Are current wound classifications valid for predicting prognosis in people treated for limb-threatening diabetic foot ulcers?

This study aims to investigate whether the current wound classifications were valid for the treatment prognosis of subjects treated for limb-threatening diabetic foot ulcers (LTDFU). A total of 1548 patients with LTDFU and infection were studied, with wounds recorded using the Wagner, Texas, PEDIS and WIfI classifications while major lower extremity amputations (LEAs) or in-hospital mortality incidences were defined as poor outcomes. Among them, 153 (9.9%) patients received major LEAs and 38 (2.5%) patients died. After adjustments, the Wagner classification and Texas stage as well as clinical factors such as comorbidity with major adverse cardiac events (MACE), being under dialysis and having serum levels of C-reactive protein (CRP) and albumin were independent factors for prognosis. For patients without dialysis, Wagner and Texas stage stood out independently for prognosis. For patients on dialysis, only levels of CRP (odds ratio [OR] = 2.2 in Wagner, OR = 2.0 in WIfI, OR = 2.2 in Texas, OR = 2.3 in PEDIS) and albumin (OR = 0.4 in four classifications) were valid predictors. The Wagner system and Texas stage were valid for predicting prognosis in treatment for LTDFUs, suggesting a role of vascular perfusion. MACE history, levels of CRP and albumin level should assist in prediction; more significantly, only levels of CRP and albumin appeared valid for those subjects undergoing dialysis.

Microbiome of limb-threatening diabetic foot ulcers indicates the association of fastidious Stenotrophomonas and major amputation.

BACKGROUND: Proper identification of the polymicrobial microorganisms in patients with limb-threatening diabetic foot ulcers (LTDFUs) using conventional culture is insufficient. This prospective study evaluates the potential value of adjuvant molecular testing assisting in identify fastidious micro-organisms in LTDFUs compared to standard treatment alone. METHODS: Ninety patients with LTDFUs received interdisciplinary and standard antibiotic treatment in a referral diabetic foot center. A simultaneous 16S amplicon sequencing (16S AS) specimen along with conventional culture collected at admission was used to retrospectively evaluate the microbiological findings and its association with amputation outcomes. RESULTS: The microorganism count revealed by 16S AS overwhelmed that of conventional culturing (17 vs. 3 bacteria/ulcer respectively). The Stenotrophomonas spp. revealed in 29 patients were highly correlated with major (above ankle) amputation (OR: 4.76, 95% CI 1.01-22.56), while only one had been concomitantly identified by conventional culturing. Thus, there were 27 cases without proper antibiotics coverage during treatment. CONCLUSIONS: Adjuvant molecular testing assisted identification of fastidious pathogens such as Stenotrophomonas infection and might be associated with major amputation in patients with LTDFUs.

Diabetic foot disease in subjects with End-stage renal Disease: A nationwide study over 14 years highlighting an emerging threat.

AIMS: To disclose prevalence, demographic, foot characteristics as well as management and lower-extremity amputations (LEAs) of subjects with end-stage renal disease (ESRD) on diabetic foot diseases (DFDs). METHODS: Data were derived from the Taiwan National Health Insurance Research Database between 2004 and 2017. DFDs were defined as ulcers, infections, or severe peripheral arterial diseases (PADs) in patients with type 2 diabetes. Clinical characteristics were analyzed between subjects with and without ESRD. RESULTS: Subjects with ESRD have increased impacts on the DFD population either from annual prevalence (2.7 % to 10.42 %, P for trend < 0.001), or proportional representation in LEAs (7.91 % to 26.37 %, P < 0.001) over 14 years. The annual trends for major-LEAs rates have decreased in both subjects with and without ESRD (13.67 % to 5.82 % and 3.48 % to 1.47 %, both P < 0.001). Notably, the concomitant increase of endovascular treatments (EVTs) (7.09 % to 29.41 %, P < 0.001) was associated with the decrease of major-LEAs (P for interaction < 0.001) in subjects with ESRD. CONCLUSIONS: As the annual prevalence of subjects with ESRD has increased 3.9-fold over years, they now account for more than 30% of annual major-LEA of the total DFD population. Interdisciplinary team approach and aggressive EVTs might reduce major-LEAs in these patients.

