Integrin α2 is an early marker for osteoclast differentiation that contributes to key steps in osteoclastogenesis.

Introduction: Osteoclasts determine bone tissue turnover. Their increased activity causes osteoporosis, their dysfunction osteopetrosis. Methods and Results: Murine monocytic ER-Hoxb8 cells differentiate into OCs upon treatment with M-CSF and RANKL and upregulate the collagen-binding integrin α2ß1 distinctly earlier than other OC markers, such as the OC-associated receptor, OSCAR. Integrin α2ß1 promotes OC differentiation at multiple levels by stimulating differentiation-relevant genes, by regulating cell matrix adhesion and the formation of adhesion-promoting protrusions, and by the upregulation of proteins involved in precursor cell fusion. The two key factors in osteoclastogenesis, RANK and NFATc1, were essentially unaffected after knocking out the ITGA2 gene encoding integrin α2 subunit. However, compared to integrin α2ß1 expressing ER-Hoxb8 cells, ITGA2-deficient cells adhered differently with more branched filopodia and significantly longer tunneling nanotubes. Despite the higher number of fusion-relevant TNTs, they form fewer syncytia. They also resorb less hydroxyapatite, because integrin α2ß1 regulates expression of lacuna proteins necessary for bone matrix resorption. The impaired syncytia formation of ITGA2-deficient OC precursor cells also correlated with reduced gene activation of fusion-supporting DC-STAMP and with an almost abolished transcription of tetraspanin CD9. CD9 only partially colocalized with integrin α2ß1 in TNTs and filopodia of integrin α2ß1-expressing OC precursors. Discussion: Our findings define integrin α2ß1 as an early marker of OC differentiation.

The efficacy of cone-beam computed tomography-guided transcatheter arterial chemoembolization in hepatocellular carcinoma survival: A systematic review.

Cone-beam computed tomography (CBCT)-guided transcatheter arterial chemoembolization (TACE) represents an alternative treatment option for advanced hepatocellular carcinoma (HCC) patients, yet a comprehensive evaluation of CBCT guidance on this procedure and CBCT's impact on patient survival remains lacking. We aimed to assess the efficacy and benefits of CBCT-guided TACE in improving survival outcomes for patients with HCC and show the importance of CBCT in interventional radiology. Meta-analysis was conducted to evaluate CBCT-guided TACE compared to conventional TACE in the treatment of HCC. PubMed and Cochrane library databases were searched for studies published. Outcomes of interest included 1- or 3-year local progression-free survival (LPFS) rates, overall survival (OS) rates, and tumor response results. A total of eight studies were included in the meta-analysis, comprising 1176 patients. The analysis showed that CBCT-guided TACE improved 1-year LPFS (odds ratio [OR] = 2.81, P < 0.001), 3-year (OR = 4.42, P = 0.002), and the 3-year OS rates (OR = 3.03, Confidence Interval = 1.65-11.80, P = 0.14) compared to conventional TACE. CBCT-guided TACE enhances survival outcomes for patients with HCC; by addressing this research gap, our study endeavors to encourage clinicians and researchers to pursue this medical technology by providing a robust synthesis of current evidence.

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.

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.

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.

Development of systemic and mucosal immune responses against gut microbiota in early life and implications for the onset of allergies.

The early microbial colonization of human mucosal surfaces is essential for the development of the host immune system. Already during pregnancy, the unborn child is prepared for the postnatal influx of commensals and pathogens via maternal antibodies, and after birth this protection is continued with antibodies in breast milk. During this critical window of time, which extends from pregnancy to the first year of life, each encounter with a microorganism can influence children's immune response and can have a lifelong impact on their life. For example, there are numerous links between the development of allergies and an altered gut microbiome. However, the exact mechanisms behind microbial influences, also extending to how viruses influence host-microbe interactions, are incompletely understood. In this review, we address the impact of infants' first microbial encounters, how the immune system develops to interact with gut microbiota, and summarize how an altered immune response could be implied in allergies.

Enhancing Forensic Diagnostics: Structured Reporting of Post-Mortem CT versus Autopsy for Laryngohyoid Complex Fractures in Strangulation.

