Youngkwon Ko

Background/Objectives: Central neuropathic pain (CNP) is difficult to manage, and comparative evidence for non-invasive brain stimulation is limited. We explored the short-term efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in CNP. Methods: In this randomized, sham-controlled crossover trial, 26 patients were allocated to active or sham stimulation and received high-frequency rTMS (10 Hz, 2000 pulses/session) and anodal tDCS (2 mA, 30 min) over the primary motor cortex for five days each, separated by a 4-week washout. The primary outcome was change in Numerical Rating Scale (NRS) pain intensity at 1 and 4 weeks, analysed using factorial linear mixed-effects models with and without age adjustment. Results: At 1 week, the difference between active and sham rTMS was 0.76 points (95% CI −0.005 to 1.53; p = 0.051) and 0.42 points after age adjustment (95% CI −0.37 to 1.21; p = 0.30). Active tDCS did not differ from sham tDCS, and active rTMS did not differ from active tDCS. No significant differences were found at 4 weeks or in responder analyses. No serious adverse events occurred. Conclusions: In this small exploratory trial, neither rTMS nor tDCS showed statistically significant superiority over modality-matched sham, and no difference between modalities was demonstrated. Adequately powered trials are needed.

Background: Among the various diaphragm-sparing alternatives to interscalene block, costoclavicular block (CCB) demonstrated a low hemidiaphragmatic paresis (HDP) occurrence but an inconsistent analgesic effect in arthroscopic shoulder surgery. We hypothesized that a larger volume of local anesthetic for CCB could provide sufficient analgesia by achieving sufficient supraclavicular spreading.Methods: Sixty patients scheduled for arthroscopic rotator cuff repair were randomly assigned to receive CCB using one of two volumes of local anesthetic (CCB20, 0.75% ropivacaine 20 ml; CCB40, 0.375% ropivacaine 40 ml). The primary outcome was the rate of complete analgesia (0 on the numeric rating scale of pain) at 1 h postoperatively. The secondary outcomes included a sonographic assessment of local anesthetic spread, diaphragmatic function, pulmonary function, postoperative opioid use, and other pain-related experiences within 24 h postoperatively. Results: The rates of complete analgesia were not significantly different (23.3% [7/30] and 33.3% [10/30] in the CCB20 and CCB40 groups, respectively; risk difference 10%, 95% CI [–13, 32], P = 0.567). There were no significant differences in other pain-related outcomes. Among the clinical factors considered, the only factor significantly associated with postoperative pain was the sonographic observation of supraclavicular spreading. There were no significant differences in the incidence of HDP and the change in pulmonary function between the two groups.Conclusions: Using 40 ml of local anesthetic does not guarantee supraclavicular spread during CCB. Moreover, it does not result in a higher rate of complete analgesia compared to using 20 ml of local anesthetic in arthroscopic shoulder surgery.

Background: Various regional analgesia techniques are used to reduce postoperative pain in patients undergoing video-assisted thoracic surgery (VATS). This study aimed to determine the relative efficacy of regional analgesic interventions for VATS using a network meta-analysis (NMA). Methods: We searched the Medline, EMBASE, Cochrane Controlled Trial Register, Web of Science, and Google Scholar databases to identify all randomized controlled trials (RCTs) that compared the analgesic effects of the following interventions: control, thoracic paravertebral block (TPVB), erector spinae plane block (ESPB), serratus plane block (SPB), and intercostal nerve block (INB). The primary outcome was opioid consumption during the first 24-h postoperative period. Pain scores were also collected during three different postoperative periods: the early (0–6 h), middle (6–18 h), and late (18–24 h) periods. Results: A total of 21 RCTs (1391 patients) were included. TPVB showed the greatest effect on opioid consumption compared with the control (mean difference [MD] = −13.2 mg; 95% CI [−16.2, −10.1]). In terms of pain scores in the early period, ESPB had the greatest effect compared to control (MD = −1.6; 95% CI [−2.3, −0.9]). In the middle and late periods, pain scores showed that TPVB, ESPB and INB had superior analgesic effects compared to controls, while SPB did not. Conclusions: TPVB had the best analgesic efficacy following VATS, though the analgesic efficacy of ESPBs was comparable. However, further studies are needed to determine the optimal regional analgesia technique to improve postoperative pain control following VATS.

