Adolescent maturation of cortical excitation-inhibition balance based on individualized biophysical network modeling.

The balance of excitation and inhibition is a key functional property of cortical microcircuits which changes through the lifespan. Adolescence is considered a crucial period for the maturation of excitation-inhibition balance. This has been primarily observed in animal studies, yet human in vivo evidence on adolescent maturation of the excitation-inhibition balance at the individual level is limited. Here, we developed an individualized in vivo marker of regional excitation-inhibition balance in human adolescents, estimated using large-scale simulations of biophysical network models fitted to resting-state functional magnetic resonance imaging data from two independent cross-sectional (N = 752) and longitudinal (N = 149) cohorts. We found a widespread relative increase of inhibition in association cortices paralleled by a relative age-related increase of excitation, or lack of change, in sensorimotor areas across both datasets. This developmental pattern co-aligned with multiscale markers of sensorimotor-association differentiation. The spatial pattern of excitation-inhibition development in adolescence was robust to inter-individual variability of structural connectomes and modeling configurations. Notably, we found that alternative simulation-based markers of excitation-inhibition balance show a variable sensitivity to maturational change. Taken together, our study highlights an increase of inhibition during adolescence in association areas using cross sectional and longitudinal data, and provides a robust computational framework to estimate microcircuit maturation in vivo at the individual level.

Identification and properties of TRPV4 mutant channels present in polycystic kidney disease patients.

Polycystic kidney disease (PKD), a disease characterized by enlargement of the kidney through cystic growth is the fourth leading cause of end-stage kidney disease world-wide. TRPV4, a calcium-permeable TRP, channel participates in kidney cell physiology and since TRPV4 forms complexes with another channel whose malfunction is associated to PKD, TRPP2 (or PKD2), we sought to determine whether patients with PKD, exhibit previously unknown mutations in TRPV4. Here, we report the presence of mutations in the TRPV4 gene in patients diagnosed with PKD and determine that they produce gain-of-function (GOF). Mutations in the sequence of the TRPV4 gene have been associated to a broad spectrum of neuropathies and skeletal dysplasias but not PKD, and their biophysical effects on channel function have not been elucidated. We identified and examined the functional behavior of a novel E6K mutant and of the previously known S94L and A217S mutant TRVP4 channels. The A217S mutation has been associated to mixed neuropathy and/or skeletal dysplasia phenotypes, however, the PKD carriers of these variants had not been diagnosed with these reported clinical manifestations. The presence of certain mutations in TRPV4 may influence the progression and severity of PKD through GOF mechanisms. PKD patients carrying TRVP4 mutations are putatively more likely to require dialysis or renal transplant as compared to those without these mutations.

Prostatic Artery Embolization: Lessons From 551 Procedures at a Single-Center.

RATIONALE AND OBJECTIVES: This retrospective study evaluates the efficacy and safety of Prostatic Artery Embolization (PAE) for the treatment of benign prostatic hyperplasia (BPH) over five years at a single center, conducted by an experienced interventional radiologist. MATERIALS AND METHODS: We analyzed 551 PAE interventions from January 2019 to July 2023. Key metrics included patient demographics, procedural details (radiation exposure, particle size), complication rates, pre- and post-interventional prostatic volume (PV), Prostate-specific Antigen (PSA) levels, International Prostate Symptom Score (IPSS), Quality of Life (QoL) scores and International Index of Erectile Function (IIEF) scores. We assessed data normality, performed group and paired sample comparisons, and evaluated correlations. RESULTS: For 551 men, the average patient age was 68.81 ± 8.61 years undergoing bilateral embolization. The particle size predominantly used was 100-300 µm (n = 441). PAE lead to significant (p < .001) reduction of both PV (-9.67 ± 14.52 mL) and PSA level (-2,65 ± 1.56 ng/mL) between pre- and three months after PAE. Substantial improvement were observed for IPSS (-9 points) and QoL scores (-2 points), with stable IIEF scores. Only minor complications (n = 16) were reported, and no major complications were observed. Between the first PAE in 2019 and the routinely performed PAE in 2023 significant (p < .0001) reductions in fluoroscopy (-25.2%), and procedural times (-26.1%) were observed. CONCLUSION: In conclusion, PAE is a safe and effective treatment for BPH, offering significant improvements in lower urinary tract symptoms (LUTS) and QoL while maintaining sexual function.

