Amputation Research Articles

Analysis of the organization and conduct of sports events in the Armed Forces of Ukraine and the armed forces of the leading states – NATO member states with military personnel with limited functional capabilities

During the full-scale invasion of the Russian Federation into Ukraine, servicemen of the Armed Forces of Ukraine, defending their country from the aggressor, received injuries of various degrees of severity, including amputation of limbs. After receiving injuries and wounds, servicemen go through significant psychological and physical disorders, which are difficult for them to deal with alone. Therefore, with the specified category of servicemen, it is necessary to carry out medical, psychological, and physical rehabilitation, as well as to develop programs for their adaptation to civilian life with the mandatory involvement of them in sports events. The Russian-Ukrainian war leads to an increase in the number of servicemen with limited functional capabilities. This indicates the search for optimal ways of their adaptation to the normal conditions of existence and functioning in the social environment and among the collective of their units and parts. Unfortunately, historical analysis shows that our servicemen with limited functional capabilities are in urgent need of social adaptation, especially with the start of hostilities on the territory of Ukraine since 2014, in connection with Russia's armed aggression against Ukraine. That is why various sports federations, public organizations and active public figures in Ukraine hold competitions involving servicemen with limited functional capabilities, namely; "National Invincible Games", "Strong of Ukraine", "Kyiv Unbreakable", "Hero Games", "Veteran Ten", "Invincible Cup" football, "Strong of Ukraine", "I am your hand" and others. According to the results of the performances, the best athletes with disabilities represent our country at international level competitions, such as the Invictus Games.

The impact of hyperbaric oxygen therapy on the redox balance of patients with diabetic foot syndrome

Diabetic foot wounds associated with oxidative stress are treated with hyperbaric oxygen (HBO), but that may also induce the stress itself; therefore, we studied the effect of HBO treatments on the oxidant–antioxidant balance in the venous blood of patients with diabetic foot syndrome. In addition, blood counts were also examined. 14 male patients (24–74 years), at risk of lower limb amputation were treated with 30 HBO procedures (60 min of the inhalation of pure oxygen at a pressure of 2.5 atm per day, 5 days a week). The control group consisted of 29 healthy male volunteers aged 25–69 years. No members of the group had been subjected to HBO therapy previously (ClinicalTrials.gov, no. NCT06401941). The analyzed redox parameters did not change during the experiment in the patients (p > 0.05). The concentration of thiobarbituric acid reactive substances (TBARS) in the plasma was higher in the patients before the first and after the thirtieth HBO treatments when compared to the control group. In contrast, the TBARS concentration in erythrocytes was lower in the patients after the first treatment vs. the controls. Moreover, the higher activity of catalase in the patients’ erythrocytes was noted before the therapy and after the first and last treatments compared to the controls. HBO therapy increased the percentage of monocytes and platelet volume, but it decreased the volume of platelets in the patients’ blood. HBO therapy does not affect the oxidant–antioxidant balance disturbed in diabetic foot patients.

Technical aspects of the new BYCROSSTM atherectomy device - preliminary results after 28 patients.

Purpose: Technical aspects are crucial for the planning and performing of the atherectomy to treat peripheral arterial disease. This report illustrates the use of a novel atherectomy device and investigates the feasibility, efficacy, and safety procedures involved in performing the atherectomy on 28 patients. We performed a prospective analysis of patients who underwent an atherectomy with the BYCROSSTM Atherectomy device between August 2022 and September 2023 at a tertiary referral centre. Patients with a lesion below the aortic bifurcation (vessel diameter ≥ 3mm) having a de novo or restenotic (stent-included) present were recruited. Major adverse events (MAE) are defined as amputation, death, myocardial infarction, or angiographic distal embolization that require a separate intervention. Of the 28 patients treated with the BYCROSS device, 23 were men with a mean age of 65.6 ± 9,6 years and a mean BMI of 24,6 ± 3.9 kg/m2. Most patients had a typical atherogenic risk profile as well as multiple preexisting comorbidities. In all patients, a symptomatic peripheral arterial disease (PAD) was the main reason for an intervention. The most common Rutherford category was 5 (12/28). The most common lesion region was the femoropopliteal segment (25/28) with 23 de novo stenosis. Mean lesion length was 218,0 ± 93,7 mm. The mean PACCS Score was 3,0 ± 1,0. Stenosis grade was by mean 99,3 ± 3,7%. Ankle Brachial Index (ABI) increased significantly after BYCROSS atherectomy (pre- 0,44 ± 0,43 vs. post-procedure 0,84 ± 0,30 P<0,001. Target lesion/vessel revascularization (TLR/TVR) within the first 30 days was 3,6% (1/28). 30-day MAE rate was 14,3% (vessel perforation in 3/28 patients, embolism in 1/28). There were no deaths, index limb amputations, or myocardial infarctions. The BYCROSSTM atherectomy system is a new device with numerous advantages in treating high-grade, calcifying stenosis and occlusion processes in PAD. Based on the above findings, the BYCROSSTM Atherectomy device represents a feasible, safe, and effective method for endovascular treatment of peripheral arterial disease.

