Peripheral Trauma Research Articles

Surgery as an Effective Therapy for Ulnar Nerve Neuropathic Pain Caused by Gunshot Wounds: A Retrospective Case Series

Peripheral nerve injuries remain a major medical problem worldwide and are associated with multiple causes, including gunshot wounds (GSWs), which are the second most common cause of brachial plexus injuries in peacetime and the main, or only, cause reported in wartime studies. The ulnar nerve (UN) is one of the most affected nerves. Peripheral nerve trauma may cause intense neuropathic pain, which is very difficult to control. Particularly UN gunshot injuries may impact individual daily life, as injuries to this nerve result in both sensory and motor deficits within the hand. We evaluated the improvement of neuropathic pain after surgical treatment in a consecutive series of 20 patients with UN injury due to GSWs. This single-center, retrospective, consecutive case series included 20 patients with UN injuries due to GSWs, who presented with excruciating neuropathic pain and underwent surgical treatment between 2005 and2017. Of injuries, 13 occurred in the right upper limb (65%); 12 patients had a high UN injury (60%). Regarding associated injuries, 8 patients had bone injuries (40%), and 4 patients had arterial injuries (20%). A neuroma in continuity was detected in 8 cases (40%), and 4 patients (20%) had shrapnel lodged within the UN. All patients had severe neuropathic pain and functional deficit, with a mean visual analog scale score of 8.45 ± 1.4 and a mean reduction of 6.95 points 12 months after surgery; 10 patients (50%) had a British Medical Research Council score ≥M3. Surgery is an effective treatment for neuropathic pain from GSWs. Early isolated external neurolysis is associated with better pain management and functional outcomes postoperatively.

Epidemiology and Outcomes of Peripheral and Non-Aortocaval Vascular Trauma in Scotland 2011 – 2018

This population based study aimed to examine the demographics, mechanisms, and outcomes of patients in Scotland suffering peripheral and non-aortocaval vascular trauma between 2011 and 2018. A retrospective observational study was conducted using prospectively collected data derived from the Scottish Trauma Audit Group (STAG) from 1 January 2011 to 31 December 2018. Peripheral and non-aortocaval vascular trauma patients were identified using Abbreviated Injury Severity (AIS) codes. Demographics, mechanisms, types of injury, severity, and outcomes were analysed. Of 30 831 patients admitted with trauma to Scottish hospitals, 569 (1.8%) patients suffered a vascular injury during the eight year study period with 275 (0.9%) patients sustaining a peripheral or non-aortocaval vascular injury. There were 221 (80%) men and 54 (20%) women with a median (range) age of 39 (14 - 88) years. Blunt trauma was responsible for 179 (65%) injuries, of which road traffic accidents were the most common mechanism. A further 67 (24%) injuries were due to penetrating trauma, of which assault was the most common cause. The most common injury was to abdominal arteries (e.g., hepatic, renal, splenic [n= 83]) with an associated mortality rate of 17%. The median (range) Injury Severity Score (ISS) was 16 (4 - 75). Sixteen (6%) patients died in the Emergency Department (ED). Two hundred and twenty-seven (83%) patients were taken to theatre during their admission with a 30 day peri-operative mortality rate of 10%, compared with an overall mortality rate of 16%. Injuries to an abdominal vein (e.g., portal, renal, splenic, superior mesenteric) had the highest number of associated deaths, with 11 (32%) of 34 cases resulting in a fatality. There is a low incidence of vascular trauma in Scotland. Blunt force was responsible for more vascular injuries than penetrating trauma. Patients with peripheral and non-aortocaval vascular injuries are likely to be severely injured and suffer a high mortality rate.

