Modic changes associated with greater pain relief following anesthetization of the adjacent lumbar intervertebral disc: A retrospective study of chronic low back pain patients.

PURPOSE: To assess the correlation between the degree of pain relief following discoblock and the presence and type of adjacent Modic changes (MC). METHOD: We retrospectively analyzed chronic low back pain (LBP) patients whose pain was suspected to originate from a specific lumbar intervertebral disc (IVD) based on a spine orthopedist's clinical evaluation and magnetic resonance imaging (MRI). Thus, patients were selected to undergo discoblock. We calculated the degree of pain relief following discoblock on Numerical Rating Scale (ΔNRS) and analyzed the MRIs on the basis of MC presence and type on the lumbar spinal segment in question. We assessed the differences in ΔNRS between the groups with absent and present MC and the groups of MC subtypes. RESULTS: Forty-five patients were included in the present study, all of whom underwent discoblock at a single level. The total MC prevalence was 77.8 % (35 patients); pure or dominant MC type 1 (MC1 group) 35.6 % (16 patients); and pure or dominant MC type 2 (MC2 group) 42.2 % (19 patients). ΔNRS was significantly greater in the group with MC compared to the group without MC (median ΔNRS -5.0 vs -2.5, respectively, P = 0.043). In pairwise comparisons, a significant difference in ΔNRS was found between the MC1 group and the group without MC (median ΔNRS -5.0 vs -2.5, respectively, P = 0.012). CONCLUSIONS: We propose that MC type 1 are associated with lumbar spinal pain, and that the pain arises at least partly from the adjacent IVD or endplate.

Correlation between the degree of pain relief following discoblock and short-term surgical disability outcome among patients with suspected discogenic low back pain.

OBJECTIVES: To evaluate how well the degree of pain relief after discoblock predicts the disability outcome of subsequent fusion or total disc replacement (TDR) surgery, based on short-term Oswestry Disability Index (ODI) scores. METHODS: We retrospectively analyzed a set of patients who had undergone discoblock and subsequent fusion or TDR surgery of the same lumbar intervertebral disc due to suspected discogenic chronic LBP between 2011 and 2018. We calculated the degree of pain relief following discoblock (ΔNRS) and the changes in both absolute and percentual ODI scores (ΔODI and ΔODI%, respectively) following fusion or TDR surgery. We analyzed the statistical significance of ΔNRS and ΔODI and the correlation (Spearman's rho) between ΔNRS and ΔODI%. The fusion and TDR group were analyzed both in combination and separately. RESULTS: Fifteen patients were eligible for the current study (fusion n=9, TDR n=6). ΔNRS was statistically significant in all groups, and ΔODI was statistically significant in the combined group and in the fusion group alone. The parameters of both decreased. We found a Spearman's rho of 0.57 (p=0.026) between ΔNRS and ΔODI% for the combined group. The individual Spearman's rho values were 0.85 (p=0.004) for the fusion group and 0.62 (p=0.191) for the TDR group. CONCLUSIONS: We suggest that discoblock is a useful predictive criterion for disability outcome prior to surgery for discogenic LBP, especially when stabilizing spine surgery is under consideration. ETHICAL COMMITTEE NUMBER: 174/2019 (Oulu University Hospital Ethics Committee).

Long-term Posttraumatic Survival of Spinal Fracture Patients in Northern Finland.

