An HLA-E-targeted TCR bispecific molecule redirects T cell immunity against Mycobacterium tuberculosis.

Peptides presented by HLA-E, a molecule with very limited polymorphism, represent attractive targets for T cell receptor (TCR)-based immunotherapies to circumvent the limitations imposed by the high polymorphism of classical HLA genes in the human population. Here, we describe a TCR-based bispecific molecule that potently and selectively binds HLA-E in complex with a peptide encoded by the inhA gene of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis in humans. We reveal the biophysical and structural bases underpinning the potency and specificity of this molecule and demonstrate its ability to redirect polyclonal T cells to target HLA-E-expressing cells transduced with mycobacterial inhA as well as primary cells infected with virulent Mtb. Additionally, we demonstrate elimination of Mtb-infected cells and reduction of intracellular Mtb growth. Our study suggests an approach to enhance host T cell immunity against Mtb and provides proof of principle for an innovative TCR-based therapeutic strategy overcoming HLA polymorphism and therefore applicable to a broader patient population.

Psoas muscle abscess simulating acute appendicits: A case report.

INTRODUCTION: Psoas abscess is a rare clinical entity with vague symptomatology. We report a psoas abscess that simulated symptoms of acute appendicitis. PRESENTATION OF CASE: A twenty-five year old male presented pain irradiating to the right iliac fossa and lumbar region associated with thigh flexion. Laboratorial exams revealed leukocytosis with a neutrophil shift to the left. Abdominal Ultrasound showed significant intestinal distension and a small quantity of free fluid at the right iliac fossa. Laparotomy and an appendectomy were performed. During immediate post-operative, the patient evolved with worsening of the pain and the leukocytosis, therefore, we chose to maintain his antalgic posture. An abdominal Computerized Tomography scan with contrast was solicited, revealing an increase of the iliac and psoas muscles of the right side, and multiple bacterial focuses. A retroperitoneal access was performed and 300ml of purulent secretion was drained. Afterwards, we implanted a Penrose Drain. The patient had a good post-op evolution, being discharged 7days after the drainage. DISCUSSION: The psoas muscle is a flexor of the thigh. Psoas abscess is an underdiagnosed condition, its main treatment is surgery associated with antibiotic therapy. CT scan seems to be the best choice of diagnostic image exam, although some authors prefer the nuclear magnetic resonance. CONCLUSION: The psoas muscle abscess is uncommon and poorly characterized in its etiology, clinical associations, and its therapeutic approach. On the other hand, acute appendicitis is the most common abdominal emergency, with a 7% death rate, and surgery is its main treatment.

Sialic acid removal from dendritic cells improves antigen cross-presentation and boosts anti-tumor immune responses.

Dendritic cells (DCs) hold promise for anti-cancer immunotherapy. However, clinically, their efficiency is limited and novel strategies to improve DC-mediated anti-tumor responses are needed. Human DCs display high content of sialic acids, which inhibits their maturation and co-stimulation capacity. Here, we aimed to understand whether exogenous desialylation of DCs improves their anti-tumor immunity. Compared to fully sialylated DCs, desialylated human DCs loaded with tumor-antigens showed enhanced ability to induce autologous T cells to proliferate, to secrete Th1 cytokines, and to specifically induce tumor cell apoptosis. Desialylated DCs showed an increased expression of MHC-I and -II, co-stimulatory molecules and an augmented secretion of IL-12. Desialylated HLA-A*02:01 DCs pulsed with gp100 peptides displayed enhanced peptide presentation through MHC-I, resulting in higher activation ofgp100280-288 specific CD8+ cytotoxic T cells. Desialylated murine DCs also exhibited increased MHC and co-stimulatory molecules and higher antigen cross-presentation via MHC-I. These DCs showed higher ability to activate antigen-specific CD4+ and CD8+ T cells, and to specifically induce tumor cell apoptosis. Collectively, our data demonstrates that desialylation improves DCs' ability to elicit T cell-mediated anti-tumor activity, due to increased MHC-I expression and higher antigen presentation via MHC-I. Sialidase treatment of DCs may represent a technology to improve the efficacy of antigen loaded-DC-based vaccines for anti-cancer immunotherapy.

