Risk Of Amputation Research Articles

Amputation-Free Survival, WIfI Stage, and GLASS Classifications in Distal Crural or Pedal Bypass for Chronic Limb-Threatening Ischemia

Background: Chronic limb-threatening ischemia (CLTI) is a severe condition with high risks of amputation and mortality, especially in patients with distal crural or pedal artery disease. Despite advances in endovascular techniques, bypass surgery remains crucial for patients with CLTI. This study aimed to investigate amputation-free survival, Wound, Ischemia, and foot Infection (WIfI) staging, and Global Limb Anatomic Staging System (GLASS) classifications in patients undergoing distal crural or pedal bypass for CLTI. Methods: This retrospective study analyzed all patients who underwent distal crural or pedal bypass for CLTI in a tertiary vascular centre from January 2010 to December 2019. The data were collected from hospital records and preoperative imaging. WIfI stages and GLASS classifications were determined for each patient, and the primary endpoint was amputation-free survival. Secondary outcomes included bypass patency, 30-day morbidity, and mortality. Results: We identified 31 bypasses performed on 29 patients with a median age of 67 years (79% male). Preoperatively, 94% of limbs were staged GLASS III and 55% were classified WIfI stage 4. Failed endovascular revascularization preceded bypass surgery in 65% of the cases. Thirty-day mortality was 3% (n = 1) and 30-day major amputation rate was 10%. Primary patency was 87%, and secondary patency was 94% at 30 days. Median duration of follow-up for survival was 59 months with a mean follow-up index (FUI) of 0.99 ± 0.05, and for major amputation and bypass patency 54 months (mean FUI 0.9 ± 0.19 and 0.85 ± 0.28, respectively). At one year, amputation-free survival was 58%, decreasing to 45% at two years, 39% at three years, and 32% at five years. Most major amputations occurred in WIfI stage 4 patients, but 53% of WIfI stage 4 and 80% of WIfI stage 3 patients were alive without major amputation after one year. Conclusions: Distal crural and pedal bypasses are essential for limb salvage in high-risk CLTI patients, particularly those with failed prior revascularization. However, the procedure is associated with limited long-term amputation-free survival. WIfI and GLASS classifications are useful for stratifying risk and guiding treatment, but outcomes suggest the need for individualized care strategies. Further research into perioperative management and alternative interventions is warranted to improve long-term outcomes in this population.

Incidence and Risk Factors for Amputations in Persons with Diabetes Mellitus: A Retrospective Cohort Study.

The aim of this study was to identify and analyze the incidence rate of amputations and their risk factors in people with Diabetes Mellitus (DM) in two specialized outpatient clinics in Brazil. This is an epidemiological, retrospective cohort study using data collected from electronic health records of 281 adult diabetic patient types 1 or 2; attended in specialized outpatient service between 2015 and 2020. Statistical analyses were performed using the 2 sample t-test or Wilcoxon-Mann-Whitney test, for quantitative variables, and the Pearson's χ2 test or Fisher's exact test for categorical variables. The investigation of the risk factors for amputation was carried out through logistic regression. The study was approved by ethical committee. The sample mean age was 65.6 years (SD 13.05), predominating male gender n = 211 (75%), type 2 DM n = 223 (86.7%), with cardiovascular disease n = 143 (63.2%), and about 68.7% (n = 156) with peripheral arterial disease (PAD). Seventy-seven had lower limb amputation (LLA), with a rate incidence of 31.9% during five years. Logistic regression analysis showed the following associations with amputation: Diabetic peripheral neuropathy increased the rate of amputation by 3.6 times (OR = 3.631, 95% CI = 1.214-11.353; P = .022), and peripheral arterial disease increased by 10 times (OR = 10.631; 95% CI = 2.969-57.029; P = .001). The LLA in individuals with DM in two specialized outpatient services was higher compared to international literature; DPN and PAD were confirmed as risk factors for amputation, according to literature. This finding suggests that the study population faces an increased risk of amputation, highlighting the urgent need for targeted interventions and implementing robust preventive strategies to transform the current scenario and mitigate these severe outcomes. A comprehensive approach is essential to proactively address the underlying issues and reduce the prevalence and impact of amputations in Brazil.

Remote Foot Temperature Monitoring Among Veterans: Large Observational Study of Noncompliance and Its Correlates.

