Background: Preclinical studies have reported anticancer properties of sodium-glucose cotransporter 2 inhibitors (SGLT2is). We aimed to elucidate the association between the use of SGLT2is and the risk of prostate cancer among male patients with type 2 diabetes mellitus (T2DM). Methods: An active-comparator, new-user cohort design using a nationwide database between September 2014 and June 2020 was conducted on 45,601 new SGLT2i users and 205,395 new users of other glucose-lowering medications (oGLMs). In the following 1:1 propensity score matched (PSM) analysis, 35,371 SGLT2i users matched with an equivalent number of oGLM users were assessed. The hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer were calculated. Results: Among the cohort, prostate cancer was diagnosed in 210 out of 45,601 SGLT2i users, corresponding to a cumulative incidence of 1.0%, in contrast to 1,880 cases among 205,395 users of oGLMs, with a cumulative incidence of 1.5%. The use of SGLT2is was significantly correlated with a reduced risk of prostate cancer based on a multivariable-adjusted HR of 0.83 (95% CI, 0.71 to 0.98). PSM analysis affirmed 18% reduction in prostate cancer risk associated with SGLT2i use (HR, 0.82; 95% CI, 0.67 to 0.99). Subgroup analyses revealed that body mass index (BMI) significantly influenced the effect of SGLT2i on prostate cancer risk, with a more pronounced reduction in the subgroup with a BMI <25 kg/m2 (P=0.037). Conclusion The use of SGLT2is in Korean male patients with T2DM is associated with a lower risk of prostate cancer.

Background/Aims: The absence of standardized clinical minimum inhibitory concentration (MIC) breakpoints for Helicobacter pylori infection has resulted in inconsistent resistance definitions, even within the same research group in Korea. Therefore, establishing epidemiological cutoff values (ECOFFs) is essential for standardization. Methods: The MIC distributions for antibiotics commonly used against H. pylori infection in South Korea were analyzed from 2015 to 2023. A total of 5,925 primary H. pylori isolates were collected from five data sources, and MIC values were determined using the serial 2-fold agar dilution method. The ECOFFinder program was used to establish ECOFFs for six antibiotics. Results: The tentative ECOFFs for amoxicillin and clarithromycin were 0.125 μg/mL. The ECOFFs for levofloxacin, metronidazole, and tetracycline were 0.5, 8.0, and 0.25 μg/mL, respec-tively. The ECOFF for rifabutin could not be determined due to insufficient data. On the basis of these ECOFFs, the resistance rate was 17.9% for amoxicillin, 31.9% for clarithromycin, 40.9% for levofloxacin, 24.7% for metronidazole, and 11.5% for tetracycline. Conclusions This comprehensive analysis defined regional antibiotic resistance patterns and established Korea-specific ECOFFs, providing a foundation for determining clinical breakpoints and optimizing H. pylori eradication strategies.

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: Cough is a prominent symptom of chronic respiratory diseases, including asthma, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and bronchiectasis (BE). Some patients develop chronic cough (CC), defined as lasting more than 8 weeks, yet its characteristics remain poorly understood. This study aimed to characterize CC across various chronic respiratory diseases using validated cough assessment tools. Methods: The Cough Assessment in Chronic Respiratory Diseases (COASESS) study, a multicenter, prospective cross-sectional study, was conducted at 10 university hospitals. CC was evaluated in terms of intensity (numeric rating scale [NRS]), frequency (cough symptom score [CSS]), and quality of life (using the cough assessment test [COAT] and Leicester cough questionnaire [LCQ]). Cough hypersensitivity was assessed with the cough hypersensitivity questionnaire (CHQ). Data on age, sex, and smoking status were also collected. Results: Among the 303 enrolled patients, 266 with chronic respiratory diseases were included in the analysis. Patients with asthma were younger, predominantly female, and non-smokers, whereas those with COPD and IPF were older males who had previously smoked (p<0.001). Scores for COAT, LCQ, NRS, and CSS showed significant differences across the diseases, with asthma and IPF patients experiencing a greater symptom burden and lower quality of life compared to those with COPD or BE (p<0.001). Although CHQ total scores were similar across groups, asthma patients more frequently reported triggers such as talking and post-nasal drip. Conclusion This study revealed distinct characteristics of CC across different chronic respiratory diseases. Asthma and IPF were associated with a higher symptom burden, and cough hypersensitivity varied depending on the underlying condition. These findings highlight the necessity for disease-specific assessments and management strategies for CC.