Prognostic factors and outcomes of chronic limb threatening ischaemia in patients post kidney transplant: a systematic review

BackgroundKidney Transplantation (KT) is widely recognized as the optimal treatment for patients with End Stage Renal Disease (ESRD), improving not only life expectancy but also quality of life. Undetected peripheral arterial disease (PAD) in patients undergoing KT may lead to lower limb ischaemic ulceration and gangrene which is associated with an increased mortality rate. If undiagnosed and untreated this may lead to limb loss and graft failure. This review aims to evaluate the current evidence related to the prognosis of chronic limb-threatening ischemia (CLTI) in patients with a KT.MethodsWe conducted a systematic review of the literature in PubMed and MEDLINE, the Cochrane database of systematic reviews, Elsevier, Web of Science, and CINAHL using relevant search keywords to identify the prognosis and progression of CLTI in patients with a KT. Outcomes of interest were CLTI and progression rate in terms of haemodynamic measurement. This systematic review adhered to the guidelines set forth by the Cochrane Collaboration. The study design, population selection, and follow-up time frame were outlined in accordance with the PRISMA guidelines.ResultsStudies have shown a decline in the ankle-brachial index (ABI) post-KT, indicating vascular deterioration. Surgical interventions and amputations are more likely, particularly on the ipsilateral side of KT. The infrapopliteal artery is the most compromised in this cohort. A low ABI was found to be an independent predictor of graft failure, doubling the risk of mortality post-KT. Quality of evidence was observed to be low primarily due to confounding and selection bias.ConclusionsThe available evidence regarding the prognosis of CLTI in individuals with KT is limited to a small number of studies offering predominantly low-quality evidence and conflicting results pertaining to PAD and its progression into CLTI. Further research is required on CLTI prognosis and progression among KT recipients.

Streptokinase or Alteplase for Acute Limb Ischemia? A Meta-Analysis

Background: Acute limb ischemia (ALI) is a vascular emergency that necessitates prompt and effective treatment to restore blood flow and prevent limb loss. Thrombolytic therapy, particularly with agents like streptokinase and alteplase, plays a pivotal role in ALI management. This meta-analysis and systematic review aimed to compare the efficacy and safety of streptokinase and alteplase in treating ALI. Methods: A comprehensive search of PubMed, Embase, Science Direct, and the Cochrane Library databases was conducted up to August 13, 2024, to identify relevant studies. The inclusion criteria encompassed clinical trials involving patients diagnosed with ALI who received either streptokinase or alteplase as the initial thrombolytic treatment. The quality of the included studies was rigorously assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and the Methodological Index for Non-Randomized Studies (MINOR) criteria. A meta-analysis was performed using the Mantel-Haenszel random-effects model to calculate risk ratios (RRs) with their corresponding 95% confidence intervals (CIs). Results: The final analysis included 20 studies, encompassing both qualitative and quantitative assessments. A comparative analysis of streptokinase and alteplase for limb salvage at 30 days revealed a significant advantage in favor of alteplase, with a relative risk ratio (RR) of 0.78 (95% CI 0.69-0.88, I² = 0%). Furthermore, streptokinase was associated with a higher rate of primary amputation, with an RR of 2.54 (95% CI 1.50-4.32, I² = 0%) compared to alteplase. The use of streptokinase also correlated with a higher risk of complications, including major bleeding (RR 1.75, 95% CI 0.04-84.30, I² = 77%) and minor bleeding (RR 1.41, 95% CI 0.60-3.32, I² = 0%). Conclusion: The findings of this meta-analysis underscore the superior efficacy of alteplase in achieving limb salvage in ALI, coupled with a more favorable safety profile. The preferential use of alteplase in clinical practice is recommended, particularly in patients with severe ischemia. However, careful patient selection and close monitoring are crucial when streptokinase therapy is considered.