BACKGROUND: The purpose of this study was to establish a standardized structured workflow to compare findings from high-resolution, optimized reconstructions from post-mortem computed tomography (pmCT) with autopsy results in the detection of fractures of the laryngohyoid complex in strangulation victims. METHOD: Forty-two strangulation cases were selected, and pmCT scans of the laryngohyoid complex were obtained. Both pmCT scans and autopsy reports were analyzed using a structured template and compared using Cohen's kappa coefficient (κ) and the McNemar test. The study also compared the prevalence of ossa sesamoidea and non-fusion of the major and minor horns of the hyoid bone between both diagnostic methods. RESULTS: The detection of fractures showed a very good correlation between autopsy and pmCT results (κ = 0.905), with the McNemar test showing no statistically significant difference between the two methods. PmCT identified 28 sesamoid bones, 45 non-fusions of the major horns, and 47 non-fusions of the minor horns of the hyoid bone, compared to four, six, and zero, respectively, identified by autopsy (p < 0.0001). CONCLUSIONS: Autopsy and pmCT findings correlate well and can be used in a complementary manner. PmCT is superior to autopsy in identifying dislocations and detecting anatomical variations in the laryngohyoid complex, which can lead to misinterpretations during autopsy. Therefore, we do not advocate replacing autopsy with pmCT but propose using a structured workflow, including our standardized reporting template, for evaluating lesions in the laryngohyoid complex.

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.

Assessment of thoracic disc degeneration using dual-energy CT-based collagen maps.

BACKGROUND: We evaluated the role of dual-energy computed tomography (DECT)-based collagen maps in assessing thoracic disc degeneration. METHODS: We performed a retrospective analysis of patients who underwent DECT and magnetic resonance imaging (MRI) of the thoracic spine within a 2-week period from July 2019 to October 2022. Thoracic disc degeneration was classified by three blinded radiologists into three Pfirrmann categories: no/mild (grade 1-2), moderate (grade 3-4), and severe (grade 5). The DECT performance was determined using MRI as a reference standard. Interreader reliability was assessed using intraclass correlation coefficient (ICC). Five-point Likert scales were used to assess diagnostic confidence and image quality. RESULTS: In total, 612 intervertebral discs across 51 patients aged 68 ± 16 years (mean ± standard deviation), 28 males and 23 females, were assessed. MRI revealed 135 no/mildly degenerated discs (22.1%), 470 moderately degenerated discs (76.8%), and 7 severely degenerated discs (1.1%). DECT collagen maps achieved an overall accuracy of 1,483/1,838 (80.8%) for thoracic disc degeneration. Overall recall (sensitivity) was 331/405 (81.7%) for detecting no/mild degeneration, 1,134/1,410 (80.4%) for moderate degeneration, and 18/21 (85.7%) for severe degeneration. Interrater agreement was good (ICC = 0.89). Assessment of DECT-based collagen maps demonstrated high diagnostic confidence (median 4; interquartile range 3-4) and good image quality (median 4; interquartile range 4-4). CONCLUSION: DECT showed an overall 81% accuracy for disc degeneration by visualizing differences in the collagen content of thoracic discs. RELEVANCE STATEMENT: Utilizing DECT-based collagen maps to distinguish various stages of thoracic disc degeneration could be clinically relevant for early detection of disc-related conditions. This approach may be particularly beneficial when MRI is contraindicated. KEY POINTS: A total of 612 intervertebral discs across 51 patients were retrospectively assessed with DECT, using MRI as a reference standard. DECT-based collagen maps allowed thoracic disc degeneration assessment achieving an overall 81% accuracy with good interrater agreement (ICC = 0.89). DECT-based collagen maps could be a good alternative in the case of contraindications to MRI.

Systemic antibody responses against gut microbiota flagellins implicate shared and divergent immune reactivity in Crohn's disease and chronic fatigue syndrome.

BACKGROUND: Elevated systemic antibody responses against gut microbiota flagellins are observed in both Crohn's disease (CD) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggesting potential serological biomarkers for diagnosis. However, flagellin-specific antibody repertoires and functional roles in the diseases remain incompletely understood. Bacterial flagellins can be categorized into three types depending on their interaction with toll-like receptor 5 (TLR5): (1) "stimulator" and (2) "silent" flagellins, which bind TLR5 through a conserved N-terminal motif, with only stimulators activating TLR5 (involving a C-terminal domain); (3) "evader" flagellins of pathogens, which entirely circumvent TLR5 activation via mutations in the N-terminal TLR5 binding motif. RESULTS: Here, we show that both CD and ME/CFS patients exhibit elevated antibody responses against distinct regions of flagellins compared to healthy individuals. N-terminal binding to Lachnospiraceae flagellins was comparable in both diseases, while C-terminal binding was more prevalent in CD. N-terminal antibody-bound flagellin sequences were similar across CD and ME/CFS, resembling "stimulator" and "silent" flagellins more than evaders. However, C-terminal antibody-bound flagellins showed a higher resemblance to the stimulator than to silent flagellins in CD, which was not observed in ME/CFS. CONCLUSIONS: These findings suggest that antibody binding to the N-terminal domain of stimulator and silent flagellins may impact TLR5 activation in both CD and ME/CFS patients. Blocking this interaction could lead commensal bacteria to be recognized as pathogenic evaders, potentially contributing to dysregulation in both diseases. Furthermore, elevated antibody binding to the C-terminal domain of stimulator flagellins in CD may explain pathophysiological differences between the diseases. Overall, these results highlight the diagnostic potential of these antibody responses and lay a foundation for deeper mechanistic studies of flagellin/TLR5 interactions and their impact on innate/adaptive immunity balance.