STUDY DESIGN: A retrospective epidemiological study. OBJECTIVE: To reveal the long-term survival and causes of death after traumatic spinal fracture (TSF) and to determine the possible factors predicting death. SUMMARY OF BACKGROUND DATA: Increased mortality following osteoporotic spinal fracture has been represented in several studies. Earlier studies concerning mortality after TSF have focused on specific types of fractures, or else only the mortality of the acute phases has been documented. In-hospital mortality has varied between 0.1% and 4.1%. METHODS: The study sample of 947 patients including all patients with TSF admitted to Oulu University Hospital, Finland, between January 1, 2007 and December 31, 2011. TSFs were identified using International Classification of Diseases 10th revision or Nordic Classification of Surgical Procedures codes and all patient records were manually reviewed. Times and causes of death, obtained from Statistics Finland's Archive of Death Certificates, were available until the end 2016 and 2015, respectively. RESULTS: At the end of the follow-up 227 (24.0%) had died. Mortality was 6.8% after the first year and 19.1% after 5 years. Mortality was increased in all age groups compared with the general population, 1-year standardized mortality ratios ranging from 3.1 in over 65-year-olds to 19.8 in under 30-year-olds. In age groups of 50 to 64 years and over 65 years, the most important risk factors for death were males with hazard ratios of 3.0 and 1.6, respectively, and low fall as trauma mechanism with hazard ratios of 9.4 and 10.2, respectively. CONCLUSION: Traumatic spinal fractures are associated with increased mortality compared with the general population, high mortality focusing especially on older people and men. The increase seems to be comparable to the increase following hip fracture. Patients who sustain spinal fracture due to falling need special attention in care, due to the observation that low fall as trauma mechanism increased the risk of death significantly. LEVEL OF EVIDENCE: 3.

Traumatic Spinal Injuries in Northern Finland.

STUDY DESIGN: A retrospective epidemiological study. OBJECTIVE: To reveal incidence and epidemiological features of traumatic spinal injuries (TSI) in Northern Finland. SUMMARY OF BACKGROUND DATA: In Finland the annual incidence of traumatic spine fractures requiring inpatient care has been found to be 27/100,000, while international incidences have varied across the range of 16-64/100,000. More specific epidemiological data from Finland is not available. Internationally, the most common mechanisms of injury are road traffic as well as low and high falls. Associated injuries occur in 30% to 55% of cases. METHODS: The study sample included patients with traumatic spinal injury admitted to Oulu University Hospital (OYS) with injury between the January 1, 2007 and December 31, 2011. Patient information was collected from the hospital care register, including all inpatient and outpatient visits and surgical procedures. Traumatic spinal column and spinal cord injuries were identified using International Classification of Diseases 10th revision or Nordic Classification of Surgical Procedures codes and all patient records were manually reviewed. RESULTS: Nine hundred seventy-one patients met the criteria for TSI. The mean annual incidence of hospitalized traumatic spinal injuries was 26/100,000 in the whole of Northern Finland and 35/100,000 in the OYS main responsibility area. The most frequent etiology of TSI was low falls, which accounted for 35.8% of the injuries, followed by road traffic and high falls. Lumbar spine was the most common site of the fracture. Spinal surgery was performed in 376 (38.7%) cases. Three hundred eight patients (31.7%) suffered from associated injuries, 101 (10.4%) had a spinal cord injury, and 71 (7.3%) a brain injury. CONCLUSION: Low falls in elderly and road traffic injuries in younger age groups were the most common etiology of traumatic spinal injuries in Northern Finland and should be given more attention in primary prevention. LEVEL OF EVIDENCE: 3.

Severe Trampoline Injuries: Incidence and Risk Factors in Children and Adolescents.

INTRODUCTION: Severe trampoline injuries in children and adolescents are rare; however, minor injuries are common and their incidence is increasing. Severe injuries are most commonly head and neck injuries. They may result in long-term morbidity. This study aimed to illustrate these severe injuries and to find out their incidence and risk factors. MATERIALS AND METHODS: This is a population-based, prospective study in the Oulu region of Finland completed over 2 years (May 1, 2015 to April 31, 2017). All children (<16 years of age) with severe trampoline injuries were included. Cervical spine fractures, chest wall and skull fractures, lesions of internal organs, hip and knee dislocations, and permanent disorders of the peripheral veins or nerves were in prior defined as severe. Multiple jumpers, stunts, younger age, previous injuries, insufficient use of safety equipment, and lack of supervision were hypothesized as risk factors. RESULTS: There were 11 injured patients (10 boys). The annual incidence was 6.28/100,000 children <16 years of age. Mean age was 11.5 years. Severe injuries included five ligamentous cervical spine injuries and two sternal bone fractures. In addition, there were one lumbar spine ligament injury, two hip dislocations, and one severe axillary plexus nerve lesion. Eight out of 11 accidents were not seen by any adult and none of them happened under professional supervision. Most injuries (N = 8) happened by failed backflips. CONCLUSION: Most severe injuries happened in unsuccessful flips. Children should have an adult supervisor and flips should not be attempted.

