Revision Rates and Functional Outcomes Among Severely, Morbidly, and Super-Obese Patients Following Primary Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: Obesity has been associated with a greater burden of symptomatic knee osteoarthritis. There is some evidence that patients with a very high body mass index (BMI) may have a higher risk of complications and poor outcomes following total knee replacement compared with non-obese patients or obese patients with a lower BMI. We hypothesized that increasing degrees of obesity would be associated with deteriorating outcomes for patients following total knee replacement. METHODS: We performed a comprehensive systematic review of 4 medical databases (MEDLINE, AMED, Ovid Healthstar, and Embase) from inception to August 2016. We extracted data to determine revision risk (all-cause, septic, and aseptic) and functional outcome scores (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC], Knee Society Score, Oxford Knee Score, EuroQol-5D, and Short Form [SF]-12 Physical Component Summary) in patients with severe obesity (BMI ≥35 kg/m), morbid obesity (BMI ≥40 kg/m), and super-obesity (BMI ≥50 kg/m) in comparison with patients with a normal BMI (<25 kg/m). Meta-analysis was performed using a random effects model. RESULTS: We screened 3,142 titles and abstracts and 454 full-text articles to identify 40 eligible studies, of which 37 were included in the meta-analysis. Compared with patients with a normal BMI, the risk ratio for an all-cause revision surgical procedure was 1.19 (95% confidence interval [CI], 1.03 to 1.37; p = 0.02) in patients with severe obesity, 1.93 (95% CI, 1.27 to 2.95; p < 0.001) in patients with morbid obesity, and 4.75 (95% CI, 2.12 to 10.66; p < 0.001) in patients with super-obesity. The risk ratio for septic revision was 1.49 (95% CI, 1.28 to 1.72; p < 0.001) in patients with severe obesity, 3.69 (95% CI, 1.90 to 7.17; p < 0.001) in patients with morbid obesity, and 4.58 (95% CI, 1.11 to 18.91; p = 0.04) in patients with super-obesity. There were no significant differences (p > 0.05) in risk of aseptic revision. Based on the Knee Society Scores reported in a single study, patients with super-obesity had outcome scores, expressed as the standardized mean difference, that were 0.52 lower (95% CI, 0.80 lower to 0.24 lower; p < 0.001) than non-obese controls; however, no difference was observed for severe or morbidly obese patients. CONCLUSIONS: The risk of septic revision is greater in patients with severe obesity, morbid obesity, and super-obesity, with progressively higher BMI categories associated with a higher risk. However, the risk of aseptic revision was similar between all obese and non-obese patients. Functional outcome improvements are also similar, except for super-obese patients, in whom data from a single study suggested slightly lower scores. These findings may serve to better inform evidence-based clinical, research, and policy decision-making. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Revision Rates and Functional Outcome Scores for Severely, Morbidly, and Super-Obese Patients Undergoing Primary Total Hip Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: We performed a systematic review and meta-analysis of the literature to quantify the impact of patients with severe obesity (body mass index [BMI] > 35 kg/m), those with morbid obesity (BMI > 40 kg/m), and those with super-obesity (BMI > 50 kg/m) on revision rates and outcome scores after primary total hip arthroplasty compared with non-obese patients (BMI < 25 kg/m). METHODS: Four electronic databases were reviewed (AMED, Embase, Ovid Healthstar, and MEDLINE) from their inception to August 2016. The search strategy used combined and/or truncated keywords, including hip replacement or arthroplasty and obesity, BMI, or any synonym of the latter in the title, abstract, or manuscript text. Abstracts and full text were reviewed by 3 pairs of reviewers to identify those assessing outcomes following primary total hip arthroplasty for different BMI categories. Outcomes evaluated were revisions (total, aseptic, and septic) and change in outcome scores (preoperative to postoperative). RESULTS: The literature search identified 1,692 abstracts; 448 were included for the full-text review, and 33 were included in the meta-analysis. The morbidly obese and super-obese groups were at an increased risk for revision, especially for septic revisions, compared with the non-obese group. The severely obese group had risk ratios of 1.40 (95% confidence interval [CI], 0.97 to 2.02) for revision, 0.70 (95% CI, 0.45 to 1.10) for aseptic revision, and 3.17 (95% CI, 2.25 to 4.47) for septic revision. Morbidly obese patients had risk ratios of 2.01 (95% CI, 1.81 to 2.23) for revision, 1.40 (95% CI, 0.84 to 2.32) for aseptic revision, and 9.75 (95% CI, 3.58 to 26.59) for septic revision. Super-obese patients had risk ratios of 2.62 (95% CI, 1.68 to 4.07) for revision, 1.98 (95% CI, 0.80 to 4.94) for aseptic revision, and 7.22 (95% CI, 1.51 to 34.60) for septic revision. However, there was no significant difference (p > 0.05) in the standardized mean difference of functional outcome scores between the severely obese cohort (0.04 [95% CI, -0.02 to 0.10]), the morbidly obese cohort (0.19 [95% CI, -0.08 to 0.46]), and the super-obese cohort (-0.12 [95% CI, -0.57 to 0.33]). CONCLUSIONS: Severely obese patients, morbidly obese patients, and super-obese patients undergoing total hip arthroplasty should be counseled that, although they have comparable outcome score improvements compared with non-obese patients, they have significantly higher risks of all-cause and septic revision. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Ninety-Day Costs, Reoperations, and Readmissions for Primary Total Hip Arthroplasty Patients of Varying Body Mass Index Levels.

