Background: Patients with septic shock frequently require tracheal intubation in the emergency department (ED). However, the criteria for tracheal intubation are subjective, based on physician experience, or require serial evaluations over relatively long intervals to make accurate predictions, which might not be feasible in the ED. We used supervised learning approaches and features routinely available during the initial stages of evaluation and resuscitation to stratify the risks of tracheal intubation within a 24-hour time window. Methods: We retrospectively analyzed the data of patients diagnosed with septic shock based on the SEPSIS-3 criteria across 21 university hospital EDs in the Republic of Korea. A principal component analysis revealed a complex, non-linear decision boundary with respect to the application of tracheal intubation within a 24-hour time window. Stratified five-fold cross validation and a grid search were used with extreme gradient boost. Shapley values were calculated to explain feature importance and preferences. Results: In total, data for 4,762 patients were analyzed; within that population, 1,486 (31%) were intubated within a 24-hour window, and 3,276 (69%) were not. The area under the receiver operating characteristic curve and F1 scores for intubation within a 24-hour window were 0.829 (95% CI, 0.801–0.878) and 0.654 (95% CI, 0.627–0.681), respectively. The Shapley values identified lactate level after initial fluids, suspected lung infection, initial pH, Sequential Organ Failure Assessment score at enrollment, and respiratory rate at enrollment as important features for prediction. Conclusions An extreme gradient boosting machine can moderately discriminate whether intubation is warranted within 24 hours of the recognition of septic shock in the ED.

Purpose: This study aimed to describe adult living donor liver transplantation (LDLT) for acute liver failure and evaluate its clinical significance by comparing its surgical and survival outcomes with those of deceased donor liver transplantation (DDLT). Methods: We retrospectively reviewed the medical records of 267 consecutive patients (161 LDLT recipients and 106 DDLT recipients) aged 18 years or older who underwent liver transplantation between January 2006 and December 2020. Results: The mean periods from hepatic encephalopathy to liver transplantation were 5.85 days and 8.35 days for LDLT and DDLT, respectively (P = 0.091). Among these patients, 121 (45.3%) had grade III or IV hepatic encephalopathy (living, 34.8% vs. deceased, 61.3%; P < 0.001), and 38 (14.2%) had brain edema (living, 16.1% vs. deceased, 11.3%; P = 0.269) before liver transplantation. There were no significant differences in in-hospital mortality (living, 11.8% vs. deceased, 15.1%; P = 0.435), 10-year overall survival (living, 90.8% vs. deceased, 84.0%; P = 0.096), and graft survival (living, 83.5% vs. deceased, 71.3%;P = 0.051). However, postoperatively, the mean intensive care unit stay was shorter in the LDLT group (5.0 days vs. 9.5 days, P < 0.001). In-hospital mortality was associated with vasopressor use (odds ratio [OR], 3.40; 95% confidence interval [CI], 1.45–7.96; P = 0.005) and brain edema (OR, 2.75; 95% CI, 1.16–6.52; P = 0.022) of recipient at the time of transplantation. However, LDLT (OR, 1.26; 95% CI, 0.59–2.66; P = 0.553) was not independently associated with in-hospital mortality. Conclusion LDLT is feasible for acute liver failure when organs from deceased donors are not available.

Background/Aims: We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. Methods: A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)–28– erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). Results: Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. Conclusions Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

Purpose: Studies have yielded contradictory results on whether donor sex and donor-recipient sex disparity affect hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT). The present study assessed whether donor sex or donor-recipient sex disparity affects HCC recurrence after LDLT at a high-volume center. Methods: This study included 772 HCC patients who underwent LDLT between January 2006 and December 2015 at Asan Medical Center. Patients were divided into 4 groups based on the sex of the donor and recipient: male-to-male (n = 490, 63.5%), male-to-female (n = 75, 9.7%), female-to-male (n = 170, 22.0%), and female-to-female (n = 37, 4.8%). Results: Disease-free survival (DFS; P = 0.372) and overall survival (OS; P = 0.591) did not differ significantly among the 4 groups. DFS also did not differ significantly between LDLT recipients with male and female donors (P = 0.792) or between male and female recipients (P = 0.084). After patient matching with an α-FP/des-γ-carboxy prothrombin/tumor volume score cutoff of 5logs, donor-recipient sex disparity did not significantly affect DFS (P = 0.598) or OS (P = 0.777). There were also no differences in DFS in matched LDLT recipients with male and female donors (P = 0.312) or between male and female recipients (P = 0.374). Conclusion Neither donor sex nor donor-recipient sex disparity significantly affected posttransplant HCC recurrence.

