Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Background: Multiple myeloma (MM) patients are at risk of skeletal-related events (SREs) like spinal cord compression, pathologic fractures, bone surgery, and radiation to bone. Realworld data regarding SREs in MM are limited. Methods: We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service (HIRA) database from 2007 to 2018. Results: Over a 12-year study period, we identified 6,717 patients who developed symptomatic MM. After a median follow-up of 35.1 months (interquartile range [IQR], 20.8–58.2 months), 43.6% of these patients experienced SREs, and 39.6% had four or more SREs. One in five patients (20.0%) experienced pathologic fractures within the first year of follow-up. The median time to first SRE was 9.6 months (IQR, 1.2–25.8 months), with 3.0 months in the group with prior SREs and 19.8 months in the group without prior SREs.During follow-up, 78.5% of patients received bisphosphonates. Multiple logistic regression analysis revealed several factors associated with an increased risk of SREs, including being female (odds ratio [OR], 1.44), aged 50 or older (OR, 1.87), having cerebrovascular disease (OR, 1.34), undergoing first-line chemotherapy regimens not containing bortezomib or lenalidomide (OR, 1.49), and being in the group with prior SREs and bisphosphonate use (OR, 5.63), compared to the group without prior SREs and without bisphosphonate use. Conclusion This population-based study is the first to report the incidence and risk factors of SREs in Korean MM patients, which can be used to assess their bone health.

Background/Aims: Prokinetic agents and neuromodulators are among the treatment options for functional dyspepsia (FD), but their comparative efficacy is unclear. We aimed to compare the efficacy of mosapride controlled-release (CR) and nortriptyline in patients with FD after 4 weeks of treatment. Methods: Participants with FD were randomly assigned (1:1) to receive mosapride CR (mosapride CR 15 mg and nortriptyline placebo) or nortriptyline (mosapride CR placebo and nortriptyline 10 mg) in double-placebo, double-blinded, randomized controlled, parallel clinical study. The primary endpoint was defined as the proportion of patients with overall dyspepsia improvement after 4 weeks treatment. The secondary endpoints were changes in individual symptom scores, anxiety, depression, and quality of life. Results: One hundred nine participants were recruited and assessed for eligibility, and 54 in the mosapride CR group and 50 in the nortriptyline group were included in the modified intention-to-treat protocol. The rate of overall dyspepsia improvement was similar between groups (53.7% vs 54.0%, P = 0.976). There was no difference in the efficacy of mosapride CR and nortriptyline in a subgroup analysis by FD subtype (59.3% vs 52.5% in postprandial distress syndrome, P = 0.615; 44.4% vs 40.0% in epigastric pain syndrome, P = > 0.999; 50.0% vs 59.1% in overlap, P = 0.565; respectively). Both treatments significantly improved anxiety, depression, and quality of life from baseline. Conclusion Mosapride CR and nortriptyline showed similar efficacy in patients with FD regardless of the subtype. Both treatments could be equally helpful for improving quality of life and psychological well-being while also relieving dyspepsia.

Background/Aims: There is growing interest in whether Helicobacter pylori eradication (HPE) can affect body weight. Methods: Data from 5 universities between January 2013 and December 2019 were analyzed retrospectively. H. pylori-positive subjects who had body weight measurements taken at least twice at intervals of 3 months or longer were included. Using propensity score (PS)-matched data, changes in body mass index (BMI) and the lipid profile after HPE were compared with the non-HPE group. Results: Among 363 eligible patients, 131 HPE patients were PS-matched to 131 non-HPE patients. The median intervals between the measurements were 610 (range, 154-1250) days and 606 (range, 154-1648) days in the HPE and non-HPE groups, respectively. In both groups, the mean BMI increased (from 24.5 kg/m2 to 24.7 kg/m2 in the HPE group, and from 24.4 kg/m2 to 24.5 kg/m2 in the non-HPE group). The 2 groups did not show significantly different changes (P = 0.921). In the lowest baseline BMI quartile, the BMI increased after HPE by 1.23 (standard deviation [SD], 3.72) kg/m2 (P = 0.060), and the non-HPE group showed a decreased BMI at the time of follow-up (by − 0.24 [SD, 5.25] kg/m2 ; P = 0.937) (between-group P = 0.214). Triglyceride levels increased after HPE (mean: 135 [SD, 78] to 153 [SD, 100] mg/dL; between-group P = 0.053). Conclusion The overall BMI change was not significantly different between the HPE and non-HPE groups, but patients with low BMI showed a tendency to gain weight after HPE. Triglyceride levels increased after HPE with marginal significance.

Purpose: To report a modified rectangular loop suture technique for patients with refractory pupillary optic capture after intraocular lens scleral fixation. Methods: A modified rectangular loop suture was performed in four patients with persistent pupillary capture despite medication and laser iridotomy. A loop suture pattern was designed in the two quadrants without the scleral fixation knot. A 2 mm loop suture point was marked 2 mm away from the corneal limbus. The suture point was similarly marked in the opposite quadrants. Small conjunctival incisions were made at a marked point and a non-absorbable 10-0 prolene long needle was passed. The needle was inserted at the 1 o’clock position through the conjunctival incision and passed between the intraocular lens and the iris plane. Then it was withdrawn using a 26-gauge (G) syringe from the 8 o’clock position in the opposite quadrant. Similarly, the needle was passed from the 7 o’clock position under the conjunctiva, and pulled out of the sclera at the 2 o’clock position. It was then passed to the 1 o’clock position under the conjunctiva and a knot was made and buried. The operation was completed without closure of the conjunctival incision. Results: In all four eyes, pupillary optic capture was corrected and remained stable without recurrence for an average of 7.25 months. Conclusions The modified rectangular loop suture may be useful for refractory pupillary capture cases. The procedure is relatively simple and minimizes scleral exposure to the conjunctival suture. It is expected that this may reduce patient discomfort.

