Extremity Amputation Research Articles

Complex trauma sequelae: Mycobacterium goodii and Priestia endophytica Hardware infection in a patient with Ehlers-Danlos syndrome

A 26-year-old man with Ehlers-Danlos syndrome, recurrent otitis externa, and chronic otitis media sustained a left lower extremity amputation and open femur fracture with internal hardware fixation after a motor vehicle collision in Arizona. He presented to the emergency department at our institution with severe left leg pain and purulent discharge despite receiving two unidentified antibiotics upon discharge. Evaluations revealed an abscess and malunion of the femur. Initial cultures yielded scant Priestia endophytica, leading to daptomycin treatment. His condition worsened until Gram-positive bacilli identified as Mycobacterium goodii, a rare nosocomial mycobacterial species, were found. Significant improvement occurred with appropriate antibiotics. This case highlights the challenges in diagnosing and managing M. goodii infections in immunocompromised patients with orthopedic complications and notes P. endophytica as a previously unreported, possibly opportunistic human pathogen.

'Leaving the Door Open': Perspectives on Decision-Making for Non-Emergency Diabetes-Related Amputation.

Having a lower extremity amputation is a life-changing decision for people living with a diabetes-related foot ulcer. Although previous research has described both positive and negative lifestyle and function outcomes of diabetes-related amputations, limited research has been conducted on the decision-making processes leading up to the amputation. This study aimed to explore the perspectives of persons, healthcare practitioners and experts (including academics and specialists) on decision-making for people with a diabetes-related foot ulcer who may require a non-emergency amputation. A qualitative descriptive study using semi-structured interviews enabled people to share their thought processes when making decisions for amputation. Twenty-six participants were interviewed, including nine people with a diabetes-related foot ulcer or amputation, nine health practitioners and eight experts located across five countries. There were 13 female and 13 male participants. Thematic analysis was used for data analysis. Four themes described the decision-making considerations for amputation: 'Balancing the evidence in decision-making', 'Trust, respect and timing of conversations inform decision-making', 'Tailoring decisions for individual circumstance' and 'Reaching the tipping point in decisions for the future'. Work commitments, functional and lifestyle impacts of amputation, the presence of support networks and clinical wound features formed the evidence for a decision for amputation. Understanding quality of life needs ensured that decisions for amputation addressed expectations and lifestyle needs. Living with a diabetes-related foot ulcer presented daily challenges that pushed people to a tipping point, at which amputation was considered to overcome these hardships and enable them to move on to the next chapter of their life. Further research is required to understand how person-centred factors can be better incorporated alongside objective clinical assessments in decisions for amputation. People with diabetes-related foot ulcers, health practitioners and experts shared their perspectives on the decision-making process for amputation through one-to-one interviews. Consideration of the person in the context of their life, environment and personal needs alongside the pathological factors is warranted.

Health care impact of lower extremity amputations in diabetes mellitus derived from Dutch insurance claims; design of the retrospective cohort study; Dutch diabetes estimate—amputation initiative (DUDE-8)

Introduction: Many individuals with diabetes mellitus (DM) experience complications that significantly impact their quality of life and life expectancy. Foot complications, arising from neuropathy, macroangiopathy, and metabolic derangements, or a combination of these factors, are a major concern. The combination of these disorders increases the risk of developing diabetic foot ulcers (DFUs), which in turn can lead to lower extremity amputations (LEAs) if not promptly and adequately treated. Globally, 80% of all nontraumatic LEAs are due to DM, and most of these were preceded by a nonhealing DFU. Studies in the Netherlands have explored the incidence of LEA in the diabetic population, reporting a range from 78 to 704 per 100 000 person-years. The current design focuses on utilizing the available all-claims data to gain valuable insights into amputation rates among individuals with DM in the Netherlands during the years 2013–2019 and develop a more comprehensive understanding of the current Dutch situation. Methods and analyses: In the Netherlands, all amputations are performed in hospitals, allowing for comprehensive financial claims data. The current project focuses on utilizing the available all-claims data to gain insights into yearly LEA rates among individuals with and without DM in the Netherlands. Over the period 2013–2019, various predefined analyses will be performed, including costs and outcomes. Individuals will be matched based on age, gender, and, where applicable, socioeconomic status. Depending on the research questions, additional analyses will take place on epidemiology, healthcare use, costs, and mortality rates.

