UDP-6-glucose dehydrogenase in hormonally responsive breast cancers.

Survival for metastatic breast cancer is low and thus, continued efforts to treat and prevent metastatic progression are critical. Estrogen is shown to promote aggressive phenotypes in multiple cancer models irrespective of estrogen receptor (ER) status. Similarly, UDP-Glucose 6-dehydrogenase (UGDH) a ubiquitously expressed enzyme involved in extracellular matrix precursors, as well as hormone processing increases migratory and invasive properties in cancer models. While the role of UGDH in cellular migration is defined, how it intersects with and impacts hormone signaling pathways associated with tumor progression in metastatic breast cancer has not been explored. Here we demonstrate that UGDH knockdown blunts estrogen-induced tumorigenic phenotypes (migration and colony formation) in ER+ and ER- breast cancer in vitro. Knockdown of UGDH also inhibits extravasation of ER- breast cancer ex vivo, primary tumor growth and animal survival in vivo in both ER+ and ER- breast cancer. We also use single cell RNA-sequencing to demonstrate that our findings translate to a human breast cancer clinical specimen. Our findings support the role of estrogen and UGDH in breast cancer progression provide a foundation for future studies to evaluate the role of UGDH in therapeutic resistance to improve outcomes and survival for breast cancer patients.

Single-cell RNA sequencing comparison of the human metastatic prostate spine tumor microenvironment.

Spinal column tumors can be difficult to process for single-cell omic studies, given the heterogeneity in tissue. Here, we present a protocol for operating room-to-benchtop single-cell processing of clinical specimens from a prostate cancer patient. We describe steps for sample homogenization, red blood cell lysis, cryopreservation, and single-cell sequencing analysis. This protocol can be used to identify prognostic markers and therapeutic targets for patients with osseous spine metastases and better inform eligibility for clinical trials.

UDP-glucose dehydrogenase (UGDH) in clinical oncology and cancer biology.

UDP-glucose-6-dehydrogenase (UGDH) is a cytosolic, hexameric enzyme that converts UDP-glucose to UDP-glucuronic acid (UDP-GlcUA), a key reaction in hormone and xenobiotic metabolism and in the production of extracellular matrix precursors. In this review, we classify UGDH as a molecular indicator of tumor progression in multiple cancer types, describe its involvement in key canonical cancer signaling pathways, and identify methods to inhibit UGDH, its substrates, and its downstream products. As such, we position UGDH as an enzyme to be exploited as a potential prognostication marker in oncology and a therapeutic target in cancer biology.

Racial disparities in inpatient clinical presentation, treatment, and outcomes in brain metastasis.

Background: Few studies have assessed the impact of race on short-term patient outcomes in the brain metastasis population. The goal of this study is to evaluate the association of race with inpatient clinical presentation, treatment, in-hospital complications, and in-hospital mortality rates for patients with brain metastases (BM). Method: Using data collected from the National Inpatient Sample between 2004 and 2014, we retrospectively identified adult patients with a primary diagnosis of BM. Outcomes included nonroutine discharge, prolonged length of stay (pLOS), in-hospital complications, and mortality. Results: Minority (Black, Hispanic/other) patients were less likely to receive surgical intervention compared to White patients (odds ratio [OR] 0.70; 95% confidence interval [CI] 0.66-0.74, p < 0.001; OR 0.88; 95% CI 0.84-0.93, p < 0.001). Black patients were more likely to develop an in-hospital complication than White patients (OR 1.35, 95% CI 1.28-1.41, p < 0.001). Additionally, minority patients were more likely to experience pLOS than White patients (OR 1.48; 95% CI 1.41-1.57, p < 0.001; OR 1.34; 95% CI 1.27-1.42, p < 0.001). Black patients were more likely to experience a nonroutine discharge (OR 1.25; 95% CI 1.19-1.31, p < 0.001) and higher in-hospital mortality than White (OR 1.13; 95% CI 1.03-1.23, p = 0.008). Conclusion: Our analysis demonstrated that race is associated with disparate short-term outcomes in patients with BM. More efforts are needed to address these disparities, provide equitable care, and allow for similar outcomes regardless of care.

Homologous Recombination Repair Gene Variants and Outcomes Among Patients With Prostate Cancer Treated With Poly (ADP-ribose) Polymerase Inhibitors.

