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The oral cavity is densely populated with microorganisms. As a result, intraoral surgical sites are prone to contamination by pathogens, potentially triggering surgical site infections (SSIs). Prophylactic antibiotics have proven beneficial in reducing the rate of SSIs. However, no consensus has been reached regarding the most effective regimen. The purpose of this study was to investigate two different antibiotic regimens - single-dose and prolonged antibiotic prophylaxis - regarding the rate and severity of postoperative SSIs in patients undergoing orthognathic surgery. Data were analysed retrospectively. Patients who underwent bilateral sagittal split ramus osteotomy or bimaxillary surgery in the study department in 2017 were screened for eligibility. Ninety-nine patients were included in the study and were divided into two groups. The prolonged-antibiotic prophylaxis group (PAP; n = 49) received a 5-day antibiotic prophylaxis regimen, while the single-dose antibiotic prophylaxis group (SDAP; n = 50) received single-dose antibiotic prophylaxis. The groups were assessed for the rate and severity of SSIs following orthognathic surgery. Five patients (10.2%) in the PAP group and seven (14%) in the SDAP group developed infections; no statistically significant difference in the occurrence of SSIs was found (P = 0.380). Single-dose antibiotic prophylaxis is as effective as a 5-day antibiotic prophylaxis regimen in preventing SSIs in orthognathic surgery and is a suitable antibiotic prophylaxis option when considering the risk of antibiotic resistance.

Cloning of the sodium iodide symporter (NIS) 25 years ago has opened an exciting chapter in molecular thyroidology with the characterization of NIS as one of the most powerful theranostic genes and the development of a promising gene therapy strategy based on image-guided selective NIS gene transfer in non-thyroidal tumors followed by application of 131I or alternative radionuclides, such as 188Re and 211At. Over the past two decades, significant progress has been made in the development of the NIS gene therapy concept, from local NIS gene delivery towards promising new applications in disseminated disease, in particular through the use of oncolytic viruses, non-viral polyplexes, and genetically engineered MSCs as highly effective, highly selective and flexible gene delivery vehicles. In addition to allowing the robust therapeutic application of radioiodine in non-thyroid cancer settings, these studies have also been able to take advantage of NIS as a sensitive reporter gene that allows temporal and spatial monitoring of vector biodistribution, replication, and elimination – critically important issues for preclinical development and clinical translation.

Abnormal fast dehydration and rehydration of light- and thermo-dual-responsive copolymer films of poly(oligo(ethylene glycol) methyl ether methacrylate-co-6-(4-phenylazophenoxy)hexyl acrylate), abbreviated as P(OEGMA300-co-PAHA), are triggered by UV radiation. Both rapid kinetic processes are probed by in situ neutron reflectivity (NR). The transition temperatures (TTs) of P(OEGMA300-co-PAHA) are 53.0 (ambient conditions) and 52.5 °C (UV radiation, λ = 365 nm). Thin P(OEGMA300-co-PAHA) films show a random distribution of OEGMA300 and PAHA segments. They swell in a D2O vapor atmosphere at 23 °C (below TT) to a swelling ratio d/das-prep of 1.61 ± 0.01 and exhibit a D2O volume fraction φ(D2O) of 39.3 ± 0.5%. After being exposed to UV radiation for only 60 s, d/das-prep and φ(D2O) significantly decrease to 1.00 ± 0.01 and 13.4 ± 0.5%, respectively. Although the UV-induced trans-cis isomerization of the azobenzene in PAHA induces increased hydrophilicity, the configuration change causes a breaking of the intermolecular hydrogen bonds between OEGMA300 and D2O molecules and unexpected film shrinkage. As compared to thermal stimulus-induced dehydration, the present dehydration rate is 100 times faster. Removal of the UV radiation causes immediate rehydration. After 200 s, d/das-prep and φ(D2O) recover to their hydrated states, which is also 30 times faster than the initial hydration. At 60 °C (above TT), thin P(OEGMA300-co-PAHA) films switch to their collapsed state and are insensitive to UV radiation. Thus, the UV-induced fast dehydration and rehydration depend on the existence of hydrogen bonds.

In organic photovoltaics, bulk heterojunctions (BHJs) of organic semiconductor substances such as conjugated polymers and fullerenes are frequently used as active layers in which light is transform...

