Search

Improved neural understanding of posttraumatic growth (PTG) is required for effective trauma care. PTG is the advantageous psychological change some individuals derive from their struggle to overcome trauma. This comprehensive review critically examined the limited neural PTG research, to identify electrophysiological training targets for future research examining neurofeedback to enhance PTG, and provides novel insights into the emerging neural theory of PTG. PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) informed the process. Findings from the studies N=8 (participants N=765) revealed PTG was correlated with left-lateralised alpha frequency power patterns. Specifically, PTG was associated with lower left frontal alpha power, higher left central alpha power, and lower parietal alpha power. Differences between studies may identify different components of PTG-related neural circuitry, or represent variations in PTG and sub-factor strength, mechanistic differences between studies, or the potential confounding presence of posttraumatic stress disorder (PTSD). While lower alpha power has been associated with higher PTSD in existing literature, higher left central alpha power was associated with lower PTSD. Therefore, alpha upregulation neurofeedback delivered over the sensorimotor cortex of the brain, around left central EEG electrode C3, presented the most promising neurofeedback target., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Patients with stable chest pain suspected of coronary artery disease (CAD) usually undergo multiple diagnostic tests to confirm or rule out obstructive CAD. Some tests may not effectively assess the presence of CAD, precluding optimal treatment. A diagnostic strategy of upfront computed tomography coronary angiography (CTCA) combined with optimal medical therapy (OMT) tailored to the extent of CAD may be superior to standard care in preventing major adverse cardiac events., Study Design: The CLEAR-CAD trial is a prospective, open-label, multicentre, randomised, superiority trial of an upfront CTCA-guided strategy in 6444 patients presenting in an outpatient setting with suspected CAD compared with standard care, in approximately 30 participating centres in the Netherlands. The upfront CTCA-guided strategy consists of an initial CTCA which is assessed using the Coronary Artery Disease-Reporting and Data System (CAD-RADS 2.0). In patients without CAD (CAD-RADS 0) no specific cardiac medication is mandated. Patients with non-obstructive CAD (CAD-RADS 1-2) are treated with preventive OMT. Patients with obstructive CAD (CAD-RADS ≥ 3) are treated with preventive and anti-anginal OMT; in the presence of pharmacologically refractory symptoms patients undergo selective revascularisation after non-invasive functional imaging for myocardial ischaemia (≥ 10%). Patients with significant left main or proximal left anterior descending coronary artery stenosis on CTCA undergo direct invasive coronary angiography and subsequent revascularisation. The primary endpoint is the composite of all-cause death and myocardial infarction., Conclusion: The CLEAR-CAD trial is the first randomised study to investigate the efficacy of a combined upfront CTCA-guided medical and selective revascularisation strategy in an outpatient setting with suspected CAD compared with standard care., (© 2024. The Author(s).)

Background and Objectives: Serum neurofilament light (sNfL) is a biomarker for neuro-axonal damage in multiple sclerosis (MS). Clinical implementation remains limited. We investigated the impact of implementation on clinical decisions using questionnaires at the MS Center Amsterdam, a tertiary outpatient clinic., Methods: sNfL assessments were added to routine clinical practice (August 2021-December 2022). Before and after the results, clinicians filled in questionnaires on context of testing, clinical decisions, certainty herein, expectation of magnetic resonance imaging (MRI) activity, urgency, and motivation to receive the sNfL result and perceived value of sNfL., Results: sNfL was assessed in 166 cases (age 41 ± 12 years, 68% female, 64% disease-modifying therapy (DMT) use) for the following contexts: "DMT monitoring" (55%), "new symptoms" (18%), "differential diagnosis" (17%), and "DMT baseline" (11%). Clinical decisions changed in 19.3% of cases post-disclosure, particularly in context "new symptoms" (38%) and with higher sNfL levels (β = 0.03, p = 0.04). Certainty increased ( p = 0.004), while expectation of MRI activity decreased with disclosure of low sNfL levels ( p = 0.01). Motivation was highest in context "differential diagnosis" ( p < 0.001); perceived value and urgency were highest in context "new symptoms" ( p = 0.02)., Conclusion: In this study, sNfL implementation had considerable impact on clinical decision-making and certainty herein. Standard implementation may complement patient care but warrants caution and more exploration in diverse clinical settings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Z.Y.G.J.v.L., M.H.J.W., W.M.L.L., B.M., S.N.H., and L.H. report no disclosures. B.A.d.J. receives research support from Dutch MS Research Foundation, National MS Foundation, Dutch MS Association, and Zorgverzekeraars Nederland (i.e. umbrella organization of health insurers in the Netherlands). N.M., L.A.M., B.W.v.O., N.S., Z.L.E.v.K., L.V., M.J.W., and E.M.M.S. report no disclosures. B.M.J.U. reports consultancy fees from Immunic Therapeutics. J.K. received research grants for multicentre investigator-initiated trials DOT-MS trial, ClinicalTrials.gov Identifier: NCT04260711 (ZonMW), and BLOOMS trial (ZonMW and Treatmeds), ClinicalTrials.gov Identifier: NCT05296161; received consulting fees for F. Hoffmann-La Roche Ltd, Biogen, Teva, Merck, Novartis, and Sanofi/Genzyme (all payments to institution); reports speaker relationships with F. Hoffmann-La Roche Ltd, Biogen, Immunic, Teva, Merck, Novartis, and Sanofi/Genzyme (all payments to institution); adjudication committee of MS clinical trial of Immunic (payments to institution only). C.E.T. reports funding from National MS Society (Progressive MS alliance) and Innovative Medicines Initiatives 3TR (Horizon 2020, grant no. 831434); has a research contract with Celgene; serves on editorial boards of Medidact Neurologie/Springer, Neurology: Neuroimmunology and Neuroinflammation, and is an editor of a Neuromethods book Springer.

Background and Objective: Biochemical recurrence (BCR) of prostate cancer (PCa) after curative radiotherapy (RT) is defined according to the Phoenix criteria, which is a prostate-specific antigen (PSA) rise of ≥2.0 ng/ml above the PSA nadir. Prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) can identify PCa recurrences at very low PSA values. Our aim was to investigate the detection rate and extent of PCa recurrences using PSMA PET/CT after curative RT among patients with a PSA rise of ≥2.0 ng/ml above the nadir (Phoenix positive, Ph + ) and patients not reaching this threshold (Phoenix negative, Ph - ) and to compare therapeutic management and clinical outcomes in terms of time to androgen deprivation therapy (ADT) and castration-resistance PCa (CRPC), as well as overall survival., Methods: We conducted a retrospective analysis of the Prostate Cancer Network Amsterdam (2015-2023) cohort of 568 patients who received curative-intent RT for PCa. Data on PSMA PET/CT outcomes, therapeutic management, and clinical follow-up were collected, including (re)initiation of ADT, progression to CRPC, and survival. Results were compared between groups using logistic regression and survival analyses., Key Findings and Limitations: The study cohort comprised 222 patients (39.1%) classified as Ph - and 346 (60.9%) classified as Ph + . PSMA-avid lesions were detected in 170 Ph - patients (76.6%) and 322 (93.1%) Ph + patients. In these groups, 75.9% of Ph - patients and 45.0% of Ph + patients were eligible for local salvage therapy (odds ratio [OR 3.84]; p < 0.001). Distant metastases were less frequent in the Ph - group (n = 37, 21.8%) than in the Ph + group (n = 157, 48.8%; OR 0.29; p < 0.001). Survival analyses revealed longer times to ADT (re)initiation and progression to CRPC, as well as lower overall mortality, in the Ph - group (log-rank p < 0.001). The retrospective study design is the main limitation., Conclusions and Clinical Implications: For patients with PCa recurrence, PSMA PET/CT can detect this recurrence in the majority of cases not meeting the Phoenix criteria for BCR. Early imaging detects recurrences at a less advanced disease stage, allowing potential salvage treatments. In addition, early PSMA PET/CT is associated with longer times to ADT (re)initiation and progression to CRPC, as well as longer overall survival. These positive clinical implications warrant confirmation of our results in prospective studies to reduce potential leadtime bias., Patient Summary: We investigated early use of a special type of scan called PSMA PET (prostate-specific membrane antigen positron emission tomography) in patients with suspicion of recurrence of their prostate cancer after radiotherapy. Early scans can detect recurrence before the cancer progresses to a more advanced stage., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Diffusion magnetic resonance imaging (dMRI) allows non-invasive assessment of brain tissue microstructure. Current model-based tissue microstructure reconstruction techniques require a large number of diffusion gradients, which is not clinically feasible due to imaging time constraints, and this has limited the use of tissue microstructure information in clinical settings. Recently, approaches based on deep learning (DL) have achieved promising tissue microstructure reconstruction results using clinically feasible dMRI. However, it remains unclear whether the subtle tissue changes associated with disease or age are properly preserved with DL approaches and whether DL reconstruction results can benefit clinical applications. Here, we provide the first evidence that DL approaches to tissue microstructure reconstruction yield reliable brain tissue microstructure analysis based on clinically feasible dMRI scans. Specifically, we reconstructed tissue microstructure from four different brain dMRI datasets with only 12 diffusion gradients, a clinically feasible protocol, and the neurite orientation dispersion and density imaging (NODDI) and spherical mean technique (SMT) models were considered. With these results we show that disease-related and age-dependent alterations of brain tissue were accurately identified. These findings demonstrate that DL tissue microstructure reconstruction can accurately quantify microstructural alterations in the brain based on clinically feasible dMRI., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Frederik Barkhof acts as a consultant for Bayer-Schering, Biogen-Idec, GeNeuro, Ixico, Merck-Serono, Novartis and Roche. He has received grants, or grants are pending, from the Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) initiative, the Biomedical Research Centre at University College London Hospitals, the Dutch MS Society, ECTRIMS–MAGNIMS, EU-H2020, the Dutch Research Council (NWO), the UK MS Society, and the National Institute for Health Research, University College London. He has received payments for the development of educational presentations from Ixico and his institution from Biogen-Idec and Merck. He is on the editorial board of Radiology, Neuroradiology, Multiple Sclerosis Journal and Neurology., (Copyright © 2024. Published by Elsevier Inc.)

