HAF Prevents Hepatocyte Apoptosis and Hepatocellular Carcinoma through Transcriptional Regulation of the NF-κB pathway.

Background: Hepatocellular carcinoma (HCC) incidence is increasing worldwide due to the obesity epidemic, which drives metabolic dysfunction-associated steatohepatitis (MASH) that can lead to HCC. However, the molecular pathways that lead to MASH-HCC are poorly understood. We have previously reported that male mice with global haploinsufficiency of hypoxia-associated factor, HAF ( SART1 +/ - ) spontaneously develop MASH/HCC. However, the cell type(s) responsible for HCC associated with HAF loss are unclear. Results: SART1 -floxed mice were crossed with mice expressing Cre-recombinase within hepatocytes (Alb-Cre; hepS -/- ) or macrophages (LysM-Cre, macS -/- ). Only hepS -/- mice (both male and female) developed HCC suggesting that HAF protects against HCC primarily within hepatocytes. HAF-deficient macrophages showed decreased P-p65 and P-p50 and in many major components of the NF-κB pathway, which was recapitulated using HAF siRNA in vitro . HAF depletion increased apoptosis both in vitro and in vivo , suggesting that HAF mediates a tumor suppressor role by suppressing hepatocyte apoptosis. We show that HAF regulates NF-κB activity by controlling transcription of TRADD and RIPK1 . Mice fed a high-fat diet (HFD) showed marked suppression of HAF, P-p65 and TRADD within their livers after 26 weeks, but manifest profound upregulation of HAF, P-65 and TRADD within their livers after 40 weeks of HFD, implicating deregulation of the HAF-NF-κB axis in the progression to MASH. In humans, HAF was significantly decreased in livers with simple steatosis but significantly increased in HCC compared to normal liver. Conclusions: HAF is novel transcriptional regulator of the NF-κB pathway that protects against hepatocyte apoptosis and is a key determinant of cell fate during progression to MASH and MASH-HCC.

Quantifying the impact of the coronavirus 2019 pandemic on youth sports-related injuries in the USA.

The purpose of this study was to estimate monthly and annual trends in youth sports-related injury over the years 2016-2020 using the National Electronic Injury Surveillance System (NEISS) database to measure the impact of COVID-19 on overall and sport-specific rates of injury. Children and adolescents (0-19 years) presenting to USA emergency departments with sport participation injury from 2016 to 2020 were identified. Descriptive statistical analyses were performed of injury patterns. An interrupted time series analysis was applied to estimate changes in injury trends during COVID-19. Proportional changes in injury characteristics during this period were examined. An estimated 5 078 490 sports-related injuries were identified with an annual incidence of 1406 injuries per 100 000 population. Seasonal peaks in injuries occurred during September and May. About 58% of injuries were associated with contact sports, such as basketball, football, and soccer, and the most common injuries were sprains and strains. After the pandemic onset, there was a statistically significant 59% decrease in national youth sports-related injuries compared with the average estimates for 2016-2019. While the distribution of injury characteristics did not appear to change, the location of injury appeared to shift away from school toward alternative settings. A significant reduction in youth sports-related injuries was identified in 2020 coinciding with the COVID-19 pandemic, persisting throughout the rest of the year. No changes in the anatomic or demographic distribution of injuries were identified. This study expands our epidemiologic understanding of youth sports-related injury trends and how they changed following the pandemic onset.

Low-Intensity Pulsed Ultrasonography Plus Arthroscopic Drilling Does Not Improve Bone Healing More Than Arthroscopic Drilling Alone in Pediatric Patients With Stable Osteochondritis Dissecans of the Knee.

