The prevalence of platelet activating factor acetylhydrolase single nucleotide polymorphisms in relationship to necrotizing enterocolitis in Northwest Louisiana infants

PURPOSE: Studies documented that platelet activating factor (PAF) and the enzyme platelet activating factor acetylhydrolase (PAFAH) play a very important role in the pathogenesis of neonatal necrotizing enterocolitis (NEC). In this retrospective, case-controlled pilot study, the authors investigated the prevalence of single nucleotide polymorphisms (Ile198Thr and Ala379Val) of the PAFAH gene. SUBJECTS AND METHODS: We screened 570 blood samples from both Caucasian and African-American preterm infants in the Northwest Louisiana population for the above mentioned PAFAH gene polymorphisms. Out of 570 infants, 36 had stage I or II NEC based on diagnostic coding, the International Classification of Diseases, 9th revision, Clinical Modification, 2009 (ICD-9-CM). The remaining infants without an ICD-9-CM diagnosis of NEC were recruited as control population. The DNA was isolated and restriction fragment length polymorphism microplate polymerase chain reaction assay was performed. RESULTS: Variants of the PAFAH gene polymorphism (Ile198Thr and Ala379Val) frequencies were not significantly different between the infants with NEC and the control group (P value of 0.26 by either multiple logistic regression analysis or the Cochran-Mantel-Haenszel test). CONCLUSIONS: This is the first study of its kind in exploring the relationship between NEC and single nucleotide polymorphisms in the coding genes of the enzyme PAFAH. Our preliminary data demonstrated that adjusted for the effect of race, PAFAH polymorphisms (Ile198Thr and Ala379Val) have no significant effect on NEC

http://www.medscape.com/viewarticle/819572_print

Abstract Introduction: Ultrasonography is being increasingly utilized in acute care settings with expanding applications. Pneumothorax evaluation by ultrasonography is a fast, safe, easy and inexpensive alternative to chest radiographs. In this review, we provide a comprehensive analysis of the current literature comparing ultrasonography and chest radiography for the diagnosis of pneumothorax. Methods: We searched English-language articles in MEDLINE, EMBASE and Cochrane Library dealing with both ultrasonography and chest radiography for diagnosis of pneumothorax. In eligible studies that met strict inclusion criteria, we conducted a meta-analysis to evaluate the diagnostic accuracy of pleural ultrasonography in comparison with chest radiography for the diagnosis of pneumothorax. Results: We reviewed 601 articles and selected 25 original research articles for detailed review. Only 13 articles met all of our inclusion criteria and were included in the final analysis. One study used lung sliding sign alone, 12 studies used lung sliding and comet tail signs, and 6 studies searched for lung point in addition to the other two signs. Ultrasonography had a pooled sensitivity of 78.6% (95% CI, 68.1 to 98.1) and a specificity of 98.4% (95% CI, 97.3 to 99.5). Chest radiography had a pooled sensitivity of 39.8% (95% CI, 29.4 to 50.3) and a specificity of 99.3% (95% CI, 98.4 to 100). Our meta-regression and subgroup analyses indicate that consecutive sampling of patients compared to convenience sampling provided higher sensitivity results for both ultrasonography and chest radiography. Consecutive versus nonconsecutive sampling and trauma versus nontrauma settings were significant sources of heterogeneity. In addition, subgroup analysis showed significant variations related to operator and type of probe used. Conclusions: Our study indicates that ultrasonography is more accurate than chest radiography for detection of pneumothorax. The results support the previous investigations in this field, add new valuable information obtained from subgroup analysis, and provide accurate estimates for the performance parameters of both bedside ultrasonography and chest radiography for pneumothorax evaluation

Inhibition of glutathione synthesis in brain endothelial cells lengthens S-phase transit time in the cell cycle: Implications for proliferation in recovery from oxidative stress and endothelial cell damage

