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BACKGROUND: Various strategies have been used to reduce pedicle screw loosening following lumbar instrumented fusion, but all strategies have limitations. In this prospective multicenter cohort study, outcomes of elderly patients with reduced bone density who underwent primary or revision fusion surgery using a novel technique of pedicle screw augmentation with demineralized bone fiber (DBF) anchors were evaluated. METHODS: This study included elderly patients (aged >65 years) with dual-energy x-ray absorptiometry-confirmed reduced bone density who required lumbar pedicle screw fixation and were treated with supplemental DBF allograft anchors during primary or revision surgery. The need for DBF anchors was determined by evaluating preoperative computed tomography (CT) scans (for revision surgery) and by the surgeons' tactile feedback intraoperatively during pedicle screw insertion and removal. After determining the pedicle screw void diameter with a sizing instrument, DBF anchors and pedicle screws of the same diameter were placed into the void. CT scans were obtained on postoperative day 2 to assess pedicle breach, pedicle fracture, or anchor material extrusion and at 6 and 12 months postoperatively to assess screw loosening. Thereafter, to minimize radiation exposure, CT scans were only performed for recurrence of pain. RESULTS: Twenty-three patients (79% women; mean age, 74 years) received 50 lumbosacral pedicle screws augmented with DBF anchors. Most surgeries (n = 18, 78%) were revisions, and most anchors were inserted into revision pedicle screw trajectories (n = 33, 66%). Day-2 CT scans revealed no pedicle breach/fracture or extrusion of anchor material. During a mean follow-up of 15 months (12-20 months), no screw loosening was detected, and no patient required pedicle screw revision surgery. There were no adverse events attributable to DBF allografts. CONCLUSIONS: DBF allograft anchors appear to be safe and effective for augmenting pedicle screws during revision surgeries in female elderly patients with reduced bone density. CLINICAL RELEVANCE: Clinically, DBF reduced the rate of pedicle screw loosening in patients with reduced bone density. A significant reduction in screw loosening can decrease the need for revision surgeries, which are costly and carry additional risks. Enhanced bone integration from the DBF may promote better healing and long-term stability.
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INTRODUCTION: The Coronavirus disease 2019 pandemic ushered a paradigm shift in medical education, accelerating the transition to virtual learning in select cases. The Virtual Global Spine Conference (VGSC), launched at the height of the pandemic, is a testament to this evolution, providing an independent educational series for spine care professionals worldwide. This study assesses VGSC's 3-year performance, focusing on accessibility, engagement, and educational value. METHODOLOGY: Through retrospective data analysis from April 2020 to August 2023, we examined our social media metrics to measure VGSC's reach and impact. RESULTS: Over the study period, VGSC's webinars successfully attracted 2337 unique participants, maintaining an average attendance of 47 individuals per session. The YouTube channel demonstrated significant growth, amassing over 2693 subscribers and releasing 168 videos. These videos collectively garnered 112,208 views and 15,823.3 hours of watch time. Viewer demographics reveal a predominant age group of 35-44 years, representing 56.81% of the audience, closely followed by the 25-34 age group at 40.2%. Male participants constituted 78.95% of the subscriber base. Geographically, the viewership primarily originates from the United States, with India, Canada, South Korea, and the United Kingdom also contributing substantial audience numbers. The VGSC's presence on the "X account" has grown to 2882 followers, significantly enlarging the digital community and fostering increased engagement. CONCLUSIONS: The VGSC has demonstrated significant value as a virtual educational tool in spine education. Its diverse content and ease of access will likely enable it to drive value well into the post-pandemic years. Maintaining and expanding engagement, beyond North America in particular, remains a priority.
