Multicentric reticulohistiocytosis post-COVID-19: a case report.

Background: Multicentric reticulohistiocytosis (MRH) stands as a rare and challenging systemic granulomatous disease characterized by its predilection for skin and joint involvement, confounding clinicians with its infrequent presentation and systemic manifestations. Case Description: This compelling case presentation unravels the intricate complexity of MRH, exemplifying its unique clinical course. Following mild upper respiratory coronavirus disease 2019 (COVID-19) symptoms, the patient manifested purplish-pink papular lesions on both the skin and mucosa, accompanied by debilitating arthralgias. A diagnostic skin biopsy, a pivotal tool in MRH diagnosis, confirmed the presence of this granulomatous disorder, underlining its systemic impact. Strategic therapeutic intervention involving a combination of steroids and methotrexate demonstrated remarkable efficacy, culminating in the resolution of symptoms within 3-month. The absence of malignancy upon thorough screening further amplifies the perplexing nature of MRH. Conclusions: This seminal case not only bridges the realms of rare systemic disorders but also marks the first known instance of MRH emerging post-COVID-19. It underscores the imperative consideration of MRH in analogous scenarios and provides invaluable insights into the nuanced interplay of MRH symptoms, diagnosis, and therapeutic strategies following viral triggers. This comprehensive exploration enriches our scientific understanding, offering nuanced perspectives on the manifestations and intricate dynamics of MRH in the context of post-viral sequelae.

Impact of Hyperglycemia on Complication and Mortality after Transarterial Chemoembolization for Hepatocellular Carcinoma.

BACKGRUOUND: Current guidelines regarding periprocedural glycemic control to prevent complications after nonsurgical invasive procedures are insufficient. Transarterial chemoembolization (TACE) is a widely used treatment for unresectable hepatocellular carcinoma. We aimed to investigate the association between diabetes mellitus (DM) per se and the degree of hyperglycemia with postprocedural complications after TACE. METHODS: A total of 22,159 TACE procedures performed at Seoul National University Hospital from 2005 to 2018 were retrospectively analyzed. The associations between DM, preprocedural glycosylated hemoglobin (HbA1c), and periprocedural average glucose with postprocedural adverse outcomes were evaluated. The primary outcome was occurrence of postprocedural bacteremia. Secondary outcomes were acute kidney injury (AKI), delayed discharge and death within 14 days. Periprocedural glucose was averaged over 3 days: the day of, before, and after the TACE procedures. Propensity score matching was applied for procedures between patients with or without DM. RESULTS: Periprocedural average glucose was significantly associated with bacteremia (adjusted odds ratio per 50 mg/dL of glucose, 1.233; 95% confidence interval, 1.071 to 1.420; P=0.004), AKI, delayed discharge, and death within 14 days. DM per se was only associated with bacteremia and AKI. Preprocedural HbA1c was associated with delayed discharge. Average glucose levels above 202 and 181 mg/dL were associated with a significantly higher risk of bacteremia and AKI, respectively, than glucose levels of 126 mg/dL or lower. CONCLUSION: Periprocedural average glucose, but not HbA1c, was associated with adverse outcomes after TACE, which is a nonsurgical invasive procedure. This suggests the importance of periprocedural glycemic control to reduce postprocedural complications.

Concomitant Use of Sodium-Glucose Cotransporter 2 Inhibitors and Overactive Bladder Drugs and the Risk of Urinary Tract Infection.

