Dipeptidyl peptidase (DPP)-4 inhibitors, or gliptins, are a class of oral hypoglycemic drugs that have been widely used as a second-line treatment for type 2 diabetes. Gliptins, which were introduced for clinical use a decade ago, have been shown to be beneficial against nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) in animals and humans. Cenicriviroc (CVC), a dual antagonist of C-C chemokine receptor type 2 and 5, is currently under investigation against NASH and fibrosis. It was previously discovered that evogliptin (EVO) reduces hepatic steatosis in diet-induced obese animals but the effectiveness of EVO on NASH remains unexplored. Here, we compared the effectiveness of EVO and CVC against NASH and fibrosis in mice fed a high-fat and high-fructose diet (HFHF). Biochemical and histological analyses showed that mice fed a HFHF for 20 weeks developed severe hepatic steatosis and inflammation with mild fibrosis. Administration of EVO (0.2% wt/wt) for the last 8 weeks of HFHF feeding significantly reduced hepatic triglyceride accumulation, inflammation, and fibrosis as well as restored insulin sensitivity, as evidenced by lowered plasma insulin levels and the improvement in insulin tolerance test curves. Treatment of mice with CVC (0.1% wt/wt) inhibited hepatic inflammation and fibrogenesis with similar efficacy to that of EVO, without affecting hepatic steatosis. CVC treatment also reduced plasma insulin concentrations, despite no improvement in insulin tolerance. In conclusion, EVO administration efficiently ameliorated the development of NASH and fibrosis in HFHF-fed mice, corroborating its therapeutic potential.
Animals ; Diet ; Dipeptidyl-Peptidase IV Inhibitors ; Fatty Liver ; Fibrosis ; Humans ; Hypoglycemic Agents ; Inflammation ; Insulin ; Insulin Resistance ; Mice ; Non-alcoholic Fatty Liver Disease ; Plasma ; Triglycerides

This study aims to establish the individual contributions of blood pressure variability (BPV) indexes, categorized into overall and linked variability, to mortality following intracerebral hemorrhage (ICH) by examining the risk factors. Methods: Patients with spontaneous ICH (n = 1,036) were identified with valid blood pressures (BP) from the first 24-h systolic BP records in the Medical Information Mart for Intensive Care IV version 2.2 database (MIMIC IV). Information on the baseline characteristics, including age, sex, initial Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores, ICH location, Charlson comorbidity index score, and presence of diabetes with or without complications, were collected. Three indexes of BPV—range, standard deviation (SD), and generalized BPV (GBPV)—were calculated using the first 24-h systolic BPs. An automated stepwise variable-selection procedure was used to develop the final logistic model for predicting in-hospital mortality. Results: Out of 1,036 patients, 802 (77.4%) survived and were discharged after spontaneous ICH. Factors associated with mortality included age; male sex; ICH in the brainstem, ventricle, or multiple locations; low GCS score (< 9); high NIHSS score (> 20); and diabetes with complications. Mean systolic BP, SD, and GBPV were also linked to mortality. Higher GBPV notably increased the risk of in-hospital death, with an odds ratio of 3.21 (95% confidence interval, 2.10 to 4.97) for every + 10 mmHg/h change in GBPV. Conclusions: This study underscores the additional impact of GBPV, herein linked to BPV, on mortality following ICH, providing further insights into the management of blood pressure in the early stages of ICH treatment.

This study aims to establish the individual contributions of blood pressure variability (BPV) indexes, categorized into overall and linked variability, to mortality following intracerebral hemorrhage (ICH) by examining the risk factors. Methods: Patients with spontaneous ICH (n = 1,036) were identified with valid blood pressures (BP) from the first 24-h systolic BP records in the Medical Information Mart for Intensive Care IV version 2.2 database (MIMIC IV). Information on the baseline characteristics, including age, sex, initial Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores, ICH location, Charlson comorbidity index score, and presence of diabetes with or without complications, were collected. Three indexes of BPV—range, standard deviation (SD), and generalized BPV (GBPV)—were calculated using the first 24-h systolic BPs. An automated stepwise variable-selection procedure was used to develop the final logistic model for predicting in-hospital mortality. Results: Out of 1,036 patients, 802 (77.4%) survived and were discharged after spontaneous ICH. Factors associated with mortality included age; male sex; ICH in the brainstem, ventricle, or multiple locations; low GCS score (< 9); high NIHSS score (> 20); and diabetes with complications. Mean systolic BP, SD, and GBPV were also linked to mortality. Higher GBPV notably increased the risk of in-hospital death, with an odds ratio of 3.21 (95% confidence interval, 2.10 to 4.97) for every + 10 mmHg/h change in GBPV. Conclusions: This study underscores the additional impact of GBPV, herein linked to BPV, on mortality following ICH, providing further insights into the management of blood pressure in the early stages of ICH treatment.