PURPOSE: Poly ADP-ribose polymerase inhibitors (PARPi) are used for patients with advanced prostate cancer bearing alterations in homologous recombination repair (HRR) genes. We sought to characterize HRR gene variants and describe real-world outcomes for patients on PARPi. METHODS: The US Department of Veterans Affairs' National Precision Oncology Program's database was reviewed to identify patients who underwent somatic DNA sequencing and were prescribed a PARPi before May 15, 2020. Somatic and germline variants within HRR genes were reported, and pathogenicity was reviewed via OncoKB. In patients treated with PARPi for > 4 weeks, the rate of those achieving a 30% decrease in prostate-specific antigen (PSA30) and composite progression-free survival (PFS) were compared between patients bearing pathogenic variants of BRCA2 and patients without these variants using Mann-Whitney and log-rank tests, respectively. RESULTS: Forty-eight patients bearing 67 total HRR gene variants were prescribed PARPi for prostate cancer. Twenty-one patients (43.8%) were found to have at least one pathogenic HRR gene variant. Eight (16.6%) were referred to genetic counseling, and five (10.4%) were ultimately confirmed with germline variants. The median PFS was 4.0 months, and PSA30 was 25.6% (11 of 43) for all 43 evaluable patients. Patients with pathogenic BRCA2 variants (n = 13) had higher PSA30 (69.2% v 4.0%; P < .001) and longer PFS (7.2 v 2.8 months; P = .0291) than those without. CONCLUSION: In a real-world setting, heavily pretreated patients with prostate cancer and pathogenic BRCA2 variants have a significant PSA response rate and a PFS > 7 months with PARPi. This work emphasizes the importance of determining pathogenicity and origin of HRR alterations to better inform clinical treatment decisions and highlights the need for provider education and other decision support tools.

Grief in Medical Students: The Short and Long-Term Impacts on Health and Well-Being.

CONTEXT: Healthcare workers often experience grief stemming from the loss of patients under their care. The impact of personal grief on healthcare workers' wellbeing is less well described, particularly for trainees. To better characterize the prevalence and impact of personal grief on the mental and physical health of medical students, we conducted a survey of medical students at our institution. METHODS: An electronic Qualtrics survey was distributed to all currently enrolled medical students at our institution. After an initial question screening for loss before or during medical school, our survey assessed (1) basic demographic data; (2) relationship to the deceased; (3) impact of the loss on trainee health; and (4) utilization of institutional supports for grief. RESULTS: A total of 344 (68.8%) students responded to our survey. Two hundred and 25 (65.4%) students had experienced personal loss prior to or during medical school. 53.7% experienced more than 1 loss, with most of these losses (62.5%) occurring more than 2 years prior to the survey date. Up to 40% of respondents reported at least 1 psychologically distressing symptom that persisted beyond 1 year. Most students (93.8%) relied on family members for support; however, 23.2% of students indicated they would use institutional resources if available. CONCLUSION: Most medical students have experienced bereavement before or during medical school, which has had significant impact on their well-being. While medical students did not typically utilize institutionally based resources, many students expressed interest in such resources.

Muscle Flap Closures in Spine Surgery: Predictors of Usage Patterns and Factors Associated With Postoperative Complications From the NSQIP Database.

STUDY DESIGN: Retrospective cohort study using the National Surgical Quality Improvement Program. OBJECTIVE: The objective of this study was to identify preoperative factors that impact the decision to perform prophylactic muscle flap closure and assess risk factors for wound healing complications in patients undergoing spinal procedures with and without muscle flap closure. SUMMARY OF BACKGROUND DATA: Prior studies suggest that muscle flap closure following complex spine surgery results in a lower risk of wound healing complications. However, these studies have been limited to single institutions and/or surgeons. METHODS: The National Surgical Quality Improvement Program database was queried for all patients undergoing spine surgery between 2005 and 2017 with and without concomitant muscle flaps. Preoperative and perioperative variables were extracted. Univariate and multivariate analyses were performed to assess risk factors influencing surgical site infection (SSI) and wound disruption, as well as to delineate which preoperative factors increased the likelihood of patients receiving flap closures a priori. RESULTS: Concomitant muscle flaps were performed on 758 patients; 301,670 patients did not receive a flap. Overall 29 (3.83%) patients in the flap group experienced SSI compared to 5154 (1.71%) in the nonflap group (P<0.0001). Preoperative steroid use [odds ratio (OR) 0.5; P<0.0001], wound infection (OR 0.24; P<0.0001), elevated white blood cell count (OR 1.034; P<0.0001), low hematocrit (OR 0.94; P<0.0001), preoperative transfusion (OR 0.22; P=0.0068) were significantly associated with utilization of muscle flaps. Perioperative factors including a contaminated wound (OR 4.72; P<0.0001), the American Society of Anesthesiologists classification of severe disease (OR 1.92; P=0.024), and longer operative time (OR 1.001; P=0.0024) were significantly associated with postoperative wound disruption. In addition, after propensity score matching for these factors that increase risk of wound complications, there was no difference in the rates of SSI between the flap and nonflap group. CONCLUSION: Our results suggest that patients with a higher burden of illness preoperatively are more likely to receive prophylactic paraspinal flaps which can reduce the rates of wound-related complications.

