Objectives: . Obstructive sleep apnea (OSA) is associated with chronic intermittent hypoxia and systemic inflammation, both of which contribute to vascular and metabolic complications. Monocytes, as key immune cells of innate immunity, have been implicated in this inflammatory state. However, the effect of OSA treatment on monocyte function and inflammatory phenotype remains poorly understood. Methods: . In this prospective cohort study, OSA patients were evaluated before and after 3 months of continuous positive airway pressure (CPAP) therapy. Circulating monocytes were isolated, and inflammatory cytokine production (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and IL-6) was assessed at baseline and post-treatment, both at rest and after lipopolysaccharide (LPS) stimulation. Monocyte polarization (M1/M2-like marker expression) was measured by flow cytometry. Clinical severity parameters, including the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI), were correlated with immune changes. Results: . Following CPAP treatment, LPS-induced inflammatory cytokine secretion and LPS responsiveness, defined as the increase in cytokine levels upon stimulation, both declined after CPAP in proportion to baseline ODI, but not AHI. Apart from TNF-α, baseline IL-1β and IL-6 levels were below the quantifiable range of the assay, which precluded reliable comparison after treatment. This effect may be explained by a parallel post-treatment shift in monocyte phenotype toward an anti-inflammatory M2-like (CD163+CD206+) profile, as demonstrated by our flow cytometry data, which was also significantly associated with baseline ODI. Conclusion . CPAP alleviates systemic inflammation in OSA by reducing hypoxic burden and reprogramming monocytes toward an anti-inflammatory phenotype. The magnitude of immune modulation was more closely linked to ODI than AHI, suggesting that oxygen desaturation burden serves as a meaningful adjunct to AHI in assessing monocyte-driven immune dysregulation in OSA.

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/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Purpose: The relationship between tacrolimus intrapatient variability (IPV) and its metabolism-associated singlenucleotide polymorphisms (SNPs) in liver transplantation (LT) remains unclear. Moreover, the influence of donor SNP on recipient IPV is poorly understood. Our objective was to investigate how SNPs affect tacrolimus IPV by analyzing both donor and recipient SNP data in LT. Methods: This retrospective study examined the association between tacrolimus IPV and eight specific SNPs in 50 adult LT recipients and 50 LT donors genotyped for CYP3A5, ABCB1, ABCC2, and POR genes and their SNPs. Recipients were divided into high IPV (≥30) and low IPV (<30) groups based on 3–12 months after LT IPV calculations. Multivariate logistic regression was used to identify risk factors for high IPV. Post-LT long-term outcomes were also compared between the groups. Results: Two SNPs were significantly associated with high IPV in multivariate analysis. Recipient ABCB1 1236C>T genotypes CT and CC (odds ratio [OR], 13.969; 95% confidence interval [CI], 1.738–112.300; P = 0.013), donors’ CYP3A5 6986A>G genotypes GA and GG (OR, 4.390; 95% CI, 1.005–19.178; P = 0.049), and glucose ≥120 mg/dL at 3 months (OR, 6.494; 95% CI, 1.300–32.168; P = 0.024) were associated with high IPV. However, post-LT long-term outcomes were similar between the groups. Conclusion SNPs of donor CYP3A5 and recipient ABCB1 can significantly influence tacrolimus IPV in patients undergoing living donor LT. Identifying these SNPs can help determine high IPV-prone patients, facilitate close monitoring of high IPVsusceptible groups, and improve outcomes.

Objectives: . This study evaluates the enduring efficacy and patient satisfaction of dupilumab with interdose interval adjustments based on the Sino-Nasal Outcome Test (SNOT-22) in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: . A retrospective analysis was conducted on 44 patients who had been treated with dupilumab for over 6 months. This study targeted individuals diagnosed with CRSwNP according to the 2020 edition of the European Position Paper on Rhinosinusitis and Nasal Polyps Criteria. The treatment involved an add-on dupilumab regimen, where the interdose interval was adjusted based on the SNOT-22 scores. Dosage adjustments were made such that patients with initial SNOT-22 scores greater than 40 were tapered to a target level of 20 or less. Similarly, for patients with initial scores of 40 or less, the treatment aimed for an improvement of 50% or more. At each visit, the effectiveness of the treatment was evaluated using SNOT-22, nasal polyp scores (NPS), and a subjective satisfaction questionnaire adapted from the Treatment Satisfaction Questionnaire for Medication (TSQM v.1.4). Results: . The adjustment of the interdose interval for dupilumab based on SNOT-22 scores demonstrated sustained improvements in patients’ subjective symptoms, satisfaction, and NPS. The mean (standard deviation) SNOT-22 scores significantly decreased from 46.04 (22.30) to 14.72 (13.66) over 6 months (P<0.001). Similarly, NPS scores improved from 3.20 (2.24) to 1.72 (1.46) within the same period (P<0.001). Satisfaction scores, ranging from 0 to 5, consistently remained above 3.5 for up to 6 months (P=0.166). Additionally, there was a significant correlation between the improvement in the nasal symptom domain of the SNOT-22 scores and higher satisfaction scores. Conclusion . Adjusting dupilumab dosing intervals based on SNOT-22 scores from the outset resulted in sustained efficacy and patient satisfaction in Korean patients with CRSwNP. This approach will meaningfully assist clinicians in determining the optimal dupilumab dosing interval.

