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1.
Front Cell Dev Biol ; 12: 1448725, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39220682

RESUMEN

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.

2.
Radiol Med ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287697

RESUMEN

PURPOSE: Preliminary dual-energy CT studies have shown that low-energy virtual monoenergetic (VMI) + reconstructions can provide superior image quality compared to standard 120 kV CTA series. The purpose of this study is to evaluate the impact of low-energy VMI reconstructions on quantitative and qualitative image quality, vascular contrast, and diagnostic assessability of the carotid artery in patients undergoing photon-counting CTA examinations. MATERIALS AND METHODS: A total of 122 patients (67 male) who had undergone dual-source photon-counting CTA scans of the carotid artery were retrospectively analyzed in this study. Standard 120 kV CT images and low-keV VMI series from 40 to 100 keV with an interval of 15 keV were reconstructed. Quantitative analyses included the evaluation of vascular CT numbers, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). CT number measurements were performed in the common, external, and internal carotid arteries. Qualitative analyses were performed by three board-certified radiologists independently using five-point scales to evaluate image quality, vascular contrast, and diagnostic assessability of the carotid artery. RESULTS: Mean attenuation, CNR and SNR values were highest in 40 keV VMI reconstructions (HU, 1362.32 ± 457.81; CNR, 33.19 ± 12.86; SNR, 34.37 ± 12.89) followed by 55-keV VMI reconstructions (HU, 736.94 ± 150.09; CNR, 24.49 ± 7.11; SNR, 26.25 ± 7.34); all three mean values at these keV levels were significantly higher compared with the remaining VMI series and standard 120 kV CT series (HU, 154.43 ± 23.69; CNR, 16.34 ± 5.47; SNR, 24.44 ± 7.14) (p < 0.0001). The qualitative analysis showed the highest rating scores for 55 keV VMI reconstructions followed by 40 keV and 70 keV VMI series with a significant difference compared to standard 120 kV CT images series regarding image quality, vascular contrast, and diagnostic assessability of the carotid artery (all comparisons, p < 0.01). CONCLUSIONS: Low-keV VMI reconstructions at a level of 40-55 keV significantly improve image quality, vascular contrast, and the diagnostic assessability of the carotid artery compared with standard CT series in photon-counting CTA.

3.
Acad Radiol ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39117465

RESUMEN

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.

4.
Radiol Med ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39123064

RESUMEN

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.

5.
J Clin Imaging Sci ; 14: 25, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39108320

RESUMEN

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.

6.
Front Allergy ; 5: 1439303, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39086886

RESUMEN

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.

7.
J Magn Reson Imaging ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39165139

RESUMEN

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.

8.
Bioengineering (Basel) ; 11(8)2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39199765

RESUMEN

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.

9.
Eur Radiol Exp ; 8(1): 95, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39186171

RESUMEN

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.


Asunto(s)
Colágeno , Degeneración del Disco Intervertebral , Imagen por Resonancia Magnética , Vértebras Torácicas , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Degeneración del Disco Intervertebral/diagnóstico por imagen , Anciano , Estudios Retrospectivos , Vértebras Torácicas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Reproducibilidad de los Resultados
10.
J Cancer Res Clin Oncol ; 150(8): 396, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39180680

RESUMEN

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.


Asunto(s)
Biomarcadores de Tumor , Metilación de ADN , Epigénesis Genética , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Anciano , Pronóstico , Persona de Mediana Edad , Estudios Retrospectivos , Biomarcadores de Tumor/genética , Prostatectomía
11.
Microbiome ; 12(1): 141, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075559

RESUMEN

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.


Asunto(s)
Enfermedad de Crohn , Síndrome de Fatiga Crónica , Flagelina , Microbioma Gastrointestinal , Receptor Toll-Like 5 , Flagelina/inmunología , Humanos , Síndrome de Fatiga Crónica/inmunología , Síndrome de Fatiga Crónica/microbiología , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/microbiología , Receptor Toll-Like 5/inmunología , Microbioma Gastrointestinal/inmunología , Femenino , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antibacterianos/sangre , Masculino , Adulto , Formación de Anticuerpos/inmunología , Persona de Mediana Edad , Clostridiales/inmunología
12.
Eur Radiol ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014087

RESUMEN

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.

13.
J Cancer Res Clin Oncol ; 150(7): 357, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39034327

RESUMEN

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.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Masculino , Colangiocarcinoma/inmunología , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Colangiocarcinoma/metabolismo , Neoplasias de los Conductos Biliares/inmunología , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/metabolismo , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Perfilación de la Expresión Génica , Transcriptoma , Regulación Neoplásica de la Expresión Génica
14.
Nat Cell Biol ; 26(8): 1261-1273, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38969763

RESUMEN

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.


Asunto(s)
Retículo Endoplásmico , Ácidos Grasos , Inflamación , Gotas Lipídicas , Metabolismo de los Lípidos , Macrófagos , Mitocondrias , Macrófagos/metabolismo , Animales , Retículo Endoplásmico/metabolismo , Gotas Lipídicas/metabolismo , Mitocondrias/metabolismo , Inflamación/metabolismo , Inflamación/patología , Ácidos Grasos/metabolismo , Peroxisomas/metabolismo , Ratones , Ratones Endogámicos C57BL , Transducción de Señal , Orgánulos/metabolismo
15.
Diagnostics (Basel) ; 14(13)2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-39001279

RESUMEN

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.

