Kuo-Chun Hung

Decrease in Irisin in Patients with Chronic Kidney Disease

Patients with chronic kidney disease have abnormal energy expenditure and metabolism. The mechanisms underlying altered energy expenditure in uremia are unknown and remain to be elucidated. Irisin is a peroxisome proliferator-activated receptor γ coactivator 1-α–dependent myokine, and it increases energy expenditure in the absence of changes in food intake or activity. We hypothesize that chronic kidney disease patients have altered irisin levels. We measured resting irisin levels in 38 patients with stage 5 chronic kidney disease and in 19 age- and sex-matched normal subjects. Plasma irisin levels were significantly decreased in chronic kidney disease patients (58.59%; 95% CI 47.9%–69.2%, p<0.0001). The decrease in irisin levels was inversely correlated with the levels of blood urea nitrogen and creatinine. Further association analysis revealed that irisin level is independently associated with high-density lipoprotein cholesterol level. Our results suggest that chronic kidney disease patients have lower than normal irisin levels at rest. Furthermore, irisin may play a major role in affecting high-density lipoprotein cholesterol levels and abnormal energy expenditure in chronic kidney disease patients.

Sitagliptin and cardiovascular outcomes in diabetic patients with chronic kidney disease and acute myocardial infarction: A nationwide cohort study

BACKGROUND The cardiovascular safety and efficacy of sitagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, in type 2 diabetic patients with chronic kidney disease (CKD) after acute myocardial infarction (AMI) are unclear. METHODS We analyzed data from the Taiwan National Health Insurance Research Database between March 1st, 2009 and December 31st, 2011. A total of 1025 AMI patients with diabetes with chronic kidney disease were selected as the study cohort. The study evaluated the cardiovascular safety and efficacy of sitagliptin by comparing 205 subjects (20%) who use sitagliptin to 820 matched subjects (80%) who do not. The primary outcomes included myocardial infarction, ischemic stroke or cardiovascular death. RESULTS Primary composite outcomes occurred in 54 patients in the sitagliptin group (26.3%) and in 164 patients in the comparison group (20.0%) (HR, 1.32; 95% CI, 0.97-1.79; P=0.079) during the mean follow-up of 1.02years (SD=0.71years). The sitagliptin group had similar risks of ischemic stroke, all-cause mortality or hospitalization for heart failure (HF) compared to the non-sitagliptin group (P=0.938, 0.523 and 0.795 respectively). However, sitagliptin use was associated with increased risks of recurrent myocardial infarction (HR, 1.73; 95% CI, 1.15-2.58; P=0.008) and percutaneous coronary revascularization (HR, 1.43; 95% CI, 1.04-1.95; P=0.026). CONCLUSIONS Among type 2 diabetic patients with CKD after AMI, the use of sitagliptin was not associated with an increased risk of cardiovascular death, ischemic stroke or hospitalization for HF but was associated with increased risks of recurrent MI and percutaneous coronary revascularization.

Role of uric acid in the link between arterial stiffness and cardiac hypertrophy: a cross-sectional study

OBJECTIVES Hyperuricaemia has been linked to atherosclerosis; however, there is limited evidence about its association with arterial stiffness and cardiac hypertrophy, which are associated with adverse cardiovascular outcomes. We studied the association of hyperuricaemia with an increased risk of arterial stiffness and cardiac hypertrophy in a population participating in a health-screening programme. METHODS In subjects who underwent health screening from 2005 to 2007, arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV), whereas cardiac hypertrophy was determined by plain chest radiography and electrocardiography. Polychotomous logistic regression was used to identify associations of hyperuricaemia with arterial stiffness and cardiac hypertrophy, after adjusting for the presence of metabolic syndrome. RESULTS Of the total 9375 subjects enrolled, 1324 (14.5%) had hyperuricaemia. Subjects with hyperuricaemia had a significantly higher baPWV [1618.8 (379.3) cm/s] than those without it [1501.8 (334.9) cm/s]. Cardiac hypertropy was observed in 1047 (11.2%) subjects. Hyperuricaemia was associated with cardiac hypertrophy with an odds ratio (OR) of 1.53 (95% CI 1.32, 1.77). Polychotomous logistic regression showed that hyperuricaemia was associated with ORs (95% CI) for coexisting abnormal baPWV and cardiac hypertrophy of 1.75 (95% CI 1.24, 2.47) and 1.41 (95% CI 1.04, 1.91) in men and women, respectively, after adjusting for age, proteinuria, high high-sensitive CRP, abnormal ankle-brachial index or a number of metabolic syndrome components present. CONCLUSION Hyperuricaemia was associated with arterial stiffness and cardiac hypertrophy. Hyperuricaemia, along with other risk factors related to atherosclerosis, could play a role in the development of cardiac hypertrophy by increasing arterial stiffness.

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.

Mechanisms and clinical significance of transient atrioventricular block during dobutamine stress echocardiography.

OBJECTIVES The purpose of this study was to investigate the possible mechanism and the clinical significance of transient atrioventricular block (AVB) during dobutamine stress echocardiography (DSE). BACKGROUND Transient AVB occurs rarely during DSE; however, the mechanisms responsible for blocks are unclear. METHODS A retrospective analysis of clinical, echocardiographic, catheterization, revascularization and head-up tilting test data was conducted in patients who developed transient AVB during DSE. RESULTS A total of 302 patients with known or suspected coronary artery disease (CAD) underwent DSE before coronary angiography between November 1997 and August 1998. Transient AVB developed in 12 patients during the test. Mobitz I block was noted in six patients and Mobitz II block in the other six patients. Nine of these 12 patients were subsequently shown to have CAD and three had no significant coronary artery stenosis. Mobitz II block was observed only in patients with CAD, while Mobitz I block occurred in three patients with and three patients without CAD (p < 0.05). Eight of the nine patients with CAD underwent a successful coronary angioplasty with or without stenting and a repeat DSE revealed no recurrence of heart block except in one patient. Head-up tilting test in the 12 patients revealed a positive response in three of the nine patients with and all three patients without CAD. A negative head-up tilting test was likely to be observed in patients with, as compared with those without, CAD in this study population (p < 0.05). CONCLUSIONS Transient AVB is not an infrequent manifestation during DSE. Both myocardial ischemia and neurally mediated vagal reflex may be responsible for this phenomenon. The development of Mobitz II block during DSE is indicative of the presence of CAD. A successful revascularization in patients with CAD who develop transient AVB may abolish this phenomenon.