Opioid modulation of T-type Ca2+ channel-dependent neuritogenesis/neurite outgrowth through the prostaglandin E2/EP4 receptor/protein kinase A pathway in mouse dorsal root ganglion neurons

Irregular regeneration or inappropriate remodeling of the axons of the primary afferent neurons after peripheral nerve trauma could be associated with the development of neuropathic pain. We analyzed the molecular mechanisms for the neuritogenesis and neurite outgrowth caused by prostaglandin E2 (PGE2) in mouse dorsal root ganglion (DRG) neurons, and evaluated their opioid modulation. PGE2 in combination with IBMX, a phosphodiesterase inhibitor, caused neuritogenesis/neurite outgrowth in DRG cells, an effect abolished by a prostanoid EP4, but not EP2, receptor antagonist, and inhibitors of adenylyl cyclase or protein kinase A (PKA). Blockers of T-type Ca2+ channels (T-channels), that are responsible for window currents involving the sustained low-level Ca2+ entry at voltages near the resting membrane potentials and can be functionally upregulated by PKA, inhibited the neuritogenesis/neurite outgrowth caused by PGE2/IBMX or dibutylyl cyclic AMP, a PKA activator, in DRG neurons, an inhibitory effect mimicked by ZnCl2 and ascorbic acid that block Cav3.2, but not Cav3.1 or Cav3.3, T-channels. Morphine and DAMGO, μ-opioid receptor (MOR) agonists, suppressed the neuritogenesis and/or neurite outgrowth induced by PGE2/IBMX in DRG neurons and also DRG neuron-like ND7/23 cells, an effect reversed by naloxone or β-funaltrexamine, a selective MOR antagonist. Our data suggest that the EP4 receptor/PKA/Cav3.2 pathway is involved in the PGE2-induced neuritogenesis/neurite outgrowth in DRG neurons, which can be suppressed by MOR stimulation. We propose that MOR agonists including morphine in the early phase after peripheral nerve trauma might delay the axonal regeneration of the primary afferent neurons but prevent the development of neuropathic pain.

Exosomal ncRNAs: The pivotal players in diabetic wound healing.

Diabetes is the most prevalent metabolic disease in the world today. In addition to elevated blood glucose, it also causes serious complications, which has a significant effect on the quality of life of patients. Diabetic trauma is one of complications as a result of the interaction of diabetic neuropathy, peripheral vascular disease, infection, trauma, and other factors. Diabetic trauma usually leads to poor healing of the trauma and even to severe foot ulcers, wound gangrene, and even amputation, causing serious psychological, physical, and financial burdens to diabetic patients. Non-coding RNAs (ncRNAs) carried by exosomes have been demonstrated to be relevant to the development and treatment of diabetes and its complications. Exosomes act as vehicle, which contain nucleic acids such as mRNA and microRNA (miRNA), and play a role in the intercellular communication and the exchange of substances between cells. Because exosomes are derived from cells, there are several advantages over synthetic nanoparticle including good biocompatibility and low immunogenicity. Exosomal ncRNAs could serve as markers for the clinical diagnosis of diabetes and could also be employed to accelerate diabetic wound healing via the regulation of the immune response and modulation of cell function. ncRNAs in exosomes can be employed to promote diabetic wound healing by regulating inflammation and accelerating re-vascularization, re-epithelialization, and extracellular matrix remodeling. Herein, exosomes in terms of ncRNA (miRNA, lncRNA, and circRNA) to accelerate diabetic wounds healing were summarized, and we discussed the challenge of the loading strategy of ncRNA into exosomes.

Tmem45b is essential for inflammation- and tissue injury–induced mechanical pain hypersensitivity

