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.

Background: The emergence of tigecycline-resistant Acinetobacter baumannii has been reported, and the need for tigecycline susceptibility testing in this strain is increasing. However, neither the Clinical & Laboratory Standards Institute, nor the European Commission on Antimicrobial Susceptibility Testing have provided definitive criteria for tigecycline susceptibility testing of A. baumannii. In this study, the disk diffusion method and the minimal inhibitory concentration (MIC) method were com pared to verify conventionally used Food and Drug Administration-identified interpretive criteria to detect tigecycline resistance of A. baumannii. Methods: Forty-four strains of A. baumannii with tigecycline resistance were collected through the Kor-GLASS (Korean Global Antimicrobial Resistance Surveillance System) study in 2022 using the disk diffusion test (DDT). This strain was retested with the MIC method using a Sensititre Gram Negative GN6F AST plate (Thermo Fisher Scientific, USA) to confirm tigecycline resistance. The confirmed strain was subjected to whole genome analysis to elucidate the tigecycline resistance mechanism. Results: Only one of the 44 isolates identified as resistant to tigecycline by the DDT showed resistance with the MIC method, thus the concordance rate of the two methods was 2.3% (1/44). Sequence type 195 strain, carrying bla OXA23 was identified. This strain had no resistance genes of the tetracycline family but had resistance genes to other antimicrobial families. Conclusions Discrepancy of the tigecycline susceptibility test of A. baumannii was identified. To detect tigecycline resistance of A. baumannii, more reliable methods are required.

Background: The emergence of tigecycline-resistant Acinetobacter baumannii has been reported, and the need for tigecycline susceptibility testing in this strain is increasing. However, neither the Clinical & Laboratory Standards Institute, nor the European Commission on Antimicrobial Susceptibility Testing have provided definitive criteria for tigecycline susceptibility testing of A. baumannii. In this study, the disk diffusion method and the minimal inhibitory concentration (MIC) method were com pared to verify conventionally used Food and Drug Administration-identified interpretive criteria to detect tigecycline resistance of A. baumannii. Methods: Forty-four strains of A. baumannii with tigecycline resistance were collected through the Kor-GLASS (Korean Global Antimicrobial Resistance Surveillance System) study in 2022 using the disk diffusion test (DDT). This strain was retested with the MIC method using a Sensititre Gram Negative GN6F AST plate (Thermo Fisher Scientific, USA) to confirm tigecycline resistance. The confirmed strain was subjected to whole genome analysis to elucidate the tigecycline resistance mechanism. Results: Only one of the 44 isolates identified as resistant to tigecycline by the DDT showed resistance with the MIC method, thus the concordance rate of the two methods was 2.3% (1/44). Sequence type 195 strain, carrying bla OXA23 was identified. This strain had no resistance genes of the tetracycline family but had resistance genes to other antimicrobial families. Conclusions Discrepancy of the tigecycline susceptibility test of A. baumannii was identified. To detect tigecycline resistance of A. baumannii, more reliable methods are required.

Background: The emergence of tigecycline-resistant Acinetobacter baumannii has been reported, and the need for tigecycline susceptibility testing in this strain is increasing. However, neither the Clinical & Laboratory Standards Institute, nor the European Commission on Antimicrobial Susceptibility Testing have provided definitive criteria for tigecycline susceptibility testing of A. baumannii. In this study, the disk diffusion method and the minimal inhibitory concentration (MIC) method were com pared to verify conventionally used Food and Drug Administration-identified interpretive criteria to detect tigecycline resistance of A. baumannii. Methods: Forty-four strains of A. baumannii with tigecycline resistance were collected through the Kor-GLASS (Korean Global Antimicrobial Resistance Surveillance System) study in 2022 using the disk diffusion test (DDT). This strain was retested with the MIC method using a Sensititre Gram Negative GN6F AST plate (Thermo Fisher Scientific, USA) to confirm tigecycline resistance. The confirmed strain was subjected to whole genome analysis to elucidate the tigecycline resistance mechanism. Results: Only one of the 44 isolates identified as resistant to tigecycline by the DDT showed resistance with the MIC method, thus the concordance rate of the two methods was 2.3% (1/44). Sequence type 195 strain, carrying bla OXA23 was identified. This strain had no resistance genes of the tetracycline family but had resistance genes to other antimicrobial families. Conclusions Discrepancy of the tigecycline susceptibility test of A. baumannii was identified. To detect tigecycline resistance of A. baumannii, more reliable methods are required.