Purpose: To investigate the characteristics and treatment results of patients aged ≥ 85 years who were diagnosed with treatment-naïve neovascular age-related macular degeneration (nAMD). Methods: The medical records of patients diagnosed with treatment-naïve nAMD who were ≥ 85 years old at the time of diagnosis with at least 12 months follow-up were retrospectively reviewed. The number of intravitreal injections of anti-vascular endothelial growth factor (VEGF) and agents used during the entire period were investigated. Best-corrected visual acuity and optical coherence tomography results before and after treatment were analyzed. Visual acuity of the fellow eye was also collected. Results: A total of 40 eyes of 40 patients with mean age of 87.5 ± 2.4 were included in the study. The mean logarithm of the minimal angle of resolution visual acuity was 0.85 ± 0.57, and the mean of the fellow eye was 0.93 ± 0.99. Compared to before the treatment, there was no significant difference after intravitreal injection in terms of visual acuity. Central retinal thickness showed significant reduction at all time points after treatment. Conclusions In patients aged ≥ 85 years at the time of diagnosis, intravitreal injections of anti-VEGF prevented deterioration of visual acuity and showed successful anatomical outcomes. Especially, many had poor visual acuity in the fellow eye, suggesting the importance of maintaining visual acuity. Therefore, active treatment is necessary in the elderly.

Background: and Purpose This study aimed to evaluate whether extracellular-vesicle-incorporated microRNAs (miRNAs) are potential biomarkers for cancer-related stroke. Methods: This cohort study compared patients with active cancer who had embolic stroke of unknown sources (cancer-stroke group) with patients with only cancer, patients with only stroke, and healthy individuals (control groups). The expression profiles of miRNAs encapsulated in plasma exosomes and microvesicles were evaluated using microarray and validated using quantitative real-time polymerase chain reaction. The XENO-QTM miRNA assay technology was used to determine the absolute copy numbers of individual miRNAs in an external validation cohort. Results: This study recruited 220 patients, of which 45 had cancer-stroke, 76 were healthy controls, 39 were cancer controls, and 60 were stroke controls. Three miRNAs (miR-205-5p, miR-645, and miR-646) were specifically incorporated into microvesicles in patients with cancer-related stroke, cancer controls, and stroke controls. The area under the receiver operating characteristic curves of these three miRNAs were 0.7692–0.8510 for the differentiation of patients with cancer-stroke from cancer-controls and 0.8077–0.8846 for the differentiation of patients with cancer-stroke from stroke controls. The levels of several miRNAs were elevated in the plasma exosomes of patients with cancer, but were lower than those in plasma microvesicles. An in vivo study showed that systemic injection of miR-205-5p promoted the development of arterial thrombosis and elevation of D-dimer levels. Conclusion Stroke due to cancer-related coagulopathy was associated with deregulated expression of miRNAs, particularly microvesicle-incorporated miR-205-5p, miR-645, and miR-646. Further prospective studies of extracellular-vesicle-incorporated miRNAs are required to confirm the diagnostic role of miRNAs in patients with stroke and to screen the roles of miRNAs in patients with cancer.

Background/Aims: Although it is near concluded that renin-angiotensin system inhibitors do not have a harmful effect on coronavirus disease 2019 (COVID-19), there is no report about whether angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) offer any protective role. This study aimed to compare the association of ARBs and ACEIs with COVID-19-related mortality. Methods: All patients with COVID-19 in Korea between January 19 and April 16, 2020 were enrolled. The association of ARBs and ACEIs with mortality within 60 days were evaluated. A comparison of hazard ratio (HR) was performed between COVID-19 patients and a retrospective cohort of pneumonia patients hospitalized in 2019 in Korea. Results: Among 10,448 COVID-19 patients, ARBs and ACEIs were prescribed in 1,231 (11.7%) and 57 (0.6%) patients, respectively. After adjusting for age, sex, and history of comorbidities, the ARB group showed neutral association (HR, 1.034; 95% CI, 0.765 to 1.399; p = 0.8270) and the ACEI groups showed no significant associations likely owing to the small population size (HR, 0.736; 95% CI, 0.314 to 1.726; p = 0.4810). When comparing HR between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia in 2019, the trend of ACEIs showed similar benefits, whereas the protective effect of ARBs observed in the retrospective cohort was absent in COVID-19 patients. Meta-analyses showed significant positive correlation with survival of ACEIs, whereas a neutral association between ARBs and mortality. Conclusions Although ARBs or ACEIs were not associated with fatal outcomes, potential beneficial effects of ARBs observed in pneumonia were attenuated in COVID-19.