Background: Research on the relationship between the progression of interstitial lung abnormalities (ILA) and serum biomarkers, including white blood cell differential counts and Krebs von den Lungen-6 (KL-6), is limited. This study aimed to examine the clinical characteristics of patients with ILA and evaluate the association between disease progression and serum biomarkers. Methods: This retrospective cohort study analyzed data from 159 patients (63 with ILA and 74 with interstitial lung diseases) between October 2021 and September 2022. Data collected included clinical characteristics, pulmonary function tests, chest computed tomography (CT), complete blood cell counts, and KL-6 levels. In 52 of these patients who had previously undergone chest CT, the utility of serum biomarkers in reflecting radiologic progression was assessed using receiver operating characteristic curve analysis. Results: Patients with ILA exhibited clinical characteristics similar to those with idiopathic pulmonary fibrosis. Serum KL-6 levels did not correlate with forced vital capacity or diffusing capacity of the lung for carbon monoxide in patients with ILA. Among the 52 patients with ILA, 13 demonstrated radiologic progression. Serum KL-6 displayed moderate predictive performance, with area under the curves ranging from 0.57 to 0.89 (p=0.014) for radiologic progression. Levels of KL-6 greater than 400 U/mL were more frequently observed in patients with radiologic progression (61.5% vs. 20.5%, p=0.006). In multivariate analysis, age and KL-6 were independently associated with radiologic progression in patients with ILA. Conclusion Serum KL-6 levels may serve as a potential indicator of ILA progression in asymptomatic patients. Those with KL-6 levels exceeding 400 U/mL should be closely monitored for radiologic progression.

Purpose: Due to chronic toxicity, tacrolimus-sparing is an important issue in kidney transplant recipients (KTRs). Several studies have shown that bisphosphonate use is associated with favorable graft outcomes in KTRs. We investigated whether the association between tacrolimus trough levels (TTLs) and graft outcomes differed according to bisphosphonate use in KTRs. Materials and Methods: We conducted a retrospective study encompassing 1441 KTRs who were administered tacrolimus-based immunosuppressants. The primary exposure was a time-dependent cross-product of TTLs (low TTLs vs. normal-high TTLs with a reference of 6 ng/mL) and bisphosphonate use. Two primary outcomes were evaluated: overall graft loss (death or conversion to kidney replacement) and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 . Results: During the median follow-up of 6.1 (3.4–9.7) years, overall graft loss occurred in 157 (10.9%) patients. Cox regression revealed that normal-high TTLs without bisphosphonate use were associated with a reduced risk of overall graft loss [adjusted hazard ratio (aHR), 0.65; 95% confidence interval (CI), 0.45–0.95] compared to low TTLs without bisphosphonate use. The use of bisphosphonate in conjunction with normal-high TTLs correlated with an even lower risk of overall graft loss (aHR, 0.25; 95% CI, 0.08–0.80) compared with low TTLs without bisphosphonate use. In patients with low TTLs, bisphosphonate use was associated with a reduced risk of overall graft loss compared with non-use (aHR, 0.20; 95% CI, 0.09–0.43). Similar trends were observed in the eGFR outcome. Conclusion The use of bisphosphonate was associated with favorable graft outcomes, even with low TTLs. Incorporating bisphosphonate into a conventional immunosuppressant regimen may potentially reduce tacrolimus requirement.

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.