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BackgroundMultiparametric MRI may cause overdiagnosis of clinically significant prostate cancer (csPCa) with the Prostate Imaging Reporting and Data System version 2.1 (PI‐RADS v2.1).ObjectivesTo investigate the diagnostic performance of stiffness as a standalone and complementary marker to PI‐RADS v2.1 for diagnosing csPCa.Study TypeProspective.SubjectsOne hundred forty‐seven participants with pathologically confirmed prostate lesions (≥1 cm), including 71 with csPCa.Field Strength/SequenceT1‐weighted fast spin‐echo, T2‐weighted fast spin‐echo, single‐shot echo‐planar diffusion‐weighted imaging, fast 3D gradient‐echo T1‐weighted dynamic contrast‐enhanced imaging, and 3D single‐shot spin‐echo based echo‐planar MR elastography at 3.0 T.AssessmentThe PI‐RADS v2.1 score was assessed by three radiologists independently. Lesion shear stiffness (SS) values at 60 Hz and 90 Hz were measured. A modified PI‐RADS integrating stiffness with PI‐RADS v2.1 was developed. Diagnostic performance for csPCa was compared between stiffness, PI‐RADS v2.1 and the modified PI‐RADS.Statistical TestSpearman's correlation, Fleiss κ and intraclass correlation, Pearson correlation, one‐way analysis of variance, area under the receiver operating characteristic curve (AUC), and the Delong test. Significance level was P < 0.05.ResultsIn the peripheral zone, csPCa (N = 35) had significantly higher SS than non‐csPCa at 60 Hz (3.22 ± 0.66 kPa vs. 2.56 ± 0.56 kPa) and at 90 Hz (5.64 ± 1.30 kPa vs. 4.48 ± 0.84 kPa). PI‐RADS v2.1 showed 100% sensitivity, 58% specificity, and 0.79 AUC for detecting csPCa. SS achieved 97% sensitivity, 52% specificity, and 0.80 AUC at 60 Hz, while SS had 63% sensitivity, 87% specificity, and 0.78 AUC at 90 Hz. The modified PI‐RADS, combing SS at 60 Hz with PI‐RADS v2.1, resulted in a significantly increased AUC (0.86) compared to that of PI‐RADS v2.1, with a sensitivity of 97% and specificity of 75%.Data ConclusionStiffness can help identifying csPCa in the peripheral zone. Combining stiffness with the PI‐RADS v2.1 improved the diagnostic accuracy and specificity for csPCa.Evidence Level1Technical EfficacyStage 2

BACKGROUND AND OBJECTIVE: This investigation evaluates the safety and efficacy of stereotactic radiosurgery (SRS) vs observation for Koos grade I vestibular schwannomas (VS). METHODS: In a multicenter study, we retrospectively analyzed data of patients with Koos grade I VS who underwent SRS (SRS group) or were observed (observation group). Propensity score matching was used to equilibrate demographics, tumor size, and audiometric data across groups. The outcome analyzed included tumor control, preservation of serviceable hearing, and neurological function. RESULTS: The study matched 142 patients, providing a median follow-up period of 36 months. SRS significantly enhanced tumor control compared with observation, with a 100% control rate at both 5- and 8-year marks in the SRS group vs 48.6% and 29.5% in the observation group at the same time intervals, respectively ( P < .001). Preservation of serviceable hearing outcomes between groups showed no significant difference at 5 and 8 years, ensuring a comparable quality of auditory function (SRS 70.1% vs observation 53.4% at 5 years; P = .33). Furthermore, SRS was associated with a reduced likelihood of tinnitus (odds ratio [OR] = 0.46, P = .04), vestibular dysfunction (OR = 0.17, P = .002), and overall cranial nerve dysfunction (OR = 0.49, P = .03) at last follow-up. CONCLUSION: SRS management of patients with Koos grade I VS was associated with superior tumor control and reduced odds for cranial nerve dysfunction, while not compromising hearing preservation compared with observation. These findings support the safety and efficacy of SRS as a primary care approach for this patient population.

