Proximal foundation anchor variations and their correlation with unplanned return to the operating room (UPROR) in children with EOS treated with magnetically controlled growing rods (MCGR).

INTRODUCTION: The evolution of MCGR technique has led to modifications in the configuration of the proximal construct to decrease the incidence of implant-related complications (IRC) and revision surgeries. However, there is no data characterizing the performance of the most used configurations reducing the risk of complications. METHODS: 487 patients were identified from an international multicenter EOS database. INCLUSION CRITERIA: EOS patients, primary dual MCGR, complete radiographs, and minimum of 2-year follow-up. 76 patients had incomplete X-rays, 5 had apical fusions, and 18 had inconclusive complications, leaving 388 patients for review. A digital spine template was created to document UIV; number of levels; number, type, and location of anchors; as well as implant configuration. First available postoperative and latest follow-up radiographs were reviewed by two senior surgeons and two spine fellows. UPROR due to IRC was defined as any change in proximal anchors between the postoperative and final follow-up radiographs. RESULTS: The most common proximal construct configuration: UIV at T2 (50.0%) with 17.5% UPROR, followed by T3 (34.0%) with 12.1% UPROR; number of levels was three (57.1%) with 16.8% UPROR and two (26.0%) with 17.0% UPROR; number of proximal anchors was six (49.9%) with 14.1% UPROR and four (27.0%) with 18.3% UPROR. The most common anchors were all screws (42.0%) with 9.9% UPROR, and all hooks (26.4%) with 31.4% UPROR (P < 0.001). The construct with the lowest rate of UPROR was a UIV at T2, with six anchors (all screws) across three levels (42 cases), with 0% UPROR. Other construct combinations that yielded 0% UPROR rates were UIV of T3, six anchors (all screws) across three levels (25 cases), and a UIV of T3 with six anchors (screws and hooks) across three3 levels (9 cases). CONCLUSION: Proximal anchor configuration impacts the incidence of UPROR due to IRC in MCGR. UIV at T2 and T3 compared to T4, and the use of all screws or combination of screws and hooks compared to all hooks were associated with a lower UPROR rate. The most common construct configuration was T2 UIV, three levels, six anchors, and all screws. The use of a combination of six anchors (screws or screws and hooks) across three levels with a UIV at T2 or T3 was associated with a lower UPROR rate. Additional research is needed to further evaluate the variables contributing to configuration selection and their association with IRC.

Fishery catch records support machine learning-based prediction of illegal fishing off US West Coast.

Illegal, unreported, and unregulated (IUU) fishing is a major problem worldwide, often made more challenging by a lack of at-sea and shoreside monitoring of commercial fishery catches. Off the US West Coast, as in many places, a primary concern for enforcement and management is whether vessels are illegally fishing in locations where they are not permitted to fish. We explored the use of supervised machine learning analysis in a partially observed fishery to identify potentially illicit behaviors when vessels did not have observers on board. We built classification models (random forest and gradient boosting ensemble tree estimators) using labeled data from nearly 10,000 fishing trips for which we had landing records (i.e., catch data) and observer data. We identified a set of variables related to catch (e.g., catch weights and species) and delivery port that could predict, with 97% accuracy, whether vessels fished in state versus federal waters. Notably, our model performances were robust to inter-annual variability in the fishery environments during recent anomalously warm years. We applied these models to nearly 60,000 unobserved landing records and identified more than 500 instances in which vessels may have illegally fished in federal waters. This project was developed at the request of fisheries enforcement investigators, and now an automated system analyzes all new unobserved landings records to identify those in need of additional investigation for potential violations. Similar approaches informed by the spatial preferences of species landed may support monitoring and enforcement efforts in any number of partially observed, or even totally unobserved, fisheries globally.

Risk Stratification Algorithm for Orthopedic Trauma Patients at Risk for Fat Embolism Syndrome.

BACKGROUND: Fat embolism syndrome (FES) is commonly reported in the setting of long bone and pelvic fractures, but the etiology and pathogenesis are unclear. The aim of this study was to identify clinical characteristics and laboratory findings that may place orthopedic trauma patients at a higher risk of developing FES. METHODS: Electronic medical records were reviewed of all patients aged 18-89 years from 2015 to 2020 with a mention of FES in the patient chart who met Gurd and Wilson's criteria for diagnosis after experiencing orthopedic trauma. A 3:1 matched pair analysis was performed between FES patients and those with similar age, gender, and FES-associated fracture (femur, tibia, humerus, or pelvis fracture). RESULTS: 18 patients with FES who met inclusion criteria were identified. Hypomagnesemia (OR = 7.43), hyperphosphatemia (OR = 6.24), hypoalbuminemia (OR = 3.78), blunt traumatic mechanism of injury (OR = 7.16) and a greater number of bones fractured (Avg/SD = 2.89/1.53) were seen more often in FES patients (all p-values < 0.05). CONCLUSION: Findings of this study suggest that patients with hypomagnesemia, hyperphosphatemia, hypoalbuminemia, a blunt trauma mechanism of injury, and an increased number of bones fractured are at increased risk for the development of FES. This may be related to their roles in physiologic oncotic pressure and inflammatory response, and thus further investigation of these variables is necessary for the evaluation of FES prevention. LEVEL OF EVIDENCE: Level 3.