Concomitant use of sodium glucose cotransporter-2 inhibitors (SGLT-2i) and overactive bladder (OAB) drugs potentially poses a risk of urinary tract infections (UTIs) due to the urinary retention of highly concentrated glucose in the urine. Thus, this study aimed to investigate the risk of UTIs among patients who initiated SGLT-2i treatment while taking OAB drugs. This population-based cohort study included new-users of SGLT-2i or comparator antidiabetics (dipeptidyl peptidase-4 inhibitor (DPP-4i); glucagon-like peptide-1 receptor agonist (GLP-1RA)) with OAB drugs between 2014 and 2020 using claim data from Korea. Primary outcome was a composite UTI event composite end point comprising pyelonephritis, cystitis, and urethritis, using both inpatient and outpatient diagnoses. Propensity score fine stratification was used to adjust for potential confounding factors. Weighted hazard ratios (HR) were calculated using the Cox proportional hazards model. In the first cohort, 796 and 9,181 new-users of SGLT-2i and DPP-4i with OAB drugs were identified, respectively. This study found a similar risk of UTIs in concomitant users of SGLT-2i and DPP-4i (weighted HR 1.08, 95% confidence interval: 0.88-1.32) with OAB drugs. In the second cohort, 2,387 and 280 new-users of SGLT-2i and GLP-1RA with OAB drugs were identified, respectively. Initiation of SGLT-2i while on OAB treatment was not associated with increased risk of UTI (0.89, 0.50-1.60), compared with initiation of GLP-1RA. These results show that the concomitant use of SGLT-2i with OAB drugs was not associated with an increased risk of UTI compared with the concomitant use of DPP-4i or GLP-1RA with OAB drugs.

Risk of thyroid cancer associated with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: A population-based cohort study.

AIMS: To determine the potential association between the use of either glucagon-like peptide-1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase-4 (DPP-4) inhibitors, and the risk of thyroid cancer in individuals with type 2 diabetes. MATERIALS AND METHODS: This population-based cohort study used claims data from the Korean National Health Insurance Database, 2014-2020. Two distinct cohorts were established to compare each incretin-based drug with sodium-glucose cotransporter-2 (SGLT2) inhibitors, chosen as active comparators because of their previous non-association with thyroid cancer, and their common usage as add-on therapy to metformin along with GLP-1RAs and DPP-4 inhibitors. The first cohort included 21 722 new users of GLP-1RAs and 326 993 new users of SGLT2 inhibitors, whereas the second cohort included 904 300 DPP-4 inhibitor new users and 112 017 SGLT2 inhibitor new users. The outcome was the time to incident thyroid cancer. Weighted Cox proportional models were used to estimate hazard ratios of thyroid cancer incidence associated with incretin-based drugs of interest. RESULTS: The use of GLP-1RAs was not associated with an increased risk of thyroid cancer (weighted hazard ratio 0.98, 95% confidence interval 0.62-1.53) compared with that of SGLT2 inhibitors. Using DPP-4 inhibitors was also not associated with an increased risk of thyroid cancer (0.95, 0.79-1.14) compared with that of SGLT2 inhibitors. No significant effect modifications were observed across subgroup analyses. Sensitivity analyses, including alternative outcome definition analysis of medullary thyroid cancer, were consistent with the primary analysis results. CONCLUSIONS: GLP-1RAs and DPP-4 inhibitors were not associated with an increased risk of thyroid cancer in individuals with type 2 diabetes.

COVID-19-Associated Portal Vein Thrombosis Post-Cholecystitis.

This case study describes a 45-year-old Caucasian male with a past medical history of obesity, hypertension, and non-insulin-dependent diabetes mellitus, who in the setting of coronavirus disease 2019 (COVID-19) pneumonia, developed portal vein thrombosis (PVT) presenting as an acute abdomen after hospital discharge from a cholecystitis episode. PVT is a very infrequent thromboembolic condition, classically occurring in patients with systemic conditions such as cirrhosis, malignancy, pancreatitis, diverticulitis, autoimmunity, and thrombophilia. PVT can cause serious complications, such as intestinal infarction, or even death, if not promptly treated. Due to the limited number of reports in the literature describing PVT in the COVID-19 setting, its prevalence, natural history, mechanism, and precise clinical features remain unknown. Therefore, clinical suspicion should be high for PVT, in any COVID-19 patient who presents with abdominal pain or associated signs and symptoms. To the best of our knowledge, this is the first report of COVID-19-associated PVT causing extensive thrombosis in the portal vein and its right branch, occurring in the setting of early-stage cirrhosis after a preceding episode of cholecystitis.

Sodium-Glucose Cotransporter 2 Inhibitors vs Incretin-Based Drugs and Risk of Fractures for Type 2 Diabetes.

