Background: Psoriasis is a persistent systemic inflammatory condition mediated by the interleukin (IL)-23/IL-17 signaling pathway. Existing murine models, including imiquimod (IMQ)-applied wild-type (WT) mice, may not reflect chronicity and systemic comorbidities of psoriasis, particularly gut-related manifestations linked to the gut–skin axis. Objective: To establish a murine model that more accurately reflects chronic psoriasis, its systemic comorbidities, and associated gut environment alterations. Methods: C57BL/6 IL-10-deficient (IL-10 knockout [KO]) and WT mice received topical IMQ or vehicle for 6 weeks. Subsequently, tissue samples from skin, colon, joints, kidneys, liver, abdominal aortas, lymph nodes, and spleens, as well as fecal and blood samples, were collected for histopathologic, immunologic, gut environment analysis. Results: IMQ-treated IL-10 KO mice developed prolonged psoriatic inflammatory responses with increased epidermal thickness and higher infiltration of CD45+, myeloperoxidase+, and IL-17+ cells. They also exhibited early-onset, severe colitis with marked weight loss, shortened colon length, and elevated colitis severity scores. While IMQ induced systemic inflammation in multiple organs, IL-10 KO mice did not show more severe joint, liver, or kidney involvement than WT mice. Elevated serum tumor necrosis factor alpha and plasminogen activator inhibitor-1 levels, increased heart/body weight ratio, enhanced gut permeability, and distinct gut microbiota profiles were observed in IL-10 KO mice. Conclusion The 6-week IMQ-applied IL-10 KO model may better reflect chronic and severe psoriasis with gut-related comorbidities, offering a valuable platform to investigate the gut–skin axis.

Digital therapeutics are emerging as treatments for diseases and disabilities. In chronic kidney disease (CKD), gait is a potential biomarker for health status and intervention effectiveness. This study aims to analyze gait characteristics in CKD patients, providing baseline data for digital therapeutics development. Methods: At baseline and after an 8-week intervention, we performed bioimpedance analysis measurements, the Timed Up and Go, Tinetti, and grip strength tests, and gait analysis in 217 healthy individuals and 276 patients with CKD. Demographic and clinical information was collected, including underlying diseases and medications, laboratory tests, and quality of life satisfaction surveys. Gait analysis was performed using skeleton data, which involved acquiring three-dimensional skeleton data of a walker using a single Kinect sensor. The performance of an artificial intelligence-based classification model in distinguishing between healthy individuals and those with CKD was then investigated. Simultaneously, inertia measurement unit analysis was conducted using measurements taken from the wrist and waist. Results: Most subjects received a health intervention via an app, and their gait was assessed for improvements after an 8-week period. Incidents such as falls, fractures, hospitalizations, and deaths will be investigated in years 1 and 3. Conclusion: This study confirmed that the gaits of healthy individuals and CKD patients were different, and the effect of the 8-week app-based health intervention will be analyzed. The study will yield important baseline data for creating digital therapeutics for CKD patients’ diet/exercise in the future.

Poor graft function (PGF) is a serious, potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation. Eltrombopag has shown multilineage responses in patients with refractory severe aplastic anemia, supporting the idea that it may improve cytopenia in patients with PGF. This retrospective, single center analysis included 8 Korean patients receiving eltrombopag for PGF. Median interval between transplant and eltrombopag treatment was 73 days, and the median duration treatment was 3.5 weeks.With median maximum daily dose of 50 mg, the time to best response was 93 days. Median hemoglobin increased from 8.2 g/dL to 10.9 g/dL, platelet from 18.5 × 109 /L to 54 × 109 /L, and absolute neutrophil count from 1.25 × 109 /L to 3.32 × 109 /L. In conclusion, eltrombopag is a good option for PGF in Korean patients, even at a lower dose compared to western patients.

