Outcomes of uninterrupted vs interrupted Periprocedural direct oral Anticoagulants in atrial Fibrillation ablation: A meta-analysis.

BACKGROUND: Studies indicate that uninterrupted anticoagulation (UA) is superior to interrupted anticoagulation (IA) in the periprocedural period during catheter ablation of atrial fibrillation. Still IA is followed in many centers considering the bleeding risk. This meta-analysis compares interrupted and uninterrupted direct oral anticoagulation during catheter ablation of atrial fibrillation. METHODS: A systematic search into PubMed, EMBASE, and the Cochrane databases was performed and five studies were selected that directly compared IA vs UA before ablation and reported procedural outcomes, embolic, and bleeding events. The primary outcome of the study was major adverse cerebro-cardiovascular events. RESULTS: The meta-analysis included 840 patients with UA and 938 patients with IA. Median follow-up was 30 days. Activated clotting time (ACT) before first heparin bolus was significantly longer with UA (P = .006), whereas mean ACT was similar between the two groups (P = .19). Total heparin dose needed was significantly higher with IA (mean, ‒1.61; 95% CI, ‒2.67 to ‒0.55; P = .003). Mean procedure time did not vary between groups (P = .81). Overall complication rates were low, with similar major adverse cerebro-cardiovascular event (P = .40) and total bleeding (P = .55) rates between groups. Silent cerebral events (SCEs) were significantly more frequent with IA (log odds ratio, ‒0.90; 95% CI, ‒1.59 to ‒0.22; P < .01; I 2, 33%). Rates of major bleeding, minor bleeding, pericardial effusion, cardiac tamponade, and puncture complications were similar between groups. CONCLUSIONS: UA during atrial fibrillation ablation has similar bleeding event rates, procedural times, and mean ACTs as IA, with fewer SCEs.

Preliminary findings of the relationship of lower heart rate variability with military sexual trauma and presumed posttraumatic stress disorder.

Decreased heart rate variability (HRV) occurs with physical and psychological disorders and is a predictor of cardiac and all-cause mortality. This study was the first of which we are aware to examine and report the relationship between military sexual trauma (MST) and HRV measures. In a historical cohort study of female veterans with (n = 27) and without (n = 99) MST who received Holter and electrocardiogram evaluation at a Veteran Affairs medical center during 2007-2010, we examined the relationship between MST and the standard deviation of all R-R intervals (SDNN) and the square root of the mean of the sum of the squares of differences between adjacent R-R intervals (RMSSD). Female veterans with MST were younger, p = .002, frequently had a probable posttraumatic stress disorder diagnosis, 80% versus 15%, p = < .0001, and had lower SDNN, p = .0001, and RMSSD, p = .001, than those without MST. The SDNN and RMSSD of a 25-year-old female veteran with MST were comparable to that of female veterans aged 69 to 81 years without MST. Further research is needed to evaluate relationships between MST and HRV measures.

Lower heart rate variability associated with military sexual trauma rape and posttraumatic stress disorder.

Low heart rate variability (HRV) can occur with psychological disorders such as posttraumatic stress disorder (PTSD). The purpose of this study was to examine the association between PTSD by trauma type and decreased HRV measures in female veterans with cardiac symptoms. This secondary analysis utilized data from a previous study of female veterans (n = 125) examined for cardiac symptoms by Holter and electrocardiogram recordings at a Veterans Affairs medical center. The mean HRV measure from three 10-s data segments with spontaneous respirations was obtained for each subject. PTSD diagnosis and type of trauma exposure were collected from mental health consult notes. Chi-square was used for frequency of subject characteristics; independent t tests and one-way analysis of variance (ANOVA) compared means of HRV measures between trauma types. Statistical significance was set at p < .05 a priori. By ANOVA, significantly lower log-transformed standard deviation of all normal sinus rhythm R-R intervals (SDNN) and log-transformed square root of the mean of the sum of the squares of differences between adjacent normal sinus rhythm R-R intervals (RMSSD) were found in the PTSD group with documented rape military sexual trauma (MST) compared to other groups including no PTSD, PTSD following MST with rape not specified, combat exposure, and nonmilitary-related trauma; lower HRV measures were not found with other PTSD types of trauma. This study suggests rape MST with concomitant PTSD may be a risk factor for decreased HRV in female veterans examined for cardiac symptoms.

Smaller cardiac cell size and reduced extra-cellular collagen might be beneficial for hearts of Ames dwarf mice.