Predictive ability of the pedal medial arterial calcification (pMAC) score for major adverse limb events among patients with Chronic Limb-Threatening Ischemia

ObjectivePedal medial arterial calcification (pMAC) is a potential predictor of major adverse limb events (MALE) among patients with critical limb-threatening ischemia (CLTI). This study aims to validate the prognostic value of the pMAC score in predicting major lower limb amputation (MLLA) and need for re-do revascularisation. MethodsA single centre study involving 196 patients diagnosed with CLTI, reviewed between 2012 and 2022. Patients’ pMAC scores were obtained through X-ray assessments. Correlations between pMAC scores and the incidence of MALE and re-do revascularisation, were analysed. A power analysis using G* Power 3 software determined a needed sample size of 157 participants. Statistical analysis employed SPSS 26, utilising descriptive statistics, Chi Square, Mann-Whitney, Kaplan-Meier with log-rank test, and Cox regression for predictor identification. ResultsThe cohort was predominantly male (79.1%) and diabetic (59.2%). Re-do revascularisation need was 15.3%, increasing with pMAC scores: 3.3% (low), 24.5% (medium), and 50% (high) (p<0.001). MLLA frequency also rose with pMAC scores: 6.7%, 27.5%, and 50% respectively (p<0.001). Higher pMAC scores correlated with a higher incidence of MALE (p=0.029). Multivariate analysis showed medium pMAC (HR 4.159, p=0.002), high pMAC (HR 7.366, p=0.015), and GLASS stage 3 (HR 3.529, p=0.011) as independent MLLA predictors. Re-do revascularisation predictors included female sex (HR 2.106, p=0.063), Black race (HR 64.498, p=0.001), medium pMAC (HR 6.812, p=0.002), high pMAC (HR 11.455, p=0.008), and GLASS stage 3 (HR 2.899, p=0.037). ConclusionThe pMAC score effectively predicts MALE in CLTI patients and enhances risk stratification. Using both, pMAC scores and GLASS stages enhances predictive accuracy, identifying patients at higher risk for MLLA, Informing clinical decision-making and therapeutic strategies.

CURRENT TRENDS IN THE REHABILITATION OF PATIENTS WITH LOWER LIMB AMPUTATION

Amputation of a lower limb is a serious intervention that has a profound impact on a person's life and ability to work. The loss of a limb often causes significant physical and psychological changes that require comprehensive rehabilitation. The patient faces new physical limitations, such as loss of mobility, changes in balance and the need to adapt to prostheses. According to a report by the Wall Street Journal, since the beginning of the Russian-Ukrainian war, the number of people in need of amputation in Ukraine has risen to levels not seen since the First World War. The publication estimates that between 20,000 and 50,000 Ukrainians have lost one or two limbs. Therefore, the study of current trends in the rehabilitation of patients with lower limb amputation in the context of war in Ukraine is extremely relevant. Purpose. To analyse and systematise current trends in the rehabilitation of patients with lower limb amputation. Materials and methods. To achieve the objectives of the study, the researchers analysed scientific literature and systematised information using electronic databases such as PubMed, Google Scholar and others. Research results. Today, physical therapy for patients with lower limb amputation is characterised by a combination of traditional rehabilitation methods and innovative approaches. Kireev and others developed an algorithm that includes rehabilitation activities at 4 main stages. Preoperative rehabilitation, stage I, is aimed at improving postoperative outcomes. It has been suggested that the preoperative programme used in the treatment of young patients with lower limb amputation should consist of chest physiotherapy, muscle and joint mobility training, focusing on maintaining strength and function. During the second stage, before prosthetics, the rehabilitation process includes the aforementioned therapeutic gymnastics and physiotherapy, as well as massage and kinesiotaping. Important issues in preparing an amputated stump for prosthetics include preparing the postoperative wound and scar, controlling edema, preventing muscle atrophy, and preventing the formation of contractures in the joints of the amputated lower limb. In addition to the above-mentioned traditional methods, innovative approaches are actively used at the stage of training with a prosthesis: robotic prostheses, biofeedback technologies, and VR technologies. Giacomo Valle's research has shown that the use of a robotic prosthesis in combination with biofeedback technology not only increases the patient's movement speed, but also increases his or her confidence. Research by Rami L. Abbas demonstrated the feasibility of using VR technologies, which showed a significant improvement in the balance markers, TUG, DGI and BBS tests (P &lt; 0.05). Lifelong rehabilitation, stage IV, involves monitoring the patient for psychosocial adaptation, stump skin pathologies, pain, musculoskeletal disorders, cardiovascular diseases, other chronic diseases, health, and ensuring the use of appropriate footwear for the contralateral limb. Conclusions. Thus, the current trends in combining traditional methods with innovative approaches in the rehabilitation of patients with lower limb amputation are appropriate and justified. It is through the use of therapeutic gymnastics, massage and kinesiotaping in combination with the use of biofeedback technologies, robotic systems and virtual reality that the best results are achieved.

