Tumor-stroma interactions contribute to tumorigenesis. Tumor cells can educate the stroma at primary and distant sites to facilitate the recruitment of heterogeneous populations of immature myeloid ...cells, known as myeloid-derived suppressor cells (MDSCs). MDSCs suppress T cell responses and promote tumor proliferation. One outstanding question is how the local and distant stroma modulate MDSCs during tumor progression. Down-regulation of β-catenin is critical for MDSC accumulation and immune suppressive functions in mice and humans. Here, we demonstrate that stroma-derived Dickkopf-1 (Dkk1) targets β-catenin in MDSCs, thus exerting immune suppressive effects during tumor progression. Mice bearing extraskeletal tumors show significantly elevated levels of Dkk1 in bone microenvironment relative to tumor site. Strikingly, Dkk1 neutralization decreases tumor growth and MDSC numbers by rescuing β-catenin in these cells and restores T cell recruitment at the tumor site. Recombinant Dkk1 suppresses β-catenin target genes in MDSCs from mice and humans and anti-Dkk1 loses its antitumor effects in mice lacking β-catenin in myeloid cells or after depletion of MDSCs, demonstrating that Dkk1 directly targets MDSCs. Furthermore, we find a correlation between CD15(+) myeloid cells and Dkk1 in pancreatic cancer patients. We establish a novel immunomodulatory role for Dkk1 in regulating tumor-induced immune suppression via targeting β-catenin in MDSCs.
Cervical spine disorders in children are relatively uncommon; therefore, paradigms for surgical and nonsurgical clinical management are not well established. The purpose of this study was to bring ...together an international, multidisciplinary group of pediatric cervical spine experts to build consensus via a modified Delphi approach regarding the clinical management of children with cervical spine disorders and those undergoing cervical spine stabilization surgery.
A modified Delphi method was used to identify consensus statements for the management of children with cervical spine disorders requiring stabilization. A survey of current practices, supplemented by a literature review, was electronically distributed to 17 neurosurgeons and orthopedic surgeons experienced with the clinical management of pediatric cervical spine disorders. Subsequently, 52 summary statements were formulated and distributed to the group. Statements that reached near consensus or that were of particular interest were then discussed during an in-person meeting to attain further consensus. Consensus was defined as ≥ 80% agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree).
Forty-five consensus-driven statements were identified, with all participants willing to incorporate them into their practice. For children with cervical spine disorders and/or stabilization, consensus statements were divided into the following categories: A) preoperative planning (12 statements); B) radiographic thresholds of instability (4); C) intraoperative/perioperative management (15); D) postoperative care (11); and E) nonoperative management (3). Several important statements reaching consensus included the following recommendations: 1) to obtain pre-positioning baseline signals with intraoperative neuromonitoring; 2) to use rigid instrumentation when technically feasible; 3) to provide postoperative external immobilization for 6-12 weeks with a rigid cervical collar rather than halo vest immobilization; and 4) to continue clinical postoperative follow-up at least until anatomical cervical spine maturity was reached. In addition, preoperative radiographic thresholds for instability that reached consensus included the following: 1) translational motion ≥ 5 mm at C1-2 (excluding patients with Down syndrome) or ≥ 4 mm in the subaxial spine; 2) dynamic angulation in the subaxial spine ≥ 10°; and 3) abnormal motion and T2 signal change on MRI seen at the same level.
In this study, the authors have demonstrated that a multidisciplinary, international group of pediatric cervical spine experts was able to reach consensus on 45 statements regarding the management of pediatric cervical spine disorders and stabilization. Further study is required to determine if implementation of these practices can lead to reduced complications and improved outcomes for children.
Lumbar spinal stenosis (LSS) is one of the most common orthopaedic conditions and affects more than half a million people over the age of 65 in the US. Patients with LSS have gait dysfunction and ...movement deficits due to pain and symptoms caused by compression of the nerve roots within a narrowed spinal canal.
