Recent advances in stem cell biology present significant opportunities to advance clinical applications of stem cell–based therapies for spinal cord injury (SCI). In this review, the authors critically analyze the basic science and translational evidence that supports the use of various stem cell sources, including induced pluripotent stem cells, oligodendrocyte precursor cells, and mesenchymal stem cells. They subsequently explore recent advances in stem cell biology and discuss ongoing clinical translation efforts, including combinatorial strategies utilizing scaffolds, biogels, and growth factors to augment stem cell survival, function, and engraftment. Finally, the authors discuss the evolution of stem cell therapies for SCI by providing an overview of completed (n = 18) and ongoing (n = 9) clinical trials.
Michael C. Jin, Zachary A. Medress, Tej D. Azad, Vanessa M. Doulames and Anand Veeravagu
Kunal Varshneya, Adrian J. Rodrigues, Zachary A. Medress, Martin N. Stienen, Gerald A. Grant, John K. Ratliff and Anand Veeravagu
Skull fractures are common after blunt pediatric head trauma. CSF leaks are a rare but serious complication of skull fractures; however, little evidence exists on the risk of developing a CSF leak following skull fracture in the pediatric population. In this epidemiological study, the authors investigated the risk factors of CSF leaks and their impact on pediatric skull fracture outcomes.
The authors queried the MarketScan database (2007–2015), identifying pediatric patients (age < 18 years) with a diagnosis of skull fracture and CSF leak. Skull fractures were disaggregated by location (base, vault, facial) and severity (open, closed, multiple, concomitant cerebral or vascular injury). Descriptive statistics and hypothesis testing were used to compare baseline characteristics, complications, quality metrics, and costs.
The authors identified 13,861 pediatric patients admitted with a skull fracture, of whom 1.46% (n = 202) developed a CSF leak. Among patients with a skull fracture and a CSF leak, 118 (58.4%) presented with otorrhea and 84 (41.6%) presented with rhinorrhea. Patients who developed CSF leaks were older (10.4 years vs 8.7 years, p < 0.0001) and more commonly had skull base (n = 183) and multiple (n = 22) skull fractures (p < 0.05). These patients also more frequently underwent a neurosurgical intervention (24.8% vs 9.6%, p < 0.0001). Compared with the non–CSF leak population, patients with a CSF leak had longer average hospitalizations (9.6 days vs 3.7 days, p < 0.0001) and higher rates of neurological deficits (5.0% vs 0.7%, p < 0.0001; OR 7.0; 95% CI 3.6–13.6), meningitis (5.5% vs 0.3%, p < 0.0001; OR 22.4; 95% CI 11.2–44.9), nonroutine discharge (6.9% vs 2.5%, p < 0.0001; OR 2.9; 95% CI 1.7–5.0), and readmission (24.7% vs 8.5%, p < 0.0001; OR 3.4; 95% CI 2.5–4.7). Total costs at 90 days for patients with a CSF leak averaged $81,206, compared with $32,831 for patients without a CSF leak (p < 0.0001).
The authors found that CSF leaks occurred in 1.46% of pediatric patients with skull fractures and that skull fractures were associated with significantly increased rates of neurosurgical intervention and risks of meningitis, hospital readmission, and neurological deficits at 90 days. Pediatric patients with skull fractures also experienced longer average hospitalizations and greater healthcare costs at presentation and at 90 days.
Ivan Cheng, Martin N. Stienen, Zachary A. Medress, Kunal Varshneya, Allen L. Ho, John K. Ratliff and Anand Veeravagu
Adult spinal deformity (ASD) surgery is complex and associated with high morbidity and complication rates. There is growing evidence in the literature for the beneficial effects of an approach to surgery in which two attending physicians rather than a single attending physician perform surgery for and oversee the surgical care of a single patient in a dual-attending care model. The authors developed a dual-attending care collaboration in August 2017 in which a neurosurgeon and an orthopedic surgeon mutually operated on patients with ASD.