A comprehensive investigation of nutritional status and psoas muscle mass in predicting five-year survival in patients with liver transplant.

BACKGROUND/PURPOSE: Although nutrition and sarcopenia have impacts on the surgery outcome of patients who have received living donor liver transplant (LDLT), the use of the prognostic nutritional index (PNI) or psoas muscle mass index (PMI) as an indicator for five-year survival in those patients is still unclear. METHODS: A total of 138 patients receiving LDLT were followed at a medical center in Taiwan. As well as analysis of clinical factors using Cox regression, time-varying PNI and PMI values as before surgery (0) and at 3-, 6-, and 12- months after LDLT were analyzed by time-dependent Cox analysis. For those 124 patients who survived after 3 months of LDLT, the values of PNI-3m, PMI-3m and their combination were further analyzed. RESULTS: PNI and PMI were noted to be highly associated with mortality at three months post-LDLT (PNI-3m hazard ratio [HR] = 0.89, 95% confidence interval [CI]: 0.85-0.94, p < 0.001; PMI-3m HR = 0.58, 95% CI: 0.41-0.82, p = 0.002). Per the Youden index, the cut-off point of PNI-3m was 42.35, and that of PMI-3m was 1.94. Compared to the subjects with higher levels of PNI-3m and PMI-3m (N-high/M-high), the HRs for subjects with N-high/M-low, N-low/M-high, and N-low/M-low were 5.27 (p = 0.004), 4.46 (p = 0.010) and 12.97 (p < 0.001) respectively. CONCLUSION: PNI and PMI at the third month post-LDLT serve as excellent predictors for 5-year survival. For patients with lower levels of PNI-3m or PMI-3m, combination use of these indexes is suggested to provide better prognostic information.

Impact of wound microbiology on limb preservation in patients with diabetic foot infection.

AIMS/INTRODUCTION: To investigate the association between specific bacterial pathogens and treatment outcome in patients with limb-threatening diabetic foot infection (LT-DFI). MATERIALS AND METHODS: Consecutive patients treated for LT-DFI in a major diabetic foot center in Taiwan were analyzed between the years 2014 and 2017. Patients with positive wound culture results at first aid were enrolled. Clinical factors, laboratory data, and wound culture results were compared. Lower-extremity amputations and in-hospital mortality were defined as a poor outcome. RESULTS: Among the 558 patients, 272 (48.7%) patients had lower extremity amputation and 22 (3.9%) patients had in-hospital mortality. Gram-negative bacterial (GNB) infection was the independent factor following factors adjustment. When all the 31 microorganisms were analyzed, only E. coli (adjusted odds ratio [aOR], 3.01; 95% CI, 1.60-5.65), Proteus spp. (aOR, 2.99; 95% CI, 1.69-5.29), and Pseudomonas aeruginosa (aOR, 2.00; 95% CI 1.20-3.32) were associated with poor outcome. The analysis of specific GNB species in association with major- or minor- amputation have been reported. No specific pathogen was associated with cause of death in patients with mortality within 30 days. The antimicrobial-resistant strains were not associated with a poor treatment outcome. CONCLUSIONS: The presence of GNB was associated with limb amputations. This study provides insight into more timely and appropriate management of the diabetic foot infection.

Survival of Patients Following First Diagnosis of Diabetic Foot Complications: A Nationwide 15-Year Longitudinal Analysis.

