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Purpose Prostate-specific membrane antigen (PSMA)-targeted PET is increasingly used for staging prostate cancer (PCa) with high accuracy to detect significant PCa (sigPCa). [68 Ga]PSMA-11 PET/MRI-guided biopsy showed promising results but also persisting limitation of sampling error, due to impaired image fusion. We aimed to assess the possibility of intraoperative quantification of [18F]PSMA-1007 PET/CT uptake in core biopsies as an instant confirmation for accurate lesion sampling. Methods In this IRB-approved, prospective, proof-of-concept study, we included five consecutive patients with suspected PCa. All underwent [18F]PSMA-1007 PET/CT scans followed by immediate PET/CT-guided and saturation template biopsy (3.1 ± 0.3 h after PET). The activity in biopsy cores was measured as counts per minute (cpm) in a gamma spectrometer. Pearson’s test was used to correlate counts with histopathology (WHO/ISUP), tumor length, and membranous PSMA expression on immunohistochemistry (IHC). Results In 43 of 113 needles, PCa was present. The mean cpm was overall significantly higher in needles with PCa (263 ± 396 cpm) compared to needles without PCa (73 ± 44 cpm, p max 8.7), 13 out of 24 needles had increased counts (100–200 cpm) but only signs of inflammation and PSMA expression in benign glands on IHC. Excluding this case, ROC analysis resulted in an AUC of 0.81, with an optimal cut-off to confirm PCa at 75 cpm (sens/spec of 65.1%/87%). In all 4 patients with PCa, the first or second PSMA PET-guided needle was positive for sigPCa with high counts (156–2079 cpm). Conclusions [18F]PSMA-1007 uptake in PCa can be used to confirm accurate lesion sampling of the dominant tumor intraoperatively. This technique could improve confidence in imaging-based biopsy guidance and reduce the need for saturation biopsy. Trial registration number NCT03187990, 15/06/2017.

Eine junge Patientin prasentiert sich mit Palpitationen. Bei der Abklarung fallen im Langzeit-EKG gehaufte ventrikulare Extrasystolen (VES) auf, echokardiographisch eine hochgradige Mitralklappeninsuffizienz mit Mitralklappenprolaps. Es wurde daher eine Mitralklappenoperation geplant, nach weiterem diagnostischen Work-up der Patientin wurde jedoch eine andere Therapie durchgefuhrt, die sich retrospektiv als hocheffizient darstellt.

Both acute myocardial infarction complicated by ventricular tachyarrhythmias (AMI–VTA) and electrical storm (ES) represent life-threatening clinical conditions. However, a direct comparison of both sub-groups regarding prognostic endpoints has never been investigated. All consecutive implantable cardioverter-defibrillator (ICD) recipients were included retrospectively from 2002 to 2016. Patients with ES apart from AMI (ES) were compared to patients with AMI accompanied by ventricular tachyarrhythmias (AMI–VTA). The primary endpoint was all-cause mortality at 3 years, secondary endpoints were in-hospital mortality, rehospitalization rates and major adverse cardiac event (MACE) at 3 years. A total of 198 consecutive ICD recipients were included (AMI–VTA: 56%; ST-segment elevation myocardial infarction (STEMI): 22%; non-ST-segment myocardial infarction (NSTEMI) 78%; ES: 44%). ES patients were older and had higher rates of severely reduced left ventricular ejection fraction (LVEF) p = 0.001; hazard ratio [HR] = 2.242; 95% CI 2.291–3.894; p = 0.004) and with increased risk of first cardiac rehospitalization (44% vs. 12%; p = 0.001; HR = 4.694; 95% CI 2.498–8.823; p = 0.001). This worse prognosis of ES compared to AMI–VTA was still evident after multivariable adjustment (long-term all-cause mortality: HR = 2.504; 95% CI 1.093–5.739; p = 0.030; first cardiac rehospitalization: HR = 2.887; 95% CI 1.240–6.720; p = 0.014). In contrast, the rates of MACE (40% vs. 32%; p = 0.326) were comparable in both groups. At long-term follow-up of 3 years, ES was associated with higher rates of all-cause mortality and rehospitalization compared to patients with AMI–VTA.

Despite a few studies evaluating the prognostic impact of coronary chronic total occlusion (CTO) in implantable cardioverter defibrillator (ICD) recipients, the impact of CTO on different types of recurrences of ventricular tachyarrhythmias, as well as their predictors has not yet been investigated in CTO patients. A large retrospective registry was used including all consecutive patients with ventricular tachyarrhythmias undergoing coronary angiography at index from 2002 to 2016. Only ICD recipients with CTO were compared to patients without (non-CTO). Kaplan–Meier and Cox regression analyses were applied for the primary end point of first recurrence of ventricular tachyarrhythmias at 5 years. Secondary end points comprised of the different types of recurrences, first appropriate ICD therapy and all-cause mortality at 5 years. From a total of 422 consecutive ICD recipients with ventricular tachyarrhythmias at index, at least one CTO was present in 25%. CTO was associated with the primary end point of first recurrence of ventricular tachyarrhythmias at 5 years (55% vs. 39%; log rank p = 0.001; HR = 1.665; 95% CI 1.221–2.271; p = 0.001), as well as increased risk of first appropriate ICD therapy (40% vs. 31%; log rank p = 0.039; HR = 1.454; 95% CI 1.016–2.079; p = 0.041) and all-cause mortality at 5 years (26% vs. 16%; log rank p = 0.011; HR = 1.797; 95% CI 1.133–2.850; p = 0.013). Less developed collaterals (i.e., either ipsi- or contralateral compared to bilateral) and a J-CTO score ≥ 3 were strongest predictors of recurrences in CTO patients at 5 years. A coronary CTO even in the presence of less developed collaterals and more complex CTO category is associated with increasing risk of recurrent ventricular tachyarrhythmias at 5 years in consecutive ICD recipients.

Prostate-specific membrane antigen (PSMA) targeted PET has a high detection rate for biochemical recurrence (BCR) of prostate cancer (PCa). Nevertheless, even at high prostate-specific antigen (PSA) levels (> 3 ng/ml), a relevant number of PSMA-PET scans are negative, mainly due to PSMA-negative PCa. Our objective was to investigate whether PSMA-expression patterns of the primary tumour on immunohistochemistry (IHC) are associated with PSMA-PET detection rate of recurrent PCa. Methods: Retrospective institutional review board approved single-centre analysis of patients who had undergone 68Ga-PSMA-11-PET for BCR after radical prostatectomy (RPE) between 04/2016 and 07/2019, with tumour specimens available for PSMA-IHC. Clinical information (age, PSA-level, ongoing androgen deprivation therapy (ADT), Gleason score) and PSMA-IHC of the primary tumour were collected and their relationship to results from PSMA-PET (positive/negative) was investigated using a multiple logistic regression analysis. Results: 120 PSMA-PET scans in 74 patients were available for this analysis. Overall detection rate was 62% (74/120 scans), with a mean PSA value at scan time of 0.99 ng/ml (IQR 0.32-4.27). Of the clinical factors, only PSA-level and ADT were associated with PSMA-PET positivity. The percentage of PSMA-negative tumour area on IHC (PSMA%neg) had a significant association to PSMA-PET negativity (OR = 2.88, p < 0.001), while membranous PSMA-expression showed no association (p = 0.73). The positive predictive value of PSMA%neg ≥ 50% for a negative PSMA-PET was 85% (13/11) and for a PSMA%neg of 80% or more, 100% (9/9). Conclusions: PSMA-negative tumour area on IHC exhibited the strongest association with negative PSMA-PET scans, beside PSA-level and ADT. Even at very high PSA levels, PSMA-PET scans were negative in most of the patients with PSMA%neg ≥ 50%.

