Citations

Background: More stringent accuracy guidelines for hospital-use glucose meters have recently been published, but it remains unclear whether glucose meters can meet these accuracy guidelines when measurement is performed on critically ill patients with fresh whole blood samples. Materials and Methods: We performed a retrospective evaluation of a conventional (Roche Diagnostics [Indianapolis, IN] AccuChek ® Inform) and a newer-generation (Nova Biomedical [Waltham, MA] StatStrip ® ) glucose system by comparing paired (drawn within 5 min of each other) whole blood glucose meter and laboratory serum glucose values obtained from intensive care unit (ICU) patients. We also performed a prospective evaluation of the accuracy of the Nova StatStrip. Results: The median (interquartile range) bias between Roche AccuChek Inform and serum laboratory glucose measurements was 11 (6–18) mg/dL, compared with a median bias between the Nova StatStrip and serum glucose measurements of 1 (−5 to 5) mg/dL. StatStrip met International Organization for Standardization 15197 and Clinical and Laboratory Standards Institute (CLSI) POCT12-A3 accuracy guidelines using both retrospective and prospective datasets. Conclusions: The newer-generation (StatStrip) glucose meter met more stringent CLSI POCT12-A3 accuracy criteria because of reduced bias compared with the previous-generation device. Reduced glucose meter bias led to fewer insulin dosing discrepancies when the insulin dose determined from serum glucose was compared with that determined from the glucose meter value using the institutional glycemic control protocol.

The Sleeping Beauty (SB) transposon system has been shown to mediate new gene sequence integration resulting in long-term expression. Here the effectiveness of hyperactive SB100X transposase was tested, and we found that hydrodynamic co-delivery of a firefly luciferase transposon (pT2/CaL) along with SB100X transposase (pCMV-SB100X) resulted in remarkably sustained, high levels of luciferase expression. However, after 4 weeks there was a rapid, animal-by-animal loss of luciferase expression that was not observed in immunodeficient mice. We hypothesized that this sustained, high-level luciferase expression achieved using the SB100X transposase elicits an immune response in pT2/CaL co-administered mice, which was supported by the rapid loss of luciferase expression upon challenge of previously treated animals and in naive animals adoptively transferred with splenocytes from previously treated animals. Specificity of the immune response to luciferase was demonstrated by increased cytokine expression in splenocytes after exposure to luciferase peptide in parallel with MHC I–luciferase peptide tetramer binding. This anti-luciferase immune response observed following continuous, high-level luciferase expression in vivo clearly impacts its use as an in vivo reporter. As both an immunogen and an extremely sensitive reporter, luciferase is also a useful model system for the study of immune responses following in vivo gene transfer and expression.

Abstract Background: Occupational stress in resident physicians has profound implications for wellness, professionalism, and patient care. This observational pilot trial measured psychological and physiological stress biomarkers before, during, and after the start of anesthesia residency. Methods: Eighteen physician interns scheduled to begin anesthesia residency were recruited for evaluation at three time points: baseline (collected remotely before residency in June 2013); first-month visit 1 (July); and follow-up visit 2 (residency months 3 to 5, September–November). Validated scales were used to measure stress, anxiety, resilience, and wellness at all three time points. During visits 1 and 2, the authors measured resting heart-rate variability, responses to laboratory mental stress (hemodynamic, catecholamine, cortisol, and interleukin-6), and chronic stress indices (C-reactive protein, 24-h ambulatory heart rate and blood pressure, 24-h urinary cortisol and catecholamines, overnight heart-rate variability). Results: Thirteen interns agreed to participate (72% enrollment). There were seven men and six women, aged 27 to 33 yr. The mean ± SD of all study variables are reported. Conclusion: The novelty of this report is the prospective design in a defined cohort of residents newly exposed to the similar occupational stress of the operating environment. Because of the paucity of literature specific to the measures and stress conditions in this investigation, no data were available to generate a priori definition of primary outcomes and a data analytic plan. These findings will allow power analysis for future design of trials examining occupational stress and stress-reducing interventions. Given the importance of physician burnout in our country, the impact of chronic stress on resident wellness requires further study.

