The catabolism of ethylene glycol by Rhodococcus jostii RHA1 and its dependence on mycofactocin.

Ethylene glycol (EG) is a widely used industrial chemical with manifold applications and also generated in the degradation of plastics such as polyethylene terephthalate. Rhodococcus jostii RHA1 (RHA1), a potential biocatalytic chassis, grows on EG. Transcriptomic analyses revealed four clusters of genes potentially involved in EG catabolism: the mad locus, predicted to encode mycofactocin-dependent alcohol degradation, including the catabolism of EG to glycolate; two GCL clusters, predicted to encode glycolate and glyoxylate catabolism; and the mft genes, predicted to specify mycofactocin biosynthesis. Bioinformatic analyses further revealed that the mad and mft genes are widely distributed in mycolic acid-producing bacteria such as RHA1. Neither ΔmadA nor ΔmftC RHA1 mutant strains grew on EG but grew on acetate. In resting cell assays, the ΔmadA mutant depleted glycolaldehyde but not EG from culture media. These results indicate that madA encodes a mycofactocin-dependent alcohol dehydrogenase that initiates EG catabolism. In contrast to some mycobacterial strains, the mad genes did not appear to enable RHA1 to grow on methanol as sole substrate. Finally, a strain of RHA1 adapted to grow ~3× faster on EG contained an overexpressed gene, aldA2, predicted to encode an aldehyde dehydrogenase. When incubated with EG, this strain accumulated lower concentrations of glycolaldehyde than RHA1. Moreover, ecotopically expressed aldA2 increased RHA1's tolerance for EG further suggesting that glycolaldehyde accumulation limits growth of RHA1 on EG. Overall, this study provides insights into the bacterial catabolism of small alcohols and aldehydes and facilitates the engineering of Rhodococcus for the upgrading of plastic waste streams.IMPORTANCEEthylene glycol (EG), a two-carbon (C2) alcohol, is produced in high volumes for use in a wide variety of applications. There is burgeoning interest in understanding and engineering the bacterial catabolism of EG, in part to establish circular economic routes for its use. This study identifies an EG catabolic pathway in Rhodococcus, a genus of bacteria well suited for biocatalysis. This pathway is responsible for the catabolism of methanol, a C1 feedstock, in related bacteria. Finally, we describe strategies to increase the rate of degradation of EG by increasing the transformation of glycolaldehyde, a toxic metabolic intermediate. This work advances the development of biocatalytic strategies to transform C2 feedstocks.

Augmented Stress Weight-bearing CT for Evaluation of Subtle Lisfranc Injuries in the Elite Athlete.

BACKGROUND: Lisfranc injuries refer to a disruption or displacement of the tarsometatarsal joint of the foot. Subtle Lisfranc injuries can go undiagnosed on conventional imaging leading to devastating consequences and poor functional outcomes for elite athletes. Objective. The objective of this case study is to present a novel imaging technique using weight-bearing computed tomography (CT) with enhanced stress to identify subtle, dynamically unstable Lisfranc injuries. We illustrate this with a case presentation of an elite athlete who ultimately required surgical fixation for a subtle Lisfranc injury. MATERIALS AND METHODS: To perform an augmented stress weight-bearing CT, the patient was positioned standing, with their feet facing forward, and weight equally distributed. The patient was then coached to symmetrically raise both heels from the scanner platform. This plantarflexion provided augmented stress on the midfoot, allowing for more sensitive imaging of the Lisfranc injury. The weight-bearing CT and augmented stress images undergo 3D reconstruction and postprocessing to render coronal and sagittal images, allowing for comparison of the standard weight-bearing and augmented stress images. RESULTS: We present the case of a 22-year-old collegiate football lineman sustaining a Lisfranc injury. The injury diagnosis was made by magnetic resonance imaging (MRI) and clinical examination, without evidence of injury on weight-bearing XR or standard weight-bearing CT. With augmented stress CT imaging, the Lisfranc instability was noted, leading to surgical fixation, and return to sport the next season. CONCLUSION: We propose this technique for diagnosing subtle, unstable Lisfranc injuries where clinical suspicion persists despite inconclusive imaging, particularly in elite athletes. Further research is needed with larger sample sizes to investigate the sensitivity of this novel imaging technique for the detection of Lisfranc injury. LEVELS OF EVIDENCE: Level 4: Case Report.

