Ubiquitin Phosphorylation at Thr12 Modulates the DNA Damage Response.

The ubiquitin system regulates the DNA damage response (DDR) by modifying histone H2A at Lys15 (H2AK15ub) and triggering downstream signaling events. Here, we find that phosphorylation of ubiquitin at Thr12 (pUbT12) controls the DDR by inhibiting the function of 53BP1, a key factor for DNA double-strand break repair by non-homologous end joining (NHEJ). Detectable as a chromatin modification on H2AK15ub, pUbT12 accumulates in nuclear foci and is increased upon DNA damage. Mutating Thr12 prevents the removal of ubiquitin from H2AK15ub by USP51 deubiquitinating enzyme, leading to a pronounced accumulation of ubiquitinated chromatin. Chromatin modified by pUbT12 is inaccessible to 53BP1 but permissive to the homologous recombination (HR) proteins RNF169, RAD51, and the BRCA1/BARD1 complex. Phosphorylation of ubiquitin at Thr12 in the chromatin context is a new histone mark, H2AK15pUbT12, that regulates the DDR by hampering the activity of 53BP1 at damaged chromosomes.

Arrhythmic risk profile in mitral valve prolapse: A systematic review and metanalysis of 1715 patients.

INTRODUCTION: Mitral valve prolapse (MVP) is a common clinical condition in the general population. A subgroup of patients with MVP may experience ventricular arrhythmias and sudden cardiac death ("arrhythmic mitral valve prolapse" [AMVP]) but how to stratify arrhythmic risk is still unclear. Our meta-analysis aims to identify predictive factors for arrhythmic risk in patients with MVP. METHODS: We systematically searched Medline, Cochrane, Journals@Ovid, Scopus electronic databases for studies published up to December 28, 2022 and comparing AMVP and nonarrhythmic mitral valve prolapse (NAMVP) for what concerns history, electrocardiographic, echocardiographic and cardiac magnetic resonance features. The effect size was estimated using a random-effect model as odds ratio (OR) and mean difference (MD). RESULTS: A total of 10 studies enrolling 1715 patients were included. Late gadolinium enhancement (LGE) (OR: 16.67; p = .005), T-wave inversion (TWI) (OR: 2.63; p < .0001), bileaflet MVP (OR: 1.92; p < .0001) and mitral anulus disjunction (MAD) (OR: 2.60; p < .0001) were more represented among patients with AMVP than in NAMVP. Patients with AMVP were shown to have longer anterior mitral leaflet (AML) (MD: 2.63 mm; p < .0001), posterior mitral leaflet (MD: 2.96 mm; p < .0001), thicker AML (MD: 0.49 mm; p < .0001), longer MAD length (MD: 1.24 mm; p < .0001) and higher amount of LGE (MD: 1.41%; p < .0001) than NAMVP. AMVP showed increased mechanical dispersion (MD: 8.04 ms; 95% confidence interval: 5.13-10.96; p < .0001) compared with NAMVP. CONCLUSIONS: Our meta-analysis proved that LGE, TWI, bileaflet MVP, and MAD are predictive factors for arrhythmic risk in MVP patients.

Increased prevalence of high-risk coronary plaques in metabolic dysfunction associated stetatotic liver disease patients: A meta-analysis.

BACKGROUND: Metabolic dysfunction associated steatotic liver disease (MASLD) is associated with an increased risk of coronary artery disease. Computed Tomography Coronary Angiography (CTCA) can assess both the extent and the features of coronary plaques. We aimed to gather evidence about the prevalence and features of coronary plaques among MASLD patients. METHODS: PubMed, Scopus, and Google Scholar databases were searched for randomized controlled trials and adjusted observational studies assessing the prevalence and features of coronary plaques by means of CTCA in MASLD patients as compared with a control group. The prevalence of coronary stenosis (defined as >30% and >50% diameter of stenosis), of increasing coronary artery calcium (CAC) score and of high-risk features (namely low-attenuation plaques, napkin ring sign, spotty calcification and positive remodelling) in MASLD patients were the endpoints of interest. RESULTS: Twenty-four observational studies were included. MASLD was associated with an increased prevalence of critical coronary stenosis compared with controls (odds ratio [OR] 1.54, 95%CI 1.23-1.93). Increased values of CAC score were observed in MASLD patients (OR 1.35, 95%CI 1.02-1.78 and OR 2.26, 95%CI 1.57-3.23 for CAC score 0-100 and >100, respectively). An increased risk of 'high-risk' coronary plaques was observed in MASLD patients (OR 2.13, 95%CI 1.42-3.19). As high-risk features plaques, a higher prevalence of positive remodelling and spotty calcification characterize MASLD patients (OR 2.92, 95%CI 1.79-4.77 and OR 2.96, 95%CI 1.22-7.20). CONCLUSIONS: Patients with MASLD are at increased risk of developing critical coronary stenosis and coronary plaques characterized by high-risk features as detected by CTCA.

Value of a short non-contrast CMR protocol in MINOCA.