In-home remote foot temperature monitoring (RTM) holds promise as a method to reduce foot ulceration in high-risk patients with diabetes. Few studies have evaluated adherence to this method or evaluated the factors associated with noncompliance. The aims of this study were to estimate noncompliance in patients who were enrolled in RTM nationwide across Department of Veterans Affairs (VA) and to evaluate characteristics associated with noncompliance. We conducted an observational study including 1137 patients in the VA who were enrolled in RTM between January 2019 and June 2021, with follow-up through October 2021. Patient information was obtained from the VA's electronic health record and RTM use was obtained from the company. Noncompliance was defined as using the mat <2 days per week for ≥4 of the 12 months of follow-up. Using a multivariable model, we calculated odds ratios (ORs) and 95% CIs for associations between various factors and noncompliance and compared using Akaike information criterion statistics, a measure of model fit. The sample was predominantly male (n=1125, 98.94%) ; 21.1% (n=230) were Black and 75.7% (n=825) were White. Overall, 37.6% (428/1137) of patients were classified as noncompliant. In the multivariable model, an intermediate area deprivation index was statistically significantly and inversely associated with noncompliance (area deprivation index 50-74 vs 1-24; OR 0.56, 95% CI 0.35-0.89); factors significantly and positively associated with noncompliance included recent history of osteomyelitis (OR 1.44, 95% CI 1.06-1.97), Gagne comorbidity index score ≥4 (vs ≤0; OR 1.81, 95% CI 1.15-2.83), telehealth encounters (28+ vs <6; OR 1.70, 95% CI 1.02-2.84), hemoglobin A1c≥10 (vs <5.7; OR 2.67, 95% CI 1.27-5.58), and current smoking (OR 2.06, 95% CI 1.32-3.20). Based on Akaike information criterion differences, the strongest factors associated with noncompliance were behavioral factors (poor glucose control [as measured by hemoglobin A1c] and smoking), and to a lesser extent, factors such as a recent history of osteomyelitis and an elevated Gagne comorbidity index, indicating a high comorbidity burden. To reduce the risk of ulcer recurrence and amputation, proactively providing additional support for self-monitoring to patients with characteristics identified in this study (poor glucose control, current smoking, high comorbidity burden) may be helpful. Furthermore, research is needed to better understand barriers to use, and whether the addition of design features, reminders, or incentives may reduce noncompliance and the risk of foot ulcers.

Transcriptomics Revealed Differentially Expressed Transcription Factors and MicroRNAs in Human Diabetic Foot Ulcers

Non-healing diabetic foot ulcers (DFUs) not only significantly increase morbidity and mortality but also cost a lot and drain healthcare resources. Persistent inflammation, decreased angiogenesis, and altered extracellular matrix remodeling contribute to delayed healing or non-healing. Recent studies suggest an increasing trend of DFUs in diabetes patients, and non-healing DFYs increase the incidence of amputation. Despite the current treatment with offloading, dressing, antibiotics use, and oxygen therapy, the risk of amputation persists. Thus, there is a need to understand the molecular and cellular factors regulating healing in DFUs. The ongoing research based on proteomics and transcriptomics has predicted multiple potential targets, but there is no definitive therapy to enhance healing in chronic DFUs. Increased or decreased expression of various proteins encoded by genes, whose expression transcriptionally and post-transcriptionally is regulated by transcription factors (TFs) and microRNAs (miRs), regulates DFU healing. For this study, RNA sequencing was conducted on 20 DFU samples of ulcer tissue and non-ulcerated nearby healthy tissues. The IPA analysis revealed various activated and inhibited transcription factors and microRNAs. Further network analysis revealed interactions between the TFs and miRs and the molecular targets of these TFs and miRs. The analysis revealed 30 differentially expressed transcription factors (21 activated and 9 inhibited), two translational regulators (RPSA and EIF4G2), and seven miRs, including mir-486, mir-324, mir-23, mir-186, mir-210, mir-199, and mir-338 in upstream regulators (p &lt; 0.05), while causal network analysis (p &lt; 0.05) revealed 28 differentially expressed TFs (19 activated and 9 inhibited), two translational regulators (RPSA and EIF4G2), and five miRs including mir-155, mir-486, mir-324, mir-210, and mir-1225. The protein–protein interaction analysis revealed the interaction of various novel proteins with the proteins involved in regulating DFU pathogenesis and healing. The results of this study highlight many activated and inhibited novel TFs and miRs not reported in the literature so far, as well as the targeted molecules. Since proteins are the functional units during biological processes, alteration of gene expression may result in different proteoforms and protein species, making the wound microenvironment a complex protein interaction (proteome complexity). Thus, investigating the effects of these TFs and miRs on protein expression using proteomics and combining these results with transcriptomics will help advance research on DFU healing and delineate potential therapeutic strategies.