Prosthesis applications and challenges in children with earthquake-related amputations

BackgroundAmputations are among the most important traumatic injuries caused by earthquakes. However, data on amputee children and prosthesis application is quite limited in the literature. The aim of the study is to evaluate the injury-related data, stump problems, prosthesis application, difficulties and complications experienced with prosthesis during follow-up of children with 2023 Kahramanmaraş earthquake-related limb loss. Patients and methodsSociodemographic and injury-related data, pre-amputation and post-amputation interventions, prosthesis application, current prosthetic problems, and revision surgeries of the amputee children were recorded. ResultsMedian age of patients (n = 102) admitted to our center was 13.0 years. 67.6 % of patients had one or more concomitant injuries. Median time and number of amputations were 4 (0–57) days and 1 (1–4), respectively. Of the total 120 amputations, 67.5 % (n = 81) were lower extremity amputations. Most common amputation levels were transtibial (29.1 %, n = 35), transfemoral (22.5 %, n = 27), and transhumeral (15.8 %, n = 19). Most amputees (56.8 %) underwent revision surgery after initial amputation. Median duration of time from amputation to prosthesis application was 184 (28–314) days. For 25 prostheses, a socket revision was required. Six patients had surgical revision of the stumps to allow prosthetic fit and mobility (due to bone overgrowth, soft tissue failure, heterotopic ossification). ConclusionLimited healthcare facilities, surgeries performed under emergency conditions, accompanying multiple traumas, inadequate follow-up conditions, and additional difficulties arising from the pediatric patient group lead to difficulties in the care of pediatric amputee patients. Our results will guide the care of this vulnerable patient population in the event of a similar unfortunate disaster.

Peripheral Nerve Blocks as a Predictor of Nerve Reconstruction Success After Major Limb Amputation.

Postamputation pain is a spectrum of debilitating sensations that impacts millions of people in the United States. While the development of postamputation pain, including phantom limb pain (PLP), is multifactorial, it has been associated with disorganized axonal sprouting, resulting in a neuroma and subsequent central nervous system changes. Nerve reconstruction surgeries, such as regenerative peripheral nerve interface (RPNI) and targeted muscle reinnervation (TMR), provide transected nerve fibers with proper target organs for reinnervationand have been shown to significantly reduce PLP. This case series aims to describe perioperative peripheral nerve blocks as a diagnostic tool for identifying patients who would benefit from RPNI or TMR. We conducted a retrospective search of patients who underwent major extremity amputation and who received a diagnostic peripheral nerve block before undergoing reconstructive nerve surgery (TMR and/or RPNI). Six patients (58-80 years old) with below-knee amputations (BKA) were examined. All patients experienced a reduction in postamputation pain (PAP), specifically PLP, after a diagnostic peripheral nerve block (PNB). The average time between amputation and revision surgery was approximately two years (Mean: 22.35 months). Following surgical intervention, all patientsreported a reduction in PLP episodes after nerve reconstruction surgery. Two patients no longer reported PLP.Ambulation rates also improved following revision (50% vs 83%). PNBs can be used as an effective diagnostic tool to identify patients that will significantly benefit from amputation revisions with TMR or RPNI.

Evaluation of MRI features of neuromas in oncological amputees, and the relation to pain.

