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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).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.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.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.

Summary: Background: Strong evidence has shown that metabolic surgery is more effective than medical treatment in the treatment of type 2 diabetic patients. However, no study demonstrated a survival benefit and reduction of diabetes-related end-organ damage. Here, we describe the study design of a large prospective cohort study, the Taiwan Diabesity Study (TDS) which would compare the long-term survival rate and end-organ damage between overweight/obese type 2 diabetic patients receiving metabolic surgery and medical treatment. Methods: Eligibility criteria include type 2 diabetic patients with duration > 6 months, body mass index (BMI) over 25 kg/m2 and age between 20 and 67 years. Exclusion criteria are serum creatinine over 2.0 mg/dL, C-peptide below 1.0 ng/ml, recent history of cancer, and major diabetic complications. Eligible participants were recruited from six medical centers in Taiwan. The survival rate and diabetes-related end organ damage will be compared between the metabolic surgery group and medical group after follow-up for 10 years. Results: In 3 years, 1016 participants were identified from 38,751 patients. The average BMI of patients was 30.6 (±2.6) kg/m2 and the average hemoglobin A1c was 8.2% (±1.5%) with 18% of them receiving insulin treatment. Among them, 126 patients received metabolic surgery and 890 patients received conventional medical treatment. The metabolic surgery group are younger, have a higher proportion of females, higher BMI and blood lipids as compared to the medical group. Conclusion: The TDS recruited 1016 overweight/obese type 2 diabetic patients including 126 patients receiving metabolic surgery and 890 patients receiving medical treatment. Keywords: Type 2 diabetes mellitus, Obesity, Diabesity, Metabolic surgery, Bariatric surgery, Recruitment

This retrospective study investigated the risk factors of sodium-glucose cotransporter 2 inhibitors (SGLT2i) -related genitourinary tract infection (GUTI).We used longitudinal claims data from May 2016 to December 2017 from the Chang Gung Research Database. Diabetic patients who used SGLT2i were included. The baseline characteristics risk factors between patients who had GUTI and no GUTI were analyzed.There were 428(3.43%) patients with the first occurrence of urinary tract infection (UTI) and 5(0.04%) patients with genital tract infection (GTI). Female patients aged ≥ 65 years with HbA1c ≥ 9%, eGFR 60 ml/min/1.73 mIn diabetic patients who had underlying disease of eGRF 45 ml/min/1.73 m

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.

AimsTo evaluate the effect of limb preservation status and body mass index (BMI) on the survival of patients with diabetic foot ulcers (DFUs).MethodsA 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.ResultsWith 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

This study aimed to investigate the nutritional status of patients with limb-threatening diabetic foot ulcers (DFUs) and its impact on treatment outcomes.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).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 trend0.001), 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.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.

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.

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.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 eGFR60, 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.Forty-two percent of patients with eGFR60 presented with ABI≤0.90. For ABI values1.40, the proportion of dialysis patients (31.3%) was greater than the proportion of patients with eGFR60 (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.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.

Background/Purpose Despite availability of effective antihypertensives, blood pressure (BP) control is usually inadequate. The Reasons for not Intensifying Antihypertensive Treatment (RIAT) registry evaluated the reasons behind not modifying treatment in an international, cross-sectional study in 16 countries. Methods and results The Taiwanese cohort of RIAT consisted of 8922 patients with untreated/uncontrolled essential hypertension recruited from 22 centers in the country. At the first visit, physicians selected target BP and antihypertensive treatment, and at the next three visits they measured BP and modified treatment/provided justification for not modifying treatment. Mean target BP selected by physicians was 134.6/84.6 ± 5.1/5.0 mmHg, respectively. Patients’ individual risk stratification determined the BP goals. More patients achieved targets according to the physicians’ opinion than based on actual BP measurements: visit 2–50.6% vs. 48.6%; visit 3–58.4% vs. 55.2%; and visit 4–61.2% vs. 57.0%. At each visit, treatment remained unchanged for >60% patients not reaching target; the most common reason for this at visit 2 was the assumption that the time was too short to assess new drug therapy and at visits 3 and 4 was the assumption that target was reached/had almost been reached. Conclusion About 40% Taiwanese hypertensive patients in RIAT did not reach BP targets after an average of 4 months’ follow-up. The most common reason for not modifying treatment was the assumption that the target had been reached or had almost been reached.

Studies indicate that environmental exposure to lead is associated with reduced renal function. Whether lead affects progressive diabetic nephropathy is unclear. Eighty-seven patients with type II diabetes and diabetic nephropathy (serum creatinine of 1.5-3.9 mg/dl) with normal body lead burden and no lead exposure history were observed over a 12-month period. Thirty subjects with high normal body lead burdens (80-600 microg) were randomly assigned to a chelation and control group. For 3 months, the 15 chelation-group patients underwent lead-chelation therapy with calcium disodium ethylenediaminetetraacetic acid weekly until body lead burden fell60 microg, and the 15 control group subjects received a weekly placebo. During the following 12 months, renal function was regularly assessed at 3-month intervals. The primary outcome was an elevation of serum creatinine to 1.5 times baseline value during the observation period. A secondary outcome was temporal changes in renal function following chelation therapy. Twenty-six patients achieved the primary outcome. Basal blood lead levels and body lead burden were the most important risk factors in predicting progressive diabetic nephropathy. Following chelation, the rates of decline in glomerular filtration rates in the chelation group and the control group, respectively, were 5.0+/-5.7 ml and 11.8+/-7.0 ml/min/year/1.73 m(2) of body surface area (P=0.0084) during follow-up, although both groups had similar rates of progression of renal function during the 12-month observation period. We concluded that low-level environmental lead exposure accelerates progressive diabetic nephropathy and lead-chelation therapy can decrease its rate of progression.

Objective: Comparison of an aggressive approach (including total mesorectal excision and combined modality adjuvant therapy) with a conventional approach in the treatment of primary rectal cancer. Design: Retrospective study. Setting: Memorial Sloan-Kettering Cancer Centre, New York (MSKCC) and University Hospital Leiden, the Netherlands (UHL). Subjects: One hundred and sixty-nine patients treated at MSKCC and 96 patients treated at UHL. Interventions: Total mesorectal excision (MSKCC) and conventional resection (UHL). Main outcome measures: Overall survival and local recurrence-free survival. Results: Five-year overall survival was 73% for MSKCC patients and 52% for UHL patients [ P P = 0.001). Relative risk of dying or developing a local recurrence was 3.37 and 2.61, respectively, for patients treated at UHL compared to patients treated at MSKCC ( P P = 0.008, respectively). Conclusions: These data suggest that an aggressive approach including total mesorectal excision and combined modality adjuvant therapy improves survival and local control compared to a conventional approach.

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.