Summary Background With increasingly precise radiotherapy and advanced medical imaging, the concept of radiotherapy target volume planning might be redefined with the aim of improving outcomes. We aimed to investigate whether target volume reduction is feasible and effective compared with conventional planning in the context of radical chemoradiotherapy for patients with locally advanced non-small-cell lung cancer. Methods We did a multicentre, open-label, randomised, controlled trial (PET-Plan; ARO-2009-09) in 24 centres in Austria, Germany, and Switzerland. Previously untreated patients (aged older than 18 years) with inoperable locally advanced non-small-cell lung cancer suitable for chemoradiotherapy and an Eastern Cooperative Oncology Group performance status of less than 3 were included. Undergoing 18F-fluorodeoxyglucose (18F-FDG) PET and CT for treatment planning, patients were randomly assigned (1:1) using a random number generator and block sizes between four and six to target volume delineation informed by 18F-FDG PET and CT plus elective nodal irradiation (conventional target group) or target volumes informed by PET alone (18F-FDG PET-based target group). Randomisation was stratified by centre and Union for International Cancer Control stage. In both groups, dose-escalated radiotherapy (60–74 Gy, 2 Gy per fraction) was planned to the respective target volumes and applied with concurrent platinum-based chemotherapy. The primary endpoint was time to locoregional progression from randomisation with the objective to test non-inferiority of 18F-FDG PET-based planning with a prespecified hazard ratio (HR) margin of 1·25. The per-protocol set was included in the primary analysis. The safety set included all patients receiving any study-specific treatment. Patients and study staff were not masked to treatment assignment. This study is registered with ClinicalTrials.gov , NCT00697333 . Findings From May 13, 2009, to Dec 5, 2016, 205 of 311 recruited patients were randomly assigned to the conventional target group (n=99) or the 18F-FDG PET-based target group (n=106; the intention-to-treat set), and 172 patients were treated per protocol (84 patients in the conventional target group and 88 in the 18F-FDG PET-based target group). At a median follow-up of 29 months (IQR 9–54), the risk of locoregional progression in the 18F-FDG PET-based target group was non-inferior to, and in fact lower than, that in the conventional target group in the per-protocol set (14% [95% CI 5–21] vs 29% [17–38] at 1 year; HR 0·57 [95% CI 0·30–1·06]). The risk of locoregional progression in the 18F-FDG PET-based target group was also non-inferior to that in the conventional target group in the intention-to-treat set (17% [95% CI 9–24] vs 30% [20–39] at 1 year; HR 0·64 [95% CI 0·37–1·10]). The most common acute grade 3 or worse toxicity was oesophagitis or dysphagia (16 [16%] of 99 patients in the conventional target group vs 17 [16%] of 105 patients in the 18F-FDG PET-based target group); the most common late toxicities were lung-related (12 [12%] vs 11 [10%]). 20 deaths potentially related to study treatment were reported (seven vs 13). Interpretation 18F-FDG PET-based planning could potentially improve local control and does not seem to increase toxicity in patients with chemoradiotherapy-treated locally advanced non-small-cell lung cancer. Imaging-based target volume reduction in this setting is, therefore, feasible, and could potentially be considered standard of care. The procedures established might also support imaging-based target volume reduction concepts for other tumours. Funding German Cancer Aid (Deutsche Krebshilfe).

OBJECTIVES With the expansion of transcatheter aortic valve replacement (TAVR) into intermediate and low risk, the number of TAVR procedures is bound to rise and along with it the number of cases of infective endocarditis following TAVR (TIE). The aim of this study was to review a multicentre experience of patients undergoing surgical intervention for TIE and to analyse the underlying indications and operative results. METHODS We retrospectively identified and analysed 69 patients who underwent cardiac surgery due to TIE at 9 cardiac surgical departments across Germany. The primary outcome was operative mortality, 6-month and 1-year survival. RESULTS Median age was 78 years (72–81) and 48(69.6%) were male. The median time to surgical aortic valve replacement was 14 months (5–24) after TAVR, with 32 patients (46.4%) being diagnosed with early TIE. Cardiac reoperations were performed in 17% of patients and 33% underwent concomitant mitral valve surgery. The main causative organisms were: Enterococcus faecalis (31.9%), coagulase-negative Staphylococcus spp. (26.1%), Methicillin-sensitive Staphylococcus aureus (15.9%) and viridians group streptococci (14.5%). Extracorporeal life support was required in 2 patients (2.9%) for a median duration of 3 days. Postoperative adverse cerebrovascular events were observed in 13 patients (18.9%). Postoperatively, 9 patients (13.0%) required a pacemaker and 33 patients (47.8%) needed temporary renal replacement therapy. Survival to discharge was 88.4% and survival at 6 months and 1 year was found to be 68% and 53%, respectively. CONCLUSIONS Our results suggest that TIE can be treated according to the guidelines for prosthetic valve endocarditis, namely with early surgery. Surgery for TIE is associated with acceptable morbidity and mortality rates. Surgery should be discussed liberally as a treatment option in patients with TIE by the ‘endocarditis team’ in referral centres.

Three-dimensional midfacial deficiency in cleft patients is common and is frequently connected to impairment of the aesthetic facial appearance. Different approaches to augment relevant facial regions are available. Alloplastic facial implants have been established as a viable alternative to autologous tissue augmentation in various circumstances. However, in cleft patients, the application of facial implants has rarely been reported. This retrospective study aimed to evaluate the use of Medpor implants for midfacial contouring in cleft patients. Fifty-one patients with orofacial clefts were assessed with regard to defined parameters. A range of Paranasal, Malar and Nasal Dorsum Medpor implants had been used. Unilateral cleft lip and palate (UCLP) represented the most common indication, followed by bilateral cleft lip and palate (BCLP). Bilateral implant insertion was performed as a general rule with few exceptions. Insertion of implants was frequently combined with other cleft-related surgical procedures. Even after orthognathic surgery, midfacial augmentation was implemented to specifically address residual volume deficiency, particularly in the malar region. The complication rate amounted to 4.9% (6/122 implants). Based on our findings, Medpor implants are reliable and long-term stable materials to successfully augment paranasal, subnasal and malar areas as well as a solid nasal dorsum material with few complications in cleft patients.

