Background: Mass spectrometry (MS) methods exhibit higher accuracy and comparability in measuring serum C-peptide concentrations than immunoassays. We developed and validated a novel isotope dilution-ultraperformance liquid chromatography-tandem MS (IDUPLC-MS/MS) assay to measure serum C-peptide concentrations. Methods: Sample pretreatment involved solid-phase extraction, ion-exchange solid-phase extraction, and derivatization with 6-aminoquinolyl-N-hydroxysuccinimidylcarbamate (Cayman Chemical, Ann Arbor, Michigan, USA). We used an ExionLC UPLC system (Sciex, Framingham, MA, USA) and a Sciex Triple Quad 6500 + MS/MS system (Sciex) for electrospray ionization in positive-ion mode with multiple charge states of [M+3H]3+ and multiple reaction monitoring transitions. The total run time was 50 mins, and the flow rate was 0.20 mL/min. We evaluated the precision, trueness, linearity, lower limit of quantitation (LLOQ), carryover, and matrix effects. Method comparison with electrochemiluminescence immunoassay (ECLIA) was performed in 138 clinical specimens. Results: The intra- and inter-run precision coefficients of variation were < 5% and the bias values for trueness were < 4%, which were all acceptable. The verified linear interval was 0.050–15 ng/mL, and the LLOQ was 0.050 ng/mL. No significant carryover or matrix effects were observed. The correlation between this ID-UPLC-MS/MS method and ECLIA was good (R = 0.995, slope = 1.564); however, the ECLIA showed a positive bias (51.8%). Conclusions The developed ID-UPLC-MS/MS assay shows acceptable performance in measuring serum C-peptide concentrations. This will be useful in situations requiring accurate measurement of serum C-peptide in clinical laboratories.

Background: Cardiovascular disease is life-threatening yet preventable for patients with type 2 diabetes mellitus (T2DM). Because each patient with T2DM has a different risk of developing cardiovascular complications, the accurate stratification of cardiovascular risk is critical. In this study, we proposed cardiovascular risk engines based on machine-learning algorithms for newly diagnosed T2DM patients in Korea. Methods: To develop the machine-learning-based cardiovascular disease engines, we retrospectively analyzed 26,166 newly diagnosed T2DM patients who visited Seoul St. Mary’s Hospital between July 2009 and April 2019. To accurately measure diabetes-related cardiovascular events, we designed a buffer (1 year), an observation (1 year), and an outcome period (5 years). The entire dataset was split into training and testing sets in an 8:2 ratio, and this procedure was repeated 100 times. The area under the receiver operating characteristic curve (AUROC) was calculated by 10-fold cross-validation on the training dataset. Results: The machine-learning-based risk engines (AUROC XGBoost=0.781±0.014 and AUROC gated recurrent unit [GRU]-ordinary differential equation [ODE]-Bayes=0.812±0.016) outperformed the conventional regression-based model (AUROC=0.723± 0.036). Conclusion GRU-ODE-Bayes-based cardiovascular risk engine is highly accurate, easily applicable, and can provide valuable information for the individualized treatment of Korean patients with newly diagnosed T2DM.

Purpose: Despite enzyme replacement therapy (ERT) and/or allogeneic hematopoietic stem cell transplantation, individuals with mucopolysaccharidosis (MPS) I or II often experience significant growth deficiencies. This study aimed to assess the safety and efficacy of recombinant human growth hormone (hGH) treatment in children diagnosed with MPS I or II. Materials and Methods: A total of nine pediatric patients—four with MPS I and five with MPS II—underwent treatment with ERT and hGH at Samsung Medical Center. Results: The mean hGH dose administered was 0.26±0.03 mg/kg/week. In the MPS I group, three patients showed an increase in height Z-score from –4.09±0.83 to –3.68±0.43 after 1 year of hGH treatment, and to –3.10±0.72 by the end of the hGH regimen. In the MPS II group, while the height Z-score of four patients decreased according to standard growth charts, it improved from 1.61±1.79 to 2.71±1.68 based on the disease-specific growth chart through hGH treatment. Two patients discontinued hGH treatment due to lack of efficacy after 22 and 6 months each of treatment, respectively. No new-onset neurological symptoms or necessity for prosthetic or orthopedic surgery were reported during hGH treatment. Conclusion This study provides insights into the impact of hGH on MPS patients, demonstrating its potential to reverse growth deceleration in some cases. Further research is needed to explore the long-term effects of hGH on changes in body composition, muscle strength, and bone health in this population.