Steady-State Visual Evoked Potentials (SSVEPs) are brain responses measurable via electroencephalography (EEG) in response to continuous visual stimulation at a constant frequency. SSVEPs have been instrumental in advancing our understanding of human vision and attention, as well as in the development of brain-computer interfaces (BCIs). Ongoing questions remain about which type of visual stimulus causes the most potent SSVEP response. The current study investigated the effects of color, size, and flicker frequency on the signal-to-noise ratio of SSVEPs, complemented by pupillary light reflex measurements obtained through an eye-tracker. Six participants were presented with visual stimuli that differed in terms of color (white, red, green), shape (circles, squares, triangles), size (10,000 to 30,000 pixels), flicker frequency (8 to 25 Hz), and grouping (one stimulus at a time vs. four stimuli presented in a 2×2 matrix to simulate a BCI). The results indicated that larger stimuli elicited stronger SSVEP responses and more pronounced pupil constriction. Additionally, the results revealed an interaction between stimulus color and flicker frequency, with red being more effective at lower frequencies and white at higher frequencies. Future SSVEP research could focus on the recommended waveform, interactions between SSVEP and power grid frequency, a wider range of flicker frequencies, a larger sample of participants, and a systematic comparison of the information transfer obtained through SSVEPs, pupil diameter, and eye movements., (Creative Commons Attribution license.)

Coronary CT angiography (CCTA) offers an efficient and reliable tool for the non-invasive assessment of suspected coronary artery disease through the analysis of coronary artery plaque and stenosis. However, the detailed manual analysis of CCTA is a burdensome task requiring highly skilled experts. Recent advances in artificial intelligence (AI) have made significant progress toward a more comprehensive automated analysis of CCTA images, offering potential improvements in terms of speed, performance and scalability. This work offers an overview of the recent developments of AI in CCTA. We cover methodological advances for coronary artery tree and whole heart analysis, and provide an overview of AI techniques that have shown to be valuable for the analysis of cardiac anatomy and pathology in CCTA. Finally, we provide a general discussion regarding current challenges and limitations, and discuss prospects for future research., (© 2024. The Author(s).)

The Coronary Artery Disease-Reporting and Data System (CAD-RADS) is a standardised reporting method which was created in order to improve communication with referring physicians as well as for management considerations. The CAD-RADS score denotes the absence or presence of stenosis, while plaque burden and potential modifiers provide insight into plaque extent and characteristics. The modifier ischaemia enables the incorporation of fractional flow reserve CT and CT perfusion, while the modifier exception is used to denote potential coronary abnormalities. Higher CAD-RADS categories demonstrate incremental prognostic value, with further improvement when taking plaque burden into account. CAD-RADS improves communication with the referring clinician as well as guiding therapeutic management and as such is relevant to uniform patient care in the Netherlands., (© 2024. The Author(s).)

Background and Purpose: Diffusion-weighted imaging (DWI) using single-shot echo planar imaging (DW-EPI) is susceptible to distortions around air-filled cavities and dental fillings, typical for the head and neck area. Non-EPI, Split acquisition of fast spin echo signals for diffusion imaging (DWSPLICE) could reduce these distortions and enhance image quality, thereby potentially improving recurrence assessment in squamous cell carcinoma (SCC) of the head and neck region. This study evaluated whether DW-SPLICE is a viable alternative to DW-EPI through quantitative and qualitative analyses., Materials and Methods: The DW-SPLICE sequence was incorporated into the standard 3.0T head and neck MRI protocol with DW-EPI. Retrospective analysis was conducted on two subgroups: firstly benign or malignant lesions, and secondly post-treatment SCC recurrence. In both subgroups Image quality and distortion were scored by two independent radiologists, blinded for DW-technique, and evaluated using mixed-effect linear models. Lesion apparent diffusion coefficient (ADC) values were assessed with inter-class correlation (ICC) and Bland-Altman analyses. DWI's delineation geometric similarity to T1-weighted post-contrast (T1Wc) MRI was evaluated using the Dice Similarity Coefficient (DSC) before and after registration. Recurrence in post-treatment SCC scans was evaluated by the same two radiologists blinded for DW-technique. Recurrence detection rates were then compared between DW-SPLICE and DW-EPI using mixed logistic regression at six months and at one-year post-scan follow-up data., Results: From August 2020 to January 2022, 55 benign or malignant lesion scans (55 patients) and 74 post-treatment SCC scans (66 patients) were analyzed. DW-SPLICE scored better on image quality and showed less overall distortion than DW-EPI (0.04

Background: Progressive isolated optic nerve glioma (ONG) in children is a rare disease, treated with various modalities. A global treatment consensus is not available., Methods: We conducted a national retrospective multicenter cohort study (1995-2020) to investigate how different treatment strategies impact outcome for ONG in children, by assessing treatment responses to systemic anticancer therapy (SAT), surgery, and radiotherapy for ONG. The primary endpoints included changes in best-corrected visual acuity (BCVA) and tumor volume (TV) on MRI, both evaluated at the start and end of therapy and at long-term follow up., Results: A total of 21 ONGs (20 patients) received SAT (n = 14 (66.7%)), surgery (n = 4 (19.0%)), and radiotherapy (n = 3 (14.3%)). After SAT BCVA stabilized or improved in 66.6% (n = 4) and the TV decreased by a median of 45.1% (range: -88.6% to +31.5%) (n = 13). Before resection two eyes were already blind. After resection BCVA decreased to blindness in one eye. In total all four eyes were blind after resection. After first-line RT BCVA decreased in 66.7% of ONG to counting fingers or less, TV increased <3 months after RT by a median of 47.3% (range: -42.8% to +245.1%) (n = 3), followed by a long-term decrease of 94.4 and 13.8% (n = 2), respectively., Conclusion: SAT appears to be the preferred modality for progressive ONG in case of potential rescue of visual functions. Complete resection of ONG appears effective to reduce proptosis in case of preexisting blindness. The use of radiotherapy requires careful consideration due to the risk of severe visual impairment and secondary disease., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Introduction: The novel positron emission tomography (PET) imaging tracer, [ 18 F]F-AraG, targets activated T-cells, offering a potential means to improve our understanding of immune-oncological processes. The aim of this study was to determine the optimal pharmacokinetic model to quantify tumour lesion [ 18 F]F-AraG uptake in patients with non-small cell lung cancer (NSCLC), and to validate simplified measures at different time intervals against the pharmacokinetic uptake parameter., Methods: Ten patients with early-stage NSCLC and three patients with advanced NSCLC underwent a dynamic PET scan of minimal 60 min. Venous and/or arterial blood sampling was obtained at maximum seven time points. Tumour lesion time activity curves and metabolite-corrected input functions were analysed using single-tissue reversible (1T2k), two-tissue irreversible (2T3k) and two-tissue reversible (2T4k) plasma input models. Simplified uptake measures, such as standardised uptake value (SUV) and tumour-to-blood (TBR) or tumour-to-plasma ratio (TPR), were evaluated for different time intervals., Results: Whole-blood and plasma radioactivity concentrations showed rapid clearance of [ 18 F]F-AraG. Metabolite analysis revealed a low rate of metabolism, at 70 min p.i., on average, 79% (SD = 9.8%) of the total radioactivity found in blood corresponded to intact [ 18 F]F-AraG. The time activity curves were best fitted by the 2T3k model. Strong positive correlations were found for SUV (body weight (BW), lean body mass (LBM) or body surface area (BSA) corrected), TBR and TPR for any time interval between 20 and 70 min p.i. against the 2T3k-derived K i . The correlation of TBR at 60-70 min p.i. with 2T3K-derived K i (r (df = 20) = 0.87, p < 0.01), was stronger than for SUV BW (r (df = 20) = 0.80, p < 0.01)., Conclusion: Tumour lesion [ 18 F]F-AraG uptake in patients with NSCLC is characterised by a 2T3k model. TBR and TPR show most potential for simplified quantification of tumour lesion [ 18 F]F-AraG uptake in patients with NSCLC., (© 2024. The Author(s).)

