Glycemia management in acute ischemic stroke: current concepts and novel therapeutic targets

Hyperglycemia on hospital admission is a common phenomenon in acute ischemic stroke patients and represents an independent predictor of poor clinical outcome with or without acute recanalization therapies (systemic thrombolysis or mechanical thrombectomy). Effective restoration of normoglycemia is considered to be beneficial, but conclusive evidence from randomized controlled clinical trials and specific recommendations are lacking. In addition, aggressive glucose control can be complicated by hypoglycemia leading to early neurological deterioration. We conducted a systematic literature review with the aim of addressing several questions: timing of glucose control, target range, type of insulin delivery, duration and practicability of glucose-lowering protocols. Special issues regarding mechanical thrombectomy and glycemic variability can then be investigated in future trials which are also being considered.     

Influence of interleukin 1alpha (IL-1alpha), IL-4, and IL-6 polymorphisms on genetic susceptibility to chronic osteomyelitis

The association between cytokine gene polymorphisms and chronic osteomyelitis was investigated in order to determine whether genetic variability in cytokine genes predisposes to osteomyelitis susceptibility. Significant genotypic and allelic associations were observed between interleukin 1α (IL-1α) −889-C/T, IL-4 −1098-G/T and −590-C/T, and IL-6 −174-G/C polymorphisms and osteomyelitis in the Greek population, pointing towards their potential involvement in osteomyelitis pathogenesis.     

Expression of nuclear factor-kappaB in human astrocytomas: relation to pI kappa Ba, vascular endothelial growth factor, Cox-2, microvascular characteristics, and survival

Although NF-kappaB has been reported to be constitutively activated in various neoplasms, little information is available about its clinical significance in astrocytomas. In this study, we investigated the association of NF kappa B1/p50 and pI kappa Ba immunohistochemical expression with clinicopathologic features, vascular endothelial growth factor, Cox-2, and microvascular parameters in paraffin-embedded tissue from 82 patients with astrocytomas. pI kappa Ba expression was positively correlated with nuclear (P = .0010) and negatively with cytoplasmic (P = .0008) NF kappa B1/p50 expression. Nuclear NF kappa B1/p50 and pI kappa Ba expression increased with tumor grade (P = .0001 and P < .0001). Nuclear NF kappa B1/p50 was associated with vascular endothelial growth factor (P = .0079), Cox-2 (P = .0500), and total vascular surface area (P = .0430), although the latter was significant only in grades II and III. pI kappa Ba was also positively correlated with microvessel caliber (pI kappa Ba/area; P = .0087). Multivariate analysis selected NF kappa B/p50 expression as an independent prognosticator not only for the entire cohort (P = .0220), but also for grades II and III (P = .0029) and grade IV cases (P = .0310). Our results suggest that nuclear NF kappa B1/p50 expression is dictated by its interaction with I kappa Ba in astrocytomas and is associated with tumor grade and angiogenic factors, denoting the importance of nuclear NF kappa B/p50 expression in patients' prognosis.     

Supracondylar process of the humerus: study on 375 Caucasian subjects in Cologne, Germany

This study documents the prevalence of the supracondylar process of the humerus in the Caucasian subjects in a German dissecting room along with its morphology, height, and site by using an electronic digimatic caliper. Seven hundred and fifty dried humeri from 375 Causcasian cadavers were examined at the Department of Anatomy in the University of Cologne, Germany. The supracondylar process was found in 10 out of the 750 (1.3%) dried humeri from 10 individuals (2.7%). In five of these 10 bones, the supracondylar process was in the form of a tubercle. In the others it was a spine of average height 9.5 mm (range, 7.7-12.3 mm). The average distance of the supracondylar process from the medial epicondyle was 59.8 mm, ranging between 40.5 and 79.0 mm. The supracondylar process was more common on the left humerus (90%) and in male subjects (60%) (both P < 0.01). None of the processes we observed was bilateral. Literature review indicated that the supracondylar process appears in 0.4-2% of Caucasians and in 0.2-2.8% of their humeri.     

Clinical significance of nuclear factor (NF)-κB levels in urothelial carcinoma of the urinary bladder

Nuclear factor (NF)-kappaB has been reported to be constitutively activated in various human neoplasms. However, its clinical significance in bladder urothelial carcinoma (UC) remains an unresolved issue. We conducted this study trying to elucidate the role of NFkappaB in bladder UC and its potential prognostic significance, by quantifying immunohistochemically the levels of p65/RelA expression in paraffin-embedded tissue from 116 patients. Some of the cases had previously been stained for cellular FLICE-like inhibitory protein (c-FLIP) and bcl-2. Seventy-four cases displayed concurrent cytoplasmic and nuclear immunoreactivity, whereas 18 only nuclear immunoexpression and 21 only cytoplasmic immunoexpression, and the remaining three cases were negative for p65/RelA. Nuclear p65/RelA expression was positively associated with tumour grade and T-category (p=0.0001 in both cases). In addition, cytoplasmic p65/RelA expression was lower in advanced T-category (p=0.0030). Moreover, p65/RelA nuclear expression was positively correlated with c-FLIP (p=0.0109) and bcl-2 (p=0.0452). p65/RelA nuclear expression adversely affected survival in both univariate and multivariate analysis in superficial (Ta-T1; p=0.0010 and p=0.0008) as well as in muscle-invasive carcinomas (T2-T4; p=0.0004 and p=0.0003). Our results demonstrate that NF-kappaB nuclear expression is correlated with histologic grade and T category in bladder UC. Moreover, NF-kappaB nuclear expression emerges as an independent prognosticator of adverse significance, conveying information beyond that obtained by standard clinicopathological prognosticators.     