This study aims to establish the individual contributions of blood pressure variability (BPV) indexes, categorized into overall and linked variability, to mortality following intracerebral hemorrhage (ICH) by examining the risk factors. Methods: Patients with spontaneous ICH (n = 1,036) were identified with valid blood pressures (BP) from the first 24-h systolic BP records in the Medical Information Mart for Intensive Care IV version 2.2 database (MIMIC IV). Information on the baseline characteristics, including age, sex, initial Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores, ICH location, Charlson comorbidity index score, and presence of diabetes with or without complications, were collected. Three indexes of BPV—range, standard deviation (SD), and generalized BPV (GBPV)—were calculated using the first 24-h systolic BPs. An automated stepwise variable-selection procedure was used to develop the final logistic model for predicting in-hospital mortality. Results: Out of 1,036 patients, 802 (77.4%) survived and were discharged after spontaneous ICH. Factors associated with mortality included age; male sex; ICH in the brainstem, ventricle, or multiple locations; low GCS score (< 9); high NIHSS score (> 20); and diabetes with complications. Mean systolic BP, SD, and GBPV were also linked to mortality. Higher GBPV notably increased the risk of in-hospital death, with an odds ratio of 3.21 (95% confidence interval, 2.10 to 4.97) for every + 10 mmHg/h change in GBPV. Conclusions: This study underscores the additional impact of GBPV, herein linked to BPV, on mortality following ICH, providing further insights into the management of blood pressure in the early stages of ICH treatment.

This study aims to establish the individual contributions of blood pressure variability (BPV) indexes, categorized into overall and linked variability, to mortality following intracerebral hemorrhage (ICH) by examining the risk factors. Methods: Patients with spontaneous ICH (n = 1,036) were identified with valid blood pressures (BP) from the first 24-h systolic BP records in the Medical Information Mart for Intensive Care IV version 2.2 database (MIMIC IV). Information on the baseline characteristics, including age, sex, initial Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores, ICH location, Charlson comorbidity index score, and presence of diabetes with or without complications, were collected. Three indexes of BPV—range, standard deviation (SD), and generalized BPV (GBPV)—were calculated using the first 24-h systolic BPs. An automated stepwise variable-selection procedure was used to develop the final logistic model for predicting in-hospital mortality. Results: Out of 1,036 patients, 802 (77.4%) survived and were discharged after spontaneous ICH. Factors associated with mortality included age; male sex; ICH in the brainstem, ventricle, or multiple locations; low GCS score (< 9); high NIHSS score (> 20); and diabetes with complications. Mean systolic BP, SD, and GBPV were also linked to mortality. Higher GBPV notably increased the risk of in-hospital death, with an odds ratio of 3.21 (95% confidence interval, 2.10 to 4.97) for every + 10 mmHg/h change in GBPV. Conclusions: This study underscores the additional impact of GBPV, herein linked to BPV, on mortality following ICH, providing further insights into the management of blood pressure in the early stages of ICH treatment.

This study aims to establish the individual contributions of blood pressure variability (BPV) indexes, categorized into overall and linked variability, to mortality following intracerebral hemorrhage (ICH) by examining the risk factors. Methods: Patients with spontaneous ICH (n = 1,036) were identified with valid blood pressures (BP) from the first 24-h systolic BP records in the Medical Information Mart for Intensive Care IV version 2.2 database (MIMIC IV). Information on the baseline characteristics, including age, sex, initial Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores, ICH location, Charlson comorbidity index score, and presence of diabetes with or without complications, were collected. Three indexes of BPV—range, standard deviation (SD), and generalized BPV (GBPV)—were calculated using the first 24-h systolic BPs. An automated stepwise variable-selection procedure was used to develop the final logistic model for predicting in-hospital mortality. Results: Out of 1,036 patients, 802 (77.4%) survived and were discharged after spontaneous ICH. Factors associated with mortality included age; male sex; ICH in the brainstem, ventricle, or multiple locations; low GCS score (< 9); high NIHSS score (> 20); and diabetes with complications. Mean systolic BP, SD, and GBPV were also linked to mortality. Higher GBPV notably increased the risk of in-hospital death, with an odds ratio of 3.21 (95% confidence interval, 2.10 to 4.97) for every + 10 mmHg/h change in GBPV. Conclusions: This study underscores the additional impact of GBPV, herein linked to BPV, on mortality following ICH, providing further insights into the management of blood pressure in the early stages of ICH treatment.

Postoperative neurocognitive disorders (PoNCDs), such as postoperative delirium and cognitive dysfunction or decline can occur after surgery, especially in older patients. This significantly affects patient morbidity and surgical outcomes. Among various risk factors, recent studies have shown that preoperative frailty is associated with developing these conditions. Although the mechanisms underlying PoNCDs remain unclear, neuroinflammation appears to play an important role in their development. For the prevention and treatment of PoNCDs, medication modification, a balanced diet, and prehabilitation and rehabilitation programs have been suggested. The risk of developing PoNCDs is thought to be lower in ambulatory patients. However, owing to technological advancements, an increasing number of older and sicker patients are undergoing more complex surgeries and are often not closely monitored after discharge. Therefore, equal attention should be paid to all patient populations. This article presents an overview of PoNCDs and highlights issues of particular interest for ambulatory surgery.

