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

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

This study aimed to investigate the curative effect of spiral embedded flap urethroplasty for the treatment of meatal stenosis after penile carcinoma surgery. From January 2015 to January 2021, we used our technique to treat strictures of the external urethral orifice in seven patients, including four cases of meatal stenosis after partial penile resection and three cases of meatal stenosis after perineal stoma. All patients had previously undergone repeat urethral dilatation. The patients underwent spiral embedded flap urethroplasty to enlarge the outer urethral opening. The patients' mean age at the time of surgery was 60 (range: 42-71) years, the mean operative time was 43 min, and the median follow-up period was 18 months. The patients voided well post-operatively, and urinary peak flow rates ranged from 18.3 ml s^-1 to 30.4 ml s^-1. All patients were successful with absence of urethral meatus stricture. The present study showed that using spiral embedded flap urethroplasty to treat meatal stenosis after penile carcinoma surgery is an effective surgical technique with good long-term outcomes.
Male ; Humans ; Urologic Surgical Procedures, Male/methods* ; Penile Neoplasms/surgery* ; Constriction, Pathologic/surgery* ; Treatment Outcome ; Urethral Stricture/surgery* ; Urethra/surgery* ; Amputation, Surgical ; Carcinoma/surgery* ; Retrospective Studies

Male ; Humans ; Penile Neoplasms/surgery* ; Constriction, Pathologic/surgery* ; Urethral Stricture/surgery* ; Surgical Flaps/surgery* ; Amputation, Surgical ; Penis/surgery* ; Plastic Surgery Procedures ; Hypospadias/surgery*

A 22-year-old male who came in contact with a high-voltage wire, with entry point at the head and exit points at the ankles, presented with flaccid paraplegia and loss of sensation of bilateral lower extremities with no radiographic abnormalities. Several burn-related medical complications arose during the admission, as well as episodes of demotivation. Bilateral below the knee amputation was done because of extensive burn injuries of the lower extremities. The rehabilitation management for a patient with multiple disabilities needed to be tailored depending on the limitations and needs of the patient at a certain point in time. Despite the challenges, satisfactory results were achieved, through telerehabilitation and employing a multidisciplinary team approach.
Spinal Cord Injuries ; Amputation, Surgical

Objectives: To determine the risk factors for recurrence and persistence of non-healing foot ulcers resulting in minor and major amputations. Methodology: This was an ambispective cohort analysis of persons with diabetic foot ulcers consulting at the diabetic foot clinic of East Avenue Medical Center. Data were analyzed through multiple logistic regression. Result: Two hundred sixteen patients with Type 2 Diabetes Mellitus and diabetic foot ulcers were included in the analysis; 50.9% were males and the mean age of the cohort was 55.8 ± 9.9 years. Outcomes of foot ulcers were: healed 44.5% (healed with no recurrence 30%, healed but with recurrence 14.5%) and not healed 55.5% (major amputation 11%, minor amputation, 21.5%, and persistently non-healing 23%). Multivariate logistic regression showed the following were independent risk factors for persistent non-healing ulcer: osteomyelitis (OR 66.5; CI 19.7, 217.8), smoking (OR 28.9; CI 6.8, 129.3, and peripheral arterial disease (PAD) (OR 56.8; CI 2.5, 877.2). Independent risk factors for ulcer recurrence were: plantar location of ulcer (OR 16.8; CI 6.8, 89.4), presence of more than one ulcer (OR 7.8; CI 3.6,31.6), and neuropathy (OR 11.2; CI 7.2, 19.9). For healed foot ulcers, mean healing time was 14 ± 3 weeks. Healing time was significantly reduced from 12 weeks to 4.5 weeks (p<0.001) if patients consulted earlier (within 4 weeks from sustaining an ulcer). Conclusion Only half (55%) of patients with diabetic foot ulcers consulting in a dedicated outpatient foot clinic had an adverse outcome of foot ulcers (major amputation 11%, minor amputation, 21.5%, and persistently non-healing ulcer 23%) while a small portion (14.5%) of patients had recurrent foot ulcers. Arterial obstruction, smoking, low hemoglobin, neuropathy, and osteomyelitis increase the likelihood of healing failure while the presence of multiple ulcers, plantar location of ulcers, and neuropathy increase the risk of ulcer recurrence.
Foot Ulcer ; Amputation, Surgical ; Peripheral Arterial Disease

Amputation ; Animals ; Atrial Appendage/surgery* ; Atrial Fibrillation ; Dogs ; Echocardiography, Transesophageal ; Stroke ; Surgical Instruments