Neuropathic pain markedly impairs quality of life and imposes a substantial socioeconomic burden, while available treatments often provide only partial relief and are limited by safety concerns. The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG-IASP) first published pharmacologic recommendations in 2007, followed by a major update in 2015 and a new guideline in 2025. This narrative review specifically compares the 2015 and 2025 NeuPSIG-IASP guidelines, outlining key methodological changes and therapeutic shifts. The 2025 guideline is based on a larger, more rigorous meta-analysis, maintains α2δ-ligands (adds mirogabalin), serotonin-noradrenaline reuptake inhibitors, and tricyclic antidepressants as first-line drugs, downgrades tramadol into the opioid third-line group. It also introduces high-frequency motor-cortex repetitive transcranial magnetic stimulation as a weakly recommended third-line option and discusses implications for Korean clinical practice.

Spontaneous intracranial hypotension (SIH) is an underrecognized cause of secondary headache resulting from spinal cerebrospinal fluid (CSF) leakage. Although traditionally considered a benign and self-limiting condition, SIH is now known to be associated with substantial disability and potentially serious complications when diagnosis and treatment are delayed. The clinical presentation is heterogeneous, often leading to misdiagnosis and prolonged diagnostic latency. Recent advances have shifted the conceptual framework of SIH from a simple reduction in CSF pressure to a disorder of CSF volume depletion with distinct etiologic subtypes, including ventral dural tears, lateral dural defects associated with meningeal diverticula, and CSF-venous fistulas. Accordingly, diagnostic strategies have evolved toward a stepwise integration of clinical history with targeted imaging modalities. Contrast-enhanced brain magnetic resonance imaging (MRI) and whole-spine MRI serve as essential initial tools to establish the diagnosis and assess complications, while dynamic myelographic techniques such as digital subtraction myelography and dynamic or decubitus computed tomography myelography play a critical role in localizing the site and mechanism of CSF leakage. Management of SIH has similarly progressed toward subtype- based, individualized treatment. Epidural blood patching remains the mainstay of initial therapy, but its effectiveness varies depending on leak type and chronicity. In selected patients, surgical repair or endovascular embolization offers definitive treatment. This review summarizes current concepts in the diagnosis and management of SIH and proposes a practical diagnostic and therapeutic algorithm, while also addressing unmet needs and real-world limitations within the Korean healthcare system.

Purpose: We evaluated the long-term clinical outcomes of pars plana Ahmed glaucoma valve (AGV) implantation combined with vitrectomy in patients with glaucoma. Methods: We included 25 eyes of glaucoma patients requiring pars plana vitrectomy who underwent combined pars plana AGV implantation and vitrectomy due to uncontrolled intraocular pressure (IOP) despite maximal medical therapy. Surgical success was defined as maintaining IOP between 6 and 21 mmHg, irrespective of topical IOP-lowering medication use. Surgical failure was defined as inadequate IOP control or a decline in visual acuity to no light perception. Preoperative and postoperative parameters, including visual acuity, IOP, number of topical IOP-lowering medications, surgical success rate, corneal endothelial cell density, and postoperative complications, were analyzed. Results: The mean follow-up period was 49.5 ± 12.5 months. The mean preoperative IOP of 32.4 ± 8.4 mmHg significantly decreased to 18.0 ± 9.2 mmHg at the final visit (p < 0.001). Based on Kaplan–Meier survival analysis, the cumulative surgical success rates were 80% at 1 year, 72% at 2 years, and 68% at 5 years postoperatively. The overall success rate at the final follow-up was 76%. Corneal endothelial cell density decreased by 16.5% compared to preoperative values. Early postoperative complications (within 1 month) included hypotony in 16% of eyes, choroidal detachment in 12%, vitreous hemorrhage in 12%, and hyphema in 4%. Late complications included corneal endothelial dysfunction in one eye (4%). Conclusions In glaucoma patients requiring pars plana vitrectomy combined pars plana Ahmed glaucoma valve implantation and vitrectomy achieved sustained IOP reduction with a relatively low rate of complications. This combined surgical approach appears to be a safe and effective long-term treatment option for refractory glaucoma cases requiring posterior segment intervention.

