Cost-Effectiveness and Clinical Outcomes of Lateral Lumbar Interbody Fusion With Tricalcium Phosphate and Iliac Bone Graft Compared With Posterior Lumbar Interbody Fusion With Local Bone Graft in Single-Level Lumbar Spinal Fusion Surgery in Thailand.

BACKGROUND: Nowadays, minimally invasive lateral lumbar interbody fusion (LLIF) is used to treat degenerative lumbar spine disease. Many studies have proven that LLIF results in less soft tissue destruction and rapid recovery compared with open posterior lumbar interbody fusion (PLIF). Our recent cost-utility study demonstrated that LLIF was not cost-effective according to the Thai willingness-to-pay threshold, primarily due to the utilization of an expensive bone substitute: bone morphogenetic protein 2. Therefore, this study was designed to use less expensive tricalcium phosphate combined with iliac bone graft (TCP + IBG) as a bone substitute and compare cost-utility analysis and clinical outcomes of PLIF in Thailand. METHODS: All clinical and radiographic outcomes of patients who underwent single-level LLIF using TCP + IBG and PLIF were retrospectively collected. Preoperative and 2-year follow-up quality of life from EuroQol-5 Dimensions-5 Levels and health care cost were reviewed. A cost-utility analysis was conducted using a Markov model with a lifetime horizon and a societal perspective. RESULTS: All enrolled patients were categorized into an LLIF group (n = 30) and a PLIF group (n = 50). All radiographic results (lumbar lordosis, foraminal height, and disc height) were improved at 2 years of follow-up in both groups (P < 0.001); however, the LLIF group had a dramatic significant improvement in all radiographic parameters compared with the PLIF group (P < 0.05). The fusion rate for LLIF (83.3%) and PLIF (84%) was similar and had no statistical significance. All health-related quality of life (Oswestry Disability Index, utility, and EuroQol Visual Analog Scale) significantly improved compared with preoperative scores (P < 0.001), but there were no significant differences between the LLIF and PLIF groups (P > 0.05). The total lifetime cost of LLIF was less than that of PLIF (15,355 vs 16,500 USD). Compared with PLIF, LLIF was cost-effective according to the Thai willingness-to-pay threshold, with a net monetary benefit of 539.76 USD. CONCLUSION: LLIF with TCP + IBG demonstrated excellent radiographic and comparable clinical health-related outcomes compared with PLIF. In economic evaluation, the total lifetime cost was lower in LLIF with TCP + IBG than in PLIF. Furthermore, LLIF with TCP + IBG was cost-effective compared with PLIF according to the context of Thailand. CLINICAL RELEVANCE: LLIF with less expensive TCP + IBG as bone graft results in better clinical and radiographic outcomes, less lifetime cost, and cost-effectiveness compared with PLIF. This suggests that LLIF with TCP + IBG could be utilized in lower- and middle-income countries for treating patients with degenerative disc disease.

Pseudarthrosis risk factors in lumbar fusion: a systematic review and meta-analysis.

This study presents a systematic literature review and meta-analysis of pseudarthrosis risk factors following lumbar fusion procedures. The odds ratio (OR) and 95% confidence interval (95% CI) were used for outcome measurements. The objective of this study was to identify the independent risk factors for pseudarthrosis after lumbar spinal fusion, which is crucial for mitigating morbidity and reoperation. Systematic searches in PubMed, Embase, and Scopus (1990-July 2021) were conducted using specific terms. The inclusion criteria included prospective and retrospective cohorts and case‒control series reporting ORs with 95% CIs from multivariate analysis. The quality assessment utilized the Newcastle-Ottawa scale. Meta-analysis, employing OR and 95% CI, assessed pseudarthrosis risk factors in lumbar fusion surgery, depicted in a forest plot. Of the 568 abstracts identified, 12 met the inclusion criteria (9 retrospective, 2006-2021). The 17 risk factors were categorized into clinical, radiographic, surgical, and bone turnover marker factors. The meta-analysis highlighted two significant clinical risk factors: age (95% CI 1.02-1.11; p = 0.005) and smoking (95% CI 1.68-5.44; p = 0.0002). The sole significant surgical risk factor was the number of fused levels (pooled OR 1.35; 95% CI 1.17-1.55; p < 0.0001). This study identified 17 risk factors for pseudarthrosis after lumbar fusion surgery, emphasizing age, smoking status, and the number of fusion levels. Prospective studies are warranted to explore additional risk factors and assess the impact of surgery and graft type.