Purpose: To determine whether adjuvant use of bone stimulation would improve the rate of healing in the operative management of stable osteochondritis dissecans (OCD) of the knee in pediatric patients. Methods: This retrospective matched case-control study was performed at a single tertiary care pediatric hospital between January 2015 and September 2018. Patients who underwent antegrade drilling for stable femoral condyle OCD with greater than 2 years' follow-up were included. Preference was for all to receive postoperative bone stimulation; however, some were denied because of insurance coverage. This enabled us to create 2 matched groups of those who received postoperative bone stimulation and those who did not. Patients were matched on skeletal maturity, lesion location, sex, and age at surgery. The primary outcome measure was the rate of healing of the lesions determined by postoperative magnetic resonance imaging measurements at 3 months. Results: Fifty-five patients were identified who met the inclusion and exclusion criteria. Twenty patients from the bone stimulator group (BSTIM) were matched to 20 patients from the no bone stimulator group (NBSTIM). Mean age for BSTIM at surgery was 13.2 years ± 2.0 (range, 10.9-16.7) and for NBSTIM at surgery 12.9 years ± 2.0 (range, 9.3-17.3). At 2 years, 36 patients (90%) in both groups went on to clinical healing without further interventions. In BSTIM, there was a mean decrease of 0.9 (±1.8) mm in lesion on coronal width and 12 patients (63%) had overall improved healing; in NBSTIM there was a mean decrease of 0.8 (±3.6) mm in coronal width and 14 patients (78%) had improved healing. No statistical differences in the rate of healing were found between the 2 groups (P = .706). Conclusion: In antegrade drilling of stable knee OCD lesions in pediatric and adolescent patients, adjuvant bone stimulator use did not appear to improve radiographic or clinical healing. Level of evidence: Level III, retrospective case-control study.

Comparison of pediatric performance athlete injuries presenting to emergency departments.

OBJECTIVE: Pediatric injuries in performance sports represent a significant healthcare burden and account for over 50,000 annual Emergency Department (ED) visits in the United States. The objective of this study was to characterize and compare pediatric injury presentation across the most common performance sports. METHODS: The National Electronic Injury Surveillance System (NEISS) database was retrospectively analyzed for pediatric injuries (3-18 years) related to gymnastics, dance, or cheerleading from 2015-2019. Cases were categorized as children (˂11 years) or adolescent (≥11 years). Injuries were categorized as orthopedic (fractures, dislocations, sprain, strains), non-orthopedic (contusion, internal injury, laceration), concussion, or other/unknown. Case narratives were used to categorize mechanism of injury as contact or non-contact. Appropriate sample NEISS weights estimation was applied for statistical analysis and Confidence Intervals (CI). RESULTS: A total of 393,110 injuries were observed over the five-year study period, with a mean of 78,622 annual injuries. Gymnastics, dance, and cheerleading accounted for 136,422 injuries, 96,416 injuries, and 160,272 injuries, respectively. Most cases were adolescent (71%; 95% CI: 68-74%) and occurred in a sports-related setting (65%, 95% CI: 57-72%). Gymnastics had the highest proportion of injuries among children (50%) as compared to dancers (25%) or cheerleaders (12%) (p < 0.01). Non-contact injuries most affected the lower extremity (43-68%) and resulted in an orthopedic diagnosis (63-71%), and contact injuries had a higher proportion of injuries affecting the head, neck, and face (29-51%) and non-orthopedic diagnoses (29-38%). Gymnastics had the most upper extremity non-contact injuries (42%) and dance the most lower extremity non-contact injuries (68%) (p < 0.01). Cheerleading had the highest incidence of overall concussions (8%), contact injuries (47%), and concussions due to contact injury (15%). CONCLUSION: Pediatric gymnasts, cheerleaders, and dancers have important similarities and differences in injury pattern which may lead to the development of sport-specific injury prevention programs for pediatric performance athletes.

Trends in pediatric baseball and softball injuries presenting to emergency departments.

