ANU Medical School

BACKGROUND:Tegoprazan, a potassium-competitive acid blocker, offers potent and sustained acid inhibition and potentially improves eradication efficacy. AIM:This study aimed to evaluate the efficacy and safety of tegoprazan-based triple therapy with two dosing regimens compared with that of lansoprazole-based therapy for first-line Helicobacter pylori eradication. METHODS:This randomized, double-blind, active-controlled, multicenter trial was conducted at 19 referral hospitals in South Korea (February 2023-April 2024). Treatment-naïve adults with H. pylori infection were randomized 1:1:1 to receive 14-day triple therapy with tegoprazan, 50 mg (TAC1), tegoprazan, 100 mg (TAC2), or lansoprazole, 30 mg (LAC), each combined with amoxicillin 1000 mg and clarithromycin 500 mg, administered twice daily. The primary endpoint was H. pylori eradication rate in the modified intention-to-treat (mITT) population, with a non-inferiority margin of -10%. Secondary endpoints included subgroup analyses based on clarithromycin resistance and safety assessments. RESULTS:Of the 564 screened patients, 382 were randomized. In the mITT analysis (mean age, 54.9 years; 54.3% male), eradication rates were 86.0%, 85.5%, and 78.7% for TAC1, TAC2, and LAC, respectively. Both tegoprazan-based regimens met the non-inferiority criteria. Among clarithromycin-resistant infections, the eradication rates were higher for TAC1 (47.8%) and TAC2 (50.0%) than for LAC (35.5%), although the difference was not statistically significant. Safety profiles were comparable across the groups, with no serious drug-related adverse events. CONCLUSION:Tegoprazan-based triple therapies, at 50- and 100-mg doses, were non-inferior to lansoprazole-based therapy and were well tolerated. Our findings indicated that tegoprazan-based triple therapy is a viable first-line option for H. pylori eradication. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT05933031.

Background:Depressive disorder affects over 300 million people globally, with only 30% to 40% of patients achieving remission with initial antidepressant monotherapy. This low response rate highlights the critical need for digital mental health tools that can identify treatment response early in the clinical pathway. Objective:This study aimed to evaluate whether reasoning-based large language models (LLMs) could accurately predict 12-week remission in patients with depressive disorder undergoing antidepressant monotherapy and to assess the clinical validity and interpretability of model-generated rationales for integration into digital mental health workflows. Methods:We analyzed data from 390 patients in the MAKE Biomarker discovery study who were undergoing first-step antidepressant monotherapy with 12 different medications, including escitalopram, paroxetine, sertraline, duloxetine, venlafaxine, desvenlafaxine, milnacipran, mirtazapine, bupropion, vortioxetine, tianeptine, and trazodone, after excluding those with uncommon medications (n=9) or missing biomarker data (n=32). Three LLMs (ChatGPT o1, o3-mini, and Claude 3.7 Sonnet) were tested using advanced prompting strategies, including zero-shot chain-of-thought, atom-of-thoughts, and our novel referencing of deep research prompt. Model performance was evaluated using balanced accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Three psychiatrists independently assessed model outputs for clinical validity using 5-point Likert scales across multiple dimensions. Results:Claude 3.7 Sonnet with 32,000 reasoning tokens using the referencing of deep research prompt achieved the highest performance (balanced accuracy=0.6697, sensitivity=0.7183, and specificity=0.6210). Medication-specific analysis revealed negative predictive values of 0.75 or higher across major antidepressants, indicating particular utility in identifying likely nonresponders. Clinical evaluation by psychiatrists showed favorable mean ratings for correctness (4.3, SD 0.7), consistency (4.2, SD 0.8), specificity (4.2, SD 0.7), helpfulness (4.2, SD 1.0), and human likeness (3.6, SD 1.7) on 5-point scales. Conclusions:These findings demonstrate that reasoning-based LLMs, particularly when enhanced with research-informed prompting, show promise for predicting antidepressant response and could serve as interpretable adjunctive tools in depressive disorder treatment planning, although prospective validation in real-world clinical settings remains essential.

