Citations

ABSTRACT A total of 120 pleural fluid specimens from 113 pediatric patients were tested using two rapid antigen detection assays for Streptococcus pyogenes . Results were compared to culture, Gram stain, and PCR results. Each rapid antigen assay detected 9 out of 10 (90%) PCR-positive samples, with 100% specificity. These antigen detection assays are useful to provide microbiological diagnosis of empyema caused by S. pyogenes .

Background: Lacosamide (LCM) is a newer antiepileptic drug (AED) with favorable properties for hospitalized patients including intravenous formulation, minimal hepatic metabolism, and no adverse respiratory effects. We sought to determine the safety profile of LCM in hospitalized patients. Methods: We performed a retrospective medical record review of patients who received LCM between July 1, 2009, and January 31, 2010, at Mayo Clinic Hospital. Data included demographics, LCM dosing, concomitant AED therapy, documented seizure activity, hemodynamic variables, electrocardiogram (ECG), and laboratory data. Adverse drug reaction and drug–drug interactions were reviewed. Results: Thirty-two patients were identified. No major hypotension or serious cardiac arrhythmias occurred. Heart rate increased, however, in seizure group compared with the prophylaxis group 2 hours postdrug infusion (median heart rate = 86 vs 164). The ECGs demonstrated a mean PR interval prolongation of about 6 milliseconds (ms) after LCM initiation (mean PR 185.5 ms, compared with baseline ECG mean of 179.3 ms). Laboratory data revealed no clinically significant changes 24 hours after LCM initiation. Three patients developed adverse events (9.4%): One with altered mental state and exceptionally prolonged ECG PR interval (212 vs 178 ms baseline); One with unexplained thrombocytopenia; and a third patient with dizziness, all of which resolved after drug discontinuation. Conclusion: The LCM demonstrated ECG PR prolongation as previously reported without systemic hypotension, with no discernable drug–drug interactions in hospitalized patients. About 9% of patients had transient adverse drug reactions after LCM, namely alteration in mental state, unexplained thrombocytopenia, and dizziness, which stopped after discontinuation of the drug.

Background— Measurement of hospital quality has traditionally focused on processes of care and postprocedure outcomes. Appropriateness measures for percutaneous coronary intervention (PCI) assess quality as it relates to patient selection and the decision to perform PCI. The association between patient selection for PCI and processes of care and postprocedural outcomes is unknown. Methods and Results— We included 203 531 patients undergoing nonacute (elective) PCI from 779 hospitals participating in the National Cardiovascular Data Registry (NCDR) CathPCI Registry between July 2009 and April 2011. We examined the association between a hospital's proportion of nonacute PCIs categorized as inappropriate by the 2009 Appropriate Use Criteria (AUC) for Coronary Revascularization and in-hospital mortality, bleeding complications, and use of optimal guideline-directed medical therapy at discharge (ie, aspirin, thienopyridines, and statins). When categorized as hospital tertiles, the range of inappropriate PCI was 0.0% to 8.1% in the lowest tertile, 8.1% to 15.2% in the middle tertile, and 15.2% to 58.6% in the highest tertile. Compared with lowest-tertile hospitals, mortality was not significantly different at middle-tertile (adjusted odds ratio [OR], 0.93; 95% confidence interval [CI], 0.73–1.19) or highest-tertile hospitals (OR, 1.12; 95% CI, 0.88–1.43; P =0.35 for differences between tertiles). Similarly, risk-adjusted bleeding did not vary significantly (middle-tertile OR, 1.13; 95% CI, 1.02–1.16; highest-tertile OR, 1.02; 95% CI, 0.91–1.16; P =0.07 for differences between tertiles) nor did use of optimal medical therapy at discharge (85.3% versus 85.7% versus 85.2%; P =0.58). Conclusions— In a national cohort of nonacute PCIs, a hospital's proportion of inappropriate PCIs was not associated with in-hospital mortality, bleeding, or medical therapy at discharge. This suggests PCI appropriateness measures aspects of hospital PCI quality that are independent of how well the procedure is performed. Therefore, PCI appropriateness and postprocedural outcomes are both important metrics to inform PCI quality.

Abstract High BAALC expression levels are associated with poor outcome in cytogenetically normal acute myeloid leukemia (CN-AML) patients. Recently, miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and prognostic interplay between miR-3151 and its host, miR-3151 and BAALC expression were measured in pretreatment blood of 179 CN-AML patients. Gene-expression profiling and miRNA-expression profiling were performed using microarrays. High miR-3151 expression was associated with shorter disease-free and overall survival, whereas high BAALC expression predicted failure of complete remission and shorter overall survival. Patients exhibiting high expression of both miR-3151 and BAALC had worse outcome than patients expressing low levels of either gene or both genes. In gene-expression profiling, high miR-3151 expressers showed down-regulation of genes involved in transcriptional regulation, posttranslational modification, and cancer pathways. Two genes, FBXL20 and USP40, were validated as direct miR-3151 targets. The results of the present study show that high expression of miR-3151 is an independent prognosticator for poor outcome in CN-AML and affects different outcome end points than its host gene, BAALC. The combination of both markers identified a patient subset with the poorest outcome. This interplay between an intronic miR and its host may have important biologic implications.

