Srinagarind Hospital (Thai: โรงพยาบาลศรีนครินทร์) is a university teaching hospital, affiliated to the Faculty of Medicine of Khon Kaen University, located in Mueang Khon Kaen District, Khon Kaen Province. It is a hospital capable of super tertiary care.
BACKGROUND:Melioidosis is an infectious disease caused by Burkholderia pseudomallei. Septicemic melioidosis patients have a high mortality rate within 48 hours. OBJECTIVE:To develop a polymerase chain reaction (PCR) combined with a lateral flow dipstick (LFD) assay for detection of B. pseudomallei in blood samples. METHODS:The PCR with wcbG gene primers and a PCR-LFD test were developed. The specificity and sensitivity were determined using the B. pseudomallei and other bacterial DNAs. They were evaluated using 43 B. pseudomallei positive blood samples and another 43 blood samples positive for other microbial infections. RESULTS:The detection limit of the PCR-LFD test was 50 fg of bacterial gDNA or 1.0 CFU per 200 μl of blood. All B. pseudomallei were positive while B. thailandensis and selected gram-negative bacterial strains were negative. The PCR-LFD gave all positives with all 43 B. pseudomallei culture positive patient blood samples and all negative with 43 blood samples that were culture positive for K. pneumoniae, E. gallinarum, E. faecium, E. coli, S. aureus, A. baumannii, A. hydrophila, S. haemolyticus, S. pneumoniae, P. aeruginosa, E. cloacae, S. hominis, E. aerogenes, P. mirabilis, C. neoformans, C. albicans, A. caviae, E. faecalis and K. variicola. CONCLUSION:The developed PCR-LFD assay provided 100% sensitivity and 100% specificity compared to the conventional blood culture. The technique took only 1.5 hours that is easy and quick to perform compared to the 3-7 days of culture method. The new method of PCR with LFD could facilitate the detection to be a semi-point-of-care testing (POCT).
BACKGROUND:Generalized pustular psoriasis (GPP) is a rare, life-threatening disease attributed to aberrant interleukin-36 (IL-36) activity, often due to variants in the IL-36 receptor antagonist gene. Imsidolimab is a novel, humanized, affinity-matured immunoglobulin G4 monoclonal antibody that binds the IL-36 receptor and antagonizes IL-36 signaling. METHODS:Two phase 3 trials were conducted at 26 clinical sites within 11 countries investigating imsidolimab treatment for GPP. GEMINI-1 was a double-blind, placebo-controlled trial that randomly assigned 45 patients (18-80 years of age) with a GPP flare to receive either a single intravenous dose of 300 mg of imsidolimab, 750 mg of imsidolimab, or placebo. The primary endpoint was GPP Physician Global Assessment (GPPPGA) scores of clear (0) or almost clear (1) at week 4 (range: 0 [clear] to 4 [severe]; minimally clinically important difference, 1.4). GEMINI-2 was a follow-on relapse prevention trial with a primary objective of evaluating the safety of imsidolimab up to 104 weeks. Patients who improved with treatment in GEMINI-1 were randomly assigned to receive either 200 mg of subcutaneous imsidolimab or placebo monthly, whereas partial responders received open-label 200 mg of subcutaneous imsidolimab monthly. RESULTS:In GEMINI-1, 53% of patients in the groups that received either 300 mg (n=8/15) or 750 mg (n=8/15) of imsidolimab had GPPPGA scores of 0 or 1 at week 4, compared to 13% in the placebo group (n=2/15) (P=0.023 for both the 300 mg vs. placebo comparison and 750 mg vs. placebo comparison). In GEMINI-2, no serious adverse events led to imsidolimab discontinuation. CONCLUSIONS:Compared with placebo, a significantly higher proportion of patients with GPP randomly assigned to receive a single intravenous dose of imsidolimab were clear or almost clear of the disease after 4 weeks based on the GPPPGA. There were no serious adverse events that led to treatment discontinuation with imsidolimab up to 104 weeks of treatment. (Funded by AnaptysBio; ClinicalTrials.gov number, NCT05352893 for GEMINI-1 and NCT05366855 for GEMINI-2.).
