INTRODUCTION:
Usage of osteobiologics is becoming increasingly common for spinal fusion procedures, but the efficacy of certain products is unclear.
METHODS:
The medical record across three medical ...centers and seven spine surgeons was retrospectively queried for patients undergoing single-level ACDF utilizing Osteocel. Pseudarthrosis was determined based on computed tomography (CT) or x-rays of the cervical spine. Patients were determined to have radiographic pseudarthrosis if they met any of the following criteria: 1) lack of bridging bone on CT obtained >300 days postoperatively, 2) evidence of instrumentation failure, or 3) motion across index level as seen on flexion/extension cervical spine x-rays. Univariate and multivariate analyses were then performed to identify independent preoperative or perioperative predictors of pseudarthrosis in this population.
RESULTS:
A total of 326 patients met inclusion criteria. Forty-three (13.2%) patients met criteria for pseudarthrosis, of which 15 underwent revision surgery (34.9%). Age (54.1 vs 53.8 years), sex (34.9% vs 47.4% male), race, prior cervical spine surgery (37.2% vs 33.6%), tobacco abuse (16.3% vs 14.5%), chronic kidney disease (2.3% vs 2.8%), and diabetes (18.6% vs 14.5%) were not significantly different between patients with or without pseudarthrosis, respectively (p > 0.05). Presence of osteoporosis (16.3% vs 3.5%) was associated with pseudarthrosis (p < 0.001). Implant-type was also significantly associated with pseudarthrosis, with a 16.4% rate of pseudarthrosis for patients with polyetherethereketone (PEEK) implants versus 8.4% for patients with allograft implant (p = 0.04). Average length of follow-up was 27.6 and 23.8 months for patients with and without pseudarthrosis, respectively. Multivariate analysis demonstrated osteoporosis (OR: 4.97, 95% CI 1.51-16.4, p < 0.01) and usage of PEEK implant (OR: 2.24, 95% CI 1.04-4.83, p = 0.04) as independent predictors of pseudarthrosis.
CONCLUSION:
The usage of Osteocel in single-level ACDF is associated with a higher rate of pseudarthrosis compared to the literature-reported fusion rates for alternative osteobiologics. This is especially true when Osteocel is combined with a PEEK implant.
Modern external ring fixation has been hypothesized to reduce complications requiring hospital readmission compared with internal fixation when treating patients with high-energy open tibial shaft ...fractures. In this study, the 1-year probability of a major limb complication was compared between external and internal fixation of severe open tibial fractures.
This multicenter randomized clinical trial included patients 18 to 64 years of age with severe open tibial shaft fractures randomly assigned to either modern external ring fixation (n = 127) or internal fixation (n = 133). The primary outcome was a major limb complication within 365 days after randomization; these complications included amputation, infection, a soft-tissue problem, nonunion, malunion, and a loss of reduction/implant failure.
Of 260 randomized patients, 254 were included in the final analysis. Their mean age (standard deviation) was 39 (13) years; 214 (84%) were men. The probability of at least 1 major limb complication was higher for external fixation (62.1% 95% confidence interval (CI): 53.4% to 70.8%) than internal fixation (43.7% 95% CI: 35.5% to 52.9%), with a risk difference of 18.4% (95% CI: 5.8% to 30.4%); p = 0.005). The most notable difference was in loss of reduction/implant failure, the rate of which was higher for external fixation (risk difference: 14.4% 95% CI: 7.0% to 21.6%; p = 0.002). There was no appreciable difference in the probability of deep infection between external fixation (26.1%) and internal fixation (29.7%) (risk difference: -3.5% 95% CI: -14.8% to 7.8%; p = 0.54). There were also no appreciable differences in the probabilities of amputation, nonunion, soft-tissue problems, malunion, or fracture healing between the groups.
These results argue against routine use of modern external ring fixation for the treatment of these severe open tibial fractures.
Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Selecting the best treatment for patients with severe terminal lower-limb injury remains a challenge. For some injuries, amputation may result in better outcomes than limb salvage. This study ...compared the outcomes of patients who underwent limb salvage with those that would have been achieved had they undergone amputation.