The prediction of the risk of developing complications after colorectal surgery for colorectal carcinoma remains imprecise. Body composition measurements on a computed tomography (CT) scan can potentially contribute to a better preoperative risk assessment. The aim of this systematic review is to evaluate the evidence for the use of body composition measurements on CT scans to predict short-term complications after colorectal cancer surgery. A literature search (in PubMed, Embase and Web of Science) was performed up to 1 August 2022. Two researchers independently screened the articles, extracted data and assessed the quality of the studies using the Quality in Prognosis Studies tool. The primary outcome measure was the occurrence of complications within 30 days after surgery. Meta-analysis was conducted using a random-effects model to synthesize a pooled odds ratio (OR). The study protocol was registered in PROSPERO (CRD42021281010). Forty-five articles with a total of 16 537 patients were included. In total, 26 body composition measures were investigated: 8 muscle-related measures, 11 adipose tissue measures, 4 combined muscle and adipose tissue measures, and 3 other measures. These were investigated as potential predictors for more than 50 differently defined postoperative complications. Meta-analysis was only possible for two measurements and showed that higher amounts of visceral fat increase the risk of developing overall complications (OR: 2.52 [1.58-4.00], P < 0.0001) and anastomotic leakage (OR: 1.76 [1.17-2.65], P = 0.006). A wide variety of body composition measurements on preoperative CT scans have been investigated as a predictive factor for postoperative complications. Visceral fat appeared to be associated with overall complications and anastomotic leakage; however, the association is weak, and its clinical relevance or applicability is questionable. The current evidence is limited by methodological heterogeneity and the risk of bias. To improve comparability of results across studies and improve decision-making, future studies should use standardized methods for measuring body composition on CT scans, outcome definitions and statistical analyses., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Purpose: The purpose of this study is to provide a detailed description of the anatomy and radiology of the medial sleeve and present an approach in its management among elite athletes., Methods: Five cases of elite athletes who underwent treatment for a medial sleeve injury of which the diagnosis was confirmed through physical examination and additional magnetic resonance imaging scan are described in this study., Results: Two patients presented with isolated medial sleeve injuries, while the other three patients suffered from concomitant ankle injuries. Non-operative treatment consisted of relative rest, soft cast immobilization and mobilization in a walking boot or kinesiotape which was successful in four of the cases with regard to the medial sleeve. One patient underwent surgery due to syndesmotic instability. Another patient presented with combined medial and lateral ankle instability which was treated surgically with an open medial and lateral ligament repair. All patients were able to return to their pre-injury sports and at the time of the last follow-up were still playing in their pre-injury level of competition., Conclusion: Medial sleeve injuries of the ankle in elite athletes should be considered in the differential diagnosis for athletes presenting with medial ankle pain. Inherent knowledge regarding anatomy is essential when guiding the management of these injuries which can be treated successfully with a non-operative approach consisting of relative rest, immobilization, kinesiotape and physical therapy. In case of persistent medial instability or rotational instability, surgical repair is a viable treatment option. Both modalities allow athletes to return to the pre-injury level of competition. However, early diagnosis is crucial to minimize the delay of appropriate treatment and avoid potential residual symptoms., Level of Evidence: Level IV., (© 2024 The Author(s). Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Introduction: Pathogenic variants in the gene encoding for BMPR2 are a major genetic risk factor for heritable pulmonary arterial hypertension. Owing to incomplete penetrance, deep phenotyping of unaffected carriers of a pathogenic BMPR2 variant through multimodality screening may aid in early diagnosis and identify susceptibility traits for future development of pulmonary arterial hypertension., Methods: 28 unaffected carriers (44±16 years, 57% female) and 21 healthy controls (44±18 years, 48% female) underwent annual screening, including cardiac magnetic resonance imaging, transthoracic echocardiography, cardiopulmonary exercise testing and right heart catheterisation. Right ventricular pressure-volume loops were constructed to assess load-independent contractility and compared with a healthy control group. A transgenic Bmpr2 Δ71Ex1/+ rat model was employed to validate findings from humans., Results: Unaffected carriers had lower indexed right ventricular end-diastolic (79.5±17.6 mL·m -2 versus 62.7±15.3 mL·m -2 ; p=0.001), end-systolic (34.2±10.5 mL·m -2 ; p=0.014) and left ventricular end-diastolic (68.9±14.1 mL·m versus 27.1±8.3 mL·m -2 ; p=0.014) and left ventricular end-diastolic (68.9±14.1 mL·m -2 versus 58.5±10.7 mL·m -2 ; p<0.001) and end-systolic elastance (0.28±0.07  Bmpr2 Δ71Ex1/+ rats were also observed to have smaller cardiac volumes than wild-type rats. Pressure-volume loop analysis showed that unaffected carriers had significantly higher afterload (arterial elastance 0.15±0.06  versus 0.27±0.08 mmHg·mL -1 1.36±0.37; p=0.006). During the 4-year follow-up period, two unaffected carriers developed pulmonary arterial hypertension, with normal N-terminal pro-brain natriuretic peptide and transthoracic echocardiography indices at diagnosis.versus 0.35±0.10 mmHg·mL -1 ; p=0.047) in addition to lower right ventricular pulmonary artery coupling (end-systolic elastance/arterial elastance 2.24±1.03 versus 1.36±0.37; p=0.006). During the 4-year follow-up period, two unaffected carriers developed pulmonary arterial hypertension, with normal N-terminal pro-brain natriuretic peptide and transthoracic echocardiography indices at diagnosis., Conclusion: Unaffected BMPR2 mutation carriers have an altered cardiac phenotype mimicked in Bmpr2 Δ71Ex1/+ transgenic rats. Future efforts to establish an effective screening protocol for individuals at risk for developing pulmonary arterial hypertension warrant longer follow-up periods., Competing Interests: Conflicts of interest: F. Perros reports grants from French National Research Agency (ANR-20-CE14-0006) and INSERM (International Research Project (IRP) (Paris – Porto Pulmonary Hypertension Collaborative Laboratory (3PH)). D. Montani reports grants from Janssen, MSD and Acceleron; consultation fees from Janssen, MSD, Ferrer and Acceleron; and payment or honoraria for lectures, presentations, manuscript writing or educational events from Bayer, Janssen, Boehringer, Chiesi, GSK, Ferrer and Merck MSD. A. Vonk Nordegraaf reports research grants from Janssen, MSD and Ferrer. L. Zhao reports grants from British Heart Foundation (PG/18/2/33446 and BHF RE/18/4/34215). F.S. de Man reports support for the present study from Royal Netherlands Academy of Sciences (CVON-2017-10 Dolphin-Genesis); grants from Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organisation for Health Research and Development, The Netherlands Organisation for Scientific Research (NWO-VICI: 918.16.610, NWO-VIDI: 917.18.338), Royal Netherlands Academy of Sciences (CVON-2012-08 PHAEDRA and CVON-2018-29 PHAEDRA-IMPACT) and Dutch Heart Foundation (Post doc Dekker 2018T05). H-J. Bogaard reports support for the present study from Royal Netherlands Academy of Sciences (CVON-2017-10 Dolphin-Genesis); grants from MSD, Ferrer, Janssen, Dutch Federation of University Medical Centres, Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Netherlands Organisation for Health Research and Development, and the Royal Netherlands Academy of Sciences (CVON-2012-08 PHAEDRA and CVON-2018-29 PHAEDRA-IMPACT). The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is often diagnosed late in acute pulmonary embolism survivors: more efficient testing to expedite diagnosis may considerably improve patient outcomes. The InShape II algorithm safely rules out CTEPH (failure rate 0.29%) while requiring echocardiography in only 19% of patients but may be improved by adding detailed reading of the computed tomography pulmonary angiography diagnosing the index pulmonary embolism., Methods: We evaluated 12 new algorithms, incorporating the CTEPH prediction score, ECG reading, N‑terminal pro-brain natriuretic peptide levels and dedicated computed tomography pulmonary angiography reading, in the international InShape II cohort (n=341) and part of the German FOCUS cohort (n=171). Evaluation criteria included failure rate, defined as the incidence of confirmed CTEPH in pulmonary embolism patients in whom echocardiography was deemed unnecessary by the algorithm, and the overall net reclassification index compared to the InShape II algorithm., Results: The algorithm starting with computed tomography pulmonary angiography reading of the index pulmonary embolism for six signs of CTEPH, followed by ECG/N-terminal pro-brain natriuretic peptide level assessment and echocardiography resulted in the most beneficial change compared to InShape II, with a need for echocardiography in 20% (+5%), a failure rate of 0% and a net reclassification index of +3.5%, reflecting improved performance over the InShape II algorithm. In the FOCUS cohort, this approach lowered echocardiography need to 24% (-6%) and missed no CTEPH cases, with a net reclassification index of +6.0%., Conclusion: Dedicated computed tomography pulmonary angiography reading of the index pulmonary embolism improved the performance of the InShape II algorithm and may improve the selection of pulmonary embolism survivors who require echocardiography to rule out CTEPH., Competing Interests: Conflict of interest: S. Barco received research support from Boston Scientific, Medtronic, Concept Medical, Sanofi and Novartis, all outside this manuscript. M. Delcroix received consulting fees from Actelion/Janssen/J&J, Acceleron/MSD, Gossamer and Ferrer; and payment or honoraria for lectures, presentations, manuscript writing or educational events from Actelion/Janssen/J&J, Acceleron/MSD and Ferrer, all outside the submitted work. L. Jara-Palomares reports grants from Daichii, Rovi, GlaxoSmithKline, BMS, Leo Pharma, MSD and Johnson and Johnson. H. Vliegen received grants from Johnson and Johnson; payment or honoraria for lectures, presentations, manuscript writing or educational events from Novartis and Boehringer Ingelheim; and participates on a data safety monitoring board or advisory board for Amarin and Daiichi Sankyo. S.V. Konstantinides reports grants or contacts from Daiichi Sankyo; consulting fees from Boston Scientific, Inari Medical, Bayer AG, Penumbra Inc. and Daiichi Sankyo; and payment or honoraria for lectures, presentations, manuscript writing or educational events from Boston Scientific and Penumbra Inc., all outside of the submitted work. F.A. Klok received research support from Bayer, BMS, BSCI, AstraZeneca, MSD, Leo Pharma, Actelion, Farm-X, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Foundation, The Dutch Heart Foundation and the Horizon Europe Program, all outside this manuscript. The remaining authors declare no competing interests., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts multiple anatomical sites. Whether this is due to the virus itself or is a secondary effect caused by the influx and activation of immune cells is not known. Positron emission tomography (PET) with immunoglobulins can provide insights into which sites and cells are activated in a living animal. Our aim is to use two nanobodies as tools to monitor (1) the distribution of antigen presenting cells (APC) by virtue of their Mafa-DR expression profile, (2) virus-infected cells and viral particles using a nanobody against the SARS-CoV-2 spike protein. Two [ 89 Zr]-labeled nanobodies that target the SARS-CoV-2 spike protein and major histocompatability complex (MHC) class II antigens (Mafa-DR), respectively, are used to monitor their distribution during an experimental SARS-CoV-2 infection in a nonhuman primate model. Scans are obtained before infection and on Day 3 and 10 post infection (pi) in two macaques each. The [ 89 Zr]anti-SARS-CoV-2 spike nanobody localized to SARS-CoV-2-associated lung lesions and the nasal mucosa, while the [ 89 Zr]anti-human leukocyte antigen (HLA)-DR nanobody was predominantly found in non-affected lung tissue after infection. We also detected, pi, upregulation of the Mafa-DR signal, indicative of recruitment of professional APCs, in the superior sagittal sinus. [ 89 Zr]-labeled nanobodies show recruitment of macrophages/monocytes in non-lesional lung tissue in cynomolgus macaques after experimental infection with SARS-CoV-2, as well as accumulation of the spike protein in both lung lesions and the nasal mucosa during infection. These results show the possibility of in vivo monitoring the quality and quantity of immune responses during the initial stages of an infection., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Background Mammographic background characteristics may stimulate human visual adaptation, allowing radiologists to detect abnormalities more effectively. However, it is unclear whether density, or another image characteristic, drives visual adaptation. Purpose To investigate whether screening performance improves when screening mammography examinations are ordered for batch reading according to mammographic characteristics that may promote visual adaptation. Materials and Methods This retrospective multireader multicase study was performed with mammograms obtained between September 2016 and May 2019. The screening examinations, each consisting of four mammograms, were interpreted by 13 radiologists in three distinct orders: randomly, by increasing volumetric breast density (VBD), and based on a self-supervised learning (SSL) encoding (examinations automatically grouped as "looking similar"). An eye tracker recorded radiologists' eye movements during interpretation. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of random-ordered readings were compared with those of VBD- and SSL-ordered readings using mixed-model analysis of variance. Reading time, fixation metrics, and perceived density were compared using Wilcoxon signed-rank tests. Results Mammography examinations (75 with breast cancer, 75 without breast cancer) from 150 women (median age, 55 years [IQR, 50-63]) were read. The examinations ordered by increasing VBD versus randomly had an increased AUC (0.93 [95% CI: 0.91, 0.96] vs 0.92 [95% CI: 0.89, 0.95]; P = .009), without evidence of a difference in specificity (89% [871 of 975] vs 86% [837 of 975], P = .04) and sensitivity (both 81% [794 of 975 vs 788 of 975], P = .78), and a reduced reading time (24.3 vs 27.9 seconds, P < .001), fixation count (47 vs 52, P < .001), and fixation time in malignant regions (3.7 vs 4.6 seconds, P < .001). For SSL-ordered readings, there was no evidence of differences in AUC (0.92 [95% CI: 0.89, 0.95]; P = .70), specificity (84% [820 of 975], P = .37), sensitivity (80% [784 of 975], P = .79), fixation count (54, P = .05), or fixation time in malignant regions (4.6 seconds, P > .99) compared with random-ordered readings. Reading times were significantly higher for SSL-ordered readings compared with random-ordered readings (28.4 seconds, P = .02). Conclusion Screening mammography examinations ordered from low to high VBD improved screening performance while reducing reading and fixation times. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Grimm in this issue.

