Objective: To compare the incidence of infection, healing and time to heal in patients treated with cryopreserved (CPAT) and lyopreserved amniotic tissue (LPAT) in complex diabetic surgical wound (CDFW). Methods: This single-blinded 12-week randomized clinical trial compared cryopreserved and lyopreserved amniotic cord tissue to treat complex diabetic foot wounds (CDFW). LPAT or CRAT was applied at baseline and again after four weeks. We enrolled subjects with UT2A-D and 3A-D wounds (depth to tendon, muscle, or bone with infection and/or PAD) and excluded subjects with ABI<0.5 or TBI<0.3, untreated osteomyelitis, and autoimmune diseases. We used a 3-D camera to evaluate wound area and volume. The Chi-squared test was used to compare clinical outcomes and the Wilcoxon Ranked Sum Test to compare wound area and volume. Results: The mean baseline wound areas were 12.9cm2 ±10.7 for CPAT and 11.7cm2 ±7.0 for LPAT. The mean baseline wound volume were 7.5cm3 ±8.1 for CPAT and 9.2cm3±10.2 for LPAT. There was no difference between CPAT and LPAT in healing (36.8% vs. 19.0%, p=0.21) and infection (10.5% vs. 9.5%, p=0.72). There was no difference in mean wound area reduction between CPAT and LPAT (75.9± 32.3% vs. 65.5±38.4%, p=0.41), nor in mean volume reduction (85.0±30.8% vs. 79.9±31.9%, p=0.61). When we stratified wound dimensions, there was no difference between CPAT and LPAT in subjects that had 90-99% wound volume reduction (36.8% vs. 47.6%), 70-89% wound volume reduction (15.8% vs 19.0%) and 0-69% wound volume reduction (10.5% vs. 19.0%). There was no difference between CPAT and LPAT in subjects that had 90-99% wound area reduction 90-99% (10.5% vs. 23.8%), 70-89% (26.3% vs. 19.0%) and 0-69% (26.3% vs. 38.1%). Conclusion: Cryopreserved and Lyopreserved amniotic tissue provided similar results in patients with complex diabetic foot wounds. Disclosure L.A.Lavery: Research Support; AstraZeneca, Tissue tech, American Diabetes Association, PolarityTE, Inc., Microbion, Jarvis, Integra Lifesciences Holdings Corp, Smith+Nephew. A.L.Killeen: Research Support; 3M/KCI, AstraZeneca, BioTissue surgical, Hologenix, LLC, Integra LifeSciences, Kent Imaging Inc., Microbion, PolarityTE, Inc., Smith+Nephew, Stark Enterprises, LLC, Xyken, VasoActiv, ViOptix. M.A.Suludere: None. P.Crisologo: None. Funding Smith & Nephew

Renal impairment considerations have largely been absent diabetic foot literature, despite evidence that people with severe renal impairment are at elevated risk complications following diabetic foot infections. We evaluated clinical outcomes in patients who were admitted to hospital with diabetic foot infections with severe renal impairment compared with patients without a disability. This was a retrospective study of patients with diabetes mellitus who had been hospitalized at a level 1 trauma center with moderate and severe diabetic foot infections. Patients were grouped according to their Glomerular Filtration Rate (GFR). Patients with severe renal impairment were defined as having a GFR < 30mL/min. Primary outcomes were mortality, wound healing and reinfection rates. Primary and secondary outcomes were compared using multivariable regression RStudio. A total of 307 patients with diabetic foot infections (62 patients with SRI and 245 patients without SRI) were included in the analysis. Multivariate analysis revealed that patients with severe renal impairment had higher rates of peripheral arterial disease (87% vs 66.9%; p = 0.003) and lower hemoglobin levels (9.8 vs 12.0; p <0.001). We found that patients with diabetes and severe renal impairment at admission had significantly lower glycosylated hemoglobin levels (7.2% vs 9.2%; p < 0.001). There was no difference in severity of infections between the two groups. We found that diabetic patients with severe renal impairment had higher mortality rates (8.1% vs 2.0%; p = 0.044) and higher rates of re-admission of new infections at different sites (51.6% vs 22.9%; p < 0.001). There was no significant difference between the other outcomes of interest (wound healing and reinfection). In conclusion, patients with severe renal impairment who were admitted to hospital moderate and severe diabetic foot infections had higher mortality rates and elevated readmission risk than those without severe renal impairment. Disclosure T.L.Coye: None. P.Crisologo: None. M.A.Suludere: None. L.A.Lavery: Research Support; AstraZeneca, Tissue tech, American Diabetes Association, PolarityTE, Inc., Microbion, Jarvis, Integra Lifesciences Holdings Corp, Smith+Nephew.