Lipid Peroxidation, Reduced Glutathione, and Glutathione Peroxidase Levels in Intervertebral Discs of Patients with Lumbar Degenerative Disc Disease.

BACKGROUND Either a reduction in antioxidant levels or an accumulation of reactive oxygen species can heighten susceptibility to oxidative damage in disc cells. To date, no research has investigated the levels of lipid peroxidation products (thiobarbituric acid reactive substances [TBARs]), reduced glutathione (GSH), and glutathione peroxidase (GPx) in excised human lumbar disc tissues affected by degenerative disease. Therefore, this study aimed to evaluate lipid peroxidation products in excised disc tissues from patients with degenerative disc disease. MATERIAL AND METHODS Forty-two patients were enrolled. Patients were divided into lumbar disc degeneration (LDD) and nonlumbar disc degeneration (nonLDD) groups according to Pfirrmann classification. Intervertebral discs were obtained from all patients during the operation and were homogenized for analysis. TBARs levels were measured using fluorometry. GSH levels and GPx activity were quantified spectrophotometrically using a kinetic method. RESULTS TBARs levels in excised discs from LDD patients (5.18±4.14) were significantly higher than those from nonLDD patients (2.56±1.23, P=0.008). The levels of TBARs tended to increase with the severity of degeneration according to the Pfirrmann classification. However, these 2 groups showed no significant differences in reduced glutathione levels or glutathione peroxidase activity (P>0.05). Patients with LDD exhibited a worse health-related quality of life, reflected in lower utility and EQ-VAS scores and higher Oswestry disability index scores. CONCLUSIONS There was a notable increase in lipid peroxidation products in the excised intervertebral discs of patients with LDD. This finding suggests that oxidative stress may contribute to the development of disc degeneration.

Vertical Relationship Ratio (VRR): A High Reliability and Accuracy Radiographic Measurement for Basilar Invagination in Rheumatoid Arthritis.

BACKGROUND Previous radiographic measurements for diagnosis of a basilar invagination or impression (BI) in rheumatoid arthritis (RA) were used as reference values based on anatomical reference distances. Due to the obscured anatomical landmarks, our group proposed a new radiographic measurement based on anatomic ratios to identify BI. MATERIAL AND METHODS The vertical relationship ratio (VRR) was developed and evaluated. The VRR is the relationship between the distance obtained with the modified Ranawat method and the C3 vertebral body height. VRR was used to assess its ability to distinguish BI in 3 patient groups (28 RA with BI, 37 RA without BI, and 56 non-RA patients). The intra- and inter-observer reliability, the sensitivities, and specificities of all measurements were analyzed. The cutoff value of VRR measurement was calculated by using the receiver operating characteristic (ROC) curve. RESULTS The VRR measurement showed excellent intra- and inter-observer reliabilities. The VRR could significantly distinguish RA patients with BI from RA patients without BI. The mean VRR of RA patients with BI (1.82±0.20) was less than for the non-RA patients (2.26±0.19) and the RA patients without BI (2.24±0.19). The cutoff value of VRR from the ROC curve was below 2.025. Its sensitivity was 92.85%, specificity was 97.85%, positive predictive value was 92.86%, and negative predictive value was 97.84%. CONCLUSIONS VRR has excellent intra-/inter-observer reliability and can distinguished BI in RA patients. We recommend using VRR in preference to the other available methods for assessment and screening BI in rheumatoid arthritis.

Safety and feasibility of ultra-long construct navigated minimally invasive spine surgery with adjuvant radiotherapy in extensive spinal metastasis : a comparative analysis.

