As classificações das fraturas do rádio distal são reprodutíveis? Concordância intra e interobservadores

CONTEXT AND OBJECTIVE: Various classification systems have been proposed for fractures of the distal radius, but the reliability of these classifications is seldom addressed. For a fracture classification to be useful, it must provide prognostic significance, interobserver reliability and intraobserver reproducibility. The aim here was to evaluate the intraobserver and interobserver agreement of distal radius fracture classifications. DESIGN AND SETTING: This was a validation study on interobserver and intraobserver reliability. It was developed in the Department of Orthopedics and Traumatology, Universidade Federal de São Paulo (UNIFESP) - Escola Paulista de Medicina. METHOD: X-rays from 98 cases of displaced distal radius fracture were evaluated by five observers: one third-year orthopedic resident (R3), one sixth-year undergraduate medical student (UG6), one radiologist physician (XRP), one orthopedic trauma specialist (OT) and one orthopedic hand surgery specialist (OHS). The radiographs were classified on three different occasions (times T1, T2 and T3) using the Universal (Cooney), Arbeitsgemeinschaft für Osteosynthesefragen/Association for the Study of Internal Fixation (AO/ASIF), Frykman and Fernández classifications. The kappa coefficient (κ) was applied to assess the degree of agreement. RESULTS: Among the three occasions, the highest mean intraobserver k was observed in the Universal classification (0.61), followed by Fernández (0.59), Frykman (0.55) and AO/ASIF (0.49). The interobserver agreement was unsatisfactory in all classifications. The Fernández classification showed the best agreement (0.44) and the worst was the Frykman classification (0.26). CONCLUSION: The low agreement levels observed in this study suggest that there is still no classification method with high reproducibility.CONTEXTO E OBJETIVO: Para que as classificações das fraturas possam ser úteis, elas devem prover o prognóstico, apresentar concordância interobservador e reprodutibilidade intraobservador. O objetivo foi avaliar a concordância intra e interobservadores das classificações das fraturas do rádio distal. TIPO DE ESTUDO E LOCAL: Estudo de validação (concordância intra e interobservadores), desenvolvido no Departamento de Ortopedia e Traumatologia da Universidade Federal de São Paulo (UNIFESP) - Escola Paulista de Medicina (UNIFESP-EPM), São Paulo, Brasil. MÉTODO: Foram avaliadas 90 fraturas do rádio distal com desvio por meio de radiografias por cinco observadores (um médico residente de Ortopedia do terceiro ano, um graduando do sexto ano de medicina, um médico radiologista, um ortopedista especializado em trauma e um ortopedista especializado em cirurgia da mão) em três momentos diferentes, empregando as classificações Universal (Cooney), AO/ASIF (Osteosynthesfragen/Association for the Study of Internal Fixation), Frykman e Fernández. Aplicou-se o coeficiente de concordância kappa (κ) para avaliação das classificações. RESULTADOS: O maior κ intraobservador médio, se considerarmos os três momentos, foi da classificação Universal (κ = 0,61), seguida da Fernández (κ = 0,59), Frykman (κ = 0,55) e AO/ASIF (κ = 0,49). A concordância interobservador foi insatisfatória em todas as classificações. A classificação de Fernández mostrou a melhor concordância (κ = 0,44) e a pior foi a de Frykman (κ = 0,26). CONCLUSÃO: Os baixos níveis de concordância observados neste estudo sugerem que atualmente ainda não há um método de classificação plenamente reprodutível

The role of membrane lipids in the induction of macrophage apoptosis by microparticles.

Microparticles are membrane-derived vesicles that are released from cells during activation or cell death. These particles can serve as mediators of intercellular cross-talk and induce a variety of cellular responses. Previous studies have shown that macrophages undergo apoptosis after phagocytosing microparticles. Here, we have addressed the hypothesis that microparticles trigger this process via lipid pathways. In these experiments, microparticles induced apoptosis in primary macrophage cells or cell lines (RAW 264.7 or U937) with up to a 5-fold increase. Preincubation of macrophages with phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)BP) reduced the microparticle-induced apoptosis in a dose-dependent manner. PtdIns(3,5)BP is a specific inhibitor of the acid sphingomyelinase and thus can block the generation of pro-apoptotic ceramides. Similarly, the pre-incubation of macrophages with PtdIns(3,5)BP prevented microparticle-induced upregulation of caspase 8, which is a major target molecule of ceramide action in the apoptosis pathway. PtdIns(3,5)BP, however, had no effect on the spontaneous rate of apoptosis. To evaluate further signaling pathways induced by microparticles, the extracellular signal regulated kinase (ERK-) 1 was investigated. This kinase plays a role in activating phospholipases A2 which cleaves membrane phospholipids into arachidonic acid; microparticles have been suggested to be a preferred substrate for phospholipases A2. As shown in our experiments, microparticles strongly increased the amount of phosphorylated ERK1/2 in RAW 264.7 macrophages in a time-dependent manner, peaking 15 min after co-incubation. Addition of PD98059, a specific inhibitor of ERK1, prevented the increase in apoptosis of RAW 264.7 macrophages. Together, these data suggest that microparticles perturb lipid homeostasis of macrophages and thereby induce apoptosis. These results emphasize the importance of biolipids in the cellular cross-talk of immune cells. Based on the fact that in clinical situations with excessive cell death such as malignancies, autoimmune diseases and following chemotherapies high levels of circulating microparticles might modulate phagocytosing cells, a suppression of the immune response might occur due to loss of macrophages

Polyethylene glycols interact with membrane glycerophospholipids: is this part of their mechanism for hypothermic graft protection?

Polyethylene glycol (PEG), a high-molecular-weight colloid present in new organ preservation solutions, protects against cold ischemia injuries leading to better graft function of transplanted organs. This protective effect cannot be totally explained by immuno-camouflaging property or signaling-pathway modifications. Therefore, we sought for an alternative mechanism dependent on membrane fluidity. Using the Langmuir–Pockles technique, we show here that PEGs interacted with lipid monolayers of defined composition or constituted by a renal cell lipid extract. High-molecular-weight PEGs stabilized the lipid monolayer at low surface pressure. Paradoxically, at high surface pressure, PEGs destabilized the monolayers. Hypothermia reduced the destabilization of saturated monolayer whereas unsaturated monolayer remained unaffected. Modification of ionic strength and pH induced a stronger stabilizing effect of PEG 35,000 Da which could explain its reported higher effectiveness on cold-induced injuries during organ transplantation. This study sheds a new light on PEG protective effects during organ preservation different from all classical hypotheses