Human cytomegalovirus seropositivity is associated with reduced patient survival during sepsis.

BACKGROUND: Sepsis is one of the leading causes of death. Treatment attempts targeting the immune response regularly fail in clinical trials. As HCMV latency can modulate the immune response and changes the immune cell composition, we hypothesized that HCMV serostatus affects mortality in sepsis patients. METHODS: We determined the HCMV serostatus (i.e., latency) of 410 prospectively enrolled patients of the multicenter SepsisDataNet.NRW study. Patients were recruited according to the SEPSIS-3 criteria and clinical data were recorded in an observational approach. We quantified 13 cytokines at Days 1, 4, and 8 after enrollment. Proteomics data were analyzed from the plasma samples of 171 patients. RESULTS: The 30-day mortality was higher in HCMV-seropositive patients than in seronegative sepsis patients (38% vs. 25%, respectively; p = 0.008; HR, 1.656; 95% CI 1.135-2.417). This effect was observed independent of age (p = 0.010; HR, 1.673; 95% CI 1.131-2.477). The predictive value on the outcome of the increased concentrations of IL-6 was present only in the seropositive cohort (30-day mortality, 63% vs. 24%; HR 3.250; 95% CI 2.075-5.090; p < 0.001) with no significant differences in serum concentrations of IL-6 between the two groups. Procalcitonin and IL-10 exhibited the same behavior and were predictive of the outcome only in HCMV-seropositive patients. CONCLUSION: We suggest that the predictive value of inflammation-associated biomarkers should be re-evaluated with regard to the HCMV serostatus. Targeting HCMV latency might open a new approach to selecting suitable patients for individualized treatment in sepsis.

CHRM3 rs2165870 polymorphism is independently associated with postoperative nausea and vomiting, but combined prophylaxis is effective.

BACKGROUND: Clinical risk factors for postoperative nausea and vomiting (PONV) are evaluated with the Apfel score, however patients with low Apfel scores still experience PONV suggesting a genetic predisposition. PONV risk associates with specific M3 muscarinic acetylcholine receptor (CHRM3) rs 2165870 polymorphism. We investigated whether the Apfel score and this genetic variation independently contribute to PONV risk and whether prophylaxis reduces PONV in patients with low Apfel score but at high genetic risk. METHODS: In a prospective, controlled study, 454 subjects undergoing elective surgery were genotyped for rs2165870 and its association with PONV was investigated with log-binomial regression analysis. Subjects were randomised to receive acustimulation/dexamethasone, acustimulation/vehicle, sham acustimulation/dexamethasone, or sham acustimulation/vehicle to investigate their effects on PONV risk. RESULTS: Early PONV occurred in 37% of subjects. The rs2165870 genotype distribution was GG in 191, GA in 207, and AA in 56 subjects. The CHRM3 polymorphism was associated with a relative risk (RR) of 1.5 for GA vs GG [95% confidence interval (CI): 1.1-1.9; P=0.003] and 1.6 for AA vs GG (95% CI: 1.1-2.2; P=0.009) genotypes to develop PONV, and this was independent from the Apfel score (RR per Apfel point: 1.3, 95% CI: 1.2-1.5; P<0.0001). While dexamethasone and acustimulation each reduced the PONV risk by 30% in AA genotype carriers with low Apfel score, combined therapy reduced the risk by 86% (P=0.015). CONCLUSIONS: The CHRM3 polymorphism and the Apfel score independently predict PONV susceptibility. Dexamethasone/acustimulation should be considered in patients with low Apfel score but at high genetic risk. CLINICAL TRIAL REGISTRATION: DRKS00005664.

Changes in breathing pattern upon 100% oxygen in children at early school age.