Nerve grafting plays a vital role in facial nerve repair and facial reanimation. It is employed in a variety of surgical concepts to restore or redirect innervation in order to reestablish facial movement. Different donor nerves can be harvested as nerve grafts. The choice is guided by requirements of the surgical approach as well as donor site morbidity. Cross-facial nerve grafting is a unique concept for facial reanimation but is entailed by certain limitations, including a two-stage surgery, long regeneration period, and uncertain outcome. New developments like cadaveric nerve allografts, fibrin adhesives, and pathway protection in cross-face nerve grafts promise ever evolving and improving surgical solutions to facial palsy.

This case report describes authors successfully attempt to perform a topographically correct sural nerve transplantation in the extracranial facial nerve stem using the intraneural facial nerve stem topography proposed by Meissl in 1979. This is the first reported case of successful fascicular nerve grafting of the facial nerve stem following extensive laceration.

Proprotein convertase subtilisin/kexin type 9 inhibition can be an effective treatment in patients with primary hypercholesterolemia, particularly in cases with concomitant coronary heart disease, peripheral artery occlusive disease or cerebrovascular occlusive disease for secondary prevention after an acute atherosclerotic ischemic event. The primary objective of the PEARL-AT study was to assess effectiveness and safety of alirocumab in a real-world setting in Austria. Non-interventional, prospective study conducted across Austria between September 2016 and July 2018. 113 patients, for whom the decision for treatment with alirocumab according to the Austrian Summary of Product Characteristics (SmPC) was made, were enrolled and were followed-up over 24 weeks. The primary endpoint of the study was the average change of low density lipoprotein cholesterol (LDL-C) levels by week 24. In total, 112 patients with at least one post-baseline visit were included. Alirocumab was initiated using 75 mg (57.1%) and 150 mg (42.9%) every two weeks. Average LDL-C levels decreased by 75.0 mg/dl at week 24 in 87 patients with available LDL-C at baseline and week 24 (in 25 patients LDL-C was missing at least at one time point). The mean relative change of LDL-C was −50.0% (median: 57.8%, SD: 28.4). Throughout the study, 46 adverse events were documented in 21 (18.6%) patients. The most frequent adverse events were gastrointestinal disorders. The present data indicate a good overall efficacy of alirocumab in a real-world Austrian population. Effectiveness and safety were both in line with the clinical trial program as well as previous real-world observations.

Background Percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) represents one of the major challenges in interventional cardiology. Physicians are still reluctant in referring for PCI, assuming non viability of the myocardium subtended by the CTO. Data are controversial in assessing the improvement of left ventricular (LV) wall motion after revascularisation and the prognostic value of viability testing to guide patient selection. Purpose The aim of this study was to determine, whether hybrid fluorodeoxyglucose positron emission tomography/magnetic resonance (FDG PET/MR) imaging allows a more accurate prediction of LV regional wall motion recovery after successful PCI of CTOs in comparison to PET or MR alone. Methods We enrolled 49 consecutive symptomatic patients with CTO and evidence of wall motion abnormality in the corresponding CTO-territory. All patients underwent hybrid FDG PET/MR imaging as semi-quantitative assessment of myocardial viability - glucose metabolism in PET and late gadolinium enhancement (LGE) transmurality in MR – prior of PCI of the CTO. Follow-up MRI was performed in 23 patients 3–6 months after successful revascularisation to evaluate wall motion changes. Results We assessed viability in 124 myocardial segments subtended by a CTO in 23 patients with successful PCI who underwent serial imaging. Segments with wall motion abnormality at baseline (n=80) were analysed. Most of these segments (n=54, 68%) were concordantly assessed viable by PET and MR, conversely only 2 (2%) segments were assessed non-viable by both imaging techniques. However, almost one third of the segments showed discordant patterns of viability either PET not viable/ MR viable (3 (4%) segments) or PET viable/ MR not viable (21 (26%) segments): particularly the latter revealed a significant wall motion improvement (p=0.033). The combination of PET and MR showed a fair accuracy in predicting myocardial segments with wall motion improvement after CTO revascularisation (PET/MR area under ROC curve (AUC) 0.72, SE 0.07, p=0.002), which was superior to MR-LGE (AUC=0.66, SE 0.09) and FDG-PET (AUC=0.58, SE 0.10) alone (Figure). Comparisons of ROC curves Conclusion Hybrid PET/MR imaging prior to successful CTO showed a better performance than PET or MR alone in predicting regional improvement of disturbed wall motion. The complimentary information derived from both modalities may particularly help to identify small amounts of viable epicardial myocardium within large scars which can improve contractility after CTO-revascularisation.

