Emerging evidence suggests that intestinal dysbiosis contributes to systemic inflammation and cardiovascular diseases in dialysis patients. The purpose of this study was to evaluate the effects of probiotic supplementation on various inflammatory parameters in hemodialysis (HD) patients. Methods: Twenty-two patients with maintenance HD were enrolled. These patients were treated twice a day with 2.0 ×1010 colony forming units of a combination of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 3 months. The microbiome and fecal short-chain fatty acids (SCFAs) were analyzed. The percentages of CD14+ CD16+ proinflammatory monocytes and CD4+ CD25+ regulatory T-cells (Tregs) before and after probiotic supplementation were determined by flow cytometry. Serum levels of calprotectin and cytokine responses upon lipopolysaccharide (LPS) challenge were compared before and after probiotic supplementation. Results: Fecal SCFAs increased significantly after probiotic supplementation. Serum levels of calprotectin and interleukin 6 upon LPS stimulation significantly decreased. The anti-inflammatory effects of probiotics were associated with a significant increase in the percentage of CD4+ CD25+ Tregs (3.5% vs. 8.6%, p < 0.05) and also with a decrease of CD14+ CD16+ proinflammatory monocytes (310/ mm2 vs. 194/mm2 , p < 0.05). Conclusion: Probiotic supplementation reduced systemic inflammatory responses in HD patients and this effect was associated with an increase in Tregs and a decrease in proinflammatory monocytes. Hence, targeting intestinal dysbiosis might be a novel strategy for decreasing inflammation and cardiovascular risks in HD patients.

Background/Aims: While switching strategies of P2Y12 receptor inhibitors (RIs) have sometimes been used in acute myocardial infarction (AMI) patients, the current status of in-hospital P2Y12RI switching remains unknown. Methods: Overall, 8,476 AMI patients who underwent successful revascularization from Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) were divided according to in-hospital P2Y12RI strategies, and net adverse cardiovascular events (NACEs), defined as a composite of cardiac death, non-fatal myocardial infarction (MI), stroke, or thrombolysis in myocardial infarction (TIMI) major bleeding during hospitalization were compared. Results: Patients with in-hospital P2Y12RI switching accounted for 16.5%, of which 867 patients were switched from clopidogrel to potent P2Y12RI (C-P) and 532 patients from potent P2Y12RI to clopidogrel (P-C). There were no differences in NACEs among the unchanged clopidogrel, the unchanged potent P2Y12RIs, and the P2Y12RI switching groups. However, compared to the unchanged clopidogrel group, the C-P group had a higher incidence of non-fatal MI, and the P-C group had a higher incidence of TIMI major bleeding. In clinical events of in-hospital P2Y12RI switching, 90.9% of non-fatal MI occurred during pre-switching clopidogrel administration, 60.7% of TIMI major bleeding was related to pre-switching P2Y12RIs, and 71.4% of TIMI major bleeding was related to potent P2Y12RIs. Only 21.6% of the P2Y12RI switching group switched to P2Y12RIs after a loading dose (LD); however, there were no differences in clinical events between patients with and without LD. Conclusions In-hospital P2Y12RI switching occurred occasionally, but had relatively similar clinical outcomes compared to unchanged P2Y12RIs in Korean AMI patients. Non-fatal MI and bleeding appeared to be mainly related to pre-switching P2Y12RIs.

Osteoprotegerin is an important regulator of bone metabolism and vascular calcification. The association between serum osteoprotegerin level and chronic kidney disease (CKD) progression has not been elucidated. We investigated the prognostic value of serum osteoprotegerin levels in nondialysis CKD patients. Methods: We analyzed 2,082 patients enrolled in the Korean Cohort Study for Outcomes in Patients with CKD between 2011 and 2016. Patients were divided into quartiles by their serum osteoprotegerin levels. The primary outcome was the occurrence of ≥1 of the following: dialysis initiation, kidney transplantation, a two-fold increase in serum creatinine level from baseline, or a 50% decrease in the estimated glomerular filtration rate (eGFR). Cox proportional hazard regression models were used to investigate the prognostic value of the serum osteoprotegerin level to CKD progression. Results: The median follow-up period was 48.9 months, and 641 patients (30.8%) experienced the primary outcome. The hazard ratio of serum osteoprotegerin for renal progression in the full extended Cox proportional hazard model was 1.064 (95% confidence interval, 1.041–1.088). Subgroup analyses by age, presence of diabetes, and eGFR showed significant results consistent with the overall analysis results. Conclusion: Serum osteoprotegerin level is independently associated with renal prognosis and could have prognostic importance in CKD progression.

