BACKGROUND/OBJECTIVES: Dietary supplement use is common among breast cancer survivors, but studies on Asian populations remain limited. This study investigated dietary supplement use among Korean breast cancer survivors, distinguishing between vitamin/ mineral (VM) and non-vitaminon-mineral (NVNM) supplements. SUBJECTS/METHODS: This cross-sectional study included 1,136 stage I–III breast cancer survivors from 12 Korean hospitals, who survived more than 6 mon post-surgery. The participants completed a questionnaire on post-diagnostic dietary supplement use. Stepwise logistic regression was applied, calculating odds ratios (ORs) and 95% confidence intervals (CIs) to identify the demographic and clinical factors associated with VM and NVNM use. RESULTS: Seventy percent of survivors reported supplement use, with 25% using a single product. The most common VM supplements were multivitamins/minerals, vitamin D, and vitamin C, while the most common NVNM supplements included omega-3 fatty acids, probiotics, and ginseng. Survivors with higher education and greater physical activity were more likely to use VM supplements (ORs [95% CIs], 2.74 [1.76–4.25] for college graduates or above vs. middle school or below; 1.38 [1.02–1.88] for the most active group vs. the least active group). NVNM use was associated with higher education, greater physical activity levels, and a history of smoking (ORs [95% CIs], 2.29 [1.46–3.58] for college graduates or above vs. middle school or below; 1.52 [1.13–2.06] for the most active group vs. the least active group; 2.00 [1.23–3.25] for ever smokers vs. never smokers). Survivors who had undergone chemotherapy were also more likely to use NVNM supplements than those who had not (OR [95% CI], 1.37 [1.02–1.84]). CONCLUSION Seventy percent of Korean breast cancer survivors used dietary supplements in this study. VM use was associated with higher education and physical activity, while higher NVNM use was associated with higher education, greater physical activity, a history of smoking, and chemotherapy.

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.

BACKGROUND/OBJECTIVES: Isoflavones are estrogen-like compounds found in plants and their health effects remain equivocal. We investigated dietary isoflavone intake and its associated factors in Korean breast cancer survivors, with a comparison to cancer-free women. SUBJECTS/METHODS: The usual dietary intake of breast cancer survivors (n = 981, mean age 52 yrs) in 9 hospitals between 2012 and 2019 was assessed using 3-day food records or food frequency questionnaires (FFQs). They were age-matched to 2,943 cancer-free women who completed FFQs as part of a nationwide study conducted between 2012 and 2016. We used the flavonoid database of common Korean foods and the Phenol-Explorer database to estimate isoflavone intake. The contribution of each food or food group to the total isoflavone intake was calculated. The adjusted least-squares means of dietary isoflavone intake according to lifestyle and clinical factors were calculated using generalized linear models. RESULTS: Breast cancer survivors had a higher mean dietary isoflavone intake (23.59 mg/day) than cancer-free women (17.81 mg/day). Major food sources, including tofu, soybeans, and doenjang, contributed to over 70% of the isoflavone intake in both groups. When we estimated dietary isoflavone intake according to lifestyle characteristics, isoflavone intake increased with higher scores of adherence to the American Cancer Society dietary guidelines but decreased with increasing body mass index in both groups. Among cancer-free women, dietary isoflavone intake was higher among those who had never smoked and among dietary supplement users. Among breast cancer survivors, dietary isoflavone intakes did not vary with clinical characteristics, including time since surgery and estrogen receptor status. CONCLUSION Breast cancer survivors were more likely to consume isoflavones than agematched cancer-free women. Dietary isoflavone intake was associated with healthy lifestyle characteristics in women both with and without breast cancer. Further research is needed to understand the role of the higher isoflavone intake among breast cancer survivors compared to cancer-free women on their prognosis.