BACKGROUND: Our study compares the outcomes of extensive spinal metastasis patients treated with Ultra-Long Construct Navigated Minimally Invasive Spine Surgery (UNMISS) with Adjuvant Radiotherapy to those receiving only radiotherapy. Spinal metastasis often necessitates interventions like radiotherapy, chemotherapy, or surgery, with an increasing trend towards surgical management. minimally invasive spine surgery has demonstrated advantages over traditional open surgery, with fewer complications and better postoperative outcomes. Radiotherapy continues as a standard for those unsuitable for surgery. METHODS: This retrospective study included extensive spinal metastasis patients treated between January 2017 and December 2020. We compared patients undergoing UNMISS in conjunction with radiotherapy to patients receiving radiotherapy alone, evaluating demographic data, disease characteristics, and treatment outcomes (VAS, survival) to establish statistical significance. RESULTS: Twenty-three patients were included in our study. Fourteen patients underwent UNMISS, and nine patients received radiotherapy alone. There was no difference in baseline characteristics of patients. The longest construct in our case series involved T1 to iliac. Both cohorts showed significant improvement in pain scores post-treatment (p = 0.01). However, the UNMISS group demonstrated significantly lower post-treatment VAS scores (p = 0.003), indicating enhanced pain relief. Survival outcomes did not differ significantly between the two groups. CONCLUSION: The UNMISS should be considered as an alternative treatment in a patient with symptomatic extensive spinal metastasis. The primary goal of this technique is to stabilize the multiple levels of spinal metastasis and decompression of the neural element if needed. This technique is safe and has a better outcome in pain improvement than the patient who received radiotherapy alone.

An effectiveness and economic analyses of tricalcium phosphate combined with iliac bone graft versus RhBMP-2 in single-level XLIF surgery in Thailand.

STUDY DESIGN: Retrospective study. OBJECTIVES: To perform effectiveness and economic analyses using data from a retrospective study of patients who underwent XLIF surgery using tricalcium phosphate combined with iliac bone graft (TCP + IBG) or BMP-2 in Thailand. METHODS: Data were collected from retrospective review of the medical charts and the spine registry of Siriraj Hospital, Bangkok, Thailand. The patients were divided into two groups (TCP + IBG group and BMP-2 group). Demographic, perioperative data, radiographic, clinical results, and quality of life related to health were collected and analyzed at 2-year follow-up. All economic data were collected during the perioperative period and presented as total charge, bone graft, implant/instrumentation, operative service, surgical supply, transfusion, medication, anesthesia, laboratory, and physical therapy. RESULTS: Twenty-five TCP + IBG and 30 BMP-2 patients with spondylolisthesis and spinal stenosis as primary diagnosis were included. There were no significant differences in all demographic parameters (gender, age, underlying disease, diagnosis, and level of spine) between these two groups. During the perioperative period, the TCP + IBG group had more mean blood loss and more postoperative complications compared to the BMP-2 group. At 2 years of follow-up, there were no significant differences between the radiographic and clinical outcomes of the TCP + IBG and BMP-2 groups. The fusion rate for TCP + IBG and BMP-2 at 2 years of follow-up was 80% and 96.7%, respectively, and no statistically significant differences were observed. All clinical outcomes (Utility, Oswestry Disability Index, and EuroQol Visual Analog Scale) at 2-year follow-up improved significantly compared to preoperative outcomes, but there were no significant differences between the TCP + IBG and BMP-2 groups, either at preoperatively or at 2-year follow-up. The total charge of TCP + IBG was statistically significantly lower than that of BMP-2. Furthermore, the charges of TCP + IBG and BMP-2 during the perioperative period in Thailand were up to three times less than those in the United States. CONCLUSIONS: Using TCP + IBG as a standalone bone substitution for XLIF surgery with additional posterior instrumentation resulted in significantly lower direct medical charge compared to those using BMP-2 in the perioperative period. However, we could not detect a difference in the long-term radiographic and clinical outcomes of patients with TCP + IBG and BMP-2. These suggest that TCP + IBG may be a valuable alterative bone graft, especially in low- and middle-income countries.

