Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

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.

Background/Aims: Chronic gastroesophageal reflux disease (GERD) requires symptom relief and treatment of associated conditions. In this study, we aimed to compare anti-reflux mucosectomy (ARMS) and Stretta radiofrequency (SRF) for treating patients with chronic GERD who are unresponsive to proton pump inhibitors (PPIs) and to identify the indications for each procedure. Methods: Data of patients who underwent ARMS or SRF between March 2021 and April 2023 were analyzed. Changes in GERD questionnaire (GERDQ) scores, endoscopic Los Angeles (LA) grade, flap valve grade (FVG) based on Hill’s type, EndoFLIP distensibility index (DI), endoscopic Barrett’s epithelium (BE) resolution rate, and PPI withdrawal rate were compared between the two groups. Results: Improvements in the GERDQ scores and PPI withdrawal rates were similar between the groups. The ARMS group showed significantly better changes in endoscopic LA grade, FVG, and EndoFLIP DI than the SRF group. The complications were more prevalent in the ARMS group than in the SRF group. Conclusions The change in endoscopic LA grade before and after the procedure was significantly higher in the ARMS group than in the SRF group. Significant improvements in endoscopic FVG, BE resolution, and EndoFLIP DI were observed only with the ARMS group.

Background: There are few safe effective ways to relieve osteoarthritis (OA) pain; as a result, off-label psychotropic drug prescriptions have increased worldwide. This study examined the change in psychotropic drug prescriptions for patients with OA from 2011 to 2020 using the Korean National Health Insurance Service dataset. Methods: The study population consisted of patients with hip or knee OA aged ≥ 65 years.Psychotropic drugs included opioids, benzodiazepines, non-benzodiazepine hypnotics (Z-drugs), anti-epileptics, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), typical antipsychotics, atypical antipsychotics, and anxiolytics. The prevalence and long-term (> 3 months) prescription rates of psychotropic drugs in OA patients were calculated. Results: The study included 1,821,158 patients with OA (mean age 71.7 years; 65.32% female).Of the cohort, 49% had comorbidities for which psychotropics were indicated. The prevalence of psychotropic prescriptions decreased from 58.2% to 52.0% in 2018 and then leveled off.The long-term prescription rate remained constant until 2018 and then increased slightly.The most commonly prescribed psychotropics were opioids and long- and short-acting benzodiazepines. The prescription rates of opioids and long-acting benzodiazepines decreased from 2011 to 2020. For those with psychiatric co-morbidities, the prescription rates of anti-epileptics and SNRIs increased, while the prescription rates of anti-epileptics, SSRIs, other antidepressants, and atypical psychotropics increased for those without such co-morbidities. The most commonly prescribed psychotropics were diazepam and alprazolam, excluding tramadol and tramadol–acetaminophen combination. For those with psychiatric co-morbidities, the prescription rates of gabapentin and fentanyl increased, while for those without such co-morbidities, the prescription rates of lorazepam, fentanyl, escitalopram and quetiapine increased. Conclusion A significant number of older Korean patients with OA were prescribed psychotropic drugs in the absence of comorbidities requiring such drugs, including drugs that have little effect on OA and unfavorable safety profiles in older adults.

Background: There are few safe effective ways to relieve osteoarthritis (OA) pain; as a result, off-label psychotropic drug prescriptions have increased worldwide. This study examined the change in psychotropic drug prescriptions for patients with OA from 2011 to 2020 using the Korean National Health Insurance Service dataset. Methods: The study population consisted of patients with hip or knee OA aged ≥ 65 years.Psychotropic drugs included opioids, benzodiazepines, non-benzodiazepine hypnotics (Z-drugs), anti-epileptics, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), typical antipsychotics, atypical antipsychotics, and anxiolytics. The prevalence and long-term (> 3 months) prescription rates of psychotropic drugs in OA patients were calculated. Results: The study included 1,821,158 patients with OA (mean age 71.7 years; 65.32% female).Of the cohort, 49% had comorbidities for which psychotropics were indicated. The prevalence of psychotropic prescriptions decreased from 58.2% to 52.0% in 2018 and then leveled off.The long-term prescription rate remained constant until 2018 and then increased slightly.The most commonly prescribed psychotropics were opioids and long- and short-acting benzodiazepines. The prescription rates of opioids and long-acting benzodiazepines decreased from 2011 to 2020. For those with psychiatric co-morbidities, the prescription rates of anti-epileptics and SNRIs increased, while the prescription rates of anti-epileptics, SSRIs, other antidepressants, and atypical psychotropics increased for those without such co-morbidities. The most commonly prescribed psychotropics were diazepam and alprazolam, excluding tramadol and tramadol–acetaminophen combination. For those with psychiatric co-morbidities, the prescription rates of gabapentin and fentanyl increased, while for those without such co-morbidities, the prescription rates of lorazepam, fentanyl, escitalopram and quetiapine increased. Conclusion A significant number of older Korean patients with OA were prescribed psychotropic drugs in the absence of comorbidities requiring such drugs, including drugs that have little effect on OA and unfavorable safety profiles in older adults.

