Interstitial Lung Disease in a Woman with Rheumatoid Arthritis Treated with Denosumab: A Case Report

The present report describes the case of an 84-year-old female Japanese patient with rheumatoid arthritis (RA) who experienced exacerbation of interstitial lung disease (ILD) after denosumab (Dmab) treatment. The onset of RA occurred in 2008, and the patient had been treated with intravenous or subcutaneous injection of tocilizumab (TCZ) since 2009. In July 2013, she experienced a lumbar vertebral fracture and began treatment with 60-mg Dmab injection every 6 months in January 2014. The patient had a history of mild ILD and was evaluated for ILD by chest computed tomography (CT) imaging prior to the start of Dmab use. The vertebral fracture did not recur after the initiation of Dmab treatment, and her osteoporosis was successfully treated. However, she expressed a concern of exacerbations of cough and respiratory discomfort that had occurred since September 2019. The chest CT image in November 2015 showed minor ILD progression, whereas the image in September 2019 showed severe exacerbation of ILD. To treat this exacerbation, 10 mg of methylprednisolone (mPSL) and 2.5 mg of tacrolimus (TAC) were administered, and Dmab was discontinued. The patient was subsequently switched to oral bisphosphonate. The patient’s respiratory discomfort and the finding of interstitial lung lesion in CT imaging improved after Dmab discontinuation. This case showed that exacerbation of ILD may occur after Dmab treatment, and physicians should consider the risks of Dmab-related ILD in patients with RA complicated by ILD.

Bone Mesenchymal Stem Cells Promote Extracellular Matrix Remodeling of Degenerated Nucleus Pulposus Cells via the miR-101-3p/EIF4G2 Axis

The etiology of lumbocrural pain is tightly concerned with intervertebral disk degeneration (IDD). Bone mesenchymal stem cell (BMSC)-based therapy bears potentials for IDD treatment. The properties of microRNA (miRNA)-modified BMSCs may be altered. This study investigated the role and mechanism of BMSCs promoting extracellular matrix (ECM) remodeling of degenerated nucleus pulposus cells (NPCs) via the miR-101-3p/EIF4G2 axis. NPCs were collected from patients with IDD and lumbar vertebral fracture (LVF). The expressions of miR-101-3p and ECM-related proteins, Collagen-I (Col-I) and Collagen-II (Col-II), were detected using the reverse transcription-quantitative polymerase chain reaction. The expressions of Col-I and Col-II, major non-collagenous component Aggrecan, and major catabolic factor Matrix metalloproteinase-13 (MMP-13) were detected using Western blotting. BMSCs were cocultured with degenerated NPCs from patients with IDD. Viability and apoptosis of NPCs were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. After the degenerated NPCs were transfected with the miR-101-3p inhibitor, the expressions of ECM-related proteins, cell viability, and apoptosis were detected. The targeting relationship between miR-101-3p and EIF4G2 was verified. Functional rescue experiments verified the effects of miR-101-3p and EIF4G2 on ECM remodeling of NPCs. Compared with the NPCs of patients with LVF, the degenerated NPCs of patients with IDD showed downregulated miR-101-3p, Col-II, and Aggrecan expressions and upregulated MMP-13 and Col-I expressions. BMSCs increased the expressions of miR-101-3p, Aggrecan, and Col-II, and decreased the expressions of MMP-13 and Col-I in degenerated NPCs. BMSCs enhanced NPC viability and repressed apoptosis. Downregulation of miR-101-3p suppressed the promoting effect of BMSCs on ECM remodeling. miR-101-3p targeted EIF4G2. Downregulation of EIF4G2 reversed the inhibiting effect of the miR-101-3p inhibitor on ECM remodeling. In conclusion, BMSCs increased the miR-101-3p expression in degenerated NPCs to target EIF4G2, thus promoting the ECM remodeling of NPCs.

Effects of pedicle screw number and insertion depth on radiographic and functional outcomes in lumbar vertebral fracture