Purpose: To investigate if changes in vessel density (VD) and the foveal avascular zone (FAZ) occur in the preclinical phase of Alzheimer's disease (pAD) over time., Methods: Optical coherence tomography angiography (OCTA) was used to image VD and FAZ at baseline and for a follow-up period of 2 years. Positron emission tomography (PET) was used to determine the amyloid beta (Aβ) status of participants., Results: The VD and FAZ of 148 participants (54% female) were analyzed at baseline and follow-up (mean time between measurements, 2.24 ± 0.35 years). The mean age of the participants was 68.3 ± 6.0 years at baseline and 70.3 ± 5.9 years at follow-up. Participants were divided into three groups: control group, participants who had negative Aβ status at both measurements (Aβ-, n = 116); converter group, participants who transitioned from negative to positive between baseline and follow-up (Aβ-+, n = 18); and participants who were consistently positive at both visits (Aβ++, n = 14). The VD of both Aβ+ groups demonstrated non-significant increases over time in both macula and optic nerve head (ONH) regions. The Aβ- group was found to be significantly higher in both ONH and macular regions. The VD of the Aβ++ group was significantly higher in the macula inner and outer rings compared to the Aβ-+ and Aβ- groups. No significant change was found in FAZ values over time., Conclusions: Alterations in VD seem to manifest already in pAD, exhibiting distinct variations between the ONH and macula. Further longitudinal studies with a longer follow-up design and known amyloid pathology should be undertaken to validate these observations.

