Utility of Ultrasound Elastography to Evaluate Poststroke Spasticity and Therapeutic Efficacy: A Narrative Review.

Poststroke spasticity (PSS) is a common complication that affects function and daily self-care. Conservative PSS treatments include traditional rehabilitation, botulinum toxin injection, and extracorporeal shock wave therapy. Currently, the Modified Ashworth Scale and Modified Tardieu Scale are widely used tools to clinically evaluate spasticity, but the best tool for PSS assessment remained controversial. Ultrasound elastography (UE), including shear wave and strain image as the emerging method to evaluate soft tissue elasticity, became popular in clinical applications. Spastic biceps and gastrocnemius muscles were reported to be significantly stiffer compared to nonparetic muscles or healthy control using shear wave or strain elastography. More studies investigated the utility, reliability, and validity of UE in patients with PSS, but the contemporary consensus for the utility of UE in the measurement and therapeutic follow-up of PSS remained lacking. Therefore, this narrative review aimed to appraise the literature on the shear wave and strain elastography on PSS and summarize the roles of UE in assessing the therapeutic efficacy of different PSS interventions.

Correction: Yang et al. Construction and Evaluation of Chitosan-Based Nanoparticles for Oral Administration of Exenatide in Type 2 Diabetic Rats. Polymers 2022, 14, 2181.

The authors wish to make the following corrections to this paper [...].

Temporalis and masseter muscle thickness as predictors of post-stroke dysphagia after endovascular thrombectomy.

PURPOSE: Post-stroke dysphagia (PSD) is a common sequela of stroke. Given the association between dysphagia and sarcopenia, we aimed to investigate the association between PSD and temporal muscle thickness (TMT) and masseter muscle thickness (MMT) following endovascular thrombectomy (EVT) in patients with large-vessel occlusion (LVO). METHODS: This retrospective cohort study included hospitalized patients with LVO stroke who underwent EVT between January 1, 2018, and October 31, 2022. TMT and MMT were measured using brain computed tomography (CT) angiography. The correlation between relevant clinicodemographic factors and both TMT and MMT was examined. The relationship between each of two parameters (TMT and MMT) and PSD, which was defined as the retention of the nasogastric (NG) tube at 4 and 12 weeks, was evaluated in adjusted logistic regression models. RESULTS: Among the 148 participants, the mean TMT and MMT was 5.9 ± 1.6 and 11.2 ± 2.3 mm, respectively. Lower age, male sex, higher body mass index (BMI), higher albumin levels, and a lower initial National Institute of Health Stroke Scale (NIHSS) score were associated with higher TMT and MMT (p < 0.05). In the logistic regression analysis adjusted for age, sex, BMI, serum albumin, and NIHSS score, lower TMT and MMT significantly correlated with PSD at weeks 4 and 12 (p < 0.001). CONCLUSION: TMT and MMT are associated with age, sex, BMI, albumin, and the initial NIHSS score. Both TMT and MMT are independent indicators of post-EVT PSD in stroke patients and serve as reliable predictors of NG removal.

Blood-cerebrospinal fluid barrier opening by modified single pulse transcranial focused shockwave.