The Potential Impact of SGLT2-I in Diabetic Foot Prevention: Promising Pathophysiologic Implications, State of the Art, and Future Perspectives—A Narrative Review

The impact of diabetic foot (DF) on the healthcare system represents a major public health problem, leading to a considerable clinical and economic burden. The factors contributing to DF’s development and progression are strongly interconnected, including metabolic causes, neuropathy, arteriopathy, and inflammatory changes. Sodium–glucose cotransporter 2 inhibitors (SGLT2-i), novel oral hypoglycemic drugs used as an adjunct to standard treatment, have recently changed the pharmacological management of diabetes. Nevertheless, data about the risk of limb amputation, discordant and limited to canagliflozin, which is currently avoided in the case of peripheral artery disease, have potentially discouraged the design of specific studies targeting DF. There is good evidence for the single immunomodulatory, neuroprotective, and beneficial vascular effects of SGLT2-i. Still, there is no clinical evidence about the early use of SGLT2-i in diabetic foot due to the lack of longitudinal and prospective studies proving the effect of these drugs without confounders. This narrative review aims to discuss the main evidence about the impact of SGLT2-i on the three complications of diabetes implicated in the development of DF, the state of the art, and the potential future implications.

037. Outcomes of Management of Adult Patients with Acute Limb Ischemia Using Catheter-Directed Thrombolysis (CDT) and Thrombectomy: A Systematic Review

Background: Acute limb ischemia (ALI) is one of the arterial emergencies of sudden decrease in limb perfusion and poses a threat to limb viability. Immediate management is required for better prognosis of the patient. Treatment with Catheter-directed thrombolysis (CDT) and thrombectomy methods have their own advantages and disadvantages that require further study. Methods: The authors completed a descriptive systematic review of retrospective cohort studies and randomised controlled trials (RCTs) based on PRISMA guidelines, including studies that included CDT and thrombectomy interventions in patients with acute limb ischemia. Data were extracted on sample size, age, diagnosis, mechanism of intervention, treatment outcome and complications. Results: Of the 304 studies, the authors included 5 cohort studies and RCTs, with a total sample size of 5,781 samples aged 60-72 years. All studies used CDT method, compared with various thrombectomy (Percutaneous aspiration thrombectomy (PAT), Pharmacomechanical thrombectomy (PMT), Percutaneous mechanical thrombectomy (PMT), Catheter-based thrombectomy (CBT), and Operative embolectomy. It was found that therapeutic outcomes based on risk of amputation, mortality and complications did not show significant differences between the two groups, but hospitalisation duration outcomes appeared longer in patients with CDT than thrombectomy (p value 0.0001 and 0.000). Conclusion: ALI is a condition that requires immediate management to reopen arterial flow so that ischaemic conditions in the tissue can be avoided, various intervention methods either with medication (thrombolysis) or invasive procedures with thrombectomy are considered to provide good outcomes in patients.

Risk factors related to amputation in diabetic foot patients: single center outcomes

Aim: This study aimed at identifying factors that worsen the prognosis of diabetic foot, one of the most common complications seen in patients with diabetes. Materials and patients: The sample included 230 patients treated in the Department of Surgery at Kaspela University Hospital in Plovdiv, Bulgaria, between January 2016 and May 2022. Of them, 55.65% were men, and 44.35% were women. The age of the patients ranged from 18 to 77 years, with a mean age of 44.4±14.7 years. Results: Diabetic foot patients of grade ≥4 were 1.8 times more likely to be amputated than the rest of the patients (AOR=1.6; 95% CI: 1.504, 4.683). The utilization of inappropriate antibiotics was associated with a 9.47-fold increased risk of amputation (p&amp;lt;0.001). Subsequently, type 2 DM was found to have a 3.63-fold higher risk (p=0.002), poor glycemic control posed a 3-fold increased risk (p&amp;lt;0.001), a body mass index (BMI) greater than 29.5 was linked to a 2.66-fold raised risk (p=0.011), neuropathy was associated with a 2-fold increased risk (p=0.017), and alcohol consumption was linked to a 1.96-fold higher risk (p=0.024). Conclusion: Our results contribute to clinical practice by identifying risk factors that should be considered in the early monitoring and education of patients with diabetes who are at risk for developing diabetic foot. To minimize the risk of developing diabetic foot ulcers, it is critical to optimize antibiotic therapy and prioritize the advantages of adopting a healthy lifestyle, which includes making informed dietary choices, weight management for reducing hyperglycemia, and refraining from harmful behaviors such as alcohol consumption.

