The Efficacy and Safety of Sodium-Glucose Co-transporter 2 (SGLT2) Inhibitors in Real-World Clinical Practice: Potential Cautionary Use in Elderly Patients with Type 2 Diabetes (T2D).

INTRODUCTION: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown safe and therapeutic efficacy in randomized controlled trials (RCT) to reduce adverse cardiorenal events in high-risk patients with type 2 diabetes (T2D). In this study, we investigated the efficacy and safety of SGLT2 intervention in patients with T2D in a real-world clinical practice to confirm the validity of the RCT results. METHODS: As a retrospective study, we evaluated medical records from 596 patients with T2D treated with SGLT2 inhibitors (dapagliflozin or empagliflozin) in addition to their prior drug regimen to improve glucose control between 2015 and 2019 in the Endocrinology Department at Chungbuk National University Hospital. No control arm was evaluated to compare the effects of adding SGLT inhibitors to the pre-existing regimen. The primary objective was the measurement of glycated hemoglobin (HbA1c) from each individual patient over a 36-month period at 6-month intervals. The secondary parameters were the measurement of fasting plasma glucose (FPG) and body weight (Bwt) changes, as well as the monitoring of adverse events (AEs) and determining the reasons for drug discontinuation. RESULTS: HbA1c levels were reduced at each of the time points throughout the 36-month period and were significantly reduced by 12.5% (P < 0.01) from time 0 (8.8 ± 1.3%) to 36 months (7.7 ± 1.0%). FPG levels [from basal (180 ± 60 mg/dL) to 36 months (138 ± 38 mg/dL)] and Bwt [from basal (74 ± 15 kg) to 36 months (72 ± 15 kg)] were also significantly reduced (P < 0.01) for both measurements in the SGLT2 inhibitor add-on group. Similar to HbA1c profile, the FPG and Bwt were measured at a consistently lower level at 6 months until the end of the study. The most common AEs were hypoglycemia (n = 57), genitourinary infection (GUI) (n = 31), and polyuria (n = 28). In the elderly population (≥ 75 years old), AEs (31%) were generally more prevalent (P < 0.001) than those (21%) in the adult (< 75 years old) patients. Over the study period, 211 (35%) patients either dropped or completely discontinued the use of the SGLT2 inhibitor, and the elderly patients tended to have a higher discontinuation rate (52%; P = 0.005) than the adults (33%). CONCLUSIONS: In this study, we demonstrated that SGLT2 inhibitors are an effective and durable hypoglycemic agent to control blood glucose levels with reduced maintenance of Bwt, but their use in the elderly (≥ 75 years old) patients with T2D may warrant some additional caution due to increased probability of AEs and discontinuation of drug use.

Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. Conclusion: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Different Oncologic Outcomes According to Margin Status (High-Grade Dysplasia vs. Carcinoma) in Patients Who Underwent Hilar Resection for Mid-Bile Duct Cancer.

Margin positivity after hilar resection (HR) for bile duct cancer is commonly observed due to its longitudinal spread along the subepithelial plane; nevertheless, we cannot draw conclusions regarding the prognostic effects of margins with high-grade dysplasia (HGD) or carcinoma. We aimed to investigate the oncologic effect according to the margin status after HR, particularly between the R1 HGD and the R1 carcinoma. From 2008 to 2017, 149 patients diagnosed with mid-bile duct cancer in Samsung Medical Center, South Korea, were divided according to margin status after HR and retrospectively analyzed. Recurrence patterns were also analyzed between the groups. There were 126 patients with R0 margins, nine with R1 HGD, and 14 with R1 carcinoma. The mean age of the patients was 68.3 (±8.1); most patients were male. The mean age was higher in R1 carcinoma patients than in R1 HGD and R0 patients (p = 0.014). The R1 HGD and R1 carcinoma groups had more patients with a higher T-stage than R0 (p = 0.079). In univariate analysis, the prognostic factors affecting overall survival were age, T- and N-stage, CA19-9, and margin status. The survival rate of R0 was comparable to that of R1 HGD, but the survival rate of R0 was significantly better compared to R1 carcinoma (R0 vs. R1 HGD, p = 0.215, R0 vs. R1 carcinoma, p = 0.042, respectively). The recurrence pattern between the margin groups did not differ significantly (p = 0.604). Extended surgery should be considered for R1 carcinoma; however, in R1 HGD, extended operation may not be necessary, as it may achieve oncologic outcomes similar to R0 margins with HR.

