Ming-Jer Hsieh

Augmentation of diabetic wound healing and enhancement of collagen content using nanofibrous glucophage-loaded collagen/PLGA scaffold membranes

This work developed nanofibrous drug-loaded collagen/poly-D-L-lactide-glycolide (PLGA) scaffold membranes that provided the sustained release of glucophage for the wounds associated with diabetes. PLGA, glucophage, and collagen were firstly dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol and were spun into nanofibrous membranes by electrospinning. High-performance liquid chromatography assay was used to characterize the in vivo and in vitro release rates of the pharmaceuticals from the membranes. High concentrations of glucophage were released for over three weeks from the nanofibrous membranes. The nanofibrous glucophage-loaded collagen/PLGA membranes were more hydrophilic than collagen/PLGA membranes and exhibited a greater water-containing capacity. The glucophage-loaded collagen/PLGA membranes markedly promoted the healing of diabetic wounds. Moreover, the collagen content of diabetic rats using drug-eluting membranes was higher than that of the control rats, because of the down-regulation of matrix metalloproteinase 9. The experimental results herein suggest that the nanofibrous glucophage-loaded collagen/PLGA membranes had effect for increasing collagen content in treating diabetic wounds and very effective promoters of the healing of such wounds in the early stages.

Enhancement of Diabetic Wound Repair Using Biodegradable Nanofibrous Metformin-Eluting Membranes: in Vitro and in Vivo

This work developed biodegradable nanofibrous drug-eluting membranes that provided sustained release of metformin for repairing wounds associated with diabetes. To prepare the biodegradable membranes, poly-d-l-lactide-glycolide (PLGA) and metformin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and were spun into nanofibrous membranes by electrospinning. An elution method and an HPLC assay were utilized to characterize the in vivo and in vitro release rates of the pharmaceuticals from the membranes. The biodegradable nanofibrous membranes released high concentrations of metformin for more than three weeks. Moreover, nanofibrous metformin-eluting PLGA membranes were more hydrophilic and had a greater water-containing capacity than virgin PLGA fibers. The membranes also improved wound healing and re-epithelialization in diabetic rats relative to the control. The experimental results in this work suggest that nanofibrous metformin-eluting membranes were functionally active in the treatment of diabetic wounds and very effective as accelerators in the early stage of healing of such wounds.

SYNTAX score: an independent predictor of long-term cardiac mortality in patients with acute ST-elevation myocardial infarction.

IntroductionThis observational study aimed to determine whether the SYNergy between percutaneous coronary intervention (PCI) with TAXUS drug-eluting stent and the cardiac surgery (SYNTAX) score can act as an independent predictor for cardiac death on long-term follow-up in patients with acute ST-elevation myocardial infarction (STEMI). MethodsOne hundred and fifty-three patients admitted to the Chang Gung Memorial Hospital in Linkou because of acute STEMI from 1 January 2008 to 31 December 2009, who subsequently underwent a primary PCI, were included in this study. SYNTAX scores were calculated immediately after the primary PCI; and the prognostic value of the SYNTAX score in relation to cardiovascular events, which were defined as low-risk (SYNTAX score 0–22) and intermediate-risk to high-risk (SYNTAX score>22), was determined. Long-term follow-up was available in 141 patients (92%, mean follow-up duration of 30±11 months). ResultsBy Kaplan–Meier estimates, cardiac death-free survival was 99.1% in the low-risk group vs. 78.6% in the intermediate-risk to high-risk group at 42 months of follow-up (P<0.001). For all-cause death, the survival rate was 93.1% in the low-risk group vs. 78.6% in the intermediate-risk to high-risk group at 42 months of follow-up (P=0.002). Multivariate Cox-regression analysis showed that independent predictors of cardiac death were the SYNTAX score (odds ratio 15.90; 95% confidence interval 1.04–244.21) and symptom to onset-to-therapy interval (odds ratio 25.57; 95% confidence interval 1.00–655.96). ConclusionThe SYNTAX score is a strong independent predictor of cardiac death in intermediate-risk to high-risk patients with acute STEMI.

