Activation of AMP-activated protein kinase inhibits ER stress and renal fibrosis.

It has been suggested that endoplasmic reticulum (ER) stress facilitates fibrotic remodeling. Therefore, modulation of ER stress may serve as one of the possible therapeutic approaches to renal fibrosis. We examined whether and how activation of AMP-activated protein kinase (AMPK) suppressed ER stress induced by chemical ER stress inducers [tunicamycin (TM) and thapsigargin (TG)] and also nonchemical inducers in tubular HK-2 cells. We further investigated the in vivo effects of AMPK on ER stress and renal fibrosis. Western blot analysis, immunofluorescence, small interfering (si)RNA experiments, and immunohistochemical staining were performed. Metformin (the best known clinical activator of AMPK) suppressed TM- or TG-induced ER stress, as shown by the inhibition of TM- or TG-induced upregulation of glucose-related protein (GRP)78 and phosphorylated eukaryotic initiation factor-2α through induction of heme oxygenase-1. Metformin inhibited TM- or TG-induced epithelial-mesenchymal transitions as well. Compound C (AMPK inhibitor) blocked the effect of metformin, and 5-aminoimidazole-4-carboxamide-1ß riboside (another AMPK activator) exerted the same effects as metformin. Transfection with siRNA targeting AMPK blocked the effect of metformin. Consistent with the results of cell culture experiments, metformin reduced renal cortical GRP78 expression and increased heme oxygenase-1 expression in a mouse model of ER stress-induced acute kidney injury by TM. Activation of AMPK also suppressed ER stress by transforming growth factor-ß, ANG II, aldosterone, and high glucose. Furthermore, metformin reduced GRP78 expression and renal fibrosis in a mouse model of unilateral ureteral obstruction. In conclusion, AMPK may serve as a promising therapeutic target through reducing ER stress and renal fibrosis.

Desmopressin improves platelet function in uremic patients taking antiplatelet agents who require emergent invasive procedures.

Uremia is associated with platelet dysfunction and can cause a bleeding tendency resulting in a major bleeding event after an invasive procedure or surgery that may be aggravated by antiplatelet agents. We prospectively investigated the potential of desmopressin to improve platelet dysfunction and to lower bleeding risk after emergent invasive procedures in uremic patients taking antiplatelet drugs. Twenty-three patients were enrolled with a mean age of 60.2 ± 11.7 years. Baseline blood urea nitrogen and creatinine were 70.5 ± 29.4 and 10.02 ± 4.52 mg/dL, respectively. Twenty-one patients took aspirin. All patients were infused with desmopressin before their invasive procedures, which were a central catheter insertion for emergent hemodialysis in 13 patients, percutaneous nephrostomy in 7 patients, and angiography through arm or leg vessels in 3 patients. After desmopressin infusion, both the hematocrit and platelet count were slightly decreased without changes in prothrombin time or activated partial thrombin time. Collagen/epinephrine-closure time was significantly shortened from 252.7 ± 40.7 to 144.6 ± 51.0 s (p < 0.001). There were minimal bleeding in 20 patients and mild bleeding in 3 patients. None experienced severe bleeding event or required additional intervention for bleeding control. There were no adverse events including the decrease of serum sodium concentration. In conclusion, a single infusion of desmopressin before invasive procedures in uremic patients on antiplatelet drugs appeared to be well tolerated and improved platelet dysfunction measured by collagen/epinephrine-closure time.

Adapting the International Dysphagia Diet Standardisation Initiative in East Asia: Feasibility study.

In dysphagia, food or water cannot be delivered safely through the oral cavity to the stomach; both are treated using texture-modified food and thickened fluid. Before, each country had its own diet modifications and texture measurement standards. In 2012, the International Dysphagia Diet Standardisation Initiative (IDDSI) was developed by several countries. Owing to cultural differences, it was necessary to determine whether the IDDSI could well be applied to clinicians and patients without difficulties in East Asia countries. To evaluate the IDDSI scale to find out the difficulties applying this scale in East Asia countries to educate the clinicians and patients. In May 2021, we enrolled physicians, nurses, nutritionists, and swallowing therapists involved in dysphagia treatment at a single center in Seoul. To evaluate the degree of understanding and difficulties of adapting IDDSI to clinicians in East Asia countries, we used the 17-item questionnaire with IDDSI sample foods and foods in Asian countries. In first 7 items, we compared IDDSI with the previously used scale based on the National Dysphagia Diet (NDD). In the next 10 questions, only the IDDSI levels were answered, and the absolute values of the answer-response differences were calculated. The IDDSI showed a significantly high intraclass correlation with the previously used NDD-based scale; the coefficient was higher for the nutritionists (0.988) and swallowing therapists (0.991). When evaluating whether the IDDSI could applied well in East Asia countries, the absolute values of the answer-response differences were lower than 0.5 in majority of levels, except for Level 4. Because the IDDSI framework might successfully be applied universally regardless of food culture, a worldwide standard for food rheology in dysphagia treatment might be possible.