Clinical events occurrence and the changes of quality of life in chronic haemodialysis patients with dry weight determined by echocardiographic method.

The maintenance of circulating blood volume within an optimal range is necessary for haemodialysis patients to avoid circulating complications, including over‐hydration and dehydration. Inferior vena cava diameter (IVCD) estimation is a non‐invasive method to obtain a well correlation with the intravascular fluid status, and it may get a reliable ideal dry weight (DW) for chronic haemodialysis patients. We try to analysis the life quality changes and circulating complication in chronic haemodialysis patients who adjust DW with this tool in comparing with the traditional method. A total of 100 chronic haemodialysis patients, ranging from 26 to 77 years old, were involved in this study. They are randomly divided into study (n = 50) and control group (n = 50). All of them received the IVCD estimation by echocardiography every month for 3 months. The patients in the study group adjusted the DW with the IVCD estimated by echocardiographic method, however, patients in the control group with the traditional method. The quality of life (QOL) was evaluated with the short form 36 questionnaire (SF‐36) in the beginning and the end of the study. The scores of physical functioning (PF), role limitation‐physical (RP), general health (GH) and role limitation‐emotional (RE) have much improvement in the patients of the study group than those in the control group. Besides, the occurrence of clinical events due to circulating complications during the study period showed significant reduction in the extents of hypotension, gastrointestinal upset, discontinuation of haemodialysis, muscular cramps, tinnitus, headache and chest discomforts with electrocardiographic changes; and these effects, especially, are significant in the patients with over‐dehydrated status, which with the IVCD < 8 mm/m2 detected by echocardiographic method. The study demonstrated that ideal DW estimated by echocardiographic method not only improved the QOL but also reduced the circulating complications during haemodialysis for chronic haemodialysis patients.

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.

Combination of Duplex Ultrasound-Guided Manual Declotting and Percutaneous Transluminal Angioplasty in Thrombosed Native Dialysis Fistulas

Background. To investigate the safety, feasibility, efficacy, and long-term patency rate of manual declotting under duplex ultrasound (US) guidance followed by percutaneous transluminal angioplasty (PTA) in thrombosed native arteriovenous fistulas (AVFs). Methods. Of 87 consecutive thrombosed AVFs evaluated by duplex US, 22 patients with 25 recently thrombotic events in 22 AVFs were suitable for manual declotting. PTA was performed following successful declotting, and long-term patency was assessed. Results. The procedure success rate of manual declotting was 80% (20 of 25), and a residual stenosis of 74 ± 9% was identified by duplex US after declotting. PTA reduced the diameter stenosis to 25 ± 6% and increased the lumen diameter from 1.33 ± 0.85 mm to 4.62 ± 0.98 mm. Neither embolic nor bleeding complications were noted during the procedure. The average procedure time and the fluoroscopy time were 28.4 ± 9.9 and 7.2 ± 4.1 minutes, respectively. Primary patency rates at 1, 2, and 3 years were 47%, 35%, and 28%; assisted primary patency rates at 1, 2, and 3 years were 71%, 63%, and 63%; and secondary patency rates at 1, 2, and 3 years were 76%, 71%, and 63%, respectively, during a maximum follow-up period of 42 months. Conclusion. The combination of duplex US-guided manual declotting and angioplasty of underlying stenosis is a safe and feasible method to treat recently thrombosed native AVFs in selected patients. It simplifies the interventional procedure, reduces cost and radiation exposure time, and extends life span of dialysis fistula with acceptable long-term patency rate.

Effects of altered volume loading on left ventricular hemodynamics and diastolic filling during hemodialysis.

Background. Changes in the circulating volume associated with hemodialysis (HD) resulted in alternations of left ventricular (LV) filling. However, previous studies offered conflicting findings. This study thus evaluated the impact of HD on LV diastolic filling indices and hemodynamics. Materials and Methods. Forty patients with end‐stage renal disease were studied by Doppler echocardiography immediately before and after HD. The cardiac size, volume and mass were determined by M‐mode and two‐dimensional echocardiography. LV diastolic filling parameters and hemodynamics were assessed from mitral inflow using Doppler echocardiography. Results. Left atrial and LV dimension, LV volume, and LV mass decreased significantly after HD (p < 0.001). Cardiac output declined from 5.74 ± 1.37 to 4.98 ± 1.27 L/min (p < 0.001), whereas, the ejection fraction remained unchanged. HD elicited marked changes in the early diastolic E (95.1 ± 20.5 to 70.3 ± 18.2 cm/s, p < 0.001) and late atrial filling A velocities (104.3 ± 20.9 to 88.9 ± 16.9 cm/s, p < 0.001). In addition, correction of the deceleration time of E and isovolumic relaxation time prolonged significantly (p = 0.011 and p < 0.001, respectively). Conclusions. Findings in this study indicate that HD altering the loading condition significantly influenced the LV diastolic function and hemodynamics. Moreover, Doppler echocardiography provides an effective means of assessing the effects on LV diastolic filling and hemodynamics during HD.