Application of a loading dose of colistin methanesulfonate in critically ill patients: population pharmacokinetics, protein binding, and prediction of bacterial kill

A previous pharmacokinetic study on dosing of colistin methanesulfonate (CMS) at 240 mg (3 million units [MU]) every 8 h indicated that colistin has a long half-life, resulting in insufficient concentrations for the first 12 to 48 h after initiation of treatment. A loading dose would therefore be beneficial. The aim of this study was to evaluate CMS and colistin pharmacokinetics following a 480-mg (6-MU) loading dose in critically ill patients and to explore the bacterial kill following the use of different dosing regimens obtained by predictions from a pharmacokinetic-pharmacodynamic model developed from an in vitro study on Pseudomonas aeruginosa. The unbound fractions of colistin A and colistin B were determined using equilibrium dialysis and considered in the predictions. Ten critically ill patients (6 males; mean age, 54 years; mean creatinine clearance, 82 ml/min) with infections caused by multidrug-resistant Gram-negative bacteria were enrolled in the study. The pharmacokinetic data collected after the first and eighth doses were analyzed simultaneously with the data from the previous study (total, 28 patients) in the NONMEM program. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.026 and 2.2 h, respectively. For colistin, a one-compartment model was sufficient and the estimated half-life was 18.5 h. The unbound fractions of colistin in the patients were 26 to 41% at clinical concentrations. Colistin A, but not colistin B, had a concentration-dependent binding. The predictions suggested that the time to 3-log-unit bacterial kill for a 480-mg loading dose was reduced to half of that for the dose of 240 mg.     

Differential expression of hypoxia-inducible factor 1α in non-small cell lung cancer and small cell lung cancer

OBJECTIVES:

The aim of this study was to compare the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in small cell lung cancer and subtypes of non-small cell lung cancer and examine their relationships with clinicopathologic factors, response to treatment and survival.

METHODS:

We examined samples obtained by bronchial endoscopic biopsy from 55 patients with inoperable lung cancer (16 with adenocarcinoma, 17 with squamous cell carcinoma, and 22 with small cell lung cancer). Hypoxia-inducible factor 1α and vascular endothelial growth factor were detected using immunohistochemistry. The diagnosis, treatment, and follow-up of patients were conducted according to the standard practice.

RESULTS:

A significant difference (p = 0.022) in hypoxia-inducible factor 1α expression was observed between non-small cell lung cancer (75.8% positive) and small cell lung cancer (45.5% positive). The frequency of hypoxia-inducible factor 1α nuclear expression was 88.2% in squamous cell carcinoma, 62.5% in adenocarcinoma, and 45.5% in small cell lung cancer. A significant correlation was observed between hypoxia-inducible factor 1α and vascular endothelial growth factor expression (Fisher''s exact test, p = 0.001) when all types of lung cancer were examined, either collectively or separately.

CONCLUSIONS:

The expression of hypoxia-inducible factor-1α differs significantly between subtypes of lung cancer. These findings could help elucidate the biology of the different types of non-operable lung carcinomas and have implications for the design of new therapeutic approaches for lung cancer.     

Real time decision support system for diagnosis of rare cancers, trained in parallel, on a graphics processing unit

In the present study a new strategy is introduced for designing and developing of an efficient dynamic Decision Support System (DSS) for supporting rare cancers decision making. The proposed DSS operates on a Graphics Processing Unit (GPU) and it is capable of adjusting its design in real time based on user-defined clinical questions in contrast to standard CPU implementations that are limited by processing and memory constrains. The core of the proposed DSS was a Probabilistic Neural Network classifier and was evaluated on 140 rare brain cancer cases, regarding its ability to predict tumors' malignancy, using a panel of 20 morphological and textural features Generalization was estimated using an external 10-fold cross-validation. The proposed GPU-based DSS achieved significantly higher training speed, outperforming the CPU-based system by a factor that ranged from 267 to 288 times. System design was optimized using a combination of 4 textural and morphological features with 78.6% overall accuracy, whereas system generalization was 73.8%±3.2%. By exploiting the inherently parallel architecture of a consumer level GPU, the proposed approach enables real time, optimal design of a DSS for any user-defined clinical question for improving diagnostic assessments, prognostic relevance and concordance rates for rare cancers in clinical practice.