Patient dissatisfaction with labial appearance in the adult cleft lip is frequently linked to poor upper lip projection. Other areas of concern include asymmetry and impaired upper lip height. Different surgical techniques are available to address volumetric deficiencies, according to extent and localization. However, data comparing outcomes in these different areas are limited. The main aim of this study was to assess the relative gains in upper lip projection. An evaluation of upper vermilion height and symmetry was also performed. Thirty-seven consecutive patients treated by a single surgeon had their pre- and postoperative results measured using standardized photographs; these were analysed using subjective and objective outcome measures. Seven examiners evaluated anonymized pre- and postoperative side and front views for subjective evaluation. The objective analysis was performed using Adobe Photoshop. Fifteen lip revisions, four Abbe flaps, 12 dermal grafts, and six PermaLip implants were performed. In bilateral cleft lip and palate patients, Abbe flaps showed the most significant improvement in labial projection, followed by PermaLip implants and dermal grafts. In unilateral cleft lip and palate patients, PermaLip implants best addressed impaired lip projection, followed by dermal grafts. Overall, functional lip revisions showed excellent outcomes for upper lip symmetry; however, only minor changes in labial projection were found.

Bei einem Carcinoma-in situ- (CIS-)Rezidiv der Harnblase nach BCG-Instillationstherapie (Bacillus Calmette-Guerin) besteht die Indikation zur radikalen Zystektomie. Im individuellen Heilversuch sollte die Vertraglichkeit und Sicherheit einer Radioimmuninstillationstherapie mit dem Alpha-Strahlerkonjugat 213Bi-anti-EGFR-mAb nach BCG-Versagen bei CIS-Patienten untersucht werden. Neun Patienten wurden bislang therapiert. Nach der Blasenentleerung uber den transurethralen Katheter wurde das Immunkonjugat 213Bi-anti-EGFR-mAb instilliert und fur 120 min belassen. Sechs Wochen nach Instillation wurde in einer Zystoskopie mit Biopsieentnahme die Effektivitat der Therapie uberpruft. Alle Patienten haben die Instillationstherapie sehr gut und ohne Nebenwirkungen vertragen. Bei 3 Patienten wurde nach 6 Wochen kein CIS mehr nachgewiesen, bei 6 Patienten zeigte sich weiterhin Tumor in der Blase. Die Radioimmuntherapie mit 213Bi-anti-EGFR-mAb ist eine vielversprechende Therapieoption fur Patienten mit persistierendem CIS-Nachweis nach erfolgter BCG-Instillationstherapie, die ihre Harnblase erhalten wollen.

Objectives The aim of this study was to determine whether noncoronary measures from cardiac computed tomography (CT) may enhance the prognostic value of this imaging technology. Background When cardiac CT is performed for quantification of coronary artery calcium (CAC) score, information on other cardiac and thoracic structures is available. Methods Participants without known cardiovascular disease from the prospective population based Heinz Nixdorf Recall study underwent noncontrast cardiac CT for CAC score quantification. From CT, epicardial adipose tissue (EAT) volume, left ventricular and left atrial (LA) axial area index, ascending and descending aortic diameters, as well as aortic valve, mitral ring, and thoracic aortic calcification (TAC) were assessed. Incident cardiovascular events included myocardial infarction, stroke, and cardiovascular death. The prognostic value of CT-derived parameters was assessed by Cox regression analysis, receiver operating characteristics, and net reclassification improvement. Results From 3,630 subjects (59 ± 8 years of age, 46% male), 241 (6.6%) developed a cardiovascular event during 9.9 ± 2.6 years of follow-up. In multivariable Cox regression analysis including Framingham Risk Score, CAC (as log[CAC + 1]), and CT parameters, LA index (hazard ratio [HR]: 1.22 [95% confidence interval [CI]: 1.05 to 1.41] per SD; p = 0.010) and EAT volume (HR: 1.15 [95% CI: 1.01 to 1.30] per SD; p = 0.031) were significantly associated with incident events. In addition, presence of TAC showed an elevated event rate (HR: 1.33 [95% CI: 0.97 to 1.81]; p = 0.08), whereas all other CT-derived parameters showed no relevant association. The LA index, EAT volume, and presence of TAC together improved the prediction of events over Framingham Risk Score and CAC in receiver operating characteristics analysis (area under the curve: 0.749 to 0.764; p = 0.011), and let to a significant net reclassification improvement (HR: 38.0%; 95% CI: 25.1% to 50.8%). Conclusion Assessment of LA index, EAT volume, and TAC from non–contrast-enhanced cardiac CT improves the prediction of incident hard cardiovascular events above CAC and established risk factors, indicating that quantification of these noncoronary measures may improve the prognostic value of this imaging technology.

Background: 68 Ga-PSMA-PET-imaging has proven to be a highly sensitive and specific diagnostic element for patients with prostate cancer (PC). Does the standard clinical target volume (CTV) cover the majority of 68 Ga-PSMA-PET detected lymph nodes (LNs) in a primary setting? Methods: 25 out of 159 patients with primary PC who underwent 68 Ga-PSMA-PET-imaging were analyzed in the process of this study. These 25 high-risk patients had a total of 126 LNs with positive 68 Ga-PSMA-ligand uptake. A standard CTV according to the 'Radiation Therapy Oncology Group' consensus was delineated and LNs were judged whether they were in- or outside of this target volume. With a Pearson correlation we additionally evaluated whether the Gleason score, the prostate-specific antigen (PSA) value or the risk according to the Roach formula correlate with a higher chance of LNs being outside of the CTV in uncommon LN locations. Results: 81 (64.3%) of 126 LNs were covered by the CTV with a complete coverag e of all positive LNs inside the respective radiation volume in 11 of 25 patients (44%). LNs that were not covered by the CTV included (para-aortic,) common-iliac, pre-sacral, obturatoric, para-rectal, para-vesical and pre-acetabular locations. In a statistical analysis neither the Gleason score, nor the PSA value, nor the calculated risk with the Roach formula correlated with LNs being inside or outside of the CTV in this patient group. Conclusion: 68 Ga-PSMA-PET-imaging proves to be a valuable asset for patients and physicians for primary diagnosis and treatment planning. In our study, trusting the RTOG consensus for CTV delineation would have led to up to 35.7% of all LNs not to be included in the clinical radiation volume, which might have resulted in insufficient radiation dose coverage.

