European ST80 community-associated methicillin-resistant Staphylococcus aureus orbital cellulitis in a neonate

<p>Abstract</p> <p>Background</p> <p>Methicillin-resistant <it>Staphylococcus aureus</it> is a serious cause of morbidity and mortality in hospital environment, but also, lately, in the community. This case report is, to our knowledge, the first detailed description of a community-associated methicillin-resistant <it>S. aureus</it> ST80 orbital cellulitis in a previously healthy neonate. Possible predisposing factors of microbial acquisition and treatment selection are also discussed.</p> <p>Case presentation</p> <p>A 28-day-old Caucasian boy was referred to our hospital with the diagnosis of right orbital cellulitis. His symptoms included right eye proptosis, periocular edema and redness. Empirical therapy of intravenous daptomycin, rifampin and ceftriaxone was initiated. The culture of pus yielded a methicillin-resistant <it>S. aureus</it> isolate and the molecular analysis revealed that it was a Panton-Valentine leukocidine-positive ST80 strain. The combination antimicrobial therapy was continued for 42days and the infection was successfully controlled.</p> <p>Conclusions</p> <p>Clinicians should be aware that young infants, even without any predisposing condition, are susceptible to orbital cellulitis caused by community-associated methicillin-resistant <it>S. aureus.</it> Prompt initiation of the appropriate empirical therapy, according to the local epidemiology, should successfully address the infection, preventing ocular and systemic complications.</p

Association of (ALR2) gene polymorphisms with retinopathy and nephropathy of diabetes mellitus type 2

