Efstratios Maltezos

Mean platelet volume in patients with type 2 diabetes mellitus

Aim of the study: To evaluate mean platelet volume (MPV) in type 2 diabetic versus non-diabetic patients, as well as to investigate the associations between MPV and diabetic complications. Materials and methods: This study included 416 patients divided into two groups. Group A comprised 265 type 2 diabetic patients (131 men) with a mean age of 67.4 ± 9.5 years and a mean diabetes duration of 14.5 ± 5.7 years. Group B comprised 151 non-diabetic patients (74 men) with a mean age of 68.6 ± 9.1 years. MPV (blood samples anticoagulated with sodium citrate) was measured in two blood cell counters (Sysmex SF 3000 and Cell-Dyn 3700). Results: MPV was significantly higher (P = 0.01) in group A (14.2 ± 2.2 fl) than in group B (7.1 ± 1.2 fl). In group A MPV was significantly higher (P = 0.043) in patients with retinopathy (15.8 ± 1.3 fl) than in patients without retinopathy (10.9 ± 1.1 fl) and also significantly higher (P = 0.044) in patients with microalbuminuria (15.6 ± 1.2 fl) than in patients without microalbuminuria (10.1 ± 1.2 fl). No association, however, was found in group A between MPV and age, gender, duration of diabetes, insulin dependency, BMI, HbA1c, coronary artery disease or dyslipidaemia. Conclusions: MPV is higher in type 2 diabetic patients than in non-diabetic patients. Among type 2 diabetic patients MPV is higher in those who have microvascular complications (retinopathy or microalbuminuria).

A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon.

BACKGROUND Observational evidence suggests that the use of a genotype-guided dosing algorithm may increase the effectiveness and safety of acenocoumarol and phenprocoumon therapy. METHODS We conducted two single-blind, randomized trials comparing a genotype-guided dosing algorithm that included clinical variables and genotyping for CYP2C9 and VKORC1 with a dosing algorithm that included only clinical variables, for the initiation of acenocoumarol or phenprocoumon treatment in patients with atrial fibrillation or venous thromboembolism. The primary outcome was the percentage of time in the target range for the international normalized ratio (INR; target range, 2.0 to 3.0) in the 12-week period after the initiation of therapy. Owing to low enrollment, the two trials were combined for analysis. The primary outcome was assessed in patients who remained in the trial for at least 10 weeks. RESULTS A total of 548 patients were enrolled (273 patients in the genotype-guided group and 275 in the control group). The follow-up was at least 10 weeks for 239 patients in the genotype-guided group and 245 in the control group. The percentage of time in the therapeutic INR range was 61.6% for patients receiving genotype-guided dosing and 60.2% for those receiving clinically guided dosing (P=0.52). There were no significant differences between the two groups for several secondary outcomes. The percentage of time in the therapeutic range during the first 4 weeks after the initiation of treatment in the two groups was 52.8% and 47.5% (P=0.02), respectively. There were no significant differences with respect to the incidence of bleeding or thromboembolic events. CONCLUSIONS Genotype-guided dosing of acenocoumarol or phenprocoumon did not improve the percentage of time in the therapeutic INR range during the 12 weeks after the initiation of therapy. (Funded by the European Commission Seventh Framework Programme and others; EU-PACT ClinicalTrials.gov numbers, NCT01119261 and NCT01119274.).

Hypoxia inducible factor 1α and 2α overexpression in inflammatory bowel disease

Aims: Hypoxia inducible factors 1α and 2α (HIF1α and HIF2α) are hypoxia regulated transcriptional factors, which control the expression of a variety of genes responsible for angiogenesis, glycolysis, and the inhibition of apoptosis. Because angiogenesis and tissue regeneration are integral components of the inflammatory process, this study was designed to investigate the role of HIFα molecules in inflammatory bowel disease. Methods: Surgical specimens from patients with active ulcerative colitis (UC) and Crohn’s disease (CD) were assessed immunohistochemically for HIF1α and HIF2α reactivity, and the expression of these molecules was compared with the expression of the angiogenic factors thymidine phosphorylase (TP), vascular endothelial growth factor (VEGF), and VEGF–KDR activated vasculature. The vascular density of the lesions was also assessed using anti-CD31 immunostaining. Results: HIF1α was expressed focally (epithelial cells, stromal fibroblasts, and myocytes) in both UC and CD, whereas HIF2α was expressed focally in UC and diffusely in CD. TP expression was uniformly positive in both diseases. VEGF expression was absent in CD, and weakly positive in UC. The VEGF–KDR reactivity of the submucosal vasculature was only slightly increased in UC and CD compared with normal tissue. The inflammatory cells stained with HIF2α and TP in all cases, but the reactivity was generalised in CD and focal in UC. In both diseases, vascular density was significantly higher than that seen in normal tissue. Conclusions: The discordant expression of HIF2α and VEGF in CD suggests an inherent deficiency of the intestine to respond to various stresses by the induction of VEGF. This finding should be investigated further.