BACKGROUND/AIMS: Although multiple myeloma (MM) is typically a disease of the elderly, a certain subset of extremely young patients exists. It is necessary to establish clinicopathological characteristics for this population. METHODS: We reviewed the medical records of MM patients whose age was 40 years or younger at diagnosis. RESULTS: A total of 32 patients were analyzed (male to female ratio 19:13, median age 37 years). According to International Staging System, 29%, 48%, and 16% were in stage I, II, and III, respectively. Light chain myeloma accounted for 30%. Clinically significant anemia, hypercalcemia, azotemia, and hypoalbuminemia were present in 29%, 28%, 13%, and 28%, respectively. Three or more lytic bone lesions were detected in 45% of the patients, whereas 13% had no lytic bone lesions. Regarding treatment, 79% of patients received autologous hematopoietic stem cell transplantation. After a median follow-up duration of 64 months, the 1-, 3-, and 5-year overall survival (OS) rates were 84%, 62%, and 54%, respectively. The median OS was 61 months for the entire cohort. CONCLUSIONS: In our study, MM patients aged 40 years or younger at diagnosis showed no superior survival compared to those of the moderately elderly patients based on historical data.
Aged ; Anemia ; Azotemia ; Cohort Studies ; Diagnosis ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Hypercalcemia ; Hypoalbuminemia ; Medical Records ; Multiple Myeloma* ; Treatment Outcome ; Young Adult

BACKGROUND: Mast cell leukemia (MCL) is the most aggressive form of systemic mastocytosis disorders. Owing to its rarity, neither pathogenesis nor standard treatment is established for this orphan disease. Hence, we tried to treat a patient with MCL based on the exome and transcriptome sequencing results of the patient's own DNA and RNA. METHODS: First, tumor DNA and RNA were extracted from bone marrow at the time of diagnosis. Germline DNA was extracted from the patient's saliva 45 days after induction chemotherapy and used as a control. Then, we performed whole-exome sequencing (WES) using the DNA and whole transcriptome sequencing (WTS) using the RNA. Single nucleotide variants (SNVs) were called using MuTect and GATK. Samtools, FusionMap, and Gene Set Enrichment Analysis were utilized to analyze WTS results. RESULTS: WES and WTS results revealed mutation in KIT S476I. Fusion analysis was performed using WTS data, which suggested a possible RARα-B2M fusion. When RNA expression analysis was performed using WTS data, upregulation of PIK3/AKT pathway, downstream of KIT and mTOR, was observed. Based on our WES and WTS results, we first administered all-trans retinoic acid, then dasatinib, and finally, an mTOR inhibitor. CONCLUSION: We present a case of orphan disease where we used a targeted approach using WES and WTS data of the patient. Even though our treatment was not successful, use of our approach warrants further validation.
Bone Marrow ; Diagnosis ; DNA ; Exome ; Humans ; Precision Medicine ; Induction Chemotherapy ; Leukemia ; Leukemia, Mast-Cell* ; Mast Cells* ; Mastocytosis, Systemic ; Rare Diseases ; RNA ; Saliva ; Transcriptome ; Tretinoin ; Up-Regulation ; Dasatinib

Catastrophic antiphospholipid syndrome (APS) is defined as a rare, life-threatening autoimmune disorder leading to multiorgan failure. Probable APS, with clinical manifestations similar to APS without antiphospholipid antibodies, was suggested to be seronegative catastrophic APS. The triggering factors of catastrophic APS are various, including infection, trauma, malignancy, and surgery. In approximately 40% of patients, catastrophic APS develops from an unknown cause. We report a case of seronegative catastrophic APS due to an unknown origin. A 20-year-old man presented with cough, abdominal pain, skin lesions, tunnel vision, and watery diarrhea without fever. His symptoms and laboratory test suggested disseminated intravascular coagulation. Considering seronegative catastrophic APS, we treated with intravenous steroid and intravenous immunoglobulin, but the effects were limited. After weekly treatment with rituximab, an immune-modulating agent, his laboratory findings including thrombocytopenia and coagulation tests, returned to normal. We conclude that rituximab can be an effective treatment for seronegative catastrophic APS.
Abdominal Pain ; Antibodies, Antiphospholipid* ; Antiphospholipid Syndrome ; Autoimmune Diseases ; Cough ; Diarrhea ; Disseminated Intravascular Coagulation* ; Fever ; Humans ; Immunoglobulins ; Skin ; Thrombocytopenia ; Young Adult ; Rituximab