Hypothyroid Cardiac Tamponade: Clinical Features, Electrocardiography, Pericardial Fluid and Management

Background:Cardiac tamponade associated with hypothyroidism has been reported, but few studies address the clinical features. This study aims to identify the patient characteristics and to propose a reasonable clinical approach for hypothyroid cardiac tamponade. Method:Patients admitted to Chang Gung Memorial Hospital between September 1998 and September 2008 with pericardial effusion secondary to hypothyroidism were enrolled. Cases involving cardiac tamponade were investigated. The clinical data, electrocardiography, echocardiography and aspirated fluid were examined. Results:Thirty-six patients with moderate or large amount of pericardial effusion as a result of hypothyroidism were examined. Eight patients (22.2%) with both clinical and echocardiographic signs of tamponade were identified and were treated by pericardiocentesis or creation of pleural-pericardial window. These patients were characterized with normal sinus rhythm (80.75 ± 13.45 beats/min), low voltage over limb leads (6 of 8, 75.0%), flat T wave (6 of 8, 75.0%) and clear yellowish pericardial fluid (7 of 8, 87.5%). Their heart rates were significantly lower (80.75 ± 13.45 beats/min versus 112.75 ± 12.87 beats/min, P < 0.01) than those of patients with cardiac tamponade from malignancy, autoimmune disease, tuberculosis and iatrogenic insult. Their interventricular septa were also significantly thicker (15.71 ± 6.70 mm versus 11.70 ± 2.11 mm, P = 0.02). Ten patients (27.8%) had echocardiographic signs of tamponade without paradoxical pulse and were successfully treated with thyroxine without pericardial drainage. Conclusion:For patients diagnosed with cardiac tamponade without sinus tachycardia, hypothyroidism should be highly suspected. Although emergent pericardiocentesis should be performed in clinical cardiac tamponade, patients with echocardiographic tamponade signs without a paradoxical pulse should be treated with thyroxine initially.

Celiac artery dissection presenting with abdominal and chest pain

Spontaneous dissection of the celiac artery is uncommon and is rarely considered in patients with acute abdomen. However, this condition has been reported frequently in recent years. Subjects are predominantly male and younger than 50 years. Mortality is reportedly high if dissection Fig. 1 Chest and abdominal CT revealed ectopic origin of the celiac trun which is intramural hematoma, along the celiac trunk, common hepatic a 0735-6757/

Local sustained delivery of acetylsalicylic acid via hybrid stent with biodegradable nanofibers reduces adhesion of blood cells and promotes reendothelialization of the denuded artery.

– see front matter

Metabolic syndrome and homocysteine level as predictors of the severity of coronary artery disease in patients with carotid stenosis.

Incomplete endothelialization, blood cell adhesion to vascular stents, and inflammation of arteries can result in acute stent thromboses. The systemic administration of acetylsalicylic acid decreases endothelial dysfunction, potentially reducing thrombus, enhancing vasodilatation, and inhibiting the progression of atherosclerosis; but, this is weakened by upper gastrointestinal bleeding. This study proposes a hybrid stent with biodegradable nanofibers, for the local, sustained delivery of acetylsalicylic acid to injured artery walls. Biodegradable nanofibers are prepared by first dissolving poly(D,L)-lactide-co-glycolide and acetylsalicylic acid in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution is then electrospun into nanofibrous tubes, which are then mounted onto commercially available bare-metal stents. In vitro release rates of pharmaceuticals from nanofibers are characterized using an elution method, and a highperformance liquid chromatography assay. The experimental results suggest that biodegradable nanofibers release high concentrations of acetylsalicylic acid for three weeks. The in vivo efficacy of local delivery of acetylsalicylic acid in reducing platelet and monocyte adhesion, and the minimum tissue inflammatory reaction caused by the hybrid stents in treating denuded rabbit arteries, are documented. The proposed hybrid stent, with biodegradable acetylsalicylic acid-loaded nanofibers, substantially contributed to local, sustained delivery of drugs to promote re-endothelialization and reduce thrombogenicity in the injured artery. The stents may have potential applications in the local delivery of cardiovascular drugs. Furthermore, the use of hybrid stents with acetylsalicylic acid-loaded nanofibers that have high drug loadings may provide insight into the treatment of patients with high risk of acute stent thromboses.