The purpose of the current systematic review was to summarize existing literature reporting biomechanical changes in gait function that occur with LSS, and identify knowledge gaps that merit future investigation in this important patient population.
This study is a systematic literature review.
The current study included biomechanical variables (e.g., kinematic, kinetic, and muscle activity parameters).
Relevant articles were selected through MEDLINE, Scopus, Embase, and Web of Science. Articles were included if they: 1) included participants with LSS or LSS surgery, 2) utilized kinematic, kinetic, or muscle activity variables as the primary outcome measure, 3) evaluated walking or gait tasks, and 4) were written in English.
A total of 11 articles were included in the current systematic review. The patients with LSS exhibited altered gait function as compared to healthy controls. Improvements in some biomechanical variables were found up to one year after surgery, but most gait changes were found within one month after surgery.
Although numerous studies have investigated gait function in patients with LSS, gait alterations in joint kinetics and muscle activity over time remain largely unknown. In addition, there are limited findings of spinal kinematics in patients with LSS during gait. Thus, future investigations are needed to investigate longer-term gait changes with regard to spinal kinematics, joint kinetics, and muscle activity beyond one month after LSS surgery.
Management of spinal giant cell tumors Luksanapruksa, Panya, MD; Buchowski, Jacob M., MD, MS; Singhatanadgige, Weerasak, MD, MS ...
The spine journal,
02/2016, Volume:
16, Issue:
2
Journal Article
Peer reviewed
Abstract Background Context Spinal giant cell tumors (SGCT) remain challenging tumors to treat. Although advancements in surgical techniques and adjuvant therapies have provided new options for ...treatment, evidence-based algorithms are lacking. Purpose This study aims to review the peer-reviewed literature that addresses current treatment options and management of SGCT, to produce an evidence-based treatment algorithm. Study Design/Setting A systematic review was performed. Methods Articles published between January 1, 1970 and March 31, 2015 were selected from PubMed and EMBASE searches using keywords “giant cell tumor” AND “spine” AND “treatment.” Relevant articles were selected by the authors and reviewed. Results A total of 515 studies were identified, of which 81 studies were included. Complete surgical resections of SCGT resulted in the lowest recurrence rates. However, morbidity of en bloc resections is high and in some cases, surgery is not possible. Intralesional resection can be coupled with adjuvant therapies, but evidence-based algorithms for use of adjuvants remain elusive. Several recent advancements in adjuvant therapy may hold promise for decreasing SGCT recurrence, specifically stereotactic radiotherapy, selective arterial embolization, and medical therapy using denosumab and interferon. Conclusions Complete surgical resection of SGCT should be the goal when possible, particularly if neurologic impairment is present. Denosumab holds promise as an adjuvant and perhaps stand-alone therapy for SGCT. Spinal giant cell tumors should be approached as a case-by-case problem, as each presents unique challenges. Collaboration of spine surgeons, radiation oncologists, and medical oncologists is the best practice for treating these difficult tumors.
Infant positioning in daily life, particularly in relation to active neck and back muscles, may affect spinal development, psychosocial progression, and motor milestone achievement. Yet the impact of ...infant body position on muscle activity is unknown. The objective of this study was to evaluate neck and back muscle activity of healthy infants in common positions and baby devices.
Healthy full-term infants (n = 22, 2–6 months) participated in this experimental study. Daily sleep and positioning were reported by caregivers. Cervical paraspinal and erector spinae muscle activity was measured using surface electromyography (EMG) in five positions: lying prone, lying supine, held in-arms, held in a baby carrier, and buckled into a car seat. Mean filtered EMG signal and time that muscles were active were calculated. Paired t-tests were used to compare positions to the prone condition. Caregivers reported that infants spent 12% of daily awake time prone, 43% in supine-lying baby gear, and 44% held in-arms or upright in a baby carrier. Infants exhibited highest erector spinae activity when prone, and lowest cervical paraspinal muscle activity in the car seat. No differences were found between in-arms carrying and babywearing. This first evaluation of the muscle activity of healthy infants supports the importance of prone time in infants’ early spinal development because it promotes neck and back muscle activity. Carrying babies in-arms or in baby carriers may also be beneficial to neck muscle development, while prolonged time spent in car seats or containment devices may be detrimental to spinal development.