Insurance status as a mediator of clinical presentation, type of intervention, and short-term outcomes for patients with metastatic spine disease.

BACKGROUND: It is well established that insurance status is a mediator of disease management, treatment course, and clinical outcomes in cancer patients. Our study assessed differences in clinical presentation, treatment course, mortality rates, and in-hospital complications for patients admitted to the hospital with late-stage cancer - specifically, metastatic spine disease (MSD), by insurance status. METHODS: The United States National Inpatient Sample (NIS) database (2012-2014) was queried to identify patients with visceral metastases, metastatic spinal cord compression (MSCC) or pathological fracture of the spine in the setting of cancer. Clinical presentation, type of intervention, mortality rates, and in-hospital complications were compared amongst patients by insurance coverage (Medicare, Medicaid, commercial or unknown). Multivariable logistical regression and age sensitivity analyses were performed. RESULTS: A total of 48,560 MSD patients were identified. Patients with Medicaid coverage presented with significantly higher rates of MSCC (p < 0.001), paralysis (0.008), and visceral metastases (p < 0.001). Patients with commercial insurance were more likely to receive surgical intervention (OR 1.43; p < 0.001). Patients with Medicaid < 65 had higher rates of prolonged length of stay (PLOS) (OR 1.26; 95% CI, 1.01-1.55; p = 0.040) while both Medicare and Medicaid patients < 65 were more likely to have non-routine discharges. In-hospital mortality rates were significantly higher for patients with Medicaid (OR 2.66; 95% CI 1.20-5.89; p = 0.016) and commercial insurance (OR 1.58; 95% CI 1.09-2.27;p = 0.013) older than 65. CONCLUSION: Given the differing severity in MSD presentation, mortality rates, and rates of PLOS by insurance status, our results identify disparities based on insurance coverage.

Animal Models of Metastatic Lesions to the Spine: A Focus on Epidural Spinal Cord Compression.

Epidural spinal cord compression (ESCC) secondary to spine metastases is one of the most devastating sequelae of primary cancer as it may lead to muscle weakness, paresthesia, pain, and paralysis. Spine metastases occur through a multistep process that can result in eventual ESCC; however, the lack of a preclinical model to effectively recapitulate each step of this metastatic cascade and the symptom burden of ESCC has limited our understanding of this disease process. In this review, we discuss animal models that best recapitulate ESCC. We start with a broad discussion of commonly used models of bone metastasis and end with a focused discussion of models used to specifically study ESCC. Orthotopic models offer the most authentic recapitulation of metastasis development; however, they rarely result in symptomatic ESCC and are challenging to replicate. Conversely, models that involve injection of tumor cells directly into the bloodstream or bone better mimic the symptoms of ESCC; however, they provide limited insight into the epithelial to mesenchymal transition and natural hematogenous spread of tumor cells. Therefore, until an ideal model is created, it is critical to select an animal model that is specifically designed to answer the scientific question of interest.

A Need for More Molecular Profiling in Brain Metastases.