BACKGROUND: The purpose of this study is to compare 90-day costs and outcomes for primary total hip arthroplasty patients between a nonobese (body mass index, 18.5-24.9) vs overweight (25-29.9), obese (30-34.9), severely obese (35-39.9), morbidly obese (40-44.9), and super obese (45+) cohorts. METHODS: We conducted a retrospective review of an institutional database of primary total hip arthroplasty patients from 2006 to 2013. Thirty-three super-obese patients were identified, and the other 5 cohorts were randomly selected in a 2:1 ratio (n = 363). Demographics, 90-day outcomes (costs, reoperations, and readmissions), and outcomes after 3 years (revisions and change scores for Short-Form Health Survey, Harris Hip Score, and Western Ontario and McMaster Universities Arthritis Index) were collected. Costs were determined using unit costs from our institutional administrative data for all in-hospital resource utilization. Comparisons between the nonobese and other groups were made with Kruskal-Wallis tests for non-normal data and chi-square and Fisher exact test for categorical data. RESULTS: The 90-day costs in the morbidly obese ($13,134 ± $7250 mean ± standard deviation, P < .01) and super-obese ($15,604 ± 6783, P < .01) cohorts were significantly greater than the nonobese cohorts ($10,315 ± 1848). Only the super-obese cohort had greater 90-day reoperation and readmission rates than the nonobese cohort (18.2% vs 0%, P < .01 and 21.2% vs 4.5%, P = .02, respectively). Reoperations and septic revisions after 3 years were greater in the super-obese cohort compared to the nonobese cohort 21.2% versus 3.0% (P = .01) and 18.2% versus 1.5% (P = .01), respectively. Improvements in Short-Form Health Survey, Harris Hip Score, and Western Ontario and McMaster Universities Arthritis Index were comparable in all cohorts. CONCLUSION: Super-obese patients have greater risks and costs compared to nonobese patients, but also have comparable quality of life improvements.

Cost-Effectiveness of Total Hip Arthroplasty Versus Nonoperative Management in Normal, Overweight, Obese, Severely Obese, Morbidly Obese, and Super Obese Patients: A Markov Model.

BACKGROUND: We estimated the cost-effectiveness of performing total hip arthroplasty (THA) vs nonoperative management (NM) among 6 body mass index (BMI) cohorts. METHODS: We constructed a state-transition Markov model to compare the cost utility of THA and NM in the 6 BMI groups over a 15-year period. Model parameters for transition probability (risk of revision, re-revision, and death), utility, and costs (inflation adjusted to 2017 US dollars) were estimated from the literature. Direct medical costs of managing hip arthritis were accounted in the model. Indirect societal costs were not included. A 3% annual discount rate was used for costs and utilities. The primary outcome was the incremental cost-effectiveness ratio (ICER) of THA vs NM. One-way and Monte Carlo probabilistic sensitivity analyses of the model parameters were performed to determine the robustness of the model. RESULTS: Over the 15-year time period, the ICERs for THA vs NM were the following: normal weight ($6043/QALYs [quality-adjusted life years]), overweight ($5770/QALYs), obese ($5425/QALYs), severely obese ($7382/QALYs), morbidly obese ($8338/QALYs), and super obese ($16,651/QALYs). The 2 highest BMI groups had higher incremental QALYs and incremental costs. The probabilistic sensitivity analysis suggests that THA would be cost-effective in 100% of the normal, overweight, obese, severely obese, and morbidly obese simulations, and 99.95% of super obese simulations at an ICER threshold of $50,000/QALYs. CONCLUSION: Even at a willingness-to-pay threshold of $50,000/QALYs, which is considered low for the United States, our model showed that THA would be cost-effective for all obesity levels. BMI cut-offs for THA may lead to unnecessary loss of healthcare access.