BACKGROUND AND OBJECTIVES: This study assessed the efficacy and safety of stereotactic radiosurgery (SRS) in comparison with watchful waiting for managing Koos grade II vestibular schwannomas (VS). METHODS: A retrospective, multicentric analysis was conducted, focusing on patients with Koos grade II VS who either received SRS (SRS group) or were observed (observation group). To ensure comparability between groups, propensity score matching was used, including factors such as demographic characteristics, tumor dimensions, and hearing assessments. The primary end points examined were tumor control, maintenance of serviceable hearing, and neurological outcomes. RESULTS: A total of 92 patients were equally matched across both cohorts, with a median follow-up of 37 months for the SRS group and 27.5 months for those observed. The SRS cohort exhibited superior tumor control over observation across 3, 5, and 8 years, achieving a 100% control rate vs 47.9%, 40.1%, and 34.3% for the observation group at these time intervals, respectively ( P < .001). Serviceable hearing preservation rates were comparable between the 2 groups throughout 3, 5, and 7 years (72.9% for SRS vs 65.4% for observation at 3 years; P = .86). Moreover, SRS management correlated with a lower incidence of vestibular symptoms (odds ratio = 0.11, P = .002), with no significant disparity in the deterioration of cranial nerve (CN) V or CN VII functions. Notably, the likelihood of experiencing any CN impairment was significantly diminished in the SRS cohort (odds ratio = 0.47, P = .04). CONCLUSION: For patients with Koos grade II VS, SRS offers superior tumor control rate and a lower risk of CN dysfunction without sacrificing hearing preservation.

Abstract Seizure localization is important for managing drug‐resistant focal epilepsy. Here, the capability of a novel deep learning‐based source imaging framework (DeepSIF) for imaging seizure activities from electroencephalogram (EEG) recordings in drug‐resistant focal epilepsy patients is investigated. The neural mass model of ictal oscillations is adopted to generate synthetic training data with spatio‐temporal‐spectra features similar to ictal dynamics. The trained DeepSIF model is rigorously validated using computer simulations and in a cohort of 33 drug‐resistant focal epilepsy patients with high‐density (76‐channel) EEG seizure recordings, by comparing DeepSIF estimates with surgical resection outcome and seizure onset zone (SOZ). These findings show that the trained DeepSIF model outperforms other methods in estimating the spatial and temporal information of origins of ictal activities. It achieves a high spatial specificity of 96% and a low spatial dispersion of 3.80 ± 5.74 mm when compared to the resection region. The source imaging results also demonstrate good coverage of SOZ, with an average distance of 10.89 ± 10.14 mm (from the SOZ to the reconstruction). These promising results suggest that DeepSIF has significant potential for advancing noninvasive imaging of the origins of ictal activities in patients with focal epilepsy, aiding management of intractable epilepsy.

AbstractObjectiveEpilepsy raises critical challenges to accurately localize the epileptogenic zone (EZ) to guide presurgical planning. Previous research has suggested that interictal spikes overlapping with high‐frequency oscillations, referred to here as pSpikes, serve as a reliable biomarker for EZ estimation, but there remains a question as to whether and to how pSpikes perform as compared to other types of epileptic spikes. This study aims to address this question by investigating the source imaging capabilities of pSpikes alongside other spike types.MethodsA total of 2819 interictal spikes from 76‐channel scalp electroencephalography (EEG) were analyzed in a cohort of 24 drug‐resistant focal epilepsy patients. All patients received surgical resection, and 16 were declared seizure‐free based on at least 1 year of postoperative follow‐up. A recently developed electrophysiological source imaging algorithm—fast spatiotemporal iteratively reweighted edge sparsity (FAST‐IRES)—was used for source imaging of the detected interictal spikes. The performance of 217 pSpikes was compared with 772 nSpikes (spikes with irregular high‐frequency activations), 1830 rSpikes (spikes with no high‐frequency activity), and all 2819 aSpikes (all interictal spikes).ResultsThe localization and extent estimation using pSpikes are concordant with the clinical ground truth; using pSpikes yields the best performance compared with nSpikes, rSpikes, and conventional spike imaging (aSpikes). For multiple spike type seizure‐free patients, the mean localization error for pSpike imaging was 6.8 mm, compared with 15.0 mm for aSpikes. The sensitivity, precision, and specificity were .41, .67, and .93 for pSpikes compared with .32, .48, and .93 for aSpikes.SignificanceThese results demonstrate the merits of noninvasive EEG source localization, and that (1) pSpike is a superior biomarker, outperforming conventional spike imaging for the localization of epileptic sources, and especially those with multiple irritative zones; and (2) FAST‐IRES provides accurate source estimation that is highly concordant with clinical ground truth, even in situations of single spike analysis with low signal‐to‐noise ratio.