As local disease control improves, the public health impact of brain metastases (BrM) continues to grow. Molecular features are frequently different between primary and metastatic tumors as a result of clonal evolution during neoplasm migration, selective pressures imposed by systemic treatments, and differences in the local microenvironment. However, biomarker information in BrM is not routinely obtained despite emerging evidence of its clinical value. We review evidence of discordance in clinically actionable biomarkers between primary tumors, extracranial metastases, and BrM. Although BrM biopsy/resection imposes clinical risks, these risks must be weighed against the potential benefits of assessing biomarkers in BrM. First, new treatment targets unique to a patient's BrM may be identified. Second, as BrM may occur late in a patient's disease course, resistance to initial targeted therapies and/or loss of previously identified biomarkers can occur by the time of occult BrM, rendering initial and other targeted therapies ineffective. Thus, current biomarker data can inform real-time treatment options. Third, biomarker information in BrM may provide useful prognostic information for patients. Appreciating the importance of biomarker analyses in BrM tissue, including how it may identify specific drivers of BrM, is critical for the development of more effective treatment strategies to improve outcomes for this growing patient population.

Severe Acute Respiratory Syndrome Coronavirus 2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study.

BACKGROUND: Child with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection typically have mild symptoms that do not require medical attention, leaving a gap in our understanding of the spectrum of SARS-CoV-2-related illnesses that the viruses causes in children. METHODS: We conducted a prospective cohort study of children and adolescents (aged <21 years) with a SARS-CoV-2-infected close contact. We collected nasopharyngeal or nasal swabs at enrollment and tested for SARS-CoV-2 using a real-time polymerase chain reaction assay. RESULTS: Of 382 children, 293 (77%) were SARS-CoV-2-infected. SARS-CoV-2-infected children were more likely to be Hispanic (P < .0001), less likely to have asthma (P = .005), and more likely to have an infected sibling contact (P = .001) than uninfected children. Children aged 6-13 years were frequently asymptomatic (39%) and had respiratory symptoms less often than younger children (29% vs 48%; P = .01) or adolescents (29% vs 60%; P < .001). Compared with children aged 6-13 years, adolescents more frequently reported influenza-like (61% vs 39%; P < .001) , and gastrointestinal (27% vs 9%; P = .002), and sensory symptoms (42% vs 9%; P < .0001) and had more prolonged illnesses (median [interquartile range] duration: 7 [4-12] vs 4 [3-8] days; P = 0.01). Despite the age-related variability in symptoms, wWe found no difference in nasopharyngeal viral load by age or between symptomatic and asymptomatic children. CONCLUSIONS: Hispanic ethnicity and an infected sibling close contact are associated with increased SARS-CoV-2 infection risk among children, while asthma is associated with decreased risk. Age-related differences in clinical manifestations of SARS-CoV-2 infection must be considered when evaluating children for coronavirus disease 2019 and in developing screening strategies for schools and childcare settings.

Patient outcomes and tumor control in single-fraction versus hypofractionated stereotactic body radiation therapy for spinal metastases.

OBJECTIVE: Stereotactic body radiation therapy (SBRT) offers efficient, noninvasive treatment of spinal neoplasms. Single-fraction (SF) high-dose SBRT has a relatively narrow therapeutic window, while hypofractionated delivery of SBRT may have an improved safety profile with similar efficacy. Because the optimal approach of delivery is unknown, the authors examined whether hypofractionated SBRT improves pain and/or functional outcomes and results in better tumor control compared with SF-SBRT. METHODS: This is a single-institution retrospective study of adult patients with spinal metastases treated with SF- or three-fraction (3F) SBRT from 2008 to 2019. Demographics and baseline characteristics, radiographic data, and posttreatment outcomes at a minimum follow-up of 3 months are reported. RESULTS: Of the 156 patients included in the study, 70 (44.9%) underwent SF-SBRT (median total dose 1700 cGy) and 86 (55.1%) underwent 3F-SBRT (median total dose 2100 cGy). At baseline, a higher proportion of patients in the 3F-SBRT group had a worse baseline profile, including severity of pain (p < 0.05), average use of pain medication (p < 0.001), and functional scores (p < 0.05) compared with the SF-SBRT cohort. At the 3-month follow-up, the 3F-SBRT cohort experienced a greater frequency of improvement in pain compared with the SF-SBRT group (p < 0.05). Furthermore, patients treated with 3F-SBRT demonstrated a higher frequency of improved Karnofsky Performance Scale (KPS) scores (p < 0.05) compared with those treated with SF-SBRT, with no significant difference in the frequency of improvement in modified Rankin Scale scores. Local tumor control did not differ significantly between the two cohorts. CONCLUSIONS: Patients who received spinal 3F-SBRT more frequently achieved significant pain relief and an increased frequency of improvement in KPS compared with those treated with SF-SBRT. Local tumor control was similar in the two groups. Future work is needed to establish the relationship between fractionation schedule and clinical outcomes.