Nitrogen multiple-breath washout (N2MBW) is an increasingly used tidal breathing test in young children to assess ventilation inhomogeneity. However, the test requires 100% oxygen to perform. We aimed to examine the potential influence of pure oxygen on breathing pattern in school-aged children. We performed tidal breathing measurements under room air followed by N2MBW in 16 former preterm children and 24 healthy controls. We compared tidal volume (VT), coefficient of variation of VT (CVVT), respiratory rate (RR), and minute ventilation (VE) between tidal breathing and N2MBW, and between the start and end of tidal breathing. Mean (range) age was 6.8 (5.9, 9.0) years. VT, RR and VE showed no significant change upon oxygen-exposure, while CVVT significantly decreased by 5% (95% CI: 1.2, 9.0; p=0.012). However CVVT was also the only parameter which significantly decreased during tidal breathing. Overall, pure oxygen has no systematic effect on breathing pattern in young school-aged children. N2MBW can reliably be used as tracer gas in this age group.

Moisture damage in home associates with systemic inflammation in children.

This study investigated the association between confirmed moisture damage in homes and systemic subclinical inflammation in children. Home inspections were performed in homes of 291 children at the age of 6 years. Subclinical inflammation at the age of 6 years was assessed by measuring the circulating levels of C-reactive protein (CRP) and leukocytes in peripheral blood and fractional exhaled nitric oxide (FeNO). Proinflammatory cytokines interleukin (IL)-1ß and IL-6 and tumor necrosis factor (TNF)-α were measured in unstimulated, and in phorbol 12-myristate 13-acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG)-stimulated whole blood. Major moisture damage in the child's main living areas (living room, kitchen, or child's bedroom) and moisture damage with mold in the bathroom were associated with increased levels of CRP and stimulated production of several proinflammatory cytokines. There were no significant associations between moisture damage/visible mold and leukocyte or FeNO values. The results suggest that moisture damage or mold in home may be associated with increased systemic subclinical inflammation and proinflammatory cytokine responsiveness.

Asthma and obesity in children: current evidence and potential systems biology approaches.

Both obesity and asthma are highly prevalent, complex diseases modified by multiple factors. Genetic, developmental, lung mechanical, immunological and behavioural factors have all been suggested as playing a causal role between the two entities; however, their complex mechanistic interactions are still poorly understood and evidence of causality in children remains scant. Equally lacking is evidence of effective treatment strategies, despite the fact that imbalances at vulnerable phases in childhood can impact long-term health. This review is targeted at both clinicians frequently faced with the dilemma of how to investigate and treat the obese asthmatic child and researchers interested in the topic. Highlighting the breadth of the spectrum of factors involved, this review collates evidence regarding the investigation and treatment of asthma in obese children, particularly in comparison with current approaches in 'difficult-to-treat' childhood asthma. Finally, the authors propose hypotheses for future research from a systems-based perspective.

The minimally invasive MitraClip™ procedure for mitral regurgitation under general anaesthesia: immediate effects on the pulmonary circulation and right ventricular function.

A relatively new minimally invasive cardiological procedure, called the MitraClip(™), does not require sternotomy and may have a number of advantages compared with open mitral valve surgery, but its acute impact on the pulmonary circulation and right ventricular function during general anaesthesia is unclear. We prospectively assessed the effects of the MitraClip procedure in 81 patients with or without pulmonary hypertension (defined as mean pulmonary artery pressure > 25 mmHg), who were anaesthetised using fentanyl (5 µg.kg(-1)), etomidate (0.2-0.3 mg.kg(-1)), rocuronium (0.5-0.6 mg.kg(-1)) and isoflurane. Placement of the MitraClip led to a 60% increase in mean (SD) right ventricular stroke work index (from 512 (321) to 820 (470) mmHg.ml.m(-2), p < 0.0001), while mean (SD) pulmonary vascular resistance index decreased by 24% (522 (330) to 399 (244) dyn.s.cm(-5), p < 0.0001), and mean (SD) pulmonary artery pressure decreased by 10% (30 (8) to 27 (8) mmHg, p < 0.0001). Patients with pulmonary hypertension experienced a similar decrease in mean pulmonary artery pressure compared with those without, and they also had a slight reduction in mean (SD) pulmonary artery occlusion pressure (22 (6) down to 20 (6) mmHg, p = 0.044). We conclude that successful MitraClip treatment for mitral regurgitation acutely improves right ventricular performance by reducing right ventricular afterload, regardless of whether patients have pre-operative pulmonary hypertension.