The impact of time on neuroma growth and morphology on pain intensity is unknown. This study aims to assess magnetic resonance imaging (MRI) differences between symptomatic and non-symptomatic neuromas in oncological amputees, and whether time influences MRI-detected neuroma dimensions and their association with pain. Oncological patients who underwent traditional extremity amputation were included. Post-amputation MRIs were assessed before decision for neuroma surgery. Chart review was performed for residual limb pain (numeric rating scale, 0-10) and the presence of neuropathic symptoms. Neuromas were classified as symptomatic or non-symptomatic, with neuroma size expressed as radiological neuroma-to-nerve-ratio (NNR). Among 78 neuromas in 60 patients, the median NNR was 2.0, and 56 neuromas (71.8%) were symptomatic with a median pain score of 3.5. NNR showed no association with symptomatology or pain intensity but correlated with a longer time-to-neuroma-excision interval and a smaller nerve caliber. Symptomatic neuromas were associated with lower extremity amputation, T2 heterogeneity, and the presence of heterotopic ossification. Lower extremity amputation, T2 heterogeneity, perineural edema, and presence of heterotopic ossification were associated with more painful neuromas. MRI features associated with symptomatic neuromas and pain intensity were identified. Awareness of the potential clinical significance of these imaging features may help in the interpretation of MRI exams and may aid clinicians in patient selection for neuroma surgery in oncological amputees.

Consumption of different types of meat and the risk of chronic limb-threatening ischemia: the Singapore Chinese Health Study

BackgroundAlthough red meat consumption has been associated with risk of atherosclerotic coronary artery disease and stroke, no prospective study has examined this with the risk of chronic limb-threatening ischemia (CLTI).MethodsIn a prospective study of 63,257 Chinese in Singapore, who were aged 45–74 years old at recruitment, diet was assessed via a validated semi-quantitative food frequency questionnaire. Incident CLTI cases were ascertained via linkage with nationwide hospital records for lower extremity amputation or angioplasty for peripheral arterial disease. Multivariable Cox models were used to examine associations between quartiles of meat intake and CLTI risk.ResultsAfter a mean follow-up of 18.8 years, there were 1069 cases of CLTI. Higher intake of red meat intake was associated with increased risk of CLTI in a stepwise manner. Comparing extreme quartiles of red meat intake, the hazard ratio (HR) for the association with CLTI risk was 1.24 [95% confidence interval (CI) = 1.03–1.49; P-trend = 0.02]. In stratified analysis, red meat intake had a stronger association with CLTI risk among those without diabetes [HR (95% CI) comparing extreme quartiles = 1.41 (1.10–1.80); P-trend = 0.03] than among those with diabetes at baseline [HR (95% CI) comparing extreme quartiles = 1.04 (0.79–1.38); P-trend = 0.05] (P-interaction = 0.03). Otherwise, the associations were not different by sex, BMI, smoking status, hypertension, alcohol consumption, or history of cardiovascular diseases. Using a theoretical model in substitution analysis that substituted three servings per week of red meat with poultry or fish/shellfish, the relative risk of CLTI was reduced by 13–14%.ConclusionsConsumption of red meat was associated with higher CLTI risk in this Asian cohort. Substituting red meat with poultry or fish/shellfish may reduce this risk.

Temporal trends in lower extremity amputation in Middle East and North Africa (MENA) region: analysis of the GBD dataset 1990–2019

BackgroundLower extremity amputations (LEAs) significantly contribute to mortality and morbidity, often resulting from peripheral artery disease and diabetes mellitus (DM). Traumatic injuries also account for many LEAs. Despite the global burden, the epidemiology of LEAs, particularly in the Middle East and North Africa (MENA) region, remains underexplored. This study utilizes the Global Burden of Disease (GBD) dataset to analyze temporal trends in LEAs in the MENA region from 1990 to 2019.MethodsThe study utilized the 2019 GBD dataset, which includes estimates for incidence, prevalence, and disability-adjusted life-years (DALYs) across 369 diseases. Age-standardized incidence rates (ASIRs) for LEAs were extracted for 21 MENA countries. Trends were analyzed using percentage change calculations and Joinpoint regression to identify significant shifts in LEA rates over time.ResultsFrom 1990 to 2019, male LEA rates generally decreased, while female rates increased. Significant increases in LEA rates were observed in Syria, Yemen, and Afghanistan, correlating with periods of conflict and instability. Conversely, countries like Iraq, Palestine, Sudan, Lebanon, Iran, and Kuwait saw marked decreases. The study highlighted a complex interplay of socio-political factors, natural disasters, and chronic diseases like DM in shaping LEA trends across the region.ConclusionThe study reveals variable LEA trends in the MENA region, influenced by conflicts, natural disasters, and chronic diseases. These findings underscore the need for targeted public health interventions, improved healthcare access, and robust data collection systems to reduce the burden of LEAs and improve patient outcomes in the MENA region.