SARS-CoV-2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study.

BACKGROUND: Children with SARS-CoV-2 infection typically have mild symptoms that do not require medical attention, leaving a gap in our understanding of the spectrum of illnesses that the virus causes in children. METHODS: We conducted a prospective cohort study of children and adolescents (<21 years of age) with a SARS-CoV-2-infected close contact. We collected nasopharyngeal or nasal swabs at enrollment and tested for SARS-CoV-2 using a real-time PCR assay. RESULTS: Of 382 children, 289 (76%) were SARS-CoV-2-infected. SARS-CoV-2-infected children were more likely to be Hispanic (p<0.0001), less likely to have a history of asthma (p=0.009), and more likely to have an infected sibling contact (p=0.0007) than uninfected children. Children ages 6-13 years were frequently asymptomatic (38%) and had respiratory symptoms less often than younger children (30% vs. 49%; p=0.008) or adolescents (30% vs. 59%; p<0.0001). Compared to children ages 6-13 years, adolescents more frequently reported influenza-like (61% vs. 39%; p=0.002), gastrointestinal (26% vs. 9%; p=0.003), and sensory symptoms (43% vs. 9%; p<0.0001), and had more prolonged illnesses [median (IQR) duration: 7 (4, 12) vs. 4 (3, 8) days; p=0.004]. Despite the age-related variability in symptoms, we found no differences in nasopharyngeal viral load by age or between symptomatic and asymptomatic children. CONCLUSIONS: Hispanic ethnicity and an infected sibling close contact are associated with increased SARS-CoV-2 infection risk among children, while a history of asthma is associated with decreased risk. Age-related differences in the clinical manifestations of SARS-CoV-2 infection must be considered when evaluating children for COVID-19 and in developing screening strategies for schools and childcare settings.

Juvenile Osteochondritis Dissecans of the Trochlea: A Cohort Study of 34 Trochlear Lesions Associated With Sporting Activities That Load the Patellofemoral Joint.

BACKGROUND: Juvenile osteochondritis dissecans (JOCD) lesions are rarely located in the trochlea and few studies have focused on the causes and outcomes of JOCD lesions in this part of the knee. The purpose of this study is to (1) evaluate the clinical characteristics and outcomes of patients who undergo surgery for JOCD in this unusual location as well as (2) assess the association between trochlear JOCD and participation in sporting activities that load the patellofemoral joint. METHODS: We conducted a retrospective cohort study of 34 trochlear JOCD lesions in 30 patients. Cases that involved traumatic cartilage shear or patella instability were excluded. Preoperative and postoperative magnetic resonance images and x-rays were evaluated and demographic data, sports played, comorbidities, surgical procedures, and clinical data were extracted from medical records. A case-control cohort of 102 femoral condyle lesions was used to assess the correlation between sports played and lesion location. RESULTS: The cohort comprised 34 consecutive trochlear JOCD lesions in 30 patients (26 males, 4 females). Average age at surgery was 13.8 years (9.3 to 18.0 y). In total, 27 (90%) patients were active, and of these active patients, soccer and basketball were the most common sports played. In the case-control comparison, the correlation between playing either basketball or soccer and the presence of a trochlear JOCD lesion was statistically significant (P=0.017). In total, 21 knees (62%) received operative treatment. Sixteen of the surgical patients underwent repair and fixation with bioabsorbable nails. The average length of clinical and radiographic follow-up was 21.1 months. All patients who underwent fixation showed radiographic and/or clinical indications of healing at most recent follow-up. Thirteen of the patients who underwent fixation were active, and all of these patients reported successful return to sports. Thirteen knees underwent nonoperative treatment, and the majority of these patients had limited follow-up. CONCLUSIONS: We report a significant association between pediatric athletes who play basketball and soccer and the development of trochlear JOCD, suggesting that repetitive loading of the patellofemoral joint may play a role in the development of JOCD lesions. Patients with trochlear JOCD lesions were likely to undergo surgery, and repair and fixation of the lesions produced good outcomes at short-term follow-up. LEVEL OF EVIDENCE: Level III-case-control study.

Utilization of a Wide Array of Nonvalidated Outcome Scales in Pediatric Orthopaedic Publications: Can't We All Measure the Same Thing?

