Patient-Derived Organoids Recapitulate Pathological Intrinsic and Phenotypic Features of Fibrous Dysplasia.

Fibrous dysplasia (FD) is a rare bone disorder characterized by the replacement of normal bone with benign fibro-osseous tissue. Developments in our understanding of the pathophysiology and treatment options are impeded by the lack of suitable research models. In this study, we developed an in vitro organotypic model capable of recapitulating key intrinsic and phenotypic properties of FD. Initially, transcriptomic profiling of individual cells isolated from patient lesional tissues unveiled intralesional molecular and cellular heterogeneity. Leveraging these insights, we established patient-derived organoids (PDOs) using primary cells obtained from patient FD lesions. Evaluation of PDOs demonstrated preservation of fibrosis-associated constituent cell types and transcriptional signatures observed in FD lesions. Additionally, PDOs retained distinct constellations of genomic and metabolic alterations characteristic of FD. Histological evaluation further corroborated the fidelity of PDOs in recapitulating important phenotypic features of FD that underscore their pathophysiological relevance. Our findings represent meaningful progress in the field, as they open up the possibility for in vitro modeling of rare bone lesions in a three-dimensional context and may signify the first step towards creating a personalized platform for research and therapeutic studies.

Sodium Intake Estimation in Hospital Patients Using AI-Based Imaging: Prospective Pilot Study.

BACKGROUND: Measurement of sodium intake in hospitalized patients is critical for their care. In this study, artificial intelligence (AI)-based imaging was performed to determine sodium intake in these patients. OBJECTIVE: The applicability of a diet management system was evaluated using AI-based imaging to assess the sodium content of diets prescribed for hospitalized patients. METHODS: Based on the information on the already investigated nutrients and quantity of food, consumed sodium was analyzed through photographs obtained before and after a meal. We used a hybrid model that first leveraged the capabilities of the You Only Look Once, version 4 (YOLOv4) architecture for the detection of food and dish areas in images. Following this initial detection, 2 distinct approaches were adopted for further classification: a custom ResNet-101 model and a hyperspectral imaging-based technique. These methodologies focused on accurate classification and estimation of the food quantity and sodium amount, respectively. The 24-hour urine sodium (UNa) value was measured as a reference for evaluating the sodium intake. RESULTS: Results were analyzed using complete data from 25 participants out of the total 54 enrolled individuals. The median sodium intake calculated by the AI algorithm (AI-Na) was determined to be 2022.7 mg per day/person (adjusted by administered fluids). A significant correlation was observed between AI-Na and 24-hour UNa, while there was a notable disparity between them. A regression analysis, considering patient characteristics (eg, gender, age, renal function, the use of diuretics, and administered fluids) yielded a formula accounting for the interaction between AI-Na and 24-hour UNa. Consequently, it was concluded that AI-Na holds clinical significance in estimating salt intake for hospitalized patients using images without the need for 24-hour UNa measurements. The degree of correlation between AI-Na and 24-hour UNa was found to vary depending on the use of diuretics. CONCLUSIONS: This study highlights the potential of AI-based imaging for determining sodium intake in hospitalized patients.

The Hospitalist-Oncologist co-ManagemEnt (HOME) system improves hospitalization outcomes of patients with cancer.