[The first dual left lobe adult-to-adult liver transplantation in Brazil]. / Primeiro transplante duplo de fígado esquerdo intervivos adultos do Brasil.

Living donor liver transplantation expanded the therapeutic possibilities for liver failure patients. The necessary correct match between the liver mass donated and received sometimes limits its use. A case that was used two left liver grafts from adult living donors is reported.

Primeiro transplante duplo de fígado esquerdo intervivos adultos do Brasil / The first dual left lobe adult-to-adult liver transplantation in Brazil

O transplante hepático inter vivos adulto expandiu as possibilidades terapêuticas para pacientes com insuficiência hepática terminal. A necessidade de um volume hepático adequado que será retirado do doador e necessário ao receptor limita sua utilização em alguns casos. Apresentamos um caso em que se utilizou dois lobos esquerdos de dois doadores vivos no intuito de prover parênquima hepático suficiente ao receptor.

Living donor liver transplantation expanded the therapeutic possibilities for liver failure patients. The necessary correct match between the liver mass donated and received sometimes limits its use. A case that was used two left liver grafts from adult living donors is reported.

Sea-land limits: a case study

The limits between sea and land were estimated at "Pulso" beach located in the Southeastern Brazilian shelf (φ = 23°33/17.4886"S; Λ = 045° 13'13.0504"W - WGS84), between the island of São Sebastião and the city of Ubatuba, SP, Brazil. The relative sea level of the year 1831 at "Pulso" beach, as per Brazilian law Number 9760 dated from 1946, was estimated and materialized. The retro-estimation allowed the demarcation of the Legal Sea-Land Limits at "Pulso" beach as per the terms of the law. The accuracy of the procedure for the transference of the long-term sea level from the research station of Ubatuba to "Pulso" beach was assessed by parallel work of geometrical leveling referred to the IBGE (Brazilian Institute of Geography and Statistics) geodetic network. The motivation, the hypotheses (Brest, Cananeia and IPCC) and the methods here used are described, together with a short history of the Legal Sea-Land Limits. The results indicated that the legal Sea-Land Limits at "Pulso" beach are well within the beach area. They were determined as per law 9760, and there is the need to reactivate the national network of sea level gauge.

Os limites entre mar e terra foram estimados na praia chamada Pulso, localizada na costa sudeste do Brasil (φ = 23°33'17, 4886"S; Λ = 045°13'13, 0504"W) entre a Ilha de São Sebastião e a cidade de Ubatuba, no Estado de São Paulo, SP, Brasil. O nível relativo do mar do ano de 1831 na praia do Pulso, ou "Praia do Pulso" (PP), foi estimado e materializado, de acordo com a Lei brasileira Número 9760 de 1946. A acurácia do procedimento foi acompanhada por trabalho paralelo de nivelamento geométrico referido ao sistema nacional de geodésia do IBGE (Instituto Brasileiro de Geografia e Estatística). A motivação, as hipóteses (Brest, Cananeia e IPCC) e os métodos utilizados são descritos, acompanhados por um breve histórico dos "Terrenos de Marinha". Os resultados indicaram que os limites em (PP) estão bem dentro da área da praia. Eles fora deterinados de acordo co a Lei No. 9760 e há a necessidade de reativar a rede nacional de medidores do nível do mar.