PURPOSE: To test the hypothesis that cardiac morphologic differences between Ames dwarf and wild-type littermates might correlate with the increased longevity observed in the Ames dwarf mice. METHODS: Hearts removed from young adult (5-7 mo) and old (24-28 mo) Ames dwarf and wild-type littermates underwent histological and morphometric analysis. Measurements of cell size, nuclear size, and collagen content were made using computerized color deconvolution and particle analysis methodology. RESULTS: In the young mice at six months of age, mean cardiomyocyte area was 46% less in Ames dwarf than in wild-type mice (p<0.0001). Cardiomyocyte size increased with age by about 52% in the wild-type mice and 44% in the Ames dwarf mice (p<0.001). There was no difference in nuclear size of the cardiomyocytes between the young adult wild-type and Ames dwarf mice. There was an age-associated increase in the cardiomyocyte nuclear size by approximately 50% in both the Ames and wild-type mice (p<0.001). The older Ames dwarf mice had slightly larger cardiomyocyte nuclei compared to wild-type (2%, p<0.05). The collagen content of the hearts in young adult Ames dwarf mice was estimated to be 57% less compared to wild-type littermates (p<0.05). Although collagen content of both Ames dwarf and wild-type mouse hearts increased with age, there was no significant difference at 24 months. CONCLUSIONS: In wild-type and Ames dwarf mice, nuclear size, cardiomyocyte size, and collagen content increased with advancing age. While cardiomyocyte size was much reduced in young and old Ames dwarf mice compared with wild-type, collagen content was reduced only in the young adult mice. Taken together, these findings suggest that Ames dwarf mice may receive some longevity benefit from the reduced cardiomyocyte cell size and a period of reduced collagen content in the heart during adulthood.

The impact of mouse passaging of Mycobacterium tuberculosis strains prior to virulence testing in the mouse and guinea pig aerosol models.

BACKGROUND: It has been hypothesized that the virulence of lab-passaged Mycobacterium tuberculosis and recombinant M. tuberculosis mutants might be reduced due to multiple in vitro passages, and that virulence might be augmented by passage of these strains through mice before quantitative virulence testing in the mouse or guinea pig aerosol models. METHODOLOGY/PRINCIPAL FINDINGS: By testing three M. tuberculosis H37Rv samples, one deletion mutant, and one recent clinical isolate for survival by the quantitative organ CFU counting method in mouse or guinea pig aerosol or intravenous infection models, we could discern no increase in bacterial fitness as a result of passaging of M. tuberculosis strains in mice prior to quantitative virulence testing in two animal models. Surface lipid expression as assessed by neutral red staining and thin-layer chromatography for PDIM analysis also failed to identify virulence correlates. CONCLUSIONS/SIGNIFICANCE: These results indicate that animal passaging of M. tuberculosis strains prior to quantitative virulence testing in mouse or guinea pig models does not enhance or restore potency to strains that may have lost virulence due to in vitro passaging. It is critical to verify virulence of parental strains before genetic manipulations are undertaken and comparisons are made.

Long-term glucose control and risk of perioperative complications.

BACKGROUND: The impact of long-term preoperative glucose control on short-term surgical complications is unclear. We investigated whether preoperative hemoglobin A1c (HA(1c)) levels correlated with the risk of postoperative complications. METHODS: A database of 38,989 patients undergoing major surgical procedures from October 1996 to May 2007 was reviewed. Of these patients, 2,960 were diagnosed diabetic with a HA(1c) level within 30 days before their operation. National Surgical Quality Improvement Program (NSQIP) definitions were used in determining postoperative complications. RESULTS: Of 36,039 nondiabetic patients, 5,095 experienced 1 or more complications (14.1%). In 2,960 diabetic patients, 780 diabetic patients had 1 or more complications (26.4%) (P

Selective astrocytic gap junctional trafficking of molecules involved in the glycolytic pathway: impact on cellular brain imaging.

To assess the specificity of metabolite trafficking among gap junction-coupled astrocytes, we developed novel, real-time, single-cell enzymatic fluorescence assays to assay cell-to-cell transfer of unlabeled glycolytic intermediates and report (i) highly restricted transfer of glucose-6-phosphate (P) and two analogs, deoxyglucose (DG)-6-P, and 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-DG-6-P, compared with DG and 2- and 6-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-DG, (ii) extensive junctional diffusion of glyceraldehyde-3-P, NADH, and NADPH plus three anionic fluorescent dyes used as internal standards for transfer assays, and (iii) stimulation of gap junctional communication by increased intracellular Na(+) that also evokes metabolic responses in nearby coupled astrocytes. Thus, dye transfer does not predict gap junctional permeability of endogenous metabolites. Intracellular retention of flux-regulating compounds (e.g. glucose-6-P) may be necessary for local metabolic control, whereas 'syncytial sharing' may dissipate the work load on peri-synaptic astrocytes. Imaging of brain functional activity depends on local accumulation of exogenous or endogenous signals, and DG-6-P is trapped in the cell where it is phosphorylated, whereas rapid dispersal of cytoplasmic NAD(P)H and labeled glucose metabolites throughout the astrocytic syncytium can interfere with cellular assessment of neuron-astrocyte relationships in autoradiographic, fluorescence microscopic, and magnetic resonance spectroscopic studies.

A correlation between growth rate, apoptosis, and tumor necrosis factor-α in umbilical cord blood cells infected with two strains of Mycobacterium tuberculosis.

