Background: Lapsi (Choerospondias axillaris), a plant native to Nepal, has been traditionally used in Asian countries to treat cardiovascular conditions. However, its effects on immune regulatory function remain largely unexplored.This study aimed to in vivo evaluate the immunoregulatory properties of Lapsi fruit extract in mice on immunotoxic responses with analysis on in vitro mechanism for immune suppression, oxidative stress, and inflammatory response.Male Balb/c mice were intragastrically administered various doses of the extract for 21 days. In some mice, immune suppression was induced with cyclophosphamide, and subsequent immune recovery was assessed. In addition, RAW264.7 cells and THP-1-derived macrophages were treated in vitro with lipopolysaccharide and different concentrations of the extract. Results: Administration of extract increased the IgG2a/IgG1 ratio while reducing serum IgE and IgG1 level compared with control mice. Tumor necrosis factor (TNF)-α and interleukin (IL)-17 levels were lower in splenic culture supernatants of mice administered extract. Lapsi extract also effectively reversed cyclophosphamide (CP)-induced immunosuppression by enhancing serum levels of IgA and IgG2a, of interferon-γ and interleukin (IL)-4 secreted by splenic T cells, and of IgG1 and IgG2a secreted by B cells, as well as by increasing immune cell counts. In cell cultures, the extract decreased the levels of inflammation markers, including nitric oxide, reactive oxygen species, prostaglandin E2, and pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β). Mechanistic analysis showed that Lapsi extract modulated the NF-κB p65, MAPK, and inflammasome pathways. Conclusions Lapsi extract may act as both an immunostimulatory and anti-inflammatory agent, indicating its potential as a candidate immunomodulatory activity under polyclonal and CP-suppressed conditions; however, further disease-specific studies, along with isolation and characterization of active phytochemicals, are warranted to evaluate its therapeutic applicability.

Subarachnoid hemorrhage (SAH) is a stroke subtype with high mortality and poor functional outcomes. Prompt occlusion of a ruptured aneurysm at an early stage is crucial to prevent rebleeding, which can result in even higher mortality and more severe disabilities. The most critical initial decision in SAH management is the choice of treatment method with surgical clipping or endovascular coiling. We aimed to develop an evidence-based clinical guideline to select the optimal initial treatment in patients with SAH. We developed this guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted across four databases (MEDLINE, Embase, Cochrane, and KoreaMed) to answer two population, intervention, comparison, outcome questions comparing clipping and coiling. The risk of bias was assessed using ROB 2.0 and the Newcastle-Ottawa Scale. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagrams and meta-analyses were generated for functional outcome and mortality. We included six randomized control trials (RCTs) and 58 observational studies. Meta-analysis of RCTs showed that coiling improved functional outcomes compared to clipping (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.86–0.97). No significant mortality difference was observed in RCTs (OR, 1.38; 95% CI, 0.91–2.09), but non-RCTs favored clipping for reduced mortality (OR, 0.77; 95% CI, 0.69–0.86). However, it is difficult to generalize these findings to all clinical situations, as patients with SAH have a highly variable clinical course. Final treatment decision should be tailored to the individual patient’s status, including aneurysm location, morphology, and the expertise available at the treatment center. Such decisions are best made by specialists such as a board-certified physician and should be explained to the patient and their caregivers, along with the rationale for selecting the most appropriate treatment at the given hospital. Korea has many certified endovascular neurosurgeons, cerebrovascular surgeons, and certified cerebrovascular centers. Proper selection of the most suitable treatment method by certified physicians and centers would greatly benefit patient outcomes and healthcare professionals.

