Osteopontin levels in plasma, muscles, and bone in patient with non-healing diabetic foot ulcers: A new player in wound healing process?

BACKGROUND: The present study was designed to investigate the impact of osteopontin (OPN) in different tissue (e.g., plasma, muscles and bone) on amputation rate (in-hospital and during one year follow-up) for non-healing diabetic foot ulcers (DFUs). METHODS: This pilot study consisted of 30 diabetic patients, hospitalized due to non-healing DFUs. Patients were divided into two groups: Group 1 included 14 patients who underwent limb-preserved debridement procedure without amputation; Group 2 included 16 subjects who underwent amputation. Additionally, recurrent amputation rate during 1 year follow-up was investigated. RESULTS: Plasma OPN was higher and bone OPN was lower in Group 2 compared to Group 1 (p = 0.016 and p = 0.004, respectively). In the logistic regression analysis, bone OPN emerged as a significant independent predictor of amputation (OR = 0.042, 95% CI 0.003-0.699, p = 0.027). Plasma OPN was also associated with amputation such that each unit increase in plasma OPN was associated with an increase in odds of amputation of 17.7% (95% CI 0.997-1.388, p = 0.045). During 1 year follow-up 11 patients underwent recurrent amputation. Plasma OPN were higher and bone osteopontin was lower in patients who underwent amputation compared to patients who did not need amputation at one year follow-up. However, in GLM analysis bone OPN was only marginally associated with one year amputation (OR 0.001, 95% CI 0.000-2.0, p = 0.076). CONCLUSIONS: Decreased levels of OPN in bone and increased plasma OPN are independently associated with in-hospital amputation. Consequently, plasma OPN may be relevant in the routine assessment of amputation risk in this patient population.

Effect of short- and long-term diabetes control on in-hospital and one year mortality rates in hospitalized patients with diabetic foot.

INTRODUCTION: It remains unclear whether diabetic patients with diabetic foot complications benefit from strict glycemic control during hospitalization The present study investigates the effect of short- and long-term diabetes control on hospital outcomes including: in-hospital and one year mortality rates, length of hospital stay and the rate of repeated admissions. METHODS: Type 2 diabetic patients (n = 341) were hospitalized for diabetic foot complications at Wolfson Medical Center over a 5 year period (2008-2012). The adequate short-term glycemic control was defined as average glucose levels between 110 and 180 mg/dL. HbA1c values below 7% were defined as adequate long-term glycemic control. RESULTS: The average glucose levels during hospitalization were 179 ±â€¯45 mg/dL and 40% of the measurements were between 110 and 180 mg/dL. Mean admission HBA1c levels were 8.43% ±â€¯2.26%, and 31% of the values were below 7%. The mean length of hospital stay was 24.3 ±â€¯22.6 days, 15.0% of the patients needed surgical intervention during admission, the in-hospital mortality rate was 10.3%, and the rate of 1-year readmission was 25.1%. Adequate diabetes control during hospitalization was not significantly associated with reduced in-hospital mortality (hazard ratio, 0.454, 95% confidence interval 0.186-1.103, p = 0.081). However, adequate diabetes control during hospitalization lead to significantly decreased one year mortality (hazard ratio, 0.269, 95% confidence interval 0.707-0.101, p = 0.009). Adequate diabetes control during hospitalization did not affect the length of hospital stay or the rate of repeated admission. CONCLUSIONS: Improved glucose control during hospital admission (levels between 110 and 180 mg/dL) was associated with reduction of one year mortality.

Elevated ferritin and circulating osteoprotegerin levels as independent predictors of hip fracture in postmenopausal women admitted for fragility fracture: time for new screening strategies?