Persistent mechanical pain hypersensitivity associated with peripheral inflammation, surgery, trauma, and nerve injury impairs patients' quality of life and daily activity. However, the molecular mechanism and treatment are not yet fully understood. Herein, we show that chemical ablation of isolectin B4-binding (IB4+) afferents by IB4-saporin injection into sciatic nerves completely and selectively inhibited inflammation- and tissue injury-induced mechanical pain hypersensitivity while thermal and mechanical pain hypersensitivities were normal following nerve injury. To determine the molecular mechanism involving the specific types of mechanical pain hypersensitivity, we compared gene expression profiles between IB4+ neuron-ablated and control dorsal root ganglion (DRG) neurons. We identified Tmem45b as one of 12 candidate genes that were specific to somatosensory ganglia and down-regulated by IB4+ neuronal ablation. Indeed, Tmem45b was expressed predominantly in IB4+ DRG neurons, where it was selectively localized in the trans Golgi apparatus of DRG neurons but not detectable in the peripheral and central branches of DRG axons. Tmem45b expression was barely detected in the spinal cord and brain. Although Tmem45b-knockout mice showed normal responses to noxious heat and noxious mechanical stimuli under normal conditions, mechanical pain hypersensitivity was selectively impaired after inflammation and tissue incision, reproducing the pain phenotype of IB4+ sensory neuron-ablated mice. Furthermore, acute knockdown by intrathecal injection of Tmem45b small interfering RNA, either before or after inflammation induction, successfully reduced mechanical pain hypersensitivity. Thus, our study demonstrates that Tmem45b is essential for inflammation- and tissue injury-induced mechanical pain hypersensitivity and highlights Tmem45b as a therapeutic target for future treatment.

Thoracic trauma promotes alpha-Synuclein oligomerization in murine Parkinson's disease

BackgroundSystemic and neuroinflammatory processes play key roles in neurodegenerative diseases such as Parkinson's disease (PD). Physical trauma which induces considerable systemic inflammatory responses, represents an evident environmental factor in aging. However, little is known about the impact of physical trauma, on the immuno-pathophysiology of PD. Especially blunt chest trauma which is associated with a high morbidity and mortality rate in the elderly population, can induce a strong pulmonary and systemic inflammatory reaction. Hence, we sought out to combine a well-established thoracic trauma mouse model with a well-established PD mouse model to characterize the influence of physical trauma to neurodegenerative processes in PD. MethodsTo study the influence of peripheral trauma in a PD mouse model we performed a highly standardized blunt thorax trauma in a well-established PD mouse model and determined the subsequent local and systemic response. ResultsWe could show that blunt chest trauma leads to a systemic inflammatory response which is quantifiable with increased inflammatory markers in bronchoalveolar fluids (BALF) and plasma regardless of the presence of a PD phenotype. A difference of the local inflammatory response in the brain between the PD group and non-PD group could be detected, as well as an increase in the formation of oligomeric pathological alpha-Synuclein (asyn) suggesting an interplay between peripheral thoracic trauma and asyn pathology in PD. ConclusionTaken together this study provides evidence that physical trauma is associated with increased asyn oligomerization in a PD mouse model underlining the relevance of PD pathogenesis under traumatic settings.

Non‐articulated hybrid glass and carbon‐reinforced shank tube for bio‐medical applications

AbstractGlobally, the most prevalent reasons of lower extremity amputation are diabetes, peripheral vascular disease, trauma, tumors and congenital abnormalities. Though modern lower limb prosthetic devices are available in the market, affordability for amputees in developing and underdeveloped nations is a concern, so it is required to make it more accessible with more economical options. This research is an initiative to develop a composite shank tube by filament winding technique as an alternative to conventional metallic tubes for prosthetic components. The composite materials used for this study included glass fiber/epoxy and hybrid fiber (glass + carbon)/epoxy. The composite tubes were manually fabricated and were subjected to axial compression test to estimate the loading bearing and energy absorption capacities. The composite's material properties were determined as per ASTM standards. The obtained properties and experimental data were used to carry out simulations for the composite tubes with ANSYS® 2021 software package under quasistatic loading conditions. Based on the research that was done, the overall performance of Hybrid Fiber tube in terms of peak loads and energy absorption indexes looks good, and there is a high possibility that they could be used as a load‐bearing part in a lower limb prosthetic system.