Myocardial protection by remote ischaemic pre-conditioning is abolished in sulphonylurea-treated diabetics undergoing coronary revascularisation.

BACKGROUND: Remote ischaemic pre-conditioning attenuates myocardial injury. Because sulphonylurea drugs interfere with ischaemic and anaesthetic pre-conditioning, we assessed whether remote ischaemic pre-conditioning effects are altered in sulphonylurea-treated diabetics. METHODS: Using the database of our ongoing randomised, placebo-controlled study (ClinicalTrials.gov NCT01406678), we assessed the troponin I concentration area under curve (measurements: baseline, 1, 6, 12, 24, 48, and 72 h post-operatively) in sulphonylurea-treated diabetics (n = 27) and non-diabetics (n = 230) without and with remote ischaemic pre-conditioning (three 5-min periods of left upper arm ischaemia with 5-min reperfusion each) during isoflurane anaesthesia before two- to three-vessel coronary artery surgery. RESULTS: Remote ischaemic pre-conditioning in non-diabetic patients evoked a 41% decrease in the troponin I concentration area under curve (514 ng/ml × 72 h ± 600 vs. 302 ± 190, P = 0.001) but no change (404 ng/ml × 72 h ± 224 vs. 471 ± 383, P = 0.62) in sulphonylurea-treated diabetics. There was no significant correlation between the troponin I concentration area under curve and arterial glucose concentrations, and the latter was not an independent confounder. CONCLUSION: Cardioprotection by remote ischaemic pre-conditioning during isoflurane anaesthesia is abolished in sulphonylurea-treated diabetics.

ß2-Adrenoceptor gene variants affect vasopressor requirements in patients after thoracic epidural anaesthesia.

BACKGROUND: While the ß2-adrenoceptor pathway is essential for cardiovascular regulation, the impact of ADRB2 gene variations on circulatory responses is unclear, possibly due to neural compensatory mechanisms. We tested the hypotheses that (i) sympathetic block by thoracic epidural anaesthesia (TEA) unmasks the influence on arterial pressure of genetic variations and (ii) vasopressor requirements during TEA depend on ADRB2 gene variation. METHODS: Ninety-three elective patients undergoing abdominal surgery were included prospectively. After epidural bupivacaine 0.5% (15 mg test dose+50 mg), arterial pressure, heart rate, and progression of sensory block were measured for 20 min in the supine awake state and for 20 min after standardized anaesthetic induction of general anaesthesia. The primary endpoint was cumulative dose of the α-adrenoreceptor agonist phenylephrine administered to sustain a mean arterial pressure >70 mm Hg. The ADRB2 polymorphisms Arg16Gly and Gln27Glu were genotyped using Slowdown-PCR. RESULTS: After TEA, 86 (93%) patients required phenylephrine. The mean dosages (sd) were significantly different between the ADRB2 genotypes [Arg16Arg 357 µg (326), Arg16Gly 776 µg (449), Gly16Gly 600 µg (443), P=0.036; Gln27Gln 356 µg (254), Gln27Glu 639 µg (354), Glu27Glu 577 µg (388), P=0.007]. Multiple linear regression analysis revealed that age, male gender, rostral extent of sensory block, lower arterial pressure before TEA, and ADRB2 Glu27 allele together explained 37% of phenylephrine dosage variation, with genetic variants being the second most important predictor (10%; P<0.001). CONCLUSIONS: The ADRB2 Glu27 allele is an independent predictor of arterial hypotension and vasopressor requirements after TEA. Neural block can unmask genetic influences on neurohumoral regulation. Clinical trial registration DRKS00005260.