Background and Aims: The long-term survival in people with type 2 diabetes following first diagnosis of diabetic foot complications (FDDFC) is unclear. The object is to evaluate the mortality rate in subjects with type 2 diabetes following FDDFC and the impacts of the major cardiovascular comorbidities. Methods: Nationwide data were analyzed for subjects with T2D and DFC between 2003 and 2017 according to ICD-9 coding. DFC was defined with the codes of ulcers, infections, or severe peripheral artery disease that required intervention (PAD) to mimic the real world diagnosis. Criteria of FDDFC were preceded by a period without any DFC for at least 5 years. Major cardiovascular comorbidities: established PAD and cardiovascular diseases (CVD: including coronary heart disease (CHD), stroke, or heart failure) before the index date as well as lower-extremity amputations (LEA) at the index episode were analyzed. Results: Among 300,115 subjects with DFC, a total of 103,396 patients had FDDFC. The mean 5-year survival rate of these subjects was 81.05%. Using subjects without associated major cardiovascular comorbidity as baseline, the adjusted hazard ratios (aHR) were1.43 (95% confidence interval 1.38-1.49) in group PAD-/CVD+, followed by 1.70 (1.59-1.80) in PAD+/CVD- and 1.98 (1.89-2.08) in PAD+/CVD+. The aHR was further increased in patients with PAD who additionally had heart failure (3.77, 3.50-4.05), stroke (2.06, 1.95-2.18), or CHD (1.89, 1.79-2.00). Subjects with PAD rather than other CVD were associated with LEA at FDDFC. Patients with major LEA (above the ankle) at FDDFC episode had lower 5-year survival rate (65.01%) followed by those with minor LEA (72.24%) and without LEA (81.61%). Conclusions: Cardiovascular comorbidity as well as LEA status at the event of FDDFCs were both associated with patient survival outcomes. Earlier identification of this large population could lead to higher survival rates.

Nationwide trends in the epidemiology of diabetic foot complications and lower-extremity amputation over an 8-year period.

Objective: To study the prevalence and trends of lower extremity complications of diabetes over an 8-year period in a single nation. Research design and methods: Nationwide data for people with type 2 diabetes (T2D) and diabetic foot complications (DFCs) were analyzed over an 8-year period (2007-2014) from National Health Insurance Research Database using the International Classification of Diseases, Ninth Revision disease coding. The DFCs were defined as ulcers, infections, gangrene, and hospitalization for peripheral arterial disease (PAD). Trends of patient characteristics, foot presentation, and the execution of major procedures were studied, including lower-extremity amputations (LEAs). Results: Along with the T2D population increasing over time, the absolute number of people with DFCs increased by 33.4%, but retained a prevalence of around 2% per year. The annual incident of LEAs decreased from 2.85 to 2.06 per 1000 T2D population (p=0.001) with the major LEA proportion decreasing from 56.2% to 47.4% (p<0.001).The mean age of patients increased from 65.3 to 66.3 years and most of the associated comorbidities of diabetes were increased. For example, end-stage renal disease increased from 4.9% to 7.7% (p=0.008). The incidence of gangrene on presentation decreased from 14.7% to 11.3% (p<0.001) with a concomitant increase in vascular interventions (6.2% to 19.5%, p<0.001). Conclusions: DFCs remain a sustained major medical problem. These nationwide long-term data suggest trends toward older people with greater comorbidities such as PAD and renal disease. Nevertheless, promising trends of reducing gangrene on presentation paired with increases in vascular interventions support continued vigilance and rapid, coordinated interdisciplinary diabetic foot care.

Diabetic Foot Infection Presenting Systemic Inflammatory Response Syndrome: A Unique Disorder of Systemic Reaction from Infection of the Most Distal Body.

Diabetic foot infection (DFI) is a major complication of diabetic foot that lead to nontraumatic lower-extremity amputation (LEA). Such distal infection of the body having systemic inflammatory response syndrome (SIRS) is rarely reported. Consecutive patients treated for limb-threatening DFI in a major diabetic foot center in Taiwan were analyzed between the years 2014 to 2017. Clinical factors, laboratory data, perfusion, extent, depth, infection and sensation (PEDIS) wound score in 519 subjects with grade 3 DFI and 203 presenting SIRS (28.1%) were compared. Major LEA and in-hospital mortality were defined as poor prognosis. Patients presenting SIRS had poor prognosis compared with those with grade 3 DFI (14.3% versus 6.6% for major LEA and 6.4% versus 3.5% for in-hospital mortality). Age, wound size, and HbA1c were independent risk factors favoring SIRS presentation. Perfusion grade 3 (odds ratio 3.37, p = 0.044) and history of major adverse cardiac events (OR 2.41, p = 0.036) were the independent factors for poor prognosis in treating patients with DFI presenting SIRS. SIRS when presented in patients with DFI is not only limb- but life-threatening as well. Clinicians should be aware of the clinical factors that are prone to develop and those affecting the prognosis in treating patients with limb-threatening foot infections.