Reducing phantom limb pain using phantom motor execution enabled by augmented and virtual reality: participants’ perspectives on an innovative treatment

Purpose Phantom limb pain (PLP) is a condition that greatly diminishes quality of life. Phantom motor execution (PME), enabled by myoelectric pattern recognition combined with virtual and augmented reality, is a novel treatment for PLP. Here we, aimed to describe patients’ experiences of this treatment. Material and Methods Qualitative, using semi-structured interviews one month after completed PME treatment. Twenty-one Swedish and Dutch patients (mean age 57, 16 males, 16 lower limb amputations) participated. The analysis followed the framework approach. Results The main themes were 1) treatment effects on the perception of the phantom limb, 2) living with PLP before and after treatment, and 3) facilitators and barriers to treatment. Most participants learned to control their phantom limb, perceived it more positively and as more complete. This control over the phantom limb became a tool for managing PLP. Most participants’ outlook on life and energy levels improved after treatment. Being mentally focused during treatment was important. Therapists were pivotal to the success of the treatment. Conclusion Controlling the phantom limb improved their perception of it and pain management, self-agency, and quality of life. The therapists’ role was invaluable. We suggest training for patients in phantom limb control before and after amputation.

New strategy for shortening the consolidation period in distraction lengthening of phalanges or metacarpal bone

Distraction lengthening of digits enhances hand function in patients with congenital phalangeal defects or traumatic hand amputations. Although callotasis is a useful distraction lengthening method, it is challenging and often results in various complications and prolonged fixation. Based on our experiences, we attempted to develop innovations to reduce the fixation period. We included 12 digits from nine patients with digital bone defects; lengthening was performed on seven proximal phalanges and five metacarpal bones using an Ilizarov mini-fixator device. In three digits, cancellous bone grafting within the cavity of the distraction callus, concomitant with internal fixation using an intramedullary screw, was performed to shorten the Healing Index. The mean achieved lengthening was 24mm for proximal phalanges and 22mm for metacarpal bones, with a Healing Index of 37.9 and 42.6 days/cm, respectively. Additionally, the Healing Index was significantly shorter in the three digits treated with cancellous bone grafting and internal fixation (mean 27.0 days/cm) than in the nine with no bone grafting (mean 44.1 days/cm). Major complications included early bone union, insufficient fingertip skin, and callus fractures during the consolidation period, affecting two, two, and one patient, respectively. Bone grafting within the distraction callus cavity promotes rapid bone formation, while internal fixation enables earlier removal of external fixators, thereby shortening the Healing Index.

Targeting hypoxia and thrombospondin-2 in diabetic wound healing.

Impaired wound healing in diabetic patients is the leading cause of diabetes-associated hospitalizations and approximately 50% of lower limb amputations. This is due to multiple factors, including elevated glucose, sustained hypoxia, and cell dysfunction. Previously, diabetic wounds were found to contain excessive levels of the matricellular protein thrombospondin-2 (TSP2) and genetic ablation of TSP2 in diabetic mice or treatment of wounds with a hydrogel derived from TSP2-null mouse skin improved healing. Previously, TSP2 has been shown to be repressed by hypoxia, but in the present study we observed sustained hypoxia and overlapping TSP2 deposition in diabetic wounds. We determined this observation was due to the insufficient HIF-1α activation verified by western blot and immunofluorescent analysis of wound tissues and invitro hypoxia experiments. Application of Dimethyloxalylglycine (DMOG), which can stabilize HIF-1α, inhibited TSP2 expression in diabetic fibroblasts in hypoxic conditions. Therefore, we prepared DMOG-containing TSP2KO hydrogel and applied it to the wounds of diabetic mice. In comparison to empty TSP2KO hydrogel or DMOG treatment, we observed improved wound healing associated with a reduction of TSP2, reduced hypoxia, and increased neovascularization. Overall, our findings shed light on the intricate interplay between hyperglycemia, hypoxia, and TSP2 in the complex environment of diabetic wounds.

Mesenchymal stromal cell therapy (REGENACIP®), a promising treatment option in chronic limb threatening ischemia - a narrative review.

