Search Results (16)

Aim: The frontal QRS-T (fQRS-T) angle serves as an electrocardiography indicator that visually represents the disparity between the frontal QRS axis and the T axis. The heterogeneity between cardiac depolarization and repolarization rises with an increase in the fQRS-T angle. Prior research has demonstrated a relationship between the fQRS-T angle and the extent of atherosclerosis, along with the risk of cardiovascular mortality. The non-alcoholic fatty liver disease fibrosis score (NFS) is a non-invasive scoring tool used to quantify the degree of liver fibrosis in individuals with non-alcoholic fatty liver disease (NAFLD). Non-alcoholic fatty liver disease increases the risk of atherosclerotic cardiovascular disease, which can be predicted using the NFS. The objective of this study is to examine the potential correlation between the fQRS-T angle and NFS in patients with stable angina pectoris. Materials and Methods: This cross-sectional study included 177 (48 women) non-alcoholic patients who underwent coronary angiography due to stable angina pectoris. Individual NFS values were calculated using clinical and laboratory data. Patients were categorized into two groups based on a NFS threshold value of 0.67. Following a minimum fasting period of 12 h, biochemical laboratory parameters were acquired using a peripheral venous sample, and electrocardiographic data were recorded. Results: The univariate logistic regression analysis revealed significant associations between hypertension (p = 0.018), coronary artery disease (p = 0.014), neutrophil (p = 0.024), hemoglobin (p = 0.038), and low-density lipoprotein (LDL, p = 0.007) with the NFS. The electrocardiographic variables related to the score included the QRS duration (p = 0.015), Pmax (p = 0.026), QTC interval (p = 0.02), and fQRS-T angle (p < 0.001). In the multivariate logistic regression analysis, NFS was independently associated with LDL (OR: 0.984, 95% CI: 0.970–0.998, p = 0.024) and fQRS-T angle (OR: 3.472, 95% CI: 1.886–6.395, p < 0.001). Conclusions: The FQRS-T angle may exhibit a distinct correlation with NAFLD. Extensive investigations should validate this link, since the fibrosis score can serve as an effective tool for monitoring patients prior to the onset of clinical symptoms associated with liver fibrosis. Full article

Ultrasound attenuation imaging (ATI) is a non-invasive method for quantifying hepatic steatosis, offering advantages over the hepatorenal index (HRI). However, its reliability can be influenced by factors such as measurement depth, ROI size, and subcutaneous fat. This paper examines the impact of these confounders on ATI measurements and discusses diagnostic considerations. In this study, 33 healthy adults underwent liver ultrasound with ATI and HRI protocols. ATI measurements were taken at depths of 2–5 cm below the liver capsule using small and large ROIs. Two operators performed the measurements, and inter-operator variability was assessed. Subcutaneous fat thickness was measured to evaluate its influence on attenuation values. The ATI measurements showed a consistent decrease in attenuation coefficient values with increasing depth, approximately 0.05 dB/cm/MHz. Larger ROI sizes increased measurement variability due to greater anatomical heterogeneity. HRI values correlated weakly with ATI and were influenced by operator technique and subcutaneous fat, the latter accounting for roughly 2.5% of variability. ATI provides a quantitative assessment of hepatic steatosis compared to HRI, although its accuracy can vary depending on the depth and ROI selection. Standardised imaging protocols and AI tools may improve reproducibility and clinical utility, supporting advancements in ultrasound-based liver diagnostics for better patient care. Full article