Midterm outcome after en bloc resection of C2 chordoma with transoral mandibular split and mesh cage reconstruction: a case report.

INTRODUCTION: Chordomas are rare, locally aggressive tumors that often occur in the axial spine, especially in the sacrum. The treatment of chordomas located in the upper cervical spine is challenging. En bloc resection is the preferred surgical option for total tumor removal. CASE PRESENTATION: We report the case of a C2 chordoma in a 47-year-old Thai woman. She was treated with a two-stage, anterior-posterior, C2 total spondylectomy with titanium mesh cage reconstruction and radiotherapy. The first stage involved posterior stabilization from the occiput to C5, a total laminectomy, and removal of the posterior rings of the bilateral foramen transversarium to preserve the bilateral vertebral arteries. The second stage comprised a transoral mandibular split with en bloc resection of C2, followed by titanium mesh cage reconstruction and kick-off anterior cervical plating. At the 5 year follow-up, no tumor recurrence was identified on magnetic resonance imaging. The patient had no neurological deficits but still had minor complications from the anterior transoral mandibular split. CONCLUSIONS: Excellent midterm results were obtained using a transoral mandibular split with reconstruction and posterior spinal fusion from the occiput to the lower cervical spine coupled with adjuvant radiotherapy. We recommend this approach as the treatment of choice for chordoma in the upper cervical spine.

Comparative effectiveness of different pedicle screw density patterns in spinal deformity correction of small and flexible operative adolescent idiopathic scoliosis: inverse probability of treatment weighting analysis.

PURPOSES: An optimal pedicle screw density for spinal deformity correction in adolescent idiopathic scoliosis (AIS) remains poorly defined. We compared radiographic correction, operative time, estimated blood loss, and implant cost among different screw density patterns in operatively treated AIS patients. METHODS: A retrospective observational cohort study of AIS patients who underwent posterior spinal fusion using all-pedicle screw instrumentation was conducted from January 2012 to December 2018. All patients were categorized into three different pedicle screw density groups: the very low density (VLD), the low density (LD), and the high density (HD) group. The comparative effectiveness between each pairwise comparison was performed under the inverse probability of the treatment weighting method to minimize the possible confounders imbalance among treatment groups. The primary endpoints in this study were the degrees of correction and deformity progression at 2 years postoperatively. RESULTS: A total of 174 AIS patients were included in this study. The adjusted treatment effects demonstrated similar degrees of deformity correction after 2 years in the three treatment groups. However, the VLD and LD group slightly increased the curve progression at 2 years compared to the HD group by 3.9° (p = 0.005) and 3.2° (p = 0.044), respectively. Nevertheless, the limited screw density patterns (VLD and LD) significantly reduced the operative time, estimated blood loss, and implant cost per operated level. CONCLUSION: The limited pedicle screw pattern (VLD and LD) in relatively flexible AIS spinal deformity correction results in similar coronal and sagittal radiological outcomes while reducing operative time, estimated blood loss, and implant cost compared to the high-density pedicle screw instrumentation.

Lateral lumbar interbody fusion (LLIF) reduces total lifetime cost compared with posterior lumbar interbody fusion (PLIF) for single-level lumbar spinal fusion surgery: a cost-utility analysis in Thailand.