Methicillin-resistant coagulase-negative staphylococci (MRCONS) are increasingly recognized for their impact on healthcare, but data on their prevalence and outcomes in Thailand remain limited. These pathogens are often colonizers rather than true infection agents, and information on drug resistance and associated mortality is scarce. Objectives To assess the prevalence of MRCONS infections and their clinical outcomes, including 28-day mortality, hospital and ICU lengths of stay, and vancomycin minimum inhibitory concentrations (MICs).*Other chronic illness: Systemic autoimmune disease: 4 (8.51%), Heart disease: 15 (31.91%), Gastrointestinal disease: 1 (2.12%), Benign prostatic hyperplasia: 1 (2.12%), HIV infection: 1 (2.12%), Bone and joint disease: 13 (27.65%), Hematologic disease: 4 (8.51%), Neurological disease: 6 (12.76%), Tuberculosis: 1 (2.12%), Chronic viral hepatitis B infection: 1 (2.12%)SSTI: skin and skin structure infection, CNS: Central nervous system infection, UTI: Urinary tract infection This retrospective study (January 2018–October 2023) included patients aged over 18 with confirmed CONS infections based on culture results and clinical signs. Among 97 patients with true CONS infections (median age: 59 [IQR 46-68] years for Methicillin-susceptible coagulase-negative staphylococci (MSCONS), 68 [IQR 53-77] years for MRCONS), 59.75% had MRCONS infection. Underlying conditions were more frequent in the MRCONS group, particularly chronic kidney disease (25.45% vs. 13.51%). The 28-day mortality rate was higher in the MRCONS group (9.8%) compared to the MSCONS group (2%), though the difference was not statistically significant (P = 0.26). Hospital stays were significantly longer for MRCONS patients, with a median duration of 26.5 days (IQR 22–51) compared to 17 days (IQR 7–23) in the MSCONS group (P < 0.001). ICU stays followed a similar pattern, with median durations of 26 days (IQR 10–49) for MRCONS group and 16 days (IQR 14–33) for MSCONS group (P = 0.93). The vancomycin MICs of the MRCONS group were categorized as follows: < 0.5, 1, 2, and > 2, with corresponding frequencies of 10.53%, 50.88%, 36.84%, and 1.75%, respectively. MRCONS infections accounted for over half of CONS cases, significantly prolonging hospital stays and showing a trend toward higher mortality and ICU stays. Physicians should remain alert to resistant strains in CONS infections. All Authors: No reported disclosures
143 Background: Biliary tract cancer (BTC) is a rare malignancy but occurs more frequently in Asian populations, where the establishment of molecularly guided treatment strategies is of particular importance. Intrahepatic cholangiocarcinoma has been classified into small-duct and large-duct types based on molecular features, each characterized by distinct genetic alterations. However, the clinical significance of RNA expression–based molecular classification in BTC remains unclear. Methods: Patients with BTC enrolled in the multinational MASTER KEY Asia registry, including the CHOICE sub-cohort, who had matched DNA sequencing and RNA expression data by NGS were included. Gene expression profiles from 93 cholangiocarcinoma tumors were analyzed using unsupervised hierarchical clustering to define transcriptomic subgroups, and heatmaps were generated using scaled expression values. Mutation profiles were aligned with clusters, and the top 10 most frequently mutated genes in each group were compared. Clinicopathological features and treatment responses were evaluated across subgroups. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier and log-rank tests, with Cox proportional hazards and logistic regression analyses performed to identify prognostic factors and determinants of cluster assignment. Results: Unsupervised clustering identified two major transcriptomic groups, designated CHOL1 (n=61) and CHOL2 (n=32), with distinct gene expression profiles. The median age was significantly lower in CHOL2 compared with CHOL1 (56.3 vs. 62.7 years, p=0.009). In addition, logistic regression analysis demonstrated that younger age and a positive family history of cancer were significantly associated with CHOL2 membership (p=0.013 and p=0.009, respectively). Distinct genetic alteration patterns were identified: KRAS (36.1% vs. 9.4%, p=0.006) and SMAD4 mutations (26.2% vs. 3.1%, p=0.005) were more frequent in CHOL1, whereas FGFR2 fusions (1.6% vs. 9.4%, p=0.11) and IDH1 mutations (0% vs. 15.6%, p=0.003) were numerically more common in CHOL2. In CHOL2, a subset of cases harbored TERT promoter mutations and exhibited gene expression signatures associated with aggressive HCC. However, no significant differences were observed in response rates to systemic therapy, PFS, or OS between clusters. Conclusions: RNA-based molecular classification of BTC identified two distinct clusters with different clinical and genomic characteristics. CHOL2 was associated with younger age and enrichment of actionable alterations such as FGFR2 fusions and IDH1 mutations. Although no differences in treatment efficacy were observed between clusters, heterogeneity in treatment regimens across countries may have limited evaluation, highlighting the need for further validation in homogeneous cohorts. Clinical trial information: NCT05217407 .