Amino acids and wound healing in people with limb-threatening diabetic foot ulcers.

BACKGROUND: Amino acids are associated with wound healing in traumatic wounds and burns, although their effects on healing in patients with diabetic foot ulcers (DFUs) are limited. This study aimed to evaluate and identify specific amino acids associated with healing outcomes of patients with DFUs. METHODS: Sixty-two out of 85 patients who completed the in-hospital treatment for limb-threatening DFUs were enrolled. All ulcers had epithelialization without clinical evidence of infection at discharge. The patients and their families were instructed on foot-care techniques and committed to regular follow-up for 1 year. Baseline characteristics, PEDIS wound classification, laboratory data and serum amino acid levels were used to analyze their predictive power. RESULTS: Fifty-seven patients completed the study in which 38 had healed and 19 had unhealed ulcers. The unhealed group had higher incidence of coronary artery disease and larger wound size. Most patients received endovascular therapy (81.6% healed group; 78.9% unhealed group) before enrollment. Following adjustments for clinical factors, the serum levels of arginine (326.4 µmol/L vs. 245.0 µmol/L, P = 0.045), isoleucine (166.7 µmol/L vs. 130.1 µmol/L, P = 0.019), leucine (325.8 µmol/L vs. 248.9 µmol/L, P = 0.039), and threonine (186.7 µmol/L vs. 152.0 µmol/L, P = 0.019) were significantly higher in the healed group. CONCLUSIONS: The amino acids associated with wound healing in DFUs differ from those reported for traditional traumatic wounds. These findings affirm the necessity for future large-scaled studies for the application of these amino acids in DFU healing, either as prognostic predictors or supplemented regimens.

The efficacy and safety of concentrated herbal extract granules, YH1, as an add-on medication in poorly controlled type 2 diabetes: A randomized, double-blind, placebo-controlled pilot trial.

BACKGROUND: In Asian countries, many patients with type 2 diabetes fail to achieve controlled glycated hemoglobin (HbA1c) levels while taking several classes of oral hypoglycemic agents (OHAs). Traditional Chinese medicine could be an alternative therapeutic option for poorly controlled type 2 diabetes. YH1 is a concentrated Chinese herbal extract formula that combines Rhizoma Coptidis and Shen-Ling-Bai-Zhu-San. This randomized, double-blind, placebo-controlled pilot study evaluated YH1 as an add-on medication for poorly controlled type 2 diabetes. METHODS: Forty-six patients with poorly controlled type 2 diabetes were randomly assigned 1:1 to the YH1 or placebo group. Before the trial, all subjects had received three or more classes of OHAs with HbA1c > 7.0% (53 mmol/mol) and a body mass index ≥ 23 kg/m2. During the 12-week trial, participants continued to take OHAs without any dose or medication changes. The primary endpoint was the percentage change in HbA1c level. Per-protocol analysis was applied to the final evaluation. RESULTS: At week 12, there was an 11.1% reduction in HbA1c from baseline and a 68.9% increase in homeostatic model assessment (HOMA) of ß cell function in the YH1 group, which also exhibited significant reductions in two-hour postprandial glucose (-26.2%), triglycerides (-29.5%), total cholesterol (-21.6%), low-density lipoprotein cholesterol (-17.4%), body weight (-0.5%), and waist circumference (-1.1%). The changes in fasting plasma glucose, HOMA insulin resistance and symptom scores were not significantly different between the YH1 and placebo groups. No serious adverse events occurred during this clinical trial. CONCLUSIONS: This pilot study indicates that YH1 together with OHAs can improve hypoglycemic action and ß-cell function in overweight/obese patients with poorly controlled type 2 diabetes. YH1 is a safe add-on medication for OHAs and has beneficial effects on weight control and lipid metabolism. A larger study population with longer treatment and follow-up periods is required for further verification.