BACKGROUND: Millions of youth participate in baseball and softball in the United States and these youth account for a large number of pediatric sports injuries. This study sought to characterize annual, seasonal, and age-related trends in pediatric softball and baseball injuries presenting to the Emergency Department (ED). METHODS: The National Electronic Injury Surveillance System (NEISS) database was retrospectively examined for all softball and baseball injuries from 2010 to 2019 involving pediatric patients aged 7-21 years. Patients were classified by age as children (ages 7-13), adolescents (ages 14-18), or young adults (ages 19-21). Case narratives were used to assign mechanisms of injury. National injury estimates were calculated using statistical weights provided by the Consumer Product Safety Commission. RESULTS: An estimated 1,372,573 pediatric softball and baseball ED visits occurred from 2010 to 2019. The mean age of the patient population was 13.6 years old (95% CI = 13.5-13.8 years), and baseball athletes were younger than softball athletes (13.2 years and 14.3 years) (p < 0.01). Moreover, baseball athletes hit by the bat were younger than their softball counterparts (11.8 years and 13.4 years). Most baseball and softball injuries were the result of being hit by the ball (52.8% and 54.2%) or sliding into a base (13.1% and 15.8%). The annual number of injuries decreased during the studied time period by 41.1% for baseball injuries and by 38.3% for softball injuries. The annual number of injuries related to all injury mechanisms decreased over the studied time period for both sports, with the exception of baseball throwing injuries, which increased by 8.6%. Baseball and softball injuries were both most likely to be present to the ED on Sunday (16.3% and 17.9%) and during the Spring (53.2% and 55.3%). CONCLUSION: Safety guidelines should focus on reducing the prevalence of injuries acquired by younger baseball and softball players during practice and educating coaches and players on existing pitch count guidelines.

A Comparison of Motorized and Nonmotorized Scooter Injuries in Pediatric Patients Seen in US Emergency Departments.

OBJECTIVES: We sought to characterize and compare trends in pediatric injuries sustained on motorized and nonmotorized scooters across the United States, to assess the use of safety equipment in children presenting with scooter-related injuries, and provide strategies for injury prevention. METHODS: The National Electronic Injury Surveillance System was queried for motorized and nonmotorized scooter-related pediatric injuries from 2014 to 2018 in patients ages 6 to 12 years. Patient demographics, diagnosis, injury location, and narrative of the incident were collected. Bivariate and regression analyses were used to determine demographic and social associations of injury characteristics. RESULTS: An estimated 146,000 (11,452 motorized and 134,548 nonmotorized) injuries occurred in children ages 6 to 12 years over the 5 years. Three of 4 injuries occurred in children younger than 10 years, and most injuries occurred in males (56%).From 2014 to 2018, the nationwide estimated incidence of motorized scooter injuries increased by 112.1%, while that of nonmotorized scooter injuries decreased by 40.3%.Upper extremity injuries were most common with nonmotorized scooters (44.4% of all injuries), while lower extremity injuries were most common with motorized scooters (39.5% of all injuries). Head and neck injuries accounted for 27.4% of nonmotorized scooter injuries and 23.4% of motorized scooter injuries. The number of concussions in motorized scooters increased from 0.4% in 2014 to 2.7% in 2018, while concussions in nonmotorized scooters decreased from 3.5% to 2.7%. Helmets were mentioned in the medical record in 6.6% of the cases. Of these, 60.5% reported no use of helmet at the time of injury. CONCLUSIONS: From 2014 to 2018, the number of motorized scooter injuries increased by 112.1% in the pediatric population ages 6 to 12 years, whereas nonmotorized scooter injuries decreased by 40.3%. In more than 60% of the cases that mentioned a helmet, the child injured was recorded as not wearing a helmet. The rise in pediatric injuries associated with motorized scooters in contrast with the reduction of injuries associated with nonmotorized scooters highlights the need for novel public health policies and interventions promoting helmet use with motorized scooters in the pediatric population.

Pediatric Softball Injuries Presenting to Emergency Departments.