There is a rapid increase in the percentage of elderly people in Europe. Consequently, the prevalence of age-related diseases will also significantly increase. Therefore, the main goal of MediHealth, an international research project, is to introduce a novel approach for the discovery of active agents of food plants from the Mediterranean diet and other global sources that promote healthy ageing. To achieve this goal, a series of plants from the Mediterranean diet and food plants from other origins are carefully selected and subjected to in silico, cell-based, in vivo (fly and mouse models), and metabolism analyses. Advanced analytical techniques complement the bio-evaluation process for the efficient isolation and identification of the bioactive plant constituents. Furthermore, pharmacological profiling of bioactive natural products, as well as the identification and synthesis of their metabolites, is carried out. Finally, optimization studies are performed in order to proceed to the development of innovative nutraceuticals, dietary supplements or herbal medicinal products. The project is based on an exchange of researchers between nine universities and four companies from European and non-European countries, exploiting the existing complementary multidisciplinary expertise. Herein, the unique and novel approach of this interdisciplinary project is presented. © 2018 by the authors.

A new method for the determination of three different classes of secondary metabolites (flavonoids, iridoids and phenylpropanoids) present in extracts of Lippia alba leaves based on CE is described. The capillary electrophoretic separation of these compounds was possible employing a 50 mM borax buffer containing 75 mM SDS and 5% isopropanol as organic modifier. The analytes could be well resolved in 25 min and accurately determined in different chemotypes of Lippia alba specimens. Method validation assured the compliance of the assay to International Conference on Harmonization standards (ICH) (correlation coefficients ≥0.9944, LOD 23.0–65.0 μg ml−1 and LOQ 38.0–119.0 μg ml−1, recovery rates from 97 to 101%, intermediate precision ≤2.1%, and repeatability ≤5.0%). The proposed method was compared with a previously validated HPLC method using eight samples as well as by statistical means (t-test). In all the samples, T calculated was less than T critical with a significance level of 5%, thus demonstrating that CE is a good alternative for the separation and quantification of polar compounds in plant extracts. © 2018

The first fully integrated combined positron emission tomography-magnetic resonance imaging (PET-MRI) scanners have been clinically available since 2010. Large prospective studies regarding indications and diagnostic accuracy of this new modality are not yet available; however, preliminary studies have shown a higher diagnostic accuracy and confidence compared to PET-computed tomography (PET-CT) in regions where MRI is known to be superior to CT, such as the liver. The benefit of MRI in accurate lesion characterization and the additional value of diffusion-weighted imaging (DWI) as a complementary functional modality by means of the apparent diffusion coefficient (ADC) is apparent in entities with low tracer uptake (e.g. due to small size) and a decreased or absent accumulation pattern on PET.

Despite increasing evidence in favor of prophylactic valganciclovir treatment in kidney transplant recipients for the prevention of cytomegalovirus (CMV) infection, the impact of preemptive vs. prophylactic treatment on long-term clinical outcomes is unclear. In this retrospective study, 187 kidney transplant recipients with serologic intermediate-risk constellation (recipient CMV IgG positive) received either preemptive or prophylactic treatment with valganciclovir. Patient survival (primary endpoint), graft survival, viremia rates, and other CMV-related outcomes were analyzed. Prophylactic therapy reduced the rates for CMV viremia during the first year (hazard ratio: 0.48, 95% confidence interval [CI] 0.30-0.75; p < 0.001). There was a trend for higher three-yr patient mortality in the prophylactic group (hazard ratio: 5.08, 95% CI 0.62-41.3; p = 0.091), and the rate of graft loss was not reduced (hazard ratio: 0.93, 95% CI 0.32-2.68; p = 0.894). Estimated glomerular filtration rate over three yr was on average 6.8 mL/min/1.73 m(2) lower in the prophylactic group (95% CI -11.68 to -1.81; p = 0.007) using a multivariate random effects model but showed more improvement over time. Prophylactic valganciclovir treatment reduced the rate of CMV infections during the first year post-transplant but no effects of prophylactic treatment on patient and graft survival or kidney function over three yr were observed.