The efficacy of a standardised product from dried leaves of Solanum glaucophyllum as source of 1,25-dihydroxycholecalciferol for poultry.

1. Chemical characterisation of an extract of Solanum glaucophyllum (SG) leaves affirmed the predominant presence of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) glycosides. The compound 1-(ß-D-glucopyranosyl)-1α,25-dihydroxycholecalciferol was isolated for the first time from a natural source. 2. Vitamin D activity of the extract was confirmed by the calcaemic properties shown in a quail eggshell bioassay. The results suggested a 1,25(OH)2D3 bioavailability of approximately 15%. 3. A broiler feeding experiment replicated in time was carried out with 6 treatments. A basic control diet containing 25 µg cholecalciferol/kg was supplemented with 2.5 and 5 µg free 1,25(OH)2D3/kg, with a product based on dried SG leaves (Panbonis) providing 10 µg of 1,25(OH)2D3-glycosides/kg, with two concentrations of an SG extract providing 8.8 and 37.8 µg of 1,25(OH)2D3-glycosides/kg. 4. Tibia breaking strength and stiffness were numerically greater in all treatment groups with free 1,25(OH)2D3 and with SG products compared to controls, though the overall treatment effects only had probabilities in the range of P = 0.07 to P = 0.1. Values for both characteristics increased progressively, with additions of synthetic 1,25(OH)2D3; values with the dried SG product were similar to those with 5 µg synthetic 1,25(OH)2D3/kg. 5. Plasma calcium was mildly elevated (P < 0.05) in treatment groups. The SG extract treatment containing 37.8 µg 1,25(OH)2D3/kg gave the highest plasma calcium concentration and lowest bodyweight, signs of marginal hypervitaminosis D. Plasma 1,25(OH)2D3 concentrations were in the normal range for all treatments. 6. Tibial dyschondroplasia occurred in only one replicate. The incidences were 31% in controls but considerably lower or zero with all other treatments. 7. Bioavailability of 1,25(OH)2D3 in the SG product seemed to be higher in broiler chickens than in Japanese quails. 8. It is concluded that the inclusion of the dried SG product as a source of vitamin D3 in broiler diets at a dietary concentration of 1 g/kg, providing 10 µg 1,25(OH)2D3/kg, is safe and efficacious.

Daily exhaled nitric oxide measurements and asthma exacerbations in children.

BACKGROUND: Fractional exhaled Nitric Oxide (FeNO) is a biomarker for eosinophilic airway inflammation and can be measured at home on a daily basis. A short-term increase in FeNO may indicate a higher risk of future asthma exacerbations. OBJECTIVE: To assess changes in FeNO before and after asthma exacerbations compared to a stable control period. METHODS: A post hoc analysis was performed on daily FeNO measurements over 30 weeks in children with asthma (n = 77). Moderate exacerbations were defined by an increase in symptom scores and severe exacerbations by prescription of prednisone. Individual mean and maximum FeNO, the variability of FeNO assessed by the coefficient of variation (CV), and slopes of FeNO in time were all quantified in 3-week blocks. Cross-correlation of FeNO with symptoms and autocorrelation of FeNO were assessed in relation to exacerbations and examined as predictors for exacerbations compared to reference periods using logistic regression. RESULTS: Fractional exhaled nitric oxide could be assessed in relation to 25 moderate and 12 severe exacerbations. The CV, slope, cross-correlation, and autocorrelation of daily FeNO increased before moderate exacerbations. Increases in slope were also randomly seen in 19% of 2-week blocks of children without exacerbations. At least 3-5 FeNO measurements in the 3 weeks before an exacerbation were needed to calculate a slope that could predict moderate exacerbations. No specific pattern of FeNO was seen before severe exacerbations. CONCLUSION: Fractional exhaled nitric oxide monitoring revealed changes in FeNO prior to moderate exacerbations. Whether this can be used to prevent loss of asthma control should be further explored.