A short-term follow-up of glycemic and body weight changes in diabetic patients who replaced dipeptidyl peptidase-4 inhibitors with the sodium-glucose cotransporter 2.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2is, gliflozins) are associated with lower all-cause mortality than other anti-diabetic agents in patients with type 2 diabetes. In patients who may benefit from SGLT2is, but cannot add them to a dipeptidyl peptidase-4 inhibitor (DPP4i, gliptin) treatment for various reasons, replacement of the DPP4i with a SGLT2i may be considered. OBJECTIVES: Evaluate changes in metabolic parameters in patients with diabetes after replacing a DPP4i with the SGLT2i empagliflozin. DESIGN: Panel study (cross-sectional and cohort hybrid). SETTING: The diabetes outpatient clinics of Chang Gung Memorial Hospital at Linkou, a university hospital in Taiwan. PATIENTS AND METHODS: We reviewed the medical records of patients who had been treated with anti-diabetic agents including a DPP4i between May 2016 and May 2017. Patients who switched from DPP4is to empagliflozin (switched-to-empagliflozin group) without changes to other anti-diabetic agents for at least 6 months were compared patients who continued taking an original antidiabetic agent. The body weight (BW), body mass index (BMI), and glycated hemoglobin (HbA1c) level at baseline and after 3 and 6 months were collected for analysis. MAIN OUTCOME MEASURES: BW, BMI, HbA1c at baseline, 3 and 6 months. SAMPLE SIZE: 236 patients. RESULTS: The HbA1c level and BMI of 110 patients (71%) in the switched-to-empagliflozin group were significantly reduced at 6 months after the switch, and there was a significant negative correlation between baseline HbA1c and change in HbA1c (rho=-0.537, P less than .001). In another 45 patients (29%) who switched to empagliflozin, HbA1c did not have improve, but BW decreased after the switch. No significant change in HbA1c occurred in the group that remained on DPP4is. In addition, BW and BMI decreased regardless of the degree of glucose reduction in the switched-to-empagliflozin group (P less than .001 for both variables at 6 months vs baseline), but not in the patients who remained on DPP4is. CONCLUSIONS: The study demonstrated the metabolic impact of switching from a DPP4i to a well-known SGLT2i, but further large-scale trials are needed to study the long-term effects of replacing a DPP4i with a SGLT2i. LIMITATIONS: Retrospective design, a short observation period, a small number of patients, no evaluations of the quality of life, side effects, or the cost, and data limited to only empagliflozin. CONFLICT OF INTEREST: No any relationship or support from the manufacturer of empagliflozin or other agents.

Antimicrobial resistance and outcomes of community-onset bacterial bloodstream infections in patients with type 2 diabetes.

OBJECTIVES: Antimicrobial resistance of bacterial pathogens in the diabetic population with infection is seldom investigated. This study evaluated the antimicrobial resistance and outcomes of community-onset bloodstream infections (CO-BSIs) in patients with diabetes. METHODS: From 2007-2014, 1271 monomicrobial CO-BSIs and 178 polymicrobial CO-BSIs were identified in patients with type 2 diabetes from three teaching hospitals in Taiwan. Antimicrobial-resistant strains of the ten most prevalent bacterial pathogens in monomicrobial CO-BSIs were recorded and were defined according to individual drug resistance. The 30-day mortality rate and factors associated with outcome were analysed. RESULTS: Antimicrobial-resistant strains were found in 33.7% (379/1125) of monomicrobial CO-BSIs involving the 10 most prevalent pathogens. The leading pathogens in these monomicrobial CO-BSIs were Staphylococcus spp. (33.8%; 430/1271), Escherichia coli (20.9%; 266/1271) and Klebsiella spp. (9.6%; 122/1271); antimicrobial-resistant strains accounted for 61.9%, 18.4% and 10.7% of each, respectively. A higher overall 30-day mortality rate was observed for patients infected by antimicrobial-resistant strains compared with antimicrobial-susceptible strains (9.5% vs. 5.5%; P=0.011, log-rank test). A lower serum albumin level was a predictor of mortality after adjusting for antimicrobial-resistant strains and C-reactive protein level. CONCLUSIONS: Antimicrobial-resistant bacterial pathogens pose a serious threat to diabetic patients with CO-BSIs owing to a higher risk of mortality.