Importance: Postmenopausal individuals with type 2 diabetes are susceptible to fractures due to the interaction of elevated blood glucose levels and a deficiency of the hormone estrogen. Despite continued concerns of fracture risks associated with sodium-glucose cotransporter 2 inhibitors (SGLT2i), existing evidence in this high-risk population is lacking. Objective: To assess the risk of fractures associated with SGLT2i vs incretin-based drugs of dipeptidyl-peptidase 4 inhibitors (DPP4i) and glucagon-like peptide 1 receptor agonists (GLP1RA), separately, in postmenopausal individuals with type 2 diabetes. Design, Setting, and Participants: This active-comparator, new-user cohort study used nationwide claims data of Korea and took place from January 1, 2013, to December 31, 2020. Postmenopausal individuals (aged ≥45 years) with type 2 diabetes were included. Exposures: New users of SGLT2i or comparator drugs. Main Outcomes and Measures: The primary outcome was overall fractures, comprising vertebral, hip, humerus, and distal radius fractures. Patients were followed up from the day after drug initiation until the earliest of outcome occurrence, drug discontinuation (90-day grace period) or switch, death, or end of the study period. After propensity score fine stratification, hazard ratios (HRs) with 95% CIs were estimated using weighted Cox models. Results: Among 37 530 (mean [SD] age, 60.6 [9.7] years) and 332 004 (mean [SD] age, 60.6 [9.9] years) new users of SGLT2i and DPP4i, respectively, a lower rate of incident overall fractures was presented with SGLT2i vs DPP4i (weighted HR, 0.78; 95% CI, 0.72-0.84). Among 111 835 (mean [SD] age, 61.4 [9.8] years) and 8177 (mean [SD] age, 61.1 [10.3] years) new users of SGLT2i and GLP1RA, respectively, no association with an increased risk of overall fractures was presented with SGLT2i vs GLP1RA (weighted HR, 0.92; 95% CI, 0.68-1.24). Results from several subgroup and sensitivity analyses presented consistent results from main analysis. Conclusions and relevance: This population-based cohort study suggests that SGLT2i was not associated with an increased rate of incident fractures compared with DPP4i and GLP1RA, separately, among postmenopausal individuals with type 2 diabetes.

Clinical Outcomes of Resectional Roux-en-Y Gastric Bypass, Compared to Sleeve Gastrectomy for Severe Obesity.

PURPOSE: Resectional Roux-en-Y gastric bypass (RRYGB) is considered an alternative bariatric surgery in countries with a high incidence of stomach cancer because there is no excluded stomach after RRYGB. This study aimed to evaluate the efficacy and safety of RRYGB. MATERIALS AND METHODS: This study included patients who underwent RRYGB and sleeve gastrectomy (SG) between 2011 and 2021. Surgical complications and metabolic and nutritional profiles were compared between the patients preoperatively and at 1, 6, and 12 months after surgery. RESULTS: Twenty and seventy-six patients underwent RRYGB and SG, respectively; 7 in the SG group were lost to follow-up within 1 year. Surgical complications and baseline characteristics were comparable between two groups, except for diabetes (90.0% vs. 44.7%, p < 0.001). The decrease of HbA1c levels and incidence of reflux esophagitis were lower in the RRYGB group compared to that of SG at 1-year postoperative (-3.0% vs. -1.8%, p = 0.014; 0% vs. 26.7%, p = 0.027). The percentage of total weight loss at 1- year postoperative and incidence of dumping syndrome were comparable between the two groups. The RRYGB group had significantly lower total cholesterol level (161.9 mg/dl vs. 196.4 mg/dl, p < 0.001), but higher incidence of vitamin B12 deficiency (30.0% vs. 3.6%, p = 0.003) at 1 year postoperative compared to those of the SG group. CONCLUSIONS: The RRYGB group had better postoperative outcomes for diabetes and dyslipidemia without increasing surgical complications compared to that of the SG group. Thus, RRYGB can be considered a safe and effective alternative in areas where gastric cancer is prevalent.

Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases.

