1.Cortical Bone Derived Stem Cells for Cardiac Wound Healing
Sadia MOHSIN ; Steven R HOUSER
Korean Circulation Journal 2019;49(4):314-325
Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. Adoptive transfer of multiple stem cell types into failing human hearts has demonstrated safety however the beneficial effects in patients with cardiovascular disorders have been modest. Modest improvement in patients with cardiac complications warrants identification of a novel stem cell population that possesses effective reparative properties and improves cardiac function after injury. Recently we have shown in a mouse model and a porcine pre-clinical animal model, that cortical bone derived stem cells (CBSCs) enhance cardiac function after MI and/or ischemia-reperfusion injury. These beneficial effects of allogeneic cell delivery appear to be mediated by paracrine mechanisms rather than by transdifferentiation of injected cells into vessels and/or immature myocytes. This review will discuss role of CBSCs in cardiac wound healing. After having modest beneficial improvement in most of the clinical trials, a critical need is to understand the interaction of the transplanted stem cells with the ischemic cardiac environment. Transplanted stem cells are exposed to pro-inflammatory factors and activated immune cells and fibroblasts, but their interactions remain unknown. We have shown that CBSCs modulate different processes including modulation of the immune response, angiogenesis, and restriction of infarct sizes after cardiac injury. This review will provide information on unique protective signature of CBSCs in rodent/swine animal models for heart repair that should provide basis for developing novel therapies for treating heart failure patients.
Adoptive Transfer
;
Animals
;
Cell- and Tissue-Based Therapy
;
Fibroblasts
;
Fibrosis
;
Heart
;
Heart Failure
;
Humans
;
Immunomodulation
;
Mice
;
Models, Animal
;
Mortality
;
Muscle Cells
;
Myocardial Infarction
;
Myocardial Ischemia
;
Reperfusion Injury
;
Stem Cells
;
Wound Healing
;
Wounds and Injuries
2.Acute kidney injury in pediatric patients with rhabdomyolysis.
Young Shin LIM ; Heeyeon CHO ; Sang Taek LEE ; Yeonhee LEE
Korean Journal of Pediatrics 2018;61(3):95-100
PURPOSE: This study aimed to evaluate the clinical findings in pediatric rhabdomyolysis and the predictive factors for acute kidney injury (AKI) in Korean children. METHODS: Medical records of 39 Korean children, who were newly diagnosed with rhabdomyolysis from January 2008 to December 2015, were retrospectively analyzed. The diagnosis was made from the medical history, elevated serum creatinine kinase level >1,000 IU/L, and plasma myoglobin level >150 ng/mL. Patients with muscular dystrophy and myocardial infarction were excluded. RESULTS: The median patient age at diagnosis was 14.0 years (range, 3–18 years), and the male to female ratio was 2.5. The most common presenting symptom was myalgia (n=25, 64.1%), and 14 patients (35.9%) had rhabdomyolysis-induced AKI. Eighteen patients (46.2%) had underlying diseases, such as epilepsy and psychotic disorders. Ten of these patients showed rhabdomyolysis-induced AKI. The common causes of rhabdomyolysis were infection (n=12, 30.7%), exercise (n=9, 23.1%), and trauma (n=8, 20.5%). There was no difference in the distribution of etiology between AKI and non-AKI groups. Five patients in the AKI group showed complete recovery of renal function after stopping renal replacement therapy. The median length of hospitalization was 7.0 days, and no mortality was reported. Compared with the non-AKI group, the AKI group showed higher levels of peak creatinine kinase and myoglobin, without statistical significance. CONCLUSION: The clinical characteristics of pediatric rhabdomyolysis differ from those observed in adult patients. Children with underlying diseases are more vulnerable to rhabdomyolysis-induced AKI. AKI more likely develops in the presence of a high degree of albuminuria.
Acute Kidney Injury*
;
Adult
;
Albuminuria
;
Child
;
Creatinine
;
Diagnosis
;
Epilepsy
;
Female
;
Hospitalization
;
Humans
;
Male
;
Medical Records
;
Mortality
;
Muscular Dystrophies
;
Myalgia
;
Myocardial Infarction
;
Myoglobin
;
Phosphotransferases
;
Plasma
;
Psychotic Disorders
;
Renal Replacement Therapy
;
Retrospective Studies
;
Rhabdomyolysis*
3.Combining fragmented QRS and TIMI score for predicting in-hospital short-term prognosis after acute myocardial infarction.