Purpose: NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC. Materials and Methods: We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts. Results: As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness. Conclusion This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.

Background: Human breast milk is essential and provides irreplaceable nutrients for early humans. However, breastfeeding is not easy for various reasons in medical institution environments. Therefore, in order to improve the breastfeeding environment, we investigated the difficult reality of breastfeeding through questionnaire responses from medical institution workers. Methods: A survey was conducted among 179 medical institution workers with experience in childbirth within the last five years. The survey results of 175 people were analyzed, with incoherent answers excluded. Results: Of the 175 people surveyed, a total of 108 people (61.7%) worked during the day, and 33 people (18.9%) worked in three shifts. Among 133 mothers who stayed with their babies in the same nursing room, 111 (93.3%) kept breastfeeding for more than a month, but among those who stayed apart, only 10 (71.4%) continued breastfeeding for more than a month (P = 0.024). Ninety-five (88.0%) of daytime workers, 32 (94.1%) two-shift workers, and 33 (100%) three-shift workers continued breastfeeding for more than a month (P = 0.026). Workers in general hospitals tended to breastfeed for significantly longer than those that worked in tertiary hospitals (P = 0.003). A difference was also noted between occupation categories (P = 0.019), but a more significant difference was found in the comparison between nurses and doctors (P = 0.012). Longer breastfeeding periods were noted when mothers worked three shifts (P = 0.037). Depending on the period planned for breastfeeding prior to childbirth, the actual breastfeeding maintenance period after birth showed a significant difference (P = 0.002). Of 112 mothers who responded to the question regarding difficulties in breastfeeding after returning to work, 87 (77.7%) mentioned a lack of time caused by being busy at work, 82 (73.2%) mentioned the need for places and appropriate circumstances. Conclusion In medical institutions, it is recommended that environmental improvements in medical institutions, the implementation of supporting policies, and the provision of specialized education on breastfeeding are necessary to promote breastfeeding.

Background: There are many models for predicting diabetes mellitus (DM), but their clinical implication remains vague. Therefore, we aimed to create various DM prediction models using easily accessible health screening test parameters. Methods: Two sets of variables were used to develop eight DM prediction models. One set comprised 62 easily accessible examination results of commonly used variables from a tertiary university hospital. The second set comprised 27 of the 62 variables included in the national routine health checkups. Gradient boosting and random forest algorithms were used to develop the models. Internal validation was performed using the stratified 10-fold cross-validation method. Results: The area under the receiver operating characteristic curve (ROC-AUC) for the 62-variable DM model making 12-month predictions for subjects without diabetes was the largest (0.928) among those of the eight DM prediction models. The ROC-AUC dropped by more than 0.04 when training with the simplified 27-variable set but still showed fairly good performance with ROC-AUCs between 0.842 and 0.880. The accuracy was up to 11.5% higher (from 0.807 to 0.714) when fasting glucose was included. Conclusion We created easily applicable diabetes prediction models that deliver good performance using parameters commonly assessed during tertiary university hospital and national routine health checkups. We plan to perform prospective external validation, hoping that the developed DM prediction models will be widely used in clinical practice.