Associations of Dietary Intake with Cardiovascular Disease, Blood Pressure, and Lipid Profile in the Korean Population: a Systematic Review and Meta-Analysis.

OBJECTIVE: Previous studies have separately reported the contributions of dietary factors to the risk of cardiovascular disease (CVD) and its markers, including blood pressure (BP) and lipid profile. This study systematically reviewed the current evidence on this issue in the Korean population. METHODS: Sixty-two studies from PubMed and Embase were included in this meta-analysis. We performed a random-effects model to analyze pooled odds ratios (ORs) and hazard ratios (HRs) and their 95% confidence intervals (CIs) for the consumption of 14 food items, three macro- and eight micro-nutrients, two dietary patterns, and three dietary indices. RESULTS: An analysis of pooled effect sizes from at least four individual study populations showed significant associations between coffee consumption and CVD (OR/HR, 0.71; 95% CI, 0.52-0.97) and elevated/high triglycerides (TG) (OR, 0.84; 95% CI, 0.78-0.90), sugar-sweetened beverage intake and elevated BP (OR/HR, 1.20; 95% CI, 1.09-1.33), and milk and dairy intake and elevated/high TG and low high-density lipoprotein cholesterol (HDL-C) (OR/HR, 0.82; 95% CI, 0.76-0.89 for both). Carbohydrate consumption and the low-carbohydrate-diet score were consistently related to an approximately 25% risk reduction for elevated TG and low HDL-C. A lower risk of elevated total cholesterol, but not low-density lipoprotein, was additionally observed for those with a higher low-carbohydrate-diet score. A healthy dietary pattern was only associated with a reduced risk of elevated TG in the Korea National Cancer Screenee Cohort (OR, 0.81; 95% CI, 0.67-0.98). CONCLUSION: This study showed that milk and dairy and coffee had protective effects for CVD and its risk factors, such as BP and lipid profile, while sugar-sweetened beverages exerted harmful effects.

Erratum: Associations of Dietary Intake with Cardiovascular Disease, Blood Pressure, and Lipid Profile in the Korean Population: a Systematic Review and Meta-Analysis.

[This corrects the article on p. 205 in vol. 9, PMID: 32821732.].

All-Cause Mortality and Cardiovascular Death between Statins and Omega-3 Supplementation: A Meta-Analysis and Network Meta-Analysis from 55 Randomized Controlled Trials.

Statins and omega-3 supplementation have shown potential benefits in preventing cardiovascular disease (CVD), but their comparative effects on mortality outcomes, in addition to primary and secondary prevention and mixed population, have not been investigated. This study aimed to examine the effect of statins and omega-3 supplementation and indirectly compare the effects of statin use and omega-3 fatty acids on all-cause mortality and CVD death. We included randomized controlled trials (RCTs) from meta-analyses published until December 2019. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated to indirectly compare the effect of statin use versus omega-3 supplementation in a frequentist network meta-analysis. In total, 55 RCTs were included in the final analysis. Compared with placebo, statins were significantly associated with a decreased the risk of all-cause mortality (RR = 0.90, 95% CI = 0.86-0.94) and CVD death (RR = 0.86, 95% CI = 0.80-0.92), while omega-3 supplementation showed a borderline effect on all-cause mortality (RR = 0.97, 95% CI = 0.94-1.01) but were significantly associated with a reduced risk of CVD death (RR = 0.92, 95% CI = 0.87-0.98) in the meta-analysis. The network meta-analysis found that all-cause mortality was significantly different between statin use and omega-3 supplementation for overall population (RR = 0.91, 95% CI = 0.85-0.98), but borderline for primary prevention and mixed population and nonsignificant for secondary prevention. Furthermore, there were borderline differences between statin use and omega-3 supplementation in CVD death in the total population (RR = 0.92, 95% CI = 0.82-1.04) and primary prevention (RR = 0.85, 95% CI = 0.68-1.05), but nonsignificant differences in secondary prevention (RR = 0.97, 95% CI = 0.66-1.43) and mixed population (RR = 0.92, 95% CI = 0.75-1.14). To summarize, statin use might be associated with a lower risk of all-cause mortality than omega-3 supplementation. Future direct comparisons between statin use and omega-3 supplementation are required to confirm the findings.