Oxidative stress-induced decrease in tissue or systemic glutathione (GSH) and damage to the vascular endothelium of the blood-brain barrier such as occurs in diabetes or stroke will have important implications for brain homeostasis. Endothelial proliferation or repair is crucial to preserving barrier function. Cell proliferation has been associated with increased intracellular GSH, but the kinetic and distribution of GSH during cell cycle is poorly understood. Here, we determined the influence of cellular GSH status on the early dynamics of nuclear-to-cytosol (N-to-C) GSH distribution (6-h interval) during proliferation in a human brain microvascular endothelial cell line (IHEC). Control IHECs exhibited two peak S-phases of the cell cycle at 48 and 60 h post seeding that temporally corresponded to peak nuclear GSH levels and expression of cdk1, the S-to-G2-to-M checkpoint controller, suggesting a link between cell cycle progression and nuclear GSH. Sustained inhibition of GSH synthesis delayed S-to-G2/M cell transition; cell arrest in the S-phase was correlated with decreased total nuclear GSH and increased nuclear expressions of chk2/phospho-chk2 and GADPH. The temporal correspondence of nuclear chk2 activation and GAPDH expression with S-phase prolongation is consistent with enhanced DNA damage response and extended time for DNA repair. Strikingly, when GSH synthesis was restored, cell transit time through S-phase remained delayed. Significantly, total nuclear GSH remained depressed, indicating a time lag between restored cellular GSH synthetic capacity and recovery of the nuclear GSH status. Interestingly, despite a delay in cell cycle recovery, nuclear expressions of chk2/phospho-chk2 and GAPDH resembled those of control cells. This means that restoration of nuclear DNA integrity preceded normalization of the cell cycle. The current results provide important insights into GSH control of endothelial proliferation with implications for cell repair or wound healing in recovery post-oxidative damage