The voluntary hip and femur fracture Bundled Payments for Care Improvement Advanced (BCPI-A) includes Diagnosis Related Groups (DRG) 480, 481, and 482, which include diverse and medically complex ...patients undergoing urgent inpatient surgery without optimization. Concern exists that this bundle is financially unfavorable for hospitals, and this study aimed to identify the costliest services.
We retrospectively reviewed a 12-month cohort of 32 consecutive patients in the DRG 480-482 bundle at our academic tertiary referral center. Cost of discharge disposition, readmission, and other variables were analyzed for all patients in the 90-day bundle.
Overall, a net financial gain averaging $2,028 per patient (range −$52,128 to +$30,199) was seen. Discharge to facilities (n = 19) resulted in higher costs than discharge to home (n = 11, P < .0001). Use of inpatient rehabilitation (n = 6) averaged a loss of $11,028 per patient and use of skilled nursing facilities (n = 15) averaged a loss of $7,250 per patient, compared to a gain of $15,011 for patients discharged home (n = 11). Episodes with readmission (n = 6) averaged a loss of only $1,390. Total index admission costs averaged $12,489 ± $2,235 per patient (range $9,329-$18,884) while post-inpatient cost averaged $30,150 per patient (range $4,803 - $77,768).
The BPCI-A hip and femur fracture bundle has a wide variability in costs, with the largest component in the post-acute care phase. Discharge home is favorable in the bundle while discharge to post-acute facilities leads to net losses. Institutions in this bundle need to develop multi-disciplinary teams to promote safe discharge home.
Over 450 adverse incidents have been reported in infant inclined sleep products over the past 17 years, with many infants found dead in both the supine and prone positions. The unique design of ...inclined sleep products may present unexplored suffocation risks related to how these products impact an infant’s ability to move. The purpose of this study was to assess body movement and muscle activity of healthy infants when they lie supine and prone on different inclined sleep products. Fifteen healthy full-term infants (age: 17.7 ± 4.9 weeks) were recruited for this IRB-approved study. Three inclined sleep products with unique features, representative of different sleeper designs, were included. Surface electromyography (EMG) was recorded from infants’ cervical paraspinal, abdominal, and lumbar erector spinae muscles for 60 s during supine and prone positioning. Neck and trunk sagittal plane movements were evaluated for each testing condition. Paired t-tests and Wilcoxon signed-rank tests were performed to compare each inclined sleeper to a flat crib mattress (0° baseline condition). During prone positioning, abdominal muscle activity significantly nearly doubled for all inclined sleep products compared to the flat crib mattress, while erector spinae muscle activity decreased by up to 48%. Trunk movement significantly increased compared to the flat crib mattress during prone lying. During prone lying, inclined sleep products resulted in significantly higher muscle activity of the trunk core muscles (abdominals) and trunk movement, which has the potential to exacerbate fatigue and contribute to suffocation if an infant cannot self-correct to the supine position.
•Mechanics of babywearing, in-arms holding, and unloaded conditions were investigated.•Greater forces and back extension found in-arms and baby carrier vs unloaded in gait.•Small (<5°) differences ...found in lower extremity kinematics during gait.•During retrieval, a more upright posture was used in-arms and carrier vs unloaded.•Babywearing may promote more similar lower extremity postures to unloaded conditions.
Human babies are carried by their caregivers during infancy, and the use of ergonomic aids to wear the baby on the body has recently grown in popularity. However, the effects of wearing or holding a baby in-arms on an individual’s mechanics during gait and a common object retrieval task are not fully understood.
What are the differences in: 1) spatiotemporal, lower extremity kinematics, and ground reaction force variables during gait, and 2) technique, center of mass motion, and kinematics during an object retrieval task between holding and wearing an infant mannequin?
