Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

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.

Purpose: To report a case of angle-closure glaucoma caused by pupillary block in a patient with familial exudative vitreoretinopathy (FEVR).Case summary: A 20-year-old man with FEVR presented with sudden-onset pain in his left eye. The best-corrected visual acuity (BCVA) was 0.04, and the intraocular pressure (IOP) was 76 mmHg. The central anterior chamber depth was reduced to twice the corneal thickness. Gonioscopy revealed 360° angle closure. Anterior segment optical coherence tomography and ultrasound biomicroscopy demonstrated a closed angle and anteriorly convex peripheral iris due to forward displacement of the lens–iris diaphragm and contact between the iris and lens. Trabeculectomy and cataract surgery were performed because the IOP was not controlled despite maximal medical therapy. At 9 months postoperatively, the IOP was 13 mmHg without the use of glaucoma medications, and the BCVA was 0.1. Conclusions In patients with FEVR, angle-closure glaucoma due to pupillary block can occur even at a young age. FEVR should be considered in young patients with acute angle-closure glaucoma.

Purpose: To report a case of angle-closure glaucoma caused by pupillary block in a patient with familial exudative vitreoretinopathy (FEVR).Case summary: A 20-year-old man with FEVR presented with sudden-onset pain in his left eye. The best-corrected visual acuity (BCVA) was 0.04, and the intraocular pressure (IOP) was 76 mmHg. The central anterior chamber depth was reduced to twice the corneal thickness. Gonioscopy revealed 360° angle closure. Anterior segment optical coherence tomography and ultrasound biomicroscopy demonstrated a closed angle and anteriorly convex peripheral iris due to forward displacement of the lens–iris diaphragm and contact between the iris and lens. Trabeculectomy and cataract surgery were performed because the IOP was not controlled despite maximal medical therapy. At 9 months postoperatively, the IOP was 13 mmHg without the use of glaucoma medications, and the BCVA was 0.1. Conclusions In patients with FEVR, angle-closure glaucoma due to pupillary block can occur even at a young age. FEVR should be considered in young patients with acute angle-closure glaucoma.

Purpose: To report a case of angle-closure glaucoma caused by pupillary block in a patient with familial exudative vitreoretinopathy (FEVR).Case summary: A 20-year-old man with FEVR presented with sudden-onset pain in his left eye. The best-corrected visual acuity (BCVA) was 0.04, and the intraocular pressure (IOP) was 76 mmHg. The central anterior chamber depth was reduced to twice the corneal thickness. Gonioscopy revealed 360° angle closure. Anterior segment optical coherence tomography and ultrasound biomicroscopy demonstrated a closed angle and anteriorly convex peripheral iris due to forward displacement of the lens–iris diaphragm and contact between the iris and lens. Trabeculectomy and cataract surgery were performed because the IOP was not controlled despite maximal medical therapy. At 9 months postoperatively, the IOP was 13 mmHg without the use of glaucoma medications, and the BCVA was 0.1. Conclusions In patients with FEVR, angle-closure glaucoma due to pupillary block can occur even at a young age. FEVR should be considered in young patients with acute angle-closure glaucoma.