Background: Over the last two decades, a fair number of echocardiographic studies have investigated the influence of metabolic dysfunction-associated steatotic liver disease (MASLD) on myocardial strain and strain rate parameters assessed by speckle tracking echocardiography (STE) in individuals without overt heart disease, reporting not univocal results. We aimed at analyzing the main findings of these studies. Methods: All studies examining conventional echoDoppler parameters by transthoracic echocardiography (TTE) and left ventricular (LV) mechanics [LV-global longitudinal strain (GLS), LV-global strain rate in systole (GSRs), in early diastole (GSRe) and late diastole (GSRl)] by STE in MASLD patients without known heart disease vs. healthy individuals, were searched on PubMed, Embase and Scopus databases. The primary endpoint was to quantify the effect of MASLD on LV-GLS in individuals without overt cardiac disease. Continuous data [LV-GLS, LV-GLSRs, LV-GLSRe, LV-GLSRl and left ventricular ejection fraction (LVEF)] were pooled as the standardized mean difference (SMD) comparing MASLD cohorts with healthy controls. Results: A total of 11 studies were included, totaling 1348 MASLD patients and 6098 healthy controls. Overall, MASLD showed a medium effect on LV-GLS (SMD −0.6894; 95%CI −0.895, −0.472, p < 0.001) and LV-GLSRs (SMD −0.753; 95%CI −1.501, −0.006, p = 0.048), a large effect on LV-GLSRe (SMD −0.837; 95%CI −1.662, −0.012, p = 0.047) and a small and not statistically significant effect on LV-GLSRl (SMD −0.375; 95%CI −1.113, 0.363, p = 0.319) and LVEF (SMD −0.134; 95%CI −0.285, 0.017, p = 0.083). The overall I² statistic was 86.4%, 89.4%, 90.9%, 89.6% and 72.5% for LV-GLS, LV-GLSRs, LV-GLSRe, LV-GLSRl and LVEF studies, respectively, indicating high between-study heterogeneity. Egger’s test for LV-GLS studies gave a p value of 0.11, 0.26, 0.40, 0.32 and 0.42 for LV-GLS, LV-GLSRs, LV-GLSRe, LV-GLSRl and LVEF studies, respectively, thus excluding publication bias. Meta-regression analysis excluded any correlation between potential confounders and LV-GLS in MASLD individuals (all p > 0.05). Sensitivity analysis confirmed the robustness of study results. Conclusions: MASLD has a medium effect on LV-GLS, independently of demographics, anthropometrics and the cardiovascular disease burden. STE analysis may allow early detection of subclinical LV systolic dysfunction in MASLD patients, potentially identifying those who may develop heart failure later in life. Full article

Introduction: Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD) is a common cause of chronic liver disease. This review assessed the efficacy of a Low-Calorie Diet (LCD) on liver health and body weight in people living with MASLD and obesity. Methods: The study was registered with PROSPERO (CRD42021296501), and a literature search was conducted using multiple databases. The key inclusion criteria were randomised controlled trials or cohort studies, obesity/overweight and MASLD. Two authors screened abstracts, reviewed full texts and performed data extraction and quality assessment. The primary outcome was the change in the serum ALT, and secondary outcomes included the changes in the serum AST, intrahepatic lipid content (IHL), quantified non-invasively via MRI/MRS, and body weight. Results: Fifteen studies were included. The LCD reduced body weight by 9.1 kg versus the control (95%CI: −12.4, −5.8) but not serum ALT (−5.9 IU/L, −13.9, 2.0). Total Dietary Replacement (TDR) reduced IHL by −9.1% vs. the control (−15.6%, −2.6%). The Mediterranean-LCD for ≥12 months reduced ALT (−4.1 IU/L, −7.6, −0.5) and for 24 months reduced liver stiffness versus other LCDs. The Green-Mediterranean-LCD reduced IHL, independent of body weight. Limited studies assessed those of Black or Asian ethnicity, and there was heterogeneity in the methods assessing the liver fat content and fibrosis. Conclusions: In people with MASLD and obesity, an LCD intervention reduces IHL and body weight. Trials should focus on the recruitment of Black and Asian ethnicity participants. Full article

In this work, a computational scheme is proposed to identify the main combinations of handcrafted descriptors and deep-learned features capable of classifying histological images stained with hematoxylin and eosin. The handcrafted descriptors were those representatives of multiscale and multidimensional fractal techniques (fractal dimension, lacunarity and percolation) applied to quantify the histological images with the corresponding representations via explainable artificial intelligence (xAI) approaches. The deep-learned features were obtained from different convolutional neural networks (DenseNet-121, EfficientNet-b2, Inception-V3, ResNet-50 and VGG-19). The descriptors were investigated through different associations. The most relevant combinations, defined through a ranking algorithm, were analyzed via a heterogeneous ensemble of classifiers with the support vector machine, naive Bayes, random forest and K-nearest neighbors algorithms. The proposed scheme was applied to histological samples representative of breast cancer, colorectal cancer, oral dysplasia and liver tissue. The best results were accuracy rates of $94.83\%$ to $100\%$, with the identification of pattern ensembles for classifying multiple histological images. The computational scheme indicated solutions exploring a reduced number of features (a maximum of 25 descriptors) and with better performance values than those observed in the literature. The presented information in this study is useful to complement and improve the development of computer-aided diagnosis focused on histological images. Full article