Evaluation of a Multisensor Armband in Estimating Energy Expenditure in Obese Individuals

Objective: To examine the reliability and validity of the SenseWear Pro 2 Armband (SWA; Body Media, Pittsburgh, PA) during rest and exercise compared with indirect calorimetry (IC) in obese individuals.

Growth Factors in the Treatment of Diabetic Foot Ulcers: New Technologies, Any Promises?

Foot ulcers remain a common problem, leading to increased morbidity in patients with diabetes. Despite the progress that has been achieved in revascularization techniques as well as in off-loading to relieve high-pressure areas, diabetic foot wounds remain a clinical challenge. Growth factors are a major technological advance that promised to change the face of wound healing. The most important of growth factors are recombinant human platelet-derived growth factor-BB and granulocyte colony-stimulating factor. The former has been approved by the FDA for the treatment of neuropathic ulcers when there is adequate blood supply. The latter is less demonstrably useful. Advances include methods of delivering growth factors.

A prospective study of the diagnostic utility of sputum Gram stain in pneumonia

INTRODUCTION Sputum Gram stain and culture have been said to be unreliable indicators of the microbiological diagnosis of bacterial pneumonia. The etiological diagnosis of pneumonia is surrounded by great degree of uncertainty. This uncertainty should be and can be calculated and incorporated in the diagnosis and treatment. STUDY OBJECTIVES To determine the diagnostic accuracy and diagnostic value of sputum Gram stain in etiological diagnosis and initial selection of antimicrobial therapy of bacterial community acquired pneumonia (CAP). DESIGN-METHOD: Prospective study of 1390 patients with CAP admitted January 2002-June 2008, to our institutions. Of the 1390 patients, 178 (12.8%) fulfilled the criteria for inclusion into this study (good-quality sputa and presence of the same microorganism in blood and sputum cultures which was used as gold standard for assessing the diagnostic accuracy and diagnostic value of sputum Gram stain). RESULTS The sensitivity of sputum Gram stain was 0.82 for Pneumococcal pneumonia, 0.76 for Staphylococcal pneumonia, 0.79 for Haemophilus influenzae pneumonia and 0.78 for Gram-negative bacilli pneumonia. The specificity of sputum Gram stain was 0.93 for Pneumococcal pneumonia, 0.96 for Staphylococcal pneumonia, 0.96 for H. influenzae pneumonia and 0.95 for Gram-negative bacilli pneumonia. The positive likelihood ratio (LR+) was 11.58 for Pneumococcal pneumonia, 19.38 for Staphylococcal pneumonia, 16.84 for H. influenzae pneumonia, 14.26 for Gram-negative bacilli pneumonia. The negative likelihood ratio (LR-) was 0.20 for Pneumococcal pneumonia, 0.25 for Staphylococcal pneumonia, 0.22 for H. influenzae pneumonia, and 0.23 for Gram-negative bacilli pneumonia. CONCLUSIONS Sputum Gram stain is a dependable diagnostic test for the early etiological diagnosis of bacterial CAP that helps in choosing orthological and appropriate initial antimicrobial therapy.

Mean Platelet Volume and Platelet Distribution Width in non-diabetic subjects with Obstructive Sleep Apnoea Syndrome: New indices of severity?

