Background: and Purpose The relationship between thrombus histology and long-term stroke patient outcomes remains unexplored. We aimed to determine whether the histological characteristics of thrombi are associated with long-term outcomes in stroke patients and to identify the thrombus features linked to these outcomes. Methods: This retrospective multicenter cohort study included 512 patients with ischemic stroke who underwent endovascular thrombectomy between July 2017 and July 2023. Patients were followed up for long-term major adverse cardiovascular events occurrence. Thrombus histology was assessed using immunohistochemistry, including the proportion of fibrin, red blood cells, and platelets, as well as the distribution patterns categorized as layered, erythrocytic, diffuse platelet, and mixed. Results: During a median follow-up of 38.1 months, 164 patients experienced major adverse cardiovascular events, with an incidence rate of 3.02 per 100 person-years. Major adverse cardiovascular events occurrence was associated with the diffuse platelet pattern and proportion of platelets and red blood cells within the thrombus. After adjusting for confounders, the diffuse platelet pattern independently predicted major adverse cardiovascular events, including mortality and stroke recurrence. Subgroup analysis also demonstrated that the association between the diffuse platelet pattern and major adverse cardiovascular events was consistent across key clinical subgroups based on age (≥65 vs. <65 yr), atrial fibrillation, cancer status, and discharge medications. Conclusions Thrombus histology could provide predictive value for long-term prognosis. In particular, histological distribution patterns may be more important than simple composition in thrombus research, including in the prediction of prognosis.

Objective: Primary frozen shoulder causes significant pain and progressively restricts shoulder movements. Diagnosis is made clinically based on patient history and physical examination. Management is mainly non-invasive owing to its self-limiting clinical course. However, clinical practice guidelines for frozen shoulder have not yet been developed in Korea. The developed guidelines aim to provide evidence-based recommendations for the diagnosis and treatment of frozen shoulder. Methods: A guideline development committee reviewed the literature from four databases (PubMed, Embase, Cochrane Library, and KMbase). Using the Population, Intervention, Comparator, and Outcome (PICO) framework, the committee formulated two backgrounds and 16 key questions to address common clinical concerns. Recommendations were made using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Results: Diabetes, thyroid disease, and dyslipidemia significantly increase the risk of developing a frozen shoulder. Although frozen shoulder is often self-limiting, some patients may experience long-term functional disabilities. Ultrasound and magnetic resonance imaging should be used as adjunctive tools alongside clinical diagnosis, and rather than as independent diagnostic methods. Noninvasive approaches, such as medications, physical modalities, exercises, electrical stimulation, and manual therapy, may reduce pain and improve shoulder function. Other noninvasive interventions have limited evidence, and their application should be based on clinical judgment. Intra-articular steroid injections are recommended for treatment, and physiotherapy or hydrodilation with steroid injections can also be beneficial. Conclusion These guidelines provide evidence-based recommendations for diagnosing and treating primary frozen shoulder.

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: and Purpose Unlike other immune-mediated neuropathies, anti-myelin-associated glycoprotein (MAG) neuropathy is often refractory to immunotherapy. It is necessary to compare the relative efficacies of various immunotherapies and develop objective biomarkers in order to optimize its clinical management. Methods: This study recruited 91 patients with high anti-MAG antibody titers from 7 tertiary hospitals in South Korea. We analyzed the baseline characteristics, therapeutic outcomes, and nerve conduction study (NCS) findings of 68 patients and excluded 23 false positive cases. Results: The rate of positive responses to treatment was highest using zanubrutinib (50%) and rituximab (36.4%), followed by corticosteroids (16.7%), immunosuppressants (9.5%), intravenous immunoglobulin (5%), and plasma exchange (0%). Disability and weakness were significantly associated with multiple NCS parameters at the time of diagnosis, especially distal compound muscle action potential (CMAP) amplitudes. Moreover, the longitudinal trajectory of the average CMAP amplitudes paralleled the clinical courses, with a 16.2 percentile decrease as an optimal cutoff for predicting a clinical exacerbation (area under the receiver operating characteristic curve=0.792). Conclusions Our study supports the use of NCS as an objective marker for estimating disease burden and tracking clinical changes in patients with anti-MAG neuropathy. We have described the beneficial effects of rituximab and a new drug, zanubrutinib, compared with conventional immunotherapies.