Pleural Ultrasound

Abstract Introduction: Ultrasonography is being increasingly utilized in acute care settings with expanding applications. Pneumothorax evaluation by ultrasonography is a fast, safe, easy and inexpensive alternative to chest radiographs. In this review, we provide a comprehensive analysis of the current literature comparing ultrasonography and chest radiography for the diagnosis of pneumothorax. Methods: We searched English-language articles in MEDLINE, EMBASE and Cochrane Library dealing with both ultrasonography and chest radiography for diagnosis of pneumothorax. In eligible studies that met strict inclusion criteria, we conducted a meta-analysis to evaluate the diagnostic accuracy of pleural ultrasonography in comparison with chest radiography for the diagnosis of pneumothorax. Results: We reviewed 601 articles and selected 25 original research articles for detailed review. Only 13 articles met all of our inclusion criteria and were included in the final analysis. One study used lung sliding sign alone, 12 studies used lung sliding and comet tail signs, and 6 studies searched for lung point in addition to the other two signs. Ultrasonography had a pooled sensitivity of 78.6% (95% CI, 68.1 to 98.1) and a specificity of 98.4% (95% CI, 97.3 to 99.5). Chest radiography had a pooled sensitivity of 39.8% (95% CI, 29.4 to 50.3) and a specificity of 99.3% (95% CI, 98.4 to 100). Our meta-regression and subgroup analyses indicate that consecutive sampling of patients compared to convenience sampling provided higher sensitivity results for both ultrasonography and chest radiography. Consecutive versus nonconsecutive sampling and trauma versus nontrauma settings were significant sources of heterogeneity. In addition, subgroup analysis showed significant variations related to operator and type of probe used. Conclusions: Our study indicates that ultrasonography is more accurate than chest radiography for detection of pneumothorax. The results support the previous investigations in this field, add new valuable information obtained from subgroup analysis, and provide accurate estimates for the performance parameters of both bedside ultrasonography and chest radiography for pneumothorax evaluation. Introduction Chest ultrasonography (US) is gaining more attention in critical care and emergency medicine literature. US has been used recently for evaluation of pneumothorax and other lung pathologies. Several early trials established the diagnostic signs of pneumothorax on US and showed a strong superiority in favor of US over chest radiography (CXR). Despite those and other cumulating original research evidence favoring ultrasonography, US remained underused. In fact, the most recent British thoracic society guidelines on pleural procedures and thoracic ultrasound stated that "The utility of thoracic ultrasound for diagnosing a pneumothorax is limited in hospital practice due to the ready availability of chest x-rays and conflicting data from published reports". By using a regression-analysis model of the published literature, Lijmer et al. We aimed to conduct an accurate meta-analysis of the available literature that included high-quality articles, and avoiding studies that evaluated populations with known pneumothorax and studies that used different verification methods. Additionally, we evaluated the studies for other possible sources of bias. We also intended to include the recent publications that were not included in previous analyses. Furthermore, we specifically planned to address the inherent heterogeneity found that could not be addressed in the previously published meta-analyses. We addressed issues related to operator, type of probe, and patient-population specifics. We believe that our study adds valuable information to the current literature in this field that could guide the application of pleural ultrasonography in the clinicians' daily practices. Materials and Methods Study Design and Data Extraction We performed a literature review and meta-analysis of published research articles evaluating the diagnostic accuracy of US in comparison with CXR. Original articles published in the English language up to March 2013 were searched in Medline, EMBASE, and the Cochrane Library. Our initial search was broad and included the following words: ("ultrasound" or "sonography" or "ultrasonography" or "radiography" or "chest film" or "chest radiograph") and ("pneumothorax" or "aerothorax") and ("sensitivity" and "specificity"). We noted a large number of articles published during the study, and so we performed three separate searches during the entire review process (December 2011, May 2012, and March 2013; EMBASE was accessed in January 2013). The number of articles and abstracts depicted in the diagram Studies Inclusion Criteria The inclusion criteria we used to select articles are as follows: (a) Original prospective blinded studies comparing the performance of US and CXR for pneumothorax diagnosis; (b) compared the two tests with one gold standard, the computed tomography (CT) scan of the chest; (c) avoided studies that included diseased populations (populations with known pneumothorax); (d) Described the diagnostic criteria for pneumothorax on US in clear details; And (e) met quality standards, as assessed by the 14-item Quality Assessment of Diagnostic Accuracy Studies (QUADAS2) All patients included in our analysis had CT scans in addition to CXR and US examinations. If a study included patients with differential verifications, only patients with CT scans were included. If a study included patients studied by US for other conditions in addition to pneumothorax, only patients evaluated for pneumothorax were included. Review Process We identified 601 potential articles in our initial searches (see http://www.medscape.com/viewarticle/819572_print 2 di 9 18/02/2014 13:57 Data Synthesis After extraction of data from the original studies, data were arranged in 2 × 2 tables expressing true positive (TP), false positive (FP), false negative (FN), and true negative (TN). In cases of uncertainty about data or the quality, the author was contacted (one case Data Analysis We assumed that US and CXR have different accuracy when applied to different patient populations by different operators. For this reason, we used a random-effect model in our meta-analysis to calculate pooled sensitivity and specificity with corresponding 95% confidence intervals (CIs). Other data such as diagnostic odds ratio (DOR) and http://www.medscape.com/viewarticle/819572_print 3 di 9 18/02/2014 13:57 receiver operative curves (ROCs) were also obtained. We used Meta-DiSc, version 1.4 software (Ramon y Cajal Hospital, Madrid, Spain). We also used Review Manager 5.2, mainly to assess quality and risk of bias. Results of analysis using both software programs were identical. However, for this report, all data and graphs were obtained from the results of Meta-DiSc analysis, as it provided more information for reporting. To explain the observed heterogeneity, we performed meta-regression and subgroup analyses, as applicable, using all observed covariates. Meta-regression is a regression analysis of the effects of covariates in relation to each other at the level of studies. The effect sizes were explained as diagnostic odds ratio (DOR) and relative diagnostic odds ratio (RDOR) in relation to the dependent variable of interest. To compare performance-parameter estimates (sensitivity, specificity, or DOR) for different diagnostic tests at 5% level, we used the calculated 95% confidence intervals (CIs) for a parameter estimate for the diagnostic tests being compared. In comparison with previous studies, we observed a