Prognosis of pancreaticoduodenectomy in octogenarians for pancreatic ductal adenocarcinoma with propensity score matched analysis.

BACKGROUND: This retrospective study investigates factors affecting surgical and oncological outcome after performing pancreaticoduodenectomy in octogenarian patients diagnosed with pancreatic ductal adenocarcinoma. METHODS: From January 2009 to December 2018, patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma were included. Data were analysed by comparing clinicopathological characteristics, complications, survival, recurrence, adjuvant treatment between octogenarians and the younger group. Propensity score matched analysis was performed due to the small size of the octogenarian group. RESULTS: A total of 666 patients were included in this study and 24 (3.6%) were included in the octogenarian group. Short term complication rates (P = 0.119) and hospital stay (P = 0.839) did not differ between two groups. Overall survival between the two groups showed significant difference (<80 median 25 months versus ≥80 median 13 months, P = 0.045). However, after propensity score matched analysis, the two groups did not differ in overall survival (<80 median 18 months versus ≥80 median survival 16 months, P = 0.565) or disease-free survival (P = 0.471). Among the octogenarians, six patients survived longer than 24 months even without satisfying all favourable prognostic factors. CONCLUSION: Considering the general condition of octogenarians diagnosed with pancreatic ductal adenocarcinoma, select patients should be treated more aggressively for the best chance of receiving curative treatment.

Survival Benefit after Shifting from Upfront Surgery to Neoadjuvant Treatment in Borderline Resectable Pancreatic Cancer.

According to the 2016 National Comprehensive Cancer Network (NCCN) guidelines, patients with borderline resectable pancreatic cancer (BRPC) should receive chemotherapy as the first-line treatment. This study examined the real-world survival benefits of modifying BRPC treatment guidelines. Patients treated for BRPC at a single institution from 2013 to 2015 (pre-guideline group) and 2017 to 2019 (post-guideline group) were retrospectively reviewed. According to the treatment method used, patients were classified into upfront surgery (US), surgery after neoadjuvant treatment (NAT), and chemotherapy only (CO) groups. Overall survival (OS) was compared according to period and treatment type. Factors associated with OS were analyzed using a Cox regression model. Among the 165 patients, 63 were in the pre-guideline group and 102 patients were in the post-guideline group. The median OS was significantly improved in the post-guideline group compared to the pre-guideline group (29 vs. 13 months, p < 0.001). According to the treatment method, the median OS of the NAT group was significantly longer than that of the US and CO groups (40 vs. 16 vs. 15 months, respectively, p < 0.001). In multivariate analysis, tumor size, differentiation, NAT, and perineural invasion were significant prognostic factors. NAT is an important treatment option for BRPC and increased patient survival in the real world.

Nationwide Trends in Osteoporosis in Koreans With Disabilities From 2008 to 2017.

This study examined the 10-year trends in the prevalence of osteoporosis according to disability grade and type compared with those without disabilities in South Korea. We linked national disability registration data with the National Health Insurance claims data. Age- and sex-standardized prevalence of osteoporosis were analyzed from 2008 to 2017 according to sex, disability type, and disability grade. Adjusted odds ratios for osteoporosis according to disability characteristics in the most recent years' data were also confirmed by multivariate analysis. Over the past decade, the prevalence of osteoporosis has increased in people with disabilities compared with people without disabilities, and the gap has gradually widened from 7% to 15%. By analysis of the most recent year data, both male and female individuals with disabilities had a higher risk of osteoporosis than those without disability (odds ratios [OR] 1.72, 95% confidence interval [CI] 1.70-1.73 in males; OR 1.28, 95% CI 1.27-1.28 in females); the multivariate-adjusted OR was especially prominent in disability related to respiratory disease (OR 2.07, 95% CI 1.93-2.21 in males; OR 1.74; 95% CI 1.60-1.90 in females), epilepsy (OR 2.16, 95% CI 1.78-2.61 in males; OR 1.71; 95% CI 1.53-1.91 in females), and physical disability types (OR 2.09, 95% CI 2.06-2.21 in males; OR 1.70; 95% CI 1.69-1.71 in females). In conclusion, the prevalence and risk of osteoporosis have increased in people with disabilities in Korea. In particular, the risk of osteoporosis increases significantly in people with respiratory diseases, epilepsy, and physical disability types. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Influenza vaccination trend and related factors among patients with diabetes in Korea: Analysis using a nationwide database.

