Showing papers by "Heart and Diabetes Center North Rhine-Westphalia published in 2016"

Nocturnal hypoxaemia is associated with increased mortality in stable heart failure patients.

Abstract: Aim This study investigated the prognostic value of sleep-disordered breathing (SDB) in a large cohort of patients with heart failure with reduced left ventricular function (HF-REF), with focus on the role of nocturnal hypoxaemia. Methods This single-centre prospective cohort study enrolled patients with chronic stable HF-REF (NYHA ≥II) receiving guideline-based treatment. Unattended in-hospital polygraphy was performed to determine the apnoea–hypopnoea index (AHI). Pulse oximetry was used to determine hypoxaemic burden [time with oxygen saturation <90% (T90)], and all-cause mortality was recorded. Results Complete data were available for 963 of 1249 patients. At baseline, 58% of patients had moderate-to-severe SDB. The median follow-up was 7.35 years; 480 of 963 (49.8%) patients died. Mortality rate (per 100 person-years) was 8.1 [95% confidence interval (CI) 7.0–9.4] in patients with no or mild SDB, but 12.2 (95% CI 10.9–13.7) in moderate-to-severe SDB. Apnoea–hypopnoea index was significantly associated with time to death from any cause in a simple Cox model [hazard ratio (HR) 1.011, P < 0.001], but was no longer significant after adjustment for confounding factors (HR 1.005, P = 0.085). T90 was significantly ( P < 0.001) associated with time to death from any cause even after adjustment for confounding factors. The risk of death increased by 16.1% (95% CI 8.6–24.2) per hour of T90. Five-year survival probabilities for patients in T90 quartiles 1, 2, 3, and 4 were 70, 63, 60, and 50%, respectively. Conclusion Hypoxaemic burden was a robust and independent predictor of all-cause mortality in chronic stable HF-REF patients. Whether or not targeting nocturnal hypoxaemia is associated with beneficial effects on mortality in HF-REF patients remains to be determined.

Prevalence and Predictors of Sleep-Disordered Breathing in Patients With Stable Chronic Heart Failure: The SchlaHF Registry

Abstract: Objectives This prospective study investigated the prevalence of sleep-disordered breathing (SDB) and its predictors in patients with stable chronic heart failure (HF). Background SDB is increasingly recognized as being important in patients with HF. Methods The multicenter SchlaHF (Sleep-Disordered Breathing in Heart Failure) registry provides demographic and clinical data on chronic, stable, symptomatic patients with HF (New York Heart Association functional class ≥II; left ventricular rejection fraction ≤45%). Moderate-to-severe SDB (apnea-hypopnea index ≥15/h) was determined by a 2-channel screening device (ApneaLink, ResMed, Sydney, Australia). Results Data from 6,876 patients were analyzed. The prevalence of moderate-to-severe SDB was 46%, with a significant sex difference: 36% in women (n = 1,448) versus 49% in men (n = 5,428). Prevalence of SDB rose with increasing age (31%, 39%, 45%, 52%, and 59% in those age ≤50, >50 to 60, >60 to 70, >70 to 80, and >80 years, respectively). Risk factors for SDB were body mass index (per 5 units; odds ratio [OR]: 1.29; 95% confidence interval [CI]: 1.22 to 1.36), left ventricular rejection fraction (per 5% decrement from 45%; OR: 1.10; 95% CI: 1.06 to 1.14), age (per 10-year difference to 60 years; OR: 1.41; 95% CI: 1.34 to 1.49), atrial fibrillation (OR: 1.19; 95% CI: 1.06 to 1.34), and male sex (OR: 1.90; 95% CI: 1.67 to 2.17). Conclusions SchlaHF registry data demonstrate a high prevalence of SDB in a representative population of stable patients with chronic HF receiving contemporary medical management. Male sex, age, body mass index, and the severity of both symptoms and left ventricular dysfunction were clinical predictors for prevalent SDB. (Prevalence, Clinical Characteristics and Type of Sleep-disordered Breathing in Patients With Chronic, Symptomatic, Systolic Heart Failure; NCT01500759)

Propensity Score: an Alternative Method of Analyzing Treatment Effects.

