PURPOSE: This prospective pilot study aims to evaluate the capabilities of novel quantitative ultrasound (QUS) methods based on attenuation (Att.PLUS) and sound speed (SSp.PLUS) for detecting liver fat. PATIENTS AND METHODS: The study included 56 individuals with biopsy-proven steatosis (percutaneous liver biopsy) ranging from 0 % to 90 % of hepatocytes containing intracellular lipid vacuoles. Histopathology was considered reference standard. Abdominal QUS examinations were conducted using Att.PLUS and SSp.PLUS techniques on the Aixplorer MACH 30 system. Comparative assessments were made using the results of liver biopsy and magnetic resonance spectroscopy (MRS) together with magnetic resonance imaging proton density fat fraction (MRI-PDFF). MR examinations were performed on the Siemens VIDA 3 T system. RESULTS: ROC analysis was conducted for two groups: (a) patients without steatosis (S0) versus those with steatosis (S1 + S2 + S3) yielded AUC values of 0.79 for Att.PLUS and 0.78 for SSp.PLUS, in contrast to an AUC > 0.95 for MRS and MRI-PDFF; and (b) patients without or with mild steatosis (S0 + S1) versus those with severe steatosis (S2 + S3), yielded AUC values of 0.93 for Att.PLUS and 0.89 for SSp.PLUS, in contrast to an AUC > 0.99 for MRS and MRI-PDFF. However, MR methods were superior in detecting liver fat content in obese patients and post-liver transplantation individuals. CONCLUSION: Both QUS parameters (Att.PLUS and SSp.PLUS) appear equivalent at differentiating S0 vs. (S1 + S2 + S3) patients, but the Att.PLUS parameter may be more effective at identifying advanced steatosis (S2 + S3). MR techniques outperformed QUS methods, making them more suitable for clinical studies.
- MeSH
- Biopsy MeSH
- Adult MeSH
- Liver diagnostic imaging pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Spectroscopy methods MeSH
- Magnetic Resonance Imaging * methods MeSH
- Pilot Projects MeSH
- Prospective Studies MeSH
- Reproducibility of Results MeSH
- Aged MeSH
- Sensitivity and Specificity MeSH
- Ultrasonography * methods MeSH
- Fatty Liver * diagnostic imaging pathology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
Background: Hypertriglyceridemia has serious health risks such as cardiovascular disease, type 2 diabetes mellitus, nephropathy, and others. Fenofibrate is an effective hypolipidemic drug, but its benefits for ameliorating disorders associated with hypertriglyceridemia failed to be proven in clinical trials. Methods: To search for possible causes of this situation and possibilities of their favorable influence, we tested the effect of FF monotherapy and the combination of fenofibrate with silymarin on metabolic disorders in a unique model of hereditary hypertriglyceridemic rats (HHTg). Results: Fenofibrate treatment (100 mg/kg BW/day for four weeks) significantly decreased serum levels of triglyceride, (-77%) and free fatty acids (-29%), the hepatic accumulation of triglycerides, and the expression of genes encoding transcription factors involved in lipid metabolism (Srebf2, Nr1h4. Rxrα, and Slco1a1). In contrast, the hypertriglyceridemia-induced ectopic storage of lipids in muscles, the heart, and kidneys reduced glucose utilization in muscles and was not affected. In addition, fenofibrate reduced the activity of the antioxidant system, including Nrf2 expression (-35%) and increased lipoperoxidation in the liver and, to a lesser extent, in the kidneys and heart. Adding silymarin (micronized form, 600 mg/kg BW/day) to fenofibrate therapy increased the synthesis of glycogen in muscles, (+36%) and reduced hyperinsulinemia (-34%). In the liver, it increased the activity of the antioxidant system, including PON-1 activity and Nrf2 expression, and reduced the formation of lipoperoxides. The beneficial effect of combination therapy on the parameters of oxidative stress and lipoperoxidation was also observed, to a lesser extent, in the heart and kidneys. Conclusions: Our results suggest the potential beneficial use of the combination of FF with SLM in the treatment of hypertriglyceridemia-induced metabolic disorders.
- Publication type
- Journal Article MeSH
Biliary drainage is then one of the necessary procedures to help patients suffering from icterus to reduce serum bilirubin levels and relieve symptoms. The aim of this study was identifying risk factors for survival in patients with cholangiocarcinoma (CCA) treated with percutaneous transhepatic biliary drainage (PTBD) and to develop a simple scoring system predicting survival from PTBD insertion. This single-centre retrospective study included 175 consecutive patients undergoing PTBD for extrahepatic CCA (perihilar and distal). Prognostic factors affecting survival of patients with CCA treated with PTBD were analysed. A multivariate analysis showed that mass forming tumor with mass larger than 5 cm and presence of metastasis at the time of PTBD served as a negative prognostic factor (p = 0.002), better survival was associated with lower preprocedural bilirubin and lower CRP (p = 0.003). Multivariate analysis identified two significant risk factors for 3-month mortality: mass-forming tumors and bilirubin levels exceeding 185 μmol/L. A simple scoring system was developed to predict 3-month mortality after PTBD in patients with advanced CCA, demonstrating 86.3% negative predictive value and 43.2% positive predictive value.