Qin-Hui SHENG ; Chih Chi HSU ; Jian-Ping LI ; Tao HONG ; Yong HUO
Journal of Zhejiang University. Science. B 2018;19(5):349-353
Acute myocardial infarction (AMI) has a high mortality rate and poor prognosis for patients. The primary causes of death are arrhythmia and heart failure. For patients admitted because of myocardial infarction, various risk evaluations are initiated to foresee possible complications. The thrombolysis in myocardial infarction (TIMI) risk score, which can be used to predict the prognosis and the need for revascularisation, is the most convenient and commonly used system, but is inadequate for AMI patients on admittance. Fragmented QRS (fQRS) has been shown to be a valuable electrocardiographic (ECG) index for predicting the prognosis of patients with coronary heart disease. Also, fQRS is considered to predict an increased likelihood of a poor outcome and mortality in patients with coronary artery disease (CAD), even for some successfully revascularized AMI patients. So what would happen if fQRS and the TIMI risk score were combined? This study focused on the investigation of the short-term prognostic value of fQRS combined with the TIMI risk score for patients with AMI.
Aged
;
Electrocardiography
;
Female
;
Humans
;
Male
;
Myocardial Infarction
;
mortality
;
therapy
;
Percutaneous Coronary Intervention
;
Prognosis
;
Risk Assessment
;
Thrombolytic Therapy
;
methods
4.From Bench to Market: Preparing Human Pluripotent Stem Cells Derived Cardiomyocytes for Various Applications.
Sung Hwan MOON ; Daekyeong BAE ; Taek Hee JUNG ; Eun Bin CHUNG ; Young Hoon JEONG ; Soon Jung PARK ; Hyung Min CHUNG
International Journal of Stem Cells 2017;10(1):1-11
Human cardiomyocytes (CMs) cease to proliferate and remain terminally differentiated thereafter, when humans reach the mid-20s. Thus, any damages sustained by myocardium tissue are irreversible, and they require medical interventions to regain functionality. To date, new surgical procedures and drugs have been developed, albeit with limited success, to treat various heart diseases including myocardial infarction. Hence, there is a pressing need to develop more effective treatment methods to address the increasing mortality rate of the heart diseases. Functional CMs are not only an important in vitro cellular tool to model various types of heart diseases for drug development, but they are also a promising therapeutic agent for cell therapy. However, the limited proliferative capacity entails difficulties in acquiring functional CMs in the scale that is required for pathological studies and cell therapy development. Stem cells, human pluripotent stem cells (hPSCs) in particular, have been considered as an unlimited cellular source for providing functional CMs for various applications. Notable progress has already been made: the first clinical trials of hPSCs derived CMs (hPSC-CMs) for treating myocardial infarction was approved in 2015, and their potential use in disease modeling and drug discovery is being fully explored. This concise review gives an account of current development of differentiation, purification and maturation techniques for hPSC-CMs, and their application in cell therapy development and pharmaceutical industries will be discussed with the latest experimental evidence.
Cell- and Tissue-Based Therapy
;
Drug Discovery
;
Drug Industry
;
Heart Diseases
;
Humans*
;
In Vitro Techniques
;
Mortality
;
Myocardial Infarction
;
Myocardium
;
Myocytes, Cardiac*
;
Pluripotent Stem Cells*
;
Stem Cells
5.Shenfu Injection () inhibits inflammation in patients with acute myocardial infarction complicated by cardiac shock.
Yan-Yan JIN ; Hai GAO ; Xin-Yong ZHANG ; Hui AI ; Xiao-Lin ZHU ; Jing WANG
Chinese journal of integrative medicine 2017;23(3):170-175
OBJECTIVESTo investigate the effect of Shenfu Injection (, SFI) on inflammatory factors in patients with acute myocardial infarction complicated by cardiogenic shock (CS) treated with and intra-aortic balloon pump (IABP).
METHODSThis study enrolled 60 patients with ST-segment elevation myocardial infarction (STEMI) complicated by CS. Patients underwent IABP and emergency percutaneous coronary intervention (PCI) were randomly divided into two groups by random number table with 30 cases in each group, one given Sfitreatment (100 mL/24 h), one not. The two groups were then compared in a clinical setting for left ventricular function, biochemical indicators and Inflammatory factors, including C-reactive proteins (CRP), interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α). Major adverse cardiac and cerebrovascular events (MACCE) events were compared between patients of the two groups both in-hospital and in follow-ups.