Mitochondria are complex metabolic organelles with manifold pathophysiological implications in diabetes. Currently published mitochondrial-encoded peptides, which are expressed from the mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), 16S rRNA (humanin and short humanin like peptide 1-6 [SHLP1-6]), or small human mitochondrial open reading frame over serine tRNA (SHMOOSE) are associated with regulation of cellular metabolism and insulin action in age-related diseases, such as type 2 diabetes mellitus. This review focuses mainly on recent advances in MOTS-c research with regards to diabetes, including both type 1 and type 2. The emerging understanding of MOTS-c in diabetes may provide insight into the development of new therapies for diabetes and other age or senescence-related diseases.

Incretin and Pancreatic ß-Cell Function in Patients with Type 2 Diabetes.

To maintain normal glucose homeostasis after a meal, it is essential to secrete an adequate amount of insulin from pancreatic ß-cells. However, if pancreatic ß-cells solely depended on the blood glucose level for insulin secretion, a surge in blood glucose levels would be inevitable after the ingestion of a large amount of carbohydrates. To avoid a deluge of glucose in the bloodstream after a large carbohydrate- rich meal, enteroendocrine cells detect the amount of nutrient absorption from the gut lumen and secrete incretin hormones at scale. Since insulin secretion in response to incretin hormones occurs only in a hyperglycemic milieu, pancreatic ß-cells can secrete a "Goldilocks" amount of insulin (i.e., not too much and not too little) to keep the blood glucose level in the normal range. In this regard, pancreatic ß-cell sensitivity to glucose and incretin hormones is crucial for maintaining normal glucose homeostasis. In this Namgok lecture 2022, we review the effects of current anti-diabetic medications on pancreatic ß-cell sensitivity to glucose and incretin hormones.

Eosinophilic Myocarditis: An Often-Overlooked Diagnosis in Patients Presenting with Heart Failure.

Introduction. Hypereosinophilic syndrome (HES) is a rare disease characterized by unexplained peripheral eosinophilia along with evidence of end-organ damage. Cardiac involvement is the most life-threatening consequence and is frequently underreported with a prevalence of around 5%. The gold standard for diagnosis is myocardial biopsy, but less-invasive imaging such as cardiac MR (CMR) has been frequently used to help with the diagnosis. We are presenting a unique case of a patient diagnosed with Eosinophilic myocarditis (EM) supported by CMR with rapid improvement after starting steroid treatment. Case Presentation. A 67-year-old African American female with extensive cardiovascular disease history presenting with chest pain was diagnosed with EM secondary to hypereosinophilic syndrome (HES). Lab workup revealed absolute eosinophils of 4.70 × 103/µL (normal 0-0.75 × 103/µL). Transthoracic echocardiography showed mild reduction in left ventricular function and a large obliterating thrombus in the right ventricular apex. CMR showed increased signal intensity at the left ventricular and right ventricular apex, consistent with myocardial edema. Subsequently, the patient was placed on dexamethasone 10 mg daily with significant symptomatic improvement. Discussion. EM is a rare complication of hypereosinophilic syndrome and can mimic common cardiovascular diseases such as acute exacerbation of heart failure or myocardial infarction. A high index of suspicion is essential especially in the setting of suggestive lab workup. CMR is a promising noninvasive and cost-effective alternative for myocardial biopsy in diagnosis.

East Asian perspectives in metabolic and bariatric surgery.

The prevalence of diabetes and obesity continues to rise in East Asia. As the risk of diabetes increases at a lower body mass index (BMI) in East Asians than in Europeans, the threshold of BMI values for metabolic and bariatric surgery (MBS) is lower in East Asians. MBS is considered upon reaching a BMI of 27.5 kg/m2 and is recommended at a BMI of ≥ 32.5 kg/m2 , depending on the status of glucose homeostasis. The most commonly performed MBS in East Asia is sleeve gastrectomy, followed by Roux-en-Y gastric bypass (RYGB). Because the incidence of gastric cancer is higher in East Asia than in other regions, concerns regarding surveillance for gastric cancer might be related to a preference for sleeve gastrectomy over RYGB in this region. Even though there is a paucity of data on direct comparisons of the efficacy of MBS among different ethnic groups, the degree of weight reduction in East Asians is not inferior to other ethnic groups. Moreover, studies suggest that the diabetes remission rate in East Asians seemed to be higher than in other ethnic groups. Future studies involving multiethnic groups are necessary to identify possible ethnic differences in diabetes remission and to determine the appropriate BMI threshold for MBS according to ethnicity.