The catabolism of lignin-derived p-methoxylated aromatic compounds by Rhodococcus jostii RHA1.

Emergent strategies to valorize lignin, an abundant but underutilized aromatic biopolymer, include tandem processes that integrate chemical depolymerization and biological catalysis. To date, aromatic monomers from C-O bond cleavage of lignin have been converted to bioproducts, but the presence of recalcitrant C-C bonds in lignin limits the product yield. A promising chemocatalytic strategy that overcomes this limitation involves phenol methyl protection and autoxidation. Incorporating this into a tandem process requires microbial cell factories able to transform the p-methoxylated products in the resulting methylated lignin stream. In this study, we assessed the ability of Rhodococcus jostii RHA1 to catabolize the major aromatic products in a methylated lignin stream and elucidated the pathways responsible for this catabolism. RHA1 grew on a methylated pine lignin stream, catabolizing the major aromatic monomers: p-methoxybenzoate (p-MBA), veratrate, and veratraldehyde. Bioinformatic analyses suggested that a cytochrome P450, PbdA, and its cognate reductase, PbdB, are involved in p-MBA catabolism. Gene deletion studies established that both pbdA and pbdB are essential for growth on p-MBA and several derivatives. Furthermore, a deletion mutant of a candidate p-hydroxybenzoate (p-HBA) hydroxylase, ΔpobA, did not grow on p-HBA. Veratraldehyde and veratrate catabolism required both vanillin dehydrogenase (Vdh) and vanillate O-demethylase (VanAB), revealing previously unknown roles of these enzymes. Finally, a ΔpcaL strain grew on neither p-MBA nor veratrate, indicating they are catabolized through the ß-ketoadipate pathway. This study expands our understanding of the bacterial catabolism of aromatic compounds and facilitates the development of biocatalysts for lignin valorization.IMPORTANCELignin, an abundant aromatic polymer found in plant biomass, is a promising renewable replacement for fossil fuels as a feedstock for the chemical industry. Strategies for upgrading lignin include processes that couple the catalytic fractionation of biomass and biocatalytic transformation of the resulting aromatic compounds with a microbial cell factory. Engineering microbial cell factories for this biocatalysis requires characterization of bacterial pathways involved in catabolizing lignin-derived aromatic compounds. This study identifies new pathways for lignin-derived aromatic degradation in Rhodococcus, a genus of bacteria well suited for biocatalysis. Additionally, we describe previously unknown activities of characterized enzymes on lignin-derived compounds, expanding their utility. This work advances the development of strategies to replace fossil fuel-based feedstocks with sustainable alternatives.

Core Muscle Injury Producing Groin Pain in the Athlete: Diagnosis and Treatment.

Groin pain is a common cause of pain in the athlete and may be the result of a variety of causes. Musculoskeletal groin injuries are often associated with muscle strain, particularly the adductor and abdominal muscles, termed "core muscle injury" (CMI). Since the early 1960s, there have been a growing number of articles intending to identify, define, prevent, and treat this condition; to date, however, the lack of a universal definition and treatment approach has complicated the narrative around CMI. This article intends to review the recent literature surrounding CMI, identifying common defining characteristics, as well as delineating treatment protocols that benefit the injured patient populations. Emphasis is placed on the clinical outcomes of different treatment methodologies and failure rates.

Current Definitions of Failure in Lateral Ankle Instability Surgery: A Systematic Review.

BACKGROUND: "Failure" is a term that is frequently used to describe an unfavorable outcome for patients who undergo surgical treatment for lateral ankle instability (LAI). A standard definition of failure for the surgical treatment of ankle instability has not been established by clinicians and researchers. PURPOSE: To identify the definitions of ankle instability treatment failure that are currently in the literature and to work toward the standardization of the definition. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic search of MEDLINE, SPORTDiscus, CINAHL, Embase, and Web of Science was conducted to identify clinical studies that included patients who underwent surgical treatment for LAI and included information about surgical failure. Studies with level of evidence 1 to 4 were included in this review. Animal studies, biomechanical studies, cadaveric studies, review articles, and expert opinions were excluded. The included studies were then reviewed for definitions of failure of any surgical procedure that was performed to correct LAI. RESULTS: Of the 1200 studies found, 3.5% (42/1200) published between 1984 and 2021 met the inclusion criteria and were analyzed. After reviewing the data, we found numerous definitions were reported in the literature for LAI surgical failure. The most common was recurrent instability (40% [17/42]), followed by rerupture (19% [8/42]). For the original surgical procedure, the anatomic Broström-Gould technique was used most frequently (57% [24/42]). The failure rate of the Broström-Gould technique ranged from 1.1% to 45.2% depending on the definition of failure. CONCLUSION: There were multiple definitions of failure for the surgical treatment of LAI, which is one of the reasons why the rate of failure can vary greatly. The literature would benefit greatly from the standardization of the definition of ankle instability treatment failure. This definition should include specific, objective physical examination findings that eliminate the ambiguity surrounding failure.

