INTRODUCTION

There is significantly increased morbidity among patients who undergo major amputation because of diabetic foot ulcers (DFU) . Various risk factors contribute to this outcome with endothelial dysfunction potentially linked to poor wound healing. The Neutrophil Lymphocyte Ratio (NLR) may indicate endothelial dysfunction.

This study aimed to evaluate the accuracy and utility of NLR as a predictor of major amputation in patients admitted for DFU, whose white blood cell counts (WBCs) were elevated or normal. Major amputation is defined as amputation above the tibiotalar joint.

This retrospective cohort analysis included patients admitted at East Avenue Medical Center for DFU. The primary endpoint was major amputation of the lower extremities. Data were analyzed using Receiver Operating Characteristic (ROC) analysis and logistic regression.

The study included 280 DFU patients, predominantly male (62.86%) with a mean age of 57.01±10.72 years. Elevated WBC was found in 176 patients (62.86%) while 104 had normal WBC (37.14%). Major amputation of the lower extremity was performed on 112 patients (40%), with 81 having elevated WBC and 31 normal WBC. The median NLR in patients with elevated WBC undergoing major amputation was 12.86 (IQR: 2.36-95) compared to 5.71 (IQR: 1.91-31.67) in those who did not, indicating NLR as an independent predictor of major amputation (Adjusted OR 1.23; 95% CI 1.14-1.34; p < 0.001). ROC analysis showed an AUC of 0.8234 with an optimal cutoff of 9.33 (72.8% sensitivity, 86.3% specificity). Other predictive variables included University of Texas Stage 3D (Adjusted OR 8.20; 95% CI 2.52-26.75; p < 0.001), Wagner Grade 4 (Adjusted OR 4.6; 95% CI 1.28-16.55; p=0.019), and severe infection (Adjusted OR 2.91; 95% CI 1.22-6.93; p=0.016). For patients with normal WBC, median NLR was 18 (IQR: 1.54-45.5) in those who had major amputation versus 3.13 (IQR: 1.14-12.29) in those who did not undergo major amputation. ROC analysis showed an AUC of 0.9068 with an optimal cutoff of 6.92 (87.1% sensitivity, 98.6% specificity). NLR was also an independent predictor in these subjects (Adjusted OR 1.48; 95% CI 1.14-1.92; p=0.003) alongside smoking history (Adjusted OR 9.14; 95% CI 1.26-66.56; p=0.029) and UT3D (Adjusted OR 17.38; 95% CI 2.21-136.59; p=0.007).

Forty percent of DFU patients had major amputations. NLR independently predicted major amputation in DFU patients with both elevated and normal WBC.

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a^-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a^-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
Animals ; Mice ; Amputation, Surgical ; Chronic Pain/pathology* ; Disease Models, Animal ; Ganglia, Spinal/pathology* ; Hyperalgesia/etiology* ; Ion Channels/metabolism* ; Macrophages ; Neuroma/pathology*

Vascular injury resulting from lower limb amputation leads to the redistribution of blood flow and changes in vascular terminal resistance, which can affect the cardiovascular system. However, there was no clear understanding of how different amputation levels affect the cardiovascular system in animal experiments. Therefore, this study established two animal models of above-knee amputation (AKA) and below-knee amputation (BKA) to explore the effects of different amputation levels on the cardiovascular system through blood and histopathological examinations. The results showed that amputation caused pathological changes in the cardiovascular system of animals, including endothelial injury, inflammation, and angiosclerosis. The degree of cardiovascular injury was higher in the AKA group than in the BKA group. This study sheds light on the internal mechanisms of amputation's impact on the cardiovascular system. Based on the amputation level of patients, the findings recommend more comprehensive and targeted monitoring after surgery and necessary interventions to prevent cardiovascular diseases.
Animals ; Animal Experimentation ; Cardiovascular System ; Cardiovascular Diseases ; Hypertension ; Amputation, Surgical

It has been found that the incidence of cardiovascular disease in patients with lower limb amputation is significantly higher than that in normal individuals, but the relationship between lower limb amputation and the episodes of cardiovascular disease has not been studied from the perspective of hemodynamics. In this paper, numerical simulation was used to study the effects of amputation on aortic hemodynamics by changing peripheral impedance and capacitance. The final results showed that after amputation, the aortic blood pressure increased, the time averaged wall shear stress of the infrarenal abdominal aorta decreased and the oscillatory shear index of the left and right sides was asymmetrically distributed, while the time averaged wall shear stress of the iliac artery decreased and the oscillatory shear index increased. The changes above were more significant with the increase of amputation level, which will result in a higher incidence of atherosclerosis and abdominal aortic aneurysm. These findings preliminarily revealed the influence of lower limb amputation on the occurrence of cardiovascular diseases, and provided theoretical guidance for the design of rehabilitation training and the optimization of cardiovascular diseases treatment.
Amputation ; Aorta, Abdominal/surgery* ; Aortic Aneurysm, Abdominal/surgery* ; Blood Flow Velocity/physiology* ; Hemodynamics/physiology* ; Humans ; Lower Extremity ; Models, Cardiovascular ; Stress, Mechanical

