Spinal cord injury (SCI) is an abrupt traumatic injury that leads to permanent functional loss, and no practical treatment is available. We have developed pharmaceutical recombinant human hepatocyte growth factor (KP-100), and its efficacy for SCI has been verified using animal models. The purpose of this study was to evaluate the safety and efficacy of intrathecal KP-100 administration for SCI patients in the acute phase. This investigation was a multi-center, randomized, double-blind study. Subjects with modified Frankel grade A/B1/B2 at 72 h after SCI were included. KP-100 was administered intrathecally. Subjects were followed up for 168 days after the first administration. Outcomes were evaluated using American Spinal Injury Association (ASIA) scores and subjected to analysis of covariance. Our results demonstrated that the subjects did not show any serious adverse events caused by KP-100. Forty-three subjects underwent neurological function testing (26 in KP-100 group; 17 in placebo group), which revealed that KP-100 contributed to motor improvement at Days 140 ( p = 0.050) and 168 ( p = 0.079). In the subset of subjects with Frankel grade A, the proportions of subjects who gained at least 1 point on their lower-extremity motor scores were 33.3% (5/15) and 6.3% (1/16) in the KP-100 and placebo groups, respectively ( p = 0.083). Therefore, KP-100 has the potential to be useful and beneficial for SCI patients during the acute phase. However, this was a phase I/II trial and did not definitely address the question of efficacy; a larger phase III trial would be required to assess the efficacy.

Hepatocyte growth factor (HGF) was first identified as a potent mitogen for mature hepatocytes, and has also gained attention as a strong neurotrophic factor in the central nervous system. We found that during the acute phase of spinal cord injury (SCI) in rats, c-Met, the specific receptor for HGF, increases sharply, while the endogenous HGF up-regulation is relatively weak. Introducing exogenous HGF into the spinal cord by injecting an HGF-expressing viral vector significantly increased the neuron and oligodendrocyte survival, angiogenesis, and axonal regeneration, to reduce the area of damage and to promote functional recovery in rats after SCI. Other recent studies in rodents have shown that exogenously administered HGF during the acute phase of SCI reduces astrocyte activation to decrease glial scar formation, and exerts anti-inflammatory effects to reduce leukocyte infiltration. We also reported that the intrathecal infusion of recombinant human HGF (intrathecal rhHGF) improves neurological hand function after cervical contusive SCI in the common marmoset, a non-human primate. Based on these collective results, we conducted a phase I/II clinical trial of intrathecal rhHGF for patients with acute cervical SCI who showed a modified Frankel grade of A/B1/B2 72 h after injury onset, from June 2014 to May 2018.

Frailty as a concept is not yet fully understood, and is not the same as comorbidity. It is associated with an increased risk of adverse events and mortality after surgery, which makes its preoperative assessment significant. Despite its relevance, it still remains unclear which scales are appropriate for use in patients with spinal pathology. To evaluate the feasibility and measurement properties of frailty scales for spine patients, specifically with adult spinal deformity (ASD), and to propose adequate scales for primary triage to prevent surgery in too frail patients and for preoperative assessment to modify patients' condition and surgical plans. Systematic review. Systematic search was performed between 2010 and 2021 including terms relating to spinal disorders, frailty scales, and methodological quality. Characteristics of the studies and frailty scales and data describing relation to treatment outcomes were extracted. The risk of bias was determined with the QAREL score. Of the 1993 references found, 88 original studies were included and 23 scales were identified. No prospective interventional study was found where the preoperative frailty assessment was implemented. Predictive value of scales for surgical outcomes varied, dependent on spinal disorders, type of surgeries, patients' age and frailty at baseline, and outcomes. Seventeen studies reported measurement properties of eight scales but these studies were not free of bias. In 30 ASD studies, ASD-Frailty Index (ASD-FI, n=14) and 11-item modified Frailty Index (mFI-11, n=11) were most frequently used. These scales were mainly studied in registry studies including young adult population, and carry a risk of sample bias and make their validity in elderly population unclear. ASD-FI covers multidisciplinary concepts of frailty with 40 items but its feasibility in clinical practice is questionable due to its length. The Risk Analysis Index, another multidisciplinary scale with 14 items, has been implemented for preoperative assessment in other surgical domains and was proven to be feasible and effective in interventional prospective studies. The FRAIL is a simple questionnaire with five items and its predictive value was confirmed in prospective cohort studies in which only elderly patients were included. No adequate scale was identified in terms of methodological quality and feasibility for daily practice. Careful attention should be paid when choosing an adequate scale, which depends on the setting of interest (eg triage or preoperative work-up). We recommend to further study a simple and predictive scale such as FRAIL for primary triage and a comprehensive and feasible scale such as Risk Analysis Index for preoperative assessment for patients undergoing spine surgery, as their adequacy has been shown in other medical domains.

Spine disorders are the leading cause of disability worldwide. To promote social inclusion, it is essential to ensure that people can participate in their societies by improving their ability, opportunities, and dignity, through access to high-quality, evidence-based, and affordable spine services for all. To achieve this goal, SPINE20 recommends six actions. - SPINE20 recommends that G20 countries deliver evidence-based education to the community health workers and primary care clinicians to promote best practice for spine health, especially in underserved communities. - SPINE20 recommends that G20 countries deliver evidence-based, high-quality, cost-effective spine care interventions that are accessible, affordable and beneficial to patients. - SPINE20 recommends that G20 countries invest in Health Policy and System Research (HPSR) to generate evidence to develop and implement policies aimed at integrating rehabilitation in primary care to improve spine health. - SPINE20 recommends that G20 countries support ongoing research initiatives on digital technologies including artificial intelligence, regulate digital technologies, and promote evidence-based, ethical digital solutions in all aspects of spine care, to enrich patient care with high value and quality. - SPINE20 recommends that G20 countries prioritize social inclusion by promoting equitable access to comprehensive spine care through collaborations with healthcare providers, policymakers, and community organizations. - SPINE20 recommends that G20 countries prioritize spine health to improve the well-being and productivity of their populations. Government health systems are expected to create a healthier, more productive, and equitable society for all through collaborative efforts and sustained investment in evidence-based care and promotion of spine health.

Objective: The purpose of our study was to investigate the risk factors of remnant tumor growth after incomplete resection (IR) of cervical dumbbell-shaped schwannomas (DS).Methods: Twenty-one patients with IR of cervical DS with at least 2 years of follow-up were included and were divided into 2 groups: the remnant tumor growth (G) (n = 10) and no growth (NG) (n = 11) groups. The tumor location in the axial plane according to Toyama classification, the location of the remnant tumor margin, and the tumor growth rate (MIB-1 index) index were compared.Results: No significant differences in Toyama classification and MIB-1 index were found. Age was significantly higher in the G group (61.4 years vs. 47.6 years; p = 0.030), but univariate logistic regression analysis revealed little correlation to the growth (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.001–1.166; p = 0.047). Seventeen patients (9 in the G and 8 in the NG group) underwent the posterior one-way approach, and significant differences in the location of the remnant tumor margin were confirmed: within the spinal canal in 1 and 0 case, at the entrance of the intervertebral foramen in 7 and 1 cases, and in the foramen distal from the entrance in 1 and 7 cases, in the G and NG groups, respectively (p = 0.007). The proximal margin was identified as a significant predictor of the growth (OR, 56.0; 95% CI, 2.93–1,072; p = 0.008).Conclusion: Remnant tumors with margins distally away from the entrance of the foramen were less likely to grow after IR of cervical DS.