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1.
J Med Microbiol ; 72(6)2023 Jun.
Article En | MEDLINE | ID: mdl-37326607

Introduction. Uninfected diabetes-related foot ulcer (DFU) progression to diabetes-related foot infection (DFI) is a prevalent complication for patients with diabetes. DFI often progresses to osteomyelitis (DFI-OM). Active (growing) Staphylococcus aureus is the most common pathogen in these infections. There is relapse in 40-60 % of cases even when the initial treatment at the DFI stage apparently clears infection.Hypothesis. S. aureus adopts the quasi-dormant Small Colony Variant (SCV) state during DFU and consequently infection, and when present in DFI cases also permits survival in non-diseased tissues as a reservoir to cause relapse.Aim. The aim of this study was to investigate the bacterial factors that facilitate persistent infections.Methodology. People with diabetes were recruited from two tertiary hospitals. Clinical and bacterial data was taken from 153 patients with diabetes (51 from a control group with no ulcer or infection) and samples taken from 102 patients with foot complications to identify bacterial species and their variant colony types, and then compare the bacterial composition in those with uninfected DFU, DFI and those with DFI-OM, of whom samples were taken both from wounds (DFI-OM/W) and bone (DFI-OM/B). Intracellular, extracellular and proximal 'healthy' bone were examined.Results. S. aureus was identified as the most prevalent pathogen in diabetes-related foot pathologies (25 % of all samples). For patients where disease progressed from DFU to DFI-OM, S. aureus was isolated as a diversity of colony types, with increasing numbers of SCVs present. Intracellular (bone) SCVs were found, and even within uninfected bone SCVs were present. Wounds of 24 % of patients with uninfected DFU contained active S. aureus. All patients with a DFI with a wound but not bone infection had previously had S. aureus isolated from an infection (including amputation), representing a relapse.Conclusion. The presence of S. aureus SCVs in recalcitrant pathologies highlights their importance in persistent infections through the colonization of reservoirs, such as bone. The survival of these cells in intracellular bone is an important clinical finding supporting in vitro data. Also, there seems to be a link between the genetics of S. aureus found in deeper infections compared to those only found in DFU.


Bacteriology , Diabetes Mellitus , Diabetic Foot , Osteomyelitis , Staphylococcal Infections , Humans , Staphylococcus aureus/genetics , Diabetic Foot/complications , Diabetic Foot/therapy , Incidence , Persistent Infection , Staphylococcal Infections/complications , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Osteomyelitis/epidemiology , Osteomyelitis/microbiology
2.
J Vasc Surg ; 67(2): 460-467, 2018 02.
Article En | MEDLINE | ID: mdl-28843791

OBJECTIVE: Preoperative sarcopenia is an established risk factor for poor outcomes after surgery. Methods for assessing sarcopenia are either complex, time consuming, or poorly validated. We aimed to assess the interobserver reliability of scoring psoas area at the level of the L3 vertebra and to evaluate whether sarcopenia scored by this simple and rapid method correlated with other fitness scoring methods or impacted on mortality and duration of stay for patients undergoing endovascular aneurysm repair (EVAR). METHODS: We had access to 191 preoperative computed tomography scans of patients who underwent EVAR. For each scan the axial slice at the most caudal level of the L3 vertebra was extracted. Three observers independently calculated the combined cross-sectional area of the left and right psoas muscle at this level. Interobserver variability was calculated as per Band and Altman. Psoas area was normalized for patient height with sarcopenia defined as total psoas area of <500 mm2/m2. The effect of sarcopenia on patient survival was assessed using Cox proportional hazards models. Kaplan-Meier curves are also presented. RESULTS: Interobserver reliability of scoring psoas area was acceptable (reproducibility coefficient as percent of mean for each observer pair: 7.92%, 7.95%, and 14.33%). Sarcopenic patients had poorer survival (hazard ratio, 2.37; P = .011) and an increased hospital duration of stay (4.0 days vs 3.0 days; P = .008) when compared with nonsarcopenic patients. Sarcopenic patients were more likely to self-report as unfit (12.4% vs 33.3%; P = .004). Sarcopenia did not correlate with an increased rate of postprocedure complications. CONCLUSIONS: Psoas area scoring has good interobserver reliability. Preoperative sarcopenia as defined by psoas area was associated with poorer survival and of longer length of stay. As all patients being worked up for an endovascular aortic aneurysm repair will undergo a computed tomography scan, this method is a rapid and effective way to highlight patients in the clinic setting who have an increased risk of morbidity and mortality after EVAR.