OBJECTIVES: In this study, we sought to evaluate the association between smoking status and subclinical coronary atherosclerosis, as detected by coronary computed tomography angiography (CCTA), in asymptomatic individuals. METHODS: We retrospectively analyzed 9,285 asymptomatic participants (mean age, 53.7±8.0 years; n=6,017, 64.8% male) with no history of coronary artery disease (CAD) who had undergone self-referred CCTA. Of these participants, 4,333 (46.7%) were considered never smokers, 2,885 (31.1%) former smokers, and 2,067 (22.3%) current smokers. We assessed the degree and characteristics of subclinical coronary atherosclerosis using CCTA, with obstructive CAD defined as a diameter stenosis of at least 50%. RESULTS: Compared with never-smokers, former smokers exhibited no significant differences in the probabilities of obstructive CAD, any coronary plaque, calcified plaque, or mixed plaque, as determined using adjusted odds ratios (aORs; p>0.05 for all). However, the risk of non-calcified plaque was significantly higher in former smokers (aOR, 1.34; 95% confidence interval [CI], 1.00 to 1.78; p=0.048). Current smokers had significantly higher rates of obstructive CAD (aOR, 1.46; 95% CI, 1.10 to 1.96; p=0.010), any coronary plaque (aOR, 1.41; 95% CI, 1.20 to 1.65; p<0.001), calcified plaque (aOR, 1.32; 95% CI, 1.13 to 1.55; p=0.001), non-calcified plaque (aOR, 1.72; 95% CI, 1.28 to 2.32; p<0.001), and mixed plaque (aOR, 2.00; 95% CI, 1.39 to 2.86; p<0.001) compared to never smokers. CONCLUSIONS This cross-sectional study revealed a significant association between current smoking and subclinical coronary atherosclerosis, as detected on CCTA. Additionally, former smoking demonstrated an association with non-calcified plaque, indicating elevated cardiovascular risk.

OBJECTIVES: In this study, we sought to evaluate the association between smoking status and subclinical coronary atherosclerosis, as detected by coronary computed tomography angiography (CCTA), in asymptomatic individuals. METHODS: We retrospectively analyzed 9,285 asymptomatic participants (mean age, 53.7±8.0 years; n=6,017, 64.8% male) with no history of coronary artery disease (CAD) who had undergone self-referred CCTA. Of these participants, 4,333 (46.7%) were considered never smokers, 2,885 (31.1%) former smokers, and 2,067 (22.3%) current smokers. We assessed the degree and characteristics of subclinical coronary atherosclerosis using CCTA, with obstructive CAD defined as a diameter stenosis of at least 50%. RESULTS: Compared with never-smokers, former smokers exhibited no significant differences in the probabilities of obstructive CAD, any coronary plaque, calcified plaque, or mixed plaque, as determined using adjusted odds ratios (aORs; p>0.05 for all). However, the risk of non-calcified plaque was significantly higher in former smokers (aOR, 1.34; 95% confidence interval [CI], 1.00 to 1.78; p=0.048). Current smokers had significantly higher rates of obstructive CAD (aOR, 1.46; 95% CI, 1.10 to 1.96; p=0.010), any coronary plaque (aOR, 1.41; 95% CI, 1.20 to 1.65; p<0.001), calcified plaque (aOR, 1.32; 95% CI, 1.13 to 1.55; p=0.001), non-calcified plaque (aOR, 1.72; 95% CI, 1.28 to 2.32; p<0.001), and mixed plaque (aOR, 2.00; 95% CI, 1.39 to 2.86; p<0.001) compared to never smokers. CONCLUSIONS This cross-sectional study revealed a significant association between current smoking and subclinical coronary atherosclerosis, as detected on CCTA. Additionally, former smoking demonstrated an association with non-calcified plaque, indicating elevated cardiovascular risk.