Cost-Effectiveness of Total Knee Arthroplasty vs Nonoperative Management in Normal, Overweight, Obese, Severely Obese, Morbidly Obese, and Super-Obese Patients: A Markov Model.

BACKGROUND: We estimated the cost-effectiveness of performing total knee arthroplasty (TKA) vs nonoperative management (NM) among 6 body mass index (BMI) cohorts. METHODS: A Markov model was used to compare the cost-utility of TKA and NM in 6 BMI groups (nonobese [BMI 18.5-24.9], overweight [25-29.9], obese [30-34.9], severely obese [35-39.9], morbidly obese [40-49.9], and super-obese [50+] patients) over a 15-year period. Model parameters for transition probability (ie, revision, re-revision, death), utility, and costs were estimated from the literature. Direct medical costs but not indirect societal costs were included in the model. Costs and utilities were discounted 3% annually. The primary outcome was the incremental cost-effectiveness ratio (ICER) of TKA vs NM. One-way and probabilistic sensitivity analyses of the model parameters were performed to determine the robustness of the model. RESULTS: Over the 15-year period, the ICERs for the TKA vs NM for the different BMI categories were nonobese ($3317/quality-adjusted life years [QALYs]), overweight ($2837/QALY), obese ($2947/QALY), severely obese ($3536/QALY), morbidly obese ($5531/QALY), and super-obese ($11,878/QALY). The higher BMI groups tended to have higher incremental QALYs and also higher incremental costs. The probabilistic sensitivity analysis with an ICER threshold of $30,000/QALY showed that TKA would be cost-effective in 100% of simulations of patients with a BMI<50 and 99.16% of super-obese simulations. CONCLUSION: While performing TKA on super-obese patients is more expensive, the substantial improvements in patient outcomes make it cost-effective. Therefore, withholding TKA care based on a BMI would lead to an unjustified loss of health-care access.

Ninety-Day Costs, Reoperations, and Readmissions for Primary Total Knee Arthroplasty Patients With Varying Body Mass Index Levels.

BACKGROUND: We compared 90-day costs and outcomes for primary total knee arthroplasty patients among nonobese (body mass index [BMI] 18.5-24.9), overweight (25-29.9), obese (30-34.9), severely obese (35-39.9), morbidly obese (40-49.9), and super-obese (50+) cohorts. METHODS: We conducted a retrospective review of an institutional database of total knee arthroplasty patients from 2006 to 2013 with a minimum of 3-year follow-up. Sixty-five super-obese patients were identified, and five other cohorts were randomly selected in a 2:1 ratio (total, n = 715). Demographics, 90-day outcomes (costs, reoperations, and readmissions), and outcomes after 3 years (revisions and change scores for Short-Form Health Survey [SF-12], Knee Society Scores, and Western Ontario and McMaster Universities Arthritis Index) were aggregated. RESULTS: The 90-day costs were significantly greater in the morbidly obese ($11,568 ± $1,960) and super-obese ($14,021 ± $7,903) cohorts relative to the smaller BMI cohorts ($9,938 - $10,352). The increased cost from readmissions was the main driver of costs. The outcome change scores were similar across all the BMI cohorts for Knee Society Scores, SF-12 Mental Health Composite Score, and Western Ontario and McMaster Universities Arthritis Index, but not for the SF-12 Physical Health Composite Score. At the midterm follow-up, there was no statistical difference in repeat surgery or aseptic revision rates. Septic revisions were significantly greater in the super-obese cohort relative to the other cohorts (6.2% vs 0.8-3.1%). CONCLUSION: Health-care policy based purely on the economic costs may place morbidly obese and super-obese patients at risk of losing arthroplasty care, thereby denying them access to the comparable quality of life improvements.