Prospective Follow-up Report on Anterior Vertebral Body Tethering for Idiopathic Scoliosis: Interim Results from an FDA IDE Study.

BACKGROUND: Anterior vertebral body tethering (aVBT) has emerged as a novel treatment option for patients with idiopathic scoliosis. We present the results from the first U.S. Food and Drug Administration (FDA) Investigational Device Exemption (IDE) study on aVBT. METHODS: In this prospective review of a retrospective data set, eligible patients underwent aVBT at a single center from August 2011 to July 2015. Inclusion criteria included skeletally immature patients with Lenke type-1A or 1B curves between 30° and 65°. Clinical and radiographic parameters were collected, with the latter measured by an independent reviewer. RESULTS: Fifty-seven patients (49 girls and 8 boys), with a mean age (and standard deviation) of 12.4 ± 1.3 years (range, 10.1 to 15.0 years), were enrolled in the study. The patients had a mean of 7.5 ± 0.6 levels tethered, the mean operative time was 223 ± 79 minutes, and the mean estimated blood loss was 106 ± 86 mL. The patients were followed for an average of 55.2 ± 12.5 months and had a mean Risser grade of 4.2 ± 0.9 at the time of the latest follow-up. The main thoracic Cobb angle was a mean of 40.4° ± 6.8° preoperatively and was corrected to 18.7° ± 13.4° at the most recent follow-up. In the sagittal plane, T5-T12 kyphosis measured 15.5° ± 10.0° preoperatively, 17.0° ± 10.1° postoperatively, and 19.6° ± 12.7° at the most recent follow-up. Eighty percent of patients had curves of <30° at the most recent follow-up. The most recent Scoliosis Research Society (SRS) scores averaged 4.5 ± 0.4, and scores on the self-image questionnaire averaged 4.4 ± 0.7. No major neurologic or pulmonary complications occurred. Seven (12.3%) of 57 patients had a revision: 5 were done for overcorrection and 2, for adding-on. CONCLUSIONS: Anterior VBT is a promising technique that has emerged as a treatment option for patients with immature idiopathic scoliosis. We present the results from the first FDA-approved IDE study on aVBT, which formed the basis for the eventual Humanitarian Device Exemption approval. The findings affirm the safety and efficacy of this technique and suggest opportunities for improvement, particularly with respect to reoperation rates. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Prevalence of Venous Thromboembolism Following Acute Spinal Cord Injury in an Urban Inner City Hospital.

BACKGROUND: Venous thromboembolism (VTE) is known to occur at high rates in patients who suffer spinal cord injury (SCI). Large population studies in the United States have shown a prevalence of approximately 4-5%, with some studies suggesting higher prevalence. While the specific mechanism behind increased VTE incidence in the SCI population is unknown, it is likely tied to immobility and functional decline. Previous studies have also linked social determinants of health to higher VTE prevalence in certain populations. The purpose of this study is to determine the prevalence of VTE after acute SCI in the inner urban city population and to identify factors that place patients at increased VTE risk. METHODS: Patients who suffered SCI between 2014 and 2019 were identified from one inner city urban hospital. A retrospective chart review was completed to record the development of VTE after SCI. Medical comorbidities, type of thromboprophylaxis used, patient demographics, injury characteristics, and postinjury sequelae were compared between individuals who did and did not develop VTE. RESULTS: A total of 148 patients were included. These patients were from a low socioeconomic demographic when compared with the larger US population. Average household income based on zip code data for included patients was $56 647, $30 315 below the national average. The prevalence of VTE in this patient population was 19.59%. Weight, deep vein thrombosis history, chemoprophylaxis use, mobility impairment postinjury, neurologic level of SCI, malignancy history, and history of smokeless tobacco were associated with VTE (all P < .05). Low molecular weight heparin (LMWH) use was associated with fewer occurrences of VTE (P < .001). CONCLUSION: Patients from our urban inner city hospital have a higher VTE prevalence after SCI than shown in previous US-based studies. These patients may be at increased risk due to increased numbers of medical comorbidities, social factors, or undiagnosed medical conditions. Thromboprophylaxis with LMWH appears to lower the risk of VTE after SCI. LEVEL OF EVIDENCE: 3. CLINICAL RELEVANCE: Patients with the previously mentioned risk factors are at increased risk for VTE development during their acute recovery process. These patients should have a much lower screening threshold for VTE evaluation and likely would benefit from more routine screening to prevent complications related to VTE development or progression. Furthermore, these patients should, when medically appropriate, be treated with low molecular weight heparin for VTE prophylaxis as previously recommended by the Consortium for Spinal Cord Medicine.