Augmented stress weightbearing CT for evaluation of subtle tibiofibular syndesmotic injuries in the elite athlete.

OBJECTIVE: We aim to present a novel imaging technique utilizing weight-bearing CT with syndesmotic stress to identify subtle, unstable syndesmotic injuries. We illustrate this with a case presentation of such an injury in an elite athlete that ultimately required operative fixation. MATERIALS AND METHODS: In order to perform an augmented stress weightbearing CT, the patient is in the standing position, feet facing forward, and with weight distributed equally. The patient is then coached to internally rotate the shin and knee. This places an external rotational moment on the TFS due to the planted foot and ankle. The augmented stress images undergo 3D reconstruction and post-processing to render coronal and sagittal images. These are subsequently compared to standard, conventional weightbearing CT images performed without the external rotation stress. RESULTS: We illustrate this technique by presenting a case in which a 21-year-old collegiate athlete sustained a Grade II syndesmotic injury, diagnosed by MRI and clinical exam without evidence of instability by standard weightbearing CT or weightbearing radiographs. After undergoing the augmented stress weightbearing CT, the instability was noted. This prompted subsequent operative fixation and ultimately return to sport. CONCLUSION: We propose this technique for diagnosing unrecognized, subtle dynamically unstable syndesmosis injuries where clinical suspicion persists despite negative imaging, particularly in the elite athlete.

Retrospective chart review: Weightbearing CT scans and the measurement of the Lisfranc ligamentous complex.

BACKGROUND: Lisfranc Ligamentous Complex (LLC) injuries are commonly misdiagnosed due to their unreliable projection on plain films. Weightbearing CT (WBCT) scans are a relatively new imaging modality that has not yet been utilized to establish widely referenced baseline anatomic positions. METHODS: A retrospective chart review was conducted of patients who had undergone weightbearing CT of the bilateral lower extremities with one-hundred and twelve being included (56 patients). Measurements of the Lisfranc joint were collected by two independent reviewers. Uninjured symmetric anatomy was used to describe a baseline for normal anatomic variation and to evaluate for sex-based or age-related differences. These measurements were then compared against the injured side. RESULTS: In patients without Lisfranc injury, the 1st metatarsal base to 2nd metatarsal base distance (Base M1-M2) was 2.7 + /- 0.7 mm; 2nd metatarsal base to medial cuneiform (M2-C1) was 3.7 + /- 0.7 mm; intercuneiform distance was 1.2 + /- 0.3 mm; and sagittal descent 12.2 + /- 5.4 mm. Patients with injury to LLC had a larger M1-M2 base distance (Δ = 0.5903, p < 0.0001) and M2-C1 interval (Δ = 1.8008, p < 0.0001) compared to uninjured side. Males had significantly higher M2-C1 (p = 0.0031), intercuneiform distance (p = 0.0039), and sagittal descent (p = 0.0008) compared to female patients. No significant differences were found between left versus right side in any of the measurements. Intercuneiform distance (p = 0.0039) was found to significantly decrease as age increased, while sagittal descent significantly increased with increased age (p = 0.0066). CONCLUSION: Weightbearing CT has high utility in identification of Lisfranc injuries particularly when comparing injured and uninjured sides, which may be its greatest utility in defining injuries. This is evident in the excellent diagnostic ability of the M2-C1 measurement. By defining baseline anatomic measurements for Lisfranc complex parameters in our patient population, we provide normal parameters for comparison when evaluating potential subtle injuries. LEVEL OF EVIDENCE: III.

A Measure of Burnout in Current NCAA Student-Athletes.

