Citations

AbstractBackgroundMany researchers have previously explored the correlation between surgical flow disruptions and adverse events in cardiac surgery; however, there is no reliable tool to prospectively categorize surgical flow disruptions and the conditions that predispose a surgical team to adverse events.MethodsTwo independent raters of different medical and human factors expertise observed 12 cardiovascular operations and iteratively designed a surgical flow disruption tool (SFDT) to characterize surgical flow disruptions and the latent factors that contribute to adverse events. Categories to characterize surgical flow disruptions were created based on human factors models of human error. After the design period, both raters observed ten surgical cases using the tool to assess validity and inter‐rater reliability.ResultsRating agreement (weighted kappa) for each category across the ten surgeries was moderate to very high, resulting in strong inter‐rater reliability for each category on the surgical flow disruption tool. Use of the SFDT was simple and clear for observers of diverse backgrounds, including human factors experts and medical personnel.ConclusionsThis research depicts the development and utility of a tool to analyze surgical flow disruptions in the cardiovascular operating room with satisfactory inter‐rater reliability. This tool is an important first step in systematically categorizing and measuring surgical flow disruptions and their impact on patient safety in the operating room.

Owing to recent progress in analytical techniques, metallomics are evolving from detecting distinct trace metals in a defined state to monitor the dynamic changes in the abundance and location of trace metals in vitro and in vivo. Vascular metallomics is an emerging field that studies the role of trace metals in vasculature. This review will introduce common metallomics techniques including atomic absorption spectrometry, inductively coupled plasma-atomic emission spectrometry, inductively coupled plasma-mass spectrometry and X-ray fluorescence spectrometry with a summary table to compare these techniques. Moreover, we will summarize recent research findings that have applied these techniques to human population studies in cardiovascular diseases, with a particular emphasis on the role of copper in these diseases. In order to address the issue of interdisciplinary studies between metallomics and vascular biology, we will review the progress of efforts to understand the role of copper in neovascularization. This recent advance in the metallomics field may be a powerful tool to elucidate the signaling pathways and specific biological functions of these trace metals. Finally, we summarize the evidence to support the notion that copper is a dynamic signaling molecule. As a future direction, vascular metallomics studies may lead to the identification of targets for diagnosis and therapy in cardiovascular disease.

Abstract Rationale Debate exists about the immunogenicity and protective efficacy of antibodies produced by the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in chronic obstructive pulmonary disease (COPD). The 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) induces a more robust immune response than PPSV23 in healthy elderly adults. Objectives We hypothesized that serotype-specific IgG antibody concentration and functional antibody activity would be superior after PCV7 vaccination compared with PPSV23 in moderate to severe COPD. We also posited that older age and prior PPSV23 vaccination would be associated with reduced vaccine responsiveness. Methods One hundred twenty patients with COPD were randomized to PPSV23 (63 subjects) or PCV7 (57 subjects). IgG concentrations were determined by ELISA; functional antibody activity was assayed with a standardized opsonophagocytosis assay and reported as an opsonization killing index (OPK). Increases in serotype-specific IgG and OPK at 1 month post vaccination were compared within and between vaccine groups. Measurements and Main Results Both vaccines were well tolerated. Within each study group, postvaccination IgG and OPK were higher than baseline (P < 0.01) for all serotypes. Adjusted for baseline levels, postvaccination IgG was higher in the PCV7 group than the PPSV23 group for all seven serotypes, reaching statistical significance for five (P < 0.05). PCV7 resulted in a higher OPK for six of seven serotypes (statistically greater for four) compared with PPSV23. In multivariate analyses, younger age, vaccine naivety, and receipt of PCV7 were associated with increased OPK responses. Conclusions PCV7 induces a superior immune response at 1 month post vaccination compared with PPSV23 in COPD. Older age and prior PPSV23 reduce vaccine responsiveness. Clinical trial registered with www.clinicaltrials.gov (NCT00457977).

