Indução de aderência intrabdominal por prótese de retícula de polipropileno : estudo experimental em ratos

INTRODUCTION: The correction of groin hernias using a transperitoneal videolaparoscopic method with a polypropylene mesh is becoming increasingly common. This could lead to an increased incidence of adhesion formation. MATERIALS AND METHODS: The incidence of adhesions induced by mesh placement and by reperitonization was observed in 40 male adult Wistar rats, randomly allocated to four groups of 10 rats (Group A = no mesh, no reperitonization; B = no mesh, reperitonization; C = mesh, no reperitonization; D = mesh and reperitonization). After opening the abdominal cavity, the iliac fossa was identified and a peritoneal opening, measuring about 2 by 2 cm, was done on the parietal wall. In the rats in which a polypropylene prosthesis was used, a piece of Marlex mesh, measuring about 1.5 by 1.5 cm was placed on the peritoneal opening. A simple suture was performed in the animals submitted to reperitonization, using a 5.0 monofilamentar polypropylene thread on a cardiovascular (atraumatic) needle. The animals were killed 15 days after the operation. Macroscopic analysis was done by an investigator blinded to intervention group. Fisher’s exact test and the c2 test were used for statistical analysis of the results. A P < 0.05 was considered as significant. RESULTS: Adhesions were significantly more common in the groups in which the prosthesis was placed (59% vs. 95%; P = 0.01), as well as in the groups in which reperitonization was performed (58% vs. 100%; P = 0.03). CONCLUSIONS: The results suggest that polypropylene mesh placement and reperitonization are each independent factors that have a role in inducing the formation of adhesions.INTRODUÇÃO: A correção de hérnias na virilha através de um método videolaparoscópico transperitoneal está se tornando cada vez mais comum. Contudo, este método poderia levar a um aumento na incidência de formação de aderências. MATERIAIS E MÉTODOS: A incidência de aderências induzidas pela colocação de retícula e pela reperitonização foram observadas em 40 ratos Wistar adultos, machos, divididos aleatoriamente em quatro grupos com 10 ratos cada um (Grupo A = sem retícula, sem reperitonização; B = sem retícula, com reperitonização; C = com retícula, sem reperitonização; D = retícula e reperitonização). Após a abertura da cavidade abdominal, a fossa ilíaca foi identificada e fez-se uma abertura de aproximadamente 2 x 2 cm na parede parietal. Nos ratos em que uma prótese de polipropileno foi utilizada, uma retícula Marlex com 1,5 x 1,5 cm foi colocada sobre a abertura peritoneal. Nos outros animais, a reperitonização foi feita com sutura simples, utilizando-se fio de polipropileno monofilamentar 5.0 com uma agulha cardiovascular (atraumática). Os animais foram sacrificados 15 dias depois da operação. A análise macroscópica foi realizada por um investigador cego quanto ao grupo de origem dos animais. A análise estatística utilizou o teste exato de Fisher e o c2. Um P < 0,05 foi considerado significativo. RESULTADOS: As aderências foram significativamente mais comuns nos grupos nos quais a prótese foi utilizada (59% vs. 95%; P = 0,01), assim como nos grupos nos quais foi feita a reperitonização (58% vs. 100%; P = 0,03). CONCLUSÕES: Os resultados sugerem que a retícula de polipropileno e a reperitonização são fatores independentes entre si quanto à indução de formação de aderências

Indução de aderência intrabdominal por prótese de retícula de polipropileno : estudo experimental em ratos

