Diagnostic Accuracy of Dual-Energy CT-Derived Metrics for the Prediction of Osteoporosis-Associated Fractures.

RATIONALE AND OBJECTIVES: This study aimed to compare the diagnostic value of dual-energy CT (DECT)-based volumetric material decomposition with that of Hounsfield units (HU)-based values and cortical thickness ratio for predicting the 2-year risk of osteoporosis-associated fractures. METHODS: The L1 vertebrae of 111 patients (55 men, 56 women; median age, 62 years) who underwent DECT between 01/2015 and 12/2018 were retrospectively analyzed. For phantomless bone mineral density (BMD) assessment, a specialized DECT postprocessing software employing material decomposition was utilized. The digital records of all patients were monitored for two years after the DECT scans to track the incidence of osteoporotic fractures. Diagnostic accuracy parameters were calculated for all metrics using receiver-operating characteristic (ROC) and precision-recall (PR) curves. Logistic regression models were used to determine associations of various predictive metrics with the occurrence of osteoporotic fractures. RESULTS: Patients who sustained one or more osteoporosis-associated fractures in a 2-year interval were significantly older (median age 74.5 years [IQR 57-83 years]) compared those without such fractures (median age 50.5 years [IQR 38.5-69.5 years]). According to logistic regression models, DECT-derived BMD was the sole predictive parameter significantly associated with osteoporotic fracture occurrence across all age groups. ROC and PR curve analyses confirmed the highest diagnostic accuracy for DECT-based BMD, with an area under the curve (AUC) of 0.95 [95% CI: 0.89-0.98] for the ROC curve and an AUC of 0.96 [95% CI: 0.85-0.99] for the PR curve. CONCLUSION: The diagnostic performance of DECT-based BMD in predicting the 2-year risk of osteoporotic fractures is greater than that of HU-based metrics and the cortical thickness ratio. DECT-based BMD values are highly valuable in identifying patients at risk for osteoporotic fractures.

Clinical Presentation, Management, and Outcome in Neurolymphomatosis: A Systematic Review.

BACKGROUND AND OBJECTIVES: Neurolymphomatosis (NL) refers to lymphomatous infiltration of the peripheral nervous system (PNS). NL diagnosis and treatment are challenging given the broad differential diagnosis of peripheral neuropathy, the lack of larger cohorts, and the subsequent unavailability of prognostic factors or consensus therapy. This study aimed to define characteristics and prognostic factors of NL. METHODS: A systematic review of the literature (2004-2023) was performed using PubMed and Scopus databases and reported following PRISMA guidelines. Studies reporting individual patient data on cases with definitive NL diagnosis were included. Clinical, radiologic, pathologic, and outcome information were extracted. Univariable and multivariable survival analyses were performed using log-rank tests and Cox proportional hazard models. RESULTS: A total of 459 NL cases from 264 studies were accumulated. NL was the first manifestation of malignancy (primary NL) in 197 patients. PNS relapse of known non-Hodgkin lymphoma (secondary NL) occurred in 262 cases after a median 12 months. NL predominantly presented with rapidly deteriorating, asymmetric painful polyneuropathy. Infiltrated structures included peripheral nerves (56%), nerve roots (52%), plexus (33%), and cranial nerves (32%). Diagnosis was established at a median of 3 months after symptom onset with substantial delays in primary NL. It mainly relied on PNS biopsy or FDG-PET, which carried high diagnostic yields (>90%). Postmortem diagnoses were rare (3%). Most cases were classified as B-cell (90%) lymphomas. Tumor-directed therapy was administered in 96% of patients and typically consisted of methotrexate or rituximab-based polychemotherapy. The median overall survival was 18 months. Primary NL without concurrent systemic disease outside the nervous system (hazard ratio [HR]: 0.44; 95% CI 0.25-0.78; p = 0.005), performance status (ECOG <2, HR: 0.30; 95% CI 0.18-0.52; p < 0.0001), and rituximab-based treatment (HR: 0.46; 95% CI 0.28-0.73; p = 0.001) were identified as favorable prognostic markers on multivariable analysis when adjusting for clinical and sociodemographic parameters. DISCUSSION: Advances in neuroimaging modalities, particularly FDG-PET, facilitate NL diagnosis and offer a high diagnostic yield. Yet, diagnostic delays in primary NL remain common. Rituximab-based therapy improves NL outcome. Findings may assist clinicians in early recognition, prognostic stratification, and treatment of NL.

Accuracy and time efficiency of a novel deep learning algorithm for Intracranial Hemorrhage detection in CT Scans.