Factors affecting in-hospital clinical outcomes in patients with acute limb ischemia undergoing endovascular therapy or fogarty thrombectomy: a large-scale analysis based on the JROAD-DPC database

Abstract Background The etiology of acute limb ischemia (ALI) involves embolism as well as atherosclerotic thrombosis. Although endovascular therapy (EVT) or Fogarty thrombectomy (Fogarty TE) is the recommended revascularization method for ALI, treatment choice based on patient characteristics remains controversial. Purpose This study aimed to evaluate the differences in clinical outcomes between primary treatments and identify predictive factors affecting clinical outcomes in patients with ALI. Methods This retrospective study used data from the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) database, from April 2012 to March 2020. We analyzed 18,701 patients with ALI and categorized them into medication and invasive treatment groups (EVT alone, Fogarty TE alone, bypass surgery alone, and hybrid treatment). The EVT-alone and Fogarty TE-alone groups were compared after propensity score matching, considering 19 clinically relevant covariates. The primary outcomes were in-hospital mortality, major amputation, and bleeding complications (anemia requiring transfusion or endoscopic hemostasis). The secondary outcomes were major adverse cardiovascular events (myocardial infarction, coronary intervention, heart failure, stroke, and cerebral hemorrhage), major amputation and/or death, hospitalization duration, and total cost during hospitalization. Results The EVT-alone group had more patients at a higher risk of atherosclerotic disease, including peripheral artery disease (PAD), chronic kidney disease (CKD), or hemodialysis. The Fogarty TE-alone group had more patients at a higher risk of embolism, including AF or AFL. After propensity score matching, in-hospital mortality (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.29–1.92, p&amp;lt;.0001), bleeding complications (OR: 1.28, 95% CI: 1.12–1.46, p=0.0002), and major amputation rates (OR: 1.44, 95% CI: 1.17–1.76, p=0.0004) were significantly higher in the EVT-alone group than in the Fogarty TE-alone group. Major amputation and/or death rates and total hospitalization costs were higher in the EVT-alone group than in the Fogarty TE-alone group. In interaction analyses, EVT demonstrated a favorable trend of lower risks of death and/or major amputation in patients with PAD, CKD, and diabetes mellitus (all risk factors for atherosclerotic disease), especially in those with PAD and CKD. Conclusions Fogarty TE may be the preferred primary treatment for patients with ALI, particularly those without PAD or CKD.Study flowchartForest plot analyzing interaction effect

New nano-chemotherapeutic chitosans- garlic oil - antibiotics against diabetic foot virulent Proteus spp

Background and Objectives: Diabetes foot ulcer is recognized to have a major side effect that raises the risk of amputation. Diabetic ulcer bacterial infections caused by virulent and resistant bacteria like Proteus mirabilis lead to serious wounds that are incurable with conventional medications. Materials and Methods: In this study, we evaluated the antibacterial activity of a natural product nanochitosan - garlic oil against ten diabetic foot isolates of Proteus mirabilis. Various chitosans (Crab (CScr) - shrimp (CSsh) - squilla (CSsq)) in nano form were prepared and coated with garlic oil (GO). GC-MS analysis was carried out to determine the main compo- nents of the essential garlic oil. The physicochemical properties of GO-NCSsq were analyzed using dynamic light scattering (DLS), zeta potentials (ZP) and subsequently scan electron microscope (SEM). Additionally, the minimum inhibitory con- centration (MIC) and fraction inhibitory concentration index (FICI) were determined. Results: GC-MS analysis revealed the presence of major palmitic fatty acid. (GO) loaded on nanochitosan squilla (NCSsq) showed high activity. Although SEM showed lower nano-size, average size of the GO-NCSsq was 330.8 nm by DLS and its zeta potential formulation was +39.6 mV. The final formulation represented by GO-NCSsq + Pipercillin (Pi) inhibited the virulence factor of P. mirabilis and reduced the MIC value (p-value &gt; 0.001). Moreover, the killing time at 9 h was found to be significantly higher for GO-NCSsq + pipercillin (Pi) against P. mirabilis. Conclusion: In order to manage diabetic foot infections, GO-NCSsq is a legitimate antibacterial agent that can be coupled with other antibiotics.