Cutaneous pseudolymphoma (CPL) is a benign skin disorder characterized by the presence of a lymphocyte-rich infiltrate resembling malignant lymphoma. As there are significant differences in management and clinical outcomes, differentiating CPL from true lymphomas is crucial. The diagnostic process involves a comprehensive approach, incorporating clinical examination, histopathological analysis, and when necessary, immunohistochemical staining to distinguish CPL from true lymphomas. Biopsy plays a key role in assessing characteristics of infiltrating lymphocytes and architectural arrangements of cells within dermal layers. Here, we present an unusual case of CPL triggered by a bee sting, outlining its clinical and pathological features.

Purpose: Long-course chemoradiotherapy (LCRT) has been widely recommended in a majority of rectal cancer patients. Recently, encouraging data on short-course radiotherapy (SCRT) for rectal cancer has emerged. In this study, we aimed to compare these two methods in terms of short-term outcomes and cost analysis under the Korean medical insurance system. Materials and Methods: Sixty-two patients with high-risk rectal cancer, who underwent either SCRT or LCRT followed by total mesorectal excision (TME), were classified into two groups. Twenty-seven patients received 5 Gy×5 with two cycles of XELOX (capecitabine 1000 mg/m 2 and oxaliplatin 130 mg/m 2 every 3 weeks) followed by TME (SCRT group). Thirty-five patients received capecitabine-based LCRT followed by TME (LCRT group). Short-term outcomes and cost estimation were assessed between the two groups. Results: Pathological complete response was achieved in 18.5% and 5.7% of patients in the SCRT and LCRT groups, respectively (p=0.223). The 2-year recurrence-free survival rate did not show significant difference between the two groups (SCRT vs. LCRT:91.9% vs. 76.2%, p=0.394). The average total cost per patient for SCRT was 18% lower for inpatient treatment (SCRT vs. LCRT: $18787 vs. $22203, p<0.001) and 40% lower for outpatient treatment (SCRT vs. LCRT: $11955 vs. $19641, p<0.001) compared to LCRT. SCRT was shown to be the dominant treatment option with fewer recurrences and fewer complications at a lower cost. Conclusion SCRT was well-tolerated and achieved favorable short-term outcomes. In addition, SCRT showed significant reduction in the total cost of care and distinguished cost-effectiveness compared to LCRT.

Immunologists have activated T cells in vitro using various stimulation methods, including phorbol myristate acetate (PMA)/ionomycin and αCD3/αCD28 agonistic antibodies. PMA stimulates protein kinase C, activating nuclear factor-κB, and ionomycin increases intracellular calcium levels, resulting in activation of nuclear factor of activated T cell. In contrast, αCD3/αCD28 agonistic antibodies activate T cells through ZAP-70, which phosphorylates linker for activation of T cell and SH2-domain-containing leukocyte protein of 76 kD. However, despite the use of these two different in vitro T cell activation methods for decades, the differential effects of chemical-based and antibody-based activation of primary human T cells have not yet been comprehensively described. Using single-cell RNA sequencing (scRNA-seq) technologies to analyze gene expression unbiasedly at the single-cell level, we compared the transcriptomic profiles of the non-physiological and physiological activation methods on human peripheral blood mononuclear cell–derived T cells from four independent donors. Remarkable transcriptomic differences in the expression of cytokines and their respective receptors were identified. We also identified activated CD4 T cell subsets (CD55+) enriched specifically by PMA/ionomycin activation. We believe this activated human T cell transcriptome atlas derived from two different activation methods will enhance our understanding, highlight the optimal use of these two in vitro T cell activation assays, and be applied as a reference standard when analyzing activated specific disease-originated T cells through scRNA-seq.