Genetic interactions in the ß-adrenoceptor/G-protein signal transduction pathway and survival after coronary artery bypass grafting: a pilot study.

BACKGROUND: In heart failure, ß-adrenergic receptor (ßAR) stimulation desensitizes the receptor, uncouples the downstream Gαs protein, and diminishes signal transduction. We tested the hypotheses that haplotype-tagging single-nucleotide polymorphisms (htSNPs) within the Gαs gene (GNAS) (i) are functionally active and alter Gαs expression, (ii) influence survival after coronary artery bypass grafting (CABG), and (iii) interact with ßAR SNPs. METHODS: Amplification of GNAS intron 1 was followed by cloning, reporter assays, electrophoretic mobility shift assays, and western blots. In a pilot study, 185 patients on ßAR blockade undergoing CABG were studied prospectively. The primary endpoint was cardiac-related mortality at 1 yr. RESULTS: Two htSNPs defined three common haplotypes with altered reporter activity, allele-specific transcription factor binding, and Gαs protein expression (highest in *3 carriers followed by *2 and *1 haplotypes, P=0.013). After CABG, mortality was GNAS diplotype-dependent: *3/*3: 0%; *3/*2: 2.4%; *3/*1: 2.9%; *2/*2: 4.5%; *2/*1: 9.1%; and *1/*1: 20.0% (P=0.004). While ß(1)AR SNPs were not associated with mortality, ß(2)AR Arg16 allele carriers were at higher risk than Gly16 allele carriers (P=0.008). Gene-gene interaction using gene-related risk alleles demonstrated the number of risk alleles to be independently associated with death (hazard ratio 2.3; 95% confidence interval: 1.5-3.5; P=0.0003). Carriers of the no-risk allele had higher maximum isoproterenol-stimulated adenylyl cyclase activities than risk allele carriers (P=0.003). CONCLUSIONS: Interactions in the ßAR/Gαs pathway may be associated with altered mortality after CABG. This could reconcile previously inconclusive data regarding the effects of ßAR SNPs on cardiovascular prognosis.

Transfemoral aortic valve implantation under sedation and monitored anaesthetic care--a feasibility study.

Surgical aortic valve replacement is the conventional treatment for symptomatic aortic valve stenosis; however, the technique of transfemoral transcatheter aortic valve implantation has recently been developed for older patients at high risk for surgery. We assessed whether this procedure could be safely performed under sedation in 100 patients. Their predicted surgical mortality was 21.6% and mean (SD) age 80 (6.6) years. Sedation was provided by remifentanil infusion (0-0.2 µg.kg(-1).min(-1)) and midazolam (1-3 mg), as required. All patients were closely haemodynamically monitored throughout by an anaesthetist and inotropic drugs administered as indicated by invasive monitoring. Sedation alone was required in 83 patients; in 17 patients sedation had to be converted to general anaesthesia, mainly because of interventional complications (n = 12). All conversions to general anaesthesia occurred after successful valve implantation. Mean (SD) anaesthesia time was 31 (12) min and procedural time 107 (77) min; 30-day and 1-year all-cause mortality were 6% and 13%, respectively. In the majority of patients, transcatheter valve implantation can safely be facilitated by sedation, provided monitoring and drug administration are carried out by an experienced cardiac anaesthetist.

Role of the GNAS1 T393C polymorphism in patients with glioblastoma multiforme.