- MeSH
- Bilirubin blood MeSH
- Cholangiocarcinoma * mortality therapy pathology MeSH
- Adult MeSH
- Drainage * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Bile Duct Neoplasms * mortality therapy pathology MeSH
- Prognosis MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
INTRODUCTION: Although the effects of carrying loads on gait biomechanics have been well-documented, to date, little evidence has been provided whether such loads may impact spatial and temporal gait asymmetries under the different foot regions. Therefore, the main purpose of the study was to examine the effects of carrying a standardized police equipment on spatiotemporal gait parameters. MATERIALS AND METHODS: In this population-based study, participants were 845 first-year police recruits (age: 21.2 ± 2.3 years; height: 178.1 ± 10.2 cm; weight: 78.4 ± 11.3 kg; body mass index: 24.7 ± 3.2 kg/m2; 609 men and 236 women; 72.1% men and 27.9% women) measured in 2 conditions: (i) "no load" and (ii) "a 3.5 kg load." Spatiotemporal gait parameters were derived from the FDM Zebris pressure platform. Asymmetry was calculated as (xright-xleft)/0.5*(xright + xleft)*100%, where "x" represented a given parameter being calculated and a value closer to 0 denoted greater symmetry. RESULTS: When compared to "no load" condition, a standardized 3.5 kg/7.7 lb load significantly increased asymmetries in spatial gait parameters as follows: gait phases of stance (mean diff. = 1.05), load response (mean diff. = 0.31), single limb support (mean diff. = 0.56), pre-swing (mean diff. = 0.22), and swing (mean diff. = 0.90) phase, while no significant asymmetries in foot rotation, step, and stride length were observed. For temporal gait parameters, we observed significant asymmetries in step time (mean diff. = -0.01), while no differences in cadence and gait speed were shown. CONCLUSIONS: The findings indicate that the additional load of 3.5 kg/7.7 lb is more likely to increase asymmetries in spatial gait cycle components, opposed to temporal parameters. Thus, external police load may have hazardous effects in increasing overall body asymmetry, which may lead to a higher injury risk and a decreased performance for completing specific everyday tasks.
- MeSH
- Biomechanical Phenomena physiology MeSH
- Gait * physiology MeSH
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Police * statistics & numerical data MeSH
- Weight-Bearing * physiology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The cardioselective β-1 receptor antagonist metoprolol is used to treat heart failure. It is metabolized in the liver, primarily by cytochrome 2D6. RESEARCH DESIGN AND METHODS: In this study, trough serum concentrations of metoprolol and its metabolite α-hydroxymetoprolol were measured in patients with heart failure with reduced ejection fraction. RESULTS: Concentrations were 1.3-122.9 μg/L for metoprolol and 1.3-125.7 μg/L for α-hydroxymetoprolol, metabolic ratios were 0.11-98.32. The median weight-adjusted apparent clearance of metoprolol was 53.07 (range 3.24-500.0). Metoprolol and α-hydroxymetoprolol concentrations correlated with both daily dose and dose per kilogram of body weight. However, metoprolol concentrations at the same daily dose showed a wide variability. Patients taking 100 mg/day had significantly lower NT-proBNP values than those taking 25 or 50 mg/day. Patients with LVEF ≤ 35% versus > 35% used significantly lower daily doses and doses per kilogram of body weight, although metoprolol concentrations did not differ. A poor cytochrome 2D6 metabolizer phenotype was detected in two patients. CONCLUSIONS: Metoprolol concentrations showed a wide interindividual variability at the same daily dose. Simultaneous determination of metoprolol and α-hydroxymetoprolol concentrations could identify patients at risk of possible accumulation of metoprolol leading to intoxication or, conversely, patients at risk of underdosing. [Figure: see text].