OBJECTIVES: To evaluate the diagnostic performance of a short non-contrast CMR (ShtCMR) protocol relative to a matched standard comprehensive CMR (StdCMR) protocol in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA). METHODS: This multicenter retrospective study included patients with a working diagnosis of MINOCA who underwent a StdCMR between January 2019 and December 2020. An expert and a non-expert reader performed a blinded reading with the ShtCMR (long-axis cine images, T2w-STIR, T1- and T2-mapping). A consensus reading of the StdCMR (reference standard) was performed at least 3 months after the ShtCMR reading session. Readers were asked to report the following: (1) diagnosis; (2) level of confidence in their diagnosis with the ShtCMR; (3) number of myocardial segments involved, and (4) functional parameters. RESULTS: A total of 179 patients were enrolled. The ShtCMR lasted 21 ± 9 min and the StdCMR 45 ± 11 min (p < 0.0001). ShtCMR allowed reaching the same diagnosis as StdCMR in 85% of patients when interpreted by expert readers (rising from 66% for poor confidence to 99% for good, p = 0.0001) and in 73% (p = 0.01) by non-expert ones (60% for poor vs 89% for good confidence, p = 0.0001). Overall, the ShtCMR overestimated the ejection fraction, underestimated cardiac volumes (p < 0.01), and underestimated the number of segments involved by pathology (p = 0.0008) when compared with the StdCMR. CONCLUSION: The ShtCMR was found to be a debatable alternative to the StdCMR in patients with MINOCA. Nevertheless, when an experienced reader reaches a good or very good diagnostic confidence using the ShtCMR, the reader may choose to stop the examination, reducing the length of the CMR without affecting the patient's diagnosis. CLINICAL RELEVANCE STATEMENT: A short non-contrast CMR protocol may be a viable alternative to standard protocols in selected CMR studies of patients with MINOCA, allowing for faster diagnosis while reducing time and resources and increasing the number of patients who can be scanned. KEY POINTS: • The ShtCMR lasted 21 ± 9 min and the StdCMR 45 ± 11 min (p < 0.0001). • In 57% of patients with MINOCA, the experienced reader considers that contrast medium is probably not necessary for diagnosis without affecting the patient's diagnosis (99% of agreement rate between ShtCMR and StdCMR).

Role of cardiac magnetic resonance in stratifying arrhythmogenic risk in mitral valve prolapse patients: a systematic review and meta-analysis.

OBJECTIVES: To perform a systematic review and meta-analysis of studies investigating the diagnostic value of cardiac magnetic resonance (CMR) features for arrhythmic risk stratification in mitral valve prolapse (MVP) patients. MATERIALS AND METHODS: EMBASE, PubMed/MEDLINE, and CENTRAL were searched for studies reporting MVP patients who underwent CMR with assessment of: left ventricular (LV) size and function, mitral regurgitation (MR), prolapse distance, mitral annular disjunction (MAD), curling, late gadolinium enhancement (LGE), and T1 mapping, and reported the association with arrhythmia. The primary endpoint was complex ventricular arrhythmias (co-VAs) as defined by any non-sustained ventricular tachycardia, sustained ventricular tachycardia, ventricular fibrillation, or aborted sudden cardiac death. Meta-analysis was performed when at least three studies investigated a CMR feature. PROSPERO registration number: CRD42023374185. RESULTS: The meta-analysis included 11 studies with 1278 patients. MR severity, leaflet length/thickness, curling, MAD distance, and mapping techniques were not meta-analyzed as reported in < 3 studies. LV end-diastolic volume index, LV ejection fraction, and prolapse distance showed small non-significant effect sizes. LGE showed a strong and significant association with co-VA with a LogORs of 2.12 (95% confidence interval (CI): [1.00, 3.23]), for MAD the log odds-ratio was 0.95 (95% CI: [0.30, 1.60]). The predictive accuracy of LGE was substantial, with a hierarchical summary ROC AUC of 0.83 (95% CI: [0.69, 0.91]) and sensitivity and specificity rates of 0.70 (95% CI: [0.41, 0.89]) and 0.80 (95% CI: [0.67, 0.89]), respectively. CONCLUSIONS: Our study highlights the role of LGE as the key CMR feature for arrhythmia risk stratification in MVP patients. MAD might complement arrhythmic risk stratification. CLINICAL RELEVANCE STATEMENT: LGE is a key factor for arrhythmogenic risk in MVP patients, with additional contribution from MAD. Combining MRI findings with clinical characteristics is critical for evaluating and accurately stratifying arrhythmogenic risk in MVP patients. KEY POINTS: MVP affects 2-3% of the population, with some facing increased risk for arrhythmia. LGE can assess arrhythmia risk, and MAD may further stratify patients. CMR is critical for MVP arrhythmia risk stratification, making it essential in a comprehensive evaluation.

Development and validation of a clinical decision support system based on PSA, microRNAs, and MRI for the detection of prostate cancer.

