Background
Preoperative prediction of tumor recurrence is important in the management of patients with hepatocellular carcinoma (HCC).
Purpose
To investigate whether tumor stiffness derived by ...magnetic resonance elastography (MRE) could predict early recurrence of HCC after hepatic resection.
Study Type
Retrospective.
Population
In all, 99 patients with pathologically confirmed HCCs after surgical resection.
Field Strength/Sequence
3.0T; preoperative MRE with 60‐Hz mechanical vibrations using an active acoustic driver.
Assessment
Regions of interest (ROIs) were manually drawn in the tumors to measure mean tumor stiffness. Surgical specimens were reviewed for histological grade, capsule, vascular invasion, and surgical margins. The early recurrence of HCC was defined as that occurring within 2 years after resection.
Statistical Tests
Cox proportional hazard models were used to evaluate risk factors associated with the time to early recurrence.
Results
HCCs with recurrence had higher tumor stiffness, higher rate of advanced T stage, vascular invasion, lower rate of capsule formation, larger tumor size, higher aspartate aminotransferase (AST), and hepatitis B virus (HBV)‐DNA level and aspartate aminotransferase / alanine aminotransferase ratio (P = 0.031, 0.007, 0.01, <0.001, 0.015, 0.034, 0.01, and 0.014, respectively) than HCCs without recurrence. Vascular invasion (hazard ratio HR = 2.922; 95% confidence interval CI: 1.079, 7.914, P = 0.035) and mean tumor stiffness (HR = 1.163; 95% CI: 1.055, 1.282, P = 0.002) were risk factors associated with early recurrence. Each 1‐kPa increase in tumor stiffness was associated with a 16.3% increase in the risk for tumor recurrence.
Data Conclusion
The mean stiffness of HCCs may be a useful, noninvasive, quantitative biomarker for the prediction of early HCC recurrence after hepatic resection.
Level of Evidence: 4
Technical Efficacy: Stage 5
J. Magn. Reson. Imaging 2019;49:719–730.
Background Individuals suffering from chronic kidney disease (CKD) frequently face a heightened likelihood of experiencing cardiovascular complications, including heart failure and cardiac mortality. ...Cardiovascular magnetic resonance feature tracking (CMR-FT) is utilized to assess the micro-contraction function of the myocardium. The objective of this research is to explore the relationship between the left ventricular anatomy, myocardial strain, and the clinical outcomes in patients with CKD. Methods A total of 77 patients with late-stage CKD were enrolled in this retrospective study. They underwent cardiac magnetic resonance imaging and were followed up, with no history of significant cardiac diseases. The patients were divided into two groups: those with a left ventricular global longitudinal strain (LVGLS) ≥ −15.2% ( n = 49) and those with LVGLS < −15.2% ( n = 28). The clinical endpoints were defined as hospitalization for heart failure or all-cause mortality. Results Over an average observation period of 22 ± 9 months, 11 (14%) patients passed away and 30 (39%) were admitted to the hospital for heart failure, with eight encountering both incidents. Those with LVGLS ≥ −15.2% had markedly lower rates of event-free survival concerning heart failure admissions and overall mortality than their counterparts (log-rank P = 0.014). Cox multivariable analysis indicated that reduced LVGLS consistently predicted a higher likelihood of combined outcomes of heart failure admissions and total mortality (HR: 3.40, 95% CI 1.35–8.56, P = 0.009), even when factoring in age, diabetes, left atrial diameter, and left ventricular mass index (LVMI). However, the LVMI showed no significant correlation with the risk of heart failure admissions or overall mortality. Conclusion Compared to patients with LVGLS < −15.2%, CKD patients with LVGLS ≥ −15.2% have an increased risk of heart failure hospitalization and all-cause mortality. The prognostic role of LVMI in assessing CKD patients among the Asian population requires further investigation.
A new kind of polypeptide bearing 1,4-dithiane pendants was synthesized and used for reactive oxygen species (ROS)-responsive drug release.