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COVID-19 , Congresos como Asunto , Humanos , Estudios Retrospectivos , Adulto , Masculino , Medios de Comunicación Sociales , Femenino , Educación a Distancia/métodos , Columna Vertebral/cirugía , Enfermedades de la Columna VertebralRESUMEN
To decrease the introduction of COVID-19, in-person visitation programs were temporarily limited at California Department of Corrections and Rehabilitation facilities. After consultation with the California Department of Public Health, and in accordance with Centers for Disease Control and Prevention guidelines, in-person visitation was reintroduced on April 10, 2021, with COVID-19 mitigation strategies. To assess the risk of visitation as a mode of entry for COVID-19 into a prison setting, data were gathered demonstrating the number of visitors who were not allowed into the prison due to a positive COVID-19 test prior to visitation. The number of patients who tested positive for COVID-19 after interaction with visitors was also assessed. Between April 10 and June 27, 2021, 33,212 visitors participated in the in-person visiting program. Eight visitors received positive test results prior to entry. Between January 1 and October 1, 2021, 19,025 patients received a total of 93,135 visitations. Of these, 66 patients received positive test results from post-visit testing. These data suggest that when appropriate mitigation strategies are implemented, the visitation process is not a significant contributor to COVID-19 entry into the prison facility when compared with the total number of COVID-19 cases among patients.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , PrisionesRESUMEN
INTRODUCTION: Adolescent idiopathic scoliosis is the most common spinal deformity encountered in adolescents and larger curves are more prevalent in girls. For females with scoliosis, women's health issues are of particular concern, especially pregnancy. The aim of this review was to summarise the best available evidence to determine the influence of pregnancy on scoliosis-related outcomes in women with scoliosis and whether scoliosis affects maternal-health outcomes, differentiating between patients who have been managed conservatively and/or surgically. EVIDENCE ACQUISITION: A search was conducted using CINAHL, Scopus, Cochrane Database, MEDLINE, and EMBASE from inception to May 2023 to identify relevant articles in any language. The scoping review followed the PRISMA-ScR guidelines. Studies were eligible if they included pregnant women (primiparous or multiparous) with a diagnosis of scoliosis of unknown aetiology. The results were summarized by outcomes, including pregnancy and scoliosis-related outcomes and type of management. EVIDENCE SYNTHESIS: Our comprehensive search strategy identified 6872 articles, of which 50 articles were eligible for this review. Back pain appears to be more prevalent in this population during pregnancy and associated with the major curve and the decrease of lumbar lordosis. There have been reports of failed attempted spinal anaesthesia among patients with instrumented scoliosis correction and minor complications related to epidural anaesthesia at a higher rate compared to non-instrumented patients and healthy controls, however successful spinal analgesia can be achieved in patients with instrumented scoliosis correction. Overall, the caesarean section rate was similar in scoliosis patients compared to controls without scoliosis and to national averages. Curve progression occurs in some but not all patients during pregnancy, and this phenomenon occurs irrespective of the treatment received. CONCLUSIONS: Higher-quality prospective longitudinal research is needed to understand the relationship between pregnancy and adolescent idiopathic scoliosis. Further, the patient's perspective, concerns and fears surrounding pregnancy with scoliosis are yet to be explored. Exploring the impact of pregnancy on women with adolescent idiopathic scoliosis would have clinically relevant outcomes and could help provide pertinent answers to patients and healthcare workers and help guide future research.