BACKGROUND: The hospitalist system has been introduced to improve the quality and safety of inpatient care. As its effectiveness has been confirmed in previous studies, the hospitalist system is spreading in various fields. However, few studies have investigated the feasibility and value of hospitalist-led care of patients with cancer in terms of quality and safety measures. This study aimed to evaluate the efficacy of the Hospitalist-Oncologist co-ManagemEnt (HOME) system. METHODS: Between January 1, 2019, and January 31, 2021, we analyzed 591 admissions before and 1068 admissions after the introduction of HOME system on January 1, 2020. We compared the length of stay and the types and frequencies of safety events between the conventional system and the HOME system, retrospectively. We also investigate rapid response system activation, cardiopulmonary resuscitation, unplanned intensive care unit transfer, all-cause in-hospital mortality, and 30-day re-admission or emergency department visits. RESULTS: The average length of stay (15.9 days vs. 12.9 days, P < 0.001), frequency of safety events (5.6% vs. 2.8%, P = 0.006), rapid response system activation (7.3% vs. 2.2%, P < 0.001) were significantly reduced after the HOME system introduction. However, there was no statistical difference in frequencies of cardiopulomonary resuscitation and intensive care unit transfer, all-cause in-hospital morality, 30-day unplanned re-admission or emergency department visits. CONCLUSIONS: The study suggests that the HOME system provides higher quality of care and safer environment compared to conventional oncologist-led team-based care, and the efficiency of the medical delivery system could be increased by reducing the hospitalization period without increase in 30-day unplanned re-admission.

Exploring quantitative traits-associated copy number deletions through reanalysis of UK10K consortium whole genome sequencing cohorts.

OBJECTIVES: We performed comprehensive association analyses of common high-confidence gnomAD-reported copy number deletions (CNDs) with 60 quantitative traits from UK10K consortium WGS data. METHODS: The study made use of data generated by the UK10K Consortium. UK10K consortium WGS data consist of TwinsUK (n = 1754, middle-aged females) and ALSPAC (n = 1867, birth to adolescence) cohorts. UK10K consortium called 18,739 CNDs (hg19) with GenomeSTRiP software. After filtering out variants with minor allele frequency < 0.05 or HWE P < 1.0 × 10- 6, 1222 (TwinsUK) and 1211 (ALSPAC) CNDs remained for association analyses with 60 normalized quantitative traits. RESULTS: We identified 23 genome-wide significant associations at 13 loci, among which 2 associations reached experiment-wide significance. We found that two common deletions in chromosome 4, located between WDR1 and ZNF518B (23.3 kb, dbVar ID:nssv15888957, 4:10211262-10,234,569 and 9.8 kb, dbVar ID:nssv15888975, 4:10392422-10,402,191), were associated with uric acid levels (P = 5.23 × 10- 11 and 2.29 × 10- 8, respectively). We also discovered a novel deletion spanning chromosome 18 (823 bp, dbVar ID: nssv15841628, 8:74347187-74,348,010) associated with low HDL cholesterol levels (P = 4.15 × 10- 7). Additionally, we observed two red blood cell traits-associated loci with genome-wide significance, a 13.2 kb deletion in 7q22.1 (nssv15922542) and a 3.7 kb deletion in 12q24.12 (nssv15813226), both of which were located in regions previously reported to be associated with red blood cell traits. Two deletions in 11q11 (nssv15803200 and nssv15802240), where clusters of multiple olfactory receptor genes exist, and a deletion (nssv15929560) upstream to DOCK5 were associated with childhood obesity. Finally, when defining Trait-Associated copy number Deletions (TADs) as CNDs with phenotype associations at sub-threshold significance (P < 10- 3), we identified 157 (97.5%) out of 161 TADs in non-coding regions, with a mean size of 4 kb (range: 209 - 47,942 bp). CONCLUSION: We conducted a reanalysis of the UK10K Whole Genome Sequencing cohort, which led to the identification of multiple high confidence copy number deletions associated with quantitative traits. These deletions have standard dbVar IDs and replicate previous findings, as well as reveal novel loci that require further replication studies.

Impact of hospitalist care model on patient outcomes in acute medical unit: a retrospective cohort study.