Scheuermann's Kyphosis: Diagnosis, Management, and Selecting Fusion Levels.

Scheuermann's kyphosis (SK) is a rigid structural deformity of the thoracic spine defined radiographically as three or more contiguous vertebrae with at least 5° of wedging anteriorly. Prevalence of the disease is thought to be between 0.4% and 10%. The true cause of SK remains unclear; however, various theories include growth irregularities, mechanical factors, genetic factors, and/or poor bone quality as the causes. Patients with mild disease (less than 70°) generally have a favorable prognosis with good clinical outcomes. Most patients with SK are successfully treated nonsurgically with observation, anti-inflammatory medications, and physical therapy. Surgical intervention is indicated in patients with greater than 70° to 75° thoracic curves, greater than 25° to 30° thoracolumbar curves, intractable pain, neurologic deficit, cardiopulmonary compromise, or poor cosmesis. Because of advances in posterior spinal instrumentation, surgery can typically be performed through a posterior-only approach. When surgical treatment is planned, appropriate selection of the upper- and lower-instrumented vertebrae is important to achieve a well-balanced spine, preserve motion segments, and reduce the risk of junctional kyphosis.

Outcomes of patients with syringomyelia undergoing spine deformity surgery: do large syrinxes behave differently from small?

BACKGROUND CONTEXT: A paucity of data exists studying outcomes of patients with syringomyelia undergoing spinal deformity correction. The literature does not stratify patients by syrinx size, which is likely a major contributor to outcomes. PURPOSE: The study aimed to compare differences in outcomes between patients with large (≥4 mm) and small syrinxes (<4 mm) undergoing spinal deformity correction. DESIGN: This is a retrospective review. PATIENT SAMPLE: The sample included 28 patients (11 with large syrinx [LS, >4 mm] and 17 with small syrinx [SS, <4 mm]). OUTCOME MEASURES: The outcome measures were radiographic, operative, and neurophysiological measures. METHODS: We retrospectively reviewed 28 patients with syringomyelia who underwent spine deformity surgery with 2-year follow-up. Demographic, surgical, and radiographic data were collected and compared preoperatively and at 2 years. RESULTS: The LS group (11 patients) trended toward more left-sided thoracic curves (36% vs. 18%, p=.38) and was more likely to have had a Chiari decompression (45% vs. 12%, p=.08). The LS patients had larger preoperative major curves (LS=66° vs. SS=57°, p=.05), more thoracic kyphosis (LS=42°, SS=24°, p<.01), and greater rib prominences (LS=16°, SS=13°, p=.04). The LS patients had more levels fused (LS=12.2, SS=11.2, p=.05), higher estimated blood loss (EBL) (LS=1068 cc, SS=832 cc, p=.04), and a trend toward less percent correction of the major curve (LS=57%, SS=65%, p=.18). Four of 11 LS patients (36%) did not have somatosensory evoked potentials, and one of these also did not have motor evoked potentials. Neuromonitoring changes occurred in 3 of 11 (27%) LS patients and in none of the SS patients, with no postoperative deficits. CONCLUSIONS: Outcomes of patients with syringomyelia undergoing spine deformity surgery are dependent on the size of the syrinx. Those with large syringomyelia are fused longer with more EBL and less correction. Spine surgeons should be aware that these patients are more likely to have less reliable neuromonitoring, with a higher chance of experiencing a change.

Factors affecting the outcome in appearance of AIS surgery in terms of the minimal clinically important difference.