- MeSH
- Adrenergic beta-1 Receptor Antagonists * administration & dosage MeSH
- Cytochrome P-450 CYP2D6 metabolism MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Metoprolol * administration & dosage pharmacokinetics analogs & derivatives pharmacology MeSH
- Natriuretic Peptide, Brain * blood MeSH
- Peptide Fragments blood MeSH
- Pilot Projects MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Heart Failure * drug therapy physiopathology MeSH
- Stroke Volume * drug effects MeSH
- Dose-Response Relationship, Drug * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Age affects disease severity and patient outcomes in pulmonary arterial hypertension. This post-hoc analysis identified prognostic age groups and associated macitentan/selexipag treatment effects. METHODS: Randomized trials evaluated macitentan (SERAPHIN; NCT00660179) and selexipag (GRIPHON; NCT01106014) versus placebo (primary endpoint: time to morbidity/mortality [M/M]). This analysis defined age thresholds differentiating M/M risk in patients randomized to placebo (Cox regression determining treatment effect by age). RESULTS: Three age groups (< 35, 35-64, ≥ 65 years) showed good M/M risk discrimination (c-statistic 0.69, SERAPHIN; 0.66, GRIPHON). M/M risk was higher in placebo patients < 35 versus 35-64 years (SERAPHIN: hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.10-2.72, p = 0.02; GRIPHON: HR 1.81, 95% CI 1.28-2.56, p < 0.001). M/M risk trended higher in patients ≥ 65 versus 35-64 years (SERAPHIN: HR 1.55, 95% CI 0.89-2.69, p = 0.12; GRIPHON (HR 1.08, 95% CI 0.75-1.55, p = 0.69). M/M risk was lower with macitentan/selexipag versus placebo: macitentan < 35 (HR 0.44, 95% CI 0.25-0.78; p = 0.005), 35-64 (HR 0.50, 95% CI 0.33-0.76; p < 0.001), ≥ 65 years (HR 0.69, 95% CI 0.30-1.58; p = 0.38); selexipag < 35 (HR 0.50, 95% CI 0.32-0.78; p = 0.002), 35-64 (HR 0.72, 95% CI 0.54-0.96; p = 0.03), ≥ 65 years (HR 0.55, 95% CI 0.33-0.91; p = 0.02). Adverse-event discontinuations were similar. CONCLUSIONS: The benefit (vs placebo) of macitentan/selexipag on reducing risk of M/M events was consistent across all ages, including the younger group where significant treatment effects were observed.
- Publication type
- Journal Article MeSH
PURPOSE OF REVIEW: This review explores the potential role of neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) for oligometastatic bladder cancer (OMBC) treatment. We focused on extrapolating evidence from studies including lymph node-positive only and metastatic bladder cancer to address the key challenges and therapeutic strategies for OMBC. RECENT FINDINGS: Current evidence for NAC and RC in OMBC is limited, with most data derived from studies in locally advanced bladder cancer. NAC has shown efficacy in downstaging and improving survival in patients with locally advanced disease, but its benefits in OMBC remain speculative. Additionally, diagnostic uncertainties, particularly regarding the inclusion of pelvic lymph nodes and the role of FDG-PET/CT, pose significant challenges to accurate staging and treatment decisions. Recent studies highlight the potential of metastasis-directed therapy, but uncertainties remain on patient selection and treatment protocols for OMBC. SUMMARY: There is need for prospective studies to evaluate neoadjuvant systemic treatments and RC specifically in OMBC. Moreover, resolving current diagnostic challenges is crucial to avoid undertreatment due to inaccurate staging. Until more concrete evidence emerges, changes to standard treatment protocols should be approached with caution and offered only within trials.
- MeSH
- Chemotherapy, Adjuvant methods MeSH
- Cystectomy * methods MeSH
- Humans MeSH
- Lymphatic Metastasis MeSH
- Urinary Bladder Neoplasms * pathology therapy surgery MeSH
- Neoadjuvant Therapy * methods MeSH
- Neoplasm Staging MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
We present new developments for an ab-initio model of the neutron relative biological effectiveness (RBE) in inducing specific classes of DNA damage. RBE is evaluated as a function of the incident neutron energy and of the depth inside a human-sized reference spherical phantom. The adopted mechanistic approach traces neutron RBE back to its origin, i.e. neutron physical interactions with biological tissues. To this aim, we combined the simulation of radiation transport through biological matter, performed with the Monte Carlo code PHITS, and the prediction of DNA damage using analytical formulas, which ground on a large database of biophysical radiation track structure simulations performed with the code PARTRAC. In particular, two classes of DNA damage were considered: sites and clusters of double-strand breaks (DSBs), which are known to be correlated with cell fate following radiation exposure. Within a coherent modelling framework, this approach tackles the variation of neutron RBE in a wide energy range, from thermal neutrons to neutrons of hundreds of GeV, and reproduces effects related to depth in the human-sized receptor, as well as to the receptor size itself. Besides providing a better mechanistic understanding of neutron biological effectiveness, the new model can support better-informed decisions for radiation protection: indeed, current neutron weighting (ICRP)/quality (U.S. NRC) factors might be insufficient for use in some radiation protection applications, because they do not account for depth. RBE predictions obtained with the reported model were successfully compared to the currently adopted radiation protection standards when the depth information is not relevant (at the shallowest depth in the phantom or for very high energy neutrons). However, our results demonstrate that great care is needed when applying weighting factors as a function of incident neutron energy only, not explicitly considering RBE variation in the target. Finally, to facilitate the use of our results, we propose look-up RBE tables, explicitly considering the depth variable, and an analytical representation of the maximal RBE vs. neutron energy.
