Usefulness of coronary calcium scoring to myocardial perfusion SPECT in the diagnosis of coronary artery disease in a predominantly high risk population

Coronary calcium scoring (CCS) adds to the diagnostic performance of myocardial perfusion single-photon emission computed tomography (SPECT) to assess the presence of significant coronary artery disease (CAD). Patients with a high pre-test likelihood are expected to have a high CCS which potentially could enhance the diagnostic performance of myocardial perfusion SPECT in this specific patient group. We evaluated the added value of CCS to SPECT in the diagnosis of significant CAD in patients with an intermediate to high pre-test likelihood. In total, 129 patients (mean age 62.7 +/- A 9.7 years, 65 % male) with stable anginal complaints and intermediate to high pre-test likelihood of CAD (median 87 %, range 22-95) were prospectively included in this study. All patients received SPECT and CCS imaging preceding invasive coronary angiography (CA). Fractional flow reserve (FFR) measurements were acquired from patients with angiographically estimated 50-95 % obstructive CAD. For SPECT a SSS > 3 was defined significant CAD. For CCS the optimal cut-off value for significant CAD was determined by ROC curve analysis. The reference standard for significant CAD was a FFR of < 0.80 acquired by CA. Significant CAD was demonstrated in 64 patients (49.6 %). Optimal CCS cut-off value for significant CAD was > 182.5. ROC curve analysis for prediction of the presence of significant CAD for SPECT, CCS and the combination of CCS and SPECT resulted in an area under the curve (AUC) of 0.88 (95 % CI 81-94), 0.75 (95 % CI 66-83 %) and 0.92 (95 % CI 87-97 %) respectively. The difference of the AUC between SPECT and the combination of CCS and SPECT was 0.05 (P = 0.12). The addition of CCS did not significantly improve the diagnostic performance of SPECT in the evaluation of patients with a predominantly high pre-test likelihood of CAD

Skeletal ¹⁸F-PSMA-1007 uptake in prostate cancer patients

Background/objectives: Accurate and uniform interpretation and reporting of metastatic prostate cancer (PCa) lesions on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) are indispensable. 18F-PSMA-1007 is increasingly used because of its favorable imaging characteristics. However, increased non-specific skeletal uptake may be an important pitfall of this radioligand. Therefore, we aimed to assess the interobserver variation in reporting skeletal 18F-PSMA-1007 uptake on PET/CT.Design/methods: In total, 33 18F-PSMA-1007 PET/CT scans of 21 patients with primary PCa and 12 patients with biochemical recurrence were included, and a total of 85 skeletal lesions were evaluated by three independent observers. The primary endpoint was the interobserver variability of the likelihood of malignancy of the skeletal lesions on both patient and lesion level (kappa analysis).Results: Observers qualified most lesions as not malignant (81–91%) and the overall mean interobserver agreement was moderate on both patient (κ: 0.54) and lesion level (κ: 0.55). In 52 lesions without corresponding CT substrate, the rating resulted in not malignant in 95–100%. Availability of additional imaging (60% of lesions) did not improve interobserver agreement (κ: 0.39 on lesion level) and resulted in unchanged rating for all observers in 78%.Conclusion: This interobserver analysis of skeletal 18F-PSMA-1007 uptake resulted in moderate agreement, in line with rates reported in literature. Importantly, the presence of non-specific skeletal uptake without CT substrate, as a potential shortcoming of 18F-PSMA-1007, did not impair interobserver agreement.</p

