Concentration-Dependent Efficacy of Recombinant Human Bone Morphogenetic Protein-2 Using a HA/ß-TCP Hydrogel Carrier in a Mini-Pig Vertebral Oblique Lateral Interbody Fusion Model.

Bone morphogenetic protein-2 (BMP-2) is used in the treatment of degenerative spinal disease and vertebral fractures, spine fusion, dental surgery, and facial surgery. However, high doses are associated with side effects such as inflammation and osteophytes. In this study, we performed spinal fusion surgery on mini-pigs using BMP-2 and a HA/ß-TCP hydrogel carrier, and evaluated the degree of fusion and osteophyte growth according to time and dosage. Increasing the dose of BMP-2 led to a significantly higher fusion rate than was observed in the control group, and there was no significant difference between the 8-week and 16-week samples. We also found that the HA + ß-TCP hydrogel combination helped maintain the rate of BMP-2 release. In conclusion, the BMP-2-loaded HA/ß-TCP hydrogel carrier used in this study overcame the drawback of potentially causing side effects when used at high concentrations by enabling the sustained release of BMP-2. This method is also highly efficient, since it provides mineral matter to accelerate the fusion rate of the spine and improve bone quality.

Surgical Versus Conservative Management for Treating Unstable Atlas Fractures: A Multicenter Study.

OBJECTIVE: This multicenter study compared radiological parameters and clinical outcomes between surgical and nonsurgical management and investigated treatment characteristics associated with the successful management of unstable atlas fractures. METHODS: We retrospectively evaluated 53 consecutive patients with unstable atlas fracture who underwent halo-vest immobilization (HVI) or surgical fixation. Clinical outcomes were assessed using neck visual analogue scale and disability index. The radiological assessment included total lateral mass displacement (LMD) and the anterior atlantodental interval (AADI). RESULTS: Thirty-two patients underwent surgical fixation and 21 received HVI (mean follow-up, 24.9 months). In the surgical fixation, but not in the HVI, LMD, and AADI showed statistically significant improvements at the last follow-up. The osseous healing rate and time-to-healing were 100% and 14.3 weeks with surgical fixation, compared with 71.43% and 20.0 weeks with HVI, respectively. Patients treated with HVI showed poorer neck pain and neck disability outcomes than those who received surgical treatment. LMD showed an association with osseous healing outcomes in nonoperative management. Clinical outcomes and osseous healing showed no significant differences according to Dickman's classification of transverse atlantal ligament injuries. CONCLUSION: Surgical internal fixation had a higher fusion rate, shorter fracture healing time, more favorable clinical outcomes, and a more significant reduction in LMD and AADI compared to nonoperative management. The pitfalls of external immobilization are inadequate maintenance and a lower probability of reducing fractured lateral masses. Stabilization by surgical reduction with interconnected fixation proved to be a more practical management strategy than nonoperative treatment for unstable atlas fractures.

A Prospective, Multi-Center, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of the Synthetic Bone Graft Material DBM Gel with rhBMP-2 versus DBM Gel Used during the TLIF Procedure in Patients with Lumbar Disc Disease.

