GLUT8 is dispensable for embryonic development but influences hippocampal neurogenesis and heart function.

GLUT8 is a glucose transporter isoform expressed at high levels in testis; at intermediate levels in the brain, including the hippocampus; and at lower levels in the heart and several other tissues. GLUT8 is located in an intracellular compartment and does not appear to translocate to the cell surface, except in blastocysts, where insulin has been reported to induce its surface expression. Here, we generated mice with inactivation of the glut8 gene. We showed that expression of GLUT8 was not required for normal embryonic development and that glut8-/- mice had normal postnatal development, glucose homeostasis, and response to mild stress. Adult glut8-/- mice showed increased proliferation of hippocampal cells but no defect in memory acquisition and retention. Absence of GLUT8 from the heart did not alter heart size and morphology but led to an increase in P-wave duration, which was not associated with abnormal Nav1.5 Na+ channel or connexin expression. Thus, absence of GLUT8 expression in the mouse caused complex but mild physiological alterations.

Audit report on the Heart of Iowa Regional Transit Agency, Des Moines, for the year ended June 30, 2007

Audit report on the Heart of Iowa Regional Transit Agency, Des Moines, for the year ended June 30, 2007

Management of major accidents with on-site 144 dispatcher

Introduction: An excellent coordination between firefighters, policemen and medical rescue is the key to success in the management of major accidents. In order to improve and assist the medical teams engaged on site, the Swiss "medical command and control system" for rescue operations is based on a binomial set up involving one head emergency doctor and one head rescue paramedic, both trained in disaster medicine. We have recently experimented an innovative on-site "medical command and control system", based on the binomial team, supported by a dedicated 144 dispatcher. Methods: A major road traffic accident took place on the highway between Lausanne and Vevey on April 9th 2008. We have retrospectively collected all data concerning the victims as well as the logistics and dedicated structures, reported by the 144, the Hospitals, the Authority of the State and the Police and Fire Departments. Results: The 72-car pileup caused one death and 26 slightly injured patients. The management on the accident site was organized around a tripartite system, gathering together the medical command and control team with the police and fire departments. On the medical side, 16 ambulances, 2 medical response teams (SMUR), the Rega crew and the medical command and control team were dispatched by the 144. On that occasion an advanced medical command car equipped with communication devices and staffed with a 144 dispatcher was also engaged, allowing efficient medical regulation directly from the site. Discussion: The specific skills of one doctor and one paramedic both trained for disaster's management proved to be perfectly complementary. The presence of a dispatcher on site with a medical command car also proved to be useful, improving orders transmission from the medical command team to all other on- and off-site partners. It relieved the need of repeated back-and-forth communication with the 144, allowing both paramedic and doctor to focus on strategy and tactics rather than communication and logistics.

Inflammatory markers and incident heart failure risk in older adults: the Health ABC (Health, Aging, and Body Composition) study.

OBJECTIVES: The purpose of this study was to evaluate the association between inflammation and heart failure (HF) risk in older adults. BACKGROUND: Inflammation is associated with HF risk factors and also directly affects myocardial function. METHODS: The association of baseline serum concentrations of interleukin (IL)-6, tumor necrosis factor-alpha, and C-reactive protein (CRP) with incident HF was assessed with Cox models among 2,610 older persons without prevalent HF enrolled in the Health ABC (Health, Aging, and Body Composition) study (age 73.6 +/- 2.9 years; 48.3% men; 59.6% white). RESULTS: During follow-up (median 9.4 years), HF developed in 311 (11.9%) participants. In models controlling for clinical characteristics, ankle-arm index, and incident coronary heart disease, doubling of IL-6, tumor necrosis factor-alpha, and CRP concentrations was associated with 29% (95% confidence interval: 13% to 47%; p < 0.001), 46% (95% confidence interval: 17% to 84%; p = 0.001), and 9% (95% confidence interval: -1% to 24%; p = 0.087) increase in HF risk, respectively. In models including all 3 markers, IL-6, and tumor necrosis factor-alpha, but not CRP, remained significant. These associations were similar across sex and race and persisted in models accounting for death as a competing event. Post-HF ejection fraction was available in 239 (76.8%) cases; inflammatory markers had stronger association with HF with preserved ejection fraction. Repeat IL-6 and CRP determinations at 1-year follow-up did not provide incremental information. Addition of IL-6 to the clinical Health ABC HF model improved model discrimination (C index from 0.717 to 0.734; p = 0.001) and fit (decreased Bayes information criterion by 17.8; p < 0.001). CONCLUSIONS: Inflammatory markers are associated with HF risk among older adults and may improve HF risk stratification.