Diabetic retinopathy (DR) and diabetic nephropathy (DN) are serious chronic microvascular complication of both type 1 and type 2 diabetes mellitus. Various predisposing factors have already been identified but the pathogenesis is not yet fully elucidated. It was convincingly proved that the single most important factor in the development of these complications is hyperglycemia. However, is strong evidence for the involvement of genetic factors in its pathophysiology. The absence, however, of an absolutely effective therapy for all DR and DN patients necessitates a further investigation of the diabetic complication pathogenesis and a more thorough study of the problem as well, leading probably to the diabetic disease prevention. Not all diabetic patients develop DR or DN indicating specific genetically defined predisposing factors. Variants of the AKR1B1 gene are implicated in the development of both microvascular complications of diabetes. Thus, a candidate-gene association study was conducted to investigate the association between five AKR1B1 gene variants (rs2259458 G/T, rs2734653 G/A, rs2670230 C/A, rs1790998 C/A, rs17188118 A/C) to the progression of diabetes type 2 and the risk of diabetes leading to complications. The cohort consisted of 169 diabetic cases with microvascular complications, 107 diseased controls (diabetics without complications) and 315 healthy controls. The disease progression was tested using the generalized odds ratio (ORG) metric, a genetic model-free approach. The risk of diabetes leading to complications was tested using the ORs of the additive and co-dominant models. The mode of inheritance was assessed using the degree of dominance index (h-index). This study concluded that AKR1B1 gene is not implicated in disease progression. In investigating the association between the AKR1B1 variants and the risk of diabetes leading to complications, significant results was derived for the additive model of the variant rs2259458 G/T [OR= 1.87 (1.01-3.50)] and the co-dominant model of the variant rs2670230 C/A [OR=1.45 (1.01-2.04)]. The mode of inheritance (h-index) for the variants rs2259458 G/T and rs2670230 C/A were “non-dominance” and “dominance of allele A”, respectively. The frequencies of three haplotypes (T-G-A-C-A, G-G-C-C-A and G-A-C-C-A) were significantly different (P≤0.05) between cases and healthy controls. Genetic variation in AKR1B1 gene may alter susceptibility to diabetes leading to complications; though, it is not implicated in disease progression.Η διαβητική αμφιβληστροειδοπάθεια (ΔΑ) και η διαβητική νεφροπάθεια(ΔΝ) αποτελούν σοβαρές επιπλοκές του σακχαρώδη διαβήτη (ΣΔ) τύπου I και ΙΙ. Για τις μικροαγγειοπάθειες αυτές ποικίλοι προδιαθεσικοί παράγοντες έχουν ήδη αναγνωριστεί, αλλά η παθογένεια δεν είναι ακόμη εξολοκλήρου τεκμηριωμένη. Η απουσία, όμως, απόλυτα αποτελεσματικού θεραπευτικού χειρισμού στις περιπτώσεις ΔΑ και ΔΝ, σε όλους ανεξαιρέτως τους ασθενείς, επιβάλουν την περαιτέρω διερεύνηση της παθογένειας των επιπλοκών του ΣΔ και τη διεξοδική μελέτη του προβλήματος που πιθανόν να οδηγήσει στην πρόληψή του. Είναι γνωστό ότι τα αυξημένα επίπεδα γλυκόζης προκαλούν την ενεργοποίηση της μεταβολικής οδού των πολυολών, όπου η αναγωγάση της αλδόζης (ALR2) είναι το πρώτο και καθοριστικό ένζυμο ρυθμού και φαίνεται να εμπλέκεται στην παθογένεια των διαβητικών μικροαγγειακών επιπλοκών. Σε αυτή τη μελέτη, ελέγχθηκαν οι συσχετίσεις μεταξύ 5 κοινών πολυμορφισμών-SNPs (rs2259458 G/T, rs2734653 G/A, rs2670230 C/A, rs1790998 C/A, rs17188118 A/C) του γονιδίου AKR1B1 με την εμφάνιση της ΔΑ και ΔΝ, σε σακχαροδιαβητικούς ασθενείς τύπου ΙΙ. Η κοόρτη αποτελείτο από 169 διαβητικούς με μικροαγγειακές επιπλοκές (ασθενείς με επιπλοκές), 107 διαβητικούς χωρίς μικροαγγειακές επιπλοκές (ομάδα ελέγχου ασθενών) και 315 υγιείς (ομάδα ελέγχου υγιών). Η εξέλιξη της ασθένειας εξετάστηκε χρησιμοποιώντας ως μέτρο τον γενικευμένο λόγο πιθανοτήτων ORG (generalized odds ratio), μία προσέγγιση ανεξάρτητη του γενετικού μοντέλου. Ο κίνδυνος ανάπτυξης διαβητικών επιπλοκών εξετάστηκε χρησιμοποιώντας τον ORG του προσθετικού και συν-κυρίαρχου μοντέλου. Η τάση κληρονομικότητας αξιολογήθηκε χρησιμοποιώντας τον δείκτη βαθμού κυριαρχίας h (degree of dominance index). To γονίδιο AKR1B1 δεν εμπλέκεται στην εξέλιξη της ασθένειας. Διερευνώντας την συσχέτιση μεταξύ των παραλλαγών του AKR1B1 και τον κίνδυνο ανάπτυξης διαβητικών επιπλοκών, στατιστικά σημαντικά αποτελέσματα υπήρξαν για το προσθετικό μοντέλο της παραλλαγής rs2259458 G/T [OR = 1.87 (1.01 – 3.50)] και το συν-κυρίαρχο μοντέλο του πολυμορφισμού rs2670230 C/A [OR = 1.45 (1.01 – 2.04)]. H τάση κληρονομικότητας (h index) για τις παραλλαγές rs2259458 G/T και rs2670230 C/A ήταν «μη – κυριαρχία» και «κυριαρχία του αλληλόμορφου Α» αντίστοιχα. Οι συχνότητες των τριών απλοτύπων (T-G-A-C-A, G-G-C-C-A and G-A-C-C-A) ήταν σημαντικά διαφορετικές (P ≤ 0.05) ανάμεσα στις ομάδες ελέγχου ασθενών και υγιών. Οι πολυμορφισμοί του γονίδιου AKR1B1 ίσως επιδρούν στην εξέλιξη του ΣΔ και γιαυτό να οδηγούν τελικά στις επιπλοκές του

Serpin Family E Member 1 Tag Single-Nucleotide Polymorphisms in Patients with Diabetic Nephropathy: An Association Study and Meta-Analysis Using a Genetic Model-Free Approach

