Functional and molecular identification of a TASK-1 potassium channel regulating chloride secretion through CFTR channels in the shark rectal gland: implications for cystic fibrosis.

In the shark rectal gland (SRG), apical chloride secretion through CFTR channels is electrically coupled to a basolateral K+ conductance whose type and molecular identity are unknown. We performed studies in the perfused SRG with 17 K+ channel inhibitors to begin this search. Maximal chloride secretion was markedly inhibited by low-perfusate pH, bupivicaine, anandamide, zinc, quinidine, and quinine, consistent with the properties of an acid-sensitive, four-transmembrane, two-pore-domain K+ channel (4TM-K2P). Using PCR with degenerate primers to this family, we identified a TASK-1 fragment in shark rectal gland, brain, gill, and kidney. Using 5' and 3' rapid amplification of cDNA ends PCR and genomic walking, we cloned the full-length shark gene (1,282 bp), whose open reading frame encodes a protein of 375 amino acids that was 80% identical to the human TASK-1 protein. We expressed shark and human TASK-1 cRNA in Xenopus oocytes and characterized these channels using two-electrode voltage clamping. Both channels had identical current-voltage relationships (outward rectifying) and a reversal potential of -90 mV. Both were inhibited by quinine, bupivicaine, and acidic pH. The pKa for current inhibition was 7.75 for shark TASK-1 vs. 7.37 for human TASK-1, values similar to the arterial pH for each species. We identified this protein in SRG by Western blot and confocal immunofluorescent microscopy and detected the protein in SRG and human airway cells. Shark TASK-1 is the major K+ channel coupled to chloride secretion in the SRG, is the oldest 4TM 2P family member identified, and is the first TASK-1 channel identified to play a role in setting the driving force for chloride secretion in epithelia. The detection of this potassium channel in mammalian lung tissue has implications for human biology and disease.

Postanesthesia care unit imaging is unnecessary when intraoperative imaging is used during anterior cervical decompression and fusion procedures.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To characterize the clinical utility of imaging in the postanesthesia care unit (PACU) after anterior cervical decompression and fusion (ACDF) procedures. SUMMARY OF BACKGROUND DATA: Two sets of imaging are often taken at the end of ACDF procedures: one intraoperatively and the other in the PACU. The latter may have low clinical utility. MATERIALS AND METHODS: One hundred four patients who underwent ACDF procedures with anterior plate/screw constructs were identified. A panel assessed intraoperative and PACU series for adequacy of images to detect potential issues with placement of the surgical construct and for any actual visible issues with placement of the surgical construct. RESULTS: Intraoperative series were adequate to detect potential issues with construct placement for 78.8% of cases, whereas PACU series were adequate for only 58.7% of cases (significant difference, P<0.001). For both series, nearly all inadequacies were because of the shoulders obstructing the lateral view. Accordingly, cases with lower inferior operative levels were much more likely to have inadequate intraoperative and PACU series than cases with higher inferior operative levels (significant differences, P<0.001 for both). In no case was an issue with construct placement visible on a PACU series that was not also visible on an intraoperative series. CONCLUSIONS: This study demonstrates that PACU images are inferior to intraoperative images and offer little or no incremental clinical utility for detecting issues with surgical construct placement after ACDF procedures. PACU imaging after ACDF procedures might be discontinued to realize savings in time, cost, and radiation exposure.

Alternatives to Traditional Pedicle Screws for Posterior Fixation of the Degenerative Lumbar Spine.