This multicenter prospective observational study included patients 18 to 60 years of age in whom a Type-III pilon or IIIB or C ankle fracture, a Type-III talar or calcaneal fracture, or an open or closed blast/crush foot injury had been treated with limb salvage (n = 488) or amputation (n = 151) and followed for 18 months. The primary outcome was the Short Musculoskeletal Function Assessment (SMFA). Causal effect estimates of the improvement that amputation would have provided if it had been performed instead of limb salvage were calculated for the SMFA score, physical performance, pain, participation in vigorous activities, and return to work.
The patients who underwent limb salvage would have had small differences in most outcomes had they undergone amputation. The most notable difference was an improvement in the SMFA mobility score of 7 points (95% confidence interval CI = 2.0 to 10.7). Improvements were largest for pilon/ankle fractures and complex injury patterns.
Amputation should be considered a treatment option rather than a last resort for the most complex terminal lower-limb injuries.
Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Abstract
Metabolic syndromes instigate substantial morbidity and mortality worldwide via its negative effects of many diseases including cancer. Obesity in particular has been deemed a causative ...factor for breast cancer in post-menopausal women, while worsening prognosis regardless of menopausal status. Importantly, progression of many metabolic syndromes can largely be slowed or reversed with aggressive lifestyle changes, thus also having the potential to mitigate cancer onset. A mouse model of environmental enrichment (EE) to improve motosensory, cognitive, and social stimulation by increasing physical engagement and social interaction triggers vast improvements in overall health. These include boosting mental health, reducing adiposity, prevention of diet-induced obesity (DIO), promoting the white to brown fat transition, enhancing insulin sensitivity, improving immune function, limiting inflammation, and inhibition of cancer growth. We have elucidated the central mechanism of EE to be the activation of the hypothalamic-sympathoneural-adipocyte (HSA) axis, a specific neuroendocrine route in which the brain communicates with adipose tissue via the sympathetic nervous system. Once activated, norepinephrine (NE) is released directly onto adipose tissue which induces the observed metabolic improvements. Breast cancer is uniquely exposed to this adipose-NE so we sought to explore this distinctive microenvironment in the context of both local and systemic endocrine and immune signaling in varied body mass states and menopausal statuses. Our data showed that EE diminished leptin levels and delayed cancer onset in the MMTV-PyMT spontaneous mouse model of breast cancer and slowed growth in a DIO allograft model. In contrast, EE failed to attenuate tumor progression in ob/ob mice in the absence of leptin, but rather enhanced tumor growth, suggesting that the leptin-NE relationship is one of the key peripheral mediators of the EE anti-breast cancer effects. We also observed significant immune cell modulation in the adipose tissue following EE. Initial characterization revealed a decrease in the proportion of tumor-associated macrophages (TAMs) and an overall anti-inflammatory response which together with the drop in leptin may contribute to the observed anti-cancer effects. We plan to further elucidate this EE-induced adipose and immune cell modulation with the ultimate goal of developing therapeutic strategies to treat both metabolic syndromes as well as associated and possibly independent cancer types.
Citation Format: Grant D. Foglesong, Stephen M. Bergin, Wei Huang, Michael A. Caligiuri, Lei Cao. Lifestyle improvements delay cancer onset and progression by adapting endocrine and immune signaling in mouse models abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1258. doi:10.1158/1538-7445.AM2017-1258
Exacerbations of obstructive lung disease are common causes of acute respiratory failure. Short-acting bronchodilators and systemic glucocorticoids are the foundation of pharmacologic management. For ...patients requiring ventilator support, use of noninvasive ventilation reduces the risk of mortality and progression to invasive mechanical ventilation. Challenges associated with invasive ventilation include ventilator dyssynchrony, air trapping, and dynamic hyperinflation. Careful monitoring and adjustment of ventilatory support parameters helps to optimize the patient-ventilator interaction and minimizes the risk of associated morbidity. Extracorporeal life support is an emerging treatment for refractory hypercapnic respiratory failure associated with obstructive lung disease.