Background: Subjects with diabetes are at higher risk of serious influenza-related complications. We aimed to investigate the yearly trend of influenza vaccination and factors associated with being unvaccinated for influenza in subjects with diabetes using a nationwide observational study performed within the recent decade. Methods: Among 105,732 subjects from the Korea National Health and Nutrition Examination Survey between 2007 and 2019, 8,632 with diabetes were included. We investigated the yearly trend of influenza vaccination and factors associated with being unvaccinated for influenza. Results: During the study period, the prevalence of influenza vaccination in subjects with diabetes showed a tendency to increase every year, reaching almost 60% in 2019, which was higher than the rate in subjects without diabetes. Younger age (adjusted hazard ratio (aHR) [95% CI] 11.29 [8.63-14.75] for < 50 years; 6.16 [5.21-7.29] for 50-65 years), male (aHR 1.67 [1.52-1.87]), current smoker (aHR 1.31 [1.00-1.72], lower-income status (aHR 1.46 [1.17, 1.84]), and high education level (aHR 1.30 [1.01-1.67]) were associated with being unvaccinated. Also, a poorer glycemic control with HbA1c ≥ 9% was found to be correlated with unvaccinated status (aHR 1.48 [1.15-1.90]). Conclusion: The influenza vaccination rate is still unsatisfactory in subjects with diabetes. Young age, males, low-income level, high education level, and poor glycemic control were associated with unvaccinated status. Considering the risk-benefits of influenza vaccination in patients with diabetes, physicians should make an effort to increase vaccination rates, especially in low vaccination rate groups.

Utilization of end to side inverted mattress pancreaticojejunostomy for Duval procedure: A case report.

Although a pancreaticojejunostomy (PJ) is not required after a distal pancreatectomy in most cases, it needs to be performed to prevent atrophy of the remnant pancreas when the proximal duct is obstructed by a tumor, stone, or etc. In these conditions, the critical postoperative pancreatic fistula (POPF) gives surgeons cause to hesitate before performing a PJ. We previously presented the modified technique of Mattress PJ named "inverted mattress PJ" (IM-PJ) and published improved outcomes in the aspects of POPF after a pancreaticoduodenectomy and a central pancreatectomy. Recently, we had a case of a patient who has chronic pancreatitis with a proximal pancreatic duct obstruction, requiring a distal pancreatectomy and PJ. Based on the previous report, we decided to apply the "inverted mattress PJ" (IM-PJ) technique for a Roux-en Y PJ after a distal pancreatectomy. The patient was discharged after surgery without complications. We reviewed a case of a patient requiring PJ following a distal pancreatectomy and discussed the safety of our technique.

Improvement of osseointegration efficacy of titanium implant through plasma surface treatment.

A novel plasma treatment source for generating cylindrical plasma on the surface of titanium dental implants is developed herein. Using the titanium implant as an electrode and the packaging wall as a dielectric barrier, a dielectric barrier discharge (DBD) plasma was generated, allowing the implant to remain sterile. Numerical and experimental investigations were conducted to determine the optimal discharge conditions for eliminating hydrocarbon impurities, which are known to degrade the bioactivity of the implant. XPS measurement confirmed that plasma treatment reduced the amount of carbon impurities on the implant surface by approximately 60%. Additionally, in vitro experiments demonstrated that the surface treatment significantly improved cell adhesion, proliferation, and differentiation. Collectively, we proposed a plasma treatment source for dental implants that successfully removes carbon impurities and facilitate the osseointegration of SLA implants.

Association between the triglyceride-glucose (TyG) index and increased blood pressure in normotensive subjects: a population-based study.