Background/Aims: We evaluated the gut microbiome using extracellular vesicles (EVs) in the urine of patients with colorectal cancer (CRC) to determine whether gut-microbe-derived EVs could be a potential biomarker for the diagnosis of CRC. Methods: EVs were isolated from the urine of patients with CRC and healthy controls. DNA was extracted from the EVs, and the bacterial composition was analyzed using next-generation sequencing of the 16S rRNA. Results: A total of 91 patients with CRC and 116 healthy controls were enrolled. We found some specific microbiomes that were more or less abundant in the CRC group than in the control group. The alpha-diversity of the gut microbiome was significantly lower in the CRC group than in the control group. A significant difference was observed in the beta-diversity between the groups. The alpha-diversity indices between patients with early- and late-stage CRC showed conflicting results; however, there was no significant difference in the beta-diversity according to the stage of CRC. There was no difference in the alpha- and beta-diversity of the gut microbiome corresponding to the location of CRC (proximal vs. distal). Conclusions A distinct gut microbiome is reflected in the urine EVs of patients with CRC compared with that in the healthy controls. Microbial signatures from EVs in urine could serve as potential biomarkers for the diagnosis of CRC.

Background/Aims: Fexuprazan is a novel potassium-competitive acid blocker that could be of benefit to patients with gastric mucosal injury. The aim of this study was to assess the 2-week efficacy and safety of fexuprazan in patients with acute or chronic gastritis. Methods: In this study, 327 patients with acute or chronic gastritis who had one or more gastric erosions on endoscopy and subjective symptoms were randomized into three groups receiving fexuprazan 20 mg once a day (q.d.), fexuprazan 10 mg twice a day (b.i.d.), or placebo for 2 weeks. The posttreatment assessments were the primary endpoint (erosion improvement rate), secondary endpoints (cure rates of erosion and edema and improvement rates of redness, hemorrhage, and subjective symptoms), and drug-related adverse events. Results: Among the patients, 57.8% (59/102), 65.7% (67/102), and 40.6% (39/96) showed erosion improvement 2 weeks after receiving fexuprazan 20 mg q.d., fexuprazan 10 mg b.i.d., and placebo, respectively. Both fexuprazan 20 mg q.d. and 10 mg b.i.d. showed superior efficacy to the placebo (p=0.017 and p<0.001, respectively). Likewise, both fexuprazan 20 mg q.d. and 10 mg b.i.d. also showed higher erosion healing rates than the placebo (p=0.033 and p=0.010, respectively). No difference was noted in the edema healing rate and the improvement rates for redness, hemorrhage, and subjective symptoms between the fexuprazan and placebo groups.No significant difference was noted in the incidence of adverse drug reactions. Conclusions Fexuprazan 20 mg q.d. and 10 mg b.i.d. for 2 weeks showed therapeutic efficacy superior to that of placebo in patients with acute or chronic gastritis (ClinicalTrials.gov identifier NCT04341454).

This study aimed to compare the pharmacokinetic (PK) and safety profiles of 2 fenofibric acid formulations under fasting and fed conditions. The reference was a 135 mg capsule, while the test was a 110 mg enteric-coated tablet. This randomized, open-label, two-sequence, two-period crossover phase 1 clinical trial was conducted in healthy Korean men. Sixty participants were enrolled in each of the fasting and feeding groups. Blood samples were collected 72 hours after drug administration. PK parameters were calculated using a noncompartmental method with Phoenix WinNonlin ® . A total of 53 and 51 participants from the fasting and feeding groups, respectively, completed the study. The geometric mean ratio and 90% confidence intervals of the maximum concentration (C max ) and area under the concentration-time curve to the last measurable plasma concentration were 0.9195 (0.8795–0.9614) and 0.8630 (0.8472–0.8791) in the fasting study and 1.0926 (1.0102–1.1818) and 0.9998 (0.9675–1.0332) in the fed study, respectively. The time to reach C max of the enteric-coated tablet compared to that of the capsule was extended by 1 and 3 hours under fasting and fed conditions, respectively. In conclusion, enteric-coated tablets have a higher bioavailability than capsules. In addition, the enteric-coated tablet was smaller than the capsule, making it easier for patients to swallow.