Abstract Rationale In studies that address health-related quality of life (QoL) and survival, subjects who die are usually censored from QoL assessments. This practice tends to inflate the apparent benefits of interventions with a high risk of mortality. Assessing a composite QoL-death outcome is a potential solution to this problem. Objectives To determine the effect of lung volume reduction surgery (LVRS) on a composite endpoint consisting of the occurrence of death or a clinically meaningful decline in QoL defined as an increase of at least eight points in the St. George's Respiratory Questionnaire total score from the National Emphysema Treatment Trial. Methods In patients with chronic obstructive pulmonary disease and emphysema randomized to receive medical treatment (n = 610) or LVRS (n = 608), we analyzed the survival to the composite endpoint, the hazard functions and constructed prediction models of the slope of QoL decline. Measurements and Main Results The time to the composite endpoint was longer in the LVRS group (2 years) than the medical treatment group (1 year) (P < 0.0001). It was even longer in the subsets of patients undergoing LVRS without a high risk for perioperative death and with upper-lobe-predominant emphysema. The hazard for the composite event significantly favored the LVRS group, although it was most significant in patients with predominantly upper-lobe emphysema. The beneficial impact of LVRS on QoL decline was most significant during the 2 years after LVRS. Conclusions LVRS has a significant effect on the composite QoL-survival endpoint tested, indicating its meaningful palliative role, particularly in patients with upper-lobe–predominant emphysema.

The molecular mechanism of autocrine regulation of vascular endothelial growth factor (VEGF) in chronic lymphocytic leukemia (CLL) B cells is unknown. Here, we report that CLL B cells express constitutive levels of HIF-1α under normoxia. We have examined the status of the von Hippel-Lindau gene product (pVHL) that is responsible for HIF-1α degradation and found it to be at a notably low level in CLL B cells compared with normal B cells. We demonstrate that the microRNA, miR-92-1, overexpressed in CLL B cells, can target the VHL transcript to repress its expression. We found that the stabilized HIF-1α can form an active complex with the transcriptional coactivator p300 and phosphorylated-STAT3 at the VEGF promoter and recruit RNA polymerase II. This is initial evidence that pVHL, without any genetic alteration, can be regulated by microRNA and explains the aberrant autocrine VEGF secretion in CLL.

Object Intraneural ganglia are nonneoplastic mucinous cysts contained within the epineurium of peripheral nerves. Their pathogenesis has been controversial. Historically, the majority of authors have favored de novo formation (degenerative theory). Because of their rarity, intraneural ganglia affecting the upper limb have been misunderstood. This study was designed to critically analyze the literature and to test the hypothesis that intraneural ganglia of the upper limb act analogously to those in the lower limb, being derived from an articular source (synovial theory). Methods Two patients with digital intraneural cysts were included in the study. An extensive literature review of intraneural ganglia of the upper limb was undertaken to provide the historical basis for the study. Results In both cases, the digital intraneural ganglia were demonstrated to have joint connections; the one patient in whom an articular branch was not appreciated initially had evidence on postoperative MR images of persistence of intraneural cyst after simple decompression was performed. Eighty-six cases of intraneural lesions were identified in varied locations of the upper limb: the most common sites were the ulnar nerve at the elbow and wrist, occurring 38 and 22 times, respectively. Joint connections were present in only 20% of the cases published by other groups. Conclusions The authors believe that the fundamental principles of the unifying articular (synovial) theory (that is, articular branch connections, cyst fluid following a path of least resistance, and the role of pressure fluxes) previously described to explain intraneural ganglia in the lower limb apply to those cases in the upper limb. In their opinion, the joint connection is often not identified because of the cysts' rarity, radiologists' and surgeons' inexperience, and the difficulty visualizing and demonstrating it because of the small size of the cysts. Furthermore, they believe that recurrence (subclinical or clinical) is not only underreported but also predictable after simple decompression that fails to address the articular branch. In contrast, intraneural recurrence can be eliminated with disconnection of the articular branch.

Abstract Rationale Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea, impaired gas exchange, and ultimate mortality. Objectives To test the hypothesis that maximal oxygen uptake during cardiopulmonary exercise testing at baseline and with short-term longitudinal measures would predict mortality in patients with idiopathic pulmonary fibrosis. Methods Data from 117 patients with IPF and longitudinal cardiopulmonary exercise tests were examined retrospectively. Survival was calculated from the date of the first cardiopulmonary exercise test. Measurements and Main Results Patients with baseline maximal oxygen uptake less than 8.3 ml/kg/min had an increased risk of death (n = 8; hazard ratio, 3.24; 95% confidence interval, 1.10–9.56; P = 0.03) after adjusting for age, gender, smoking status, baseline forced vital capacity, and baseline diffusion capacity for carbon monoxide. We were unable to define a unit change in maximal oxygen uptake that predicted survival in our cohort. Conclusions We conclude that a threshold maximal oxygen uptake of 8.3 ml/kg/min during cardiopulmonary exercise testing at baseline adds prognostic information for patients with IPF.