Accurate staging is of major importance to determine the optimal treatment modality for patients with prostate cancer. Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) is a promising technique that outperformed conventional imaging in the detection of nodal and distant metastases in previous studies. However, it is still unclear whether the superior sensitivity and specificity also translate into improved patient management. The aim of this study was to assess the performance of 68Ga-PSMA-11 PET for staging of intermediate and high-risk prostate cancer and its potential impact on disease management. In this retrospective analysis, 116 patients who underwent 68Ga-PSMA-11 PET/CT or MRI scans for staging of their intermediate or high-risk prostate cancer between April 2016 and May 2018 were included. The potential impact of 68Ga-PSMA-11 PET staging on patient management was assessed within a simulated multidisciplinary tumour board where hypothetical treatment decisions based on clinical information and conventional imaging alone was determined. This treatment decision was compared with the treatment recommendation based on clinical information and 68Ga-PSMA-11 PET imaging. The primary tumour was positive on 68Ga-PSMA-11 PET in 113 patients (97%). Nodal metastases were detected in 28 patients (24%) and bone metastases in 14 patients (12%). Compared with clinical staging and conventional imaging, 68Ga-PSMA-11 PET resulted in new information in 42 of 116 patients (36%). In 32 of 116 patients (27%), this information would most likely have changed the management into a different therapy modality (15 patients, 13%) or adjusted treatment details (e.g. modification of radiotherapy field or lymph node dissection template; 17 patients, 14%). Information from 68Ga-PSMA-11 PET staging has the potential to change the management in more than a fourth of the patients who underwent PET staging for their intermediate to high-risk prostate cancer. Whether these more personalized 68Ga-PSMA-11 PET-based treatment decisions will improve patient outcome needs further investigation.

Background Recent studies have reported the additive value of combined gallium 68 (68Ga)-labeled Glu-urea-Lys (Ahx)-HBED-CC ligand targeting the prostate-specific membrane antigen (PSMA) (hereafter called 68Ga-PSMA-11) PET/MRI for the detection and localization of primary prostate cancer compared with multiparametric MRI. Purpose To compare the diagnostic accuracy and interrater agreement of multiparametric MRI and 68Ga-PSMA-11 PET/MRI for the detection of extracapsular extension (ECE) and seminal vesicle infiltration (SVI) in patients with prostate cancer. Materials and Methods Retrospective analysis of 40 consecutive men who underwent multiparametric MRI and 68Ga-PSMA-11 PET/MRI within 6 months for suspected prostate cancer followed by radical prostatectomy between April 2016 and July 2018. Four readers blinded to clinical and histopathologic findings rated the probability of ECE and SVI at multiparametric MRI and PET/MRI by using a five-point Likert-type scale. The prostatectomy specimen served as the reference standard. Accuracy was assessed with a multireader multicase analysis and by calculating reader-average areas under the receiver operating characteristics curve (AUCs), sensitivity, and specificity for ordinal and dichotomized data in a region-specific and patient-specific approach. Interrater agreement was assessed with the Fleiss multirater κ. Results For multiparametric MRI versus PET/MRI in ECE detection, respectively, AUC, sensitivity, and specificity in the region-specific analysis were 0.67 and 0.75 (P = .07), 28% (21 of 76) and 47% (36 of 76) (P = .09), and 94% (529 of 564) and 90% (509 of 564) (P = .007). For the patient-specific analysis, AUC, sensitivity, and specificity were 0.66 and 0.73 (P = .19), 46% (22 of 48) and 69% (33 of 48) (P = .04), and 75% (84 of 112) and 67% (75 of 112) (P = .19), respectively. For multiparametric MRI versus PET/MRI in SVI detection, respectively, AUC, sensitivity, and specificity of the region-specific analysis were 0.66 and 0.74 (P = .21), 35% (seven of 20) and 50% (10 of 20) (P = .25), and 98% (295 of 300) and 94% (282 of 300) (P < .001). For the patient-specific analysis, AUC, sensitivity, and specificity were 0.65 and 0.79 (P = .25), 35% (seven of 20) and 55% (11 of 20) (P = .20), and 98% (137 of 140) and 94% (131 of 140) (P = .07), respectively. Interrater reliability for multiparametric MRI versus PET/MRI did not differ for ECE (κ, 0.46 vs 0.40; P = .24) and SVI (κ, 0.23 vs 0.33; P = .39). Conclusion Our results suggest that gallium 68 (68Ga)-labeled Glu-urea-Lys (Ahx)-HBED-CC ligand targeting the prostate-specific membrane antigen (PSMA) (68Ga-PSMA-11) PET/MRI and multiparametric MRI perform similarly for local staging of prostate cancer in patients with intermediate-to-high-risk prostate cancer. The increased sensitivity of 68Ga-PSMA-11 PET/MRI for the detection of extracapsular disease comes at the cost of a slightly reduced specificity. © RSNA, 2019.

Introduction Aim of this study was to evaluate efficacy and safety of ventricular tachycardia (VT) catheter ablation in patients with structural heart disease (SHD) in relation to the presence of an intramural septal substrate. Methods Consecutive patients undergoing VT ablation between January 2019 and October 2020 were included. All patients were stratified based on the presence of relevant septal substrate and freedom from VT recurrences were analyzed. Results In total, 199 consecutive patients (64.2 ± 13.0 years; 89% male; 55% ischemic cardiomyopathy (ICM)) undergoing VT ablation were included. 129/199 patients (65%) showed significant septal substrate (55/90 patients (61%) with non-ischemic cardiomyopathy (NICM) compared to 74/109 patients (68%) with ICM; p = 0.37). Acute procedural success with elimination of all inducible VTs was achieved in 66/70 patients (94%) without and in 103/129 patients (80%) with a septal substrate (p = 0.007). In the cohort including patients with a clinical FU, 15/60 patients (25%) without a septal substrate and 48/123 patients (39%) with a septal substrate experienced VT recurrence during a FU of 8.1 ± 5.9 months (p = 0.069). Conclusion Presence of septal VT substrate in patients with a structural heart disease or coronary artery disease is common. Acute success of VT catheter ablation was significantly higher and mid-term success tended to be higher in patients without a septal substrate.