Optimization of window settings for coronary arteries assessment using spectral CT-derived virtual monoenergetic imaging.

PURPOSE: To determine the optimal window setting for virtual monoenergetic images (VMI) reconstructed from dual-layer spectral coronary computed tomography angiography (DE-CCTA) datasets. MATERIAL AND METHODS: 50 patients (30 males; mean age 61.1 ± 12.4 years who underwent DE-CCTA from May 2021 to June 2022 for suspected coronary artery disease, were retrospectively included. Image quality assessment was performed on conventional images and VMI reconstructions at 70 and 40 keV. Objective image quality was assessed using contrast-to-noise ratio (CNR). Two independent observers manually identified the best window settings (B-W/L) for VMI 70 and VMI 40 visualization. B-W/L were then normalized with aortic attenuation using linear regression analysis to obtain the optimized W/L (O-W/L) settings. Additionally, subjective image quality was evaluated using a 5-point Likert scale, and vessel diameters were measured to examine any potential impact of different W/L settings. RESULTS: VMI 40 demonstrated higher CNR values compared to conventional and VMI 70. B-W/L settings identified were 1180/280 HU for VMI 70 and 3290/900 HU for VMI 40. Subsequent linear regression analysis yielded O-W/L settings of 1155/270 HU for VMI 70 and 3230/880 HU for VMI 40. VMI 40 O-W/L received the highest scores for each parameter compared to conventional (all p < 0.0027). Using O-W/L settings for VMI 70 and VMI 40 did not result in significant differences in vessel measurements compared to conventional images. CONCLUSION: Optimization of VMI requires adjustments in W/L settings. Our results recommend W/L settings of 1155/270 HU for VMI 70 and 3230/880 HU for VMI 40.

Probing the neurocardiac circuit in trauma and posttraumatic stress.

The neurocardiac circuit is integral to physiological regulation of threat and trauma-related responses. However, few direct investigations of brain-behavior associations with replicable physiological markers of PTSD have been conducted. The current study probed the neurocardiac circuit by examining associations among its core regions in the brain (e.g., insula, hypothalamus) and the periphery (heart rate [HR], high frequency heart rate variability [HF-HRV], and blood pressure [BP]). We sought to characterize these associations and to determine whether there were differences by PTSD status. Participants were N = 315 (64.1 % female) trauma-exposed adults enrolled from emergency departments as part of the prospective AURORA study. Participants completed a deep phenotyping session (e.g., fear conditioning, magnetic resonance imaging) two weeks after emergency department admission. Voxelwise analyses revealed several significant interactions between PTSD severity 8-weeks posttrauma and psychophysiological recordings on hypothalamic connectivity to the prefrontal cortex (PFC), insula, superior temporal sulcus, and temporoparietaloccipital junction. Among those with PTSD, diastolic BP was directly correlated with right insula-hypothalamic connectivity, whereas the reverse was found for those without PTSD. PTSD status moderated the association between systolic BP, HR, and HF-HRV and hypothalamic connectivity in the same direction. While preliminary, our findings may suggest that individuals with higher PTSD severity exhibit compensatory neural mechanisms to down-regulate autonomic imbalance. Additional study is warranted to determine how underlying mechanisms (e.g., inflammation) may disrupt the neurocardiac circuit and increase cardiometabolic disease risk in PTSD.

Optimizing resource allocation: Cost-effectiveness of specified D-dimer cut-offs in cancer patients with suspected venous thromboembolism.

