To evaluate the efficacy of wearable transcutaneous electrical nerve stimulation (TENS) combined with transcranial direct current stimulation (tDCS) in the middle-aged person with mild knee osteoarthritis (KOA). Double-blind, randomized clinical trial. A general hospital. Participants aged 60–70 with mild KOA (Kellgren–Lawrence grade 1–2). The experimental group received TENS + tDCS, and the control group received TENS + sham tDCS for four weeks from Monday through Friday. The primary outcome was Brief Pain Inventory (BPI). The secondary outcomes included participants’ Visual Analog Scale (VAS), step length, cadence, 6-minute walking test (6MWT), active knee range of motion (ROM), and quadriceps strength. The indexes were assessed one week before treatment (T0), two weeks after treatment commencement (T1), four weeks after treatment commencement (T2), one month after treatment cessation (T3), and two months after treatment cessation (T4). A total of 110 participants (55 per group) completed the intervention and follow-up. Repeated-measures ANOVA indicated that tDCS significantly improved the efficacy of TENS in alleviating pain and enhancing walking ability among patients with mild KOA. Statistically significant differences in BPI scores were observed between the experimental and control groups at T1 (2.16 vs. 2.45, P = 0.038), T2 (1.17 vs. 1.73, P < 0.001), and T3 (2.17 vs. 2.41, P = 0.021). However, no significant difference was detected at T4 (2.50 vs. 2.63, P = 0.293). The four-week combined intervention demonstrated that tDCS potentiated the therapeutic efficacy of TENS in managing mild KOA. The combined protocol exhibited superiority over TENS monotherapy, with sustained benefits observed up to one-month post-intervention. This research has been registered in chictr.org.cn (registration number: ChiCTR2200064735) on 15 October 2022, https://www.chictr.org.cn/showproj.html?proj=182561 .

Background: ATTR amyloidosis is a disease caused by abnormal deposition of TTR (transthyretin) protein in tissues. ART001 is an in vivo gene therapy drug using lipid nanoparticle (LNP) to deliver mRNA encoding SpCas9 ( Streptococcus pyogenes Cas9) and a single guide RNA (sgRNA) for knocking-out of the TTR gene in hepatocytes and reducing serum TTR levels. Methods: In an investigator-initiated trial (IIT) of ART001 for 10 ATTR Amyloidosis patients, each patient was given one dose of ART001 which ranged from 0.05 mg/kg to 1.0 mg/kg. The aim was to evaluate ART001’s safety, side effects, PK, PD, and efficacy based on circulating TTR protein levels. Results: At 0.7 mg/kg in 3 subjects and 1 mg/kg in 3 subjects, TTR protein reductions averaged 84 and 92% at 72 weeks. No infusion-related reactions (IRRs), serious adverse events (SAEs) or serious adverse reactions (SARs) were observed. Conclusion: A single injection of ART001 achieved > 80% TTR knock-down at doses > 0.5 mg/kg and lasted for at least 72 weeks without IRRs, SARs or SAEs. ART001 has the potential to be a safe, effective and permanent therapeutic option for ATTR Amyloidosis patients. (Funded by Accuredit Therapeutics). Clinical trial registration: Trial registration: ChiCTR, ChiCTR2400081216. Registered 26 ^th Feb, 2024 - retrospectively registered, https://www.chictr.org.cn/showprojEN.html?proj=210566 .

Background and purpose: Perforator artery disease (PAD) is an important subtype of ischemic stroke. The risk factors affecting the prognosis of patients with PAD are unclear. This study aimed to investigate the risk factors affecting the unfavorable prognosis of PAD.Methods: Patients with PAD were enrolled from Dushu Lake Hospital Affiliated to Soochow University and diagnosed as stroke with PAD during the period from September 2021 to July 2023 and followed up with a modified Rankin Scale (mRS) after 90 days, defining the mRS of 0–2 as a group with favorable prognosis, and 3–6 as a group with unfavorable functional outcome. Logistic regression was used to identify predictors for PAD. Multiple logistic regression analysis and receiver operating characteristics (ROC) were used to identify predictors of unfavorable prognosis.Results: Of the 181 enrolled patients, 48 (26.5%) were identified with unfavorable prognosis. On multivariate analysis, increased age (OR = 1.076, 95% CI: 1.012 ~ 1.144, p = 0.019), higher National Institutes of Health Stroke Scale (NIHSS) score at admission (OR = 2.930, 95% CI: 1. 905 ~ 4.508, p < 0.001), and increased neutrophil-to-lymphocyte ratio (NLR) (OR = 3.028, 95% CI: 1.615 ~ 5.675, p = 0.001) were independent risk factors for unfavorable prognosis in patients with PAD, and the area under the receiver operating characteristic curve was 0.590, 0.905, and 0.798, and the multi-factor diagnostic model (Model 2) showed reliable diagnostic specificity and sensitivity (area under the curve = 0.956, p < 0.001, specificity 0.805, sensitivity 0.958, accuracy 0.845).Conclusion: Increased baseline NLR and NIHSS score and aging may be independent risk factors for unfavorable prognosis of patients with PAD. NLR can be used as a potential biological indicator to predict the prognosis of stroke with PAD.

Introduction: Symptomatic intracranial hemorrhage (sICH) is a serious complication of acute ischemic stroke (AIS) after endovascular treatment (EVT). Limited data exist regarding predictors and clinical implications of sICH after EVT, underscoring the significance of identifying risk factors to enhance prevention strategies. Therefore, the main objective of this study was to evaluate the incidence of sICH and identify its predictors after EVT in patients with large infarct core-AIS in the pre-circulation stage.Methods: Using data from the EVT for the Pre-circulation Large Infarct Core-AIS Study, we enrolled patients who were treated with EVT from the Prospective Multicenter Cohort Study of Early Treatment in Acute Stroke (MAGIC) registry. Baseline demographics, medical history, vascular risk factors, blood pressure, stroke severity, radiographic features, and EVT details were collected. The patients were classified into three groups: without intracranial hemorrhage (ICH), with asymptomatic intracranial hemorrhage (aICH), and sICH, based upon the occurrence of sICH. The main outcomes were the occurrence of sICH according to the Heidelberg Bleeding Classification and functional condition at 90 days. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to identify independent predictors of sICH after EVT.Results: The study recruited a total of 490 patients, of whom 13.3% (n = 65) developed sICH. Patients with sICH had less favorable outcomes than those without intracranial hemorrhage (ICH) and those with aICH (13.8% vs. 43.5% vs. 32.2%, respectively; p < 0.001). The overall mortality was 41.8% (n = 205) at 90 days post-EVT. The univariate analysis revealed significant differences among the three groups in terms of blood glucose levels at admission, probability of favorable outcomes, incidence of brain herniation, and 90-day mortality. The multifactorial logistic regression analysis revealed that the blood glucose level at admission [odds ratio (OR) 1.169, p < 0.001, confidence interval (CI) 1.076–1.269] was an independent predictor of sICH. A blood glucose level of 6.95 mmol/L at admission was the best predictor of sICH, with an area under the ROC curve (AUC) of 0.685 (95% CI: 0.616–0.754).Discussion: The study findings demonstrated that the probability of sICH after EVT was 13.3% in patients with pre-circulation large infarct core-AIS, and sICH increased the risk of an unfavorable prognosis. Higher blood glucose levels at admission were associated with sICH after EVT in patients with pre-circulation large infarct core AIS. These findings underscore the importance of early management strategies to mitigate this risk.

[This corrects the article DOI: 10.3389/fneur.2024.1367177.].