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Escoliosis , Embarazo , Animales , Adolescente , Femenino , Humanos , Escoliosis/diagnóstico , Escoliosis/terapia , Cesárea , Estudios Prospectivos , Bases de Datos Factuales , MiedoRESUMEN
BACKGROUND: The practice of cement augmentation in pedicle screw fixation is well established. However, there is a lack of consensus regarding the optimal screw design or cement type. This remains a clinically important question given the incidence of cement augmentation-associated complications. While fenestrated screws have become widely used in clinical practice, the relationship between fenestration placement along the screw axis and cement plume geometry and pullout strength have yet to be clarified. This study was designed to evaluate the mechanical and geometric properties of different fenestrated screw designs and cement viscosities in pedicle screw fixation. METHODS: Three different screw fenestration configurations and 2 different cement viscosities were examined in this study. Axial pullout tests were conducted in both foam blocks and cadaveric vertebrae. All vertebral specimens underwent tests of bone mineral density. In the foam blocks, 6 tests were conducted for each augmentation combination and also for nonaugmented controls. In the cadaveric testing, 36 lumbar vertebrae were instrumented with a cemented and uncemented control screw to compare features of fixation. Computed tomography (CT) images were taken to assess the geometric profile of the cement plumes in both the foam blocks and the cadaveric vertebrae. RESULTS: In both foam blocks and vertebral specimens, cementation was shown to confer a significant increase in pullout strength. Significant correlations existed between the anterior-posterior and lateral cement plume diameters and pullout strength in cadaveric vertebra and foam blocks, respectively. Within instrumented vertebra, variables such as the width of the vertebral body and screw insertion were found to significantly correlate with enhanced fixation. CT analysis of the instrumented vertebra demonstrated that a centrally distributed pattern of fenestrations was found to result in a cement plume with consistently predictable distribution within the vertebral body, without evidence of leak. CONCLUSION: Cementation of fenestrated pedicle screws increases overall pullout forces; however, there is an unclear relationship between the geometric properties of the cement plume and the overall strength of the screw-bone interface. This study demonstrates that the plume diameter, vertebral body width, and angle of screw insertion are correlated with enhanced pullout strength. Furthermore, varying the fenestration design of injectable screws resulted in a set of predictable plume patterns, which may be associated with fewer complications. Further investigation is required to clarify the optimal geometric and biomechanical properties of injectable pedicle screws and their role in establishing the cement-bone interface. CLINICAL RELEVANCE: This study is relevant to currently practicing spinal surgeons and biomechanical engineers.
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STUDY DESIGN: Retrospective case control study. OBJECTIVES: Adjacent-level ossification development (ALOD) is a distinct form of adjacent segmental degeneration that has been recognized to occur after anterior cervical discectomy and fusion (ACDF). It is unclear whether ACDF with plate versus standalone has an effect on rates of ALOD. This retrospective case-control study aims to assess the rate of ALOD in a large series of patients undergoing ACDF with and without plate and factors causing ALOD. METHODS: Data was collected for patients undergoing ACDF from January 2009 to July 2016. Data collected was from multiple centers and included demographic data, surgical data, radiological imaging at time of surgery, and serial follow-up imaging. The radiology for ALOD was independently reviewed. Cohorts were divided into ACDF with plate (Group P = plate) and ACDF without plate (Groups S = standalone) and outcomes were compared. RESULTS: There were 260 patients with 138 (53%) in Group P and 122 (47%) in Group S. ALOD was observed in 15.3% of patients overall, 29% in group P and 2.8% in group S (P < .001). Following multivariate adjustment, statistically significant association was found between use of plate and ALOD (odds ratio = 12.8, 95% confidence interval = 3.52-45.45, P < .001). Plate-to-disc distance <5 mm was significantly associated with ALOD (odds ratio = 13.5, 95% confidence interval = 3.83-47.62, P < .001). CONCLUSION: The use of anterior plate with ACDF was associated with ALOD. Plate-to-disc distance <5 mm was significantly associated with ALOD even after adjustment for confounding factors. We conclude utilization of standalone cages or cages with plate with more than 5 mm distance from adjacent disc to minimize ALOD.
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Odd-nosed monkeys 'arm-swing' more frequently than other colobines. They are therefore somewhat behaviorally analogous to atelines and apes. Scapular morphology regularly reflects locomotor mode, with both arm-swinging and climbing anthropoids showing similar characteristics, especially a mediolaterally narrow blade and cranially angled spine and glenoid. However, these traits are not expressed uniformly among anthropoids. Therefore, behavioral convergences in the odd-nosed taxa of Nasalis, Pygathrix, and Rhinopithecus with hominoids may not have resulted in similar structural convergences. We therefore used a broad sample of anthropoids to test how closely odd-nosed monkey scapulae resemble those of other arm-swinging primates. We used principal component analyses on size-corrected linear metrics and angles that reflect scapular size and shape in a broad sample of anthropoids. As in previous studies, our first component separated terrestrial and above-branch quadrupeds from clambering and arm-swinging taxa. On this axis, odd-nosed monkeys were closer than other colobines to modern apes and Ateles. All three odd-nosed genera retain glenoid orientations that are more typical of other colobines, but Pygathrix and Rhinopithecus are closer to hominoids than to other Asian colobines in mediolateral blade breadth, spine angle, and glenoid position. This suggests that scapular morphology of Pygathrix may reflect a significant reliance on arm-swinging and that the morphology of Rhinopithecus may reflect more reliance on general climbing. As 'arm-swinging' features are also found in taxa that only rarely arm-swing, we hypothesize that these features are also adaptive for scrambling and bridging in larger bodied anthropoids that use the fine-branch component of their arboreal niches.