BACKGROUND: Lumbar interbody fusion techniques treat degenerative lumbar diseases effectively. Minimally invasive lateral lumbar interbody fusion (LLIF) decreases soft tissue disruption and accelerates recovery better than standard open posterior lumbar interbody fusion (PLIF). However, the material cost of LLIF is high, especially in Thailand. The cost-effectiveness of LLIF and PLIF in developing countries is unclear. This study compared the cost-utility and clinical outcomes of LLIF and PLIF in Thailand. METHODS: Data from patients with lumbar spondylosis who underwent single-level LLIF and PLIF between 2014 and 2020 were retrospectively reviewed. Preoperative and 1-year follow-up EuroQol-5D-5L and healthcare costs were collected. A cost-utility analysis with a lifetime time horizon was performed using a societal perspective. Outcomes are reported as the incremental cost-effectiveness ratio (ICER) and quality-adjusted life-year (QALY) gained. A Thai willingness-to-pay threshold of 5003 US dollars (USD) per QALY gained was used. RESULTS: The 136 enrolled patients had a mean age of 62.26 ± 11.66 years. Fifty-nine patients underwent LLIF, while 77 underwent PLIF. The PLIF group experienced greater estimated blood loss (458.96 vs 167.03 ml; P < 0.001), but the LLIF group had a longer operative time (222.80 vs 194.62 min; P = 0.007). One year postoperatively, the groups' Oswestry Disability Index and EuroQol-Visual Analog Scale scores were improved without statistical significance. The PLIF group had a significantly better utility score than the LLIF group (0.89 vs 0.84; P = 0.023). LLIF's total lifetime cost was less than that of PLIF (30,124 and 33,003 USD). Relative to PLIF, LLIF was not cost-effective according to the Thai willingness-to-pay threshold, with an ICER of 19,359 USD per QALY gained. CONCLUSIONS: LLIF demonstrated lower total lifetime cost from a societal perspective. Regard to our data, at the 1-year follow-up, the improvement in patient quality of life was less with LLIF than with PLIF. Additionally, economic evaluation modeling based on the context of Thailand showed that LLIF was not cost-effective compared with PLIF. A strategy that facilitates the selection of patients for LLIF is required to optimize patient benefits.

Bilateral Lumbar Facet Synovial Cysts as a Cause of Radiculopathy.

Remarkable advancements in endoscopic spinal surgery have led to successful outcomes comparable to those of conventional open surgery with the benefits of less traumatization and postoperative spinal instability. Bilateral lumbar facet cysts are rarely found in the spinal canal. We report a rare case of L4-L5 bilateral lumbar facet cysts compressing the nerve root in a patient who presented with L5 radiculopathy. Endoscopic decompression and removal of the cysts without fusion were performed. Histopathology revealed synovial cysts. Postoperatively, the patient showed a total resolution of symptoms with sustained benefits at the final evaluation. No recurrence of pain and no further segmental instability were observed at the 1-year follow-up.

Surgical outcome of scoliosis in patients with Marfan syndrome.

PURPOSE: To evaluate clinical and radiographic outcomes after surgical scoliosis correction and posterior instrumented fusion in SMF patients. METHODS: A single-center medical database was reviewed to identify MF patients who presented with scoliosis from 2000 to 2015. Patients who underwent spinal fusion surgery were included. Demographic, operative and clinical data were reviewed, and the preoperative, postoperative, and latest follow-up radiographic parameters were compared. RESULTS: Twelve patients were identified (2 males, 10 females) with an average age at surgery of 14.4 ± 2.6 years. Comorbidities were found in 84.6%. Most patients (90.9%) presented with a right thoracic curve. The average preoperative Cobb angle was 75.6 ± 15.5 degrees. Posterior instrumented spinal fusion was performed in all patients (1 hook/pedicular screw and 11 pedicle screws only). The average follow-up period was 6.8 ± 3.1 years. The mean postoperative Cobb angle after surgery and at the final follow-up was 33.4 ± 18.0 degrees and 35.5 ± 18.4 degrees, respectively. There was a statistically significant difference among the preoperative and postoperative Cobb angles (p < 0.001), but no significant difference among the sagittal angles. Two perioperative complications including superficial wound infection and broken rods were observed. CONCLUSIONS: Posterior scoliosis correction and instrumented spinal fusion resulted in a satisfactory outcome in MF patients. Perioperative complications are not uncommon; however, no neurological complication or spinal decompensation was observed in this study. LEVEL OF EVIDENCE: IV.

Total neurological recovery after surgical decompression and treatment with denosumab of large unresectable spinal giant cell tumour expanding to mediastinum.

