Blood Polymorphonuclear Leukocyte Activation in Atherosclerosis: Effects of Aspirin

The aim of the study was to demonstrate an activation of polymorpho-nuclear leukocytes (PMNs) in chronic progressive atherosclerosis (ATH). A group of patients with ATH, and a group of ATH patients under aspirin (ASA) therapy were compared with control persons without atherosclerotic alterations (healthy controls). Each group comprised 15 male age-matched subjects. The following inflammatory parameters related to PMN activities were measured: the polymorphonuclear leukocyte (PMN) blood count; blood PMN migration and reactive oxygen species release in vitro; the blood levels of PMN elastase, malondialdehyde, antibodies to oxidized LDL and soluble ICAM-1. In ATH patients, the PMN blood counts and the share of blood PMNs migrating upon platelet activating factor and leukotriene B4 stimulation were significnatly above the values of the healthy controls, while the other parameters were not significantly altered. ASA treatment attenuated the inflammatory response and reduced the differences between ATH and the healthy controls. It can be concluded that, in patients with chronic progressive atherosclerosis, PMNs are involved in the inflammatory process underlying the disease.     

Lipidomic Profiling of Bronchoalveolar Lavage Fluid Extracellular Vesicles Indicates Their Involvement in Lipopolysaccharide-Induced Acute Lung Injury

Emerging data support the pivotal role of extracellular vesicles (EVs) in normal cellular physiology and disease conditions. However, despite their abundance, there is much less information about the lipid mediators carried in EVs, especially in the context of acute lung injury (ALI). Our data demonstrate that C57BL/6 mice subjected to intranasal Escherichia coli lipopolysaccharide (LPS)-induced ALI release, a higher number of EVs into the alveolar space, compared to saline-treated controls. EVs released during ALI originated from alveolar epithelial cells, macrophages, and neutrophils and carry a diverse array of lipid mediators derived from ω-3 and ω-6 polyunsaturated fatty acids (PUFA). The eicosanoids in EVs correlated with cellular levels of arachidonic acid, expression of cytosolic phospholipase A2, cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome epoxygenase p450 proteins in pulmonary macrophages. Furthermore, EVs from LPS-toll-like receptor 4 knockout (TLR4^-/-) mice contained significantly lower amounts of COX and LOX catalyzed eicosanoids and ω-3 PUFA metabolites. More importantly, EVs from LPS-treated wild-type mice increased TNF-α release by macrophages and reduced alveolar epithelial monolayer barrier integrity compared to EVs from LPS-treated TLR4^−/− mice. In summary, our study demonstrates for the first time that the EV carried PUFA metabolite profile in part depends on the inflammatory status of the lung macrophages and modulates pulmonary macrophage and alveolar epithelial cell function during LPS-induced ALI.     

Clinical and Radiological Characteristics Associated with Respiratory Failure in Unilateral Lateral Medullary Infarction

BackgroundThe prognosis for unilateral lateral medullary infarction (ULMI) is generally good but may be aggravated by respiratory failure with fatal outcome. Respiratory failure has been reported in patients with severe bulbar dysfunction and large rostral medullary lesions, but its associated factors have not been systematically studied. We aimed to assess clinical and radiological characteristics associated with respiratory failure in patients with pure acute ULMI.Materials and MethodsSeventy-one patients (median age 55 years, 59 males) with MRI-confirmed acute pure ULMI were studied retrospectively. Clinical characteristics were assessed and bulbar symptoms were scored using a scale developed for this study. MRI lesions were classified into 4 groups based on their vertical extent (localized/extensive) and the involvement of the open and/or closed medulla. Clinical characteristics, bulbar scores and MRI lesion characteristics were compared between patients with and without respiratory failure.ResultsRespiratory failure occurred in 8(11%) patients. All patients with respiratory failure were male (p = 0.336), had extensive lesions involving the open medulla (p = 0.061), progression of bulbar symptoms (p=0.002) and aspiration pneumonia (p < 0.001). Peak bulbar score (OR, 7.9 [95% CI, 2.3–160.0]; p < 0.001) and older age (OR, 1.2 [95%CI, 1.0-1.6]; p=0.006) were independently associated with respiratory failure.ConclusionsExtensive damage involving the open/rostral medulla, clinically presenting with severe bulbar dysfunction, in conjunction with factors such as aspiration pneumonia and older age appears to be crucial for the development of respiratory failure in pure ULMI. Further prospective studies are needed to identify other potential risk factors, pathophysiology, and effective preventive measures for respiratory failure in these patients.     

Comparison of two-dimensional manual and three-dimensional SurgiCase and BLUEPRINT planning software measurements of glenoid version,inclination, and humeral subluxation