BACKGROUND: Kidney transplantation is the preferred treatment for patients with end-stage renal disease, significantly preserving kidney function and patient quality of life. However, post-transplant diabetes mellitus (PTDM) is a common complication, occurring in approximately one-third of renal transplant recipients. This study aims to evaluate the role of pulse wave parameters in predicting PTDM and to identify other pre-transplant risk factors. METHODS: This prospective cohort study included 105 patients on the kidney transplant waiting list from 2017 to 2022. Exclusion criteria included any pre-existing diabetes mellitus. Patients underwent physical examinations, laboratory analyses, and pulse wave analysis before transplantation and one year post-transplant. PTDM diagnosis followed International Consensus Guidelines. Data were analyzed using Wilcox test, Bonferroni correction, May-Whitney U-test, and Fisher's exact test, with p < 0.05 considered statistically significant. RESULTS: Post-transplant, 21% of patients were diagnosed with PTDM, increasing to 35% 3months post-transplant and 43% at one year post-transplant. Significant findings included: Pre-transplat risk factors for developing PTDM: Proteinuria (p = 0.037, OR = 3.942) and perioperative hyperglycemia (p = 0.003, OR = 4.219 at 3 months; p = 0.001, OR = 4.571 at 1 year). Pulse wave parameters for developing PTDM: Pre-transplant Aortic PP > 45 mmHg (AUC = 0.757) and PWV > 8.5 m/s (AUC = 0.730) were strong predictors of the development of PTDM after 3 months (p < 0.0001). Moreover, we found significant improvements in aortic pulse pressure (Aortic PP) and pulse wave velocity (PWV) post-transplant (p < 0.0001). CONCLUSION: Our study confirms that pulse wave parameters, such as Aortic PP and PWV, are significant predictors of PTDM in kidney transplant recipients (KTR). These findings support incorporating pulse wave analysis into routine pre-transplant evaluations to identify high-risk patients. Additionally, monitoring these parameters post-transplant may aid in early intervention and prevention of PTDM, ultimately improving patient outcomes. TRIAL REGISTRATION: Ethical approval was obtained from the Ethics Committee of Medical faculty and University Hospital Olomouc (approval no. 94/15).
- MeSH
- Pulse Wave Analysis * MeSH
- Kidney Failure, Chronic surgery etiology MeSH
- Diabetes Mellitus * etiology epidemiology MeSH
- Adult MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Postoperative Complications * etiology diagnosis MeSH
- Prospective Studies MeSH
- Proteinuria etiology MeSH
- Risk Factors MeSH
- Kidney Transplantation * adverse effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The cannulation of the internal jugular vein (IJV) is a frequent procedure in critically ill patients. According to the guidelines, real-time ultrasound navigation is recommended. Traditional techniques pose several disadvantages, such as suboptimal needle visualization. Therefore, this non-inferiority trial aimed to describe the novel approach and compare the novel lateral in-plane short-axis approach for IJV access with the conventional short-axis out-of-plane approach. OBJECTIVES: The primary objective of the trial was to prove that the first attempt success rate in the novel technique is non-inferior to the conventional technique. The secondary objectives were to demonstrate that the complication rate and the functional duration of the catheter in the novel technique are not inferior to those in the conventional technique. METHODS: Patients eligible for IJV cannulation were randomly assigned to either the novel technique (Group A) or the conventional one (Group B). The procedure duration, success rate and the number of attempts required were documented. The functionality of the catheter and complications were monitored from insertion until the catheter removal. Standard descriptive statistical methods were employed for the analysis. RESULTS: A total of 200 subjects were equally divided between Group A and Group B. For the primary outcome, there was no significant difference in first attempt success rate (Group A: 79, Group B: 77, p = 0.434). Secondary outcomes, including complications and catheter functional time, did not differ significantly between the groups. However, the novel technique demonstrated a significantly faster procedure time (Group A: 315 s, Group B: 330 s, p = 0.016). Notably, the novel approach was linked with significantly larger IJV diameter measured during the procedure (Group A: 18.2 mm, Group B: 12.1 mm, p < 0.001). CONCLUSION: The novel lateral in-plane short-axis approach for IJV cannulation is a non-inferior alternative with a lower incidence of posterior vessel wall puncture compared to the conventional approach.
- Publication type
- Journal Article MeSH
