Background: Bladder cancer is characterized by frequent mutations, which provide potential therapeutic targets for most patients. The effectiveness of emerging personalized therapies depends on an accurate molecular diagnosis, for which the accurate estimation of the neoplastic cell percentage (NCP) is a crucial initial step. However, the established method for determining the NCP, manual counting by a pathologist, is time-consuming and not easily executable. Methods: To address this, artificial intelligence (AI) models were developed to estimate the NCP using nine convolutional neural networks and the scanned images of 39 cases of urinary tract cancer. The performance of the AI models was compared to that of six pathologists for 119 cases in the validation cohort. The ground truth value was obtained through multiplexed immunofluorescence. The AI model was then applied to 41 cases in the application cohort that underwent next-generation sequencing testing, and its impact on the copy number variation (CNV) was analyzed. Results: Each AI model demonstrated high reliability, with intraclass correlation coefficients (ICCs) ranging from 0.82 to 0.88. These values were comparable or better to those of pathologists, whose ICCs ranged from 0.78 to 0.91 in urothelial carcinoma cases, both with and without divergent differentiation/ subtypes. After applying AI-driven NCP, 190 CNV (24.2%) were reclassified with 66 (8.4%) and 78 (9.9%) moved to amplification and loss, respectively, from neutral/minor CNV. The neutral/minor CNV proportion decreased by 6%. Conclusions These results suggest that AI models could assist human pathologists in repetitive and cumbersome NCP calculations.

Acquired fluconazole resistance (FR) in bloodstream infection (BSI) isolates of Candida albicans is rare. We investigated the FR mechanisms and clinical features of 14 fluconazole non-susceptible (FNS; FR and fluconazole-susceptible dose-dependent) BSI isolates of C. albicans recovered from Korean multicenter surveillance studies during 2006–2021. Mutations causing amino acid substitutions (AASs) in the drug-target gene ERG11 and the FR-associated transcription factor genes TAC1 , MRR1, and UPC2 of the 14 FNS isolates were compared with those of 12 fluconazole-susceptible isolates. Of the 14 FNS isolates, eight and seven had Erg11p (K143R, F145L, or G464S) and Tac1p (T225A, R673L, A736T, or A736V) AASs, respectively, which were previously described in FR isolates. Novel Erg11p, Tac1p, and Mrr1p AASs were observed in two, four, and one FNS isolates, respectively. Combined Erg11p and Tac1p AASs were observed in seven FNS isolates. None of the FR-associated Upc2p AASs were detected. Of the 14 patients, only one had previous azole exposure, and the 30-day mortality rate was 57.1% (8/14). Our data show that Erg11p and Tac1p AASs are likely to contribute to FR in C. albicans BSI isolates in Korea and that most FNS C. albicans BSIs develop without azole exposure.

The correct identification of filamentous fungi is challenging. We evaluated the performance of the VITEK MS v3.0 system (bioMérieux, Marcy-l’Étoile, France) for the identification of a wide spectrum of clinically relevant filamentous fungi using a Korean collection. Strains that were added to the upgraded v3.2 database were additionally identified by the VITEK MS v3.2 system. Of the 105 tested isolates, including 37 Aspergillus (nine species), 41 dermatophytes (seven species), and 27 other molds (17 species), 43 (41.0%) showed “no identification” or “multiple species identification” results at the initial VITEK MS testing; these isolates were retested using the same method. Compared with sequence-based identification, the correct identification rate using VITEK MS for Aspergillus, dermatophytes, other molds, and total mold isolates was 67.6%, 56.1%, 48.1%, and 58.1% at the initial testing and 94.6%, 78.0%, 55.6%, and 78.1% with retesting, respectively. Following retesting, 19 (18.1%) and two (1.9%) isolates showed “no identification” and “misidentification” results, respectively. VITEK MS reliably identified various filamentous fungi recovered in Korea, with a very low rate of misidentification

Purpose: The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated. Materials and Methods: A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core. Results: The density of CD8+ T cells, FoxP3- CD4+ helper T cells, and FoxP3+ CD4+ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8+ T cell and FoxP3- CD4+ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3- CD4+ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3- CD4+ helper T cells in the tumor margin was independently associated with favorable PFS and OS. Conclusion The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3- CD4+ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.

Objective: Muscle depletion in patients undergoing liver transplantation affects the recipients’ prognosis and therefore cannot be overlooked. We aimed to evaluate whether changes in muscle and fat mass during the preoperative period are associated with prognosis after deceased donor liver transplantation (DDLT). Materials and Methods: This study included 72 patients who underwent DDLT and serial computed tomography (CT) scans.Skeletal muscle index (SMI) and fat mass index (FMI) were calculated using the muscle and fat area in CT performed 1 year prior to surgery (1 yr Pre-LT), just before surgery (Pre-LT), and after transplantation (Post-LT). Simple aspects of serial changes in muscle and fat mass were analyzed during three measurement time points. The rate of preoperative changes in body composition parameters were calculated (preoperative ΔSMI [%] = [SMI at Pre-LT - SMI at 1 yr Pre-LT] / SMI at Pre-LT x 100;preoperative ΔFMI [%] = [FMI at Pre-LT - FMI at 1 yr Pre-LT] / FMI at Pre-LT x 100) and assessed for correlation with patient survival. Results: SMI significantly decreased during the preoperative period (mean preoperative ΔSMI, -13.04%, p < 0.001). In the multivariable analysis, preoperative ΔSMI (p = 0.016) and model for end-stage liver disease score (p = 0.011) were independent prognostic factors for overall survival. The mean survival time for patients with a threshold decrease in the preoperative ΔSMI (≤ -30%) was significantly shorter than for other patients (p = 0.007). Preoperative ΔFMI was not a prognostic factor but FMI increased during the postoperative period (p = 0.009) in all patients. Conclusion A large reduction in preoperative SMI was significantly associated with reduced survival after DDLT. Therefore, changes in muscle mass during the preoperative period can be considered as a prognostic factor for survival after DDLT.