BACKGROUND: Traditional pedicle screws are currently the gold standard to achieve stable 3-column fixation of the degenerative lumbar spine. However, there are cases in which pedicle screw fixation may not be ideal. Due to their starting point lateral to the pars interarticularis, pedicle screws require a relatively wide dissection along with a medialized trajectory directed toward the centrally located neural elements and prevertebral vasculature. In addition, low bone mineral density remains a major risk factor for pedicle screw loosening, pullout, and pseudarthrosis. The purpose of this article is to review the indications, advantages, disadvantages, and complications associated with posterior fixation techniques of the degenerative lumbar spine beyond the traditional pedicle screws. METHODS: Comprehensive literature searches of the PubMed, Scopus, and Web of Science databases were performed for 5 methods of posterior spinal fixation, including (1) cortical bone trajectory (CBT) screws, (2) transfacet screws, (3) translaminar screws, (4) spinous process plates, and (5) fusion mass screws and hooks. Articles that had been published between January 1, 1990, and January 1, 2020, were considered. Non-English-language articles and studies involving fixation of the cervical or thoracic spine were excluded from our review. RESULTS: After reviewing over 1,700 articles pertaining to CBT and non-pedicular fixation techniques, a total of 284 articles met our inclusion criteria. CBT and transfacet screws require less-extensive exposure and paraspinal muscle dissection compared with traditional pedicle screws and may therefore reduce blood loss, postoperative pain, and length of hospital stay. In addition, several methods of non-pedicular fixation such as translaminar and fusion mass screws have trajectories that are directed away from or posterior to the spinal canal, potentially decreasing the risk of neurologic injury. CBT, transfacet, and fusion mass screws can also be used as salvage techniques when traditional pedicle screw constructs fail. CONCLUSIONS: CBT and non-pedicular fixation may be preferred in certain lumbar degenerative cases, particularly among patients with osteoporosis. Limitations of non-pedicular techniques include their reliance on intact posterior elements and the lack of 3-column fixation of the spine. As a result, transfacet and translaminar screws are infrequently used as the primary method of fixation. CBT, transfacet, and translaminar screws are effective in augmenting interbody fixation and have been shown to significantly improve fusion rates and clinical outcomes compared with stand-alone anterior lumbar interbody fusion. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The Pedicles Are Not the Densest Regions of the Lumbar Vertebrae: Implications for Bone Quality Assessment and Surgical Treatment Strategy.

STUDY DESIGN: Cadaver study. OBJECTIVE: To determine the bone density of lumbar vertebral anatomic subregions. Bone mineral density (BMD) is a major factor in osseous fixation construct strength. The standard region for implant fixation of the spine is the pedicle; however, other regions may be more viable options with higher bone quality. METHODS: Using computed tomography images, the spine was digitally isolated by applying a filter for adult bone. The spine model was separated into 5 lumbar vertebrae, followed by segmentation of each vertebra into 7 regions and determination of average Hounsfield units (HU). HU was converted to BMD with calibration phantoms of known BMD. RESULTS: Overall mean BMD in vertebral regions ranged from 172 to 393 mg/cm3 with the highest and lowest BMD in the lamina and vertebral body, respectively. Vertebral regions formed 3 distinct groups (P < .03). The vertebral body and transverse processes represent one group with significantly lower BMD than other regions. Spinous process, pedicles, and superior articular processes represent a second group with moderate BMD. Finally, inferior articular process (IAP) and lamina represent a third group with significantly higher BMD than other regions. CONCLUSIONS: Standard lumbar fusion currently uses the vertebral body and pedicles as primary locations for fixation despite their relatively low BMD. Utilization of posterior elements, especially the lamina and IAP, may be advantageous as a supplement to modern constructs or the primary site for fixation, possibly mitigating construct failures due to loosening or pullout.

