Aims and objectives: In order to evaluate the responses of hepatic lesions to treatment in terms of tissue stiffness and heterogeneity, this work investigated the robustness of 2D shear-wave elastography (2D SWE) stiffness measurements and texture analyses in vitro and in vivo in terms of repeatability and variability. Methods and materials: A multioperator (n = 5) study was performed with an ultrasonic elastography device on two sets of phantoms. For the first set of phantoms, 10 measurements for each of the eight inclusions were performed by each observer, whereas the second set of phantoms was used to evaluate the influence of depth on the stiffness measurements. Variability of the stiffness measurements was evaluated in vivo on 10 healthy livers, with 10 measurements for each hepatic segment. Texture analyses were performed in B-mode, obtaining elastography images for every hepatic segment. Results: Stiffness measurements were influenced by depth, particularly when exceeding 7 cm. In vivo measurements demonstrated that measurements of segments I, VII, and VIII were less reliable, mainly due to their deeper locations. The protocols used were more flexible in terms of acquisition setup and probe placement than those currently used with Fibroscan^®. For texture analysis on the B-mode images, 12 features showed low variability regardless of the evaluated hepatic segment. On elastogram, only two features showed low variability, but not in every segment. Conclusion: We demonstrated the robustness of two methodologies for the quantification of liver stiffness and heterogeneity. Further clinical studies should evaluate whether these techniques can assess tumor responses to treatment and, therefore, have the potential to be used as imaging biomarkers. Full article

Pediatric renal cancer is rare, and robust evidence for treatment recommendations is lacking. In the perspective of personalized medicine, clinicians need new biomarkers to improve risk stratification and patients’ follow-up. Herein, we analyzed some liquid biopsy tools, which have been never tested in pediatric renal cancer: namely, circulating tumor cells (CTCs); the expression of M30, an apoptosis marker, to test CTC metastatic potential; and c-MET expression in CTCs, because of its role in renal cancer progression and drug-resistance. Furthermore, we evaluated the Circulating Endothelial Cells (CECs), whose utility we previously demonstrated in adult metastatic renal cancer treated with anti-angiogenic therapy. We compared two renal cell carcinomas of clear-cell type, stage I and IV, which underwent surgery and surgery plus Sunitinib, respectively. Baseline CTC level and its changes during follow-up were consistent with patients’ outcome. In case 2, stage IV, the analysis of CECs performed during Sunitinib revealed a late response to treatment consistent with poor outcome, as the finding of M30-negative, viable cells. Noteworthily, few CTCs were MET-positive in both cases. Our study highlights the feasibility for a change in the prognostic approach and follow-up of childhood renal cancer, with a view to guide a better treatment design. Full article

Objectives: To predict the role of different clinical and biochemical parameters in identifying nonalcoholic fatty liver disease (NAFLD) among patients with type 2 diabetes mellitus (T2DM) in Abha city, southwestern Saudi Arabia. Methods: A stratified random sample was selected. A detailed clinical and biochemical examinations were performed. Using portable abdominal ultrasound examination, NAFLD was identified. The study used receiver operating characteristic (ROC) analysis. Results: The study covered 237 T2DM patients. NAFLD was detected among 174 patients. Area under the curve (AUC) calculations showed that the ability of age, duration of DM in years, and body mass index to predict NAFLD was poor (AUC < 0.6). Similarly, biochemical factors like HbA1c%, AST, cholesterol, triglycerides, HDL, LDL, and VLDL were poor in discriminating between those with and without NAFLD among T2DM. On the other hand, the ability of ALT to predict NAFLD among T2DM was good (AUC = 0.701, 95% CI: 0.637–0.761). The analysis identified the optimal cutoff point of ALT to be ≤22.1 nmol/L. The corresponding sensitivity was 60.7% (95% CI: 53.0–68.0) and specificity was 62.5% (95% CI: 49.5–74.3). Conclusions: Early identification of NAFLD among T2DM is important. A threshold cutoff value of 22.1 nmol/L of ALT has been identified to predict NAFLD. They should be referred for ultrasound examination for NAFLD. Full article