An accurate diagnosis of venous thromboembolism (VTE) is crucial, given the potential for high mortality in undetected cases. Strategic D-dimer testing may aid in identifying low-risk patients, preventing overdiagnosis and reducing imaging costs. We conducted a retrospective, comparative analysis to assess the potential cost savings that could be achieved by adopting different approaches to determine the most effective D-dimer cut-off value in cancer patients with suspected VTE, compared to the commonly used rule-out cut-off level of 0.5 mg/L. The study included 526 patients (median age 65, IQR 55-75) with a confirmed cancer diagnosis who underwent D-dimer testing. Among these patients, the VTE prevalence was 29% (n = 152). Each diagnostic strategy's sensitivity, specificity, negative likelihood ratio (NLR), as well as positive likelihood ratio (PLR), and the proportion of patients exhibiting a negative D-dimer test result, were calculated. The diagnostic strategy that demonstrated the best balance between specificity, sensitivity, NLR, and PLR, utilized an inverse age-specific cut-off level for D-dimer [0.5 + (66-age) × 0.01 mg/L]. This method yielded a PLR of 2.9 at a very low NLR for the exclusion of VTE. We observed a significant cost reduction of 4.6% and 1.0% for PE and DVT, respectively. The utilization of an age-adjusted cut-off [patient's age × 0.01 mg/L] resulted in the highest cost savings, reaching 8.1% for PE and 3.4% for DVT. Using specified D-dimer cut-offs in the diagnosis of VTE could improve economics, considering the limited occurrence of confirmed cases among patients with suspected VTE.

Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study.

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD. METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men. RESULTS: Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects. CONCLUSIONS: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Temporal dissociation between local and global functional adaptations of the maternal brain to childbirth: a longitudinal assessment.

The maternal brain undergoes significant reorganization during birth and the postpartum period. However, the temporal dynamics of these changes remain unclear. Using resting-state functional magnetic resonance imaging, we report on local and global brain function alterations in 75 mothers in their first postpartum week, compared to 23 nulliparous women. In a subsample followed longitudinally for the next six months, we observed a temporal and spatial dissociation between changes observed at baseline (cluster mass permutation: pFWE < 0.05). Local activity and connectivity changes in widespread neocortical regions persisted throughout the studied time period (ANCOVAs vs. controls: pFDR < 0.05), with preliminary evidence linking these alterations to behavioral and psychological adaptations (interaction effect with postpartum time: uncorrected p < 0.05). In contrast, the initially reduced whole-brain connectivity of putamen-centered subcortical areas returned to control levels within six to nine weeks postpartum (linear and quadratic mixed linear models: pFDR < 0.05). The whole-brain spatial colocalization with hormone receptor distributions (Spearman correlations: pFDR < 0.05) and preliminary blood hormone associations (interaction effect with postpartum time: uncorrected p < 0.05) suggested that the postpartum restoration of progesterone levels may underlie this rapid normalization. These observations enhance our understanding of healthy maternal brain function, contributing to the identification of potential markers for pathological postpartum adaptation processes, which in turn could underlie postpartum psychiatric disorders.

Intensive longitudinal assessment following index trauma to predict development of PTSD using machine learning.

There are significant challenges to identifying which individuals require intervention following exposure to trauma, and a need for strategies to identify and provide individuals at risk for developing PTSD with timely interventions. The present study seeks to identify a minimal set of trauma-related symptoms, assessed during the weeks following traumatic exposure, that can accurately predict PTSD. Participants were 2185 adults (Mean age=36.4 years; 64% women; 50% Black) presenting for emergency care following traumatic exposure. Participants received a 'flash survey' with 6-8 varying symptoms (from a pool of 26 trauma symptoms) several times per week for eight weeks following the trauma exposure (each symptom assessed ∼6 times). Features (mean, sd, last, worst, peak-end scores) from the repeatedly assessed symptoms were included as candidate variables in a CART machine learning analysis to develop a pragmatic predictive algorithm. PTSD (PCL-5 ≥38) was present for 669 (31%) participants at the 8-week follow-up. A classification tree with three splits, based on mean scores of nervousness, rehashing, and fatigue, predicted PTSD with an Area Under the Curve of 0.836. Findings suggest feasibility for a 3-item assessment protocol, delivered once per week, following traumatic exposure to assess and potentially facilitate follow-up care for those at risk.