Factors Influencing Outcomes of Diabetic Foot Management: Retrospective Study at Mwananyamala Regional Referral Hospital

Background: Diabetic foot ulcers (DFUs) contribute to significant morbidity and mortality worldwide, with the global prevalence of diabetes expected to rise to 12.2% by 2045, an increasing number of people are at risk for complications like DFUs, which affect 19% to 34% of diabetic patients. People with DFUs carry a 20% lifetime risk of limb amputation and mortality rate of 50% to 70%. In Tanzania DFUs account for 41.9% of major limb amputations and mortality rate of 54%. Methods: A retrospective observational study aimed to investigate the clinical factors, and treatment modalities that influence the management outcomes of diabetic foot among patients attending Mwananyamala Regional Referral Hospital (MRRH). The study reviewed existing patient records. Results: A total of 143 participants were enrolled in the study, of which 94 (65.73%) were female. The participants had a mean age of 57 ± 13.9 years. And approximately half (50.35%) were married. Nearly, all patients, 140 (97.90%), underwent surgical treatment, nearly half (41.96%) had DFU Wagner Class 3 while most of participants (69.93%) had hypertension. The mean hospital stay was 9.2 days. In binary logistic regression model output, marital status, level of education, working diagnosis, surgical management, patient progress and number of readmissions were identified as determinants of the outcome (P-value &lt; 0.05). Conclusion: This study identified key factors influencing diabetic foot outcomes, including gender, marital status, co-morbidities and ulcer grade. These findings underscore the importance of early diagnosis, targeted interventions, and comprehensive management to improve patient outcomes.

Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to Support Empirical Antibiotic Therapy Decisions in Infected Ischemic Leg Ulcers-A Feasibility Study.

Objective: Patients with peripheral artery occlusive disease (PAD) are at risk of developing foot ulcers, which can subsequently lead to foot infections and an increased risk of amputation. In cases of severe ischemic foot infections (IFIs), the empirical use of antibiotics can be limb-saving. However, there is currently no evidence-based guidance on the choice of empirical antibiotic therapy for IFI. Methods and Design: This retrospective single-center cohort study included 216 hospitalized patients with severe IFI undergoing endovascular revascularization. Weighted-Incidence Syndromic Combination Antibiograms (WISCAs) were calculated to guide empirical antibiotic choice. Results: The two most common causative pathogens for IFI were S. aureus and P. aeruginosa, with frequencies of 19.8% and 6.1%, respectively. The calculation of WISCAs revealed a low empirical coverage of amoxicillin (AMX) or clindamycin (CLN) with 21.6% and 27.7%, respectively. The empirical coverage of amoxicillin/clavulanic-acid (AMC), trimethoprim/sulfmethoxazole (SXT), and ciprofloxacin (CIP) was 50.6%, 53.1%, and 55.4%, respectively. Piperacillin/tazobactam (PT) exhibited the highest empirical coverage, with 82.5% as calculated by WISCAs. The calculated WISCAs did not significantly alter when stratified by the clinical characteristics of the patients. Conclusions: The empirical antibiotic coverage of CLN and AMX was low. SXT represents a promising empirical alternative in the case of IFI, irrespective of comorbidities and the WIfI score. WISCAs can assist in the decision-making process regarding empirical antibiotic therapy choices in cases of IFI.

Descriptive Analysis of Types and Diagnoses Associated with Lower Extremity Amputation: Analysis of the US Veterans Health Administration Database 2019-2023.

Veterans in the US have higher rates of lower extremity amputation (LEA) compared to the general population and these rates have increased between 2008 and 2018. There is limited data which directly evaluate the potential underlying comorbidities associated with LEA in the veterans' population especially with the most recent data. Such information is critical to help inform clinical management strategies to reduce the risk of amputations among our veterans. This was a retrospective observational study of adults in the Veterans Health Administration database who underwent LEA from January 1, 2019 to December 31, 2023. The date of the first LEA procedure was defined as the index date. Index LEA type, patient demographic at baseline, and clinical characteristics (including diagnoses for conditions associated with LEA and other comorbidities) 1year before and 30days after the index LEA procedure (except for bacterial infections which the identification period was 30days before and 30days after the index LEA procedure) were described. Of the 27,134 Veterans with LEA, 67.3% were ≥ 65years of age, 97.0% were male, and 65.3% were non-Hispanic white. The most common type of LEA was transmetatarsal (52.9%), followed by toe (21.9%), above-knee (15.4%), and below-knee (9.8%). The most prevalent diagnoses associated with LEA were diabetes (81.6%), bacterial infections (79.1%), and peripheral artery disease (PAD; 63.3%). Only 15 Veterans (< 0.1%) had a diagnosis for combat-related injuries to lower extremities. Diabetes and PAD are highly prevalent and among the main conditions associated with LEA among US Veterans. Earlier and more effective preventative and clinical management of these conditions offer an opportunity to significantly reduce the rates of LEA in this population.