4591 Background: EV-302 and CheckMate 901 demonstrated significant survival benefit with enfortumab vedotin-pembrolizumab (EVPembro) and gemcitabine-cisplatin-nivolumab (GemCisNivo) as 1L therapy, respectively, in patients (pts) with la/mUC. However, whether these treatments are cost-effective or not remains unclear. Methods: A three-state Markov model (progression-free, progression and death) was developed. State utilities were derived from published literature. State transition probabilities were informed from point-probabilities and hazard ratios for OS and PFS obtained from the latest follow-up of eligible trials. Average sales price (2024 USD) for individual treatments (excluding ancillary charges) were obtained from the center of medicare and medicaid services (US payer’s perspective). Treatment strategies were modeled in accordance with the dose/schedule reported in the eligible trials. Pts who received GemCis or Gem-carboplatin (GemCarbo) and did not progress were modeled to receive Avelumab maintenance. Half-cycle corrected costs and utilities were accrued over a 10-year lifetime horizon and were discounted at 3%. Monte Carlo simulation was used to estimate quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). A willingness-to-pay threshold (WTP) of 100,000$ per QALY was used. Results: In cisplatin-eligible pts, GemCisNivo demonstrated a 0.8 QALY gain over GemCis at an ICER of 21,127 ($/QALY). GemCisNivo was also associated with an incremental net monetary benefit (INMB) of 63,099$ relative to GemCis. EVPembro demonstrated a 2.4 QALY gain over GemCis at an ICER of 915,283 and a 1.6 QALY gain over GemCisNivo at an ICER of 1,406,308. In cisplatin-ineligible pts, EVPembro demonstrated a 2.4 QALY gain over Gem-carboplatin (GemCarbo) at an ICER of 934,761. Price threshold analyses demonstrated that EVPembro is likely to be cost-effective at a cost of 12,344$ for cisplatin-eligible and 13,374$ per cycle for cisplatin-ineligible pts (original cost: 35,665.60$ per cycle). Sensitivity analysis using a total of 12 cycles for EVPembro showed cost-effectiveness at an ICER of 69,594 relative to GemCisNivo in cisplatin-eligible pts, and at an ICER of 53,099 relative to GemCarbo in cisplatin-ineligible pts. Conclusions: In terms of US payer’s perspective, GemCisNivo is most likely to be cost-effective in cisplatin-eligible pts at the WTP of 100,000 $/QALY. Limiting the number of cycles for EVPembro may render it as a cost-effective 1L treatment in la/mUC pts regardless of cisplatin-eligibility status.

Abstract Background Hemoglobin S (HbS) causes sickling disorders. In the laboratory, confirmation of HbS in patient samples with varying percentages is essential. Assessment is routinely performed using capillary electrophoresis (CE) and/or high-performance liquid chromatography. Sickle solubility (SS) exploits decreased solubility of HbS under reducing conditions and is a confirmatory test. SS is unreliable with low HbS, elevated HbF, severe anemia, erythrocytosis, hyperglobulinemia, extreme leukocytosis, hyperlipidemia, or increased serum proteins. Infant samples commonly have low percentages of HbS, high HbF, and limited sample volume. Intact globin chain Mass Spectrometry (MS) is used to identify abnormal hemoglobin variants by detecting the mass change (normal α/β/γ mass =15127/15867/15996 amu), respectively). MS has potential advantages in sensitivity and efficiency over SS and requires lower input sample volume. Herein we compare the utility of MS versus SS for confirmation of HbS. Methods Twenty-three EDTA-anticoagulated blood samples containing low percentages of HbS were identified. SS was performed on 30μL washed packed cells (requires 200μL whole blood) per standard methods. Intact Quadrupole Time-of-Flight MS (Accurate-Mass Q-TOF LC/MS 6520, Agilent Technologies, California) was performed using 10μL whole blood sample in acetonitrile solution reagent and results were compared. HbS and HbF levels were assayed by capillary electrophoresis (Sebia, France) per standard methods. Results Select results are summarized in Table 1. SS detected HbS percentages to 4.8% when HbF was low but not 6% HbS when Hb F is high. MS showed no HbF interference and identified HbS peaks (at 15837 amu) down to 3.1%. HbS percentages &lt;3.1 were undetected by both methods. Conclusions Overall, MS was superior to SS for confirming HbS, particularly in samples with low variant percentage and/or elevated HbF. MS is also optimal when sample volume is minimal, such as for infants. Percentages of HbS &lt;3% require methods such as IEF or DNA sequencing for confirmation.