OBJECTIVE: This study is to evaluate the efficacy and safety of demineralized bone matrix (DBM) gel versus DBM gel with recombinant human bone morphogenetic protein-2 (rhBMP-2) used in transforaminal lumbar interbody fusion (TLIF). METHODS: This study was designed as a prospective, multi-center, double-blind method, randomized study. All randomized subjects underwent TLIF with DBM gel with rhBMP-2 group (40 patients) as an experimental group or DBM gel group (36 patients) as a control group. Post-operative observations were performed at 12, 24, and 48 weeks. The spinal fusion rate on computed tomography scans and X-rays films, Visual analog scale pain scores, Oswestry disability index and SF-36 quality of life (QOL) scores were used for the efficacy evaluation. The incidence rate of adverse device effects (ADEs) and serious adverse device effects (SADEs) were used for safety evaluation. RESULTS: The spinal fusion rate at 12 weeks for the DBM gel with rhBMP-2 group was higher with 73.68% compared to 58.82% for the DBM gel group. The 24 and 48 weeks were 72.22% and 82.86% for the DBM gel with rhBMP-2 group and 78.79% and 78.13%, respectively, for the DBM gel group. However, there were no significant differences between two groups in the spinal fusion rate at 12, 24, and 48 weeks post-treatment (p=0.1817, p=0.5272, p=0.6247). There was no significant difference between the two groups in the incidence rate of ADEs (p=0.3836). For ADEs in the experimental group, 'Pyrexia' (5.00%) was the most common ADE, followed by 'Hypesthesia', 'Paresthesia', 'Transient peripheral paralysis', 'Spondylitis' and 'Insomnia' (2.50%, respectively). ADEs reported in control group included 'Pyrexia', 'Chest discomfort', 'Pain', 'Osteoarthritis', 'Nephropathy toxic', 'Neurogenic bladder', 'Liver function analyses' and 'Urticaria' (2.86%, respectively). There was no significant difference between the two groups in the incidence rate of SADEs (p=0.6594). For SADE in the experimental group, ''Pyrexia' and 'Spondylitis' were 2.50%. SADE reported in the control group included 'Chest discomfort', 'Osteoarthritis' and 'Neurogenic bladder'. All SADEs described above were resolved after medical treatment. CONCLUSION: This study demonstrated that the spinal fusion rates of DBM gel group and DBM gel with rhBMP-2 group were not significantly different. But, this study provides knowledge regarding the earlier postoperative effect of rhBMP-2 containing DBM gel and also supports the idea that the longer term follow-up results are essential to confirm the safety and effectiveness.

Feasibility of Using the Epidural Space Detecting Device (EPI-DetectionTM) for Interlaminar Cervical Epidural Injection.

Cervical epidural injection (CEI), which is widely used for the treatment of cervical radiculopathy, sometimes has been associated with post-operative complications. Recently, EPI-DetectionTM, which detects the negative pressure of the epidural space and notifies the proceduralist by flashing a light and producing a beeping sound, was introduced. We assumed that the newly developed device could be as safe and efficient as the conventional loss of resistance (LOR) method. Therefore, we aimed to evaluate the effectiveness of the EPI-DetectionTM and compare it to that of the conventional LOR method. We randomly assigned 57 patients to the LOR and EPI-Detection groups (29 and 28 patients, respectively). Subjects were treated with interlaminar CEI (ILCEI) using one of two methods. The measured parameters, i.e., operation time and radiation dose were lower in the EPI-DetectionTM group (4.6 ± 1.2 min vs. 6.9 ± 2.1 min; and 223.2 ± 206.7 mGy·cm2 vs. 380.3 ± 340.9 mGy·cm2, respectively; all p < 0.05) than in the LOR group. There were no complications noted in either group. Both the EPI-DetectionTM and LOR methods were safe and effective in detecting the epidural space, but the former was superior to the latter in terms of operation time and radiation exposure. The EPI-DetectionTM may help perform ILCEI safely.

Synthesis and Characterization of Polyfumarateurethane Nanoparticles for Sustained Release of Bupivacaine.

Biodegradable polyfumarateurethane (PFU) for use as a bupivacaine delivery vehicle, synthesized using di-(2-hydroxypropyl fumarate) (DHPF), polyethylene glycol (PEG) and 1,6-hexamethylene diisocyanate (HMDI), was designed to be degradable through the hydrolysis and enzymatic degradation of the ester bonds in its polymer backbone. Using a water-in-oil-in-water double emulsion techniques, nanoparticles encapsulating water or fluorescein isothiocyanate (FITC) were fabricated to avoid the immune system owing to the presence of PEG on their surface. The morphologies of these nanoparticles were characterized by DLS, TEM, FE-SEM, and fluorescent microscopies. The present study explored the encapsulation, loading efficiency and in vitro drug release of bupivacaine encapsulated with biodegradable PFU nanoparticles for the treatment of local anesthesia. Various concentrations of bupivacaine were encapsulated into nanoparticles and their encapsulation efficiencies and drug loading were investigated. Encapsulation efficiency was highest when 2.5% bupivacaine was encapsulated. Drug release behavior from the bupivacaine-loaded PFU nanoparticles followed a sustained release profile.