Background 68Ga-PSMA-PET-imaging has proven to be a highly sensitive and specific diagnostic element for patients with prostate cancer (PC). Does the standard clinical target volume (CTV) cover the majority of 68Ga-PSMA-PET detected lymph nodes (LNs) in a primary setting? Methods 25 out of 159 patients with primary PC who underwent 68Ga-PSMA-PET-imaging were analyzed in the process of this study. These 25 high-risk patients had a total of 126 LNs with positive 68Ga-PSMA-ligand uptake. A standard CTV according to the ‘Radiation Therapy Oncology Group’ consensus was delineated and LNs were judged whether they were in- or outside of this target volume. With a Pearson correlation we additionally evaluated whether the Gleason score, the prostate-specific antigen (PSA) value or the risk according to the Roach formula correlate with a higher chance of LNs being outside of the CTV in uncommon LN locations. Results 81 (64.3%) of 126 LNs were covered by the CTV with a complete coverage of all positive LNs inside the respective radiation volume in 11 of 25 patients (44%). LNs that were not covered by the CTV included (para-aortic,) common-iliac, pre-sacral, obturatoric, para-rectal, para-vesical and pre-acetabular locations. In a statistical analysis neither the Gleason score, nor the PSA value, nor the calculated risk with the Roach formula correlated with LNs being inside or outside of the CTV in this patient group. Conclusion 68Ga-PSMA-PET-imaging proves to be a valuable asset for patients and physicians for primary diagnosis and treatment planning. In our study, trusting the RTOG consensus for CTV delineation would have led to up to 35.7% of all LNs not to be included in the clinical radiation volume, which might have resulted in insufficient radiation dose coverage.

BACKGROUND AND PURPOSE: Inter- and intratumor heterogeneity and the variable course of disease in patients with glioma motivate the investigation of new prognostic factors to optimize individual treatment. Here we explore the usefulness of standard static and more sophisticated dynamic 18 F-fluoroethyltyrosine-PET imaging for the assessment of patient prognosis. MATERIALS AND METHODS: Thirty-four consecutive patients with untreated, first-diagnosed, histologically proved glioma were included in this retrospective study. All patients underwent dynamic PET scans before surgery (± standard treatment) and were followed up clinically and by MR imaging. Static and dynamic tumor-to-background ratio, TTP, and slope-to-peak were obtained and correlated with progression-free survival. RESULTS: Twenty of 34 patients experienced progression, with a median progression-free survival of 28.0 ± 11.1 months. Dynamic TTP was highly prognostic for recurrent disease, showing a strong correlation with progression-free survival (hazard ratio, 6.050; 95% CI, 2.11–17.37; P P = .044), but not when using established static imaging parameters, such as maximum tumor-to-background ratio and mean tumor-to-background ratio. In the high-grade glioma subgroup, both dynamic and static parameters correlated with progression-free survival. The best results were achieved by defining ROIs around “hot spots” in earlier timeframes, underlining the concept of intratumor heterogeneity. CONCLUSIONS: 18 F-fluoroethyltyrosine-PET can predict recurrence in patients with glioma, with dynamic analysis showing advantages over static imaging, especially in the low-grade subgroup.

Knowledge of the presence and extent of bone infiltration is crucial for planning the resection of potential bone-infiltrating squamous cell carcinomas of the head and neck (HNSCC). Routinely, plain-film radiography, multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) are used for preoperative staging, but they show relatively high rates of false-positive and false-negative findings. Scintigraphy with (99m)Tc-bisphosphonate has the ability to show increased metabolic bone activity. If combined with anatomical imaging (e.g. (SPECT)/CT), it facilitates the precise localization of malignant bone lesions. The aim of this study was to analyse the indications and advantages of SPECT/CT compared with standard imaging modalities and histology with regard to specificity and sensitivityA longitudinally evaluated group of 30 patients with biopsy-proven HNSCC adjacent to the mandible underwent (99m)Tc-bisphosphonate SPECT/CT, MRI, MSCT and conventional radiography before partial or rim resection of the mandible was performed. Bone infiltration was first evaluated with plain films, MSCT and MRI. In a second reading, SPECT/CT data were taken into account. The results (region and certainty of bone invasion) were evaluated among the different imaging modalities and finally compared with histological specimens from surgical resection as the standard of reference. For a better evaluation of the hybrid property of SPECT/CT, a retrospectively evaluated group of 20 additional patients with tumour locations similar to those of the longitudinally examined SPECT/CT group underwent SPECT, MSCT and MRI. To assess the influence of dental foci on the specificity of the imaging modalities, all patients were separated into two subgroups depending on the presence or absence of teeth in the area of potential tumour-bone contact.Histologically proven bone infiltration was found in 17 patients (57 %) when analysed by conventional imaging modalities. SPECT/CT data revealed bone infiltration in two additional patients (7 %), who both showed discrete cortical bone erosion not visible by MSCT or MRI. There were no false-positive or false-negative findings on SPECT/CT. The quality criteria for detecting bone involvement in HNSCC by SPECT/CT were as follows: sensitivity 100 % (lower 95 % confidence interval limit 80 %), specificity 100 % (75 %), positive predictive value 100 % (80 %) and negative predictive value 100 % (75 %). Corresponding data for MRI were 95 % (76 %), 94 % (73 %), 95 % (76 %) and 94 % (73 %), and for MSCT were 89 % (71 %), 100 % (85 %), 100 % (86 %) and 88 % (69 %). In the retrospective evaluation SPECT showed results similar to SPECT/CT.Hybrid SPECT/CT has a high specificity as it can provide additional information about the existence and local extent of malignant bone infiltration of the mandible. Although the sensitivity of conventional SPECT is similar to that of SPECT/CT, the latter provides a much better delineation of the local tumour-bone contact area. Based on this information, surgical intervention of the rim versus partial resection can be planned and performed more precisely. Patient outcome can be improved by avoiding undertreatment and unnecessary or overextended bone resections.