Methods to shorten [ 18 F]FDG Patlak PET imaging procedures ranging from 65-90 to 20-30 min after injection, using a population-averaged input function (PIF) scaled to patient-specific image-derived input function (IDIF) values, were recently evaluated. The aim of the present study was to explore the feasibility of ultrashort 10-min [ 18 F]FDG Patlak imaging at 55-65 min after injection using a PIF combined with direct Patlak reconstructions to provide reliable quantitative accuracy of lung tumor uptake, compared with a full-duration 65-min acquisition using an IDIF. Methods: Patients underwent a 65-min dynamic PET acquisition on a long-axial-field-of-view (LAFOV) Biograph Vision Quadra PET/CT scanner. Subsequently, direct Patlak reconstructions and image-based (with reconstructed dynamic images) Patlak analyses were performed using both the IDIF (time to relative kinetic equilibrium between blood and tissue concentration (t*) = 30 min) and a scaled PIF at 30-60 min after injection. Next, direct Patlak reconstructions were performed on the system console using only the last 10 min of the acquisition, that is, from 55 to 65 min after injection, and a scaled PIF using maximum crystal ring difference settings of both 85 and 322. Tumor lesion and healthy-tissue uptake was quantified and compared between the differently obtained parametric images to assess quantitative accuracy. Results: Good agreement was obtained between direct- and image-based Patlak analyses using the IDIF (t* = 30 min) and scaled PIF at 30-60 min after injection, performed using the different approaches, with no more than 8.8% deviation in tumor influx rate value ( K i ) (mean difference ranging from -0.0022 to 0.0018 mL/[min × g]). When direct Patlak reconstruction was performed on the system console, excellent agreement was found between the use of a scaled PIF at 30-60 min after injection versus 55-65 min after injection, with 2.4% deviation in tumor K i (median difference, -0.0018 mL/[min × g]; range, -0.0047 to 0.0036 mL/[min × g]). For different maximum crystal ring difference settings using the scan time interval of 55-65 min after injection, only a 0.5% difference (median difference, 0.0000 mL/[min × g]; range, -0.0004 to 0.0013 mL/[min × g]) in tumor K i was found. Conclusion: Ultrashort whole-body [ 18 F]FDG Patlak imaging is feasible on an LAFOV Biograph Vision Quadra PET/CT system without loss of quantitative accuracy to assess lung tumor uptake compared with a full-duration 65-min acquisition. The ultrashort 10-min direct Patlak reconstruction with PIF allows for its implementation in clinical practice., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Progressive cerebral volume loss on MRI is a hallmark of Alzheimer's disease and has been widely used as an outcome measure in clinical trials, with the prediction that disease-modifying treatments would slow loss. However, in trials of anti-amyloid immunotherapy, the participants who received treatment had excess volume loss. Explanations for this observation range from reduction of amyloid β plaque burden and related inflammatory changes through to treatment-induced toxicity. The excess volume changes are characteristic of only those immunotherapies that achieve amyloid β lowering; are compatible with plaque removal; and evidence to date does not suggest an association with harmful effects. Based on the current evidence, we suggest that these changes can be described as amyloid-removal-related pseudo-atrophy. Better understanding of the causes and consequences of these changes is important to enable informed decisions about treatments. Patient-level analyses of data from the trials are urgently needed, along with longitudinal follow-up and neuroimaging data, to determine the long-term trajectory of these volume changes and their clinical correlates. Post-mortem examination of cerebral tissue from treated patients and evaluation of potential correlation with antemortem neuroimaging findings are key priorities., Competing Interests: Declaration of interests DB has been a consultant or advisor relating to Alzheimer immunisation programmes for: Elan Pharmaceuticals (travel and accommodation) and Biogen (consultancy fees). JARN has been a consultant or advisor relating to Alzheimer immunisation programmes for: Elan Pharmaceuticals (travel and accommodation), GlaxoSmithKline (consultancy fees), Novartis, Roche (consultancy fees), Janssen (consultancy fees), Pfizer, Biogen (consultancy fees, travel, and accommodation), and Eisai. HZ has served at scientific advisory boards or as a consultant for AbbVie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave; has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche; is chair of the Alzheimer's Association Global Biomarker Standardization Consortium; is a cofounder of Brain Biomarker Solutions in Gothenburg (Brain Biomarker Solutions), which is a part of the GU Ventures Incubator Program. JMS has received tracer from Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) and Alliance Medical and has consulted for Roche Pharmaceuticals, Biogen, and Eli Lilly. FB has received consulting fees from Combinostics, Roche, and IXICO; has participated in data safety monitoring or advisory boards for EISAI, Biogen, Prothena, and Merck; and is a cofounder of Queen Square Analytics. NCF reports consulting fees from Biogen, Eisai, Ionis, Lilly, Roche/Genentech, and Siemens—paid to University College London; he has served on a data safety monitoring board for Biogen. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Understanding which patients with human epidermal growth factor receptor 2 (HER2)-negative or -low metastatic breast cancer (MBC) benefit from HER2-targeted strategies is urgently needed. We assessed the whole-body heterogeneity of HER2 expression on 89 Zr-trastuzumab PET (HER2 PET) and the diagnostic performance of HER2 PET in a large series of patients, including HER2-negative and -low MBC. Methods: In the IMPACT-MBC study, patients with newly diagnosed and nonrapidly progressive MBC of all subtypes were included. Metastasis HER2 status was determined by immunohistochemistry and in situ hybridization. 89 Zr-trastuzumab uptake was quantified as SUV max and SUV mean HER2 immunohistochemistry was related to the quantitative 89 Zr-trastuzumab uptake of all metastases and corresponding biopsied metastasis, uptake heterogeneity, and qualitative scan evaluation. A prediction algorithm for HER2 immunohistochemistry positivity based on uptake was developed. Results: In 200 patients, 89 Zr-trastuzumab uptake was quantified in 5,163 metastases, including 186 biopsied metastases. With increasing HER2 immunohistochemistry status, uptake was higher (geometric mean SUV max of 7.0, 7.6, 7.3, and 17.4 for a HER2 immunohistochemistry score of 0, 1, 2, or 3+, respectively; P < 0.001). High uptake exceeding 14.6 (90th percentile) was observed in one third of patients with a HER2-negative or -low metastasis biopsy. The algorithm performed best when lesion site and size were incorporated (area under the curve, 0.86; 95% CI, 0.79-0.93). Conclusion: HER2 PET had good diagnostic performance in MBC, showing considerable whole-body HER2 heterogeneity and uptake above background in HER2-negative and -low MBC. This provides novel insights into HER2-negative and -low MBC compared with standard HER2 immunohistochemistry on a single biopsy., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated demyelinating disease that is challenging to differentiate from multiple sclerosis (MS), as the clinical phenotypes overlap, and people with MOGAD can fulfil the current MRI-based diagnostic criteria for MS. In addition, the MOG antibody assays that are an essential component of MOGAD diagnosis are not standardized. Accurate diagnosis of MOGAD is crucial because the treatments and long-term prognosis differ from those for MS. This Expert Recommendation summarizes the outcomes from a Magnetic Resonance Imaging in MS workshop held in Oxford, UK in May 2022, in which MS and MOGAD experts reflected on the pathology and clinical features of these disorders, the contributions of MRI to their diagnosis and the clinical use of the MOG antibody assay. We also critically reviewed the literature to assess the validity of distinctive imaging features in the current MS and MOGAD criteria. We conclude that dedicated orbital and spinal cord imaging (with axial slices) can inform MOGAD diagnosis and also illuminate differential diagnoses. We provide practical guidance to neurologists and neuroradiologists on how to navigate the current MOGAD and MS criteria. We suggest a strategy that includes useful imaging discriminators on standard clinical MRI and discuss imaging features detected by non-conventional MRI sequences that demonstrate promise in differentiating these two disorders., (© 2024. Springer Nature Limited.)

Progressive inflammation of one hemisphere characterises Rasmussen's encephalitis (RE), but contralesional epileptiform activity has been repeatedly reported. We aimed to quantify contralesional epileptiform activity in RE and uncover its functional and structural underpinnings. We retrospectively ascertained people with RE treated between 2000 and 2018 at a tertiary centre (Centre 1) and reviewed all available EEG datasets. The temporal occurrence of preoperative contralesional epileptiform activity (interictal/ictal) was evaluated using mixed-effects logistic regression. Cases with/without contralesional epileptiform activity were compared for cognition, inflammation (ipsilesional brain biopsies), and MRI (cortical and fixel-based morphometry). EEG findings were validated in a second cohort treated at another tertiary centre (Centre 2) between 1995 and 2020. We included 127 people with RE and 687 EEG samples. Preoperatively, contralesional epileptiform activity was seen in 30/68 (44%, Centre 1) and 8/59 (14%, Centre 2). In both cohorts, this activity was associated with younger onset age (OR = 0.9; 95% CI 0.83-0.97; P = 0.006). At centre 1, contralesional epileptiform activity was associated with contralesional MRI alterations, lower intelligence (OR = 5.19; 95% CI 1.28-21.08; P = 0.021), and impaired verbal memory (OR = 10.29; 95% CI 1.97-53.85; P = 0.006). After hemispherotomy, 11/17 (65%, Centre 1) and 28/37 (76%, Centre 2) were seizure-free. Contralesional epileptiform activity was persistent postoperatively in 6/12 (50%, Centre 1) and 2/34 (6%, Centre 2). Preoperative contralesional epileptiform activity reduced the chance of postoperative seizure freedom in both cohorts (OR = 0.69; 95% CI 0.50-0.95; P = 0.029). Our findings question the concept of strict unilaterality of RE and provide the evidence of contralesional epileptiform activity as a possible EEG predictor for persisting postoperative seizures., (© 2024. The Author(s).)

Purpose: Hepatic fibrosis develops as a response to chronic liver injury, resulting in the formation of fibrous scars. This process is initiated and driven by collagen-producing activated myofibroblasts which reportedly express high levels of platelet derived growth factor receptor-β (PDGFRβ). We therefore regard PDGFRβ as an anchor for diagnosis and therapy. The Fibrobody® SP02SP26-ABD is a biparatopic VHH-construct targeting PDGFRβ. Here, we explore its potential as a theranostic vector for liver fibrosis., Methods: Specificity, cross-species binding, and cellular uptake of SP02SP26-ABD was assessed using human, mouse and rat PDGFRβ ectodomains and PDGFRβ-expressing cells. Cellular uptake by PDGFRβ-expressing cells was also evaluated by equipping the Fibrobody® with auristatinF and reading out in vitro cytotoxicity. The validity of PDGFRβ as a marker for active fibrosis was confirmed in human liver samples and 3 mouse models of liver fibrosis (DDC, CCl 4 , CDA-HFD) through immunohistochemistry and RT-PCR. After radiolabeling of DFO*-SP02SP26-ABD with 89 Zr, its in vivo targeting ability was assessed in healthy mice and mice with liver fibrosis by PET-CT imaging, ex vivo biodistribution and autoradiography., Results: SP02SP26-ABD shows similar nanomolar affinity for human, mouse and rat PDGFRβ. Cellular uptake and hence subnanomolar cytotoxic potency of auristatinF-conjugated SP02SP26-ABD was observed in PDGFRβ-expressing cell lines. Immunohistochemistry of mouse and human fibrotic livers confirmed co-localization of PDGFRβ with markers of active fibrosis. In all three liver fibrosis models, PET-CT imaging and biodistribution analysis of [ 89 Zr]Zr-SP02SP26-ABD revealed increased PDGFRβ-specific uptake in fibrotic livers. In the DDC model, liver uptake was 12.15 ± 0.45, 15.07 ± 0.90, 20.23 ± 1.34, and 20.93 ± 4.35%ID/g after 1,2,3 and 4 weeks of fibrogenesis, respectively, compared to 7.56 ± 0.85%ID/g in healthy mice. Autoradiography revealed preferential uptake in the fibrotic (PDGFRβ-expressing) periportal areas., Conclusion: The anti-PDGFRβ Fibrobody® SP02SP26-ABD shows selective and high-degree targeting of activated myofibroblasts in liver fibrosis, and qualifies as a vector for diagnostic and therapeutic purposes., (© 2024. The Author(s).)