Abstract: BACKGROUND In intervention trials, only randomization guarantees equal distributions of all known and unknown patient characteristics between an intervention group and a control group and enables causal statements on treatment effects. However, randomized controlled trials have been criticized for insufficient external validity; non-randomized trials are an alternative here, but come with the danger of intervention and control groups differing with respect to known and/or unknown patient characteristics. Non-randomized trials are generally analyzed with multiple regression models, but the so-called propensity score method is now being increasingly used. METHODS The authors present, explain, and illustrate the propensity score method, using a study on coronary artery bypass surgery as an illustrative example. This article is based on publications retrieved by a selective literature earch and on the authors' scientific experience. RESULTS The propensity score (PS) is defined as the probability that a patient will receive the treatment under investigation. In a first step, the PS is estimated from the available data, e.g. in a logistic regression model. In a second step, the actual treatment effect is estimated with the aid of the PS. Four methods are available for this task: PS matching, inverse probability of treatment weighting (IPTW), stratification by PS, and regression adjustment for the PS. CONCLUSION The propensity score method is a good alternative method for the analysis of non-randomized intervention trials, with epistemological advantages over conventional regression modelling. Nonetheless, the propensity score method can only adjust for known confounding factors that have actually been measured. Equal distributions of unknown confounding factors can be achieved only in randomized controlled trials.

Frequency, Phenotypic Characteristics and Progression of Atrophy Associated With a Diseased Bruch's Membrane in Pseudoxanthoma Elasticum.

Abstract: PURPOSE To characterize atrophy of the outer retina and the retinal pigment epithelium in patients with pseudoxanthoma elasticum (PXE). METHODS In this retrospective cross-sectional study, the frequency and phenotypic characteristics of manifest atrophy were investigated in 276 eyes of 139 patients using color fundus photography, fundus autofluorescence (AF) imaging, and spectral domain optical coherence tomography. Progression rates of atrophy were quantified in eyes with longitudinal AF recordings. RESULTS Atrophy was present in 90 eyes (32%; mean age, 60; range, 32-88 years). In 19 eyes (7%; mean age, 56; range, 37-77 years) atrophy occurred without any signs for an active or fibrotic choroidal neovascularization (CNV). The frequency of both, atrophy and CNV, increased with age. In those > 60 years of age, atrophy and/or CNV were almost universally present but varied considerably in severity. Eyes with emerging pure atrophy (n = 13, no signs of CNV) showed pattern dystrophy-like changes (100%), reticular pseudodrusen (82%), and reduced choroidal thickness. Advanced atrophy was multifocal, reached beyond the arcades, and was present nasal to the optic disc. The average expansion rate of atrophy was 3.3 ± 1.3 and 1.6 ± 1.1 mm2/year (mean ± SD), in those without or with signs for CNV, respectively. CONCLUSIONS Atrophy of the outer retina and the retinal pigment epithelium is a common finding in PXE patients characterized by early onset and fast progression with subsequent visual loss independent from CNV. This suggests that atrophy is the natural endpoint of Bruch's membrane disease. Phenotypic similarities with multifactorial geographic atrophy in age-related macular degeneration suggest common pathogenic pathways at the level of Bruch's membrane.

Prevalence of Sleep-Disordered Breathing and Patient Characteristics in a Coronary Artery Disease Cohort Undergoing Cardiovascular Rehabilitation.

