Subcutaneous granulocyte colony-stimulating factor administration for subacute traumatic spinal cord injuries, report of neurological and functional outcomes: a double-blind randomized controlled clinical trial

OBJECTIVEGranulocyte-colony stimulating factor (G-CSF) is a major cytokine that has already been clinically verified for chronic traumatic spinal cord injuries (TSCIs). In this study, the authors set out to determine the safety and efficacy of G-CSF administration for neurological and functional improvement in subacute, incomplete TSCI.METHODSThis phase II/III, prospective, double-blind, placebo-controlled, parallel randomized clinical trial was performed in 60 eligible patients (30 treatment, 30 placebo). Patients with incomplete subacute TSCIs with American Spinal Injury Association Impairment Scale (AIS) grades B, C, and D were enrolled. Patients were assessed using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) scale, Spinal Cord Independence Measure (SCIM-III) and International Association of Neurorestoratology Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS), just before intervention and at 1, 3, and 6 months, after 7 daily subcutaneous administrations of 300 μg/day of G-CSF in the treatment group and placebo in the control group.RESULTSAmong 60 participants, 28 patients (93.3%) in the G-CSF group and 26 patients (86.6%) in the placebo group completed the study protocol. After 6 months of follow-up, the AIS grade remained unchanged in the placebo group, while in the G-CSF group 5 patients (45.5%) improved from AIS grade B to C, 5 (45.5%) improved from AIS grade C to grade D, and 1 patient (16.7%) improved from AIS grade D to E. The mean ± SEM change in ISNCSCI motor score in the G-CSF group was 14.9 ± 2.6 points, which was significantly greater than in the placebo group (1.4 ± 0.34 points, p < 0.001). The mean ± SEM light-touch and pinprick sensory scores improved by 8.8 ± 1.9 and 10.7 ± 2.6 points in the G-CSF group, while those in the placebo group improved by 2.5 ± 0.60 and 1.2 ± 0.40 points, (p = 0.005 and 0.002, respectively). Evaluation of functional improvement according to the IANR-SCIFRS instrument revealed significantly more functional improvement in the G-CSF group (10.3 ± 1.3 points than in the placebo group (3.0 ± 0.81 points; p < 0.001). A significant difference was also observed between the 2 groups as measured by the SCIM-III instrument (29.6 ± 4.1 vs 10.3 ± 2.2, p < 0.001).CONCLUSIONSIncomplete subacute TSCI is associated with significant motor, sensory, and functional improvement after administration of G-CSF.Clinical trial registration no.: IRCT201407177441N3 (www.irct.ir

Predictive Value of Braden Risk Factors in Pressure Ulcers of Outpatients With Spinal Cord Injury

Pressure Ulcers (PUs) remain among the most common complications after traumatic spinal cord Injuries (SCIs). The main goal of risk factor assessment with different tools has been to provisionally estimate the chance of developing pressure ulcers in patients with Spinal Cord Injury (SCI). Braden tool has been of good predictive value and most commonly employed in hospital communities for risk assessment of pressure sore development. The objective of this study was to determine the Braden risk factors as well as the prevalence of pressure injuries in SCI patients. This cross-sectional study was performed from June 2013 to December 2015 on 163 consecutive referred outpatients with chronic traumatic SCI in our tertiary SCI rehabilitation clinic. We assessed pressure induced skin injuries as well as their Braden risk factors and analyzed their association with stage and location of Pressure Ulcer (PU) and calculated prevalence of PU. One hundred and sixty-three patients out of 580 were found to have active pressure sores, with a prevalence of 28.1%. In the multiple models, only the Braden scale had significant association with the presence of active pressure sore. Patients with severe and moderate Braden scores were 2.36 and 1.82 times, more at risk of pressure sore development, as compared with those having mild scores (P≤0.01). It may be deduced that in various stages of SCI rehabilitation, the Braden scale may be calculated, and patients with moderate and severe risks (according to Braden sale) may need more attention and/or inpatient care for PU prevention. 