OBJECTIVES: The aims of this study are to develop and validate a clinical decision support system based on demographics, prostate-specific antigen (PSA), microRNA (miRNA), and MRI for the detection of prostate cancer (PCa) and clinical significant (cs) PCa, and to assess if this system performs better compared to MRI alone. METHODS: This retrospective, multicenter, observational study included 222 patients (mean age 66, range 46-75 years) who underwent prostate MRI, miRNA (let-7a-5p and miR-103a-3p) assessment, and biopsy. Monoparametric and multiparametric models including age, PSA, miRNA, and MRI outcome were trained on 65% of the data and then validated on the remaining 35% to predict both PCa (any Gleason grade [GG]) and csPCa (GG ≥ 2 vs GG = 1/negative). Accuracy, sensitivity, specificity, positive and negative predictive value (NPV), and area under the receiver operating characteristic curve were calculated. RESULTS: MRI outcome was the best predictor in the monoparametric model for both detection of PCa, with sensitivity of 90% (95%CI 73-98%) and NPV of 93% (95%CI 82-98%), and for csPCa identification, with sensitivity of 91% (95%CI 72-99%) and NPV of 95% (95%CI 84-99%). Sensitivity and NPV of PSA + miRNA for the detection of csPCa were not statistically different from the other models including MRI alone. CONCLUSION: MRI stand-alone yielded the best prediction models for both PCa and csPCa detection in biopsy-naïve patients. The use of miRNAs let-7a-5p and miR-103a-3p did not improve classification performances compared to MRI stand-alone results. CLINICAL RELEVANCE STATEMENT: The use of miRNA (let-7a-5p and miR-103a-3p), PSA, and MRI in a clinical decision support system (CDSS) does not improve MRI stand-alone performance in the detection of PCa and csPCa. KEY POINTS: • Clinical decision support systems including MRI improve the detection of both prostate cancer and clinically significant prostate cancer with respect to PSA test and/or microRNA. • The use of miRNAs let-7a-5p and miR-103a-3p did not significantly improve MRI stand-alone performance. • Results of this study were in line with previous works on MRI and microRNA.

PARP1 proximity proteomics reveals interaction partners at stressed replication forks.

PARP1 mediates poly-ADP-ribosylation of proteins on chromatin in response to different types of DNA lesions. PARP inhibitors are used for the treatment of BRCA1/2-deficient breast, ovarian, and prostate cancer. Loss of DNA replication fork protection is proposed as one mechanism that contributes to the vulnerability of BRCA1/2-deficient cells to PARP inhibitors. However, the mechanisms that regulate PARP1 activity at stressed replication forks remain poorly understood. Here, we performed proximity proteomics of PARP1 and isolation of proteins on stressed replication forks to map putative PARP1 regulators. We identified TPX2 as a direct PARP1-binding protein that regulates the auto-ADP-ribosylation activity of PARP1. TPX2 interacts with DNA damage response proteins and promotes homology-directed repair of DNA double-strand breaks. Moreover, TPX2 mRNA levels are increased in BRCA1/2-mutated breast and prostate cancers, and high TPX2 expression levels correlate with the sensitivity of cancer cells to PARP-trapping inhibitors. We propose that TPX2 confers a mitosis-independent function in the cellular response to replication stress by interacting with PARP1.

Phase separation of 53BP1 determines liquid-like behavior of DNA repair compartments.

The DNA damage response (DDR) generates transient repair compartments to concentrate repair proteins and activate signaling factors. The physicochemical properties of these spatially confined compartments and their function remain poorly understood. Here, we establish, based on live cell microscopy and CRISPR/Cas9-mediated endogenous protein tagging, that 53BP1-marked repair compartments are dynamic, show droplet-like behavior, and undergo frequent fusion and fission events. 53BP1 assembly, but not the upstream accumulation of γH2AX and MDC1, is highly sensitive to changes in osmotic pressure, temperature, salt concentration and to disruption of hydrophobic interactions. Phase separation of 53BP1 is substantiated by optoDroplet experiments, which further allowed dissection of the 53BP1 sequence elements that cooperate for light-induced clustering. Moreover, we found the tumor suppressor protein p53 to be enriched within 53BP1 optoDroplets, and conditions that disrupt 53BP1 phase separation impair 53BP1-dependent induction of p53 and diminish p53 target gene expression. We thus suggest that 53BP1 phase separation integrates localized DNA damage recognition and repair factor assembly with global p53-dependent gene activation and cell fate decisions.

Imaging for the assessment of the arrhythmogenic potential of mitral valve prolapse.