Frostbite in Southwestern China has been overlooked due to its low incidence, relatively mild temperature and lack of literature published before. However, it needs to be further studied for religious diversity and distinct geomorphology. In this article, we reported an 18-year-old Tibetan girl who suffered from blizzard attack during pilgrimage. Her feet and several fingers showed mummified gangrene upon physical examination with poor movement. She was diagnosed with 3rd to 4th degree of frostbite. The girl was given oral ibuprofen, debridement and other regular treatment daily, but she was eventually amputated due to insufficient thrombolytic management in primary hospital, delayed informing consent in the referral hospital and ethnic conflict between religion and guidelines. This case enriched the experience of managing complex frostbite in Tibetan population and alarms that efforts should be integrated to protect pilgrims and mountaineers in the Tibetan region.
Adolescent ; Amputation ; China ; Female ; Frostbite/therapy* ; Humans ; Incidence ; Tibet

INTRODUCTION: Percutaneous transluminal angioplasty (PTA) is commonly used to treat patients with chronic limb-threatening ischaemia (CLTI). This study aimed to examine the mortality and functional outcomes of patients with CLTI who predominantly had diabetes mellitus in a multi-ethnic Asian population in Singapore. METHODS: Patients with CLTI who underwent PTA between January 2015 and March 2017 at the Vascular Unit at Singapore General Hospital, Singapore, were studied. Primary outcome measures were 30-day unplanned readmission, two-year major lower extremity amputation (LEA), mortality rates, and ambulation status at one, six and 12 months. RESULTS: A total of 221 procedures were performed on 207 patients, of whom 184 (88.9%) were diabetics. The one-, six- and 12-month mortality rate was 7.7%, 16.4% and 21.7%, respectively. The two-year LEA rate was 30.0%. At six and 12 months, only 96 (46.4%) and 93 (44.9%) patients were ambulant, respectively. Multivariate analysis revealed that preoperative ambulatory status, haemoglobin, Wound Ischaemia and foot Infection (WIfI) score, and end-stage renal failure (ESRF) were independent predictors of one-year ambulatory status. Predictors of mortality at one, six and 12 months were ESRF, preoperative albumin level, impaired functional status and employment status. CONCLUSION PTA for CLTI was associated with low one-year mortality and two-year LEA rates but did not significantly improve ambulation status. ESRF and hypoalbuminaemia were independent predictors of mortality. ESRF/CKD and WIfI score were independent predictors of loss of ambulation at six months and one year. We need better risk stratification for patients with CLTI to decide between initial revascularisation and an immediate LEA policy.
Amputation ; Chronic Disease ; Chronic Limb-Threatening Ischemia ; Humans ; Ischemia/surgery* ; Limb Salvage/methods* ; Lower Extremity/surgery* ; Peripheral Arterial Disease/surgery* ; Retrospective Studies ; Risk Factors ; Singapore ; Treatment Outcome

Objective: To analyze the treatment and clinical prognosis of lower extremity arterial injury caused by trauma. Methods: The clinical data of 77 patients with traumatic lower extremity arterial injury admitted to Department of Vascular Surgery,Yichang Central People's Hospital from January 2013 to June 2021 were collected retrospectively. There were 65 males and 12 females, with an average age of 47.4 years (range: 7 to 75 years). Among the 77 patients, 56 cases (72.7%) had open injury and 21 cases (27.3%) had closed injury. Iliac artery was injured in 9 cases (11.7%), common femoral artery in 7 cases (9.1%), superficial femoral artery in 1 case (1.3%), popliteal artery in 11 cases (14.3%) and inferior knee artery in 49 cases (63.6%). The treatment methods and clinical effects were analyzed. Results: One case with pelvic fracture combined the internal iliac artery injury and 1 case with multiple injuries involving the common femoral artery died of circulatory failure before surgery. Seventy-five cases received vascular-related operations, including arterial ligation in 24 cases, arterial reconstruction in 40 cases, stent graft implantation in 1 case, primary amputation in 2 cases, and arterial embolization in 8 cases. The overall mortality rate was 6.5% (5/77), all of which were closed injuries. Except for 2 cases who died before surgery, 3 cases with pelvic fracture combined the internal iliac artery injury died of multiple organ failure after internal iliac artery embolization. There were 8 cases received amputation (10.4%, 8/77), 5 cases with closed injury and 3 cases with open injury. In addition to 2 cases with primary amputation, 6 cases underwent secondary amputation due to ischemia-reperfusion injury after revascularization (4 cases with popliteal artery injury and 2 cases with subpatellar artery injury). The average followed-up time was 17 months (range: 2 months to 8 years). One patient with femoral artery injury underwent autologous great saphenous vein bypass, and lower limb artery CT angiography was re-examined 6 months after the operation, and 30% distal anastomotic stenosis was found. Ankle brachial index<0.8 was found in two patients 1 year after popliteal artery repair, but none of the patients had intermittent claudication symptoms, and no further intervention was performed. Five patients suffered delayed healing due to severe lower limb injury, fracture and skin injury. Among them, 2 cases had poor wound healing at the stump of amputation, which gradually healed 3 to 5 months after several debridements. The other 3 vascular injury combined with tibial fracture patients had delayed tibial healing after surgery, but no symptoms of vascular ischemia occurred. All the other patients recovered well and no other serious complications occurred. Conclusions: The proportion of death and disability in patients with lower limb artery injury caused by trauma is high. Active and orderly surgical repair according to the site and type of injury can reduce the mortality, save the function of the affected limb, and promote the healing of injury.
Amputation ; Female ; Femoral Artery ; Humans ; Lower Extremity ; Male ; Middle Aged ; Popliteal Artery/surgery* ; Retrospective Studies ; Treatment Outcome ; Vascular System Injuries/surgery*