Background: The emergence of tigecycline-resistant Acinetobacter baumannii has been reported, and the need for tigecycline susceptibility testing in this strain is increasing. However, neither the Clinical & Laboratory Standards Institute, nor the European Commission on Antimicrobial Susceptibility Testing have provided definitive criteria for tigecycline susceptibility testing of A. baumannii. In this study, the disk diffusion method and the minimal inhibitory concentration (MIC) method were com pared to verify conventionally used Food and Drug Administration-identified interpretive criteria to detect tigecycline resistance of A. baumannii. Methods: Forty-four strains of A. baumannii with tigecycline resistance were collected through the Kor-GLASS (Korean Global Antimicrobial Resistance Surveillance System) study in 2022 using the disk diffusion test (DDT). This strain was retested with the MIC method using a Sensititre Gram Negative GN6F AST plate (Thermo Fisher Scientific, USA) to confirm tigecycline resistance. The confirmed strain was subjected to whole genome analysis to elucidate the tigecycline resistance mechanism. Results: Only one of the 44 isolates identified as resistant to tigecycline by the DDT showed resistance with the MIC method, thus the concordance rate of the two methods was 2.3% (1/44). Sequence type 195 strain, carrying bla OXA23 was identified. This strain had no resistance genes of the tetracycline family but had resistance genes to other antimicrobial families. Conclusions Discrepancy of the tigecycline susceptibility test of A. baumannii was identified. To detect tigecycline resistance of A. baumannii, more reliable methods are required.

Background: The emergence of tigecycline-resistant Acinetobacter baumannii has been reported, and the need for tigecycline susceptibility testing in this strain is increasing. However, neither the Clinical & Laboratory Standards Institute, nor the European Commission on Antimicrobial Susceptibility Testing have provided definitive criteria for tigecycline susceptibility testing of A. baumannii. In this study, the disk diffusion method and the minimal inhibitory concentration (MIC) method were com pared to verify conventionally used Food and Drug Administration-identified interpretive criteria to detect tigecycline resistance of A. baumannii. Methods: Forty-four strains of A. baumannii with tigecycline resistance were collected through the Kor-GLASS (Korean Global Antimicrobial Resistance Surveillance System) study in 2022 using the disk diffusion test (DDT). This strain was retested with the MIC method using a Sensititre Gram Negative GN6F AST plate (Thermo Fisher Scientific, USA) to confirm tigecycline resistance. The confirmed strain was subjected to whole genome analysis to elucidate the tigecycline resistance mechanism. Results: Only one of the 44 isolates identified as resistant to tigecycline by the DDT showed resistance with the MIC method, thus the concordance rate of the two methods was 2.3% (1/44). Sequence type 195 strain, carrying bla OXA23 was identified. This strain had no resistance genes of the tetracycline family but had resistance genes to other antimicrobial families. Conclusions Discrepancy of the tigecycline susceptibility test of A. baumannii was identified. To detect tigecycline resistance of A. baumannii, more reliable methods are required.