Socioeconomic disparities in reception of limb-sparing surgery versus amputation for lower extremity sarcoma

BackgroundIn lower extremity sarcoma treatment, limb salvage approaches present superior alternatives to amputation due to reduced postoperative morbidity and improved quality of life. This study provides a novel analysis of socioeconomic disparities that may affect reception of limb-sparing surgery. MethodsPatients with lower extremity bone or soft tissue sarcoma who received either limb-sparing surgery or amputation from 2007 to 2021 were identified in the Surveillance, Epidemiology and End Results (SEER) database. Demographic, socioeconomic, and oncologic variables were collected for each patient. Multivariate binary logistic regression was conducted to assess preoperative demographic and oncologic risk factors for amputation (p < 0.05). ResultsA total of 6465 patients were identified in the final cohort, 586 (9.1%) of whom received amputation. After controlling for tumor size, stage, and neoadjuvant therapy administration, non-Hispanic American Indian/Alaskan Native race/ethnicity predicted the highest odds of amputation (OR: 1.78, 95% CI: 1.12–2.85, p = 0.015). Nonmetropolitan residence (OR: 1.69, 95% CI: 1.43–2.00, p < 0.001) also conferred higher risk of amputation compared with residence in a large metropolitan area. Overall, amputation was associated with a higher risk of ten-year cancer-specific mortality (p < 0.001) even when controlled by sociodemographic and clinical characteristics. ConclusionsThere are significant disparities in limb-sparing surgery and amputation rates in lower extremity sarcoma management, even when accounting for differences in baseline oncologic characteristics. Further study into socioeconomic drivers of these trends will allow the development of initiatives that improve disparities in reconstructive outcomes.

Diabetic Charcot neuroarthropathy: A threat to both limb and life.

Diabetic Charcot neuroarthropathy (DCN), first described in 1936, occurs in less than 1% of diabetic patients, but in those diabetic subjects with distal symmetrical polyneuropathy, the overall incidence increases to 30% and the risk is even greater in those with type 1 diabetes. Factors that precipitate DCN are trauma, ischaemia due to arterio-venous shunting, increased osteoclastic activity and inflammation. DCN usually presents with a painless swollen foot and/or ankle which is 'hot to the touch'. These clinical findings are soon followed by characteristic magnetic resonance imaging (MRI) abnormalities and later X-ray changes. The joints that are most typically involved in chronological order are the tarsometatarsals followed by the naviculocuniform, sub-tarsal, talonavicular and metatarsal and tarsophalangeal. The cornerstone of therapy is prolonged (3-12 months) offloading with immobilization. Bisphosphonates may possibly accelerate recovery, whereas other unproven possible therapies include rhPTH, 1-34, calcitonin and methylprednisolone, which are not only ineffective but in some cases may also prolong the time to healing. Denosumab is potentially an efficacious, if unproven, therapy to accelerate healing. The risk of amputation is high and increases in the presence of a foot ulcer. DCN is associated with manifestations of autonomic neuropathy, including cardiac denervation, so that the risks of a cardiac event and heart failure are increased with DCN. Mortality is also increased with DCN, especially in the presence of a foot ulcer. To avoid the recurrence of DCN and especially to lower the risk of the recurrence of a foot ulcer recurrence reconstructive, surgery may be needed.

A comparative analysis of vacuum assisted closure therapy and conventional dressings: outcomes in chronic diabetic foot ulcers among Indian patients

Background: India faces a growing diabetes epidemic, with approximately 77 million individuals affected. Chronic non-healing diabetic foot ulcers (DFUs) are a common complication of diabetes and a major healthcare challenge in Conventional wound care methods often result in prolonged healing times, increasing the risk of infection, hospitalization, and amputations. Vacuum-assisted closure (VAC) therapy, a modern treatment modality, offers a potentially more effective approach to managing these ulcers. Methods: This prospective, observational study was conducted at a tertiary care hospital in India from March 2022 to March 2024. One hundred patients with chronic non-healing DFUs were randomized into VAC therapy or conventional dressing groups. The primary outcomes included wound size reduction and healing time, while secondary outcomes involved patient satisfaction and cost-effectiveness. Results: VAC therapy significantly reduced wound size (65.2% vs. 40.5%) and shortened healing time (6.2 vs. 10.9 weeks) compared to conventional dressings. Additionally, VAC therapy led to higher patient satisfaction and proved more cost-effective due to fewer dressing changes and shorter hospital stays. Conclusions: VAC therapy outperforms conventional dressings in managing DFUs, offering faster healing, better patient satisfaction, and cost-effectiveness. Expanding its use in India could greatly improve diabetic foot care outcomes.

Residual diabetic foot osteomyelitis after surgery leads to poor clinical outcomes: A systematic review and meta-analysis.