Background: Activin A is involved in the inflammatory response, wound repair, and skin fibrosis. Serum activin A concentrations change during the menstrual cycle, and this can lead to periodic exacerbation of atopic dermatitis. Objective: To determine the effect of activin A on the cytokine expression profiles of human fibroblasts and keratinocytes under atopic dermatitis-like conditions. Methods: Cultured human fibroblasts and keratinocytes were treated with activin A in combination with interleukin (IL)-4 and IL-13 to determine the changes in cytokine concentrations. Results: Activin A decreased the expression of IL-1β and IL-23 mRNA in fibroblasts. IL-4 and IL-13 increased the expression of IL-6 and IL-16 and decreased the expression of IL-1α, IL-1β, IL-8, IL-10, and IL-23 in fibroblasts. In keratinocytes, IL-4 and IL-13 increased the expression of IL-1α and IL-1β and decreased the expression of IL-8. Activin A treatment in combination with IL-4 and IL-13 significantly increased the expression of IL-1α, IL-6, IL-8, IL-10, IL-16, and IL-23 and decreased the expression of IL-1β in fibroblasts. In keratinocytes, only IL-8 expression was significantly increased following treatment with activin A, IL-4, and IL-13. Conclusion Activin A modulates cytokine expression in a cell type dependent manner under conditions mimicking atopic dermatitis, suggesting its potential involvement in cutaneous inflammatory regulation.

Background: Psoriasis is a chronic inflammatory skin disorder typified by well-demarcated erythematous plaques with scales. While considered an immune-driven condition, its underlying molecular triggers remain insufficiently defined. Cold-inducible RNA-binding protein (CIRP), a stress-response protein, has recently been recognized as a damage-associated molecular pattern that can stimulate immune responses. Objective: This study aimed to explore the potential association between circulating CIRP levels and the clinical as well as histological characteristics of psoriasis. Methods: Serum CIRP concentrations were analyzed in 67 individuals diagnosed with psoriasis and 20 healthy controls. Relationships between CIRP expression and various clinical and histological indices were also examined. Results: Patients with psoriasis exhibited significantly elevated serum CIRP levels compared to healthy individuals. Although correlations were observed between CIRP and certain clinical and histological indicators, CIRP levels did not significantly differ based on disease severity (Psoriasis Area and Severity Index score), joint involvement, or nail changes. Conclusion Our findings support the notion that CIRP may be involved in the immunopathogenesis of psoriasis and could be considered a prospective target for therapeutic modulation.

Background: Alitretinoin, a pan-retinoid receptor agonist approved for chronic hand eczema, exhibits immunomodulatory effects that may benefit alopecia areata (AA). However, clinical evidence for its use in AA is limited. Objective: To evaluate alitretinoin's clinical efficacy and immunological mechanism in patients with AA. Methods: We reviewed retrospectively twenty-one patients with AA who were treated with alitretinoin, either as monotherapy (n=9) or add-on therapy (n=12). Treatment response was assessed using the Severity of Alopecia Tool (SALT) scores, and in vitro studies used human outer root sheath cells stimulated with interferon-γ and polyinosinic:polycytidylic acid to investigate the drug’s effects on inflammatory pathways. Results: Both groups showed significant reductions in SALT scores (p=0.04 and p=0.02, respectively). Patients with baseline SALT scores below 50 demonstrated superior improvement.Adverse events were mild, with headache (33.3%) and cheilitis (4.8%) being the most common. In vitro, alitretinoin suppressed interleukin-6 and tumor necrosis factor-α expression, decreased phosphorylation of signal transducer and activator of transcription (STAT) 1/STAT3, and downregulated major histocompatibility complex class I expression, suggesting restoration of hair follicle immune privilege. Conclusion Alitretinoin appears to be a safe and potentially effective treatment for patients with mild to moderate AA unresponsive to conventional therapies. Its role as a monotherapy or adjunctive option in selected cases warrants further investigation through larger controlled studies.