(1) Background: Prolonged neck flexion is thought to cause harmful loading on the cervical spine. Along with the degenerative process, cervical alignment tends to change toward lordotic curvature. The association between cervical alignment and cervical spondylosis remains unclear. (2) Methods: Three raters retrospectively assessed cervical radiographies of outpatients at a tertiary center in 2019 using degenerative cervical spondylosis score (DCS score; a newly developed scoring system), C2-7 absolute rotational angle (ARA), and C2-7 sagittal vertical axis (SVA). (3) Results: A total of 561 patients were included in the analysis. Multiple regression analysis with adjustments for age and sex revealed that C2-7 ARA, rather than SVA, was a significant parameter for degenerative spondylosis. The interaction between age and C2-7 ARA was significant, indicating that the increase in DCS score with increasing age was more pronounced in patients with kyphotic cervical alignment. The direct effect of age on DCS score was 0.349 (95% CI 0.319 to 0.380, p < 0.001) and the proportion of the mediation effect of C2-7 ARA was −0.125 (p < 0.001). (4) Conclusions: C2-7 ARA was significantly associated with DCS after adjustment for both age and sex. Subjects with more kyphotic cervical alignment showed a greater correlation between increased DCS score and older age.

Objective: This study investigated whether a new sustained-release (SR) pregabalin formulation is noninferior to immediate-release (IR) pregabalin in alleviating peripheral neuropathic pain in Korean patients. Materials and Methods: This was a randomized, double-blind, active-controlled phase 3 study of patients with diabetic peripheral neuropathy or postherpetic neuralgia from 41 sites in South Korea in 2017-2018. Eligible patients were randomized (1:1) to receive once-daily SR pregabalin or twice-daily IR pregabalin (150 to 600 mg/d) in a double-dummy manner for 12 weeks according to a stratified permuted block randomization scheme. The primary endpoint was the Daily Pain Rating Scale score at the end of treatment, averaged from the last 7 available scores. Results: A total of 319 of 371 (86.0%) randomized patients completed the 12-week treatment (SR pregabalin: n=154; IR pregabalin: n=165; per-protocol set: n=296). The least square mean difference between both groups for the primary endpoint was 0.06 (SE 0.19); (95% confidence interval −0.31 to 0.42), with the lower limit of the confidence interval above the pre-specified margin (−0.78; P _{noninferiority}<0.0001). Drug-related treatment-emergent adverse events (TEAEs) were comparable between both groups. The incidence of drug-related TEAEs leading to treatment discontinuation was low (SR pregabalin: 2.7%; IR pregabalin: 1.1%). No serious drug-related TEAEs or deaths occurred. Discussion: The results demonstrate that the new once-daily SR pregabalin formulation is noninferior to twice-daily IR pregabalin in reducing peripheral neuropathic pain and is well tolerated in Korean patients with diabetic peripheral neuropathy or postherpetic neuralgia after 12 weeks of treatment.

(1) Background: Although radiography performed on the subject in an upright position is considered the standard method for assessing sagittal cervical alignment, it is frequently determined, or reported, based on MRI performed on the subject in a supine position. (2) Methods: Cervical alignment observed in both imaging modalities was assessed using four methods: the C2-7 Cobb angle, the absolute rotation angle (ARA), Borden’s method, and the sagittal vertical axis (SVA). Cervical alignment was determined (lordosis, kyphosis, and straight) based on radiography. Then, the diagnostic cut-off values for the MRI images and their corresponding diagnostic accuracies were assessed. (3) Results: The analysis included 142 outpatients. The determined diagnostic cut-off values for lordosis, using three measurements (Cobb angle, ARA, and Borden’s method), were −8.5°, −12.5°, and 3.5 mm, respectively, and the cut-off values for kyphosis were −4.5°, 0.5°, and −1.5 mm, respectively. The cut-off value for SVA > 40 mm was 19.5 mm. The Cobb angle, ARA, and Borden’s method, on MRI, showed high negative predictive values for determining kyphosis. The SVA on MRI measurements also showed high negative predictive values for determining >40 mm. (4) Conclusions: MRI measurements may be predictive of cervical alignment, especially for the exclusion of kyphosis and SVA > 40 mm. However, caution is needed in the other determinations using MRI, as their accuracies are limited.

