Surgical Decision Making for Unstable Thoracolumbar Spine Injuries: Results of a Consensus Panel Review by the Spine Trauma Study Group

Objectives: The optimal surgical approach and treatment of unstable thoracolumbar spine injuries are poorly defined owing to a lack of widely accepted level I clinical literature. This lack of evidence based standards has led to varied practice patterns based on individual surgeon preferences. The purpose of this study was to survey the leaders in the field of spine trauma to define the major characteristics of thoracolumbar injuries that influence their surgical decision making. In the absence of good scientific data, expert consensus opinions may provide surgeons with a practical framework to guide therapy and to conduct future research. Methods: A panel of 22 leading spinal surgeons from 20 level I trauma centers in seven countries met to discuss the indications for surgical approach selection in unstable thoracolumbar injuries. Injuries were presented to the surgeons in a case scenario survey format. Preferred surgical approaches to the clinical scenarios were tabulated and comments weighed. Results: All members of the panel agreed that three independent characteristics of thoracolumbar injuries carry primary importance in surgical decision making: the injury morphology, the neurologic status of the patient, and the integrity of the posterior ligaments. Six clinical scenarios based on the neurologic status of the patient (intact, incomplete, or complete) and on the status of the posterior ligamentous complex (intact or disrupted) were created, and consensus treatment approaches were described. Additional circumstances capable of altering the treatments were acknowledged. Conclusions: Decision making for the surgical treatment of thoracolumbar injuries is largely dependent on three patient characteristics: injury morphology, neurologic status, and posterior ligament integrity. A logical and practical decision-making process based on these characteristics may guide treatment even for the most complicated fracture patterns

Intestinal Epithelial Cell-Specific Deletion of PLD2 Alleviates DSS-Induced Colitis by Regulating Occludin

Ulcerative colitis is a multi-factorial disease involving a dysregulated immune response. Disruptions to the intestinal epithelial barrier and translocation of bacteria, resulting in inflammation, are common in colitis. The mechanisms underlying epithelial barrier dysfunction or regulation of tight junction proteins during disease progression of colitis have not been clearly elucidated. Increase in phospholipase D (PLD) activity is associated with disease severity in colitis animal models. However, the role of PLD2 in the maintenance of intestinal barrier integrity remains elusive. We have generated intestinal specific Pld2 knockout mice (Pld2 IEC-KO) to investigate the mechanism of intestinal epithelial PLD2 in colitis. We show that the knockout of Pld2 confers protection against dextran sodium sulphate (DSS)-induced colitis in mice. Treatment with DSS induced the expression of PLD2 and downregulated occludin in colon epithelial cells. PLD2 was shown to mediate phosphorylation of occludin and induce its proteasomal degradation in a c-Src kinase-dependent pathway. Additionally, we have shown that treatment with an inhibitor of PLD2 can rescue mice from DSS-induced colitis. To our knowledge, this is the first report showing that PLD2 is pivotal in the regulation of the integrity of epithelial tight junctions and occludin turn over, thereby implicating it in the pathogenesis of colitis

Induction of a depression-like negativity bias by cathodal transcranial direct current stimulation

Cognitive control (CC) over emotional distraction is of particular importance for adaptive human behaviour and is associated with activity in the left dorsolateral prefrontal cortex (dlPFC). Deficient CC, e.g., presenting as negativity bias, has been suggested to underlie many of the core symptoms of major depression (MD) and is associated with impairments of dlPFC function. Correspondingly, enhancement of dlPFC activity with anodal transcranial direct current stimulation (tDCS) can ameliorate these impairments in patients with MD. Here, we tested the hypothesis that a reduction of dlPFC activity by cathodal tDCS induces CC deficits, thus triggering a depression-like negativity bias in healthy subjects. Twenty-eight individuals participated in a double-blinded, balanced randomized crossover trial of cathodal (1 mA, 20 min) and sham tDCS applied to the left dlPFC. To assess CC we conducted a delayed response working memory (DWM) task and an arithmetic inhibition task (AIT) with pictures of varying valent content (negative, neutral, positive) during and immediately after stimulation. Cathodal tDCS led to impaired CC specifically over negative material as assessed by reduced response accuracy in the DWM and prolonged response latency in the AIT. Hence, the current study supports the notion that left dlPFC is critically involved in CC over negative material. Together with previously reported beneficial anodal effects, it indicates that the hypoactivation of left dlPFC causes deficits in CC over negative material, which is a possible aetiological mechanism of depression

Posterior thoracic segmental pedicle screw instrumentation: evolving methods of safe and effective placement

The use of pedicle screw instrumentation in the spine has evolved over the last two decades. The initial use of pedicle screws began in the lumbar spine. As surgeons have become more comfortable with the complex anatomy required for accurate screw placement, the use of pedicle instrumentation has evolved to include their use in the thoracolumbar and thoracic spine. The impetus behind their increased use is a result of the many advantages that pedicle screw anchorage offers over traditional hook and rod constructs. Improved deformity correction and overall construct rigidity are two important advantages of pedicle screw instrumentation due its three-column control over the spinal elements. First, pedicle screw instrumentation obviates the need to place instrumentation within the spinal canal with its inherent risk of neurologic injury. Second, the placement of pedicle screws is independent of facet or laminar integrity and thus has been extremely useful in traumatic, neoplastic, and degenerative conditions. The benefits of pedicle screws in the thoracic spine has been tempered by the potential for catastrophic neurological or soft tissue injuries due to the close proximity of these structures. The narrow and inconsistent shape of the thoracic pedicles, especially in spinal deformity, makes their placement technically challenging. As a result, surgeons have employed a number of techniques to ensure the safe and efficacious placement of thoracic pedicle screws. Detailed anatomic landmarks used to determine pedicle location, intraoperative imaging including navigation, and neurophysiological monitoring are some of the techniques currently used by surgeons. The implementation of these techniques and a thorough understanding of the complex three-dimensional anatomy have allowed surgeons to successfully place thoracic and thoracolumbar pedicle screws

The gsp oncogene disrupts Ras/ERK-dependent prolactin gene regulation in gsp inducible somatotroph cell line.

International audienceThe MAPK ERK1/2 cascade regulates all the critical cellular functions, and in many pathological situations, these regulatory processes are perturbed. It has been clearly established that this cascade is an integrative point in the control of the pituitary functions exerted by various extracellular signals. In particular, ERK1/2 cross talk with the cAMP pathway is determinant in the control of somatolactotroph hormonal secretion exerted via neuropeptide receptors. GH-secreting adenomas are characterized by frequent cAMP pathway alterations, such as constitutive activation of the α-subunit of the heterotrimeric Gs protein (the gsp oncogene), overexpression of Gsα, and changes in the protein kinase A regulatory subunits. However, it has not yet been established exactly how these alterations result in GH-secreting adenomas or how the ERK1/2 cascade contributes to the process of GH-secreting adenoma tumorigenesis. In this study on the conditional gsp-oncogene-expressing GH4C1 cell line, expression of the gsp oncogene, which was observed in up to 40% of GH-secreting adenomas, was found to induce sustained ERK1/2 activation, which required activation of the protein kinase A and the GTPases Ras and Rap1. All these signaling components contribute to the chronic activation of the human prolactin promoter. The data obtained here show that Ras plays a crucial role in these processes: in a physiopathological context, i.e. in the presence of the gsp oncogene, it switched from being a repressor of the cAMP/ protein kinase A ERK-sensitive prolactin gene control exerted by neuropeptides to an activator of the prolactin promoter