Yu-Yao Huang

Risk factors for lower extremity amputation in diabetic foot disease categorized by Wagner classification

AIMS To elucidate the risk factors for lower extremity amputation (LEA) in patients of diabetic foot disease with different Wagner gradings. METHODS This study was conducted in a multidisciplinary diabetic foot care center. Demographic characteristics, laboratory data, disease history, ankle brachial pressure index (ABI) and Wagner classification were considered as independent variables to predict the therapeutic outcome (major LEA, minor LEA, and non-amputation). Risk factors for LEA in different Wagner grades were further analyzed. Multivariate stepwise ordinal logistic regression was performed. RESULTS Of 789 study subjects, 19.9% received major LEA and 22.9% received minor LEA. Higher Wagner grade, lower ABI, serum albumin and hemoglobin, and elevated white blood cell (WBC) count were significantly associated with an increased risk of LEA. When stratified by Wagner classification, most of the above predictors and estimated glomerular filtration (eGFR) were detected only in grade 3. While in grades 2 and 4, WBC count was identified as primary predictor positively associated with an increased risk of LEA. CONCLUSIONS Wagner classification remarkably influenced the potential risk factors for LEA, showing different predictors in different grades. The traditionally recognized predictors for diabetic foot amputation such as lower ABI, albumin or eGFR were almost exclusively found in patients with Wagner grade 3.

Demonstration of reserved anterior pituitary function among patients with amenorrhea after postpartum hemorrhage

To demonstrate the residual pituitary function of patients with Sheehan s syndrome years after the obstetric complication, 14 patients with postpartum hemorrhage followed by secondary amenorrhea and agalactia were included in this review. Due to their unfamiliarity with the clinical symptoms, these patients did not receive pretreatment hormonal therapy. The mean age at their last delivery was 29 years (range 21–38 years). The mean duration between postpartum hemorrhage and the subsequent clinical manifestations leading to the endocrine investigation was 18 years (range 1–33 years). Eight patients presented with symptoms of severe hyponatremia (serum sodium less than 125 mmol/l) more than 16 years (mean 23 ± 10) after the occurrence of postpartum hemorrhage. The electrolyte abnormality was primarily due to adrenal dysfunction. Seven out of 14 patients had normal basal luteinizing hormone (LH) levels and adequate LH responses to gonadotropin releasing hormone stimulation. Administration of thyrotropin releasing hormone provoked thyrotropin release and/or prolactin secretion in four cases. The manifestation of clinical hypopituitarism and the degree of empty sella on computed tomography scanning did not accurately indicate the secreting ability of the pituitary in patients with Sheehans syndrome. Although all the patients had amenorrhea, the gonadotropic functions of the pituitary still remain in some patients. Various degrees of other pituitary functions can also been demonstrated even several decades after the occurrence of obstetric complications. Our data suggest that the amenorrhea of Sheehans patients is not simply due to a dysfunction of the pituitary gonadotrophs.

C-reactive protein as an outcome predictor for percutaneous transluminal angioplasty in diabetic patients with peripheral arterial disease and infected foot ulcers

AIM Although percutaneous transluminal angioplasty (PTA) is an effective therapeutic procedure for critical limb ischemia, several clinical factors can influence the outcome of PTA for peripheral arterial disease (PAD). The aim of this study is to identify the outcome predictors of PTA in infected diabetic foot patients with PAD. METHODS Eighty-five diabetic patients with a total of 90 infected limbs treated by PTA participated in this study. Patients were initially admitted for infected foot ulcers and were later diagnosed with PAD. Even though all patients underwent successful PTA within 15 days of admission, limb salvage was successful in 66 cases while 24 underwent subsequent amputation. The clinical characteristics and laboratory variables of both groups before PTA were compared and analyzed. RESULTS Significantly higher level of C-reactive protein (CRP) was observed in the major amputation group before PTA. The cutoff value via receiver operating characteristic curve was 50mg/L (81.8% specificity, 70.7% sensitivity). Multivariate logistic regression analysis revealed that CRP levels may serve as valuable marker in determining a successful outcome. CONCLUSION Reduced CRP levels (<50mg/L), which indicates a low infection severity, may serve as a major predictor of successful PTA outcome in diabetic patients with infected foot ulcers.

