Predictors for limb loss among patient with diabetic foot infections: an observational retrospective multicentric study in Turkey.

We aimed to investigate the predictors for limb loss among patients with diabetes who have complicated skin/soft-tissue infections. In this observational study, consecutive patients with diabetic foot infection (DFI) from 17 centres in Turkey, between May 2011 and May 2013 were included. The Turkish DFI Working Group performed the study. Predictors of limb loss were investigated by multivariate analysis. In total, 455 patients with DFI were included. Median age was 61 years, 68% were male, 65% of the patients were hospitalized, 52% of the patients had used antibiotics within the last month, and 121 (27%) had osteomyelitis. Of the 208 microorganisms isolated, 92 (44.2%) were Gram-positive cocci and 114 (54.8%) were Gram-negative rods (GNR). The most common GNR was Pseudomonas; the second was Escherichia coli, with extended spectrum ß-lactamase positivity of 33%. Methicillin-resistant Staphylococcus species were found in 14% (29/208). Amputations were performed in 126/455 (28%) patients, 44/126 (34%) of these were major amputations. In multivariate analysis, significant predictors for limb loss were, male gender (OR 1.75, 95% CI 1.04-2.96, p 0.034), duration of diabetes >20 years (OR 1.9, 95% CI 1.18-3.11, p 0.008), infected ulcer versus cellulitis (OR 1.9, 95% CI 1.11-3.18, p 0.019), history of peripheral vascular disease (OR 2, 95% CI 1.26-3.27, p 0.004), retinopathy (OR 2.25, 95% CI 1.19-4.25, p 0.012), erythrocyte sedimentation rate >70 mm/hr (OR 1.6, 95% CI 1.01-2.68, p 0.05), and infection with GNR (OR 1.8, 95% CI 1.08-3.02, p 0.02). Multivariate analysis revealed that, besides the known risk factors such as male gender, duration of diabetes >20 years, infected ulcers, history of peripheral vascular disease and retinopathy, detection of GNR was a significant predictor of limb loss.

Prevalence of the DNA repair enzyme-NEIL1 gene mutation in patients with type 2 diabetes in the Turkish population.

In spite of the fact that an indirect relationship between NEIL1 gene and Type 2 diabetes has been demonstrated in animal model studies, there have been no human studies showing this relationship. In our study, we aimed to show the relationship between NEIL1 mutation and Type 2 diabetes in humans. The study group consisted 70 patients with Type 2 diabetes and the control group consisted of 50 healthy individuals. The mean age was 53±11 yr and 49±11 yr, respectively. Two NEIL1 mutations (2.9%) were detected in the patient group. There was A→G change (133A→G) at the 133. position of the 8th exon with 257 bp length in base sequencing. There was no mutation in the control group. We searched NEIL1 gene mutation for the first time in patients with Type 2 diabetes. This mutation was "silent" as it did not cause any amino acid change. The effects of these mutations on the etiopathogenesis of disease are not known. Although the lysine encoded by AAG was identical to the lysine encoded by AAA, it is not clear if they have functional differences due to the changing environmental conditions. NEIL1 gene mutation may have causative role in the development of Type 2 diabetes.

Hyperammonemic encephalopathy in a patient with primary hepatic neuroendocrine carcinoma.

A 53-year-old male patient was admitted to our hospital with abdominal pain in the right upper quadrant. There was no change in laboratory investigations other than a slight increase in serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT). Computed tomography (CT) of the abdomen showed multiple hepatic nodular lesions in the liver. Tru-cut biopsy of the lesions was reported as well-differentiated neuroendocrine carcinoma. The patient received sandostatin treatment. After a few days, the patient was hospitalized in the intensive care unit with disturbance of consciousness and clinical features suggestive of encephalopathy. Serum ammonia level was found highly elevated. After the treatment with L-ornithine-L-aspartate, a remarkable improvement in the level of patient's sensorium occurred as well as a reduction in serum ammonia level within a few days. Transarterial chemoembolization (TACE) was performed one week later. The patient's condition began to worsen along with increase in serum ammonia level and he died because of hyperammonemic encephalopathy. There are case reports of hyperammonemia with some malignancies such as multiple myeloma, plasma cell leukemia, and leiomyosarcoma, or in some patients who have received chemotherapy. This case may suggest an association between hyperammonemia and neuroendocrine tumors.