Transcranial focused shockwave (FSW) is a novel noninvasive brain stimulation that can open blood-brain barriers (BBB) and blood-cerebrospinal fluid barriers (BCSFB) with a single low-energy (energy flux density 0.03 mJ/mm2) pulse and low-dose microbubbles (2 × 106/kg). Similar to focused ultrasound, FSW deliver highly precise stimulation of discrete brain regions with adjustable focal lengths that essentially covers the whole brain. By opening the BCSFB, it allows for rapid widespread drug delivery to the whole brain by cerebrospinal fluid (CSF) circulation. Although no definite adverse effect or permeant injury was noted in our previous study, microscopic hemorrhage was infrequently observed. Safety concerns remain the major obstacle to further application of FSW in brain. To enhance its applicability, a modified single pulse FSW technique was established that present 100% opening rate but much less risk of adverse effect than previous methods. By moving the targeting area 2.5 mm more superficially on the left lateral ventricle as compared with the previous methods, the microscopic hemorrhage rate was reduced to zero. We systemically examine the safety profiles of the modified FSW-BCSFB opening regarding abnormal behavior and brain injury or hemorrhage 72 hr after 0, 1, and 10 pulses of FSW-treatment. Animal behavior, physiological monitor, and brain MRI were examined and recorded. Brain section histology was examined for hemorrhage, apoptosis, inflammation, oxidative stress related immunohistochemistry and biomarkers. The single pulse FSW group demonstrated no mortality or gross/microscopic hemorrhage (N = 30), and no observable changes in all examined outcomes, while 10 pulses of FSW was found to be associated with microscopic and temporary RBC extravasation (N = 6/30), and abnormal immunohistochemistry biomarkers which showed a trend of recovery at 72 hrs. The results suggest that single pulse low-energy FSW-BCSFB opening is effective, safe and poses minimal risk of injury to brain tissue (Sprague Dawley, SD rats).

Association of clinical factors to functional outcomes in patients with stroke with large-vessel occlusion after endovascular thrombectomy.

BACKGROUND/PURPOSE: Multiple clinical factors have been reported to be associated with functional outcomes in patients with stroke. However, little is known about prognostic predictors of functional independence in patients with stroke undergoing endovascular thrombectomy (EVT). Our study aimed to investigate the correlation between multiple prognostic variables (including EVT and rehabilitation-related parameters) and functional outcomes in patients post-EVT. METHODS: This retrospective cohort study recruited patients hospitalized between December 2018 and March 2022. Patients with stroke with large-vessel occlusion who underwent EVT were eligible for inclusion in the study. Prognostic factors, including premorbid characteristics, laboratory data, EVT- and rehabilitation-related parameters, functional activity level, balance ability, swallowing, and sphincter function, were collected. Logistic regression and generalized linear models were used to analyze their correlations with functional outcomes. RESULTS: A total of 148 patients were included. In the univariate logistic regression analysis, younger age, premorbid functional independence, higher hemoglobin (Hb) level, lower National Institute of Health Stroke Scale (NIHSS) score, absence of hemorrhagic transformation in 14 days, no nasogastric (NG) tube placement, earlier rehabilitation, frequent daily rehabilitation sessions, more out-of-bed rehabilitation, better ability of sitting up, better initial sitting balance, higher Barthel index (BI), absence of immobility, and neurological complications were associated with favorable outcomes at 3 months. In the stepwise regression model, the predictors of favorable function at 3 months included age, ability to sit up, and frequency of daily rehabilitation sessions; favorable outcomes at 6 months were associated with age, ability to sit up, and swallowing function. CONCLUSION: In patients with stroke post-EVT, better functional outcomes were associated with prognostic variables, including younger age, better ability to sit up, normal swallowing function, and frequent daily rehabilitation sessions.

Impaired median nerve mobility in patients with carpal tunnel syndrome: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis investigated the mobility of the median nerve (MN) in carpal tunnel syndrome (CTS) patients compared to healthy people. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed and the electronic databases including PubMed, Scopus, EMBASE, and Cochrane Library were searched up to April 2022. All published observational studies comparing the excursion of MN between participants with and without CTS were included. The quality of research was assessed by the Newcastle-Ottawa Scale tool. The primary outcome was the excursion of the MN under dynamic examination, representing nerve mobility quantified by the standardized mean difference (SMD) for random effect meta-analysis. RESULTS: Fourteen studies were included in the qualitative review, and twelve entered the meta-analysis involving a total of 375 CTS patients and 296 healthy controls. The forest plot revealed that the mobility of the MN significantly decreased in the CTS group compared to the non-CTS control (SMD = -1.47, 95% CI: -1.91, -1.03, p < 0.001, heterogeneity 82%). In subgroup analysis, both transverse and longitudinal methods for nerve excursion showed less nerve mobility in CTS than in non-CTS. CONCLUSIONS: This meta-analysis showed that the patients with CTS exhibited less mobility of the MN than those without CTS, suggesting MN mobility as a potential CTS marker. KEY POINTS: • The patients with CTS revealed less mobility of the median nerve than those without CTS. • The mobility of the median nerve could be regarded as a potential CTS marker.

