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.

Background/Aims: The SAMe-TT2R2 score is used for assessing anticoagulation control (AC) quality with warfarin. However, it is hard to apply SAMe-TT2R2 score in Asian patients with atrial fibrillation (AF), because it has not been proven in those populations. This study aimed to validate the SAMe-TT2R2 score in Asian patients with AF and suggest a modified SAMe- TT2R2 score for this population. Methods: We analyzed 710 Korean patients with AF who were using warfarin. The AC quality was assessed as the mean time in therapeutic range (TTR). Each component of SAMe-TT2R2 score was evaluated for the relationship with AC. Further clinical factors that predict AC were analyzed. Identified factors were re-assorted and constructed as SA2Me-TTR scoring system. Results: Of the components of the SAMe-TT2R2 score, female, age, and rhythm control were associated with AC. Heart failure and renal insufficiency were newly identified factors associated with AC. The modified SA2Me-TTR score was reconstructed with the relevant risk factors (S, female gender, 1 point; A, age < 60 yr, 2 points; Me, medical history of heart failure, 1 point; T, treatment for rhythm control, 1 point; T, history of stroke or transient ischemic attack, 1 point; R, renal insufficiency, 1 point). The modified SA2Me-TTR score demonstrated an excellent relationship with the grading of AC. The modified SA2Me-TTR score ≤ 1 identified patients with good AC (hazard ratio 2.46, 95% CI 1.75–3.47). Conclusions The modified SA2Me-TTR score was useful for guiding oral anticoagulants selection in Asian patients with AF.

Purpose: This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). Materials and Methods: A web-based database system was established to collect prospective cohort data for patients with mHSPC in Korea. From May 2019 to November 2022, 928 patients with mHSPC from 15 institutions were enrolled. Among these patients, data from 122 patients who received ADT+abiraterone/prednisone or ADT+docetaxel as the primary systemic treatment for mHSPC were collected. The patients were divided into two groups: ADT+abiraterone/prednisone group (n=102) and ADT+docetaxel group (n=20). We compared the demographic characteristics, medical histories, baseline cancer status, initial laboratory tests, metastatic burden, oncological outcomes for mHSPC, progression after mHSPC treatment, adverse effects, follow-up, and survival data between the two groups. Results: No significant differences in the demographic characteristics, medical histories, metastatic burden, and baseline cancer status were observed between the two groups. The ADT+abiraterone/prednisone group had a lower prostate-specific antigen (PSA) progression rate (7.8% vs. 30.0%; p=0.011) and lower systemic treatment discontinuation rate (22.5% vs. 45.0%; p=0.037). No significant differences in adverse effects, oncological outcomes, and total follow-up period were observed between the two groups. Conclusions ADT+abiraterone/prednisone had lower PSA progression and systemic treatment discontinuation rates than ADT+docetaxel. In conclusion, further studies involving larger, double-blinded randomized trials with extended follow-up periods are necessary.

Objectives: The aim of this study was to determine the most effective treatment approach by comparing the impacts of various otolith reduction techniques in patients with apogeotropic lateral semicircular canal benign paroxysmal positional vertigo (LC-BPPV). Methods: We performed a multicenter randomized prospective study from January to December 2015, involving 72 consecutive patients with apogeotropic LC-BPPV. The patients were divided into three treatment groups: therapeutic head-shaking (group A), the Gufoni-Appiani maneuver (group B), and the cupulolith repositioning maneuver (CuRM; group C). Each group underwent evaluation and treatment up to the fourth week. Treatment success was defined as the disappearance of positional vertigo and nystagmus. Results: This study included 72 patients (49 male and 23 female), with a mean (±standard deviation) age of 55.4±13.5 years. The mean duration of vertigo experienced prior to treatment was 3.9±4.4 days. The mean latency and duration of nystagmus were 2.7±3.0 seconds and 47.9±15.8 seconds, respectively. The overall treatment frequency was 2.0±0.9. The number of treatments differed significantly among the three groups (P<0.05). After 4 weeks, the success rates for groups A, B, and C were 90.5%, 92.3%, and 100%, respectively. No significant difference was observed in the success rate across treatment methods and periods (P>0.05). However, CuRM was the only method with a 100% treatment success rate. Conclusion While no clear difference was observed among the three treatments for LC-BPPV, CuRM was found to be superior to the other approaches in the long term.

Background: The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. Results: K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. Conclusion Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

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.

Background: Pediatric alopecia areata (AA) can affect the quality of life (QoL) of patients and their family members. Research on the QoL and burden on family members in pediatric AA is limited. Objective: This nationwide multicenter questionnaire study described the QoL and burden of the family members of patients with pediatric AA. Methods: This nationwide multicenter questionnaire study enrolled AA patients between the ages of 5 and 18 years from March 1, 2017 to February 28, 2018. Enrolled patients and their parents completed the modified Children’s Dermatology Life Quality Index (CDLQI) and the modified Dermatitis Family Impact (mDFI). The disease severity was measured using the Severity of Alopecia Tool (SALT) survey scores. Results: A total of 268 patients with AA from 22 hospitals participated in this study. Our study found that the efficacy and satisfaction of previous treatments of AA decreased as the severity of the disease increased. The use of home-based therapies and traditional medicines increased with the increasing severity of the disease, but the efficacy felt by patients was limited. CDLQI and mDFI scores were higher in patients with extensive AA than those with mild to moderate AA. The economic and time burden of the family members also increased as the severity of the disease increased. Conclusion The severity of the AA is indirectly proportional to the QoL of patients and their family members and directly proportional to the burden. Physicians need to understand these characteristics of pediatric AA and provide appropriate intervention to patients and their family members.

