Laryngotracheal stenosis and restenosis. What has the influence on the final outcome?

The aim of this study is to analyze the impact of various parameters on the course and treatment outcome in patients with laryngotracheal stenosis and recurrent stenosis. Two groups of patients were compared: Group I included 29 patients with primary stenosis, and Group II included 22 patients with recurrent stenosis. The most frequent etiological factor for the development of stenosis was prolonged endotracheal intubation (79.3:77.3%), with subglottic-tracheal (44.8:45.5%) and tracheal (48.3:36.4%) localization being the most affected. Subglottic-tracheal stenosis was more common in men. There were no significant differences between the groups in regard to the grade of lumen obstruction and the length of the resected segment. In male patients, the length of the resected stenotic segment was significantly longer. Subglottic-tracheal stenoses were longer than tracheal ones. Various surgical procedures were performed, with additional management of recurrent laryngeal nerve paralysis, if necessary. Laryngotracheal reconstruction (LTR) with costal cartilage grafting (CCG) was statistically significantly more often performed in Group II, while cricotracheal resection (CTR) was more common in Group I. The incidence of complications in Group I was 24.1%, and in Group II it was 31.8%. Satisfactory airway lumen with undisturbed breathing was achieved in 93.1% of patients in Group I, and in 95.3% in Group II. Since the success rate was similar in both groups of the patients, it could be concluded that treatment outcome depends less on the factors associated with the stenosis, and more on adequate choice of surgical procedure and surgical team know-how.     

Vesicle-bound EBV-BART13-3p miRNA in circulation distinguishes nasopharyngeal from other head and neck cancer and asymptomatic EBV-infections

Cell-free microRNA (miRNA) in biofluids released by tumors in either protein or vesicle-bound form, represent promising minimally-invasive cancer biomarkers. However, a highly abundant non-tumor background in human plasma and serum complicates the discovery and detection of tumor-selective circulating miRNAs. We performed small RNA sequencing on serum and plasma RNA from Nasopharyngeal Carcinoma (NPC) patients. Collectively, Epstein Barr virus-encoded miRNAs, more so than endogenous miRNAs, signify presence of NPC. However, RNAseq-based EBV miRNA profiles differ between NPC patients, suggesting inter-tumor heterogeneity or divergent secretory characteristics. We determined with sensitive qRT-PCR assays that EBV miRNAs BART7-3p, BART9-3p and BART13-3p are actively secreted by C666.1 NPC cells bound to extracellular vesicles (EVs) and soluble ribonucleoprotein complexes. Importantly, these miRNAs are expressed in all primary NPC tumor biopsies and readily detected in nasopharyngeal brushings from both early and late-stage NPC patients. Increased levels of BART7-3p, BART9-3p and particularly BART13-3p, distinguish NPC patient sera from healthy controls. Receiver operating characteristic curve analysis using sera from endemic NPC patients, other head and neck cancers and individuals with asymptomatic EBV-infections reveals a superior diagnostic performance of EBV miRNAs over anti-EBNA1 IgA serology and EBV-DNA load (AUC 0.87–0.96 vs 0.86 and 0.66 respectively). The high specificity of circulating EBV-BART13-3p (97%) for NPC detection is in agreement with active secretion from NPC tumor cells. We conclude EV-bound BART13-3p in circulation is a promising, NPC-selective, biomarker that should be considered as part of a screening strategy to identify NPC in endemic regions.     

Genotype phenotype correlation in a pediatric population with antithrombin deficiency

Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the AT gene (SERPINC1). Considering that the genotype phenotype relationship in AT deficiency patients remains unclear, especially in pediatric patients, the aim of our study was to evaluate genotype phenotype correlation in a Serbian pediatric population. A retrospective cohort study included 19 children younger than 18 years, from 15 Serbian families, with newly diagnosed AT deficiency. In 21% of the recruited families, mutations affecting exon 4, 5, and 6 of the SERPINC1 gene that causes type I AT deficiency were detected. In the remaining families, the mutation in exon 2 causing type II HBS (AT Budapest 3) was found. Thrombosis events were observed in 1 (33%) of those with type I, 11 (85%) of those with AT Budapest 3 in the homozygous respectively, and 1(33%) in the heterozygous form. Recurrent thrombosis was observed only in AT Budapest 3 in the homozygous form, in 27% during initial treatment of the first thrombotic event. Abdominal venous thrombosis and arterial ischemic stroke, observed in almost half of the children from the group with AT Budapest 3 in the homozygous form, were unprovoked in all cases.