Mitral valve prolapse (MVP) is the most common valve disease in the western world and recently emerged as a possible substrate for sudden cardiac death (SCD). It is estimated an annual risk of sudden cardiac death of 0.2 to 1.9% mostly caused by complex ventricular arrhythmias (VA). Several mechanisms have been recognized as potentially responsible for arrhythmia onset in MVP, resulting from the combination of morpho-functional abnormality of the mitral valve, structural substrates (regional myocardial hypertrophy, fibrosis, Purkinje fibers activity, inflammation), and mechanical stretch. Echocardiography plays a central role in MVP diagnosis and assessment of severity of regurgitation. Several abnormalities detectable by echocardiography can be prognostic for the occurrence of VA, from morphological alteration including leaflet redundancy and thickness, mitral annular dilatation, and mitral annulus disjunction (MAD), to motion abnormalities detectable with "Pickelhaube" sign. Additionally, speckle-tracking echocardiography may identify MVP patients at higher risk for VA by detection of increased mechanical dispersion. On the other hand, cardiac magnetic resonance (CMR) has the capability to provide a comprehensive risk stratification combining the identification of morphological and motion alteration with the detection of myocardial replacement and interstitial fibrosis, making CMR an ideal method for arrhythmia risk stratification in patients with MVP. Finally, recent studies have suggested a potential role in risk stratification of new techniques such as hybrid PET-MR and late contrast enhancement CT. The purpose of this review is to provide an overview of the mitral valve prolapse syndrome with a focus on the role of imaging in arrhythmic risk stratification. CLINICAL RELEVANCE STATEMENT: Mitral valve prolapse is the most frequent valve condition potentially associated with arrhythmias. Imaging has a central role in the identification of anatomical, functional, mechanical, and structural alterations potentially associated with a higher risk of developing complex ventricular arrhythmia and sudden cardiac death. KEY POINTS: • Mitral valve prolapse is a common valve disease potentially associated with complex ventricular arrhythmia and sudden cardiac death. • The mechanism of arrhythmogenesis in mitral valve prolapse is complex and multifactorial, due to the interplay among multiple conditions including valve morphological alteration, mechanical stretch, myocardial structure remodeling with fibrosis, and inflammation. • Cardiac imaging, especially echocardiography and cardiac magnetic resonance, is crucial in the identification of several features associated with the potential risk of serious cardiac events. In particular, cardiac magnetic resonance has the advantage of being able to detect myocardial fibrosis which is currently the strongest prognosticator.

Patient-reported persistent symptoms after radiotherapy and association with quality of life for prostate cancer survivors.

PURPOSE: To evaluate the persistence of symptoms after radiotherapy (RT) for localised prostate cancer (PCa) and the association with quality of life (QOL). MATERIALS AND METHODS: Prospective patient-reported outcome (PRO) from a multi-institutional study on PCa treated with radical RT (2010-2014) was analysed. Data was collected at baseline (BL) and follow-ups (FUPs) up to 5 years. Patients with BL and ≥3 late FUPs (≥6 months) were analysed. PRO was scored by means of the IPSS and ICIQ-SF (urinary), LENT-SOMA (gastrointestinal [GI]), and EORTC-C30 (pain, insomnia, fatigue, and QOL) questionnaires. Symptoms were defined 'persistent' if the median score over FUPs was ≥3 (urinary) or ≥2 (GI, pain, insomnia, and fatigue), and worse than BL. Different thresholds were chosen to have enough events for each symptom. QOL was linearly transformed on a continuous scale (0-100). Linear-mixed models were used to identify significant differences between groups with and without persistent symptoms including age, smoking status, previous abdominal surgery, and diabetes as confounders. Mean QOL differences between groups were evaluated longitudinally over FUPs. RESULTS: The analysis included 293 patients. Persistent urinary symptoms ranged from 2% (straining) to 12% (weak stream, and nocturia). Gastrointestinal symptoms ranged from 7% (rectal pain, and incontinence) to 30% (urgency). Proportions of pain, insomnia, and fatigue were 6, 13, and 18%. Significant QOL differences of small-to-medium clinical relevance were found for urinary incontinence, frequency, urgency, and nocturia. Among GI symptoms, rectal pain and incontinence showed small-to-medium differences. Fatigue was associated with the largest differences. CONCLUSIONS: The analysis showed that symptoms after RT for PCa occur with different persistence and their association with QOL varies in magnitude. A number of persistent urinary and GI symptoms showed differences in a comparable range. Urinary incontinence and frequency, rectal pain, and faecal incontinence more often had significant associations. Fatigue was also prevalent and associated with largely deteriorated QOL.

Management of radiation-induced oral mucositis in head and neck cancer patients: a real-life survey among 25 Italian radiation oncology centers.

AIM: Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian RT centers. METHODS: A 40-question survey was administered to 25 radiation oncologists working in 25 different RT centers across Italy. RESULTS: A total of 1554 HNC patients have been treated in the participating centers in 2021, the majority (median across the centers 91%) with curative intent. Median treatment time was 41 days, with a mean percentage of interruption due to toxicity of 14.5%. Eighty percent of responders provide written oral cavity hygiene recommendations. Regarding RIOM prevention, sodium bicarbonate mouthwashes, oral mucosa barrier agents, and hyaluronic acid-based mouthwashes were the most frequent topic agents used. Regarding RIOM treatment, 14 (56%) centers relied on literature evidence, while internal guidelines were available in 13 centers (44%). Grade (G)1 mucositis is mostly treated with sodium bicarbonate mouthwashes, oral mucosa barrier agents, and steroids, while hyaluronic acid-based agents, local anesthetics, and benzydamine were the most used in mucositis G2/G3. Steroids, painkillers, and anti-inflammatory drugs were the most frequent systemic agents used independently from the RIOM severity. CONCLUSION: Great variety of strategies exist among Italian centers in RIOM management for HNC patients. Whether different strategies could impact patients' compliance and overall treatment time of the radiation course is still unclear and needs further investigation.

Myocardial Late Contrast Enhancement CT in Troponin-Positive Acute Chest Pain Syndrome.

