A multibody simulation of the spine for objectification of biomechanical quantities after VBT: a proof of concept and description of baseline data.

PURPOSE: Vertebral Body Tethering (VBT), an alternative treatment for adolescent idiopathic scoliosis, shows satisfactory post-operative results. However, the biomechanical quantities and consequences after VBT surgery remain largely unknown. Therefore, the aim of this study is to analyze the spinal biomechanics during different motions using a multibody simulation approach. METHODS: The tether and intervertebral compression forces were simulated in a validated spine model during different physiological movements at different pre-tensions and screw positions, while considering the anatomical muscle and ligament properties. RESULTS: The simulations showed that an augmentation of the pre-tension and an alteration of the screw position have both significant impact on the intervertebral compression and tether forces. The forces also vary depending on the movement performed, with the highest tether forces measured during lateral bending. In the upright position, with a pre-tension of 200 N, the maximum compression force increases by up to 157% compared to the untethered maximum compression force. The screw position can lead to large differences in the distribution of forces in the spine. CONCLUSION: The biomechanical data provide a first impression of the forces that occur along the spine during various physiological movements and are consistent with published clinical data. Forces are not evenly distributed along the spine, with higher lumbar forces. The tether forces reach values during lateral bending that can potentially destroy the tether´s integrity and thus may explain the common post-operative complication, namely tether breakage. The results of the model can therefore have an impact on future directions for improved surgical VBT treatment.

Pubic symphysis tethering technique under endoscopic approach for treatment of pelvic open-book injury: A cadaver study.

Purpose: Pubic symphysis disruption is common in pelvic trauma. Open reduction and internal fixation with a plate is the gold standard technique. Despite increasing interest in an endoscopic approach, the challenges of specific endoscopic instrumentation, reduction and fixation remains. In this feasibility cadaveric study, we aimed to describe a novel endoscopic technique of fixation of pubic symphysis disruption with a spinal vertebral tethering system. Methods: Endoscopic pubic symphysis fixation with the tethering method was performed on a female cadaver specimen as well as an artificial pelvic model. Results: We describe a step-by-step technique where three abdominal portals were utilized in order to insert screws in the pubic body and superior pubic ramus under endoscopic visualization. The synthetic tether ligament was introduced through a lateral portal and fixed and tensioned to reduce and compress the pubic symphysis. Conclusions: While open plate fixation is the current gold standard of pubic symphysis disruption there is increasing interest in the minimally invasive endoscopic approach. In this feasibility cadaveric study, we present a new minimally invasive endoscopic fixation method to treat pubic symphysis disruption with a synthetic ligament.

Accuracy of screw placement during vertebral body tethering using fluoroscopic guidance and anatomic landmarks.

PURPOSE: To determine the accuracy of screw placement using fluoroscopy and anatomic landmarks during vertebral body tethering (VBT) surgery. METHODS: Ten patients with 73 VBT screws were converted to posterior spinal fusion (PSF) after continued curve progression. The positions of each VBT screw were analyzed using intraoperative computed tomography (CT) scans performed for image guidance during VBT. Differences for screws placed using an open versus thoracoscopic approach were noted for the screw position in each vertebra, distance from the spinal canal, unicortical versus bicortical placement, the distance of screw tips from the thoracic aorta, and impingement of screws on adjacent rib heads. RESULTS: Seventy three (73) screws in ten (10) patients were available for analysis. Only 21% of screws were placed traversing the middle one-third of the vertebral body, without spinal canal penetration, with the distal tip placed unicortically or bicortically as planned, and without touching the thoracic aorta. The rates of non-ideal screw placement were not significantly different for screws placed via thoracoscopic versus open approaches. Five (5) screws (6.8%) penetrated the spinal canal 1-2 mm, but without known clinical sequelae. CONCLUSION: The majority of VBT screws available for analysis were placed in non-ideal positions, suggesting that accurate screw placement using intraoperative fluoroscopy and anatomic landmarks can be challenging, but without adverse clinical consequences.

Synthetic Dimerization Approaches for In Vivo Studies in Saccharomyces cerevisiae.