Fructose oxidase-like activity of CuO nanoparticles supported by phosphate for a tandem catalysis-based fructose sensor.

A surge of nanozymes with oxidase-like activities is emerging in various fields, whereas nanozymes with the ability to catalyze the oxidation of saccharides have less been explored. Herein, CuO nanoparticles (NPs) with phosphate-supported fructose oxidase-like activity have been reported. Notably, reactive oxygen species (ROS) have been confirmed as the products during the process. By coupling the fructose oxidase-like activity with the peroxidase-like activity of CuO NPs, a tandem catalysis-based fructose sensor can be fabricated. In detail, CuO NPs can catalyze the fructose oxidation under O2 to yield ROS (e.g., H2O2, •OH, and O2·-) and effectively decompose H2O2 into ·OH. After that, terephthalic acid can be oxidized by •OH produced from the tandem catalysis to generate a fluorescent product. This sensor shows a linear range toward fructose (0.625-275 µÐœ) with a low limit of detection (0.5 µÐœ), which can be successfully conducted to detect fructose from real samples. Overall, this work aims to expand the catalytic types of nanozymes and provide a desirable fructose sensor.

Construction and Evaluation of Chitosan-Based Nanoparticles for Oral Administration of Exenatide in Type 2 Diabetic Rats.

Oral delivery of therapeutic peptides has been a daunting challenge due to poor transport across the tight junctions and susceptibility to enzymatic degradation in the gastrointestinal tract. Numerous advancement in nanomedicine has been made for the effective delivery of protein and peptide. Owing to the superior performance of chitosan in opening intercellular tight junctions of epithelium and excellent mucoadhesive properties, chitosan-based nanocarriers have recently garnered considerable attention, which was formulated in this paper to orally deliver the GLP-1 drug (Exenatide). Against this backdrop, we used chitosan (CS) polymers to encapsulate the exenatide, sodium tripolyphosphate (TPP) as the cross-linking agent and coated the exterior with sodium alginate (ALG) to impart the stability in an acidic environment. The chitosan/alginate nanoparticles (CS-TPP-ALG) functioned as a protective exenatide carrier, realized efficient cellular uptake and controlled release, leading to a steady hypoglycemic effect and a good oral bioavailability in vivo. Trimethyl chitosan (TMC), a chitosan derivative with stronger positive electrical properties was additionally selected as a substitute for chitosan to construct the TMC-TPP-ALG nanoparticle, and its oral peptide delivery capacity was explored in terms of both characterization and pharmacodynamics studies. Overall, our study demonstrated that functional chitosan/alginate nanoparticles can protect proteins from enzymatic degradation and enhance oral absorption, which presents important research value and application prospects.

Automated Segmentation of Median Nerve in Dynamic Sonography Using Deep Learning: Evaluation of Model Performance.

There is an emerging trend to employ dynamic sonography in the diagnosis of entrapment neuropathy, which exhibits aberrant spatiotemporal characteristics of the entrapped nerve when adjacent tissues move. However, the manual tracking of the entrapped nerve in consecutive images demands tons of human labors and impedes its popularity clinically. Here we evaluated the performance of automated median nerve segmentation in dynamic sonography using a variety of deep learning models pretrained with ImageNet, including DeepLabV3+, U-Net, FPN, and Mask-R-CNN. Dynamic ultrasound images of the median nerve at across wrist level were acquired from 52 subjects diagnosed as carpal tunnel syndrome when they moved their fingers. The videos of 16 subjects exhibiting diverse appearance and that of the remaining 36 subjects were used for model test and training, respectively. The centroid, circularity, perimeter, and cross section area of the median nerve in individual frame were automatically determined from the inferred nerve. The model performance was evaluated by the score of intersection over union (IoU) between the annotated and model-predicted data. We found that both DeepLabV3+ and Mask R-CNN predicted median nerve the best with averaged IOU scores close to 0.83, which indicates the feasibility of automated median nerve segmentation in dynamic sonography using deep learning.