Background Patients with unrepaired cyanotic congenital heart disease (CHD) suffer from aggravated hypoxemia during exercise. We tested the hypothesis that supplemental oxygen improves exercise performance in these patients. Methods In this randomized, sham-controlled, single-blind, cross-over trial cyanotic CHD-patients underwent four cycle exercise tests to exhaustion, while breathing either oxygen-enriched (FiO2 0.50, oxygen) or ambient air (FiO2 0.21, air) using incremental (IET) or constant work-rate (CWRET) exercise test protocols (75% of maximal work rate achieved under FiO2 0.21). Pulmonary gas-exchange, electrocardiogram, arterial blood gases, oxygen saturation (SpO2), cerebral and quadriceps muscle tissue oxygenation (CTO and QMTO) by near-infrared spectroscopy were measured. Results We included seven patients with cyanotic CHD (4 Eisenmenger syndrome, 3 unrepaired cyanotic defects, 4 women) median (quartiles) age 36 (32;50) years, BMI 23 (20;26) kg/m2 and SpO2 at rest 87 (83;89) %. When comparing supplemental oxygen with air during exercise, maximal work-rate in IET increased from 76 (58;114) watts to 83 (67;136) watts, median difference 9 (0;22) W (p = 0.046) and CWRET-time increased from 412 s (325;490) to 468 s (415;553), median increase 56 (39;126) s (p = 0.018). In both IET and CWRET SpO2 was significantly higher and ventilatory equivalent for carbon dioxide significantly lower at end-exercise with oxygen compared to air, whereas CTO and QMTO did not significantly differ. Conclusions Patients with cyanotic CHD significantly improved their exercise performance, in terms of maximal work-rate and endurance time along with an improved arterial oxygenation and ventilatory efficiency with supplemental oxygen compared to air.

Cardiovascular diseases are accompanied by disorders in the cardiac metabolism. Furthermore, comorbidities often associated with cardiovascular disease can alter systemic and myocardial metabolism contributing to worsening of cardiac performance and health status. Biomarkers such as natriuretic peptides or troponins already support diagnosis, prognosis and treatment of patients with cardiovascular diseases and are represented in international guidelines. However, as cardiovascular diseases affect various pathophysiological pathways, a single biomarker approach cannot be regarded as ideal to reveal optimal clinical application. Emerging metabolomics technology allows the measurement of hundreds of metabolites in biological fluids or biopsies and thus to characterize each patient by its own metabolic fingerprint, improving our understanding of complex diseases, significantly altering the management of cardiovascular diseases and possibly personalizing medicine. This review outlines current knowledge, perspectives as well as limitations of metabolomics for diagnosis, prognosis and treatment of cardiovascular diseases such as heart failure, atherosclerosis, ischemic and non-ischemic cardiomyopathy. Furthermore, an ongoing research project tackling current inconsistencies as well as clinical applications of metabolomics will be discussed. Taken together, the application of metabolomics will enable us to gain more insights into pathophysiological interactions of metabolites and disease states as well as improving therapies of patients with cardiovascular diseases in the future.

Limited data regarding the prognostic impact of ventricular tachyarrhythmias related to out-of-hospital (OHCA) compared to in-hospital cardiac arrest (IHCA) is available. A large retrospective single-center observational registry with all patients admitted due to ventricular tachyarrhythmias was used including all consecutive patients with ventricular tachycardia (VT) and fibrillation (VF) on admission from 2002 to 2016. Survivors discharged after OHCA were compared to those after IHCA using multivariable Cox regression models and propensity-score matching for evaluation of the primary endpoint of long-term all-cause mortality at 2.5 years. Secondary endpoints were all-cause mortality at 6 months and cardiac rehospitalization at 2.5 years. From 2.422 consecutive patients with ventricular tachyarrhythmias, a total of 524 patients survived cardiac arrest and were discharged from hospital (OHCA 62%; IHCA 38%). In about 50% of all cases, acute myocardial infarction was the underlying disease leading to ventricular tachyarrhythmias with consecutive aborted cardiac arrest. Survivors of IHCA were associated with increased long-term all-cause mortality compared to OHCA even after multivariable adjustment (28% vs. 16%; log rank p = 0.001; HR 1.623; 95% CI 1.002–2.629; p = 0.049) and after propensity-score matching (28% vs. 19%; log rank p = 0.045). Rates of cardiac rehospitalization rates at 2.5 years were equally distributed between OHCA and IHCA survivors. In patients presenting with ventricular tachyarrhythmias, survivors of IHCA were associated with increased risk for all-cause mortality at 2.5 years compared to OHCA survivors.

A first analysis of simultaneous 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/MRI showed some improvement in the detection of recurrent disease at low serum prostate specific antigen (PSA) values below 0.5 ng/mL compared with the already high detection rate of 68Ga-PSMA-11 PET/CT. We therefore focused on all patients with biochemical recurrence and PSA values no higher than 0.5 ng/mL to assess the detection rate for 68Ga-PSMA-11 PET/MRI. Methods: We retrospectively analyzed a cohort of 66 consecutive patients who underwent 68Ga-PSMA-11 PET/MRI for biochemical recurrence with a PSA value no higher than 0.5 ng/mL at our institution. Median PSA level was 0.23 ng/mL (range, 0.03-0.5 ng/mL). Detection of PSMA-positive lesions within the prostate fossa, local and distant lymph nodes, bones, or visceral organs was recorded. In addition, all scans with 68Ga-PSMA-11 PET/MRI-positive lesions were retrospectively assessed to analyze if lesions were detected inside or outside a standard salvage radiotherapy volume. Results: Overall, in 36 of 66 patients (54.5%) PSMA-positive lesions were detected; in 26 of 40 (65%) patients with a PSA level between 0.2 and 0.5 ng/mL and in 10 of 26 (38.5%) patients with a PSA level less than 0.2 ng/mL. Even at those low PSA values, only 8 of 66 (12.1%) patients had exclusive local recurrence. Lymph nodes were detected in 23 patients and bone metastases in 5 on 68Ga-PSMA-11 PET/MRI. In 26 of 66 patients (39.4%), PSMA-positive lesions were located outside a standard salvage radiotherapy volume. Conclusion: Our data confirm that 68Ga-PSMA-11 PET/MRI has a high detection rate for recurrent prostate cancer, even at low PSA levels no higher than 0.5 ng/mL. In addition, we show that 68Ga-PSMA-11 PET/MRI detected PSMA-positive lesions outside a standard salvage radiotherapy volume in 39.4% of all patients.

