Follicular thyroid carcinoma invades venous rather than lymphatic vessels

Follicular thyroid carcinoma (FTC) tends to metastasize to remote organs rather than local lymph nodes. Separation of FTC from follicular thyroid adenoma (FTA) relies on detection of vascular and/or capsular invasion. We investigated which vascular markers, CD31, CD34 and D2-40 (lymphatic vessel marker), can best evaluate vascular invasion and why FTC tends to metastasize via blood stream to remote organs. Thirty two FTCs and 34 FTAs were retrieved for evaluation. The average age of patients with FTA was 8 years younger than FTC (p = 0.02). The female to male ratio for follicular neoplasm was 25:8. The average size of FTC was larger than FTA (p = 0.003). Fourteen of 32 (44%) FTCs showed venous invasion and none showed lymphatic invasion, with positive CD31 and CD34 staining and negative D2-40 staining of the involved vessels. The average number of involved vessels was 0.88 ± 1.29 with a range from 0 to 5, and the average diameter of involved vessels was 0.068 ± 0.027 mm. None of the 34 FTAs showed vascular invasion. CD31 staining demonstrated more specific staining of vascular endothelial cells than CD34, with less background staining. We recommended using CD31 rather than CD34 and/or D2-40 in confirming/excluding vascular invasion in difficult cases. All identified FTCs with vascular invasions showed involvement of venous channels, rather than lymphatic spaces, suggesting that FTCs prefer to metastasize via veins to distant organs, instead of lymphatic vessels to local lymph nodes, which correlates with previous clinical observations

Angiotensin II Infusion Induces Marked Diaphragmatic Skeletal Muscle Atrophy

Advanced congestive heart failure (CHF) and chronic kidney disease (CKD) are characterized by increased angiotensin II (Ang II) levels and are often accompanied by significant skeletal muscle wasting that negatively impacts mortality and morbidity. Both CHF and CKD patients have respiratory muscle dysfunction, however the potential effects of Ang II on respiratory muscles are unknown. We investigated the effects of Ang II on diaphragm muscle in FVB mice. Ang II induced significant diaphragm muscle wasting (18.7±1.6% decrease in weight at one week) and reduction in fiber cross-sectional area. Expression of the E3 ubiquitin ligases atrogin-1 and muscle ring finger-1 (MuRF-1) and of the pro-apoptotic factor BAX was increased after 24 h of Ang II infusion (4.4±0.3 fold, 3.1±0.5 fold and 1.6±0.2 fold, respectively, compared to sham infused control) suggesting increased muscle protein degradation and apoptosis. In Ang II infused animals, there was significant regeneration of injured diaphragm muscles at 7 days as indicated by an increase in the number of myofibers with centralized nuclei and high expression of embryonic myosin heavy chain (E-MyHC, 11.2±3.3 fold increase) and of the satellite cell marker M-cadherin (59.2±22.2% increase). Furthermore, there was an increase in expression of insulin-like growth factor-1 (IGF-1, 1.8±0.3 fold increase) in Ang II infused diaphragm, suggesting the involvement of IGF-1 in diaphragm muscle regeneration. Bone-marrow transplantation experiments indicated that although there was recruitment of bone-marrow derived cells to the injured diaphragm in Ang II infused mice (267.0±74.6% increase), those cells did not express markers of muscle stem cells or regenerating myofibers. In conclusion, Ang II causes marked diaphragm muscle wasting, which may be important for the pathophysiology of respiratory muscle dysfunction and cachexia in conditions such as CHF and CKD

Prevention and Therapy of Hepatocellular Carcinoma by Vaccination with TM4SF5 Epitope-CpG-DNA-Liposome Complex without Carriers