Incidents and complications of totally implanted vascular access devices in children: a prospective study.

BACKGROUND: Totally implanted vascular access devices are frequently used in children for repeated blood samples or intravenous treatments. This prospective study aims at identifying the risk factors associated with infections, obstructions and surgical complications of these devices in pediatric patients. METHODS: From January 2006 to January 2008, all children older than one year of age with a diagnosis of solid or blood cell malignancy were included in the study. Insertion was performed by the surgeon according to a standardized protocol after landmark-guided puncture of the subclavian or internal jugular vein by a senior anesthesiologist. Dressing and post-operative care were standardized. Every manipulation was prospectively recorded by specialized dedicated nurses, and all patients were screened for complications one month post-surgery. RESULTS: 45 consecutive patients 1 to 16 years old were enrolled in the study. Mean age at the time of procedure was 8.5 years (range 1.3-15.6; SD +/- 4.88). There were 12 peroperative adverse events in 45 procedures (27%), detailed as follows: 3 pneumothoraces (7%), 3 hematomas (7%), 6 arterial punctures (13%). Among these events, intervention was necessary for two pneumothorax and one arterial puncture. There was no air embolism. At one month, we recorded 5 post-operative complications (11%): 2 thrombotic obstructions, one unsightly scar, and one scapular pain of unknown etiology. One patient needed repositioning of the catheter. There was no catheter-related infection. CONCLUSION: Prospective recording of TIVA insertion in children reveals a significant number of early incidents and complications, mainly associated with the percutaneous puncture technique. We found no infection in this series. Results of a longer follow-up in the same population are pending.

Abnormal Lung Function and Risk for Heart Failure in the Elderly: The Health, Aging, and Body Composition Study

Background: Chronic obstructive pulmonary disease (COPD) has been associated with increased risk for heart failure (HF). The impact of subclinical abnormal spirometric findings on HF risk among older adults without history of COPD is not well elucidated. Methods: We evaluated 2125 participants (age 73.6±2.9 years; 50.5% men; 62.3% white; 45.6/9.4% past/current smokers; body mass index [BMI] 27.2±4.6 kg/m2) without prevalent COPD or HF who underwent baseline spirometry in the Health ABC Study. Abnormal lung function was defined either as forced vital capacity (FVC) below lower limit of normal (LLN) or forced expiratory volume in 1st sec (FEV1) to FVC ratio below LLN. Results: On follow-up (median, 9.4 years), 68 of 350 (19.4%) participants with abnormal lung function developed HF, as compared to 172 of 1775 (9.7%) participants with normal lung function (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.74 -3.06; P<.001). This increased risk persisted after adjusting for all other independent predictors of HF in the Health ABC Study, BMI, incident coronary events, and several inflammatory markers (HR, 1.82; 95% CI, 1.30 -2.54; P<.001), and remained constant over time. Baseline FVC and FEV1 had a linear association with HF risk (Figure). In adjusted models, HF risk increased by 21% (95% CI, 10 -36%) per 10% decrease in FVC and 18% (95% CI, 10 -28%) per 10% decrease in FEV1 (both P<.001); this association persisted among participants with normal lung function at baseline. Findings were consistent across sex, race, and smoking status. Conclusions: Subclinical abnormal spirometric findings are prevalent among older adults and are independently associated with risk for incident HF.