Residence could influence the surgical outcome after corrective surgery in adult spinal deformity: comparison study between urban and rural area in Korea.

PURPOSE: Numerous factors affect the surgical outcomes in patients with adult spinal deformity (ASD). However, no study has examined the relationship between residence and physical factors and surgical outcomes in patients with ASD. Here, we analysed the impact of residence and physical factors on the post-operative outcomes of patients with ASD residing in urban (U) and rural (R) environments. METHODS: We retrospectively reviewed data from patients who had undergone ASD surgery with sacropelvic fixation at a single institution between June 2011 and May 2017 with a minimum 1 year follow-up. We divided the patients into two groups (U and R). Preoperative demographic data were reviewed, and radiographic parameters were measured preoperatively, immediately postoperatively, at 1, 3, and 6 months, and at the final follow-up. The L4 axial paraspinal muscles were measured preoperatively using magnetic resonance imaging. RESULTS: There were 25 and 34 patients in the U and R groups, respectively. Both groups had similar preoperative demographic and radiological parameters. There were no differences between the groups in post-operative radiographic parameters, clinical outcomes, and complications, but proximal junctional kyphosis (PJK) was significantly higher in the R group. Additionally, muscle mass in the multifidus and erector spinae was lower in the R than in the U group. CONCLUSIONS: Patient residence influenced PJK in patients with ASD. Mass reduction in the trunk extensor muscle is an important and existing risk factor for PJK. Surgeons should be aware of this information for preoperative counselling, informed consent, and post-operative education of patients with ASD. These slides can be retrieved from Electronic Supplementary Material.

Surgical Management of Gorham-Stout Disease in Cervical Compression Fracture with Cervicothoracic Fusion: Case Report and Review of Literature.

BACKGROUND: Gorham-Stout disease (GSD) or "vanishing bone" disease is characterized by progressive osteolysis with intraosseous lymphangiomatosis (hemangiomatosis). Given its rarity, with about 300 reported cases, its pathophysiology, etiology, and treatment guidelines are not established yet. CASE DESCRIPTION: A 22-year-old man was admitted to Severance Hospital with the chief complaint of neck pain from an injury due to falling. Initial cervical radiography showed a C4 burst fracture, and cervical magnetic resonance imaging revealed diffuse osteolytic lesions with coarse trabeculation with T2 hyperintensity and T1 enhancement in the entire cervical and upper thoracic area. He had a previous history of chylothorax that was still noticeable on a chest radiograph at the time of admission. A 2-stage operation was conducted. First, anterior corpectomy of C4 and anterior plate fixation of C3-5 were performed. Second, a week later, posterior fixation of C3-5 was performed. Thereafter, the patient was discharged without any neurologic complications. However, during the 1-month follow-up, asymptomatic progressive kyphosis was detected via radiography, and posterior cervical fusion of C2-T4 was performed. A minimal postoperative symptom of an intermittent left arm pain of 4-5 on the visual analog scale was experienced. No further deformity progression was noted until the last outpatient follow-up. CONCLUSIONS: Spinal GSD can cause severe deformity and neurologic deficits such as paralysis. Although treatment for GSD is not established, surgical treatment is recommended in severe deformity or aggravated neurologic deficit. The appropriate timing of surgery is after the arrest of osteolysis. Magnetic resonance imaging could be helpful in determining stable GSD.

Diversity in Surgical Decision Strategies for Adult Spine Deformity Treatment: The Effects of Neurosurgery or Orthopedic Training Background and Surgical Experience.