BACKGROUND: Using umbilical cord blood (UCB) cells, it was demonstrated that three virulent isolates, two highly transmissible clinical isolates and the virulent laboratory strain, demonstrated rapid growth in the UCB cells, which was significantly faster than the growth rate observed for a unique isolate. There was also a significant increase in the amount of tumor necrosis factor (TNF)-a elicited from the UCB cells after infection with the unique isolate compared to the hypervirulent isolates. This study investigated whether neutralization or addition of TNF-a within this system would alter growth rates and apoptosis. STUDY DESIGN AND METHODS: Ten UCB samples were obtained for these experiments and adherent cells were isolated. Two clinical isolates, one virulent and one unique, were used. Colony-forming units were assessed at 3 hours postinfection (Day 0) and on Day 7 to generate growth ratios. TNF-a antibody or exogenous TNF-a was added after the 3-hour incubation period. Viability of the UCB cells was assessed. Apoptosis was measured using terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining. RESULTS: There was no significant difference in the growth ratio for the virulent strain regardless of the presence of TNF-a antibody. There was a significant increase for the nonvirulent strain after the addition of antibody. There was an increase in viability for the UCB cells in the presence of antibody, suggesting a decrease in TNF-a­dependent apoptosis. Addition of exogenous TNF-a to the UCB cells after infection with the virulent strain decreased the growth ratio with a significant increase in apoptosis. CONCLUSIONS: The TNF-a response of the UCB cells is related to the infecting strain and the intracellular growth of the strain of Mycobacterium tuberculosis is not directly controlled by the level of TNF-a. This cytokine is at the start of a powerful cascade of transcription factors with numerous pleiotropic effects; consequently abrogating/enhancing a single direct outcome was difficult, with only slight alterations in growth.

Association of tobacco and alcohol use with earlier development of colorectal cancer: should we modify screening guidelines?

BACKGROUND: Current guidelines recommend initial colorectal cancer screening at age 50 years for average-risk patients. Alcohol and tobacco use can be associated with earlier onset of colorectal cancer. We hypothesized an earlier age at diagnosis and/or more advanced stage in patients with these habits. METHODS: We queried our tumor registry for colorectal cancer diagnosed between January 1997 and December 2006. Data were analyzed to evaluate effects of alcohol and tobacco use. RESULTS: Of 335 colorectal cancer patients, 81% used tobacco, 51% used alcohol, 45% used both, and 14% used neither. Current tobacco and alcohol use were associated with younger ages at onset of colorectal cancer. Thirteen of 332 patients were diagnosed with colorectal cancer before age 50 years. All had exposure to alcohol and tobacco. Fifty-four percent (7/13) of these patients presented at stage 3/4 compared with 34% of the overall population. CONCLUSIONS: Modification of screening guidelines to include these habits as "high-risk" factors may be indicated.

Differences in the growth of paired Ugandan isolates of Mycobacterium tuberculosis within human mononuclear phagocytes correlate with epidemiological evidence of strain virulence.

Previous studies have suggested that isolates of Mycobacterium tuberculosis responsible for tuberculosis outbreaks grow more rapidly within human mononuclear phagocytes than do other isolates. Clinical scenarios suggesting virulence of specific M. tuberculosis isolates are readily identified. Determination of appropriate "control" isolates for these studies is more problematic, but equally important for validating these assays and, ultimately, for identifying biologic differences between M. tuberculosis strains that contribute to virulence. We utilized the database from a study of Ugandan tuberculosis patients and their household (HH) contacts to identify M. tuberculosis isolates transmitted within HH and nontransmitted control isolates. Isolate pairs were evaluated from matched HH in each of three clinical scenarios: (i) coprevalent disease and no disease, (ii) incident disease and no disease, and (iii) M. tuberculosis infection (purified protein derivative [PPD] positive) and no infection (PPD negative). Intracellular growth of paired organisms was determined in a blinded fashion using two models of intracellular infection in which we have previously demonstrated correlation between intracellular growth and strain virulence, primary human monocytes (MN) and THP-1 human macrophage-like cells. In both models, transmitted isolates from coprevalent disease HH displayed more rapid growth than nontransmitted control isolates. In the THP-1 model, this was also true of transmitted isolates from HH with incident disease and their controls. Differences in production of tumor necrosis factor alpha and interleukin-10 by matched isolates showed correlation with growth patterns in the THP-1 cells but not in MN. Paired isolates characterized in this manner may be of particular interest for further investigations of the virulence of M. tuberculosis.

Intracellular macrophage growth rates and cytokine profiles of Mycobacterium tuberculosis strains with different transmission dynamics.

Mycobacterium tuberculosis strains associated with IS6110 restriction fragment-length polymorphism (RFLP) pattern clusters and strains demonstrating unique IS6110 RFLP patterns were investigated in interferon- gamma -activated THP-1 cells by measurement of binding, intracellular growth rate, and cytokine production. Binding was the same for all strains; however, strains from clusters grew significantly more rapidly than did unique strains. Maximal concentration of tumor necrosis factor (TNF)-alpha was detected at 2 days after infection, with unique strains eliciting significantly greater amounts than did strains from clusters. Interleukin (IL)-10 levels peaked at 1 day after infection with strains from clusters, whereas they peaked at 5 days after infection with unique strains. Rapid growth demonstrated by strains from clusters was highly correlated with rapid production of IL-10 and suppression of TNF-alpha in THP-1 cells during the early stages of infection. Characterization of this phenotype will further advance the investigation of virulence factors in M. tuberculosis.