Inhibition of prolyl 4-hydroxylase prevents left ventricular remodelling in rats with thoracic aortic banding

BACKGROUND: Pressure overload leads to myocardial remodelling with collagen accumulation, left ventricular hypertrophy (LVH), neurohormonal activation and myocardial dysfunction. Prolyl 4-hydroxylases (P4H) are involved in collagen maturation. Inhibition of P4H has been shown to prevent LV remodelling and improve survival post-myocardial infarction. AIM: To evaluate the role of P4H in pressure overload-induced myocardial remodelling. METHODS: Male Wistar rats underwent thoracic aortic banding (AoB) and were treated with a P4H inhibitor (P4HI) or vehicle (control). Echocardiography and haemodynamic measurements were performed after 4 weeks. Collagens, matrix metalloproteinases (MMP), tissue inhibitors of MMPs (TIMP), growth factors and neurohormonal markers were quantitated in LV samples. RESULTS: AoB led to LVH, increased LV enddiastolic pressure (LVEDP) and decreased contractility compared to sham. P4HI reversed these effects. AoB increased collagen I and III expression, which was normalized by P4HI. AoB led to deregulation of matrix remodelling enzymes, enhanced expression of growth factors and activation of the endothelin system. P4HI partially prevented deregulation of the MMP/TIMP system, inhibited upregulation of growth factors and normalized AoB-induced ECE-1 and ETB expression. CONCLUSIONS: P4HI leads to an improvement of AoB-associated LV dysfunction and reduces imbalance of extracellular matrix turnover and hypertrophy-associated gene expression. P4H inhibition could therefore be of value in treatment of myocardial remodelling accompanying pressure overload hypertrophy.     

Mid-term results after Epic xenograft implantation for aortic, mitral, and double valve replacement

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the mid-term results after implantation of the stented porcine xenograft (Epic valve with Linx anticalcification treatment) in elderly patients. METHODS: A total of 1,368 patients undergoing aortic valve replacement (AVR; n = 1,168), mitral valve replacement (MVR; n = 101) or double valve replacement (DVR; n = 105) between November 2001 and November 2006, was evaluated. The indication for Epic implantation was patient age > or = 70 years, with pathology not amenable to valve repair. Outcome was assessed by reviewing a prospectively acquired hospital database, in addition to annual clinical follow up. RESULTS: The mean patient age was 76 +/- 6 years (AVR), 73.7 +/- 6 years (MVR), and 73.1 +/- 7 years (DVR); among these patient subgroups, 50.3%, 65.3% and 57.7%, respectively, were female, and 16.4%, 25.5% and 40.0% presented with endocarditis. The logistic EuroSCORE predicted risk for mortality was 14.1 +/- 14%, 19.3 +/- 18%, and 20.3 +/- 20%, respectively. Additional surgical procedures included mitral valve repair in 103 patients (all AVR), CABG in 587 patients (515 AVR, 29 MVR, 43 DVR), left atrial ablation therapy in 70, 16 and nine patients respectively, and surgery on the thoracic aorta in 54, zero and 12 patients, respectively. The mean aortic cross-clamp time was 72 +/- 28, 84 +/- 44 and 133 +/- 48 min after AVR, MVR and DVR, respectively. Freedom from stroke events after five years was 99.0 +/- 0.3%, 97.3 +/- 1.9% and 100%, respectively; freedom from bleeding events after five years was 99.5 +/- 0.2%, 100% and 99.0 +/- 1.0%, and actuarial freedom from reoperation due to prosthetic valve endocarditis 98.9 +/- 0.7%, 96.7 +/- 1.9% and 92.4 +/- 3.4%. Among these patients groups, early mortality was 8.0 +/- 0.8%, 17.8 +/- 3.8% and 21.9 +/- 4.0%, and five-year survival 77.0 +/- 4.1%, 71.7 +/- 4.5% and 55.5 +/- 6.3%. Perioperative survival in non-endocarditis patients undergoing isolated valve surgery was 95.8 +/- 0.9%, 96.4 +/- 3.5% and 90.0 +/- 6.7% after AVR, MVR or DVR, respectively, while the five-year survival was 90.6 +/- 1.5%, 89.3 +/- 5.8% and 90.0 +/- 6.7%. CONCLUSION: Clinical outcome at five years after porcine valve replacement using the Epic xenograft was satisfactory in elderly patients. The clinical effectiveness of the Linx anticalcification treatment remains to be proven during longer-term follow up.     

Parental Recognition of Developmental Problems in Toddlers with Autism Spectrum Disorders

Symptoms of Autism Spectrum Disorders (ASD) begin to manifest during the first 2 years; there is limited evidence regarding type and timing of symptom onset. We examined factors related to parental age of recognition (AOR) of early abnormalities and the association between AOR and diagnosis and levels of functioning at 2 and 4 years in 75 toddlers with ASD. Results suggest significant differences between autism and PDD-NOS in the AOR and type of first concerns. Early social and motor delays as well as maternal age was associated with AOR. Later AOR was associated with poorer social-communicative and nonverbal cognitive functioning at 2 and 4. The findings are discussed in a context of identifying distinct developmental trajectories within the autism spectrum.     