Root Cause Analysis of Delayed Emergency Department Computed Tomography Scans.

Introduction: A solution for emergency department (ED) congestion remains elusive. As reliance on imaging grows, computed tomography (CT) turnaround time has been identified as a major bottleneck. In this study we sought to identify factors associated with significantly delayed CT in the ED. Methods: We performed a retrospective analysis of all CT imaging completed at an urban, tertiary care ED from May 1-July 31, 2021. During that period, 5,685 CTs were performed on 4,344 patients, with a median time from CT order to completion of 108 minutes (Quartile 1 [Q1]: 57 minutes, Quartile 3 [Q3]: 182 minutes, interquartile range [IQR]: 125 minutes). Outliers were defined as studies that took longer than 369 minutes to complete (Q3 + 1.5 × IQR). We systematically reviewed outlier charts to determine factors associated with delay and identified five factors: behaviorally non-compliant or medically unstable patients; intravenous (IV) line issues; contrast allergies; glomerular filtration rate (GFR) concerns; and delays related to imaging protocol (eg, need for IV contrast, request for oral and/or rectal contrast). We calculated confidence intervals (CI) using the modified Wald method. Inter-rater reliability was assessed with a kappa analysis. Results: We identified a total of 182 outliers (4.2% of total patients). Fifteen (8.2%) cases were excluded for CT time-stamp inconsistencies. Of the 167 outliers analyzed, 38 delays (22.8%, 95% confidence interval [CI] 17.0-29.7) were due to behaviorally non-compliant or medically unstable patients; 30 (18.0%, 95% CI 12.8-24.5) were due to IV issues; 24 (14.4%, 95% CI 9.8-20.6) were due to contrast allergies; 21 (12.6%, 95% CI 8.3-18.5) were due to GFR concerns; and 20 (12.0%, 95% CI 7.8-17.9) were related to imaging study protocols. The cause of the delay was unknown in 55 cases (32.9%, 95% CI 26.3-40.4). Conclusion: Our review identified both modifiable and non-modifiable factors associated with significantly delayed CT in the ED. Patient factors such as behavior, allergies, and medical acuity cannot be controlled. However, institutional policies regarding difficult IV access, contrast administration in low GFR settings, and study protocols may be modified, capturing up to 42.6% of outliers.

Predictive Value of Dual-Energy CT-Derived Metrics for the Use of Bone Substitutes in Distal Radius Fracture Surgery.

(1) Background: Low bone mineral density (BMD) is a significant risk factor for complicated surgery and leads to the increased use of bone substitutes in patients with distal radius fractures (DRFs). No accepted model has yet been established to predict the use of bone substitutes to facilitate preoperative planning. (2) Methods: Unenhanced dual-energy CT (DECT) images of DRFs were retrospectively acquired between March 2016 and September 2020 using the internal PACS system. Available follow-up imaging and medical health records were reviewed to determine the use of bone substitutes. DECT-based BMD, trabecular Hounsfield units (HU), cortical HU, and cortical thickness ratio were measured in non-fractured segments of the distal radius. Diagnostic accuracy parameters were calculated for all metrics using receiver-operating characteristic (ROC) curves and associations of all metrics with the use of bone substitutes were evaluated using logistic regression models. (3) The final study population comprised 262 patients (median age 55 years [IQR 43-67 years]; 159 females, 103 males). According to logistic regression analysis, DECT-based BMD was the only metric significantly associated with the use of bone substitutes (odds ratio 0.96, p = 0.003). However, no significant associations were found for cortical HU (p = 0.06), trabecular HU (p = 0.33), or cortical thickness ratio (p = 0.21). ROC-curve analysis revealed that a combined model of all four metrics had the highest diagnostic accuracy with an area under the curve (AUC) of 0.76. (4) Conclusions: DECT-based BMD measurements performed better than HU-based measurements and cortical thickness ratio. The diagnostic performance of all four metrics combined was superior to that of the individual parameters.