[Severe trampoline injuries and their risk factors among children and the young]. / Lasten ja nuorten vakavat trampoliinivammat ja niiden riskitekijät.

BACKGROUND: Although the majority of trampoline injuries in children are minor, severe injuries occur as well. METHODS: We have analyzed the risk factors, treatment and outcome of severe trampoline injuries treated in the Oulu University Hospital in children and the young between April and November 2105. RESULTS: There was a total of eight severe injuries. Five injuries involved a danger of death. Almost all severe trampoline injuries resulted from an unsuccessful trick. A safety net was in use in half of the cases. CONCLUSIONS: All cervical spine injuries would have been avoided provided that the children would have refrained from doing a somersault on the trampoline.

Association of Modic changes with health-related quality of life among patients referred to spine surgery.

Background and purpose Modic changes (MC) are bone marrow and vertebral endplate lesions seen in magnetic resonance imaging (MRI) which have been found to be associated with low back pain (LBP), but the association between MC and health-related quality of life (HRQoL) is poorly understood. The aim of this study was to assess the relationship between MC and HRQoL among patients referred to spine surgery. Methods The study population consisted of 181 patients referred to lumbar spine surgery in Northern and Eastern Finland between June 2007 and January 2011. HRQoL was assessed using RAND-36 health survey. Lumbar MC were evaluated and classified into 'No MC', 'Type I' (Type I or I/II), and 'Type II' (Type II, II/III or III). Results In total, 84 patients (46%) had MC. Of these, 37% had 'Type I' and 63% 'Type II'. Patients with MC were older, more likely females, had longer duration of LBP and a higher degree of disc degeneration than patients without MC. The total physical component or physical dimensions did not differ significantly between the groups. The total mental component of RAND-36 (P = 0.010), and dimensions of energy (P = 0.023), emotional well-being (P = 0.012) and emotional role functioning (P = 0.016) differed significantly between the groups after adjustments for age and gender. In the mental dimension scores, a statistically significant difference was found between 'No MC' and 'Type II'. Conclusions Among patients referred to spine surgery, MC were not associated with physical dimensions of HRQoL including dimension of pain. However, 'Type II' MC were associated with lower mental status of HRQoL. Implications Our study would suggest that Type II MC were associated with a worse mental status. This may affect the outcome of surgery as it is well recognized that patients with depression, for instance, have smaller improvements in HRQoL and disability. Thus the value of operative treatment for these patients should be recognized and taken into consideration in treatment. Our study shows that MC may affect outcome and thus clinicians and researchers should be cognizant of this and take this into account when comparing outcomes of surgical treatment in the future. A longitudinal study would be needed to properly address the relationship of MC with surgical outcome.

HIF-1α is upregulated in human mesenchymal stem cells.

Human mesenchymal stem cells (hMSCs) are multipotent cells that have aroused great expectations in regenerative medicine. They are assumed to originate from hypoxic stem cell niches, especially in the bone marrow. This suggests that O2 is of importance in their regulation. In order to characterize regulation of the oxygen sensing pathway in these cells, we studied hMSCs isolated from three origins, adult and pediatric bone marrow and umbilical cord blood (UCB). Surprisingly, pediatric bone marrow and UCB MSCs showed normoxic stabilization of hypoxia-inducible factor-1α (HIF-1α) that is normally degraded completely by HIF prolyl 4-hydroxylases in the presence of oxygen. This was due to a high expression level of HIF-1α mRNA rather than inappropriate post-translational degradation of HIF-1α protein. HIF-1α mRNA was also induced in normoxic adult bone marrow MSCs, but 40% less than in the pediatric cells, and this was apparently not enough to stabilize the protein. The high normoxic HIF expression in all the hMSCs studied was accompanied by increased expression of a large number of glycolytic HIF target genes and increased glycolysis. Osteogenic differentiation of bone marrow-derived hMSCs reduced HIF-1α mRNA and protein expression and the expression of glycolytic mRNAs, resulting in decreased glycolysis and induction of oxidative metabolism. Induced mitochondrial biogenesis, changes in mitochondrial morphology and size indicative of increased oxidative phosphorylation, and induction of extracellular matrix synthesis were observed following osteogenic differentiation. Altogether, these data suggest that HIF-1α is a general regulator controlling the metabolic fate and multipotency of the hMSCs.