Due to the heterogeneity of ultrasound (US) images and the indeterminate US texture of liver fibrosis (LF), automatic evaluation of LF based on US images is still challenging. Thus, this study aimed to propose a hierarchical Siamese network that combines the information from liver and spleen US images to improve the accuracy of LF grading. There were two stages in the proposed method. In stage one, a dual-channel Siamese network was trained to extract features from paired liver and spleen patches that were cropped from US images to avoid vascular interferences. Subsequently, the L1 distance was used to quantify the liver–spleen differences (LSDs). In stage two, the pretrained weights from stage one were transferred into the Siamese feature extractor of the LF staging model, and a classifier was trained using the fusion of the liver and LSD features for LF staging. This study was retrospectively conducted on US images of 286 patients with histologically proven liver fibrosis stages. Our method achieved a precision and sensitivity of 93.92% and 91.65%, respectively, for cirrhosis (S4) diagnosis, which is about 8% higher than that of the baseline model. The accuracy of the advanced fibrosis (≥S3) diagnosis and the multi-staging of fibrosis (≤S2 vs. S3 vs. S4) both improved about 5% to reach 90.40% and 83.93%, respectively. This study proposed a novel method that combined hepatic and splenic US images and improved the accuracy of LF staging, which indicates the great potential of liver–spleen texture comparison in noninvasive assessment of LF based on US images. Full article

Triple-negative breast cancers (TNBCs) currently have limited treatment options; however, PD-L1 is an indicator of susceptibility to immunotherapy. Currently, assessment of PD-L1 is limited to biopsy samples. These limitations may be overcome with molecular imaging. In this work, we describe chemistry development and optimization, in vitro, in vivo, and dosimetry of [⁸⁹Zr]-Atezolizumab for PD-L1 imaging. Atezolizumab was conjugated to DFO and radiolabeled with ⁸⁹Zr. Tumor uptake and heterogeneity in TNBC xenograft and patient-derived xenograft (PDX) mouse models were quantified following [⁸⁹Zr]-Atezolizumab-PET imaging. PD-L1 expression in TNBC PDX models undergoing therapy and immunohistochemistry (IHC) was used to validate imaging. SUV from PET imaging was quantified and used to identify heterogeneity. PET/CT imaging using [⁸⁹Zr]-Atezolizumab identified a significant increase in tumor:muscle SUV_mean 1 and 4 days after niraparib therapy and revealed an increased trend in PD-L1 expression following other cytotoxic therapies. A preliminary dosimetry study indicated the organs that will receive a higher dose are the spleen, adrenals, kidneys, and liver. [⁸⁹Zr]-Atezolizumab PET/CT imaging reveals potential for the noninvasive detection of PD-L1-positive TNBC tumors and allows for quantitative and longitudinal assessment. This has potential significance for understanding tumor heterogeneity and monitoring early expression changes in PD-L1 induced by therapy. Full article

The use of super-paramagnetic iron oxide nanoparticles (SPIONs) as an MRI contrast agent (SPION-CA) can safely label hepatic macrophages and be localized within hepatic parenchyma for T2*- and R2*-MRI of the liver. To date, no study has utilized the R2*-MRI with SPIONs for quantifying liver heterogeneity to characterize functional liver parenchyma (FLP) and hepatic tumors. This study investigates whether SPIONs enhance liver heterogeneity for an auto-contouring tool to identify the voxel-wise functional liver parenchyma volume (FLPV). This was the first study to directly evaluate the impact of SPIONs on the FLPV in R2*-MRI for 12 liver cancer patients. By using SPIONs, liver heterogeneity was improved across pre- and post-SPION MRI sessions. On average, 60% of the liver [range 40–78%] was identified as the FLPV in our auto-contouring tool with a pre-determined threshold of the mean R2* of the tumor and liver. This method performed well in 10 out of 12 liver cancer patients; the remaining 2 needed a longer echo time. These results demonstrate that our contouring tool with SPIONs can facilitate the heterogeneous R2* of the liver to automatically characterize FLP. This is a desirable technique for achieving more accurate FLPV contouring during liver radiation treatment planning. Full article

Background: Frailty has been associated with increased mortality among hepatobiliary pancreatic (HBP) cancer patients. Nevertheless, estimates of frailty prevalence in HBP cancers and the precise average effect regarding mortality remains uncertain. The present systematic review and meta-analysis aimed to quantify: (1) the prevalence of frailty in patients with liver and pancreatic cancers and (2) the impact of frailty on mortality in patients affected by liver and pancreatic cancers. Methods: MEDLINE/PubMed database search was conducted from inception until 1 November 2021, the pooled prevalence and relative risk (RR) estimate were calculated. Results: A total of 34,276 patients were identified and the weighted prevalence of frailty was 39%; (95% [C.I.] 23–56; I2 = 99.9%, p < 0.0001). Frailty was significantly associated with increased mortality RR 1.98 (95% [C.I.] 1.49–2.63; I2 = 75.9%, p = 0.006). Conclusions: Frailty prevalence is common among HBP cancer patients and exerts a significant negative impact on survival. These findings are characterized by significant heterogeneity and caution is warranted on their interpretation. However, stratification of patients with HBP cancer by frailty status may provide prognostic information and may inform priorities for decision-making strategy. Full article