Background The influence of pedicle screw number and insertion depth on outcomes of lumbar fixation remains uncertain. The purpose of this study was to compare the imaging balance stability and clinical functional improvement of lumbar fracture patients with different pedicle screw numbers and insertion depths. Methods Sixty-five patients undergoing lumbar pedicle screw fixation from January 2016 to January 2018 were enrolled. They were included in long screw (LS) group and short screw (SS) group or 6 screw (6S) group and 4 screw (4S) group. The radiographic outcomes were assessed with lumbar lordosis (LL), segmental lordosis (SL), fractured vertebral lordosis (FL), sacral slope (SS), pelvic incidence (PL), and pelvic tilt (PT). The visual analog scale (VAS) and the Oswestry Disability Index (ODI) score were used for functional assessment. Multiple linear regression was performed to identify the risk factors of FL, SL, and LL correction at the final follow-up. Results FL, SL, and LL were significantly different in all matching subgroups to compare long and short screws and in most matching subgroups to compare 6 and 4 screws. The SS, PT, and PI seem to be similar in all subgroups in different periods. Significant differences of VAS and ODI were found between LS and SS in the 4S group and between 4S and 6S in the SS group. Insertion depth, screw number, BMD, age, and preoperative imaging data were significant factors for imaging balance stability correction at the final follow-up. Conclusions Long screws and 6 screws showed better fracture vertebral restoration and lumbar spinal sagittal stabilities. The surgery type, age, and BMD are important focus points for the treatment of lumbar vertebral fractures.

Can we use shorter constructs while maintaining satisfactory sagittal plane alignment for adult spinal deformity?

OBJECTIVEIssues with spinopelvic fixation for adult spinal deformity (ASD) include loss of the physiological mobility of the entire lumbar spine, perioperative complications, and medical costs. Little is known about the factors associated with successful short fusion for ASD. The authors evaluated radiographic and clinical outcomes after shorter fusion for different subtypes of ASD at 2 years postoperatively and examined factors associated with successful short fusion.METHODSThis was a single-center study of 37 patients who underwent short fusion and a minimum 2 years of follow-up for ASD in which lumbar kyphosis was the main deformity. The exclusion criteria were 1) age < 40 years, 2) previous lumbar vertebral fracture, 3) severe osteoporosis, 4) T10–L2 kyphosis > 20°, 5) scoliotic deformity with an upper end vertebra (UEV) above T12, and 6) concomitant Parkinson’s disease or neurological disease. The surgical procedures, radiographic course, and Oswestry Disability Index (ODI) were assessed, and correlations between radiographic parameters and postoperative ODI at 2 years were analyzed.RESULTSA mean of 3.5 levels were fused. The mean radiographic parameters preoperatively, at 2 weeks, and at 2 years, respectively, were as follows: coronal Cobb angle: 22.9°, 11.5°, and 12.6°; lumbar lordosis (LL): 12.9°, 35.8°, and 32.2°; pelvic incidence (PI) minus LL: 35.5°, 14.7°, and 19.2°; pelvic tilt: 29.4°, 23.1°, and 25.0°; and sagittal vertical axis 85.3, 36.7, and 59.2 mm. Abnormal proximal junctional kyphosis occurred in 8 cases. Revision surgery was performed to extend the length of fusion from a lower thoracic vertebra to the pelvis in 2 cases. The mean ODI scores preoperatively and at 2 years were 50.7% and 24.1%, respectively. Patient age, number of fused intervertebral segments, and radiographic parameters were analyzed by the stepwise method to identify factors contributing to the ODI score at 2 years, preoperative PI, and sagittal vertical axis at 2 years. On receiver operating characteristic curve analysis of the minimal clinically important difference of ODI (15%) and preoperative PI, the cutoff value of the preoperative PI was 47° (area under the curve 0.75).CONCLUSIONSIn terms of subtypes of ASD in which lumbar kyphosis is the main deformity, if the PI is < 47°, then the use of short fusion preserving mobile intervertebral segments can produce adequate LL for the PI, improving both postoperative global spinal alignment and quality of life.

UNSTABLE LUMBAR FRACTURE-DISLOCATION TREATED BY LONG SEGMENT POSTERIOR PEDICLE SCREW INSTRUMENTATION

Background: Among all the thoracolumbar fractures, 50-60% affects the thoracolumbar transitional zone, and 51% AO Type C Fractures has a neurological deficit. We experienced treating a case of unstable lumbar fracture-dislocation treated with long segment pedicle screw instrumentation.Case: A 26-year-old man came to the ER after his back hit by a canopy while working 2 hours before admission. The motoric function was diminished from the L2-S1 level and hypoesthesia at the T12 level. Plain X-Ray showed Fracture-Dislocation Lumbar Vertebral 1-2 Denis Classification Flexion Rotation (AO Type C) ASIA A. The patient underwent reduction, decompression, and long-segment posterior pedicle screw instrumentation.Discussion: The surgery’s primary purpose is to restore alignment and stability to improve the patient’s quality of life by enabling daily activity in a wheelchair without significant pain. Short segment or long segment pedicle screw instrumentation remains a debate. In this case report, we apply long segment pedicle screw instrumentation for lumbar vertebral fracture-dislocation.Conclusion: Thoracolumbar fracture and dislocation fixation aim to restore alignment and stability, to reduce kyphotic deformity, and to decompress the spinal canal. The long segment pedicle screw instrumentation can resist the deforming force of thoracolumbar fractures and dislocations that will inevitably collapse into further kyphosis, resulting in a better outcome.

