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: A healthcare system’s collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. Methods: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. Results: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. Conclusion In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.

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.

Background: Several cases of pediatric acute hepatitis of unknown etiology related to adenoviral infections have been reported in Europe since January 2022. The aim of this study was to compare the incidence, severity, possible etiology, and prognosis of the disease with those in the past in Korea. Methods: The surveillance group collected data between May and November 2022 using a surveillance system. Acute hepatitis of unknown etiology was defined in patients aged < 16 years with a serum transaminase level > 500 IU/L, not due to hepatitis A-E or other underlying causes. For comparison, data from 18 university hospitals were retrospectively collected as a control group between January 2021 and April 2022. Results: We enrolled 270 patients (mean age, 5 years). The most common symptom was fever. However, the incidence was similar between 2021 and 2022. Liver function test results, number of patients with acute liver failure (ALF), liver transplantation (LT), death, and adenovirus detection rates did not differ between the two groups. None of the adenoviruspositive patients in either group experienced ALF, LT, or death. In the surveillance group, adenovirus-associated virus-2 was detected in four patients, one of whom underwent LT. Patients with an unknown etiology showed significantly higher bilirubin levels, a lower platelet count, and a higher LT rate than patients with a possible etiology. Conclusion The incidence of pediatric acute hepatitis of unknown etiology and adenovirus detection rate have not increased in Korea.

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.

Owing to in-hospital transmission of coronavirus disease 2019 (COVID-19), Uijeongbu St.Mary’s Hospital, a university-affiliated hospital in South Korea, was temporarily closed for disinfection in March 2020. This study aimed to investigate the impact of both the hospital shutdown and the prolonged COVID-19 pandemic on short-term outcomes of colorectal cancer (CRC) patients. We retrospectively reviewed the clinicopathologic data of 607 patients who were surgically treated for CRC from May 2018 to September 2021. Nodal upstaging, higher lymphatic invasion and abdominoperineal resection rates for 3 months after the hospital resumed surgery following the shutdown in the first wave of the COVID-19 pandemic were detected, without worse short-term morbidity or mortality. The incidence of adverse pathologic features of CRC such as lymphatic, venous, and perineural invasion was higher throughout the COVID-19 pandemic era. Further follow-up of CRC patients treated in the pandemic era for long-term oncologic outcomes is needed.

Background: Ear cartilage is a preferred graft material in rhinoplasty. However, after harvest, instability of the auricular framework may arise as a form of donor site morbidity. In the harvest of ear cartilage, the posterior auricular ligament (PAL) is usually sacrificed in order to obtain as much cartilage as possible. Since damage to the PAL may cause auricular instability, we studied the periauricular anatomy using cadavers and evaluated auricular stability during surgery. Methods: Six ears from hemifacial cadavers were studied to clarify the exact anatomy of the PAL. Then, the recoil force of the auricle was serially measured to evaluate the stability of the auricular framework in 30 patients during surgery: before making the skin incision (M1), before and after cutting the PAL (M2, M3), and after harvesting the cymba concha (M4). The differences in force observed after cutting the PAL (ΔM2–M3) and after harvesting the cymba concha (ΔM3–M4) were statistically analyzed. Results: In the cadaveric study, the PAL was identified between the superficial and deep mastoid fasciae and connected the caudal aspect of the cymba concha to the deep mastoid fascia. During surgery, the PAL accounted for 16.20% of the total auricular recoil force. The recoil force decreased by 13.61 N and 11.25 N after cutting the PAL and harvesting the cymba concha, respectively. These decreases were statistically significant (P<0.05). Conclusions The results suggest that the PAL is a supporting structure of the auricle. Therefore, to preserve auricular stability, minimizing damage to the PAL while harvesting the ear cartilage may be helpful.