Human Herpesvirus 6 (HHV-6) Encephalitis in a Non-Transplant Patient With Polymyositis.

Human herpesvirus 6 (HHV-6) was initially labeled as a human B lymphotropic virus because it was isolated in patients diagnosed with lymphoproliferative disorders. There are two variants of HHV-6: HHV-6A and HHV-6B. A considerable majority of recorded primary infections and reactivation events are primarily due to HHV-6B. We report a case of HHV-6 encephalitis reactivation in a 75-year-old Caucasian diabetic female with a past medical history of polymyositis treated with prednisone for a long time who presented with generalized weakness and drowsiness. She developed her symptoms after contact with her grandchildren, who recently had viral-like symptoms treated with antibiotics. Magnetic resonance imaging (MRI) of the brain without contrast showed 14 mm high transverse relaxation time (T2)/fluid-attenuated inversion recovery (FLAIR) signal intensity focus on the left temporal lobe, suspicious for primary versus metastatic neoplasm. Cerebrospinal fluid analysis found that protein concentration was 75 mg/dl, glucose concentration 55 mg/dl, white blood cell count was 22/mm3, with a lymphocytic predominance. Meningitis/encephalitis polymerase chain reaction (PCR) panel detected HHV-6. She was discharged after treatment with ganciclovir for 14 days. It is crucial to recognize HHV-6 infections in immunocompromised patients who present with a T2/FLAIR signal intensity focus in the left temporal lobe. In a hospital setting, rapid HHV-6 encephalitis testing is important to make a correct diagnosis to avoid any delay to prevent further morbidity and mortality.

Mitohormesis in Hypothalamic POMC Neurons Mediates Regular Exercise-Induced High-Turnover Metabolism.

Low-grade mitochondrial stress can promote health and longevity, a phenomenon termed mitohormesis. Here, we demonstrate the opposing metabolic effects of low-level and high-level mitochondrial ribosomal (mitoribosomal) stress in hypothalamic proopiomelanocortin (POMC) neurons. POMC neuron-specific severe mitoribosomal stress due to Crif1 homodeficiency causes obesity in mice. By contrast, mild mitoribosomal stress caused by Crif1 heterodeficiency in POMC neurons leads to high-turnover metabolism and resistance to obesity. These metabolic benefits are mediated by enhanced thermogenesis and mitochondrial unfolded protein responses (UPRmt) in distal adipose tissues. In POMC neurons, partial Crif1 deficiency increases the expression of ß-endorphin (ß-END) and mitochondrial DNA-encoded peptide MOTS-c. Central administration of MOTS-c or ß-END recapitulates the adipose phenotype of Crif1 heterodeficient mice, suggesting these factors as potential mediators. Consistently, regular running exercise at moderate intensity stimulates hypothalamic MOTS-c/ß-END expression and induces adipose tissue UPRmt and thermogenesis. Our findings indicate that POMC neuronal mitohormesis may underlie exercise-induced high-turnover metabolism.

Vertical sleeve gastrectomy induces distinctive transcriptomic responses in liver, fat and muscle.

Vertical sleeve gastrectomy (VSG) is the most commonly performed bariatric/metabolic surgery, exhibiting a high rate of diabetes remission in humans. To elucidate the molecular mechanisms of VSG, we performed transcriptomic analysis of the liver, fat, and muscle in VSG mice. C57BL/6 mice fed a high-fat diet were randomly assigned to sham or VSG surgery. The sham-operated mice were fed ad libitum (sham group) or pair-fed (sham-PF group) matching their food intake to the VSG-operated mice. Comparative transcriptomic analysis of the liver, fat, and muscle using RNA sequencing was performed. VSG reduced body weight and improved glucose tolerance compared to the sham group, but not more than the sham-PF group. Improvement in fatty liver and adipose tissue inflammation was comparable between VSG and sham-PF. However, global gene expression profiles showed distinctive changes in the liver, fat, and muscle of the VSG group compared to both the sham or sham-PF groups. The liver showed the most prominent gene expression changes. Immune response-related pathways were commonly upregulated in the three organs of the VSG group compared to the sham or sham-PF. VSG induces organ-specific gene expression changes in the liver, fat, and muscle, which may play critical roles in metabolic improvements after VSG.

