The Damaged Spinal Cord Is a Suitable Target for Stem Cell Transplantation.

Background. Given individuals with spinal cord injury (SCI) approaching 2 million, viable options for regenerative repair are desperately needed. Human central nervous system stem cells (HuCNS-SC) are self-renewing, multipotent adult stem cells that engraft, migrate, and differentiate in appropriate regions in multiple animal models of injured brain and spinal cord. Preclinical improved SCI locomotor function provided rationale for the first-in-human SCI clinical trial of HuCNS-SC cells. Evidence of feasibility and long-term safety of cell transplantation into damaged human cord is needed to foster translational progression of cellular therapies. Methods. A first-ever, multisite phase I/IIa trial involving surgical transplantation of 20 million HuCNS-SC cells into the thoracic cord in 12 AIS A or B subjects (traumatic, T2-T11 motor-complete, sensory-incomplete), aged 19 to 53 years, demonstrated safety and preliminary efficacy. Six-year follow-up data were collected (sensory thresholds and neuroimaging augmenting clinical assessments). Findings. The study revealed short- and long-term surgical and medical safety (well-tolerated immunosuppression in population susceptible to infections). Preliminary efficacy measures identified 5/12 with reliable sensory improvements. Unfortunately, without thoracic muscles available for manual muscle examination, thoracic motor changes could not be measured. Lower limb motor scores did not change during the study. Cervical cord imaging revealed, no tumor formation or malformation of the lesion area, and secondary supralesional structural changes similar to SCI control subjects. Interpretation. Short- and long-term safety and feasibility support the consideration of cell transplantation for patients with complete and incomplete SCI. This report is an important step to prepare, foster, and maintain the therapeutic development of cell transplantation for human SCI.

Clinical Outcomes from a Multi-Center Study of Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury.

Human neural stem cell transplantation (HuCNS-SC®) is a promising central nervous system (CNS) tissue repair strategy in patients with stable neurological deficits from chronic spinal cord injury (SCI). These immature human neural cells have been demonstrated to survive when transplanted in vivo, extend neural processes, form synaptic contacts, and improve functional outcomes after experimental SCI. A phase II single blind, randomized proof-of-concept study of the safety and efficacy of HuCNS-SC transplantation into the cervical spinal cord was undertaken in patients with chronic C5-7 tetraplegia, 4-24 months post-injury. In Cohort I (n = 6) dose escalation from 15,000,000 to 40,000,000 cells was performed to determine the optimum dose. In Cohort II an additional six participants were transplanted at target dose (40,000,000) and compared with four untreated controls. Within the transplant group, there were nine American Spinal Injury Association Impairment Scale (AIS) B and three AIS A participants with a median age at transplant of 28 years with an average time to transplant post-injury of 1 year. Immunosuppression was continued for 6 months post-transplant, and immunosuppressive blood levels of tacrolimus were achieved and well tolerated. At 1 year post-transplantation, there was no evidence of additional spinal cord damage, new lesions, or syrinx formation on magnetic resonance (MR) imaging. In summary, the incremental dose escalation design established surgical safety, tolerability, and feasibility in Cohort I. Interim analysis of Cohorts I and II demonstrated a trend toward Upper Extremity Motor Score (UEMS) and Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) motor gains in the treated participants, but at a magnitude below the required clinical efficacy threshold set by the sponsor to support further development resulting in early study termination.

Emerging Safety of Intramedullary Transplantation of Human Neural Stem Cells in Chronic Cervical and Thoracic Spinal Cord Injury.

BACKGROUND: Human central nervous system stem cells (HuCNS-SC) are multipotent adult stem cells with successful engraftment, migration, and region-appropriate differentiation after spinal cord injury (SCI). OBJECTIVE: To present data on the surgical safety profile and feasibility of multiple intramedullary perilesional injections of HuCNS-SC after SCI. METHODS: Intramedullary free-hand (manual) transplantation of HuCNS-SC cells was performed in subjects with thoracic (n = 12) and cervical (n = 17) complete and sensory incomplete chronic traumatic SCI. RESULTS: Intramedullary stem cell transplantation needle times in the thoracic cohort (20 M HuCNS-SC) were 19:30 min and total injection time was 42:15 min. The cervical cohort I (n = 6), demonstrated that escalating doses of HuCNS-SC up to 40 M range were well tolerated. In cohort II (40 M, n = 11), the intramedullary stem cell transplantation needle times and total injection time was 26:05 ± 1:08 and 58:14 ± 4:06 min, respectively. In the first year after injection, there were 4 serious adverse events in 4 of the 12 thoracic subjects and 15 serious adverse events in 9 of the 17 cervical patients. No safety concerns were considered related to the cells or the manual intramedullary injection. Cervical magnetic resonance images demonstrated mild increased T2 signal change in 8 of 17 transplanted subjects without motor decrements or emerging neuropathic pain. All T2 signal change resolved by 6 to 12 mo post-transplant. CONCLUSION: A total cell dose of 20 M cells via 4 and up to 40 M cells via 8 perilesional intramedullary injections after thoracic and cervical SCI respectively proved safe and feasible using a manual injection technique.