Fenofibrate to prevent amputation and reduce vascular complications in patients with diabetes: FENO-PREVENT

BackgroundThe potential preventive effect of fenofibrate on lower extremity amputation (LEA) and peripheral arterial disease (PAD) in patients with type 2 diabetes (T2D) is not fully elucidated.MethodsWe selected adult patients ≥ 20 years of age with T2D from the Korean National Health Insurance Service Database (2009–2012). The fenofibrate users were matched in a 1:4 ratio with non-users using propensity scores (PS). The outcome variables were a composite of LEA and PAD and the individual components. The risks of outcomes were implemented as hazard ratio (HR) with 95% confidence intervals (CI). For safety issues, the risks of acute kidney injury, rhabdomyolysis and resulting hospitalization were analyzed.ResultsA total of 114,920 patients was included in the analysis with a median follow-up duration of 7.6 years (22,984 and 91,936 patients for the fenofibrate user and non-user groups, respectively). After PS matching, both groups were well balanced. The fenofibrate group was associated with significantly lower risks of composite outcome of LEA and PAD (HR 0.81; 95% CI 0.70–0.94), LEA (HR 0.76; 95% CI 0.60–0.96), and PAD (HR 0.81; 95% CI 0.68–0.96). The risk of acute kidney injury, rhabdomyolysis, or hospitalization for these events showed no significant difference between the two groups. Subgroup analyses revealed consistent benefits across age groups, genders, and baseline lipid profiles.ConclusionsThis nationwide population-based retrospective observational study suggests that fenofibrate can prevent LEA and PAD in patients with T2D who are on statin therapy.

Transfemoral amputation due to uncontrollable infections after implantation of a total knee endoprosthesis

In the evaluation of an internal analysis of data on the increased effort for nursing during rehabilitation of patients with amputations in the Baumrainklinik of the HELIOS Rehabilitation Center Bad Berleberg, the number of patients with transfemoral amputations (TFA) due to uncontrollable multiple infections after implantation of a total knee endoprosthesis (total knee arthroplasty, TKA) was clearly emphasized. This article discusses the results of a retrospective, patient-controlled trial (PCT) and compares these with the data of the German Endoprosthesis Registry (EPRD). The study concentrated on patients who were admitted to rehabilitation after a TFA due to an uncontrollable infection after implantation of a knee TKA. The primary aims were the identification of patients who developed an uncontrollable infection after TKA with subsequent TFA and the comparison with national and international revision and amputation rates after TKA. An analysis of the medical history questionnaire was carried out for all 787 patients with amputation of the lower extremities who underwent rehabilitation in the time period from 1st January 2007 to 31st December 2015. The patient records were systematically analyzed based on the standardized documentation methods of the medical and nursing personnel using the Barthel index, the activity/function classes, phantom pain and length of stay, including demography, infection history and insurance company. The analysis showed that 10 patients, 2.29% of all TFA, suffered the loss of a lower extremity due to an uncontrollable TKA infection. The revision rate 3 years after primary TKA in Germany is 3.0% (EPRD annual report 2023), whereas values of 1-4% are given in the international literature (status 2020). In the patient group of the EPRD, in 2022 revision surgery was necessary due to an infection in 15.0% of the cases. The current statistics of the EPRD (annual report 2023) show that 3 years after the initial revision surgery due to an infected TKA another revision was necessary in 23.5-30% of cases. These numbers are alarming and should be critically evaluated and monitored. The future aim is to identify the causes of infections, systematic errors in the TKA and the pathogens that lead to infections after TKA and to correlate the associations.