Introduction: The prevalence of athletes who specialize in sports has increased in recent years. Substantial literature on youth sports has linked early sport specialization to negative consequences, such as burnout and injury. However, empirical evidence comparing rates of burnout and specialization in NCAA athletes is limited. The purpose of this study was to survey current NCAA Division I student-athletes to compare levels of burnout to sex, year of NCAA eligibility, and age at the beginning of sport specialization. Methods: A self-reported survey was distributed to student-athletes at two NCAA Division I institutions, which included demographics, sport specialization history, injury history, and the Athlete Burnout Questionnaire. Results from the three measures of the Athlete Burnout Questionnaire (reduced sense of accomplishment, exhaustion, sport devaluation) were compared to sex, year of NCAA eligibility, age of beginning sport specialization, and injury history. Results: A total of 267 athletes (95 males and 172 females) completed the survey. Of those, 156 (58.4%) were in their first or second year of NCAA eligibility, and 111 (41.6%) were in their third, fourth, or fifth year. Of the total, 121 (46.4%) reported specializing before the age of 15, and 140 (53.6%) specialized at age 16 or older. Females reported significantly higher levels of exhaustion than males (Difference of means (M) = 0.43, 95% confidence interval (CI) = [0.20, 0.66], p < 0.01). Athletes in their third, fourth, or fifth year of eligibility reported significantly higher levels of sport devaluation (M = 0.27, 95% CI = [0.05, 0.48], p < 0.05) than athletes in their first or second year. Athletes who specialized before age 15 did not report significantly higher levels of burnout than athletes who specialized at age 16 or later. In total, 203 athletes (77.2%) reported experiencing any injury. Athletes who reported a history of experiencing any injury demonstrated significantly higher feelings of reduced sense of accomplishment than athletes with no injury history (Difference of means (M) = 0.24, 95% confidence interval (CI) = [0.03, 0.45], p < 0.05). Conclusions: Athletes were more likely to experience elevated levels of burnout if they reported female sex, older NCAA eligibility, or a past injury history. However, athletes were not more likely to experience increased burnout based on age of beginning specialization. The results demonstrated a need to address burnout in athletes following injury and to be aware that females and older athletes are more prone to burnout.

Characterization of a phylogenetically distinct extradiol dioxygenase involved in the bacterial catabolism of lignin-derived aromatic compounds.

The actinobacterium Rhodococcus jostii RHA1 grows on a remarkable variety of aromatic compounds and has been studied for applications ranging from the degradation of polychlorinated biphenyls to the valorization of lignin, an underutilized component of biomass. In RHA1, the catabolism of two classes of lignin-derived compounds, alkylphenols and alkylguaiacols, involves a phylogenetically distinct extradiol dioxygenase, AphC, previously misannotated as BphC, an enzyme involved in biphenyl catabolism. To better understand the role of AphC in RHA1 catabolism, we first showed that purified AphC had highest apparent specificity for 4-propylcatechol (kcat/KM ∼106 M-1 s-1), and its apparent specificity for 4-alkylated substrates followed the trend for alkylguaiacols: propyl > ethyl > methyl > phenyl > unsubstituted. We also show AphC only poorly cleaved 3-phenylcatechol, the preferred substrate of BphC. Moreover, AphC and BphC cleaved 3-phenylcatechol and 4-phenylcatechol with different regiospecificities, likely due to the substrates' binding mode. A crystallographic structure of the AphC·4-ethylcatechol binary complex to 1.59 Å resolution revealed that the catechol is bound to the active site iron in a bidentate manner and that the substrate's alkyl side chain is accommodated by a hydrophobic pocket. Finally, we show RHA1 grows on a mixture of 4-ethylguaiacol and guaiacol, simultaneously catabolizing these substrates through meta-cleavage and ortho-cleavage pathways, respectively, suggesting that the specificity of AphC helps to prevent the routing of catechol through the Aph pathway. Overall, this study contributes to our understanding of the bacterial catabolism of aromatic compounds derived from lignin, and the determinants of specificity in extradiol dioxygenases.

Sex-specific differences in outcomes after anterior shoulder surgical stabilization: a meta-analysis and systematic review of literature.

