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.

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.

Cardiovascular disease is an important risk factor for mortality among kidney transplant recipients. In this study, we aimed to investigate the association between cardiovascular risk score at kidney transplantation and long-term outcomes of patients. Methods: In this prospective, observational cohort study, we enrolled kidney transplant recipients who participated in the Korean Organ Transplantation Registry and underwent transplantation between April 2014 and December 2019. The cardiovascular risk status of kidney transplant recipients was assessed using the Framingham risk score. All-cause mortality, major adverse cardiovascular events, allograft failure, estimated glomerular filtration rates (eGFRs), and composite outcomes were evaluated after kidney transplantation. Results: Of the 4,682 kidney transplant recipients, 96 died during 30.7 ± 19.1 months of follow-up. The Kaplan-Meier survival analysis results showed that high Framingham risk scores were associated with all-cause mortality, major adverse cardiovascular events, and composite outcomes. According to the multivariable Cox analysis, high Framingham risk scores were associated with an increased risk of mortality (hazard ratio [HR], 3.20; 95% confidence interval [CI], 1.30–7.91), major adverse cardiovascular events (HR, 8.43; 95% CI, 2.41–29.52), and composite outcomes (HR, 2.05; 95% CI, 1.19–3.46). The eGFRs after transplantation were significantly higher among patients in the low Framingham risk score group (p < 0.001). However, Framingham risk scores were not associated with graft loss or rapid decline in eGFRs. Conclusion: The Framingham risk score is a useful indicator of cardiovascular events, mortality, and kidney function after kidney transplantation.

Background and Objectives: Until now, apical hypertrophic cardiomyopathy (HCM) has been considered to have a benign prognosis in terms of cardiovascular mortality. The prevalence of sudden cardiac arrest and the current status of implantable cardioverter-defibrillator (ICD) implantations in patients with apical HCM remain to be elucidated. Methods: Between July 2001 and May 2021, 96 HCM patients who had undergone ICD implantations from 3 tertiary hospitals were reviewed. We evaluated the prevalence of apical HCM and the indication for an ICD implantation. Results: Fifteen patients (15.6%) had apical HCM and 81 (84.4%) the non-apical type including septal (n = 56) and diffuse (n = 25) types, respectively. Sixty-four patients (66.7%) received ICD implantations for primary prevention and 32 (33.3%) for secondary prevention.Among those with apical HCM, 7 patients (46.7%) presented with an aborted sudden cardiac death or documented ventricular fibrillation, therefore, they received ICD implantations for secondary prevention. The proportion of secondary prevention ICD implantations did not significantly differ between apical and non-apical HCM subtypes (46.7% [7/15] vs. 30.9% [25/81], P = 0.233). Conclusions The proportion of secondary prevention ICD implantations did not differ significantly by HCM subtype. ICD implantations should be considered for high-risk patients with apical HCM.

Objective: This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). Methods: We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women.In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load. Results: A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (−98.61%; 95% confidence interval=−99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed. Conclusion The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads.

Objective: This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). Methods: We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women.In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load. Results: A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (−98.61%; 95% confidence interval=−99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed. Conclusion The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads.

Objective: This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). Methods: We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women.In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load. Results: A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (−98.61%; 95% confidence interval=−99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed. Conclusion The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads.

Objectives: This study aimed to analyze the treatment outcomes and to evaluate the clinicopathological prognostic factors of oral tongue cancer. Patients and Methods: We retrospectively analyzed treatment results and prognostic factors in 205 patients with oral tongue squamous cell carcinoma who were admitted to the National Cancer Center, South Korea, between January 2001 and December 2020. The patients were treated with surgery and postoperative, definitive radiotherapy (RT) or chemoradiotherapy (CRT). Results: Eighteen patients (8.8%) were treated with curative RT or CRT, while the rest (91.2%) were treated with surgery with or without postoperative RT or CRT. The median follow-up period was 30 months (range, 0-234 months). The 5-year overall survival (OS) and 5-year disease-free survival (DFS) were 72% and 63%, respectively. Multivariate analysis revealed that a positive neck nodal status (N1, N2-3) was significantly associated with poorer 5-year OS and DFS, while perineural invasion was associated with poorer 5-year DFS. Conclusion Cervical metastasis and perineural invasion are significant prognostic predictors, and combination treatments are necessary for improving OS and DFS in patients with these factors.

Activated phosphoinositide 3-kinase δ syndrome (APDS)1 is caused by gain-of-function mutations in PIK3CD, which encodes the catalytic p110δ subunit of phosphoinositide 3 kinase. We describe three patients with APDS1, the first thereof in Korea. Therein, we investigated clinical manifestations of APDS1 and collected data on the efficacy and safety profile of sirolimus, a mammalian target of rapamycin inhibitor and pathway-specific targeted medicine. The same heterozygous PIK3CD mutation was detected in all three patients (E1021K). After genetic diagnosis, all patients received sirolimus and experienced an excellent response, including amelioration of lymphoproliferation and improvement of nodular mucosal lymphoid hyperplasia in the gastrointestinal tract. The median trough level of sirolimus was 5.5 ng/mL (range, 2.8–7.5) at a dose of 2.6–3.6 mg/m2. Two patients who needed highdose, short-interval, immunoglobulin-replacement treatment (IGRT) had a reduced requirement for IGRT after initiating sirolimus, and the dosing interval was extended from 2 and 3 weeks to 4 weeks. The IgG trough level after sirolimus treatment (median, 594 mg/dL; range, 332–799 mg/dL) was significantly higher than that before sirolimus treatment (median, 290 mg/dL; range, 163–346 mg/dL) (p<0.001). One episode of elevated serum creatinine with a surge of sirolimus (Patient 2) and episodes of neutropenia and oral stomatitis (Patient 1) were observed. We diagnosed the first three patients with APDS1 in Korea. Low-dose sirolimus may alleviate clinical manifestations thereof, including hypogammaglobulinemia.

Objective: To investigate the distribution, side involvement, phenotype, and associated anomalies of Korean patients with craniofacial clefts (CFC). Methods: The samples consisted of 38 CFC patients, who were treated at Seoul National University Dental Hospital during 1998–2018. The Tessier cleft type, sex, side involvement, phenotype, and associated anomalies were investigated using nonparametric statistical analysis. Results: The three most common types were #7 cleft, followed by #0 cleft and #14 cleft. There was no difference between the frequency of male and female. Patients with #0 cleft exhibited nasal deformity, bony defect, and missing teeth in the premaxilla, midline cleft lip, and eye problems. A patient with #3 cleft (unilateral type) exhibited bilateral cleft lip and alveolus. All patients with #4 cleft were the bilateral type, including a combination of #3 and #4 clefts, and had multiple missing teeth. A patient with #5 cleft (unilateral type) had a posterior openbite. In patients with #7 cleft, the unilateral type was more prevalent than the bilateral type (87.0% vs. 13.0%, p < 0.001). Sixteen patients showed hemifacial microsomia (HFM), Goldenhar syndrome, and unilateral cleft lip and palate (UCLP). There was a significant match in the side involvement of #7 cleft and HFM (87.5%, p < 0.01). Patients with #14 cleft had plagiocephaly, UCLP, or hyperterorbitism. A patient with #30 cleft exhibited tongue tie and missing tooth. Conclusions Due to the diverse associated craniofacial anomalies in patients with CFC, a multidisciplinary approach involving a well-experienced cooperative team is mandatory for these patients.