Accurate and early identification of stroke and large vessel occlusion (LVO) in emergency settings is essential for improving patient outcomes and ensuring the efficient allocation of medical resources. This clinical practice guideline systematically reviews domestic and international literature and conducts meta-analyses to evaluate the utility and diagnostic accuracy of stroke assessment tools used in prehospital emergency medical services (EMS). We developed a guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted to evaluate the usefulness of diagnostic EMS assessment tools for diagnosing stroke and LVO. Overall, 70 non-randomized control studies were selected for this study. A meta-analysis was conducted with a subgroup analysis to distinguish between patients with stroke and those with LVO. EMS tools demonstrated high sensitivity but low specificity for diagnosing stroke. In the prehospital setting, using validated EMS stroke assessment tools is recommended for the early identification of stroke and LVO. Upon hospital arrival, stroke specialists should conduct further evaluation and triage to confirm the diagnosis and guide appropriate management. Delays in diagnosing LVO are frequently unacceptable. While experts advocate for the use of EMS assessment tools to facilitate early identification of LVO, these tools alone lack adequate sensitivity. Therefore, further diagnostic evaluations and consultation with stroke specialists upon hospital arrival are recommended.

The mothership (MS) model, where patients are directly transferred to a thrombectomy-capable center, and the drip-and-ship (DS) model, where thrombolysis is initiated at the nearest primary stroke center before transfer for thrombectomy, are the primary transport modes for patients with stroke. We aimed to establish guidelines for selecting the appropriate transfer strategy based on emergent large vessel occlusion (LVO). We developed this guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted across four databases (MEDLINE, Embase, Cochrane, and KoreaMed) to answer three Population, Intervention, Comparison, and Outcome questions comparing MS and DS models. The risk of bias was assessed using the Newcastle-Ottawa Scale. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagrams and meta-analyses were generated for functional outcomes, mortality, and successful recanalization. Twenty-six non-randomized controlled studies showed that the MS model improved good functional outcomes by approximately 14% compared with the DS model (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.00–1.30). Fifteen studies reported that mortality in the MS and DS models showed no significant differences (OR, 0.97; 95% CI, 0.84–1.11). Twenty-four studies revealed no significant difference in successful recanalization between the MS and DS models (OR, 0.87; 95% CI, 0.68–1.10). The MS model should be considered first to improve the functional outcome of patients with LVO. However, if thrombectomy cannot be performed immediately after thrombolysis, or if a thrombectomy-enabled hospital is not nearby, the DS model should be considered by stroke specialists depending on transportation time and regional factors. We suggest a mixed approach with the DS model based on specific circumstances or regions to ensure the optimum treatment of patients with acute ischemic stroke (AIS). Appropriate transport for patients with LVO improves the prognosis of AIS.

Background: Left bundle branch block (LBBB) significantly increases the risk of left ventricular systolic dysfunction (LVSD) due to cardiac dyssynchrony. Although artificial intelligence–enabled electrocardiography (AI-ECG) mod‑ els show promise in detecting LVSD, their performance in LBBB patients remains underexplored. We hypothesized that an AI-ECG model clinically validated for detecting LVSD would accurately detect LVSD and predict future clinical outcomes in LBBB patients. Methods: In this retrospective multicenter study, 5,689 expert-validated LBBB ECGs collected from 2,813 patients between 2016 and 2024 were analyzed using a previously developed and validated AI-ECG model. LVSD was defined as an ejection fraction of ≤ 40%. Model performance was assessed using the area under the receiver operating char‑ acteristic curve (AUROC), the area under the precision-recall curve (AUPRC), sensitivity, and specificity. Patients were stratified into high- and low-risk groups based on a threshold that achieved 90% sensitivity. A Kaplan–Meier analysis was used to compare clinical outcomes. Results: Among the 2,813 LBBB patients (mean age, 70.7 years; male sex, 43.7%), hypertension and a history of heart failure were common. The AiTiALVSD model showed strong diagnostic performance for LVSD (AUROC, 0.930 [95% CI, 0.924–0.937]; AUPRC, 0.913 [95% CI, 0.902–0.923]; sensitivity, 0.979; specificity, 0.473). During the mean follow-up of 4.1 years, high-risk patients had significantly higher hazards than low-risk patients for all-cause mortality (adjusted hazard ratio [HR], 1.87; 95% CI, 1.53–2.28), implantable cardioverter defibrillator/cardiac resynchronization therapy implantation (adjusted HR, 15.2; 95% CI, 7.51–30.77), and cardiovascular hospitalization (adjusted HR, 1.11; 95% CI, 0.96–1.28). Conclusions AiTiALVSD effectively detects LVSD and stratifies long-term cardiovascular risk in LBBB patients, support‑ ing its clinical utility for early detection and patient management.

