Impact of repetitive transcranial magnetic stimulation on cortical activity: a systematic review and meta-analysis utilizing functional near-infrared spectroscopy evaluation.

BACKGROUND: Repeated transcranial magnetic stimulation (rTMS) could induce alterations in cortical excitability and promote neuroplasticity. To precisely quantify these effects, functional near-infrared spectroscopy (fNIRS), an optical neuroimaging modality adept at detecting changes in cortical hemodynamic responses, has been employed concurrently alongside rTMS to measure and tailor the impact of diverse rTMS protocols on the brain cortex. OBJECTIVE: This systematic review and meta-analysis aimed to elucidate the effects of rTMS on cortical hemodynamic responses over the primary motor cortex (M1) as detected by fNIRS. METHODS: Original articles that utilized rTMS to stimulate the M1 cortex in combination with fNIRS for the assessment of cortical activity were systematically searched across the PubMed, Embase, and Scopus databases. The search encompassed records from the inception of these databases up until April, 2024. The assessment for risk of bias was also conducted. A meta-analysis was also conducted in studies with extractable raw data. RESULTS: Among 312 studies, 14 articles were eligible for qualitative review. 7 studies were eligible for meta-analysis. A variety of rTMS protocols was employed on M1 cortex. In inhibitory rTMS, multiple studies observed a reduction in the concentration of oxygenated hemoglobin [HbO] at the ipsilateral M1, contrasted by an elevation at the contralateral M1. Meta-analysis also corroborated this consistent trend. Nevertheless, certain investigations unveiled diminished [HbO] in bilateral M1. Several studies also depicted intricate inhibitory or excitatory interplay among distinct cortical regions. CONCLUSION: Diverse rTMS protocols led to varied patterns of cortical activity detected by fNIRS. Meta-analysis revealed a trend of increasing [HbO] in the contralateral cortices and decreasing [HbO] in the ipsilateral cortices following low frequency inhibitory rTMS. However, due to the heterogeneity between studies, further research is necessary to comprehensively understand rTMS-induced alterations in brain activity.

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.

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.

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.

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.

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.

Intracellular Restructured Reduced Glutathione-Responsive Peptide Nanofibers for Synergetic Tumor Chemotherapy.

Self-assembled peptide nanofibers have been widely studied in cancer nanotherapeutics with their excellent biocompatibility and low toxicity of degradation products, showing the significant potential in inhibiting tumor progression. However, poor solubility prevents direct intravenous administration of nanofibers. Although water-soluble peptide precursors have been formed via the method of phosphorylation for intravenous administration, their opportunities for broad in vivo application are limited by the weak capacity of encapsulating drugs. Herein, we designed a novel restructured reduced glutathione (GSH)-responsive drug delivery system encapsulating doxorubicin for systemic administration, which achieved the intracellular restructuration from three-dimensional micelles into one-dimensional nanofibers. After a long blood circulation, micelles endocytosed by tumor cells could degrade in response to high GSH levels, achieving more release and accumulation of doxorubicin at desired sites. Further, the synergistic chemotherapy effects of self-assembled nanofibers were confirmed in both in vitro and in vivo experiments.

The effectiveness of cardiac rehabilitation in non-ischemic dilated cardiomyopathy patients: A pilot study.

BACKGROUND/PURPOSE: We aimed to investigate the efficacy of cardiac rehabilitation (CR) through parameters of cardiopulmonary exercise testing (CPET) and echocardiography in non-ischemic dilated cardiomyopathy (DCM) patients. METHODS: We retrospectively identified non-ischemic DCM patients through medical records (between October 2011 and October 2018) in rehabilitation outpatient-clinics. Patients were divided into rehabilitation and control groups. Patients in the rehabilitation group eligible for inclusion had CR for 3-6 months. Control group patients were without rehabilitation. We recorded CPET and echocardiography parameters at the baseline and follow-up time-points. For safety evaluation, we investigated all adverse effects during training sessions. We utilized Mann-Whitney U test for between- and Wilcoxon signed-rank test for within-group comparisons. RESULTS: Twenty-five patients (14 in rehabilitation and 11 in control group) were included. In the rehabilitation group, significantly increased peak V˙O2/kg, peak V˙O2%, peak workload and peak O2 pulse were observed after completing CR, and echocardiographic parameters including left ventricular ejection fraction and end-systolic volume. Rehabilitation group patients demonstrated better improvement (change from the baseline) in peak V˙O2/kg, peak V˙O2% and peak workload vs. control. No adverse effects during rehabilitation trainings were observed. CONCLUSION: For non-ischemic DCM, rehabilitation led to superior cardiopulmonary outcomes vs. no rehabilitation, without adverse effects.

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.

Co-Delivery of Metformin Enhances the Antimultidrug Resistant Tumor Effect of Doxorubicin by Improving Hypoxic Tumor Microenvironment.