Overall survival in patients with malignant glioma may be significantly longer with tumors located in deep grey matter

BACKGROUND: The aim of this study was to assess the correlation of overall survival with tumor location (lobar vs. deep grey matter) and with other clinical and imaging variables in a cohort of patients with high grade gliomas. METHODS: Adult patients with newly diagnosed supratentorial WHO grade 3 and 4 gliomas were evaluated. Clinical data included demographics, symptoms at presentation, treatment variables, and overall survival. Radiological data included tumor side, site (deep vs. lobar) and size, extent of peritumoral edema, and presence of midline shift. Biostatistics were carried out using log rank tests and univariate and multivariate Cox regression models. RESULTS: A total of 121 patients were investigated, 23 (19.0%) with WHO grade 3 and 98 (81.0%) with WHO grade 4 gliomas. Tumors had lobar location in 96 cases (79.3%) and deep grey matter location in 25 cases (20.7%). Median survival time for all patients was 26 weeks (IQR: 14-53). Patients with deep tumors survived significantly longer than those with lobar gliomas (log rank test, p=0.0083). Extensive brain edema significantly shortened survival (log rank test, p=0.0003). Presence of midline shift (>1 cm) was a statistically significant risk factor for shorter survival (log rank test, p<0.0001). The univariate Cox regression model demonstrated statistical significance for the variables age, side, site and size of tumor, presence of extensive edema, and presence of mass effect (>1 cm). In the multivariate Cox models, tumor grade, site and size showed statistical significance. CONCLUSIONS: This study suggests that patients with deep grey matter gliomas may survive significantly longer after the initial diagnosis than those with tumors in a lobar location. This is a potentially novel finding, which may corroborate the theory of differential invasion of glioma cells in different microenvironments of the brain, but remains to be confirmed in future prospective studies.     

Chirurgische Koronarrevaskularisation am schlagenden Herzen

Since the introduction of off-pump coronary artery bypass grafting (OPCAB) for coronary multivessel disease there was growing interest to evaluate the impact of OPCAB surgery compared to conventional coronary artery bypass grafting (CCAB) with cardiopulmonary bypass and cardioplegic arrest. However, subsequent prospective randomized studies and meta-analyses comparing OPCAB and CCAB surgery were performed on low-risk patients or mixed-risk populations. They usually failed to demonstrate a significant benefit of OPCAB surgery on early mortality or perioperative major cardiac and cerebrovascular events. In recent years, efforts were made to analyze the meaning of beating-heart concepts for patients with specific cardiac and extracardiac risks like ischemic cardiomyopathy, older age, renal failure, acute coronary syndrome, left main stenosis and others. For these subsets of patients several mono- and multicenter studies are available today. Even if most of them were nonrandomized and thus failed to reach evidence level A according to the AHA/ACC (American Heart Association/American College of Cardiology) definition, they still allow analyzing interim results for each specific perioperative risk factor. Particularly multi-risk patients and patients with severely reduced left ventricular function seem to benefit in terms of perioperative mortality and major morbidity by avoiding cardiopulmonary bypass and cardioplegic arrest. Analyzing early results and long-term follow-up of 364 patients with severely reduced ejection fraction<20%, the authors found a long-term benefit for patients when using OPCAB strategies particularly due to reduced perioperative mortality. Moreover, for most subsets of patients with significant extracardiac risk factors the incidence or perioperative stroke was reduced. In patients with preoperative renal and pulmonary dysfunction a decrease of corresponding organ failure was found for OPCAB strategy. For most risk populations transfusion requirements were significantly lower in OPCAB compared to CCAB surgery. In none of the patients an unfavorable outcome of beating-heart surgery compared to CCAB was shown. For emergency patients with an acute coronary syndrome presenting stable and unstable hemodynamics the authors found a clinical benefit by using beating-heart strategies. Particularly in patients with cardiogenic shock, cardiopulmonary bypass was often required to guarantee adequate perioperative organ perfusion. However, these patients seemed to benefit from avoiding global cardiac ischemia and maintaining native coronary blood flow. Follow-up results were comparable for these patients. In conclusion, beating-heart coronary artery bypass grafting seems to be advantageous in various risk populations and should be considered for patients with more than average risks for cardiopulmonary bypass and cardioplegic arrest.     