BACKGROUND: Anterior shoulder instability frequently occurs in young, physically active individuals and may be treated with surgical stabilization. Previous studies have shown that males more often require surgical management for anterior shoulder instability and may have a higher frequency of recurrent instability episodes after surgical management, but females have been found to have increased incidence of apprehension after surgical stabilization. The purpose of this study is to review the literature and assess anterior shoulder surgical stabilization postoperative outcomes between males and females to identify and describe sex-based differences. METHODS: A systematic search of electronic databases was conducted to identify level I-IV clinical studies on anterior shoulder instability published between 1960 and August 2020. We included studies that evaluated sex-specific outcomes in patients who underwent anterior shoulder instability procedures. A meta-analysis of the data was performed to analyze sex-specific outcomes. RESULTS: Thirty studies (2.1%) met inclusion criteria, representing 9829 patients. Of the studies that reported the number of male and female patients, 74% were male and 26% were female. Twenty-six studies used Bankart repair alone, two used open Latarjet procedure alone, and two had a Bankart repair group and Latarjet procedure group. Instability recurrence, return to sport, and apprehension were included in the meta-analysis. Our meta-analysis demonstrated a significantly higher rate of instability recurrence for males than for females who underwent arthroscopic Bankart repair (risk ratio [RR] = 1.25; 95% confidence interval [CI] = 1.03, 1.52; P = .0239). We did not identify a significant difference between males and females in rates of apprehension (RR = 0.68; 95% CI = 0.37, 1.27; P = .2300) or return to sport (RR = 0.98; 95% CI = 0.81, 1.18; I2 = 0%; P = .8110) for arthroscopic Bankart repair or open Latarjet procedure. CONCLUSION: For patients who underwent arthroscopic Bankart repair for anterior shoulder stabilization, recurrent rates of instability were significantly higher for males than for females. When open Bankart and Latarjet procedures were included, there was no difference. No difference was seen between males and females after arthroscopic Bankart repair or open Latarjet procedures with regard to return to sport or apprehension.

Cytochromes P450 in the biocatalytic valorization of lignin.

The valorization of lignin is critical to establishing sustainable biorefineries as we transition away from petroleum-derived feedstocks. Advances in lignin fractionation and depolymerization are yielding new opportunities for the biocatalytic upgrading of lignin-derived aromatic compounds (LDACs) using microbial cell factories. Given their roles in lignin metabolism and their catalytic versatility, cytochromes P450 are attractive enzymes in engineering such biocatalysts. Here we highlight P450s that catalyze aromatic O-demethylation, a rate-limiting step in the conversion of LDACs to valuable chemicals, including efforts to engineer the specificity of these enzymes and to use them in developing biocatalysts. We also discuss broader opportunities at the intersection of biochemistry, structure-guided enzyme engineering, and metabolic engineering for application of P450s in the emerging area of microbial lignin valorization.

A reduced concentration femoral nerve block is effective for perioperative pain control following ACL reconstruction: a retrospective review.

INTRODUCTION: Femoral nerve block (FNB) is a routinely used regional analgesic technique for anterior cruciate ligament (ACL) reconstruction. One method to balance the analgesic effect and functional impairment of FNBs may be to control the concentration of local anesthetics utilized for the block. MATERIALS AND METHODS: Retrospective chart review was performed on 390 consecutive patients who underwent ACL reconstruction between June 2014 and May 2017. Patients were divided into those who received a standard (0.5%-bupivacaine) or low (0.1-0.125%-bupivacaine) concentration single-shot FNB performed with ultrasound guidance. Maximum postoperative VAS, Post-Anaesthesia Care Unit (PACU) time prior to discharge, need for additional 'rescue' block, and intravenous postoperative narcotic requirements were recorded. RESULTS: A total of 268 patients (28.4 ± 11.9 years) were included for final analysis, with 72 patients in the low-concentration FNB group and 196 patients receiving the standard concentration. There were no differences in the maximum postoperative VAS between the low (6.4 ± 2.5) and standard (5.7 ± 2.9) concentration groups (P = 0.08). Similarly, the time from PACU arrival to discharge was not different between groups (P = 0.64). A sciatic rescue block was needed in 22% of patients with standard-dose FNB compared to 30% of patients receiving the low-concentration FNB (P = 0.20). Patients with a hamstring autograft harvest were more likely to undergo a postoperative sciatic rescue block compared to a bone-patellar tendon autograft (P = 0.005), regardless of preoperative block concentration. Quadriceps activation was preserved with low-concentration blocks. CONCLUSIONS: Using 1/5th to 1/4th the standard local anesthetic concentration for preoperative femoral nerve block in ACL reconstruction did not significantly differ in peri-operative outcomes, PACU time, need for rescue blockade, or additional immediate opioid requirements. LEVEL OF EVIDENCE: III.