Doxorubicin (DOX) is a first-line chemo drug for cancer therapy, yet it fails to treat multi-drug-resistant tumors. Hypoxia is a major causative factor leading to chemotherapy failure. Particularly, hypoxia up-regulates its responsive transcription factor-hypoxia-inducible factors (HIF)-to induce the overexpression of drug resistant genes. Metformin (MET) is recently found to cooperate with DOX against multiple tumors. As a mitochondrial inhibitor, MET could suppress tumor oxygen consumption, and thereby modulate the hypoxic tumor microenvironment. In this study, we used cationic liposomes to codeliver both DOX and MET for treating multi-drug-resistant breast cancer cells-MCF7/ADR. Faster release of MET enhanced the cytotoxicity of DOX through attenuating hypoxic stress both in vivo and in vitro. MET diminished the cellular oxygen consumption and inhibited HIF1α and P-glycoprotein (Pgp) expression in vitro. In addition, the dual-drug-loaded liposomes increased tumor targeting and intratumoral blood oxygen saturation, which suggested that the tumor reoxygenation effect of MET facilitated the exertion of its synergistic activity with DOX against MCF7/ADR xenografts. In general, our study represents a feasible strategy to boost the therapeutic effect in treating multi-drug-resistant cancer by improving the hypoxic tumor microenvironment.

Comparative Efficacy of Noninvasive Neurostimulation Therapies for Acute and Subacute Poststroke Dysphagia: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To investigate the effectiveness of noninvasive neurostimulation therapies in patients with poststroke dysphagia. DATA SOURCES: Electronic databases, including Embase, PubMed, Scopus, and the Cochrane Library, were searched up to May 31, 2018. STUDY SELECTION: All published randomized controlled trials (RCTs) comparing neurostimulation therapies, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), surface neuromuscular electrical stimulation (sNMES), and pharyngeal electrical stimulation (PES), in patients with acute and subacute poststroke dysphagia were included. Nineteen RCTs were enrolled in the meta-analysis. DATA EXTRACTION: Full texts were independently reviewed. Two independent raters assessed the risk of bias of RCTs with the Cochrane risk-of-bias tool. The primary outcome measure was swallowing function evaluated before and after neurostimulation therapy. DATA SYNTHESIS: Both pairwise and network meta-analysis revealed that rTMS, tDCS, and sNMES significantly improved poststroke dysphagia compared with placebo. Differences in functional improvement between PES and placebo were not significant. Based on probability ranking, rTMS seemed the best treatment among the 4 neurostimulation therapies. In the network meta-analysis, rTMS showed the best efficacy compared with placebo (standardized mean difference=1.02, 95% confidence interval, 0.61-1.43). CONCLUSIONS: Among the 4 noninvasive neurostimulation therapies, rTMS, tDCS, and sNMES were effective for treating poststroke dysphagia; furthermore, rTMS may be the most effective therapy according to probability ranking.

Comparative Effectiveness of Injection Therapies in Rotator Cuff Tendinopathy: A Systematic Review, Pairwise and Network Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To compare the effectiveness of diverse injections in patients with rotator cuff tendinopathy using pairwise and network meta-analysis. DATA SOURCES: PubMed, EMBASE, Scopus, and Cochrane Library were searched for studies published up to September 31, 2017. STUDY SELECTION: We included all published or unpublished randomized controlled trials (RCTs) comparing diverse injections including corticosteroid, nonsteroidal anti-inflammatory drugs, hyaluronic acid, botulinum toxin, platelet-rich plasma (PRP), and prolotherapy in patients with rotator cuff tendinopathy. Among the 1495 records screened, 18 studies were included in the meta-analysis. DATA EXTRACTION: The quality of RCTs was assessed with Cochrane Risk of Bias Tool by 2 independent raters. The primary outcome was pain reduction, and the secondary outcome was functional improvement. DATA SYNTHESIS: Standardized mean difference (SMD) was used for pairwise and network meta-analysis. In pairwise meta-analysis, corticosteroid was more effective only in the short term in both pain reduction and functional improvement. Network meta-analysis indicated that prolotherapy significantly reduced pain compared with placebo in the long term (over 24wk; SMD: 2.63; 95% confidence interval [CI], 1.88-3.38); meanwhile PRP significantly improved shoulder function compared with placebo in the long term (over 24wk; SMD: 0.44; 95% CI, 0.05-0.84). CONCLUSIONS: For patients with rotator cuff tendinopathy, corticosteroid plays a role in the short term (3-6wk) but not in long-term (over 24wk) pain reduction and functional improvement. By contrast, PRP and prolotherapy may yield better outcomes in the long term (over 24wk). On account of heterogeneity, interpreting these results with caution is warranted.

Doxorubicin derivative loaded acetal-PEG-PCCL micelles for overcoming multidrug resistance in MCF-7/ADR cells.