Protein-Assisted Osmium Nanoclusters with Intrinsic Peroxidase-like Activity and Extrinsic Antifouling Behavior.

Extensive studies have laid the groundwork for understanding peroxidase-like nanozymes. However, improvements are still required before their practical applications. On one hand, it is significant to explore highly reactive nanozymes. On the other hand, it is necessary to avoid fouling formed on the surface of nanozymes, which will affect their activity and the results of H2O2 sensors or H2O2-related applications. Herein, a strategy is reported to design osmium nanoclusters (Os NCs) with the existence of bovine serum albumin (BSA) through biomineralization. BSA-Os NCs were found to possess intrinsic peroxidase-like activity with a high specific activity (6120 U/g). Studies also found that the catalytic activity of BSA-Os NCs was better than those of reported protein-assisted metal nanozymes (e.g., BSA-Pt NPs and BSA-Au NCs). More significantly, BSA has been confirmed as a protective shell to give Os NCs extrinsic antifouling property in some typical ions (e.g., Hg2+, Ag+, Pb2+, I-, Cr6+, Cu2+, Ce3+, S2-, etc.), saline (0-2 M), or protein (0-100 mg/mL) conditions. Under optimal conditions, a colorimetric sensor was established to realize a linear range of H2O2 from 1.25 to 200 µM with a low detection limit of 300 nM. On this basis, remarkable features enable a BSA-Os NCs-based colorimetric sensor to detect H2O2 from complex systems with clear color gradients. Together, this work highlights the advantages of protein-assisted Os nanozymes and provides a paragon for peroxidase-like nanozymes in H2O2-related applications.

Effect of Perineural Injection with Different Dextrose Volumes on Median Nerve Size, Elasticity and Mobility in Hands with Carpal Tunnel Syndrome.

This study aimed to investigate the effect of different injectate volumes on ultrasonographic parameters and the correlation to clinical outcomes under perineural dextrose injection (PDI). In this post hoc analysis of the randomized, double-blinded, three-arm trial, ultrasound-guided PDI with either 1 mL, 2 mL, and 4 mL 5% dextrose water was administered, respectively, in 14, 14, and 17 patients. Ultrasound outcomes included mobility, shear-wave elastography (SWE), and cross-sectional area (CSA) of the median nerve; clinical outcomes were Visual Analog Scale (VAS) and Boston Carpal Tunnel Questionnaire (BCTQ) score. Outcomes were measured before injection, and after injection at the 1st, 4th, 12th, and 24th week. For ultrasound outcomes, CSA decreased significantly from baseline data at all follow-up time-points in the 2 mL group (p = 0.005) and the 4 mL group (p = 0.015). The mean change of mobility from baseline showed a greater improvement on the 4 mL group than the other groups at the 1st week post-injection. For clinical outcomes, negative correlation between the VAS and mobility at the 1st (p = 0.046) and 4th week (p = 0.031) post-injection in the 4 mL group were observed. In conclusion, PDI with higher volume yielded better nerve mobility and decreased CSA of median nerve, but no changes of nerve elasticity.

Real-world evidence of the safety and effectiveness of regorafenib in Taiwanese patients with metastatic colorectal cancer: CORRELATE Taiwan.