Many of the effector functions of antibodies rely on the binding of antibodies/immune complexes to cellular Fcγ receptors (FcγRs). Since the majority of innate immune effector cells express both activating and inhibitory Fc receptors, the outcome of the binding of immune complexes to cells of a given population is influenced by the relative affinities of the respective IgG subclasses to these receptors, as well as by the numbers of activating and inhibitory FcγRs on the cell surface. A group of immune cells that has come into focus more recently is the various subsets of tissue-resident macrophages. The central functions of FcγRs on tissue macrophages include the clearance of opsonized pathogens, the removal of small immune complexes from the circulation and the depletion of antibody-opsonized cells in the therapy of autoimmunity and cancer. Despite these essential functions of FcγRs on tissue-resident macrophages, an in-depth quantification of FcγRs is lacking. Thus, the aim of our current study was to quantify the various Fcγ receptors on macrophages in murine liver, lung, kidney, brain, skin and spleen. Our study identified a pronounced heterogeneity between FcγR expression patterns of the different tissue macrophages, which may reflect their specialized functions within their unique niches in different organ environments. Full article

Although neuroendocrine tumours (NETs) are intensively studied, their diagnosis and consequently personalised therapy management is still puzzling due to their tumoral heterogeneity. In their theragnosis algorithm, receptor somatostatin scintigraphy takes the central place, the diagnosis receptor somatostatin analogue (RSA) choice depending on laboratory experience and accessibility. However, in all cases, the results depend decisively on correct radiotracer tumoral uptake quantification, where unfortunately there are still unrevealed clues and lack of standardization. We propose an improved method to quantify the biodistribution of gamma-emitting RSA, using tissular corrected uptake indices. We conducted a bi-centric retrospective study on 101 patients with different types of NETs. Three uptake indices obtained after applying new corrections to areas of interest drawn for the tumour and for three reference organs (liver, spleen and lung) were statistically analysed. For the corrected pathological uptake indices, the results showed a significant decrease in the error of estimating the occurrence of errors and an increase in the diagnostic predictive power for NETs, especially in the case of lung-referring corrected index. In conclusion, these results support the importance of corrected uptake indices use in the analysis of ^99mTcRSA biodistribution for a better personalised diagnostic accuracy of NETs patients. Full article

To treat colorectal liver metastases, intra-arterial chemotherapies may complete therapeutic arsenal. Drugs using intra-arterially are very heterogeneous. The aim of this study was to select the most efficient drug on a panel of colorectal cancer (CRC) cell lines (Caco-2, HCT 116, HT 29, SW 48, SW 480, SW 620) exposed for 30 min to 12 cytotoxic agents (doxorubicin, epirubicin, idarubicin, 5-FU, raltitrexed, gemcitabine, cisplatin, oxaliplatin, mitomycin C, irinotecan, streptozocin, paclitaxel) at different concentrations. The effect on cell viability was measured using the WST-1 cell viability assay. For each drug and cell line, the IC₅₀ and IC₉₀ were calculated, which respectively correspond to the drug concentration (mg/mL) required to obtain 50% and 90% of cell death. We also quantified the cytotoxic index (CyI₉₀ = C Max/IC₉₀) to compare drug efficacy. The main findings of this study are that idarubicin emerged as the most cytotoxic agent to most of the tested CRC cell lines (Caco-2, HT29, HCT116, SW620 and SW480). Gemcitabine seemed to be the most efficient chemotherapy for SW48. Interestingly, the most commonly used cytotoxic agents in the systemic and intra-arterial treatment of colorectal liver metastasis (CRLM) (oxaliplatin, 5-FU, irinotecan) showed very limited cytotoxicity to all the cell lines. Full article