The T393C polymorphism of the GNAS1 locus, which encodes the Gαs protein, has recently been found to be associated with patient outcome in various malignancies. We investigated the association between GNAS1 genotype and survival among patients suffering from glioblastoma multiforme (GBM). One hundred and sixty-two patients with GBM were retrospectively investigated. Inclusion criteria were availability of DNA and, for surviving patients, a follow-up of at least 24 months. The results were analysed based on clinical data, type of surgical intervention, adjuvant therapy, and 2-year survival. At the 2-year follow up, 79.6% of patients had died. Two-year survival rates were as follows: CC-homozygous patients, 15.8%; CT-heterozygous patients, 23.1%; and TT-homozygous patients, 18.2% (p = 0.461). Subgroup analysis revealed different 2-year survival rates in the group that underwent stereotactic biopsy, with 0% for CC-homozygous, 2.8% for CT-heterozygous, and 15.4% survival for TT-homozygous patients, but the differences were not statistically significant (p = 0.229). Our results indicate that there is no association between the GNAS1 T393C polymorphism and 2-year survival among patients with GBM.

Respiratory symptoms in preterm infants: burden of disease in the first year of life.

OBJECTIVE: While respiratory symptoms in the first year of life are relatively well described for term infants, data for preterm infants are scarce. We aimed to describe the burden of respiratory disease in a group of preterm infants with and without bronchopulmonary dysplasia (BPD) and to assess the association of respiratory symptoms with perinatal, genetic and environmental risk factors. METHODS: Single centre birth cohort study: prospective recording of perinatal risk factors and retrospective assessment of respiratory symptoms during the first year of life by standardised questionnaires. MAIN OUTCOME MEASURES: Cough and wheeze (common symptoms), re-hospitalisation and need for inhalation therapy (severe outcomes). PATIENTS: 126 preterms (median gestational age 28.7 weeks; 78 with, 48 without BPD) hospitalised at the University Children's Hospital of Bern, Switzerland 1999-2006. RESULTS: Cough occurred in 80%, wheeze in 44%, re-hospitalisation in 25% and long term inhalation therapy in wheezers in 13% of the preterm infants. Using logistic regression, the main risk factor for common symptoms was frequent contact with other children. Severe outcomes were associated with maximal peak inspiratory pressure, arterial cord blood pH, APGAR- and CRIB-Score. CONCLUSIONS: Cough in preterm infants is as common as in term infants, whereas wheeze, inhalation therapy and re-hospitalisations occur more often. Severe outcomes are associated with perinatal risk factors. Preterm infants who did not qualify for BPD according to latest guidelines also showed a significant burden of respiratory disease in the first year of life.

Normative data for lung function and exhaled nitric oxide in unsedated healthy infants.

Despite association with lung growth and long-term respiratory morbidity, there is a lack of normative lung function data for unsedated infants conforming to latest European Respiratory Society/American Thoracic Society standards. Lung function was measured using an ultrasonic flow meter in 342 unsedated, healthy, term-born infants at a mean ± sd age of 5.1 ± 0.8 weeks during natural sleep according to the latest standards. Tidal breathing flow-volume loops (TBFVL) and exhaled nitric oxide (eNO) measurements were obtained from 100 regular breaths. We aimed for three acceptable measurements for multiple-breath washout and 5-10 acceptable interruption resistance (R(int)) measurements. Acceptable measurements were obtained in ≤ 285 infants with high variability. Mean values were 7.48 mL·kg⁻¹ (95% limits of agreement 4.95-10.0 mL·kg⁻¹) for tidal volume, 14.3 ppb (2.6-26.1 ppb) for eNO, 23.9 mL·kg⁻¹ (16.0-31.8 mL·kg⁻¹) for functional residual capacity, 6.75 (5.63-7.87) for lung clearance index and 3.78 kPa·s·L⁻¹ (1.14-6.42 kPa·s·L⁻¹) for R(int). In males, TBFVL outcomes were associated with anthropometric parameters and in females, with maternal smoking during pregnancy, maternal asthma and Caesarean section. This large normative data set in unsedated infants offers reference values for future research and particularly for studies where sedation may put infants at risk. Furthermore, it highlights the impact of maternal and environmental risk factors on neonatal lung function.