BACKGROUND: Insulin resistance (IR) is an important contributor to the development of hypertension (HTN), and the triglyceride-glucose (TyG) index has been proposed as a simple, reliable marker of IR. This study investigated the association between the TyG index and blood pressure (BP) elevation in a large general population. METHODS: The study enrolled 15,721 adults with no history of cardiometabolic diseases from the 2016-2019 Korea National Health and Nutrition Examination Survey. Participants were classified into quartiles based on the TyG index and BP was categorized as normal BP, elevated BP, pre-HTN, and HTN. The associations of the TyG index with BP categories were assessed using multivariate multinomial logistic regression models with normal BP as the reference group. RESULTS: The mean systolic/diastolic BP and prevalence of HTN increased with the TyG index (P for trend < 0.001). The continuous TyG index had a strong dose-response relationship with increased odds of elevated BP, pre-HTN, and HTN. Compared with the lowest TyG index quartile, the highest TyG index quartile was significantly associated with higher odds of having elevated BP (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.24-1.87; P for trend < 0.001), pre-HTN (OR, 2.22; 95% CI, 1.95-2.53; P for trend < 0.001), and HTN (OR, 4.24; 95% CI, 3.49-5.16; P for trend < 0.001). CONCLUSION: We found that a higher TyG index was positively associated with the risk of increased BP in normal healthy individuals. This study suggests that the TyG index might serve as a potential predictor of HTN. However, further studies with larger sample sizes and various target populations in longitudinal designs are needed.

Various types of reconstruction after pancreaticoduodenectomy for the patients who underwent all types of gastrectomy: a single-enter experience.

Purpose: The incidence of patients requiring pancreaticoduodenectomy (PD) following any type of gastrectomy is increasing as the population of elderly patients is increasing, especially in endemic areas of gastric cancer such as Korea. All types of gastrectomy can be categorized as subtotal gastrectomy with Billroth I (BI), Billroth II (BII), and total gastrectomy with Roux-en-Y anastomosis. In this paper, we reviewed our experiences of PD for patients who previously underwent gastrectomy. Methods: We reviewed the medical records of the patients who underwent PD following any type of gastrectomy among 505 consecutive patients who underwent PD in a single institution between 2011 and 2020 retrospectively. Results: There were 13 patients who had undergone gastrectomy including 7 patients of BI, 1 patient of BII, and 5 patients of total gastrectomy. For all 7 patients of BI, the reconstruction was not different from conventional PD. For the 1 patient of BII, previous gastrojejunal anastomosis was preserved and reconstruction was performed in Roux-en-Y method. For the 5 patients with total gastrectomy, 2 different types of reconstruction were performed. In one patient, we removed the remaining jejunum with the specimen, and reconstruction was performed. For the other 4 patients, the remaining jejunum, distal to the Treitz ligament, was preserved and was utilized for anastomosis. Surgeries for all patients were uneventful. Conclusion: PD following any type of gastrectomy can be safe. Especially, if the length of remained jejunum is long enough, its utilization for the reconstruction can be an appropriate option.

Discussing POLST-facilitated hospice care enrollment in patients with terminal cancer.

PURPOSE: A multicenter prospective study to evaluate the feasibility of Physician Orders for Life-Sustaining Treatment (POLST) in oncology practice was conducted between June and December 2017. Factors associated with POLST completion and follow-up outcomes were analyzed. METHODS: Patients with terminal cancer, aged ≥ 20 years and capable of communicating, were enrolled from seven hospitals. Demographic data were collected and updated in February 2021. Descriptive statistics and logistic regression analyses were conducted. RESULTS: Among 336 patients, 105 (31.3%) completed POLST, which was more common in male (p = 0.029), patients with better performance (p < 0.001), longer duration of follow-up (p = 0.037), and those living with children (p = 0.023). Male (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.17-3.51; p = 0.012), having good performance status (OR, 2.38; 95% CI, (1.35-4.19); p = 0.003), transferred from other departments (OR, 0.50; 95% CI, (0.26-0.98); p = 0.045), and living with children (OR, 1.94; 95% CI, (1.11-3.47); p = 0.020) were significant predictors of POLST completion. Patients who completed POLST were more likely to enroll in hospice care (p = 0.012) or experience out-of-hospital death (p = 0.016) at end-of-life (EOL). POLST completion showed a strong association with hospice enrollment at EOL (OR, 2.61; 95% CI, (1.08-6.32); p = 0.033). CONCLUSION: Gender, patient performance, timing of POLST discussion, and type of household were associated with POLST completion. Earlier discussions on POLST could reinforce hospice enrollment or non-aggressive EOL care.