Renal sympathetic denervation in patients with vasospastic angina

Background. Sympathetic overactivity has been linked to vasospastic angina (VSA), although the exact pathophysiology of VSA is poorly understood. The purpose of this study is to assess if renal sympathetic denervation (RDN) reduces cardiac sympathetic nerve activity with a subsequent beneficial effect on angina relief in patients with refractory VSA. Methods and results. Cardiac sympathetic nerve activity was assessed prior to procedure and at 6 months post-procedure using iodine-123 labeled meta-iodobenzylguanidine ( 123I-MIBG) imaging. The Seattle Angina questionnaire (SAQ) was used to assess the degree to which the disease impacts quality of life. No significant change was observed in early HMR (pre-RDN: 2.74 [2.10 to 3.21] vs 6 months post-RDN: 2.57 [2.20 to 3.00]; P = 0.76), and late HMR (pre-RDN: 2.56 [2.18 to 3.20] vs 6 months post-RDN: 2.36 [2.13 to 3.22]; P = 0.22). Additionally, no change was seen in WR (P = 0.22). SAQ results revealed significant improvements in perceived physical limitation, angina frequency, and quality of life at 6 months (P < 0.05 for all). Conclusion. RDN resulted in improvements in angina class and quality of life at 6 months in patients with refractory VSA. RDN, however, did not result in significant changes in cardiac sympathetic nerve activity as measured using 123I-MIBG. The latter observation should be considered with caution given the small sample size of this study. Larger studies are needed to assess this further

Is quantitative analysis superior to visual analysis of planar thallium 201 myocardial exercise scintigraphy in the evaluation of coronary artery disease? - Analysis of a prospective clinical study

Quantitative analysis of myocardial exercise scintigraphy has been previously reported to be superior to visual image interpretation for detection of the presence and extent of coronary artery disease. Computer analysis of perfusion defects and washout rate of thallium 201 was performed on scintigrams from a group of 131 consecutive patients (prospective group), using criteria defined from a previous group of 72 patients (initial group), and compared with visual interpretation of scintigrams for detection and evaluation of coronary artery disease. The sensitivity of the quantitative technique with regard to overall detection of coronary artery disease was not significantly different from the visual method (69% and 74%, respectively), whereas the specificity was higher (86% and 68%). Quantitative analysis did not increase the sensitivity of thallium imaging over the visual method in the left anterior descending artery (46% vs 65%) and the right coronary artery (51% vs 72%) but did increase sensitivity in the left circumflex artery (75% vs 47%). Whereas in the initial group quantitative analysis resulted in a better identification of multivessel disease (sensitivity 81 % vs 57%), in the prospective group sensitivity decreased (54% vs 67%) without significant loss of specificity. The initial group had a 40% incidence of three-vessel disease and the prospective group, 22% (P < 0.05). One-vessel disease was higher in the prospective group (32% vs 11%, P < 0.05). Thus, assessing the quantitative technique in a larger prospective patient population, there was no improvement of detection of the presence and extent of coronary artery disease when compared with visual interpretation

インドの人口：1981年センサス概報より

Coronary calcium scoring (CCS) adds to the diagnostic performance of myocardial perfusion single-photon emission computed tomography (SPECT) to assess the presence of significant coronary artery disease (CAD). Patients with a high pre-test likelihood are expected to have a high CCS which potentially could enhance the diagnostic performance of myocardial perfusion SPECT in this specific patient group. We evaluated the added value of CCS to SPECT in the diagnosis of significant CAD in patients with an intermediate to high pre-test likelihood. In total, 129 patients (mean age 62.7 ± 9.7 years, 65 % male) with stable anginal complaints and intermediate to high pre-test likelihood of CAD (median 87 %, range 22-95) were prospectively included in this study. All patients received SPECT and CCS imaging preceding invasive coronary angiography (CA). Fractional flow reserve (FFR) measurements were acquired from patients with angiographically estimated 50-95 % obstructive CAD. For SPECT a SSS > 3 was defined significant CAD. For CCS the optimal cut-off value for significant CAD was determined by ROC curve analysis. The reference standard for significant CAD was a FFR of 182.5. ROC curve analysis for prediction of the presence of significant CAD for SPECT, CCS and the combination of CCS and SPECT resulted in an area under the curve (AUC) of 0.88 (95 % CI 81-94), 0.75 (95 % CI 66-83 %) and 0.92 (95 % CI 87-97 %) respectively. The difference of the AUC between SPECT and the combination of CCS and SPECT was 0.05 (P = 0.12). The addition of CCS did not significantly improve the diagnostic performance of SPECT in the evaluation of patients with a predominantly high pre-test likelihood of CA

Lutetium-177-PSMA-I&amp;T as metastases directed therapy in oligometastatic hormone sensitive prostate cancer, a randomized controlled trial

