Clinical significance of the isolation of Staphylococcus epidermidis from bone biopsy in diabetic foot osteomyelitis

Introduction: Coagulase-negative staphylococci are considered as microorganisms with little virulence and usually as contaminants. In order to establish the role of Staphylococcus epidermidis as a pathogen in diabetic foot osteomyelitis, in addition to the isolation of the sole bacterium from the bone it will be necessary to demonstrate the histopathological changes caused by the infection. Methods: A consecutive series of 222 diabetic patients with foot osteomyelitis treated surgically in the Diabetic Foot Unit at La Paloma Hospital (Las Palmas de Gran Canaria, Canary Islands, Spain) between 1 October 2002 and 31 October 2008. From the entire series including 213 bone cultures with 241 isolated organisms, we have analyzed only the 139 cases where Staphylococci were found. We analyzed several variables between the two groups: Staphylococcus aureus versus Staphylococcus epidermidis. Results: Of the 134 patients included in this study, Staphlylococcus epidermidis was found as the sole bacterium isolated in 11 cases and accompanied by other bacteria in 12 cases. Staphlylococcus aureus was found as the sole bacterium isolated in 72 cases and accompanied by other bacteria in 39 cases. Histopathological changes were found in the cases of osteomyelitis where Staphylococcus epidermidis was the sole bacterium isolated. Acute osteomyelitis was found to a lesser extent when Staphylococcus epidermidis was the sole bacterium isolated but without significant differences with the cases where Staphylococcus aureus was the sole bacterium isolated. Conclusion: Staphylococcus epidermidis should be considered as a real pathogen, not only a contaminant, in diabetic patients with foot osteomyelitis when the bacterium is isolated from the bone. No differences in the outcomes of surgical treatment have been found with cases which Staphlylococcus aureus was isolated

The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients with Maturity-Onset Diabetes of the Young (MODY)-3

OBJECTIVE—The clinical expression of maturity-onset diabetes of the young (MODY)-3 is highly variable. This may be due to environmental and/or genetic factors, including molecular characteristics of the hepatocyte nuclear factor 1-α (HNF1A) gene mutation. RESEARCH DESIGN AND METHODS—We analyzed the mutations identified in 356 unrelated MODY3 patients, including 118 novel mutations, and searched for correlations between the genotype and age at diagnosis of diabetes. RESULTS—Missense mutations prevailed in the dimerization and DNA-binding domains (74%), while truncating mutations were predominant in the transactivation domain (62%). The majority (83%) of the mutations were located in exons 1- 6, thus affecting the three HNF1A isoforms. Age at diagnosis of diabetes was lower in patients with truncating mutations than in those with missense mutations (18 vs. 22 years, P = 0.005). Missense mutations affecting the dimerization/DNA-binding domains were associated with a lower age at diagnosis than those affecting the transactivation domain (20 vs. 30 years, P = 10−4). Patients with missense mutations affecting the three isoforms were younger at diagnosis than those with missense mutations involving one or two isoforms (P = 0.03). CONCLUSIONS—These data show that part of the variability of the clinical expression in MODY3 patients may be explained by the type and the location of HNF1A mutations. These findings should be considered in studies for the search of additional modifier genetic factors

Clinical Characteristics and Diagnostic Criteria of Maturity-Onset Diabetes Of The Young (MODY) due to Molecular Anomalies of the HNF1A Gene

Context: The diagnosis of maturity-onset diabetes of the young type 3 (MODY3), associated with HNF1A molecular abnormalities, is often missed.Objective: The objective of the study was to describe the phenotypes of a large series of MODY3 patients and to reassess parameters that may improve its diagnosis. Design, Setting, and Patients: This retrospective multicenter study included 487 unrelated patients referred because of suspicion of MODY3. Genetic analysis identified 196 MODY3 and 283 non-MODY3 cases. Criteria associated with MODY3 were assessed by multivariate analysis. The capacity of the model to predict MODY3 diagnosis was assessed by the area under the receiver-operating characteristic curve and was further validated in an independent sample of 851 patients (165 MODY3 and 686 non-MODY3). Results: In the MODY3 patients, diabetes was revealed by clinical symptoms in 25% of the cases and was diagnosed by screening in the others. Age at diagnosis of diabetes was more than 25 yr in 40% of the MODY3 patients. There was considerable variability and overlap of all assessed parameters in MODY3 and non-MODY3 patients. The best predictive model was based on criteria available at diagnosis of diabetes, including age, body mass index, number of affected generations, presence of diabetes symptoms, and geographical origin. The area under the curve of the receiver-operating characteristic analysis was 0.81. When sensitivity was set to 90%, specificity was 49%. Conclusions: Differential diagnosis between MODY3 and early-onset type 2 diabetes remains difficult. Whether the proposed model will improve the pick-up rate of MODY3 diagnosis needs to be confirmed in independent populations

Polymicrobial Nature of Chronic Diabetic Foot Ulcer Biofilm Infections Determined Using Bacterial Tag Encoded FLX Amplicon Pyrosequencing (bTEFAP)