Perfil dos portadores de GIST operados no Estado do Rio de Janeiro: estudo multicêntrico SBCO / Profile of GIST's patients operated in the State of Rio de Janeiro: SBCO multi-centric trial

Objetivo: o presente estudo tem como objetivo conhecer o perfil dos portadores de tumores estromais gastrointestinais (GISTs) tratados pelos cirurgiões no Estado do Rio de Janeiro. Método: estudo multicêntrico, retrospectivo, implementado pela Sociedade Brasileira de Cirurgia Oncológica (SBCO), tendo início em dezembrode 2006 e término em dezembro de 2007. Foram incluídos 47 casos de GIST tratados cirurgicamente. Resultados: houve predominância do sexo feminino (29 mulheres e 18 homens) e a idade variou de 10 a 81 anos, com mediana de idade de 62 anos. O estômago foi o sítio mais frequente de localização do tumor (44 casos), seguido do intestino delgado (2 casos) e do reto (1 caso). Os sintomas mais comuns foram dor abdominal (48,9 por cento dos casos), massa palpável (46,8 por cento) e sangramento digestivo (27,6 por cento). O tamanho tumoral variou de 0,8 cm a 28 cm, com mediana de 12 cm. A gastrectomia segmentar foi o procedimento cirúrgico mais empregado (21 casos). A incidência de metástase linfonodal foi de 4,2 por cento. A taxa de recidiva foi de 40,4 por cento (todos os casos classificados como GIST de alto risco). Conclusão: a presente casuística revela que o perfil dos portadores de GIST tratados por cirurgiões do Estado do Rio de Janeiro difere em alguns pontos dos relatos da literatura estrangeira, havendo necessidade de estudos nacionais com maior amostragem para confirmação dos dados.

Emprego de exclusão vascular hepática total nas ressecções tumorais do fígado / Tumoral hepatic resection under total vascular exclusion

Racional - O controle do sangramento perioperatório em cirurgia hepática é fator essencial tanto da morbidade, quanto da mortalidade pós-operatória. Atualmente diferentes métodos de controle vascular são utilizados de maneira corrente, desde clampeamento seletivo segmentar, até a exclusão total do fígado que é o método mais efetivo de controle vascular hepático em cirurgia hepática de grande porte. Porém dado ao efeito isquêmico desta técnica no fígado remanescente, suas indicações são bastante limitadas. Relato dos Casos - Dois casos de operações hepáticas de grande porte com uso de exclusão total do fígado obtiveram boa evolução, com hospitalização de curta duração sem complicações. A hepatectomia foi realizada com exclusão total do fígado por 45 minutos, e ressecção do parênquima hepático com bisturi ultrasônico. Após revascularização do fígado, a hemostasia foi realizada, principalmente, com cauterização por agônio. Conclusão - A exclusão total do fígado é a técnica de controle vascular mais efetiva no controle de sangramento cirúrgico, com bons resultados nas suas indicações.

Resultados do transplante pancreático em um centro brasileiro / Results of pancreatic transplantation in a Brazilian center

Objetivo: O transplante de pâncreas (TP) é atualmente o único tratamento disponível capaz de estabelecer estado euglicêmico permanente e de independência da insulina nos portadores de Diabetes Mellitus Tipo 1. Neste estudo são apresentados os resultados do TP realizados em um centro paranaense. Método: De janeiro de 2001 até abril de 2003, foram realizados 24 transplantes de pâncreas-rim simultâneos (TPRS), e um Transplante de Pâncreas Isolado (TPI) no Hospital e Maternidade Angelina Caron. Resultados: No seguimento de 8,2 meses (1-27), a taxa de sucesso para pâncreas e rim foi de 74 %. A sobrevida dos pacientes foi de 76 %. A principal causa de insucesso foi trombose pancreática em três casos (12%) e renal em dois (8%). Não ocorreu nenhum episódio de rejeição. Todos os doentes com enxertos funcionantes apresentam-se normoglicêmicos sem necessidade de insulina. Conclusões: O transplante simultâneo de rim e pâncreas é terapêutica com alto índice de sucesso para pacientes diabéticos com insuficiência renal terminal.

