Complications of the Prone Transpsoas Lateral Lumbar Interbody Fusion for Degenerative Lumbar Spine Disease: A Multicenter Study.

BACKGROUND AND OBJECTIVES: The prone transpsoas (PTP) approach for lateral lumbar interbody fusion (LLIF) is a novel technique for degenerative lumbar spine disease. However, there is a paucity of information in the literature on the complications of this procedure, with all published data consisting of small samples. We aimed to report the intraoperative and postoperative complications of PTP in the largest study to date. METHODS: A retrospective electronic medical record review was conducted at 11 centers to identify consecutive patients who underwent LLIF through the PTP approach between January 1, 2021, and December 31, 2021. The following data were collected: intraoperative characteristics (operative time, estimated blood loss [EBL], intraoperative complications [anterior longitudinal ligament (ALL) rupture, cage subsidence, vascular and visceral injuries]), postoperative complications, and hospital stay. RESULTS: A total of 365 patients were included in the study. Among these patients, 2.2% had ALL rupture, 0.3% had cage subsidence, 0.3% had a vascular injury, 0.3% had a ureteric injury, and no other visceral injuries were reported. Mean operative time was 226.2 ± 147.9 minutes. Mean EBL was 138.4 ± 215.6 mL. Mean hospital stay was 2.7 ± 2.2 days. Postoperative complications included new sensory symptoms-8.2%, new lower extremity weakness-5.8%, wound infection-1.4%, cage subsidence-0.8%, psoas hematoma-0.5%, small bowel obstruction and ischemia-0.3%, and 90-day readmission-1.9%. CONCLUSION: In this multicenter case series, the PTP approach was well tolerated and associated with a satisfactory safety profile.

Acute failure of S2-alar-iliac screw pelvic fixation in adult spinal deformity: novel failure mechanism, case series, and review of the literature.

OBJECTIVE: Pelvic fixation with S2-alar-iliac (S2AI) screws is an established technique in adult deformity surgery. The authors' objective was to report the incidence and risk factors for an underreported acute failure mechanism of S2AI screws. METHODS: The authors retrospectively reviewed a consecutive series of ambulatory adults with fusions extending 3 or more levels, and which included S2AI screws. Acute failure of S2AI screws was defined as occurring within 6 months of the index surgery and requiring surgical revision. RESULTS: Failure occurred in 6 of 125 patients (5%) and consisted of either slippage of the rods or displacement of the set screws from the S2AI tulip head, with resultant kyphotic fracture. All failures occurred within 6 weeks postoperatively. Revision with a minimum of 4 rods connecting to 4 pelvic fixation points was successful. Two of 3 (66%) patients whose revision had less fixation sustained a second failure. Patients who experienced failure were younger (56.5 years vs 65 years, p = 0.03). The magnitude of surgical correction was higher in the failure cohort (number of levels fused, change in lumbar lordosis, change in T1-pelvic angle, and change in coronal C7 vertical axis, each p < 0.05). In the multivariate analysis, younger patient age and change in lumbar lordosis were independently associated with increased failure risk (p < 0.05 for each). There was a trend toward the presence of a transitional S1-2 disc being a risk factor (OR 8.8, 95% CI 0.93-82.6). Failure incidence was the same across implant manufacturers (p = 0.3). CONCLUSIONS: All failures involved large-magnitude correction and resulted from stresses that exceeded the failure loads of the set plugs in the S2AI tulip, with resultant rod displacement and kyphotic fractures. Patients with large corrections may benefit from 4 total S2AI screws at the time of the index surgery, particularly if a transitional segment is present. Salvage with a minimum of 4 rods and 4 pelvic fixation points can be successful.

Is the Implant in Bone? The Accuracy of CT and Fluoroscopic Imaging for Detecting Malpositioned Pelvic Screw and SI Fusion Implants.

BACKGROUND: Spine fusions to the pelvis have been associated with increased strain to the sacroiliac joint (SI) and possibly continued postoperative low back pain. To minimize this, concomitant SI joint fusion at the time of lumbopelvic fixation has been advocated. This requires concomitant placement of sacral alar iliac screws (S2AI) for lumbopelvic fixation and triangular titanium rods (TTR) for the SI joint fusion. Traditionally, surgeons have mostly relied on fluoroscopic images to confirm final implant position and patient safety after pelvic instrumentation, although computer tomography (CT) has also been used. METHODS: We wanted to know which imaging modality, if any, was superior in helping to identify malpositioned implants during concomitant lumbopelvic fixation and SI joint fusion. We instrumented pelvic sawbones models with S2AI screws, TTR's, or both in the correct anatomic positions or malpositioned variants that led to known cortical breaches. Pelvic models were then imaged with fluoroscopy and CT, and the images assessed by blinded reviewers (spine surgeons and a musculoskeletal radiologist) for the presence of cortical breaches, the identity of the breached implant, and its direction. The responses of the blinded reviewers were then compared to the known position of the implants and Kappa coefficient calculated to determine agreement. RESULTS: We found that thorough evaluation of implant position with multiple fluoroscopic views (kappa 0.641) or CT imaging (kappa 0.906) allowed reviewers to assess implant position, identity, and breach direction. CONCLUSION: These findings suggest that intraoperative CT imaging allows surgeons to make the best decision regarding implant position prior to leaving the operating room, thus potentially improving patient safety and unplanned returns to the operating room.Level of Evidence: V.