Synthetic tethering approaches induced by chemical means offer precise control over protein interactions in cells. They enable the manipulation of when, where, and how proteins interact, making it possible to study their functions, dynamics, and cellular consequences at a molecular level. These methods are versatile, reversible, and adaptable, allowing the dissection of complex cellular processes and the engineering of cellular functions. Here, we describe two chemically induced dimerization systems in the model organism Saccharomyces cerevisiae. Using the autophagy pathway as an example, we show how these approaches can be used to dissect molecular events in cells.

Associations of overweight status with spinal curve correction and complications in patients undergoing vertebral body tethering: a multicenter retrospective review.

PURPOSE: Our purpose was to determine associations between body mass index (BMI) category and outcomes of vertebral body tethering (VBT), a non-fusion treatment for adolescent idiopathic scoliosis (AIS) and juvenile idiopathic scoliosis (JIS). METHODS: Using a multicenter database, we identified patients with AIS or JIS who underwent VBT from 2012 to 2018 and had minimum 2-year follow-up (median, 3.0 [interquartile range 2.2, 3.8]). BMI percentiles were used to classify patients as overweight (≥ 85th percentile) or non-overweight (< 85th percentile). Univariate and multivariate regressions assessed associations between complication rates and curve correction between groups, controlling for sex, triradiate cartilage closure, and preoperative curve magnitude. RESULTS: Of 271 patients, 48 (18%) were overweight. Complication rates did not differ between groups. Factors associated with less correction from preoperative to first postoperative-erect imaging were overweight (ß = - 10, p < 0.001), male sex (ß = - 8.8 p < 0.01), closed triradiate cartilage (ß = 6.0, p = 0.01), and smaller preoperative curve (ß = 0.3, p < 0.01). Factors associated with a larger curve at latest follow-up were overweight (ß = 4.0, p = 0.02) and larger preoperative curve (ß = 0.5, p < 0.001), but tether breakage did not differ between groups (p = 0.31). CONCLUSION: In patients who were overweight, VBT was associated with less curve correction at first erect imaging and larger final curve. However, complications and curve correction during the modulation phase were not different from those of non-overweight patients. These findings suggest that surgeons should expect less correction with VBT in patients who are overweight but similar correction over time. LEVEL OF EVIDENCE: Prognostic, Level III.

Adeno-Associated Virus Engineering and Load Strategy for Tropism Modification, Immune Evasion and Enhanced Transgene Expression.

Gene therapy aims to add, replace or turn off genes to help treat disease. To date, the US Food and Drug Administration (FDA) has approved 14 gene therapy products. With the increasing interest in gene therapy, feasible gene delivery vectors are necessary for inserting new genes into cells. There are different kinds of gene delivery vectors including viral vectors like lentivirus, adenovirus, retrovirus, adeno-associated virus et al, and non-viral vectors like naked DNA, lipid vectors, polymer nanoparticles, exosomes et al, with viruses being the most commonly used. Among them, the most concerned vector is adeno-associated virus (AAV) because of its safety, natural ability to efficiently deliver gene into cells and sustained transgene expression in multiple tissues. In addition, the AAV genome can be engineered to generate recombinant AAV (rAAV) containing transgene sequences of interest and has been proven to be a safe gene vector. Recently, rAAV vectors have been approved for the treatment of various rare diseases. Despite these approvals, some major limitations of rAAV remain, namely nonspecific tissue targeting and host immune response. Additional problems include neutralizing antibodies that block transgene delivery, a finite transgene packaging capacity, high viral titer used for per dose and high cost. To deal with these challenges, several techniques have been developed. Based on differences in engineering methods, this review proposes three strategies: gene engineering-based capsid modification (capsid modification), capsid surface tethering through chemical conjugation (surface tethering), and other formulations loaded with AAV (virus load). In addition, the major advantages and limitations encountered in rAAV engineering strategies are summarized.

Tdh3 and Rom2 are functional modulators of a conserved condensate-resident RNA-binding protein, Scd6 in Saccharomyces cerevisiae.