The aim of this meta-analysis is to compare the clinical outcomes in patients with and without residual osteomyelitis (ROM) after surgical bone resection for diabetic foot osteomyelitis (DFO). We completed a systematic literature search using PubMed, Scopus, and Embase using keywords DFO, Residual OM (ROM), and positive bone margins. The study outcomes included wound healing, antibiotic duration, amputation, and re-infection. Five hundred and thirty patients were included in the analysis; 319 had no residual osteomyelitis (NROM), and 211 had ROM. There was not a significant difference in the proportion of wounds that healed 0.6 (p = 0.1, 95% confidence intervals [95% CI] 0.3-1.3). The risk of infection was 2.0 times higher (OR = 2.0, p = 0.02, 95% CI 1.1-3.4), and the risk of amputation was 4.3 times higher (OR = 4.3, p = 0.0001, 95% CI 2.4-7.6) in patients with ROM. Patients with ROM received antibiotics significantly longer. The mean difference was 16.3 days (p = 0.02, 95% CI 11.1-21.1).

6663 Amputation Rate in Hospitalized Patients With Diabetic Foot Ulcer at Montefiore Medical Center, Bronx, NY

Abstract Disclosure: R. Lopez Fanas: None. A. Herrera Chancay: None. H. Tabassum: None. J. Milosavljevic: None. S. Xu: None. J. Daily: None. A.K. Myers: None. Introduction: Diabetic foot ulcers (DFU) are associated with poor outcomes including lower extremity amputations and death in individuals with diabetes. Our study aims to define health outcomes and explore the association of sociodemographic and clinical factors on amputation rates in patients hospitalized with DFU addressing an existing knowledge gap in our population. Methods: This was a retrospective review of the electronic health record of adult patients hospitalized with DFU at one of the three major Montefiore Medical Center hospitals in the Bronx, New York between 06/01/2016 and 05/30/2021. Patient data extracted from the index admission included demographics, comorbidities, and laboratory values. Survival and amputation rates were calculated for each patient over the five-year study period. Results: In our analysis of 650 patients, 88% self-identified as non-white, and only 23% had commercial insurance. The amputation rate during the initial DFU admission was 44%, with 76% experiencing at least one amputation over five years. Male sex, low BMI, and smoking were associated with amputation during the study period, with an OR of 0.62 (p=0.01), 0.98 (p=0.05), and 1.45 (p=0.05) respectively. Patients with history of osteomyelitis had a higher risk of any amputation during the index admission (OR 2.05, p&amp;lt;0.0001), and the 5-year study period (OR 3.03, p&amp;lt;0.0001). PAD or prior history of amputation increased the risk of any amputation during the study period, OR 2.11 (p=0.0002) and OR 7.92 (p&amp;lt;0.001) ESRD was associated with a higher risk of AKA and BKA during the index admission (OR 2.31, p=0.05). Elevated ESR, CRP, WBC, and low albumin were associated with amputation during admission, with ORs of 1.01 (p=0.0006), 1.05 (p&amp;lt;0.0001), 1.11 (p&amp;lt;0.0001), and 0.41 (p&amp;lt;0.0001), respectively. Discussion: This study revealed a 44% amputation rate during the initial DFU admission, with 76% experiencing at least one amputation within five years. Bivariate analyses identified male sex, lower BMI, and smoking as correlated with a heightened amputation risk, consistent with previous studies. Prior amputation, PAD, ESRD, and osteomyelitis were also associated with an increased risk. Multiple regression analysis found significant associations between elevated ESR, CRP, WBC, and low albumin with amputations. As a result, interventions need to be devised for patients with these characteristics to prevent this high rate of amputation. Presentation: 6/2/2024

Multimodal Identification of Molecular Factors Linked to Severe Diabetic Foot Ulcers Using Artificial Intelligence.