[Tubular ectasia of rete testis: a pitfall in ultrasonographic diagnostics of intratesticular cysts]. / Tubuläre Ektasie des Rete testis : Die Differenzialdiagnose von zystischen Veränderungen im Hoden.

BACKGROUND: Tubular ectasia of the rete testis (TERT) sonographically consists of a cluster of anechoic foci located at the mediastinum testis. TERT is important diagnostically, because it might be confused with malignant teratoma that may likewise contain cystic areas. PATIENTS AND METHODS: Twenty-four patients with TERT were identified sonographically. Ten of these patients underwent additional magnetic resonance imaging (1.5 T), and three had contrast-enhanced scrotal sonography. A descriptive analysis was done regarding clinical details and sizes of the single anechoic foci and of the entire areas involved with cystic changes. RESULTS: The median age of the patients with TERT was 60 years. Diagnosis was based on incidental findings or uncharacteristic symptoms in three quarters of the cases. The size of the single cysts was ≤ 3 mm, 4-6 mm and ≥ 7 mm in 12, 6 and 6 patients, respectively. The size of the entire area involved with cystic changes ranged from 0.5 x 1.2 cm to 2.5 x 3.0 cm. Six patients had TERT bilaterally, and 18 had concomitant spermatoceles. T2-weighted MRI demonstrated high signal intensity of the cystic areas. No signal enhancement was found in these areas after application of contrast agent. Contrast-enhanced sonography did not show uptake in the TERT areas. Histological evidence for dilatation of the rete testis was found in the two patients undergoing diagnostic surgery. CONCLUSIONS: TERT is a benign lesion of the testis that is increasingly detected sonographically. Knowledge of TERT is essential for the urologic sonographer to avoid unwarranted diagnostics and surgery as well as costs.

GNAS1 T393C polymorphism and disease progression in patients with malignant melanoma.

BACKGROUND: Once metastasized, despite a variety of therapeutic options, the prognosis of patients with malignant melanoma (MM) is still poor. Therefore, the search for reliable markers to identify patients with high risk of disease progression is of high clinical importance. We have recently shown that TT genotypes of the single-nucleotide polymorphism (SNP) T393C in the gene GNAS1 are significantly associated with better outcome in a variety of carcinomas. - PATIENTS: In the present study we assessed whether the T393C SNP is also related to the clinical course in MM. 328 patients with MM were retrospectively genotyped and genotypes were correlated with clinical outcome. - RESULTS: While the allele frequency in the MM group (fC 0.52) did not significantly differ from that of healthy blood donors, the T393C SNP was associated with tumor progression of MM. Carriers of the C-allele showed a significantly more severe tumor progression as estimated from the time period to develop metastasis (HR 2.2, 95% CI 1.1-3.2, p = 0.017). Proportions of 5-year metastasis-free intervals were 87.1% for TT genotypes and 66.0% for C-allele carriers. Moreover, multivariable Cox regression analysis including tumor stage and melanoma subtype proved the T393C polymorphism to be an independent factor for metastasis (p = 0.012). - CONCLUSIONS: In summary, the GNAS1 T393C SNP represents a genetic host factor for predicting tumor progression also in patients with MM; genotyping of this SNP may contribute to better define patients who could benefit from an early individualized therapy.

B-flow and color Doppler sonography findings in iatrogenic carotid-jugular arteriovenous fistula.

We describe the case of a 66-year-old woman with an aortic valve reconstruction. Subsequently she presented with an arteriovenous fistula (AVF) between the left common carotid artery and internal jugular vein following several attempts of jugular catheter insertion. Due to aliasing, correct visualization of the fistula track was hindered by conventional color Doppler. However, by using the B-flow imaging technique, the fistula track could be detected without aliasing or overwriting. Duplex examination revealed an AVF between both vessels with an arterialized waveform in the left jugular vein and a high-velocity turbulent flow inside the fistula. Due to these findings we will change our routine scanning protocol for extracranial vessels and will use B-flow in indistinctive or difficult conditions to obtain additional informations.