Advancing Differentiation of Hepatic Metastases in Malignant Melanoma through Dual-Energy Computed Tomography Rho/Z Maps.

OBJECTIVES: The aim of this study is to evaluate the diagnostic accuracy of dual-energy computed tomography (DECT)-based Rho/Z maps in differentiating between metastases and benign liver lesions in patients diagnosed with malignant melanoma compared to conventional CT value measurements. METHODS: This retrospective study included 73 patients (mean age, 70 ± 13 years; 43 m/30 w) suffering from malignant melanoma who had undergone third-generation DECT as part of tumor staging between December 2017 and December 2021. For this study, we measured Rho (electron density) and Z (effective atomic number) values as well as Hounsfield units (HUs) in hypodense liver lesions. Values were compared, and diagnostic accuracy for differentiation was computed using receiver operating characteristic (ROC) curve analyses. Additional performed MRI or biopsies served as a standard of reference. RESULTS: A total of 136 lesions (51 metastases, 71 cysts, and 14 hemangiomas) in contrast-enhanced DECT images were evaluated. The most notable discrepancy (p < 0.001) between measured values and the highest diagnostic accuracy for distinguishing melanoma metastases from benign cysts was observed for the Z (0.992; 95% CI, 0.956-1) parameters, followed by Rho (0.908; 95% CI, 0.842-0.953) and finally HU120kV (0.829; 95% CI, 0.751-0.891). Conversely, when discriminating between liver metastases and hemangiomas, the HU120kV parameters showed the most significant difference (p < 0.001) and yielded the highest values for diagnostic accuracy (0.859; 95% CI, 0.740-0.937), followed by the Z parameters (0.790; 95% CI, 0.681-0.876) and finally the Rho values (0.621; 95% CI, 0.501-0.730). CONCLUSIONS: Rho and Z measurements derived from DECT allow for improved differentiation of liver metastases and benign liver cysts in patients with malignant melanoma compared to conventional CT value measurements. In contrast, in differentiation between liver hemangiomas and metastases, Rho/Z maps show inferior diagnostic accuracy. Therefore, differentiation between these two lesions remains a challenge for CT imaging.

Emergency physician resource utilization varies by years of experience.

Objectives: One of the most pivotal decisions an emergency physician (EP) makes is whether to admit or discharge a patient. The emergency department (ED) work-up leading to this decision involves several resource-intensive tests. Previous studies have demonstrated significant differences in EP resource utilization, measured by lab tests, advanced imaging (magnetic resonance imaging [MRI], computed tomography [CT], ultrasound), consultations, and propensity to admit a patient. However, how an EP's years of experience may impact their resource utilization and propensity to admit patients has not been well characterized. This study seeks to better understand how EPs' years of experience, post-residency, relates to their use of advanced imaging and patient disposition. Methods: Ten years of ED visits were analyzed for this study from a single, academic tertiary care center in the urban Northeast United States. The primary outcomes were utilization of advanced imaging during the visit (CT, MRI, or formal ultrasound) and whether the patient was admitted. EP years of experience was categorized into 0-2 years, 3-5 years, 6-8 years, 9-11 years, and 12 or more years. Patient age, sex, Emergency Severity Index (ESI), and the attending EP's years of experience were collected. The relationship between EP years of experience and each outcome was assessed with a linear mixed model with a random effect for provider and patient age, sex, and ESI as covariates. Results: A total of 460,937 visits seen by 65 EPs were included in the study. Over one-third (37.6%) of visits had an advanced imaging study ordered and nearly half (49.5%) resulted in admission. Compared to visits with EPs with 0-2 years of experience, visits with EPs with 3-5 or 6-8 years of experience had significantly lower odds of advanced imaging occurring. Visits seen by EPs with more than 2 years of experience had lower odds of admission than visits by EPs with 0-2 years of experience. Conclusion: More junior EPs tend to order more advanced imaging studies and have a higher propensity to admit patients. This may be due to less comfort in decision-making without advanced imaging or a lower risk tolerance. Conversely, the additional clinical experience of the most senior EPs, with greater than 9 years of experience, likely impacts their resource utilization patterns such that their use of advanced imaging does not significantly differ from the most junior EPs.