Radiation therapy plays a crucial role in cancer treatment, necessitating precise delivery of radiation to tumors while sparing healthy tissues over multiple days. Computed tomography (CT) is integral for treatment planning, offering electron density data crucial for accurate dose calculations. However, accurately representing patient anatomy is challenging, especially in adaptive radiotherapy, where CT is not acquired daily. Magnetic resonance imaging (MRI) provides superior soft-tissue contrast. Still, it lacks electron density information, while cone beam CT (CBCT) lacks direct electron density calibration and is mainly used for patient positioning. Adopting MRI-only or CBCT-based adaptive radiotherapy eliminates the need for CT planning but presents challenges. Synthetic CT (sCT) generation techniques aim to address these challenges by using image synthesis to bridge the gap between MRI, CBCT, and CT. The SynthRAD2023 challenge was organized to compare synthetic CT generation methods using multi-center ground truth data from 1080 patients, divided into two tasks: (1) MRI-to-CT and (2) CBCT-to-CT. The evaluation included image similarity and dose-based metrics from proton and photon plans. The challenge attracted significant participation, with 617 registrations and 22/17 valid submissions for tasks 1/2. Top-performing teams achieved high structural similarity indices (≥0.87/0.90) and gamma pass rates for photon (≥98.1%/99.0%) and proton (≥97.3%/97.0%) plans. However, no significant correlation was found between image similarity metrics and dose accuracy, emphasizing the need for dose evaluation when assessing the clinical applicability of sCT. SynthRAD2023 facilitated the investigation and benchmarking of sCT generation techniques, providing insights for developing MRI-only and CBCT-based adaptive radiotherapy. It showcased the growing capacity of deep learning to produce high-quality sCT, reducing reliance on conventional CT for treatment planning., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matteo Maspero reports financial support was provided by EWUU alliance. Manya Afonso, Maureen van Eijnatten reports financial support was provided by EWUU alliance. Runqi Wang, Tao Song, Zhihao Zhang, Long Wang reports a relationship with Subtle Medical that includes: employment. Alexandra Alain-Beaudoin, Silvain Bériault reports a relationship with Elekta Ltd that includes: employment. Alexandra Alain-Beaudoin, Silvain Beriault has patent pending to Elekta Ltd. Pengxin Yu reports a relationship with Infervision Medical Technology Co., Ltd that includes: employment. Gengwan Li, Xueru Zhang reports a relationship with Canon Medical Systems Corporation that includes: employment. Lujia Zhong, Zhiwei Deng reports financial support was provided by University of Southern California. Valentin Boussot reports financial support was provided by French National Research Agency. Valentin Boussot reports financial support was provided by Rennes Métropole. Cédric Hémon reports financial support was provided by Elekta AB. Cédric Hémon reports financial support was provided by CominLabs. Valentin Boussot reports a relationship with University of Rennes that includes: employment. Cédric Hémon reports a relationship with University of Rennes that includes: employment. Cédric Hémon reports a relationship with Centre Eugène Marquis that includes: employment. Lu Bai, Shaobin Wang reports a relationship with MedMind Technology Co. Ltd that includes: employment. Lu Bai and Shaobing Wang had adopted some training ideas from Du Yi who is a staff in Institute of Medical Technology, Peking University Health Science Center, Beijing, China Derk Mus, Bram Kooiman reports a relationship with MRI Guidance BV that includes: employment. Chelsea Sargeant reports a relationship with Elekta AB that includes: funding grants and travel reimbursement. Edward Henderson reports a relationship with Manchester Cancer Research Centre that includes: funding grants and travel reimbursement. Zijie Chen, Enpei Wang reports a relationship with Shenying Medical Technology (Shenzhen) Co., Ltd that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background & Aims: Accurate diagnosis of sarcopenia requires evaluation of muscle quality, which refers to the amount of fat infiltration in muscle tissue. In this study, we aim to investigate whether we can independently predict mortality risk in transcatheter aortic valve implantation (TAVI) patients, using automatic deep learning algorithms to assess muscle quality on procedural computed tomography (CT) scans., Methods: This study included 1199 patients with severe aortic stenosis who underwent transcatheter aortic valve implantation (TAVI) between January 2010 and January 2020. A procedural CT scan was performed as part of the preprocedural-TAVI evaluation, and the scans were analyzed using deep-learning-based software to automatically determine skeletal muscle density (SMD) and intermuscular adipose tissue (IMAT). The association of SMD and IMAT with all-cause mortality was analyzed using a Cox regression model, adjusted for other known mortality predictors, including muscle mass., Results: The mean age of the participants was 80 ± 7 years, 53% were female. The median observation time was 1084 days, and the overall mortality rate was 39%. We found that the lowest tertile of muscle quality, as determined by SMD, was associated with an increased risk of mortality (HR 1.40 [95%CI: 1.15-1.70], p < 0.01). Similarly, low muscle quality as defined by high IMAT in the lowest tertile was also associated with increased mortality risk (HR 1.24 [95%CI: 1.01-1.52], p = 0.04)., Conclusions: Our findings suggest that deep learning-assessed low muscle quality, as indicated by fat infiltration in muscle tissue, is a practical, useful and independent predictor of mortality after TAVI., Competing Interests: Declaration of competing interest Pim Moeskops is an employee of Quantib-U, Bob D. de Vos is Artificial Intelligence lead and co-founder of Quantib-U and Ivana Išgum is also co-founder and Scientific lead at Quantib-U. All other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In non-small cell lung cancer (NSCLC), chemoradiotherapy (CRT) yields pathological complete response (pCR) rates of approximately 30%. We investigated using ipilimumab plus nivolumab (IPI-NIVO) with neoadjuvant CRT in resectable, and borderline resectable NSCLC., Methods: This single-arm, phase-II trial enrolled operable T3-4N0-2 patients with NSCLC without oncogenic drivers. Primary study endpoints were safety, major pathological response (MPR) and pCR. Treatment encompassed platinum-doublet concurrent CRT, IPI 1 mg/kg intravenous and NIVO 360 mg intravenous on day-1, followed by chemotherapy plus NIVO 360 mg 3 weeks later. Thoracic radiotherapy was 50 or 60 Gy, in once-daily doses of 2 Gy. Resections were 6 weeks post-radiotherapy., Results: In a total of 30 patients in the intention-to-treat (ITT) population, grades 3-4 treatment-related adverse events (TRAEs) occurred in 70%, one TRAE grade 5 late-onset pneumonitis on day 96 post-surgery (1/30, 3.3%) occurred, and one non-TRAE COVID-19 death (1/30, 3.3%). pCR and MPR were achieved in 50% (15/30) and 63% (19/30) of the ITT; and in 58% (15/26) and 73% (19/26) of the 26 patients who underwent surgery, respectively. Postoperative melanoma was seen in one non-pCR patient. The R0 rate was 100% (26/26), and no patient failed surgery due to TRAEs. In peripheral blood, proliferative CD8 + T cells were increased, while proliferative regulatory T cells (Tregs) were not. On-treatment, pCR-positives had higher CD8 + CD39 + T cells and lower HLA-DR + Tregs., Conclusions: Neoadjuvant IPI-NIVO-CRT in T3-4N0-2 NSCLC showed acceptable safety with pCR and MPR in 58% and 73% of operated patients, respectively. No patient failed surgery due to TRAEs., Trial Registration Number: NCT04245514., Competing Interests: Competing interests: The authors have disclosed the following conflicts of interest: DEO-L received grants from Janssen and Curium, honoraria from EANM, EAU, ESMO, and Curium, travel support from EANM, ESMO, EAU, and Bayer, and serves on a Bayer advisory board. CD received institutional fees for advisory roles with BMS, AstraZeneca, and MSD. SMSH has research contracts with several pharmaceutical companies and received honoraria from Janssen. IB’s institution received support from BMS, AstraZeneca, and Boehringer Ingelheim, and he received honoraria from AstraZeneca, MSD, and BMS. FLS received a research grant from ViewRay and honoraria from AstraZeneca. SS’s institution received grants from Varian, ViewRay, and AstraZeneca; he received consulting fees and honoraria from AstraZeneca and MSD, and serves on advisory boards for AstraZeneca and MSD. TDdG’s institution received grants from Idera Pharmaceuticals, consulting fees from LAVA Therapeutics and Mendus, and she holds stock in LAVA Therapeutics. All other authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To assess the diagnostic performance of Diffusion Weighted Imaging (DWI) and provide optimal apparent diffusion coefficient (ADC) cut-off values for differentiating between benign and metastatic lymph nodes in women with uterine cervical cancer., Method: MEDLINE and EMBASE databases were searched. Methodological quality was assessed with QUADAS-2. Data analysis was performed for three subgroups: (1) All studies; (2) Studies with maximum b-values of 800 s/mm², and (3) Studies containing b-values of 1000 s/mm². Receiver-operating characteristics (ROC) curves were constructed and the area under the curve (AUC) was calculated. The maximum Youden index was used to determine optimal ADC cut-off values, following calculations of sensitivity and specificity., Results: 16 articles (1156 patients) were included. Overall, their quality was limited. For all studies combined, the optimum ADC cut-off value was 0.985×10⁻³ mm²/s at maximum Youden Index of 0.77, resulting in sensitivity and specificity of 84%, and 94%, respectively. Studies with b-values up to 800 s/mm², gave an optimum ADC cut-off value of 0.985×10⁻³ mm²/s at maximum Youden Index of 0.62, with a sensitivity and specificity of 62%, and 100%. Studies containing b-values of 1000 s/mm² gave an optimum ADC cut-off value of 0.9435×10⁻³ mm²/s at maximum Youden Index of 0.93, with a sensitivity and specificity of 100%, and 93%, respectively., Conclusion: Studies using DWI including b-values of 1000 s/mm² have higher sensitivity and specificity than those with b-values up to 800 s/mm². At the cut-off value of 0.9435×10⁻³ mm²/s DWI can sufficiently discriminate between benign and metastatic lymph nodes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objectives: The leukodystrophy "vanishing white matter" (VWM) and "metachromatic leukodystrophy" (MLD) affect the brain's white matter, but have very different underlying pathology. We aim to determine whether quantitative MRI reflects known neuropathological differences and correlates with clinical scores in these leukodystrophies., Methods: VWM and MLD patients and controls were prospectively included between 2020 and 2023. Clinical scores were recorded. MRI at 3 T included multi-compartment relaxometry diffusion-informed myelin water imaging (MCR-DIMWI) and multi-echo T2-relaxation imaging with compressed sensing (METRICS) to determine myelin water fractions (MWF). Multi-shell diffusion-weighted data were used for diffusion tensor imaging measures and neurite orientation dispersion and density imaging (NODDI) analysis, which estimates neurite density index, orientation dispersion index, and free water fraction. As quantitative MRI measures are age-dependent, ratios between actual and age-expected MRI measures were calculated. We performed the multilevel analysis with subsequent post-hoc and correlation tests to assess differences between groups and clinico-radiological correlations., Results: Sixteen control (age range: 2.3-61.3 years, 8 male), 37 VWM (2.4-56.5 years, 20 male), and 14 MLD (2.2-41.7 years, 6 male) subjects were included. Neurite density index and MWF were lower in patients than in controls (p < 0.001). Free water fraction was highest in VWM (p = 0.01), but similar to controls in MLD (p = 0.99). Changes in diffusion tensor imaging measures relative to controls were generally more pronounced in VWM than in MLD. In both patient groups, MCR-DIMWI MWF correlated strongest with clinical measures., Conclusion: Quantitative MRI correlates to clinical measures and yields differential profiles in VWM and MLD, in line with differences in neuropathology., Key Points: Question Can quantitative MRI reflect known neuropathological differences and correlate with clinical scores for these leukodystrophies? Finding Quantitative MRI measures, e.g., MWF, neurite density index, and free water fraction differ between leukodystrophies and controls, in correspondence to known histological differences. Clinical relevance MRI techniques producing quantitative, biologically-specific, measures regarding the health of myelin and axons deliver more comprehensive information regarding pathological changes in leukodystrophies than current approaches, and are thus viable tools for monitoring patients and providing clinical trial outcome measures., (© 2024. The Author(s).)

