Atopic dermatitis (AD) is the most prevalent inflammatory skin condition, with approximately 80% of cases originating in childhood and some emerging in adulthood. In South Korea, the estimated prevalence of AD ranges between 10% and 20% in children and 1% and 3% in adults. Severe/recalcitrant AD manifests as a chronic, relapsing skin disorder, persisting with uncontrolled symptoms even after topical steroid treatment. Corticosteroids and systemic immunosuppression, conventionally the standard care for difficult-to-treat diseases, cause numerous undesirable side effects. When AD persists despite topical steroid application, systemic therapies like cyclosporine or systemic steroids become the second treatment strategy. The desire for targeted treatments, along with an enhanced understanding of AD’s pathophysiology, has spurred novel therapeutic development. Recent advances introduce novel systemic options, such as biological agents and small-molecule therapy, tailored to treat severe or recalcitrant AD. Notably, dupilumab, a monoclonal antibody inhibiting interleukin 4 and 13, marked a transformative breakthrough upon gaining approval from the U.S. Food and Drug Administration (FDA) in 2017, leading to a paradigm shift in the systemic treatment of AD. Furthermore, both dupilumab and Janus kinase inhibitors, including baricitinib, abrocitinib, and tofacitinib, now approved by the Korean FDA, have established their applicability in clinical practice. These innovative therapeutic agents have demonstrated favorable clinical outcomes, effectively addressing moderate to severe AD with fewer side reactions than those associated with previous systemic immunosuppressants. This review summarizes the latest advancements and evidence regarding systemic treatments for AD, including newly approved drugs in Korea.

Background: Although poor oral health is a common comorbidity in individuals with airflow limitation (AFL), few studies have comprehensively evaluated this association. Furthermore, the association between oral health and the severity of AFL has not been well elucidated. Methods: Using a population-based nationwide survey, we classified individuals according to the presence or absence of AFL defined as pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity < 0.7. Using multivariable logistic regression analyses, we evaluated the association between AFL severity and the number of remaining teeth; the presence of periodontitis; the Decayed, Missing, and Filled Teeth (DMFT) index; and denture wearing. Results: Among the 31,839 participants, 14% had AFL. Compared with the control group, the AFL group had a higher proportion of periodontitis (88.8% vs. 79.4%), complete denture (6.2% vs. 1.6%), and high DMFT index (37.3% vs. 27.8%) (P < 0.001 for all). In multivariable analyses, denture status: removable partial denture (adjusted odds ratio [aOR], 1.12; 95% confidence interval [95% CI], 1.04–1.20) and complete denture (aOR, 1.52; 95% CI, 1.01– 2.05), high DMFT index (aOR, 1.13; 95% CI, 1.02–1.24), and fewer permanent teeth (0–19;aOR, 1.32; 95% CI, 1.12–1.52) were significantly associated with AFL. Furthermore, those with severe to very severe AFL had a significantly higher proportion of complete denture (aOR, 2.41; 95% CI, 1.11–3.71) and fewer remaining teeth (0–19; aOR, 2.29; 95% CI, 1.57–3.01). Conclusion Denture wearing, high DMFT index, and fewer permanent teeth are significantly associated with AFL. Furthermore, a reduced number of permanent teeth (0–19) was significantly related to the severity of AFL. Therefore, physicians should pay attention to oral health in managing patients with AFL, such as chronic obstructive pulmonary disease.

Background: This study examined possible risk factors for myringosclerosis formation after ventilation tube insertion (VTI). Methods: A retrospective study was performed in a single tertiary referral center. A total of 582 patients who underwent VTI were enrolled in this study. Patients were divided into two groups based on the presence or absence of myringosclerosis: MS+ and MS−. Characteristics of patients were collected through medical chart review; these included age, gender, nature and duration of effusion, type of ventilation tube (VT), duration and frequency of VTI, incidence of post-VTI infection, incidence of intraoperative bleeding, and presence of postoperative perforation. Incidences of risk factors for myringosclerosis and the severity of myringosclerosis in association with possible risk factors were analyzed. Results: Myringosclerosis developed in 168 of 582 patients (28.9%) after VTI. Patients in the MS+ group had an older mean age than those in the MS− group. The rates of myringosclerosis were higher in patients with older age, serous otitis media, type 2 VT, post-VTI perforation, and frequent VTI. However, there were no differences in occurrence of myringosclerosis based on gender, duration of effusion, duration of VT placement, incidence of post-VTI infection, or incidence of intraoperative bleeding. The severity of myringosclerosis was associated with the duration of effusion and frequency of VTI. Conclusion Older age, serous effusion, type 2 VT, presence of post-VTI perforation, and frequent VTI may be risk factors for myringosclerosis after VTI; the severity of myringosclerosis may vary based on the duration of effusion and frequency of VTI.