Background Acute chest pain with mild troponin rise and inconclusive diagnosis after clinical evaluation represents a diagnostic challenge. Triple-rule-out (TRO) CT may exclude coronary artery disease (CAD), as well as acute aortic syndrome and pulmonary embolism, but cannot help identify other causes of myocardial injury. Purpose To investigate the diagnostic value of a comprehensive CT protocol including both an angiographic and a late contrast enhancement (LCE) scan in participants with troponin-positive acute chest pain. Materials and Methods In this prospective study, consecutive patients with troponin-positive acute chest pain or anginal equivalent and inconclusive diagnosis after clinical evaluation (symptoms, markers, electrocardiography, and echocardiography) who underwent TRO CT between June 2018 and September 2020 were enrolled. TRO CT was performed to evaluate the presence of obstructive CAD (stenosis ≥50%), acute aortic syndrome, and pulmonary embolism. If the findings on the TRO CT scan were negative, an LCE CT scan was acquired after 10 minutes to assess the presence and pattern of scar and quantify the myocardial extracellular volume fraction. CT-based diagnoses were compared with diagnoses obtained with reference standard methods, including invasive coronary angiography, cardiac MRI, and endomyocardial biopsy. Results Eighty-four patients (median age, 69 years [interquartile range, 50-77 years]; 45 men) were enrolled. TRO CT helped identify obstructive CAD in 35 participants (42%), acute aortic syndrome in one (1.2%), and pulmonary embolism in six (7.1%). LCE CT scans were acquired in the remaining 42 participants. The following diagnoses were reached with use of LCE CT: myocarditis (22 of 42 participants [52%]), takotsubo cardiomyopathy (four of 42 [10%]), amyloidosis (three of 42 [7.1%]), myocardial infarction with nonobstructed coronary arteries (three of 42 [7.1%]), dilated cardiomyopathy (two of 42 [4.8%]), and negative or inconclusive findings (eight of 42 [19%]). The addition of LCE CT improved the diagnostic rate of TRO CT from 42 of 84 participants (50% [95% CI: 38.9, 61.1]) to 76 of 84 (90% [95% CI: 82.1, 95.8]) (P < .001). Conclusion A CT protocol including triple-rule-out and late contrast enhancement CT scans improved diagnostic rate in participants presenting with acute chest pain syndrome. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Nagpal and Bluemke in this issue.

Diagnostic accuracy of coronary computed tomography angiography for the evaluation of obstructive coronary artery disease in patients referred for transcatheter aortic valve implantation: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of coronary computed tomography angiography (CCTA) for the evaluation of obstructive coronary artery disease (CAD) in patients referred for transcatheter aortic valve implantation (TAVI). METHODS: EMBASE, PubMed/MEDLINE, and CENTRAL were searched for studies reporting accuracy of CCTA for the evaluation of obstructive CAD compared with invasive coronary angiography (ICA) as the reference standard. QUADAS-2 tool was used to assess the risk of bias. A bivariate random effects model was used to analyze, pool, and plot the diagnostic performance measurements across studies. Pooled sensitivity, specificity, positive ( + LR) and negative (-LR) likelihood ratio, diagnostic odds ratio (DOR), and hierarchical summary ROC curve (HSROC) were evaluated. Prospero registration number: CRD42021252527. RESULTS: Fourteen studies (2533 patients) were included. In the intention-to-diagnose patient-level analysis, sensitivity and specificity for CCTA were 97% (95% CI: 94-98%) and 68% (95% CI: 56-68%), respectively, and + LR and -LR were 3.0 (95% CI: 2.1-4.3) and 0.05 (95% CI: 0.03 - 0.09), with DOR equal to 60 (95% CI: 30-121). The area under the HSROC curve was 0.96 (95% CI: 0.94-0.98). No significant difference in sensitivity was found between single-heartbeat and other CT scanners (96% (95% CI: 90 - 99%) vs. 97% (95% CI: 94-98%) respectively; p = 0.37), whereas the specificity of single-heartbeat scanners was higher (82% (95% CI: 66-92%) vs. 60% (95% CI: 46 - 72%) respectively; p < 0.0001). Routine CCTA in the pre-TAVI workup could save 41% (95% CI: 34 - 47%) of ICAs if a disease prevalence of 40% is assumed. CONCLUSIONS: CCTA proved an excellent diagnostic accuracy for assessing obstructive CAD in patients referred for TAVI; the use of single-heartbeat CT scanners can further improve these findings. KEY POINTS: • CCTA proved to have an excellent diagnostic accuracy for assessing obstructive CAD in patients referred for TAVI. • Routine CCTA in the pre-TAVI workup could save more than 40% of ICAs. • Single-heartbeat CT scanners had higher specificity than others in the assessment of obstructive CAD in patients referred for TAVI.

mEPE-score: a comprehensive grading system for predicting pathologic extraprostatic extension of prostate cancer at multiparametric magnetic resonance imaging.