Objectives: . This study evaluates the enduring efficacy and patient satisfaction of dupilumab with interdose interval adjustments based on the Sino-Nasal Outcome Test (SNOT-22) in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: . A retrospective analysis was conducted on 44 patients who had been treated with dupilumab for over 6 months. This study targeted individuals diagnosed with CRSwNP according to the 2020 edition of the European Position Paper on Rhinosinusitis and Nasal Polyps Criteria. The treatment involved an add-on dupilumab regimen, where the interdose interval was adjusted based on the SNOT-22 scores. Dosage adjustments were made such that patients with initial SNOT-22 scores greater than 40 were tapered to a target level of 20 or less. Similarly, for patients with initial scores of 40 or less, the treatment aimed for an improvement of 50% or more. At each visit, the effectiveness of the treatment was evaluated using SNOT-22, nasal polyp scores (NPS), and a subjective satisfaction questionnaire adapted from the Treatment Satisfaction Questionnaire for Medication (TSQM v.1.4). Results: . The adjustment of the interdose interval for dupilumab based on SNOT-22 scores demonstrated sustained improvements in patients’ subjective symptoms, satisfaction, and NPS. The mean (standard deviation) SNOT-22 scores significantly decreased from 46.04 (22.30) to 14.72 (13.66) over 6 months (P<0.001). Similarly, NPS scores improved from 3.20 (2.24) to 1.72 (1.46) within the same period (P<0.001). Satisfaction scores, ranging from 0 to 5, consistently remained above 3.5 for up to 6 months (P=0.166). Additionally, there was a significant correlation between the improvement in the nasal symptom domain of the SNOT-22 scores and higher satisfaction scores. Conclusion . Adjusting dupilumab dosing intervals based on SNOT-22 scores from the outset resulted in sustained efficacy and patient satisfaction in Korean patients with CRSwNP. This approach will meaningfully assist clinicians in determining the optimal dupilumab dosing interval.

Purpose: Few studies have investigated the association between smoking and microvascular complications in the Asian population with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between smoking status and microvascular complications in Korean patients with T2DM. Materials and Methods: From the Korean National Diabetes Program cohort, we included 2316 Korean male with T2DM who had baseline clinical information available, including their smoking status, and underwent diabetic complication studies. Results: Compared to non-smokers, current smokers had higher odds of any-microvascular complications [adjusted odds ratio (aOR) 1.45, 95% confidence interval (CI) 1.07–1.97, p=0.016]. The odds of neuropathy were significantly higher; however, the odds of retinopathy were significantly lower in current smokers than in nonsmokers (all p<0.05). Among those who underwent repeated complication tests after 3 years, the risk of newly developed retinopathy was significantly increased in ex-smokers [aOR 3.77 (95% CI 1.61–8.87), p=0.002]. Within ex-smokers, long smoking duration and smoking cessation within the recent 5 years were associated with an increased risk of newly developed retinopathy (all p<0.05). Conclusion Male smokers had higher odds of having overall diabetic microvascular complications, including neuropathy. However, the odds of having retinopathy were significantly lower among current smokers. More attention and research are needed regarding the increased risk of retinopathy development in ex-smokers who have recently stopped smoking after a long history of smoking.

Objectives: . This study evaluates the enduring efficacy and patient satisfaction of dupilumab with interdose interval adjustments based on the Sino-Nasal Outcome Test (SNOT-22) in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: . A retrospective analysis was conducted on 44 patients who had been treated with dupilumab for over 6 months. This study targeted individuals diagnosed with CRSwNP according to the 2020 edition of the European Position Paper on Rhinosinusitis and Nasal Polyps Criteria. The treatment involved an add-on dupilumab regimen, where the interdose interval was adjusted based on the SNOT-22 scores. Dosage adjustments were made such that patients with initial SNOT-22 scores greater than 40 were tapered to a target level of 20 or less. Similarly, for patients with initial scores of 40 or less, the treatment aimed for an improvement of 50% or more. At each visit, the effectiveness of the treatment was evaluated using SNOT-22, nasal polyp scores (NPS), and a subjective satisfaction questionnaire adapted from the Treatment Satisfaction Questionnaire for Medication (TSQM v.1.4). Results: . The adjustment of the interdose interval for dupilumab based on SNOT-22 scores demonstrated sustained improvements in patients’ subjective symptoms, satisfaction, and NPS. The mean (standard deviation) SNOT-22 scores significantly decreased from 46.04 (22.30) to 14.72 (13.66) over 6 months (P<0.001). Similarly, NPS scores improved from 3.20 (2.24) to 1.72 (1.46) within the same period (P<0.001). Satisfaction scores, ranging from 0 to 5, consistently remained above 3.5 for up to 6 months (P=0.166). Additionally, there was a significant correlation between the improvement in the nasal symptom domain of the SNOT-22 scores and higher satisfaction scores. Conclusion . Adjusting dupilumab dosing intervals based on SNOT-22 scores from the outset resulted in sustained efficacy and patient satisfaction in Korean patients with CRSwNP. This approach will meaningfully assist clinicians in determining the optimal dupilumab dosing interval.