Septic shock/severe sepsis is a deregulated host immune system response to infection that leads to life-threatening organ dysfunction. Lung inflammation as a form of acute lung injury (ALI) is often induced in septic shock. Whereas macrophages and neutrophils have been implicated as the principal immune cells regulating lung inflammation, group two innate lymphoid cells (ILC2s) have recently been identified as a new player regulating immune homeostasis. ILC2 is one of the three major ILC subsets (ILC1s, ILC2s, and ILC3s) comprised of newly identified innate immune cells. These cells are characterized by their ability to rapidly produce type 2 cytokines. ILC2s are predominant resident ILCs and, thereby, have the ability to respond to signals from damaged tissues. ILC2s regulate the immune response, and ILC2-derived type 2 cytokines may exert protective roles against sepsis-induced lung injury. This focused review not only provides readers with new insights into the signaling mechanisms by which ILC2s modulate sepsis-induced lung inflammation, but also proposes ILC2 as a novel therapeutic target for sepsis-induced ALI. Full article

In this systematic review, we investigate the epidemiology, pathogenesis, risk factors, clinical manifestations, diagnosis and treatment of COVID-19-associated pulmonary aspergillosis (CAPA). We identified 85 cases from 22 studies. The frequency of CAPA is currently unknown but ranges between <5% to >30% in different case series; the possibility of colonization rather than invasive disease is the most important confounder. The vast majority of patients with CAPA did not have any of the classic host risk factors, such as immunosuppression from organ transplant or neutropenia, although a significant proportion (46%) had received corticosteroids. Age, pulmonary comorbidities and male sex were associated with higher mortality. Patients treated with voriconazole had numerically lower case-fatality rate. Clinical vigilance for CAPA is advisable in critically ill patients with COVID-19 who are not improving, even those who do not meet classic host criteria for invasive mycoses, especially if they are receiving corticosteroids. A thorough, multi-faceted diagnostic work-up and early initiation of a mold-active triazole may be lifesaving. Further research studies using standardized, uniform definitions of invasive disease and colonization are urgently needed. Full article

Prostate cancer represents the most encountered urinary malignancy in males over 50 years old, and the second most diagnosed after lung cancer globally. Digital rectal examination and prostatic specific antigen were the long-time standard tools for diagnosis but with a significant risk of overdiagnosis and overtreatment. Magnetic resonance imaging recently entered the diagnosis process, but to this date, there is no specific biomarker that accurately indicates whether to proceed with the prostate biopsy. Research in this area has gone towards this direction, and recently, serum, urine, imagistic, tissue biomarkers, and Risk Calculators promise to help better diagnose and stratify prostate cancer. In order to eliminate the comorbidities that appear along with the diagnosis and treatment of this disease, there is a constant need to implement new diagnostic strategies. Important uro-oncology associations recommend the use of novel biomarkers in the grey area of prostate cancer, to better distinguish the next step in the diagnostic process. Although it is not that simple, they should be integrated according to the clinical policies, and it should be considered that statistical significance does not always equal clinical significance. In this review, we analyzed the contribution of prostate-specific antigen (PSA)-based biomarkers (PHI, PHID, 4Kscore, STHLM3), imagistic techniques (mp-MRI and mp-US), and combined tests in the early diagnosis process of localized prostate cancer. Full article

Background/aim: We aimed to derive a model representing the dynamic status of cirrhosis and to discriminate patients with poor prognosis even if the Model for End-Stage Liver Disease (MELD) score is low. Methods: This study retrospectively enrolled 700 cirrhotic patients with a MELD score of less than 20 who underwent hepatic venous pressure gradient (HVPG) measurement. A model named H6C score (= HVPG + 6 × CTP score) to predict overall survival was derived and internal and external validations were conducted with the derivation and validation cohorts. Results: The H6C score using the HVPG was developed based on a multivariate Cox regression analysis. The H6C score showed a great predictive power for overall survival with a time-dependent AUC of 0.733, which was superior to that of a MELD of 0.602. In patients with viral etiology, the performance of the H6C score was much improved with a time-dependent AUC of 0.850 and was consistently superior to that of the MELD (0.748). Patients with an H6C score below 45 demonstrated an excellent overall survival with a 5-year survival rate of 91.5%. Whereas, patients with an H6C score above 64 showed a dismal prognosis with a 5-year survival rate of 51.1%. The performance of the H6C score was further verified to be excellent in the validation cohort. Conclusion: This new model using the HVPG provides an excellent predictive power in cirrhotic patients, especially with viral etiology. In patients with H6C above 64, it would be wise to consider early liver transplantation to positively impact long-term survival, even when the MELD score is low. Full article