Development of a clinical risk score for incident diabetes: A 10-year prospective cohort study.

AIMS/INTRODUCTION: We developed a self-assessable Korean Diabetes Risk score using the data of the Korean Genome and Epidemiology Study. MATERIALS AND METHODS: A total of 8,740 participants without diabetes at baseline were followed up biannually over a period of 10 years. We included variables that were significantly different between participants who developed diabetes mellitus and those who did not in the development cohort at baseline. We assigned a maximum score of 100 to the selected variable in each gender group. Next, the 10-year probability of incident diabetes was calculated and validated in the validation cohort. Finally, we compared the predictive power of Korean Diabetes Risk score with models including fasting plasma glucose or glycated hemoglobin and other cohort models of Atherosclerosis Risk in Communities and Korea National Health and Nutrition Examination Survey. RESULTS: During a median follow-up period of 9.7 years, 22.7% of the participants progressed to diabetes. The Korean Diabetes Risk score included age, living location (urban or rural area), waist circumference, hypertension, family history of diabetes and smoking history. The developed risk score yielded acceptable discrimination for incident diabetes (area under the curve 0.657) and the predictive power was improved when the model included fasting plasma glucose (area under the curve 0.690) or glycated hemoglobin (area under the curve 0.746). In addition, our model predicted incident diabetes more accurately than previous Western or Korean models. CONCLUSIONS: This newly developed self-assessable diabetes risk score is easily applicable to predict the future risk of diabetes even without the necessity for laboratory tests. This score is useful for the Korean diabetes prevention program, because high-risk individuals can be easily screened.

Long-term efficacy and safety of oral semaglutide and the effect of switching from sitagliptin to oral semaglutide in patients with type 2 diabetes: a 52-week, randomized, open-label extension of the PIONEER 7 trial.

INTRODUCTION: The PIONEER 7 trial demonstrated superior glycemic control and weight loss with once-daily oral semaglutide with flexible dose adjustment versus sitagliptin 100 mg in type 2 diabetes. This 52-week extension evaluated long-term oral semaglutide treatment and switching from sitagliptin to oral semaglutide. RESEARCH DESIGN AND METHODS: A 52-week, open-label extension commenced after the 52-week main phase. Patients on oral semaglutide in the main phase continued treatment (n=184; durability part); those on sitagliptin were rerandomized to continued sitagliptin (n=98) or oral semaglutide (n=100; initiated at 3 mg) (switch part). Oral semaglutide was dose-adjusted (3, 7, or 14 mg) every 8 weeks based on glycated hemoglobin (HbA1c) (target <7.0% (<53 mmol/mol)) and tolerability. Secondary endpoints (no primary) included changes in HbA1c and body weight. RESULTS: In the durability part, mean (SD) changes in HbA1c and body weight from week 0 were -1.5% (0.8) and -1.3% (1.0) and -2.8 kg (3.8) and -3.7 kg (5.2) at weeks 52 and 104, respectively. In the switch part, mean changes in HbA1c from week 52 to week 104 were -0.2% for oral semaglutide and 0.1% for sitagliptin (difference -0.3% (95% CI -0.6 to 0.0); p=0.0791 (superiority not confirmed)). More patients achieved HbA1c <7.0% with oral semaglutide (52.6%) than sitagliptin (28.6%; p=0.0011) and fewer received rescue medication (9% vs 23.5%). Respective mean changes in body weight were -2.4 kg and -0.9 kg (difference -1.5 kg (95% CI -2.8 to -0.1); p=0.0321). Gastrointestinal adverse events were the most commonly reported with oral semaglutide. CONCLUSIONS: Long-term oral semaglutide with flexible dose adjustment maintained HbA1c reductions, with additional body weight reductions, and was well tolerated. Switching from sitagliptin to flexibly dosed oral semaglutide maintained HbA1c reductions, helped more patients achieve HbA1c targets with less use of additional glucose-lowering medication, and offers the potential for additional reductions in body weight. TRIAL REGISTRATION NUMBER: NCT02849080.