PURPOSE: Clinical changes are best evaluated with standardized, validated outcomes, including both patient-reported outcome measures and surgeon-reported outcome measures (PROMs and SROMs). The purpose of this study was to describe the spectrum of outcome measures used in pediatric orthopaedic publications over the past 10 years and to determine the proportion that are in fact age-appropriate, validated, and appropriately applied in terms of condition and population. METHODS: The Journal of Bone and Joint Surgery, The Bone and Joint Journal, Journal of Pediatric Orthopaedics A and B, and Journal of Children's Orthopaedics were systematically searched for studies including children aged 18 and below, over a 10-year period from January 2005 to December 2014. Economic evaluations, letters, editorials, review articles, and clinical guidelines were excluded. SROMs and PROMs used were extracted, as were details on subject age and condition for which they were used. Each outcome scale was assessed for validity, and the proportion of scales used appropriately was calculated. Cochrane-Armitage test of trend was used to determine changes in PROM and SROM utilization over the study period. RESULTS: A total of 4614 articles were identified, of which 2251 met inclusion and exclusion criteria. In total, 259 (11.5%) of studies used a PROM, whereas 326 (14.5%) used a SROM. A total of 230 different outcome scales were identified; 115 were patient reported and 115 were surgeon reported. However, only 18.7% of SROMs and 38.3% of PROMs were applied to an age and disease-appropriate demographic. Overall, there was a significant increase in the overall utilization of PROMs during the study period (P=0.004), but no corresponding increase in pediatric-validated PROMs (P=0.164). SROM utilization did not significantly change over the study period (P=0.337). CONCLUSIONS: Within the field of pediatric orthopaedics, an expansive variety of outcome scales are used, many of which have not been validated in children. Improved uniformity in reporting of outcomes and use of disease and age-validated outcomes scales is essential to improve multicenter research collaboration and data quality to generate appropriate evidence-based conclusions and treatment strategies in pediatric orthopaedics. LEVEL OF EVIDENCE: Level IV-systematic review.

Surgical options for anterior cruciate ligament reconstruction in the young child.

Injury to the anterior cruciate ligament (ACL) is becoming increasingly common in the skeletally immature population. Historically, there was a reluctance to operate on skeletally immature patients due to potential damage to the physis and subsequent growth disturbances; however, more recently, ACL reconstruction techniques specifically developed for this young population have shown good outcomes and low complication rates. In this article, we briefly discuss the modifiable and non-modifiable risk factors for ACL injury in children, options for conservative management for ACL rupture, and outcomes for delayed operative management. The main focus of the manuscript is to describe three operative technique options designed for ACL reconstruction in skeletally immature patients and to review the literature on outcomes and complications of these techniques. Two of these techniques, namely the Modified MacIntosh and the all-epiphyseal techniques, are often referred to as physeal-sparing, while the third, i.e. the transphyseal technique, is not. While different in approach and technique, these procedures have been shown to produce good outcomes and minimal complications in the skeletally immature population. Despite these positive reports, it is also essential to be aware of potential complications and the potential risk of recurrence.

Nonmodifiable risk factors for anterior cruciate ligament injury.

PURPOSE OF REVIEW: As anterior cruciate ligament (ACL) injury is becoming increasingly prevalent in the population of active children and young adolescents, it is crucial to be aware of both the modifiable and nonmodifiable factors that place this population at increased ACL injury risk. Historically, there has not been a definitive consensus on all of these risk factors-particularly the nonmodifiable ones. RECENT FINDINGS: The present review has accumulated the most recent evidence for the nonmodifiable risk factors in ACL injury focusing particularly on female gender, generalized joint laxity, knee recurvatum, increased lateral tibial slope, decreased intercondylar notch width, structural lower extremity valgus, limb length discrepancy, family history, and history of contralateral knee ACL injury. SUMMARY: Physicians should be aware of the nonmodifiable risk factors for ACL tears in active children and adolescents and should also encourage avoidance of modifiable risk factors in this population. Young athletes with nonmodifiable risk factors are at a particularly increased risk of recurrent injury following ACL reconstruction (ACLR). We believe that a primary extra-articular augmentation via iliotibial band tenodesis at the same time of ACLR may decrease the rate of reinjury for the high risk athlete with multiple nonmodifiable risk factors.