The rescue effect of 15-deoxyspergualin on intraperitoneal microencapsulated xenoislets.

Because the development of surface neogrowth composed mainly of macrophages and fibroblasts precedes the recurrence of hyperglycemia in treated diabetic animals, the pericapsular macrophages may adversely affect the graft function of IP alginate-poly-L-lysine-alginate (A-P-A) microencapsulated islets. In order to clarify the role of pericapsular macrophages on late islet xenograft dysfunction, we investigated whether 15-deoxyspergualin (15-DSG), a macrophage inhibitor, has a rescue effect on the recurrent hyperglycemia in streptozotocin-induced diabetic mice that had been treated with IP transplantation of A-P-A microencapsulated rat islets. The mean duration of normoglycemia (whole blood glucose level below 8.3 mmol/l) in streptozotocin-induced diabetic mice treated with implantation of about 2200–2400 of A-P-A microencapsulated rat islets was 75 days. When the blood glucose levels were higher than 11.1 mmol/l for two consecutive determinations, 15-DSG at a dose of 0.625 mg/kg body weight or isotonic sodium chloride solution (control group) was given daily SC. The blood glucose levels decreased significantly from 13.9 ± 0.5 mmol/l to 11.0 ± 1.3 mmol/l (n = 18, p < 0.05) at the fourth day and to 7.6 ± 1.0 mmol/l (n = 18) at the 14th day of 15-DSG administration. That was not significantly different from the mean glycemic level during the normoglycemic period (7.6 ± 1.0 vs. 7.0 ±1.7 mmol/l, n = 18, p = NS). Isotonic sodium chloride solution injections did not reduce glycemic levels of mice in the control group. As another control, 10 streptozotocin-induced diabetic mice were given the same daily doses of 15-DSG for 14 days. 15-DSG did not decrease the blood glucose levels of diabetic mice in the control group. We further studied the effect of 15-DSG on the expression of interleukin-1β (IL-1β) in peritoneal exudate mononuclear cells (PEMCs) using reverse transcription-polymerase chain reaction. It was found that the mRNA of IL-1β was undetectable in PEMCs of 15-DSG-treated diabetic mice even after those cells were stimulated by lipopolysaccharides in vitro. Administration of 15-DSG at a daily dose of 0.625 mg/kg body weight from the 22nd to the 28th day after transplantation and 7 consecutive days every 3 weeks thereafter did not prolong graft survival of IP microencapsulated rat islets. Our data suggest that 15-DSG has a rescue effect when A-P-A microencapsulated islets have induced cellular overgrowth that threatens the survival of the graft. It is possible that the surface overgrowth composed of macrophages is involved in the pathophysiology of late failure of A-P-A microencapsulated xenogeneic islets.

The value of Doppler waveform analysis in predicting major lower extremity amputation among dialysis patients treated for diabetic foot ulcers

AIMS This study examined the predictors for lower extremity amputation (LEA) in patients with diabetic foot ulcers according to kidney function and, in the case of dialysis patients, specifically evaluated the vasculature with the ankle-brachial index (ABI) and Doppler waveforms. METHODS Among 658 diabetic patients admitted to the Diabetic Foot Care Center, 286 had an estimated glomerular filtration rate (eGFR)≥ 60 ml/min per 1.73 m(2), 275 had an eGFR<60, and 97 patients were under maintenance dialysis. All clinical variables were analyzed. A specialist retrospectively reviewed Doppler images of 78 of the patients in dialysis to evaluate peripheral arterial disease. RESULTS Forty-two percent of patients with eGFR<60 presented with ABI≤0.90. For ABI values>1.40, the proportion of dialysis patients (31.3%) was greater than the proportion of patients with eGFR<60 (5.3%). Wagner wound classifications, reduced serum albumin levels, and low ABI values were the predictors for major LEA among patients in the non-dialysis groups. Nevertheless, these indicators were not predictive of the risk of amputation in diabetic patients on dialysis. The presence of poor monophasic waveforms in the dorsalis pedis artery or posterior tibial artery served as an independent predictor (odds ratio: 7.61; P=0.008) for major LEA among dialysis patients. The sensitivity and specificity were 88.0% and 59.6%, respectively. CONCLUSIONS Poor monophasic Doppler waveforms of below-the-knee arteries, commonly found among dialysis patients in treatment for diabetic foot ulcers, can serve as an independent predictor for major LEA.