Background/objectives: This study reassesses the diagnostic value of PSMA PET/CT in unfavorable intermediate-risk prostate cancer (PCa) and validates the Prostate Cancer Network the Netherlands (PCNN) subclassification., Subjects/methods: Men subjected to PSMA PET/CT were analyzed, evaluating the incidence of metastatic disease and its correlation with PCNN subgroups., Results: Metastatic disease was identified in 12.4% of patients. Higher PCNN subgroups correlated with increased metastatic potential; odds were significantly lower in low metastatic potential cases (OR: 0.19, 95% CI 0.06-0.62; p = 0.01)., Conclusions: Our findings reaffirm PSMA PET/CT's diagnostic value in unfavorable intermediate-risk PCa and validate the PCNN subclassification, reducing scan burden by 48.1%., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Purpose: To develop and test a decision tree for predicting contrast enhancement quality and shape using precontrast magnetic resonance imaging (MRI) sequences in a large adult-type diffuse glioma cohort., Methods: Preoperative MRI scans (development/optimization/test sets: n = 31/38/303, male = 17/22/189, mean age = 52/59/56.7 years, high-grade glioma = 22/33/249) were retrospectively evaluated, including pre- and postcontrast T1-weighted, T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted imaging sequences. Enhancement prediction decision tree (EPDT) was developed using development and optimization sets, incorporating four imaging features: necrosis, diffusion restriction, T2 inhomogeneity, and nonenhancing tumor margins. EPDT accuracy was assessed on a test set by three raters of variable experience. True enhancement features (gold standard) were evaluated using pre- and postcontrast T1-weighted images. Statistical analysis used confusion matrices, Cohen's/Fleiss' kappa, and Kendall's W. Significance threshold was p < .05., Results: Raters 1, 2, and 3 achieved overall accuracies of .86 (95% confidence interval [CI]: .81-.90), .89 (95% CI: .85-.92), and .92 (95% CI: .89-.95), respectively, in predicting enhancement quality (marked, mild, or no enhancement). Regarding shape, defined as the thickness of enhancing margin (solid, rim, or no enhancement), accuracies were .84 (95% CI: .79-.88), .88 (95% CI: .84-.92), and .89 (95% CI: .85-.92). Intrarater intergroup agreement comparing predicted and true enhancement features consistently reached substantial levels (≥.68 [95% CI: .61-.75]). Interrater comparison showed at least moderate agreement (group: ≥.42 [95% CI: .36-.48], pairwise: ≥.61 [95% CI: .50-.72]). Among the imaging features in the EPDT, necrosis assessment displayed the highest intra- and interrater consistency (≥.80 [95% CI: .73-.88])., Conclusion: The proposed EPDT has high accuracy in predicting enhancement patterns of gliomas irrespective of rater experience., (© 2024 The Author(s). Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Background: Adjunctive catheter-directed thrombolysis shows variable efficacy in preventing postthrombotic syndrome (PTS), despite restored patency., Objectives: This Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome (CAVA) trial subanalysis investigated the effect of ultrasound-accelerated catheter-directed thrombolysis (UACDT) on patency, reflux, and their relevance in PTS development., Methods: This multicenter, randomized, single-blind trial enrolled patients (aged 18-85 years) with a first iliofemoral deep vein thrombosis and symptom duration ≤14 days. Patency and reflux were assessed by duplex ultrasound at 12 months (T12) and long-term (LT) follow-up (median, 39.5 months; IQR, 24.0-63.0 months). PTS was diagnosed using the Villalta score., Results: UACDT significantly improved patency in all vein segments at T12 (60.3% UACDT vs 25.9% standard treatment [ST]; P = .002) and LT (45.2% UACDT vs 11.9% ST; P < .001). Popliteal patency, however, was similar between groups (87.9% UACDT vs 83.3% ST; P = .487). Reflux was similar between groups at T12 and LT; only popliteal reflux was significantly reduced in the UACDT group at LT (22.6% UACDT vs 44.8% ST; P = .010). Absent iliac patency at T12 was associated with increased PTS risk in the ST group only (odds ratio [OR], 10.84; 95% CI, 1.93-60.78; P = .007). In the UACDT group, popliteal reflux at T12 was associated with moderate-to-severe PTS at T12 (OR, 4.88; 95% CI, 1.10-21.57; P = .041) and LT (OR, 5.83; 95% CI, 1.44-23.63; P = .009). Combined popliteal reflux and absent iliac patency significantly amplified PTS risk (OR, 10.79; 95% CI, 2.41-48.42; P < .001)., Conclusion: UACDT improved patency and reduced popliteal reflux. Iliac patency and popliteal reflux are independently associated with moderate-to-severe PTS and contribute synergistically to its development. However, a proportion of moderate-to-severe PTS cases lacks an evident underlying cause., Competing Interests: Declaration of competing interests H.t.C. reports personal fees from Alveron, Galapagos, AstraZeneca, and Novostia, and he is shareholder with Coagulation Profile; all revenues are deposited at the Cardiovascular Research Institute Maastricht for research. The remaining authors have no disclosures to report., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Voriconazole administered concomitantly with flucloxacillin may result in subtherapeutic plasma concentrations as shown in a patient with Staphylococcus aureus sepsis and a probable pulmonary aspergillosis. After switching our patient to posaconazole, therapeutic concentrations were reached. The aim of this study was to first test our hypothesis that flucloxacillin competes with voriconazole not posaconazole for binding to albumin ex vivo, leading to lower total concentrations in plasma., Methods: A physiologically based pharmacokinetic (PBPK) model was then applied to predict the mechanism of action of the drug-drug interaction (DDI). The model included non-linear hepatic metabolism and the effect of a severe infectious disease on cytochrome P450 (CYP) enzymes activity., Results: The unbound voriconazole concentration remained unchanged in plasma after adding flucloxacillin, thereby rejecting our hypothesis of albumin-binding site competition. The PBPK model was able to adequately predict the plasma concentration of both voriconazole and posaconazole over time in healthy volunteers. Upregulation of CYP3A4, CYP2C9, and CYP2C19 through the pregnane X receptor (PXR) gene by flucloxacillin resulted in decreased voriconazole plasma concentrations, reflecting the DDI observations in our patient. Posaconazole metabolism was not affected, or was only limitedly affected, by the changes through the PXR gene, which agrees with the observed plasma concentrations within the target range in our patient., Conclusions: Ex vivo experiments reported that the unbound voriconazole plasma concentration remained unchanged after adding flucloxacillin. The PBPK model describes the potential mechanism driving the drug-drug and drug-disease interaction of voriconazole and flucloxacillin, highlighting the large substantial influence of flucloxacillin on the PXR gene and the influence of infection on voriconazole plasma concentrations, and suggests a more limited effect on other triazoles., (© 2024. The Author(s).)