Effect of limb preservation status and body mass index on the survival of patients with limb-threatening diabetic foot ulcers.

AIMS: To evaluate the effect of limb preservation status and body mass index (BMI) on the survival of patients with diabetic foot ulcers (DFUs). METHODS: A total of 1346 patients treated for limb-threatening DFUs at a major diabetic foot center in Taiwan from 2002 to 2009 were tracked until December 2012. The patients were classified into three groups: limb-preserved (n=858), minor lower-extremity amputation (LEA) (n=249), and major LEA (n=239). Clinical data during treatment were used for survival analysis. RESULTS: With 729 deaths, the median survival time (MST) was 6.14 (95% CI 5.63-6.65) years. Major LEA and BMI were two independent factors associated with mortality after adjusting for age, diabetic duration, HbA1c level, comorbidities and peripheral artery diseases. The mortality hazard ratios for the minor and major LEA groups were 0.92 (95% CI 0.74-1.16) and 1.34 (95% CI 1.07-1.68), respectively, to the reference group (limb-preserved). After stratifying BMI into four categories (underweight, normal weight, overweight and obesity, according to the Taiwanese definition), the MSTs for each category were 2.57, 5.24, 7.47 and 7.85years, respectively (P for trend <0.01). This "obesity paradox" was not observed in the major LEA group (P for trend 0.25). For patients with LEA, the obesity patients had lower MST than those in overweight category (7.97 and 8.84 in minor and 3.25 and 5.42 in major LEA, respectively). CONCLUSIONS: For the patients treated for DFUs, major - but not minor - LEA was associated with poor survival compared with the limb-preserved group. The MST had positive correlation with BMI levels for patients with limb-preserved and minor LEA, but not for those with major LEA.

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

AIMS/INTRODUCTION: To investigate the effect of pitavastatin on glucose control in patients with type 2 diabetes. MATERIALS AND METHODS: Medical records of 340 patients with type 2 diabetes treated with pitavastatin or atorvastatin between 1 August 2013 and 31 May 2014 were reviewed. A total of 96 patients who had not received statins were treated with pitavastatin (N to P group). A total of 100 patients who had previously used atorvastatin were switched to pitavastatin (A to P group). A total of 144 patients continued with atorvastatin treatment. Data were collected at baseline, 3 and 6 months of treatment. Changes in glycated hemoglobin (HbA1c) level were analyzed in 222 patients who did not change their antidiabetic agent during 6 months of treatment. RESULTS: A negative correlation between baseline HbA1c and delta HbA1c at 6 months was found in the pitavastatin-treated patients (N to P group: ρ = -0.329, P = 0.006; A to P group: ρ = -0.480, P < 0.001). The correlation remained similar after adjusting for age, body mass index, dose of pitavastatin, estimated glomerular filtration rate and high-density lipoprotein cholesterol. After 6 months of treatment, the benefit of pitavastatin on HbA1c in the patients with poorly controlled diabetes was significant in both the N to P (8.1 vs 7.4%, P = 0.018) and A to P (9.7 vs 9.0%, P = 0.015) groups. CONCLUSIONS: Pitavastatin decreases HbA1c in patients with type 2 diabetes with a higher baseline HbA1c level. The benefit on HbA1c was also observed in patients with previous use of atorvastatin.

The impact of nutritional status on treatment outcomes of patients with limb-threatening diabetic foot ulcers.