RESULTSThe IABP support treatment times of patients in the IABP+Sfigroup were signifificantly shorter than the IABP group (52.87±28.84 vs. 87.45±87.31, P=0.047). In the patients of the IABP+Sfigroup, the CRP peak appeared in 24 h after PCI operation. The CRP peak in the patients of the IABP+Sfigroup was signifificantly lower than that in the IABP group (31.27±3.93 vs. 34.62±3.47, P=0.001). The increases in range of TNF-α in the patients of the IABP+Sfigroup were signifificantly lower than those of the IABP group (182.29±22.79 vs. 195.54±12.02, P=0.007). The increases in range of IL-1 in the patients of the IABP+Sfigroup were signifificantly lower than those of the IABP group (214.98±29.22 vs. 228.60±7.03, P=0.019). The amplitude elevated TNF-α 72 h after admission was an independent risk factor of in-hospital MACCE events (OR 0.973, 95% CI 0.890-0.987, P=0.014) in patients with STEMI and CS.
CONCLUSIONPatients with STEMI complicated by CS treated by IABP and Sfihad a reduced inflammatory reaction, a reduced dependence of CS on IABP and shortened the course of disease.
Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Hospital Mortality ; Humans ; Inflammation ; blood ; complications ; drug therapy ; Inflammation Mediators ; metabolism ; Injections ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Myocardial Infarction ; blood ; complications ; drug therapy ; mortality ; Shock, Cardiogenic ; complications ; drug therapy ; Treatment Outcome
6.Percutaneous Coronary Intervention Is More Beneficial Than Optimal Medical Therapy in Elderly Patients with Angina Pectoris.
Hoyoun WON ; Ae Young HER ; Byeong Keuk KIM ; Yong Hoon KIM ; Dong Ho SHIN ; Jung Sun KIM ; Young Guk KO ; Donghoon CHOI ; Hyuck Moon KWON ; Yangsoo JANG ; Myeong Ki HONG
Yonsei Medical Journal 2016;57(2):382-387
PURPOSE: Data comparing the clinical benefits of medical treatment with those of percutaneous coronary intervention (PCI) in an elderly population with angina pectoris are limited. Therefore, we evaluated the efficacy of elective PCI versus optimal medical treatment (OMT) in elderly patients (between 75 and 84 years old) with angina pectoris. MATERIALS AND METHODS: One hundred seventy-seven patients with significant coronary artery stenosis were randomly assigned to either the PCI group (n=90) or the OMT group (n=87). The primary outcome was a composite of major adverse events in the 1-year follow-up period that included cardiovascular death, non-fatal myocardial infarction, coronary revascularization, and stroke. RESULTS: Major adverse events occurred in 5 patients (5.6%) of the PCI group and in 17 patents (19.5%) of the OMT group (p=0.015). There were no significant differences between the PCI group and the OMT group in cardiac death [hazard ratio (HR) for the PCI group 0.454; 95% confidence interval (CI) 0.041-5.019, p=0.520], myocardial infarction (HR 0.399; 95% CI 0.039-4.050, p=0.437), or stroke (HR 0.919; 95% CI 0.057-14.709, p=0.952). However, the PCI group showed a significant preventive effect of the composite of major adverse events (HR 0.288; 95% CI 0.106-0.785, p=0.015) and against the need for coronary revascularization (HR 0.157; 95% CI 0.035-0.703, p=0.016). CONCLUSION: Elective PCI reduced major adverse events and was found to be an effective treatment modality in elderly patients with angina pectoris and significant coronary artery stenosis, compared to OMT.
Aged
;
Aged, 80 and over
;
Angina Pectoris/mortality/*therapy
;
Coronary Stenosis/therapy
;
Female
;
Humans
;
Male
;
Myocardial Infarction/prevention & control/*therapy
;
*Percutaneous Coronary Intervention
;
Proportional Hazards Models
;
Prospective Studies
;
Republic of Korea
;
Stroke/epidemiology
;
Treatment Outcome
7.Angiotensin II type 1 receptor blockers as a first choice in patients with acute myocardial infarction.