Radiation exposure and estimated risk of radiation-induced cancer from thoracic and abdominal radiographs in 1307 neonates.

OBJECTIVE: This study examined radiation exposure and the possible risk of radiation-induced cancer in a large sample of newborn and premature patients. MATERIAL AND METHODS: In this retrospective study, we included all hospitalised neonates treated at our university hospital who received at least one X-ray examination from 1 January 2013 to 31 December 2018. We evaluated the dose area product (DAP), effective dose (ED), and estimated risk. The International Commission on Radiological Protection Publication 60 defines values (2.8-13 × 10-2 Sv-1) to calculate the estimated risk in relation to the ED. RESULTS: Of the 3843 patients (aged 241.1 ± 35.45 days) treated in the neonatal care unit, 1307 (34%) received at least one X-ray. The mean number of X-ray examinations per patient was 3.19 and correlated negatively with birth weight. The mean cumulative DAP was 5.9 mGy*cm2, and the cumulative ED was 23.7 µSv per hospital stay. Patients with a birth weight of < 1000 g showed the highest cumulative ED and DAP (p < 0.001). Patients with a birth weight of < 2500 g had the highest ED and DAP per image (p < 0.001). The highest radiation exposure (ED/DAP) occurred for thoracic/abdominal examinations, especially for neonates < 500 g (p < 0.001). CONCLUSION: There is a strong correlation between immaturity, the number of X-ray examinations, and radiation exposure. The total exposure was minimal, and the number of X-rays per patient has been decreasing in recent years. CLINICAL RELEVANCE: Possible risks to newborns and premature infants caused by ionising X-rays are often the subject of scientific and clinical discussion. Nevertheless, conventional X-ray imaging remains a frequently used tool, and total exposure remains at a very low level. KEY POINTS: The number of X-rays per patient has been decreasing in a large university hospital. Half of all patients received only one X-ray; most had a birth weight over 1500 g. This radiation risk can be classified as 'minimal' for patients with a birth weight of < 500 g and as 'negligible' for others.

Prevalence and prognostic role of thoracic lymphadenopathy in Covid-19. / Prävalenz und prognostische Rolle der thorakalen Lymphadenopathie bei Covid-19.

PURPOSE: The prevalent coronavirus disease 2019 (COVID-19) pandemic has spread throughout the world and is considered a serious threat to global health. The prognostic role of thoracic lymphadenopathy in COVID-19 is unclear. The aim of the present meta-analysis was to analyze the prognostic role of thoracic lymphadenopathy for the prediction of 30-day mortality in patients with COVID-19. MATERIALS AND METHODS: The MEDLINE library, Cochrane, and SCOPUS databases were screened for associations between CT-defined features and mortality in COVID-19 patients up to June 2021. In total, 21 studies were included in the present analysis. The quality of the included studies was assessed by the Newcastle-Ottawa Scale. The meta-analysis was performed using RevMan 5.3. Heterogeneity was calculated by means of the inconsistency index I2. DerSimonian and Laird random-effect models with inverse variance weights were performed without any further correction. RESULTS: The included studies comprised 4621 patients. The prevalence of thoracic lymphadenopathy varied between 1 % and 73.4 %. The pooled prevalence was 16.7 %, 95 % CI = (15.6 %; 17.8 %). The hospital mortality was higher in patients with thoracic lymphadenopathy (34.7 %) than in patients without (20.0 %). The pooled odds ratio for the influence of thoracic lymphadenopathy on mortality was 2.13 (95 % CI = [1.80-2.52], p < 0.001). CONCLUSION: The prevalence of thoracic lymphadenopathy in COVID-19 is 16.7 %. The presence of thoracic lymphadenopathy is associated with an approximately twofold increase in the risk for hospital mortality in COVID-19. KEY POINTS: · The prevalence of lymphadenopathy in COVID-19 is 16.7 %.. · Patients with lymphadenopathy in COVID-19 have a higher risk of mortality during hospitalization.. · Lymphadenopathy nearly doubles mortality and plays an important prognostic role.. CITATION FORMAT: · Bucher AM, Sieren M, Meinel F et al. Prevalence and prognostic role of thoracic lymphadenopathy in Covid-19. Fortschr Röntgenstr 2024; DOI: 10.1055/a-2293-8132.