Lesion Length Impacts Long Term Outcomes of Drug-Eluting Stents and Bare Metal Stents Differently

Background:Coronary artery disease (CAD) is the most important cause of mortality and morbidity in patients who have undergone carotid artery endovascular or surgical intervention. Metabolic syndrome (MetS) and hyperhomocysteinemia (HHCY) have been reported to be associated with CAD. However, no study has investigated the association between MetS or HHCY and the severity of CAD in patients with carotid stenosis. Methods:Total of 148 consecutive patients with at least 1 side of the extracranial internal carotid artery were enrolled. Further, on the basis of the results of coronary angiography, the patients were divided into the CAD group (n = 85) and the non-CAD group (n = 63). Results:Multiple regression analysis revealed that CAD was independently associated with HHCY (odds ratio: 4.07; 95% confidence interval: 1.93–8.57; P < 0.0001) and MetS (odds ratio: 3.38; 95% confidence interval: 1.56–7.29; P = 0.002). Furthermore, multivariate stepwise linear regression revealed that the MetS score and total plasma homocysteine level were significantly correlated with affected vessel number in CAD and the extent of coronary atherosclerosis. Conclusions:MetS and HHCY can predict the presence of CAD in patients with carotid stenosis. Furthermore, the MetS score and total plasma homocysteine level are significantly associated with the extent of coronary atherosclerosis.

Long-term outcomes of drug-eluting stents versus bare-metal stents in large coronary arteries

Background Long lesions have been associated with adverse outcomes in percutaneous coronary interventions with bare metal stents (BMS). However, the exact impact of lesion length on the short- and long-term outcomes of drug-eluting stent (DES) implantations is not as clear. Methods and Results This study compared the impact of lesion length on angiographic and clinical outcomes of BMS and DES in a single-center prospective registry. Lesion length was divided into tertiles. The primary endpoints were angiographically defined binary in-stent restenosis (ISR) rate and major adverse cardiac event (MACE). Of the 4,312 de novo lesions in 3,447 consecutive patients in the CAPTAIN registry, 2,791 lesions (of 2,246 patients) received BMS, and the remaining 1,521 lesions (of 1,201 patients) received DES. The mean follow-up duration was 4.5 years. The longer the lesion, the higher the ISR rate (14%, 18%, and 29%, p<0.001) and the lower the MACE-free survivals (p = 0.007) in the BMS group. However, lesion length showed no such correlation with ISR rates (4.7%, 3.3%, and 7.8%, p = 0.67) or MACE-free survivals (p = 0.19) in the DES group. Conclusions In our single-center prospective registry, lesion length defined in tertiles has no impact on the short-term (ISR) or long-term (MACE) outcomes of patients implanted with DES. In contrast, longer lesion correlates with higher ISR and MACE rates in BMS group.

The prognostic significance of SYNTAX score after early percutaneous transluminal coronary angioplasty for acute ST elevation myocardial infarction.

BACKGROUND Long-term (>3 years) outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in large coronary arteries were not conclusive. In addition, large coronary vessels were defined using a wide size range (≥3.0 mm) in previous studies. The aim of this study was to assess the long-term efficacy of DES versus BMS in subgroups of different vessel sizes. METHODS A total of 1096 patients (1342 lesions) who underwent either DES or BMS implantation in large coronary vessels was followed for a mean duration of 4.5 years. Patients were divided into 4 subgroups by the reference vessel diameters (Q1: 3.0-3.25 mm, Q2: 3.26-3.50 mm, Q3: 3.51-3.75 mm, and Q4: 3.76-4.50 mm). The primary endpoint was major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, target vessel revascularization, and stent thrombosis. The propensity score-adjusted Cox regression method was applied. RESULTS In the 3 subgroups with smaller vessel sizes, the adjusted risk of MACE in DES recipients was reduced by 82% in Q1 (hazard ratio [HR]: 0.18, 95% confidence interval [CI]: 0.09-0.38), 49% in Q2 (HR: 0.51, 95% CI: 0.26-0.98), and 67% in Q3 (HR: 0.33, 95% CI: 0.15-0.73). However, in the largest vessel subgroup (>3.75 mm), all clinical outcomes were not significantly different irrespective of the stent type used. CONCLUSIONS The incidence of MACE in 3.0-3.75 mm vessels was significantly reduced by the use of DES than by the use of BMS during a long-term follow-up. However, DES lost its benefit in >3.75 mm vessels.