Background: In recent years, there is increasing evidence showing a beneficial outcome (e.g. progression free survival; PFS) after metastases-directed therapy (MDT) with external beam radiotherapy (EBRT) or targeted surgery for oligometastatic hormone sensitive prostate cancer (oHSPC). However, many patients do not qualify for these treatments due to prior interventions or tumor location. Such oligometastatic patients could benefit from radioligand therapy (RLT) with 177Lu-PSMA; a novel tumor targeting therapy for end-stage metastatic castration-resistant prostate cancer (mCRPC). Especially because RLT could be more effective in low volume disease, such as the oligometastatic status, due to high uptake of radioligands in smaller lesions. To test the hypothesis that 177Lu-PSMA is an effective treatment in oHSPC to prolong PFS and postpone the need for androgen deprivation therapy (ADT), we initiated a multicenter randomized clinical trial. This is globally, the first prospective study using 177Lu-PSMA-I&T in a randomized multicenter setting. Methods & design: This study compares 177Lu-PSMA-I&T MDT to the current standard of care (SOC); deferred ADT. Fifty-eight patients with oHSPC (≤5 metastases on PSMA PET) and high PSMA uptake (SUVmax > 15, partial volume corrected) on 18F-PSMA PET after prior surgery and/or EBRT and a PSA doubling time of < 6 months, will be randomized in a 1:1 ratio. The patients randomized to the interventional arm will be eligible for two cycles of 7.4GBq 177Lu-PSMA-I&T at a 6-week interval. After both cycles, patients are monitored every 3 weeks (including adverse events, QoL- and xerostomia questionnaires and laboratory testing) at the outpatient clinic. Twenty-four weeks after cycle two an end of study evaluation is planned together with another 18F-PSMA PET and (whole body) MRI. Patients in the SOC arm are eligible to receive 177Lu-PSMA-I&T after meeting the primary study objective, which is the fraction of patients who show disease progression during the study follow up. A second primary objective is the time to disease progression. Disease progression is defined as a 100% increase in PSA from baseline or clinical progression. Discussion: This is the first prospective randomized clinical study assessing the therapeutic efficacy and toxicity of 177Lu-PSMA-I&T for patients with oHSPC. Trial registration: Clinicaltrials.gov identifier: NCT04443062

Update to a randomized controlled trial of lutetium-177-PSMA in Oligo-metastatic hormone-sensitive prostate cancer:the BULLSEYE trial

Background: The BULLSEYE trial is a multicenter, open-label, randomized controlled trial to test the hypothesis if 177Lu-PSMA is an effective treatment in oligometastatic hormone-sensitive prostate cancer (oHSPC) to prolong the progression-free survival (PFS) and postpone the need for androgen deprivation therapy (ADT). The original study protocol was published in 2020. Here, we report amendments that have been made to the study protocol since the commencement of the trial. Changes in methods and materials: Two important changes were made to the original protocol: (1) the study will now use 177Lu-PSMA-617 instead of 177Lu-PSMA-I&T and (2) responding patients with residual disease on 18F-PSMA PET after the first two cycles are eligible to receive additional two cycles of 7.4 GBq 177Lu-PSMA in weeks 12 and 18, summing up to a maximum of 4 cycles if indicated. Therefore, patients receiving 177Lu-PSMA-617 will also receive an interim 18F-PSMA PET scan in week 4 after cycle 2. The title of this study was modified to; “Lutetium-177-PSMA in Oligo-metastatic Hormone Sensitive Prostate Cancer” and is now partly supported by Advanced Accelerator Applications, a Novartis Company. Conclusions: We present an update of the original study protocol prior to the completion of the study. Treatment arm patients that were included and received 177Lu-PSMA-I&T under the previous protocol will be replaced. Trial registration: ClinicalTrials.gov NCT04443062. First posted: June 23, 2020

Patterns and Mechanisms of Ancestral Histone Protein Inheritance in Budding Yeast

Tracking of ancestral histone proteins over multiple generations of genome replication in yeast reveals that old histones move along genes from 3′ toward 5′ over time, and that maternal histones move up to around 400 bp during genomic replication