Evaluating Receipt of Optimal Medical Therapy Among Structurally Disadvantaged Groups Undergoing Amputation

Optimal medical therapy (OMT) for peripheral artery disease (PAD) is associated with decreased major amputation and mortality. OMT has several components, including antiplatelet and high-intensity statin therapy, blood pressure control, etc. While there are disparities in receipt of OMT among PAD patients, it is unknown if patients from disadvantaged neighborhoods, measured by the area deprivation index (ADI), are less likely to be on OMT. We performed a retrospective review of patients that underwent major lower extremity amputation between 2015 and 2019 at two large academic healthcare systems. Primary exposure was high ADI, defined as ADI ≥60th percentile, and secondary exposure was non-Hispanic Black (NHB) race. For each analysis, the primary outcome of interest was receipt of OMT, defined here as at least one antiplatelet agent and a high-intensity statin. The exposure outcome relationship was assessed using multivariable logistic regression. Among 354 patients with median age of 66 (interquartile range [IQR] 58-74), 267 (75.4%) were male, 219 (61.9%) identified as NHB and 116 (32.8%) as non-Hispanic White. Overall, 91 (25.7%) patients were on OMT at time of amputation despite 57.3% of the cohort being established with a vascular surgeon. Compared to those with low ADI, the category high ADI had a higher proportion of NHB patients (48.1% vs 70.3%, p= 0.001) and patients were more often hospitalized at the University-affiliated facilities (47.4% vs 63.0%, p= 0.004). High ADI was not associated with receipt of OMT prior to major amputation (adjusted odds ratio [aOR] 0.72, 95% confidence interval [CI] 0.42-1.24). In secondary analysis, NHB race was not associated with receipt of OMT. Stratification by facility type (Veterans Affairs and University-affiliated facilities) also showed no association between high ADI or race and receipt of OMT. Neighborhood economic well-being is not associated with receipt of OMT prior to major amputation. While the absence of socioeconomic disparities is notable, the proportion of patients on OMT is suboptimal. Care processes should be critically evaluated and quality measures potentially created to improve the rate of receipt of OMT among patients at risk for amputation.

Percentage area reduction at week 4 as a prognostic indicator of complete healing in patients treated with standard of care: a post hoc analysis.

Early indicators of healing provide valuable information on the potential benefit of treatment. In patients with hard-to-heal (chronic) diabetic foot ulcers (DFUs), timely intervention is critical. Ulcers that fail to show measurable progress within four weeks of treatment are considered recalcitrant. These ulcers increase the risk of soft tissue infection, osteomyelitis and lower extremity amputation. A prognostic indicator or surrogate marker allows for rapid evaluation of treatment efficacy and safety. An inverse correlation between a percentage area reduction (PAR) of ≤50% at week 4 and complete healing by week 12 has been previously established; however, the data were derived from a standard of care (SoC) arm of clinical trials that are over a decade old. In this post hoc analysis, data from a large multicentre prospective randomised controlled trial were reviewed to assess PAR at week 4 as a prognostic indicator in patients treated with SoC. Overall, 65.4% (17/26) of patients with PAR >50% at week 4 achieved complete closure at week 12. The receiver operating characteristic (ROC) curve for area reduction by week 4 showed strong discrimination for predicting non-healing (area under the ROC curve: 0.92; p<0.001; positive predictive value: 70.6%; negative predictive value: 87.2%). These findings are consistent with previous studies and support the use of four-week PAR as a prognostic indicator.

A multicentre clinical trial evaluating the outcomes of two application regimens of a unique keratin-based graft in the treatment of Wagner grade one non-healing diabetic foot ulcers.

