais das arteriopatias no idoso: arteriopatias e envelhecimento / Arterypathia and oldness

Apresenta o fator idade no processo de envelhecimento e determinante para um comprometimento para a qualidade de vida e limitações impostas para o idoso