Objective: This study was aimed to develop DOX-TPP loaded acetal-PEG-PCCL micelles to improve the clinical efficacy of drug resistance tumor. Significance: Chemotherapy is one of the main treatments for breast cancer but is plagued by multidrug resistance (MDR). DOX-TPP-loaded micelles can enhance the specific concentration of drugs in the tumor and improve the efficacy and overcome MDR. Methods: In this study, DOX-TPP-loaded micelles based on acetal-PEG-PCCL were prepared and their physicochemical properties were characterized. The cellular uptake and ability to induce apoptosis of the micelles was confirmed by flow cytometry in MCF-7/ADR cells. In addition, cytotoxicity of the micelles was studied in MCF-7 cells and MCF-7/ADR cells. Confocal is used to study the subcellular distribution of DOX. Free DOX-TPP or DOX-TPP-loaded acetal-PEG-PCCL micelles were administered via intravenous injection in the tail vain for the biodistribution study in vivo. Results: The diameter of micelles was about 102.4 nm and their drug-loading efficiency is 61.8%. The structural characterization was confirmed by 1H NMR. The micelles exhibited better antitumor efficacy compared to free doxorubicin in MCF-7/ADR cells by MTT assay. The apoptotic rate and the cellular uptake of micelles were significantly higher than free DOX and DOX-TPP. Micelles can efficiently deliver mitochondria-targeting DOX-TPP to tumor cells. The result of bio-distribution showed that the micelles had stronger tumor infiltration ability than free drugs. Conclusions: In this study, mitochondriotropic DOX-TPP was conjugated to the nanocarrier acetal-PEG-PCCL via ionic interaction to form a polymer, which spontaneously formed spherical micelles. The cytotoxicity and cellular uptake of the micelles are superior to free DOX and exhibit mitochondrial targeting and passive tumor targeting, indicating that they have potential prospects.

Mitochondrial Targeted Doxorubicin-Triphenylphosphonium Delivered by Hyaluronic Acid Modified and pH Responsive Nanocarriers to Breast Tumor: in Vitro and in Vivo Studies.

Multidrug resistance (MDR) is the major obstacle for chemotherapy. In a previous study, we have successfully synthesized a novel doxorubicin (DOX) derivative modified by triphenylphosphonium (TPP) to realize mitochondrial delivery of DOX and showed the potential of this compound to overcome DOX resistance in MDA-MB-435/DOX cells. (1) To introduce specificity for DOX-TPP to cancer cells, here we report on the conjugation of DOX-TPP to hyaluronic acid (HA) by hydrazone bond with adipic acid dihydrazide (ADH) as the acid-responsive linker, producing HA- hydra-DOX-TPP nanoparticles. Hyaluronic acid (HA) is a natural water-soluble linear glycosaminoglycan, which was hypothesized to increase the accumulation of nanoparticles containing DOX-TPP in the mitochondria of tumor cells upon systemic administration, overcoming DOX resistance, in vivo. Our results showed HA- hydra-DOX-TPP to self-assemble to core/shell nanoparticles of good dispersibility and effective release of DOX-TPP from the HA- hydra-DOX-TPP conjugate in cancer cells, which was followed by enhanced DOX mitochondria accumulation. The HA- hydra-DOX-TPP nanoparticles also showed improved anticancer effects, better tumor cell apoptosis, and better safety profile compared to free DOX in MCF-7/ADR bearing mice.

Comparative Efficacy of Intra-Articular Steroid Injection and Distension in Patients With Frozen Shoulder: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To compare the efficacy of intra-articular (IA) steroid injection and distension in patients with frozen shoulder. DATA SOURCES: Databases, including MEDLINE (via PubMed), Embase, Scopus, and Cochrane Library, were searched for studies published up to November 2016. STUDY SELECTION: We included all published randomized controlled trials (RCTs), quasi-experimental studies, and observational studies investigating the effectiveness of IA steroid injection, distension, and physiotherapy in patients with frozen shoulder. Sixteen RCTs and 1 observational study were enrolled in meta-analysis. DATA EXTRACTION: Full texts were independently reviewed, and quality of RCTs was assessed with The Cochrane Collaboration's tool. The primary outcome was functional improvement; the secondary outcomes included pain reduction and external rotation (ER) improvement. DATA SYNTHESIS: In pairwise meta-analysis, pooled standardized mean difference (SMD) of functional improvement and pain reduction revealed equal efficacy at 3 follow-up time points. With respect to ER improvement, distension has a superior effect compared with IA steroid injection in the short term [(2-4wk; SMD, -.36; 95% confidence interval [CI], -.68 to -.04) and medium term (6-16wk; SMD, -0.80; 95% CI, -1.32 to -0.29). The network meta-analysis indicated a better efficacy for distension than for IA steroid injection in ER improvement only in the medium term (6-16wk; SMD, -0.70; 95% CI, -1.19 to -0.21). CONCLUSIONS: IA steroid injection was as effective as distension in shoulder function improvement, pain reduction, and increasing ER of the shoulder. Distension yielded better ER improvement in the medium term but to a minor extent in the long term. For patients with predominant ER limitation, early distension could be considered the primary choice of treatment.