The current model of murine innate lymphoid cell (ILC) development holds that mouse ILCs are derived downstream of the common lymphoid progenitor through lineage-restricted progenitors. However, ...corresponding lineage-restricted progenitors in humans have yet to be discovered. Here we identified a progenitor population in human secondary lymphoid tissues (SLTs) that expressed the transcription factor RORγt and was unique in its ability to generate all known ILC subsets, including natural killer (NK) cells, but not other leukocyte populations. In contrast to murine fate-mapping data, which indicate that only ILC3s express Rorγt, these human progenitor cells as well as human peripheral blood NK cells and all mature ILC populations expressed RORγt. Thus, all human ILCs can be generated through an RORγt+developmental pathway from a common progenitor in SLTs. These findings help establish the developmental signals and pathways involved in human ILC development.
Macro-environmental factors, including a patient’s physical and social environment, play a role in cancer risk and progression. Our previous studies show that living in an enriched environment (EE) ...providing complex stimuli confers an anticancer phenotype in mice mediated in part by a specific neuroendocrine axis, with brain-derived neurotrophic factor (BDNF) as the key brain mediator. Here we investigated how an EE modulated T-cell immunity and its role in the EE-induced anticancer effects. Our data demonstrated that CD8 T cells were required to mediate the anticancer effects of an EE in an orthotropic model of melanoma. In secondary lymphoid tissue (SLT), an EE induced early changes in the phenotype of T-cell populations, characterized by a decrease in the ratio of CD4 T helper to CD8 cytotoxic T lymphocytes (CTLs). Overexpression of hypothalamic BDNF reproduced EE-induced T-cell phenotypes in SLT whereas knockdown of hypothalamic BDNF inhibited EE-induced immune modulation in SLT. Both propranolol and mifepristone blocked the EE-associated modulation of CTLs in SLT suggesting both the sympathetic nervous system and hypothalamic-pituitary-adrenal axis were involved. Our results demonstrated that enhanced anticancer effect of an EE was mediated at least in part through modulation of T-cell immunity and provided support to the emerging concept of manipulating a single gene in the brain to improve cancer immunotherapy. Environmental and social factors are profound determinants of metabolic health and impact immune homeostasis. Here we investigated how EE housing activates a brain-adipocyte axis to coordinate the adipose immune microenvironment. EE housing induces expression of hypothalamic BDNF, which increases sympathetic innervation to adipose tissue and results in early accumulation of classical-Natural Killer (cNK) cells. The EE-induced increase of adipose cNK cells occurred when mice were fed a normal-chow but was eliminated when fed a high-fat diet. Our mechanistic studies demonstrated that this hypothalamic-sympathoneural-adipocyte axis increases adipocyte gene expression of IL-15, which, if blocked, eliminates the accumulation of adipose-cNKs. Interrogation of ß-adrenergic signaling revealed a ß3-receptor pathway, which increased cNKs in association with increase adipocyte IL-15. These results demonstrate how environmental intervention, acting through a single gene in the brain, regulates adipose cNKs.
Abstract The peroneus tertius muscle arises in the anterior compartment of the leg and demonstrates significant morphologic variation. Its function is not yet clearly delineated. We present the case ...of a 12-year-old patient with an isolated tear of the peroneus tertius tendon that resulted in lateral based ankle pain. After surgical reconstruction, the patient's pain resolved, and he was able to return to his normal activities.
This article describes how the dimensions of nanowires affect the transmittance and sheet resistance of a random nanowire network. Silver nanowires with independently controlled lengths and diameters ...were synthesized with a gram-scale polyol synthesis by controlling the reaction temperature and time. Characterization of films composed of nanowires of different lengths but the same diameter enabled the quantification of the effect of length on the conductance and transmittance of silver nanowire films. Finite-difference time-domain calculations were used to determine the effect of nanowire diameter, overlap, and hole size on the transmittance of a nanowire network. For individual nanowires with diameters greater than 50 nm, increasing diameter increases the electrical conductance to optical extinction ratio, but the opposite is true for nanowires with diameters less than this size. Calculations and experimental data show that for a random network of nanowires, decreasing nanowire diameter increases the number density of nanowires at a given transmittance, leading to improved connectivity and conductivity at high transmittance (>90%). This information will facilitate the design of transparent, conducting nanowire films for flexible displays, organic light emitting diodes and thin-film solar cells.
Experimental measurements of films composed of nanowires with well-defined lengths and widths were combined with 3D finite-difference time-domain calculations to determine the structure-property relationships of transparent, conducting nanowire networks.
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