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Evolución Biológica , Hominidae/anatomía & histología , Locomoción , Presbytini/anatomía & histología , Escápula/anatomía & histología , Animales , Hominidae/fisiología , Filogenia , Presbytini/fisiologíaRESUMEN
Modern human bipedality is unique and requires lumbar lordosis, whereas chimpanzees, our closest relatives, have short lumbar spines rendering them incapable of lordosis. To facilitate lordosis, humans have longer lumbar spines, greater lumbosacral angle, dorsally wedged lumbar vertebral bodies, and lumbar zygapophyseal joints with both increasingly coronal orientation and further caudal interfacet distances. These features limit modern lower lumbar spine and lumbosacral joint ailments, albeit imperfectly. The more coronal zygapophyseal orientation limits spondylolisthesis, while increasing interfacet distance may limit spondylolysis. Common back pain, particularly in people who are obese or pregnant, may result from increased lumbar lordosis, causing additional mass transfer through the zygapophyseal joints rather than vertebral bodies. Reduction in lumbar lordosis, such as in flatback syndrome from decreased lumbosacral angle, can also cause back pain. Human lumbar lordosis is necessary for placing the trunk atop the pelvis and presents a balancing act not required of our closest primate relatives.
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Evolución Biológica , Lordosis , Vértebras Lumbares/anatomía & histología , Primates , Articulación Cigapofisaria/anatomía & histología , Animales , HumanosRESUMEN
PURPOSE: Time is a critical factor in drug action. The duration of inhibition of the target or residence time of the drug molecule on the target often guides drug scheduling. METHODS: The effects of time on the concentration-dependent cytotoxicity of approved and investigational agents [300 compounds] were examined in the NCI60 cell line panel in 2D at 2, 3, 7 and in 3D 11 days. RESULTS: There was a moderate positive linear relationship between data from the 2-day NCI60 screen and the 3-, 7- and 11-day and a strong positive linear relationship between 3-, 7- and 11-day luminescence screen IC50s by Pearson correlation analysis. Cell growth inhibition by agents selective for a specific cell cycle phase plateaued when susceptible cells were growth inhibited or killed. As time increased the depth of cell growth inhibition increased without change in the IC50. DNA interactive agents had decreasing IC50s with increasing exposure time. Epigenetic agents required longer exposure times; several were only cytotoxic after 11 days' exposure. For HDAC inhibitors, time had little or no effect on concentration response. There were potency differences amongst the three BET bromodomain inhibitors tested, and an exposure duration effect. The PARP inhibitors, rucaparib, niraparib, and veliparib reached IC50s < 10 µM in some cell lines after 11 days. CONCLUSIONS: The results suggest that variations in compound exposure time may reflect either mechanism of action or compound chemical half-life. The activity of slow-acting compounds may optimally be assessed in spheroid models that can be monitored over prolonged incubation times.