Background: The corner pocket (CP) approach for supraclavicular block (SCB) prevents ulnar nerve (UN) sparing due to needle proximity to the lower trunk. Improved ultrasound resolution has suggested that the intertruncal (IT) approach is a suitable alternative method. We compared efficiency of these two approaches on the UN blockade.Methods: Sixty patients were randomized to undergo SCB using the ultrasound-guided CP or IT approach. For lower trunk blockade, 10 ml of local anesthetic agents (1 : 1 mixture of 0.75% ropivacaine and 1% lidocaine) were injected in the CP (CP approach) or between the lower and middle trunks (IT approach). Additional 15 ml was injected identically to block the middle and upper trunks in both groups. Sensory and motor blockade was evaluated after intervention. Results: Complete sensory blockade (75.9% [22/29] vs. 43.3% [13/30], P = 0.023) and complete motor blockade (82.8% [24/29] vs. 50.0% [15/30], P = 0.017) of the UN at 15 min after SCB were significantly more frequent in the IT than in the CP group. Sensory block onset time of the UN was significantly shorter in the IT compared to the CP group (15.0 [10.0; 15.0] min vs. 20.0 [15.0; 20.0] min; P = 0.012). Conclusions: The IT approach provided a more rapid onset of UN blockade than the CP approach. These results suggest that the IT approach is a suitable alternative to the CP approach and can provide faster surgical readiness.

Background: The optimal insertion length for right subclavian vein catheterization in infants has not been determined. This study retrospectively compared landmark-based and linear regression model-based estimation of optimal insertion length for right subclavian vein catheterization in pediatric patients of corrected age < 1 year. Methods: Fifty catheterizations of the right subclavian vein were analyzed. The landmark related distances were: from the needle insertion point (I) to the tip of the sternal head of the right clavicle (A) and from A to the midpoint (B) of the perpendicular line drawn from the sternal head of the right clavicle to the line connecting the nipples. The optimal length of insertion was retrospectively determined by reviewing post-procedural chest radiographs. Estimates using a landmark-based equation (IA + AB – intercept) and a linear regression model were compared with the optimal length of insertion. Results: A landmark-based equation was determined as IA + AB – 5. The mean difference between the landmark-based estimate and the optimal insertion length was 1.0 mm (95% limits of agreement –18.2 to 20.3 mm). The mean difference between the linear regression model (26.681 – 4.014 × weight + 0.576 × IA + 0.537 × AB – 0.482 × postmenstrual age) and the optimal insertion length was 0 mm (95% limits of agreement –16.7 to 16.7 mm). The difference between the estimates using these two methods was not significant. Conclusion: A simple landmark-based equation may be useful for estimating optimal insertion length in pediatric patients of corrected age < 1 year undergoing right subclavian vein catheterization.

Background: Sedation using dexmedetomidine is frequently associated with hypotension. In contrast, epinephrine, a commonly used adjunctive agent in regional anesthesia, is a potent vasopressor. We hypothesized that perineural epinephrine used in brachial plexus blockade may reduce hypotension during dexmedetomidine infusion. Methods: Patients scheduled for upper extremity surgery were randomly allocated into a control and an epinephrine group. All patients received brachial plexus blockade, consisting of 25 mL of a 1:1 mixture of 1% lidocaine and 0.75% ropivacaine, with patients in the epinephrine group also receiving 125 μg epinephrine. Intraoperative sedation was induced using dexmedetomidine at a loading dose of 1 µg/kg and maintenance dose of 0.4 µg/kg/hr. The primary outcome was the incidence of intraoperative hypotension or hypotension in the post-anesthesia care unit (PACU). Results: One hundred and thirty patients were included (65 per group). The incidence of hypotension was significantly higher in the epinephrine than in the control group (80.6% vs. 56.9%, p = 0.009). The duration of hypotension and the maximal change in blood pressure were also greater in the epinephrine group. Conclusions: Perineural epinephrine for brachial plexus blockade does not reduce hypotension due to dexmedetomidine infusion and may actually augment the occurrence of hypotensive events.

Activation of nuclear factor-kappa B (NF-κB) in microglia plays a decisive role in the progress of neuropathic pain, and the inhibitor of kappa B (IκB) is a protein that blocks the activation of NF-κB and is degraded by the inhibitor of NF-κB kinase subunit beta (IKBKB). The role of IKBKB is to break down IκB, which blocks the activity of NF-kB. Therefore, it prevents the activity of NK-kB. This study investigated whether neuropathic pain can be reduced in spinal nerve ligation (SNL) rats by reducing the activity of microglia by delivering IKBKB small interfering RNA (siRNA)-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles. PLGA nanoparticles, as a carrier for the delivery of IKBKB genes silencer, were used because they have shown potential to enhance microglial targeting. SNL rats were injected with IKBKB siRNA-encapsulated PLGA nanoparticles intrathecally for behavioral tests on pain response. IKBKB siRNA was delivered for suppressing the expression of IKBKB. In rats injected with IKBKB siRNA-encapsulated PLGA nanoparticles, allodynia caused by mechanical stimulation was reduced, and the secretion of pro-inflammatory mediators due to NF-κB was reduced. Delivering IKBKB siRNA through PLGA nanoparticles can effectively control the inflammatory response and is worth studying as a treatment for neuropathic pain.