Image-based quantitative methods for liver heterogeneity (L_Het) and nodularity (L_Nod) provide helpful information for evaluating liver fibrosis; however, their combinations are not fully understood in liver diseases. We developed an integrated software for assessing L_Het and L_Nod and compared L_Het and L_Nod according to fibrosis stages in chronic liver disease (CLD). Overall, 111 CLD patients and 16 subjects with suspected liver disease who underwent liver biopsy were enrolled. The procedures for quantifying L_Het and L_Nod were bias correction, contour detection, liver segmentation, and L_Het and L_Nod measurements. L_Het and L_Nod scores among fibrosis stages (F0–F3) were compared using ANOVA with Tukey’s test. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristics (AUROC) curve. The mean L_Het scores of F0, F1, F2, and F3 were 3.49 ± 0.34, 5.52 ± 0.88, 6.80 ± 0.97, and 7.56 ± 1.79, respectively (p < 0.001). The mean L_Nod scores of F0, F1, F2, and F3 were 0.84 ± 0.06, 0.91 ± 0.04, 1.09 ± 0.08, and 1.15 ± 0.14, respectively (p < 0.001). The combined L_Het × L_Nod scores of F0, F1, F2, and F3 were 2.96 ± 0.46, 5.01 ± 0.91, 7.30 ± 0.89, and 8.48 ± 1.34, respectively (p < 0.001). The AUROCs of L_Het, L_Nod, and L_Het × L_Nod for differentiating F1 vs. F2 and F2 vs. F3 were 0.845, 0.958, and 0.954; and 0.619, 0.689, and 0.761, respectively. The combination of L_Het and L_Nod scores derived from routine MR images allows better differential diagnosis of fibrosis subgroups in CLD. Full article

Background and Aims: Statins are the first-line medication to treating hypercholesterolemia. Several studies have investigated the impact of statins on the risk of hepatocellular carcinoma (HCC). However, the extent to which statins may prevent HCC remains uncertain. Therefore, we performed a meta-analysis of relevant studies to quantify the magnitude of the association between statins use and the risk of HCC. Methods: A systematic literature search of PubMed, EMBASE, Google Scholar, Web of Science, and Scopus was performed for studies published between January 1, 1990, and September 1, 2019, with no restriction of language. Two reviewers independently evaluated the literature and included observational and experimental studies that reported the association between statin use and HCC risk. The random-effect model was used to calculate the overall risk ratio (RR) with a 95% confidence interval (CI), and the heterogeneity among the studies was assessed using the Q statistic and I² statistic. The Newcastle Ottawa Scale (NOS) was also used to evaluate the quality of the included studies. Results: A total of 24 studies with 59,073 HCC patients was identified. Statin use was associated with a reduced risk of HCC development (RR: 0.54, 95% CI: 0.47–0.61, I² = 84.39%) compared with nonusers. Moreover, the rate of HCC reduction was also significant among patients with diabetes (RR: 0.44, 95% CI: 0.28–0.70), liver cirrhosis (RR: 0.36, 95% CI: 0.30–0.42), and antiviral therapy (RR: 0.21, 95% CI: 0.08–0.59) compared with nonusers. Conclusion: This study serves as additional evidence supporting the beneficial inhibitory effect of statins on HCC incidence. The subgroup analyses of this study also highlight that statins are significantly associated with a reduced risk of HCC and may help to direct future prevention efforts. Additional large clinical studies are needed to determine whether statins are associated with a lower risk of HCC. Full article

Tumor microenvironments expose cancer cells to heterogeneous, dynamic environments by shifting availability of nutrients, growth factors, and metabolites. Cells integrate various inputs to generate cellular memory that determines trajectories of subsequent phenotypes. Here we report that short-term exposure of triple-negative breast cancer cells to growth factors or targeted inhibitors regulates subsequent tumor initiation. Using breast cancer cells with different driver mutations, we conditioned cells lines with various stimuli for 4 hours before implanting these cells as tumor xenografts and quantifying tumor progression by means of bioluminescence imaging. In the orthotopic model, conditioning a low number of cancer cells with fetal bovine serum led to enhancement of tumor-initiating potential, tumor volume, and liver metastases. Epidermal growth factor and the mTORC1 inhibitor ridaforolimus produced similar but relatively reduced effects on tumorigenic potential. These data show that a short-term stimulus increases tumorigenic phenotypes based on cellular memory. Conditioning regimens failed to alter proliferation or adhesion of cancer cells in vitro or kinase signaling through Akt and ERK measured by multiphoton microscopy in vivo, suggesting that other mechanisms enhanced tumorigenesis. Given the dynamic nature of the tumor environment and time-varying concentrations of small-molecule drugs, this work highlights how variable conditions in tumor environments shape tumor formation, metastasis, and response to therapy. Full article