RGG-motif proteins play a crucial role in determining mRNA fate. Suppressor of clathrin deficiency 6 (Scd6) is a conserved RGG-motif containing RNP condensate-resident, translation repressor, and decapping activator protein in Saccharomyces cerevisiae. Identifying protein factors that can modulate Scd6 function is critical to understanding the regulation of mRNA fate by Scd6. In this study, using an approach that combined mRNA tethering assay with flow cytometry, we screened 50 genes for their role in modulating the translation repression activity of Scd6. We identified eight conserved modulators with human homologs. Of these, we further characterised in detail guanine nucleotide exchange factor (GEF) Rom2 (Rho1 multicopy suppressor) and glycolytic enzyme Tdh3 (Triose phosphate dehydrogenase 3), which, respectively, impede and promote translation repression activity of Scd6. Our study reveals that Rom2 negatively regulates the arginine methylation of Scd6 and antagonises its localisation to P-bodies. Tdh3, on the other hand, promotes Scd6 interaction with Hmt1, thereby promoting the arginine methylation of Scd6 and enhanced eIF4G1 interaction, which is known to promote its repression activity. Identifying these novel modulators provides exciting new insights into the role of a metabolic enzyme of the glycolytic pathway and guanine nucleotide exchange factor implicated in the cell wall integrity pathway in regulating Scd6 function and, thereby, cytoplasmic mRNA fate.

Current Concepts in the Treatment of Early Onset Scoliosis.

Despite many surgical advances in the treatment of early onset scoliosis (EOS) over the past two decades, this condition remains a challenge to address. While otherwise healthy children can have EOS, many of these patients have complicated comorbidities making proper treatment algorithms extraordinarily difficult. Non-operative measures can be successful when initiated early, but are many times utilized as a delay tactic until growth-friendly operative procedures can be safely performed. This article will summarize the current concepts in the treatment of EOS with a focus on the surgical advances that have recently been made.

Chest tube management following two row vertebral body tethering for adolescent idiopathic scoliosis.

BACKGROUND: The current gold standard of scoliosis correction procedures is still posterior spinal fusion, an extensively studied procedure. anterior vertebral body tethering is a newer surgical technique for the correction of scoliotic curves. Consequently, best practices have yet to be determined. METHODS: A single-institution, retrospective, review of all patients diagnosed with adolescent idiopathic scoliosis who underwent two row anterior vertebral body tethering between June 2020 and April 2022 was performed. RESULTS: Over the study period, 95 patients met inclusion: 79 females (83.2%) and 16 males (16.8%), age 14.4 ± 2.5 years, with a body mass index of 20.0 ± 2.9, and an average of 8.4 ± 2.1 levels treated. 28 (29.5%) procedures were for double curves and 67 (70.5%) for single curves. After tethering, a chest tube was positioned in each corrected side. A total of 123 chest tubes were analyzed, including 67 single curves and 28 double curves. The average chest tube duration was 2.5 ± 1.1 days and the average length of stay was 5.0 ± 2.0 days. The average chest tube output eight hours prior to removal was 61.1 ± 45.6 mL. There was no significant difference in average length of stay for patients who underwent correction of a single curve versus a double curve nor was there a difference in average length of stay or chest tube duration for revisions compared to primary procedures. For the entire cohort, the 30-day emergency department visit rate was 7.4% (n = 7) and the readmission rate was 4.2% (n = 4). CONCLUSIONS: This early review of a 2-year two row vertebral body tethering postoperative experience provides a report of a safe and effective approach to chest tube management at a single academic center.

The WDR11 complex is a receptor for acidic-cluster-containing cargo proteins.

Vesicle trafficking is a fundamental process that allows for the sorting and transport of specific proteins (i.e., "cargoes") to different compartments of eukaryotic cells. Cargo recognition primarily occurs through coats and the associated proteins at the donor membrane. However, it remains unclear whether cargoes can also be selected at other stages of vesicle trafficking to further enhance the fidelity of the process. The WDR11-FAM91A1 complex functions downstream of the clathrin-associated AP-1 complex to facilitate protein transport from endosomes to the TGN. Here, we report the cryo-EM structure of human WDR11-FAM91A1 complex. WDR11 directly and specifically recognizes a subset of acidic clusters, which we term super acidic clusters (SACs). WDR11 complex assembly and its binding to SAC-containing proteins are indispensable for the trafficking of SAC-containing proteins and proper neuronal development in zebrafish. Our studies thus uncover that cargo proteins could be recognized in a sequence-specific manner downstream of a protein coat.