Successful Treatment of Acute Invasive Rhino-Orbito-Cerebral Mucormycosis Associated with COVID -19: Case Report and Literature Review

Background and Aim: Mortality associated with post-coronavirus disease 2019 (COVID-19) rhino-orbital cerebral mucormycosis (ROCM) is an evolving concern. Association of COVID-19, corticosteroid therapy, and uncontrolled diabetes mellitus (DM) are considered predisposing factors for ROCM. We present two cases of successful treatment leading to patient survival for post-COVID-19, stage 4c-ROCM. Case Presentation: Two middle-aged men with poorly controlled DM were referred to our hospital for post-COVID-19 ROCM. They had received intravenous antivirals and dexamethasone as treatment in a primary center. Both patients had unilateral oculofacial pain and swelling followed by acute visual loss, unilateral proptosis, facial palsy, and trigeminal hypoesthesia. A computed tomography scan revealed opacity and bony erosion of paranasal sinuses (PNS). Obtained specimens confirmed mucormycosis agent on histopathological examination. After the failure of conservative treatments, retrobulbar injections of liposomal-amphotericin B, PNS debridement, and orbital exenteration, both patients developed blurred consciousness owing to the extension of the infection into the intracranial cavity. Brain magnetic resonance imaging revealed a right frontal lobe abscess in case 1 and a left frontal sinus abscess and involvement in case 2. Both underwent transcranial debridement and resection of necrotic tissue and drainage of the abscess. At follow-up, the patients were in good condition, and the fungal cultures were negative for mucormycosis agents. Conclusion: ROCM may be a complication of COVID-19 in high-risk patients. Control of the patient’s underlying systemic condition and prompt treatment with antifungal agents, along with timely aggressive resection of cerebral abscess and necrotic paranasal tissues, are the mainstays of management for ROCM

Case Report: Combination Therapy with Mesenchymal Stem Cells and Granulocyte-Colony Stimulating Factor in a Case of Spinal Cord Injury

Introduction: Various neuroregenerative procedures have been recently employed along with neurorehabilitation programs to promote neurological function after Spinal Cord Injury (SCI), and recently most of them have focused on the acute stage of spinal cord injury. In this report, we present a case of acute SCI treated with neuroprotective treatments in conjunction with conventional rehabilitation program. Methods: A case of acute penetrative SCI (gunshot wound), 40 years old, was treated with intrathecal bone marrow derived stem cells and parenteral Granulocyte-Colony Stimulating Factor (G-CSF) along with rehabilitation program. The neurological outcomes as well as safety issues have been reported. Results: Assessment with American Spinal Injury Association (ASIA), showed neurological improvement, meanwhile he reported neuropathic pain, which was amenable to oral medication. Discussion: In the acute setting, combination therapy of G-CSF and intrathecal Mesenchymal Stem Cells (MSCs) was safe in our case as an adjunct to conventional rehabilitation programs. Further controlled studies are needed to find possible side effects, and establish net efficacy

Safety of Intramedullary Autologous Peripheral Nerve Grafts for Post-Rehabilitated Complete Motor Spinal Cord Injuries: A Phase I Study

Many experimental studies have reported behavioral improvement after transplantation of peripheral nerve tissue into the contused spinal cord, even in large animals. The safety of this treatment in human remains unknown. In this translational phase 1 study, safety of peripheral nerve grafting for chronic spinal cord injuries and possible outcomes are being reported. Twelve complete motor spinal cord injury patients, who had finished their rehabilitation program, were enrolled. There were 4 thoracic and 8 cervical cases. Patients underwent sural nerve preconditioning in the calf, followed 1 week later, by intramedullary transplantation of the harvested nerve fascicles. The patients were followed up for potential complications periodically, and final assessment by American Spinal Injury association (ASIA) and Spinal Cord Independence Measure (SCIM) III were reported after 2 years of follow-up. The median duration of the spinal cord injury was 31 months. At two years of follow up, out of 7 cases with ASIA Impairment Scale (AIS) A, 4(57.1%) cases improved to AIS B and 1 (14.3%) case became AIS C. There were 1 patient with transient increased spasm, one case of transient cystitis, 3 patients with transient increased neuropathic pain and 1 case with transient episode of autonomic dysreflexia, all being managed medically. There was no case of donor site infection. The above complications were transient as they responded to temporary medical treatment. It may be deduced that after two years follow-up of patients that the procedure may be safe, however further controlled studies are needed to prove its efficacy