OBJECTIVES The study sought to assess the prognostic impact of recurrences of electrical storm (ES-R) on mortality, rehospitalization and major adverse cardiac events (MACE). BACKGROUND Data on the prognostic impact of ES-R is rare. METHODS All consecutive ES patients with an implantable cardioverter defibrillator (ICD) were included retrospectively from 2002 to 2016. Patients with ES-R were compared to patients without ES-R. The primary endpoint was all-cause mortality, secondary endpoints were in-hospital mortality, rehospitalization and MACE. RESULTS A total of 87 consecutive ES patients with an ICD were included, of which 26% presented with ES-R at 2.5 years of follow-up. ES-R patients revealed lower LVEF compared to non-ES-R patients (91% vs. 61%; p = .081). There was a numerically higher rate of the primary endpoint of all-cause mortality at 2.5 years (50% vs. 32%; log-rank p = .137). Furthermore, ES-R was associated with increasing rates of rehospitalization (64% vs. 37%; p = .031; HR 1.985; 95% CI 1.025-3.845; log-rank p = .042), especially of acute heart failure (32% vs. 12%; p = .001; HR 3.262; 95% CI 1.180-9.023; log rank p = .023). MACE were higher in ES-R patients (55% vs. 35%; p = .113; log rank p = .141). ES patients with LVEF ≤35% were 12.4 times more likely to develop ES-R (HR 12.417; 95% CI 1.329-115.997; p = .027). CONCLUSION At long-term follow-up of 2.5 years, ES-R was associated with numerically higher rates of long-term all-cause mortality and significantly higher rates of rehospitalization due to acute heart failure. LVEF ≤35% was associated with increased risk of ES-R. Condensed Abstract This study examined retrospectively the impact of recurrences of electrical storm (ES-R) on survival in 87 patients. ES-R was associated with numerically higher long-term all-cause mortality, whereas significantly higher rates of rehospitalization, respectively of acute heart failure were observed. Highlights ES-R is associated with numerically higher rates of all-cause mortality at long-term follow-up. ES-R is associated with significantly higher rates of rehospitalization and numerically higher rates of MACE at long-term follow-up, mainly due to acute heart failure. Patients with LVEF ≤35% were 12.4 times more likely to develop ES-R.

The intense accumulation of prostate-specific membrane antigen (PSMA) radioligands in salivary glands is still not well understood. It is of concern for therapeutic applications of PSMA radioligands, because therapeutic radiation will damage these glands. A better understanding of the uptake mechanism is, therefore, crucial to find solutions to reduce toxicity. The aim of this study was to investigate whether the accumulation of PSMA-targeting radioligands in submandibular glands (SMGs) can be explained with PSMA expression levels using autoradiography (ARG) and immunohistochemistry (IHC). Methods: All patients gave written informed consent for further utility of the biologic material. The SMG of 9 patients, pancreatic tissue of 4 patients, and prostate cancer (PCA) lesions of 9 patients were analyzed. Tissue specimens were analyzed by means of PSMA-IHC (using an anti–PSMA-antibody and an immunoreactivity score system [IRS]) and ARG using 177Lu-PSMA-617 (with quantification of the relative signal intensity compared with a PSMA-positive standard). The SUVmax in salivary glands, pancreas, and PCA tissues were quantified in 60 clinical 68Ga-PSMA-11 PET scans for recurrent disease as well as the 9 primary tumors selected for ARG and IHC. Results: PCA tissue samples revealed a wide range of PSMA staining intensity on IHC (IRS = 70–300) as well as in ARG (1.3%–22% of standard). This variability on PCA tissue could also be observed in 68Ga-PSMA-11 PET (SUVmax, 4.4–16) with a significant correlation between ARG and SUVmax (P

High-intensity focused ultrasound (HIFU) is a promising new modality for the treatment of localized prostate cancer (PCa). Follow-up of patients is recommended with biopsies and multiparametric MRI (mpMRI). However, mpMRI in the postinterventional setting is often false-negative. It was our aim to investigate if the new tracer targeting the prostate-specific membrane antigen (68Ga-PSMA-11) could be used to localize recurrent disease with PET/MR in patients with discrepant findings between mpMRI and template biopsies. Methods: Interim analysis was performed of the first 10 patients scanned between September 2016 and May 2018 with positive template biopsy and negative mpMRI after HIFU from an ongoing clinical trial (NCT02265159). All patients underwent 68Ga-PSMA-11 PET/MRI within 3 mo. Four prostatic quadrants were defined, and for every quadrant suspicion for recurrence was rated on a 5-point Likert scale from definitely no recurrence (1) to highly suspected of recurrence (5), with 4 used as a cutoff for suspected disease based on PET/MRI by a masked reader. 68Ga-PSMA-11 uptake of suspected lesions and background areas was measured with the SUVmax The apparent diffusion coefficient values of lesions and background were given for each segment. PET/MRI scans were compared with the template biopsy results, including corresponding Gleason scores (GS), number of positive cores, and tumor length. Results: The quadrant-based sensitivity, specificity, and positive and negative predictive values for PET/MRI were 55%, 100%, 100%, and 85%, respectively. Patient-based PET/MRI was negative in 4 cases with GS 3 + 4 and a tumor length between 0.1 and 3 mm. All tumor lesions with GS 4 + 3 or higher were detected on PET/MRI. Conclusion: Our preliminary results indicate that 68Ga-PSMA-11-PET/MR has the potential to localize PCa recurrence after HIFU occult on mpMRI.

Background: Data regarding the prognostic impact of atrial fibrillation (AF) in patients with electrical storm (ES) is rare. Objectives: This study sought to assess the prognostic impact of AF in patients with ES on mortality, rehospitalization, major adverse cardiovascular events (MACE) and recurrence of ES (ES-R). Methods: All consecutive implantable cardioverter defibrillator (ICD) patients presenting with ES were included retrospectively from 2002 to 2016. Patients with AF were compared to non-AF patients. The primary prognostic endpoint was all-cause mortality. Secondary endpoints were in-hospital mortality, rehospitalization rates, MACE and ES-R. Results: A total of 87 ES patients with ICD were included and followed up to 2.5 years; 43% suffered from AF. The presence of AF was associated with increased all-cause mortality (47 vs. 29%, log-rank p = 0.052; hazard ratio [HR] 1.969, 95% confidence interval [CI] 0.981–3.952, p = 0.057), which was no longer present after multivariable adjustment for age, diabetes and dilated cardiomyopathy. Furthermore, AF was associated with increased rates of overall rehospitalization (61 vs. 31%, log-rank p = 0.013; HR 2.381, 95% CI 1.247–4.547, p = 0.009), especially due to AF (14 vs. 0%, p = 0.001) and acute heart failure (AHF) (28 vs. 10%, p = 0.018; HR 3.754, 95% CI 1.277–11.038, p = 0.016). Notably, AF was not associated with differences in MACE (55 vs. 37%, log rank p = 0.339) and ES-R (28 vs. 25%, log rank p = 0.704). Conclusion: In ES patients, presence of AF was univariably associated with increased rates of all-cause mortality at 2.5 years. Furthermore, AF was multivariably associated with overall rehospitalization, especially due to AF and AHF.