Updated pathophysiological overview of functional MR (ventricular and atrial).

Basic mechanism of ventricular functional mitral regurgitation (FMR) is subvalvular tethering. Left ventricular (LV) dilatation, in association with mitral valve (MV) annular dilatation, causes outward displacement of papillary muscles (PMs), which abnormally pulls or tethers MV leaflets, resulting in MV tenting, reduction in leaflets coaptation and MR. Because surgical annuloplasty does shorten distance between anterior and posterior MV annuli to improve coaptation but does not address this subvalvular tethering, ventricular FMR frequently persists or recurs in the chronic stage after surgical annuloplasty. This high incidence of persistent/recurrent MR requires additional procedures to reduce subvalvular tethering. Although patients occasionally show marked improvements after annuloplasty with surgical tethering reduction procedures such as PM approximation, evidence to support benefits of such surgery is limited, requiring further trials. Recently, MV adaptation or MV leaflets tissue growth associated with LV dilatation attracts attention. Patients with larger MV leaflets with significant LV dilatation/dysfunction show less MV tethering and MR compared to those with smaller MV leaflets but with similar LV remodeling, suggesting the protective or beneficial role of MV leaflets tissue growth against LV remodeling. The MV leaflets tissue growth has the potential to lead to novel strategies of treatment for ventricular FMR. It is well known that atrial FMR is frequent in patients with left atrial dilatation, typically in those with isolated atrial fibrillation. The degree of atrial FMR is usually mild, even when it is present, and occasionally moderate, and severe atrial FMR is really rare. It is known that only severe regurgitation causes heart failure in primary MR, resulting in description on indications of surgery or intervention for only severe MR in current guidelines. Therefore, this atrial FMR up to moderate degree did not attract attention for a long time. However, recent studies have shown that patients with only moderate atrial FMR develop severe heart failure, suggesting more aggressive indication of MV surgery or intervention for "moderate" regurgitation in patients with atrial FMR. Therefore, atrial FMR is now recognized highly important. The unveiled malignant nature of atrial FMR arises many questions, including (1) why patients with only moderate atrial FMR develop heart failure? (2) do patients with mild atrial FMR develop heart failure or not?, and many others. Atrial FMR seems even more mysterious after the unveiling of its significance.

A Comparative Evaluation of Unilateral and Bilateral Sequential Lung Isolation for Vertebral Body Tethering: A Retrospective Propensity Matched Analysis.

BACKGROUND: Vertebral body tethering (VBT) requires a thoracoscopic approach to visualize the vertebral bodies. Lung collapse and re-expansion have the potential to cause acute lung injury, resulting in increased oxygen and ventilation requirements. AIMS: We compared the intraoperative ventilator management, intra- and postoperative blood gas determinations, and hospital stay information between adolescents undergoing unilateral versus bilateral lung isolation for vertebral body tethering. METHODS:  A study cohort of 132 propensity-matched cases (66 unilateral and 66 bilateral) was derived from 351 consecutive VBT cases. Patient demographic information, case information, fluid administration, ventilatory settings data, blood gas parameters, and complete blood count and differential data were entered into a datasheet. Derived parameters included values calculated from the alveolar gas equation to develop an oxygen cascade and measures of inflammatory response. Chi-square was used for categorical data, and independent samples and t-tests were used for continuous data. RESULTS: The double lung isolation group required higher peak inspiratory pressures (SL 29±5 vs. DL 31±5, p=0.026), resulting in higher tidal volume (SL 246±63 vs. DL 334±101, p<0.001) and tidal volume per kg (SL 5.6±1.4 vs. DL 6.9±2, p<0.001) as compared to the single lung group. The double lung group required a higher partial pressure of inspired and alveolar oxygen as well as a higher alveolar to arterial oxygen tension gradient (SL 417±126 vs. DL 485±96, p=0.001) to achieve optimal arterial oxygen tension. Patients with double lung isolation had similar intensive care lengths of stay but a longer hospital stay than single lung isolation patients. CONCLUSION: Patients undergoing double lung isolation required greater ventilatory support and had more evidence of acute lung injury, as evidenced by a higher postoperative alveolar to arterial oxygen gradient; however, these healthy adolescents tolerated the procedure well and only differed in the hospital length of stay by a day.

