Citations

ABSTRACT Purpose Standard spatial‐spectral excitation pulses apply a fly‐back gradient between sub‐pulses, limiting, for example, how thin the slices can be (> 4 mm). Without fly‐back gradients, slices can be as thin as 1.7 mm but require a phase calibration for the sub‐pulses with inverted gradients due to system imperfections. Here we propose and test a fast (< 1 s), localized pre‐scan enabling thin‐slice frequency‐selective excitation. Methods The calibration pre‐scan determines the correction phase between even and odd sub‐pulses by measuring the phase difference of two FIDs excited with either the last or second‐to‐last RF sub‐pulse of the spatial‐spectral pulse. Non‐localized and localized versions of the calibration pre‐scan are tested and validated for water‐only excitation in phantoms and the human heart. As an example, breath‐held coronary MR angiography is performed with a spiral multi‐slice sequence employing the proposed pulses with a slice thickness of 1.7 mm. Results The proposed calibration pre‐scan takes 11.1 ms per slice, whether it is localized or not. Localized calibration phases are validated with an image‐based calibration map. Slice profiles are visualized for pulses with different time‐bandwidth products. Fat is suppressed to below 20% and 25% of the surrounding water signal in both phantoms and the human heart, respectively. High‐quality coronary angiograms are demonstrated in all test subjects. Conclusion Spatial‐spectral pulses without fly‐back gradients can be calibrated quickly (up to 90 slices in 1 s), enabling thinner slices, higher excitation angles, or pulses with sharper slice profiles using waveforms with higher time‐bandwidth products.

Abstract INTRODUCTION Face identification algorithms have increased the risk of study participants being identified through different neuroimaging modalities. De‐facing algorithms can de‐identify neuroimages; however, none are validated in individuals with Down syndrome (DS) – a population at high risk of Alzheimer's disease and the focus of numerous Alzheimer's disease cohort studies. METHODS Overall, 37 adults with DS were parcellated using FreeSurfer before and after de‐facing with mri_reface . A group of neurotypically developed individuals balanced on age, sex, and magnetic resonance imaging scanner manufacturer served as controls. RESULTS De‐facing produced no effect on cortical thickness or volumetrics in adults with DS compared to controls or regional discrimination based on an area under the receiver operating characteristic curve analysis after correcting for multiple comparisons. DISCUSSION FreeSurfer‐derived volumetric and cortical thickness measures changed minimally following de‐facing with mri_reface in adults with DS and are unlikely to influence study outcomes. De‐facing should be considered prior to data sharing in studies of adults with DS.

Through a Delphi process, all 33 panelists reached consensus on topics relating to MRI reporting of knee meniscus lesions, demonstrating that interdisciplinary and multi-institutional standardization is possible.

Abstract Purpose: VV1 is designed to induce selective oncolysis of tumor cells and amplify cellular antitumor immune responses. This open-label, phase I, multicenter clinical trial assessed the safety and tolerability of VV1 monotherapy administered intratumorally or intravenously or administered intravenously in combination with avelumab. Patients and Methods: Patients with advanced solid tumors received intratumoral (n = 27) or intravenous VV1 monotherapy (n = 33) or intravenous VV1 plus avelumab (n = 16). Infusion durations (15–180 minutes) and viral dose (1.7 × 1010 or 1 × 1011 TCID50) were also evaluated. Study objectives included VV1 safety and tolerability, pharmacokinetics, pharmacodynamics, preliminary efficacy, and immune responses. Results: Intratumoral and intravenous VV1 were well tolerated, and injection reactions were infrequent. The most common adverse events of any grade related to VV1 were cytokine release syndrome (58%), fatigue (33%), and decreased lymphocyte count (32%). Virus infection of tumors was confirmed by NIS imaging and increases in serum levels of virally encoded interferon-β (IFNβ). Histologic tumor analysis at 28 days after intratumoral VV1 administration indicated increases in tumor-infiltrating immune cells. Two durable partial responses were recorded: a patient with pheochromocytoma after one intravenous dose of VV1 and a patient with thymic cancer in the combination arm. Stable disease was observed in 17 of 49 patients (34.7%) who received intravenous VV1. Conclusions: This first-in-human study demonstrates that intratumoral or intravenous VV1 administration had an acceptable safety profile as monotherapy and intravenously in combination with avelumab. There is preliminary antitumor activity. Intratumoral VV1 plus cemiplimab is now showing promise in the neoadjuvant setting. Significance: VV1 is a tumor-selective oncolytic vesicular stomatitis virus engineered to express IFNβ and the thyroidal NIS reporter gene. In this phase I study, we have demonstrated that a single administration of VV1, as a monotherapy or with an immune checkpoint inhibitor is safe, infects tumor lesions resulting in intratumoral infiltration of immune cells, and exhibits early signs of antitumor activity in patients with advanced unresectable and metastatic solid tumors.