Pre- and Post-Operative Cone Beam Computed Tomography Assessment of the Temporomandibular Joint in Patients with Orthognathic Surgery.

This study aimed to compare the pre- and post-operative temporomandibular joint (TMJ) condylar position in dentofacial deformity (DFD) patients who had orthognathic surgeries using cone beam computed tomography (CBCT). A retrospective study evaluating the pre- and post-operative CBCT for 79 DFD patients (equivalent to 158 TMJs) (mean age = 26.62 ± 9.5 years) with a bilateral sagittal split osteotomy with or without Le Fort I surgeries (n = 29 Class II DFD, n = 50 Class III DFD) was performed. This included the compartmental measurement of TMJ spaces, in addition to the measurement of intercondylar distances and angles. Condylar position centricity was assessed using the Pullinger and Hollender formula. Clinical data were analysed for DFD class, the type of surgery and post-operative CBCT timing. Pre- and post-operative measurements were compared statistically using a paired t-test, Wilcoxon signed-rank test, and Stuart-Maxwell test. TMJ condyles tended to relocate post-operatively in a posterosuperior position with internal rotation in Class II DFD and a superior position with internal rotation in Class III DFD. However, the overall changes were within <0.5 mm translation and <4° rotation and the number of concentrically positioned condyles (according to the Pullinger and Hollender formula) did not change significantly. Orthognathic surgery is associated with minor post-operative translational and rotational condylar positional changes in Class II and III DFDs.

CT-Guided Percutaneous Cryoablation of Breast Cancer: A Single-Center Experience.

This study shall retrospectively evaluate the efficacy and safety of liquid-nitrogen based CT-guided cryoablation (CA) as a minimal-invasive technique for the curative treatment of primary breast cancer. A total of 45 female patients with 56 tumors were treated by CT-guided CA in analgosedation as an outpatient procedure. We used a liquid-nitrogen based system with a single cryoprobe and performed two freeze cycles with an intermediate thawing. The mean tumor diameter was 1.6 ± 0.7 cm. Follow-up was conducted via contrast-enhanced MR images of the breast. No complications were observed in all 56 ablations. Initial complete ablation was achieved in 100% of cases. Four cases of local tumor progression were reported, resulting in a rate of 8.9%, and 6 cases of intramammary distant recurrence at a rate of 13.3%. The extramammary tumor progression was observed in 7 patients at a rate of 15.6%. The mean overall survival was 4.13 years (95% CI: 3.7-4.5). The mean overall progression-free survival was 2.5 years (95% CI: 1.8-3.2) and the mean local progression-free survival was 2.9 years (95% CI: 2.3-3.6). Cryoablation is a safe and effective treatment for primary breast cancer tumors, which can be performed in analgosedation and as an outpatient procedure. However, potential for improvement exists and further evidence is necessary.

Radiomics and visual analysis for predicting success of transplantation of heterotopic glioblastoma in mice with MRI.

BACKGROUND: Quantifying tumor growth and treatment response noninvasively poses a challenge to all experimental tumor models. The aim of our study was, to assess the value of quantitative and visual examination and radiomic feature analysis of high-resolution MR images of heterotopic glioblastoma xenografts in mice to determine tumor cell proliferation (TCP). METHODS: Human glioblastoma cells were injected subcutaneously into both flanks of immunodeficient mice and followed up on a 3 T MR scanner. Volumes and signal intensities were calculated. Visual assessment of the internal tumor structure was based on a scoring system. Radiomic feature analysis was performed using MaZda software. The results were correlated with histopathology and immunochemistry. RESULTS: 21 tumors in 14 animals were analyzed. The volumes of xenografts with high TCP (H-TCP) increased, whereas those with low TCP (L-TCP) or no TCP (N-TCP) continued to decrease over time (p < 0.05). A low intensity rim (rim sign) on unenhanced T1-weighted images provided the highest diagnostic accuracy at visual analysis for assessing H-TCP (p < 0.05). Applying radiomic feature analysis, wavelet transform parameters were best for distinguishing between H-TCP and L-TCP / N-TCP (p < 0.05). CONCLUSION: Visual and radiomic feature analysis of the internal structure of heterotopically implanted glioblastomas provide reproducible and quantifiable results to predict the success of transplantation.

