21 research outputs found

    Sealless Pumps

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    Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

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    Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship

    Large-magnitude Pelvic and Retroperitoneal Tissue Damage Predicts Organ Failure

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    BACKGROUND: Pelvic and retroperitoneal trauma is a major cause of morbidity and mortality in multiply injured patients. The Injury Severity Score (ISS) has been criticized for underrepresenting and inaccurately defining mechanical injury. The influence of pelvic injury volume on organ dysfunction and multiple organ failure (MOF) has not been described. Through the use of CT, this investigation sought to precisely define volumes of mechanical tissue damage by anatomic region and examine its impact on organ failure. QUESTIONS/PURPOSES: (1) Do patients with MOF have a greater volume of pelvic and retroperitoneal tissue damage when compared with those without MOF? (2) In patients who sustained pelvic trauma, does the magnitude of pelvic injury differ in patients with MOF? (3) Does the magnitude of organ dysfunction correlate with pelvic tissue damage volume? METHODS: Seventy-four multiply injured patients aged 18 to 65 years with an ISS ≥ 18 admitted to the intensive care unit for a minimum of 6 days with complete admission CT scans were analyzed. Each identifiable injury in the head/neck, chest, abdomen, and pelvis underwent volumetric determination using CT to generate regional tissue damage volume scores. Primary outcomes were the development of MOF as measured by the Denver MOF score and the degree of organ dysfunction by utilization of the Sequential Organ Failure Assessment (SOFA) score. Mean pelvic and retroperitoneal tissue damage volumes were compared in patients who developed MOF and those who did not develop MOF using Student's t-test. Among patients who sustained pelvic injuries, we compared mean volume of tissue damaged in patients who developed MOF and those who did not. We assessed whether there was a correlation between organ dysfunction, as measured by the SOFA score as a continuous variable, and the volume of pelvic and retroperitoneal tissue damage using the Pearson product-moment correlation coefficient. RESULTS: The average volume of tissue damage was greater in patients with MOF when compared with those without (MOF: 685.667 ± 1081.344; non-MOF: 195.511 ± 381.436; mean difference 490.156 cc [95% confidence interval {CI}, 50.076-930.237 cc], p = 0.030). Among patients who sustained pelvic injuries, those with MOF had higher average tissue damage volumes than those without MOF (MOF: 1322.000 ± 1197.050; non-MOF: 382.750 ± 465.005; mean difference 939.250 [95% CI, 229.267-1649.233], p = 0.013). Organ dysfunction (SOFA score) correlated with higher volumes of pelvic tissue damage (r = 0.570, p < 0.001). CONCLUSIONS: This investigation demonstrated that greater degrees of pelvic and retroperitoneal tissue damage calculated from injury CT scans in multiply injured patients is associated with more severe organ dysfunction and an increased risk of developing MOF. Early identification of polytrauma patients at risk of MOF allows clinicians to implement appropriate resuscitative strategies early in the disease course. Improved stratification of injury severity and a patient's anticipated clinical course may aid in the planning and execution of staged orthopaedic interventions. Future avenues of study should incorporate the ischemic/hypoperfusion component of pelvic injury in conjunction with the mechanical component presented here for improved stratification of multiply injured patients at higher risk of MOF. LEVEL OF EVIDENCE: Level III, prognostic study