BACKGROUND: Exogenous Cushing’s syndrome, which results from prolonged glucocorticoid treatment, is associated with metabolic abnormalities. Previously, we reported the inhibitory effect of tonsil-derived mesenchymal stem cell conditioned medium (T-MSC CM) on glucocorticoid signal transduction. In this study, we investigated the therapeutic efficacy of T-MSCs in a mouse model of exogenous Cushing’s syndrome. METHODS: Exogenous Cushing’s syndrome model mice was generated by corticosterone administration in the drinking water for 5 weeks, and T-MSCs were injected intraperitoneally twice during the third week. Serum lipid profiles were measured using a chemistry analyzer. HepG2 cells were treated with dexamethasone and co-cultured with T-MSCs.Expression levels of genes involved in cholesterol metabolism were examined using real-time PCR. Low-density lipoprotein receptor (LDLR) protein levels were determined using western blotting and immunohistochemistry. Liver RNA extracted from the CORT and CORT ? MSC mouse groups was used for transcriptome sequencing analysis and protein– protein interaction analysis. RESULTS: Weight reduction and improvements in dyslipidemia by T-MSC administration were observed only in female mice. T-MSCs reduce circulating LDL cholesterol levels by downregulating liver X receptor a (LXRa) and inducible degrader of LDLR (IDOL) expression, thereby stabilizing LDLRs in the liver. Transcriptome analysis of liver tissue revealed pathways that are regulated by T-MSCs administration. CONCLUSION Administration of MSCs to female mice receiving chronic corticosterone treatment reduced the circulating LDL cholesterol level by downregulating the LXRa–IDOL axis in hepatocytes. These results suggest that T-MSCs may offer a novel therapeutic strategy for managing exogenous Cushing’s syndrome by regulating cholesterol metabolism.

Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.

Purpose: The metabolism of tamoxifen is influenced by various cytochrome p450 enzymes, including CYP2D6 and CYP2C19, leading to variations in the levels of endoxifen, even with the same tamoxifen dose. However, the clinical significance of endoxifen for the prognosis of breast cancer patients remains controversial. This study aimed to elucidate the relevance of endoxifen level to recurrence-free survival censored with tamoxifen discontinuation (RFSt), representing the RFS for tamoxifen itself, of breast cancer patients and determine a suitable cutoff for prognostication. Materials and Methods: The study included 478 breast cancer patients. Tamoxifen and its metabolites, including endoxifen, were measured using liquid chromatography-tandem mass spectrometry. An optimal cutoff was determined with maximally selected rank statistics. Survival analysis and Cox regression were conducted based on this cutoff. Results: An endoxifen level of 21.00 ng/mL was the optimal cutoff for prognostication. Survival analysis revealed a statistically significant difference in RFSt between the low endoxifen group (≤ 21.00 ng/mL) and the high endoxifen group (> 21.00 ng/mL) (log-rank test, p=0.032). The 10-year probability of RFSt was 83.2% (95% confidence interval [CI], 77.0 to 89.9) and 88.3% (95% CI, 83.3 to 93.5) in the low and high endoxifen groups, respectively. Multivariable Cox proportional hazards regression indicated endoxifen concentration as a significant factor associated with prognosis. Conclusion Endoxifen could serve as a marker for appropriate tamoxifen treatment with a cutoff of 21.00 ng/mL. Based on this cutoff, therapeutic drug monitoring would benefit patients displaying suboptimal endoxifen concentrations.

Objective: Multiple cohort studies have investigated the potential link between anesthesia and dementia. However, mixed findings necessitate closer examination. This study aimed to investigate the association between anesthesia exposure and the incidence of dementia, considering different anesthesia types and anesthetic agents. Methods: This nationwide cohort study utilized data from the South Korean Health Insurance Review and Assessment Service database, covering 62,541 participants, to investigate the correlation between anesthesia exposure and dementia incidence. Results: Results revealed an increased risk of dementia in individuals who underwent general (hazard ratio [HR], 1.318;95% confidence interval [CI], 1.061−1.637) or regional/local anesthesia (HR, 2.097; 95% CI, 1.887−2.329) compared to those who did not. However, combined general and regional/local anesthesia did not significantly increase dementia risk (HR, 1.097; 95% CI, 0.937−1.284). Notably, individual anesthetic agents exhibited varying risks; desflurane and midazolam showed increased risks, whereas propofol showed no significant difference. Conclusion This study provides unique insights into the nuanced relationship between anesthesia, individual anesthetic agents, and the incidence of dementia. While confirming a general association between anesthesia exposure and dementia risk, this study also emphasizes the importance of considering specific agents. These findings under-score the need for careful evaluation and long-term cognitive monitoring after anesthesia.