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Stimuli-responsive polypeptides have been ...intensively investigated for controlled drug release, owing to their favorable biocompatibility and biodegradability. In this work, we designed and synthesized a new kind of polypeptide bearing 1,4-dithiane pendants for reactive oxygen species (ROS)-responsive drug release. The polypeptide-based block copolymer was facilely synthesized by ring-opening polymerization (ROP) of 1,4-dithian-substituted l-glutamate N-carboxyanhydride (DTG-NCA) monomer using an amino-terminated poly(ethylene glycol) methyl ether (mPEG-NH2) as the macromolecular initiator. The resultant block copolymer, mPEG-b-PDTG, could self-assemble into uniform micelles in aqueous medium owing to its amphiphilic structure. Then, the H2O2-triggered oxidation behaviors of the mPEG-b-PDTG micelles were studied by dynamic light scattering (DLS), FT-IR and turbidimetric assay. It was revealed that the oxidation of thioether into sulfoxide in the side chains would result in disassembly of the micelles. Furthermore, the ROS-responsive drug release behavior of the mPEG-b-PDTG micelles was verified by using Nile Red as a model drug. MTT assay also proved that mPEG-b-PDTG was non-toxic in B16F10 and L929 cells. Therefore, such a new class of oxidation-responsive polypeptide might provide a promising platform for ROS-responsive drug delivery.
The location of joint distribution center (JDC) is of great importance in urban freight system. This work aims to minimize the total cost, including the fixed cost, the transportation cost, and the ...penalty cost for the missed deliveries, considering the joint distribution willingness (JDW) of restaurant and the coverage radius of JDC. The integer programming model is formulated to select the optimal location of JDC and opens no more than k-JDCs. To solve the problem, an improved K-means (I-K-means) algorithm combining local search with penalty is proposed. The delivery problems obtained by freight survey from 114 restaurants in Beijing, China are taken as a case study. The formulation in this paper can reduce the cost of deliveries in restaurant industry, decrease the number of freight vehicles on road, and promote the joint distribution mode in urban freight system.
To assess breast cancer receptor status and molecular subtypes by using the CAIPIRINHA-Dixon-TWIST-VIBE and readout-segmented echo-planar diffusion weighted imaging techniques.
A total of 165 breast ...cancer patients were retrospectively recruited. Patient age, estrogen receptor, progesterone receptor, human epidermal growth factorreceptor-2 (HER-2) status, and the Ki-67 proliferation index were collected for analysis. Quantitative parameters (K
, V
, K
), semiquantitative parameters (W
, W
, TTP), and apparent diffusion coefficient (ADC) values were compared in relation to breast cancer receptor status and molecular subtypes. Statistical analysis were performed to compare the parameters in the receptor status and molecular subtype groups.Multivariate analysis was performed to explore confounder-adjusted associations, and receiver operating characteristic curve analysis was used to assess the classification performance and calculate thresholds.
Younger age (<49.5 years, odds ratio (OR) =0.95,
=0.004), lower K
(<0.704,OR=0.14,
=0.044),and higher TTP (>0.629 min, OR=24.65,
=0.011) were independently associated with progesterone receptor positivity. A higher TTP (>0.585 min, OR=28.19,
=0.01) was independently associated with estrogen receptor positivity. Higher K
(>0.892, OR=11.6,
=0.047), lower TTP (<0.582 min, OR<0.001,
=0.004), and lower ADC (<0.719 ×10
mm
/s, OR<0.001,
=0.048) had stronger independent associations with triple-negative breast cancer (TNBC) compared to luminal A, and those parameters could differentiate TNBC from luminal A with the highest AUC of 0.811.
K
and TTP were independently associated with hormone receptor status. In addition, the K
, TTP, and ADC values had stronger independent associations with TNBC than with luminal A and could be used as imaging biomarkers for differentiate TNBC from Luminal A.
Introduction
Nirsevimab is an extended half-life (M252Y/S254T/T256E YTE-modified) monoclonal antibody to the pre-fusion conformation of the respiratory syncytial virus (RSV) Fusion protein, with ...established efficacy in preventing RSV-associated lower respiratory tract infection in infants for the duration of a typical RSV season. Previous studies suggest that nirsevimab confers protection via direct virus neutralization. Here we use preclinical models to explore whether fragment crystallizable (Fc)-mediated effector functions contribute to nirsevimab-mediated protection.
Methods
Nirsevimab, MEDI8897* (i.e., nirsevimab without the YTE modification), and MEDI8897*-TM (i.e., MEDI8897* without Fc effector functions) binding to Fc γ receptors (FcγRs) was evaluated using surface plasmon resonance. Antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent cellular phagocytosis (ADCP), antibody-dependent complement deposition (ADCD), and antibody-dependent cellular cytotoxicity (ADCC) were assessed through
in vitro
and
ex vivo
serological analyses. A cotton rat challenge study was performed with MEDI8897* and MEDI8897*-TM to explore whether Fc effector functions contribute to protection from RSV.