Segond Fractures Involve the Anterolateral Knee Capsule But Not the Iliotibial Band.

PURPOSE: To investigate the relationship between the Segond fracture and the anterolateral complex of the knee. METHODS: Between January 2014 and March 2020, patients who presented with an anterior cruciate ligament (ACL) tear requiring acute surgical reconstruction (within 10 days from trauma) were evaluated for inclusion in this study. Patients were included if they had an acute ACL tear with an associated Segond fracture (or "Segond lesion") as detected by radiograph or magnetic resonance imaging. The lateral compartment was exposed in all cases using a 5-cm lateral hockey-stick incision, which was carried down to the iliotibial band. The fascia lata was first inspected and then longitudinally divided along its fibers to expose lateral compartment. The posterolateral corner to Gerdy's tubercle anteriorly was exposed and examined. Once the Segond fracture was identified, it was recorded and photographed. RESULTS: Seventeen patients were enrolled in the study. Dissection of the Segond fracture demonstrated attachment to the anterolateral capsule only. No other discernible attachment to the Segond fracture was noted. Surgical exploration of the anterolateral knee did not reveal injury to the iliotibial band. CONCLUSIONS: Careful dissection of Segond fractures during repair revealed that there is a discernible attachment with the anterolateral capsule to the bone injury in all patients with acute ACL tears undergoing surgical reconstruction and no connections to the iliotibial band. CLINICAL RELEVANCE: The precise pathogenesis of Segond fractures has been the subject of debate, partially due to the complexity of the anatomy of the anterolateral aspect of the knee. Proper understanding of the anatomy of type IV ALL injures with Segond fractures is important to improve treatment of these injuries.

Measurement technique for posterior tibial slope on radiographs can affect its relationship to the risk of anterior cruciate ligament rupture.

PURPOSE: The purpose of this study was to determine the most reliable radiographic measurement method to evaluate PTS as a risk factor for ACL reconstruction failure. METHODS: Patients who underwent ACL reconstruction or ACL revision reconstruction between January 2009 and December 2014 by a single surgeon were included. Fifty-two consecutive patients who underwent ACL revision reconstruction were compared to a random selection of 52 patients who underwent primary ACL reconstruction and a control group of 52 patients without ACL injury. ACL reconstruction was performed using either ipsilateral (primary) or contralateral (revision) quadrupled hamstring autograft. Lateral knee radiographs were evaluated using three methods: (1) longitudinal axis, (2) anterior tibial cortex axis, and (3) posterior tibial cortex. RESULTS: A significant difference was found between subjects who underwent ACL reconstruction and control knees (6.79° vs. 5.31°, p = 0.046) using the posterior tibial cortex method. No other statistical significance was found between groups. A multiple linear regression analysis found that the PTS as measured by any method was not affected by the patient's age, sex, height, weight, and BMI. All methods of measurement for PTS demonstrated excellent (ICC > 0.90) intra-rater and inter-rater reliability, but only the posterior tibial cortex method maintained excellent intra-rater and inter-rater reliability (ICC > 0.90) when evaluating patients with ACL revision reconstruction. CONCLUSIONS: The posterior tibial cortex measurement is the most reliable method for analyzing the PTS on lateral knee radiographs in patients undergoing ACL revision reconstruction.

Glioma Stem Cell-Specific Superenhancer Promotes Polyunsaturated Fatty-Acid Synthesis to Support EGFR Signaling.

Glioblastoma ranks among the most aggressive and lethal of all human cancers. Functionally defined glioma stem cells (GSC) contribute to this poor prognosis by driving therapeutic resistance and maintaining cellular heterogeneity. To understand the molecular processes essential for GSC maintenance and tumorigenicity, we interrogated the superenhancer landscapes of primary glioblastoma specimens and in vitro GSCs. GSCs epigenetically upregulated ELOVL2, a key polyunsaturated fatty-acid synthesis enzyme. Targeting ELOVL2 inhibited glioblastoma cell growth and tumor initiation. ELOVL2 depletion altered cellular membrane phospholipid composition, disrupted membrane structural properties, and diminished EGFR signaling through control of fatty-acid elongation. In support of the translational potential of these findings, dual targeting of polyunsaturated fatty-acid synthesis and EGFR signaling had a combinatorial cytotoxic effect on GSCs. SIGNIFICANCE: Glioblastoma remains a devastating disease despite extensive characterization. We profiled epigenomic landscapes of glioblastoma to pinpoint cell state-specific dependencies and therapeutic vulnerabilities. GSCs utilize polyunsaturated fatty-acid synthesis to support membrane architecture, inhibition of which impairs EGFR signaling and GSC proliferation. Combinatorial targeting of these networks represents a promising therapeutic strategy.See related commentary by Affronti and Wellen, p. 1161.This article is highlighted in the In This Issue feature, p. 1143.