Background/Aims: We investigated the concordance rate of the classification of polymyositis (PM) and dermatomyositis (DM) between the Bohan and Peter criteria and the 2017 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for idiopathic inflammatory myopathies (IIMs) (the 2017 EULAR/ACR criteria) in Korean patients. Methods: We retrospectively reviewed the medical records of 137 patients with PM and DM. We finally included 72 PM patients and 49 DM patients who fulfilled the Bohan and Peter criteria for PM and DM and reclassified them by the 2017 EULAR/ ACR criteria. Results: Three patients (4.2%) with probable PM were newly reclassified as non-IIM due to a total score of 5.3 or smaller. Meanwhile, one patient with possible PM was newly reclassified as probable PM due to the presence of dysphagia. In addition, eight patients (16.3%) with possible DM with DM-specific typical skin rash were newly reclassified as amyopathic DM (ADM) due to the absence of proximal muscle weakness. The concordance rate of the classification between the Bohan and Peter criteria and the 2017 EULAR/ACR criteria was 95.8% for PM patients and 83.7% for DM patients. Conclusions The Bohan and Peter criteria were comparable to the 2017 EULAR/ ACR criteria for classifying PM and DM in Korean patients. Considering the convenience of the Bohan and Peter criteria in the real clinical settings, we suggest that the old criteria should be preferentially applied and then performing muscle biopsy should be considered in a patient suspected of PM without antihistidyl tRNA synthetase (anti-Jo-1). Moreover, we suggest that ADM could also clinically be classified by the old criteria.

Hypoglycemia is one of the severe complications of diabetes. To prevent hypoglycemia, an emphasis is placed on maintaining an appropriate balance between nutrition, activity, and treatment, which can be achieved by the repetition of self-trials based on self-monitoring. Clinicians routinely focus on patients’ contribution, including timely intake of an adequate amount of carbohydrates, physical activity, antidiabetic medication, and abstinence from alcohol. Recently, many guidelines have highlighted the importance of clinicians’ factors and recommend individualized treatments according to lifestyle patterns and specific needs following the de-intensification of treatment. The optimal value of hemoglobin A1c (HbA1c) levels for blood glucose level regulation remains controversial among countries, but it generally does not exceed 8.0%. In populations that are at a risk of hypoglycemia, such as the older adults, it is advisable to adjust the target blood glucose level to less than 8.0%. Meanwhile, a blood glucose level of 7.0%–7.5% is generally recommended for healthy older adults. If the expected lifetime is shorter than 10 years or in patients with chronic kidney disease and severe cardiovascular disease, the HbA1c level target can be increased to 7.5%–8.0%. For even shorter lifetime expectancy, the target can be adjusted up to 8.0%–9.0%. To prevent hypoglycemia, the target blood glucose level needs to be adjusted, particularly in older adult patients. Ultimately, it is important to identify the maximum blood glucose levels that do not cause hypoglycemia and the minimum blood glucose levels that do not cause hyperglycemia-associated complications.

Background/Aims: Measures of body composition, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle area (SMA), are considered important prognostic factors in chronic diseases. The association of these measures with auto-inflammatory disorders, such as anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), remains unclear. We investigated the clinical significance of VAT, SAT, and SMA in patients with AAV. Methods: Patients with AAV subjected to chest computed tomography (CT), abdominal CT, or positron emission tomography-CT on diagnosis of AAV were evaluated. Quantitative assessment of VAT, SAT, and SMA was performed at the third lumbar vertebral level and computed by summing the pixel attenuation for tissue-specific Hounsfield units in the corresponding region. Associations of VAT, SAT, and SMA with clinical and laboratory data and clinical outcome measures were evaluated. Results: Of the 117 patients, 61 (52.1%) were classified as having microscopic polyangiitis, 28 (23.9%) as granulomatosis with polyangiitis, and 28 (23.9%) as eosinophilic granulomatosis with polyangiitis. VAT significantly correlated with age, weight, body mass index (BMI), and Birmingham Vasculitis Activity Score, whereas SAT correlated with weight, BMI, and creatinine levels. A significant association was found between SMA and age, height, weight, BMI, and the Five-Factor Score. Cox proportional hazards analysis showed that creatinine levels (odds ratio [OR], 1.346; 95% confidence interval [CI], 1.034 to 1.753; p = 0.027) and high VAT (OR, 7.137; 95% CI, 1.343–37.946; p = 0.021) were independently associated with all-cause mortality during follow-up. Conclusions Evaluation of VAT using CT is useful for estimating disease activity and all-cause mortality in patients with AAV.