AIM To evaluate the feasibility of T1-weighted (T1W) three-dimensional (3D) fat saturated Cartesian volumetric interpolated breath-hold examination (VIBE) magnetic resonance imaging (MRI) sequence for the diagnosis of aortitis in patients with suspected large vessel vasculitis (LVV) applying fully integrated 2-[18F]-fluoro-2-deoxy- d- glucose (18F-FDG) positron-emission tomography (PET)/MRI. MATERIAL AND METHODS Fourteen patients with aortitis and 14 patients with a negative study for aortitis using 18F-FDG PET as the standard of reference for the evaluation of inflammatory aortic involvement were included retrospectively. All patients were imaged at 3 T using T1W VIBE pre- and post-contrast. Four aortic segments were evaluated for image quality (IQ), diagnostic confidence (DC), and the degree of inflammatory activity (IA) using a Likert scale. Binomial and generalised estimating equation model tests were used to assess the diagnostic performance of T1W VIBE. Cohen's k was applied to test for interobserver reproducibility with respect to IA. Spearman's rank correlation coefficient was calculated to examine correlations between IQ, DC, IA, and PET results. RESULTS On a patient- and segment-based analysis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 85.7% and 59.8%, 100% and 100%, 100% and 100%, 87.5% and 68%, and 92.9% and 82.1%, respectively. IQ and DC were acceptable to good in all examinations and substantial interobserver agreement was observed for IA (Cohen's k = 0.69). IQ and DC as well as IA and 18F-FDG vessel wall uptake were significantly correlated (r=0.763 and 0.679, respectively; p CONCLUSION T1W 3D fat saturated VIBE MRI allows diagnosis of aortitis and may aid in the management of patients with suspected LVV.

A novel 18F-labeled tracer, LMI1195 (N-[3-bromo-4-(3-18F-fluoro-propoxy)-benzyl]-guanidine), is being developed for sympathetic nerve imaging; its high specificity for neural uptake-1 mechanism has previously been demonstrated in cell associative studies and in rabbit and nonhuman primate studies assessing heart uptake. The aim of this study was to investigate the mechanisms of 18F-LMI1195 cardiac uptake in the rat, which is known to contain norepinephrine uptake mechanisms beyond uptake-1. Methods: Tracer accumulation in the heart was studied over time after intravenous administration of 18F-LMI1195 in healthy male Wistar rats by quantitative in vivo PET imaging. The uptake mechanism was assessed by pretreatment with the nonselective norepinephrine uptake-1 and norepinephrine uptake-2 inhibitor phenoxybenzamine (50 mg/kg intravenously; n = 4), the selective norepinephrine uptake-1 inhibitor desipramine (2 mg/kg intravenously; n = 4), or saline control (intravenously; n = 4). Results:18F-LMI1195 produced high and sustained heart uptake allowing clear delineation of the left ventricular wall over 60 min after tracer administration. Pretreatment with phenoxybenzamine markedly reduced the 18F-LMI1195 cardiac uptake when compared with controls. In contrast, there was preserved 18F-LMI1195 uptake after desipramine pretreatment. Conclusion: In rats, cardiac uptake of 18F-LMI1195 was significantly inhibited by phenoxybenzamine but not desipramine, suggesting 18F-LMI1195 is a substrate for the uptake-2 mechanism and is consistent with the rat heart having a dominant level of the mechanism.

ZusammenfassungDiese Leitlinie ist die Kurzfassung der bei der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) publizierten Leitlinie zur Myokard-Perfusions-Szintigraphie. Sie soll eine praxisorientierte Hilfestellung zur Indikation, Durchführung und Auswertung der Myokard-Perfusions-Szintigraphie geben und den aktuellen Stand des Verfahrens darstellen.Nach der Einführung in die Grundlagen folgen konkrete und detaillierte Angaben zur Indikationsstellung, zur Untersuchungsvorbereitung, zu Belastungsverfahren, Radiopharmaka, Akquisitionsprotokollen und -techniken, Strahlenexposition, Datenrekonstruktion sowie zur visuellen und quantitativen Bildanalyse und -interpretation. Zusätzlich werden Fehlerquellen behandelt und Grundelemente des Befundberichtes aufgezeigt.