Abstract: Purpose Coronary artery disease (CAD) is a leading cause of death and identification of risk factors for CAD is crucial. One such potential risk factor is sleep-disordered breathing (SDB). This prospective cohort study investigated the prevalence of SDB and determined risk factors for the presence of SDB in a large CAD cohort undergoing cardiac rehabilitation. Methods A total of 1425 patients with confirmed CAD starting rehabilitation were screened for SDB using cardiorespiratory polygraphy (n = 921) or polygraphy plus pulse oximetry (n = 484). Results A total of 1408 patients were included; 69.5% were male, 78% had acute coronary syndrome, and 22% had stable CAD. The prevalence of SDB (apnea-hypopnea index [AHI] ≥5/h) was 83%. Moderate to severe SDB (AHI ≥15/h) was present in 53%. Up to 70% of coronary artery bypass graft (CABG) recipients had an AHI ≥15/h versus 33% of those who had not undergone CABG. SDB severity did not vary significantly in patients with stable CAD or on the basis of left ventricular ejection fraction. SDB was more severe and the frequency of oxygen desaturation was higher in men than in women. Multivariate logistic regression identified age, sex, body mass index, and CABG as independent risk factors for severe SDB. Conclusion SDB is a highly prevalent comorbidity in patients with CAD, particularly those who have undergone CABG. These results strengthen existing associations and emphasize the importance of diagnosing and monitoring SDB in patients with CAD entering a cardiac rehabilitation program. Early diagnosis and intervention has the potential to have a beneficial effect on CAD prognosis.

Eisenmenger syndrome and long-term survival in patients with Down syndrome and congenital heart disease

Abstract: Objective To characterise patients with trisomy 21 (Down syndrome, DS) based on the data of the German National Register for Congenital Heart Defects, to identify changes in the availability of surgical therapy over time and to analyse the impact of these changes on developing Eisenmenger syndrome (ES) as well as survival. Methods Out of 1549 patients with DS with congenital heart disease in the National Register for Congenital Heart Defects, 894 patients (55% female, mean age 17.5 years) had a post-tricuspid shunt lesion (atrioventricular septal defect 69.5%, ventricular septal defect 27.7%, patent arterial duct 2.6%) and were included in the current study. Results The likelihood of being treated interventionally or surgically before the age of 1 year increased significantly over time. In parallel, the likelihood of developing ES decreased over time (53% birth cohort during 1950s/1960s vs 0.5% birth cohort during 2000–2009, p Conclusions The availability of surgical correction was associated with a decrease in the likelihood of developing ES. Patients with DS still have reduced survival prospects compared with the general population, but this effect is largely driven by patients developing ES who still have a very poor prognosis.

Cardioversion of atrial fibrillation or atrial flutter into sinus rhythm reduces nocturnal central respiratory events and unmasks obstructive sleep apnoea.

Abstract: Aims Sleep-disordered breathing (SDB), in particular obstructive sleep apnoea, is associated with an increased risk of onset or recurrence of atrial fibrillation (AF) and atrial flutter. This prospective study investigated the relationship between restoration of sinus rhythm and SDB in patients with AF or atrial flutter.

The JUPITER registry: 1-year results of transapical aortic valve implantation using a second-generation transcatheter heart valve in patients with aortic stenosis