PURPOSE: To evaluate a deep learning-based pipeline using a Dense-UNet architecture for the assessment of acute intracranial hemorrhage (ICH) on non-contrast computed tomography (NCCT) head scans after traumatic brain injury (TBI). MATERIALS AND METHODS: This retrospective study was conducted using a prototype algorithm that evaluated 502 NCCT head scans with ICH in context of TBI. Four board-certified radiologists evaluated in consensus the CT scans to establish the standard of reference for hemorrhage presence and type of ICH. Consequently, all CT scans were independently analyzed by the algorithm and a board-certified radiologist to assess the presence and type of ICH. Additionally, the time to diagnosis was measured for both methods. RESULTS: A total of 405/502 patients presented ICH classified in the following types: intraparenchymal (n = 172); intraventricular (n = 26); subarachnoid (n = 163); subdural (n = 178); and epidural (n = 15). The algorithm showed high diagnostic accuracy (91.24%) for the assessment of ICH with a sensitivity of 90.37% and specificity of 94.85%. To distinguish the different ICH types, the algorithm had a sensitivity of 93.47% and a specificity of 99.79%, with an accuracy of 98.54%. To detect midline shift, the algorithm had a sensitivity of 100%. In terms of processing time, the algorithm was significantly faster compared to the radiologist's time to first diagnosis (15.37 ± 1.85 vs 277 ± 14 s, p < 0.001). CONCLUSION: A novel deep learning algorithm can provide high diagnostic accuracy for the identification and classification of ICH from unenhanced CT scans, combined with short processing times. This has the potential to assist and improve radiologists' ICH assessment in NCCT scans, especially in emergency scenarios, when time efficiency is needed.

Factors influencing timely diagnosis in neurolymphomatosis.

BACKGROUND: Neurolymphomatosis refers to infiltration of the peripheral nervous system (PNS) by non-Hodgkin lymphoma (NHL). Diagnostic intervals in neurolymphomatosis and factors delaying diagnosis have not been evaluated. We therefore aimed to analyze diagnostic intervals in a large cohort. METHODS: The quality control database at Yale Cancer Center, Section of Neuro-Oncology, was searched for neurolymphomatosis cases diagnosed between 2001 and 2021. Univariate analyses were performed to identify parameters influencing diagnostic intervals. RESULTS: We identified 22 neurolymphomatosis cases including 7 with primary and 15 with secondary disease, which occurred a median (range: 4-144) of 16 months after initial NHL diagnosis. Patients typically presented with painful polyneuropathy (73%), that was asymmetrical and rapidly progressive. Diagnosis was based on PNS biopsy (50%) or integration of neuroimaging findings (50%) with NHL history and diagnostic cerebrospinal fluid examinations. Median interval from symptom onset to diagnosis was 3 months (range: 1-12). Secondary neurolymphomatosis compared to primary disease (median 2 vs. 6 months, p = 0.02), and cases with rapidly-progressive asymmetrical neuropathy as opposed to other presentations (median 2 vs. 6 months; p < 0.001) were diagnosed earlier. Upfront conventional CT compared to other modalities (median 2 vs. 5 months p = 0.04) and nerve root localization as opposed to other disease sites (median 1.5 vs. 4 months; p = 0.04) delayed diagnosis. CONCLUSIONS: NL type and localization, neuropathy course and distribution, and imaging modality selected for initial evaluation influence diagnostic intervals in neurolymphomatosis. Knowledge of this rare entity is critical for early suspicion, and diagnosis.

Biomechanical Assessment of Liver Integrity: Prospective Evaluation of Mechanical Versus Acoustic MR Elastography.