Functional multi-organelle units control inflammatory lipid metabolism of macrophages.

Eukaryotic cells contain several membrane-separated organelles to compartmentalize distinct metabolic reactions. However, it has remained unclear how these organelle systems are coordinated when cells adapt metabolic pathways to support their development, survival or effector functions. Here we present OrgaPlexing, a multi-spectral organelle imaging approach for the comprehensive mapping of six key metabolic organelles and their interactions. We use this analysis on macrophages, immune cells that undergo rapid metabolic switches upon sensing bacterial and inflammatory stimuli. Our results identify lipid droplets (LDs) as primary inflammatory responder organelle, which forms three- and four-way interactions with other organelles. While clusters with endoplasmic reticulum (ER) and mitochondria (mitochondria-ER-LD unit) help supply fatty acids for LD growth, the additional recruitment of peroxisomes (mitochondria-ER-peroxisome-LD unit) supports fatty acid efflux from LDs. Interference with individual components of these units has direct functional consequences for inflammatory lipid mediator synthesis. Together, we show that macrophages form functional multi-organellar units to support metabolic adaptation and provide an experimental strategy to identify organelle-metabolic signalling hubs.

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.

Comparison of 96-kV and 120-kV cone-beam CT for the assessment of cochlear implants.

BACKGROUND: To compare the diagnostic value of 120-kV with conventional 96-kV Cone-Beam CT (CBCT) of the temporal bone after cochlear implant (CI) surgery. METHODS: This retrospective study included CBCT scans after CI surgery between 06/17 and 01/18. CBCT allowed examinations with 96-kV or 120-kV; other parameters were the same. Two radiologists independently evaluated following criteria on 5-point Likert scales: osseous spiral lamina, inner and outer cochlear wall, semi-circular canals, mastoid trabecular structure, overall image quality, metal and motion artefacts, depiction of intracochlear electrode position and visualisation of single electrode contacts. Effective radiation dose was assessed. RESULTS: Seventy-five patients (females, n = 39 [52.0%], mean age, 55.8 ± 16.5 years) were scanned with 96-kV (n = 32, 42.7%) and 120-kV (n = 43, 57.3%) protocols including CI models from three vendors (vendor A n = 7; vendor B n = 43; vendor C n = 25). Overall image quality, depiction of anatomical structures, and electrode position were rated significantly better in 120-kV images compared to 96-kV (all p < = 0.018). Anatomical structures and electrode position were rated significantly better in 120-kV CBCT for CI models from vendor A and C, while 120-kV did not provide improved image quality in CI models from vendor B. Radiation doses were significantly higher for 120-kV scans compared to 96-kV (0.15 vs. 0.08 mSv, p < 0.001). CONCLUSIONS: 120-kV and 96-kV CBCT provide good diagnostic images for the postoperative CI evaluation. While 120-kV showed improved depiction of temporal bone and CI electrode position compared to 96-kV in most CI models, the 120-kV protocol should be chosen wisely due to a substantially higher radiation exposure.

Antibody signatures against viruses and microbiome reflect past and chronic exposures and associate with aging and inflammation.

Encounters with pathogens and other molecules can imprint long-lasting effects on our immune system, influencing future physiological outcomes. Given the wide range of microbes to which humans are exposed, their collective impact on health is not fully understood. To explore relations between exposures and biological aging and inflammation, we profiled an antibody-binding repertoire against 2,815 microbial, viral, and environmental peptides in a population cohort of 1,443 participants. Utilizing antibody-binding as a proxy for past exposures, we investigated their impact on biological aging, cell composition, and inflammation. Immune response against cytomegalovirus (CMV), rhinovirus, and gut bacteria relates with telomere length. Single-cell expression measurements identified an effect of CMV infection on the transcriptional landscape of subpopulations of CD8 and CD4 T-cells. This examination of the relationship between microbial exposures and biological aging and inflammation highlights a role for chronic infections (CMV and Epstein-Barr virus) and common pathogens (rhinoviruses and adenovirus C).

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.