PURPOSE: The minimal clinically important difference (MCID) of the Appearance domain of the SRS-22 questionnaire is an increase ≥1.0 in surgically treated patients with adolescent idiopathic scoliosis (AIS). However, no study has sought to identify the factors associated with an SRS-22 Appearance score increase greater than the MCID at 2 years. METHODS: A retrospective analysis was performed on a prospectively collected multicenter database of 1020 surgically treated AIS patients with a minimum 2-year follow-up. Patients were divided into two cohorts: "I" = Improved after surgery (Δ Appearance ≥1.0) and "NI" = Not improved after surgery (Δ Appearance <1.0). Univariate regression was used to find a significant difference between the cohorts for individual measures. Multivariate logistic regression was used to find continuous predictors. RESULTS: 663 (65%) patients were improved greater than the MCID, and 357 were not improved (35%). The improved cohort trended toward a greater percentage of underweight patients (p = 0.074) with lower preoperative SRS Appearance scores (p < 0.001) and larger preoperative trunk shifts (p = 0.033). Postoperatively, those patients with greater percent correction of thoracic (p = 0.021) and lumbar (p = 0.003) Cobb angles, smaller apical lumbar translation (p = 0.006), and a greater correction in trunk shift (p = 0.003) were most likely to attain the MCID. CONCLUSION: Several factors influence which patients are most likely to attain the MCID following surgery for AIS. Factors such as preoperative appearance scores and body weight are patient specific; other factors such as percent correction of the thoracic and lumbar Cobb angles, trunk shift, and lumbar apical translation may be influenced by the surgeon. LEVEL OF EVIDENCE: II.

Reversible Intraoperative Neurophysiologic Monitoring Alerts in Patients Undergoing Arthrodesis for Adolescent Idiopathic Scoliosis: What Are the Outcomes of Surgery?

BACKGROUND: Confidence in intraoperative neurophysiologic monitoring (IONM) data can allow scoliosis surgeons to proceed with surgery even after a monitoring alert, assuming the recovery of signals. We sought to determine the outcomes of surgical treatment of adolescent idiopathic scoliosis (AIS) after a notable IONM alert. METHODS: We identified 676 patients who underwent arthrodesis with use of IONM for the treatment of AIS. The patients were divided into 2 cohorts: those who experienced a lower-extremity IONM alert and those who did not. An alert was defined as a notable change in IONM data, specifically, a ≥50% drop in somatosensory evoked potentials (SSEPs) and/or in transcranial motor evoked potentials (tcMEPs). RESULTS: Of the 676 patients, 36 (5.3%) experienced IONM alerts. Those patients had a larger preoperative major Cobb angle (mean of 61° ± 13° compared with 55° ± 12° for the no-alert group; p < 0.01), a greater number of levels fused (mean of 12 ± 2 compared with 11 ± 2; p < 0.01), a longer operative duration (mean of 357 ± 157 minutes compared with 298 ± 117 minutes; p < 0.01), a higher estimated blood loss (1,857 ± 1,323 mL compared with 999 ± 796 mL; p < 0.01), and a greater volume of autologous blood transfused (mean of 527 ± 525 mL compared with 268 ± 327 mL; p < 0.01). Among patients who experienced an alert and had a completed operation (34 of 36 patients), mean postoperative radiographic measurements were similar to those of the no-alert group in terms of the percentage of correction of the major Cobb angle (alert, 66% ± 13%; no alert, 64% ± 19%; p = 0.53) and of rib prominence (alert, 49% ± 36%; no alert, 47% ± 46%; p = 0.83) and measurement of thoracic kyphosis (alert, 23° ± 10°; no alert, 22° ± 2°; p = 0.58). The Scoliosis Research Society (SRS)-22 outcome scores were also similar between the 2 cohorts. CONCLUSIONS: Notable IONM changes occurred in 5.3% of the patients who underwent arthrodesis for AIS. Those patients had larger preoperative deformity, a longer operative duration, a greater number of levels fused, a higher estimated blood loss, and a greater volume of autologous blood transfused. Return of IONM data guided the surgeon to safely complete the procedure in 34 of 36 patients, with correction similar to that of patients who did not experience an alert. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Gene Expression in Mammalian Cells Using BacMam, a Modified Baculovirus System.

BacMams are modified baculoviruses that contain mammalian expression cassettes for gene delivery and expression in mammalian cells. BacMams have become an integral part of the recombinant mammalian gene expression toolbox in research labs worldwide. Construction of transfer vectors is straightforward using basic molecular biology protocols. Virus generation is based on common methods used with the baculovirus insect cell expression system. BacMam transduction of mammalian cells requires minimal modifications to familiar cell culture methods. This chapter highlights the BacMam transfer vector pHTBV.

Identification and characterization of PERK activators by phenotypic screening and their effects on NRF2 activation.