Conclusion: Type II HBS (AT Budapest 3) in the homozygous form is a strong risk factor for arterial and venous thrombosis in pediatric patients.

How much are children and their parents objective about the children's eating behaviour and body composition?

The primary objective of our research was to investigate the nutritional status in Belgrade schoolchildren (aged 12–15). The second objective was to compare the children and parents view about the children nutritional status. The study was carried out in two phases: (a) questionnaires for children and parents (questionnaire‐c and questionnaire‐p) were administrated; (b) anthropometrical measurement was conducted among children. There were 2263 participants, randomly chosen from seven Belgrade (Serbia and Montenegro) primary schools. At the end of the study, 1555 children completed the questionnaires and had been measured. According to our results, there were 18.1% boys and 11.3% girls who were overweight/obese. Children were more objective in estimating their nutritional status than their parents. Although the participants were offered free counselling, low response rate of only 4.71% was achieved, suggesting that parents should take an active and unbiased role in children's nutritional education. Copyright © 2006 John Wiley & Sons, Ltd and Eating Disorders Association.     

Glial response in the rat models of functionally distinct cholinergic neuronal denervations

Alzheimer's disease (AD) involves selective loss of basal forebrain cholinergic neurons, particularly in the nucleus basalis (NB). Similarly, Parkinson's disease (PD) might involve the selective loss of pedunculopontine tegmental nucleus (PPT) cholinergic neurons. Therefore, lesions of these functionally distinct cholinergic centers in rats might serve as models of AD and PD cholinergic neuropathologies. Our previous articles described dissimilar sleep/wake‐state disorders in rat models of AD and PD cholinergic neuropathologies. This study further examines astroglial and microglial responses as underlying pathologies in these distinct sleep disorders. Unilateral lesions of the NB or the PPT were induced with rats under ketamine/diazepam anesthesia (50 mg/kg i.p.) by using stereotaxically guided microinfusion of the excitotoxin ibotenic acid (IBO). Twenty‐one days after the lesion, loss of cholinergic neurons was quantified by nicotinamide adenine dinucleotide phosphate‐diaphorase histochemistry, and the astroglial and microglial responses were quantified by glia fibrillary acidic protein/OX42 immunohistochemistry. This study demonstrates, for the first time, the anatomofunctionally related astroglial response following unilateral excitotoxic PPT cholinergic neuronal lesion. Whereas IBO NB and PPT lesions similarly enhanced local astroglial and microglial responses, astrogliosis in the PPT was followed by a remote astrogliosis within the ipslilateral NB. Conversely, there was no microglial response within the NB after PPT lesions. Our results reveal the rostrorostral PPT‐NB astrogliosis after denervation of cholinergic neurons in the PPT. This hierarchically and anatomofunctionally guided PPT‐NB astrogliosis emerged following cholinergic neuronal loss greater than 17% throughout the overall rostrocaudal PPT dimension. © 2014 Wiley Periodicals, Inc.     

Serum activity of DPPIV and its expression on lymphocytes in patients with melanoma and in people with vitiligo

Background

Evidence is accumulating that chronic inflammation may have an important role in prostate cancer (PCa). The COX-2 polymorphism rs2745557 (+202 C/T) has been extensively investigated as a potential risk factor for PCa, but the results have thus far been inconclusive. This meta-analysis was performed to derive a more precise estimation of the association.

Methods

A comprehensive search was conducted to identify all case-control studies of COX-2 rs2745557 polymorphism and PCa risk. We used odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) give a sense of the precision of the estimate. Statistical analyses were performed by Review Manage, version 5.0 and Stata 10.0.

Results

A total of 8 available studies were considered in the present meta-analysis, with 11356 patients and 11641 controls for rs2745557. When all groups were pooled, there was no evidence that rs2745557 had significant association with PCa under co-dominant, recessive, over-dominant, and allelic models. However, our analysis suggested that rs2745557 was associated with a lower PCa risk under dominant model in overall population (OR = 0.85, 95%CI = 0.74-0.97, P = 0.02). When stratifying for race, there was a significant association between rs2745557 polymorphism and lower PCa risk in dominant model comparison in the subgroup of Caucasians (OR = 0.86, 95%CI = 0.75-0.99, P = 0.04), but not in co-dominant, recessive, over-dominant and allelic comparisons.

Conclusion

Based on our meta-analysis, COX-2 rs2745557 was associated with a lower PCa risk under dominant model in Caucasians.