BACKGROUND: Osteoporosis, characterized by decreased bone mineral density due to an imbalance between osteoblast and osteoclast activity, poses significant challenges in bone healing, particularly in postmenopausal women. Current treatments, such as bisphosphonates, are effective but associated with adverse effects like medication-related osteonecrosis of the jaw, necessitating safer alternatives. METHODS: This study investigated the use of L-serine-incorporated gelatin sponges for bone regeneration in calvarial defects in an ovariectomized rat model of osteoporosis. Thirty rats were divided into three groups: a control group, a group treated with a gelatin sponge containing an amino acid mixture, and a group treated with a gelatin sponge containing L-serine. Bone regeneration was assessed using micro-computed tomography (micro-CT) and histological analyses. RESULTS: The L-serine group showed a significant increase in bone volume (BV) and bone area compared to the control and amino acid groups. The bone volume to total volume (BV/TV) ratio was also significantly higher in the L-serine group.Immunohistochemical analysis demonstrated that L-serine treatment suppressed the expression of cathepsin K, a marker of osteoclast activity, while increasing serine racemase activity. CONCLUSION These findings suggest that L-serine-incorporated gelatin sponges not only enhance bone formation but also inhibit osteoclast-mediated bone resorption, providing a promising and safer alternative to current therapies for osteoporosis-related bone defects. Further research is needed to explore its clinical applications in human patients.

Purpose: Although upper eyelid retraction is commonly associated with thyroid eye disease, its etiology remains unclear. This study evaluated the clinical features and treatment outcomes of patients with upper eyelid retraction caused by idiopathic orbital myositis (IOM). Methods: We conducted a retrospective analysis of the medical records of patients who presented with unilateral upper eyelid retraction. IOM was diagnosed based on normal thyroid function tests (TFT), including thyroid-stimulating immunoglobulin (TSI). Orbital imaging demonstrated contrast-enhanced enlargement of the superior rectus-levator palpebrae superioris complex (SR-LC). Pre- and post-systemic steroid treatment, margin-reflex distance 1 (MRD1), MRD1 difference between affected and unaffected eyes, exophthalmos, and diplopia were assessed. Results: In total, five patients (male: 4, female: 1) with a median age of 36.4 years were diagnosed with IOM. Three patients presented with diplopia on upgaze and supraduction limitation. Orbital imaging revealed levator palpebrae superioris muscle enlargement with distinct borders and homogeneous contrast enhancement. All cases with superior rectus enlargement demonstrated tendon involvement. The median duration from symptom onset to treatment initiation was 2.2 months. Four patients received oral prednisolone, whereas one received intravenous methylprednisolone. Although no significant improvements were observed in MRD1, MRD1 difference, or exophthalmos post-treatment, diplopia resolved in all three patients. Conclusions IOM can present with upper eyelid retraction, emphasizing the importance of differentiating it from thyroid eye disease. TFT, including TSIs, and orbital imaging are essential diagnostic tools. These findings indicate that systemic corticosteroids can effectively manage diplopia associated with IOM, emphasizing the potential benefit of early and aggressive treatment.

BACKGROUND: Osteoporosis, characterized by decreased bone mineral density due to an imbalance between osteoblast and osteoclast activity, poses significant challenges in bone healing, particularly in postmenopausal women. Current treatments, such as bisphosphonates, are effective but associated with adverse effects like medication-related osteonecrosis of the jaw, necessitating safer alternatives. METHODS: This study investigated the use of L-serine-incorporated gelatin sponges for bone regeneration in calvarial defects in an ovariectomized rat model of osteoporosis. Thirty rats were divided into three groups: a control group, a group treated with a gelatin sponge containing an amino acid mixture, and a group treated with a gelatin sponge containing L-serine. Bone regeneration was assessed using micro-computed tomography (micro-CT) and histological analyses. RESULTS: The L-serine group showed a significant increase in bone volume (BV) and bone area compared to the control and amino acid groups. The bone volume to total volume (BV/TV) ratio was also significantly higher in the L-serine group.Immunohistochemical analysis demonstrated that L-serine treatment suppressed the expression of cathepsin K, a marker of osteoclast activity, while increasing serine racemase activity. CONCLUSION These findings suggest that L-serine-incorporated gelatin sponges not only enhance bone formation but also inhibit osteoclast-mediated bone resorption, providing a promising and safer alternative to current therapies for osteoporosis-related bone defects. Further research is needed to explore its clinical applications in human patients.