OBJECTIVE: To assess a newly introduced, hospitalist-run, acute medical unit (AMU) care model at a tertiary care hospital in the Republic of Korea. DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital in the Republic of Korea. PARTICIPANTS: We evaluated 6391 medical inpatients admitted through the emergency department (ED) from 1 June 2016 to 31 May 2017. INTERVENTIONS: The study compared multiple outcomes among medical inpatients from the ED between the non-hospitalist group and the AMU hospitalist group. OUTCOME MEASURES: In-hospital mortality (IHM), intensive care unit (ICU) admission rate, hospital length of stay (LOS), ED-LOS and unscheduled readmission rates were defined as patient outcomes and compared between the two groups. RESULTS: Compared with the non-hospitalist group, the AMU hospitalist group had lower IHM (OR: 0.43, p<0.001), a lower ICU admission rate (OR: 0.72, p=0.013), a shorter LOS (coefficient: -0.984, SE: 0.318; p=0.002) and a shorter ED-LOS (coefficient: -3.021, SE: 0.256; p<0.001). There were no significant differences in the 10-day or 30-day readmission rates (p=0.974, p=0.965, respectively). CONCLUSIONS: The AMU hospitalist care model was associated with reductions in IHM, ICU admission rate, LOS and ED-LOS. These findings suggest that the AMU hospitalist care model has the potential to be adopted into other healthcare systems to improve care for patients with acute medical needs.

Effect of Active Surgical Co-Management by Medical Hospitalists in Urology Inpatient Care: A Retrospective Cohort Study.

PURPOSE: This study aimed to evaluate the use of active surgical co-management (SCM) by medical hospitalists for urology inpatient care. MATERIALS AND METHODS: Since March 2019, a hospitalist-SCM program was implemented at a tertiary-care medical center, and a retrospective cohort study was conducted among co-managed urology inpatients. We assessed the clinical outcomes of urology inpatients who received SCM and compared passive SCM (co-management of patients by hospitalists only on request; March 2019 to June 2020) with active SCM (co-management of patients based on active screening by hospitalists; July 2020 to October 2021). We also evaluated the perceptions of patients who received SCM toward inpatient care quality, safety, and subjective satisfaction with inpatient care at discharge or when transferred to other wards. RESULTS: We assessed 525 patients. Compared with the passive SCM group (n=205), patients in the active SCM group (n=320) required co-management for a significantly shorter duration (p=0.012) and tended to have a shorter length of stay at the urology ward (p=0.062) and less frequent unplanned readmissions within 30 days of discharge (p=0.095) while triggering significantly fewer events of rapid response team activation (p=0.002). No differences were found in the proportion of patients transferred to the intensive care unit, in-hospital mortality rates, or inpatient care questionnaire scores. CONCLUSION: Active surveillance and co-management of urology inpatients by medical hospitalists can improve the quality and efficacy of inpatient care without compromising subjective inpatient satisfaction.

Nationwide survey of internal medicine hospitalists in Korea: motivation and sustainability of a hospitalist career.

BACKGROUND/AIMS: Although a management fee for hospitalist service was established in Korea, the number of hospitalists required for the system to run remains outmatched. METHODS: In January 2020 and February 2022, before and after the establishment of the hospitalist fee system respectively, cross-sectional online surveys were conducted among internal medicine board-certified hospitalists. RESULTS: There were 59 and 64 respondents in the 2020 and 2022 surveys, respectively. The percentage of respondents who cited financial benefits as a motive for becoming a hospitalist was higher in the 2022 survey than in the 2020 survey (34.4% vs. 10.2%; p = 0.001). The annual salary of respondents was also higher in the 2022 survey than in the 2020 survey (mean, 182.9 vs. 163.0 million in South Korean Won; p = 0.006). A total of 81.3% of the respondents were willing to continue a hospitalist career in the 2022 survey. In multivariate regression analysis, the possibility of being appointed as a professor was found to be an independent predictive factor of continuing a hospitalist career (odds ratio, 4.00; 95% confidence interval, 1.09-14.75; p = 0.037). CONCLUSION: Since the establishment of the hospitalist fee system, monetary compensation has improved for hospitalists. The possibility of being appointed as a professor could predict long-term work as hospitalists.

Effect of the Concomitant Use of Subcutaneous Basal Insulin and Intravenous Insulin Infusion in the Treatment of Severe Hyperglycemic Patients.