The fast-increasing use of positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) ligand for the imaging of prostate cancer (PCA) biochemical recurrence has led to a rapid change in treatment concepts. Since the superiority of 68Ga-PSMA-11 PET in detecting recurrent PCA is well established, the aim of our study was to assess its effect on management and outcome in all patients imaged during the first year after its introduction into clinical routine. Of 327 patients imaged, 223 were referred for recurrent PCA and gave written informed consent for further analysis of their data for this retrospective consecutive cohort analysis. Twenty patients were lost to further follow-up. The rate of detection of recurrence by 68Ga-PSMA-11 PET was based on the clinical reports. Management before the availability of PET diagnostic information was assessed according to guidelines (therapy option without 68Ga-PSMA-11 PET). In the 203 patients with follow-up 6 months after 68Ga-PSMA-11 PET, the therapies effectively implemented as well as follow-up PSA levels were evaluated, with a PSA value of

Upon activation, neutrophils release neutrophil extracellular traps (NETs), which contribute to circulating DNA burden and thrombosis, including ST-segment elevation myocardial infarction (STEMI). Deoxyribonuclease (DNase) 1 degrades circulating DNA and NETs. Lower DNase activity correlates with NET burden and infarct size. The DNase 1 Q222R single nucleotide polymorphism (SNP), impairing DNase 1 function, is linked with myocardial infarction. We assessed whether the Q222R SNP is connected to increased NET burden in STEMI and influences long-term outcomes. We enrolled 711 STEMI patients undergoing primary percutaneous coronary intervention (pPCI), and 1422 controls. Genotyping was performed for DNase 1 Q222R SNP. DNase activity, double-stranded (ds)DNA and citrullinated histone H3 were determined in culprit site and peripheral plasma during pPCI. The association of the Q222R variant on cardiovascular and all-cause mortality was assessed by multivariable Cox regression adjusted for cardiovascular risk factors. Homozygous Q222R DNase 1 variant was present in 64 (9.0%) STEMI patients, at the same frequency as in controls. Patients homozygous for Q222R displayed less DNase activity and increased circulating DNA burden. In overall patients, median survival was 60 months. Homozygous Q222R variant was independently associated with cardiovascular and all-cause mortality after STEMI. dsDNA/DNase ratio independently predicted cardiovascular and all-cause mortality. These findings highlight that the Q222R DNase 1 SNP is associated with increased NET burden and decreased compensatory DNase activity, and may serve as an independent risk factor for poor outcome after STEMI. Supplementary Information The online version contains supplementary material available at 10.1007/s00395-021-00864-w.

Objective: To evaluate the effects of breathing oxygen-enriched air (oxygen) on exercise performance in patients with pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF). Methods: Ten patients with PH-HFpEF (five women, age 60 ± 9 y, mPAP 37 ± 14 mmHg, PAWP 18 ± 2 mmHg, PVR 3 ± 3 WU, resting SpO2 98 ± 2%) performed two-cycle incremental exercise tests (IET) and two constant-work-rate exercise test (CWRET) at 75% maximal work-rate (Wmax), each with ambient air (FiO2 0.21) and oxygen (FiO2 0.5) in a randomized, single-blinded, cross-over design. The main outcomes were the change in Wmax (IET) and cycling time (CWRET) with oxygen vs. air. Blood gases at rest and end-exercise, dyspnea by Borg CR10 score at end-exercise; continuous SpO2, minute ventilation (V'E), carbon dioxide output (V'CO2), and cerebral and quadricep muscle tissue oxygenation (CTO and QMTO) were measured. Results: With oxygen vs. air, Wmax (IET) increased from 94 ± 36 to 99 ± 36 W, mean difference (95% CI) 5.4 (0.9–9.8) W, p = 0.025, and cycling time (CWRET) from 532 ± 203 to 680 ± 76 s, +148 (31.8–264) s, p = 0.018. At end-exercise with oxygen, Borg dyspnea score and V'E/V'CO2 were lower, whereas PaO2 and end-tidal PaCO2 were higher. Other parameters were unchanged. Conclusion: Patients with PH-HFpEF not revealing resting hypoxemia significantly improved their exercise performance while breathing oxygen-enriched air along with less subjective dyspnea sensation, a better blood oxygenation, and an enhanced ventilatory efficiency. Future studies should investigate whether prolonged training with supplemental oxygen would increase the training effect and, potentially, daily activity for PH-HFpEF patients. Clinical Trial Registration: [clinicaltrials.gov], identifier [NCT04157660].

Background Data is limited evaluating novel biomarkers in right ventricular dysfunction. Normal right heart function improves the prognosis of patients with heart failure. Therefore, this study investigates the association between the novel biomarker copeptin and right heart function compared to NT-proBNP. Methods Patients undergoing routine echocardiography were enrolled prospectively. Right ventricular function was assessed by tricuspid annular plane systolic excursion (TAPSE) and further right ventricular and atrial parameters. Exclusion criteria were age under 18 years, left ventricular ejection fraction Results Ninety-one patients were included. Median values of copeptin increased significantly according to decreasing values of TAPSE ( P = 0.001; right heart function grade I: tricuspid annular plane systolic excursion; TAPSE > 24 mm: 5.20 pmol/L; grade II: TAPSE 18–24 mm: 8.10 pmol/L; grade III: TAPSE Conclusions This study demonstrates that the novel biomarker copeptin reflects longitudinal right heart function assessed by standardized transthoracic echocardiography compared with NT-proBNP.

Human brown adipose tissue (BAT) is a thermogenic tissue activated by the sympathetic nervous system in response to cold exposure. It contributes to energy expenditure (EE) and takes up glucose and lipids from the circulation. Studies in rodents suggest that BAT contributes to the transient rise in EE after food intake, so-called diet-induced thermogenesis (DIT). We investigated the relationship between human BAT activity and DIT in response to glucose intake in 17 healthy volunteers. We assessed DIT, cold-induced thermogenesis (CIT), and maximum BAT activity at three separate study visits within 2 wk. DIT was measured by indirect calorimetry during an oral glucose tolerance test. CIT was assessed as the difference in EE after cold exposure of 2-h duration as compared with warm conditions. Maximal activity of BAT was assessed by 18-F-fluoro-deoxyglucose (18F-FDG) 18F-FDG-PET/MRI after cold exposure and concomitant pharmacological stimulation with mirabegron. Seventeen healthy men (mean age = 23.4 yr, mean body mass index = 23.2 kg/m2) participated in the study. EE increased from 1,908 (±181) kcal/24 h to 2,128 (±277) kcal/24 h (P < 0.0001, +11.5%) after mild cold exposure. An oral glucose load increased EE from 1,911 (±165) kcal/24 h to 2,096 (±167) kcal/24 h at 60 min (P < 0.0001, +9.7%). The increase in EE in response to cold was significantly associated with BAT activity (R2 = 0.43, P = 0.004). However, DIT was not associated with BAT activity (R2 = 0.015, P = 0.64). DIT after an oral glucose load was not associated with stimulated 18F-FDG uptake into BAT, suggesting that DIT is independent from BAT activity in humans (Clinicaltrials.gov Registration No. NCT03189511).NEW & NOTEWORTHY Cold-induced thermogenesis (CIT) was related to BAT activity as determined by FDG-PET/MRI after stimulation of BAT. Diet-induced thermogenesis (DIT) was not related to stimulated BAT activity. Supraclavicular skin temperature was related to CIT but not to DIT. DIT in humans is probably not a function of BAT.