Diabetic foot complications that lead to lower extremity amputations pose a significant challenge to the entire global health system. In this multicentre clinical trial, 26 patients with chronic Wagner one diabetic foot ulcers (DFUs) were treated with a unique human keratin matrix graft applied either weekly or bi-weekly, in addition to standard of care. The hypothesis was that bi-weekly application would be similar to weekly application. The primary endpoint was complete wound closure by 12 weeks, and secondary endpoints included healing time, percent area reduction and weekly changes in peripheral neuropathy, pain and quality of life. In the intent-to-treat population, 77% (10/13) of DFUs treated with bi-weekly application healed compared with 69% (9/13) treated with weekly application. The mean time to heal within 12 weeks in the bi-weekly group was 61 days and in the weekly group was 54 days. The mean percent area reduction at 12 weeks was 94.7% in the bi-weekly group compared with 84.8% in the weekly group. The number of grafts used in the bi-weekly group was 3.9 compared with 6.2 in the weekly group. The results of this trial confirm our hypothesis that whether bi-weekly or weekly application of the unique keratin matrix graft is used to treat nonhealing indolent DFUs, there is a high rate of complete healing. Based on these results, future studies should be conducted that further investigate the use of this novel human keratin matrix graft for the treatment of chronic DFUs.

Geographic Variation in First Lower Extremity Amputations Related to Diabetes and/or Peripheral Arterial Disease

BackgroundTo assess trends of first cases of lower extremity amputation (LEA) related to diabetes and/or peripheral arterial disease (PAD), according to areas of residency and neighbourhood material and social deprivation quintiles, in the province of Quebec, Canada. MethodsUsing the Quebec Integrated Chronic Disease Surveillance System, we calculated crude and age-standardized annual incidence rates of first LEA (total, minor, and major) among adults 40 years of age and older with diabetes and/or PAD in fiscal years 2006 and 2019. Area of residency was compiled in 3 categories: (1) Montreal and other census metropolitan areas; (2) midsize agglomerations (10,000-100,000 inhabitants); and (3) small towns and rural areas (< 10,000 inhabitants). We also stratified according to neighbourhood material and social deprivation quintiles. One-year and 5-year all-cause mortality after first LEA were compared according to area of residency. ResultsAmong the 10,275 individuals who had a first LEA, age-standardized LEA rates remained stable between 2006 and 2019, whereas major LEA rates declined in all geographical areas and minor LEA rates increased (31.6%) in small towns and rural areas. In 2019, age-standardized LEA rates were higher in midsize agglomerations and small towns and rural areas compared with census metropolitan areas. Age-standardized LEA rates in 2019 were higher among the most deprived quintile compared with the most privileged quintile for material and social deprivation. No difference was observed in mortality after first LEA according to area of residency. ConclusionsThere are health disparities in the burden of diabetes and PAD related to first LEA in the province of Quebec. To improve preventive care and reduce the burden of LEA, targeted actions should be taken among the most deprived groups and rural settings.

Peripheral neuropathy prevalence and effect on mobility 12 months after prosthesis prescription among individuals with dysvascular lower extremity amputation.

To determine the prevalence of peripheral neuropathy (PN) and its effect on mobility in patients who were prescribed a lower limb prosthesis (LLP) after an incident dysvascular transtibial (TT) or transfemoral (TF) lower extremity amputation (LEA). We also sought to determine if the effect of PN on mobility was modified by amputation level or depression. Participants were identified retrospectively through the Veterans Affairs (VA) Corporate Data Warehouse (CDW) from March 1, 2018, to November 30, 2020, then were contacted prospectively to obtain their self-reported mobility. Multiple logistic regression was used to control for potential confounders and identify potential effect modifiers. The VA CDW, the National Prosthetics Patient Database, participant mailings and phone calls. Three hundred fifty-seven individuals who underwent a TT or TF amputation due to diabetes and/or peripheral arterial disease and were fitted with a qualifying LLP. Not applicable. The Locomotor Capabilities Index basic and advanced mobility subscale scores. Two-hundred thirty seven participants (66%) had a diagnosis of PN prior to prosthesis prescription. The detrimental effect of PN on achieving basic and advanced mobility was significant after adjusting for potential confounding factors (adjusted odds ratio [aOR], 0.53; 95% confidence interval [CI], 0.30-0.94; p = .03 and aOR, 0.43; 95% CI, 0.24-0.77; p = .005, respectively). The detrimental effect of PN was more pronounced in patients with depression, especially for advanced mobility (aOR, 0.36; 95% CI, 0.14-0.95; p = .04) versus no depression (aOR, 0.53; 95% CI, 0.27-1.0; p = .07). PN is common in patients who have undergone an LEA due to diabetes and/or vascular disease and patients with this diagnosis should be carefully evaluated. Targeted rehabilitation programs to mitigate its potential detrimental effects on mobility are important and should specifically include mental health assessment and treatment.