INTRODUCTION: This study sought to characterize the mechanisms of injury responsible for common softball-related injuries in recent years. METHODS: The National Electronic Injury Surveillance System database was queried for all pediatric softball-related injuries presenting to participating US emergency departments from 2010 to 2019. Patients were classified by age as children (7-12 years), adolescents (13-18 years), or young adults (19-21 years). The case narrative of each injury was used to establish the mechanism of injury: hit by bat, hit by ball, sliding into base, collision with another player, catching, running, and throwing. Statistical weights provided by the Consumer Product Safety Commission were used to produce national injury estimates. RESULTS: There were an estimated 511,117 pediatric softball injuries presenting to the emergency department over the study period, with a mean patient age of 14.3 years (95% confidence interval [CI], 14.1-14.4 years). The head/neck was the most commonly affected body part, making up 30.2% of cases (95% CI, 28.2%-32.2%). Injuries to the head/neck were most often caused by being hit by the ball (78.4%; 95% CI, 76.4%-80.3%) and most commonly resulted in a superficial injury (36.9%), internal injury (22.2%), or concussion (16.3%). Foot/ankle injuries were most frequently caused by sliding into base (51.5%; 95% CI, 47.0%-55.2%) and typically resulted in a sprain/strain (65.5%). The most frequent causes of shoulder/elbow injuries were being hit by the ball (33.3%; 95% CI, 28.6%-38.3%) and throwing the ball (27.6%; 95% CI, 22.8%-32.9%). These resulted most frequently in a sprain or strain (39.5%), followed by a superficial injury (28.2%). The proportion of softball injuries affecting the shoulder and elbow and the lower extremities increased with athlete age, whereas the proportion of injuries affecting the remainder of the upper extremities decreased with athlete age. CONCLUSION: Being hit by the ball was the most common mechanism of injury, especially in the head/neck region, and shoulder/elbow injuries increase with athlete age. Coaches and leagues may consider mandating helmets for infielders and pitch counts for pitchers, especially among adolescent athletes.

Incidence of Deep Vein Thrombosis in Cerebral Palsy Following an Orthopaedic Surgical Event.

PURPOSE: The purpose of this study was to identify the incidence of venous thromboembolism (VTE) and characterize the demographics, comorbidities, and risk factors for patients with cerebral palsy (CP) having orthopaedic surgery. METHODS: All patients diagnosed with CP who underwent an orthopaedic surgical procedure at one institution between 2008 and 2017 were identified. Diagnosis codes and associated patient events were recovered from the electronic medical record. Each VTE event was reviewed to ascertain an actual VTE episode related to a surgical event. RESULTS: The review included 2583 orthopaedic surgical events in 1371 patients. Of the initial 88 cases identified, 28 cases had a deep thrombosis documented. Six cases of VTE occurred within 3 months following the surgical event. Three of these cases had thigh thrombosis, and 2 patients had upper arm thrombosis, and 1 patient had a superior vena cava thrombosis. On further workup, 5 of these 6 patients were identified as having a congenital hypercoagulable condition. CONCLUSIONS: VTE is a relatively rare occurrence after orthopaedic surgery in pediatric patients with CP, but when it occurs, a full hematologic workup for a congenital hypercoagulable condition is indicated. Based on the low incidence of thigh thrombosis, routine pharmacological or intermittent mechanical calf compression is not recommended. A careful clinical and family history should be performed to identify patients with possible genetic hypercoagulable conditions who would merit prophylaxis. LEVEL OF EVIDENCE: Level IV.

Recovery After ACL Reconstruction in Male Versus Female Adolescents: A Matched, Sex-Based Cohort Analysis of 543 Patients.