Multiple filtering devices for the estimation of cyclical DSGE models

We propose a method to estimate time invariant cyclical DSGE models using the informationprovided by a variety of filters. We treat data filtered with alternative procedures as contaminated proxies of the relevant model-based quantities and estimate structural and non-structuralparameters jointly using a signal extraction approach. We employ simulated data to illustratethe properties of the procedure and compare our conclusions with those obtained when just onefilter is used. We revisit the role of money in the transmission of monetary business cycles.

Transcatheter aortic valve implantation (TAVI): state of the art techniques and future perspectives.

Transcatheter aortic valve therapies are the newest established techniques for the treatment of high risk patients affected by severe symptomatic aortic valve stenosis. The transapical approach requires a left anterolateral mini-thoracotomy, whereas the transfemoral method requires an adequate peripheral vascular access and can be performed fully percutaneously. Alternatively, the trans-subclavian access has been recently proposed as a third promising approach. Depending on the technique, the fine stent-valve positioning can be performed with or without contrast injections. The transapical echo-guided stent-valve implantation without angiography (the Lausanne technique) relies entirely on transoesophageal echocardiogramme imaging for the fine stent-valve positioning and it has been proved that this technique prevents the onset of postoperative contrast-related acute kidney failure. Recent published reports have shown good hospital outcomes and short-term results after transcatheter aortic valve implantation, but there are no proven advantages in using the transfemoral or the transapical technique. In particular, the transapical series have a higher mean logistic Euroscore of 27-35%, a procedural success rate above 95% and a mean 30-day mortality between 7.5 and 17.5%, whereas the transfemoral results show a lower logistic Euroscore of 23-25.5%, a procedural success rate above 90% and a 30-day mortality of 7-10.8%. Nevertheless, further clinical trials and long-term results are mandatory to confirm this positive trend. Future perspectives in transcatheter aortic valve therapies would be the development of intravascular devices for the ablation of the diseased valve leaflets and the launch of new stent-valves with improved haemodynamic, different sizes and smaller delivery systems.

The predictive value of preoperative B-type natriuretic peptide in children undergooing heart surgery.

Introduction: Low cardiac output syndrome is frequent in childrenafter heart surgery for congenital heart disease and may result in pooroutcome and increased morbidity. In the adult population, preoperativebrain natriuretic peptide (BNP) was shown to be predictive of postoperative complications. In children, the value of preoperative BNP onpostoperative outcome is not so clear. The aim of this study was todetermine the predictive value of preoperative BNP on postoperativeoutcome and low cardiac output syndrome in children after heartsurgery for congenital heart disease.Methods: We examined, retrospectively, the postoperative course of97 pediatric patients (mean age 3.7 years, range 0-14 years old) whounderwent heart surgery in a tertiary care pediatric intensive caresetting. NTproBNP was measured preoperatively in all patients(median 412 pg/ml, range 12-35'000 pg/ml). Patients were divided intothree groups according to their NTproBNP levels (group 1: 0-300 pg/ml, group 2: 300-600 pg/ml, group 3: >600 pg/ml) and then,correlations with postoperative outcomes were examined.Results: We found that patients with a high preoperative BNP requiredmore frequently prolonged (>2 days) mechanical ventilation (33%vs 40% vs 61%, p = 0.045) and stayed more frequently longer than6 days in the intensive care unit (42% vs 50% vs 71%, p = 0.03).However, high preoperative BNP was not correlated with occurrenceof low cardiac output syndrome.Conclusion: Preoperative BNP cannot be used, in children, as areliable and sole predictor of postoperative low cardiac outputsyndrome. However it may help identify, before surgery, those patientsat risk of having a difficult postoperative course.

Audit report on the Heart of Iowa Regional Transit Agency, Des Moines, for the year ended June 30, 2008

Audit report on the Heart of Iowa Regional Transit Agency, Des Moines, for the year ended June 30, 2008

Use of 2D Sensitivity Encoding for Slow-Infusion Contrast-Enhanced Isotropic 3-T Whole-Heart Coronary MR Angiography.