Plasma osteoprotegerin concentrations in type 2 diabetic patients and its association with neuropathy.

BACKGROUND AND AIMS: To investigate the association of plasma osteoprotegerin (OPG) levels with diabetic neuropathy. METHODS: Forty-two diabetic patients (21 female and 21 male) and twenty-four non-diabetic healthy control subjects (12 female and 12 male) were included in the study. All consecutive diabetic patients who came for routine follow-up at our outpatient clinic were invited to participate in this clinical study. We studied EMG and neuropathy symptom score in all study subjects. Fasting plasma glucose, HbA1 C, hs-CRP, OPG levels and lipid profile were measured for each subject. RESULTS: Serum fasting glucose, HbA1c, HOMA-IR, total cholesterol, triglyserid, LDL-Cholesterol, HDL-Cholesterol, lipoprotein (a), apolipoprotein-b, hs-CRP, OPG levels, and neuropathy symptom score were statistically higher in diabetic patients than in healthy control subjects. Plasma OPG levels was statistically higher in diabetic patients than it was in nondiabetic control subjects. However, plasma OPG levels were not significantly different between diabetic patients without neuropathy and healthy control subjects. On the other hand, OPG levels were statistically higher in diabetic patients with neuropathy than in patients without neuropathy. In addition to that serum fasting glucose, HbA1c, hs-CRP, diabetes duration, neuropathy symptom score were statistically higher in diabetic patients with neuropathy than they were in patients without neuropathy. In total group of subjects, plasma OPG levels were correlated significantly with age, diabetes duration, HbA1c, total cholesterol, HDL-cholesterol, lipoprotein (a), apolipoprotein b, hs-CRP. In diabetic patients, plasma OPG correlated significantly with age, diabetes duration, neuropathy symptom score, HbA1c, lipoprotein (a), apolipoprotein b levels. CONCLUSIONS: The major findings of this study were that the plasma OPG concentrations were higher in type 2 diabetic patients than OPG concentrations in healthy control subjects and they were positively correlated with diabetic neuropathy. This finding supports the growing concept that OPG acts as an important regulator in the development of vascular dysfunction in diabetes.

Necrotizing fasciitis: A life-threatening clinical disorder in uncontrolled type 2 diabetic patients.

We presented 23 patients with necrotizing fasciitis (NF), 15 of whom had uncontrolled diabetes mellitus (DM), for risk factors, clinical signs, laboratory findings and prognosis during the period 1998 and 2006 in Istanbul. A hospital incidence of NF was 14.2/100,000 admissions. Other risk factors were obesity in 9 and recent surgical trauma in 10 patients. The mean age of the patients with DM was higher than that of the patients with non-DM (58.6+/-12.8 vs 43.0+/-17.2 years, p=0.028). The most frequently isolated microorganisms from tissue cultures were Escherichia coli, Klebsiella pneumoniae and Group A streptococci. Of the 23 patients, 9 (39%), of whom 8 had DM, died between 2 and 29 days after admission. The mortality rate and length of hospitalization were longer in diabetic patients than in others (p=0.02 and p=0.286, respectively). The mean blood glucose levels and HbA1C were higher in non-survival group than in survival group (195.6+/-41.5 vs 133.7+/-22.1 and 10.6 vs 7.4) (p=0.04, r=0.39 and p=0.03, r=0.50, respectively). In the univariate analysis, the hospitalization time (r=0.72), white blood cell count (r=0.52) and surgical debridement count (r=0.47) were found to be prognostic risk factors. Our results showed that NF is a very serious life-threatening disorder in especially diabetic patients with bad metabolic control.

Comparison of the therapeutic efficacy of 4-methylpyrazole and N-acetylcysteine on acetaminophen (paracetamol) hepatotoxicity in rats.