BACKGROUND: Magnetic resonance elastography (MRE) can quantify tissue biomechanics noninvasively, including pathological hepatic states like metabolic dysfunction-associated steatohepatitis. PURPOSE: To compare the performance of 2D/3D-MRE using the gravitational (GT) transducer concept with the current commercial acoustic (AC) solution utilizing a 2D-MRE approach. Additionally, quality index markers (QIs) were proposed to identify image pixels with sufficient quality for reliably estimating tissue biomechanics. STUDY TYPE: Prospective. POPULATION: One hundred seventy participants with suspected or confirmed liver disease (median age, 57 years [interquartile range (IQR), 46-65]; 66 females), and 11 healthy volunteers (median age, 31 years [IQR, 27-34]; 5 females). FIELD STRENGTH/SEQUENCE: Participants were scanned twice at 1.5 T and 60 Hz vibration frequency: first, using AC-MRE (2D-MRE, spin-echo EPI sequence, 11 seconds breath-hold), and second, using GT-MRE (2D- and 3D-MRE, gradient-echo sequence, 14 seconds breath-hold). ASSESSMENT: Image analysis was performed by four independent radiologists and one biomedical engineer. Additionally, superimposed analytic plane shear waves of known wavelength and attenuation at fixed shear modulus were used to propose pertinent QIs. STATISTICAL TESTS: Spearman's correlation coefficient (r) was applied to assess the correlation between modalities. Interreader reproducibility was evaluated using Bland-Altman bias and reproducibility coefficients. P-values <0.05 were considered statistically significant. RESULTS: Liver stiffness quantified via GT-2D/3D correlated well with AC-2D (r ≥ 0.89 [95% CI: 0.85-0.92]) and histopathological grading (r ≥ 0.84 [95% CI: 0.72-0.91]), demonstrating excellent agreement in Bland-Altman plots and between readers (κ ≥ 0.86 [95% CI: 0.81-0.91]). However, GT-2D showed a bias in overestimating stiffness compared to GT-3D. Proposed QIs enabled the identification of pixels deviating beyond 10% from true stiffness based on a combination of total wave amplitude, temporal sinusoidal nonlinearity, and wave signal-to-noise ratio for GT-3D. CONCLUSION: GT-MRE represents an alternative to AC-MRE for noninvasive liver tissue characterization. Both GT-2D and 3D approaches correlated strongly with the established commercial approach, offering advanced capabilities in abdominal imaging compared to AC-MRE. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Epigenetic profiling of prostate cancer reveals potential prognostic signatures.

PURPOSE: While epigenetic profiling discovered biomarkers in several tumor entities, its application in prostate cancer is still limited. We explored DNA methylation-based deconvolution of benign and malignant prostate tissue for biomarker discovery and the potential of radiomics as a non-invasive surrogate. METHODS: We retrospectively included 30 patients (63 [58-79] years) with prostate cancer (PCa) who had a multiparametric MRI of the prostate before radical prostatectomy between 2014 and 2019. The control group comprised four patients with benign prostate tissue adjacent to the PCa lesions and four patients with benign prostatic hyperplasia. Tissue punches of all lesions were obtained. DNA methylation analysis and reference-free in silico deconvolution were conducted to retrieve Latent Methylation Components (LCMs). LCM-based clustering was analyzed for cellular composition and correlated with clinical disease parameters. Additionally, PCa and adjacent benign lesions were analyzed using radiomics to predict the epigenetic signatures non-invasively. RESULTS: LCMs identified two clusters with potential prognostic impact. Cluster one was associated with malignant prostate tissue (p < 0.001) and reduced immune-cell-related signatures (p = 0.004) of CD19 and CD4 cells. Cluster one comprised exclusively malignant prostate tissue enriched for significant prostate cancer and advanced tumor stages (p < 0.03 for both). No radiomics model could non-invasively predict the epigenetic clusters. CONCLUSION: Epigenetic clusters were associated with prognostically and clinically relevant metrics in prostate cancer. Further, immune cell-related signatures differed significantly between prognostically favorable and unfavorable clusters. Further research is necessary to explore potential diagnostic and therapeutic implications.

Neighborhood Resources Associated With Psychological Trajectories and Neural Reactivity to Reward After Trauma.

Importance: Research on resilience after trauma has often focused on individual-level factors (eg, ability to cope with adversity) and overlooked influential neighborhood-level factors that may help mitigate the development of posttraumatic stress disorder (PTSD). Objective: To investigate whether an interaction between residential greenspace and self-reported individual resources was associated with a resilient PTSD trajectory (ie, low/no symptoms) and to test if the association between greenspace and PTSD trajectory was mediated by neural reactivity to reward. Design, Setting, and Participants: As part of a longitudinal cohort study, trauma survivors were recruited from emergency departments across the US. Two weeks after trauma, a subset of participants underwent functional magnetic resonance imaging during a monetary reward task. Study data were analyzed from January to November 2023. Exposures: Residential greenspace within a 100-m buffer of each participant's home address was derived from satellite imagery and quantified using the Normalized Difference Vegetation Index and perceived individual resources measured by the Connor-Davidson Resilience Scale (CD-RISC). Main Outcome and Measures: PTSD symptom severity measured at 2 weeks, 8 weeks, 3 months, and 6 months after trauma. Neural responses to monetary reward in reward-related regions (ie, amygdala, nucleus accumbens, orbitofrontal cortex) was a secondary outcome. Covariates included both geocoded (eg, area deprivation index) and self-reported characteristics (eg, childhood maltreatment, income). Results: In 2597 trauma survivors (mean [SD] age, 36.5 [13.4] years; 1637 female [63%]; 1304 non-Hispanic Black [50.2%], 289 Hispanic [11.1%], 901 non-Hispanic White [34.7%], 93 non-Hispanic other race [3.6%], and 10 missing/unreported [0.4%]), 6 PTSD trajectories (resilient, nonremitting high, nonremitting moderate, slow recovery, rapid recovery, delayed) were identified through latent-class mixed-effect modeling. Multinominal logistic regressions revealed that for individuals with higher CD-RISC scores, greenspace was associated with a greater likelihood of assignment in a resilient trajectory compared with nonremitting high (Wald z test = -3.92; P < .001), nonremitting moderate (Wald z test = -2.24; P = .03), or slow recovery (Wald z test = -2.27; P = .02) classes. Greenspace was also associated with greater neural reactivity to reward in the amygdala (n = 288; t277 = 2.83; adjusted P value = 0.02); however, reward reactivity did not differ by PTSD trajectory. Conclusions and Relevance: In this cohort study, greenspace and self-reported individual resources were significantly associated with PTSD trajectories. These findings suggest that factors at multiple ecological levels may contribute to the likelihood of resiliency to PTSD after trauma.