There is a controversy over the medical treatment of unresectable spinal giant cell tumour (GCT) regarding dosing and duration. We studied a spinal GCT case that had expanded to the thoracic spinal canal and mediastinum and was successfully treated by surgical decompression and denosumab. A woman in her 30s presented with weakness in both the lower extremities. MRI revealed a large tumour in the posterior mediastinum expanding from the thoracic vertebrae (T3-6), which compressed the spinal cord. The patient underwent urgent spinal decompression with instrumentation and her tissue was sent for a pathology study. Histologically and immunohistochemistry confirmed the diagnosis of GCT. Since it was an unresectable tumour, this patient was treated with denosumab. Her neurological problem resolved after 6 months of treatment. After 4 years of follow-up, the patient displayed no further progression and no side effects from long-term denosumab usage.

Surgeons' Perspective, Learning Curve, Motivation, and Obstacles of Full-Endoscopic Spine Surgery in Thailand: Results From A Nationwide Survey.

Objective: To report a nationwide survey of the endoscopic spine surgeons across Thailand. Furthermore, the survey will be focused on the perspective of experience, learning curve, motivations, and obstacles at the beginning of their practices. Materials and Methods: The online survey consisting of 16 items was distributed to spine surgeons who are performing endoscopic spine surgery in Thailand via the Google forms web-based questionnaire to investigate participants' demographics, backgrounds, experience in endoscopic spine surgery, motivations, obstacles, and future perspectives. The data was recorded from January 7, 2020 to January 21, 2022. Descriptive statistics were used for analysis. Results: A total of 42 surveys were submitted by 6 neurosurgeons (14.3%) and 36 orthopedic surgeons (85.7%). From the surgeons' perspective, the average number of cases that should be performed until one feels confident, consistently good outcomes, and has minimal complications was 27.44 ± 32.46 cases. For surgeons who starting the endoscopic spine practice, at least 3 workshop participation is needed. Personal interest (39 selected responses) and trending marketing or business purpose (25 selected responses) were the primary motivators for endoscopic spine surgery implementation. Lack of support (18 selected responses) and afraid of complications (16 selected responses) were pertinent obstacles to endoscopic spine surgery implementation. Conclusions: The trend of endoscopic spine surgery has continued to grow in Thailand, shown by the rate of implementation of endoscopic spine surgery reported by Thai spine surgeons. The number of appropriate cases until one feels confident was around 28 cases. The primary motivator and obstacles were personal interest and lack of support.

Epidemiologic Study of Operative Treatment for Spinal Metastasis in Thailand : A Review of National Healthcare Data from 2005 to 2014.

OBJECTIVE: To study the factors relating to operative treatment for spinal metastasis in Thailand during 2005-2014 and to determine the hospital costs, mortality rate, and incidence of perioperative complication. METHODS: Inpatient reimbursement data from 2005 to 2014 was reviewed from three national healthcare organizations, including the National Health Security Office, the Social Security Office, and the Comptroller General's Department. The search criteria were secondary malignant neoplasm of bone and bone marrow patients (International Classification of Diseases 10th revision, Thai modification codes [ICD 10-TM], C79.5 and C79.8) who underwent spinal surgical treatment (ICD 9th revision, clinical modification procedure with extension codes [ICD 9-CM], 03.0, 03.4, 03.09, and 81.0) during 2005-2014. Epidemiology, comorbidity, and perioperative complication were analyzed. RESULTS: During the study period, the number of spinal metastasis patients who underwent operative treatment was significantly increased from 0.30 to 0.59 per 100000 (p<0.001). More males (56.14%) underwent surgical treatment for spinal metastasis than females. The most common age group was 45-64 (55.1%). The most common primary tumor sites were the unknown origin, lung, breast, prostate, and hepatocellular/bile duct. Interestingly, the proportion of hepatocellular/bile duct, breast, and lung cancer was significantly increased (p<0.001). The number of patients who had comorbidity or in-hospital complication significantly increased over time (p<0.01); however, the in-hospital mortality rate decreased. CONCLUSION: During the last decade, operative treatment for spinal metastasis increased in Thailand. The overall in-hospital complication rate increased; however, the in-hospital mortality rate decreased.

Non-fusion palliative spine surgery without reconstruction is safe and effective in spinal metastasis patients: retrospective study.