Post-Discharge Care Duration, Charges, and Outcomes Among Medicare Patients After Primary Total Hip and Knee Arthroplasty.

BACKGROUND: In April 2016, the U.S. Centers for Medicare & Medicaid Services initiated mandatory 90-day bundled payments for total hip and knee arthroplasty for much of the country. Our goal was to determine duration of care, 90-day charges, and readmission rates by discharge disposition and U.S. region after hip or knee arthroplasty. METHODS: Using the 2008 Medicare Provider Analysis and Review database 100% sample, we identified patients who had undergone elective primary total hip or knee arthroplasty. We collected data on patient age, sex, comorbidities, U.S. Census region, discharge disposition, duration of care, 90-day charges, and readmission. Multivariate regression was used to assess factors associated with readmission (logistic) and charges (linear). Significance was set at p < 0.01. RESULTS: Patients undergoing 138,842 total hip arthroplasties were discharged to home (18%), home health care (34%), extended-care facilities (35%), and inpatient rehabilitation (13%); patients undergoing 329,233 total knee arthroplasties were discharged to home (21%), home health care (38%), extended-care facilities (31%), and inpatient rehabilitation (10%). Patients in the Northeast were more likely to be discharged to extended-care facilities or inpatient rehabilitation than patients in other regions. Patients in the West had the highest 90-day charges. Approximately 70% of patients were discharged home from extended-care facilities, whereas after inpatient rehabilitation, >50% of patients received home health care. Among those discharged to home, 90-day readmission rates were highest in the South (9.6%) for patients undergoing total hip arthroplasty and in the Midwest (8.7%) and the South (8.5%) for patients undergoing total knee arthroplasty. Having ≥4 comorbidities, followed by discharge to inpatient rehabilitation or an extended-care facility, had the strongest associations with readmission, whereas the region of the West and the discharge disposition to inpatient rehabilitation had the strongest association with higher charges. CONCLUSIONS: Among Medicare patients, discharge disposition and number of comorbidities were most strongly associated with readmission. Inpatient rehabilitation and the West region had the strongest associations with higher charges. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Inpatient Mortality and Morbidity for Dialysis-Dependent Patients Undergoing Primary Total Hip or Knee Arthroplasty.

BACKGROUND: Dialysis-dependent patients can develop osteoarthritis or osteonecrosis, warranting hip or knee arthroplasty. Their comorbidities predispose them to complications. Our goal was to determine inpatient outcomes of dialysis-dependent patients after primary elective total hip or knee arthroplasty. METHODS: In the National Inpatient Sample, we identified 2934 dialysis-dependent patients who had undergone total hip or knee arthroplasty from 2000 through 2009 and compared them with 6,186,475 patients who had undergone the same procedures and were not dialysis-dependent. We described demographic characteristics, comorbidities, and outcomes and assessed associations of dialysis status with inpatient mortality and complications. RESULTS: In the hip arthroplasty group, dialysis-dependent patients were younger (63.2 compared with 65.2 years; p = 0.0476) and more commonly diagnosed with osteonecrosis (34.29% compared with 10.94%; p < 0.0001) than non-dialysis-dependent patients. Dialysis-dependent patients had higher inpatient mortality rates (1.88% compared with 0.13%; p < 0.0001) and greater overall complication rates (9.98% compared with 4.97%; p = 0.0001). Dialysis was an independent risk factor for mortality (odds ratio, 6.66; 95% confidence interval [95% CI], 2.66 to 16.66) and complications (odds ratio, 1.53; 95% CI, 1.01 to 2.33). In the knee arthroplasty group, dialysis-dependent patients were similar in age (66.7 compared with 66.8 years; p = 0.8085) and were more commonly diagnosed with osteonecrosis (3.32% compared with 0.74%; p < 0.0001) than non-dialysis-dependent patients. Dialysis-dependent patients had higher inpatient mortality rates (0.92% compared with 0.10%; p < 0.0001) and greater overall complication rates (12.48% compared with 5.00%; p < 0.0001). Dialysis status was an independent risk factor for mortality (odds ratio, 3.31; 95% CI, 1.04 to 10.54) and complications (odds ratio, 1.86; 95% CI, 1.34 to 2.60). CONCLUSIONS: Total hip and knee arthroplasty in dialysis-dependent patients presents high risk, with inpatient mortality rates ten to twenty times greater and overall complication rates two times greater than in non-dialysis-dependent patients. Arthroplasty should be approached with caution and preferably should be delayed until after renal transplantation.