Obtaining effective analgesia with a minimal erosive effect on gastric mucosal tissue has increased the consumption of acetaminophen (paracetamol), especially among the elderly. However, the hepatotoxic effects of acetaminophen have also increased. We aimed to compare the effects of 4-methylpyrazole (4-MP), N-acetylcysteine (NAC) and their combined use on the hepatotoxicity of acetaminophen in a rat model. Male Wistar Albino rats were divided into six groups. Groups 1-5 received 2,000 mg/kg acetaminophen by gavage while the control group was group 6. Group 2 animals were given NAC (loading dose 140 mg/kg followed by seven doses at 4 h intervals); group 3 received 50 mg/kg 4-MP; group 4 received 200mg/kg 4-MP; and group 5 received NAC as in group 2 plus 200 mg/kg 4-MP. Blood samples were taken for measurements of serum AST and ALT levels. The livers of the rats were removed for microscopic examination and grading of hepatic necrosis. AST and ALT levels in groups 2-5 were lower than that of group 1 (p < 0.001), although no significant difference was noted between groups 2-5 (p > 0.05). Higher levels of ALT were found in group 5 than in group 2 (p < 0.05), and higher levels of AST were found in group 5 than in group 3 (p < 0.01). Median necrosis scores were 3.36 for rats receiving acetaminophen alone (p < 0.001, compared with groups 2-6), 1.45-1.81 for groups 2-5 (p > 0.05, compared with each other), and 0.18 for control rats (p < 0.001, compared with groups 1-5). In conclusion, the administration of 4-MP and/or NAC after 4 h of administering toxic dose of acetaminophen, inhibits hepatotoxicity in rats. There was no difference between the 4-MP and NAC-treated groups as reflected by comparable levels of serum transaminases and the degree of hepatic necrosis. Combining of 4-MP and NAC offers no benefit.

Hospital-acquired infections following the 1999 Marmara earthquake.

In this study, medical records of all casualties admitted to our hospital following the Marmara earthquake, which struck northwest Turkey and resulted in the destruction of several towns in the Marmara region, were evaluated retrospectively. The time buried under the rubble, demographic data, type of medical and surgical therapies performed, type of injury and data on infection were analysed. Between 17 August and 25 September 1999, 630 trauma victims were received at our hospital and 532 (84%) of them were hospitalized. The mean age of hospitalized patients (312 males, 220 females) was 32 years (2-90 years). Two hundred and twenty patients were hospitalized for more than 48 h. Forty-one of them (18.6%) had 43 hospital-acquired infection (HAI) episodes, which were mostly wound infections (46.5%). A total of 143 culture specimens was collected and 48 yielded the following potential pathogens: 15 Acinetobacter baumanii (31.2%), nine Staphylococcus aureus (18.7%), seven Pseudomonas aeruginosa (14.6%), six Escherichia coli (12.5%), six Klebsiella pneumoniae (12.5%), two Stenotrophomonas maltophilia (4.2%) and three various Pseudomonas spp. (6.3%). All S. aureus strains were found to be resistant to methicillin in vitro. Two strains of A. baumannii and one P. aeruginosa were found to be resistant to all antimicrobials including carbapenems. Fifty-three victims died (10%) and 36 of those died during the first 48 h because of severe injuries and multi-organ failure. After 48 h of hospitalization, the mortality rate was significantly higher in those patients with HAI (14/41) than those without (3/179) (34.1% vs. 1.7%, P<0.05). In conclusion, trauma is the significant factor associated with HAI and a high incidence of Acinetobacter strains was responsible for HAI in trauma patients.

The effects of valsartan on insulin sensitivity in patients with primary hypertension.

Insulin resistance is an important risk factor of cardiovascular disease. This study was performed to determine the effects of valsartan on insulin sensitivity in patients with primary hypertension. In this study, non-obese subjects with primary hypertension and a reference group of healthy subjects matched by age, sex and body mass index were evaluated; patients with any other causes of peripheral insulin resistance and hyperlipidaemia were excluded. The effect of valsartan on insulin resistance, assessed by homeostasis model assessment (HOMA-IR), fasting serum insulin levels, determined by radioimmunoassay, and fasting blood glucose concentrations, measured by the glucose oxidase method, were evaluated. All obtained data were evaluated by Pearson correlation analysis. Before valsartan treatment, the fasting serum insulin levels were significantly elevated in the 20 hypertensive patients with primary hypertension compared with the 20 subjects in the reference group (19.6 +/- 7.1 versus 8.7 +/- 1.9 microIU/ml). The fasting serum insulin levels correlated with HOMA-IR. Correlation analysis also showed a significant relationship between HOMA-IR and both systolic and diastolic blood pressures (r = 0.71 and r = 0.77, respectively). In our study, we showed that patients with primary hypertension have a decreased insulin sensitivity that was reflected in high serum fasting insulin levels. Anti-hypertensive treatment with valsartan increases insulin sensitivity.