Results
Nirsevimab and MEDI8897* exhibited binding to a range of FcγRs, with expected reductions in FcγR binding affinities observed for MEDI8897*-TM. Nirsevimab exhibited
in vitro
ADNP, ADCP, ADCD, and ADCC activity above background levels, and similar ADNP, ADCP, and ADCD activity to palivizumab. Nirsevimab administration increased
ex vivo
ADNP, ADCP, and ADCD activity in participant serum from the MELODY study (NCT03979313). However, ADCC levels remained similar between nirsevimab and placebo. MEDI8897* and MEDI8897*-TM exhibited similar dose-dependent reduction in lung and nasal turbinate RSV titers in the cotton rat model.
Conclusion
Nirsevimab possesses Fc effector activity comparable with the current standard of care, palivizumab. However, despite possessing the capacity for Fc effector activity, data from RSV challenge experiments illustrate that nirsevimab-mediated protection is primarily dependent on direct virus neutralization.
Spinal cord injuries (SCIs) are devastating. In SCIs, a powerful traumatic force impacting the spinal cord results in the permanent loss of nerve function below the injury level, leaving the patient ...paralyzed and wheelchair-bound for the remainder of his/her life. Unfortunately, clinical treatment that depends on surgical decompression appears to be unable to handle damaged nerves, and high-dose methylprednisolone-based therapy is also associated with problems, such as infection, gastrointestinal bleeding, femoral head necrosis, obesity, and hyperglycemia. Nanomaterials have opened new avenues for SCI treatment. Among them, performance-based nanomaterials derived from a variety of materials facilitate improvements in the microenvironment of traumatic injury and, in some cases, promote neuron regeneration. Nanoparticulate drug delivery systems enable the optimization of drug effects and drug bioavailability, thus contributing to the development of novel treatments. The improved efficiency and accuracy of gene delivery will also benefit the exploration of SCI mechanisms and the understanding of key genes and signaling pathways. Herein, we reviewed different types of nanomaterials applied to the treatment of SCI and summarized their functions and advantages to provide new perspectives for future clinical therapies.
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Excellent biocompatibility, mechanical properties, chemical stability, and elastic modulus close to bone tissue make polyetheretherketone (PEEK) a promising orthopedic implant material. However, ...biological inertness has hindered the clinical applications of PEEK. The immune responses and inflammatory reactions after implantation would interfere with the osteogenic process. Eventually, the proliferation of fibrous tissue and the formation of fibrous capsules would result in a loose connection between PEEK and bone, leading to implantation failure. Previous studies focused on improving the osteogenic properties and antibacterial ability of PEEK with various modification techniques. However, few studies have been conducted on the immunomodulatory capacity of PEEK. New clinical applications and advances in processing technology, research, and reports on the immunomodulatory capacity of PEEK have received increasing attention in recent years. Researchers have designed numerous modification techniques, including drug delivery systems, surface chemical modifications, and surface porous treatments, to modulate the post-implantation immune response to address the regulatory factors of the mechanism. These studies provide essential ideas and technical preconditions for the development and research of the next generation of PEEK biological implant materials. This paper summarizes the mechanism by which the immune response after PEEK implantation leads to fibrous capsule formation; it also focuses on modification techniques to improve the anti-inflammatory and immunomodulatory abilities of PEEK. We also discuss the limitations of the existing modification techniques and present the corresponding future perspectives.
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•The FBR produced by PEEK implantation in the body leads to the formation of fibrous capsule and inhibits the binding of PEEK to bone.•The drug molecule delivery system constructed on PEEK surface can steadily release anti-inflammatory drugs for a long time, and inhibit the inflammatory response and the formation of fibrous capsule after implantation.•The surface chemical modification technique improves the surface properties of PEEK while retaining the structure and properties of the PEEK body.•Nanopore structure can change the surface roughness of PEEK and convert mechanical signals into biological signals to further modulate the local immune microenvironment.
