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: Altering wrist biomechanics, Kienbock’s disease leads to progressive carpal collapse that results in early arthritis and degenerative changes. By shifting the loading axis toward the radioscaphoid joint, scaphocapitate arthrodesis (SCA) has been reported as a salvage procedure effective in treating symptomatic patients with advanced Kienbock’s disease. In this study, we aimed to evaluate the clinical and radiological outcomes of arthroscopic SCA in symptomatic patients with advanced stages of Kienbock’s disease. Methods: Between March 2010 and February 2021, we included 15 patients with symptomatic stage IIIA (n=2) and stage IIIB (n=13) Kienbock’s disease who were followed up for a minimum of 24 months after arthroscopic SCA with or without lunate excision. The lunate was excised in 6 patients and retained in 9. Visual analog scale (VAS) pain score, grip strength, range of motion (ROM), active flexion-extension arc, and modified Mayo wrist score (MMWS) were measured preoperatively and at each follow-up examination after surgery. Operation-related complications and radiographic changes were also assessed. Results: There were 13 women and 2 men, with a mean age of 57.6 years (range, 21–74 years) at the time of undergoing arthroscopic SCA. Follow-up ranged from 24 to 116 months, with an average of 56.9 ± 32.3 months. Bony union was achieved in all patients. At preoperative examination, wrist ROM (67%) and grip strength (48%) significantly decreased, compared to the contralateral wrist. At the final follow-up, there were significant improvements in VAS, grip strength, and MMWS, whereas the active wrist ROM showed no significant change. Radioscaphoid angle recovered after surgery, while radiographic carpal collapse and ulnar translation of the carpus occurred. In subgroup analysis according to excision of the lunate, there were no significant differences in VAS, MMWS, grip strength, or total ROM. However, increased ulnar translation and decreased radial deviation were noted in the lunate excision group. Conclusions Arthroscopic SCA achieved significant improvements in pain and wrist function in patients with advanced Kienbock’s disease without any complications. Excision of the lunate when performing arthroscopic SCA seemed to induce progressive carpal ulnar translation, with no apparent clinical benefits over retaining it.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson’s disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors.Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

Background: This study described the surgical technique of a robot-assisted retroauricular anterior scalenectomy and assessed clinical outcomes and complications for patients with neurogenic thoracic outlet syndrome (nTOS). Methods: Between February 2014 and August 2016, 5 patients underwent robot-assisted retroauricular anterior scalenectomy using the da Vinci Xi system for nTOS. For clinical assessment, visual analog scale (VAS) symptom score, pinch and grip strength, and disabilities of arm, shoulder and hand (DASH) score were assessed to compare preoperative and postoperative outcomes. Postoperative complications were also reviewed. Results: The VAS symptom, pinch and grip strength, and DASH scores improved 1 year after the operation. All patients were satisfied with the surgical scars. Temporary postoperative complications, which spontaneously resolved within 3 months, were noticed in 2 patients: one with vocal cord palsy and the other with upper brachial plexus palsy. Conclusions The robot-assisted retroauricular anterior scalenectomy for patients with nTOS seems feasible and safe, providing satisfactory cosmetic results.

Purpose: Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea. Materials and Methods: From January 2001 to December 2015, data of pediatric patients (0–18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. Results: Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001). Conclusion The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.