Background: Non-thermal atmospheric pressure plasma (NTAP) generates reactive oxygen species, reactive nitrogen species, and ultraviolet radiation, which can inactivate microorganisms.Onychomycosis treatment is challenging, and its prognosis is poor owing to mixed infections and dermatophytosis. Although NTAP has shown in vitro antifungal effects against dermatophytes and yeast, its efficacy against non-dermatophyte molds (NDMs) and in clinical or nail model studies remains poorly understood. Objective: We evaluated the effects of NTAP on fungi, including NDMs, and infected nail plates. Methods: For the in vitro experiments, Trichophyton rubrum, Candida albicans, Aspergillus fumigatus, and Fusarium oxysporum strains were exposed to NTAP. After NTAP exposure (2,4 and 6 minutes), growth curve, cell viability, and biofilm biomass were assessed by absorbance wavelength of 600 nm, XTT assay, and crystal violet staining, respectively. For the ex vivo experiments, infected nail plates were analyzed using a scanning electron microscope. Results: T. rubrum and C. albicans showed greater growth inhibition with increasing NTAP exposure time, whereas A. fumigatus showed enhanced growth after 6 minutes exposure. Many fungal elements within the subungual hyperkeratosis of the ex vivo specimen were all damaged following NTAP exposure. Conclusion NTAP has antifungal effects on dermatophytes, yeast, and NDMs. We suggest that the intensity and time of NTAP application should be adjusted according to each strain and can be more effective when NTAP directly reaches the hyphae on the nail bed or subungual hyperkeratosis.

Background: A novel botulinum toxin type A (Protoxin; Protox Inc.) has been developed. Objective: To evaluate the efficacy and safety of the newly developed Protoxin compared to the approved drug onabotulinumtoxinA (OBoNT) in moderate to severe glabellar lines. Methods: Adults with a glabellar line Facial Wrinkle Scale (FWS) score of 2 (moderate) or 3 (severe) were enrolled in the study. Subjects were randomized in a 1:1 ratio to receive either Protoxin or OBoNT. A total of 20 units of botulinum toxin was injected at five sites in the glabellar region (4 units at each site). FWS scores were assessed at baseline and at weeks 4, 8, 12, and 16 post-injection. The primary endpoint was the proportion of subjects at week 4 who had a reduction of 2 or more points in FWS and a final score of 0 (none) or 1 (mild). Results: A total of 274 subjects were randomized, of whom 78.1% were female. At week 4 post-treatment, the improvement rate of glabellar lines was 62.22% in the Protoxin group and 62.96% in the OBoNT group. The lower limit of the two-sided 95% confidence interval (−12.24%) exceeded the −15% margin, confirming the non-inferiority of the new drug. Safety profiles were comparable between the two groups. Conclusion Protoxin demonstrated efficacy and safety profiles comparable to those of OBoNT in the treatment of moderate to severe glabellar lines.

Background: Current guidelines recommend factor IIa- or Xa-specific inhibitors over warfarin analogs for preventing thromboembolic stroke in patients with atrial fibrillation (AF).However, their plasma concentrations in Korean patients are not well understood. Methods: We conducted a single-center laboratory study to determine the distribution ranges of peak and trough concentrations of three factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban) prescribed for preventing strokes in patients with AF. Patients receiving one of these drugs and undergoing blood specimen collection for laboratory tests were screened. Blood specimens were obtained from patients who had adhered to the prescribed drug regimen consistently for at least 1 week. Drug plasma concentrations were measured using heparin liquid-reagent technology-based anti-Xa chromogenic assays. Results: We selected 459 patients who were taking standard or on-label-reduced doses of apixaban (N = 252), edoxaban (N = 182), or rivaroxaban (N = 25). The 5th–95th percentile ranges of the peak concentrations were 84–414 ng/mL (apixaban), 72–424 ng/mL (edoxaban), and 97–517 ng/mL (rivaroxaban). The respective 5th–95th percentile ranges of the trough concentrations were 44–237 ng/mL, 23–93 ng/mL, and 13–219 ng/mL. Approximately 19.6% (apixaban), 33.3% (edoxaban), and 64.0% (rivaroxaban) of patients in each group had peak concentrations out of the predicted distribution ranges based on pharmacokinetic data. Approximately 7.3%, 52.8%, and 8.3% of patients had trough concentrations out of the predicted distribution ranges. Conclusions A considerable proportion of Korean patients with AF taking factor Xa inhibitors may require population-specific reference ranges to guide therapeutic monitoring.

Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.