In this prospective biomechanics study, 10 healthy females performed over-ground walking and an object retrieval task in three conditions, holding: (1) nothing (unloaded), (2) an infant mannequin in-arms, and (3) an infant mannequin in a baby carrier. Mechanics were compared using repeated measures ANOVA.
During gait, greater vertical ground reaction force and impulse and braking force was found during the in-arms and carrier conditions compared to unloaded. Significant but small (<5°) differences were found between conditions in lower extremity kinematics. Increased back extension was found during carrier and in-arms compared to unloaded. Step length was the only spatiotemporal parameter that differed between conditions. During object retrieval, most participants used a squatting technique to retrieve the object from the floor. They maintained a more upright posture, with less trunk flexion and anteroposterior movement of their center of mass, and also did not try to fold forward over their hips during the two loaded conditions. Lower extremity kinematics did not differ between unloaded and carrier, suggesting that babywearing may promote more similar lower extremity mechanics to not carrying anything.
Holding or wearing an infant provides a mechanical constraint that impacts the forces and kinematics, which has implications for caregivers’ pain and dysfunction.
The alpha-defensin test known as Synovaure has been very effective in diagnosis of prosthetic joint infections (PJIs). Being able to easily and accurately differentiate septic and inflammatory ...arthropathies in native joints would improve diagnostic workup and management. We tested the ability of an alpha-defensin test to distinguish septic from inflammatory or crystalline arthropathy in the native knee.
40 native knee joint fluid specimens were tested with cell count, fluid analysis, and culture and alpha-defensin testing. We determined the sensitivity and specificity of the alpha-defensin test using culture-positive fluid as the gold standard for septic arthropathy and positive crystals as the gold standard for crystalline arthropathy.
The Synovasure PJI test had 100% specificity for septic arthritis coupled with a 28% false-positive rate when applied to native knee aspirations. False-positive rate was 5.3 times higher in patients with crystals found in the joint fluid.
Alpha-defensin testing, in the form of the Synovasure PJI test, has a high-false-positive rate when used to distinguish septic and inflammatory arthritis in the native knee joint. Future work will need to determine the sensitivity and specificity of the newer native joint panel. Clinicians should be cognizant of the specific alpha-defensin test used when sampling native knee synovial fluid.
STUDY DESIGN.Single-surgeon retrospective case series.
OBJECTIVE.To validate and further describe clinical and radiographic outcomes of patients undergoing vertebral body stapling (VBS), with the ...goal of learning if VBS is a safe and effective alternative to bracing for treating moderate idiopathic scoliosis (IS) in the growing pediatric patient.
SUMMARY OF BACKGROUND DATA.VBS is a growth-modulation technique to control moderate idiopathic scoliosis (IS) while avoiding fusion. Existing studies state successful curve control rates equivalent to bracing, but the majority of reports have come from a single institution.
METHODS.All IS patients who underwent VBS by 1 surgeon were included. Indications were brace intolerance and a structural coronal curve of 25° to 40°. Proportional nitinol staples were used in all cases. Pre- and postoperative radiographs, pulmonary function testing, and physical exam measurements were serially recorded.
RESULTS.VBS was performed on 35 patients (28 females, 7 males) with mean age 10.5 years (range 7.0–14.6 years). Total of 31 patients (33 stapled curves) completed follow-up. Preoperative Risser grade was 0 in 31 patients, 1 in 1 patient, and 2 in 3 patients. Stapled curves were controlled with <10° of progression in 61% of cases. Curves <35° had a control rate of 75%, and patients <10 years had a 62% curve control rate. Eleven patients (31%) required subsequent fusions; two curves (6%) over-corrected. Preoperative supine flexibility > 30% was predictive of ultimate curve control. No neurologic complications were encountered; 5 patients (14%) developed small pneumothoraces.
CONCLUSION.This series contains the most patients and longest followup reported for VBS. Successful curve control was achieved less frequently than in previous reports, particularly in patients <10 years.Level of Evidence4
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