Endoplasmic reticulum stress plays a critical role to restore the homeostasis of protein production in eukaryotic cells. This vital process is hence involved in many types of diseases including COPD. PERK, one branch in the ER stress signaling pathways, has been reported to activate NRF2 signaling pathway, a known protective response to COPD. Based on this scientific rationale, we aimed to identify PERK activators as a mechanism to achieve NRF2 activation. In this report, we describe a phenotypic screening assay to identify PERK activators. This assay measures phosphorylation of GFP-tagged eIF2α upon PERK activation via a cell-based LanthaScreen technology. To obtain a robust assay with sufficient signal to background and low variation, multiple parameters were optimized including GFP-tagged eIF2α BacMam concentration, cell density and serum concentration. The assay was validated by a tool compound, Thapsigargin, which induces phosphorylation of eIF2α. In our assay, this compound showed maximal signal window of approximately 2.5-fold with a pEC50 of 8.0, consistent with literature reports. To identify novel PERK activators through phosphorylation of eIF2α, a focused set of 8,400 compounds was screened in this assay at 10 µM. A number of hits were identified and validated. The molecular mechanisms for several selected hits were further characterized in terms of PERK activation and effects on PERK downstream components. Specificity of these compounds in activating PERK was demonstrated with a PERK specific inhibitor and in PERK knockout mouse embryonic fibroblast (MEF) cells. In addition, these hits showed NRF2-dependent anti-oxidant gene induction. In summary, our phenotypic screening assay is demonstrated to be able to identify PERK specific activators. The identified PERK activators could potentially be used as chemical probes to further investigate this pathway as well as the link between PERK activation and NRF2 pathway activation.

Management of spinal cord injury-related scoliosis using pedicle screw-only constructs.

OBJECT: Almost all pediatric patients who incur a spinal cord injury (SCI) will develop scoliosis, and younger patients are at highest risk for curve progression requiring surgical intervention. Although the use of pedicle screws is increasing in popularity, their impact on SCI-related scoliosis has not been described. The authors retrospectively reviewed the radiographic outcomes of pedicle screw-only constructs in all patients who had undergone SCI-related scoliosis correction at a single institution. METHODS: Medical records and radiographs from Shriner's Hospital for Children-Philadelphia for the period between November 2004 and February 2011 were retrospectively reviewed. RESULTS: Thirty-seven patients, whose mean age at the index surgery was 14.91±3.29 years, were identified. The cohort had a mean follow-up of 33.2±22.8 months. The mean preoperative coronal Cobb angle was 65.5°±25.7°, which corrected to 20.3°±14.4°, translating into a 69% correction (p<0.05). The preoperative coronal balance was 24.4±22.6 mm, with a postoperative measurement of 21.6±20.7 mm (p=1.00). Preoperative pelvic obliquity was 12.7°±8.7°, which corrected to 4.1°±3.8°, translating into a 68% correction (p<0.05). Preoperative shoulder balance, as measured by the clavicle angle, was 8.2°±8.4°, which corrected to 2.7°±3.1° (67% correction, p<0.05). Preoperatively, thoracic kyphosis measured 44.2°±23.7° and was 33.8°±11.5° postoperatively. Thoracolumbar kyphosis was 18.7°±12.1° preoperatively, reduced to 8.1°±7.7° postoperatively, and measured 26.8°±20.2° at the last follow-up (p<0.05). Preoperatively, lumbar lordosis was 35.3°±22.0°, which remained stable at 35.6°±15.0° postoperatively. CONCLUSIONS: Pedicle screw constructs appear to provide better correction of coronal parameters than historically reported and provide significant improvement of sagittal kyphosis as well. Although pedicle screws appear to provide good radiographic results, correlation with clinical outcomes is necessary to determine the true impact of pedicle screw constructs on SCI-related scoliosis correction.

Anterior vertebral body tethering for immature adolescent idiopathic scoliosis: one-year results on the first 32 patients.

PURPOSE: This retrospective chart review evaluates the clinical and radiographic outcomes of anterior vertebral body tethering (VBT) at 1-year follow-up. Anterior VBT offers a fusionless treatment option for skeletally immature patients with adolescent idiopathic scoliosis. It is a growth-modulation technique, which utilizes patients' growth to attain progressive scoliosis correction. Numerous animal models support its promise; however, clinical data remain sparse. METHODS: Clinical and radiographic data were retrospectively analyzed. We reviewed 32 patients who underwent thoracic VBT with a minimum one-year follow-up. Pertinent clinical and radiographic data were collected. ANOVA, Student's t test and Fisher's exact test were utilized to compare different time points. RESULTS: 32 patients with thoracic idiopathic scoliosis (72 % female) with a minimum one-year follow-up were identified; mean age at surgery was 12 years. All patients were considered skeletally immature pre-operatively; mean Risser score 0.42, mean Sanders score 3.2. Patients underwent tethering of an average of 7.7 levels (range 7-11). Median blood loss was 100 cc. The mean pre-operative thoracic curve magnitude was 42.8° ± 8.0° which corrected to 21.0° ± 8.5° on first erect and 17.9° ± 11.4° at most recent. The pre-operative lumbar curve of 25.2° ± 7.3° demonstrated progressive correction (first erect = 18.0° ± 7.1°, 1 year = 12.6° ± 9.4°, p < 0.00001). Thoracic axial rotation measured 13.4° pre-operatively and 7.4° at the most recent measurement (p < 0.00001). One patient experienced prolonged atelectasis which required a bronchoscopy; otherwise, no major complications were observed. CONCLUSIONS: Our early results indicate that anterior VBT is a safe and potentially effective treatment option for skeletally immature patients with idiopathic scoliosis. These patients experienced an improvement of their scoliosis with minimal major complications. However, longer term follow-up of this cohort will reveal the true benefits of this promising technique. LEVEL OF EVIDENCE: IV.