Jang Hoon LEE ; Myung Hwan BAE ; Dong Heon YANG ; Hun Sik PARK ; Yongkeun CHO ; Won Kee LEE ; Myung Ho JEONG ; Young Jo KIM ; Myeong Chan CHO ; Chong Jin KIM ; Shung Chull CHAE
The Korean Journal of Internal Medicine 2016;31(2):267-276
BACKGROUND/AIMS: Angiotensin II type 1 receptor blockers (ARBs) have not been adequately evaluated in patients without left ventricular (LV) dysfunction or heart failure after acute myocardial infarction (AMI). METHODS: Between November 2005 and January 2008, 6,781 patients who were not receiving angiotensin-converting enzyme inhibitors (ACEIs) or ARBs were selected from the Korean AMI Registry. The primary endpoints were 12-month major adverse cardiac events (MACEs) including death and recurrent AMI. RESULTS: Seventy percent of the patients were Killip class 1 and had a LV ejection fraction > or = 40%. The prescription rate of ARBs was 12.2%. For each patient, a propensity score, indicating the likelihood of using ARBs during hospitalization or at discharge, was calculated using a non-parsimonious multivariable logistic regression model, and was used to match the patients 1:4, yielding 715 ARB users versus 2,860 ACEI users. The effect of ARBs on in-hospital mortality and 12-month MACE occurrence was assessed using matched logistic and Cox regression models. Compared with ACEIs, ARBs significantly reduced in-hospital mortality(1.3% vs. 3.3%; hazard ratio [HR], 0.379; 95% confidence interval [CI], 0.190 to0.756; p = 0.006) and 12-month MACE occurrence (4.6% vs. 6.9%; HR, 0.661; 95% CI, 0.457 to 0.956; p = 0.028). However, the benefit of ARBs on 12-month mortality compared with ACEIs was marginal (4.3% vs. 6.2%; HR, 0.684; 95% CI, 0.467 to 1.002; p = 0.051). CONCLUSIONS: Our results suggest that ARBs are not inferior to, and may actually be better than ACEIs in Korean patients with AMI.
Angiotensin II Type 1 Receptor Blockers/adverse effects/*therapeutic use
;
Angiotensin-Converting Enzyme Inhibitors/adverse effects/*therapeutic use
;
Chi-Square Distribution
;
Hospital Mortality
;
Humans
;
Kaplan-Meier Estimate
;
Logistic Models
;
Multivariate Analysis
;
Myocardial Infarction/diagnosis/*drug therapy/mortality/physiopathology
;
Proportional Hazards Models
;
Prospective Studies
;
Recurrence
;
Registries
;
Republic of Korea
;
Risk Factors
;
Secondary Prevention/*methods
;
Stroke Volume
;
Time Factors
;
Treatment Outcome
;
Ventricular Function, Left
8.Temporal trends and in-hospital outcomes of primary percutaneous coronary intervention in nonagenarians with ST-segment elevation myocardial infarction.
Joon Young KIM ; Myung Ho JEONG ; Yong Woo CHOI ; Yong Keun AHN ; Shung Chull CHAE ; Seung Ho HUR ; Taek Jong HONG ; Young Jo KIM ; In Whan SEONG ; In Ho CHAE ; Myeong Chan CHO ; Jung Han YOON ; Ki Bae SEUNG
The Korean Journal of Internal Medicine 2015;30(6):821-828
BACKGROUND/AIMS: Data regarding the outcomes of primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) in nonagenarians are very limited. The aim of the present study was to evaluate the temporal trends and in-hospital outcomes of primary PCI in nonagenarian STEMI patients. METHODS: We retrospectively reviewed data from the Korea Acute Myocardial Infarction Registry (KAMIR) from November 2005 to January 2008, and from the Korea Working Group on Myocardial Infarction (KorMI) from February 2008 to May 2010. RESULTS: During this period, the proportion of nonagenarians among STEMI patients more than doubled (0.59% in KAMIR vs. 1.35% in KorMI), and the rate of use of primary PCI also increased (from 62.5% in KAMIR to 81.0% in KorMI). We identified 84 eligible study patients for which the overall in-hospital mortality rate was 21.4% (25.0% in KAMIR vs. 20.3% in KorMI, p = 0.919). Multivariate analysis identified two independent predictors of in-hospital mortality, namely a final Thrombolysis in Myocardial Infarction (TIMI) flow < 3 (odds ratio [OR], 13.7; 95% confidence interval [CI], 3.2 to 59.0; p < 0.001) and cardiogenic shock during hospitalization (OR, 6.7; 95% CI, 1.5 to 30.3; p = 0.013). CONCLUSIONS: The number of nonagenarian STEMI patients who have undergone primary PCI has increased. Although a final TIMI flow < 3 and cardiogenic shock are independent predictors of in-hospital mortality, primary PCI can be performed with a high success rate and an acceptable in-hospital mortality rate.
Age Factors
;
Aged, 80 and over
;
Chi-Square Distribution
;
Female
;
Hospital Mortality/trends
;
Humans
;
Logistic Models
;
Male
;
Multivariate Analysis
;
Myocardial Infarction/diagnosis/mortality/*therapy
;
Odds Ratio
;
Percutaneous Coronary Intervention/adverse effects/mortality/*trends
;
Registries
;
Republic of Korea
;
Retrospective Studies
;
Risk Factors
;
Shock, Cardiogenic/etiology
;
Time Factors
;
Treatment Outcome
9.Treatment outcomes of neoadjuvant concurrent chemoradiotherapy followed by esophagectomy for patients with esophageal cancer.