Background: Pancreatic transplantation (PT) is the only treatment available to keep long term normoglicemic state and insulin independence in type 1 diabetic patients. We present the results of PTperformed in a center at the State of Paraná. Methods : From January 2001 until april 2003, 24 patients received simultaneous pancreas-kidney transplant (SPK) and one isolated pancreatic transplant at Hospital Angelina Caron. Results : With a mean follow-up of 8,2 months (range 1-27), the pancreas and kidney success rate was 74%. Patient survival was 76%. Leading cause of pancreas and kidney losses was thrombosis in three pancreas (12%) and two kidneys (8%). No episode of rejection occurred in anyof the transplanted patients. All patients with successful grafts are insulin-free since transplantation. Conclusions : This series confirms that SPK is a highly successful procedure for diabetic patients with renal failure.

Major hepatectomy for isolated metastases from gastric adenocarcinoma.

BACKGROUND: Liver metastases from gastric adenocarcinoma denote a poor prognosis. Most gastric metastases will be diffuse, and for these chemotherapy remains the only useful treatment modality. The treatment of isolated liver metastases is still unclear. The Japanese literature has reported good results with surgical resection, but Western series were unable to achieve the same results. We report our results with resection of liver metastases from gastric cancer in nine patients. METHODS: A retrospective analysis was undertaken to determine the results of the surgical treatment of hepatic metastases from gastric carcinoma over the last five decades. Only nine patients underwent such treatment. Variables analysed were age, gender, the primary tumour, the type of liver operation performed, the time of occurrence of liver metastasis, the morbidity and mortality and the overall survival. Follow-up was complete. RESULTS: There were eight patients with gastric carcinoma staged as T3 and one as T4 (UICC-97). All patients had positive lymph nodes. The hepatic procedure performed was a hemihepatectomy in eight patients and a left lateral segmentectomy in one patient. Right hepatectomy was performed in six cases. There were four patients with synchronous liver metastasis: three involved the right liver and the other involved segments II/III. All were treated by one-step surgery. The five metachronous metastases involved the right liver in three patients (accounting for half of the right hepatectomies), while the other two underwent left hepatectomies. There was a high postoperative mortality rate (33%, 3/9), two of the deaths occurring in the first decade of the study (1956, 1966) secondary to hepatic insufficiency and one from sepsis. One patient died suddenly without recurrence after 3 months. The other five died with evidence of disease at between 2 and 11 months. DISCUSSION: Despite some anecdotal reports of treatment with chemotherapy, either systemic or intrahepatic, the more consistent results for the treatment of patients with hepatic metastases from gastric adenocarcinoma come from the Japanese literature with the use of radical surgery. Unfortunately, Western series, including our own, do not achieve the same results. At the present time, in view of these results, we are performing less aggressive treatment such as radio-frequency ablation.

O sedentarismo na Polícia Militar do Paraná / The sedentarism of the Military Police of the Parana's State

Tendo-se comprovada, a posiçäo adotada pelo homem em ser um sedentário, tendendo a acomodar-se por inúmeros fatores, entre os quais: a idade, o envelhecimento, a desmotivaçäo profissional e o desinteresse das instituiçöes públicas e privadas no que tange a qualidade de vida. O presente estudo teve por objetivo identificar a condiçäo de sedentarismo dos integrantes da Polícia Militar do Paraná (PMPR), visando demonstrar as causas e consequencias da vida sedentária. As causas convergem para dois pontos básicos: a falta de consciência da atividade física na promoçäo da saúde e um melhor planejamento da instituiçäo pesquisada, enquanto que as consequências representam efeitos negativos ao policial militar, à PMPR e à comunidade paranaense. Concluiu-se entäo que, a vida sedentária influi decisivamente para a ineficiëncia profissional, como para a saúde do indivíduo, comprometendo-o danosamente de forma gradativa, diminuindo a qualidade de vida, até roubar por completo a sua vitalidade