Perioperative blood transfusions in orthopaedic surgery.

Blood transfusion after orthopaedic surgery accounts for 10% of all packed red blood-cell transfusions, but use varies substantially across hospitals and surgeons. Transfusions can cause systemic complications, including allergic reactions, transfusion-related acute lung injury, transfusion-associated circulatory overload, graft-versus-host disease, and infections. Tranexamic acid is a new cost-effective blood management tool to reduce blood loss and decrease the risk of transfusion after total joint arthroplasty. Current clinical evidence does not justify transfusions for a hemoglobin level of >8 g/dL in the absence of symptoms. Studies have also supported the use of this trigger in patients with a history or risk of cardiovascular disease.

Functional assessment of the acute local and distal transplantation of human neural stem cells after spinal cord injury.

BACKGROUND CONTEXT: Spinal cord injury can lead to severe functional impairments secondary to axonal damage, neuronal loss, and demyelination. The injured spinal cord has limited regrowth of damaged axons. Treatment remains controversial, given inconsistent functional improvement. Previous studies demonstrated functional recovery of rats with spinal cord contusion after transplantation of rat fetal neural stem cells. PURPOSE: We hypothesized that acute transplantation of human fetal neural stem cells (hNSCs) both locally at the injury site as well as distally via intrathecal injection would lead to improved functional recovery compared with controls. STUDY DESIGN/SETTING: Twenty-four adult female Long-Evans hooded rats were randomized into four groups with six animals in each group: two experimental and two control. Functional assessment was measured after injury and then weekly for 6 weeks using the Basso, Beattie, and Bresnahan Locomotor Rating Score. Data were analyzed using two-sample t test and linear mixed-effects model analysis. METHODS: Posterior exposure and laminectomy at T10 level was used. Moderate spinal cord contusion was induced by the Multicenter Animal Spinal Cord Injury Study Impactor with 10-g weight dropped from a height of 25 mm. Experimental subjects received either a subdural injection of hNSCs locally at the injury site or intrathecal injection of hNSCs through a separate distal laminotomy. Controls received control media injection either locally or distally. RESULTS: Statistically significant functional improvement was observed in local or distal hNSCs subjects versus controls (p=.034 and 0.016, respectively). No significant difference was seen between local or distal hNSC subjects (p=.66). CONCLUSIONS: Acute local and distal transplantation of hNSCs into the contused spinal cord led to significant functional recovery in the rat model. No statistical difference was found between the two techniques.

Nerve mapping for prostatectomies: novel technologies under development.

Prostatic neuroanatomy is difficult to visualize intraoperatively and can be extremely variable. Damage to these nerves during prostatectomies may lead to postoperative complications such as erectile dysfunction and incontinence. This review aims to discuss the prostatic neuroanatomy, sites of potential nerve damage during a prostatectomy, and nerve-mapping technologies being developed to prevent neural injury. These technologies include stimulation, dyes, and direct visualization. Nerve stimulation works by testing an area and observing a physiologic response but is limited by the long half-life for an erectile response; examples include CaverMap, ProPep, and optical nerve stimulation. Few nerve dyes have been approved by the Food and Drug Administration (FDA) because of the extensive testing required; examples of nerve dyes include compounds from Avelas and General Electric, fluorescent cholera toxin subunit B, indocyanine green, fluorescent inactivated herpes simplex 2, and Fluoro-Gold. Direct visualization techniques have a simpler FDA approval process; examples include optical coherence tomography, multiphoton microscopy, ultrasound, coherent anti-Stokes Raman scattering. Many researchers are developing several novel technologies that can be categorized as stimulation based, dye-based, or direct visualization. As of yet, none has shown clear evidence to improve surgical outcomes and consequently lack wide adoption. Further development of these technologies may lead to improved complication rates after prostatectomies. Clinically, some technologies have demonstrated utility in predicting the development of complications. By using that information, more aggressive rehabilitation programs may lead to improved long-term function. These technologies can also be applied for research to improve our knowledge of the neuroanatomy and physiology of erection and incontinence.