Abstract: Objectives Transcatheter aortic valve replacement (TAVR) is an established therapy for patients with aortic stenosis (AS) at high surgical risk. The JenaValve™ is a second-generation, self-expanding transcatheter heart valve (THV), implanted through transapical access (TA). During stent deployment, a specific 'clipping-mechanism' engages native aortic valve cusps for fixation. We present 1-year outcomes of the JUPITER registry, a post-market registry of the JenaValve for TA-TAVR. Methods The JUPITER registry is a prospective, multicentre, uncontrolled and observational European study to evaluate the long-term safety and effectiveness of the Conformite Europeenne-marked JenaValve THV. A total of 180 patients with AS were enrolled between 2012 and 2014. End-points were adjudicated in accordance with the valve academic research consortium document no. 1 definitions. Results The mean age was 80.4 ± 5.9 years and the mean logistic European system for cardiac operative risk evaluation I 21.2 ± 14.7%. The procedure was successful in 95.0% (171/180), implantation of a second THV (valve-in-valve) was performed in 2.2% (4/180) and conversion to surgical aortic valve replacement (SAVR) was necessary in 2.8% (5/180). No annular rupture or coronary ostia obstruction occurred. Two patients required SAVR after the day of index procedure (1.1%). All-cause mortality at 30 days was 11.1% (20/180), being cardiovascular in 7.2% (13/180). A major stroke occurred in 1.1% (2/180) at 30 days, no additional major strokes were observed during 1 year. All-cause mortality after 30 days was 13.1% (21/160) and combined efficacy at 1 year was 80.8% (122/151). At 1-year follow-up, no patient presented with more than moderate paravalvular leakage, while 2 patients (3.2%) showed moderate, 12 (19.0%) mild and 49 (82.4%) trace/none paravalvular regurgitation. Conclusions In a high-risk cohort of patients undergoing TA-TAVR for AS, the use of the JenaValve THV is safe and effective. In patients at higher risk for coronary ostia obstruction, annular rupture or with limited aortic valve calcification, the JenaValve might be preferable for implantation due to its clipping-mechanism engaging native aortic valve cusps for fixation with reduced radial forces of the self-expanding stent.

Systemic Thrombolysis Versus Device Exchange for Pump Thrombosis Management: A Single-Center Experience.

Abstract: In patients with left ventricular assist device (LVAD) implants, pump thrombosis is a potential life-threatening complication. In a retrospective data analysis, we compared clinical outcomes in 50 patients with HeartWare (HW) or HeartMate II implants undergoing device exchange (DEx; n = 21) or systemic thrombolysis (STL; n = 29) for pump thrombosis. Primary end-point was survival up to 90 days postintervention. Secondary end-points were the need for blood products postintervention, duration of intensive care unit stay, in-hospital stay, 90 day and 2 year therapy failure (the need for additional surgical or nonsurgical intervention because of pump thrombosis), and 2 year survival. Ninety-day survival was 89.3% in the STL group and 91.0% in the DEx group (p = 0.901). Compared with the DEx group, the average use of different blood products was lower (p < 0.001), and duration of intensive care unit stay and in-hospital stay tended to be shorter in the STL group (p values = 0.086 and 0.048, respectively). However, 90 day freedom from therapy failure was significantly lower in the STL group than in the DEx exchange group (p = 0.027) and so was 2 year freedom from therapy failure (p = 0.006). Two-year survival was comparable between groups (p = 0.267). Our data indicate that STL can be considered as a therapeutic option in LVAD patients with pump thrombosis.

Cytochrome P450 17A1 inhibitor abiraterone attenuates cellular growth of prostate cancer cells independently from androgen receptor signaling by modulation of oncogenic and apoptotic pathways

Abstract: Abiraterone provides significant survival advantages in prostate cancer (PC), however, the current understanding of the molecular mechanisms of abiraterone is still limited. Therefore, the abiraterone impact on androgen receptor (AR)-positive LNCaP and AR-negative PC-3 cells was assessed by cellular and molecular analyses. The present study demonstrated, that abiraterone treatment significantly decreased cell growth, AR expression, and AR activity of AR-positive LNCaP cells. Notably, AR-negative PC-3 cells exhibited comparable reductions in cellular proliferation, associated with DNA fragmentation and pro-apoptotic modulation of p21, caspase-3, survivin, and transforming growth factor β (TGFβ). Our observations suggest that the attenuation of AR signaling is not the only rationale to explain the abiraterone anticancer activity. Abiraterone efficacy may play a more global role in PC progression control than originally hypothesized. In this regard, abiraterone is not only a promising drug for treatment of AR-negative PC stages, even more, abiraterone may represent an alternative for treatment of other malignancies besides prostate cancer.

Nuclear cardiology practice and associated radiation doses in Europe: results of the IAEA Nuclear Cardiology Protocols Study (INCAPS) for the 27 European countries

Abstract: Purpose Nuclear cardiology is widely used to diagnose coronary artery disease and to guide patient management, but data on current practices, radiation dose-related best practices, and radiation doses are scarce. To address these issues, the IAEA conducted a worldwide study of nuclear cardiology practice. We present the European subanalysis.

