Purpose: While TP53 mutations are well known to be associated with adverse prognosis in hematological diseases, their functional impact remains incompletely understood. This study examines the spectrum of TP53 mutations across various hematologic malignancies and evaluates their functional impact. Materials and Methods: Using targeted sequencing panels, we analyzed TP53 mutations in the bone marrow aspiration samples of a retrospective cohort of 856 patients diagnosed with hematologic malignancies. To assess the impact of TP53 mutations, we applied the evolutionary action (EAp53) score and the relative fitness score (RFS), previously proposed functional scoring methods. The effects of variant allele frequency (VAF), disruptive mutations, EAp53 score, and RFS on overall survival (OS) were evaluated. Results: TP53 mutations were associated with inferior OS compared with wildtype TP53 (median OS 10.0 months versus not estimable; hazard ratio (HR) 4.6; p<0.001). In the acute myeloid leukemia, multiple myeloma, and myelodysplastic syndrome subgroups, TP53 mutations had a significant adverse impact on OS. (HRs 3.8, 4.2, 6.0, respectively; p<0.001, p=0.005, p<0.001, respectively). Patients with VAF >50% had significantly poorer OS compared to those with VAF ≤50% (median OS 7.5 months versus 22.8 months; HR 2.2, p=0.016). Moreover, patients in the high-risk RFS group (RFS >0.22) had significantly worse OS compared to those in the low-risk RFS group (RFS ≤0.22) (median OS 5.6 months versus 16.3 months; HR 2.2, p=0.041). However, no significant survival difference was observed between the EAp53 high-risk (>75) and low-risk (≤75) groups, or between patients with disruptive and non-disruptive mutations. Conclusion Our findings highlight VAF and RFS as valuable tools for stratifying TP53-mutant patients into high-risk and low-risk groups.

Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents—tofacitinib, filgotinib, and upadacitinib—differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.

Background: The effectiveness of intravenous tissue plasminogen activator (IV tPA) in patients with large-vessel occlusion (LVO) receiving endovascular treatment (EVT) for acute ischemic stroke (AIS) has been questioned. We investigated IV tPA effectiveness in real-world AIS patients, including those with intracranial LVO receiving EVT. Methods: We identified patients with AIS who presented to hospital with National Institutes of Health Stroke Scale ≥4 within 8 hours of symptom onset from the institutional stroke registry. The association of IV tPA use with effectiveness and safety outcomes was analyzed in overall enrolled AIS patients; LVO patients; and patients treated with EVT. The effect of IV tPA was assessed using multiple logistic regression. Results: Among the 654 patients meeting study entry criteria, 238 (36.4%) received IV tPA and 416 (63.6%) did not. Multiple logistic regression analysis and shift analysis revealed IV tPA was associated with improved outcomes in overall enrolled AIS population, LVO, and EVT-treated subgroups. Among EVT-treated patients, IV tPA was associated with higher likelihood of ambulatory or better outcome (modified Rankin Scale 0–3) with odds ratio of 1.95 (P=0.03). Conclusions In this real-world study, IV tPA use was associated with improved outcomes for patients with AIS, including among LVO patients treated and not treated with EVT, in the contemporary mechanical thrombectomy era.

Purpose: We assessed human papillomavirus (HPV) genotype-based risk stratification and the efficacy of cytology testing for cervical cancer screening in patients with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL). Materials and Methods: Between 2010 and 2021, we monitored 1,273 HPV-positive women with ASCUS/LSIL every 6 months for up to 60 months. HPV infections were categorized as persistent (HPV positivity consistently observed post-enrollment), negative (HPV negativity consistently observed post-enrollment), or non-persistent (neither consistently positive nor negative). HPV genotypes were grouped into high-risk (Hr) groups 1 (types 16, 18, 31, 33, 45, 52, and 58) and 2 (types 35, 39, 51, 56, 59, 66, and 68) and a low-risk group. Hr1 was subdivided into types (a) 16 and 18; (b) 31, 33, and 45; and (c) 52 and 58. Cox regression and machine learning (ML) algorithms were used to analyze progression rates. Results: Among 1,273 participants, 17.6% with persistent HPV infections experienced disease progression versus no progression in the HPV-negative group (p < 0.001). Cox analysis revealed the highest hazard ratios (HRs) for Hr1-a (11.6, p < 0.001), followed by Hr1-b (9.26, p < 0.001) and Hr1-c (7.21, p < 0.001). HRs peaked at 12-24 months, with Hr1-a maintaining significance at 24-36 months (10.7, p=0.034). ML analysis identified the final cytology change pattern as the most significant factor, with 14-15 months the optimal time for detecting progression from the first examination. Conclusion In ASCUS/LSIL cases, follow-up strategies should be based on HPV risk types. Annual follow-up was the most effective monitoring for detecting progression/regression.

Purpose: The optimal reconstruction method following distal gastrectomy has not been elucidated. Since Billroth-II (B-II) reconstruction is commonly associated with increased bile reflux, Braun jejunojejunostomy has been proposed to reduce this complication. Materials and Methods: We retrospectively analyzed 325 patients with gastric cancer who underwent distal gastrectomy with B-II reconstruction between January 2015 and December 2017, comprising 159 patients without Braun anastomosis and 166 with Braun anastomosis.Outcomes were assessed over three years using annual gastroscopy based on the residual food, gastritis, and bile reflux criteria and the Los Angeles classification for reflux esophagitis. Results: In the first postoperative year, the group with Braun anastomosis showed a significant reduction in bile reflux compared to the group without Braun anastomosis (75.9% vs. 86.2%; P=0.019). Moreover, multivariate analysis identified Braun anastomosis as the sole factor associated with this outcome. Additionally, the group with Braun anastomosis had a lower incidence of heartburn (12.0% vs. 20.1%; P=0.047) and reduced use of prokinetics (P<0.001) and acid reducers (P=0.002) compared to the group without Braun anastomosis.However, these benefits diminished in subsequent years, with no significant differences in residual food, gastritis, or reflux esophagitis between the groups. Both groups showed similar body mass index scores and nutritional outcomes over the 3-year follow-up period. Conclusions Although Braun anastomosis offers short-term benefits in reducing bile reflux after B-II reconstruction, these effects are not sustainable. The routine use of Braun anastomosis should be reconsidered, though either approach remains a viable option depending on the patient’s circumstances.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background: Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better. Methods: We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention. We categorized the patients as those treated with complete revascularization (n=295) or incomplete revascularization (n=104). The study endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, ischemia-driven revascularization, stent thrombosis, and stroke. We performed propensity score matching (PSM) and analyzed the incidence of MACCE at 1 year. Results: After PSM, the two groups were well balanced. There was no significant difference between the two groups in MACCE at 1 year (12.1% vs. 15.2%; hazard ratio, 1.28; 95% confidence interval, 0.60–2.74; p=0.524) after PSM. The components of MACCE and major bleeding were also not significantly different. Conclusion There was no significant difference in clinical outcomes between the groups treated with complete or incomplete revascularization for LM culprit lesion AMI with multivessel disease.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.