Diabetic extremity ulcers are associated with chronic infections. Such ulcer infections are too often followed by amputation because there is little or no understanding of the ecology of such infections or how to control or eliminate this type of chronic infection. A primary impediment to the healing of chronic wounds is biofilm phenotype infections. Diabetic foot ulcers are the most common, disabling, and costly complications of diabetes. Here we seek to derive a better understanding of the polymicrobial nature of chronic diabetic extremity ulcer infections. spp. and against difficult to culture bacteria such as anaerobes. While PCR methods also have bias, further work is now needed in comparing traditional culture results to high-resolution molecular diagnostic methods such as bTEFAP

Diabetic foot infections: a team-oriented review of medical and surgical management

As the domestic and international incidence of diabetes and metabolic syndrome continues to rise, health care providers need to continue improving management of the long-term complications of the disease. Emergency department visits and hospital admissions for diabetic foot infections are increasingly commonplace, and a like-minded multidisciplinary team approach is needed to optimize patient care. Early recognition of severe infections, medical stabilization, appropriate antibiotic selection, early surgical intervention, and strategic plans for delayed reconstruction are crucial components of managing diabetic foot infections. The authors review initial medical and surgical management and staged surgical reconstruction of diabetic foot infections in the inpatient setting

Evaluation de différents moyens diagnostiques de l'artériopathie des membres inférieurs chez les patients diabétiques

L'artérite chez le patient diabétique est un problème de santé publique du fait des complications majeures qu'elle entraîne (plaie du pied, amputations...). On peut l'évaluer par la clinique, la mesure de l'index cheville-bras, la mesure de la pression transcutanée en oxygène (TcPO2) et par un écho-doppler artériel des membres inférieurs. Ces moyens diagnostiques ont été validés sur d'anciennes études dont le critère de jugement n'est pas toujours fiable. Le standard habituel proposé est l'artériographie mais elle peut présenter des complications notables. Chez 94 diabétiques, la clinique, l'ICB ne sont pas corrélés à la mesure de la TcPO2. Par contre, une gradation en 4 stades doppler est très corrélée à la TcPO(p1,3) est corrélé significativement à un allongement du délai de cicatrisation (p=0,03). La TcPO2 et le Doppler sont significativement liés au délai de cicatrisation (p=0,007 et p=0,02).La présence d'une hypertension artérielle est corrélée significativement à un allongement du délai de cicatrisation. Le doppler peut remplacer la TcPO2 dans l'évaluation de l'artérite diabétique et dans la prédiction du délai de cicatrisation. Mais le doppler, pour avoir une évaluation fiable de l'artérite et prédire le délai de cicatrisation des plaies, doit être effectué par des mains entraînées. Il doit explorer de façon complète les artères distales du pied (artère pédieuse comprise) ce qui n'est pas systématiquement fait dans l'évaluation de l'artérite diabétiquePARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Effets des lipides alimentaires sur la glycémie post-prandiale chez le patient diabétique de type 1 (implications en insulinothérapie fonctionnelle)

La glycémie post-prandiale comme la glycémie à jeun participe à l équilibre glycémique moyen et l on sait que c est cet équilibre glycémique qui déterminera en grande partie la survenue ou non de complications du diabète notamment micro-angiopathiques (rétinopathie, néphropathie et neuropathie). L insulinothérapie fonctionnelle dans le diabète de type 1 a apporté des progrès majeurs tant en terme de qualité de vie qu en terme de contrôle glycémique. Mais habituellement cette adaptation des doses d insuline prandiale ne se fait que par rapport aux apports glucidiques sans prendre en compte la composition lipidique des repas. Lors d une hospitalisation au sein de la structure d éducation thérapeutique du service de diabétologie de l Hôpital de la Pitié-Salpêtrière, 20 patients diabétiques de type 1 ont consommé un repas du midi normal en lipides appelé LF (composé de 30g de lipides) et le lendemain un repas riche en lipides appelé HF (composé de 60g de lipides). L apport glucidiques (80g) et l index glycémique des deux repas étaient identiques. Nos résultats montrent que les lipides alimentaires influent fortement sur la régulation de la glycémie post-prandiale, et suggèrent que certains patients diabétiques de type 1 seraient plus sensibles à cette influence. Le mécanisme physiopathologique pourrait intervenir tant au niveau de la régulation de la vidange gastro-intestinale qu au niveau de mécanismes mettant en jeu l insulino-résistance périphérique.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Définition des sous-populations lymphocytaires T impliquées dans la pathogénie du diabète de type 1 (nouvelles opportunités thérapeutiques)

1)La population régulatrice spontanée médiée par les lymphocytes T CD4+ ne serait pas de nature Th2 chez la souris NOD 2) les lymphocytes CD8+/TC2, sécrétant de l'IL-4, de l'IL-10 et de faibles quantités IFNy, ont une capacité cytotoxique comparable à celle des TC1 , mais une capacité diabétogènes réduite en raison d'un défaut d'accumulation/multiplication dans le pancréas. 3) l'injection systémique unique de peptide in vivo deplète massivement les lymphocytes T CD8+ auto-réactifs dirigés contre un antigène pancréatique, et entraine un état de non-réponse prolongé,permettant ainsi la préservation des îlots pancréatiques 4)in vivo les conséquences sur la fonctionnalité de lymphocytes T CD8+ spécifiques d'un peptide exprimé dans le pancréas de l'administration systémiquePARIS5-BU-Necker : Fermée (751152101) / SudocSudocFranceF