ABSTRACTThe Bruker Biotyper and Vitek MS matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry (MS) instruments were evaluated for the identification of nonfermenting Gram-negative bacilli (NFGNB) by a blinded comparison to conventional biochemical or molecular methods. Two hundred NFGNB that were recovered from cultures from cystic fibrosis patients in the University of Iowa Health Care (UIHC) Microbiology Laboratory between 1 January 2006 and 31 October 2010 were sent to Mayo Clinic for analysis with the Bruker Biotyper (software version 3.0) and to bioMérieux for testing with Vitek MS (SARAMIS database version 3.62). If two attempts at direct colony testing failed to provide an acceptable MALDI-TOF identification, an extraction procedure was performed. The MS identifications from both of these systems were provided to UIHC for comparison to the biochemical or molecular identification that had been reported in the patient record. Isolates with discordant results were analyzed by 16S rRNA gene sequencing at UIHC. After discrepancy testing, the Bruker Biotyper result agreed with the biochemical or molecular method, with 72.5% of isolates to the species level, 5.5% to the complex level, and 19% to the genus level (3% not identified). The level of agreement for Vitek MS was 80% species, 3.5% complex, 6% genus, and 3.5% family (7% not identified). Both MS systems provided rapid (≤3 min per isolate) and reliable identifications. The agreement of combined species/complex/genus-level identification with the reference method was higher for the Bruker Biotyper (97% versus 89.5%,P= 0.004) but required an extraction step more often. Species-level agreement with the reference method was similar for both MS systems (72.5% and 80%,P= 0.099).

AbstractMicroRNAs (miRNAs) are small, regulatory non‐coding RNAs that have potent effects on gene expression. Several miRNA are deregulated in cellular processes involved in human liver diseases and regulation of cellular processes. Recent studies have identified the involvement of miR‐29 in hepatic fibrosis and carcinogenesis. Although several targets of miR‐29 have been identified, there is limited information regarding the cell‐type specific roles of miR‐29 in the liver, and we sought to evaluate the role of this miRNA in hepatic pathobiology. We report the generation of a tissue–specific knockout mouse to evaluate the role of miR‐29 in hepatic fibrosis and carcinogenesis in response to injury. We hypothesized that miR‐29 contributes to the hepatocyte driven response to chronic cellular injury that results in fibrosis. In support of this hypothesis, fibrosis and mortality were enhanced in miR29 knockout mice in response to carbon tetrachloride. Genome‐wide gene expression analysis identified an over‐representation of genes associated with fibrosis. The oncofetal RNA H19 was modulated in a miR‐29 dependent manner following exposure to carbon tetrachloride in vivo. The impact of a hepatocyte specific miR‐29 knockout on survival following chronic hepatic injury in vivo implicates this miRNA as a potential target for intervention. These results provide evidence of the involvement of miR‐29 in chronic hepatic injury, and suggest a role for deregulated hepatocyte expression of miR‐29 in the response to hepatic injury, fibrosis and carcinogenesis.

AbstractThe systemic capillary leak syndrome (SCLS) is a rare disorder characterized by transient episodes of hypotensive shock and anasarca thought to arise from reversible microvascular barrier dysfunction. Although the high prevalence of a monoclonal gammopathy of unknown significance in SCLS suggests a pathogenic contribution of endogenous immunoglobulins, the mechanisms of vascular hyperpermeability remain obscure. Herein, we report clinical and molecular findings on 23 patients, the largest SCLS case series to date. Application of episodic SCLS sera, but neither the purified immunoglobulin fraction nor sera obtained from patients during remission, to human microvascular endothelial cells caused vascular endothelial cadherin internalization, disruption of interendothelial junctions, actin stress fiber formation, and increased permeability in complementary functional assays without inducing endothelial apoptosis. Intravenous immunoglobulin, one promising therapy for SCLS, mitigated the permeability effects of episodic sera. Consistent with the presence of endogenous, nonimmunoglobulin, circulating permeability factor(s) constrained to SCLS episodes, we found that vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2), were elevated in episodic SCLS sera but not in remission sera. Ab-based inhibition of Ang2 counteracted permeability induced by episodic SCLS sera. Comparable experiments with anti-VEGF Ab (bevacizumab) yielded less interpretable results, probably because of endothelial toxicity of VEGF withdrawal. Our results support a model of SCLS pathogenesis in which nonimmunoglobulin humoral factors such as VEGF and Ang2 contribute to transient endothelial contraction, suggesting a molecular mechanism for this highly lethal disorder.

Benign tumors of the esophagus are uncommon, representing <0.5% of esophageal tumors. Fibrolipomas are a subset of benign fibrovascular tumors, which present with dysphagia, odynophagia, and substernal fullness. These intraluminal tumors can become elongated and molded into a long pedunculated polyp by constant peristaltic movements. They can cause esophageal obstruction if large and long enough and can cause asphyxiation if they become lodged into the glottis. A barium swallow is the main diagnostic tool; treatment is surgical via a transoral, transcervical, or transthoracic approach. We report the excision of a large esophageal fibrolipoma through a transoral laser microsurgical approach.

ABSTRACT Mycoplasma salivarium infections outside the oral cavity are rare. We describe a 49-year-old man with laryngeal cancer and right pleural space infection with M. salivarium . To our knowledge, this is the first report of empyema due to Mycoplasma salivarium .

ABSTRACT Identification of Corynebacterium species may be challenging. Corynebacterium species are occasional causes of prosthetic joint infection (PJI), but few data are available on the subject. Based on the literature, C. amycolatum , C. aurimucosum , C. jeikeium , and C. striatum are the most common Corynebacterium species that cause PJI. We designed a rapid PCR assay to detect the most common human Corynebacterium species, with a specific focus on PJI. A polyphosphate kinase gene identified using whole-genome sequence was targeted. The assay differentiates the antibiotic-resistant species C. jeikeium and C. urealyticum from other species in a single assay. The assay was applied to a collection of human Corynebacterium isolates from multiple clinical sources, and clinically relevant species were detected. The assay was then tested on Corynebacterium isolates specifically associated with PJI; all were detected. We also describe the first case of C. simulans PJI.