OBJECTIVE The study sought to assess the prognostic impact of treatment with mineralocorticoid receptor antagonists (MRA) on recurrences of ventricular tachyarrhythmias in implantable cardioverter-defibrillator (ICD) recipients with systolic heart failure (HF). BACKGROUND Data regarding the outcome of patients with ventricular tachyarrhythmias treated with MRA is limited. METHODS A large retrospective registry was used including consecutive ICD recipients with systolic HF (i.e., left ventricular ejection fraction

This study sought to assess the prognostic impact of treatment with single beta-blocker (BB) compared to combined therapy with BB plus amiodarone (BB-AMIO) on recurrences of ventricular tachyarrhythmias in implantable cardioverter-defibrillator (ICD) recipients. A large retrospective registry was used including consecutive ICD recipients with index episodes of ventricular tachyarrhythmias from 2002 to 2016. Patients treated with BB were compared to patients treated with BB-AMIO. Kaplan-Meier and Cox regression analyses were applied for the evaluation of the primary end-point defined as first recurrences of ventricular tachyarrhythmias at five years. Secondary end-points comprised first appropriate ICD therapies, first cardiac rehospitalization and all-cause mortality at five years. Among 512 ICD recipients, 81% were treated with BB and 19% with BB-AMIO. BB and BB-AMIO were associated with comparable risk of first recurrences of ventricular tachyarrhythmias (46% vs. 43%; log rank P = .941; HR = 1.013; 95% CI 0.725-1.415; P = .941) and appropriate ICD therapies (35% vs. 37%; log rank P = .389; HR = 0.852; 95% CI 0.591-1.228; P = .390). BB was associated with decreased long-term all-cause mortality within an univariable analysis only (20% vs. 28%; log rank p = 0.023). In conclusion, BB and BB-AMIO were associated with comparable risks regarding recurrences of ventricular tachyarrhythmias at five years.

Summary Background Data regarding recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) recipients according to atrial fibrillation is limited. Objective To assess the prognostic impact of atrial fibrillation on recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator recipients. Methods A large retrospective registry was used, including all ICD recipients with episodes of ventricular tachycardia or fibrillation from 2002 to 2016. Patients with atrial fibrillation were compared to those without atrial fibrillation. The primary endpoint was first recurrence of ventricular tachyarrhythmias at 5 years. Secondary endpoints comprised recurrences of ICD-related therapies, first cardiac rehospitalization and all-cause mortality at 5 years. Cox regression, Kaplan-Meier and propensity score-matching analyses were applied. Results A total of 592 consecutive ICD recipients were included (33% with atrial fibrillation). Atrial fibrillation was associated with reduced freedom from recurrent ventricular tachyarrhythmias (42% vs. 50%, log-rank P = 0.004; hazard ratio 1.445, 95% confidence interval 1.124–1.858), mainly attributable to recurrent ventricular fibrillation in secondary-preventive ICD recipients. Accordingly, atrial fibrillation was associated with reduced freedom from first appropriate ICD therapies (31% vs. 42%, log-rank P = 0.001; hazard ratio 1.598, 95% confidence interval 1.206–2.118). Notably, the primary endpoint of freedom from first episode of recurrent ventricular tachyarrhythmias was still reduced in those with atrial fibrillation compared to those without atrial fibrillation after propensity score matching. Regarding secondary endpoints, patients with atrial fibrillation still showed a trend towards reduced freedom from appropriate ICD therapies. Conclusions Atrial fibrillation was associated with increased rates of recurrent ventricular tachyarrhythmias and appropriate device therapies in ICD recipients with ventricular tachyarrhythmias.

Only few data evaluating the prognostic impact of blood-derived potassium levels (K) on arrhythmic endpoints in patients with implantable cardioverter-defibrillators (ICD) is available. Therefore, this study evaluates the prognostic impact of potassium levels on recurrences of ventricular tachyarrhythmias in consecutive ICD recipients.A large retrospective registry was used including all consecutive patients presenting with ventricular tachyarrhythmias on admission from 2002 to 2016 at one institution. Patients were divided into three subgroups: hypokalemia (i.e., K3.3 mmol/L), normokalemia (i.e., K 3.3 - 4.5 mmol/L), and hyperkalemia (i.e., K4.5 mmol/L). Kaplan-Meier and Cox regression analyses were applied for the evaluation of the primary endpoint of first recurrences of ventricular tachyarrhythmias at one year. Secondary endpoints comprised of first appropriate ICD therapy, first cardiac rehospitalization, and all-cause mortality at one year.Five hundred and thirty ICD recipients with a median potassium level of 4.23 mmol/L were included (67%: normokalemia, 27%: hyperkalemia, and 6%: hypokalemia). Whereas hyperkalemia was not associated with increasing risk of recurrent ventricular tachyarrhythmias, hypokalemia was associated with decreasing freedom from recurrent ventricular tachyarrhythmias (HR = 2.135; 95% CI 1.158 - 3.937; p = 0.015), even after mul-tivariable adjustment (HR = 2.577; 95% CI 1.236 - 5.372; p = 0.012). Higher risk of recurrences was especially attributed to higher rates of electrical storm in the presence of hypokalemia (15% vs. 3 - 4%). Negative impact of hypokalemia was mainly attributed to secondary preventive ICD (HR = 2.637; 95% CI 1.325 - 5.248; p = 0.006). Moreover, hypokalemia was associated with increasing risk of appropriate ICD therapies (HR = 1.920; 95% CI 0.912 - 4.042; statistical trend: p = 0.086), which was still demonstrated after multivariable adjustment. In contrast, risk of first cardiac rehospitalization and all-cause mortality were not affected by potassium levels.In consecutive ICD recipients with ventricular tachyarrhythmias at index, hypokalemia - but not hyperkalemia - was associated with increasing risk of recurrent ventricular tachyarrhythmias and appropriate ICD therapies.

Background In contrast to ordered subset expectation maximization (OSEM), block sequential regularized expectation maximization (BSREM) positron emission tomography (PET) reconstruction algorithms can run until full convergence while controlling image quality and noise. Recent studies with BSREM and 18F-FDG PET reported higher signal-to-noise ratios and higher standardized uptake values (SUV). In this study, we investigate the optimal regularization parameter (β) for clinical 68Ga-PSMA PET/MR reconstructions in the pelvic region applying time-of-flight (TOF) BSREM in comparison to TOF OSEM. Two-minute emission data from the pelvic region of 25 patients who underwent 68Ga-PSMA PET/MR were retrospectively reconstructed. Reference OSEM reconstructions had 28 subsets and 2 iterations. BSREM reconstructions were performed with 15 β values between 150 and 1200. Regions of interest (ROIs) were drawn around lesions and in uniform background. Background SUVmean (average) and SUVstd (standard deviation), and lesion SUVmax (average of 5 hottest voxels) were calculated. Differences were analyzed using the Wilcoxon matched pairs signed-rank test. Results A total of 40 lesions were identified in the pelvic region. Background noise (SUVstd) and lesions SUVmax decreased with increasing β. Image reconstructions with β values lower than 400 have higher (p