Identification of risk factors may help us to understand the pathogenesis of osteoporotic hip fracture as well as to formulate development of better diagnostic, prevention and treatment strategies. The present study was designed to determine the impact of multiple metabolic risk factors such as markers of systemic inflammation (C-reactive protein), immune responses-acute phase reactants (ferritin), insulin resistance (HOMA-IR) and bone remodeling (osteoprotegerin), for the prediction of hip fractures in postmenopausal osteoporotic women. The study group consisted of 115 postmenopausal women divided into two groups: Group 1 consisted of 49 women hospitalized in the Orthopedic Department, Wolfson Medical Center for the diagnosis of non-traumatic hip fracture and Group 2 contained 66 postmenopausal osteoporotic women without a history of hip fracture. Metabolic parameters were determined. Circulating OPG was significantly higher in Group 1 than in Group 2 (205.2 ± 177.1 vs 60.0 =/-22.3, p < 0.0001). While levels of hemoglobin (Hbg) as well as MCV and MCH did not differ between groups, circulating ferritin was significantly increased in Group 1 compared to the control Group 2 (217.9 ± 195.1 vs 49.7 ± 31.3, p < 0.0001). In multiple linear regression analysis, which explains about 40 % of the variability in CRP, 42 % in OPG, and 28 % in ferritin, significant by-group differences in terms of these parameters persisted even after adjustment. Elevated serum ferritin concentrations and bone remodeling marker, osteoprotegerin, are independent predictors of hip fracture in postmenopausal women hospitalized for fragility fracture.

Bone remodelling markers in hypertensive patients with and without diabetes mellitus: link between bone and glucose metabolism.

OBJECTIVE: Growing evidence suggests the presence of a complex interplay between hypertension as well as type 2 diabetes mellitus (DM) and osteoporosis. The present study was designed to investigate a possible effect of type 2 DM on bone remodelling markers such as osteoprotegerin and N-terminal propeptide of type 1 collagen (P1NP) in hypertensive patients. DESIGN AND METHODS: The 100 study participants were divided into three groups according to the presence of DM and hypertension: group one included diabetic hypertensive subjects, group 2 included hypertensive subjects without diabetes and group 3 included subjects without hypertension and without DM (controls). Blood sampling for metabolic parameters, including osteoprotegerin, P1NP, adiponectin, fasting glucose, HbA1c , CRP, homeostasis model assessment-insulin resistance, homeostasis model assessment-beta function was performed. RESULTS: Circulating P1NP increased from group 1 to group 3 in a continuous fashion. P1NP was significantly lower in hypertensive subjects with DM (group 1), than in groups 2 and 3 (p < 0.0001). P1NP, was marginally lower in diabetic hypertensive subjects as compared with nondiabetic subjects with hypertension (p = 0.079). Circulating osteoprotegerin did not differ significantly between groups (p = 0.593). CONCLUSIONS: In the present study, bone formation marker, P1NP, was significantly lower in diabetic hypertensive subjects as compared with nondiabetic subjects with and without hypertension. P1NP was inversely associated with parameters of glucose homeostasis such as fasting glucose, HbA1c and positively with homeostasis model assessment-beta cell function. Type 2 DM was associated with an adverse effect on bone formation independently of age, sex and exposure to anti-diabetic drugs.

Changes in the pattern of fractures of the hip in patients 60 years of age and older between 2001 and 2010: A radiological review.

The purpose of this study was to identify changing trends in the pattern of distribution of the type and demographics of fractures of the hip in the elderly between 2001 and 2010. A retrospective cross-sectional comparison was conducted between 179 fractures of the hip treated in 2001, 357 treated in 2006 and 454 treated in 2010. Patients aged < 60 years and those with pathological and peri-prosthetic fractures were excluded. Fractures were classified as stable extracapsular, unstable extracapsular or intracapsular fractures. The mean age of the 179 patients (132 women (73.7%)) treated in 2001 was 80.8 years (60 to 96), 81.8 years (61 to 101) in the 357 patients (251 women (70.3%)) treated in 2006 and 82.0 years (61 to 102) in the 454 patients (321 women (70.1%)) treated in 2010 (p = 0.17). There was no difference in the gender distribution between the three study years (p = 0.68). The main finding was a steep rise in the proportion of unstable peritrochanteric fractures. The proportion of unstable extracapsular fractures was 32% (n = 57) in 2001, 35% (n = 125) in 2006 and 45% (n = 204) in 2010 (p < 0.001). This increase was not significant in patients aged between 60 and 69 years (p = 0.84), marginally significant in those aged between 70 and 79 years (p = 0.04) and very significant in those aged > 80 years (p < 0.001). The proportion of intracapsular fractures did not change (p = 0.94). At present, we face not only an increasing number of fractures of the hip, but more demanding and complex fractures in older patients than a decade ago. This study does not provide an explanation for this change.