Circulating 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Concentrations and Postoperative Infections in Cardiac Surgical Patients: The CALCITOP-Study.

Abstract: Background Vitamin D has immunomodulatory properties and seems to reduce the risk of infections. Whether low vitamin D concentrations are independent risk factors for nosocomial postoperative infections in surgical patients remains to be studied in detail. Methods In 3,340 consecutive cardiac surgical patients, we investigated the association of circulating 25-hydroxyvitamin D (25OHD; indicator of nutritional vitamin D status) and 1,25-dihydroxyvitamin D (1,25[OH]2D; active vitamin D hormone) with nosocomicial infections. The primary endpoint was a composite of thoracic wound infection, sepsis, and broncho-pulmonary infection. Vitamin D status was measured on the last preoperative day. Infections were assessed until discharge. Logistic regression analysis was used to examine the association between vitamin D metabolite concentrations and the composite endpoint. Results The primary endpoint was reached by 5.6% (n = 186). In patients who reached and did not reach the endpoint, in-hospital mortality was 13.4% and 1.5%, respectively (P 81.0 pmol/l), the multivariable–adjusted odds ratio of infection was 2.57 (95%CI:1.47–4.49) for the lowest 1,25(OH)2D quintile (<31.5 pmol/l) and 1.85 (95%CI:1.05–3.25) for the second lowest quintile (31.5–49.0 pmol/l). There was no significant association between 25OHD concentrations and the primary endpoint. Conclusions Our data indicate an independent association of low 1,25(OH)2D levels with the risk of postoperative infections in cardiac surgical patients. Future studies should pay more attention on the clinical relevance of circulating 1,25(OH)2D and its regulation.

Measurement of Circulating 1,25-Dihydroxyvitamin D: Comparison of an Automated Method with a Liquid Chromatography Tandem Mass Spectrometry Method

Abstract: Background. The clinical relevance of circulating 1,25-dihydroxyvitamin D (1,25(OH)2D) is probably underappreciated, but variations in the measurement of this difficult analyte between different methods limit comparison of results. Methods. In 129 clinical samples, we compared a new automated assay with a commercially available liquid chromatography tandem mass spectrometry (LC-MS/MS) kit. Results. Median (interquartile range) 1,25(OH)2D concentrations with the automated assay and the LC-MS/MS method were 26.6 pg/mL (18.5–39.0 pg/mL) and 23.6 pg/mL (16.1–31.3 pg/mL), respectively ( ). Using the method-specific cut-offs for deficient 1,25(OH)2D levels (<20 pg/mL for the automated assay and <17 pg/mL for the LC-MS/MS method), the percentage of patients classified as 1,25(OH)2D deficient was 28.7% and 27.1%, respectively. However, concordance between the two methods for deficient levels was only 62% and the concordance correlation coefficient was poor (0.534). The regression equation resulted in an intercept of −1.99 (95% CI: −7.33–1.31) and a slope of 1.27 (95% CI: 1.04–1.52) for the automated assay. The mean bias with respect to the mean of the two methods was −3.8 (1.96 SD: −28.3–20.8) pg/mL for the LC-MS/MS method minus the automated assay. Conclusions. The two methods show only modest correlation and further standardization is required to improve reliability and comparability of 1,25(OH)2D test procedures.

Vitamin D metabolites and fibroblast growth factor-23 in patients with left ventricular assist device implants: association with stroke and mortality risk.