Stroke is a top leading cause of death, which occurs due to interference in the blood flow of the brain. Ischemic stroke (blockage) accounts for most cases (87%) and is further subtyped into cardioembolic, atherosclerosis, lacunar, other causes, and cryptogenic strokes. The main value of subtyping ischemic stroke patients is for a better therapeutic decision-making process. The current classification methods are complex and time-consuming (hours to days). Specific blood-based biomarker measurements have promising potential to improve ischemic stroke mechanism classification. Over the past decades, the hypothesis that different blood-based biomarkers are associated with different ischemic stroke mechanisms is increasingly investigated. This review presents the recent studies that investigated blood-based biomarker characteristics differentiation between ischemic stroke mechanisms. Different blood-based biomarkers are specifically discussed (b-type natriuretic peptide, d-dimer, c-reactive protein, tumor necrosis factor-α, interleukin-6, interleukin-1β, neutrophil–lymphocyte ratio, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein and apolipoprotein A), as well as the different cut-off values that may be useful in specific classifications for cardioembolic and atherosclerosis etiologies. Lastly, the structure of a point-of-care biosensor device is presented, as a measuring tool on-site. The information presented in this review will hopefully contribute to the major efforts to improve the care for stroke patients. Full article

The early detection and rapid quantification of acute ischemic lesions play pivotal roles in stroke management. We developed a deep learning algorithm for the automatic binary classification of the Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) using diffusion-weighted imaging (DWI) in acute stroke patients. Three hundred and ninety DWI datasets with acute anterior circulation stroke were included. A classifier algorithm utilizing a recurrent residual convolutional neural network (RRCNN) was developed for classification between low (1–6) and high (7–10) DWI-ASPECTS groups. The model performance was compared with a pre-trained VGG16, Inception V3, and a 3D convolutional neural network (3DCNN). The proposed RRCNN model demonstrated higher performance than the pre-trained models and 3DCNN with an accuracy of 87.3%, AUC of 0.941, and F1-score of 0.888 for classification between the low and high DWI-ASPECTS groups. These results suggest that the deep learning algorithm developed in this study can provide a rapid assessment of DWI-ASPECTS and may serve as an ancillary tool that can assist physicians in making urgent clinical decisions. Full article

Increased sympathetic activity is suggested to be part of the pathogenesis in several diseases. Methods to evaluate sympathetic activity and renal nervous denervation procedural success are lacking. Scintigraphy using the norepinephrine analog Iodine-123 Metaiodobenzylguanidine (¹²³I-MIBG) might provide information on renal sympathetic nervous activity. Renal transplantation induces complete denervation of the kidney and as such represents an ideal model to evaluate the renal ¹²³I-MIBG scintigraphy method. The aim of this study was to evaluate whether renal ¹²³I-MIBG scintigraphy can detect changes in renal sympathetic nervous activity following renal transplantation. Renal ¹²³I-MIBG scintigraphy was performed in eleven renal transplant recipients at 1, 3, and 6 months following transplantation and in their respective living donors prior to their kidney donation. Relative uptake as well as washout was obtained. In transplanted patients, the relative 4 h uptake of ¹²³I-MIBG, as measured by the kidney/background ratio, was 2.7 (0.4) (mean (SD)), 2.7 (0.5), and 2.5 (0.4) at 1, 3, and 6 months post-transplantation, respectively, as compared with the 4.0 (0.4) value in the donor kidney before donor nephrectomy (p < 0.01). There was no significant change in washout-rate between pre-transplantation and any of the follow-up time points. Living donor kidney transplantation was at 6 months post transplantation, associated with an almost 40% reduction in the relative 4 h ¹²³I-MIBG uptake of the kidney. Further studies will help to fully establish its implications as a marker of renal innervation or denervation. Full article

Colorectal cancer is a highly heterogeneous malignancy in the Asian population, and it is considered an important prognostic factor for baseline characteristics, tumor burden, and tumor markers. This study investigated the effect of baseline characteristics and tumor burden on tumor marker expression and progressive disease in colorectal cancer by using partial least squares variance-based path modeling (PLS-PM). PLS-PM can be used to evaluate the complex relationship between prognostic variables and progressive disease status with a small sample of measurements and structural models. A total of 89 tissue samples of colorectal cancer were analyzed. Our results suggested that the expression of visceral adipose tissue-derived serpin (vaspin) is a potential indicator of colorectal cancer progression and may be affected by baseline characteristics such as age, sex, body mass index, and diabetes mellitus. Moreover, according to the characteristics of tumor burden, the expression of vaspin was generally higher in each progressive disease patient. The overall findings suggest that vaspin is a potential indicator of the progressive disease and may be affected by the baseline characteristics of patients. Full article