Purpose: With advances in surgical techniques, reduced-port laparoscopic surgery is increasingly being performed for the treatment of gastric carcinoma. Many studies have reported satisfactory short-term outcomes after reduced 3-port laparoscopic gastrectomy (LG). The aim of this study was to investigate the long-term oncological outcomes of 3-port LG in patients with gastric carcinoma. Materials and Methods: We reviewed the medical records of 1,117 patients who underwent LG for gastric carcinoma in three major institutions between 2012 and 2015. The data showed that 460 patients underwent 3-port LG without assistance, and 657 underwent conventional 5-port LG. We compared the overall and disease-free survival rates between the 2 groups. Results: There were 642 male and 475 female patients with a mean age of 56.1 years.Among them, 1,028 (92.0%) underwent distal gastrectomy and 89 (8.0%) underwent total gastrectomy. In the final pathologic examination, 1,027 patients (91.9%) were stage I, 73 (6.5%) were stage II, and 17 (1.5%) were stage III, and there were no significant difference in the pathologic stage between groups. The 3- and 5-port LG groups showed no significant differences in the 5-year overall survival (94.3% vs. 96.7%, P=0.138) or disease-free survival (94.3% vs. 95.9%, P=0.231). Stratified analyses according to pT and pN stages also showed no significant differences in overall or disease-free survival between the two groups. Conclusions Long-term survival after 3- and 5-port LG was comparable in patients with early-stage gastric carcinoma. The 3-port technique requiring limited surgical assistance may be an appropriate surgical option for this patient population.

Background/Aims: Both hepatic venous pressure gradient (HVPG) and liver stiffness (LS) are useful tools for predicting mortality in patients with cirrhosis. We investigated the combined effect of HVPG and LS on long-term mortality in patients with cirrhosis. Methods: We retrospectively collected data from 103 patients with cirrhosis, whose HVPG and LS were measured between November 2009 and September 2013. The patients were divided into four groups according to the results of the HVPG and LS measurements. Long-term mortality and the risk factors for mortality were analyzed. Results: Of the 103 patients, 35 were in group 1 (low HVPG and low LS), 16 in group 2 (high HVPG and low LS), 24 in group 3 (low HVPG and high LS), and 28 in group 4 (high HVPG and high LS). Over a median follow-up of 47.3 months, 18 patients died. The mortality rate of patients in group 4 was significantly higher than in the other three groups (vs. group 1, p = 0.005; vs. group 2, p = 0.049; vs. group 3, p = 0.004), but there were no significant differences in survival between groups 1, 2, and 3. In multivariable analyses, both HVPG and LS were identified as independent risk factors for mortality (hazard ratio [HR], 1.127, p = 0.018; and HR, 1.062, p = 0.009, respectively). Conclusions In patients with cirrhosis, those with concurrent elevation of HVPG and LS had the highest long-term mortality rates. However, when either HVPG or LS alone was elevated, mortality did not increase significantly.

Purpose: To determine the frequency of ossification of the transverse ligament of the atlas (OTLA) and to investigate the associated findings on cervical spine CT and plain radiography. Materials and Methods: We reviewed 5201 CT scans of the cervical spine of 3975 consecutive patients over an 11-year period for the presence of OTLA and compared them with those of ageand sex-matched controls. The frequency and associated findings of OTLA were investigated and statistically correlated. Results: The overall frequency of OTLA was 1.1% (45 of 3975 patients) and increased with age (p < 0.005). The frequency of OTLA in patients over 80 years was 12%. The space available for the spinal cord (SAC) was smaller in patients with OTLA (p < 0.005). Mineralization of the complex of the anterior atlantooccipital membrane and Barkow ligament, ossification of the ligamentum flavum, and kyphosis of the cervical spine positively correlated to the presence of OTLA (p < 0.005). Conclusion OTLA was associated with age, SAC narrowing, cervical kyphosis, and ossification of other cervical ligaments and may be associated with degenerative spondylosis, systemic hyperostotic status, or mechanical stress or instability.

Globally and in Africa specifically, female sex workers (FSWs) are at an extraordinarily high risk of contracting human immunodeficiencyvirus (HIV). Pre-exposure prophylaxis (PrEP) has emerged as an effective and ethical method with which to preventHIV infection among FSWs. PrEP efficacy is, however, closely linked to adherence, and adherence to PrEP among FSWs is a complexand interrelated process that has been shown to be of importance to public health policies and HIV control and interventionprograms. This comprehensive review categorizes barriers to and facilitators of adherence to HIV PrEP for FSWs, and describes fivestrategies for promoting PrEP adherence among FSWs. These strategies encompass 1) a long-term educational effort to decreasethe stigma associated with sex work and PrEP use, 2) education on how PrEP works, 3) lifestyle modification, 4) research on nextgenerationPrEP products to address the inconvenience of taking daily pills, and 5) integration of PrEP into existing services, suchas social services and routine primary care visits, to reduce the economic burden of seeking the medication. Our review is expectedto be useful for the design of future PrEP intervention programs. Multidisciplinary intervention should be considered to promotePrEP adherence among FSWs in order to help control the HIV epidemic.

Purpose: Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC). Materials and Methods: We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017. Results: CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively).Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival. Conclusions CLDN18.2 expression was reduced in patients with PM but significantly intactin those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.