BACKGROUND: Differences in postoperative recovery after anterior cruciate ligament reconstruction (ACLR) between men and women have been demonstrated in the adult population. Sex-based differences have been incompletely investigated in adolescents, which represent the subpopulation most affected by ACL injury. PURPOSE/HYPOTHESIS: The purpose of this study was to compare the 6-month postoperative functional recovery after ACLR between adolescent boys and girls. It was hypothesized that significant differences in postoperative strength, dynamic balance, and functional hop test performance would be seen between the sexes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Included in this study were athletes aged 12 to 19 years with closed or closing growth plates who underwent ACLR with hamstring autograft between May 2014 and May 2018 at a single institution. All athletes had undergone strength and functional testing between 5 and 8 months postoperatively. Exclusion criteria were previous knee surgery (contralateral or ipsilateral knee), concomitant injury/surgery other than meniscal tear/repair, allograft supplementation, and incomplete medical records. The limb symmetry index (LSI) for strength (measured with handheld dynamometer), as well as dynamic Y-balance and functional hop test performance, was compared between groups. To account for differences in physical characteristics between the sexes, 1-way between-group multivariate analysis of covariance was used to analyze the data. RESULTS: Overall, 543 patients (211 boys, 332 girls) were included. There was no significant difference in age, body mass index, incidence of concomitant meniscal pathology, use of regional anesthesia, or time to functional testing between cohorts. Female athletes demonstrated a statistically significantly greater deficit in quadriceps strength LSI compared with male athletes (boys, +3.4%; girls, -2.3%; P = .011). Both male and female athletes demonstrated 33% hamstring strength deficits, with no statistically significant sex-based differences in dynamic balance or functional hop testing. CONCLUSION: Female athletes demonstrated greater quadriceps strength deficits than male athletes at 6 months after ACLR with hamstring autograft. Severe hamstring strength deficits persisted in both male and female patients at this time point. The correlation of such deficits to risk of ACL retear warrants continued study in the adolescent population and may support a delay in return to sports, which has been suggested in the more recent literature.

Quadriceps Tendon Autograft in Pediatric ACL Reconstruction: Graft Dimensions and Prediction of Size on Preoperative MRI.

BACKGROUND: There is increased interest in quadriceps autograft anterior cruciate ligament (ACL) reconstruction in the pediatric population. PURPOSE: To evaluate children and adolescents who underwent ACL reconstruction using a quadriceps autograft to determine the properties of the harvested graft and to assess the value of demographic, anthropometric, and magnetic resonance imaging (MRI) measurements in predicting the graft size preoperatively. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A retrospective database search was performed from January 2018 through October 2020 for patients undergoing ACL reconstruction. Patients <18 years old at the time of surgery in whom a quadriceps tendon autograft was used were selected. Demographic data and anthropometric measurements were recorded, and graft measurements were abstracted from the operative notes. Knee MRI scans were reviewed to measure the quadriceps tendon thickness on sagittal cuts. Graft length and diameter were then correlated with anthropometric and radiographic data. RESULTS: A total of 169 patients (98 male) were included in the final analysis, with a median age of 15 years (range, 9-17 years). A tendon length ≥65 mm was harvested in 159 (94%) patients. The final graft diameter was 8.4 ± 0.7 mm (mean ± SD; range, 7-11 mm). All patients had a graft diameter ≥7 mm, and 139 (82%) had a diameter ≥8 mm. Preconditioning decreased the graft diameter by a mean 0.67 ± 0.23 mm. Age (P = .04) and quadriceps thickness on MRI (P = .003) were significant predictors of the final graft diameter. An MRI sagittal thickness >6.7 mm was 97.4% sensitive for obtaining a graft ≥8 mm in diameter. CONCLUSION: Our findings suggest that tendon-only quadriceps autograft is a reliable graft source in pediatric ACL reconstruction, yielding a graft diameter ≥8 mm in 82% of pediatric patients. Furthermore, preoperative MRI measurements can be reliably used to predict a graft of adequate diameter in children and adolescents undergoing ACL reconstruction, with a sagittal thickness >6.7 mm being highly predictive of a final graft size ≥8 mm.

Epidemiology of Pediatric Baseball and Softball Player Injuries.