Resting-State Changes in Aging and Parkinson's Disease Are Shaped by Underlying Neurotransmission: A Normative Modeling Study.

BACKGROUND: Human healthy and pathological aging is linked to a steady decline in brain resting-state activity and connectivity measures. The neurophysiological mechanisms that underlie these changes remain poorly understood. METHODS: Making use of recent developments in normative modeling and availability of in vivo maps for various neurochemical systems, we tested in the UK Biobank cohort (n = 25,917) whether and how age- and Parkinson's disease-related resting-state changes in commonly applied local and global activity and connectivity measures colocalize with underlying neurotransmitter systems. RESULTS: We found that the distributions of several major neurotransmitter systems including serotonergic, dopaminergic, noradrenergic, and glutamatergic neurotransmission correlated with age-related changes across functional activity and connectivity measures. Colocalization patterns in Parkinson's disease deviated from normative aging trajectories for these, as well as for cholinergic and GABAergic (gamma-aminobutyric acidergic) neurotransmission. The deviation from normal colocalization of brain function and GABAA correlated with disease duration. CONCLUSIONS: These findings provide new insights into molecular mechanisms underlying age- and Parkinson's-related brain functional changes by extending the existing evidence elucidating the vulnerability of specific neurochemical attributes to normal aging and Parkinson's disease. The results particularly indicate that alongside dopamine and serotonin, increased vulnerability of glutamatergic, cholinergic, and GABAergic systems may also contribute to Parkinson's disease-related functional alterations. Combining normative modeling and neurotransmitter mapping may aid future research and drug development through deeper understanding of neurophysiological mechanisms that underlie specific clinical conditions.

Synthesis of PEGylated amphiphilic block copolymers with pendant linoleic moieties by combining ring-opening polymerization and click chemistry.

This study focused on synthesizing and characterizing PEGylated amphiphilic block copolymers with pendant linoleic acid (Lin) moieties as an alternative to enhance their potential in drug delivery applications. The synthesis involved a two-step process, starting with ring-opening polymerization of ε-caprolactone (CL) and propargylated cyclic carbonate (MCP) to obtain PEG-b-P(CL-co-MCP) copolymers, which were subsequently modified via click chemistry. Various reaction conditions were explored to improve the yield and efficiency of the click chemistry step. The use of anisole as a solvent, N-(3-azidopropyl)linoleamide as a substrate, and a reaction temperature of 60°C proved to be highly efficient, achieving nearly 100% conversion at a low catalyst concentration. The resulting copolymers exhibited controlled molecular weights and low polydispersity, confirming the successful synthesis. Furthermore, click chemistry allows for the attachment of Lin moieties to the copolymer, enhancing its hydrophobic character, as deduced from their significantly lower critical micelle concentration than that of traditional PEG-b-PCL systems, which is indicative of enhanced stability against dilution. The modified copolymers exhibited improved thermal stability, making them suitable for applications that require high processing temperatures. Dynamic light scattering and transmission electron microscopy confirmed the formation of micellar structures with sizes below 100 nm and minimal aggregate formation. Additionally, 1H NMR spectroscopy in deuterated water revealed the presence of core-shell micelles, which provided higher kinetic stability against dilution.

Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk.

Background: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD. Methods: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables. Results: At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated. Conclusion: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata.

Potential of Dual-Energy CT-Based Collagen Maps for the Assessment of Disk Degeneration in the Lumbar Spine.

RATIONALE AND OBJECTIVES: Lumbar disk degeneration is a common condition contributing significantly to back pain. The objective of the study was to evaluate the potential of dual-energy CT (DECT)-derived collagen maps for the assessment of lumbar disk degeneration. PATIENTS AND METHODS: We conducted a retrospective analysis of 127 patients who underwent dual-source DECT and MRI of the lumbar spine between 07/2019 and 10/2022. The level of lumbar disk degeneration was categorized by three radiologists as follows: no/mild (Pfirrmann 1&2), moderate (Pfirrmann 3&4), and severe (Pfirrmann 5). Recall (sensitivity) and accuracy of DECT collagen maps were calculated. Intraclass correlation coefficient (ICC) was used to evaluate inter-reader reliability. Subjective evaluations were performed using 5-point Likert scales for diagnostic confidence and image quality. RESULTS: We evaluated a total of 762 intervertebral disks from 127 patients (median age, 69.7 (range, 23.0-93.7), female, 56). MRI identified 230 non/mildly degenerated disks (30.2%), 484 moderately degenerated disks (63.5%), and 48 severely degenerated disks (6.3%). DECT collagen maps yielded an overall accuracy of 85.5% (1955/2286). Recall (sensitivity) was 79.3% (547/690) for the detection of no/mild lumbar disk degeneration, 88.7% (1288/1452) for the detection of moderate disk degeneration, and 83.3% (120/144) for the detection of severe disk degeneration (ICC=0.9). Subjective evaluations of DECT collagen maps showed high diagnostic confidence (median 4) and good image quality (median 4). CONCLUSION: The use of DECT collagen maps to distinguish different stages of lumbar disk degeneration may have clinical significance in the early diagnosis of disk-related pathologies in patients with contraindications for MRI or in cases of unavailability of MRI.

Value of Dual-Energy CT-Derived Metrics for the Prediction of Bone Non-union in Distal Radius Fractures.

RATIONALE AND OBJECTIVES: Bone non-union is a serious complication of distal radius fractures (DRF) that can result in functional limitations and persistent pain. However, no accepted method has been established to identify patients at risk of developing bone non-union yet. This study aimed to compare various CT-derived metrics for bone mineral density (BMD) assessment to identify predictive values for the development of bone non-union. MATERIALS AND METHODS: CT images of 192 patients with DRFs who underwent unenhanced dual-energy CT (DECT) of the distal radius between 03/2016 and 12/2020 were retrospectively identified. Available follow-up imaging and medical health records were evaluated to determine the occurrence of bone non-union. DECT-based BMD, trabecular Hounsfield unit (HU), cortical HU and cortical thickness ratio were measured in normalized non-fractured segments of the distal radius. RESULTS: Patients who developed bone non-union were significantly older (median age 72 years vs. 54 years) and had a significantly lower DECT-based BMD (median 68.1 mg/cm3 vs. 94.6 mg/cm3, p < 0.001). Other metrics (cortical thickness ratio, cortical HU, trabecular HU) showed no significant differences. ROC and PR curve analyses confirmed the highest diagnostic accuracy for DECT-based BMD with an area under the curve (AUC) of 0.83 for the ROC curve and an AUC of 0.46 for the PR curve. In logistic regression models, DECT-based BMD was the sole metric significantly associated with bone non-union. CONCLUSION: DECT-derived metrics can accurately predict bone non-union in patients who sustained DRF. The diagnostic performance of DECT-based BMD is superior to that of HU-based metrics and cortical thickness ratio.