Aim: To evaluate the incidence of MRSA infection, re-infection, and the conversion of non-MRSA bacterial pathogens to MRSA in re-infections. Methods: This was a post hoc analysis of 233 patients that participated in an RCT for moderate and severe diabetic foot infections with 12-month outcomes. We used bone culture and/or pathology to define osteomyelitis (OM). Soft tissue infections (STI) were defined based on negative bone biopsy or negative MRI. Moderate and severe infection was based on criteria of the International. Working Group on the Diabetic Foot infection classification. All subjects required surgery. We evaluated bacterial pathogens from bone and deep soft tissue from their initial infection and when there was re-infection. We defined conversion when a subject did not have MRSA in either their first OM or STI culture and had MRSA when there was re-infection. We used χ2 for comparison of clinical events, with alpha of <0.05. Results: OM was present in 73.0% (n=170) of cases. MRSA incidence was 8.6% (n=20), with no difference between STI and OM (14.3% vs. 6.5%, p=0.06). Reinfection occurred in 29.2% (n=68), with no difference between STI and OM (36.5% vs. 26.5%, p=0.14). MRSA was seen in 29.4% (n=20) of the reinfections, with no difference between STI and OM (13.0% vs. 28.9%, p=0.16). Conversion to MRSA was seen in 14.7% (n=10), with no difference between STI and OM (4.3% vs. 20%, p=0.12). MRSA was 4.4 times more likely in re-infection compared to index infections (29.4% vs 8.6%, CI 2.2-8.9, p<0.01). Conclusion: The incidence of MRSA is 4.4-fold higher after re-infection. The incidence of MRSA for the first infection (8.6%) was low. Re-infection with MRSA (29.4%) and conversion to MRSA (14.7%) were common. There was no difference seen in the incidence rates for reinfection, MRSA, reinfection with MRSA, and conversion to MRSA between patients with STI and OM. Disclosure M.A.Suludere: None. A.L.Killeen: Research Support; 3M/KCI, AstraZeneca, BioTissue surgical, Hologenix, LLC, Integra LifeSciences, Kent Imaging Inc., Microbion, PolarityTE, Inc., Smith+Nephew, Stark Enterprises, LLC, Xyken, VasoActiv, ViOptix. P.Crisologo: None. L.A.Lavery: Research Support; AstraZeneca, Tissue tech, American Diabetes Association, PolarityTE, Inc., Microbion, Jarvis, Integra Lifesciences Holdings Corp, Smith+Nephew.

In diabetic patients on dialysis, glycemic control may improve spontaneously, leading to normal glycated hemoglobin (HbA1c) levels and termination of antidiabetic medications; this phenomenon is known as “burnt-out diabetes.” It has been previously shown that diabetic patients on dialysis with normal and less than normal glycated hemoglobin levels may have a higher risk of mortality. The aim of this systematic review and meta-analysis is to determine the prevalence of diabetic burn-out in patients with diabetic nephropathy on dialysis. Web of Science, Scopus, and PubMed were searched from inception to January 2023. Only studies that obtained samples from populations which reported the number of patients with diabetic burn-out, defined as: HgbA1c < 6.0%, cessation of antidiabetic medication, and on dialysis were included. The primary meta-analysis outcome was prevalence of diabetic burn-out. A random effects meta-analysis was carried out using RStudio software. Four studies, conducted between 2007 and 2018, met the inclusion criteria and contributed 139,690 diabetic patients (sample size range, 1296-60,019). The pooled estimation of prevalence of diabetic burn out in patients on dialysis was 28.8% (95% CI, 28.6%-29.0%). Prevalence in the included studies varied from 18.6% to 39.7%. We found a high heterogeneity (I2= 100%, p < 0.000, Q = 6641.79) in prevalence reported among studies. In conclusion, we found that the “burnt-out diabetes” phenomenon may exist in 28.8% of HD patients with diabetes in terms of HbA1c levels. Additional studies are needed to determine the optimal target for hemoglobin A1c levels in hemodialysis patients with diabetes. Disclosure T.L.Coye: None. P.Crisologo: None. L.A.Lavery: Research Support; AstraZeneca, Tissue tech, American Diabetes Association, PolarityTE, Inc., Microbion, Jarvis, Integra Lifesciences Holdings Corp, Smith+Nephew.

Osteomyelitis is the leading cause of non-traumatic lower limb amputation in patients living with diabetes. The pathophysiology of diabetic foot osteomyelitis (DFO) is complex and incompletely understood. Using FFPE bone biopsies obtained from patients with suspicious clinical presentation of DFO, we characterized the proteome of bone infection in the diabetic microenvironment. A discovery LC/MS approach was used to identify molecules of interest in subjects diagnosed with DFO versus no DFO based on histopathology findings. In total, 2,135 proteins were identified across 18 DFO and 12 non-DFO TMT labeled samples. After applying data filtering and imputing missing values, 668 proteins were retained for statistical analysis. Of 66 significant proteins (p<0.05) , 8 demonstrated twofold abundance decreases in DFO with respect to non-DFO samples, while 8 proteins were enriched by at least onefold. Ontological analysis suggested that proteins regulating chemokine signaling and integrin mediated cascades are reduced in DFO, potentially resulting in suppression of downstream MAPK pathways, and impairing inflammatory response and cellular adhesion. Our analysis demonstrates that archived FFPE samples are a rich source for elucidating molecular mechanisms associated with diabetic foot infection and may improve accuracy of diagnosis, contribute to novel therapeutic approaches, and uncover new disease biomarkers. Disclosure A.Sherwood: None. K.L.Rubitschung: None. P.Crisologo: None. H.Hwang: None. L.A.Lavery: Advisory Panel; Acera Surgical Inc., Uluru, Research Support; Integra, Smith+Nephew, Tissue tech. O.K.Oz: None. Funding American Diabetes Association (1-17-ICTS-056) ;