Yong Hyub KIM ; Sang Yun SONG ; Hyun Jeong SHIM ; Woong Ki CHUNG ; Sung Ja AHN ; Mee Sun YOON ; Jae Uk JEONG ; Ju Young SONG ; Taek Keun NAM
Radiation Oncology Journal 2015;33(1):12-20
PURPOSE: To evaluate treatment outcomes and determine prognostic factors in patients with esophageal cancer treated with esophagectomy after neoadjuvant chemoradiotherapy (NCRT). MATERIALS AND METHODS: We retrospectively evaluated 39 patients with esophageal cancer who underwent concurrent chemoradiotherapy followed by esophagectomy between 2002 and 2012. Initial clinical stages of patients were stage IB in 1 patient (2.6%), stage II in 5 patients (12.9%), and stage III in 33 patients (84.6%). RESULTS: The median age of all the patients was 62 years, and the median follow-up period was 17 months. The 3-year overall survival (OS) rate was 33.6% in all the patients. The 3-year locoregional recurrence-free survival (LRFS) rate was 33.7%. In multivariate analysis with covariates of age, the Eastern Cooperative Oncology Group performance status, hypertension, diabetes mellitus, tumor length, clinical response, clinical stage, pathological response, pathological stage, lymphovascular invasion, surgical type, and radiotherapy to surgery interval, only pathological stage was an independent significant prognostic factor affecting both OS and LRFS. The complications in postoperative day 90 were pneumonia in 9 patients, anastomotic site leakage in 3 patients, and anastomotic site stricture in 2 patients. Postoperative 30-day mortality rate was 10.3% (4/39); the cause of death among these 4 patients was respiratory failure in 3 patients and myocardial infarction in one patient. CONCLUSION: Only pathological stage was an independent prognostic factor for both OS and LRFS in patients with esophageal cancer treated with esophagectomy after NCRT. We could confirm the significant role of NCRT in downstaging the initial tumor bulk and thus resulting in better survival of patients who gained earlier pathological stage after NCRT.
Cause of Death
;
Chemoradiotherapy*
;
Constriction, Pathologic
;
Diabetes Mellitus
;
Esophageal Neoplasms*
;
Esophagectomy*
;
Follow-Up Studies
;
Humans
;
Hypertension
;
Mortality
;
Multivariate Analysis
;
Myocardial Infarction
;
Neoadjuvant Therapy
;
Pneumonia
;
Radiotherapy
;
Respiratory Insufficiency
;
Retrospective Studies
10.The Effect of Admission at Weekends on Clinical Outcomes in Patients with Non-ST-segment Elevation Acute Coronary Syndrome and Its Contributing Factors.
Hyun Jin KIM ; Kwang Il KIM ; Young Seok CHO ; Jeehoon KANG ; Jin Joo PARK ; Il Young OH ; Chang Hwan YOON ; Jung Won SUH ; Tae Jin YOUN ; In Ho CHAE ; Dong Ju CHOI
Journal of Korean Medical Science 2015;30(4):414-425
We investigated the effects of weekend admission on adverse cardiac events in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Patients with NSTEACS treated with percutaneous coronary intervention (PCI) were divided into a "weekend group" and a "weekday group" according to the emergency room arrival time. The primary outcome was 30-day major adverse cardiac events (MACE) including cardiac death, recurrent myocardial infarction, repeat revascularization, and urgent PCI. Of 577 patients, 168 patients were allocated to the weekend and 409 patients to the weekday group. The incidence of 30-day MACE was significantly higher in the weekend group (Crude: 15.5% vs. 7.3%, P = 0.005; propensity score matched: 12.8% vs. 4.8%, P = 0.041). After adjustment for all the possible confounding factors, in Cox proportional hazard regression analysis, weekend admission was associated with a 2.1-fold increased hazard for MACE (HR, 2.13; 95% CI, 1.26-3.60, P = 0.005). These findings indicate that weekend admission of patients with NSTE-ACS is associated with an increase in 30-day adverse cardiac event.
Acute Coronary Syndrome/*complications/mortality/therapy
;
Adult
;
Aged
;
*Death
;
Female
;
Humans
;
Male
;
Middle Aged
;
Myocardial Infarction/*epidemiology
;
Patient Admission
;
Percutaneous Coronary Intervention/*statistics & numerical data
;
Propensity Score
;
Proportional Hazards Models
;
Time Factors
;
Treatment Outcome

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