Abstract: Stroke and mortality risk in patients with left ventricular assist device (LVAD) implants continue to be high. Whether nonclassical cardiovascular risk markers such as vitamin D metabolites and fibroblast growth factor (FGF)-23 contribute to this risk remains to be studied, and this was the objective of our work. In 154 LVAD patients (91 HeartWare and 63 HeartMate II implants), we measured circulating 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), parathyroid hormone (PTH) and FGF-23 shortly before LVAD implantation and investigated their association with stroke and mortality risk during 1-year follow-up. Of the study cohort, 34.4 and 92.2 %, respectively, had deficient 25OHD ( 6.7 pmol/l) and FGF-23 values above the reference range (100 RU/ml). One-year freedom from stroke was 80.9 %, and 1-year survival was 64.3 %. The multivariable-adjusted hazard ratio of stroke was 2.44 (95 % CI: 1.09–5.45; P = 0.03) for the subgroup of 25OHD levels <25 nmol/l (reference group: 25OHD levels ≥25 nmol/l). The multivariable-adjusted hazard ratio of 1-year mortality was 2.78 (95 % CI: 1.52–5.09; P = 0.001) for patients with 25OHD levels <25 nmol/l compared with patients with 25OHD levels ≥25 nmol/l. PTH, FGF-23 and 1,25(OH)2D3 were not associated with stroke or mortality risk. In LVAD patients, deficient 25OHD levels are independently associated with high stroke and mortality risk. If confirmed in randomized controlled trials, preoperative correction of deficient vitamin D status could be a promising measure to reduce stroke and mortality risk in LVAD patients.

Calciotropic and phosphaturic hormones in heart failure.

Abstract: Aims Despite adherence to evidence-based guidelines, heart failure [HF] still results in 5-year mortality rates of 50%, indicating a need to implement additional preventive/intervention strategies. This review summarizes data on alterations in the calciotropic and phosphaturic hormones 1,25-dihydroxyvitamin D [1,25(OH) 2 D] and fibroblast growth factors-23 [FGF-23] in HF and discusses non-pharmacological measures for targeting these hormones. Data synthesis The role of 1,25(OH) 2 D in the regulation of calcium and phosphate homeostasis is central. 1,25(OH) 2 D also plays a pivotal role in cardiac function, but is downregulated by FGF-23. There is accumulating evidence from epidemiological data that HF is associated with decreased circulating 1,25(OH) 2 D and elevated FGF-23 levels. In patients with failing hearts, very low 1,25(OH) 2 D and extremely high FGF-23 levels have been reported. Experimental data support the assumption that vitamin D deficiency and high serum phosphate/FGF-23 levels increase the risk of HF. This review provides a hypothesis of how vitamin D deficiency, high calcium/phosphorus intake, physical inactivity, and age-related renal impairment may all contribute to HF by adversely affecting calcium- and phosphate-regulating hormones. Several case series in infants and a meta-analysis of randomized controlled trials in adults have already reported successful treatment of or a significant risk reduction in HF by vitamin D supplements. The association of calcium/phosphorus intake, physical activity, or renal function with calciotropic/phosphaturic hormones and HF is however less well documented. Conclusions More attention should be paid in future to the association of circulating 1,25(OH) 2 D and FGF-23 levels with HF and to (non-pharmacological) measures for targeting these calciotropic/phosphaturic hormones.

Acute improvement of pulmonary hemodynamics does not alleviate Cheyne-Stokes respiration in chronic heart failure—a randomized, controlled, double-blind, crossover trial

