Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL-NT) is the most common subtype of Epstein-Barr virus-associated NK/T-cell lymphomas. ENKTCL-NT occurs infrequently in the gastrointestinal tract. In particular, reports of ENKTCL-on NT arising from the stomach are extremely rare. Several clusters of differentiation (CDs) have been useful in recognizing NK-cells, T-cells, and tumor cells of NK/T-cell lymphomas. Among them, the CD56 antigen is considered the most sensitive marker for ENKTCL-NT and is expressed in almost all cases of ENKTCL-NT. Thus, the development of CD56-negative ENKTCL-NT is highly atypical. This paper reports a case of a young Asian female who presented with gastric ulcer bleeding. The patient was histologically diagnosed with ENKTCL-NT. No tumor cells for CD56 were observed, whereas no monoclonality of the T-cell receptor gamma gene rearrangement was detected in the tumor cells. The patient was scheduled for systemic chemotherapy six times and achieved complete remission. Peripheral blood-hematopoietic stem cell transplantation was performed later.

Background: Benign esophageal strictures are treated endoscopically, often with balloon dilatation (BD) or bougie dilators. However, recurrent esophageal strictures have been reported after BD, and severe complications sometimes occur. The aim of this study was to compare the efficacy and complications of endoscopic incisional therapy (EIT) and BD for benign esophageal strictures. Methods: We retrospectively reviewed patients who underwent BD or EIT as primary treatment for benign esophageal strictures between July 2014 and June 2021. Technical success was defined as restoration of the lumen diameter with <30% residual stenosis. Clinical success was defined as no recurrence of dysphagia within 1 month after BD or EIT and an increase of 1 grade or more on the Functional Oral Intake Scale. Results: Thirty patients with benign esophageal stricture were enrolled. There were 16 patients in the BD group and 14 patients in the EIT group. No significant differences in technical and clinical success rates were found between the two groups. Furthermore, no significant differences in the re-stricture rate were observed between the groups. There was one complication in the EIT group and three complications in the BD group. Three patients who underwent BD had re-stricture and underwent EIT thereafter, and we regrouped patients who underwent EIT at least once. The clinical success rate was significantly higher in patients regrouped to the EIT group than in patients who underwent BD only. Conclusions EIT is not inferior to BD as the primary treatment for benign esophageal strictures, especially for recurrent cases.

Background/Aims: Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. Methods: Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. Results: Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. Conclusions The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

Duodenal varices are a serious complication of portal hypertension. Bleeding from duodenal varices is rare, but when bleeding does occur, it is massive and can be fatal. Unfortunately, the optimal therapeutic modality for duodenal variceal bleeding is unclear. This paper presents a patient with duodenal variceal bleeding that was managed successfully using percutaneous trans-splenic variceal obliteration (PTVO). A 56-year-old man with a history of alcoholic cirrhosis presented with a 6-day history of melena. Emergency esophagogastroduodenoscopy revealed a large, bluish mass with a nipple sign in the second portion of the duodenum. Coil embolization of the duodenal varix was performed via a trans-splenic approach (i.e., PTVO). The patient no longer complained of melena after treatment. The duodenal varix was no longer visible at the follow-up esophagogastroduodenoscopy performed three months after PTVO. The use of PTVO might be a viable option for the treatment of duodenal variceal bleeding.

Duodenal varices are a serious complication of portal hypertension. Bleeding from duodenal varices is rare, but when bleeding does occur, it is massive and can be fatal. Unfortunately, the optimal therapeutic modality for duodenal variceal bleeding is unclear. This paper presents a patient with duodenal variceal bleeding that was managed successfully using percutaneous trans-splenic variceal obliteration (PTVO). A 56-year-old man with a history of alcoholic cirrhosis presented with a 6-day history of melena. Emergency esophagogastroduodenoscopy revealed a large, bluish mass with a nipple sign in the second portion of the duodenum. Coil embolization of the duodenal varix was performed via a trans-splenic approach (i.e., PTVO). The patient no longer complained of melena after treatment. The duodenal varix was no longer visible at the follow-up esophagogastroduodenoscopy performed three months after PTVO. The use of PTVO might be a viable option for the treatment of duodenal variceal bleeding.

Background: β-blockers (BBs) are considered primary therapy in stable heart failure (HF) with reduced ejection fraction (HFrEF) without atrial fibrillation (AF); evidence-based benefits of BB on outcome have been documented. However, BBs have not been shown to improve mortality or reduce hospital admissions in HF patients with AF. This study assessed the relationship between BBs at discharge and relevant clinical outcomes in acute heart failure (AHF) patients with AF. Methods: From the Korean Acute Heart Failure Registry, 936 HFrEF and 639 HF patients with preserved ejection fraction (HFpEF) and AF were selected. Propensity score (PS) matching accounted for BB selection bias when assessing associations. Results: BB-untreated patients in the overall cohort of HFrEF and HFpEF had greater deteriorated clinical and laboratory characteristics. In the 670 PS-matched cohort of HFrEF patients, incidences of all clinical events at 60 days and 1 year were not different according to use of BBs. In the 470 PS-matched cohort of HFpEF, rehospitalization and composite outcome at 6 months and 1 year more frequently occurred in non-users of BBs. After adjusting for covariates in the multivariable Cox model of matched cohorts, BB was not associated with clinical outcomes at 60 days and 1 year in HFrEF with AF patients. In HFpEF patients with AF, BB use was associated with reduced 6-month (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20–0.74) and 1-year rehospitalization (HR, 0.53; 95% CI, 0.34–0.82). Conclusion In the HFrEF with AF PS-matched cohort, the use of BBs at discharge was not associated with clinical outcome. However, in HFpEF with AF, the use of BB was associated with reduced rehospitalization during the 6-month and 1-year follow up.