The role of Arp2/3 in growth cone actin dynamics and guidance is substrate dependent.

During development extrinsic guidance cues modulate the peripheral actin network in growth cones to direct axons to their targets. We wanted to understand the role of the actin nucleator Arp2/3 in growth cone actin dynamics and guidance. Since growth cones migrate in association with diverse adhesive substrates during development, we probed the hypothesis that the functional significance of Arp2/3 is substrate dependent. We report that Arp2/3 inhibition led to a reduction in the number of filopodia and growth cone F-actin content on laminin and L1. However, we found substrate-dependent differences in growth cone motility, actin retrograde flow, and guidance after Arp2/3 inhibition, suggesting that its role, and perhaps that of other actin binding proteins, in growth cone motility is substrate dependent.

Activation of ezrin/radixin/moesin mediates attractive growth cone guidance through regulation of growth cone actin and adhesion receptors.

The development of a functioning neural network relies on responses of axonal growth cones to molecular guidance cues that are encountered en route to their target tissue. Nerve growth factor (NGF) and neurotrophin-3 serve as attractive cues for chick embryo sensory growth cones in vitro and in vivo, but little is known about the actin-binding proteins necessary to mediate this response. The evolutionarily conserved ezrin/radixin/moesin (ERM) family of proteins can tether actin filaments to the cell membrane when phosphorylated at a conserved threonine residue. Here we show that acute neurotrophin stimulation rapidly increases active phospho-ERM levels in chick sensory neuron growth cone filopodia, coincident with an increase in filopodial L1 and ß-integrin. Disrupting ERM function with a dominant-negative construct (DN-ERM) results in smaller and less motile growth cones with disorganized actin filaments. Previously, we found that NGF treatment increases actin-depolymerizing factor (ADF)/cofilin activity and growth cone F-actin (Marsick et al., 2010). Here, we show this F-actin increase, as well as attractive turning to NGF, is blocked when ERM function is disrupted despite normal activation of ADF/cofilin. We further show that DN-ERM expression disrupts leading edge localization of active ADF/cofilin and free F-actin barbed ends. Moreover, filopodial phospho-ERM levels are increased by incorporation of active ADF/cofilin and reduced by knockdown of L1CAM.Together, these data suggest that ERM proteins organize actin filaments in sensory neuron growth cones and are crucial for neurotrophin-induced remodeling of F-actin and redistribution of adhesion receptors.

Cell dedifferentiation and epithelial to mesenchymal transitions during intestinal regeneration in H. glaberrima.

BACKGROUND: Determining the type and source of cells involved in regenerative processes has been one of the most important goals of researchers in the field of regeneration biology. We have previously used several cellular markers to characterize the cells involved in the regeneration of the intestine in the sea cucumber Holothuria glaberrima. RESULTS: We have now obtained a monoclonal antibody that labels the mesothelium; the outer layer of the gut wall composed of peritoneocytes and myocytes. Using this antibody we studied the role of this tissue layer in the early stages of intestinal regeneration. We have now shown that the mesothelial cells of the mesentery, specifically the muscle component, undergo dedifferentiation from very early on in the regeneration process. Cell proliferation, on the other hand, increases much later, and mainly takes place in the mesothelium or coelomic epithelium of the regenerating intestinal rudiment. Moreover, we have found that the formation of the intestinal rudiment involves a novel regenerative mechanism where epithelial cells ingress into the connective tissue and acquire mesenchymal phenotypes. CONCLUSIONS: Our results strongly suggest that the dedifferentiating mesothelium provides the initial source of cells for the formation of the intestinal rudiment. At later stages, cell proliferation supplies additional cells necessary for the increase in size of the regenerate. Our data also shows that the mechanism of epithelial to mesenchymal transition provides many of the connective tissue cells found in the regenerating intestine. These results present some new and important information as to the cellular basis of organ regeneration and in particular to the process of regeneration of visceral organs.

Regeneration of the radial nerve cord in the sea cucumber Holothuria glaberrima.