BACKGROUND/PURPOSE: This analysis reports safety and effectiveness data from the Taiwanese cohort of the CORRELATE study. METHODS: CORRELATE was a prospective, observational study to assess the safety and effectiveness of regorafenib for the treatment of metastatic colorectal cancer (CRC) in real-world clinical practice that was conducted in 13 different countries in Asia, Europe and Latin America. The primary endpoint of the study was incidence of all treatment-emergent AEs (TEAEs), and secondary endpoints included overall survival (OS), progression-free survival (PFS), and disease control rate (DCR). RESULTS: The global study population (N = 1037) included 128 Taiwanese patients with a median age of 64 years, median weight of 62.02 kg and 66.41% were male. Reduced initiating doses of regorafenib and dose interruptions were common in Taiwanese patients (71.87% and 50.00%, respectively). The safety profile of regorafenib was consistent with that seen in Asian patients in the clinical development trials, including the CORRECT and CONCUR studies, with hand-foot-skin reactions (HFSR) of any grade occurring in 33.59% of patients. Median OS was 11.64 months in the Taiwanese patients (95% confidence interval [CI], 8.36-13.82) and median PFS was 2.17 months (95% CI, 1.97-2.89). CONCLUSION: The safety and effectiveness of regorafenib in this real-world study was generally consistent with the known efficacy and safety profile in Asian patients in clinical trials. TRIAL REGISTRATION: NCT02042144.

Mitochondrial targeted doxorubicin derivatives delivered by ROS-responsive nanocarriers to breast tumor for overcoming of multidrug resistance.

Multidrug resistance (MDR) is a serious challenge in chemotherapy and also a major threat to breast cancer treatment. As an intracellular energy factory, mitochondria provide energy for drug efflux and are deeply involved in multidrug resistance. Mitochondrial targeted delivery of doxorubicin can overcome multidrug resistance by disrupting mitochondrial function. By incorporating a reactive oxygen species (ROS)-responsive hydrophobic group into the backbone structure of hyaluronic acid - a natural ligand for the highly expressed CD44 receptor on tumor surfaces, a novel ROS-responsive and CD44-targeting nano-carriers was constructed. In this study, mitochondria-targeted triphenylphosphine modified-doxorubicin (TPP-DOX) and amphipathic ROS-responsive hyaluronic acid derivatives (HA-PBPE) were synthesized and confirmed by 1H NMR. The nanocarriers TPP-DOX @ HA-PBPE was prepared in a regular shape and particle size of approximately 200 nm. Compared to free DOX, its antitumor activity in vitro and tumor passive targeting in vivo has been enhanced. The ROS-responsive TPP-DOX@HA-PBPE nanocarriers system provide a promising strategy for the reverse of MDR and efficient delivery of doxorubicin derivatives into drug-resistant cancer cells.

Platinum group element-based nanozymes for biomedical applications: an overview.

With a rapid advancement of nanotechnology and the close integration of disciplines, research on nanozymes (nanomaterials with enzyme-like activities), is becoming an expeditiously developing field. In recent years, platinum group element (PGE)-based (Pt, Pd, Ru, Rh, Ir, and Os) nanozymes developed successively, have not only promoted the research of nanozymes but also expanded the biomedical applications of nanomaterials. Generally speaking, PGE-based nanozymes process high catalytic efficiency, specific surface area, stability, and other physical/chemical properties, which benefit for their applications in biosensing, biological medicine, biomedical imaging, and environmental protection. This paper will introduce the research progress of PGE-based nanozymes including their synthesis, characterization, enzyme-like activities, stability, biocompatibility, toxicity, and applications for biological detection and clinical relevance. Our emphasis is put on unfolding the roles of PGE-based nanozymes in biomedical applications and how they overcome the limitations. Last but not least, trends and future perspectives of PGE-based nanozymes in biomedical applications are also provided.

An Unusual Volar Wrist Mass: Radial Artery Pseudoaneurysm Following Transradial Catheterization.