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Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Línea Celular Tumoral , HumanosRESUMEN
BACKGROUND: Analysis was performed of two patient cohorts who underwent fixation without fusion for unstable thoracolumbar and lumbar fractures: (I) minimally invasive surgery (MIS) group using combined monoaxial-polyaxial pedicle screws inserted percutaneously; (II) open surgery (OS) group using Schanz screw constructs. Our aim was to compare radiographic and clinical indices of the 'gold standard' of open Schanz screw to MIS monoaxial-polyaxial screw constructs. METHODS: There were 13 patients in the MIS group and 19 in the OS group. Primary outcomes were the correction of fracture angulation and percentage loss of reduction until fracture union. Patient demographics, fracture classification, perioperative data and complications were also collected. RESULTS: There was no significant difference in cohorts when comparing demographics and fracture classification. Operative time was 50 minutes less and haemoglobin drop was 9 g/L less in the MIS group. Radiation exposure was significantly higher in the MIS group. Pre-operatively, the mean kyphotic angle was 22° in the MIS and 16° in the OS group. Both groups achieved similar on-table correction. On immediate postoperative erect radiographs, the MIS group lost 15% of correction vs. 55% in the OS group. At final follow-up, both groups had a further loss of position, but significantly higher in the OS group (28% vs. 96%). CONCLUSIONS: Combined polyaxial-monoaxial screw MIS constructs demonstrate favorable radiological and clinical outcomes for treatment of unstable thoracolumbar and lumbar fractures. Our study also demonstrates higher rates of radiological collapse in the OS cohort.
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STUDY DESIGN: Prospective cohort study. OBJECTIVES: To evaluate the role of magnetic resonance imaging (MRI) in evaluation of fusion status following anterior lumbar interbody fusion (ALIF) and compare agreement and confidence in assessing fusion or its absence on MRI to the current standard computed tomography (CT). METHODS: A prospective follow up of patients undergoing surgery by 2 spine surgeons between 2012 and 2015 at a single institution. Fusion was assessed at different time points in these patients by 2 independent musculoskeletal radiologists. Fusion was analyzed in coronal and sagittal planes using both imaging modalities, with confidence being attributed on a scale of 0 to 3. Assessors were blinded to patient data. RESULTS: Fourteen patients (25 levels) with mean follow-up of 10.2 months (range 2.4-20.3 years) and age of 41 years (range 20.7-61.5 years) were assessed. MRI within the interbody cage in coronal (κ = .58) and sagittal (κ = .50) planes had the highest interobserver agreement. CT anterior to the cage in coronal (κ = .48) and sagittal (κ = .44) planes, as well as within the cage in coronal (κ = .50) and sagittal planes (κ = .44) showed moderate agreement. Confidence anterior to the interbody cage using MRI scan was reduced when compared with remaining angles and imaging modalities. CONCLUSIONS: The study demonstrates that MRI may be a useful tool in the assessment of fusion following ALIF with results comparable to CT, and that it may have a useful role in select patients especially considering marked radiation exposure reduction.
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BACKGROUND: To compare the outcome of minimally invasive fracture stabilization to traditional open methods in the thoracolumbar region in patients with an ankylosing disorder of the spine. METHODS: A prospective, ethics-approved database (Spine Tango) at a tertiary referral center was retrospectively reviewed for results of surgery on fractures of the ankylosed thoracolumbar spine. These were then split by surgical technique into two cohorts: minimally invasive surgical fixation (MIS group) or standard open surgery (open group). RESULTS: We identified 17 patients who presented with fractures in an ankylosed spine from 2010 to 2017. MIS fixation was performed on 10 and open surgery and fixation on 7. Average age in the MIS group was older than the traditional cohort. There was no difference in the average number of levels stabilized (open =6.9, MIS =7). There was a shorter duration in the operative time and a significant difference in blood loss in favor of the MIS group (P=0.00079). Radiation exposure time and dose were significantly higher in the MIS group (P=0.006). There were no cases of non-union, implant malposition or failure in either group. Two significant complications occurred with the death of one patient in the MIS group, and one death in the open group. CONCLUSIONS: The MIS technique for fractures of the ankylosed spine has shown an acceptable complication rate and good results comparable to open surgery for a high-risk patient population.