Interplay Between FoxM1 and Dab2 Promotes Endothelial Cell Responses in Diabetic Wound Healing.

Diabetes mellitus can cause impaired and delayed wound healing, leading to lower extremity amputations; however, the mechanisms underlying the regulation of vascular endothelial growth factor (VEGF)-dependent angiogenesis remain uncertain and could reveal new therapeutic targets. In our study, the molecular underpinnings of endothelial dysfunction in diabetes were investigated, focusing on the roles of Disabled-2 (Dab2) and Forkhead Box M1 (FoxM1) in VEGF receptor 2 (VEGFR2) signaling and endothelial cell (EC) function. Bulk RNA-sequencing analysis identified significant downregulation of Dab2 in high concentrations glucose treated primary mouse skin ECs, simulating hyperglycemic conditions in diabetes mellitus. In diabetic mice with a genetic EC deficiency of Dab2 angiogenesis was reduced in vivo and in vitro when compared with wild-type mice. Restoration of Dab2 expression by injected mRNA-containing lipid nanoparticles rescued impaired angiogenesis and wound healing in diabetic mice. At the same time, FoxM1 was downregulated in skin ECs subjected to high glucose conditions as determined by RNA-sequencing analysis. FoxM1 was found to bind to the Dab2 promoter, regulating its expression and influencing VEGFR2 signaling. The FoxM1 inhibitor FDI-6 reduced Dab2 expression and phosphorylation of VEGFR2. These findings indicate that restoring Dab2 expression through targeted therapies can enhance angiogenesis and wound repair in diabetes. To explore this therapeutic potential, we tested LyP-1-conjugated lipid nanoparticles (LNPs) containing Dab2 or control mRNAs to target ECs and found the former significantly improved wound healing and angiogenesis in diabetic mice. This study provides evidence of the crucial roles of Dab2 and FoxM1 in diabetic endothelial dysfunction and establishes targeted delivery as a promising treatment for diabetic vascular complications.

Etiologies of non-traumatic extremity compartment syndrome: A multi-center retrospective review

Determine the etiologies of non-traumatic extremity compartment syndrome (NTECS), understand the demographics of NTECS patients, describe their diagnostic workup and treatment, and establish their rate and cause of in-hospital mortality.This is a retrospective cohort study of all patients diagnosed with NTECS at two level 1 trauma centers between January 2006 and December 2019. Data pertaining to the etiology of NTECS, patient demographics, diagnostic and treatment modalities, and in-hospital mortality were collected from electronic medical records.A total of 572 patients were included in this study with an average age of 54±18 years. The etiologies of NTECS were categorized into one of seven groups: 233 hypercoagulable state, 113 found-down secondary to substance use, 68 hypocoaguable state, 58 perioperative positioning, 55 shock, 30 infection, and 15 intravenous/intraosseous (IV/IO) infiltration. Approximately 13 % of patients underwent a skin graft or flap procedures, while 13 % of patients required an extremity amputation. The in-hospital mortality was highest in patients who developed NTECS due to shock (58 %). The average in hospital-mortality for all NTECS etiologies was 20 %.While uncommon, many etiologies of NTECS exist and often manifest insidiously. 13% of patients who develop NTECS will require a skin graft / flap, or extremity amputation. 20 % of patients who develop NTECS die during their hospitalization. High clinical suspicion and future research in this field are necessary to improve clinical outcomes for these patients.Level IV: Retrospective review

Limb amputation versus salvage: Evaluating how reliable YouTube is as a source for patient education