Steinmann Pins and Polymethylmethacrylate Repair of Fourth Lumbar Vertebral Fracture and Dorsocranial Luxation in PuppySteinmann Pins and Polymethylmethacrylate Repair of Fourth Lumbar Vertebral Fracture and Dorsocranial Luxation in Puppy

Background: Acute spinal traumas can lead to irreversible damage associated with vascular and inflammatory changes in neural tissue. Since spine and spinal cord traumas have an unfavorable prognosis in small animals, and reports of the use of Steinmann pins and polymethylmethacrylate repair of lumbar vertebra fracture-luxation in puppies are rare in the literature, the present paper aimed to report the surgical treatment of transversal fracture through the body of the fourth lumbar vertebra, with dorsocranial displacement of the caudal fragment by using Steinmann pins and polymethylmethacrylate in a 7-month-old Labrador Retriever male dog.Case: A 7-month-old intact male Labrador Retriever dog, weighing 24.0 kg was attended at School Veterinary Hospital with a history of hit by car and paraplegia of the hind limbs. On neurological examination was observed no proprioception and no deep pain sensitivity on the both pelvic limbs. The lumbar spinal palpation showed intense pain, and the motor function and patellar reflexes were reduced. The values of haematological and biochemical analysis remained within the reference values for the species. Radiographs revealed a transversal fracture through the body of the fourth lumbar vertebra, with dorsocranial displacement of the caudal fragment, and was decided to perform a surgical treatment by open reduction and internal fixation of the fracture. The dog was positioned in ventral recumbency for surgery, and a dorsal midline incision was made from the second lumbar vertebra to the sixth lumbar vertebra. Two crossed 1.5 mm Kirschner wires were placed through the caudal articular facets of the fourth lumbar vertebra to provide initial stability. Two 2.0 mm Steinmann pins were placed at 60° angle of the bodies of the second and fifth lumbar vertebrae, and third and fourth lumbar vertebrae. This procedure was repeated on the other side of the vertebral bodies. Sixty grams of polymethylmethacrylate bone cement was applied and the fixation was checked for stability. Muscular, subcutaneous tissue and skin was closed routinely. The dog was paraplegic without any pain and used a wheelchair to assist in locomotion, although it still had urinary and faecal incontinence; no tail control; and the implants were not removed.Discussion: Lumbar vertebral injuries, as in the present case frequently, occur secondary to severe trauma (e.g. hit by car) and seem to have a characteristic fracture pattern. The patient became paraplegic due to spinal cord injury and failure of sensitivity and elimination of urine and feces which can be associated with progressive destruction of neuronal tissue due to secondary vascular and inflammatory events. The radiographic exam was used to confirm the spinal injury and determine whether by conservative or surgical treatment. The treatment choice is related to the number of fractured compartments, and the presence or not of compression. Fractures in two or more compartments are indicative of surgical treatment, similar as the present case. Use of Steinmann pins was to make a rigid fixing system compared with block plates used for the same function. Use of polymethylmethacrylate may also become a complication due to the infection, for this reason was prescribed an antibiotic for 15 days. This procedure proved to be effective since the dog showed no signs of infection. According to the characteristics of the present case report, the use of Steinmann pins and polymethylmethacrylate for repair of transversal fracture through the body of the fourth lumbar vertebra, with dorsocranial displacement of the caudal fragment provided an effective and practical means of stabilisation, promoting decompression, and thus, improving the patient's quality of life.

Spinal Subdural Abscess following Transforaminal Lumbar Interbody Fusion

Spinal subdural abscesses are rare lesions. We report the case of surgical site infection complicated with meningitis and rapidly progressive spinal subdural abscess caused by P. aeruginosa following transforaminal lumbar interbody fusion (TLIF). A 72-year-old woman was admitted to our hospital complaining of drop foot syndrome and sciatica caused by stenosis of the L5/6 intervertebral foramen accompanied by L5 lumbar vertebral fracture. Accordingly, TLIF of L5-L6 and balloon kyphoplasty of L5 were performed. On the 3rd postoperative day (POD), she was diagnosed with surgical site infection complicated with bacterial meningitis. Subcutaneous fluid, blood, and cerebrospinal fluid cultures indicated P. aeruginosa. On the 7th POD, a repeat MRI showed a large dorsal fluid collection consistent with a subdural infection and massive cauda equina compression. We performed debridement and instrument removal and found a dural laceration that was not observed during the first operation. An intraoperative insensible dural laceration may cause bacteria intrusion into the subdural space.