Chronic Limb Threatening Ischemia (CLTI) is a challenging clinical problem associated with high morbidity and mortality. Endovascular interventions have been the cornerstone of treatment whenever possible. It is estimated that CLTI represents < 10% of all Peripheral Artery Disease patients, yet 50% of the patients end up either with a major amputation of the lower limbs or die of cardiovascular causes within one year period, especially in those with unsuccessful revascularization or "no-option" CLTI. Cell-based therapeutics, especially bone marrow-derived mesenchymal stromal cells have emerged as a potential, promising, and novel alternate therapeutic modality in the management of CLTI, bolstered with positive results in numerous research, including randomized and nonrandomized trials. REGENACIP® is one such BM-MSC therapy approved by Central Drugs Standard Control Organization in India for the management of "no-option" Atherosclerotic Peripheral Arterial disease / Buerger's disease patients with established critical limb ischemia in Rutherford Grade III-5 or III-6, not eligible for or have failed traditional revascularization treatment, with rest pain and / or ulcers in the affected limb. The current review aims to deliberate upon the various aspects of CLTI and clinical benefits of REGENACIP® therein.

Hybrid bionic control system for prostheses: a review

The legs and hands are the most susceptible to loss and this is due to the fact that they are prominent external organs in the human body. With increasing disasters, accidents, wars and diseases the loss of limbs is increasing, making the individual restricted in freedom and movement and pursuing to find alternatives to improve the individual's life is extremely important. Modern bionic prostheses are the best alternatives to replace amputated ones to perform both aesthetic and functional tasks. On this basis and by analyzing the most common and used methods in prosthetics management as the electroencephalography (EEG), electromyography (EMG), and functional near- infrared spectroscopy (fNIRS) methods, knowing their advantages and disadvantages, comparing them and documenting their results from the outputs of literature and previous experimental studies, whether in individual use or hybrid use.In the light of these data, this article highlights the most common technologies and considers their superiority and insuperiority, which can be suitable for the formation of a hybrid bionic control system for prostheses or rehabilitation and restoration of lost functions. Based on the most important studies that have dealt with these technologies whereas individually or in their hybrid state. In addition, this article provides an encouraging outlook for those interested in scientific research to research, compare, identify and characterise superior hybrid systems related to exoskeletal control systems and in particular prostheses.

Multiplexed Piezoelectric Electronic Skin with Haptic Feedback for Upper Limb Prosthesis

AbstractUpper limb amputation severely impairs tactile perception, limiting daily activities. Developing a near‐natural replacement with prosthetic devices requires improving user sensory experiences during object interactions. The ideal upper limb prosthesis should provide real‐time sensory feedback, mirroring natural experiences. Current prostheses struggle with providing adequate tactile feedback due to sensory limitations. Inspired by the sensory properties of skin, we present a micro‐fabricated, multiplexed electronic skin (e‐skin) with actuators for sensory feedback in upper limb amputation. The piezoelectric‐capacitive sensor array detects static pressure, temperature, vibration, and texture, with integrated actuators stimulating the skin to provide real‐time feedback. The sensors integrate with actuators via readout electronics, making the system standalone and easy to use. The flexible, compact sensor array design (two pixels within a 1 cm² footprint) detects a wide range of pressure (0.5–10 kPa), temperature (22–60 °C), vibration (35–100 Hz), and texture (2.5–45 Hz), suitable for daily use. The e‐skin, attached to a prosthetic finger, is tested for feasibility on human volunteers with wrist‐mounted actuators. Statistics are used to quantitatively assess system performance. The integration of multiplexed sensors and actuators enhances tactile feedback, improving the quality of life for people with upper limb amputations.

Duration, Cost, and Escalation of Care Events for Physical Therapy Management of Low Back Pain in Service Members With Limb Loss.

Physical therapy (PT) is recommended as a primary treatment for low back pain (LBP), a common and impactful musculoskeletal condition after limb loss. The purpose of this brief report is to report the duration and cost of PT care, and subsequent escalation of care events, for LBP in service members with and without limb loss. This was a retrospective cohort, descriptive study. Service members with and without limb loss (matched) who received PT for LBP at a military treatment facility from 2015 to 2017 were included. Duration of PT care, number of PT visits, and escalation of care events 1 year after PT were extracted from medical records. Escalation of care events was identified as epidural steroid injections, referrals to specialists (e.g., orthopedists, spine surgeons, and pain management), and LBP-related hospitalizations.LBP-related PT encounters were queried; duration of care, number of visits, and cost of care were quantified. Escalation of care events, including opioid prescription, epidural steroid injections, specialty referrals, and hospitalizations, were identified up to 1 year after PT care. The average course of PT care for LBP was 12.9 more visits, 48.7 days longer, and $764.50 more expensive in service members with limb loss (n = 16) vs. those without limb loss (n = 48). Higher rates of opioid prescriptions and specialty referrals were observed in service members with limb loss. This study suggests that service members with limb loss and LBP received higher quantities and longer durations of PT than those without limb loss, yielding a nearly 4 times higher cost of PT.