AIM: This study aimed to investigate the nutritional status of patients with limb-threatening diabetic foot ulcers (DFUs) and its impact on treatment outcomes. METHODS: A total of 478 consecutive patients (mean age, 65.4years) treated for limb-threatening DFUs were enrolled. Nutritional status assessment using the Mini Nutritional Assessment (MNA) and Geriatric Nutritional Risk Index (GNRI) was performed by three qualified dieticians within 48hours of admission. Limb-preservation outcomes were stratified into major lower extremity amputation (LEA) (above the ankle, n=33), minor LEA (distal to ankle, n=117) and no amputation (non-LEA, n=328). RESULTS: Most patients were identified as being at risk of malnutrition (70.5%) or malnourished (14.6%) (mean MNA score, 20.6±3.4). MNA scores decreased with increasing severity of LEA (mean, 21.1, 20.0, and 17.9, respectively; P for linear trend <0.001), associated inversely with the tendency to require LEA (P for linear trend was 0.001), and associated independently with both major and minor LEA outcomes (adjusted odds ratio [aOR]=0.80, 95% confidence interval [CI], 0.65-0.99, P=0.042 and aOR=0.89, 95% CI, 0.80-0.99, P=0.032, respectively). The predictive value was sustained in patients younger than age 65years. Though GNRI results had similar associations with outcomes, its predictive value was limited in minor LEA and younger population. CONCLUSIONS: Patients' nutritional status was shown to have significant influence on limb-preservation outcomes for limb-threatening DFUs. Nutritional assessment of this patient population using the MNA is recommended.

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

Patients 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.

Risk factors for in-hospital mortality in patients with type 2 diabetes complicated by community-acquired Klebsiella pneumoniae bacteremia.

BACKGROUND/PURPOSE: Patients with diabetes are at a high risk of infection-related morbidity and mortality. Klebsiella pneumoniae bacilli are prevalent among diabetic patients, especially in Asian populations. The present study aimed to identify risk factors for in-hospital mortality among diabetic patients complicated by community-acquired K. pneumoniae bacteremia. METHODS: We evaluated the clinical characteristics of 341 Taiwanese type 2 diabetic patients who were treated for community-acquired K. pneumoniae bacteremia. We then analyzed outcome predictors, and in particular comorbidities and the site of infection. RESULTS: The overall in-hospital mortality rate was 14.1%. Comorbid cancer was the leading factor, accounting for 32.1% of all cases of mortality. Pulmonary infection, primary bacteremia, afebrile or shock presentation and low serum albumin level were risk factors for in-hospital mortality. Regardless of comorbidities, pulmonary infection [odds ratio (OR) 10.74, 95% confidence interval (CI) 2.02-57.09] and albumin level (OR 0.15, 95% CI 0.03-0.76) were the main risk predictors. The receiver operating characteristic curve indicated that a serum albumin level lower than 2.4 g/dL (71.1% sensitivity and 77.4% specificity) suggested a poor prognosis in the diabetic patients with K. pneumoniae bacteremia. In patients with pulmonary infection, the capsular serotypes of K. pneumoniae were not related to poor outcomes, and an initial presentation of blunted fever or shock were independent factors for mortality. CONCLUSION: Cancer, pulmonary infection, and low serum albumin levels were independent indicators of in-hospital mortality in the diabetic patients complicated by K. pneumoniae bacteremia. The sites of infection and host characteristics should always elicit medical attention when treating these patients.

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.

High-fat diet aggravates islet beta-cell toxicity in mice treated with clozapine.

BACKGROUND: Clozapine, an atypical antipsychotic drug, induces derangements in glucose homeostasis in certain patients. This study investigated the mechanisms of clozapine-induced beta-cell toxicity. METHODS: Fifty-two healthy C57BL/6 male mice were randomized into 4 groups to study the effects of clozapine (group C, D) and a high-fat diet (group B, D). Three mice from each group were randomly selected to determine the amount of food intake on days 8-10, and their pancreases were removed for histological examination on day 11. The remaining 10 mice in each group were sacrificed at the 8th week to measure pancreatic insulin content (PIC). RESULTS: Mice given clozapine for 8 weeks demonstrated trends of lower PIC. The histological examination of the pancreases retrieved on day 11 already revealed apoptotic changes and suppression of cell proliferation. Although mice fed high-fat chow gained weight, mice given both clozapine and a high-fat diet showed less weight gain and more severe histological deterioration, and had the lowest PIC levels of the 4 groups. CONCLUSION: Pancreatic beta-cell apoptosis, suppression of cell proliferation, and trends of reduction in pancreatic insulin content were observed in mice taking clozapine. The findings of clozapine induced beta-cell toxicity were further aggravated when mice were concomitantly fed a high-fat diet.