INTRODUCTION: The correction of groin hernias using a transperitoneal videolaparoscopic method with a polypropylene mesh is becoming increasingly common. This could lead to an increased incidence of adhesion formation. MATERIALS AND METHODS: The incidence of adhesions induced by mesh placement and by reperitonization was observed in 40 male adult Wistar rats, randomly allocated to four groups of 10 rats (Group A = no mesh, no reperitonization; B = no mesh, reperitonization; C = mesh, no reperitonization; D = mesh and reperitonization). After opening the abdominal cavity, the iliac fossa was identified and a peritoneal opening, measuring about 2 by 2 cm, was done on the parietal wall. In the rats in which a polypropylene prosthesis was used, a piece of Marlex mesh, measuring about 1.5 by 1.5 cm was placed on the peritoneal opening. A simple suture was performed in the animals submitted to reperitonization, using a 5.0 monofilamentar polypropylene thread on a cardiovascular (atraumatic) needle. The animals were killed 15 days after the operation. Macroscopic analysis was done by an investigator blinded to intervention group. Fisher’s exact test and the c2 test were used for statistical analysis of the results. A P < 0.05 was considered as significant. RESULTS: Adhesions were significantly more common in the groups in which the prosthesis was placed (59% vs. 95%; P = 0.01), as well as in the groups in which reperitonization was performed (58% vs. 100%; P = 0.03). CONCLUSIONS: The results suggest that polypropylene mesh placement and reperitonization are each independent factors that have a role in inducing the formation of adhesions.INTRODUÇÃO: A correção de hérnias na virilha através de um método videolaparoscópico transperitoneal está se tornando cada vez mais comum. Contudo, este método poderia levar a um aumento na incidência de formação de aderências. MATERIAIS E MÉTODOS: A incidência de aderências induzidas pela colocação de retícula e pela reperitonização foram observadas em 40 ratos Wistar adultos, machos, divididos aleatoriamente em quatro grupos com 10 ratos cada um (Grupo A = sem retícula, sem reperitonização; B = sem retícula, com reperitonização; C = com retícula, sem reperitonização; D = retícula e reperitonização). Após a abertura da cavidade abdominal, a fossa ilíaca foi identificada e fez-se uma abertura de aproximadamente 2 x 2 cm na parede parietal. Nos ratos em que uma prótese de polipropileno foi utilizada, uma retícula Marlex com 1,5 x 1,5 cm foi colocada sobre a abertura peritoneal. Nos outros animais, a reperitonização foi feita com sutura simples, utilizando-se fio de polipropileno monofilamentar 5.0 com uma agulha cardiovascular (atraumática). Os animais foram sacrificados 15 dias depois da operação. A análise macroscópica foi realizada por um investigador cego quanto ao grupo de origem dos animais. A análise estatística utilizou o teste exato de Fisher e o c2. Um P < 0,05 foi considerado significativo. RESULTADOS: As aderências foram significativamente mais comuns nos grupos nos quais a prótese foi utilizada (59% vs. 95%; P = 0,01), assim como nos grupos nos quais foi feita a reperitonização (58% vs. 100%; P = 0,03). CONCLUSÕES: Os resultados sugerem que a retícula de polipropileno e a reperitonização são fatores independentes entre si quanto à indução de formação de aderências

Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production.

Diseases that cause hemolysis or myonecrosis lead to the leakage of large amounts of heme proteins. Free heme has proinflammatory and cytotoxic effects. Heme induces TLR4-dependent production of tumor necrosis factor (TNF), whereas heme cytotoxicity has been attributed to its ability to intercalate into cell membranes and cause oxidative stress. We show that heme caused early macrophage death characterized by the loss of plasma membrane integrity and morphologic features resembling necrosis. Heme-induced cell death required TNFR1 and TLR4/MyD88-dependent TNF production. Addition of TNF to Tlr4−/− or to Myd88−/− macrophages restored heme-induced cell death. The use of necrostatin-1, a selective inhibitor of receptor-interacting protein 1 (RIP1, also known as RIPK1), or cells deficient in Rip1 or Rip3 revealed a critical role for RIP proteins in heme-induced cell death. Serum, antioxidants, iron chelation, or inhibition of c-Jun N-terminal kinase (JNK) ameliorated heme-induced oxidative burst and blocked macrophage cell death. Macrophages from heme oxygenase-1 deficient mice (Hmox1−/−) had increased oxidative stress and were more sensitive to heme. Taken together, these results revealed that heme induces macrophage necrosis through 2 synergistic mechanisms: TLR4/Myd88-dependent expression of TNF and TLR4-independent generation of ROS.Fil: Fortes, Guilherme B.. Universidade Federal do Rio de Janeiro; BrasilFil: Alves, Leticia S.. Universidade Federal do Rio de Janeiro; BrasilFil: Olivera, Rosane de. University of Massachussets; Estados Unidos. Universidade Federal do Rio de Janeiro; BrasilFil: Dutra, Fabianno F.. Universidade Federal do Rio de Janeiro; BrasilFil: Rodrigues, Danielle. Universidade Federal do Rio de Janeiro; BrasilFil: Fernandez, Patricia F.. Instituto de Investigaciones Científicas y Servicios de Alta Tecnología; PanamáFil: Souto Padron, Thais. Instituto de Investigaciones Cientificas y Servicios de alta Tecnología; PanamáFil: de Rosa, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Kelliher, Michelle. University of Massachussets; Estados UnidosFil: Golenbock, Douglas. University of Massachussets; Estados UnidosFil: Chan, Francis K. M.. University of Massachussets; Estados UnidosFil: Bozza, Marcelo T.. Universidade Federal do Rio de Janeiro; Brasi

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used