8640 Thyroid Orbitopathy in Pregnancy

Abstract Disclosure: Z. Maisonet -Feliciano: None. M. Alvarado: None. L.A. Gonzalez-Rodriguez: None. M. Ramirez: None. L. El Musa Penna: None. J. Segarra-Villafane: None. I.C. Arroyo: None. W. Medina-Torres: None. L.R. Sepulveda-Garcia: None. Thyroid orbitopathy, often associated with Graves' disease, is characterized by the inflammation and swelling of ocular tissues. Its occurrence or exacerbation during pregnancy is infrequent, primarily due to the immunosuppressive state inherent in pregnancy. In most instances, the immunosuppression associated with pregnancy leads to a reduction in TRAb levels, although they continue to be present in women who have an active form of the disease. The course and severity of ocular manifestation do not always correlate with thyroid hormone levels. Strict control of thyroid function is crucial in patients with thyroid eye disease. This report sheds light on the rare occurrence of thyroid orbitopathy during pregnancy, a condition that complicates treatment due to potential risks to both the mother and the child. In this case, a 35-year-old pregnant woman with no prior history of thyroid issues exhibited symptoms of hyperthyroidism in her first trimester, including unintended weight loss, anxiety, and tremors in the upper limbs. She also presented with ocular discomfort, diplopia, and eyelid lag. Thyroid tests confirmed Graves Disease, with a significant elevation in Thyroid Stimulating Immunoglobulin (TSI): 243 %, Free thyroxine (T4): 1.08 ng/dl and Triiodothyronine (T3): &amp;gt;1.89 units and decreased Thyroid Stimulation Hormone (TSH): 0.001 uIU/ml. Ophthalmic examination revealed mild Graves orbitopathy due to bilateral exophthalmos (measured by Hertel’s exophthalmometer) 21mm on both sides, Marginal reflex distance (MDR) 1: right eye 9 mm and left 7mm. MDR 2: right eye 6mm and left eye 7mm. Right upper eyelid retraction, lagophthalmos of the right eye, limitation in the upward movement of the left eye, and vertical diplopia on extreme gazes without signs of orbital compression. Considering her normal FT4 levels and the mild nature of her hyperthyroidism, the decision was made to prioritize the mother's treatment while minimizing fetal risk, thus opting not to initiate antithyroid medication but to closely monitor her thyroid function. Symptomatic management of her orbitopathy was provided including lubricating eye drops and an eye patch. Throughout the progression of her pregnancy, her TSI levels exhibited a decreasing trend while FT4 remained within normal limits. Following delivery, there was a notable improvement in her ocular symptoms, and her TSH started increasing up to normal values of 1.29 uIU/ml and FT4 remained in range. This report underscores the importance of recognizing uncommon presentations of autoimmune thyroid conditions, such as thyroid orbitopathy, during pregnancy. It emphasizes the complexities and necessary considerations in treating these cases. A collaborative approach involving endocrinology, ophthalmology, and obstetrics is essential to safeguard the health of both the mother and the fetus. Presentation: 6/1/2024

8418 Association of GLP-1 Receptor Agonists and SGLT-2 Inhibitors with Major Adverse Cardiovascular Events and Serious Liver Events among Patients with Type 2 Diabetes and MASLD