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Dolor de Espalda/terapia , Absceso Epidural/inducido químicamente , Absceso Epidural/diagnóstico por imagen , Proloterapia/efectos adversos , Administración Intravenosa , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Dolor de Espalda/diagnóstico , Absceso Epidural/tratamiento farmacológico , Humanos , Enfermedad Iatrogénica , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Paracentesis/métodosRESUMEN
PURPOSE: The purpose of this study is to perform a citation analysis on the most frequently cited articles in the topic of cervical spine surgery and report on the top 100 most cited publication in this topic. METHODS: We used the Thomson Reuters Web of Science to search citations of all articles from 1945 to 2015 relevant to cervical spine surgery and ranked them according to the number of citations. The 100 most cited articles that matched the search criteria were further analyzed by number of citations, first author, journal, year of publication, country and institution of origin. RESULTS: The top 100 cited articles in the topic of cervical spine surgery were published from 1952-2011. The number of citations ranged from 106 times for the 100th paper to 1206 times for the top paper. The decade of 1990-1999 saw the most publications. The Journal of Spine published the most articles, followed by Journal of Bone and Joint Surgery America. Investigators from America authored the most papers and The University of California contributed the most publications. Cervical spine fusion was the most common topic published with 36 papers, followed by surgical technique and trauma. CONCLUSION: This article identifies the 100 most cited articles in cervical spine surgery. It has provided insight to the history and development in cervical spine surgery and many of which have shaped the way we practice today.
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The SCLC combination screen examined a 9-point concentration response of 180 third agents, alone and in combination with etoposide/carboplatin. The predominant effect of adding a third agent to etoposide/carboplatin was additivity. Less than additive effects occurred frequently in SCLC lines sensitive to etoposide/carboplatin. In SCLC lines with little or no response to etoposide/carboplatin, greater than additive SCLC killing occurred over the entire spectrum of SCLC lines but never occurred in all SCLC lines. Exposing SCLC lines to tubulin-targeted agents (paclitaxel or vinorelbine) simultaneously with etoposide/carboplatin resulted primarily in less than additive cell killing. As single agents, nuclear kinase inhibitors including Aurora kinase inhibitors, Kinesin Spindle Protein/EG5 inhibitors, and Polo-like kinase-1 inhibitors were potent cytotoxic agents in SCLC lines; however, simultaneous exposure of the SCLC lines to these agents along with etoposide/carboplatin, generally, resulted in less than additive cell killing. Several classes of agents enhanced the cytotoxicity of etoposide/carboplatin toward the SCLC lines. Exposure of the SCLC lines to the MDM2 inhibitor JNJ-27291199 produced enhanced killing in 80% of the SCLC lines. Chk-1 inhibitors such as rabusertib increased the cytotoxicity of etoposide/carboplatin to the SCLC lines in an additive to greater than additive manner. The combination of GSK-3ß inhibitor LY-2090314 with etoposide/carboplatin increased killing in approximately 40% of the SCLC lines. Exposure to the BET bromodomain inhibitor MK-8628 increased the SCLC cell killing by etoposide/carboplatin in 20-25% of the SCLC lines. Only 10-15% of the SCLC lines had an increased response to etoposide/carboplatin when simultaneously exposed to the PARP inhibitor talazoparib.
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Antineoplásicos/farmacología , Carboplatino/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Etopósido/farmacología , Línea Celular Tumoral , Biología Computacional/métodos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales/métodos , Sinergismo Farmacológico , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Bibliotecas de Moléculas PequeñasRESUMEN
OBJECTIVES: The higher primate scapula has been subject to many explanations of the putative "adaptive value" of its individual traits. However, the shift from the bone's position in above branch quadrupeds to its more posterolateral position in recent hominoids obviously required fundamental changes to its general form. We hypothesize that most features argued to be individually adaptive are more likely secondary consequences of changes in its fundamental bauplan, a view more consistent with modern developmental biology. MATERIALS AND METHODS: We tested this hypothesis with scapular metrics and angles from a broad anthropoid sample. RESULTS: Our results support our hypothesis. Contrary to earlier predictions, vertebral border length differs little relative to body size in anthropoids, inferior angle position primarily reflects mediolateral scapular breadth, and supraspinous and infraspinous fossa sizes largely reflect scapular spine orientation. Suspensory taxa have cranially oriented glenoids, whereas slow clamberers and humans do not. Australopithecus most closely resembles the latter. DISCUSSION: Most scapular features can be explained by only two primary changes: (1) reduction in mediolateral breadth and (2) change in the glenoid position relative to the vertebral border with increased reliance on suspension, which led to a more cranially angled scapular spine. Virtually all other scapular traits appear to be byproducts of these two changes. Based on fossil morphology, hominids1 were derived from a last common ancestor primarily adapted for clambering and not for suspension. Scapular form in early hominids such as Australopithecus is therefore primitive and largely reflects the genus's general clambering heritage.