Purpose: DA-8010 is a novel muscarinic M3 receptor antagonist with significant selectivity for bladder over salivary gland in preclinical studies. We evaluated the clinical efficacy and safety of DA-8010 in overactive bladder (OAB) patients. Methods: This phase 2, randomized, double-blind, parallel-group, active reference- and placebo-controlled trial was conducted at 12 centers in South Korea (NCT03566134). Patients aged ≥19 years with OAB symptoms for ≥3 months were enrolled. Three hundred six patients (30.07% male) were randomized to 12 weeks of treatment among 4 groups; 2 experimental groups (DA-8010 2.5 or 5 mg), an active reference group (solifenacin 5 mg), and a placebo group. The change from the baseline of (=∆) 24-hour frequency at 12 weeks (primary endpoint), episodes of urgency, overall/urgency urinary incontinence, average/ maximum voided volume, nocturia, and patients’ subjective responses were analyzed. Results: In the full analysis set, the mean (standard deviation) [median] values for ∆ 24-hour frequency at 12 weeks were -1.01 (2.44) [-1.33] for placebo, -1.22 (2.05) [-1.33] for DA-8010 2.5 mg, and -1.67 (2.25) [-1.67] for DA-8010 5 mg; DA-8010 5 mg showed a significant decrease compared with placebo (P=0.0413). At 4 and 8 weeks, both DA-8010 2.5 mg (P=0.0391 at 4 weeks, P=0.0335 at 8 weeks) and DA-8010 5 mg (P=0.0001 at 4 weeks, P=0.0210 at 8 weeks) showed significant decrease in ∆ 24-hour frequency compared with placebo. DA-8010 5 mg achieved a significant decrease in ∆ number of urgency episodes, compared with placebo at 4 (P=0.0278) and 8 (P=0.0092) weeks. Adverse drug reactions (ADRs) were observed in 3.95% of placebo, 6.67% of DA-8010 2.5 mg, 18.42% of DA-8010 5 mg, and 17.33% of solifenacin 5 mg groups. No serious ADRs were observed in any patient. Conclusions Both DA-8010 2.5 mg and 5 mg showed therapeutic efficacy for OAB without serious ADRs. Therefore, both dosages of DA-8010 can advance to a subsequent large-scale phase 3 trial.

Purpose: Most of the causes of small bowel obstruction (SBO) in patients without a history of abdominal surgery are unclear at initial assessment. This study was conducted to identify the etiology and clinical characteristics of SBO in virgin abdomens and discuss the proper management. Methods: A retrospective review involving operative cases of SBO from a single institute, which had no history of abdominal surgery, was conducted between January 2010 and December 2020. Clinical information, including radiological, operative, and pathologic findings, was investigated to determine the etiology of SBO. Results: A total of 55 patients were included in this study, with a median age of 57 years and male sex (63.6%) constituting the majority. The most frequently reported symptoms were abdominal pain and nausea or vomiting. Neoplasm as an underlying cause accounted for 34.5% of the cases, of which 25.5% were malignant cases. In patients aged ≥60 years (n=23), small bowel neoplasms were the underlying cause in 12 (52.2%), of whom 9 (39.1%) were malignant cases. Adhesions and Crohn disease were more frequent in patients aged <60 years. Coherence between preoperative computed tomography scans and intraoperative findings was found in 63.6% of the cases. Conclusion There were various causes of surgical cases of SBO in virgin abdomens. In older patients, hidden malignancy should be considered as a possible cause of SBO in a virgin abdomen. Patients with symptoms of recurrent bowel obstruction who have no history of prior abdominal surgery require thorough medical history and close follow-up.

Purpose: When splitting a liver for adult and pediatric graft recipients, the retained left medial section (S4) will undergo ischemic necrosis and the right trisection graft becomes an extended right liver (ERL) graft. We investigated the fates of the retained S4 and its prognostic impact in adult split liver transplantation (SLT) using an ERL graft. Methods: This was a retrospective analysis of 25 adult SLT recipients who received split ERL grafts. Results: The mean model for end-stage liver disease (MELD) score was 27.3 ± 10.9 and graft-recipient weight ratio (GRWR) was 1.98 ± 0.44. The mean donor age was 26.5 ± 7.7 years. The split ERL graft weight was 1,181.5 ± 252.8 g, which resulted in a mean GRWR of 1.98 ± 0.44. Computed tomography of the retained S4 parenchyma revealed small ischemic necrosis in 16 patients (64.0%) and large ischemic necrosis in the remaining 9 patients (36.0%). No S4-associated biliary complications were developed. The mean GRWR was 1.87 ± 0.43 in the 9 patients with large ischemic necrosis and 2.10 ± 0.44 in the 15 cases with small ischemic necrosis (P = 0.283). The retained S4 parenchyma showed gradual atrophy on follow-up imaging studies. The amount of S4 ischemic necrosis was not associated with graft (P = 0.592) or patient (P = 0.243) survival. A MELD score of >30 and pretransplant ventilator support were associated with inferior outcomes. Conclusion The amount of S4 ischemic necrosis is not a prognostic factor in adult SLT recipients, probably due to a sufficiently large GRWR.