Background: Arsenic trioxide (ATO) is the standard treatment for relapsed acute promyelocytic leukemia (APL). However, consensus on post-remission therapies is still lacking. Methods: We evaluated 52 patients who experienced relapse following initial treatment of APL between 2000 and 2019 at Catholic Hematology Hospital. Among them, 41 patients received reinduction treatment, 30 with ATO-based regimen, whereas 11 with conventional intensive chemotherapy (IC). Results: The ATO reinduction group showed a significantly higher second molecular complete remission (mCR2) rate, superior neutrophil and platelet recovery, and a lower infection rate than the IC reinduction group. No significant differences were observed in survival outcomes after post-remission treatment among the ATO-based (N=19), autologous (N=12), and allogeneic (N=6) hematopoietic stem cell transplantation (HSCT) groups. In the ATO-based and autologous HSCT groups, among patients with mCR2 after ATO reinduction, nine and five patients experienced a second relapse, respectively (50.7% vs. 41.7%, P =0.878). Among these patients, seven received salvage allogeneic HSCT; six remained alive. The other seven patients received ATO without HSCT. Five died from disease progression, and two survived and have been in mCR2 since. Conclusion Post-remission treatment outcomes of patients with relapsed APL were not significantly different, regardless of the treatment option, suggesting the feasibility of ATO-based treatment without HSCT in mCR2. Allogeneic HSCT may be an effective salvage treatment modality for patients with a second relapse. Owing to a few cases of relapsed APL, multicenter prospective studies may help elucidate the efficacy of each post-remission treatment.

Background/Aims: Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) can serve as biomarkers for diagnosing and assessing disease activity in ulcerative colitis (UC). We investigated their clinical significance in UC. Methods: We analyzed 48 patients with UC who underwent measurement of fecal calprotectin (FC) and endoscopy and 96 age- and sex-matched healthy controls. NLR and PLR were compared between the patients and healthy controls. The endoscopic activity was divided into 2 groups: group 1 (mild to moderate inflammation) and group 2 (severe inflammation) according to the Mayo endoscopic subscore in UC. Results: To diagnose UC, the optimal cutoff of NLR and PLR was 2.26 (sensitivity 54.2%; specificity 90.6%; positive likelihood ratio 5.778, 95% confidence interval [CI] 2.944–11.339; area under the curve [AUC] 0.774, 95% CI, 0.690–0.859) and 179.8 (sensitivity 35.4%; specificity 90.6%; positive likelihood ratio 3.778, 95% CI 1.821–7.838; AUC 0.654, 95% CI 0.556–0.753), respectively. The optimal cutoff to differentiate group 1 and group 2 was 3.44, 175.9, and 453 µg/g for NLR, PLR, and FC, respectively (sensitivity, 63.6% vs. 90.9% vs. 81.8%; specificity, 81.1% vs. 78.4% vs. 73.0%; positive likelihood ratio, 3.364 vs. 4.205 vs. 3.027; AUC, 0.714 vs. 0.897 vs. 0.813). PLR had the highest AUC and positive likelihood ratio. Conclusions NLR and PLR help differentiate patients with UC from healthy controls. NLR, PLR, and FC indicate endoscopic activity and may reflect intestinal mucosal conditions.

Background/Aims: Idiopathic multicentric Castleman disease (iMCD) comprises approximately 30% of all cases of Castleman disease. It is characterized by constitutional symptoms, enlarged lymph nodes at multiple anatomical sites, and laboratory test abnormalities, which are primarily related to the overproduction of interleukin 6 (IL-6). Siltuximab is a human-mouse chimeric immunoglobulin G1κ monoclonal antibody against human IL-6. In view of the limited treatment options for iMCD, this study aimed to evaluate the efficacy and safety of siltuximab in the management of this condition. Methods: In this real-world retrospective study, we administered siltuximab to 15 patients with iMCD who previously received conventional chemotherapy and/or steroid pulse therapy. The median time to a durable symptomatic response was 22 days (range, 17 to 56). The serum hemoglobin and albumin levels and erythrocyte sedimentation rates significantly normalized after the first 3 months of siltuximab treatment. Lymph node involution, assessed using imaging, was relatively gradual, demonstrating a complete or partial response at 6 months. Results: On an average, the improvements in clinical, laboratory, and radiologic parameters of iMCD in responders were observed after one, three, and eight cycles of siltuximab treatment, respectively. Siltuximab demonstrated a favorable safety profile, and prolonged treatment was well-tolerated. Conclusions Despite the small sample size of the present study, the results are encouraging and demonstrate the potential of siltuximab as the first-line treatment of iMCD. Further large multicenter studies are needed to evaluate the clinical outcomes and adverse events associated with siltuximab.