The lived experiences of aboriginal adolescent survivors of childhood cancer during the recovering process in Taiwan: A descriptive qualitative research.

PURPOSE: The purpose of this study was to understand the experiences of Taiwanese aboriginal adolescent survivors of childhood cancer during the process of recovery. METHOD: A snowball sampling strategy was used to recruit participants from the pediatrics unit of a medical center in the eastern region of Taiwan. In-depth interviews were conducted with 11 aboriginal adolescent childhood cancer survivors. The data were analyzed using content analysis. RESULTS: The results revealed three major themes with subthemes within each theme. The three major themes are: roots of resilience, transformation and growth, and meaning of traditional rituals for resilience. The three subthemes within "roots of resilience" include: "feeling secure through company of family, care and financial support", "receiving support from the important others and religion" and "learning to self-adjust". The three subthemes revealed within "transformation and growth" are: restructuring the relationship with peers, "appreciating parents' hard work", and "learning to seize the moment". The two subthemes within "meaning of traditional rituals to resilience" include: "feeling blessed with the power of ancestral spirits" and "strengthening ethnic identity". CONCLUSION: This study provided insight into the experiences of aboriginal adolescents as they recovered from childhood cancer. The experiences made positive impacts by inspiring growth in maturity and consolidating aboriginal ethnic identity. The adolescents were empowered by support from family, friends and clansmen, and by their participation in aboriginal rituals. As healthcare professionals care for the aboriginal adolescents, it is critical to consider this culturally and ethnically specific knowledge/experience of surviving cancer to improve quality of care.

Nurses' perceptions of e-portfolio use for on-the-job training in Taiwan.

Electronic portfolios can be used to record user performance and achievements. Currently, clinical learning systems and in-service education systems lack integration of nurses' clinical performance records with their education or training outcomes. For nurses with less than 2 years' work experience (nursing postgraduate year), use of an electronic portfolio is essential. This study aimed to assess the requirements of using electronic portfolios in continuing nursing education for clinical practices. Fifteen nurses were recruited using a qualitative purposive sampling approach between April 2013 and May 2013. After obtaining participants' consent, data were collected in a conference room of the study hospital by one-on-one semistructured in-depth interviews. Through data analyses, the following five main themes related to electronic learning portfolios were identified: instant access to in-service education information, computerized nursing postgraduate year training manual, diversity of system functions and interface designs, need for sufficient computers, and protection of personal documents. Because electronic portfolios are beginning to be used in clinical settings, a well-designed education information system not only can meet the needs of nurses but also can facilitate their learning progress.

Can traumatic injury trigger psoriatic arthritis? A review of the literature.

Traumatic injury as a trigger for the subsequent development of psoriatic arthritis (PsA) has been implicated by several case reports and case series. However, it is still unclear whether trauma is the inciting event or just an incidental finding. It is thought that the interplay of genetic, immunologic, and environmental factors, such as trauma, may trigger the development of PsA. At least two hypotheses of how trauma may be linked to the development of PsA have surfaced and involve a "deep Koebner effect," the concept of a synovio-entheseal complex and activation of the innate immune system by biomechanical factors. The role of neuropeptides such as substance P and vasoactive intestinal peptide has been highlighted in the synovium after trauma. Better understanding of this phenomenon would shed light into the pathophysiology of Psa and help the development of preventive and therapeutic strategies.

Neuropathic pain post spinal cord injury part 2: systematic review of dorsal root entry zone procedure.

BACKGROUND: Pharmacotherapy may not sufficiently reduce neuropathic pain in many individuals post spinal cord injury (SCI). The use of alternative therapies such as surgery may be effective in reducing neuropathic pain in these individuals. However, because of the invasive nature of surgery, it is important to examine the evidence for use of this treatment. OBJECTIVE: The purpose of this study was to conduct a systematic review of published literature on the surgical treatment of neuropathic pain after SCI. METHODS: MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched for articles in which surgical treatment of pain after SCI was examined. Articles were restricted to the English language. Article selection was conducted by 2 independent reviewers with the following inclusion criteria: the subjects participated in a surgical intervention for neuropathic pain; at least 50% of the subjects had an SCI; at least 3 subjects had an SCI; and a definable intervention involving the dorsal root entry zone (DREZ) procedure was used to reduce pain. Data extracted included study design, study type, subject demographics, inclusion and exclusion criteria, sample size, outcome measures, and study results. Randomized controlled trials (RCTs) were assessed for quality using the Physiotherapy Evidence Database (PEDro) assessment scale. Levels of evidence were assigned to each intervention using a modified Sackett scale. RESULTS: Eleven studies met the inclusion criteria. One study provided level 2 evidence, and the rest provided level 4 evidence. The DREZ procedure was shown to be more effective for segmental pain than for diffuse pain after SCI. Further, individuals with conus medullaris level injury were found to have a higher level of neuropathic pain relief than those with cervical, thoracic, or cauda equina injury. CONCLUSIONS: The studies demonstrated that the DREZ procedure may be effective in reducing segmental pain. Hence, DREZ may be important in treatment of neuropathic pain in individuals resistant to less invasive treatments. Because the studies lacked control conditions and examination of long-term effects, there is a need for larger trials with more stringent conditions.