Leukocyte invasion of the brain after peripheral trauma in zebrafish (Danio rerio)

Despite well-known systemic immune reactions in peripheral trauma, little is known about their roles in posttraumatic neurological disorders, such as anxiety, sickness, and cognitive impairment. Leukocyte invasion of the brain, a common denominator of systemic inflammation, is involved in neurological disorders that occur in peripheral inflammatory diseases, whereas the influences of peripheral leukocytes on the brain after peripheral trauma remain largely unclear. In this study, we found that leukocytes, largely macrophages, transiently invaded the brain of zebrafish larvae after peripheral trauma through vasculature-independent migration, which was a part of the systemic inflammation and was mediated by interleukin-1b (il1b). Notably, myeloid cells in the brain that consist of microglia and invading macrophages were implicated in posttraumatic anxiety-like behaviors, such as hyperactivity (restlessness) and thigmotaxis (avoidance), while a reduction in systemic inflammation or myeloid cells can rescue these behaviors. In addition, invading leukocytes together with microglia were found to be responsible for the clearance of apoptotic cells in the brain; however, they also removed the nonapoptotic cells, which suggested that phagocytes have dual roles in the brain after peripheral trauma. More importantly, a category of conserved proteins between zebrafish and humans or rodents that has been featured in systemic inflammation and neurological disorders was determined in the zebrafish brain after peripheral trauma, which supported that zebrafish is a translational model of posttraumatic neurological disorders. These findings depicted leukocyte invasion of the brain during systemic inflammation after peripheral trauma and its influences on the brain through il1b-dependent mechanisms.

ID:16289 Dorsal Root Ganglion Stimulation Reduces Pain and Improves Physical Function for Causalgia Patients

Causalgia, also known as complex regional pain syndrome type II, develops after a peripheral nerve injury or trauma.1 Causalgia patients have chronic pain that interferes with physical function and lowers their quality of life so treatments are implemented to improve physical function and reduce pain.2 Dorsal Root Ganglion Stimulation (DRG-S) is an effective treatment for CRPS-II of the lower extremities.3 The sub-analysis of data from the prospective, multi-center, REALITY study (NCT03876054) is to demonstrate the effectiveness of DRG-S in patients with causalgia.

E74-like factor 1 contributes to nerve trauma-induced nociceptive hypersensitivity through transcriptionally activating matrix metalloprotein-9 in dorsal root ganglion neurons.

Nerve trauma-induced alternations of gene expression in the neurons of dorsal root ganglion (DRG) participate in nerve trauma-caused nociceptive hypersensitivity. Transcription factors regulate gene expression. Whether the transcription factor E74-like factor 1 (ELF1) in the DRG contributes to neuropathic pain is unknown. We report here that peripheral nerve trauma caused by chronic constriction injury (CCI) of unilateral sciatic nerve or unilateral fourth lumbar spinal nerve ligation led to the time-dependent increases in the levels of Elf1 mRNA and ELF1 protein in injured DRG, but not in the spinal cord. Preventing this increase through DRG microinjection of adeno-associated virus 5 expressing Elf1 shRNA attenuated the CCI-induced upregulation of matrix metallopeptidase 9 (MMP9) in injured DRG and induction and maintenance of nociceptive hypersensitivities, without changing locomotor functions and basal responses to acute mechanical, heat, and cold stimuli. Mimicking this increase through DRG microinjection of AAV5 expressing full-length Elf1 upregulated DRG MMP9 and produced enhanced responses to mechanical, heat, and cold stimuli in naive mice. Mechanistically, more ELF1 directly bond to and activated Mmp9 promoter in injured DRG neurons after CCI. Our data indicate that ELF1 participates in nerve trauma-caused nociceptive hypersensitivity likely through upregulating MMP9 in injured DRG. E74-like factor 1 may be a new target for management of neuropathic pain.

Ultrasound Evaluation of Peripheral Nerve Trauma

Ultrasound Evaluation of Peripheral Nerve Trauma

Sex-Specific B Cell and Anti-Myelin Autoantibody Response After Peripheral Nerve Injury.