OBJECTIVE: To investigate the diagnostic accuracy of the PI-RADS v2.1 multiparametric magnetic resonance imaging (mpMRI) features in predicting extraprostatic extension (mEPE) of prostate cancer (PCa), as well as to develop and validate a comprehensive mpMRI-derived score (mEPE-score). METHODS: We retrospectively reviewed all consecutive patients admitted to two institutions for radical prostatectomy for PCa with available records of mpMRI performed between January 2015 and December 2020. Data from one institution was used for investigating diagnostic performance of each mEPE feature using radical prostatectomy specimens as benchmark. The results were implemented in a mEPE-score as follows: no mEPE features: 1; capsular abutment: 2; irregular or spiculated margin: 3; bulging prostatic contour, or asymmetry of the neurovascular bundles, or tumor-capsule interface > 1.0 cm: 4; ≥ 2 of the previous three parameters or measurable extraprostatic disease: 5. The performance of mEPE features was evaluated using the five diagnostic parameters and ROC curve analysis. RESULTS: Two-hundred patients were enrolled at site 1 and 76 at site 2. mEPE features had poor sensitivities ranging from 0.08 (0.00-0.15) to 0.71 (0.59-0.83), whereas specificity ranged from 0.68 (0.58-0.79) to 1.00. mEPE-score showed excellent discriminating ability (AUC > 0.8) and sensitivity = 0.82 and specificity = 0.77 with a threshold of 3. mEPE-score had AUC comparable to ESUR-score (p = 0.59 internal validation; p = 0.82 external validation), higher than or comparable to mEPE-grade (p = 0.04 internal validation; p = 0.58 external validation), and higher than early-and-late-EPE (p < 0.0001 internal and external validation). There were no significant differences between readers having different expertise with EPE-score (p = 0.32) or mEPE-grade (p = 0.45), but there were significant differences for ESUR-score (p = 0.02) and early-versus-late-EPE (p = 0.03). CONCLUSIONS: The individual mEPE features have low sensitivity and high specificity. The use of mEPE-score allows for consistent and reliable assessment for pathologic EPE. KEY POINTS: • Individual PI-RADS v2.1 mpMRI features had poor sensitivities ranging from 0.08 (0.00-0.15) to 0.71 (0.59-0.83), whereas Sp ranged from 0.68 (0.58-0.79) to 1.00. • mEPE-score is an all-inclusive score for the assessment of pEPE with excellent discriminating ability (i.e., AUC > 0.8) and Se = 0.82, Sp = 0.77, PPV = 0.74, and NPV = 0.84 with a threshold of 3. • The diagnostic performance of the expert reader and beginner reader with pEPE-score was comparable (p = 0.32).

Cardiac magnetic resonance imaging of myocarditis and pericarditis following COVID-19 vaccination: a multicenter collection of 27 cases.

OBJECTIVES: To assess clinical and cardiac magnetic resonance (CMR) imaging features of patients with peri-myocarditis following Coronavirus Disease 2019 (COVID-19) vaccination. METHODS: We retrospectively collected a case series of 27 patients who underwent CMR in the clinical suspect of heart inflammation following COVID-19 vaccination, from 16 large tertiary centers. Our patient's cohort was relatively young (36.6 ± 16.8 years), predominately included males (n = 25/27) with few comorbidities and covered a catchment area of approximately 8 million vaccinated patients. RESULTS: CMR revealed typical mid-subepicardial non-ischemic late gadolinium enhancement (LGE) in 23 cases and matched positively with CMR T2 criteria of myocarditis. In 7 cases, typical hallmarks of acute pericarditis were present. Short-term follow-up (median = 20 days) from presentation was uneventful for 25/27 patients and unavailable in two cases. CONCLUSIONS: While establishing a causal relationship between peri-myocardial inflammation and vaccine administration can be challenging, our clinical experience suggests that CMR should be performed for diagnosis confirmation and to drive clinical decision-making and follow-up. KEY POINTS: • Acute onset of dyspnea, palpitations, or acute and persisting chest pain after COVID-19 vaccination should raise the suspicion of possible myocarditis or pericarditis, and patients should seek immediate medical attention and treatment to help recovery and avoid complications. • In case of elevated troponin levels and/or relevant ECG changes, cardiac magnetic resonance should be considered as the best non-invasive diagnostic option to confirm the diagnosis of myocarditis or pericarditis and to drive clinical decision-making and follow-up.

Quantitative assessment of HCC wash-out on CT is a predictor of early complete response to TACE.