Considering the shorter life expectancy and poorer prognosis of metastatic epidural spinal cord compression patients, anterior reconstruction and fusion may be unnecessary. This study aimed to investigate the outcomes of palliative surgery for metastatic epidural spinal cord compression with neurological deficit among patients who underwent posterior decompression and instrumentation without fusion or anterior reconstruction. This single-center retrospective review included all patients aged > 18 years with thoracic or lumbar spinal metastasis who were surgically treated for metastatic spinal cord compression without fusion or anterior reconstruction at the Department of Orthopaedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during July 2015 to December 2017. Data from preoperation to the 1-year follow-up, including demographic and clinical data, Frankel classification, pain scores, complication, revision surgery, health-related quality-of-life scores, and survival data, were collected and analyzed. A total of 30 patients were included. The mean age was 59.83 ± 11.73 years, and 20 (66.7%) patients were female. The mean operative time was 208.17 ± 58.41 min. At least one Frankel grade improvement was reported in 53.33% of patients. The pain visual analog scale, the EuroQOL five-dimension five-level utility score, and the Oswestry Disability Index were all significantly improved at a minimum of 3 months after surgery. No intraoperative mortality or instrument-related complication was reported. The mean survival duration was 11.4 ± 8.97 months. Palliative non-fusion surgery without anterior reconstruction may be considered as a preferable choice for treating spinal metastasis patients with spinal cord compression with neurological deficits.

Intravitreal autologous mesenchymal stem cell transplantation: a non-randomized phase I clinical trial in patients with retinitis pigmentosa.

BACKGROUND: Retinitis pigmentosa (RP) is a progressive inherited retinal disease with great interest for finding effective treatment modalities. Stem cell-based therapy is one of the promising candidates. We aimed to investigate the safety, feasibility, and short-term efficacy of intravitreal injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) in participants with advanced stage RP. METHODS: This non-randomized phase I clinical trial enrolled 14 participants, categorized into three groups based on a single dose intravitreal BM-MSC injection of 1 × 106, 5 × 106, or 1 × 107 cells. We evaluated signs of inflammation and other adverse events (AEs). We also assessed the best corrected visual acuity (BCVA), visual field (VF), central subfield thickness (CST), and subjective experiences. RESULTS: During the 12-month period, we noticed several mild and transient AEs. Interestingly, we found statistically significant improvements in the BCVA compared to baseline, although they returned to the baseline at 12 months. The VF and CST were stable, indicating no remarkable disease progression. We followed 12 participants beyond the study period, ranging from 1.5 to 7 years, and observed one severe but manageable AE at year 3. CONCLUSION: Intravitreal injection of BM-MSCs appears to be safe and potentially effective. All adverse events during the 12-month period required observation without any intervention. For the long-term follow-up, only one participant needed surgical treatment for a serious adverse event and the vision was restored. An enrollment of larger number of participants with less advanced RP and long-term follow-up is required to evaluate the safety and efficacy of this intervention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01531348 . Registered on February 10, 2012.

Patterns of Lumbar Disc Degeneration: Magnetic Resonance Imaging Analysis in Symptomatic Subjects.

STUDY DESIGN: Cross-sectional study. PURPOSE: To evaluate lumbar disc degeneration (LDD) on magnetic resonance imaging (MRI) in symptomatic subjects to accumulate baseline data on the pattern of degeneration. OVERVIEW OF LITERATURE: LDD plays an important role in the diagnosis and treatment of low-back pain in patients. Few studies have focused on the pattern of LDD to understand how the lumbar spine ages. METHODS: This study included 1,095 patients (mean age, 44.29 years; range, 16-85 years) who underwent upright lumbar MRI. LDD was graded into five categories (I-V). Positive LDD was defined as grade III or greater. The prevalence and pattern of LDD were analyzed, and the correlations between age and total grade of LDD were evaluated. RESULTS: The average number of LDD levels and the total grade of LDD increased with age. LDD moved cephalad with age. The rate of LDD increased rapidly during the decade before the prevalence of LDD and became >50%. In the single-level LDD group, the levels L5-S1 were the most common levels (60.3%). In the two-level group, L4-L5 and L5-S1 were the most common levels (53.5%). In the three-level group, L3-L4, L4-L5, and L5-S1 were the most common levels (55.7%). In the multilevel LDD group, contiguous multilevel disc degeneration (CMDD) was more common than the skipped level disc degeneration (SLDD). The levels L4-L5 were the most common levels in the CMDD group, and L5-S1 were the most common levels among SLDD. CONCLUSIONS: LDD was found to correlate with age, and the specific patterns and rates of LDD depended on lumbar disc level and age. These LDD pattern data can be used before spinal procedures to predict the probability of natural LDD progression with age.