Aortic Aneurysm, Abdominal/surgery , Aortography/methods , Blood Vessel Prosthesis Implantation/mortality , Endovascular Procedures/mortality , Frailty/mortality , Psoas Muscles/diagnostic imaging , Sarcopenia/mortality , Tomography, X-Ray Computed , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/mortality , Australia , Blood Vessel Prosthesis Implantation/adverse effects , Chi-Square Distribution , Databases, Factual , Endovascular Procedures/adverse effects , Frailty/diagnostic imaging , Health Status , Humans , Kaplan-Meier Estimate , Length of Stay , Male , Observer Variation , Postoperative Complications/mortality , Predictive Value of Tests , Proportional Hazards Models , Reproducibility of Results , Retrospective Studies , Risk Factors , Sarcopenia/diagnostic imaging , Self Report , Time Factors , Treatment Outcome
5.
Reprod Biol Endocrinol ; 8: 51, 2010 May 18.
Article En | MEDLINE | ID: mdl-20482803

BACKGROUND: Reproductive function following chemotherapy is of increasing importance given that survival rates are improving. We assessed whether a gonadotropin-releasing hormone antagonist (GnRHant; cetrorelix) could promote ovarian protection against damage due to chemotherapy. METHODS: Forty-two female Wistar rats were used in this study. Animals were divided into four groups: group I (n=9) received placebo twice; group II (n=12) received placebo+cyclophosphamide (CPA); group III (n=12) received GnRHant+CPA; and group IV (n=9) received GnRHant+placebo. After medication, the estrous cycle was studied through vaginal smears. Rats were mated, pregnancy was documented and the number of live pups evaluated. Afterwards, rat ovaries were removed and prepared for histological studies. The ovarian cross-sectional area was measured and follicles were counted. RESULTS: Cyclic changes in vaginal smears were observed in all but one animal after treatment, but group II had a significantly lower rate of animals with proestrus or estrus (p<0.01). The offspring was markedly reduced by CPA treatment (group II, 3.00+/-1.33 pups vs. group I, 11.44+/-0.78 pups, p<0.01) and this effect was partly reversed by pre-treatment with GnRHant (group III, 7.00+/-1.31 pups). The ovarian cross-sectional area was not significantly different between groups, neither was the number of individual follicle types. However, rats in Group IV had a higher total number of ovarian follicles than those in the control group (17.1+/-1.22 vs. 10.9+/-0.70, p<0.05). CONCLUSION: The use of a GnRHant before CPA chemotherapy provided protection of fertility.


Cyclophosphamide/adverse effects , Fertility/drug effects , Gonadotropin-Releasing Hormone/antagonists & inhibitors , Hormone Antagonists/therapeutic use , Infertility, Female/prevention & control , Ovary/drug effects , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Cell Count , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Drug Administration Schedule , Drug Evaluation, Preclinical , Female , Gonadotropin-Releasing Hormone/administration & dosage , Gonadotropin-Releasing Hormone/analogs & derivatives , Gonadotropin-Releasing Hormone/therapeutic use , Hormone Antagonists/administration & dosage , Infertility, Female/chemically induced , Neoplasms/drug therapy , Neoplasms/rehabilitation , Ovary/cytology , Placebos , Pregnancy , Pregnancy Rate , Rats , Rats, Wistar
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