Stenosis of the left main coronary artery (LM stenosis) is associated with significant mortality and morbidity due to the large area of affected myocardium. Evidence on the use of percutaneous coronary intervention (PCI) for the treatment of LM stenosis is growing. However, the role of Western guidelines on patients in the Asian-Pacific region is unclear due to anatomical variations, substantial heterogeneity in healthcare resources and infrastructure, and the lack of consensus on the optimal management of LM stenosis in the Asia-Pacific region. Hence, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the use of PCI in the management of LM stenosis in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were in support of ‘agree’ or ‘neutral’. The resulting 12 statements provide guidance for clinical practitioners in the region on the use of PCI in the treatment of patients with LM stenosis.

Summary Introduction Obesity is characterized by chronic low‐grade inflammation. This study presents an updated systematic review and meta‐analysis on the effect of caloric restriction (CR) and intermittent fasting (IF) on plasma inflammatory biomarkers (C‐reactive protein [CRP], tumor necrosis factor [TNF]‐alpha, and interleukin [IL]‐6) in individuals with obesity/overweight compared with unrestricted or ad libitum feeding. Methods PubMed, Web of Science, and SCOPUS databases were searched for randomized controlled trials (RCTs) reporting inflammatory biomarkers after at least 8 weeks of intervention. Standardized mean differences (SMDs) were calculated using a fixed effect model. Heterogeneity was determined using I 2 statistics. Sensitivity analysis was conducted using the “leave‐one‐out” approach. Results Relatively few RCTs have investigated the effect of IF on inflammatory biomarkers than with CR (6 vs. 15). Analysis of pooled data showed that CR was associated with a significant reduction in CRP with low heterogeneity (SMD −0.15 mg/L [95% CI −0.30 to −0.00], p = 0.04; I 2 = 0%, p = 0.69) and IL‐6 with high heterogeneity (SMD −0.31 pg/mL [95% CI −0.51 to −0.10], p = 0.004; I 2 = 73%, p = 0.001). IF was associated with a significant decrease in TNF‐alpha with moderate heterogeneity (SMD −0.32 pg/mL [95% CI −0.63 to −0.02], p = 0.04; I 2 = 44%, p = 0.13). No associations were detected between IF and CRP or IL‐6 and CR and TNF‐alpha. Conclusion CR may be more effective in reducing chronic low‐grade inflammation than IF. However, there were some concerns regarding the included studies' randomization and allocation sequence concealment process.

BackgroundVariable flip angle (VFA) and modified Look–Locker inversion recovery (MOLLI) are frequently used for noninvasive evaluation of renal interstitial fibrosis (IF) in chronic kidney disease (CKD). However, controversy remains over which method is preferred.PurposeTo compare the diagnostic efficacy of VFA and MOLLI for T1 mapping in evaluating renal IF.Study TypeProspective.SubjectsFifty‐one participants with CKD (CKD stage 1–5, 35 males) and 18 healthy volunteers (eight males).Field Strength/Sequence3.0 T, three‐dimensional gradient echo sequence for B1+ VFA, and two‐dimensional gradient echo sequence for MOLLI.AssessmentImage quality was assessed on a five‐point scale. Cortex and medulla T1 values (cT1 and mT1), corticomedullary T1 value difference (ΔT1, medulla − cortex), and corticomedullary T1 value ratio (ratio T1, cortex:medulla) were compared between VFA and MOLLI as well as between IF grade (0–4) based on biopsy.Statistical TestsIntraclass correlation coefficient, Bland–Altman analysis, analysis of variance, Kruskal–Wallis test, correlation analysis, and receiver operating characteristics analysis with the area under the curve (AUC). P‐value <0.05 was considered significant.ResultsMOLLI provided significantly better image quality compared to VFA. cT1 and mT1 values significantly differed between VFA and MOLLI (cT1‐VFA: 1771.4 ± 139.4 msec vs. cT1‐MOLLI: 1729.9 ± 132.1 msec; mT1‐VFA: 2076.0 [interquartile range (IQR): 2045.9–2129.9] msec vs. mT1‐MOLLI: 2039.2 [IQR: 1997.8–2071.6] msec). ΔT1 and ratio T1 values were not different between VFA and MOLLI (ΔT1: 300.8 ± 71.4 vs. 306.0 ± 78.4, respectively, P = 0.33 and ratio T1: 0.85 ± 0.038 vs. 0.85 ± 0.041, respectively, P = 0.064). No difference was observed between T1 variables and T1 mapping methods in diagnosing IF.Data ConclusionΔT1 and ratio T1 were not different between VFA and MOLLI. Both VFA and MOLLI are effective for noninvasive assessment of renal IF.Level of Evidence2Technical EfficacyStage 2