Purpose: The severity of a patient’s medical condition, changing pharmacodynamics and pharmacokinetics, and variability in medication highlight the importance of pharmacological intervention by intensive care unit (ICU) specialized pharmacists.
Methods: Retrospective observations of ICU interventions (omission, changes in medicine, side effects, changes in administration route and dosage, redundancy, and nutritional care) performed between April 2017 and March 2018, determined by an interdisciplinary team (including a specialized ICU pharmacist and a surgical intensivist) on their surgical ICU round, were analyzed. Medicinal prescriptions were screened weekly during the surgical ICU round, and interventions were made if any corrections were necessary. Two days later another team including a surgical intensivist, a pharmacist, and a nutritionist evaluated the patients’ nutritional status (performed weekly).
Results: In the 23-bed ICU, the average number of patients whose prescriptions were examined was 22.38 per surgical round. There were 382 interventions made over 1 year, which was 9.68 interventions per day. The interventions were for nutritional care (161 cases, 42.2%), followed by changes in administration route and dosage (94 cases, 24.6%), omission (59 cases, 15.5%), redundancy (40 cases, 10.4%), changes in medicine (15 cases, 3.9%), and side effects (13 cases, 3.4%).
Conclusion The conditions of patients admitted to ICU are typically unstable. Pharmacological interventions suggested by a specialized pharmacist may help control the changing medical condition of patients in ICU. A higher participation of pharmacists specialized in working in an interdisciplinary ICU team-based system could lead to safer treatments.

Purpose: The severity of a patient’s medical condition, changing pharmacodynamics and pharmacokinetics, and variability in medication highlight the importance of pharmacological intervention by intensive care unit (ICU) specialized pharmacists.
Methods: Retrospective observations of ICU interventions (omission, changes in medicine, side effects, changes in administration route and dosage, redundancy, and nutritional care) performed between April 2017 and March 2018, determined by an interdisciplinary team (including a specialized ICU pharmacist and a surgical intensivist) on their surgical ICU round, were analyzed. Medicinal prescriptions were screened weekly during the surgical ICU round, and interventions were made if any corrections were necessary. Two days later another team including a surgical intensivist, a pharmacist, and a nutritionist evaluated the patients’ nutritional status (performed weekly).
Results: In the 23-bed ICU, the average number of patients whose prescriptions were examined was 22.38 per surgical round. There were 382 interventions made over 1 year, which was 9.68 interventions per day. The interventions were for nutritional care (161 cases, 42.2%), followed by changes in administration route and dosage (94 cases, 24.6%), omission (59 cases, 15.5%), redundancy (40 cases, 10.4%), changes in medicine (15 cases, 3.9%), and side effects (13 cases, 3.4%).
Conclusion The conditions of patients admitted to ICU are typically unstable. Pharmacological interventions suggested by a specialized pharmacist may help control the changing medical condition of patients in ICU. A higher participation of pharmacists specialized in working in an interdisciplinary ICU team-based system could lead to safer treatments.