Renal osteodystrophy: neurosurgical considerations and challenges.

BACKGROUND: Dialysis-associated destructive spondyloarthropathy (DSA) is the major bony complication of end-stage renal disease, most commonly found in the lower cervical region. The risk factors for developing dialysis-associated DSA include duration of hemodialysis and patient age. Patients with DSA have a higher incidence of osteoporosis and poor bone mineral density, which may place them at greater risk of atraumatic fractures, instrumentation failure, and neurologic compromise. METHODS: We describe a case of cervical radiculopathy due to dialysis-associated DSA atraumatic vertebral body fractures with a postoperative course that was complicated by instrumentation failure. We reviewed the literature regarding all 138 published cases, presenting the complications, surgical treatment options, and outcomes. RESULTS: A 44-year-old dialysis-dependent man presented with acute neck pain, radiculopathy, and weakness due to atraumatic fracture of C5 and C6 vertebral bodies. He underwent anterior C5 and C6 corpectomies, reconstruction with mesh cage and plate, and supplemental posterior instrumentation (C4-T1). Six weeks later, a computed tomography scan revealed anterior translation across the instrumented area with failure of the posterior instrumentation. He subsequently underwent traction, revision reinstrumentation from C2 to T5, and placement of external halo ring/jacket for 6 months. At 18 months later, he remains ambulatory without evidence of construct failure. CONCLUSIONS: Patients with renal osteodystrophy present a challenge for the spine surgeon due to compromised bone density. Hardware failure at the bone-construct interface is common in these patients, with revision surgery needed in 22% of published cases. Longer constructs with circumferential instrumentation and halo immobilization may minimize the risk of pseudoarthrosis and construct pull-out.

Instrumentation of the osteoporotic spine: biomechanical and clinical considerations.

BACKGROUND CONTEXT: Osteoporosis is a major health-care problem that is increasing in magnitude with the aging population. Such patients are more prone to develop painful and debilitating spinal deformities but are difficult to treat. Currently, no definitive treatment algorithm has been established. PURPOSE: To review the failure modes of instrumentation and novel surgical treatments of spinal deformities in patients with osteoporosis with the goal of improving surgical care. STUDY DESIGN/SETTING: Review article. METHODS: We systematically searched PubMed for articles regarding instrumentation failure modes and surgical treatments of spinal deformities in patients with osteoporosis and summarized current treatment options. RESULTS: The surgical treatment options are severely limited because of the tendency for instrument failure secondary to pullout and subsidence, leading to revision procedures; multiple levels and multiple fixation points are recommended to minimize the risk. The literature supports the use of vertebroplasty in conjunction with pedicle screw-based instrumentation for treating more severe spinal deformities. Other techniques and modifications with evidence of reduced failure risk are bicortical screws, hydroxyapatite coatings, double screws, and expandable screws. Anterior approaches may provide another avenue of treatment, but only a few studies have been conducted on these implants in patients with osteoporosis. CONCLUSIONS: Spinal deformities in patients with osteoporosis are difficult to treat because of their debilitating and progressive nature. Novel surgical approaches and instruments have been designed to decrease construct failures in this patient population by reducing implant pullout, subsidence, and incidence of revision surgery. The success of these techniques depends on integrating biomaterial, biologic, and biomechanical aspects with clinical considerations. Synthesizing this myriad of aspects will lead to improved treatment options for patients with osteoporosis who are suffering from spinal deformities.

Robotic approaches to the posterior spine.

