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.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background: This study investigated the effect of an excess and a deficit of spinal 5-hydroxytryptamine (5-HT) on the mechanical allodynia and neuroglia activation in a rodent pain model of carrageenan inflammation. Methods: Male Sprague–Dawley rats were implanted with an intrathecal (i.t.) catheter to administer the drug. To induce an excess or deficit of 5-HT in the spinal cord, animals were given either three i.t. 5-HT injections at 24-hour intervals or a single i.t. injection of 5,7-dihydroxytryptamine (5,7-DHT) before carrageenan inflammation.Mechanical allodynia was measured using the von Frey test for 0–4 hours (early phase) and 24–28 hours (late phase) after carrageenan injection. The changes in the activation of microglia and astrocyte were examined using immunofluorescence of the dorsal horn of the lumbar spinal cord. Results: Both an excess and a deficit of spinal 5-HT had no or a minimal effect on the intensity of mechanical allodynia during the early phase but prevented the attenuation of mechanical allodynia during the late phase, which was observed in animals not treated with i.t. 5-HT or 5,7-DHT. Animals with an excess or deficit of 5-HT showed stronger activation of microglia, but not astrocyte, during the early and late phases, than did normal animals. Conclusions Imbalance in the descending 5-HT pathway in the spinal cord could aggravate the mechanical allodynia and enhance the activation of microglia, suggesting that the spinal 5-HT pathway plays an essential role in maintaining the nociceptive processing in balance between facilitation and inhibition in inflammatory pain caused by carrageenan inflammation.

Background/Aims: Immunocompromised patients with acute colonic diverticulitis are at high risk for complications and failure of non-surgical treatment. However, evidence on the comparative outcomes of immunocompromised and immunocompetent patients with diverticulitis is lacking. This systematic review and meta-analysis investigated the outcomes of medical treatment in immunocompromised and immunocompetent patients with diverticulitis. Methods: A comprehensive literature search was conducted in PubMed, Embase, and the Cochrane Library. Studies comparing the clinical outcomes of immunocompromised and immunocompetent patients with diverticulitis were included. Results: A total of 10 studies with 1,946,461 subjects were included in the quantitative synthesis. The risk of emergency surgery and postoperative mortality after emergency surgery was significantly higher in immunocompromised patients than in immunocompetent patients with diverticulitis (risk ratio [RR], 1.76; 95% confidence interval [CI], 1.31–2.38 and RR, 3.05; 95% CI, 1.70–5.45, respectively). Overall risk of complications associated with diverticulitis was non-significantly higher in immunocompromised than in immunocompetent patients (RR, 1.24; 95% CI, 0.95–1.63). Overall mortality irrespective of surgery was significantly higher in immunocompromised than in immunocompetent patients with diverticulitis (RR, 3.65; 95% CI, 1.73–7.69). By contrast, postoperative mortality after elective surgery was not significantly different between immunocompromised and immunocompetent patients with diverticulitis. In subgroup analysis, the risk of emergency surgery and recurrence was significantly higher in immunocompromised patients with complicated diverticulitis, whereas no significant difference was shown in mild disease. Conclusions Immunocompromised patients with diverticulitis should be given the best medical treatment with multidisciplinary approach because they had increased risks of surgery, postoperative morbidity, and mortality than immunocompetent patients.

Background/Aims: Some management strategies for acute colonic diverticulitis remain controversial in Korean real-world practice because their clinical features differ from those in the West. This study aimed to investigate the opinions of Korean physicians regarding the diagnosis and treatment of acute diverticulitis. Methods: A web-based survey was conducted among gastroenterologists specializing on treating lower gastrointestinal disorders. The questionnaires concerned overall management strategies for colonic diverticulitis, including diagnosis, treatment, and follow-up. Results: In total, 209 gastroenterologists responded to the survey. Less than one-fourth of the respondents (23.6%) answered that left-sided colonic diverticulitis is more likely to be complicated than right-sided colonic diverticulitis. Most respondents agreed that immunocompromised patients with diverticulitis have worse clinical outcomes than immunocompetent patients (71.3%). Computed tomography was the most preferred tool for diagnosing diverticulitis (93.9%). Approximately 89% of the respondents answered that they believed antibiotic treatment is necessary to treat acute uncomplicated diverticulitis. Most respondents (92.6%) agreed that emergency surgery is not required for diverticulitis with an abscess or microperforation without panperitonitis. Further, 94.7% of the respondents agreed that colon cancer screening is necessary in patients aged ≥ 50 years with diverticulitis after they have recovered from acute illness. Many respondents (71.4%) agreed that surgery for recurrent diverticulitis should be individualized. Conclusions Opinions regarding management strategies for colonic diverticulitis among Korean gastroenterologists were well agreed upon in some areas but did not agree well in other areas. Evidence-based guidelines that meet the practical needs of the Korean population should be developed.

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, is threatening global health worldwide with unprecedented contagiousness and severity. The best strategy to overcome COVID-19 is a vaccine. Various vaccines are currently being developed, and mass vaccination is in progress. Despite the very encouraging clinical trial results of these vaccines, there is insufficient information on the safety and efficacy of vaccines for inflammatory bowel disease (IBD) patients facing various issues. After reviewing current evidence and international guidelines, the Korean Association for the Study of Intestinal Diseases developed an expert consensus statement on COVID-19 vaccination issues for Korean IBD patients. This expert consensus statement emphasizes that severe acute respiratory syndrome coronavirus 2 vaccination be strongly recommended for IBD patients, and it is safe for IBD patients receiving immunomodulatory therapy.