Background: A healthy microbiome helps maintain the gut barrier and mucosal immune tolerance. Previously, we demonstrated that acute kidney injury (AKI) provoked dysbiosis, gut inflammation, and increased permeability. Here, we investigated the renoprotective effects of the probiotic Bifidobacterium bifidum BGN4 and the underlying mechanisms thereof. Methods: C57BL/6 mice were subjected to bilateral renal ischemia-reperfusion injury (IRI) or sham operation. In the probiotic-treated group, BGN4 was administered by gavage once daily, starting 2 weeks before injury. Results: Administration of BGN4 significantly increased gut microbiome diversity and prevented expansion of the Enterobacteriaceae and Bacteroidetes that were the hallmarks of AKI-induced dysbiosis. Further, BGN4 administration also significantly reduced other IRI-induced changes in the colon microenvironment, including effects on permeability, apoptosis of colon epithelial cells, and neutrophil and proinflammatory macrophage infiltration. Mononuclear cells co-cultured with BGN4 expressed significantly increased proportions of CD103+/CD11c+ and CD4+ CD25+ Treg cells, suggesting a direct immunomodulatory effect. BGN4 induced Treg expansion in colon, mesenteric lymph nodes (MNL), and kidney. BGN4 also reduced CX3CR1intermediateLy6Chigh monocyte infiltration and interleukin (IL)-17A suppression in the small intestine, which may have attenuated AKI severity, kidney IL-6 messenger RNA expression, and AKI-induced liver injury. Conclusion Prior supplementation with BGN4 significantly attenuated the severity of IRI and secondary liver injury. This renoprotective effect was associated with increased Foxp3 and reduced IL-17A expression in the colon, MNL, and kidney, suggesting that BGN4-induced immunomodulation might contribute to its renoprotective effects. Probiotics may therefore be a promising strategy to reduce AKI severity and/or remote organ injury.

BACKGROUND AND OBJECTIVES: There is a paucity of data regarding the benefit of clopidogrel monotherapy after dual antiplatelet therapy (DAPT) in patients treated with drug-eluting stents (DES). This study compared outcome between clopidogrel versus aspirin as monotherapy after DES for acute myocardial infarction (MI).METHODS: From Korea Acute Myocardial Infarction Registry-National Institute of Health database, 1,819 patients treated with DES who were switched to monotherapy with clopidogrel (n=534) or aspirin (n=1,285) after uneventful 12-month DAPT were analyzed. The primary endpoint was net adverse clinical events (NACE), defined as a composite of death from any cause, MI, repeat percutaneous coronary intervention (PCI), stent thrombosis, ischemic stroke, or major bleeding during the period from 12 to 24 months.RESULTS: After adjustment using inverse probability of treatment weighting, patients who received clopidogrel, compared with those treated with aspirin, had a similar incidence of NACE (0.7% and 0.7%; hazard ratio, 1.06; 95% confidence interval, 0.31–3.60; p=0.923). The 2 groups had similar rates of death from any cause (0.1% in each group, p=0.789), MI (0.3% and 0.1%, respectively; p=0.226), repeat PCI (0.1% and 0.3%, respectively; p=0.548), stent thrombosis (0.1% and 0%, respectively; p=0.121), major bleeding (0.2% in each group, p=0.974), and major adverse cardiovascular and cerebrovascular events (0.5% in each group, p=0.924).CONCLUSIONS: Monotherapy with clopidogrel, compared to aspirin, after DAPT showed similar clinical outcomes in patients with acute MI treated with DES.
Aspirin ; Drug-Eluting Stents ; Hemorrhage ; Humans ; Incidence ; Korea ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; Stents ; Stroke ; Thrombosis

BACKGROUND AND OBJECTIVES: Although complete revascularization is known superior to incomplete revascularization in ST elevation myocardial infarction (STEMI) patients with multi-vessel coronary artery disease (MVCD), there are no definite instructions on the optimal timing of non-culprit lesions percutaneous coronary intervention (PCI). We compared 1-year clinical outcomes between 2 different complete multi-vessel revascularization strategies.METHODS: From the Korea Acute Myocardial Infarction Registry-National Institute of Health, 606 patients with STEMI and MVCD who underwent complete revascularization were enrolled from November 2011 to December 2015. The patients were assigned to multi-vessel single-staged PCI (SS PCI) group (n=254) or multi-vessel multi-staged PCI (MS PCI) group (n=352). Propensity score matched 1-year clinical outcomes were compared between the groups.RESULTS: At one year, MS PCI showed a significantly lower rate of all-cause mortality (hazard ratio [HR], 0.42; 95% confidential interval [CI], 0.19–0.92; p=0.030) compared with SS PCI. In subgroup analysis, all-cause mortality increased in SS PCI with cardiogenic shock (HR, 4.60; 95% CI, 1.54–13.77; p=0.006), age ≥65 years (HR, 4.00; 95% CI, 1.67–9.58, p=0.002), Killip class III/IV (HR, 7.32; 95% CI, 1.68–31.87; p=0.008), and creatinine clearance ≤60 mL/min (HR, 2.81; 95% CI, 1.10–7.18; p=0.031). After propensity score-matching, MS PCI showed a significantly lower risk of major adverse cardiovascular event than SS PCI.CONCLUSIONS: SS PCI was associated with worse clinical outcomes compared with MS PCI. MS PCI for non-infarct-related artery could be a better option for patients with STEMI and MVCD, especially high-risk patients.
Arteries ; Coronary Artery Disease ; Coronary Vessels ; Creatinine ; Humans ; Korea ; Mortality ; Myocardial Infarction ; Myocardial Revascularization ; Percutaneous Coronary Intervention ; Propensity Score ; Shock, Cardiogenic