PURPOSE: We prospectively investigated clinical changes and long-term outcomes after administration of the drugs recommended by the Age-Related Eye Disease Study-2 to patients with intermediate age-related macular degeneration (AMD). METHODS: This prospective multicenter study enrolled 79 eyes of 55 patients taking lutein and zeaxanthin. The primary endpoint was contrast sensitivity; this was checked every 12 months for a total of 36 months after treatment commenced. The secondary endpoints were visual acuity, central macular thickness, and drusen volume; the latter two parameters were assessed using spectral domain optical coherence tomography. RESULTS: The mean patient age was 72.46 ± 7.16 years. Contrast sensitivity gradually improved at both three and six cycles per degree. The corrected visual acuity was 0.13 ± 0.14 logMAR and did not change significantly over the 36 months. Neither the central macular thickness nor drusen volume changed significantly. CONCLUSIONS: Contrast sensitivity markedly improved after treatment, improving vision and patient satisfaction. Visual acuity, central retinal thickness, and drusen volume did not deteriorate. Therefore, progression of AMD and visual function deterioration were halted.
Contrast Sensitivity ; Eye Diseases ; Humans ; Lutein ; Macular Degeneration ; Patient Satisfaction ; Prospective Studies ; Retinaldehyde ; Tomography, Optical Coherence ; Visual Acuity ; Zeaxanthins

BACKGROUND AND PURPOSE: The benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients. METHODS: This randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naive stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days. RESULTS: This trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53-1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2+/-1.0 mm3 vs. placebo: 0.3+/-1.3 mm3; P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups. CONCLUSIONS: The efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation.
Cerebral Hemorrhage ; Follow-Up Studies ; Hemorrhage ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Infarction ; Magnetic Resonance Imaging ; Random Allocation ; Recurrence ; Stroke* ; Rosuvastatin Calcium

BACKGROUND AND PURPOSE: The benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients. METHODS: This randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naive stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days. RESULTS: This trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53-1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2+/-1.0 mm3 vs. placebo: 0.3+/-1.3 mm3; P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups. CONCLUSIONS: The efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation.
Cerebral Hemorrhage ; Follow-Up Studies ; Hemorrhage ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Infarction ; Magnetic Resonance Imaging ; Random Allocation ; Recurrence ; Stroke* ; Rosuvastatin Calcium

p21-activated kinases (PAKs) are key regulators of actin dynamics, cell proliferation and cell survival. Deregulation of PAK activity contributes to the pathogenesis of various human diseases, including cancer and neurological disorders. Using an ELISA-based screening protocol, we identified naphtho(hydro)quinone-based small molecules that allosterically inhibit PAK activity. These molecules interfere with the interactions between the p21-binding domain (PBD) of PAK1 and Rho GTPases by binding to the PBD. Importantly, they inhibit the activity of full-length PAKs and are selective for PAK1 and PAK3 in vitro and in living cells. These compounds may potentially be useful for determining the details of the PAK signaling pathway and may also be used as lead molecules in the development of more selective and potent PAK inhibitors.
Actins ; Cell Proliferation ; Cell Survival ; Humans ; In Vitro Techniques ; Mass Screening ; Nervous System Diseases ; p21-Activated Kinases ; Phosphotransferases* ; rho GTP-Binding Proteins