OBJECTIVES: To investigate the predictive value of four-phase contrast-enhanced CT (CECT) for early complete response (CR) to drug-eluting-bead transarterial chemoembolization (DEB-TACE), with a particular focus on the quantitatively assessed wash-in and wash-out. METHODS: A retrospective analysis of preprocedural CECTs was performed for 129 HCC nodules consecutively subjected to DEB-TACE as first-line therapy. Lesion size, location, and margins were recorded. For the quantitative analysis, the following parameters were computed: contrast enhancement ratio (CER) and lesion-to-liver contrast ratio (LLC) as estimates of wash-in; absolute and relative wash-out (WOabs and WOrel) and delayed percentage attenuation ratio (DPAR) as estimates of wash-out. The early radiological response of each lesion was assessed by the mRECIST criteria and dichotomized in CR versus others (partial response, stable disease, and progressive disease). RESULTS: All quantitatively assessed wash-out variables had significantly higher rates for CR lesions (WOabs p = 0.01, WOrel p = 0.01, and DPAR p = 0.00002). However, only DPAR demonstrated an acceptable discriminating ability, quantified by AUC = 0.80 (95% CI0.73-0.88). In particular, nodules with DPAR ≥ 120 showed an odds ratio of 3.3(1.5-7.2) for CR (p = 0.0026). When accompanied by smooth lesion margins, DPAR ≥ 120 lesions showed a 78% CR rate at first follow-up imaging. No significative association with CR was found for quantitative wash-in estimates (CER and LLC). CONCLUSIONS: Based on preprocedural CECT, the quantitative assessment of HCC wash-out is useful in predicting early CR after DEB-TACE. Among the different formulas for wash-out quantification, DPAR has the best discriminating ability. When associated, DPAR ≥ 120 and smooth lesion margins are related to relatively high CR rates. KEY POINTS: • A high wash-out rate, quantitatively assessed during preprocedural four-phase contrast-enhanced CT (CECT), is a favorable predictor for early radiological complete response of HCC to drug-eluting-bead chemoembolization (DEB-TACE). • The arterial phase of CECT shows great dispersion of attenuation values among different lesions, even when a standardized protocol is used, limiting its usefulness for quantitative analyses. • Among the different formulas used to quantify the wash-out rate (absolute wash-out, relative wash-out, and delayed percentage attenuation ratio), the latter (DPAR), based only on the delayed phase, is the most predictive (AUC = 0.80), showing a significant association with complete response for values above 120.

MRI index lesion radiomics and machine learning for detection of extraprostatic extension of disease: a multicenter study.

OBJECTIVES: To build a machine learning (ML) model to detect extraprostatic extension (EPE) of prostate cancer (PCa), based on radiomics features extracted from prostate MRI index lesions. METHODS: Consecutive MRI exams of patients undergoing radical prostatectomy for PCa were retrospectively collected from three institutions. Axial T2-weighted and apparent diffusion coefficient map images were annotated to obtain index lesion volumes of interest for radiomics feature extraction. Data from one institution was used for training, feature selection (using reproducibility, variance and pairwise correlation analyses, and a correlation-based subset evaluator), and tuning of a support vector machine (SVM) algorithm, with stratified 10-fold cross-validation. The model was tested on the two remaining institutions' data and compared with a baseline reference and expert radiologist assessment of EPE. RESULTS: In total, 193 patients were included. From an initial dataset of 2436 features, 2287 were excluded due to either poor stability, low variance, or high collinearity. Among the remaining, 14 features were used to train the ML model, which reached an overall accuracy of 83% in the training set. In the two external test sets, the SVM achieved an accuracy of 79% and 74% respectively, not statistically different from that of the radiologist (81-83%, p = 0.39-1) and outperforming the baseline reference (p = 0.001-0.02). CONCLUSIONS: A ML model solely based on radiomics features demonstrated high accuracy for EPE detection and good generalizability in a multicenter setting. Paired to qualitative EPE assessment, this approach could aid radiologists in this challenging task. KEY POINTS: • Predicting the presence of EPE in prostate cancer patients is a challenging task for radiologists. • A support vector machine algorithm achieved high diagnostic accuracy for EPE detection, with good generalizability when tested on multiple external datasets. • The performance of the algorithm was not significantly different from that of an experienced radiologist.

Feature tracking myocardial strain analysis in patients with bileaflet mitral valve prolapse: relationship with LGE and arrhythmias.

OBJECTIVES: Anatomical substrate and mechanical trigger co-act in arrhythmia's onset in patients with bileaflet mitral valve prolapse (bMVP). Feature tracking (FT) may improve risk stratification provided by cardiac magnetic resonance (CMR). The aim was to investigate differences in CMR and FT parameters in bMVP patients with and without complex arrhythmias (cVA and no-cVA). METHODS: In this retrospective study, 52 patients with bMVP underwent 1.5 T CMR and were classified either as no-cVA (n = 32; 12 males; 49.6 ± 17.4 years) or cVA (n = 20; 3 males; 44.7 ± 11.2 years), the latter group including 6 patients (1 male; 45.7 ± 12.7 years) with sustained ventricular tachycardia or ventricular fibrillation (SVT-FV). Twenty-four healthy volunteers (11 males, 36.2 ± 12.5 years) served as control. Curling, prolapse distance, mitral annulus disjunction (MAD), and late gadolinium enhancement (LGE) were recorded and CMR-FT analysis performed. Statistical analysis included non-parametric tests and binary logistic regression. RESULTS: LGE and MAD distance were associated with cVA with an odds ratio (OR) of 8.51 for LGE (95% CI 1.76, 41.28; p = 0.008) and of 1.25 for MAD (95% CI 1.02, 1.54; p = 0.03). GLS 2D (- 11.65 ± 6.58 vs - 16.55 ± 5.09 1/s; p = 0.04), PSSR longitudinal 2D (0.04 ± 1.62 1/s vs - 1.06 ± 0.35 1/s; p = 0.0001), and PSSR radial 3D (3.95 ± 1.97 1/s vs 2.64 ± 1.03 1/s; p = 0.0001) were different for SVT-VF versus the others. PDSR circumferential 2D (1.10 ± 0.54 vs. 0.84 ± 0.34 1/s; p = 0.04) and 3D (0.94 ± 0.42 vs. 0.69 ± 0.17 1/s; p = 0.04) differed between patients with and without papillary muscle LGE. CONCLUSIONS: CMR-FT allowed identifying subtle myocardial deformation abnormalities in bMVP patients at risk of SVT-VF. LGE and MAD distance were associated with cVA. KEY POINTS: • CMR-FT allows identifying several subtle myocardial deformation abnormalities in bMVP patients, especially those involving the papillary muscle. • CMR-FT allows identifying subtle myocardial deformation abnormalities in bMVP patients at risk of SVT and VF. • In patients with bMVP, the stronger predictor of cVA is LGE (OR = 8.51; 95% CI 1.76, 41.28; p = 0.008), followed by MAD distance (OR = 1.25; 95% CI 1.02, 1.54; p = 0.03).

