Felipe Fregni

Background/Objectives: Thread-embedding acupuncture (TEA) involves the implantation of suture threads into therapeutic points for sustained stimulation; however, its safety evidence remains limited. This systematic review and meta-analysis evaluated adverse events (AEs) associated with TEA to establish its safety profile. Methods: Ten databases were searched up to April 5, 2026 for randomized controlled trials (RCTs) of TEA. Reported AEs were standardized using MedDRA terminology, WHO-UMC causality criteria, and CTCAE version 5.0. Pooled incidence proportions were estimated using generalized linear mixed models, and risk ratios (RRs) were pooled using random-effects models with 95% confidence intervals (CIs). Results: Of the 90 RCTs included, most were conducted in China (81, 90.0%). For TEA monotherapy, pooled AE incidence proportion was 3% (95% CI: 2–7%; I² = 53.7%). Local AEs were most common (111, 5.9%), followed by systemic (5, 0.3%) and other AEs (2, 0.1%). Among 118 participants with AEs, most were classified as Grade 1 (95, 80.5%), with Grade 2 (8, 6.8%) and unassessable cases (15, 12.7%). In comparative analyses, TEA showed no significant increase in AE risk versus sham TEA (RR: 1.15, 95% CI: 0.83–1.60), acupuncture (RR: 0.97, 95% CI: 0.64–1.49), or conventional medicine (RR: 0.28, 95% CI: 0.18–0.45). Only one serious TEA-related AE was reported among 1697 participants (0.06%); the withdrawal rate due to TEA-related AEs was 0.36% (9/2524). Conclusions: TEA demonstrated a favorable safety profile when used alone or as an add-on therapy, with most AEs mild and transient. However, inconsistencies in AE definitions and reporting highlight the need for standardized terminology and more rigorous safety evaluation in future studies.

Transcranial direct-current stimulation (tDCS) over the prefrontal cortex can improve signs of consciousness in patients in a minimally conscious state. Transcranial pulsed-current stimulation (tPCS) over the mastoids can modulate brain activity and connectivity in healthy controls. This study investigated the feasibility of tPCS as a therapeutic tool in patients with disorders of consciousness (DoC) and compared its neurophysiological and behavioral effects with prefrontal tDCS. This pilot study was a randomized, double-blind sham-controlled clinical trial with three sessions: bi-mastoid tPCS, prefrontal tDCS, and sham. Electroencephalography (EEG) and behavioral assessments were collected before and after each stimulation session. Post minus pre differences were compared using Kruskal–Wallis and Wilcoxon signed-rank tests. Twelve patients with DoC were included in the study (eight females, four traumatic brain injury, 50.3 ± 14 y.o., 8.8 ± 10.5 months post-injury). We did not observe any side-effects following tPCS, nor tDCS, and confirmed their feasibility and safety. We did not find a significant effect of the stimulation on EEG nor behavioral outcomes for tPCS. However, consistent with prior findings, our exploratory analyses suggest that tDCS induces behavioral improvements and an increase in theta frontal functional connectivity.