Arterial pseudoaneurysms can develop secondary to a vessel injury, for example, an arterial line installation. We present a case of an 18-year-old female with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome who developed left radial artery and right brachial artery pseudoaneurysms secondary to arterial line placement and repeated blood draws, respectively. The ultrasonographic features of pulsating mass in connection with an artery and the yin-yang sign, combined with the patient's history, allowed accurate diagnosis. She was referred to vascular surgery for definitive treatment.

Silk Fibroin-Modified Disulfiram/Zinc Oxide Nanocomposites for pH Triggered Release of Zn2+ and Synergistic Antitumor Efficacy.

Disulfiram (DSF) is an FDA-approved anti-alcoholic drug that has recently proven to be effective in cancer treatment. However, the short half-life in the bloodstream and the metal ion-dependent antitumor activity significantly limited the further application of DSF in the clinical field. To this end, we constructed a silk fibroin modified disulfiram/zinc oxide nanocomposites (SF/DSF@ZnO) to solubilize and stabilize DSF, and, more importantly, achieve pH triggered Zn2+ release and subsequent synergistic antitumor activity. The prepared SF/DSF@ZnO nanocomposites were spherical and had a high drug loading. Triggered by the lysosomal pH, SF/DSF@ZnO could induce the rapid release of Zn2+ under the acidic conditions and caused nanoparticulate disassembly along with DSF release. In vitro experiments showed that cytotoxicity of DSF could be enhanced by the presence of Zn2+, and further amplified when encapsulated into SF/DSF@ZnO nanocomposites. It was confirmed that the significantly amplified cytotoxicity of SF/DSF@ZnO was resulted from pH-triggered Zn2+ release, inhibited cell migration, and increased ROS production. In vivo study showed that SF/DSF@ZnO nanocomposites significantly increased the tumor accumulation and prolonged the retention time. In vivo antitumor experiments in the xenograft model showed that SF/DSF@ZnO exerted the highest tumor-inhibition rate among all the drug treatments. Therefore, this exquisite study established silk fibroin-modified disulfiram/zinc oxide nanocomposites, SF/DSF@ZnO, where ZnO not only acted as a delivery carrier but also served as a metal ion reservoir to achieve synergistic antitumor efficacy. The established DSF nanoformulation displayed excellent therapeutic potential in future cancer treatment.

Effectiveness of Platelet-Rich Plasma Injection in Rotator Cuff Tendinopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: To investigate the effectiveness of platelet-rich plasma (PRP) injection among patients with rotator cuff tendinopathy in comparison with sham injection, no injection, or physiotherapy alone. METHODS: From the earliest records to November 1, 2018, all published or unpublished randomized controlled trial (RCTs) comparing PRP injection with a control group (sham injection, no injection, or physiotherapy alone) in patients with rotator cuff tendinopathy were included. Eligible trials were included from the search results of electronic databases including PubMed, EMBASE, Scopus, The Cochrane Library, as well as the bibliographies of relevant trials. Five RCTs were enrolled in our meta-analysis. Two authors independently assessed the quality of RCTs with the Cochrane risk of bias tool. We designated pain reduction as the primary outcome and functional improvement as the secondary outcome. Standardized mean difference (SMD) was applied for random-effect meta-analysis. RESULTS: In the short term (3-6 weeks) and medium term (12 weeks), the effectiveness of PRP injection and control group was indistinguishable in terms of both outcomes (pain reduction and functional improvement). Nevertheless, PRP injection led to significant long-term (>24 weeks) pain relief (SMD: 0.42, 95% confidence interval (CI): 0.12-0.72, without heterogeneity). For functional improvement in the long term, PRP injection was not more effective than the control group (SMD: 1.20, 95% CI: -0.20-2.59, with heterogeneity). CONCLUSIONS: PRP injection may provide benefit over the control group (sham injection, no injection, or physiotherapy alone) in reducing pain at long-term follow-up for patients with rotator cuff tendinopathy.