Background: Many lines of evidence highlight the genetic contribution on the development of diabetic nephropathy (DN). One of the studied genes is SERPINE1 whose the role in the risk of developing DN remains questionable. In order to elucidate the contribution of SERPINE1 in DN progression in the context of type 2 diabetes mellitus (T2DM), we conducted an association study and meta-analysis of SERPINE1 genetic variants. Materials and Methods: A total of 190 patients with DN, 150 T2DM (type 2 diabetes mellitus) patients without DN and 238 healthy controls were recruited. We selected five tag single-nucleotide polymorphisms (SNPs) from the HapMap. The generalized odds ratio (ORG) was calculated to estimate the risk on DN development. Subgroup analyses based on ethnicity and type of diabetes were also performed. Results: Both the present association study regarding SERPINE1 SNPs (rs2227667, rs2070682, rs1050813, rs2227690, rs2227692) did not found any significant association between SERPINE1 variants and DN and the meta-analysis of variant 4G>5G (rs1799889) did not also reveal a significant association between 4G>5G variant and DN in main and subgroup analyses. Discussion: In conclusion, the present association study and meta-analysis provides strong evidence that SERPINE1 genetic variant 4G>5G is not implicated in the risk or development of DN in Caucasians. Further studies in other populations remain to further investigate the role of this variant in the course of DN

Serpin Family E Member 1 Tag Single-Nucleotide Polymorphisms in Patients with Diabetic Nephropathy: An Association Study and Meta-Analysis Using a Genetic Model-Free Approach

Background: Many lines of evidence highlight the genetic contribution on the development of diabetic nephropathy (DN). One of the studied genes is SERPINE1 whose the role in the risk of developing DN remains questionable. In order to elucidate the contribution of SERPINE1 in DN progression in the context of type 2 diabetes mellitus (T2DM), we conducted an association study and meta-analysis of SERPINE1 genetic variants. Materials and Methods: A total of 190 patients with DN, 150 T2DM (type 2 diabetes mellitus) patients without DN and 238 healthy controls were recruited. We selected five tag single-nucleotide polymorphisms (SNPs) from the HapMap. The generalized odds ratio (ORG) was calculated to estimate the risk on DN development. Subgroup analyses based on ethnicity and type of diabetes were also performed. Results: Both the present association study regarding SERPINE1 SNPs (rs2227667, rs2070682, rs1050813, rs2227690, rs2227692) did not found any significant association between SERPINE1 variants and DN and the meta-analysis of variant 4G&gt;5G (rs1799889) did not also reveal a significant association between 4G&gt;5G variant and DN in main and subgroup analyses. Discussion: In conclusion, the present association study and meta-analysis provides strong evidence that SERPINE1 genetic variant 4G&gt;5G is not implicated in the risk or development of DN in Caucasians. Further studies in other populations remain to further investigate the role of this variant in the course of DN

Plasminogen Activator Inhibitor Type-1 Tag Single-Nucleotide Polymorphisms in Patients with Diabetes Mellitus Type 2 and Diabetic Retinopathy

<p><i>Background</i>: There is accumulating evidence for genetic susceptibility to the development of diabetic retinopathy (DR). The role of plasminogen activator inhibitor-1 (PAI-1) in DR risk remains controversial.</p> <p><i>Objective</i>: The present study was designed to investigate possible influence of PAI-1 gene region polymorphisms on the risk of DR and on the risk of developing DR early vs late in the course of type 2 diabetes mellitus (T2DM).</p> <p><i>Methods</i>: A total of 138 patients with DR, 107 patients with T2DM without DR, and 315 healthy controls were recruited. To cover the majority of the genetic variability across the extended region of PAI-1 gene, five tag single-nucleotide polymorphisms (SNPs) from the HapMap using a pairwise approach and an <i>r</i>² ≥ 0.8 and a minor allele frequency (MAF) of >0.05 were identified. Using logistic regression analyses, tag SNPs and haplotypes were tested for associations with DR risk and risk of DR development early or late in the course of T2DM. The generalized odds ratio (OR_G) was calculated to estimate the mutational load effect on DR development among all participants. Corrections for multiple comparisons were carried out (<i>p</i>-value < 0.01).</p> <p><i>Results</i>: A significant effect of rs2070682 on the risk of early DR onset was found in the codominant model of inheritance [odds ratio, OR (95% confidence interval, CI): 5.04 (1.47–17.28), <i>p</i> = 0.018]. However, this association marginally did not survive multiple testing corrections. No other significant association between PAI-1 tag-SNPs and haplotypes was revealed. Furthermore, no significant mutational load effect of PAI-1 tag SNPs on the risk of DR development in T2DM course was found.</p> <p><i>Conclusions</i>: In conclusion, the present study does not provide any strong evidence that <i>PAI-1</i> gene variants are implicated in the risk of DR or the development of DR during T2DM course.</p