Concentrations of moxifloxacin in serum and synovial fluid, and ex vivo bactericidal activity against arthritis-causing pathogens.

Three doses of moxifloxacin 400 mg qd were administered orally to 20 candidates for knee arthroscopy (mean age, 71.2 years). The procedure was scheduled at four different points of time after the last dose: 2, 6, 12, and 24 h. Five patients were studied at each point of time. Drug levels were determined by the bioassay method. Bactericidal activity against four bacterial pathogens (two strains of each) was studied on serum and synovial fluid samples obtained during arthroscopy using the NCCLS guidelines. Mean (+/-S.D.) peak serum and synovial fluid concentrations were 3.46 +/- 0.78 mg/L and 3.42 +/- 0.51 mg/L, respectively. Levels above 1.0 mg/L were detected as long as 24 h. The peak bactericidal titers were (in serum and synovial fluid, respectively) 1:18.3 and 1:32 against Staphylococcus aureus, 1:18.3 and 1:22.6 against Streptococcus pyogenes, 1:45.2 and 1:64.0 against Klebsiella pneumoniae, and 1:2.3 and 1:1.7 against Pseudomonas aeruginosa. Bactericidal titers >1:2 were documented against the first three pathogens up to 24 h after dosing. On the basis of its pharmacokinetic and pharmacodynamic characteristics, moxifloxacin seems to be an excellent candidate for the treatment of joint infections, except those caused by P. aeruginosa.

Muscle imbalance in the aetiology of idiopathic club foot. An electromyographic study.

We performed electrophysiological studies on both legs of 52 children, aged from 3 months to 15 years, with idiopathic club foot. In only nine (17%) was no abnormality found. Isolated peroneal nerve damage was seen in 14 (27%). Abnormality of both peroneal and posterior tibial nerves was found in five (10%). Four patients (8%) had evidence of isolated spinal-cord dysfunction, whereas combined spinal-cord and peripheral-nerve lesions were seen in 14 (27%). Six patients (11%) had variable neurogenic electrophysiological patterns. In 13 patients in whom the studies were repeated neither progression nor improvement of the electrophysiological parameters was observed. Pathological electrophysiological findings were found in 66% of conservatively-treated patients. In the 43 patients treated surgically, all 16 with fair and poor results had pathological electrophysiological findings and 12 required further operations. Multiplicity of the pathological findings was related to the severity of the deformity of the foot; normal studies represent a good prognostic sign. Electrophysiological studies are useful in idiopathic club foot with residual deformities after conservative or operative treatment. Our findings support the theory that muscle imbalance is an aetiological factor in idiopathic club foot.

Clinical presentation of suspected carotid artery disease. Screening of candidates for arteriography with the assistance of the vascular laboratory.

The evaluation of suspected carotid artery disease was reviewed in a consecutive series of 292 patients referred by attending physicians in a university hospital. Twenty-three percent of the patients presented with classical transient ischemic attacks, and all those suitable for eventual surgery were recommended for arteriography. In 75% of the patients the presenting symptoms were nonlateralizing or equivocal. In this group the results of noninvasive vascular tests were decisive as to the recommendation for arteriography, which was positive in 79% of those performed. Among 100 surveyed patients who did not undergo arteriography, cerebrovascular accidents occurred in 3 patients: carotid disease was detected in 2 of them, in whom arteriography had been postponed for clinical reasons, while in the third a subsequent arteriography demonstrated no carotid lesion. Expert clinical assessment assisted by vascular studies prevented unnecessary arteriography in 62% and detected carotid pathology with atypical presentation in 13% of the patients.