PURPOSE:Owing to concerns about overdiagnosis and overtreatment associated with prostate-specific antigen (PSA) screening for early prostate cancer detection, recent guidelines have lowered the PSA cutoff value for recommending biopsy. This study aimed to evaluate the diagnostic accuracy of a lower PSA cutoff value in Korean men and to explore whether additional clinically useful criteria can be proposed. MATERIALS AND METHODS:A retrospective cohort study of 17,539 Korean men who underwent their first prostate biopsy due to lower urinary tract symptoms was conducted at six tertiary hospitals between 2011 and 2019. The diagnostic performance of various PSA and PSA density (PSAD) cutoff values across age groups was evaluated by analyzing the data on demographics, PSA levels, PSAD, and biopsy results. RESULTS:Among the participants, 44.1% were diagnosed with prostate cancer, of whom 73.7% had clinically significant cancer (Gleason score ≥7). No significant differences in cancer detection rates were found between PSA levels of 3-4 ng/mL and 4-5 ng/mL across age groups. PSAD further increased the area under the receiver operating characteristic curve by 5.5%-11.4%. CONCLUSIONS:These findings suggest that diagnostic yield may not be impacted by merely lowering the PSA cutoff. Rather, combining PSA, PSAD, and patient age enhances screening accuracy while minimizing unnecessary biopsies and overdiagnosis. Our results highlight the need for more data to refine national screening guidelines and promote a more tailored approach to prostate cancer screening in Korea.

Genome-wide association studies (GWAS) have identified over 200 genetic risk loci for breast cancer, yet the target genes in these loci remain largely unknown. To address this knowledge gap, we conducted a series of multi-ancestry transcriptome-wide association studies (TWAS) to discover potential breast cancer susceptibility genes. We developed and validated ancestry-specific genetic models to predict levels of gene expression, alternative splicing, and 3' UTR alternative polyadenylation, using genomic and transcriptomic data from normal breast tissue samples of 652 females of African, Asian, or European ancestry. These models were then applied to GWAS data of 178,534 breast cancer cases and 248,300 controls from these ancestry groups for association analyses. We identified 290 genes associated with breast cancer risk, including 103 previously unreported in TWAS and 46 located at least 500Kb away from any previously identified risk variants. Among them, 39 genes exhibited distinct associations with breast cancer risk by estrogen receptor status. The identified genes were enriched in pathways related to homologous recombination, apoptosis, p53, PI3K/AKT/mTOR, estrogen, and IL-2/STAT5 signaling. Single-cell RNA sequencing and in vitro experiment data provided additional functional evidence for 169 genes. Our study uncovered large numbers of candidate breast cancer susceptibility genes and contributed valuable insights into the genetics and biology of this common cancer.

Introduction: Spontaneous subcapsular liver hematomas are rare and carry significant morbidity, particularly in patients with advanced malignancy and severe hematological compromise. Management must balance hemostatic control with procedural risk and often requires multidisciplinary input. Presentation of case: We report a 50-year-old female with stage IV metastatic melanoma complicated by immune checkpoint inhibitor-induced aplastic anemia. She presented with a large spontaneous subcapsular hematoma arising from hepatic metastasis. Severe thrombocytopenia and immunosuppression rendered open surgery high-risk; hence, a less invasive approach was undertaken with targeted focal transarterial embolization (TAE), utilizing embolization-guidance software to selectively treat tumor-feeding vessels. Symptomatic improvement and early prevention of re-bleeding were achieved; however, recurrence from a second source prompted another round of more diffuse embolization of the right hepatic arterial supply, with good effect. Subsequent palliative liver radiotherapy aimed to reduce the risk of further re-bleeding. Discussion: TAE provided effective hemostasis while avoiding the risks of operative intervention in a profoundly thrombocytopenic, immunocompromised patient. This approach reflects an expanding role for interventional radiology in the acute management of complex hepatic hemorrhage. Conclusion: In selected high-risk patients, TAE can achieve bleeding control and symptom relief for spontaneous subcapsular liver hematomas. This case highlights the value of tailored, multidisciplinary management strategies in challenging surgical scenarios where operative management carries a prohibitive risk.