Purpose: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) has wide histologic diversity. This study investigated the effects of cHCC-CC histology, according to the 2010 World Health Organization (WHO) classification, on patient prognosis. Methods: The medical records of patients who underwent surgical resection for cHCC-CC at our institution between July 2012 and June 2019 were retrospectively evaluated. Results: During the study period, 168 patients, 122 males (72.6%) and 46 females (27.4%), underwent surgical resection for cHCC-CC, including 159 patients (94.6%) who underwent R0 resection. Mean tumor diameter was 4.4 ± 2.8 cm, and 161 patients (95.8%) had solitary tumors. Histologically, 86 patients (51.2%) had classical type, and 82 (48.8%) had tumors with stem cell (SC) features, including 33 (19.6%) with intermediate-cell and 23 (13.7%) each with typical SC and cholangiolocellular features; 3 tumors (1.8%) were unclassifiable. At 1, 3, and 5 years, tumor recurrence rates were 31.9%, 49.6%, and 58.1%, respectively, and patient survival rates were 91.0%, 70.2%, and 60.3%, respectively. Univariate analysis showed that tumor size of >5 cm, microscopic and macroscopic vascular invasion, lymph node metastasis, 8th edition of the American Joint Committee on Cancer (AJCC) tumor stage, and 2010 WHO classification were significantly prognostic. Multivariate analysis showed that the 8th AJCC tumor stage and 2010 WHO histologic classification were independently prognostic for tumor recurrence and patient survival. There were no significant prognostic differences among the 3 SC subtypes. Conclusion Postresection outcomes are better in patients with SC-type than with classical-type cHCC-CC.

Background: Although long-term dopamine agonist (DA) therapy is recommended as a first-line treatment for prolactinoma, some patients may prefer surgical treatment because of the potential adverse effects of long-term medication, or the desire to become pregnant. This study aimed to determine whether surgical treatment of prolactinomas could be an alternative to DA therapy. Methods: In this retrospective study, 96 consecutive patients (74 female, 22 male) underwent primary pituitary surgery without long-term DA treatment for prolactinomas at a single institution from 1990 to 2010. All patients underwent primary surgical treatment in the microscopic transsphenoidal approach (TSA). Results: The median age and median follow-up period were 31 (16–73) years and 139.1 (12.2–319.6) months, respectively. An initial overall remission was accomplished in 47.9% (46 of 96 patients, 33 macroadenomas, and 13 microadenomas) of patients. DA dose reduction was achieved in all patients after TSA. A better remission rate was independently predicted by lower diagnostic prolactin levels and by a greater extent of surgical resection. Overall remission at the last follow-up was 33.3%, and the overall recurrence rate was 30.4%. The permanent complication rate was 3.1%, and there was no mortality. Conclusion TSA can be considered a safe and potentially curative treatment for selective microprolactinomas as an alternative to treatment with a long-term DA.

Background/Aims: Multiplication of α-fetoprotein, des-γ-carboxy prothrombin, and tumor volume (ADV score) is a surrogate marker for post-resection prognosis of hepatocellular carcinoma (HCC). This study aimed to validate the predictive power of the ADV score-based prognostic prediction model for patients with solitary huge HCC. Methods: Of 3,018 patients, 100 patients who underwent hepatic resection for solitary HCC ≥13 cm between 2008 and 2012 were selected. Results: The median tumor diameter and tumor volume were 15.0 cm and 886 mL, respectively. Tumor recurrence and overall survival (OS) rates were 70.7% and 66.0% at one year and 84.9% and 34.0% at five years, respectively. Microvascular invasion (MVI) was the only independent risk factor for disease-free survival (DFS) and OS. DFS and OS, stratified by ADV score with 1-log intervals, showed significant prognostic contrasts (P=0.007 and P=0.017, respectively). DFS and OS, stratified by ADV score with a cut-off of 8-log, showed significant prognostic contrasts (P=0.014 and P=0.042, respectively). The combination of MVI and ADV score with a cut-off of 8-log also showed significant prognostic contrasts in DFS (P<0.001) and OS (P=0.001) considering the number of risk factors. Prognostic contrast was enhanced after combining the MVI and ADV score. Conclusions The prognostic prediction model with the ADV score could reliably predict the risk of tumor recurrence and long-term patient survival outcomes in patients with solitary huge HCC ≥13 cm. The results of this study suggest that our prognostic prediction models can be used to guide surgical treatment and post-resection follow-up for patients with huge HCCs.