Growth modulation response in vertebral body tethering depends primarily on magnitude of concave vertebral body growth.

PURPOSE: There is variability in clinical outcomes with vertebral body tethering (VBT) partly due to a limited understanding of the growth modulation (GM) response. We used the largest sample of patients with 3D spine reconstructions to characterize the vertebra and disc morphologic changes that accompany growth modulation during the first two years following VBT. METHODS: A multicenter registry was used to identify idiopathic scoliosis patients who underwent VBT with 2 years of follow-up. Calibrated biplanar X-rays obtained at longitudinal timepoints underwent 3D reconstruction to obtain precision morphological measurements. GM was defined as change in instrumented coronal angulation from post-op to 2-years. RESULTS: Fifty patients (mean age: 12.5 ± 1.3yrs) were analyzed over a mean of 27.7 months. GM was positively correlated with concave vertebra height growth (r = 0.57, p < 0.001), 3D spine length growth (r = 0.36, p = 0.008), and decreased convex disc height (r = - 0.42, p = 0.002). High modulators (patients experiencing GM > 10°) experienced an additional 1.6 mm (229% increase) of mean concave vertebra growth during study period compared to the Poor Modulators (GM < - 10°) group, (2.3 vs. 0.7 mm, p = 0.039), while convex vertebra height growth was similar (1.3 vs. 1.4 mm, p = 0.91). CONCLUSION: When successful, VBT enables asymmetric vertebra body growth, leading to continued postoperative coronal angulation correction (GM). A strong GM response is correlated with concave vertebral body height growth and overall instrumented spine growth. A poor GM response is associated with an increase in convex disc height (suspected tether rupture). Future studies will investigate the patient and technique-specific factors that influence increased growth remodeling.

Efficient, specific, and combinatorial control of endogenous exon splicing with dCasRx-RBM25.

Efficient targeted control of splicing is a major goal of functional genomics and therapeutic applications. Guide (g)RNA-directed, deactivated (d)Cas CRISPR enzymes fused to splicing effectors represent a promising strategy due to the flexibility of these systems. However, efficient, specific, and generalizable activation of endogenous exons using this approach has not been previously reported. By screening over 300 dCasRx-splicing factor fusion proteins tethered to splicing reporters, we identify dCasRx-RBM25 as a potent activator of exons. Moreover, dCasRx-RBM25 efficiently activates the splicing of ∼90% of targeted endogenous alternative exons and displays high on-target specificity. Using gRNA arrays for combinatorial targeting, we demonstrate that dCasRx-RBM25 enables multiplexed activation and repression of exons. Using this feature, the targeting of neural-regulated exons in Ptpb1 and Puf60 in embryonic stem cells reveals combinatorial effects on downstream alternative splicing events controlled by these factors. Collectively, our results enable versatile, combinatorial exon-resolution functional assays and splicing-directed therapeutic applications.

How can biomaterial-conjugated antimicrobial peptides fight bacteria and be protected from degradation?

The emergence of antibiotic-resistant bacteria is a serious threat to public health. Antimicrobial peptides (AMP) are a powerful alternative to antibiotics due to their low propensity to induce bacterial resistance. However, cytotoxicity and short half-lives have limited their clinical translation. To overcome these problems, AMP conjugation has gained relevance in the biomaterials field. Nevertheless, few studies describe the influence of conjugation on enzymatic protection, mechanism of action and antimicrobial efficacy. This review addresses this gap by providing a detailed comparison between conjugated and soluble AMP. Additionally, commonly employed chemical reactions and factors to consider when promoting AMP conjugation are reviewed. The overall results suggested that AMP conjugated onto biomaterials are specifically protected from degradation by trypsin and/or pepsin. However, sometimes, their antimicrobial efficacy was reduced. Due to limited conformational freedom in conjugated AMP, compared to their soluble forms, they appear to act initially by creating small protuberances on bacterial membranes that may lead to the alteration of membrane potential and/or formation of holes, triggering cell death. Overall, AMP conjugation onto biomaterials is a promising strategy to fight infection, particularly associated to the use of medical devices. Nonetheless, some details need to be addressed before conjugated AMP reach clinical practice. STATEMENT OF SIGNIFICANCE: Covalent conjugation of antimicrobial peptides (AMP) has been one of the most widely used strategies by bioengineers, in an attempt to not only protect AMP from proteolytic degradation, but also to prolong their residence time at the target tissue. However, an explanation for the mode of action of conjugated AMP is still lacking. This review extensively gathers works on AMP conjugation and puts forward a mechanism of action for AMP when conjugated onto biomaterials. The implications of AMP conjugation on antimicrobial activity, cytotoxicity and resistance to proteases are all discussed. A thorough review of commonly employed chemical reactions for this conjugation is also provided. Finally, details that need to be addressed for conjugated AMP to reach clinical practice are discussed.