BACKGRUOUND: No consensus exists regarding the early use of subcutaneous (SC) basal insulin facilitating the transition from continuous intravenous insulin infusion (CIII) to multiple SC insulin injections in patients with severe hyperglycemia other than diabetic ketoacidosis. This study evaluated the effect of early co-administration of SC basal insulin with CIII on glucose control in patients with severe hyperglycemia. METHODS: Patients who received CIII for the management of severe hyperglycemia were divided into two groups: the early basal insulin group (n=86) if they received the first SC basal insulin 0.25 U/kg body weight within 24 hours of CIII initiation and ≥4 hours before discontinuation, and the delayed basal insulin group (n=79) if they were not classified as the early basal insulin group. Rebound hyperglycemia was defined as blood glucose level of >250 mg/dL in 24 hours following CIII discontinuation. Propensity score matching (PSM) methods were additionally employed for adjusting the confounding factors (n=108). RESULTS: The rebound hyperglycemia incidence was significantly lower in the early basal insulin group than in the delayed basal insulin group (54.7% vs. 86.1%), despite using PSM methods (51.9%, 85.2%). The length of hospital stay was shorter in the early basal insulin group than in the delayed basal insulin group (8.5 days vs. 9.6 days, P=0.027). The hypoglycemia incidence did not differ between the groups. CONCLUSION: Early co-administration of basal insulin with CIII prevents rebound hyperglycemia and shorten hospital stay without increasing the hypoglycemic events in patients with severe hyperglycemia.

Effect of outpatient physician involvement on the physician orders for life-sustaining treatment completed by hospitalists: a cross-sectional study.

BACKGROUND: Hospitalists are becoming increasingly involved in end-of-life (EOL) care decision making. They participate in the completion of physician orders for life-sustaining treatment (POLST) for patients who have not yet decided whether to proceed with life-sustaining treatment (LST) at the EOL. However, hospitalists are not physicians who have continuously treated patients in outpatient settings; hence, the continuity of care may be poor. We aimed to analyze the effect of outpatient physician involvement on the POLST completed by hospitalists. METHODS: A retrospective cohort study was conducted in patients aged 18 years or older treated by hospitalists who completed POLST at Seoul National University Bundang Hospital from February 2018 to March 2020. The clinical and sociodemographic data were obtained through a medical chart review, and the differences in the characteristics of POLST were analyzed depending on the status of outpatient physician involvement. RESULTS: A total of 3,533 POLST forms were written, of which 175 (5.22%) were completed by the hospitalists. The proportion of POLSTs completed by hospitalists gradually increased from 2.53% in 2018 to 4.58% in 2019 and 15.9% in 2020. A total of 144 (82.3%) patients had malignancies, while 31 (17.7%) patients had non-cancer illnesses. In 47.4% of the patients, outpatient physicians were involved in completing physician's orders for LST. When the outpatient physicians were involved, more patients signed the POLST form themselves (P=0.02) and chose comfort measures only when asked to determine their preferred LST type (P=0.00). CONCLUSIONS: The completion of POLST by hospitalists is gradually increasing. LST was reduced when the outpatient physicians participated in the completion of POLST. Using measures to increase the involvement of outpatient providers in goal care discussions, the quality and goal concordance of EOL care can be improved.

rs2671655 single nucleotide polymorphism modulates the risk for gastric cancer in Helicobacter pylori-infected individuals: a genome-wide association study in the Korean population.