Given the good correlation between PSMA expression and intraglandular tumour aggressiveness based on immunohistochemistry, there is increasing interest in 68Ga-PSMA-11 PET/MRI for staging prostate cancer (PCA). Therefore, accurate knowledge of prostate anatomy as well as normal distribution of PSMA within the prostate gland is becoming essential. The aim of this study was to investigate the physiological intraprostatic distribution of 68Ga-PSMA-11. We retrospectively analysed all patients who underwent a staging 68Ga-PSMA-11 PET/MRI scan between June 2016 and January 2018 for high-risk PCA, underwent radical prostatectomy in our institution, and gave written consent for further data analysis. In each patient, standardized volumes of interest (VOIs) were placed bilaterally in the central, transition and peripheral zones within the zonal anatomy according to T2 weighted sequences in the axial and coronal planes. VOIs were only placed if they were safely within healthy tissue without spillover from the PCA. SUVmax and SUVmean were determined and their differences among the regions were assessed using the Wilcoxon signed-ranks test. Of 283 consecutive patients scanned with 68Ga-PSMA-11 PET/MR, 31 were analysed. A total of 133 VOIs were placed, 46 in the central zone, 41 in the transition zone and 46 in the peripheral zone. Differences in SUVmax between the central zone (mean 3.9 ± 0.58) and transition zone (mean 3.2 ± 0.59) and between the central zone and peripheral zone (mean 2.7 ± 0.54) were statistically significant (both p

Leukocyte-mediated inflammation is central in atherothrombosis and ST-segment elevation myocardial infarction (STEMI). Neutrophil extracellular traps (NETs) have been shown to enhance atherothrombosis and stimulate fibroblast function. We analyzed the effects of NETs on cardiac remodeling after STEMI. We measured double-stranded (ds)DNA and citrullinated histone H3 (citH3) as NET surrogate markers in human culprit site and femoral blood collected during primary percutaneous coronary intervention (n = 50). Fibrocytes were characterized in whole blood by flow cytometry, and in culprit site thrombi and myocardium by immunofluorescence. To investigate mechanisms of fibrocyte activation, isolated NETs were used to induce fibrocyte responses in vitro. Enzymatic infarct size was assessed using creatine-phosphokinase isoform MB area under the curve. Left ventricular function was measured by transthoracic echocardiography. NET surrogate markers were increased at the culprit site compared to the femoral site and were positively correlated with infarct size and left ventricular dysfunction at follow-up. In vitro, NETs promoted fibrocyte differentiation from monocytes and induced fibrocyte activation. Highly activated fibrocytes accumulated at the culprit site and in the infarct transition zone. Our data suggest that NETs might be important mediators of fibrotic remodeling after STEMI, possibly by stimulating fibrocytes. Electronic supplementary material The online version of this article (10.1007/s00395-019-0740-3) contains supplementary material, which is available to authorized users.

INTRODUCTION AND OBJECTIVES:Simultaneous 68Ga-PSMA-11 PET/MRI showed some improvement in the detection of recurrent prostate cancer at low serum prostate specific antigen (PSA) levels between 0.2 -...

Background Because data on electrical storm (ES) is limited, this study sought to compare the prognosis of patients with ES to those with ventricular tachyarrhythmias on mortality, rehospitalization and major adverse cardiac events (MACE). Methods In this retrospective study consecutive implantable cardioverter defibrillator (ICD) recipients presenting with ES were compared to patients surviving ventricular tachyarrhythmias (ventricular tachycardia (VT) or fibrillation (VF); non-ES) on admission from 2002 to 2016. The primary endpoint was all-cause mortality, secondary endpoints were rehospitalization and MACE at 2.5 years of follow-up. Results 764 consecutive patients with an ICD were included (11% with ES, 89% with VTA). ES was associated with higher rates of all-cause mortality (37% vs. 20%, log-rank p = 0.001; HR 2.084; 95% CI 1.416–3.065, p = 0.001). However, only in secondary preventive ICD recipients, ES remained significantly associated with mortality (39% vs. 20%; log rank p = 0.001; HR 2.235, 95% CI 1.378–3.625, p = 0.001). Furthermore, ES was associated with higher rates of rehospitalization (44% vs. 12%, log-rank p = 0.001; HR 4.763, 95% CI 3.237–7.009, p = 0.001), mainly due to VT (22% vs. 4%, p = 0.001) and acute heart failure (AHF) (17% vs. 4%, p = 0.001) and higher rates of MACE (40% vs. 23%; log rank p = 0.001; HR 1.838; 95% CI 1.273–2.654, p = 0.002). Increasing risks of death and rehospitalization were still observed even after multivariable adjustment. Conclusion ES was associated with increased rates of all-cause mortality, rehospitalization, respectively due to VT and AHF, as well as MACE at 2.5 years compared to patients with ventricular tachyarrhythmias apart from ES.

Objective: The study sought to assess the long-term prognostic impact of different pharmacotherapies, including angiotensin-converting enzyme inhibitor-inhibitor/angiotensin receptor blocker (ACEi/ARB), statins, and amiodarone in patients with electrical storm (ES). Background: Data regarding the outcome of patients with ES is limited. Methods: Consecutive patients with ES from 2002 to 2016 were included. Patients on ACEi/ARB were compared to patients without ACEi/ARB, respectively, for statin and amiodarone therapy. The primary prognostic endpoint was all-cause mortality at 4 years. Secondary endpoints comprised ES recurrences, rehospitalization, and major adverse cardiac events (MACE) at 4 years. Kaplan-Meier survival curves and multivariable Cox regression analyses were applied. Results: A total of 84 consecutive patients surviving episodes of ES was included. Beta-blocker was given in 95%, ACEi/ARB in 80%, statin in 60%, and amiodarone in 54%. ACEi/ARB patients were associated with improved all-cause mortality at 4 years (mortality rate 34 vs. 65%, log rank p = 0.018; HR 0.428; 95% CI 0.208–0.881; p = 0.021), as well as improved freedom from MACE. In contrast, statin and amiodarone therapy had no impact on long-term outcomes in ES patients. Conclusion: ACEi/ARB therapy is associated with improved survival and MACE in patients with ES, whereas statins and amiodarone therapy had no impact on long-term prognostic endpoints.

The study sought to assess retrospectively the prognostic impact of left ventricular ejection fraction (LVEF) in patients with electrical storm (ES). Data regarding the prognostic impact of impaired LVEF in ES patients is rare. Consecutive patients presenting with ES from 2002 to 2016 were included retrospectively. Patients with LVEF ≤ 35% were compared to patients with LVEF > 35%. The primary prognostic endpoint was long-term all-cause mortality, and secondary endpoints were rates of in-hospital mortality, rehospitalization, major adverse cardiac events (MACE), and ES recurrences (ES-R) at long-term follow-up. A total of 80 patients with ES were included at 2.5 years of follow-up. 69% of patients suffered from LVEF ≤ 35%. ES patients with LVEF ≤ 35% were associated with higher rates of the primary endpoint of all-cause mortality (53% versus 8%, log-rank p = 0.0001; HR 8.524; 95% CI 2.030–35.793, p = 0.003), as well as the secondary endpoints of MACE (53% versus 20%; log rank p = 0.011; HR 3.213, 95% CI 1.241–8.316, p = 0.016) and ES-R (35% versus 8%; log rank p = 0.019; HR 4.821, 95% CI 1.122–20.706, p = 0.034). Furthermore, ES patients with LVEF ≤ 35% showed higher rates of rehospitalization due to acute heart failure (24% versus 8%, statistical trend p = 0.096). Notably, ES patients with LVEF > 35% were associated with increased rates of rehospitalization due to ventricular tachycardia (36% versus 18%, statistical trend p = 0.083). ES patients with LVEF ≤ 35% were associated with increased rates of all-cause mortality, MACE, ES-R and heart failure-related rehospitalization at long-term follow-up. This study evaluated retrospectively the prognostic impact of LVEF in patients with ES. LVEF ≤ 35% was associated with increased long-term all-cause mortality (53% versus 8%; HR 8.524; 95% CI 2.030–35.793, p = 0.003), MACE (53% versus 20%; HR 3.213, 95% CI 1.241–8.316, p = 0.016), and ES recurrences (35% versus 8%; HR 4.821, 95% CI 1.122–20.706, p = 0.034), while trends were observed for higher rates of heart-failure related rehospitalization (24% versus 8%, p = 0.096) and MACE (49% versus 28%; p = 0.081).