Pitavastatin improves glycated hemoglobin in patients with poorly controlled type 2 diabetes

To investigate the effect of pitavastatin on glucose control in patients with type 2 diabetes.

Clinical Characteristics and Risk Factor Analysis for Lower-Extremity Amputations in Diabetic Patients With Foot Ulcer Complicated by Necrotizing Fasciitis.

AbstractPatients with diabetes are at a higher risk of having diabetic foot ulcers (DFUs) or necrotizing fasciitis (NF). The present study aims to examine the clinical characteristics and associated risk factors for lower-extremity amputation (LEA) in patients with DFU complicated by NF.We retrospectively reviewed patients treated at a major diabetic foot center in Taiwan between 2009 and 2014. Of the 2265 cases 110 had lower-extremity NF. Limb preservation outcomes were classified as major LEA, minor LEA, or limb-preserved. Clinical characteristics, laboratory data, and bacterial culture results were collected for analysis.Of the 110 patients with NF, 100 had concomitant DFUs (NF with DFU) and the remaining 10 had no DFU (NF without DFU). None of the NF patients without DFU died nor had their leg amputated. Two NF patients with DFU died of complications. The amputation rate in the surviving 98 NF patients with DFU was 72.4% (46.9% minor LEA and 25.5% major LEA). Seventy percent of the NF patients without DFU had monomicrobial infections (60% with Streptococcus species), and 81.4% NF patients with DFU had polymicrobial infections. Anaerobic organisms were identified in 66% of the NF patients with DFU. Multinomial logistic regression analysis revealed an association between high-grade Wagner wound classification (Wagner 4 and Wagner 5) and LEA (adjusted odds ratio [aOR] = 21.856, 95% confidence interval [95% CI] = 1.625–203.947, P = 0.02 and aOR = 20.094, 95% CI = 1.968–205.216, P = 0.01 for major and minor LEA, respectively) for NF patients with DFU. In addition, a lower serum albumin level was associated with major LEA (OR = 0.066, P = 0.002).In summary, once DFUs were complicated by NF, the risk of amputation increased. Empirical treatment for NF patients with DFU should cover polymicrobial infections, including anaerobic organisms. The high-grade wound classification and low serum albumin level were associated with LEA.

Glucose Variability and β - Cell Response by GLP-1 Analogue added-on CSII for Patients with Poorly Controlled Type 2 Diabetes

The effects of twice-daily GLP-1 analogue injections added on continuous subcutaneous insulin infusion (CSII) in patients with poorly controlled type 2 diabetes (T2DM) were unknown. After optimization of blood glucose in the first 3 days by CSII during hospitalization, patients with poorly controlled T2DM were randomized to receive CSII combined with injections of exenatide or placebo for another 3 days. A total of 51 patients (30 in exenatide and 21 in placebo groups) with mean A1C 11% were studied. There was no difference in mean glucose but a significant higher standard deviation of plasma glucose (SDPG) was found in the exenatide group (50.51 ± 2.43 vs. 41.49 ± 3.00 mg/dl, p = 0.027). The improvement of incremental area under the curve (AUC) of glucose and insulinogenic index (Insulin0–peak/ Glucose0–peak) in 75 g oral glucose tolerance test was prominent in the exenatide group (p < 0.01). The adiponectin level was significantly increased with exenatide added on (0.39 ± 0.32 vs. −1.62 ± 0.97 μg/mL, in exenatide and placebo groups, respectively, p = 0.045). In conclusion, the add-on of GLP-1 analogue to CSII increased glucose variability and the β - cell response in patients with poorly controlled T2DM.