Unfavorable effect of high postoperative fluid balance on outcome of pancreaticoduodenectomy.

Purpose: Despite the many efforts to overcome postoperative complications, pancreaticoduodenectomy (PD) is still accompanied with considerable concerns of lethal complications. The clinical factors are known to affect postoperative outcomes such as diameter of pancreatic duct, texture of pancreas, and comorbidity of the patients are mostly uncorrectable. Thus, investigation for correctable risk factors is required. Recently, perioperative fluid volume was reported to be associated with complications after PD. This study aims to determine the relationship between postoperative fluid balance and surgical outcome after open PD. Methods: We reviewed, retrospectively, 172 consecutive patients who underwent open PD in a single institution between 2015 and 2019. The status of perioperative fluid balance 2 days after surgery and clinical factors were investigated to determine the association with postoperative outcome including postoperative pancreatic fistula (POPF). According to postoperative fluid balance, patients were divided into high- and low-balance groups, and clinical features and surgical outcomes were compared between both groups. Multivariate analysis were performed to identify risk factors for POPF. Results: The percentage of morbidity and the incidence of POPF were higher in the high-balance group compared to the low-balance group (61.6% vs. 37.2%, P = 0.001; 15.1% vs. 3.5%, P = 0.009). High postoperative fluid balance and the presence cardiovascular disease were correlated with POPF on multivariate analysis (odds ratio [OR], 4.574; 95% confidence interval [CI], 1.229-17.029; P = 0.023 and OR, 3.517; 95% CI, 1.209-12.017; P = 0.045). Conclusion: Higher amount of postoperative fluid balance and the presence of cardiovascular disease are associated with POPF after PD.

Nationwide trends in prevalence of underweight, overweight, and obesity among people with disabilities in South Korea from 2008 to 2017.

OBJECTIVES: This study investigated the 10-year trends of weight and prevalence of underweight, overweight and obesity according to disability grade and types compared with those without disabilities. METHODS: This serial cross-sectional analysis was conducted using national disability registration data with national general health checkup data from 2008 to 2017. Age-standardized prevalence of underweight and obesity were analyzed for each year, according to the presence, type, and severity of disabilities. Odds of underweight, overweight, obesity, and severe obesity were examined by multinomial logistic regression after adjusting for socio-demographic and clinical variables using data in 2017. RESULTS: Over 10 million subjects in each year were included in the analysis. In 2017, 14,246,785 people with age between 19 and 110 years were included and 53.1% was men. For 10 years, age-standardized prevalence of obesity and severe obesity showed significant increases regardless of sex and presence of disability. However, age-standardized underweight prevalence in people without disability tended to decrease whereas it was an increase in 2012 and the prevalence has remained steady since in people with disability. People with disabilities had higher odds of underweight compared to those without disability (OR 1.41, 95% CI 1.38-1.44 in male and OR 1.31, 95% CI 1.28-1.34 in female), especially in those with severe disabilities (OR 2.00, 95% CI 1.94-2.06 in male and OR 1.83, 95% CI 1.77-1.89 in female). Women with disabilities are more likely to be obese than those without disabilities regardless of disability severity (OR 1.40, 95% CI 1.38-1.41). Participants with mental disorder showed the highest prevalence of obesity, followed by epilepsy and developmental disability. CONCLUSIONS: Having a disability was associated with higher odds/probability of both obesity and underweight. The intersection of female, severe disability, and mental/developmental disabilities was associated with probability of severe obesity. Simultaneous efforts are needed to develop health policy to reduce both the prevalence of obesity and underweight.

Pathological Response Predicts Survival after Pancreatectomy following Neoadjuvant FOLFIRINOX for Pancreatic Cancer.