Recurrent Shoulder Instability: Do Morbidity and Treatment Differ Based on Insurance?

BACKGROUND: Patients with public insurance often face barriers to obtaining prompt orthopaedic care. For patients with recurrent traumatic anterior shoulder instability, delayed care may be associated with increasing bone loss and subsequently more extensive surgical procedures. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate whether differences exist in patients undergoing treatment for shoulder instability between those with Medicaid versus non-Medicaid insurance. We hypothesized that at the time of surgery, Medicaid patients would have experienced greater delays in care, would have a more extensive history of instability, would have more bone loss, and would require more extensive surgical procedures than other patients. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients were identified who underwent surgical stabilization for traumatic anterior shoulder instability between January 1, 2011, and December 1, 2015, at a single sports medicine practice. Clinic, billing, and operative records were reviewed for each patient to determine age, sex, insurance type, total number of instability episodes, time from first instability episode to surgery, intraoperative findings, and procedure performed. Glenoid bone loss was quantified by use of preoperative imaging studies. RESULTS: During this time period, 206 patients (55 Medicaid, 131 private insurance, 11 Tricare, 9 workers' compensation) underwent surgical stabilization for traumatic anterior shoulder instability. Average wait time from initial injury to surgery was 1640 days (95% CI, 1155-2125 days) for Medicaid patients compared with 1237 days (95% CI, 834-1639 days) for others (P = .005). Medicaid patients were more likely to have sustained 5 or more instability events at the time of surgery (OR, 3.3; 95% CI, 1.64-6.69; P = .001), had a higher risk of having 15% or more glenoid bone loss on preoperative imaging (OR, 3.5; 95% CI, 1.3-10.0; P = .01), and had a higher risk of requiring Latarjet or other open stabilization procedures as opposed to an arthroscopic repair (OR, 3.0; 95% CI, 1.5-6.2; P = .002) when compared with other patients. CONCLUSION: Among patients undergoing surgery for traumatic anterior shoulder instability, patients with Medicaid had significantly more delayed care. Correspondingly, they reported a more extensive history of instability, were more likely to have severe bone loss, and required more invasive stabilization procedures.

Anterolateral Ligament Repair Augmented With Suture Tape in Acute Anterior Cruciate Ligament Reconstruction.

Several extra-articular surgical techniques in addition to anterior cruciate ligament reconstruction have been proposed to better restore rotational instability of the knee. One option is surgical repair of the anterolateral ligament in acute cases to achieve an anatomic reconstruction. An additional augmentation to the repair could allow a load-sharing-and thus protective-effect for the repair during the healing process. The purpose of this Technical Note is to describe a primary repair of the anterolateral ligament with suture tape augmentation (Internal Brace; Arthrex, Naples, FL) in a patient with an acute anterior cruciate ligament tear.

Revision Anterior Cruciate Ligament Reconstruction With Hamstrings and Extra-articular Tenodesis: A Mid- to Long-Term Clinical and Radiological Study.

PURPOSE: To present the mid- to long-term clinical and radiographic outcomes of a series of patients who underwent revision anterior cruciate ligament (ACL) reconstruction with doubled gracilis and semitendinosus (DGST) autograft and a lateral extra-articular tenodesis (LET). METHODS: Patients who underwent revision ACL reconstruction with DGST and LET by a single surgeon between January 1997 and December 2013 were included. Revision was indicated by ACL failure noted on magnetic resonance imaging, persistent clinical instability, or laxity on clinical exam. Patients were evaluated preoperatively and at latest follow-up by an independent board-certified orthopaedic surgeon. Outcomes included Lachman and pivot shift tests, validated clinical and patient reported outcomes scores, and radiographic analysis. The presence of previous meniscectomy or chondral injury was recorded intraoperatively. RESULTS: A total of 118/132 potential patients (89.4%) was available for follow-up at a mean 10.6 years (3-19 years) postoperatively. Lachman and pivot shift examinations as well as the side-to-side difference on an KT-1000 arthrometer demonstrated significant improvement at latest follow-up (P < .05) versus preoperative evaluation. Severe degenerative disease was present in 25% of patients on radiograph and correlated with worsened clinical outcomes. Previous meniscectomy was the only risk factor analyzed that correlated with worsened radiographic grade. No patients had a graft tear based on clinical and/or magnetic resonance imaging evaluation, but 9 (7.6%) failed based on a side-to-side difference of >5 mm on the KT-1000, a grade ≥2+ on pivot shift, or report of continued instability. CONCLUSIONS: Revision ACL reconstruction with DGST and LET at mid- to long-term follow-up provides continued improvement in clinical and radiological outcomes from preoperative assessment. Meniscectomy was the only factor related to worsened radiological grades and clinical outcomes. LEVEL OF EVIDENCE: Level IV, case series.