Purpose: Although upper eyelid retraction is commonly associated with thyroid eye disease, its etiology remains unclear. This study evaluated the clinical features and treatment outcomes of patients with upper eyelid retraction caused by idiopathic orbital myositis (IOM). Methods: We conducted a retrospective analysis of the medical records of patients who presented with unilateral upper eyelid retraction. IOM was diagnosed based on normal thyroid function tests (TFT), including thyroid-stimulating immunoglobulin (TSI). Orbital imaging demonstrated contrast-enhanced enlargement of the superior rectus-levator palpebrae superioris complex (SR-LC). Pre- and post-systemic steroid treatment, margin-reflex distance 1 (MRD1), MRD1 difference between affected and unaffected eyes, exophthalmos, and diplopia were assessed. Results: In total, five patients (male: 4, female: 1) with a median age of 36.4 years were diagnosed with IOM. Three patients presented with diplopia on upgaze and supraduction limitation. Orbital imaging revealed levator palpebrae superioris muscle enlargement with distinct borders and homogeneous contrast enhancement. All cases with superior rectus enlargement demonstrated tendon involvement. The median duration from symptom onset to treatment initiation was 2.2 months. Four patients received oral prednisolone, whereas one received intravenous methylprednisolone. Although no significant improvements were observed in MRD1, MRD1 difference, or exophthalmos post-treatment, diplopia resolved in all three patients. Conclusions IOM can present with upper eyelid retraction, emphasizing the importance of differentiating it from thyroid eye disease. TFT, including TSIs, and orbital imaging are essential diagnostic tools. These findings indicate that systemic corticosteroids can effectively manage diplopia associated with IOM, emphasizing the potential benefit of early and aggressive treatment.

Purpose: Although upper eyelid retraction is commonly associated with thyroid eye disease, its etiology remains unclear. This study evaluated the clinical features and treatment outcomes of patients with upper eyelid retraction caused by idiopathic orbital myositis (IOM). Methods: We conducted a retrospective analysis of the medical records of patients who presented with unilateral upper eyelid retraction. IOM was diagnosed based on normal thyroid function tests (TFT), including thyroid-stimulating immunoglobulin (TSI). Orbital imaging demonstrated contrast-enhanced enlargement of the superior rectus-levator palpebrae superioris complex (SR-LC). Pre- and post-systemic steroid treatment, margin-reflex distance 1 (MRD1), MRD1 difference between affected and unaffected eyes, exophthalmos, and diplopia were assessed. Results: In total, five patients (male: 4, female: 1) with a median age of 36.4 years were diagnosed with IOM. Three patients presented with diplopia on upgaze and supraduction limitation. Orbital imaging revealed levator palpebrae superioris muscle enlargement with distinct borders and homogeneous contrast enhancement. All cases with superior rectus enlargement demonstrated tendon involvement. The median duration from symptom onset to treatment initiation was 2.2 months. Four patients received oral prednisolone, whereas one received intravenous methylprednisolone. Although no significant improvements were observed in MRD1, MRD1 difference, or exophthalmos post-treatment, diplopia resolved in all three patients. Conclusions IOM can present with upper eyelid retraction, emphasizing the importance of differentiating it from thyroid eye disease. TFT, including TSIs, and orbital imaging are essential diagnostic tools. These findings indicate that systemic corticosteroids can effectively manage diplopia associated with IOM, emphasizing the potential benefit of early and aggressive treatment.