A Genetic Test Predicts Providence Brace Success for Adolescent Idiopathic Scoliosis When Failure Is Defined as Progression to >45 Degrees.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To determine whether a genetic test is associated with successful Providence bracing for adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Genetic factors have been defined that predict the risk of progression of AIS in a polygenic fashion. From these data, a commercially available genetic test, ScoliScore, was developed. It is now used in clinical practice for counseling and to guide clinical management. Bracing is a mainstay of treatment for AIS. Large efforts have been made recently to reduce potential confounding across studies of different braces; however, none of these have considered genetics as a potential confounder. In particular, ScoliScore has not been evaluated in a population undergoing bracing. METHODS: We conducted a retrospective cohort study in which we identified a population of AIS patients who were initiated with Providence bracing and followed over time. Although these patients did not necessarily fit the commercial indications for ScoliScore, we contacted the patients and obtained a saliva sample from each for genetic analysis. We then tested whether ScoliScore correlated with the outcome of their bracing therapy. RESULTS: We were able to contact and invite 25 eligible subjects, of whom 16 (64.0%) returned samples for laboratory analysis. Patients were followed for an average of 2.3 years (range, 1.1-4 y) after initiation of the Providence brace. Eight patients (50.0%) progressed to >45 degrees, whereas the other 8 patients (50.0%) did not. The mean ScoliScore among those who progressed to >45 degrees was higher than that among those who did not (176 vs. 112, P=0.030). CONCLUSIONS: We demonstrate that a genetic test correlates with bracing outcome. It may be appropriate for future bracing studies to include analysis of genetic predisposition to limit potential confounding.

Biomechanical demands on posterior fusion instrumentation during lordosis restoration procedures.

OBJECTIVE The goal of this study was to investigate the forces placed on posterior fusion instrumentation by 3 commonly used intraoperative techniques to restore lumbar lordosis: 1) cantilever bending; 2) in situ bending; and 3) compression and/or distraction of screws along posterior fusion rods. METHODS Five cadaveric torsos were instrumented with pedicle screws at the L1-5 levels. Specimens underwent each of the 3 lordosis restoration procedures. The pedicle screw pullout force was monitored in real time via strain gauges that were mounted unilaterally at each level. The degree of correction was noted through fluoroscopic imaging. The peak loads experienced on the screws during surgery, total demand on instrumentation, and resting loads after corrective maneuvers were measured. RESULTS A mean overall lordotic correction of 10.9 ± 4.7° was achieved. No statistically significant difference in lordotic correction was observed between restoration procedures. In situ bending imparted the largest loads intraoperatively with an average of 1060 ± 599.9 N, followed by compression/distraction (971 ± 534.1 N) and cantilever bending (705 ± 413.0 N). In situ bending produced the largest total demand and postoperative loads at L-1 (1879 ± 1064.1 and 487 ± 118.8 N, respectively), which were statistically higher than cantilever bending and compression/distraction (786 ± 272.1 and 138 ± 99.2 N, respectively). CONCLUSIONS In situ bending resulted in the highest mechanical demand on posterior lumbar instrumentation, as well as the largest postoperative loads at L-1. These results suggest that the forces generated with in situ bending indicate a greater chance of intraoperative instrumentation failure and postoperative proximal pedicle screw pullout when compared with cantilever bending and/or compression/distraction options. The results are aimed at optimizing correction and fusion strategies in lordosis restoration cases.

Effectiveness of Providence nighttime bracing in patients with adolescent idiopathic scoliosis.

Interest has increased in adolescent idiopathic scoliosis braces that are worn only part time. One such brace, the Providence brace, is being used with increasing frequency despite limited literature evaluating its ability to alter the natural course of disease. The authors retrospectively identified 34 patients meeting modified Scoliosis Research Society (SRS) inclusion criteria who were treated with the Providence brace. In accordance with SRS criteria, patients were followed for progression more than 5°, progression to more than 45°, and recommendation for or performance of surgical fusion. Seventeen (50%) patients progressed more than 5°, and 9 (26%) progressed to more than 45° and had fusion surgery recommended or performed. Noncompliance was associated with progression to more than 45° (P=.045) and having fusion surgery recommended or performed (P=.045). Males had a higher rate of progression more than 5° than did females (100% vs 41%; P=.015). This is only the second study of the Providence brace to be guided by SRS criteria. The somewhat higher rates of progression more than 5° reported in these 2 studies compared with those reported in earlier studies likely result from this distinction. This study suggests a rate of progression that is similar to or lower than rates reported in natural history studies, possibly supporting the efficacy of the Providence brace. Additional studies using SRS criteria, including high-quality randomized, controlled trials, will be important to further understanding the relative effectiveness of this and other bracing protocols.