Prognosis of Patients with Colorectal Cancer with Diabetes According to Medication Adherence: A Population-Based Cohort Study.

BACKGROUND: Diabetes mellitus is known to have a negative effect on colorectal cancer survival due to hyperinsulinemia or hyperglycemia, and medications such as metformin, which targets insulin resistance and hyperinsulinemia, have a preventive effect on the risk of death. The aim of this study was to compare the risk of death among patients with colorectal cancer with diabetes with different levels of adherence to oral antidiabetics. METHODS: National Health Information Database was used, which has all claims data for those who are registered for national health insurance in Korea, from 2002 to 2016, for conducting a retrospective cohort study. Newly diagnosed patients with colorectal cancer among diabetics were followed up from the date of diagnosis until death or December 31, 2016. The medication adherence was calculated as the proportion of days covered (PDC). The HR and 95% confidence interval (CI) for death were estimated using the low-adherence patients as a reference. RESULTS: A total of 33,841 diabetic patients with newly diagnosed colorectal cancer were followed for an average of 4.7 years. Patients with colorectal cancer with good adherence (PDC ≥ 80%) showed a reduced risk of death [HR (95% CI), 0.82 (0.78-0.86)] compared with those with poor adherence (PDC < 80%). A reduced risk of death was observed for all cancer subsites. CONCLUSIONS: The maintenance of good medication adherence for diabetes mellitus was related to a favorable prognosis of colorectal cancer. IMPACT: This study provides evidence that patients with colorectal cancer who are adherent to their diabetes medication will have better survival than patients who are not adherent.

Economic benefit of prescribing an adjusted renal dose of dipeptidyl peptidase IV inhibitors in type 2 diabetes patients with chronic kidney disease.

Highlights Based on nationwide insurance data in Korea, the use of dipeptidyl peptidase IV inhibitors (DPP-IVi) not requiring renal dose adjustment (NRDA DPP-IVi) is widespread in the type 2 diabetes chronic kidney disease (T2D CKD) population. Instead of prescribing NRDA DPP-IVi, the use of DPP-IVi requiring renal dose adjustment with appropriate renal dose adjustments in T2D CKD patients can achieve a considerable annual cost saving of up to 7.8%.

Effects of MOTS-c on the mitochondrial function of cells harboring 3243 A to G mutant mitochondrial DNA.

Mitochondrial derived peptides (MDPs) are a class of peptide encoded in small open reading frames of mitochondrial DNA (mtDNA). MOTS-c, a recently discovered MDP, participates in retrograde signaling from the mitochondria to the nucleus to control cellular metabolism. Humanin, another MDP, has cytoprotective properties and enhances mitochondrial function. However, it has not yet been tested whether MOTS-c can affect mitochondrial function. We investigated the effect of exogenous and endogenous MOTS-c on mitochondrial function in a cybrid cell harboring 3243 A to G mutant mtDNA, which causes significant mitochondrial dysfunction. To test the effects of endogenous MOTS-c, the cybrid cell was transfected with a MOTS-c EGFP expression vector. Exogenous (synthetic) MOTS-c did not show a significant effect on the ATP content or the mRNA and protein levels of the mitochondrial complex in the mutant cybrid cells. Basal and stimulated mitochondrial respiration were also not affected by exogenous MOTS-c. The mutant cybrid cells transfected with the MOTS-c EGFP expression vector stably expressed MOTS-c, but ATP production and mRNA and protein levels of the mitochondrial complex were not affected. In contrast to other MDPs, MOTS-c does not improve mitochondrial dysfunction in cybrid cells with mutant mtDNA, which suggests the heterogeneous nature of MDPs.