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Evolución Biológica , Hominidae/anatomía & histología , Escápula/anatomía & histología , Animales , Antropología Física , Fósiles , Humanos , Análisis de Componente PrincipalRESUMEN
BACKGROUND: C7 has relatively unique anatomy compared to the remainder of the subaxial cervical spine (C3-C6) and upper thoracic spine. The C7 laminar has been previously reported in feasibility and biomechanical studies as an adequate fixation point in contrast to the lateral mass or pedicles, with few reports of its use in clinical practice. The purpose of this study was to review the safety and efficacy of using the C7 laminar as a fixation point in constructs involving the cervical spine and cervicothoracic junction. METHODS: Between February 2013 and July 2016, 10 patients (6 males, 4 females) had 19 C7 intra-laminar screws sited (bilateral in 9 patients, unilateral in 1 patient). Six patients had trauma as an underlying etiology, 2 of which had pseudoarthrosis from prior surgery. Three patients had cervical myelopathy from degenerative disease, 2 of which required anterior and posterior instrumentation for correction of deformity and 1 which had stand-alone posterior fixation. One patient had stabilization for an underlying malignancy. RESULTS: One patient died 2 weeks following their high cervical injury secondary to complications of respiratory failure. None of the remaining 9 patients were noted to have construct failure at a median follow up of 1 year (range, 6 months to 4 years) and all were noted to have satisfactory positioning of the instrumentation on post-operative imaging. The patient with malignancy died 6 months later from extra-spinal disease, there was one wound breakdown requiring debridement without infection in a revision case, and one patient required laminectomy for post-traumatic syrinx formation. CONCLUSIONS: The C7 laminar provides an alternative fixation point for constructs involving the subaxial cervical spine and cervicothoracic junction, with excellent safety and efficacy in this small series. Larger series are required to more clarify the risk profile of this technique.
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BACKGROUND: Small cell lung carcinoma (SCLC) is an aggressive, recalcitrant cancer, often metastatic at diagnosis and unresponsive to chemotherapy upon recurrence, thus it is challenging to treat. METHODS: Sixty-three human SCLC lines and three NSCLC lines were screened for response to 103 US Food and Drug Administration-approved oncology agents and 423 investigational agents. The investigational agents library was a diverse set of small molecules that included multiple compounds targeting the same molecular entity. The compounds were screened in triplicate at nine concentrations with a 96-hour exposure time using an ATP Lite endpoint. Gene expression was assessed by exon array, and microRNA expression was derived by direct digital detection. Activity across the SCLC lines was associated with molecular characteristics using pair-wise Pearson correlations. RESULTS: Results are presented for inhibitors of targets: BCL2, PARP1, mTOR, IGF1R, KSP/Eg5, PLK-1, AURK, and FGFR1. A relational map identified compounds with similar patterns of response. Unsupervised microRNA clustering resulted in three distinct SCLC subgroups. Associating drug response with micro-RNA expression indicated that lines most sensitive to etoposide and topotecan expressed high miR-200c-3p and low miR-140-5p and miR-9-5p. The BCL-2/BCL-XL inhibitors produced similar response patterns. Sensitivity to ABT-737 correlated with higher ASCL1 and BCL2. Several classes of compounds targeting nuclear proteins regulating mitosis produced a response pattern distinct from the etoposide response pattern. CONCLUSIONS: Agents targeting nuclear kinases appear to be effective in SCLC lines. Confirmation of SCLC line findings in xenografts is needed. The drug and compound response, gene expression, and microRNA expression data are publicly available at http://sclccelllines.cancer.gov.