OBJECTIVE: This study is aimed to investigate whether surgical strategies for adult spinal deformity (ASD) treatment differed among Korean physicians. METHODS: This study is retrospective questionnaire-based study. ASD is challenging to manage, with a broad range of clinical and radiological presentations. To investigate possible nationality- or ethnicity-related differences in the surgical strategies adopted for ASD treatment, the International Spine Study Group surveyed physicians' responses to 16 cases of ASD. We reviewed the answers to this survey from Korean physicians. Korean orthopedic surgeons (OS) and neurosurgeons (NS) received a questionnaire containing 16 cases and response forms via email. After reviewing the cases, physicians were asked to indicate whether they would treat each case with decompression or fusion. If fusion was chosen, physicians were also asked to indicate whether they would perform 3-column osteotomy. Retrospective chi-square analyses were performed to investigate whether the answers to each question differed according to training specialty or amount of surgical experience. RESULTS: Twenty-nine physicians responded to our survey, of whom 12 were OS and 17 were NS. In addition, 18 (62.1%) had more than 10 years of experience in ASD correction and were assigned to the M10 group, while 11 (37.9%) had less than 10 years of experience and were assigned to the L10 group. We found that for all cases, the surgical strategies favored did not significantly differ between OS and NS or between the M10 and L10 groups. However, for both fusion surgery and 3-column osteotomy, opinions were divided regarding the necessity of the procedures in 4 of the 16 cases. CONCLUSION: The surgical strategies favored by physicians were similar for most cases regardless of their training specialty or experience. This suggests that these factors do not affect the surgical strategies selected for ASD treatment, with patient clinical and radiological characteristics having greater importance.

Comparison of Cervical Alignment and Clinical Outcomes in Patients with Os Odontoideum versus Non-Os Odontoideum after Atlantoaxial Fixation.

OBJECTIVE: The purpose of this study was to compare the effect of atlantoaxial fixation on cervical alignment and clinical outcomes in patients with os odontoideum (OO) versus non-os odontoideum (non-OO). METHODS: A total of 119 patients who underwent atlantoaxial fixation for instability were identified between January 1998 and January 2014. Inclusion criteria included age more than 21 years and diagnosis of OO and non-OO. There were 22 OO patients, and 20 non-OO patients. Measuring the Oc-C1 Cobb angle, C1-2 Cobb angle, C2-7 Cobb angle, and C2-7 sagittal vertical axis (SVA) was assessed. Clinical outcome was assessment of suboccipital pain was determined using a visual analogue scale (VAS), and Japanese Orthopedic Association (JOA) scores were obtained in all patients pre- and postoperatively. RESULTS: The preoperative C1-2 angle in the OO group (26.02°±10.53°) was significantly higher than the non-OO group (p=0.04). After C1-2 fixation, the OO group had significantly higher kyphotic change in the C1-2 angle (ΔC1-2) (3.2°±7.3° [OO] vs. -1.46°±7.21° [non-OO]) (p=0.04), and higher decrease in postoperative C2-7 SVA (ΔC2-7 SVA) (5.64±11.56 mm [OO] vs. -0.51± 6.57 mm [non-OO]) (p=0.04). Both groups showed improvements in the health related quality of life (HRQOL) after surgery based on the VAS and JOA score (p<0.001). CONCLUSION: After fixation, kyphotic angular change in atlantoaxial joint and decrease C2-7 SVA were marked in the OO group. Both the OO and non-OO groups improved in neurological function and outcome after surgery.

Clinical Analysis of Delayed Surgical Epidural Hematoma.

OBJECTIVE: A small epidural hematoma (EDH) that has been diagnosed to be nonsurgical by initial brain computed tomography (CT) can increase in size and need surgical removal, resulting in a poor prognosis. However, there have been few studies, which focused delayed operated EDH. Therefore, we analyzed the clinical factors to determine the predicting factors of delayed operated EDH. METHODS: Between January 2011 and January 2014, 90 patients, who were admitted due to EDH, were enrolled in this study. None of the patients were indicated for operation initially. Based on the presence of surgery, we classified the patients into a delayed-surgery group (DG) and a non-surgical group (NG). Additionally, we analyzed them according to the following: time interval between the trauma and the initial CT, gender, age, medical history, drinking, change of mean arterial pressure (MAP), volume of EDH and other traumatic brain lesion. RESULTS: Among the 90 patients, the DG was 19 patients. Compared with NG, the DG revealed increased MAP, less presence of drinking, and a short time interval (DG vs. NG: +9.684 mm Hg vs. -0.428 mm Hg, 5.26% vs. 29.58%, 1.802 hours vs. 5.707 hours, respectively, p<0.05). Analyzing the time interval with receiver operating characteristic, there was 88.2% sensitivity and 68.3% specificity at the 2.05-hour cut-off value (area under the curve=0.854). CONCLUSION: According to our results, the time interval between the trauma and the initial CT along with blood pressure change are potential predicting factors in the cases of delayed operation of EDH.