Abstract: This randomized, controlled trial aimed to investigate whether acute improvement of pulmonary congestion would reduce the severity of Cheyne-Stokes respiration (CSR) in patients with chronic heart failure (CHF). Twenty-one consecutive patients with CHF and CSR (apnea-hypopnea index [AHI] ≥15/h) underwent right heart catheterization with titration of intravenous (IV) glyceryltrinitrate (GTN) to a maximum tolerable dosage and inhalation of iloprost 10 μg/mL after a washout phase. Maximum tolerable dosages of GTN and iloprost were randomly applied during full cardiorespiratory polysomnography within two split-night procedures and compared with IV or inhaled sodium chloride (NaCl) 0.9 %, respectively. GTN (6.2 ± 1.5 mg/h) and iloprost significantly lowered \mean pulmonary artery pressure (20.1 ± 9.0 to 11.6 ± 4.2 mmHg, p < 0.001 and 16.9 ± 7.9 to 14.2 ± 6.4 mmHg, p < 0.01, respectively). Pulmonary capillary wedge pressure was only reduced by GTN (14.0 ± 5.6 to 7.2 ± 3.9 mmHg, p < 0.001), and there was no significant change in the cardiac index. Sleep studies revealed no significant improvement in markers of CSR severity, including AHI, central apnea index, and CSR cycle length following GTN or iloprost treatment. Significant decreases in blood pressure, mean oxygen saturation, and S3 sleep were documented during GTN infusion. Acute improvement of pulmonary congestion by GTN had no immediate impact on CSR severity. Future investigations must therefore include longer treatment periods and treatment regimens that have positive, rather than negative, additional effects on peripheral and central chemoreceptors and sleep structure. German Clinical Trial Registry-ID:DRKS00000467 ( www.germanctr.de )

Outcome of fetuses with gastroschisis after modification of prenatal management strategies : Prenatal management and outcome of gastroschisis.

Abstract: Purpose To improve the outcome of fetuses with gastrochisis several studies evaluated prenatal predictors. But there are different guidelines established and therefore the prenatal care is not standardized. With our study we wanted to evaluate the outcome of fetuses with gastroschisis after modification of prenatal management strategies at the Department of Obstetrics and Gynecology of the University Hospital Munster.

Update Reference Charts: Fetal Biometry between the 15th and 20th Week of Gestation

Abstract: Objective: The aim of this study was to derive reference charts between the 15th and 20th week of gestation for biparietal diameter (BPD), occipito-frontal diamet

New Diagnostic Strategies in Infection Safety: The (R)evolution?