Background: The clinical course of complete pathologic response (cPR) in pancreatic cancer after neoadjuvant chemotherapy is not well known. The aim of this study was to investigate the clinical course of patients according to pathological response, including cPR, who received only FOLIFIRNOX in advanced pancreatic cancer. Methods: Patients who underwent pancreatectomy after FOLFIRINOX for pancreatic ductal adenocarcinoma (PDAC) from 2017 to 2019 were retrospectively reviewed. cPR was defined as an absence of residual tumor on pathologic report. A nearly complete pathologic response (ncPR) was defined as a tumor confined to pancreas parenchyma, less than 1 cm without lymph-node metastasis. cPR and ncPR were assigned into a favorable pathologic response group (fPR). Kaplan−Meier method and Cox proportional hazard models were used for analysis. Results: Of a total 64 patients, 8 (12.5%) had a cPR and 8 (12.5%) had a ncPR. In the fPR group, median OS and DFS were superior to those of non-pathologic response group (more than 60 months vs. 38 months, p < 0.001; more than 42 months vs. 10 months, p < 0.001). On multivariable analyses, fPR and adjuvant therapy were independent prognostic factors for OS (HR: 0.12; 95% CI: 0.02−0.96, p = 0.05; HR: 0.26; 95% CI: 0.09−0.74, p = 0.01) and DFS (HR: 0.31; 95% CI: 0.12−0.86, p = 0.02; HR:0.31; 95% CI: 0.13−0.72, p = 0.01). Conclusions: pathologic response predicts survival after pancreatectomy following neoadjuvant FOLFIRINOX for pancreatic cancer, and adjuvant chemotherapy following neoadjuvant treatment might be beneficial for OS and DFS.

Clinical Outcome of Resected Non-Ampullary Duodenal Adenocarcinoma: A Single Center Experience.

(1) Background: This study identified the clinical outcome and prognostic factors of resected non-ampullary duodenal adenocarcinoma (NADA) in a single tertiary cancer center. (2) Methods: The medical records of 109 patients with NADA who underwent curative surgery between 2000 and 2018 were reviewed retrospectively. (3) Results: The mean age was 62.4 years with a male predominance (70.6%). The majority of tumors were located at the 2nd portion (58.7%). Fifty-seven patients (52.3%) had symptoms at diagnosis. CA19-9 was elevated in 32 patients (29.4%). Of this cohort, most patients were diagnosed as stage III (64.2%). The median overall survival was 92.9 months, and the 1-, 3-, and 5-year survival rates were 84.4%, 71.6%, and 53.7%, respectively. In univariate and multivariate analysis, age, symptoms, CA19-9, and margin status were associated with overall survival and symptoms, CA19-9 and margin status were also associated with recurrence. When correlating symptoms with stages, patients with symptoms at diagnosis had more advanced stages (all p < 0.001). (4) Conclusion: Old age, elevated CA19-9, symptoms, and margin status were independent prognostic factors of NADA, and the patients with symptoms at diagnosis tend to have more advanced stages and a poor prognosis.

Long-term effectiveness and safety of quadruple combination therapy with empagliflozin versus dapagliflozin in patients with type 2 diabetes: 3-year prospective observational study.

AIMS: To investigate the long-term effectiveness and safety of two distinct sodium-glucose co-transporter 2 (SGLT2) inhibitors, empagliflozin and dapagliflozin, in inadequately controlled type 2 diabetes (T2D) despite a combined administration of metformin, glimepiride and dipeptidyl peptidase-4 inhibitor. METHODS: A total of 362 patients with T2D were enrolled for this 3-year open-label, prospective observational study. Empagliflozin (25 mg/day, n = 185) or dapagliflozin (10 mg/day, n = 177) was added to the existing triple drug regimen. HbA1c, fasting plasma glucose (FPG), body weight, and other cardiometabolic variables and adverse events were evaluated. RESULTS: At 3 years, changes in HbA1c and FPG were -1.7% (standard error [SE] 0.10) and -60.0 mg/dL(2.2), and -1.1%(0.12) and -48.1 mg/dL(3.6), for empagliflozin and dapagliflozin group, respectively (P = 0.001 and P = 0.055). Empagliflozin group showed significantly greater body weight reduction (-4.5 kg [SE 0.35] vs. -1.0 kg [SE 0.40], P = 0.024) and had beneficial effects on HDL cholesterol and LDL cholesterol (both P < 0.05). The overall incidence of adverse events, cardiovascular events and mortality did not differ between the two groups. CONCLUSIONS: Quadruple combination therapy with either empagliflozin or dapagliflozin showed a positive long-term effect in the glycemic control and body weight reduction with generally well tolerance. In general, the use of empagliflozin performed better than dapagliflozin. Clinical Trial Number NCT03748810 (ClinicalTrials.gov).