Middle Meningeal Artery Embolization in Recurrent Chronic Subdural Hematoma Combined with Arachnoid Cyst.

Chronic subdural hematoma (CSDH) is a collection of old blood and its breakdown products between the surface of the brain parenchyma and the outermost layer called the dura. The most common treatment option for primary CSDH is burr-hole trephination; however, the treatment method for recurrent CSDH is still widely debated. An arachnoid cyst (AC) is a sac filled with cerebrospinal fluid located between the brain or spinal cord and the arachnoid membrane, which is one of the three meninges covering the brain or spinal cord. Although it is rare, the cyst is associated with CSDH in juveniles, and the recurrence rate of CSDH increases in such cases. Much of the literature has supported the preventive role of middle meningeal artery (MMA) embolization in recurrent CSDH. We report a 13-year-old male patient with recurrent CSDH and AC where the early intervention of MMA embolization was proven effective in preventing the further recurrence of CSDH.

Effect of quercetin on impaired immune function in mice exposed to irradiation.

Radiation used in cancer treatment may cause side effects such as inflammation. Quercetin is a polyphenol that reduces inflammation. This study evaluated the recovery efficacy of quercetin on impaired immune function in irradiation-induced inflammatory mice. Quercetin administered at two concentrations of 10 and 40 mg/kg body weight was initiated 2 weeks before irradiation and was continued 30 days after irradiation. The animals exposed/not exposed to radiation were sacrificed on radiation days 10 and 30. Splenocyte proliferation, which was diminished after irradiation, was enhanced significantly by quercetin supplementation after 30 days of irradiation. Cytokine secretion increased in the radiation group compared to that in the non-radiation control group. After 30 days of radiation, interleukin (IL)-1ß and IL-6 secretion decreased significantly in the radiation-quercetin groups. When quercetin was administered for 44 days, it showed a possible protective effect against irradiation-induced inflammation in mice. Quercetin could be beneficial in the recovery of irradiation-induced increases in cytokine secretion.

Acute sensorineural hearing loss and severe otalgia due to scrub typhus.

BACKGROUND: Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. CASE PRESENTATIONS: We encountered a patient with sensorineural hearing loss complicating scrub typhus, and three patients with scrub typhus who complained of otalgia, which was sudden onset, severe, paroxysmal, intermittent yet persistent pain lasting for several seconds, appeared within 1 week after the onset of fever and rash. The acute sensorineural hearing loss and otalgia were resolved after antibiotic administration. CONCLUSION: When patients in endemic areas present with fever and rash and have sensorineural hearing loss or otalgia without otoscopic abnormalities, clinicians should suspect scrub typhus and consider empirical antibiotic therapy.

Deferasirox plus ciprofloxacin combination therapy after rapid diagnosis of Vibrio vulnificus sepsis using real-time polymerase chain reaction.

We report a case of Vibrio vulnificus sepsis developed during deferoxamine therapy for transfusional iron overload due to secondary hemochromatosis of myelodysplastic syndrome. The patient was treated with adjuvant deferasirox in combination with ciprofloxacin, after rapid diagnosis of V. vulnificus sepsis using real-time polymerase chain reaction (PCR). This case suggests that since V. vulnificus DNA can be detected by real-time PCR for several days even after patients receive antibiotics, real-time PCR for V. vulnificus is a very useful test for establishing an early diagnosis, even if a patient has been treated with antibiotics prior to admission.