Osteoporosis management in post-menopausal women focuses on fracture prevention, with denosumab as a key therapeutic option. Despite its proven efficacy in reducing fracture risk and increasing bone mineral density (BMD) over 10 years, its long-term impact remains uncertain. We evaluated the literature on its efficacy and safety beyond the initial decade. Clinical trials and real-world studies confirm denosumab’s sustained efficacy, especially in lumbar spine BMD, with hip BMD stabilizing. Concerns about adverse events (AEs) like hypocalcemia and osteonecrosis of the jaw necessitate vigilant monitoring. Risks of atypical femoral fractures and malignancies also require attention, despite unclear links to treatment duration. Clinical guidelines for denosumab beyond 10 years are limited, emphasizing the need for careful monitoring. In certain scenarios, such as advanced chronic kidney disease, prolonged denosumab may be required to balance AE risks with fracture prevention benefits. Denosumab shows potential for long-term efficacy in augmenting BMD; however, monitoring for AEs is crucial to guide clinical decision-making effectively.

Background: and Purpose We aimed to determine the proportion of Korean patients with early Alzheimer’s disease (AD) who are eligible to receive lecanemab based on the United States Appropriate Use Recommendations (US AUR), and also identify the barriers to this treatment. Methods: We retrospectively enrolled 6,132 patients with amnestic mild cognitive impairment or mild amnestic dementia at 13 hospitals from June 2023 to May 2024. Among them, 2,058 patients underwent amyloid positron emission tomography (PET) and 1,199 (58.3%) of these patients were amyloid-positive on PET. We excluded 732 patients who did not undergo brain magnetic resonance imaging between June 2023 and May 2024. Finally, 467 patients were included in the present study. Results: When applying the criteria of the US AUR, approximately 50% of patients with early AD were eligible to receive lecanemab treatment. Among the 467 included patients, 36.8% did not meet the inclusion criterion of a Mini-Mental State Examination (MMSE) score of ≥22. Conclusions Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education.

Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.

Multiple cranial neuropathies are complex neurological disorders that present significant treatment challenges due to their intricate and multifaceted underlying causes. Persistent trigeminal artery variant (PTAV) is an unusual anastomosis that connects the internal carotid artery to the cerebellar artery, bypassing the basilar artery. The incidence of PTAVs is approximately 0.18% and neurovascular compression is rarely reported. Patients with schwannomatosis typically have multiple schwannomas without vestibular nerve involvement, which may develop in the spinal nerve roots and, less commonly, in the cranial nerves. We report the case of a 53-year-old female with trigeminal neuralgia associated with PTAV and schwannomatosis in the abducens and lower cranial nerves as dual etiologies for multiple cranial neuropathies.

Background: The prognosis of end-of-life patients is challenging, and clinicians have attempted to predict survival more accurately. High serum creatinine (sCr) levels are associated with lower survival rates in patients with various cancers; however, low sCr levels are commonly expected in patients with terminal cancer because of muscle wasting and malnutrition. Therefore, we investigated the prevalence of low and high sCr levels and their association with survival duration in patients with terminal cancer in a palliative care unit. Methods: We analyzed the medical records of 280 patients admitted to a palliative care unit. Patients were divided into low (<0.5 mg/dL), normal (0.5–1.2 mg/dL), and high (>1.2 mg/dL) sCr groups. Kaplan-Meier survival curves using sCr levels were plotted and compared using the log-rank test. Using stepwise selection, a multivariable Cox proportional hazards model was used to identify the significant prognostic factors. Results: The median survival durations in the high-, low-, and normal-sCr groups were 9.57 days, 22.26 days, and 27.51 days, respectively. Multivariable Cox proportional hazard model identified that males (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.16–2.85), poor performance status (HR, 3.43; 95% CI, 1.12–10.54), total parenteral nutrition use (HR, 1.84; 95% CI, 1.09–3.1), high sCr (HR, 2.74; 95% CI, 1.52–4.94), and low sCr (HR, 1.22; 95% CI, 1.07–1.43) were significantly associated with a shorter survival time. Conclusion Low and high serum creatinine levels were significantly associated with poor survival in patients with cancer at the end-of-life stage. Therefore, readily available and simple biomarkers may help plan advanced care in palliative care settings.

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.