Background: Emergency department (ED) overcrowding poses a global challenge, particularly for critically ill patients requiring intensive care unit (ICU) admission. Although delays in ICU transfer increase mortality in critically ill populations, the optimal timing for septic shock remains uncertain. Methods: We conducted a target trial emulation using a prospective cohort of 815 septic shock patients from 19 Korean hospitals. Delayed ICU transfer was defined using restricted cubic splines. The primary outcome was in-hospital mortality. Multivariable logistic regression and inverse probability treatment weighting were used to adjust for confounders of age, sex, comorbidities, severity of illness, and mechanical ventilation use. Subgroup analyses were performed to assess the effect across patient characteristics. Results: The median time of ED-to-ICU transfer was 6.7 hours (interquartile range, 4.7–11.4), and only 7% of patients were transferred within 3 hours. ICU transfer within 3 hours was associated with significantly lower in-hospital mortality (odds ratio, 0.48; 95% CI, 0.24–0.94) compared to later transfers. Mortality risk increased with elapsing time up to 6 hours and then plateaued. The benefit of early ICU transfer was consistent across subgroups but was particularly pronounced in patients requiring extracorporeal membrane oxygenation or continuous renal replacement therapy (P for interaction=0.02). Conclusions Early ICU transfer within 3 hours significantly reduces mortality in patients with septic shock, with the greatest benefit observed in those requiring advanced organ support. These findings highlight the need for system-wide strategies to reduce ED boarding time and prioritize timely ICU admission for septic shock management.

Background: The effectiveness of electronic medical record-based alert systems, response protocols for sepsis diagnosis, and treatment in hospitalized patients remains unclear. This study aimed to determine whether the introduction of an electronic medical record-based sepsis response protocol (SRP) along with a 24/7 operating rapid response system affects the prognosis for patients with hospital-onset sepsis. Methods: In August 2022, a SRP based on the National Early Warning Score was implemented in the electronic medical record system at Asan Medical Center. We retrospectively analyzed patients screened by the detection system for 1 year after the SRP implementation. Patients of the first 6 months (preliminary group) and those of the second 6 months (SRP group) were matched 1:1 based on propensity scores. The primary outcome was 30-day mortality. Results: Of the 608 hospitalized patients screened by the system, 176 were assigned to each group after 1:1 propensity score matching. Patients in the SRP group were significantly more likely to receive blood cultures (58.5%) compared with the preliminary group (45.5%) (P=0.019). The SRP group showed a lower 30-day mortality risk (hazard ratio, 0.56; 95% CI, 0.36–0.86; P=0.017) compared to the preliminary group. A restricted cubic spline curve showed that SRP survival benefit began to manifest after the first 4 months (P=0.036). Conclusions Alongside an existing rapid response system, the National Early Warning Score-based SRP in the electronic medical record reduced mortality for hospital-onset sepsis within 1 year.

Purpose: Rare diseases occur in <50 per 100000 people and require lifelong management. However, essential epidemiological data on such diseases are lacking, and a consecutive monitoring system across time and regions remains to be established. Standardized digital phenotypes are required to leverage an international data network for research on rare endocrine diseases. We developed digital phenotypes for rare endocrine diseases using the observational medical outcome partnership common data model. Materials and Methods: Digital phenotypes of three rare endocrine diseases (medullary thyroid cancer, hypoparathyroidism, pheochromocytoma/paraganglioma) were validated across three databases that use different vocabularies: Severance Hospital’s electronic health record from South Korea; IQVIA’s United Kingdom (UK) database for general practitioners; and IQVIA’s United States (US) hospital database for general hospitals. We estimated the performance of different digital phenotyping methods based on International Classification of Diseases (ICD)-10 in the UK and the US or systematized nomenclature of medicine clinical terms (SNOMED CT) in Korea. Results: The positive predictive value of digital phenotyping was higher using SNOMED CT-based phenotyping than ICD-10-based phenotyping for all three diseases in Korea (e.g., pheochromocytoma/paraganglioma: ICD-10, 58%–62%; SNOMED CT, 89%). Estimated incidence rates by digital phenotyping were as follows: medullary thyroid cancer, 0.34–2.07 (Korea), 0.13–0.30 (US); hypoparathyroidism, 0.40–1.20 (Korea), 0.59–1.01 (US), 0.00–1.78 (UK); and pheochromocytoma/paraganglioma, 0.95–1.67 (Korea), 0.35–0.77 (US), 0.00–0.49 (UK). Conclusion Our findings demonstrate the feasibility of developing digital phenotyping of rare endocrine diseases and highlight the importance of implementing SNOMED CT in routine clinical practice to provide granularity for research.

Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.

Background: This study aimed to report the short- and midterm outcomes of arthroscopic rotator cuff repair (ARCR) and reverse shoulder arthroplasty (RSA) in weight-bearing shoulders. Methods: This retrospective multicenter study included 19 cases of ARCR and 10 cases of RSA performed in weight-bearing shoulders from 2009 to 2021. In the ARCR group, postoperative 6-month magnetic resonance imaging confirmed the tendon integrity. In the RSA group, scapular notching, acromial fracture, and implant failure were assessed using plain radiographs, and complications were recorded. In both groups, preoperative and postoperative range of motion and functional scores were documented, along with subjective satisfaction and arm use for weight-bearing on the shoulders. For patients followed up for > 5 years, a midterm analysis was performed. Results: The ARCR group included 8 men and 11 women (average age, 58.8 ± 8.0 years). Initially, Patte types 1, 2, and 3 were noted in 9, 8, and 2 patients, respectively, and 4 patients exhibited full-thickness subscapularis tears. Four patients showed supraspinatus retear, and 2 patients showed subscapularis retear. Retear of any rotator cuff was observed in 5 patients (26.3%). Twelve patients were followed up for > 5 years; 11 (91.7%) used their operated arm for weight-bearing and 9 (75.0%) were satisfied. The RSA group included 5 men and 5 women (average age, 74.3 ± 7.9 years). Procedures included RSAs for cuff tear arthropathy (n = 6), osteoarthritis (n = 3), and fracture nonunion (n = 1). No cases of dislocation, prosthesis loosening, or disassociation were observed throughout the follow-up. However, 1 patient required implant removal due to infection, and 4 patients showed stage 1 scapular notching. Five patients were followed up for > 5 years, all of whom expressed satisfaction and used their operated arms for weight-bearing, despite mean forward flexion (107.5° ± 12.6°) and American Shoulder and Elbow Surgeons score (61.5 ± 5.3) being less than reported patient acceptable symptomatic state (110° and 76, respectively). Conclusions Both ARCR and RSA showed promising outcomes in terms of weight-bearing on the operated arm and subjective satisfaction at short- and midterm follow-up. Therefore, neither of these surgeries should be considered contraindicated for patients with weight-bearing shoulder conditions.

Background/Aims: Small bowel capsule endoscopy (SBCE) has become the standard for initial evaluation in the diagnosis of small bowel lesions. Although optimal visualization of the mucosa is important, patients experience difficulty in consuming a large volume of bowel preparation agents. This study aimed to compare the efficacy and safety of 1-L polyethylene glycol (PEG) with ascorbic acid (AA) and 2-L PEG with AA. Methods: In this prospective, multicenter, non-inferiority study, patients who received SBCE were randomly assigned to consume 1-L PEG with AA or 2-L PEG with AA for small bowel preparation. The primary outcome was adequate small bowel visibility quality (SBVQ). The secondary outcomes included diagnostic yield, cecal complete rate, and adverse events. Results: One hundred and forty patients were enrolled in this study, 70 patients per group. In the per-protocol analysis, there were no significant differences in the adequate SBVQ rate (94.0% vs 94.3%; risk difference, –0.3; 95% confidence interval, –8.1 to 7.6; p=1.000), diagnostic yield rate (49.3% vs 48.6%, p=0.936), or cecal complete rate (88.1% vs 92.9%, p=0.338) between the 1-L PEG with AA group and 2-L PEG with AA group. The incidence of adverse events did not differ significantly between the groups (12.9% vs 11.9%, p=0.871). Conclusions One liter-PEG with AA is not inferior to 2-L PEG with AA in terms of adequate SBVQ for SBCE. One liter-PEG with AA can be recommended as the standard method for bowel cleansing for SBCE.