Immunotherapy holds promise as a non-addictive treatment of refractory chronic pain states. Increasingly, sex is recognized to impact immune regulation of pain states, including mechanical allodynia (pain from non-painful stimulation) that follows peripheral nerve trauma. This study aims to assess the role of B cells in sex-specific responses to peripheral nerve trauma. Using a rat model of sciatic nerve chronic constriction injury (CCI), we analyzed sex differences in (i) the release of the immunodominant neural epitopes of myelin basic protein (MBP); (ii) the levels of serum immunoglobulin M (IgM)/immunoglobulin G (IgG) autoantibodies against the MBP epitopes; (iii) endoneurial B cell/CD20 levels; and (iv) mechanical sensitivity behavior after B cell/CD20 targeting with intravenous (IV) Rituximab (RTX) and control, IV immunoglobulin (IVIG), therapy. The persistent MBP epitope release in CCI nerves of both sexes was accompanied by the serum anti-MBP IgM autoantibody in female CCI rats alone. IV RTX therapy during CD20-reactive cell infiltration of nerves of both sexes reduced mechanical allodynia in females but not in males. IVIG and vehicle treatments had no effect in either sex. These findings provide strong evidence for sexual dimorphism in B-cell function after peripheral nervous system (PNS) trauma and autoimmune pathogenesis of neuropathic pain, potentially amenable to immunotherapeutic intervention, particularly in females. A myelin-targeted serum autoantibody may serve as a biomarker of such painful states. This insight into the biological basis of sex-specific response to neuraxial injury will help personalize regenerative and analgesic therapies.

Erythropoietin promotes M2 macrophage phagocytosis of Schwann cells in peripheral nerve injury

Following acute sciatic nerve crush injury (SNCI), inflammation and the improper phagocytic clearance of dying Schwann cells (SCs) has effects on remodeling that lead to morbidity and incomplete functional recovery. Therapeutic strategies like the use of erythropoietin (EPO) for peripheral nerve trauma may serve to bring immune cell phagocytotic clearance under control to support debris clearance. We evaluated EPO’s effect on SNCI and found EPO treatment increased myelination and sciatic functional index (SFI) and bolstered anti-apoptosis and phagocytosis of myelin debris via CD206+ macrophages when compared to saline treatment. EPO enhanced M2 phenotype activity, both in bone marrow-derived macrophages (BMMØs) and peritoneal-derived macrophages (PMØs) in vitro, as well as in PMØs in vivo. EPO increased efferocytosis of apoptotic sciatic nerve derived Schwann cells (SNSCs) in both settings as demonstrated using immunofluorescence (IF) and flow cytometry. EPO treatment significantly attenuated pro-inflammatory genes (IL1β, iNOS, and CD68) and augmented anti-inflammatory genes (IL10 and CD163) and the cell-surface marker CD206. EPO also increased anti-apoptotic (Annexin V/7AAD) effects after lipopolysaccharide (LPS) induction in macrophages. Our data demonstrate EPO promotes the M2 phenotype macrophages to ameliorate apoptosis and efferocytosis of dying SCs and myelin debris and improves SN functional recovery following SNCI.

Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma: erratum.

Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma: erratum.

Peripheral Vascular Trauma among Vascular Surgery Cases Operated in a Tertiary Care Hospital: A Descriptive Cross-sectional Study.

Peripheral vascular trauma can result in limb or life-threatening injuries. Early surgical intervention leads to a better outcome. Diagnosis is made clinically, by non-invasive and invasive imaging modalities. Our aim in this study is to find out the prevalence of peripheral vascular trauma among vascular surgery cases operated in a tertiary care centre of Nepal. This is a descriptive cross-sectional study of peripheral vascular injuries that underwent operative management in a tertiary care hospital of Nepal from January 2018 to May 2020. Ethical approval was taken from the Institutional Review Committee of Kathmandu University School of Medical Sciences (Registration Number 79/20). Convenience sampling technique was used. Data for the study was retrieved from operation records of the patients along with their treatment summaries and entered and analyzed in the Statistical Package for Social Sciences version 20.0. All cases with complete records were included. Conservatively managed cases and cases that underwent primary amputation were not included in the study. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. Among 624 vascular surgery patients, 40 (6.41%) (4.48-8.33 at 95% Confidence Interval) patients had presented with peripheral vascular trauma during the study period. There were 26 (65%) cases where the upper limb was involved. The prevalence of vascular surgery for peripheral vascular trauma among vascular surgeries operated in our study was similar to other studies done in similar settings. Vascular injury needs urgent intervention and appropriate management will result in a high chance of limb salvage and survival.