Abstract: Infection safety of blood components is still a major topic in transfusion medicine. In the last decades the worldwide routine implementation of nucleic acid amplification techniques (NAT) has led to the prevention of several transfusion-transmitted infections. The main emphasis was placed on the Big Three: hepatitis C virus (HCV), human immunodeficiency virus (HIV), and hepatitis B virus (HBV). In addition, further targets were tested (e.g. hepatitis A virus (HAV), parvovirus B19 (B19V)) due to the requirements of the plasma fractionation industry or, in the case of West-Nile virus (WNV) or hepatitis E virus (HEV), due to new risk assessments. In 1997, the German blood centers were global forerunners in the introduction of viral NAT screening [1]. Despite the cost and logistical challenges to blood banks, NAT testing was implemented in a voluntary, later mandated manner. The molecular genetic techniques evolved from manually to fully automated performed steps, including sample pooling, nucleic acid extraction, amplification of specific targets, and detection. Today, terms like hands-on time, walk-away time, time to result, and high throughput are in the front line when thinking about NAT screening in blood centers. At present, previously known problems with PCR contamination using open systems have almost become unknown in practice. Standardization of NAT enables comparison and rating of NAT assays regarding specificity, sensitivity, and robustness [2]. Today, the focus is set on quality assurance, maximal automation, and consolidation regarding personal and material resources. In the present issue of Transfusion Medicine and Hemotherapy, two blood screening platforms are presented that fulfil the requirements of modern NAT screening. Heim [3] reports the results of the evaluation of the Procleix Ultrio Elite Assay and the Panther system (Grifols) for individual NAT screening of blood, hematopoietic stem cell, tissue and organ donors. Furthermore, other highly automated NAT testing systems, like the autoX 2.0 (GFE Blut), are used for high-throughput blood donation testing. The launching of the new all-in-one NAT testing platform, called Poet, is imminent. In 2015, the new challenge for the German blood centers was the decision made by the Paul Ehrlich Institute (PEI) that all blood components must be tested by HIV-1 NAT systems that are able to exclude or compensate for the potential underestimation or non-recognition of the respective target region [4]. A potential approach could be an NAT test with two different target regions (dual-target NAT). De Zolt et al. [5] present an assay design of a HIV-1 triple-target NAT and routine testing of more than 3.5 million German blood donations. The appearance of HIV-1 variants shows once again that not even all problems of blood safety have been solved. Apart from the ‘old friends’ HIV-1, HCV, and HBV, the emerging pathogens are especially an ongoing challenge and motivation for the development of new testing strategies and/or assays. The current focus of health authorities, with the World Health Organization (WHO) at the forefront, is on arthropod-borne viruses (arbovirus) like Zika virus, Chikungunya virus, Dengue virus, and last but not least the WNV. Considerable risk of transfusion transmission of arboviruses exists due to short periods of asymptomatic viremia in populations with variable and sometimes extremely high incidence of arboviral infections. Apart from the WNV, few arbovirus transfusion transmissions have been proven, mostly due to difficulties in ruling out vector-borne transmission in recipients with arbovirus disease [6]. Pisani et al. [7] review the current situation of the WNV in Europe, focusing on Italy, an endemic region for this virus. Besides the emerging viral threats and, of course, the bacterial contamination risks of platelets and other cell components, the protozoan parasites must not be forgotten regarding blood safety. Currently, this is a minor problem for European blood centers, but due to globalization, transport of goods and travel activity of blood donors, this topic also has to be considered, and risk assessment has to be performed. In the case of the malaria pathogen Plasmodium spec., blood donors have to be tested for Plasmodium antibodies after residence in or visits to endemic regions. In Switzerland, the local blood centers are confronted with increasing international migration and travel from Latin America to Europe. Central and South America are endemic regions for several tropical diseases, e.g. the Chagas disease, a zoonosis also known as American trypanosomiasis, which is a potentially life-threatening infection caused by the hemoflagellate protozoan Trypanosoma cruzi. In the absence of its vector, blood-sucking triatomine bugs, one of the potential modes of transmission of Chagas disease in non-endemic regions is through blood and blood products [8]. Experience with selective testing of at-risk blood donors for Trypanosoma cruzi and Plasmodium spp. in Switzerland is presented by Niederhauser et al. [9]. Altogether, this issue of Transfusion Medicine and Hemotherapy provides an insight into new developments in NAT screening of blood donations, focusing on novel targets and full automation of testing, leading to the further improvement of blood safety.

The effect of beta blocker withdrawal on myocardial SPECT modeled from adenosine 13N-ammonia PET

Abstract: Aim: The effect of beta blockers (BB) on myocardial imaging has been studied in several SPECT and PET studies with divergent results concerning perfusion and impact on diagnostic accuracy. The present study evaluated the effect of BB withdrawal on virtual SPECT studies modeled from quantitative PET perfusion scans. Patients, methods: Data from 20 CAD patients scheduled for adenosine 13N-ammonia imaging with and without BB were considered. Modeling the uptake characteristics of 99mTc-MIBI, all parametric stress PET polarmaps were transferred to virtual 20-segment SPECT polarmaps. The SPECT studies were categorized with a 5-point score and read to assess the effect of the BB withdrawal on scan result and interpretation. Results: The SPECT analysis revealed a mean score of 6.0 ± 4.7 with, and of 5.9 ± 4.5 without BB (p = 0.84). In 260 (74.9%) segments the scores were equal in both conditions. Without BB a downstaging was recorded in 44 segments (12.7%), an upstaging in 43 segments (12.4%). An essentially different interpretation (shift from medical therapy recommendation to angiography) was recorded in one patient. In six cases the interpretation differed mildly. Conclusion: In the majority of patients studied, scan results and interpretation remain unchanged after discontinuation of the BB. Nevertheless, the segmental scan results are not uniformly affected. The recommendation to stop BBs prior to stress testing in order to ensure the highest MBF remains advisable. If temporary BB withdrawal is unfeasible due to contraindications, a tight clinical schedule, or because a patient forgot to withhold the BB, it is appropriate to perform adenosine stress testing according to the results of this study.