p21-activated kinases (PAKs) are key regulators of actin dynamics, cell proliferation and cell survival. Deregulation of PAK activity contributes to the pathogenesis of various human diseases, including cancer and neurological disorders. Using an ELISA-based screening protocol, we identified naphtho(hydro)quinone-based small molecules that allosterically inhibit PAK activity. These molecules interfere with the interactions between the p21-binding domain (PBD) of PAK1 and Rho GTPases by binding to the PBD. Importantly, they inhibit the activity of full-length PAKs and are selective for PAK1 and PAK3 in vitro and in living cells. These compounds may potentially be useful for determining the details of the PAK signaling pathway and may also be used as lead molecules in the development of more selective and potent PAK inhibitors.
Actins ; Cell Proliferation ; Cell Survival ; Humans ; In Vitro Techniques ; Mass Screening ; Nervous System Diseases ; p21-Activated Kinases ; Phosphotransferases* ; rho GTP-Binding Proteins

BACKGROUND: Since the treatment guidelines for atopic dermatitis (AD) were issued by the Korean Atopic Dermatitis Association (KADA) work group in 2006, there have been further advances in the systemic treatment of AD. OBJECTIVE: We aimed to establish updated evidence- and experience-based systemic treatment guidelines for Korean AD. METHODS: We compiled a database of references from relevant systematic reviews and guidelines regarding the systemic management of AD, including antihistamines, antimicrobials, systemic immunomodulators, allergen-specific immunotherapy, phototherapy, adjunctive treatment, and complementary and alternative medicines. Evidence for each statement was graded and classified based on the strength of the recommendation. Thirty-nine council members of KADA participated in the three rounds of votes and expert consensus recommendations were established. RESULTS: The use of antihistamines is recommended to relieve pruritus and to prevent exacerbation due to scratching in AD patients. Infection should be controlled as needed and long-term medication should be avoided. For moderate to severe AD patients, concomitant active treatments with systemic immunomodulators are indicated. Cyclosporine is the first choice among systemic immunomodulators and others should be considered as second-line alternatives. Allergen-specific immunotherapy could be effective in AD patients with aeroallergen hypersensitivity. Phototherapy can be useful for moderate to severe AD patients and narrow-band ultraviolet B is the most effective option. Complementary and alternative medicines cannot be recommended for treating AD. CONCLUSION: We expect these recommendations to be a reference guide for physicians and AD patients in choosing the appropriate treatment to improve quality of life and decrease unnecessary social medical costs.
Consensus* ; Cyclosporine ; Dermatitis ; Dermatitis, Atopic* ; Histamine Antagonists ; Humans ; Hypersensitivity ; Immunologic Factors ; Immunotherapy ; Korea* ; Phototherapy ; Pruritus ; Quality of Life

BACKGROUND: Since the treatment guidelines for atopic dermatitis (AD) were released by the Korean Atopic Dermatitis Association (KADA) work group in 2006, there have been several advances in AD management. OBJECTIVE: We aimed to establish updated evidence- and experience-based treatment guidelines for Korean AD. METHODS: We collected a database of references from relevant systematic AD reviews and guidelines regarding general AD management such as bathing and skin care, avoidance of exacerbating factors, education and psychosocial support, and the use of moisturizers and topical anti-inflammatory and antipruritic drugs. Evidence for each statement was graded and the strength of the recommendation for each statement classified. Thirty-nine KADA council members participated in three rounds of voting to establish an expert consensus of recommendations. RESULTS: Basic AD treatment includes proper bathing and skin care, avoidance of exacerbating factors, proper education and psychosocial support, and use of moisturizers. The regular use of moisturizer has a steroid-sparing effect and reduces relapse episodes. The short- and long-term use of topical corticosteroids and calcineurin inhibitors improves AD symptoms and should be encouraged to use in an active and proactive treatment. Wet-wrap therapy can be used for rapid recovery of acute exacerbation. Topical antipruritic drugs cannot be recommended for the treatment of AD. CONCLUSION: This report provides up-to-date evidence- and experience-based treatment guidelines for AD regarding general management and topical treatment. In addition, the average agreement scores obtained by a panel of experts based on the Korean healthcare system and patient adherence are presented.
Adrenal Cortex Hormones ; Antipruritics ; Baths ; Calcineurin ; Consensus* ; Delivery of Health Care ; Dermatitis, Atopic* ; Education ; Korea* ; Patient Compliance ; Politics ; Recurrence ; Skin Care