The authors recorded data for 2 years of experience with ASD patients operated on by dual attending surgeons. Analyses included estimated blood loss (EBL), transfusions, length of stay (LOS), discharge disposition, complication rates, emergency room visits and readmissions, subjective health status improvement, and disability (Oswestry Disability Index [ODI] score) and pain (visual analog scale [VAS] score) at last follow-up. In addition, the pertinent literature for dual-attending spinal deformity correction was systematically reviewed.
The study group comprised 19 of 254 (7.5%) consecutively operated patients who underwent thoracolumbar fusion during the period from January 2017 to June 2019 (68.4% female; mean patient age 65.1 years, ODI score 44.5, VAS pain score 6.8). The study patients were matched by age, sex, anesthesia risk, BMI, smoking status, ODI score, VAS pain score, prior spine surgeries, and basic operative characteristics (type of interbody implants, instrumented segments, pelvic fixation) to 19 control patients (all p > 0.05). There was a trend toward less EBL (mean 763 vs 1524 ml, p = 0.059), fewer intraoperative red blood cell transfusions (mean 0.5 vs 2.3, p = 0.079), and fewer 90-day readmissions (0% vs 15.8%, p = 0.071) in the dual-attending group. LOS and discharge disposition were similar, as were the rates of any < 30-day postsurgery complications, < 90-day postsurgery emergency room visits, and reoperations, and ODI and VAS pain scores at last follow-up (all p > 0.05). At last follow-up, 94.7% vs 68.4% of patients in the dual- versus single-attending group stated their health status had improved (p = 0.036). In the authors’ literature search of prior articles on spinal deformity correction, 5 of 8 (62.5%) articles reported lower EBL and 6 of 8 (75%) articles reported significantly lower operation duration in dual-attending cases. The literature contained differing results with regard to complication- or reoperation-sparing effects associated with dual-attending cases. Similar clinical outcomes of dual- versus single-attending cases were reported.
Establishing a dual-attending care management platform for ASD correction was feasible at the authors’ institution. Results of the use of a dual-attending strategy at the authors’ institution were favorable. Positive safety and outcome profiles were found in articles on this topic identified by a systematic literature review.
Thomas J. Buell and Justin S. Smith
Kunal Varshneya, Rayyan T. Jokhai, Parastou Fatemi, Martin N. Stienen, Zachary A. Medress, Allen L. Ho, John K. Ratliff and Anand Veeravagu
This was a retrospective cohort study in which the authors used a nationally representative administrative database. Their goal was to identify the risk factors for reoperation in Medicare patients undergoing primary thoracolumbar adult spinal deformity (ASD) surgery. Previous literature reports estimate that 20% of patients undergoing thoracolumbar ASD correction undergo revision surgery within 2 years. Most published data discuss risk factors for revision surgery in the general population, but these have not been explored specifically in the Medicare population.
Using the MarketScan Medicare Supplemental database, the authors identified patients who were diagnosed with a spinal deformity and underwent ASD surgery between 2007 and 2015. The interactions of patient demographics, surgical factors, and medical factors with revision surgery were investigated during the 2 years following primary ASD surgery. The authors excluded patients without Medicare insurance and those with any prior history of trauma or tumor.
Included in the data set were 2564 patients enrolled in Medicare who underwent ASD surgery between 2007 and 2015. The mean age at diagnosis with spinal deformity was 71.5 years. A majority of patients (68.5%) were female. Within 2 years of follow-up, 661 (25.8%) patients underwent reoperation. Preoperative osteoporosis (OR 1.58, p < 0.0001), congestive heart failure (OR 1.35, p = 0.0161), and paraplegia (OR 2.41, p < 0.0001) independently increased odds of revision surgery. The use of intraoperative bone morphogenetic protein was protective against reoperation (OR 0.71, p = 0.0371). Among 90-day postoperative complications, a wound complication was the strongest predictor of undergoing repeat surgery (OR 2.85, p = 0.0061). The development of a pulmonary embolism also increased the odds of repeat surgery (OR 1.84, p = 0.0435).
Approximately one-quarter of Medicare patients with ASD who underwent surgery required an additional spinal surgery within 2 years. Baseline comorbidities such as osteoporosis, congestive heart failure, and paraplegia, as well as short-term complications such as pulmonary embolism and wound complications significantly increased the odds of repeat surgery.