OBJECTIVE. The purpose of this study was to improve the blood-pool signal-to-noise ratio (SNR) and blood-myocardium contrast-to-noise ratio (CNR) of slow-infusion 3-T whole-heart coronary MR angiography (MRA).SUBJECTS AND METHODS. In 2D sensitivity encoding (SENSE), the number of acquired k-space lines is reduced, allowing less radiofrequency excitation per cardiac cycle and a longer TR. The former can be exploited for signal enhancement with a higher radiofrequency excitation angle, and the latter leads to noise reduction due to lower data-sampling bandwidth. Both effects contribute to SNR gain in coronary MRA when spatial and temporal resolution and acquisition time remain identical. Numeric simulation was performed to select the optimal 2D SENSE pulse sequence parameters and predict the SNR gain. Eleven patients underwent conventional unenhanced and the proposed 2D SENSE contrast-enhanced coronary MRA acquisition. Blood-pool SNR, blood-myocardium CNR, visible vessel length, vessel sharpness, and number of side branches were evaluated.RESULTS. Consistent with the numeric simulation, using 2D SENSE in contrast-enhanced coronary MRA resulted in significant improvement in aortic blood-pool SNR (unenhanced vs contrast-enhanced, 37.5 +/- 14.7 vs 121.3 +/- 44.0; p < 0.05) and CNR (14.4 +/- 6.9 vs 101.5 +/- 40.8; p < 0.05) in the patient sample. A longer length of left anterior descending coronary artery was visualized, but vessel sharpness, coronary artery coverage, and image quality score were not improved with the proposed approach.CONCLUSION. In combination with contrast administration, 2D SENSE was found effective in improving SNR and CNR in 3-T whole-heart coronary MRA. Further investigation of cardiac motion compensation is necessary to exploit the SNR and CNR advantages and to achieve submillimeter spatial resolution.

Neurally adjusted ventilatory assist can improve arterial oxygenation

INTRODUCTION. Neurally Adjusted Ventilatory Assist (NAVA) [1] is a new spontaneousassisted ventilatory mode which uses the diaphragmatic electrical activity (Eadi) to pilot the ventilator. Eadi is used to initiate the ventilator's pressurization and cycling off. Delivered inspiratory assistance is proportional to Eadi. NAVA can improve patient-ventilator synchrony [2] compared to pressure support (PS), but little is known about its effect on minute ventilation and oxygenation. OBJECTIVES. To compare the effects of NAVA and PS on minute ventilation and oxygenation and to analyze potential determinant factors for oxygenation. METHODS. Comparison between two 20-min periods under NAVA and PS. NAVA gain (proportionality factor between Eadi and delivered pressure) set as to obtain the same peak pressure as in PS. FIO2 and positive end-expiratory pressure (PEEP) were the same in NAVA and PS. Blood gas analyses were performed at the end of both recording periods. Statistical analysis: groups were compared with paired t tests or non parametric Wilcoxon signed-rank tests. p\0.05 was considered significant. RESULTS. [Mean ± SD]: 22 patients (age 66 ± 12 year, 7 M/15F, BMI 23.4 ± 3.1 kg/m2), 8 patients with COPD. Initial settings: PS 13 ± 3 cmH2O, PEEP 7 ± 2 cmH2O, NAVA gain 2.2 ± 1.8. Minute ventilation and PaCO2 were the same with both modes (p = 0.296 and 0.848, respectively). Tidal volume was lower with NAVA (427 ± 102 vs. 477 ± 102 ml, p\0.001). In contrast respiratory rate was higher with NAVA (25.6 ± 9.5 vs. 22.3 ± 8.9 cycles/min). Arterial oxygenation was improved with NAVA (PaO2 85.1 ± 28.9 vs. 75.8 ± 11.9 mmHg, p = 0.017, PaO2/FIO2 210 ± 53 vs. 195 ± 58 mmHg, p = 0.019). Neural inspiratory time (Tin) was comparable between NAVA and PS (p = 0.566). Among potential determinant factors for oxygenation, mean airway pressure (Pmean) was lower with NAVA (10.6 ± 2.6 vs. 11.1 ± 2.4 cmH2O, p = 0.006), as was the pressure time product (PTP) (6.8 ± 3.0 vs. 9.2 ± 3.5 cmH2O 9 s, p = 0.004). There were less asynchrony events with NAVA (2.3 ± 2.0 vs. 4.4 ± 3.8, p = 0.009).Tidal volume variability was higher with NAVA (variation coefficient: 30 ± 19.5 vs. 13.5 ± 8.6, p\0.001). Inspiratory time in excess (Tiex) was lower with NAVA (56 ± 23 vs. 202 ± 200 ms, p = 0.001). CONCLUSION. Despite lower Pmean and PTP in NAVA, arterial oxygenation was improved compared to PS. As asynchronies may be associated with an increased work of breathing and a higher oxygen consumption, their decrease in number with NAVA could be an explanation for oxygenation improvement. Another explanation could be the increase in VT variability. Further studies should now be performed to confirm the potential of NAVA in improving arterial oxygenation and explore the underlying mechanisms.