Purpose: We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs). Materials and Methods: Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector–based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer. Results: Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs. Conclusion CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

Objective: We compared appendiceal visualization on 2-mSv CT vs. conventional-dose CT (median 7 mSv) in adolescents and young adults and analyzed the undesirable clinical and diagnostic outcomes that followed appendiceal nonvisualization. Materials and Methods: A total of 3074 patients aged 15–44 years (mean ± standard deviation, 28 ± 9 years; 1672 female) from 20 hospitals were randomized to the 2-mSv CT or conventional-dose CT group (1535 vs. 1539) from December 2013 through August 2016. A total of 161 radiologists from 20 institutions prospectively rated appendiceal visualization (grade 0, not identified; grade 1, unsure or partly visualized; and grade 2, clearly and entirely visualized) and the presence of appendicitis in these patients. The final diagnosis was based on CT imaging and surgical, pathologic, and clinical findings. We analyzed undesirable clinical or diagnostic outcomes, such as negative appendectomy, perforated appendicitis, more extensive than simple appendectomy, delay in patient management, or incorrect CT diagnosis, which followed appendiceal nonvisualization (defined as grade 0 or 1) and compared the outcomes between the two groups. Results: In the 2-mSv CT and conventional-dose CT groups, appendiceal visualization was rated as grade 0 in 41 (2.7%) and 18 (1.2%) patients, respectively; grade 1 in 181 (11.8%) and 81 (5.3%) patients, respectively; and grade 2 in 1304 (85.0%) and 1421 (92.3%) patients, respectively (p < 0.001). Overall, undesirable outcomes were rare in both groups. Compared to the conventional-dose CT group, the 2-mSv CT group had slightly higher rates of perforated appendicitis (1.1% [17] vs. 0.5% [7], p = 0.06) and false-negative diagnoses (0.4% [6] vs. 0.0% [0], p = 0.01) following appendiceal nonvisualization. Otherwise, these two groups were comparable. Conclusion The use of 2-mSv CT instead of conventional-dose CT impairs appendiceal visualization in more patients. However, appendiceal nonvisualization on 2-mSv CT rarely leads to undesirable clinical or diagnostic outcomes.

Crohn’s disease (CD) is a chronic destructive inflammatory bowel disease that affects young people and is associated with significant morbidity. The clinical spectrum and disease course of CD are heterogeneous and often difficult to predict based on the initial presentation. In this article, changes in the disease location, behavior, clinical course during long-term follow-up, and predictive factors are reviewed. Generally, four different patterns of clinical course are discussed: remission, stable disease, chronic relapsing disease, and chronic refractory disease. Understanding the long-term disease course of CD is mandatory to reveal the underlying pathophysiology of the disease and to move toward a more optimistic disease course, such as remission or stability, and less adverse outcomes or devastating sequelae.

Remission is a primary end point of in clinical practice and trials of treatments for rheumatoid arthritis (RA). The 2011 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria were developed to provide a consensus definition of remission. This study aimed to assess the concordance between the new remission criteria and the physician’s clinical judgment of remission and also to identify factors that affect the discordance between these two approaches. A total of 3,209 patients with RA were included from the KORean Observational Study Network for Arthritis (KORONA) database. The frequency of remission was evaluated based on each approach. The agreement between the results was estimated by Cohen's kappa (κ). Patients with remission according to the 2011 ACR/EULAR criteria (i.e. the Boolean criteria) and/or physician judgment (n = 855) were divided into three groups: concordant remission, the Boolean criteria only, and physician judgment only. Multinomial logistic regression analysis was used to identify factors responsible for the assignment of patients with remission to one of the discordant groups rather than the concordant group. The remission rates using the Boolean criteria and physician judgment were 10.5% and 19.9%, respectively. The agreement between two approaches for remission was low (κ = 0.226) and the concordant remission rate was only 5.5% (n = 177). Pain affected classification in both discordant groups, whereas fatigue was associated with remission only by physician clinical judgment. The Boolean criteria were more stringent than clinical judgment. Patient subjective symptoms such as pain and fatigue were associated with discordance between the two approaches.
Arthritis ; Arthritis, Rheumatoid* ; Classification ; Consensus ; Fatigue ; Humans ; Judgment* ; Logistic Models ; Observational Study ; Rheumatic Diseases