Anterior vertebral body tethering for idiopathic scoliosis: two-year results.

STUDY DESIGN: Retrospective review. OBJECTIVE: To report the 2-year results of the initial cohort undergoing anterior vertebral body tethering (VBT). SUMMARY OF BACKGROUND DATA: Anterior VBT is a promising new technique with abundant preclinical studies but very few clinical results. It is a growth modulation technique, which utilizes patients' growth to attain progressive correction of their scoliosis. We report 2-year results of the initial cohort undergoing this procedure. METHODS: After obtaining institutional review board approval, we retrospectively reviewed our first 11 consecutive patients who underwent anterior VBT with 2-year follow-up. We collected pertinent preoperative, intraoperative, and most recent clinical and radiographical data. Student t test and Fisher exact test were utilized to compare different time points. RESULTS: Eleven patients with thoracic idiopathic scoliosis (8 females) were identified, with a mean age of 12.3 ± 1.6 years. Preoperatively, all were skeletally immature (Sanders mean = 3.4 ± 1.1; Risser mean = 0.6 ± 1.1). All underwent tethering of an average of 7.8 ± 0.9 (range: 7-9) levels, with the most proximal being T5 and the most distal L2. Preoperative thoracic Cobb angle averaged 44.2 ± 9.0° and corrected to 20.3 ± 11.0° on first erect, with progressive improvement at 2 years (Cobb angle = 13.5 ± 11.6°, % correction = 70%; P < 0.00002). Similarly, the preoperative lumbar curve of 25.1 ± 8.7° demonstrated progressive correction (first erect = 14.9 ± 4.9°, 2 yr = 7.2 ± 5.1°, % correction = 71%; P < 0.0002). Thoracic axial rotation as measured by a scoliometer went from 12.4 ± 3.3° preoperatively to 6.9 ± 3.4° at the most recent measurement (P < 0.01). No major complications were observed. As anticipated, 2 patients returned to the operating room at 2 years postoperatively for loosening of the tether to prevent overcorrection. CONCLUSION: Anterior VBT is a promising technique for skeletally immature patients with idiopathic scoliosis. This technique can be performed safely and can result in progressive correction. LEVEL OF EVIDENCE: 4.

Development of phenotypic screening assays for γ-globin induction using primary human bone marrow day 7 erythroid progenitor cells.

Sickle cell anemia (SCA) is a genetic disorder of the ß-globin gene. SCA results in chronic ischemia with pain and tissue injury. The extent of SCA symptoms can be ameliorated by treatment with drugs, which result in increasing the levels of γ-globin in patient red blood cells. Hydroxyurea (HU) is a Food and Drug Administration-approved drug for SCA, but it has dose-limiting toxicity, and patients exhibit highly variable treatment responses. To identify compounds that may lead to the development of better and safer medicines, we have established a method using primary human bone marrow day 7 erythroid progenitor cells (EPCs) to screen for compounds that induce γ-globin production. First, human marrow CD34(+) cells were cultured and expanded for 7 days and characterized for the expression of erythroid differentiation markers (CD71, CD36, and CD235a). Second, fresh or cryopreserved EPCs were treated with compounds for 3 days in 384-well plates followed by γ-globin quantification by an enzyme-linked immunosorbent assay (ELISA), which was validated using HU and decitabine. From the 7408 compounds screened, we identified at least one new compound with confirmed γ-globin-inducing activity. Hits are undergoing analysis in secondary assays. In this article, we describe the method of generating fit-for-purpose EPCs; the development, optimization, and validation of the ELISA and secondary assays for γ-globin detection; and screening results.

The posterior pedicle screw construct: 5-year results for thoracolumbar and lumbar curves.