Aim of the study: To evaluate Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) in non-diabetic subjects, according to obstructive sleep apnoea syndrome (OSAS) severity and the associations of these indices with anthropometric characteristics and parameters of breathing function during sleep. Materials and methods: We included 610 non-diabetic subjects with suspected OSAS, evaluated by polysomnography. According to their apnoea-hypopnoea index (AHI), patients were divided into Group A (n = 148) with AHI < 5/h; Group B (n = 121) with AHI: 5–14.9/h; Group C (n = 85) with AHI: 15–29.9/h and Group D (n = 256) with AHI ≥ 30/h. MPV and PDW were measured using an automated blood cell counter. Results: MPV was significantly higher in group D (mean value 12.1 ± 1.3 fl) than in groups A (9.8 ± 1.1 fl), B (9.8 ± 1.6 fl), and C (11.5 ± 1.3 fl) (p < 0.001). The same pattern was observed in PDW values (15.9 ± 2.2 fl for group D and 13.2 ± 2.2 fl for group A, 14.1 ± 2.8 fl for group B, and 15 ± 2.2 fl for group C, p < 0.001). Significant correlations were seen between MPV and AHI (p < 0.001), average pulse oxygen saturation (SpO2) (p < 0.001), minimum SpO2 (p < 0.001) and percent of the total sleep time with SpO2 lower than 90% (t < 90%) (p < 0.001) during sleep, Arousal Index (p < 0.001) and Epworth sleepiness scale (ESS) (p = 0.028). Similarly, PDW was correlated with AHI (p < 0.001), average SpO2 (p = 0.001), minimum SpO2 (p < 0.001), t < 90% (p = 0.002), and Arousal Index (p < 0.001). Conclusions: MPV and PDW are higher in non-diabetic patients with severe OSAS and are correlated with different parameters of breathing function during sleep.

Markers of glycemic control and insulin resistance in non-diabetic patients with Obstructive Sleep Apnea Hypopnea Syndrome: Does adherence to CPAP treatment improve glycemic control?

BACKGROUND AND AIM Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) is associated with glucose dysmetabolism and insulin resistance, therefore the amelioration of breathing disturbances during sleep can allegedly modify the levels of markers of glucose regulation and insulin resistance, such as glycated hemoglobin, fasting glucose, insulin and HOMA(IR). The aim of this study was to explore the association between these parameters and sleep characteristics in non-diabetic OSAHS patients, as well as the effect of 6 months CPAP therapy on these markers, according to adherence to CPAP treatment. METHODS Euglycemic patients (n=56; mean age+/-SD: 46.07+/-10.67 years) with newly diagnosed OSAHS were included. Glycated hemoglobin, fasting glucose, insulin levels and HOMA(IR) were estimated at baseline and 6 months after CPAP application. According to CPAP adherence, patients were classified as follows: group 1 (mean CPAP use 4 h/night), group 2 (mean CPAP use < 4 h/night) and group 3 (refused CPAP treatment), and comparisons of levels of the examined parameters were performed. RESULTS At baseline, average SpO(2) during sleep was negatively correlated with insulin levels and HOMA(IR) while minimum SpO(2) during sleep was also negatively correlated with insulin levels. After 6 months, only group 1 patients demonstrated a significant decrease in glycated hemoglobin (p=0.004) accompanied by a decrease in hs-CRP levels (p=0.002). No other statistically significant change was observed. CONCLUSIONS Nighttime hypoxia can affect fasting insulin levels in non-diabetic OSAHS patients. Good adherence to long-term CPAP treatment can significantly reduce HbA(1C) levels, but has no effect on markers of insulin resistance.

Association of −634G/C and 936C/T polymorphisms of the vascular endothelial growth factor with spontaneous preterm delivery

Background.  There is convincing evidence for a central role of vascular endothelial growth factor (VEGF) in fetal and placental angiogenesis. Our present study was undertaken to examine the possible relationship between two common functional VEGF gene polymorphisms (− 634G/C and 936C/T), linked with altered VEGF gene responsiveness, and spontaneous preterm delivery.

Benefit-Risk Assessment of Becaplermin in the Treatment of Diabetic Foot Ulcers

Becaplermin is a recombinant platelet-derived growth factor composed of two B chains that is approved for the treatment of neuropathic diabetic foot ulcers extending into or beyond the subcutaneous tissue in patients with adequate arterial perfusion. The aim of this review is to assess the benefits and risks associated with the use of this agent. Randomized controlled trials have provided evidence for the efficacy of becaplermin in increasing healing rates, and cost analyses have repeatedly shown a favourable cost-effectiveness ratio. However, clinical experience has not met these high expectations and becaplermin is not widely used. Moreover, this agent has not been compared with other additional treatment modalities, notably bioengineered skin substitutes and extracellular matrix proteins, and such comparisons are eagerly awaited. Of particular note, increased cancer risk has been reported in patients treated with more than three tubes of becaplermin; thus, this agent should be used only when the anticipated benefits outweigh the potential harm, and with extreme caution in patients with diagnosed malignancy. Finally, longer follow-up data are necessary to shed more light on the potential risk of malignancy in connection with becaplermin use.