Ruling out coronary heart disease in primary care patients with chest pain: a clinical prediction score.

ABSTRACT: BACKGROUND: Chest pain raises concern for the possibility of coronary heart disease. Scoring methods have been developed to identify coronary heart disease in emergency settings, but not in primary care. METHODS: Data were collected from a multicenter Swiss clinical cohort study including 672 consecutive patients with chest pain, who had visited one of 59 family practitioners' offices. Using delayed diagnosis we derived a prediction rule to rule out coronary heart disease by means of a logistic regression model. Known cardiovascular risk factors, pain characteristics, and physical signs associated with coronary heart disease were explored to develop a clinical score. Patients diagnosed with angina or acute myocardial infarction within the year following their initial visit comprised the coronary heart disease group. RESULTS: The coronary heart disease score was derived from eight variables: age, gender, duration of chest pain from 1 to 60 minutes, substernal chest pain location, pain increases with exertion, absence of tenderness point at palpation, cardiovascular risks factors, and personal history of cardiovascular disease. Area under the receiver operating characteristics curve was of 0.95 with a 95% confidence interval of 0.92; 0.97. From this score, 413 patients were considered as low risk for values of percentile 5 of the coronary heart disease patients. Internal validity was confirmed by bootstrapping. External validation using data from a German cohort (Marburg, n = 774) revealed a receiver operating characteristics curve of 0.75 (95% confidence interval, 0.72; 0.81) with a sensitivity of 85.6% and a specificity of 47.2%. CONCLUSIONS: This score, based only on history and physical examination, is a complementary tool for ruling out coronary heart disease in primary care patients complaining of chest pain.

Recent decrease in the prevalence of congenital heart defects in europe.

OBJECTIVES: To examine trends in the prevalence of congenital heart defects (CHDs) in Europe and to compare these trends with the recent decrease in the prevalence of CHDs in Canada (Quebec) that was attributed to the policy of mandatory folic acid fortification. STUDY DESIGN: We used data for the period 1990-2007 for 47 508 cases of CHD not associated with a chromosomal anomaly from 29 population-based European Surveillance of Congenital Anomalies registries in 16 countries covering 7.3 million births. We estimated trends for all CHDs combined and separately for 3 severity groups using random-effects Poisson regression models with splines. RESULTS: We found that the total prevalence of CHDs increased during the 1990s and the early 2000s until 2004 and decreased thereafter. We found essentially no trend in total prevalence of the most severe group (group I), whereas the prevalence of severity group II increased until about 2000 and decreased thereafter. Trends for severity group III (the most prevalent group) paralleled those for all CHDs combined. CONCLUSIONS: The prevalence of CHDs decreased in recent years in Europe in the absence of a policy for mandatory folic acid fortification. One possible explanation for this decrease may be an as-yet-undocumented increase in folic acid intake of women in Europe following recommendations for folic acid supplementation and/or voluntary fortification. However, alternative hypotheses, including reductions in risk factors of CHDs (eg, maternal smoking) and improved management of maternal chronic health conditions (eg, diabetes), must also be considered for explaining the observed decrease in the prevalence of CHDs in Europe or elsewhere.