OBJECT: Several studies of the outcomes of patients with adolescent idiopathic scoliosis (AIS) with thoracolumbar and lumbar curves after treatment with posterior pedicle screws have been reported, but most of these studies reported only 2-year follow-up. The authors analyzed the radiographic and clinical outcomes of patients with thoracolumbar and lumbar curves treated with posterior pedicle screws after 5 years of follow-up. METHODS: A multicenter database was retrospectively queried to identify patients with AIS who underwent spinal fusion for Lenke 3C, 5C, and 6C curves. Radiographs from the following times were compared: preoperative, first follow-up visit, 1-year follow-up visit, 2-year follow-up visit, and 5-year follow-up visit. Chart review included scoliometer measurements, Scoliosis Research Society (SRS)-22 questionnaires, and complications requiring return to the operating room. RESULTS: Among 26 patients with Lenke 3C, 5C, and 6C curves, the mean (± SD) age was 14.6 ± 2.1 years. From the time of the preoperative radiographs to the 5-year follow-up radiographs, there was a statistically significant improvement in the mean coronal lumbar Cobb angles (p < 0.0001), and from the time of the first postoperative radiographs to the 5-year follow-up radiographs, the lumbar curve remained stable (p = 0.14). From the time of the preoperative radiographs to the 5-year follow-up radiographs, there was a statistically significant improvement in the mean coronal thoracic Cobb angles (p < 0.0001), and from the time of the first postoperative radiographs to the 5-year follow-up radiographs, the thoracic curve remained stable (p = 0.10). From the first postoperative visit to the 5-year follow-up visit, the thoracic kyphosis (T5-12) remained stable (p = 0.10), and from the time of the preoperative radiographs to the 5-year follow-up radiographs, the lumbar lordosis (T-12 to top of sacrum) remained stable (p = 0.44). From the preoperative visit to the 5-year follow-up visit, the coronal balance improved significantly (p < 0.05) and remained stable from the first postoperative visit to the 5-year follow-up visit (p = 0.20). The SRS-22 total scores improved significantly from before surgery to 5 years after surgery (p < 0.0001). No patients required reoperation because of complications. CONCLUSIONS: Correction of the coronal, sagittal, and axial planes in this cohort of patients was maintained from the first follow-up measurements to 5 years after surgery. In addition, at 5 years after surgery total SRS-22 scores and inclinometer readings were improved from preoperative scores and measurements.

Microbial-based inoculants impact nitrous oxide emissions from an incubated soil medium containing urea fertilizers.

There is currently much interest in developing crop management practices that will decrease NO emissions from agricultural soils. Many different approaches are being investigated, but to date, no studies have been published on how microbial inoculants affect NO emissions. This study was conducted to test the hypothesis that microbial-based inoculants known to promote root growth and nutrient uptake can reduce NO emissions in the presence of N fertilizers under controlled conditions. Carbon dioxide and CH fluxes were also measured to evaluate microbial respiration and determine the aerobic and anaerobic conditions of the incubated soil. The microbial-based treatments investigated were SoilBuilder (SB), a metabolite extract of SoilBuilder (SBF), and a mixture of four strains of plant growth-promoting spp. Experiments included two different N fertilizer treatments, urea and urea-NHNO 32% N (UAN), and an unfertilized control. Emissions of NO and CO were determined from soil incubations and analyzed with gas chromatography. After 29 d of incubation, cumulative NO emissions were reduced 80% by SB and 44% by SBF in soils fertilized with UAN. Treatment with spp. significantly reduced NO production on Days 1 and 2 of the incubation in soils fertilized with UAN. In the unfertilized treatment, cumulative emissions of NO were significantly reduced 92% by SBF. Microbial-based treatments did not reduce NO emissions associated with urea application. Microbial-based treatments increased CO emissions from soils fertilized with UAN, suggesting a possible increase in microbial activity. Overall, the results demonstrated that microbial-based inoculants can reduce NO emissions associated with N fertilizer application, and this response varies with the type of microbial-based inoculant and fertilizer.

The impact of direct vertebral body derotation on the lumbar prominence in Lenke Type 5C curves.