OBJECTIVE: To identify genetic variations which is associated with gastric cancer (GC) risk according to Helicobacter pylori infection. METHODS: This study incorporated 527 GC patients and 441 controls from a cohort at Seoul National University Bundang Hospital. The associations between GC risk and single nucleotide polymorphisms were calculated, stratified by H. pylori status, adjusting for age, sex, and smoking. mRNA expression from non-cancerous gastric mucosae was evaluated using reverse transcription quantitative polymerase chain reaction. RESULTS: In the entire cohort, genome-wide association study showed no significant variants reached the genome-wide significance level. In the H. pylori-positive group, rs2671655 (chr17:47,468,020;hg19, GH17J049387 enhancer region) was identified at a genome-wide significance level, which was more pronounced in diffuse type GC. There was no significant variant in the H. pylori-negative group, indicating the effect modification of rs2671655 by H. pylori. Among the target genes of GH17J049387 enhancer (PHB1, ZNF652 and SPOP), PHB1 mRNA was expressed more in cases than in controls, who were not affected by H. pylori. By contrast, an increase in ZNF652 and SPOP in GC was observed only in the H. pylori-negative group (P < 0.05). Mediation analysis showed that PHB1 (P = 0.0238) and SPOP (P = 0.0328) mediated the effect of rs2671655 on GC risk. The polygenic risk score was associated with the number of rs2671655 risk alleles only in the H. pylori-positive group (P = 0.0112). CONCLUSION: After H. pylori infection, rs2671655 may increase GC risk, especially in diffuse-type GC, by regulating the expression of several genes that consequently modify susceptibility to GC.

Role of bicarbonate and volume therapy in the prevention of acute kidney injury in rhabdomyolysis: a retrospective propensity score-matched cohort study.

BACKGROUND: Although bicarbonate has traditionally been used to treat patients with rhabdomyolysis at high risk of acute kidney injury (AKI), it is unclear whether this is beneficial. This study compared bicarbonate therapy to non-bicarbonate therapy for the prevention of AKI and mortality in rhabdomyolysis patients. METHODS: In a propensity score-matched cohort study, patients with a creatine kinase (CK) level of >1,000 U/L during hospitalization were divided into bicarbonate and non-bicarbonate groups. Patients were subgrouped based on low-volume (<3 mL/kg/hr) or high-volume (≥3 mL/kg/hr) fluid resuscitation in the first 72 hours. Logistic regression analyses were used to identify the impacts of bicarbonate use and fluid resuscitation on AKI risk and need for dialysis. The Kaplan-Meier method was used to estimate survival. Volume overload and electrolyte imbalances were assessed. RESULTS: Among 4,077 patients, we assembled a cohort of 887 pairs of patients treated with and without bicarbonate. Bicarbonate group had a higher incidence of AKI, higher rate of dialysis dependency, higher 30-day mortality, and longer hospital stay than the non-bicarbonate group. Further, patients who received high-volume fluid therapy had worse renal outcomes and a higher mortality than those who received low-volume fluids regardless of bicarbonate use. Bicarbonate use, volume overload, and AKI were associated with higher mortality. Volume overload was significantly higher in the bicarbonate group than in the non-bicarbonate group. CONCLUSION: Bicarbonate or high-volume fluid therapy for patients with rhabdomyolysis did not reduce AKI or improve mortality compared to non-bicarbonate or low-volume fluid therapy. Limited use of bicarbonate and adjustment of fluid volume may improve the short- and long-term outcomes of patients with rhabdomyolysis.

Clinical and economic impact of medication reconciliation by designated ward pharmacists in a hospitalist-managed acute medical unit.

BACKGROUND: Minimizing unintended medication errors after admission is a common goal for clinical pharmacists and hospitalists. OBJECTIVE: We assessed the clinical and economic impact of a medication reconciliation service in a model of designated ward pharmacists working in a hospitalist-managed acute medical unit as part of a multidisciplinary team. METHODS: In this retrospective observational study, we compared pharmacist intervention records before and after the implementation of a medication reconciliation service by designated pharmacists. The frequency and type of intervention were assessed and their clinical impact was estimated according to the length of hospital stay and 30-day readmission rate. A cost analysis was performed using the average hourly salary of a pharmacist, cost of interventions (time spent on interventions), and cost avoidance (avoided costs generated by interventions). RESULTS: After the implementation of the medication reconciliation service, the frequency of pharmacist interventions increased from 3.9% to 22.1% (p < 0.001). Intervention types were also more diverse than those before the implementation. The most common interventions included identifying medication discrepancies between pre-admission and hospitalization (22.7%) and potentially inappropriate medication use in the elderly (13.1%). The median length of hospital stay decreased from 9.6 to 8.9 days (p = 0.024); the 30-day readmission rate declined significantly from 7.8% to 4.8% (p = 0.046). Over two-thirds of interventions accepted by hospitalists were considered clinically significant or greater in severity. The cost difference between avoided cost and cost of interventions was 9838.58 USD in total or 1967.72 USD per month. CONCLUSIONS: The implementation of a designated pharmacist-led medication reconciliation service had a positive clinical and economic impact in our hospitalist unit.