Dual-Energy CT Material Decomposition: The Value in the Detection of Lymph Node Metastasis from Breast Cancer.

PURPOSE: To evaluate the diagnostic performance of a dual-energy computed tomography (DECT)-based material decomposition algorithm for iodine quantification and fat fraction analysis to detect lymph node metastases in breast cancer patients. MATERIALS AND METHODS: 30 female patients (mean age, 63.12 ± 14.2 years) diagnosed with breast cancer who underwent pre-operative chest DECT were included. To establish a reference standard, the study correlated histologic repots after lymphadenectomy or confirming metastasis in previous/follow-up examinations. Iodine concentration and fat fraction were determined through region-of-interest measurements on venous DECT iodine maps. Receiver operating characteristic curve analysis was conducted to identify the optimal threshold for differentiating between metastatic and non-metastatic lymph nodes. RESULTS: A total of 168 lymph nodes were evaluated, divided into axillary (metastatic: 46, normal: 101) and intramammary (metastatic: 10, normal: 11). DECT-based fat fraction values exhibited significant differences between metastatic (9.56 ± 6.20%) and non-metastatic lymph nodes (41.52 ± 19.97%) (p < 0.0001). Absolute iodine concentrations showed no significant differences (2.25 ± 0.97 mg/mL vs. 2.08 ± 0.97 mg/mL) (p = 0.7999). The optimal fat fraction threshold for diagnosing metastatic lymph nodes was determined to be 17.75%, offering a sensitivity of 98% and a specificity of 94%. CONCLUSIONS: DECT fat fraction analysis emerges as a promising method for identifying metastatic lymph nodes, overcoming the morpho-volumetric limitations of conventional CT regarding lymph node assessment. This innovative approach holds potential for improving pre-operative lymph node evaluation in breast cancer patients, offering enhanced diagnostic accuracy.

Lifetime and 10-year risks of cardiovascular mortality in relation to risk factors in middle and old age: 50-year follow-up of the Whitehall study of London Civil Servants.

BACKGROUND: Cardiovascular disease (CVD)-related mortality has declined substantially in the United Kingdom (UK) in recent decades, but the continued relevance of conventional risk factors for prediction of CVD mortality throughout the life-course is uncertain. We compared the 10-year risks and lifetime risks of CVD mortality associated with conventional risk factors recorded in middle and old age. METHODS: The Whitehall study was a prospective study of 19,019 male London civil servants (mean age 52 years) when enrolled in 1967-1970 and followed-up for 50 years for cause-specific mortality. In 1997, 7044 (83%) survivors (mean age 77 years) were re-surveyed. The 10-year and lifetime risks of CVD mortality were estimated by levels of CVD risk factors recorded in middle-age and old-age, respectively. RESULTS: By July 2020, 97% had died (22%, 51% and 80% before age 70, 80 and 90 years, respectively) and 7944 of 17,673 deaths (45%) were from CVD. The 10-year and lifetime risks of CVD death increased linearly with higher levels of CVD risk factors recorded in middle-age and in old-age. Individuals in the top versus bottom 5% of CVD risk scores in middle age had a 10.3% (95% CI:7.2-13.4) vs 0.6% (0.1-1.2) 10-year risk of CVD mortality, a 61.4% (59.4-65.3) vs 31.3% (24.1-34.5) lifetime risk of CVD mortality and a 12-year difference in life expectancy from age 50 years. The corresponding differences using a CVD risk score in old-age were 11.0% (4.4-17.5) vs 0.8% (0.0-2.2) for 10-year risk and 42.1% (28.2-50.0) vs 30.3% (6.0-38.0) for lifetime risk of CVD mortality and a 6-year difference in life expectancy from age 70 years. CONCLUSIONS: Conventional risk factors remained highly predictive of CVD mortality and life expectancy through the life-course. The findings highlight the relevance of estimation of both lifetime risks of CVD and 10-year risks of CVD for primary prevention of CVD.