Effect of Dipeptidyl Peptidase-4 Inhibitors on Bone Health in Patients with Type 2 Diabetes Mellitus.

Patients with type 2 diabetes (T2DM) have a higher risk of bone fracture even when bone mineral density (BMD) values are normal. The trabecular bone score (TBS) was recently developed and used for evaluating bone strength in various diseases. We investigated the effect of DPP-4 inhibitors on bone health using TBS in patients with T2DM. This was a single-center, retrospective case-control study of 200 patients with T2DM. Patients were divided into two groups according to whether they were administered a DPP-4 inhibitor (DPP-4 inhibitor group vs. control group). Parameters related to bone health, including BMD, TBS, and serum markers of calcium homeostasis, were assessed at baseline and after one year of treatment. We found TBS values increased in the DPP-4 group and decreased in the control, indicating a significant difference in delta change between them. The BMD increased in both groups, with no significant differences in delta change between the two groups observed. Serum calcium and 25-hydroxy vitamin D3 increased only in the DPP-4 inhibitor group, while other glycemic parameters did not show significant differences between the two groups. Treatment with DPP-4 inhibitors was associated with favorable effects on bone health evaluated by TBS in patients with T2DM.

Polymorphism in the HaeIII single nucleotide polymorphism of the SLC2A1 gene and cardiovascular disease in the early type 2 diabetes mellitus.

INTRODUCTION: SLC2A1 polymorphism may play a role in the smooth muscle cell proliferation and extracellular matrix synthesis in vessels. However, the role of SLC2A1 polymorphism on diabetic cardiovascular disease (CVD) have not yet been identified. In this study, we aimed to investigate the association between SLC2A1 HaeIII polymorphism and CVD in Korean patients with type 2 diabetes mellitus (T2DM) according to disease duration. METHODS: A total of 846 patients with T2DM who visited the Chungbuk National University Hospital were investigated. The HaeIII polymorphism of SLC2A1 gene was determined by real time polymerase chain reaction method. Genotyping results were presented GG, AG, or AA. Subgroup analysis was performed according to duration of T2DM (⩽10, 11-20, >20 years). RESULTS: The AA genotype was significantly associated with higher prevalence of CVD in patients with DM duration less than 10 years (26.3% vs 9.2%, p = 0.014). There was no significant association between SLC2A1 HaeIII polymorphism and other diabetic complications including, retinopathy, nephropathy, neuropathy, cerebrovascular disease, and peripheral artery disease. CONCLUSIONS: The SLC2A1 HaeIII polymorphism was associated with CVD in Korean patients with T2DM with short disease duration.

RANTES 59029A/G Polymorphisms Associated with Diabetic Compilations in Korean Patients with Type 2 Diabetes for over 15 Years.

BACKGROUND: Polymorphisms in the RANTES gene are known to be associated with several diseases related to insulin resistance. In this study, we investigated the association between RANTES 59029A/G polymorphisms and the prevalence of diabetic complications relative to obesity in Korean patients who had type 2 diabetes (T2D) for over 15 years. METHODS: A single-center, retrospective case-control study was performed. We included 271 patients with a duration of diabetes greater than 15 years. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze RANTES polymorphisms, identifying genotypes as GG, AG, or AA. Obesity was defined using the body mass index with a cutoff value of 25 kg/m2. Both microvascular (retinopathy and nephropathy) and macrovascular (coronary artery disease and cerebrovascular disease) complications were evaluated. RESULTS: The duration of T2D and hemoglobin A1c values at enrollment were 24.4 ± 5.0 years and 7.8 ± 1.6%, respectively, in the non-obese group, and 25.4 ± 6.1 years and 7.7 ± 1.7%, respectively, in the obese group. The prevalence of microvascular complications was significantly higher in the obese group compared with that in the non-obese group (83.5% vs. 72.0%, p = 0.039). Compared to the non-obese group, the obese group showed a higher proportion of the patients with AA or AG genotypes (64.3% vs. 84.5%, p = 0.001). CONCLUSIONS: The A allele of the RANTES gene is associated with obesity and may affect diabetic microvascular complications in patients with T2D for over 15 years.