A Smart Diaper System Using Bluetooth and Smartphones to Automatically Detect Urination and Volume of Voiding: Prospective Observational Pilot Study in an Acute Care Hospital.

BACKGROUND: Caregivers of patients who wear conventional diapers are required to check for voiding every hour because prolonged wearing of wet diapers causes health problems including diaper dermatitis and urinary tract infections. However, frequent checking is labor intensive and disturbs patients' and caregivers' sleep. Furthermore, assessing patients' urine output with diapers in an acute care setting is difficult. Recently, a smart diaper system with wetness detection technology was developed to solve these issues. OBJECTIVE: We aimed to evaluate the applicability of the smart diaper system for urinary detection, its accuracy in measuring voiding volume, and its effect on incontinence-associated dermatitis (IAD) occurrence in an acute care hospital. METHODS: This prospective, observational, single-arm pilot study was conducted at a single tertiary hospital. We recruited 35 participants aged ≥50 years who were wearing diapers due to incontinence between August and November 2020. When the smart diaper becomes wet, the smart diaper system notifies the caregiver to change the diaper and measures voiding volume automatically. Caregivers were instructed to record the weight of wet diapers on frequency volume charts (FVCs). We determined the voiding detection rate of the smart diaper system and compared the urine volume as automatically calculated by the smart diaper system with the volume recorded on FVCs. Agreement between the two measurements was estimated using a Bland-Altman plot. We also checked for the occurrence or aggravation of IAD and bed sores. RESULTS: A total of 30 participants completed the protocol and 390 episodes of urination were recorded. There were 108 records (27.7%) on both the FVCs and the smart diaper system, 258 (66.2%) on the FVCs alone, 18 (4.6%) on the smart diaper system alone, and 6 (1.5%) on the FVCs with sensing device lost. The detection rate of the smart diaper system was 32.8% (126/384). When analyzing records concurrently listed in both the FVCs and the smart diaper system, linear regression showed a strong correlation between the two measurements (R2=0.88, P<.001). The Bland-Altman assessment showed good agreement between the two measurements, with a mean difference of -4.2 mL and 95% limits of agreement of -96.7 mL and 88.3 mL. New occurrence and aggravation of IAD and bed sores were not observed. Bed sores improved in one participant. CONCLUSIONS: The smart diaper system showed acceptable accuracy for measuring urine volume and it could replace conventional FVCs in acute setting hospitals. Furthermore, the smart diaper system has the potential advantage of preventing IAD development and bed sore worsening. However, the detection rate of the smart diaper system was lower than expected. Detection rate polarization among participants was observed, and improvements in the user interface and convenience are needed for older individuals who are unfamiliar with the smart diaper system.

Family-based exome sequencing combined with linkage analyses identifies rare susceptibility variants of MUC4 for gastric cancer.