Abstract Disclosure: A. Kutz: None. D.J. Wexler: None. J. Liu: None. J.M. Paik: None. E. Patorno: None. Introduction and study question Little is known about the cardiovascular (CV) and hepatic effectiveness of glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium–glucose cotransporter 2 inhibitors (SGLT-2i) in people with type 2 diabetes (T2D) and known metabolic dysfunction-associated steatotic liver disease (MASLD) in clinical practice. We assessed the comparative CV and hepatic effectiveness and the safety of GLP-1 RA and SGLT-2i in people with T2D and prevalent MASLD. Methodology Using pooled data from Medicare fee-for-service (2013–2020) and a large U.S. health insurance database (2013-June 2022), we conducted two propensity-score fine stratification weighted cohort studies including adults with T2D and a diagnosis of MASLD who initiated GLP-1RA, SGLT-2i, or dipeptidyl peptidase 4 inhibitors (DPP-4i, reference). Using Cox proportional hazards models, we assessed the primary CV effectiveness composite outcome of acute myocardial infarction, ischemic stroke, hospitalization for heart failure, or all-cause mortality. The primary hepatic effectiveness outcome was a composite of serious liver events (hospitalization for ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, bleeding esophageal varices, hepatic encephalopathy, or liver transplantation). The safety outcome was a composite of severe adverse events (lower limb amputation, non-vertebral fracture, emergency admission for hypoglycemia, or hospitalization for acute kidney injury, diabetic ketoacidosis [DKA], severe genital or urinary tract infection, acute pancreatitis, or biliary event). Major results Compared with DPP-4i (n=17,084 initiators), the hazard ratio (HR) for the primary CV outcome associated with GLP-1 RA (n=13,666 initiators) was 0.67 (95% CI, 0.56 to 0.81), corresponding to an incidence rate difference (IRD) per 1,000 person-years of -21.6 (95% CI, -26.7 to -16.6). The HR for the primary hepatic outcome was 0.47 (95% CI, 0.25 to 0.90), the IRD -2.1 (95% CI -3.4 to -0.9). Similar CV benefits were observed for SGLT-2i (n=11,108) vs DPP-4i (n=16,979), with a HR for the primary CV outcome of 0.82 (95% CI 0.70–0.96) and an IRD of -11.0 (95% CI -16.2 to -5.8). For the primary hepatic outcome, the HR was 0.81 (95% CI 0.45 to 1.44) and the IRD -1.1 (95% CI -2.4 to 0.3). Severe adverse events were not more frequent with GLP-1RA or SGLT-2i compared with DPP-4i. Interpretation and conclusion Among people with T2D and MASLD, the use of GLP-1 RA or SGLT-2i was associated with fewer CV events, vs DPP-4i, while GLP-1 RA also reduced serious liver events. Compared with DPP-4i, GLP-1RA or SGLT-2i were not associated with higher safety adverse event rates. Presentation: 6/2/2024

Return to Work and Employment after Lower Limb Amputation: A Narrative Review

Return to Work and Employment after Lower Limb Amputation: A Narrative Review

A-059 Validation of self-collected capillary dried blood spot collection for clinical HbA1c testing

Abstract Background The increased prevalence of diabetes in socially disadvantaged populations requires solutions that are amenable to these communities. Unmanaged diabetes can cause cardiovascular disease, kidney damage, blindness, and limb amputation. Diabetes is traditionally diagnosed using fasting/oral glucose tolerance or hemoglobin A1c (HbA1c) tests; both of which require access to medical and laboratory facilities. Self-collected capillary dried blood spot (DBS) testing for HbA1c could alleviate health disparities by offering access to low cost and minimally invasive remote collection. The objective of this study was to validate self-collected capillary DBS specimens for clinical HbA1c testing. Methods DBS HbA1c was measured using the hemolysate application of the Roche cobas c513 Tina-quant Hemoglobin A1cDx Gen.3 assay. Calibration was performed according to the manufacturer’s package insert. Patient samples were prepared by collecting two 3mm DBS punches. Non-biological standards were prepared by placing two blank 3mm DBS punches into an empty tube and adding 10uL of standard. After 24 hours, samples were resuspended in 750uL of hemolyzing reagent and incubated for 75 minutes at room temperature (RT) while shaking at 800 RPM. Preliminary data showed that non-biological standards spotted onto DBS cards did not behave like real patient samples. A correction factor (CF) was derived (n=134) and challenged (n=20) to account for the systematic bias observed between matched patient DBS and venous specimens. Imprecision was established by running two patient DBS specimens as controls. Accuracy was evaluated using residual College of American Pathologists (CAP) proficiency testing (PT) material (n=32). Linearity was confirmed by running 5 levels of Maine Standards Linearity HbA1c Kit in triplicate. Stability of the DBS specimen and the hemolysate supernatant extracted from the DBS specimen were observed at RT. Results Specimens tested between venous and DBS HbA1c to derive the CF (n=134) had a bias of 0.26% (4.32%) and a linear equation of (y=0.938x +0.631; R=0.996). The resulting CF is: reported HbA1c% = (DBS HbA1c% - 0.631)/0.938. Matched venous and DBS specimens that challenged the CF (n=20) had a bias of -0.10% (-1.83%) and a linear equation of (y=1.06x -0.41; R=0.988). Imprecision was 2.3% and 1.3% for patient DBS control specimens with mean concentrations of 5.3% and 5.9%, respectively. Residual CAP PT samples (n=32) had an average bias of -0.05% (-0.40%). DBS HbA1c concentrations from 4.2-15.5% were linear (y=0.903x +1.15; R=0.999). The DBS specimen is stable for 60 days at RT and the hemolysate supernatant is stable for at least 10 hours at RT. Conclusions Self-collected capillary DBS specimens are acceptable for the clinical measurement of HbA1c, and effectively increase accessibility to diabetes screening and monitoring. Applying a CF to DBS patient samples removes the systematic bias observed between matched venous and DBS samples. Non-biological standards and capillary whole blood do not behave the same on DBS cards. Alternative PT for DBS specimens should be investigated as at-home collection advances.

