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.

Composite gangliocytomaeuroma and neuroendocrine tumors (CoGNETs) are extremely rare periampullary neoplasms composed of neuroendocrine epithelial, Schwannian spindle, and ganglion cells. Although endoscopic papillectomy or surgery have been used to treat ampullary CoGNETs, underwater endoscopic mucosal resection (UEMR) for periampullary lesions has not been previously described. In this study, we present a case of a 53-year-old man referred to our hospital with an incidentally detected subepithelial tumor in the second portion of the duodenum. Endoscopic ultrasound revealed a 13×10-mm homogeneous, hypoechoic, and well-demarcated submucosal mass. UEMR was performed under conscious sedation without submucosal injection, achieving safe en bloc resection within 12 min. Histopathology revealed a 2.0×1.5×1.2-cm lesion composed of mixed neuroendocrine epithelial, Schwannian spindle, and ganglion cells. Immunohistochemical staining was positive for chromogranin A, synaptophysin, CD56, neuron-specific enolase, and S-100, confirming CoGNET with a Ki-67 index of <1% and no lymphovascular or perineural invasion. Follow-up endoscopy 3 months later revealed only a post-resection scar without residual or recurrent tumors. This appears to be the first reported case of periampullary CoGNET successfully treated with UEMR. Therefore, UEMR might represent a safe and effective therapeutic option for selected periampullary subepithelial tumors.

Objective: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Methods: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Results: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Conclusion Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Purpose: The objective of this study was to investigate the change in near visual function after the administration of oral silodosin to patients with lower urinary tract symptoms (LUTS). Methods: This prospective study included treatment-naive patients who were scheduled to start treatment with silodosin for LUTS. A comprehensive ophthalmological evaluation including the near vision and the automated pupillometry was performed at baseline and after 3 months of silodosin treatment. For subjective assessment of near visual ability and satisfaction, a Near Activity Visual Questionnaire-10 (NAVQ-10) was also used at the same time (higher scores indicating worse quality). Results: Of 23 patients enrolled in this study, 15 continued with silodosin (8 mg once daily) treatment for 3 months and completed a follow-up evaluation. The mean age of participants was 60.4±8.4 years. Distant visual acuity and spherical error were unchanged after silodosin treatment. However, near vision acuity (logMAR) was improved after treatment (right, 0.47±0.36 vs. 0.38±0.39, P=0.018; left, 0.41±0.37 vs. 0.31±0.34, P=0.068; both, 0.27±0.26 vs. 0.21±0.27, P=0.043). Pupil size under room light decreased significantly in both eyes (right, 3.77±0.60 vs. 3.16±0.58, P=0.001; left, 3.72±0.80 vs. 3.21±0.75, P=0.002). The Rasch scale at NAVQ-10 improved from 54.7±9.9 to 48.5±11.2 (P=0.004). Conclusions This preliminary study demonstrated that highly selective alpha-1A adrenergic receptor antagonists such as silodosin improve near visual acuity and quality in patients with LUTS/benign prostatic hyperplasia. Decrease in pupil size caused by inhibition of adrenergic alpha 1 mediated contraction of iris dilator muscle is a possible mechanism underlying improved near vision.

Urinary tract infections (UTIs) are the most common infectious disease and are mainly caused by Escherichia coli. In this review, we introduce the current concept of recurrent UTI (rUTI) based on recent research dealing with pathophysiology of the disease. Although urine is considered sterile, recent studies dealing with microbiome have proposed different ideas. UTIs have typically been considered as extracellular infections, but recently, uropathogenic Escherichia coli (UPEC) has been shown to bind and replicate in the urothelium to make intracellular bacterial communities. Binding UPECs might proceed in many ways including extracellular expulsion for clearance or survival and quiescent intracellular reservoirs that can cause rUTI. Moreover, it is also suggested that other important factors, such as lipopolysaccharide and multimicrobial infection, can be the cause of rUTI. This review article reveals a key mechanism of recurrence and discusses what makes a pathway of resolution or recurrence in a host after initial infection.

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: The objective of this study was to investigate the change in near visual function after the administration of oral silodosin to patients with lower urinary tract symptoms (LUTS). Methods: This prospective study included treatment-naive patients who were scheduled to start treatment with silodosin for LUTS. A comprehensive ophthalmological evaluation including the near vision and the automated pupillometry was performed at baseline and after 3 months of silodosin treatment. For subjective assessment of near visual ability and satisfaction, a Near Activity Visual Questionnaire-10 (NAVQ-10) was also used at the same time (higher scores indicating worse quality). Results: Of 23 patients enrolled in this study, 15 continued with silodosin (8 mg once daily) treatment for 3 months and completed a follow-up evaluation. The mean age of participants was 60.4±8.4 years. Distant visual acuity and spherical error were unchanged after silodosin treatment. However, near vision acuity (logMAR) was improved after treatment (right, 0.47±0.36 vs. 0.38±0.39, P=0.018; left, 0.41±0.37 vs. 0.31±0.34, P=0.068; both, 0.27±0.26 vs. 0.21±0.27, P=0.043). Pupil size under room light decreased significantly in both eyes (right, 3.77±0.60 vs. 3.16±0.58, P=0.001; left, 3.72±0.80 vs. 3.21±0.75, P=0.002). The Rasch scale at NAVQ-10 improved from 54.7±9.9 to 48.5±11.2 (P=0.004). Conclusions This preliminary study demonstrated that highly selective alpha-1A adrenergic receptor antagonists such as silodosin improve near visual acuity and quality in patients with LUTS/benign prostatic hyperplasia. Decrease in pupil size caused by inhibition of adrenergic alpha 1 mediated contraction of iris dilator muscle is a possible mechanism underlying improved near vision.

Urinary tract infections (UTIs) are the most common infectious disease and are mainly caused by Escherichia coli. In this review, we introduce the current concept of recurrent UTI (rUTI) based on recent research dealing with pathophysiology of the disease. Although urine is considered sterile, recent studies dealing with microbiome have proposed different ideas. UTIs have typically been considered as extracellular infections, but recently, uropathogenic Escherichia coli (UPEC) has been shown to bind and replicate in the urothelium to make intracellular bacterial communities. Binding UPECs might proceed in many ways including extracellular expulsion for clearance or survival and quiescent intracellular reservoirs that can cause rUTI. Moreover, it is also suggested that other important factors, such as lipopolysaccharide and multimicrobial infection, can be the cause of rUTI. This review article reveals a key mechanism of recurrence and discusses what makes a pathway of resolution or recurrence in a host after initial infection.

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.