Vascular Surgery Role in Vascular Trauma: An 11-year Analysis of Peripheral Vascular Trauma Management at a Level 1 Trauma Center

Vascular surgeons are increasingly relied upon in the management of complex peripheral vascular trauma. However, the degree to which vascular surgery (VS) is involved in vascular trauma care is not well-established. We hypothesize that VS consultation is required in a high portion of complex lower extremity vascular trauma.

Clinical study and surgical management of diabetic foot: An observational study

Background and Aim: The most frequent reason for hospitalization for patients with diabetes is foot complications, which accounts for up to 25% of all diabetic admissions. The clinical triad most commonly seen in diabetic foot ulcer is peripheral sensory neuropathy, trauma and deformity. Diabetes continues to be one of the most common underlying causes of nontraumatic lower extremity amputations (LEAs). The aim of the study was to study the benefit and outcome of the different treatment modalities for the diabetic foot.Material and Methods: This study was conducted comprising 200 patients with diabetic foot in the department of general surgery at Gujarat Adani Institute of Medical Science, Bhuj, Kutch for 10 months. Data were collected by detailed history, clinical examination, wound or ulcer and were recorded in the pre-designed proforma. Wagner’s classification, examination findings, blood investigations, renal function test, a swab of the wound, X-ray and treatment provided were collected.Results: Most of the patients had diabetes duration for about 6-10 years (28%). Out of 200 SG cases, 88 (44%) cases presented with ulcers, 40 (20%) cases with cellulitis 32 (16%) of cases abscess, 48 (24%) of cases gangrene and 8 (4%) of cases neuropathic ulcer. The most common site of lesion in the diabetic foot was the dorsum of the foot which was in about 64 patients (32%). Out of the 200 cases studied 120 patients (60%) not had a history of trauma and 80 patients (40%) not had a history of trauma.Conclusion: The commonest presenting lesion was ulcers, followed by gangrene and cellulitis. The commonest site of lesion was the dorsum of the foot followed by forefoot and toes. The most common microorganisms grown from culture taken from the lesion was S. aureus followed by Pseudomonas. Ulceration, infection, gangrene and lower extremity amputation are complications often encountered in patients with DM.

Information for Authors and Editorial Policies

Journal of Vascular Surgery Aims to be the premier international journal of medical, endovascular, and surgical care of vascular diseases. It aims to improve the management of patients with vascular disorders by publishing relevant papers focusing on investigation, management and prevention of aortic, cerebrovascular and peripheral arterial diseases, vascular access, trauma and malformations. The journal reports important medical advances, tests new hypotheses, and addresses current controversies.

Movement Disorders and Musculoskeletal System: A Reciprocal Relationship.

The association of movement disorders (MDs) with musculoskeletal (MSK) disorders is observed in two principal scenarios. First, MDs patients may present with MSK issues. This phenomenon is primarily observed in parkinsonian syndromes, but may also be seen in patients with dystonia, Tourette syndrome, and some gene-related MDs. Second, there are MSK disorders that may produce or mimic MDs. Important primary MSK disorders producing MDs are joint hyperlaxity syndrome, non-traumatic craniovertebral junction anomalies, congenital muscular torticollis, and rheumatoid arthritis. Peripheral trauma to the MSK system may also lead to MDs commonly referred to as peripherally induced MDs. The exact pathogenesis of these disorders is not clear, however many patients have associated sensory phenomena such as complex regional pain syndrome. Herein, we provide an overview of disorders that may manifest with a combination of MSK and MDs, as detailed above. The most common MDs are discussed in each section, along with important clinical points, suggested diagnostic workups, and possible differential diagnoses.

Pediatric peripheral vascular injuries and associated orthopedic considerations

Pediatric peripheral vascular trauma is a rare but highly morbid injury in children and is frequently associated with concomitant orthopedic injuries. These children require multidisciplinary care by pediatric, vascular, and orthopedic surgery. In this review, we describe elements of the complex care required for children with peripheral vascular trauma.