BACKGROUND: Regeneration of neurons and fibers in the mammalian spinal cord has not been plausible, even though extensive studies have been made to understand the restrictive factors involved. New experimental models and strategies are necessary to determine how new nerve cells are generated and how fibers regrow and connect with their targets in adult animals. Non-vertebrate deuterostomes might provide some answers to these questions. Echinoderms, with their amazing regenerative capacities could serve as model systems; however, very few studies have been done to study the regeneration of their nervous system. RESULTS: We have studied nerve cord regeneration in the echinoderm Holothuria glaberrima. These are sea cucumbers or holothurians members of the class Holothuroidea. One radial nerve cord, part of the echinoderm CNS, was completely transected using a scalpel blade. Animals were allowed to heal for up to four weeks (2, 6, 12, 20, and 28 days post-injury) before sacrificed. Tissues were sectioned in a cryostat and changes in the radial nerve cord were analyzed using classical dyes and immunohistochemistry. In addition, the temporal and spatial distribution of cell proliferation and apoptosis was assayed using BrdU incorporation and the TUNEL assay, respectively.We found that H. glaberrima can regenerate its radial nerve cord within a month following transection. The regenerated cord looks amazingly similar in overall morphology and cellular composition to the uninjured cord. The cellular events associated to radial cord regeneration include: (1) outgrowth of nerve fibers from the injured radial cord stumps, (2) intense cellular division in the cord stumps and in the regenerating radial nerve cords, (3) high levels of apoptosis in the RNC adjacent to the injury and within the regenerating cord and (4) an increase in the number of spherule-containing cells. These events are similar to those that occur in other body wall tissues during wound healing and during regeneration of the intestine. CONCLUSION: Our data indicate that holothurians are capable of rapid and complete regeneration of the main component of their CNS. Regeneration involves both the outgrowth of nerve fibers and the formation of neurons. Moreover, the cellular events employed during regeneration are similar to those involved in other regenerative processes, namely wound healing and intestinal regeneration. Thus, holothurians should be viewed as an alternative model where many of the questions regarding nervous system regeneration in deuterostomes could be answered.

Common cellular events occur during wound healing and organ regeneration in the sea cucumber Holothuria glaberrima.

BACKGROUND: All animals possess some type of tissue repair mechanism. In some species, the capacity to repair tissues is limited to the healing of wounds. Other species, such as echinoderms, posses a striking repair capability that can include the replacement of entire organs. It has been reported that some mechanisms, namely extracellular matrix remodeling, appear to occur in most repair processes. However, it remains unclear to what extent the process of organ regeneration, particularly in animals where loss and regeneration of complex structures is a programmed natural event, is similar to wound healing. We have now used the sea cucumber Holothuria glaberrima to address this question. RESULTS: Animals were lesioned by making a 3-5 mm transverse incision between one of the longitudinal muscle pairs along the bodywall. Lesioned tissues included muscle, nerve, water canal and dermis. Animals were allowed to heal for up to four weeks (2, 6, 12, 20, and 28 days post-injury) before sacrificed. Tissues were sectioned in a cryostat and changes in cellular and tissue elements during repair were evaluated using classical dyes, immmuohistochemistry and phalloidin labeling. In addition, the temporal and spatial distribution of cell proliferation in the animals was assayed using BrdU incorporation. We found that cellular events associated with wound healing in H. glaberrima correspond to those previously shown to occur during intestinal regeneration. These include: (1) an increase in the number of spherule-containing cells, (2) remodeling of the extracellular matrix, (3) formation of spindle-like structures that signal dedifferentiation of muscle cells in the area flanking the lesion site and (4) intense cellular division occurring mainly in the coelomic epithelium after the first week of regeneration. CONCLUSION: Our data indicate that H. glaberrima employs analogous cellular mechanisms during wound healing and organ regeneration. Thus, it is possible that regenerative limitations in some organisms are due either to the absence of particular mechanisms associated with repair or the inability of activating the repair process in some tissues or stages.

Identification of nerve plexi in connective tissues of the sea cucumber Holothuria glaberrima by using a novel nerve-specific antibody.

The echinoderm nervous system is one of the least studied among invertebrates, partly because the tools available to study the neurobiology of this phylum are limited. We have now produced a monoclonal antibody (RN1) that labels a nervous system component of the sea cucumber Holothuria glaberrima. Western blots show that our antibody recognizes a major band of 66 kDa and a minor band of 53 kDa. Immunohistological experiments show that, in H. glaberrima, the antibody distinctly labels most of the known nervous system structures and some components that were previously unknown or little studied. A surprising finding was the labeling of nervous plexi within the connective tissue compartments of all organs studied. Double labeling with holothurian neuropeptides and an echinoderm synaptotagmin showed that RN1 labeled most, if not all, of the fibers labeled by these neuronal markers, but also a larger component of cells and fibers. The presence of a distinct connective tissue plexus in holothurians is highly significant since these organisms possess mutable connective tissues that change viscosity under the control of the nervous system. Therefore, the cells and fibers recognized by our monoclonal antibodies may be involved in controlling tensility changes in echinoderm connective tissue.