Flexible posterior vertebral tethering for the management of Scheuermann's kyphosis: correction by using growth modulation-clinical and radiographic outcomes of the first 10 patients with at least 3 years of follow-up.

PURPOSE: The present prospective cohort study was intended to present the minimum 3 years' results of flexible posterior vertebral tethering (PVT) applied to 10 skeletally immature patients with SK to question, if it could be an alternative to fusion. METHODS: Ten skeletally immature patients with radiographically confirmed SK, who had flexible (minimum 35%) kyphotic curves (T2-T12), were included. A decision to proceed with PVT was based on curve progression within the brace, and/or persistent pain, and/or unacceptable cosmetic concerns of the patient/caregivers, and/or non-compliance within the brace. RESULTS: Patients had an average age of 13.1 (range 11-15) and an average follow-up duration of 47.6 months (range 36-60). Posterior vertebral tethering (PVT) was undertaken to all patients by utilizing Wiltse approach and placing monoaxial pedicle screws intermittently. At the final follow-up: mean pre-operative thoracic kyphosis and lumbar lordosis improved from 73.6°-45.7° to 34.7°-32.1°. Mean sagittal vertical axis, vertebral wedge angle and total SRS-22 scores improved significantly. A fulcrum lateral X-ray obtained at the latest follow-up, showed that the tethered levels remained mobile. CONCLUSION: This study, for the first time in the literature, concluded, that as a result of growth modulation applied to skeletally immature patients with SK, flexible PVT was detected to yield gradual correction of the thoracic kyphosis by reverting the pathological vertebral wedging process, while keeping the mobility of the tethered segments in addition to successful clinical-functional results. The successful results of the present study answered the role of the PVT as a viable alternative to fusion in skeletally immature patients with SK. LEVEL OF EVIDENCE: IV.

lVentral tethering-is the prognosis worse than in dorsal tethering in the dysraphic spine?

OBJECTIVE: To compare cases of dysraphism with ventral tethering of cord with those with dorsal tethering and to find out any differences in the outcome of surgery in them. METHODS: We collected the data of 188 consecutively operated tethered cord patients at our institute in the past 7 years and divided them into ventral tethering and dorsal tethering groups. Those that we felt had both dorsal and ventral tethering were excluded. Their preoperative clinical, radiological, and baseline neurophysiological parameters as well as postoperative clinical and radiological parameters were analyzed in a retrospective study. RESULTS: Among the 188 tethered cord patients, 52 (28%) had ventral tethering and 136 (72%) had posterior tethering. Preoperative neurodeficit and cord signal changes as well as absent baseline MEP (of any one muscle) were significantly more associated with ventral tethered cord than the dorsal tethered cord. The neurological deterioration after surgery occurred significantly in the ventral tethered cord group than in the dorsal tethered cord group. Also, the postoperative MRI had more incomplete detethering cases in the ventral group than in the dorsal tethered cord group. CONCLUSION: Ventral tethered cord is more likely to present with preoperatively neurological deficits. It should be carefully identified in the preoperative MRI, so that the intraoperative difficulties in complete detethering and postoperative deterioration can be anticipated.

The efficacy of anterior vertebral body tethering in lenke type 6 curves for adolescent idiopathic scoliosis.