CD200 positive human mesenchymal stem cells suppress TNF-alpha secretion from CD200 receptor positive macrophage-like cells.

Human mesenchymal stem cells (hMSCs) display immunosuppressive properties in vitro and the potential has also been transferred successfully to clinical trials for treatment of autoimmune diseases. OX-2 (CD200), a member of the immunoglobulin superfamily, is widely expressed in several tissues and has recently been found from hMSCs. The CD200 receptor (CD200R) occurs only in myeloid-lineage cells. The CD200-CD200R is involved in down-regulation of several immune cells, especially macrophages. The present study on 20 hMSC lines shows that the CD200 expression pattern varied from high (CD200Hi) to medium (CD200Me) and low (CD200Lo) in bone marrow-derived mesenchymal stem cell (BMMSC) lines, whereas umbilical cord blood derived mesenchymal stem cells (UCBMSCs) were constantly negative for CD200. The role of the CD200-CD200R axis in BMMSCs mediated immunosuppression was studied using THP-1 human macrophages. Interestingly, hMSCs showed greater inhibition of TNF-α secretion in co-cultures with IFN-γ primed THP-1 macrophages when compared to LPS activated cells. The ability of CD200Hi BMMSCs to suppress TNF-α secretion from IFN-γ stimulated THP-1 macrophages was significantly greater when compared to CD200Lo whereas UCBMSCs did not significantly reduce TNF-α secretion. The interference of CD200 binding to the CD200R by anti-CD200 antibody weakened the capability of BMMSCs to inhibit TNF-α secretion from IFN-γ activated THP-1 macrophages. This study clearly demonstrated that the efficiency of BMMSCs to suppress TNF-α secretion of THP-1 macrophages was dependent on the type of stimulus. Moreover, the CD200-CD200r axis could have a previously unidentified role in the BMMSC mediated immunosuppression.

Mitochondrial function and energy metabolism in umbilical cord blood- and bone marrow-derived mesenchymal stem cells.

Human mesenchymal stem cells (hMSCs) are an attractive choice for a variety of cellular therapies. hMSCs can be isolated from many different tissues and possess unique mitochondrial properties that can be used to determine their differentiation potential. Mitochondrial properties may possibly be used as a quality measure of hMSC-based products. Accordingly, the present work focuses on the mitochondrial function of hMSCs from umbilical cord blood (UCBMSC) cells and bone marrow cells from donors younger than 18 years of age (BMMSC <18) and those more than 50 years of age (BMMSC >50). Changes of ultrastructure and energy metabolism during osteogenic differentiation in all hMSC types were studied in detail. Results show that despite similar surface antigen characteristics, the UCBMSCs had smaller cell surface area and possessed more abundant rough endoplasmic reticulum than BMMSC >50. BMMSC <18 were morphologically more UCBMSC-like. UCBMSC showed dramatically higher mitochondrial-to-cytoplasm area ratio and elevated superoxide and manganese superoxide dismutase (MnSOD) levels as compared with BMMSC >50 and BMMSC <18. All hMSCs types showed changes indicative of mitochondrial activation after 2 weeks of osteogenic differentiation, and the increase in mitochondrial-to-cytoplasm area ratio appears to be one of the first steps in the differentiation process. However, BMMSC >50 showed a lower level of mitochondrial maturation and differentiation capacity. UCBMSCs and BMMSCs also showed a different pattern of exocytosed proteins and glycoproteoglycansins. These results indicate that hMSCs with similar cell surface antigen expression have different mitochondrial and functional properties, suggesting different maturation levels and other significant biological variations of the hMSCs. Therefore, it appears that mitochondrial analysis presents useful characterization criteria for hMSCs intended for clinical use.