Patterns of Cervical Disc Degeneration: Analysis of Magnetic Resonance Imaging of Over 1000 Symptomatic Subjects.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: The aim of this study was to evaluate cervical disc degeneration on magnetic resonance imaging (MRI) in a large population of symptomatic patients and to provide baseline data on the pattern of degeneration in order to understand how the cervical spine ages. METHODS: We performed a cross-sectional study of 1059 patients who underwent upright cervical MRI for neck pain with and without neurological symptoms. A total of 6354 cervical discs from C2/3 to C7/T1 were evaluated. Cervical disc degeneration was evaluated on T2-weighted MRI and graded into 4 categories (Grades 0-III). Positive degeneration was defined as greater than Grade II. The correlation between age and total grade of degeneration of each patient was evaluated, as well as the prevalence and pattern of degeneration. RESULTS: The average number of degenerated disc levels and the total grade of cervical disc degeneration significantly increase with age. In the patient group with 1-level degeneration, C5/6 was the most common degenerated level followed by C4/5 and C6/7. In the group with 2-level degeneration, C5/6 & C6/7 was most common followed by C4/5 & C5/6 and C3/4 & C4/5. Skip level degeneration was significantly rarer than contiguous level degeneration, and C7/T1 and C2/3 were the most unlikely to degenerate in multilevel degeneration. CONCLUSION: Disc degeneration is most common in the middle cervical spine (C5/6) and progresses to contiguous levels, except for C7/T1 and C2/3. This pattern may play a role in adjacent-level disc degeneration associated with spinal fusion.

Magnetic Resonance Classification System of Cervical Intervertebral Disk Degeneration: Its Validity and Meaning.

STUDY DESIGN: Retrospective analysis of kinetic magnetic resonance images (kMRIs). OBJECTIVE: (1) To analyze the changes seen on MRI related to disk degeneration and to develop a new grading system for cervical disk degeneration. (2) To evaluate the reliability and validity of the grading system. SUMMARY OF BACKGROUND DATA: Few have studied the relationship between changes seen on MRI with cervical disk degeneration and the chronological order of disk degeneration. A few grading systems for cervical disk degeneration have been reported; however, there have been problems related to subjectivity and lack of a clear, reliable algorithm. METHODS: A total of 300 cervical intervertebral disks were graded for nucleus color, structure, disk bulge, and disk height. On the basis of the analysis, a new grading system consisting of 4 grades (grade 0-III) and algorithm were developed. Intraobserver and interobserver reliabilities were assessed. A total of 2802 intervertebral disks were then evaluated using the grading system to correlate disk degeneration grades with patient age and function and to evaluate the validity of the new system. RESULTS: On the basis of cross-table analysis, disk degeneration presents in the following order: (1) decrease and/or change of nucleus intensity; (2) loss of distinction between nucleus and annulus; (3) positive disk bulge; and (4) disk height decrease. The κ-coefficients for intraobserver and interobserver agreements were 0.96 and 0.90, respectively. Severe disk degeneration is most common at C5/C6 followed by C6/C7 and C4/C5, and total disk degeneration grade is correlated with age (R=0.467). There was a decrease of angular motion in grades I-III and an increase in translational motion and decrease of space available for the cord in grades II-III. CONCLUSIONS: We developed a new classification system of cervical disk degeneration based on analysis of the changes seen on MRI. Reliability tests indicated high reproducibility of this system, and further analysis confirmed its validity and clinical significance.