Genome-wide association studies of gastric cancer (GC) cases have revealed common gastric cancer susceptibility loci with low effect size. We investigated rare variants with high effect size via whole-exome sequencing (WES) of subjects with familial clustering of gastric cancer. WES of DNAs from the blood of 19 gastric cancer patients and 36 unaffected family members from 14 families with two or more gastric cancer patients were tested. Linkage analysis combined with association tests were performed using Pedigree Variant Annotation, Analysis, and Search Tool (pVAAST) software. Based on the logarithm of odds (LOD) and permutation-based composite likelihood ratio test (CLRT) from pVAAST, MUC4 was identified as a predisposing gene (LOD P-value = 1.9×10-5; permutation-based P-value of CLRT ≤ 9.9×10-9). In a larger cohort consisting of 597 GC patients and 9,759 healthy controls genotyped with SNP array, we discovered common variants in MUC4 regions (rs148735556, rs11717039, and rs547775645) significantly associated with GC supporting the association of MUC4 with gastric cancer. And the MUC4 variants were found in higher frequency in The Cancer Genome Atlas Study (TCGA) germline samples of patients with multiple cancer types. Immunohistochemistry indicated that MUC4 was downregulated in the noncancerous gastric mucosa of subjects with MUC4 germline missense variants, suggesting that loss of the protective function of MUC4 predisposes an individual to gastric cancer. Rare variants in MUC4 can be novel gastric cancer susceptibility loci in Koreans possessing the familial clustering of gastric cancer.

The Effect of Coffee Consumption on the Prevalence of Diabetes Mellitus: The 2012-2016 Korea National Health and Nutrition Examination Survey.

An inverse association between coffee consumption and the risk of diabetes mellitus (DM) has been observed. However, little is known about this association in Koreans, although they are now among the top global consumers of coffee. Therefore, the aim of this study was to evaluate the association between the prevalence of DM and the amount of coffee consumption using a unit of exact measurement, regardless of the type of coffee consumed. This study was based on data acquired from the Korea National Health and Nutrition Examination Survey 2012-2016. The participants who completed the survey were included in the statistical analysis (n = 14,578). Subjects were stratified by age (19-39 years old: young adult; 40-64 years old: middle-aged adult) and gender (men, women). The amount of coffee was measured using a teaspoon (tsp) unit corresponding to 5 mL of powdered coffee and was analyzed as a continuous variable. The mean powdered coffee intake per day was 1.97 tsp in women groups, 2.24 tsp in young adult men, and 2.72 tsp in middle-aged men. The frequency of coffee consumption showed an inverse relationship with the amount of coffee intake at a time. With each 1-tsp increment in daily coffee intake, the odds of DM were 0.89 (95% confidence interval (CI): 0.86-0.92, p < 0.001) and 0.93 (95% CI: 0.90-0.95, p = 0.003) in middle-aged women and men, respectively. Coffee consumption was inversely correlated with the prevalence of DM even with adjustment for covariates in middle-aged adults. We delineated that the prevalence for DM decreased as coffee intake increased in Korean middle-aged adults. Therefore, our data represented an inverse association between coffee consumption and the prevalence of DM, although Koreans have a unique coffee-drinking habit.

Carnitine induces autophagy and restores high-fat diet-induced mitochondrial dysfunction.

OBJECTIVE: Autophagy is suppressed in skeletal muscle and the liver with insulin resistance induced by a high-fat diet. Autophagy is essential for maintaining mitochondrial function, and dysfunctional mitochondria are associated with insulin resistance. As carnitine treatment is well known to improve insulin resistance by promoting mitochondrial function, we investigated if carnitine affects autophagy in the skeletal muscle of a high-fat diet-induced rodent model of obesity. RESULTS: After 6weeks on a high-fat diet (48kcal% fat), mice developed glucose intolerance, and the gastrocnemius muscle showed a decrease in insulin signaling and mitochondrial function, which was reversed after carnitine (100mg/kg/day) treatment by oral gavage for 2weeks. Swollen mitochondria with destroyed cristae were observed in the skeletal muscle of high-fat diet-fed mice but were not there after carnitine treatment. High-fat diet decreased LC3B-II, a marker of autophagosome formation, and increased sequestosome 1 (SQSTM1), expression of which was reversed after carnitine treatment. In C2C12 myotubes, prolonged treatment with palmitate suppressed autophagy, which was relieved by carnitine treatment. However, the induction of autophagy by carnitine in C2C12 myotubes was not observed after knock-down of peroxisome proliferator-activated receptor γ (PPARγ), which is known to regulate autophagy. CONCLUSION: We conclude that the removal of dysfunctional mitochondria by induction of autophagy through PPARγ may be a novel mechanism by which carnitine improves insulin resistance and mitochondrial dysfunction in obesity.