Purpose: To analyse diagnostic accuracy of MRI-DWI in detecting residual disease after cholesteatoma surgery and propose an optimum follow-up (FU) scheme., Method: A retrospective chart review of patients who had cholesteatoma surgery in a tertiary referral centre. 3.0 T non-echo planar diffusion weighted imaging was performed as part of routine FU or indicated on the basis of clinical suspicion of disease. Imaging outcome was verified per-operatively during a second-look procedure or ossicular chain reconstruction. Diagnostic parameters were calculated and stratified by FU length., Results: For the FU of 664 cholesteatoma surgeries, 1208 MRI-DWI were obtained and 235 second-look procedures were performed. Most MRI-DWI were obtained within 1.5 yrs of surgery. In this period, significantly less true positive MRI-DWI and significantly more false negative MRI-DWI for residual disease were found compared to other FU periods. Scanning after approximately 3 yrs yielded a significantly higher rate of true positive MRI-DWI, while sensitivity surpassed 80%. Younger patients had a higher risk of developing residual disease. Patients undergoing canal wall up surgery, as well as patients < 12 yrs, were at risk for false negative MRI-DWI. Obliteration reduces the risk of residual disease, while leading to less false negative MRI-DWI., Conclusion: A novel radiologic FU scheme for detecting residual disease is suggested for stable ears after cholesteatoma surgery: standard MRI-DWI approximately 3 and 5 yrs after primary surgery, as well as MRI-DWI after approximately 9 yrs for patients with specific risk factors (i.e., patients < 12 yrs or patients undergoing canal wall up surgery without obliteration)., (© 2024. The Author(s).)

Background: The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS., Methods: We conducted a post hoc analysis of participants in the MS-Secondary Progressive Multi-Arm Randomisation Trial (NCT01910259), a multicentre randomised placebo-controlled trial of the neuroprotective potential of three agents in SPMS. Physical disability was measured by Expanded Disability Status Scale (EDSS), 9-hole peg test (9HPT) and 25-foot timed walk test (T25FW) at baseline, 48 and 96 weeks. MLBG was estimated by baseline intracranial volume (ICV). Multivariable time-varying Cox regression models were used to investigate the association between MLBG and physical disability progression., Results: 383 participants (mean age 54.5 years, 298 female) were followed up over 96 weeks. Median baseline EDSS was 6.0 (range 4.0-6.5). Adjusted for covariates, larger MLBG was associated with a reduced risk of EDSS progression (HR 0.84,95% CI:0.72 to 0.99;p=0.04). MLBG was not independently associated with time to progression as measured by 9HPT or T25FW., Conclusion: Larger MLBG is independently associated with physical disability progression over 96 weeks as measured by EDSS in SPMS. This suggests that MLBG as a proxy for brain reserve may continue to confer protection against disability when in the secondary progression phase of MS., Trail Registration Number: NCT01910259., Competing Interests: NJ is a local principal investigator on commercial MS studies funded by Novartis, Roche and Sanofi. He has received speakers honoraria from Merck and congress sponsorship covering registration and travel from Novartis. FB serves on the editorial boards of Brain, European Radiology, Journal of Neurology, Neurosurgery & Psychiatry, Neurology, Multiple Sclerosis and Neuroradiology, and serves as consultant for Bayer Schering Pharma, Sanofi-Aventis, Biogen-Idec, TEVA Pharmaceuticals, Genzyme, Merck-Serono, Novartis, Roche, Synthon, Jansen Research and Lundbeck. CAGW-K has received research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon 2020, NIHR/MRC, MRC and is a shareholder of Queen Square Analytics. In the last 3 years, JC has received support from the Efficacy and Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership and the Health Technology Assessment (HTA) Programme (NIHR), the UK MS Society, the US National MS Society and the Rosetrees Trust. He is supported in part by the National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London, UK. He has been a local principal investigator for a trial in MS funded by the Canadian MS Society. A local principal investigator for commercial trials funded by: Actelion, Biogen, Novartis and Roche; has received an investigator grant from Novartis; and has taken part in advisory boards/consultancy for Azadyne, Biogen, Celgene, Janssen, MedDay, Merck, NervGen, Novartis and Roche., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Left atrial appendage (LAA) slow-flow may increase the risk of ischemic stroke. We studied LAA attenuation on cardiac computed tomography in patients with acute ischemic stroke., Methods and Results: We used data from a prospective cohort of patients with acute ischemic stroke undergoing cardiac computed tomography during the acute stroke imaging protocol. We compared characteristics, functional outcome (modified Rankin scale: higher scores indicating worse outcome), stroke recurrence and major adverse cardiovascular events after 2-year follow-up between patients with LAA thrombus (filling defect<100 Hounsfield Unit (HU)), slow-flow (filling defect ≥100 HU) and normal filling. Of 421 patients, 31 (7%) had LAA thrombus, 69 (16%) slow-flow, and 321 (76%) normal filling. Patients with thrombus or slow-flow more often had known atrial fibrillation compared with normal filling (45%, 39%, and 9%, P <0.001). Patients with thrombus had higher National Institutes of Health Stroke Scale-scores compared with slow-flow and normal filling (18 [interquartile range, 9-22], 6 [interquartile range, 3-17], and 5 [interquartile range, 2-11], P <0.001). Compared with normal filling, there was no difference with slow-flow in functional outcome (median modified Rankin scale, 3 versus 2; acOR 0.8 [95% CI, 0.5-1.4]), stroke recurrence (adjusted hazard ratio, 0.8 [95% CI, 0.3-1.9]) or major adverse cardiovascular events (adjusted hazard ratio, 1.2 [95% CI, 0.7-2.1]), while patients with thrombus had worse functional outcome (median modified Rankin scale, 6, acOR, 3.3 [95% CI, 1.5-7.4]). In cryptogenic stroke patients (n=156) slow-flow was associated with stroke recurrence (27% versus 6%, aHR, 4.1 [95% CI, 1.1-15.7])., Conclusions: Patients with slow-flow had similar characteristics to patients with thrombus, but had less severe strokes. Slow-flow was not significantly associated with functional outcome or major adverse cardiovascular events, but was associated with recurrent stroke in patients with cryptogenic stroke.

Background: Currently thioguanine is solely used as treatment for inflammatory bowel disease after azathioprine and/or mercaptopurine failure. This study aimed to determine the safety, effectiveness, and 12-month drug survival of thioguanine in thiopurine-naïve patients with inflammatory bowel disease., Methods: A retrospective cohort study was performed in thiopurine-naïve patients with inflammatory bowel disease treated with thioguanine as first thiopurine derivate. Clinical effectiveness was defined as the continuation of thioguanine without the (re)initiation of concurrent biological therapy, systemic corticosteroids, or a surgical intervention. All adverse events were categorized by the Common Terminology Criteria for Adverse Events., Results: A total of 114 patients (male 39%, Crohn's disease 53%) were included with a median treatment duration of 25 months and a median thioguanine dosage of 20 mg/d. Clinical effectiveness at 12 months was observed in 53% of patients, and 78% of these responding patients remained responsive until the end of follow-up. During the entire follow-up period, 26 patients were primary nonresponders, 8 had a secondary loss of response, and 11 patients were unable to cease therapy with systemic corticosteroids within 6 months and were therefore classified as nonresponders. After 12 months, thioguanine was still used by 86% of patients. Fifty (44%) patients developed adverse events (grade 1 or 2) and 9 (8%) patients ceased therapy due to the occurrence of adverse events. An infection was documented in 3 patients, none of them requiring hospitalization and pancytopenia occurred in 2 other patients. No signs of nodular regenerative hyperplasia or portal hypertension were observed., Conclusions: At 12 months, first-line thioguanine therapy was clinically effective in 53% of thiopurine-naïve inflammatory bowel disease patients with an acceptable safety profile., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)