Purpose
To evaluate histologic differentiation of hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs) using apparent diffusion coefficient (ADC) and intravoxel incoherent motion ...(IVIM)-derived metrics and to compare findings with alpha-fetoprotein (AFP) levels alone and in combination.
Materials and method
One hundred and six chronic HBV-related HCC patients who underwent IVIM diffusion-weighted magnetic resonance imaging with eleven
b
values were enrolled. Mean ADC, diffusion coefficient (
D
), pseudodiffusion coefficient (
D
*), and perfusion fraction (
f
) values were determined for all detected lesions. The metrics and AFP levels of different histologically differentiated groups were compared. Spearman’s rank correlation was used to assess the statistical dependence among the histologically differentiated HCCs. Receiver operating characteristic (ROC) analysis was performed to evaluate diagnostic performance of these metrics and AFP levels alone and in combination.
Results
ADC,
D
, and
f
values and AFP levels were significantly different among well-, moderately, and poorly differentiated HCCs. The four metrics were significantly correlated with histologic differentiation. The area under the ROC curve (AUC-ROC) of ADC,
D
,
f
, and AFP for diagnosing well-differentiated HCCs was 0.903, 0.84, 0.782, and 0.806, respectively, and the AUC-ROC of above metrics for diagnosing poorly differentiated HCCs was 0.787, 0.726, 0.624, and 0.633, respectively. The combination of ADC and AFP provided an AUC-ROC of 0.945 for well-differentiated HCC. However, this did not provide better performance for diagnosing poorly differentiated HCC.
Conclusion
ADC, IVIM metrics, and AFP levels may be useful for evaluating histologic differentiation of HBV-related HCCs, and the combination of ADC and AFP provides better diagnostic performance for well-differentiated HCC.
Background Preoperative evaluation of aggressiveness, including tumor histological subtype, grade of differentiation, Federation International of Gynecology and Obstetrics (FIGO) stage, and depth of ...myometrial invasion, is significant for treatment planning and prognosis in endometrial carcinoma (EC). The purpose of this study was to evaluate whether three-dimensional (3D) magnetic resonance elastography (MRE) can help predict the aggressiveness of EC. Methods From August 2015 to January 2019, 82 consecutive patients with suspected uterine tumors underwent pelvic MRI and MRE scans, and 15 patients with confirmed EC after surgical resection were enrolled. According to pathological results (tumor grade, histological subtype, FIGO stage, and myometrial invasiveness), the patients were divided into two subgroups. The independent-samples t-test or Mann-Whitney U test was used to compare the stiffness between different groups. The diagnostic performance was determined with receiver operating characteristic (ROC) curve analysis. Results The stiffness of EC with greater than or equai to 50 % (n = 6) myometrial invasion was significantly higher than that with < 50 % (n = 9) myometrial invasion (3.68 + or - 0.59 kPa vs. 2.61 + or - 0.72 kPa, p = 0.009). Using a stiffness of 3.04 kPa as a cutoff value resulted in 100 % sensitivity and 77.8 % specificity for differentiating greater than or equai to 50 % myometrial invasion from < 50 % myometrial invasion of EC. The stiffness of poorly differentiated EC (n = 8) was significantly higher than that of well/moderately differentiated EC (n = 7) (3.47 + or - 0.64 kPa vs. 2.55 + or - 0.82 kPa, p = 0.028). Using a stiffness of 3.04 kPa as a cutoff value resulted in 75 % sensitivity and 71.4 % specificity for differentiating poorly differentiated from well/moderately differentiated EC. The stiffness of FIGO stage II/III EC was significantly higher than that of FIGO stage I EC (3.69 + or - 0.65 kPa vs. 2.72 + or - 0.76 kPa, p = 0.030). Using a stiffness of 3.04 kPa as a cutoff value resulted in 100 % sensitivity and 70 % specificity for differentiating FIGO stage I EC from FIGO stage II/III EC. The tumor stiffness value in type II (n = 3) EC was higher than that in type I (n = 12) EC (3.67 + or - 0.59 kPa vs. 2.88 + or - 0.85 kPa), but the difference was not significant (p = 0.136). Conclusions Tumor stiffness measured by 3D MRE may be potentially useful for predicting tumor grade, FIGO stage and myometrial invasion of EC and can aid in the preoperative risk stratification of EC. Keywords: Magnetic resonance elastography (MRE), Tumor stiffness, Endometrial carcinoma (EC), Tumor aggressiveness
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