Magnetic particle imaging (MPI) is a cutting-edge imaging technique that is attracting increasing attention. This novel technique collects signals from superparamagnetic nanoparticles as its imaging tracer. It has characteristics such as linear quantitativity, positive contrast, unlimited penetration, no radiation, and no background signal from surrounding tissue. These characteristics enable various medical applications. In this paper, we first introduce the development and imaging principles of MPI. Then, we discuss the current major applications of MPI by dividing them into four categories: cell tracking, blood pool imaging, tumor imaging, and visualized magnetic hyperthermia. Even though research on MPI is still in its infancy, we hope this discussion will promote interest in the applications of MPI and encourage the design of tracers tailored for MPI. Full article

Introduction. Neutrophil/lymphocyte ratio (NLR) is known as a prognostic for the outcome of the patients with gastric cancer. As no definite risk marker for anastomotic leakage after gastric resection was identified, we investigated the possible role of NLR. Methods. Peripheral blood count for neutrophils and lymphocytes was done at the patient’s admission. We retrospectively evaluated 204 gastric cancer patients, who underwent gastric resection, comparing the values of NLR between the group of patients with anastomotic leakage and those without complications. Results. Using the ROC curve, we found the cutoff value of NLR, which permitted the comparison of the group with low NLR, presenting increased NLR. The cutoff value for NLR was 3.54. Between the two groups, we could observe statistically significant differences in developing fistula (p < 0.01) and complications leading to death (p < 0.025). The odds ratio for patients with NLR greater than 3.54 to develop anastomotic leak was 17.62, compared to those with lower NLR. Conclusion. Peripheral blood NLR proved to be a predictor for anastomotic leakage. Full article

Branched-chain amino acids (BCAAs) are involved in immune system’s metabolic pathways and play fundamental role in gut health. Our aim was to assess BCAA plasma levels in patients with ulcerative colitis (UC) and associations of plasma BCAAs with disease-related parameters. This was a case-control study in adult patients with UC and BMI-matched controls. A total of 150 volunteers were screened between May 2016 and June 2017; 43 patients and 34 healthy controls were enrolled. Medical and dietary history (3 × 24 h recalls, MedDiet score), anthropometric measurements, blood and fecal samples were collected. We measured BCAAs in plasma with gas chromatography-mass spectrometry. In patients, fecal calprotectin, lactoferrin, lysozyme and defensin were quantified. Dietary pattern was similar in patients and controls. Plasma-free BCAA profiles did not differ between groups. Regression analysis showed that i) valine was inversely associated with calprotectin (p = 0.007) and ii) isoleucine with age (p = 0.031), after adjusting for age, sex, PMS and smoking. Leucine was negatively associated with age (p = 0.015) after adjusting for age, sex and PMS, but this association vanished when smoking was introduced. No correlation was observed between total BCAAs with any of the parameters. Plasma-free valine is negatively associated with calprotectin in patients with UC. Full article

Musculoskeletal pain (MSP), specifically low back pain (LBP), is often associated with several adipose tissue-derived cytokines (adipokines) and body composition, but their correlations with the LBP-related disability/severity phenotypes remain poorly understood. In this cross-sectional study, two self-reported validated questionnaires were used to collect back pain and disability data in an ethnically homogeneous family-based population sample (N = 1078). Plasma levels of relatively new adipokines, vaspin and adipsin, were detected by ELISA. Body composition parameters, including fat, skeletal muscle mass, extracellular water (ECW), and others were assessed through bioelectrical impedance analysis (BIA) technology. Statistical analysis was conducted, accounting for the familial composition of the sample. The multiple regression analyses with four LBP-related phenotypes as dependent variables consistently showed, for the first time, the significant associations with vaspin levels, regardless of other covariates. The odds ratios (OR)/SD ranged between 1.24 (95%CI = 1.03–1.50) and 1.33 (95%CI = 1.07–1.64), depending on the LBP phenotype. Among the tested body composition covariates, only ECW levels displayed consistent and highly significant associations with all tested LBP phenotypes (OR from 1.43, 95%CI = 1.14–1.79 to 1.68, 95%CI = 1.26–2.24). The results clearly suggest that circulating concentrations of vaspin and ECW levels could serve as biomarkers of MSP/LBP severity and complications. Full article