Several groups have reported cases of rectal cancer with carcinomatous involvement of the lumbosacral plexus and sciatic, obturator, pudendal, or spinal nerves. To our best knowledge, clear examples of perineural tumor spread in rectal carcinoma have not yet been described. We retrospectively reviewed clinical data and imaging studies of three patients with primary or recurrent rectal cancer involving the lumbosacral plexus. Imaging studies included MRI and 18FDG PET/CT scans in all (n = 3) patients, histological samples were available in two (n = 2). Imaging studies demonstrated distinct features of tumor spread from the organ to the plexus and beyond in all cases (n = 3), histological specimens demonstrated perineural involvement thus supporting our theory (n = 2). We present these three cases of perineural tumor spread in rectal cancer as a proof of concept. We hypothesize that not only our cases, but other similar reported cases can be explained anatomically by extension of the rectal cancer to the inferior hypogastric plexus with perineural tumor spread to the lumbosacral plexus using the pelvic and sacral splanchnic nerves as conduits. Once the tumor reaches the lumbosacral plexus, it can continue to spread proximally or distally. We believe that perineural spread of colon cancer represents an important, under‐recognized mechanism of recurrence to neighboring major nerves in the pelvis. Clin. Anat. 28:136–143, 2015. © 2014 Wiley Periodicals, Inc.

Abstract Life-threatening infections caused by Staphylococcus aureus, particularly the community-acquired methicillin-resistant strains of S. aureus, continue to pose serious problems. Greater virulence and increased pathogenicity of certain S. aureus strains are attributed to higher prevalence of exotoxins. Of these exotoxins, the superantigens (SAg) are likely most pathogenic because of their ability to rapidly and robustly activate the T cells even in extremely small quantities. Therefore, countering SAg-mediated T cell activation using T regulatory cells (Tregs) might be beneficial in diseases such as toxic shock syndrome (TSS). As the normal numbers of endogenous Tregs in a typical host are insufficient, we hypothesized that increasing the Treg numbers by administration of IL-2/anti–IL-2 Ab immune complexes (IL2C) or by adoptive transfer of ex vivo expanded Tregs might be more effective in countering SAg-mediated immune activation. HLA-DR3 transgenic mice that closely recapitulate human TSS were treated with IL2C to increase endogenous Tregs or received ex vivo expanded Tregs. Subsequently, they were challenged with SAg to induce TSS. Analyses of various parameters reflective of TSS (serum cytokine/chemokine levels, multiple organ pathology, and SAg-induced peripheral T cell expansion) indicated that increasing the Tregs failed to mitigate TSS. On the contrary, serum IFN-γ levels were increased in IL2C-treated mice. Exploration into the reasons behind the lack of protective effect of Tregs revealed IL-17 and IFN-γ–dependent loss of Tregs during TSS. In addition, significant upregulation of glucocorticoid-induced TNFR family-related receptor on conventional T cells during TSS could render them resistant to Treg-mediated suppression, contributing to failure of Treg-mediated immune regulation.

ProblemSeveral pregnancy complications have disparities based on the sex of the fetus. It is unknown whether the sex of the fetus differentially alters the maternal immune milieu, potentially contributing to the observed differences.Method of studyUsing maternal plasma collected during 38 uncomplicated pregnancies (19 males, 19 females), we compared levels of cytokines, sex hormones, and angiogenic factors throughout gestation and postpartum.ResultsMale fetal sex was associated with higher levels of proinflammatory cytokines (G‐CSF, IL‐12p70, IL‐21, and IL‐33) and angiogenic factors (PlGF and VEGF‐A) compared with female fetal sex at multiple timepoints. Female fetal sex was associated with higher levels of regulatory cytokines (IL‐5, IL‐9, IL‐17, and IL‐25). IL‐27 increased throughout pregnancy regardless of fetal sex. There was no fetal sex‐based difference in analyte concentrations at the postpartum measurement.ConclusionWomen carrying a male fetus exhibit a more proinflammatory/proangiogenic immune milieu than women carrying a female fetus.

Pulmonary hypertension (PH) has been found to have significant morbidity and mortality. The treatment of PH has advanced considerably with increasingly more effective and safer options. With an increasing effort to diagnose patients early, non-invasive techniques are often used to screen those patients likely to have PH. Computerized tomography (CT) chest scans are increasingly utilized in the evaluation of patients with exertional dyspnea, including those with suspected PH. The main role of the CT scan is to evaluate for any associated underlying diseases. There have been attempts to address the utility of CT to predict the presence of PH. This article reviews previously published investigations to summarize the relationship between pulmonary artery dimensions and PH to determine both the strength of the correlation and its discriminatory ability for use in clinical practice.