Background: and Purpose This study evaluated the diagnostic utility of an anti-signal-recognition particle 54 (anti-SRP54) antibody-based enzyme-linked immunosorbent assay (ELISA) as well as the clinical, serological, and pathological characteristics of patients with SRP immune-mediated necrotizing myopathy (IMNM). Methods: We evaluated 87 patients with idiopathic inflammatory myopathy and 107 healthy participants between January 2002 and December 2023. The sensitivity and specificity of the ELISA for anti-SRP54 antibodies were assessed, and the clinical profiles of patients with antiSRP54 antibodies were determined. Results: The ELISA for anti-SRP54 antibodies had a sensitivity and specificity of 88% and 99%, respectively, along with a test–retest reliability of 0.92 (p<0.001). The 32 patients diagnosed with anti-SRP IMNM using a line-blot immunoassay included 28 (88%) who tested positive for anti-SRP54 antibodies using the ELISA, comprising 12 (43%) males and 16 (57%) females whose median ages at symptom onset and diagnosis were 43.0 years and 43.5 years, respectively. Symptoms included proximal muscle weakness in all 28 (100%) patients, neck weakness in 9 (32%), myalgia in 15 (54%), dysphagia in 5 (18%), dyspnea in 4 (14%), dysarthria in 2 (7%), interstitial lung disease in 2 (7%), and myocarditis in 2 (7%). The median serum creatine kinase (CK) level was 7,261 U/L (interquartile range: 5,086–10,007 U/L), and the median anti-SRP54 antibody level was 2.0 U/mL (interquartile range: 1.0–5.6 U/mL). The serum CK level was significantly higher in patients with coexisting anti-Ro-52 antibodies. Conclusions This study has confirmed the reliability of the ELISA for anti-SRP54 antibodies and provided insights into the clinical, serological, and pathological characteristics of South Korean patients with anti-SRP IMNM.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

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.

Background/Aims: Chronic gastroesophageal reflux disease (GERD) requires symptom relief and treatment of associated conditions. In this study, we aimed to compare anti-reflux mucosectomy (ARMS) and Stretta radiofrequency (SRF) for treating patients with chronic GERD who are unresponsive to proton pump inhibitors (PPIs) and to identify the indications for each procedure. Methods: Data of patients who underwent ARMS or SRF between March 2021 and April 2023 were analyzed. Changes in GERD questionnaire (GERDQ) scores, endoscopic Los Angeles (LA) grade, flap valve grade (FVG) based on Hill’s type, EndoFLIP distensibility index (DI), endoscopic Barrett’s epithelium (BE) resolution rate, and PPI withdrawal rate were compared between the two groups. Results: Improvements in the GERDQ scores and PPI withdrawal rates were similar between the groups. The ARMS group showed significantly better changes in endoscopic LA grade, FVG, and EndoFLIP DI than the SRF group. The complications were more prevalent in the ARMS group than in the SRF group. Conclusions The change in endoscopic LA grade before and after the procedure was significantly higher in the ARMS group than in the SRF group. Significant improvements in endoscopic FVG, BE resolution, and EndoFLIP DI were observed only with the ARMS group.

Background: and Purpose This study evaluated the diagnostic utility of an anti-signal-recognition particle 54 (anti-SRP54) antibody-based enzyme-linked immunosorbent assay (ELISA) as well as the clinical, serological, and pathological characteristics of patients with SRP immune-mediated necrotizing myopathy (IMNM). Methods: We evaluated 87 patients with idiopathic inflammatory myopathy and 107 healthy participants between January 2002 and December 2023. The sensitivity and specificity of the ELISA for anti-SRP54 antibodies were assessed, and the clinical profiles of patients with antiSRP54 antibodies were determined. Results: The ELISA for anti-SRP54 antibodies had a sensitivity and specificity of 88% and 99%, respectively, along with a test–retest reliability of 0.92 (p<0.001). The 32 patients diagnosed with anti-SRP IMNM using a line-blot immunoassay included 28 (88%) who tested positive for anti-SRP54 antibodies using the ELISA, comprising 12 (43%) males and 16 (57%) females whose median ages at symptom onset and diagnosis were 43.0 years and 43.5 years, respectively. Symptoms included proximal muscle weakness in all 28 (100%) patients, neck weakness in 9 (32%), myalgia in 15 (54%), dysphagia in 5 (18%), dyspnea in 4 (14%), dysarthria in 2 (7%), interstitial lung disease in 2 (7%), and myocarditis in 2 (7%). The median serum creatine kinase (CK) level was 7,261 U/L (interquartile range: 5,086–10,007 U/L), and the median anti-SRP54 antibody level was 2.0 U/mL (interquartile range: 1.0–5.6 U/mL). The serum CK level was significantly higher in patients with coexisting anti-Ro-52 antibodies. Conclusions This study has confirmed the reliability of the ELISA for anti-SRP54 antibodies and provided insights into the clinical, serological, and pathological characteristics of South Korean patients with anti-SRP IMNM.