16.
Cancers (Basel) ; 16(13)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-39001435

RESUMEN

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.

17.
Rofo ; 2024 Jul 22.
Artículo en Inglés, Alemán | MEDLINE | ID: mdl-39038457

RESUMEN

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.

18.
J Neurooncol ; 169(2): 257-267, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38960965

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Imagen por Resonancia Magnética , Trasplante de Neoplasias , Animales , Femenino , Humanos , Masculino , Ratones , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular , Modelos Animales de Enfermedad , Glioblastoma/diagnóstico por imagen , Glioblastoma/cirugía , Glioblastoma/patología , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/métodos , Trasplante de Neoplasias/métodos , Radiómica
19.
EBioMedicine ; 105: 105178, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38889481

RESUMEN

BACKGROUND: The accuracy of blood-based early tumour recognition is compromised by signal production at non-tumoral sites, low amount of signal produced by small tumours, and variable tumour production. Here we examined whether tumour-specific enhancement of vascular permeability by the particular tumour homing peptide, iRGD, which carries dual function of binding to integrin receptors overexpressed in the tumour vasculature and is known to promote extravasation via neuropilin-1 receptor upon site-specific cleavage, might be useful to improve blood-based tumour detection by inducing a yet unrecognised vice versa tumour-to-blood transport. METHODS: To detect an iRGD-induced tumour-to-blood transport, we examined the effect of intravenously injected iRGD on blood levels of α-fetoprotein (AFP) and autotaxin in several mouse models of hepatocellular carcinoma (HCC) or in mice with chronic liver injury without HCC, and on prostate-specific antigen (PSA) levels in mice with prostate cancer. FINDINGS: Intravenously injected iRGD rapidly and robustly elevated the blood levels of AFP in several mouse models of HCC, but not in mice with chronic liver injury. The effect was primarily seen in mice with small tumours and normal basal blood AFP levels, was attenuated by an anti-neuropilin-1 antibody, and depended on the concentration gradient between tumour and blood. iRGD treatment was also able to increase blood levels of autotaxin in HCC mice, and of PSA in mice with prostate cancer. INTERPRETATION: We conclude that iRGD induces a tumour-to-blood transport in a tumour-specific fashion that has potential of improving diagnosis of early stage cancer. FUNDING: Deutsche Krebshilfe, DKTK, LOEWE-Frankfurt Cancer Institute.


Asunto(s)
Biomarcadores de Tumor , Carcinoma Hepatocelular , Modelos Animales de Enfermedad , Neoplasias Hepáticas , Hidrolasas Diéster Fosfóricas , Animales , Ratones , Biomarcadores de Tumor/sangre , Hidrolasas Diéster Fosfóricas/sangre , Hidrolasas Diéster Fosfóricas/metabolismo , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , alfa-Fetoproteínas/metabolismo , Masculino , Humanos , Línea Celular Tumoral , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Oligopéptidos/administración & dosificación
20.
Sci Rep ; 14(1): 13295, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858499

RESUMEN

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is considered a growing health concern. The majority of NTM-PD cases in Europe are caused by slow-growing mycobacteria (SGM). However, distinct radiological features of different SGM remain largely uninvestigated. We applied a previously described radiological score to a patient cohort consisting of individuals with isolation of different SGM. Correlations between clinical data, species and computed tomography (CT) features were examined by logistic and linear regression analyses, as well as over the course of time. Overall, 135 pulmonary CT scans from 84 patients were included. The isolated NTM-species were mainly Mycobacterium avium complex (MAC, n = 49), as well as 35 patients with non-MAC-species. Patients with isolation of M. intracellulare had more extensive CT findings compared to all other SGM species (coefficient 3.53, 95% Cl - 0.37 to 7.52, p = 0.075) while patients meeting the ATS criteria and not undergoing therapy exhibited an increase in CT scores over time. This study provides insights into differential radiological features of slow-growing NTM. While M. intracellulare exhibited a tendency towards higher overall CT scores, the radiological features were similar across different SGM. The applied CT score might be a useful instrument for monitoring patients and could help to guide antimycobacterial therapy.


Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Micobacterias no Tuberculosas , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Infecciones por Mycobacterium no Tuberculosas/diagnóstico por imagen , Infecciones por Mycobacterium no Tuberculosas/microbiología , Tomografía Computarizada por Rayos X/métodos , Anciano , Persona de Mediana Edad , Micobacterias no Tuberculosas/aislamiento & purificación , Micobacterias no Tuberculosas/crecimiento & desarrollo , Complejo Mycobacterium avium/aislamiento & purificación , Pulmón/microbiología , Pulmón/diagnóstico por imagen , Estudios Retrospectivos , Adulto , Infección por Mycobacterium avium-intracellulare/diagnóstico por imagen , Infección por Mycobacterium avium-intracellulare/microbiología
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