SummaryThe aim of this study was to determine whether [11C]choline can be used for docetaxel therapy response assessment in a LNCaPprostate cancer xenograft mouse model using [11C]choline small-animal PET/CT. Animals, methods: The androgen-dependent human prostate cancer cell line LNCaP was implanted subcutaneously into the left flanks of 17 SCID-mice, 12.5 mg testosterone platelets were implanted in the neck wrinkle. All mice were injected 4–6 weeks after xenograft implantation with 37 MBq [11C]choline via the tail vein. Dynamic imaging was performed for 60 minutes with a small-animal PET/CT scanner. After the first [11C]choline PET/CT imaging 8 mice were subsequently injected intravenously with docetaxel twice (days 1 and 5) at a dose of 3 mg/kg body weight. 8 mice were treated with PBS as a control. [11C]choline PET/CT imaging was performed on day 7, 14 and 21 after treatment. Image analysis was performed using tumor/ muscle (T/M) ratios (ROIT/ROIM = T/M ratio). Results: All LNCaP tumours could be visualized by [11C]choline PET/CT. Before treatment the mean T/M ratio was 2.0 ± 0.2 in the docetaxel-treated group and 1.9 ± 0.2 in the control group (p = 0.837). There was a reduction in the mean [11C]choline uptake after docetaxel treatment of the tumours of the LNCaP cell line as early as 1 week after initiation of therapy (T/Mmean ratio 1.5 ± 0.2 after one week, 1.3 ± 0.2 after 2 weeks and 1.4 ± 0.2 after 3 weeks). There was no decrease in [11C]choline uptake in the control group. Conclusion: Our results show that [11C]choline has the potential for use in the early monitoring of the therapeutic effect of docetaxel in a LNCaP prostate cancer xenograft animal model.

Background: Computed tomography (CT) allows estimation of coronary artery calcium (CAC) progression. We evaluated several progression algorithms in our unselected, population-based cohort for risk prediction of coronary and cardiovascular events. Methods: In 3281 participants (45–74 years of age), free from cardiovascular disease until the second visit, risk factors, and CTs at baseline (b) and after a mean of 5.1 years (5y) were measured. Hard coronary and cardiovascular events, and total cardiovascular events including revascularization, as well, were recorded during a follow-up time of 7.8±2.2 years after the second CT. The added predictive value of 10 CAC progression algorithms on top of risk factors including baseline CAC was evaluated by using survival analysis, C-statistics, net reclassification improvement, and integrated discrimination index. A subgroup analysis of risk in CAC categories was performed. Results: We observed 85 (2.6%) hard coronary, 161 (4.9%) hard cardiovascular, and 241 (7.3%) total cardiovascular events. Absolute CAC progression was higher with versus without subsequent coronary events (median, 115 [Q1–Q3, 23–360] versus 8 [0–83], P 5y and 5-year risk factors. An excellent prognosis was found for 921 participants with double-zero CAC b =CAC 5y =0 (10-year coronary and hard/total cardiovascular risk: 1.4%, 2.0%, and 2.8%), which was for participants with incident CAC 1.8%, 3.8%, and 6.6%, respectively. When CAC b progressed from 1 to 399 to CAC 5y ≥400, coronary and total cardiovascular risk were nearly 2-fold in comparison with subjects who remained below CAC 5y =400. Participants with CAC b ≥400 had high rates of hard coronary and hard/total cardiovascular events (10-year risk: 12.0%, 13.5%, and 30.9%, respectively). Conclusions: CAC progression is associated with coronary and cardiovascular event rates, but adds only weakly to risk prediction. What counts is the most recent CAC value and risk factor assessment. Therefore, a repeat scan >5 years after the first scan may be of additional value, except when a double-zero CT scan is present or when the subjects are already at high risk.

In failure to respond to bacillus Calmette-Guérin (BCG) in patients with carcinoma in situ (CIS) of the urinary bladder, radical cystectomy remains the mainstay after BCG failure.The aim of this pilot study was to evaluate tolerability and safety of the α‑emitter radioimmunoconjugate instillation in patients after BCG failure.Nine patients were included. After emptying the bladder via a transurethral catheter, Bi-213-anti-EGFR-mAb was instilled. Treatment was terminated by emptying of the radioimmunoconjugate from the bladder 120 min after instillation. Efficacy was evaluated via endoscopy and histology 6 weeks after instillation.All patients showed excellent toleration of the treatment without any side effects. Treatment resulted in complete eradication of tumor cells in 3 patients and persistent tumor detection in the other 6 patients.Intravesical instillation of Bi-213-anti-EGFR-mAb is a promising therapeutic option for treatment of in situ bladder cancer after BCG failure for patients who wish to preserve the bladder.

Purpose Despite recent advances in clinical imaging modalities, differentiation of pancreatic masses remains difficult. Here, we tested the diagnostic accuracy of molecular-based imaging including 3′-deoxy-3′-[18F]fluorothymidine (FLT) positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) PET/CT in patients with suspected pancreatic masses scheduled to undergo surgery.

Prostate cancer is one of the most frequent cancers in men and constitutes the third most common cause of cancer deaths. Early diagnosis of primary prostate cancer, accurate staging, as well as accurate restaging in the case of cancer recurrence after primary treatment, are important for delivering the appropriate therapy. In the last ten years, functional and molecular imaging by means of PET and PET/CT are increasingly being used for such indications. This article provides a radiolabeled tracer-based review of the diagnostic value of PET and PET/CT in primary and recurrent prostate cancer. [18F]FDG, [11C]acetate, [18F]fluoride, and [18F]- and [11C]choline are reviewed in this frame with an emphasis on the radiolabeled choline derivates. PET/CT with radioactively labeled choline derivates is a promising molecular imaging technique for restaging prostate cancer patients with biochemical recurrence after definite primary therapy. However, for the diagnosis of primary prostate cancer, choline PET/CT cannot ...