Abstract Genome sequencing of the heterogeneous primary mitochondrial disorders (PMD) frequently reveals variants of uncertain significance that require functional tests for diagnosis, and does not identify variants in all patients. We analyzed mitochondrial enzyme assays, blue native polyacrylamide gel electrophoresis (BN-PAGE) with in-gel activity staining, complex I assembly blot, and select protein abundances in fibroblasts of a case series of 204 PMD patients divided into functional classes, in comparison to 51 controls and 53 differential diagnostic conditions. Overall, sensitivity and specificity for respiratory chain enzyme assays were 46% and 93% respectively, for BN-PAGE 40% and 98%, for complex I assembly assay 49% and 99%. The overall sensitivity of all tests was 76%, specificity 93%, with positive predictive value 96% and negative predictive value 67%. Categories with high sensitivity were isolated complex deficiencies, nuclear DNA-encoded mitochondrial protein synthesis defects, co-factor defects, and mitochondrial amino-acyl-tRNA synthetase conditions when aided by protein abundance. Mitochondrial DNA mutations and maintenance disorders showed poor sensitivities. Secondary dysfunctions were rare. A complete battery of functional tests showed strong diagnostic clinical utility in fibroblasts. One sentence summary A combination of four mitochondrial functional tests to identify or confirm suspected primary mitochondrial disease in fibroblasts had good sensitivity and excellent specificity, well beyond what was perceived using enzyme assays only.

Introduction The introduction of the purpose‐built single‐port (SP) robotic platform has allowed for the advent of regionalized minimally invasive surgical approaches for robotic radical prostatectomy (RARP), including the extraperitoneal and transvesical techniques. This study sought to develop a best practice consensus on the key principles, patient selection, surgical techniques, expected clinical outcomes, and learning curves pertaining to SP‐RARP. Methods A modified Delphi consensus was developed by a panel of experts, consisting of a 33‐item questionnaire, with each statement rated using a binary Likert scale (‘agree’ or ‘disagree’). The survey was distributed via email to all practicing SP‐RARP surgeons across the USA and Europe. Consensus was defined as ≥75% agreement on a given statement. Results A total of 53 surgeons participated in the Delphi Consensus across the two rounds. Of 33 statements, 28 (84.8%) reached agreement in the first round. The remaining consensus was achieved in the second round, involving 35 surgeons, and with one additional statement. The panel agreed that, although are no absolute contraindications to SP‐RARP, the preference towards specific SP‐RARP techniques should remain guided by the individual patients and surgical expertise. Although the SP extraperitoneal technique is recommended to pursue pelvic lymph node dissections, the panel agreed that transvesical SP‐RARP showed promise in promoting shorter hospital stay, faster recovery of urinary continence, and utility in patients with extensive prior abdominal surgery. Consensus was also reached on the need for a structured training pathway, with most recommending beginning with extraperitoneal SP‐RARP before advancing to the transvesical approach. Conclusion This Delphi consensus demonstrates broad agreement among experienced SP surgeons in the USA and Europe, forming the foundation for future research on the clinical utility and necessary training pathways for SP‐RARP. Nevertheless, empirical validation based on clinical data from large cohort studies remains important.