Although peptide vaccines have been actively studied in various animal models, their efficacy in treatment is limited. To improve the efficacy of peptide vaccines, we previously formulated an efficacious peptide vaccine without carriers using the natural phosphodiester bond CpG-DNA and a special liposome complex (Lipoplex(O)). Here, we show that immunization of mice with a complex consisting of peptide and Lipoplex(O) without carriers significantly induces peptide-specific IgG2a production in a CD4+ cells- and Th1 differentiation-dependent manner. The transmembrane 4 superfamily member 5 protein (TM4SF5) has gained attention as a target for hepatocellular carcinoma (HCC) therapy because it induces uncontrolled growth of human HCC cells via the loss of contact inhibition. Monoclonal antibodies specific to an epitope of human TM4SF5 (hTM4SF5R2-3) can recognize native mouse TM4SF5 and induce functional effects on mouse cancer cells. Pre-immunization with a complex of the hTM4SF5R2-3 epitope and Lipoplex(O) had prophylactic effects against tumor formation by HCC cells implanted in an mouse tumor model. Furthermore, therapeutic effects were revealed regarding the growth of HCC when the vaccine was injected into mice after tumor formation. These results suggest that our improved peptide vaccine technology provides a novel prophylaxis measure as well as therapy for HCC patients with TM4SF5-positive tumors

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial: study protocol for a multicentre international trial of cardiac output-guided fluid therapy with low-dose inotrope infusion compared with usual care in patients undergoing major elective gastrointestinal surgery.

INTRODUCTION: Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice. METHODS: The Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide. ETHICS/DISSEMINATION: The OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: ISRCTN39653756.The OPTIMISE II trial is supported by Edwards Lifesciences (Irvine, CA) and the UK National Institute for Health Research through RMP’s NIHR Professorship

Pulsed LLLT improves tendon healing in rats: a biochemical, organizational, and functional evaluation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)In the last decades, the tendon injuries have increased substantially. Previous results suggested that low-level laser treatment (LLLT) promotes synthesis of extracellular matrix and improves the functional properties of the tendon. The aim of this study was to evaluate the effects of different protocols of LLLT on partially tenotomized tendons. Adult male rats were divided into the following: G1-intact, G2-injured, G3-injured + LLLT (4 J/cm(2) continuous), G4-injured + LLLT (4 J/cm(2) at 20 Hz). G2, G3, and G4 were euthanized 8 days after injury. G5-injured, G6-injured + LLLT (4 J/cm(2) continuous), and G7-injured + LLL (4 J/cm(2) at 20 Hz until the seventh day and 2 kHz from 8 to 14 days). G5, G6, and G7 were euthanized on the 15th day. Glycosaminoglycan (GAG) level was quantified by dimethylmethylene blue method and analyzed on agarose gel. Toluidine blue (TB) stain was used to observe metachromasy. CatWalk system was used to evaluate gait recovery. Collagen organization was analyzed by polarization microscopy. The GAG level increased in all transected groups, except G5. In G6 and G7, there was a significant increase in GAG in relation to G5. In G3 and G4, the presence of dermatan sulfate band was more prominent than G2. TB stains showed intense metachromasy in the treated groups. Birefringence analysis showed improvement in collagen organization in G7. The gait was significantly improved in G7. In conclusion, pulsed LLLT leads to increased organization of collagen bundles and improved gait recovery.292SI805811Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [2010/52383-2

Tabagismo e suas peculiaridades durante a gestação: uma revisão crítica Smoking and its peculiarities during pregnancy: a critical review

A gestação é uma ocasião especial para a promoção da cessação do tabagismo. A preocupação com a saúde do feto gera uma motivação extraordinária na gestante. Os resultados e a relação custo-efetividade das intervenções são melhores neste grupo do que na população em geral. Os ganhos extrapolam os benefícios à saúde da mulher, pois permitem também o desenvolvimento de um feto mais saudável. O conhecimento das peculiaridades do tabagismo durante a gestação é fundamental para uma abordagem direcionada e com maior probabilidade de sucesso. Este trabalho de revisão tem o objetivo de ressaltar a extensão dos malefícios do fumo, tanto para a mulher gestante quanto para seu feto, e estimular o uso de técnicas apropriadas para a suspensão do tabagismo nesta população.<br>Pregnancy presents a special opportunity to promote smoking cessation. Concern for the health of the fetus can be extraordinarily motivating for the pregnant woman. Results and cost-effectiveness of antismoking interventions are better for this group than for the general population, and the advantages exceed the benefits to the health of the mother alone, since they also allow for the development of a healthy fetus. Knowledge of the peculiarities of smoking during pregnancy is fundamental to developing a directed approach, which increases the probability of success. This review investigates the extent of the harmful effects that smoking has on pregnant women and fetuses alike and advocates the use of appropriate techniques to encourage pregnant women to stop smoking