Background: There is still unmet need in treating neuropathic pain and increasing awareness regarding the use of drug combinations to increase the effectiveness of treatment and reduce adverse effects in patients with neuropathic pain. Methods: This study was performed to determine the individual and combined effects of pregabalin, tianeptine, and clopidogrel in a rat model of neuropathic pain.The model was created by ligation of the L5-L6 spinal nerve in male Sprague–Dawley rats; mechanical allodynia was confirmed using von Frey filaments. Drugs were administered to the intrathecal space and mechanical allodynia was assessed; drug interactions were estimated by isobolographic or fixed-dose analyses. Results: Intrathecal pregabalin and tianeptine increased the mechanical withdrawal threshold in a dose-dependent manner, but intrathecal clopidogrel had little effect on the mechanical withdrawal threshold. An additive effect was noted between pregabalin and tianeptine, but not between pregabalin and clopidogrel. Conclusions These findings suggest that intrathecal coadministration of pregabalin and tianeptine effectively attenuated mechanical allodynia in the rat model of neuropathic pain. Thus, pregabalin plus tianeptine may be a valid option to enhance the efficacy of neuropathic pain treatment.

Purpose: We investigated the relationship between nocturia and mortality risk in the United States. Methods: Data were obtained from the National Health and Nutrition Examination Survey 2005–2010. Mortality data were obtained by linking the primary database to death certificate data found in the National Death Index with mortality follow-up up to December 31, 2015. Nocturia was defined based on symptoms reported in the symptom questionnaire. We categorized patients into 2 groups: mild nocturia (2–3 voidsight) and moderate-to severe nocturia (≥4 voidsight). Multiple Cox regression analyses were performed with adjustment for confounding variables at the baseline survey. Results: This study included 9,892 adults (4,758 men, 5,134 women). Nocturia occurred in 3,314 individuals (33.5%). Nocturia was significantly associated with all-cause mortality (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.10–1.39) and cardiovascular disease (CVD) mortality (HR, 1.55; 95% CI, 1.19–2.01). Moreover, the mortality risk increased with increasing nocturia severity. Further analysis with propensity score matching showed that nocturia was still significantly associated with all-cause mortality and CVD mortality. In subgroup analysis according to sex, nocturia was significantly associated with allcause mortality and CVD mortality in men. In women, moderate-to-severe nocturia was significantly associated with allcause mortality and CVD mortality. In subgroup analysis according to cardio-metabolic diseases, nocturia was associated with CVD mortality in patients with diabetes mellitus, hypertension, dyslipidemia, or CVD at baseline. In subgroup analysis of patients without diabetes mellitus, hypertension or CVD, nocturia was significantly associated with all-cause mortality. Conclusions Nocturia was significantly associated with mortality in men and women after adjusting for major confounding factors.

Purpose: DA-8010 is a novel muscarinic M3 receptor antagonist with significant selectivity for bladder over salivary gland in preclinical studies. We evaluated the clinical efficacy and safety of DA-8010 in overactive bladder (OAB) patients. Methods: This phase 2, randomized, double-blind, parallel-group, active reference- and placebo-controlled trial was conducted at 12 centers in South Korea (NCT03566134). Patients aged ≥19 years with OAB symptoms for ≥3 months were enrolled. Three hundred six patients (30.07% male) were randomized to 12 weeks of treatment among 4 groups; 2 experimental groups (DA-8010 2.5 or 5 mg), an active reference group (solifenacin 5 mg), and a placebo group. The change from the baseline of (=∆) 24-hour frequency at 12 weeks (primary endpoint), episodes of urgency, overall/urgency urinary incontinence, average/ maximum voided volume, nocturia, and patients’ subjective responses were analyzed. Results: In the full analysis set, the mean (standard deviation) [median] values for ∆ 24-hour frequency at 12 weeks were -1.01 (2.44) [-1.33] for placebo, -1.22 (2.05) [-1.33] for DA-8010 2.5 mg, and -1.67 (2.25) [-1.67] for DA-8010 5 mg; DA-8010 5 mg showed a significant decrease compared with placebo (P=0.0413). At 4 and 8 weeks, both DA-8010 2.5 mg (P=0.0391 at 4 weeks, P=0.0335 at 8 weeks) and DA-8010 5 mg (P=0.0001 at 4 weeks, P=0.0210 at 8 weeks) showed significant decrease in ∆ 24-hour frequency compared with placebo. DA-8010 5 mg achieved a significant decrease in ∆ number of urgency episodes, compared with placebo at 4 (P=0.0278) and 8 (P=0.0092) weeks. Adverse drug reactions (ADRs) were observed in 3.95% of placebo, 6.67% of DA-8010 2.5 mg, 18.42% of DA-8010 5 mg, and 17.33% of solifenacin 5 mg groups. No serious ADRs were observed in any patient. Conclusions Both DA-8010 2.5 mg and 5 mg showed therapeutic efficacy for OAB without serious ADRs. Therefore, both dosages of DA-8010 can advance to a subsequent large-scale phase 3 trial.