ABSTRACT Background Readmission is considered as a surgical quality indicator. More data regarding predictors of readmission and outcomes after surgery for colorectal liver metastasis are needed. Using a propensity score match to create a 1:2 match of cases:controls for 90‐day. Readmission, the matching variables used for balance included age, tumor size, estimated blood loss, and type of resection (minor or major). T‐tests were used for continuous measures, Fisher's exact test was used for categorical data, and the Kaplan–Meier method was used to estimate survival. p < 0.05 was considered significant. Methods Retrospectively examined 935 patients with CLM from 2000 to 2018. Using a propensity score match to create a 1:2 match of cases:controls for 90‐day. Readmission, the matching variables used for balance included age, tumor size, estimated blood loss, and type of resection (minor or major). T‐tests were used for continuous measures, Fisher's exact test was used for categorical data, and the Kaplan–Meier method was used to estimate survival. p < 0.05 was considered significant. Results 935 patients were included in the initial sample with 896 eligible for inclusion in the propensity matching. The average age of the population was 59% and 59% male. Overall readmission rate was 8.0%. Median time to readmission was 14 days. In the propensity score matched sample, readmitted patients had higher rates of organ space infection (28% vs 2% and p < 0.0001), bile leak (26% vs 1% and p < 0.0001), and liver failure (9% vs 2% and p = 0.042). There was no difference in LOS (7 days versus six days and p = 0.40), overall survival (median 39.7 vs 41.0 months and p = 0.79), or rate of adjuvant therapy (68% for both and p > 0.99). Conclusion Patients readmitted for intermediate and late complications after surgery for CLM can recover and receive adjuvant therapy with no adverse effect on overall survival. Organ space infection, bile leak, and liver failure are highly associated with readmission.

ABSTRACT Background and Objectives Converging evidence hints at neurodevelopmental effects in genetic frontotemporal degeneration (FTD). In cross-sectional studies, for some genes, young adult FTD variant carriers show differences in brain volumes and cognition compared to familial non-carriers. However, longitudinal trajectories may more sensitively capture FTD-related neurodevelopmental vs. neurodegenerative changes than cross-sectional approaches. This study examined longitudinal trajectories of brain volumes, executive function, and plasma biomarkers in young adult carriers compared to familial non-carriers, as measures of neurodevelopmental and neurodegenerative outcomes of FTD-causing variants. Methods This longitudinal cohort study comprised participants, aged 18-30 years, from the FTD Prevention Initiative across Europe, Canada, and the USA. Genetic groups included C9orf72 (47%), MAPT (30%), and GRN (23%). Linear mixed-effects models were computed to assess longitudinal outcomes across age between groups, controlling for sex, scanner (for brain volumes), and education (for executive function); random effects accounted for between-subject variability nested within family membership. Results Variant carriers ( n =147) and familial non-carriers ( n =113) did not differ in age (mean±SD, 25.9±3.2 years), sex (53% female), or number of visits (2.1±1.7). Young adult C9orf72 repeat expansion carriers exhibited smaller thalamic volumes than non-carriers at the reference age of 26 years ( b =-982.8mm 3 , SE=317.0, p= 0.0046, f 2 =0.32), with relatively stable trajectories across ages 18-30 (i.e., no change over time). Trajectories of rostral anterior cingulate volumes differed in C9orf72 carriers and non-carriers across age, where carriers showed relatively stable trajectories and non-carriers showed age-appropriate declines ( b =64.4mm 3 , SE=29.9, p= 0.035, f 2 =0.07). For MAPT and GRN , there were little to no differences in total brain, cortical, or subcortical volumes between groups and over time. No longitudinal differences were observed between carriers and non-carriers in executive function, or plasma NfL or GFAP for any genetic group. Discussion C9orf72 repeat expansions were linked to smaller average thalamic volumes and stable trajectories between ages 18 to 30, supporting potential neurodevelopmental origins. The modest evidence supporting an absence of difference in neurodegenerative biomarkers and executive function suggests minimal early neurodegeneration and functional preservation in young adulthood.