The objective of this study was to assess the educational quality and reliability of YouTube videos related to lower extremity amputation (LEA) versus limb salvage. Pertinent YouTube videos were identified using specific search terms and video educational quality was assessed via validated assessment tools. Fifty-nine videos met inclusion criteria and the mean Journal of the American Medical Association (JAMA) score was 2.3 ± 0.65 (range: 0–4), indicating poor reliability. The mean Global Quality Score (GQS) was 2.66 ± 0.99 (range: 1–5), reflecting suboptimal educational quality. The mean Limb Salvage versus Amputation (LSA) score was 5.59 ± 3.66 (range: 0–15), indicating limited content quality specifically related to LEA versus limb salvage. Longer video duration was positively correlated with higher JAMA, GQS, and LSA scores. Hospital/University-sponsored videos had higher JAMA and GQS scores and videos by Healthcare Professionals (Nonphysician: PhDs and medical educators) content creators had the highest LSA scores. The study highlights the need for improved patient educational resources on LEA versus limb salvage, as the overall reliability and educational quality of YouTube videos on this topic is poor.

Prevalence and incidence of peripheral neuropathy, peripheral artery disease, foot disease, and lower extremity amputation in people with diabetes in Ireland; a systematic review protocol.

Internationally, the prevalence of diabetes is increasing, and with this comes an increase in diabetes related complications. Diabetic foot disease is the most common lower extremity complication in people with diabetes causing 2% of the global disease burden. It, is associated with major morbidity, mortality, and costs to health services. Despite this burden, the incidence and prevalence of diabetic foot disease is unknown in Ireland. This paper presents a protocol for a systematic review to examine the incidence and prevalence of diabetic foot disease in the Irish population. A systematic review will be performed using the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Pubmed, EMBASE, and Lenus, the Irish Health Research repository, will be searched for publications in any language and without restrictions to date. Title, abstract, and full text screening will be carried out independently by two investigators. Publications reporting on the incidence or prevalence of peripheral neuropathy, peripheral artery disease, ulceration, or amputation in people with diabetes in Ireland, from a defined geographical catchment area of Ireland, will be included. Joanna Briggs Institute (JBI) Critical Appraisal tool will be used to assess included studies methodological quality. Results will be reported in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. The results of this systematic review can be used to inform appropriate stakeholders on the incidence and prevalence of diabetic foot disease in Irish populations, enabling decision making around appropriate use of resources to help prevent, and improve management of this disease. CRD42023472904.

Analysis of amputations occurring in the earthquakes centered in Kahramanmaraş: Adıyaman experience.

Amputations are a common surgical procedure resulting from trauma during earthquakes, leading to severe disability. This study aims to investigate surgical outcomes specific to amputations that occurred in Adıyaman after the Kahramanmaraş earthquakes. This descriptive study included amputees who presented to Adıyaman University Training and Research Hospital. Between March 6, 2024 and March 29, 2024, amputees were contacted by phone and asked the questions in the form. Data analyzed included demographic information, number and level of amputated extremities, phantom limb pain, stump infection, extrication time, time to initiation of rehabilitation, number of revision, and whether a prosthesis was fitted. The study reached 75 amputees. The mean age was 37.9 ± 19.2, and the most frequently amputated age group was adults. Stump infection was observed in 40 amputees (53.3%), phantom limb pain in 47 (62.6%),and revision in 29 (38.7%). The median extrication time was 36h and initiation of rehabilitation time was 45 days. It was noted that 35 amputees (62.5%) used prostheses. A statistically significant relationship was found between fasciotomy and stump infection (p = .000). Infection was detected in 65% of those who underwent fasciotomy. Earthquake-related amputations most frequently affected the adult age group and primarily involved lower extremity amputations, such as transfemoral and transtibial amputations. Phantom limb pain, need for revision, and infection are common in earthquake-induced amputations. Delayed fasciotomy increases the risk of stump infection. The data obtained in this study will help plan local health services to coordinate amputation care in disasters.