The continuous emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has provided insights for updating current coronavirus disease 2019 (COVID-19) vaccines. We examined the neutralizing activity of Abs induced by a BA.4/5-containing bivalent mRNA vaccine against Omicron subvariants BN.1 and XBB.1.5. We recruited 40 individuals who had received a monovalent COVID-19 booster dose after a primary series of COVID-19 vaccinations and will be vaccinated with a BA.4/5-containing bivalent vaccine. Sera were collected before vaccination, one month after, and three months after a bivalent booster.Neutralizing Ab (nAb) titers were measured against ancestral SARS-CoV-2 and Omicron subvariants BA.5, BN.1, and XBB.1.5. BA.4/5-containing bivalent vaccination significantly boosted nAb levels against both ancestral SARS-CoV-2 and Omicron subvariants. Participants with a history of SARS-CoV-2 infection had higher nAb titers against all examined strains than the infection-naïve group. NAb titers against BN.1 and XBB.1.5 were lower than those against the ancestral SARS-CoV-2 and BA.5 strains. These results suggest that COVID-19 vaccinations specifically targeting emerging Omicron subvariants, such as XBB.1.5, may be required to ensure better protection against SARS-CoV-2 infection, especially in high-risk groups.

Purpose: This study proposed the optimal definition of biochemical recurrence (BCR) after salvage radiotherapy (SRT) following radical prostatectomy for prostate cancer. Materials and Methods: Among 1,117 patients who had received SRT, data from 205 hormone-naïve patients who experienced post-SRT prostate-specific antigen (PSA) elevation were included in a multi-institutional database. The primary endpoint was to determine the PSA parameters predictive of distant metastasis (DM). Absolute serum PSA levels and the prostate-specific antigen doubling time (PSA-DT) were adopted as PSA parameters. Results: When BCR was defined based on serum PSA levels ranging from 0.4 ng/mL to nadir+2.0 ng/mL, the 5-year probability of DM was 27.6%-33.7%. The difference in the 5-year probability of DM became significant when BCR was defined as a serum PSA level of 0.8 ng/ml or higher (1.0-2.0 ng/mL). Application of a serum PSA level of ≥ 0.8 ng/mL yielded a c-index value of 0.589. When BCR was defined based on the PSA-DT, the 5-year probability was 22.7%-39.4%. The difference was significant when BCR was defined as a PSA-DT ≤ 3 months and ≤ 6 months. Application of a PSA-DT ≤ 6 months yielded the highest c-index (0.660). These two parameters complemented each other; for patients meeting both PSA parameters, the probability of DM was 39.5%-44.5%; for those not meeting either parameter, the probability was 0.0%-3.1%. Conclusion A serum PSA level > 0.8 ng/mL was a reasonable threshold for the definition of BCR after SRT. In addition, a PSA-DT ≤ 6 months was significantly predictive of subsequent DM, and combined application of both parameters enhanced predictability.

Background/Aims: As pancreatic mucinous cystic neoplasms (MCNs) are considered premalignant lesions, the current guidelines recommend their surgical resection. We aimed to investigate the concordance between preoperative and postoperative diagnoses and evaluate preoperative clinical parameters that could predict the malignant potential of MCNs. Methods: Patients who underwent surgical resection at Samsung Medical Center for pancreatic cystic lesions and whose pathology was confirmed to be MCN, between July 2000 and December 2017, were retrospectively analyzed. Results: Among a total of 132 patients 99 (75%) were diagnosed with MCN preoperatively. The most discordant preoperative diagnosis was an indeterminate pancreatic cyst. The proportion of male patients was higher (24.2% vs 7.1%, p=0.05) in the diagnosis-discordance group and the presence of worrisome features in radiologic imaging studies, such as wall thickening/enhancement (12.1% vs 37.4%, p=0.02) or solid component/mural nodule (3.0% vs 27.3%, p=0.02), was lower in the diagnosis-discordance group. The presence of symptoms (57.7% vs 34.9%, p=0.02), tumor size greater than 4 cm (80.8% vs 55.7%, p=0.04), and radiologic presence of a solid component/mural nodule (42.3% vs 16.0%, p=0.01) or duct dilatation (19.2% vs 6.6%, p=0.01) were significantly associated with malignant MCNs. Conclusions In our study, the overall diagnostic concordance rate was confirmed to be 75%, and our findings suggest that MCNs have a low malignancy potential when they are less than 4cm in size, are asymptomatic and lack worrisome features on preoperative images.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.