STUDY DESIGN: This anatomic study described robotic approaches to the posterior thoracolumbar spine in a porcine model. Ergonomics, control, and approach and technical difficulties were noted. OBJECTIVE: The objective of this study was to develop a robotic approach to the posterior thoracolumbar spine maximizing surgeon ergonomics and control. SUMMARY OF BACKGROUND DATA: Surgery is both physically and mentally demanding, and strains from ergonomics and the aging process may negatively impact surgical skills. In spine surgery, control and precision are extremely important due to the close proximity to the spinal cord. The da Vinci robotic surgery system has offered better ergonomics and control in urology, gynecology, and cardiac surgery, and is rapidly gaining adoption. To date, there have been no published reports of da Vinci robotic spine surgery, motivating us to assess its potential in posterior spine surgery. METHODS: Posterior spine da Vinci approaches were tested on a pig without spinal pathology with an open subperiosteal dissection. A laser instrument and prototype robotic burr and rongeur instruments were tested on laminotomy, laminectomy, disc incision, and dural suturing procedures. RESULTS: Open dissection of the posterior spine provided sufficient access to successfully perform laminotomy, laminectomy, disc incision, and dural suturing procedures. Prototype burr and rongeur instruments were effective with good control. The laser instrument coagulated the epidural venous plexus and incised the anulus. Robot ergonomics allowed the surgeon to perform procedures for a full day with significantly less fatigue and reduced hand tremor. CONCLUSION: The da Vinci could perform the major noninstrumented procedures of the posterior spine with improved ergonomics and control. Surgeon fatigue and tremor were reduced. With some modification of prototype and commercial instruments a posterior spine surgery instrument kit can be developed. Future clinical studies can better assess patient and surgeon benefits of using the da Vinci robot for posterior spine surgeries.

Molecular genetic analysis of FGFR1 signalling reveals distinct roles of MAPK and PLCgamma1 activation for self-renewal of adult neural stem cells.

BACKGROUND: Neural stem cells (NSCs) are present in the adult mammalian brain and sustain life-long adult neurogenesis in the dentate gyrus of the hippocampus. In culture, fibroblast growth factor-2 (FGF-2) is sufficient to maintain the self-renewal of adult NSCs derived from the adult rat hippocampus. The underlying signalling mechanism is not fully understood. RESULTS: In the established adult rat NSC culture, FGF-2 promotes self-renewal by increasing proliferation and inhibiting spontaneous differentiation of adult NSCs, accompanied with activation of MAPK and PLC pathways. Using a molecular genetic approach, we demonstrate that activation of FGF receptor 1 (FGFR1), largely through two key cytoplasmic amino acid residues that are linked to MAPK and PLC activation, suffices to promote adult NSC self-renewal. The canonical MAPK, Erk1/2 activation, is both required and sufficient for the NSC expansion and anti-differentiation effects of FGF-2. In contrast, PLC activation is integral to the maintenance of adult NSC characteristics, including the full capacity for neuronal and oligodendroglial differentiation. CONCLUSION: These studies reveal two amino acid residues in FGFR1 with linked downstream intracellular signal transduction pathways that are essential for maintaining adult NSC self-renewal. The findings provide novel insights into the molecular mechanism regulating adult NSC self-renewal, and pose implications for using these cells in potential therapeutic applications.

G9a and Jhdm2a regulate embryonic stem cell fusion-induced reprogramming of adult neural stem cells.

Somatic nuclei can be reprogrammed to pluripotency through fusion with embryonic stem cells (ESCs). The underlying mechanism is largely unknown, primarily because of a lack of effective approaches to monitor and quantitatively analyze transient, early reprogramming events. The transcription factor Oct4 is expressed specifically in pluripotent stem cells, and its reactivation from somatic cell genome constitutes a hallmark for effective reprogramming. Here we developed a double fluorescent reporter system using engineered ESCs and adult neural stem cells/progenitors (NSCs) to simultaneously and independently monitor cell fusion and reprogramming-induced reactivation of transgenic Oct4-enhanced green fluorescent protein (EGFP) expression. We demonstrate that knockdown of a histone methyltransferase, G9a, or overexpression of a histone demethylase, Jhdm2a, promotes ESC fusion-induced Oct4-EGFP reactivation from adult NSCs. In addition, coexpression of Nanog and Jhdm2a further enhances the ESC-induced Oct4-EGFP reactivation. Interestingly, knockdown of G9a alone in adult NSCs leads to demethylation of the Oct4 promoter and partial reactivation of the endogenous Oct4 expression from adult NSCs. Our results suggest that ESC-induced reprogramming of somatic cells occurs with coordinated actions between erasure of somatic epigenome and transcriptional resetting to restore pluripotency. These mechanistic findings may guide more efficient reprogramming for future therapeutic applications of stem cells. Disclosure of potential conflicts of interest is found at the end of this article.