BACKGROUND: The elimination of anesthetic agents is a decisive factor in the emergence from general anesthesia. In this pilot study, we hypothesized that hypercapnia would decrease the emergence time from propofol anesthesia by increasing cardiac output and cerebral blood flow. METHODS: A total of 32 patients were randomly divided into two groups based on the end-tidal carbon dioxide values: 30 mmHg (the hypocapnia group) and 50 mmHg (the hypercapnia group). Propofol and remifentanil were infused to maintain a bispectral index of 40–50. Remifentanil infusion was stopped 10 min before the discontinuation of propofol. After cessation of propofol infusion, ventilation settings in the hypocapnia group were maintained constant; a rebreathing tube was connected to the respiratory circuit in the hypercapnia group. The time to spontaneous respiration, eye opening (primary endpoint), mouth opening, and tracheal extubation was recorded and analyzed. RESULTS: Time to eye opening was 9.7 (1.3) min in the hypocapnia group and 9.0 (1.0) min in the hypercapnia group. The difference in the mean times to eye opening between groups was −0.7 min (95% CI, −4.0 to 2.7, P = 0.688). On multiple regression analysis, there was a significant difference in the mean time to eye opening between males and females. Females recovered about 3.6 min faster than males (95% CI, −6.1 to −1.1, P = 0.009). CONCLUSIONS: We could not detect a beneficial effect of hypercapnia on propofol emergence time. Irrespective of hypercapnia, females seemed to recover faster than males.
Airway Extubation ; Anesthesia* ; Anesthesia, General ; Anesthetics ; Carbon Dioxide ; Cardiac Output ; Cerebrovascular Circulation ; Clinical Study* ; Female ; Humans ; Hypercapnia* ; Hypocapnia ; Male ; Mouth ; Pilot Projects ; Propofol* ; Respiration ; Ventilation

PURPOSE: Although Roux-en-Y (R-Y) reconstruction after distal gastrectomy has several advantages, such as prevention of bile reflux into the remnant stomach, it is rarely used because of the technical difficulty. This prospective randomized clinical trial aimed to show the efficacy of a novel method of R-Y reconstruction involving the use of 2 circular staplers by comparing this novel method to Billroth-I (B-I) reconstruction. MATERIALS AND METHODS: A total of 118 patients were randomly allocated into the R-Y (59 patients) and B-I reconstruction (59 patients) groups. R-Y anastomosis was performed using two circular staplers and no hand sewing. The primary end-point of this clinical trial was the reflux of bile into the remnant stomach evaluated using endoscopic and histological findings at 6 months after surgery. RESULTS: No significant differences in clinicopathological findings were observed between the 2 groups. Although anastomosis time was significantly longer for the patients of the R-Y group (P<0.001), no difference was detected between the 2 groups in terms of the total surgery duration (P=0.112). Endoscopic findings showed a significant reduction of bile reflux in the remnant stomach in the R-Y group (P<0.001), and the histological findings showed that reflux gastritis was more significant in the B-I group than in the R-Y group (P=0.026). CONCLUSIONS: The results of this randomized controlled clinical trial showed that compared with B-I reconstruction, R-Y reconstruction using circular staplers is a safe and feasible procedure. This clinical trial study was registered at www.ClinicalTrials.gov (registration No. NCT01142271).
Bile ; Bile Reflux ; Gastrectomy* ; Gastric Stump ; Gastritis ; Hand ; Humans ; Methods ; Prospective Studies ; Stomach Neoplasms*

PURPOSE: In order to examine the significance of a sentinel lymph node for gastric cancer, we investigated single node metastases that were hypothesized to represent the sentinel lymph node. METHODS: Of 2, 265 primary gastric cancers patients we experienced from 1994 to 2003, 140 patients having gastric carcinoma with a single node metastasis were enrolled in this study. The factors we studied including age, gender, tumor size, location, cellular differentiation, stage, and the patients' survival rate. RESULTS: Single node metastases were found in 30.7% of T1, 35.0% of T2, 29.3% of T3 and 5.0% of T4 staged tumor. Metastatic lymph nodes were mainly located near the tumor in 122 of 140 patients (87.1%). Skip metastases, which were defined as metastases that were found at more distant locations, were found in 18 patients (12.7%), and they were mainly located around the left gastric artery, the common hepatic artery, the proper hepatic artery and the splenic artery. The frequency of skip metastases significantly increased when the tumor was located upper part of the stomach, the tumor size was more than 5 cm in diameter and depth of tumor invasion was deeper (P<0.05). We found more frequent skip metastases in lymph nodes for the diffuse type of tumor infiltration than the macronodular type (P<0.05). The patients' overall 5 year survival was 76.9%, and skip metastasis did not affect on the survival rate. CONCLUSION: Our study supports the understanding of the biology of sentinel nodes. During gastrectomy in gastric cancer patients, great attention should be paid to remove the sentinel nodes and D2 dissection should be done when skip metastasis is suspected.
Arteries ; Biology ; Gastrectomy ; Hepatic Artery ; Humans ; Lymph Nodes ; Neoplasm Metastasis* ; Splenic Artery ; Stomach ; Stomach Neoplasms ; Survival Rate