Commentary: revision lumbar surgery and revisiting the role of preoperative depression screening.

COMMENTARY ON: Adogwa O, Parker SL, Shau DN, et al. Preoperative Zung Depression Scale predicts outcome after revision lumbar surgery for adjacent segment disease, recurrent stenosis, and pseudarthrosis. Spine J 2012;12:179-85 (in this issue).

Do presence and location of annular tear influence clinical outcome after lumbar total disc arthroplasty? A prospective 1-year follow-up study.

BACKGROUND: Lumbar total disc arthroplasty is often performed in patients with axial back pain. There are multiple etiologies for axial back pain, including disc degeneration and annular tears. The location of these annular tears can vary, producing differing preoperative symptomatology. Intraoperatively, disruptions in the annulus are identifiable, and it has been suggested that patients with discrete annular tears may have better clinical outcomes after surgery. The purpose of this study was to investigate whether the presence and location of annular tears have an effect on clinical outcomes after lumbar total disc arthroplasty. METHODS: Patients undergoing a single-level anterior disc replacement from L3-S1 at a single site by a single surgeon were evaluated preoperatively for the presence or absence of annular tears with magnetic resonance imaging. All patients were part of either the ProDisc (n = 41) (Synthes, Paoli, Pennsylvania) or Activ-L (n = 19) (Aesculap [B. Braun Melsungen AG], Tuttlingen, Germany) lumbar prospective clinical trials. In those patients with annular tears, the location of the tear (central, paracentral, or lateral) was documented. Patients were assessed at 6 and 12 months after lumbar total disc arthroplasty with the Oswestry Disability Index (ODI), visual analog scale (VAS) score for back pain, VAS score for leg pain, and radiographic imaging. All radiographic evaluations were conducted by an attending neuroradiologist and an attending spinal surgeon, and reliability testing was performed. An analysis of variance was performed among the 3 anatomic locations of annular tears. RESULTS: A total of 60 patients were included and had complete 12-month follow-up. The prevalence of annular tears among all patients was 42% (n = 25). Outcome data in patients without annular tears were as follows: ODI, 66% preoperatively and 26% postoperatively; VAS score for back pain, 8.0 preoperatively and 2.6 postoperatively; and VAS score for leg pain, 2.9 preoperatively and 1.2 postoperatively. Among those patients with tears, the prevalence of central tears was 80%, the prevalence of paracentral tears was 12%, and the prevalence of lateral tears was 8%. Outcome data in patients with central tears were as follows: ODI, 66% preoperatively and 26% postoperatively; VAS score for back pain, 7.8 preoperatively and 2.6 postoperatively; and VAS score for leg pain, 5.2 preoperatively and 0.5 postoperatively. Outcome data in patients with paracentral tears were as follows: ODI, 86% preoperatively and 59% postoperatively; VAS score for back pain, 8.8 preoperatively and 3.3 postoperatively; and VAS score for leg pain, 5.0 preoperatively and 5.4 postoperatively. Outcome data in patients with lateral tears were as follows: ODI, 6.5 preoperatively and 2.6 postoperatively; VAS score for back pain, 9.2 preoperatively and 0.2 postoperatively; and VAS score for leg pain, 1.4 preoperatively and 0.7 postoperatively. In those patients with paracentral tears, there was a significantly higher incidence of postoperative radicular symptoms both from an intensity standpoint and from a duration standpoint. Other complications did not vary among those patients with or without annular tears. CONCLUSIONS: Although patients with annular tears and patients without annular tears improve after lumbar artificial disc replacement, those with central annular tears or without tears have significantly lower disability scores than those with paracentral tears or lateral tears, whose outcome scores showed significantly less improvement (P ≤ .03). In particular, patients with central tears have less postoperative leg pain than those with paracentral annular tears. In this study the presence or absence of an annular tear on magnetic resonance imaging was not a significant predictive factor for clinical outcome. Further investigation regarding the effects of paracentral annular tears and surgical techniques should be explored.