BACKGROUND AND OBJECTIVES: There is a paucity of data regarding the benefit of clopidogrel monotherapy after dual antiplatelet therapy (DAPT) in patients treated with drug-eluting stents (DES). This study compared outcome between clopidogrel versus aspirin as monotherapy after DES for acute myocardial infarction (MI). METHODS: From Korea Acute Myocardial Infarction Registry-National Institute of Health database, 1,819 patients treated with DES who were switched to monotherapy with clopidogrel (n=534) or aspirin (n=1,285) after uneventful 12-month DAPT were analyzed. The primary endpoint was net adverse clinical events (NACE), defined as a composite of death from any cause, MI, repeat percutaneous coronary intervention (PCI), stent thrombosis, ischemic stroke, or major bleeding during the period from 12 to 24 months. RESULTS: After adjustment using inverse probability of treatment weighting, patients who received clopidogrel, compared with those treated with aspirin, had a similar incidence of NACE (0.7% and 0.7%; hazard ratio, 1.06; 95% confidence interval, 0.31–3.60; p=0.923). The 2 groups had similar rates of death from any cause (0.1% in each group, p=0.789), MI (0.3% and 0.1%, respectively; p=0.226), repeat PCI (0.1% and 0.3%, respectively; p=0.548), stent thrombosis (0.1% and 0%, respectively; p=0.121), major bleeding (0.2% in each group, p=0.974), and major adverse cardiovascular and cerebrovascular events (0.5% in each group, p=0.924). CONCLUSIONS Monotherapy with clopidogrel, compared to aspirin, after DAPT showed similar clinical outcomes in patients with acute MI treated with DES.

BACKGROUND AND OBJECTIVES: Although complete revascularization is known superior to incomplete revascularization in ST elevation myocardial infarction (STEMI) patients with multi-vessel coronary artery disease (MVCD), there are no definite instructions on the optimal timing of non-culprit lesions percutaneous coronary intervention (PCI). We compared 1-year clinical outcomes between 2 different complete multi-vessel revascularization strategies. METHODS: From the Korea Acute Myocardial Infarction Registry-National Institute of Health, 606 patients with STEMI and MVCD who underwent complete revascularization were enrolled from November 2011 to December 2015. The patients were assigned to multi-vessel single-staged PCI (SS PCI) group (n=254) or multi-vessel multi-staged PCI (MS PCI) group (n=352). Propensity score matched 1-year clinical outcomes were compared between the groups. RESULTS: At one year, MS PCI showed a significantly lower rate of all-cause mortality (hazard ratio [HR], 0.42; 95% confidential interval [CI], 0.19–0.92; p=0.030) compared with SS PCI. In subgroup analysis, all-cause mortality increased in SS PCI with cardiogenic shock (HR, 4.60; 95% CI, 1.54–13.77; p=0.006), age ≥65 years (HR, 4.00; 95% CI, 1.67–9.58, p=0.002), Killip class III/IV (HR, 7.32; 95% CI, 1.68–31.87; p=0.008), and creatinine clearance ≤60 mL/min (HR, 2.81; 95% CI, 1.10–7.18; p=0.031). After propensity score-matching, MS PCI showed a significantly lower risk of major adverse cardiovascular event than SS PCI. CONCLUSIONS SS PCI was associated with worse clinical outcomes compared with MS PCI. MS PCI for non-infarct-related artery could be a better option for patients with STEMI and MVCD, especially high-risk patients.