PURPOSE: Spinal fusion is the standard treatment for severe forms of adolescent idiopathic scoliosis (AIS). However, with the lowest instrumented vertebra that is usually located at L3 or L4, patients are prone to develop adjacent segment degeneration in the long term. Vertebral body tethering (VBT) as motion preserving technique has become an alternative for select patients with AIS. Several studies have presented the outcome after thoracic VBT but no study has analyzed the outcome after VBT for Lenke type 6 curves. METHODS: This is a retrospective single center data analysis of patients who have had bilateral VBT for Lenke type 6 curves and a minimum follow up of 24 months. Radiographic analysis was performed on several time points. Suspected tether breakages were additionally analyzed with respect to location and time at occurrence. RESULTS: 25 patients were included. Immediate thoracic curve correction was 55.4% and 71.7% for TL/L curves. Loss of correction was higher for TL/L curves and resulted in a correction rate of 48.3% for thoracic curves and 48.9% for TL/L curves at 24 months post-operatively. 22 patients were suspected to have at least one segment with a tether breakage. Three patients required a re-VBT but no patient received posterior spinal fusion. CONCLUSION: Bilateral VBT for Lenke type 6 curves is feasible and shows a significant curve correction for thoracic and TL/L curves at a minimum of 24 months post-operatively. Tether breakage rate and loss of correction remain an unfavorable observation that needs to be improved in the future.

Delayed hemothorax after anterior vertebral body tethering in adolescent idiopathic scoliosis: a case report.

PURPOSE: The aim of this case report is to report that delayed hemothorax is possible after anterior vertebral body tethering (aVBT) and to illustrate the course of treatment. METHODS: We present a 15-year-old boy with adolescent idiopathic scoliosis who underwent an anterior thoracoscopic assisted vertebral body tethering who developed a massive right-sided hemothorax 12 days post-operatively. A chest tube was placed to drain the hemothorax and later required embolectomy with tissue plasminogen activator (TPA) to drain the retained hemothorax. RESULTS: At 1 month follow up post discharge the patient was asymptomatic, and radiograph did not demonstrate evidence of residual hemothorax and scoliosis. We have followed this patient for 5 years postoperative and he continues to do well clinically and radiographically. CONCLUSIONS: Pulmonary complications are a known drawback of anterior thoracoscopic spinal instrumentation. Delayed hemothorax is possible after aVBT. In the case of a retained hemothorax, chest tube treatment with TPA is a safe and effective method of embolectomy.

Testosterone Promotes Nerve Tethering and Acellular Biomaterial Perineural Fibrosis in a Rat Wound Repair Model.

Objective: Nerve scarring after traumatic or iatrogenic exposure can lead to impaired function and pain. Nerve-adjacent biomaterials promoting a regenerative tissue response may help reduce perineural fibrosis. Our prior work suggests that testosterone may promote fibrotic skin scarring, but it is unknown how testosterone alters nerve fibrosis or shifts the response to biomaterials. Approach: Sterilized Lewis rats received either testosterone cypionate (+T) or placebo (-T) biweekly. Fifteen days later, wounds were created over the sciatic nerve and covered with an acellular matrix (AM) or closed via primary closure (PC). At day 42, force gauge testing measured the force required to mobilize the nerve, and wound tissue was analyzed. Results: Nerve mobilization force was greater in +T versus -T wounds (p < 0.01). Nerves tore before gliding in 60% of +T versus 6% of -T rats. Epidermal gap (p < 0.01), scar width (p < 0.01), and cross-sectional scar tissue area (p = 0.02) were greater in +T versus -T rats. +T versus -T rats expressed less Col-3 (p = 0.02) and CD68 (p = 0.02). Nerve mobilization force trended nonsignificantly higher for PC versus AM wounds and for +T versus -T wounds within the AM cohort. Innovation: Testosterone increases nerve tethering in the wound healing milieu, altering repair and immune cell balances. Conclusion: Testosterone significantly increases the force required to mobilize nerves in wound beds and elevates histological markers of scarring, suggesting that testosterone-induced inflammation may increase perineural adhesion. Testosterone may reduce the potential anti-tethering protective effect of AM. Androgen receptor antagonism may represent a therapeutic target to reduce scar-related nerve morbidity.