Meta-analysis Comparing Autologous Blood-Derived Products (Including Platelet-Rich Plasma) Injection Versus Placebo in Patients With Achilles Tendinopathy.

PURPOSE: To compare the effectiveness of autologous blood-derived products (ABP) injection with that of placebo (sham injection, no injection, or physiotherapy alone) in patients with Achilles tendinopathy. METHODS: Electronic databases, including PubMed, Scopus, EMBASE, and Cochrane Library were searched up to June 2017. All published or unpublished randomized controlled trials (RCTs) were included. Two independent raters assessed the risk of bias of RCTs with the Cochrane Risk of Bias Tool. The primary outcome was Victorian Institute of Sports Assessment-Achilles (VISA-A) score. Weighted mean differences (WMDs) were used for random effect meta-analysis. RESULTS: Seven RCTs were enrolled in meta-analysis. The ABP injection and placebo revealed equal effectiveness in VISA-A score improvement at 4 to 6 weeks (short term, WMD 2.29, 95% confidence interval [CI]: -1.69, 6.27), 12 weeks (medium term, WMD 2.63, 95% CI: -1.72, 6.98), 24 weeks (long term, WMD 4.61, 95% CI: -1.25, 10.47), and 48 weeks (very long term, WMD 4.16, 95% CI: -6.82, 15.14). In meta-regression, there was no association between change in VISA-A score and duration of symptoms at 4 to 6 weeks (short term), 12 weeks (medium term), and 24 weeks (long term). CONCLUSIONS: This meta-analysis revealed that ABP injection was not more effective than placebo (sham injection, no injection, or physiotherapy alone) in Achilles tendinopathy and that no association was found between therapeutic effects and duration of symptoms. LEVEL OF EVIDENCE: Level I, meta-analysis of Level I studies.

Recent Trends in Potential Therapeutic Applications of the Dietary Flavonoid Didymin.

Didymin (isosakuranetin 7-O-rutinoside) is an orally bioactive dietary flavonoid glycoside first found in citrus fruits. Traditionally, this flavonoid has long been used in Asian countries as a dietary antioxidant. Recent studies have provided newer insights into this pleiotropic compound, which could regulate multiple biological activities of many important signaling molecules in health and disease. Emerging data also presented the potential therapeutic application of dietary flavonoid glycoside didymin against cancer, neurological diseases, liver diseases, cardiovascular diseases, and other diseases. In this review, we briefly introduce the source and extraction methods of didymin, and summarize its potential therapeutic application in the treatment of various diseases, with an emphasis on molecular targets and mechanism that contributes to the observed therapeutic effects. The dietary flavonoid didymin can be used to affect health and disease with multiple therapeutic targets, and it is anticipated that this review will stimulate the future development of this potential dietary medicine.

Quality of life in polyneuropathy: association with biomarkers of small fiber impairment.

BACKGROUND: Polyneuropathy presumably lowers quality of life (QoL). However, there is a lack of systematic studies that assess QoL changes and biomarkers of polyneuropathy as determinants of QoL. We aimed to investigate the relationship between every specific aspect of QoL and the clinical parameters used to assess the impairment of motor, sensory (large and small fibers), and autonomic nerves in polyneuropathy. METHODS: Polyneuropathy patients were recruited from September 2013 to March 2014; QoL was assessed using (1) the WHO Quality of Life-BREF (WHOQoL), (2) the European Quality of Life-5 Dimensions, and (3) the Brief Pain Inventory Short Form. Neuropathy examinations included nerve conduction studies, autonomic function tests, quantitative sensory testing (QST), and intraepidermal nerve fiber (IENF) density assessment of skin biopsies. RESULTS: There were 61 polyneuropathy patients (male/female = 38/23, mean age 58.14 ± 12.95 years). Patients had a lower QoL than age-and gender-matched controls in the physical and psychological domains of the WHOQoL. Among the biomarkers for different nerve fiber categories, only the small fiber neuropathy assessments were significantly related to all domains of the WHOQoL. In contrast, the parameters of the large fiber neuropathy were independent of QoL. Patients with abnormal temperature thresholds and a lower IENF density had lower WHOQoL scores compared to patients with normal thresholds and IENF densities. Warm threshold of the foot in QST was linearly correlated with all domains of the WHOQoL. CONCLUSIONS: QoL scores were reduced in polyneuropathy, and biomarkers of small fiber neuropathy, i.e., warm threshold and IENF density were discriminating predictors of QoL.