Person: Giurini, John
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Giurini
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Giurini, John
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Publication Mechanisms Involved in the Development and Healing of Diabetic Foot Ulceration(American Diabetes Association, 2012) Dinh, Thanh; Tecilazich, Francesco; Kafanas, Antonios; Doupis, John; Gnardellis, Charalambos; Leal, Ermelindo; Tellechea, Ana; Pradhan, Leena; Lyons, Thomas E.; Giurini, John; Veves, AristidisWe examined the role of vascular function and inflammation in the development and failure to heal diabetic foot ulcers (DFUs). We followed 104 diabetic patients for a period of 18.4 ± 10.8 months. At the beginning of the study, we evaluated vascular reactivity and serum inflammatory cytokines and growth factors. DFUs developed in 30 (29%) patients. DFU patients had more severe neuropathy, higher white blood cell count, and lower endothelium-dependent and -independent vasodilation in the macrocirculation. Complete ulcer healing was achieved in 16 (53%) patients, whereas 13 (47%) patients did not heal. There were no differences in the above parameters between the two groups, but patients whose ulcers failed to heal had higher tumor necrosis factor-α, monocyte chemoattractant protein-1, matrix metallopeptidase 9 (MMP-9), and fibroblast growth factor 2 serum levels when compared with those who healed. Skin biopsy analysis showed that compared with control subjects, diabetic patients had increased immune cell infiltration, expression of MMP-9, and protein tyrosine phosphatase-1B (PTP1B), which negatively regulates the signaling of insulin, leptin, and growth factors. We conclude that increased inflammation, expression of MMP-9, PTP1B, and aberrant growth factor levels are the main factors associated with failure to heal DFUs. Targeting these factors may prove helpful in the management of DFUs.Publication Invasive Systemic Infection After Hospital Treatment for Diabetic Foot Ulcer: Risk of Occurrence and Effect on Survival(Oxford University Press (OUP), 2017-02-01) Chen, Shey-Ying; Giurini, John; Karchmer, AdolfBackground Diabetic foot ulcers (DFUs) threaten limbs and prompt hospitalization. After hospitalization, remote-site invasive systemic infection related to DFU (DFU-ISI) may occur. The characteristics of DFU-ISIs and their effect on mortality risk have not been defined. Methods We conducted a retrospective cohort study of 819 diabetic patients hospitalized for treatment of 1212 unique DFUs during a 9-year period. We defined the index ulcer as that present at the first (index) DFU admission to our hospital. We defined DFU-ISI as a nonfoot infection that occurred after the index hospitalization and was caused by a microorganism concomitantly or previously cultured from the index ulcer. We determined the frequency, risk factors, and mortality risk associated with DFU-ISIs. Results After 1212 index DFU hospitalizations, 141 patients had 172 DFU-ISIs. Of the initial 141 DFU-ISIs, 64% were bacteremia, 13% deep abscesses, 10% pneumonia, 7% endocarditis, and 6% skeletal infections. Methicillin-resistant Staphylococcus aureus (MRSA) caused 57% of the ISIs. Patients with initial DFU cultures yielding MRSA and protracted open ulcers had a high 24-month cumulative probability of DFU-ISI (31%) and all-cause mortality rate (13%). Analysis with Cox regression modeling showed that complicated ulcer healing (hazard ratio, 3.812; 95% confidence interval, 2.434–5.971) and initial DFU culture yielding MRSA (2.030; 1.452–2.838) predicted DFU-ISIs and that DFU-ISIs were associated with increased mortality risk (1.987; 1.106–3.568). Conclusions DFU-ISIs are important late complications of DFUs. Prevention of DFU-ISIs should be studied prospectively. Meanwhile, clinicians should aggressively incorporate treatment to accelerate ulcer healing and address MRSA into the care of diabetic patients with foot ulcers.Publication Foot Muscle Energy Reserves in Diabetic Patients Without and With Clinical Peripheral Neuropathy(American Diabetes Association, 2009) Doupis, John; Kuchibhotla, Sarada; Julliard, Walker; Gnardellis, Charalambos; Dinh, Thanh; Lyons, Thomas Edward; Rosenblum, Barry; Wang, Xiaoen; Giurini, John; Greenman, Robert L.; Veves, AristidisObjective: To investigate changes in the foot muscle energy reserves in diabetic non-neuropathic and neuropathic patients. Research Design and Methods: We measured the phosphocreatinine (PCr)/inorganic phosphate (Pi) ratio, total \(^{31}\)P concentration, and the lipid/water ratio in the muscles in the metatarsal head region using MRI spectroscopy in healthy control subjects and non-neuropathic and neuropathic diabetic patients. Results: The PCr/Pi ratio was higher in the control subjects (3.23 \(\pm\) 0.43) followed by the non-neuropathic group (2.61 \(\pm\) 0.36), whereas it was lowest in the neuropathic group (0.60 \(\pm\) 1.02) (P < 0.0001). There were no differences in total \(^{31}\)P concentration and lipid/water ratio between the control and non-neuropathic groups, but both measurements were different in the neuropathic group (P < 0.0001). Conclusions: Resting foot muscle energy reserves are affected before the development of peripheral diabetic neuropathy and are associated with the endothelial dysfunction and inflammation.