Recent research focusing on brown adipose tissue (BAT) function emphasizes its importance in systemic metabolic homeostasis. We show here that genetic and pharmacological inhibition of the mevalonate pathway leads to reduced human and mouse brown adipocyte function in vitro and impaired adipose tissue browning in vivo. A retrospective analysis of a large patient cohort suggests an inverse correlation between statin use and active BAT in humans, while we show in a prospective clinical trial that fluvastatin reduces thermogenic gene expression in human BAT. We identify geranylgeranyl pyrophosphate as the key mevalonate pathway intermediate driving adipocyte browning in vitro and in vivo, whose effects are mediated by geranylgeranyltransferases (GGTases), enzymes catalyzing geranylgeranylation of small GTP-binding proteins, thereby regulating YAP1/TAZ signaling through F-actin modulation. Conversely, adipocyte-specific ablation of GGTase I leads to impaired adipocyte browning, reduced energy expenditure, and glucose intolerance under obesogenic conditions, highlighting the importance of this pathway in modulating brown adipocyte functionality and systemic metabolism.

Restaging local recurrence after high-intensity focused ultra-sound (HIFU) is based on multiparametric MRI (mpMRI). However, postinterventional changes of the tissue, such as edema or hemorrhage, are limiting tumor detection on mpMRI. We present a case of a rising prostate-specific antigen values, negative mpMRI, and a Gleason score of 4+4 on template biopsy after HIFU. On F-choline PET/MR, high focal uptake was detected at the location of positive biopsy. Re-HIFU based on the fused F-choline PET/MR images was performed, followed by a recurrence-free period of 11 months. Thus, F-choline PET/MR could improve guiding retreatment in patients with recurrence after HIFU.

Sensitive visualization of recurrent prostate cancer foci is a challenge in patients with early biochemical recurrence (EBR). The recently established 68Ga-PSMA-11 PET/CT has significantly improved the detection rate with published values of up to 55% for patients with a serum PSA concentration between 0.2–0.5 ng/mL. The increased soft tissue contrast in the pelvis using simultaneous 68Ga-PSMA-11 PET/MRI might further improve the detection rate in patients with EBR and low PSA values over PET/CT. We retrospectively analyzed a cohort of 56 consecutive patients who underwent a 68Ga-PSMA-11 PET/MRI for biochemical recurrence in our institution between April and December 2016 with three readers. Median PSA level was 0.99 ng/mL (interquartile range: 3.1 ng/mL). Detection of PSMA-positive lesions within the prostate fossa, local and distant lymph nodes, bones, or visceral organs was recorded. Agreement among observers was evaluated with Fleiss’s kappa (k). Overall, in 44 of 56 patients (78.6%) PSMA-positive lesions were detected. In four of nine patients (44.4%) with a PSA 2.0 ng/mL, suspicious lesions were detected. The overall interreader agreement for cancer detection was excellent (κ = 0.796, CI 0.645–0.947). Our data show that 68Ga-PSMA-11 PET/MRI has a high detection rate for recurrent prostate cancer even at very low PSA levels

Objective Follow-up of patients with oral cavity squamous cell carcinoma (OCSCC) after tumor resection and reconstruction with tissue transfer is challenging. We compared contrast-enhanced computed tomography (ceCT), 18F-fluorodeoxyglucose-positron emission tomography combined with noncontrast enhanced CT (18F-FDG-PET/CT), and 18F-FDG-PET combined with ceCT (18F-FDG-PET/ceCT) to determine the accuracy for detection of residual/recurrent disease after flap reconstruction for OCSCC. Study Design and Methods Two readers (R1, R2) retrospectively reviewed a total of 27 18F-FDG-PET/ceCT scans in patients after resection of stage II to IV OCSCC. They recorded the presence of local persistence/recurrence (LR), lymph node metastasis, or distant metastasis independently for ceCT, 18F-FDG-PET/CT, and 18F-FDG-PET/ceCT. Histological workup, imaging follow-up, or clinical follow-up served as the standard of reference. Maximum standardized uptake value (SUVmax) was evaluated to discriminate between physiological uptake and LR. Results The highest accuracy to detect LR was achieved with 18F-FDG-PET/ceCT, with a sensitivity/specificity of 88%/89% and 88%/79% for R1 and R2, respectively, as compared to ceCT with 75%/79% for R1 and 88%/68% for R2 and 18F-FDG-PET/CT with 88%/58% for both R1 and R2. Receiver-operating-characteristic analysis determined a cutoff value for SUVmax of 7.2, yielding a sensitivity and specificity of 75% and 94%, respectively, to distinguish LR from physiological 18F-FDG uptake. Conclusion 18F-FDG-PET/ceCT seems to be the most reliable tool for locoregional surveillance of OCSCC patients after resection and reconstruction. Level of Evidence 4. Laryngoscope, 125:1861–1868, 2015

This paper analyses the political-economic content of the recent ‘revolutionary’ shift in financial accounting rules for listed companies, specifically the rise of IFRS and fair value. It connects this shift to the socio-economic changes that are currently being discussed in the literature on financialisation, e.g. the rise of shareholder value and the proprietary view of the firm. Two ideal-typical accounting systems are constructed on the basis of normative accounting theory and extant standards – historical cost accounting (HCA) and fair value accounting (FVA). The ‘accounting revolution’ of the past 10–15 years can be understood as a qualitative shift from HCA to FVA. It is further argued that these ideal-typical systems are related to different circuits or forms of capital – productive and money capital respectively – and to the particular perspective that these afford on the, capitalist firm. Inasmuch as financialisation is related to the circuit of money capital one can make sense of the rise to prominence of FVA, which represents the dominance of a financial view of the firm in the field of financial accounting. Throughout this paper, however, the limits to financialisation are also highlighted and traced back to the ineradicable manifestation of the circuit of productive capital.

African mole-rats (family Bathyergidae) are small to medium sized, long-lived and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN) correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of one year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin). Solitary Cape mole-rats (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean rodents.