significant difference in the estimated parameter for two values being compared if the 95% CI for the parameter of interest in our estimate did not include the parameter estimate in the other studies' estimates or vice versa. Results From the 13 chosen studies (), we extracted the data from each study and conducted a random-effect model meta-analysis. In addition to quality assessment, we assessed for risk of bias and considered covariates that can affect heterogeneity. A total of 3,028 hemithoraces from 1,514 patients were included in the analysis. Our study revealed a clear superiority of US over CXR. For US, both trauma settings (RDOR = 32.87; 95% CI, 2.42 to 447.03; P = 0.018) and consecutive sampling (RDOR = 21.99; 95% CI, 1.98 to 244.93; P = 0.021) were significant contributors to heterogeneity by using meta-regression analysis (Additional file 1: eTable S3). Subgroup analysis also showed that in consecutive sampling studies, the pooled sensitivity improved to 85.3% (95% CI, 68 to 100), whereas in nonconsecutive (convenience) sampling studies, the pooled sensitivity decreased to 73.6% (95% CI, 60.4 to 86.7). Studies that used the high-frequency linear array probe had a pooled sensitivity of 82.2% (95% CI, 68.8 to 95.5), whereas those using a convex array probe had a pooled sensitivity of 76% (95% CI, 59.8 to 92.3). Operator (radiologist versus others) was not a significant variable in our analysis. However, emergency physician-performed US had better sensitivity than nonemergency physicians-performed US (82.3% versus 72.8%). (Additional file 1contains statistical tables for both CXR and US subanalyses). In the discussion sections of the reviewed articles, Ultrasonography time, when assessed, Discussion In the past 3 years, at least nine published original prospective research articles addressed the diagnostic accuracy of pleural ultrasonography for the diagnosis of pneumothorax, reflecting the growing interest in this valuable test as an alternative to CXR. Six of those articles versus 88% We believe that our study provides better estimates of the test parameters because of the inclusion of a large number of good-quality standardized studies and patients (total of 1,514 patients) in the analysis. Our meta-analysis allowed, for the first time, the identification of significant sources of variation in the effect size among the included studies. It is the first to compare CT scan, US, and CXR in the same population on this large scale. On all counts US remains superior to CXR for detection of pneumothorax, even after controlling for possible sources of heterogeneity (the lowest US http://www.medscape.com/viewarticle/819572_print 5 di 9 18/02/2014 13:57 subgroup sensitivity was 73.6%). With positive test results, patients tested with US have greater odds of having an accurate diagnosis of pneumothorax than do those tested with CXR (DOR, 279.31 versus 87.19). The majority of studies included in our analysis were in trauma settings; this was expected, as an indication for CT scan of the chest is readily available in this setting. Our results indicated that a linear probe provided better sensitivity (82% versus 76%); this is likely because of the better views of the lung sliding sign obtained with this high-resolution probe. In our study, emergency physicians performed better US than did nonemergency physicians (sensitivity, 82.3% versus 72.8%). This could be related to their early experience in thoracic US use as part of the eFAST (Extended Focused Assessment with Sonography for Trauma) that emphasized the importance of training and experience in this operatordependent test. Our study is not without limitations. Despite meticulous efforts to explain possible causes of heterogeneity, we were unable to account for some minor sources, especially on the US analysis, which had some minimal residual heterogeneity after meta-regression ( T 2 = 0.2; Additional file 1: eTable S3). We did not evaluate our meta-analysis for publication bias. We kept our search very broad initially to overcome this issue but included all studies that performed US and CXR as well as CT scan as the gold standard to maintain accuracy and avoid overestimates of diagnostic accuracy. Studies published in languages other than English, with the exception of one, As stated earlier, most of our included studies were in trauma/emergency department settings. This was mainly the result of including studies that compared both tests with the gold standard (CT scan of the chest). It should be noted that the severity of trauma was not assessed in the majority of those studies. The consecutive-sampling studies (which showed higher sensitivity) may have allowed a wide spectrum of patients to be included in those studies. Furthermore, most pneumothoraces missed by CXR were occult and detected only by US and CT scans. In one study It is important to note that the test characteristics are only part of the assessment of a diagnostic test performance, and the value of any test ultimately lies in its effects on patient outcome. Other important factors such as potential of harm as a consequence of the test (in our case, possible exposure to unnecessary procedures to treat a small pneumothorax or exposure to ionizing radiation), physician's perception and confidence in test results, as well as the ability to make treatment decisions based on test results were not addressed in our study. [25] Future research can be designed to address the downstream effects of two separate testing strategies specifically for pneumothorax: one that uses CXR and another for US. Possible outcome measures are number of invasive procedures and subsequent tests resulting from the index test, and total condition-related cost of care. We expect US to be safer, more convenient, more cost effective, and to outperform CXR in most aspects. Conclusion Despite the lower sensitivity and lower DOR found in our analysis, US remains much more sensitive than CXR for identification of pneumothorax. Our analysis supports the available evidence in favor of ultrasonography over chest radiography and provides an objective assessment of the diagnostic performance of both tests in the well-designed published studies that we included in our meta-analysis. Our analysis identifies several important factors that increase the accuracy of US in detection of pneumothorax, including operator experience, patient population, and the type of probe used. Sidebar Key Message

Quantification of the Advantages of the Extended Frontal Approach to Skull Base

This anatomic study evaluated the extent that a fronto-orbital osteotomy (FOO) added to a bilateral frontal craniotomy widened the exposure to the midline compartment of the anterior, middle, and posterior cranial fossae. The goal was to determine if osteotomy would significantly increase angles for two targets: the foramen magnum (FM) and anterior clinoid process (ACP). Stepwise dissections were performed on five cadaveric heads. A bilateral frontal craniotomy was made, followed by FOO. After the ethmoids were removed, the planum sphenoidale was drilled to enter the sphenoid sinus. Further drilling exposed the anterior clivus, which was drilled down to FM. Excellent exposure of the basilar artery, vertebral artery, and brain stem was achieved. With and without FOO, angles of exposure were measured for two targets: the ACP and FM. The angle of exposure after FOO increased markedly with an average gain of 76% for the ACP and of 80% for FM. Compared with a conventional bifrontal craniotomy, the addition of FOO increased the surgical exposure and minimized frontal lobe retraction for accessing lesions of the anterior, middle, and posterior cranial fossae