Tracheobronchial anomalies and stenoses: detection with low-dose multidetector CT with virtual tracheobronchoscopy--comparison with flexible tracheobronchoscopy

PURPOSE: To prospectively assess the sensitivity and specificity of low-dose multidetector computed tomography (CT) with virtual tracheobronchoscopy (VT) for evaluation of suspected airway stenoses and/or abnormalities by using flexible tracheobronchoscopy (FT) as the reference standard. MATERIALS AND METHODS: The study was approved by the local ethics committee; parental consent was obtained. Forty-five patients with clinically and/or radiographically suspected tracheobronchial stenosis and/or anomaly underwent FT and contrast material-enhanced single-phase multidetector CT with VT. CT was performed with an age- and weight-adjusted low-dose protocol: 120 or 80 kV; 120 or 60 mA; collimation, 1.5 or 0.75 mm; gantry rotation, 0.5 second. Mean effective dose was calculated for all examinations. Postprocessing was performed with surface rendering of VT images and multiplanar reformations. CT images were analyzed in consensus by two radiologists who were blinded to FT results. Statistical analysis was performed with 2 x 2 contingency tables; 95% confidence intervals (CIs) were calculated with the Blyth-Still-Casella procedure. RESULTS: Mean patient age was 4.4 years (range, 2 months to 16 years; 53% male patients). Tracheobronchial narrowing and/or abnormality were depicted at FT in 38 of 45 patients. In 33 of 38 patients, multidetector CT with VT depicted a tracheobronchial narrowing and/or anomaly. In 10 of 38 patients, tracheobronchial stenosis was induced by vascular anomalies. Five patients with normal findings at multidetector CT with VT had tracheobronchomalacia with inspiratory airway stenosis at FT. Sensitivity and specificity of CT with VT were 86.8% (95% CI: 73.3%, 94.7%) and 85.7% (95% CI: 44.6%, 99.3%), respectively. Positive and negative predictive values were 97.1% (95% CI: 84.9%, 99.9%) and 54.5% (95% CI: 25.0%, 80.0%), respectively. Overall accuracy was 86.7% (95% CI: 74.3%, 94.0%). Mean effective dose was 1.1 mSv (range, 0.5-1.8 mSv). CONCLUSION: Multidetector CT with VT with a low-dose protocol had high sensitivity and specificity for depiction of tracheobronchial narrowings and/or anomalies. However, tracheal narrowing due to tracheobronchomalacia was difficult to diagnose at single-phase multidetector CT with VT.     

Image quality and radiation exposure at pulmonary CT angiography with 100- or 120-kVp protocol: prospective randomized study

PURPOSE: To prospectively compare 16-section multidetector computed tomography (CT) at 100 and 120 kVp for image quality and radiation dose. MATERIALS AND METHODS: The study had institutional review board approval; written informed consent was obtained. Sixty patients were referred for evaluation of suspected pulmonary embolism with CT angiography. Patients were randomly assigned to a 100-kVp (n = 30; 17 men, 13 women; mean age, 66 years +/- 17 [standard deviation]; range, 19-89 years) or 120-kVp (n = 30; 15 men, 15 women; mean age, 62 years +/- 15; range, 28-86 years) protocol. Other scanning parameters were kept constant. Contrast medium was injected automatically with bolus tracking. Pulmonary vessel enhancement and image noise were quantified; signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Subjective vessel contrast was assessed by two radiologists in consensus. Effective dose was calculated on the basis of dose length product and volume CT dose index. Results of both protocols were compared by using the chi(2) test and Student t test. RESULTS: The 100-kVp protocol had a nonsignificantly higher mean vessel attenuation than the 120-kVp protocol (386.8 HU +/- 130.1 vs 317.9 HU +/- 112.5; P = .56) and a nonsignificantly higher image noise (16.9 HU +/- 5.8 vs 13.7 HU +/- 6.2; P = .84), which resulted in almost identical SNR (25.3 +/- 11.7 vs 27.0 +/- 14.5; P = .37) and CNR (22.0 +/- 11.2 vs 22.9 +/- 13.1; P = .51). There was no significant difference in subjective image quality between protocols. Mean effective dose for the 100-kVp protocol was significantly lower than that for the 120-kVp protocol (1.37 mSv +/- 0.39 vs 2.44 mSv +/- 0.97; -44%; P < .001). CONCLUSION: Reduction of kilovoltage from 120 to 100 kVp resulted in significant reduction of effective dose at pulmonary CT angiography, without significant loss of objective or subjective image quality.     

Unilateral hyperplasia of a cervical spinous process as a rare congenital variant of the spine

Congenital variants of the cervical spine may mimic traumatic lesions and may cause recurrent episodes of pain. We report a 24-year-old female patient with chronic neck pain who had marked unilateral hyperplasia of the spinous process of the seventh cervical vertebra. CT and MRI clearly depicted the abnormality and, furthermore, ruled out posttraumatic spinal changes. To our knowledge, our case is the first patient reported with this rare congenital variant diagnosed by cross-sectional imaging.