Using scoping review methods to describe current capacity and prescribe change in Canadian SCI rehabilitation service delivery.

OBJECTIVE: To describe the methodology used to conduct a scoping review of spinal cord injury (SCI) rehabilitation service delivery in Canada, and to explain the reporting process intended to advance future service delivery. EVIDENCE ACQUISITION: A SCI rehabilitation framework derived from the International Classification of Function, Disability and Health was developed to describe the goals and interprofessional processes of rehabilitation. An adapted Arksey and O'Malley (2005) methodological framework was used to conduct a scoping review of SCI rehabilitation services in Canada. Data were obtained from multiple relevant sources via survey (N = 3572 data fields) from 13 of 15 Canadian tertiary SCI rehabilitation sites, systematic reviews, white papers, literature reviews, clinical practice resources, and clinicians. Multidisciplinary teams of content experts (N = 17), assisted with data interpretation and validation by articulating practice trends, gaps, and priorities. EVIDENCE SYNTHESIS: The findings will be presented in an atlas, which includes aggregate national data regarding impairment and demographic characteristics, service utilization, available resources (staff and capital equipment), specialized services, local expertise, and current best practice indicators, outcome measures, and clinical guidelines. Data were collated and synthesized relative to specific rehabilitation goals. The current state of SCI rehabilitation service delivery (specific to each rehabilitation goal) is summarized in a report card within three domains, knowledge generation, clinical application, and policy change, and specifies key 2020 priorities. CONCLUSION: These findings should prompt critical evaluation of current Canadian SCI rehabilitation service delivery while specifying enhancements in knowledge generation, clinical application and policy change domains likely to assist with achievement of best practices by 2020.

Comparison of weight loss and body composition changes with four surgical procedures.

BACKGROUND: A paucity of information is available on the comparative body composition changes after bariatric procedures. The present study reports on the body mass index (BMI) and body composition changes after 4 procedures by a single group. METHODS: At the initial consultation, the weight and body composition of the patients undergoing 4 different bariatric procedures were measured by bioimpedance (Tanita 310). Follow-up examinations were performed at 1 year and at subsequent visits after surgery. Analysis of variance was used to compare the postprocedure BMI and body composition. Analysis of covariance was used to adjust for baseline differences. RESULTS: A total of 101 gastric bypass (GB) patients were evaluated at 19.1 + or - 10.6 months, 49 biliopancreatic diversion with the duodenal switch (BPD/DS) patients at 27.5 + or - 16.3 months, 41 adjustable gastric band (AGB) patients at 21.4 + or - 9.2 months, and 30 sleeve gastrectomy (SG) patients at 16.7 + or - 5.6 months (P <.0001). No differences were found in patient age or gender among the 4 groups. The mean preoperative BMI was significantly different among the 4 groups (P <.0001): 61.4 kg/m(2), 53.2, 46.7, and 44.3 kg/m(2) for the SG, BPD/DS, GB, and AGB group, respectively. The postoperative BMI adjusted for baseline differences was 27.8 (difference 23.6 + or - 8.3), 32.5 (difference 15.6 + or - 5.0), 37.2 (difference 18.2 + or - 8.2), and 39.5 kg/m(2) (difference 7.5 + or - 4.3) for the BPD/DS, GB, SG, and AGB groups, respectively (P <.0001). The percentage of excess weight loss was 84%, 70%, 49%, and 38% for the BPD/DS, GB, SG, and AGB groups, respectively (P <.0001). The postoperative percentage of body fat adjusted for baseline differences was 25.7% (23.9% + or - 7.0%) 32.7% (16.1% + or - 10.5%) 37.7% (16.7% + or - 5.6%), and 42% (6.0% + or - 6.8%) for the BPD/DS, GB, SG, and AGB groups, respectively (P <.0001). The lean body mass changes were reciprocal. CONCLUSION: Although the BPD/DS procedure reduced the BMI the most effectively and promoted fat loss, all the procedures produced weight loss. The AGB procedure resulted in less body fat loss within 21.5 months than SG within 16.7 months. Longer term observation is indicated.

Spinal Cord Injury Rehabilitation Evidence: Methods of the SCIRE Systematic Review.

The Spinal Cord Injury Rehabilitation Evidence (SCIRE) is a synthesis of the research evidence underlying rehabilitation interventions to improve the health of people living with SCI. SCIRE covers a comprehensive set of topics and in this issue we present six papers relevant to SCI rehabilitation clinicians (SCI inpatient rehabilitation practices, gait strategies, upper extremity reconstructive surgery, spasticity treatments, cardiovascular health and bone health). The SCIRE used a systematic and well-defined protocol to assess and synthesize the evidence. Each article was scored for its methodological quality using either the Physiotherapy Evidence Database (PEDro) Score for randomized controlled trials or the Downs and Black Tool for other types of studies. Following the individual study assessment, conclusions were drawn about the accumulated studies for each topic of interest based on the levels of evidence, quality of studies and concurring evidence. The SCIRE project was designed for health professionals to inform them of best practices.