Surgical Treatment of Segond Fractures in Acute Anterior Cruciate Ligament Reconstruction.

BACKGROUND: The Segond fracture is an avulsion-type fracture located on the anterolateral aspect of the tibia associated with a ligament recently termed the anterolateral ligament. This injury has been described as pathognomonic for an anterior cruciate ligament (ACL) tear and is associated with a higher grade pivot shift. PURPOSE: To present and report 2-year clinical outcomes of a surgical technique for acute ACL reconstruction with fixation of a concomitant Segond fracture. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective chart review was performed of patients who underwent acute reconstruction for a complete ACL tear with concomitant Segond fracture fixation between January 2010 and December 2014; surgery was performed by a single surgeon. Patients underwent direct Segond fracture repair by either suture alone, suture anchor, or cannulated screw fixation based on the size of the lesion, followed by a 2-incision hamstring autograft intra-articular reconstruction. Pre- and postoperative KT-1000 arthrometer assessment, Lachman test, and pivot-shift test were performed, and patients were administered validated subjective outcome surveys. RESULTS: Twelve patients met inclusion criteria for this review. The measured pre- and postoperative objective and subjective scores were significantly improved in all patients. Side-to-side anterior laxity was significantly improved in all patients based on Lachman and KT-1000 arthrometer testing. A significant pivot shift demonstrated preoperatively (3+, n = 11 [92%]; 2+, n = 1 [8%]) was corrected after fixation, except in 1 patient (8%), who maintained a 1+ pivot shift. Lysholm, Tegner, and International Knee Documentation Committee subjective and objective scores were significantly improved. At a minimum 2-year follow-up, no patients reported rerupture, and only 1 patient (8%) underwent a subsequent procedure (a meniscectomy). No major or minor complications were reported, and all patients returned to their previous activity levels at a mean of 6 months postoperatively. CONCLUSION: Direct repair of the Segond fracture and plication of the anterolateral capsule in patients with an ACL rupture and a high-grade pivot shift demonstrate good clinical outcomes, restoration of rotational stability, and maintenance of knee range of motion at 2 years postoperatively, with no major complications.

Video Movement Analysis Using Smartphones (ViMAS): A Pilot Study.

The use of smartphones in clinical practice is steadily increasing with the availability of low cost/freely available "apps" that could be used to assess human gait. The primary aim of this manuscript is to test the concurrent validity of kinematic measures recorded by a smartphone application in comparison to a 3D motion capture system in the sagittal plane. The secondary aim was to develop a protocol for clinicians on the set up of the smartphone camera for video movement analysis. The sagittal plane knee angle was measured during heel strike and toe off events using the smart phone app and a 3D motion-capture system in 32 healthy subjects. Three trials were performed at near (2-m) and far (4-m) smartphone camera distances. The order of the distances was randomized. Regression analysis was performed to estimate the height of the camera based on either the subject's height or leg length. Absolute measurement errors were least during toe off (3.12 ± 5.44 degrees) compared to heel strike (5.81 ± 5.26 degrees). There were significant (p < 0.05) but moderate agreements between the application and 3D motion capture measures of knee angles. There were also no significant (p > 0.05) differences between the absolute measurement errors between the two camera positions. The measurement errors averaged between 3 - 5 degrees during toe off and heel strike events of the gait cycle. The use of smartphone apps can be a useful tool in the clinic for performing gait or human movement analysis. Further studies are needed to establish the accuracy in measuring movements of the upper extremity and trunk.