IntroductionVirtual planning for shoulder arthroplasty using preoperative computed tomography (CT) has been gaining popularity, and it is imperative for surgeons to recognize any differences in measurements that may exist amongst software platforms. The purpose of this study is to compare measurements of glenoid version, inclination, and humeral head subluxation between a manual approach and two varying automated software platforms using either a best-fit sphere technique (Wright-Medical BLUEPRINT) or an anatomic landmarks technique (Materalise SurgiCase).MethodsA case control study of 289 CT images from patients preoperatively planned for a total shoulder arthroplasty or reverse shoulder arthroplasty using SurgiCase (v3.0.110.5) were also successfully analyzed by BLUEPRINT (v2.1.6). Glenoid version, inclination, and subluxation were measured manually in a blind fashion by two separate investigators using axial and coronal images oriented to the scapular plane; interobserver and intraobserver reliabilities were measured using intraclass correlation coefficients (ICCs). Concordance correlation coefficients (CCCs), mean differences, and clinically relevant agreement in measurements between the software platforms and with the manual technique were compared. The impact of greater glenoid retroversion on the differences in measurements between the software platforms was further studied by correlation analysis.ResultsThe mean differences between SurgiCase and BLUEPRINT were + 0.5° for glenoid inclination (P = .064; CCC = 0.84), -0.9° for glenoid version (P < .001; CCC = 0.92), and -1.4% for humeral subluxation (P = .002; CCC = 0.88). Agreement within 5 units was 78.9% for inclination, 89.3% for version, and 64.1% for subluxation. Glenoid retroversion had no relation with the degree of variation in measured inclination (P = .59) or version (P = .56). There were significant differences between manual and 3D software measurements for glenoid inclination, version, and subluxation (P < .001). Both software measurements were more inferiorly inclined (average difference, SurgiCase -3.2° and BLUEPRINT -3.9°), more retroverted (average difference, SurgiCase -4.0° and BLUEPRINT -3.2°), and more posteriorly subluxated (average difference, SurgiCase + 3.4% and BLUEPRINT + 4.8%).ConclusionThe SurgiCase and BLUEPRINT preoperative planning software yield clinically similar measurements for glenoid version, inclination, and subluxation. The degree of glenoid retroversion does not impact the variability of inclination or version between the landmark and best-fit sphere software techniques. Compared to the 2D manual technique, both 3D software programs reported greater inferior inclination, retroversion, and posterior subluxation.Level of evidenceLevel III; Retrospective Diagnostic Study     

Management decisions for adolescent idiopathic scoliosis significantly affect patient radiation exposure

Background contextAdolescent idiopathic scoliosis (AIS) patients treated before the 1990s have a 1% to 2% increased lifetime risk of developing breast and thyroid cancer as a result of ionizing radiation from plain radiographs. Although present plain radiographic techniques have been able to reduce some of the radiation exposure, modern treatment algorithms for scoliosis often include computed tomography (CT) and intraoperative fluoroscopy. The exact magnitude of exposure to ionizing radiation in adolescents during modern scoliosis treatment is therefore unclear.PurposeTo determine the difference in radiation exposures in patients undergoing various forms of treatment for AIS.Study designRetrospective cohort.Patient samplePatients aged 9 to 18 years with a diagnosis of AIS, followed and/or treated with nonoperative or operative management for a minimum of 2 years.Outcome measuresNumber of radiographs and total radiation exposure calculated.MethodsThe charts and radiographs of patients managed for AIS at a single institution between September 2007 and January 2012 were reviewed. Patients were divided into three groups: operative group, braced group, and observation group. Patient demographics, Cobb angles, and curve types were recorded. The number of radiographs per year that each patient received and the total radiation dose were recorded. The plain radiographic radiation exposure was then combined with the direct exposure recording from ancillary tests, such as fluoroscopy and CT, and a radiation exposure rate was calculated (mrad/y). A single-factor analysis of variance (α=0.01) with a Tukey honest significant difference post hoc analysis was used to test significance between groups.ResultsTwo hundred sixty-seven patients were evaluated: 86 operative, 80 brace, and 101 observation. All groups had similar demographics and curve type distribution. The mean initial Cobb angle at presentation was significantly different between the groups: operative (57°±11°), brace (24°±7.9°), and observation (18°±9.4°) (p<.01). There was a significant difference among the groups in terms of the mean number of radiographs received per year; operative group, 12.2 (95% confidence interval [CI]: 10.8–13.5; p<.001); braced group, 5.7 (95% CI: 5.2–6.2; p<.001), and observed group, 3.5 (95% CI: 3.160–3.864; p<.001). The operative group received 1,400 mrad per year (95% CI: 1,350–1,844; p<.001), braced group received 700 mrad per year (95% CI: 598–716; p<.001), and observed group received 400 mrad per year (95% CI: 363–444; p<.001). Importantly, 78% of radiation in the operative group was attributable to the operative fluoroscopy exposure.ConclusionsSignificant differences exist in the total radiation exposure in scoliosis patients with different treatment regimens, with operative patients receiving approximately 8 to 14 times more radiation than braced patients or those undergoing observation alone, respectively. Operative patients also receive more than twice the radiation per year than braced or observed patients. Almost 78% of the annual radiation exposure for operative patients occurs intraoperatively. Because children are notably more sensitive to the carcinogenic effects of ionizing radiation, judicious use of present imaging methods and a search for newer imaging methods with limited ionizing radiation should be undertaken.     

Basic presynaptic functions in hippocampal neurons are not affected by acute or chronic lithium treatment

Lithium is an effective mood-stabilizer in the treatment of bipolar affective disorder. While glycogen synthase kinase 3-mediated and inositol depletion-dependent effects of lithium have been described extensively in literature, there is very little knowledge about the consequences of lithium treatment on vesicle recycling and neurotransmitter availability. In the present study we have examined acute and chronic effects of lithium on synaptic vesicle recycling using primary hippocampal neurons. We found that exocytosis of readily releasable pool vesicles as well as recycling pool vesicles was unaffected by acute and chronic treatment within the therapeutic range or at higher lithium concentrations. Consistent with this observation, we also noticed that the network activity and number of active synapses within the network were also not significantly altered after lithium treatment. Taken together, as lithium treatment does not affect synaptic vesicle release at even high concentrations, our data suggest that therapeutic effects of lithium in bipolar affective disorder are not directly related to presynaptic function.