OBJECTIVES: In this study, we sought to evaluate the association between smoking status and subclinical coronary atherosclerosis, as detected by coronary computed tomography angiography (CCTA), in asymptomatic individuals. METHODS: We retrospectively analyzed 9,285 asymptomatic participants (mean age, 53.7±8.0 years; n=6,017, 64.8% male) with no history of coronary artery disease (CAD) who had undergone self-referred CCTA. Of these participants, 4,333 (46.7%) were considered never smokers, 2,885 (31.1%) former smokers, and 2,067 (22.3%) current smokers. We assessed the degree and characteristics of subclinical coronary atherosclerosis using CCTA, with obstructive CAD defined as a diameter stenosis of at least 50%. RESULTS: Compared with never-smokers, former smokers exhibited no significant differences in the probabilities of obstructive CAD, any coronary plaque, calcified plaque, or mixed plaque, as determined using adjusted odds ratios (aORs; p>0.05 for all). However, the risk of non-calcified plaque was significantly higher in former smokers (aOR, 1.34; 95% confidence interval [CI], 1.00 to 1.78; p=0.048). Current smokers had significantly higher rates of obstructive CAD (aOR, 1.46; 95% CI, 1.10 to 1.96; p=0.010), any coronary plaque (aOR, 1.41; 95% CI, 1.20 to 1.65; p<0.001), calcified plaque (aOR, 1.32; 95% CI, 1.13 to 1.55; p=0.001), non-calcified plaque (aOR, 1.72; 95% CI, 1.28 to 2.32; p<0.001), and mixed plaque (aOR, 2.00; 95% CI, 1.39 to 2.86; p<0.001) compared to never smokers. CONCLUSIONS This cross-sectional study revealed a significant association between current smoking and subclinical coronary atherosclerosis, as detected on CCTA. Additionally, former smoking demonstrated an association with non-calcified plaque, indicating elevated cardiovascular risk.

OBJECTIVES: In this study, we sought to evaluate the association between smoking status and subclinical coronary atherosclerosis, as detected by coronary computed tomography angiography (CCTA), in asymptomatic individuals. METHODS: We retrospectively analyzed 9,285 asymptomatic participants (mean age, 53.7±8.0 years; n=6,017, 64.8% male) with no history of coronary artery disease (CAD) who had undergone self-referred CCTA. Of these participants, 4,333 (46.7%) were considered never smokers, 2,885 (31.1%) former smokers, and 2,067 (22.3%) current smokers. We assessed the degree and characteristics of subclinical coronary atherosclerosis using CCTA, with obstructive CAD defined as a diameter stenosis of at least 50%. RESULTS: Compared with never-smokers, former smokers exhibited no significant differences in the probabilities of obstructive CAD, any coronary plaque, calcified plaque, or mixed plaque, as determined using adjusted odds ratios (aORs; p>0.05 for all). However, the risk of non-calcified plaque was significantly higher in former smokers (aOR, 1.34; 95% confidence interval [CI], 1.00 to 1.78; p=0.048). Current smokers had significantly higher rates of obstructive CAD (aOR, 1.46; 95% CI, 1.10 to 1.96; p=0.010), any coronary plaque (aOR, 1.41; 95% CI, 1.20 to 1.65; p<0.001), calcified plaque (aOR, 1.32; 95% CI, 1.13 to 1.55; p=0.001), non-calcified plaque (aOR, 1.72; 95% CI, 1.28 to 2.32; p<0.001), and mixed plaque (aOR, 2.00; 95% CI, 1.39 to 2.86; p<0.001) compared to never smokers. CONCLUSIONS This cross-sectional study revealed a significant association between current smoking and subclinical coronary atherosclerosis, as detected on CCTA. Additionally, former smoking demonstrated an association with non-calcified plaque, indicating elevated cardiovascular risk.

Owing to a large-jeopardized myocardium, left main coronary artery disease (LMCAD) represents the substantial high-risk anatomical subset of obstructive coronary artery disease.For several decades, coronary artery bypass grafting (CABG) has been the “gold standard” treatment for LMCAD. Along with advances in CABG, percutaneous coronary intervention (PCI) has also dramatically evolved over time in conjunction with advances in the stent or device technology, adjunct pharmacotherapy, accumulated experiences, and practice changes, establishing its position as a safe, reasonable treatment option for such a complex disease. Until recently, several randomized clinical trials, meta-analyses, and observational registries comparing PCI and CABG for LMCAD have shown comparable long-term survival with tradeoffs between early and late risk-benefit of each treatment. Despite this, there are still several unmet issues for revascularization strategy and management for LMCAD. This review article summarized updated knowledge on evolution and clinical evidence on the treatment of LMCAD, with a focus on the comparison of state-of-the-art PCI with CABG.