OBJECT: The thoracic rib hump, caused by axial rotation of the spine, is one of the most dissatisfying cosmetic features associated with adolescent idiopathic scoliosis (AIS). However, advances in instrumentation and surgical techniques, such as direct vertebral body derotation (DVBD), have allowed improved correction in the axial plane and the rib hump. In cases of thoracolumbar/lumbar curves (Lenke Type 5), the lumbar prominence can be equally disfiguring and is often associated with waist asymmetry, another cosmetic concern. Although DVBD has been evaluated in the thoracic spine, little is known about its impact on the lumbar spine. The authors investigated the outcomes of DVBD on the lumbar prominence. METHODS: A prospectively collected multicenter database was queried for pediatric patients with AIS and Lenke Type 5 curves. All patients who underwent thoracoplasty procedures were excluded. A total of 34 patients underwent surgical correction via a posterior-only approach using pedicle screw constructs. Nineteen patients underwent concurrent DVBD, and the remaining 15 patients served as a control group and did not undergo DVBD. All patients had a minimum of 2 years of follow-up. RESULTS: The mean age of the entire cohort was 14.9 ± 2.3 years, and the majority of patients were female (88%). All patients had Lenke Type 5C curves with a mean major curve of 46.0° ± 8.7°, which corrected to 13.7° ± 7.2° (70% correction). A mean of 10.7 ± 3.0 levels were fused. Only thoracic kyphosis was significantly different between the groups preoperatively. Similarly, postoperative radiographic parameters were comparable between the groups, with equivalent percentages of correction. Although improvement in the thoracic rib hump was comparable between the groups, the DVBD group had 56.2% correction of the lumbar prominence, and the control group had 76% improvement (p = 0.05). CONCLUSIONS: Although DVBD has been a valuable tool in the management of AIS, the authors' results suggest that its application for thoracolumbar curves may be limited. Further analysis with a larger cohort is required to better ascertain the impact of DVBD on thoracolumbar curves.

Comparison of 5-year outcomes between pedicle screw and hybrid constructs in adolescent idiopathic scoliosis.

OBJECT: Pedicle screw fixation has been theorized to provide better correction of scoliotic deformity, but controversy over the benefits of pedicle screw-only constructs remains, and the longer-term impact of pedicle screw fixation as compared with hybrid constructs is unclear. In this study, a retrospective review of a prospectively collected database was conducted to determine the longer-term impact of pedicle screw fixation as compared with hybrid constructs in patients with adolescent idiopathic scoliosis (AIS). METHODS: The authors retrospectively reviewed a multicenter database of pediatric patients (ages ≤ 18) from 1995 to 2006 and identified 127 patients with Lenke Type 1-4 AIS curves with a minimum 5 years of follow-up. Patients were divided into 2 cohorts based on whether they had undergone pedicle screw fixation or fixation with hybrid constructs. RESULTS: The mean main thoracic curvature of 56.1° ± 13.0°, which corrected to 14.9° ± 9.3°, translated into a mean correction of 73% (p < 0.01). The curve was 19.4° ± 10.6° at 2-year follow-up and 20.5° ± 10.4° at 5 years. When comparing preoperative parameters between the groups, differences were noted in the magnitude of the main thoracic curve (p = 0.04), flexibility of the main thoracic curve (p = 0.02), coronal balance (p = 0.04), T2-12 kyphosis (p = 0.02), and sex (p = 0.02). The pedicle screw cohort had fewer spinal segments instrumented (p < 0.01), fewer anterior releases performed (p = 0.02), and fewer thoracoplasties performed (p < 0.01). By 5 years of follow-up, significant differences were apparent between the two cohorts with respect to upper thoracic curvature (p = 0.01), T2-12 (p = 0.02) and T5-12 (p = 0.02) kyphosis, lumbar lordosis (p < 0.01), and sagittal balance (p = 0.01). CONCLUSIONS: Although some preoperative differences did exist, outcomes were comparable between hybrid and screw constructs at 2 and 5 years. However, hybrid constructs required more concurrent anterior releases and thoracoplasties to achieve similar results.

The development of a high-content screening binding assay for the smoothened receptor.

In this study, the development of an image-based high-content screening (HCS) binding assay for the seven-transmembrane (7TM) receptor Smoothened (Smo) is described. Using BacMam-based gene delivery of Smo, BODIPY-cyclopamine as a fluorescent probe, and a confocal imaging system, a robust 384-well assay that could be used for high-throughput compound profiling activities was developed. The statistically robust HCS binding assay was developed through optimization of multiple parameters, including cell transduction conditions, Smo expression levels, the image analysis algorithm, and staining procedures. Evaluation of structurally diverse compounds, including functional Smo activators, inhibitors, and related analogs, demonstrated good compound potency correlations between high-content imaging binding, membrane fluorescence polarization binding, and gene reporter assays. Statistical analysis of data from a screening test set of compounds at a single 10-µM concentration suggested that the high-content imaging Smo binding assay is amenable for use in hit identification. The 384-well HCS assay was rapidly developed and met statistical assay performance targets, thus demonstrating its utility as a fluorescent whole-cell binding assay suitable for compound screening and profiling.