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.

Although the use of mesh reinforcement during large hiatal hernia repair may reduce the rate of recurrence, various mesh-related complications have been reported. A 65-year-old woman presented with dysphagia. The patient was diagnosed with a large hiatal hernia and treated with laparoscopic fundoplication and Collis gastroplasty with mesh repair. Six months after surgery, the patient presented with dysphagia and vomiting. Esophagogastroduodenoscopy showed migration of mesh material into the esophagogastric junction. We performed a proximal gastrectomy with mesh removal. The patient was discharged without any postoperative complications. Herein, we encountered a rare case requiring surgical treatment to resolve mesh-induced esophagogastric perforation after hiatal hernia repair. Meshassociated complications, such as erosion or migration, should be considered as they may be more common than previously reported. Additionally, these complications are currently underscored in clinical practice. Regarding mesh applications, symptoms of mesh-related complications, such as dysphagia, should be carefully monitored for early detection.

Objective: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Methods: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Results: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Conclusion Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Purpose: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. Methods: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. Results: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. Conclusion Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Purpose: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. Methods: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. Results: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. Conclusion Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

BACKGROUND: Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment. RESULTS: After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups. CONCLUSION The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.

Background: and Purpose: The importance of the specialized management of neurocritical patients is being increasingly recognized. We evaluated the impact of neurointensivist comanagement on the clinical outcomes (particularly the mortality rate) of neurocritical patients admitted to a semiclosed neurocritical-care unit (NCU). Methods: We retrospectively included neurocritical patients admitted to the NCU between March 2015 and February 2018. We analyzed the clinical data and compared the outcomes between patients admitted before and after the initiation of neurointensivist co-management in March 2016. Results: There were 1,785 patients admitted to the NCU during the study period. Patients younger than 18 years (n=28) or discharged within 48 hours (n=200) were excluded. The 1,557 remaining patients comprised 590 and 967 who were admitted to the NCU before and after the initiation of co-management, respectively. Patients admitted under neurointensivist co-management were older and had higher Acute Physiologic Assessment and Chronic Health Evaluation II scores. The 30-day mortality rate was significantly lower after neurointensivist co-management (p=0.042). A multivariate logistic regression analysis demonstrated that neurointensivist co-management significantly reduced mortality rates in the NCU and in the hospital overall [odds ratio=0.590 (p=0.002) and 0.585 (p=0.001), respectively]. Conclusions Despite the higher severity of the condition during neurointensivist co-management, co-management significantly improved clinical outcomes (including the mortality rate) in neurocritical patients.

PURPOSE: Rectovaginal fistula can result from various causes and diverse surgical procedures have developed as a result. We investigated the outcomes of surgical treatments for rectovaginal fistula according to causes and procedures. METHODS: Between 1998 and 2016, 92 patients underwent 128 operations for rectovaginal fistula. Prospectively collected data were recorded, and a retrospective review was conducted. RESULTS: The median age was 49 years, and low fistula occurred in 58 patients (63.0%). The most common cause was radiation therapy, followed by pelvic operation, birth injury, perineal operation, cancer invasion, and trauma. The most common procedure during the first operation was diverting ostomy alone, followed by transanal rectal advancement flap, sphincteroplasty with perineoplasty, bowel resection, fistulectomy with seton placement, and Martius flap. Thirty-one patients (33.7%) experienced successful closure after the first operation. Repeated operations were performed in 16 patients (17.4%), including gracilis muscle transpositions, stem cell injections, and Martius flaps. The overall success rate was 42.4% (n = 39). Radiation therapy and pelvic operation as cause of fistula were significantly poor prognostic factors (P = 0.010, P = 0.045) and Crohn disease had a tendency for poor prognostic factors (P = 0.058). CONCLUSION: Radiation therapy and pelvic operation for cancer were more common causes than birth injury, and these causes of rectovaginal fistula were the most important prognostic factors. An individualized approach and repeated surgeries with complex or newly developed procedures, even among high-risk causes of fistula, may be necessary to achieve successful closure.
Birth Injuries ; Crohn Disease ; Fistula ; Humans ; Ostomy ; Prospective Studies ; Rectovaginal Fistula ; Rectum ; Retrospective Studies ; Stem Cells ; Tertiary Care Centers ; Vagina