Relationship between Nutrition Intake and 28-Day Mortality Using Modified NUTRIC Score in Patients with Sepsis.

In critically ill patients, malnutrition is known to increase morbidity and mortality. We investigated the relationship between nutritional support and 28-day mortality using the modified NUTrition RIsk in the Critically ill (NUTRIC) score in patients with sepsis. This retrospective cohort study included patients with sepsis admitted to the medical intensive care unit (ICU) between January 2011 and June 2017. Nutritional support for energy and protein intakes at day 7 of ICU admission were categorized into <20, 20 to <25, and ≥25 kcal/kg and <1.0, 1.0 to <1.2, and ≥1.2 g/kg, respectively. NUTRIC scores ≥4 were considered to indicate high nutritional risk. Among patients with low nutritional risk, higher intakes of energy (≥25 kcal/kg) and protein (≥1.2 g/kg) were not significantly associated with lower 28-day mortality. In patients with high nutritional risk, higher energy intakes of ≥25 kcal/kg were significantly associated with lower 28-day mortality compared to intakes of <20 kcal/kg (adjusted hazard ratio (aHR): 0.569, 95% confidence interval (CI): 0.339-0.962, p = 0.035). Higher protein intakes of ≥1.2 g/kg were also significantly associated with lower 28-day mortality compared to intakes of <1.0 g/kg (aHR: 0.502, 95% CI: 0.280-0.900, p = 0.021). Appropriate energy (≥25 kcal/kg) and protein (≥1.2 g/kg) intakes during the first week may improve outcomes in patients with sepsis having high nutritional risk.

Comparison of Accuracy of NUTRIC and Modified NUTRIC Scores in Predicting 28-Day Mortality in Patients with Sepsis: A Single Center Retrospective Study.

The NUTRIC (Nutrition Risk in the Critically Ill) and modified NUTRIC scores are nutrition risk assessment tools specifically for intensive care unit (ICU) patients. A modified NUTRIC score is composed of all variables except for IL-6 level in the NUTRIC score. Their use in qualifying critically ill patients at nutritional risk has been extensively evaluated, although not in studies of patients with sepsis, when interleukin 6 levels, which are not included in the modified NUTRIC score, may be elevated. The present study was a retrospective comparison of the accuracy of the NUTRIC and modified NUTRIC scores in predicting 28-day mortality of 482 adult patients with sepsis who were admitted to the medical ICU of a tertiary referral hospital in South Korea between January 2011 and June 2017 and who had ICU stays longer than 24 h. The NUTRIC and modified NUTRIC scores were calculated using data from the patients' electronic medical records relating to the first 24 h of admission to the ICU. The area under the curve of the NUTRIC Score for predicting 28-day mortality was 0.762 (95% confidence interval (CI): 0.718⁻0.806) and of the modified NUTRIC Score 0.757 (95% CI: 0.713⁻0.801). There was no significant difference between the two scores (p = 0.45). The modified NUTRIC score was a good nutritional risk assessment tool for critically ill septic patients.

A Case of Peritoneal Tuberculosis Developed after Infliximab Therapy for Refractory RA.

Recently, interferon gamma releasing assay has been recommended to compensate the tuberculin skin test (TST) for screening for latent tuberculosis infection (LTBI). Although it improved the detection of LTBI before treatment with tumor necrosis factor blocker, its application to immune suppressed patients is limited. We report a case of peritoneal tuberculosis (TB) developed in a patient who tested positive for TST and QuantiFERON-TB Gold (QFT-G) before infliximab therapy, to emphasize the importance of monitoring during treatment. A 52-year-old woman presented with abdominal distension. She had been diagnosed with seropositive rheumatoid arthritis six years ago. She had started taking infliximab six months ago. All screening tests for TB were performed and the results of all were negative. At admission, the results of repeated TST and QFT-G tests were positive. Histopathological examination confirmed peritoneal TB. The patient started anti-TB therapy and the symptoms were relieved.