DNA methylation profiles in sibling pairs discordant for intrauterine exposure to maternal gestational diabetes.

Intrauterine exposure to hyperglycemia is reported to confer increased metabolic risk in later life, supporting the 'developmental origins of health and disease' hypothesis. Epigenetic alterations are suggested as one of the possible underlying mechanisms. In this study, we compared pairwise DNA methylation differences between siblings whose intrauterine exposure to maternal gestational diabetes (GDM) were discordant. Methylation of peripheral blood DNA of 18 sibling pairs was measured using Infinium HumanMethylation450 BeadChip assays. Of the 465,447 CpG sites analyzed, 12 showed differential methylation (false discovery rate <0.15), including markers within genes associated with monogenic diabetes (HNF4A) or obesity (RREB1). The overall methylation at HNF4A showed inverse correlations with mRNA expression levels, though non significant. In a gene set enrichment analysis, metabolism and signal transduction pathways were enriched. In conclusion, we found DNA methylation markers associated with intrauterine exposure to maternal GDM, including those within genes previously implicated in diabetes or obesity.

An Acute Medical Unit in a Korean Tertiary Care Hospital Reduces the Length of Stay and Waiting Time in the Emergency Department.

A hospitalist-run acute medical unit (AMU) opened at a tertiary care hospital on August 2015 for the first time in Korea. Patients visiting the emergency department (ED) with acute medical problems are admitted to the AMU. They stay in that unit for less than 72 hours and are discharged or transferred to specialty wards if longer treatment is necessary. We reviewed 19,450 medical admissions through the ED from January 2014 to September 2016. The median length of stay (LOS) significantly decreased from 10.0 days (interquartile range [IQR], 5.5-16.7) to 9.1 days (IQR, 5.1-15.0) (P < 0.001) after the establishment of the AMU. The median waiting time in the ED significantly shortened by 40% (P < 0.001). Future studies on the impact of AMU on in-patient morbidity, mortality, re-admission rate, and patient or staff satisfaction are necessary.

Small heterodimer partner (SHP) deficiency protects myocardia from lipid accumulation in high fat diet-fed mice.

The small heterodimer partner (SHP) regulates fatty acid oxidation and lipogenesis in the liver by regulating peroxisome proliferator-activated receptor (PPAR) γ expression. SHP is also abundantly expressed in the myocardium. We investigated the effect of SHP expression on myocardia assessing not only heart structure and function but also lipid metabolism and related gene expression in a SHP deletion animal model. Transcriptional profiling with a microarray revealed that genes participating in cell growth, cytokine signalling, phospholipid metabolism, and extracellular matrix are up-regulated in the myocardia of SHP knockout (KO) mice compared to those of wild-type (WT) mice (nominal p value < 0.05). Consistent with these gene expression changes, the left ventricular masses of SHP KO mice were significantly higher than WT mice (76.8 ± 20.5 mg vs. 52.8 ± 6.8 mg, P = 0.0093). After 12 weeks of high fat diet (HFD), SHP KO mice gained less weight and exhibited less elevation in serum-free fatty acid and less ectopic lipid accumulation in the myocardium than WT mice. According to microarray analysis, genes regulated by PPARγ1 and PPARα were down-regulated in myocardia of SHP KO mice compared to their expression in WT mice after HFD, suggesting that the reduction in lipid accumulation in the myocardium resulted from a decrease in lipogenesis regulated by PPARγ. We confirmed the reduced expression of PPARγ1 and PPARα target genes such as CD36, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, and very long-chain acyl-CoA dehydrogenase by SHP KO after HFD.