Background: Pyoderma gangrenosum is a rare ulcerative skin disease that can present as an ulcerative skin disease with the prominence of pain. The pathogenesis may be related to disruptions in the immune pathways. Targeted therapy is lacking and current treatment is largely empirical and consists of corticosteroids and cyclosporine first line. Early recognition can improve clinical outcomes. Case: This case is a 67-year-old male diabetic who was admitted for a progressive ulcerative lesion on the right leg. Arterial Doppler studies and CT angiogram of the right lower extremity were normal. Blood and deep wound cultures of the lesion showed Klebsiella pneumoniae and Pseudomonas aeruginosa. Multiple antibiotic regimens were given with no improvement of the ulcerating lesions of the leg. Pain on the lesion remained persistent. The tissue biopsy of the lesion taken during debridement revealed that it was a pyoderma gangrenosum with dystrophic sclerosis. Oral prednisone at 1 mg/kg was added to the regimen which improved pain but the lesion did not improve. The persistence of the pain and progression to sepsis during the hospital course prompted the decision to do an above-knee amputation of the right leg. He was discharged improved. Conclusion Pyoderma gangrenosum is a rare non-infectious cause of an ulcerative lesion in the lower extremity. Diabetes is a strong risk factor for this disease. The course is prolonged with the possibility of secondary infections. Upon histopathologic confirmation, an anti-inflammatory regimen could help improve outcomes.
Pyoderma Gangrenosum ; Diabetic Foot ; Leg Ulcer ; Inflammation ; Anti-Bacterial Agents ; Amputation, Surgical

Humans ; Chronic Limb-Threatening Ischemia ; Singapore ; Lower Extremity/surgery* ; Vascular Surgical Procedures ; Ischemia/surgery* ; Treatment Outcome ; Retrospective Studies ; Amputation, Surgical ; Risk Factors

Lower limb amputation is a significant change in body structure. Loss of muscle, blood vessels, and blood leads to a redistribution of blood flow and changes in resistance at the end of blood vessels. In view of the significant increase in the prevalence of cardiovascular disease after lower limb amputation, the mechanism of which is still unclear, this study aims to establish an animal research model that can verify and explore the effects of amputation on cardiovascular system, and provide the experimental basis for subsequent animal experiments when exploring the effect of different amputation levels on the cardiovascular system. SPF New Zealand rabbits were divided into normal group ( n = 6) and amputation group ( n = 6). The amputation group was treated with above-knee amputation. The changes of low-density liptein cholesterol (LDL-C) and total cholesterol (TC) in serum of all the rabbits were monitored regularly after the surgery. The arterial pathological examination was conducted after the experimental rabbits were executed. The results showed that compared with the normal group, serum LDL-C content and TC content in the amputation group were significantly increased ( P<0.05); The blood vessels of the amputated rabbits had pathological changes such as degeneration and necrosis of smooth muscle cells in the middle membrane layer and rupture of elastic fibers. At the abdominal aorta and aortic arch, the elastic fiber area expression percentage (EFEP) of the experimental group was significantly lower than that of the normal group. The results suggest that the cardiovascular system of rabbits has the tendency of decreased arterial elasticity and lipid deposition in blood after amputation, indicating that the animal research model on the effect of amputation on the cardiovascular system has been successfully established, and can provide an experimental platform for further study on the mechanism of the effect of amputation on the cardiovascular system.
Rabbits ; Animals ; Cholesterol, LDL ; Disease Models, Animal ; Amputation, Surgical ; Myocytes, Smooth Muscle ; Arteries