Diabetic foot ulcers (DFUs) are a severe complication of diabetes mellitus (DM), which often lead to hospitalization and non-traumatic amputations in the United States. Diabetes prevalence estimates in South Texas exceed the national estimate and the number of diagnosed cases is higher among Hispanic adults compared to their non-Hispanic white counterparts. San Antonio, a predominantly Hispanic city, reports significantly higher annual rates of diabetic amputations compared to Texas. The late identification of severe foot ulcers minimizes the likelihood of reducing amputation risk. The aim of this study was to identify molecular factors related to the severity of DFUs by leveraging a multimodal approach. We first utilized electronic health records (EHRs) from two large demographic groups, encompassing thousands of patients, to identify blood tests such as cholesterol, blood sugar, and specific protein tests that are significantly associated with severe DFUs. Next, we translated the protein components from these blood tests into their ribonucleic acid (RNA) counterparts and analyzed them using public bulk and single-cell RNA sequencing datasets. Using these data, we applied a machine learning pipeline to uncover cell-type-specific and molecular factors associated with varying degrees of DFU severity. Our results showed that several blood test results, such as the Albumin/Creatinine Ratio (ACR) and cholesterol and coagulation tissue factor levels, correlated with DFU severity across key demographic groups. These tests exhibited varying degrees of significance based on demographic differences. Using bulk RNA-Sequenced (RNA-Seq) data, we found that apolipoprotein E (APOE) protein, a component of lipoproteins that are responsible for cholesterol transport and metabolism, is linked to DFU severity. Furthermore, the single-cell RNA-Seq (scRNA-seq) analysis revealed a cluster of cells identified as keratinocytes that showed overexpression of APOE in severe DFU cases. Overall, this study demonstrates how integrating extensive EHRs data with single-cell transcriptomics can refine the search for molecular markers and identify cell-type-specific and molecular factors associated with DFU severity while considering key demographic differences.

Diuretics and risk of major adverse limb events in patients with type-2 diabetes: An observational retrospective study

AimIn patients with type-2 diabetes mellitus (T2DM), sodium-glucose co-transporter 2 inhibitors are suspected to increase the risk of amputation. “Traditional” diuretics may increase major adverse limb events (MALEs), but the evidence is weak. We studied the association between common diuretics (i.e. thiazides, loop- and potassium-sparing diuretics) and MALEs/amputations in patients with T2DM. MethodsConsecutive T2DM patients without cardiovascular history referred to our center for cardiovascular check-ups were retrospectively studied. Follow-up data on MALEs were collected. We used Cox models to assess the association between diuretics and MALEs, or amputation alone. A propensity score with inverse probability of diuretic treatment weighting (IPTW) analysis was performed. ResultsWe studied 1309 patients, (59.5 ± 10.7 years, 51 % females) with diabetes duration of 9.1 ± 8.5 years, among whom 402 (30 %) were taking diuretics. During a follow-up of 3.8 ± 1.64 years, 121 (9.1 %) had MALEs, including 19 (1.4 %) amputations. Death occurred in 111 patients and the proportion of death was significantly different between groups: patients with diuretics n = 49, 44.1% vs patients without diuretics n = 62, 55.9 %, P = 0.001. Diuretics, in multivariable analysis, were associated with MALEs (aHR[95 %CI] 1.96[1.32;2.91] P = 0.001), even after adjustment on propensity score (aHR 1.66[1.08;2.56] P = 0.02) and IPTW analysis (aHR 1.76[1.67;1.84] P < 0.0001). This risk was particularly increased in case of an abnormal ankle-brachial index (aHR 2.29[1.32;3.96], P = 0.003) at baseline. Looking at diuretic classes separately, the adjusted risk was increased with loop diuretics (aHR 2.56[1.16;5.64] P = 0.020), thiazides (aHR 2.21[1.37;3.57] P = 0.001) or potassium sparing diuretics (aHR 2.56[1.16;5.64] P = 0.020). ConclusionDiuretic treatment weighting may be associated with increased risk of MALEs. We identified several markers of increased risk of limb events where the use of diuretics should be considered with caution.

Preventive interventions for diabetic foot ulcer adopted in different healthcare settings: A scoping review protocol.

Diabetic foot ulcers are challenging to heal, increase the risk of lower extremity amputation, and place a significant burden on patients, families, and healthcare systems. Prioritizing preventive interventions holds the promise of reducing patient suffering, lowering costs, and improving quality of life. This study describes a scoping review protocol that will be used to delineate the preventive interventions for diabetic foot ulcers employed in different healthcare settings. The scoping review methodology was formulated in accordance with the PRISMA extension guidelines for scoping reviews and informed by the procedural insights provided by the JBI methodology group. Studies with participants diagnosed with type 1 and type 2 diabetes, aged 18 years or older, without an active ulcer at baseline, and studies of preventive interventions for foot ulcers in various healthcare settings will be screened. The search strategy was developed in collaboration with a research librarian using the PRESS checklist and no time or language limitations were applied. Data will be analyzed and summarized descriptively, including characteristics of studies, participants, and interventions. Understanding the strategies and gaps in diabetic foot ulcer prevention is critical. The literature can provide valuable insights for developing tailored interventions and strategies to effectively address these gaps, potentially accelerating progress toward improved outcomes in diabetic foot ulcer prevention. Open Science Framework DOI 10.17605/OSF.IO/FRZ97 [June 19, 2023].