Small duct and large duct type intrahepatic cholangiocarcinoma reveal distinct patterns of immune signatures.

PURPOSE: Dedicated gene signatures in small (SD-iCCA) and large (LD-iCCA) duct type intrahepatic cholangiocarcinoma remain unknown. We performed immune profiling in SD- and LD-iCCA to identify novel biomarker candidates for personalized medicine. METHODS: Retrospectively, 19 iCCA patients with either SD-iCCA (n = 10, median age, 63.1 years (45-86); men, 4) or LD-iCCA (n = 9, median age, 69.7 years (62-85); men, 5)) were included. All patients were diagnosed and histologically confirmed between 04/2009 and 01/2021. Tumor tissue samples were processed for differential expression profiling using NanoString nCounter® PanCancer Immune Profiling Panel. RESULTS: With the exception of complement signatures, immune-related pathways were broadly downregulated in SD-iCCA vs. LD-iCCA. A total of 20 immune-related genes were strongly downregulated in SD-iCCA with DMBT1 (log2fc = -5.39, p = 0.01) and CEACAM6 (log2fc = -6.38, p = 0.01) showing the strongest downregulation. Among 7 strongly (log2fc > 2, p ≤ 0.02) upregulated genes, CRP (log2fc = 5.06, p = 0.02) ranked first, and four others were associated with complement (C5, C4BPA, C8A, C8B). Total tumor-infiltrating lymphocytes (TIL) signature was decreased in SD-iCCA with elevated ratios of exhausted-CD8/TILs, NK/TILs, and cytotoxic cells/TILs while having decreased ratios of B-cells/TILs, mast cells/TILs and dendritic cells/TILs. The immune profiling signatures in SD-iCCA revealed downregulation in chemokine signaling pathways inclulding JAK2/3 and ERK1/2 as well as nearly all cytokine-cytokine receptor interaction pathways with the exception of the CXCL1/CXCR1-axis. CONCLUSION: Immune patterns differed in SD-iCCA versus LD-iCCA. We identified potential biomarker candidate genes, including CRP, CEACAM6, DMBT1, and various complement factors that could be explored for augmented diagnostics and treatment decision-making.

Protector Role of Cx30.2 in Pancreatic ß-Cell against Glucotoxicity-Induced Apoptosis.

Glucotoxicity may exert its deleterious effects on pancreatic ß-cell function via a myriad of mechanisms, leading to impaired insulin secretion and, eventually, type 2 diabetes. ß-cell communication requires gap junction channels to be present among these cells. Gap junctions are constituted by transmembrane proteins of the connexins (Cxs) family. Two Cx genes have been identified in ß cells, Cx36 and Cx30.2. We have found evidence that the glucose concentration on its own is sufficient to regulate Cx30.2 gene expression in mouse islets. In this work, we examine the involvement of the Cx30.2 protein in the survival of ß cells (RIN-m5F). METHODS: RIN-m5F cells were cultured in 5 mM D-glucose (normal) or 30 mM D-glucose (high glucose) for 24 h. Cx30.2 siRNAs was used to downregulate Cx30.2 expression. Apoptosis was measured by means of TUNEL, an annexin V staining method, and the cleaved form of the caspase-3 protein was determined using Western blot. RESULTS: High glucose did not induce apoptosis in RIN-m5F ß cells after 24 h; interestingly, high glucose increased the Cx30.2 total protein levels. Moreover, this work found that the downregulation of Cx30.2 expression in high glucose promoted apoptosis in RIN-m5F cells. CONCLUSION: The data suggest that the upregulation of Cx30.2 protects ß cells from hyperglycemia-induced apoptosis. Furthermore, Cx30.2 may be a promising avenue of therapeutic investigation for the treatment of glucose metabolic disorders.

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.

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.

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.

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.

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.

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.

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.

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.