Routine anteroposterior radiographs have limited utility for patients after anterior cervical decompression and fusion.

STUDY DESIGN: A retrospective case series. OBJECTIVE: To assess the diagnostic utility of sequential anteroposterior (AP) radiographs for following patients with postoperative anterior cervical decompression and fusion (ACDF). SUMMARY OF BACKGROUND DATA: There are currently no widely accepted standards for radiographical follow-up after ACDF. Many spine surgeons routinely obtain at least AP and lateral films at serial follow-up visits. It is generally accepted that lateral films are of utility to assess overall alignment, evaluate union, and detect any potential construct-related issues. It is our perception that the AP view adds little or no clinical value after documentation of alignment on an initial film. METHODS: All follow-up imaging series were evaluated for 100 patients who underwent ACDF. Variables thought to be potentially detected on the AP film were evaluated on both the AP and lateral films (visualization of the implant and instrumented vertebral bodies and any construct-related issues). In addition, angulation of the implant relative to the vertebral axis of the instrumented levels was measured on the AP film. RESULTS: For the 100 patients evaluated, the follow-up period was 1.2 ± 0.5 months (mean ± SD), with 4.39 ± 1.52 imaging series obtained per patient. Instrumented vertebral bodies were fully visualized in 99.5% of AP and 86.7% of lateral films obtained at follow-up visits. The entire implant was visualized in 100% of AP films and 95.6% of lateral films. No hardware-related issues were seen (screw disengagement, pullout, breakage, etc.). No patients were found to have progression of coronal plate angulation beyond 3° at their last follow-up series relative to the first follow-up visit. CONCLUSION: Using rigorous evaluation methods, we found no significant incremental utility of AP films obtained in addition to lateral films. Therefore, given the inherent cost, time, and radiation exposure associated with each additional view, we propose that AP films should not be part of routine follow-up imaging after ACDF.

Neck motion due to the halo-vest in prone and supine positions.

STUDY DESIGN: An in vitro biomechanical study of the effectiveness of halo-vest fixation. OBJECTIVE: The objective was to evaluate motion of the injured cervical spine with normal halo-vest application and vest loose in the prone and supine positions. SUMMARY OF BACKGROUND DATA: Snaking motion of the neck is defined as rotation in opposing directions throughout the cervical spine. Previous clinical studies have suggested snaking neck motion due to the halo-vest may lead to inadequate healing or nonunion. METHODS: The halo-vest was applied to a Human Model of the Neck, which consisted of a cervical spine specimen mounted to the torso of an anthropometric test dummy and carrying a surrogate head. The model was transitioned from prone, to upright, to supine with the halo-vest applied normally and with the vest loose. Average peak spinal motions were computed in the prone and supine positions and contrasted with the physiologic rotation range, obtained from the intact flexibility test, and statistically compared (P < 0.05) between normal halo-vest application and vest loose. RESULTS: Snaking motion of the neck was observed in the prone and supine positions, consisting of extension at head/C1 and C1/2 and flexion at the inferior spinal levels. The intervertebral rotation peaks generally exceeded the physiologic range throughout the cervical spine due to the loose vest in the prone position. Significant increases in the extension peaks at head/C1 (16.9 degrees vs. 5.7 degrees) and flexion peaks at C4/5 (6.9 degrees vs. 3.6 degrees) and C7-T1 (5.2 degrees vs. 0.7 degrees) were observed in the prone position due to the loose vest, as compared to normal halo-vest application. Axial neck separation was consistently observed in the prone and supine positions. CONCLUSION: The present results, which document snaking motion of the cervical spine due to the halo-vest, indicate that an inadequately fitting or loose vest may significantly diminish its immobilization capacity leading to delayed healing or nonunion.