Granular Porous Nanofibrous Microspheres Enhance Cellular Infiltration for Diabetic Wound Healing.

Diabetic foot ulcers (DFUs) are a significant challenge in the clinical care of diabetic patients, often necessitating limb amputation and compromising the quality of life and life expectancy of this cohort. Minimally invasive therapies, such as modular scaffolds, are at the forefront of current DFU treatment, offering an efficient approach for administering therapeutics that accelerate tissue repair and regeneration. In this study, we report a facile method for fabricating granular nanofibrous microspheres (NMs) with predesigned structures and porosities. The proposed technology combines electrospinning and electrospraying to develop a therapeutic option for DFUs. Specifically, porous NMs were constructed using electrospun poly(lactic-co-glycolic acid) (PLGA):gelatin short nanofibers, followed by gelatin cross-linking. These NMs demonstrated enhanced cell adhesion to human dermal fibroblasts (HDF) during an in vitro cytocompatibility assessment. Notably, porous NMs displayed superior performance owing to their interconnected pores compared to nonporous NMs. Cell-laden NMs demonstrated higher Young's modulus values than NMs without loaded cells, suggesting improved material resiliency attributed to the reinforcement of cells and their secreted extracellular matrix. Dynamic injection studies on cell-laden NMs further elucidated their capacity to safeguard loaded cells under pressure. In addition, porous NMs promoted host cell infiltration, neovascularization, and re-epithelialization in a diabetic mouse wound model, signifying their effectiveness in healing diabetic wounds. Taken together, porous NMs hold significant potential as minimally invasive, injectable treatments that effectively promote tissue integration and regeneration.

National Trends and Outcomes of Pedal Bypass Surgery

ObjectiveThe technical demands associated with pedal bypass (PB) surgery place it at risk of underutilization and may be limiting its widespread adoption as a valuable revascularization modality. This study aims to evaluate trends in PB performance, assess its outcomes, and compare its results between high- and low-volume centers. MethodsAll patients receiving a PB between 2003 and 2023 were identified in the Vascular Quality Initiative (VQI) infrainguinal bypass (IIB) module. The ratio of PB to total IIB performed was calculated for each year and trended over the study period. Centers performing PB were categorized according to their annual PB volume into tertiles of low-volume centers (LVC, <2 PB/year), medium-volume centers (MVC, 2-4 PB/year), and high-volume centers (HVC, >4 PB/year) for comparison. Patient characteristics and outcomes were compared using the χ2 or Fisher exact test as appropriate for categorical variables and the analysis of variance test or Kruskal-Wallis test as appropriate for continuous variables. Cox regression analysis was used to study the association between center volume and the primary outcomes of primary patency, primary-assisted patency, secondary patency, reintervention, amputation, and major adverse limb events (MALE), defined as the composite outcome of amputation and/or reintervention. ResultsA total of 3466 patients received a PB during the study period. The ratio of PB to IIB dropped from 14% to 4% between 2003 and 2023. Primary, primary-assisted, and secondary patency rates were 65%, 76%, and 80%, respectively, and limb salvage rate was 83% at 1 year. Nineteen percent of centers performing IIBs in the VQI did not perform any PBs during the study period. Of the 246 centers performing PBs, 78% were LVC, 15% were MVC, and only 7% were HVC. On Cox regression analysis, HVCs were associated with a lower risk of primary patency loss (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.66-0.95; P = .010), reintervention (HR, 0.75; 95% CI, 0.60-0.95; P = .016), amputation (HR, 0.77; 95% CI, 0.61-0.98; P = .034), and MALE (HR, 0.78; 95% CI, 0.66-0.93; P = .005) compared with LVCs. No difference in secondary patency between high- and low-volume centers was observed (P = .680). ConclusionsThe utilization of PB operations experienced a four-fold decrease over the past 20 years, despite favorable patency and limb salvage outcomes. Centers with a higher operative volume in PB achieve better outcomes than LVCs, and accordingly, patients with extensive tibioperoneal disease may benefit from evaluation at centers with documented expertise in PB before resorting to an alternative revascularization modality or a major limb amputation.