Treatment for Diabetic Foot Ulcers Complicated by Major Cardiac Events

OBJECTIVE Diabetic foot ulcer (DFU) is a major complication in patients with diabetes mellitus and the leading cause of non-traumatic amputation in adults. Patients with DFU are usually fragile due to chronic diabetic comorbidities; therefore, tedious debridement and intervention procedures may not be well tolerated in patients with DFU. This study aimed to identify a casual relationship between in-hospital complications and treatment for limb-threatening DFUs. METHODS From 2009 to 2011, 1130 consecutive patients who were admitted to the Diabetic Foot Care Center in Chang Gung Medical Center were surveyed. Rates of in-hospital mortality or events that lead to transfer to the intensive care unit (ICU) for various severe complications were retrospectively analyzed. RESULTS Forty-seven patients (4.2%) experienced in-hospital complications (28 patients died). Major adverse cardiac events (MACE) (n=21, 44.7%) were the most common complications, followed by nosocomial infection (n=18, 38.3%). Previous myocardial infarction was a risk factor for MACE. The presentation of MACE was fulminant (eg, acute pulmonary edema, cardiogenic shock,cardiac arrest), and occurred within 10 days of admission or within 10 days following a major procedure in most cases. ST-T segment abnormality at rest was the most common presentation of electrocardiography for MACE. CONCLUSION MACE should be prevented during treatment for limb-threatening DFU in high-risk patients. Acute stress might have caused MACE during the first 10 days after admission or a major procedure.

The plasminogen-plasmin fibrinolytic system accelerates degradation of alginate-poly-l-lysine-alginate microcapsules in vitro

Abstract Inspired by the idea of “artificial cell” proposed by Dr T.M. Chang 30 years ago, Dr A.M. Suns group developed alginate-poly- l -lysine-alginate (A-P-A) microcapsules in 1980 to immunoisolate rat islet transplant which reversed hyperglycemia of streptozotocin-induced diabetic mice for a couple of weeks. Although reversal of hyperglycemia in various diabetic animal models and human subjects by A-P-A microencapsulated islets have been reported since 1980, the graft function was found to be variable in degree and duration. In 1994, Dr Soon-Shiong and colleagues presented a case of insulin-dependent diabetes (IDDM) who received a total of 960,000 A-P-A microencapsulated human islets intraperitoneally had a period, although for only 2 months, without the heed of exogenous insulin. We intend to identify and correct adverse factors that reduce graft survival of A-P-A microencapsulated islets to maintain long-term normoglycemia of treated diabetic patients. The pathogenesis of graft rejection of A-P-A microencapsulated xenoislet is not clear. It was noted that pericapsular cellular infiltration of A-P-A microencapsulated xenoislet grafts occurred as early as 28 days after intraperitoneal implantation. Many researchers found that the majority of pericapsular cellular components were macrophages and fibroblasts. Pericapsular macrophages may secrete proinflammatory cytokines, such as interleukin-1β which may suppress islet beta-cells and result in graft dysfunction. The inflammatory reaction induced by A-P-A microencapsulated islets may suffocate the islets by exhausting oxygen. Many unidentified factors are possibly involved in degradating A-P-A microcapsules in vivo. It is interesting to note that macrophages secreted urokinase plasminogen activator in response to inflammation. One of the principal players of the fibrinolytic system is plasminogen which binds to the exposed lysyl residues in fibrin. Polylysine was found to mimic the cofactor (enhancing) function of fibrin in tissue activator-induced and low molecular weight urokinase-induced plasminogen activation. Since A-P-A microcapsules were formed by polycondensation of poly- l -lysine and alginate, it contained terminal and interchain lysine residues on their surface. The exposed lysine residues of A-P-A microcapsule confer binding sites for plasminogen and its activators. If the membrane-bound tissue activator is activated for plasminogen activation, the catalytic domain of plasmin will cleave poly- l -lysine and disintegrate capsular membrane. Therefore, we hypothesize that the plasminogen-plasmin fibrinolytic system is involved in degradation of A-P-A microcapsules. To verify this hypothesis, we studied the lytic activity of the plasminogen-plasmin fibrinolytic system on the physical durability of A-P-A microcapsules in vitro.