Effects of different levels of CT iterative reconstruction on low-contrast detectability and radiation dose in patients of different sizes: an anthropomorphic phantom study.

PURPOSE: The purpose of this study was to verify the maintenance of low-contrast detectability at different CT dose reduction levels, in patients of different sizes, as a consequence of the application of iterative reconstruction at different strengths combined with tube current modulation. METHODS: Anthropomorphic abdominal phantoms of two sizes (small and large) were imaged at a fixed noise with iterative algorithm ASIR-V percentages in the range between 0 and 70% and corresponding dose reductions in the range of 0-83%. A total of 1400 images with and without liver low-contrast simulated lesions were evaluated by five radiologists, using the receiver operating characteristics (ROC) paradigm and evaluating the area under the ROC curve (AUC). The human observer results were then compared with AUC obtained with a channelized Hotelling observer (CHO). CNR values were also calculated. RESULTS: For the small phantom, the AUC values lie between 0.90 and 0.93 for human evaluations of images acquired without iterative reconstruction, with 30% ASIR-V and with 50% ASIR-V. The AUC decreased significantly to 0.81 (p = 0.0001) at 70% ASIR-V. The CHO results were in coherence with human observer scores. Also, similar results were observed for the large size phantom. CNR values were stable for the different ASIR-V percentages. CONCLUSIONS: The iterative algorithm maintained the low-contrast detectability up to a dose reduction of about 70%, following application of a 50% ASIR-V combined with automatic tube current modulation, regardless of the phantom size. At further dose reductions using greater iterative percentages, a significant decrease in detectability was observed.

Early T1 Myocardial MRI Mapping: Value in Detecting Myocardial Hyperemia in Acute Myocarditis.

Background Hyperemia is a key component of acute myocarditis (AM). Early gadolinium uptake because of myocardial hyperemia may be quantified by using T1 mapping. Purpose To evaluate the value of early enhanced T1 shortening for the diagnosis of acute myocarditis. Materials and Methods Study participants suspected of having AM and healthy control (HC) participants were prospectively enrolled from September 2016 to May 2019. Participants underwent 1.5-T cardiac MRI including Lake Louise criteria, T2 mapping, native T1, and extracellular volume, with the addition of early enhanced T1 mapping (2 minutes after intravenous administration of 0.15 mmol/kg gadobutrol). Color-coded maps of the percentage of T1 shortening from precontrast to early postcontrast were generated. Optimal early T1 shortening cut-off value and its diagnostic performance in the identification of acute myocarditis were calculated. Results Forty-five study participants with AM (median age, 40 years; interquartile range [IQR], 20-46 years; 22 women) diagnosed according to multidisciplinary clinical evaluation, electrocardiography, laboratory test, echocardiography, cardiac MRI, and coronary CT and/or invasive angiography. Findings were confirmed by endomyocardial biopsy in 64% (29 of 45) of participants. MRI parameters were compared with 19 HC participants (median age, 39 years; IQR, 28-46 years; seven women). Median early T1 shortening was 75% (IQR, 72%-78%) in participants with AM versus 65% (IQR, 61%-66%) in HC participants (P < .001). Early T1 shortening showed high diagnostic performance (area under the receiver operating characteristic curve [AUC], 0.97; 95% confidence interval [CI]: 0.94, 1.00) and excellent interobserver reproducibility (intraclass correlation coefficient: 0.98; 95% CI: 0.96, 1.00). Early T1 shortening of 70% or greater identified acute myocarditis with 93% sensitivity, 100% specificity, and 95% diagnostic accuracy. Early T1 shortening had better diagnostic performance than late percentage T1 shortening (AUC, 0.97 vs 0.90, respectively; P = .03) and extracellular volume (AUC, 0.97 vs 0.88, respectively; P = .046), and similar to native T1 (AUC, 0.97 vs 0.93, respectively; P = .63) and T2 mapping (AUC, 0.97 vs 0.97, respectively; P > .99). Conclusion In this proof-of-concept study, percentage of T1 shortening at early enhanced T1 mapping showed high accuracy for the diagnosis of acute myocarditis. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by De Cecco and Monti in this issue.