BACKGROUND: Baseball and softball are popular sports in the United States and are responsible for a large number of youth sports injuries each year. PURPOSE: To investigate recent differences in youth baseball and softball injuries evaluated in nationwide emergency departments. STUDY DESIGN: Descriptive epidemiology study. METHODS: The National Electronic Injury Surveillance System (NEISS) database was examined for softball and baseball injuries in pediatric patients (age, 7-21 years) from 2010 through 2019. Patients were classified as children (age, 7-13 years), adolescents (age, 14-18 years), or young adults (age, 19-21 years). Case narratives were used to categorize injuries as contact injuries (hit by bat or ball), field injuries (sliding into base, collision with another player, catching, or running), throwing injuries, or other. RESULTS: An unweighted total of 24,717 baseball injuries and 13,162 softball injuries were recorded. A nationwide estimate of 861,456 baseball injuries and 511,117 softball injuries were sustained during the studied time period, with estimated respective injury rates of 86,146 and 51,112 per year. Injured softball players were most commonly adolescent (47%) and female (92%), while injured baseball players were most commonly children (54%) and male (90%). There was a greater proportion of baseball-related injuries involving the head/neck (41%) as compared with softball-related injuries (30%) (P < .01). Conversely, a greater proportion of softball-related injuries involved the lower extremity (32%) as compared with baseball-related injuries (19%) (P < .01). When comparing diagnosis, softball injuries were more often sprains/strains (28%) than baseball injuries (18%) (P < .01). When comparing mechanisms of injury, baseball athletes were more likely to be evaluated with contact injuries than were softball athletes (49% vs 40%, P < .01). CONCLUSION: Youth baseball athletes were more likely to be injured through contact mechanisms and had a higher proportion of injuries related to the head/neck/face, whereas softball injuries more frequently involved the lower extremity and resulted in a sprain/strain. League guidelines should focus on reducing contact injuries within youth baseball, and injury-prevention programs should focus on reducing lower extremity injuries in youth softball.

Predicting Outcomes of Talar Osteochondritis Dissecans Lesions in Children.

BACKGROUND: Reports detailing the rates of radiographic healing after treatment of talar osteochondritis dissecans (TOCD) remain scarce. There is also a paucity of data characterizing treatment outcomes and the risk factors associated with poor outcomes in children with TOCD. PURPOSE: To identify factors associated with healing, assess treatment outcomes, and develop a clinically useful nomogram for predicting healing of TOCD in children. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: This was a retrospective review of all patients ≤18 years of age with TOCD from a single pediatric institution over a 12-year period. Surgical treatment was left to the discretion of the treating surgeon based on standard treatment techniques. Medical records and radiographs were reviewed for patient and clinical data, lesion characteristics, and skeletal maturity. Radiographic healing was evaluated at the 1-year follow-up, and patients with complete versus incomplete healing were compared using multivariable logistic regression models to examine the predictive value of the variables. RESULTS: The authors analyzed 92 lesions in 74 patients (mean age, 13.1 ± 2.7 years [range, 7.1-18.0 years]; 61% female). Of these, 58 (63%) lesions were treated surgically (drilling, debridement, microfracture, bone grafting, or loose body removal), and the rest were treated nonoperatively. Complete radiographic healing was seen in 43 (47%) lesions. In bivariate analysis, patients with complete healing were younger (P = .006), were skeletally immature (P = .013), and had a lower body mass index (BMI; P < .001) versus those with incomplete healing. In a multivariate regression model, the factors that correlated significantly with the rate of complete healing were age at diagnosis, BMI, and initial surgical treatment. The lesion dimensions were not significantly associated with the likelihood of healing. A nomogram was developed using the independent variables that correlated significantly with the likelihood of complete radiographic healing. CONCLUSION: Complete radiographic healing of TOCD lesions was more likely in younger patients with a lower BMI. The effect of initial surgical treatment on potential healing rate was greater in older patients with a higher BMI.

Scoliosis Surgery Normalizes Cardiac Function in Adolescent Idiopathic Scoliosis Patients.

STUDY DESIGN: Single-center retrospective chart review with minimum 2-year follow up. OBJECTIVE: To determine incidence of pulmonary hypertension in adolescent idiopathic scoliosis patients and to determine the effect of scoliosis surgery on pulmonary hypertension. SUMMARY OF BACKGROUND DATA: Spinal deformity in adolescent idiopathic scoliosis can increase right atrial and ventricular pressures secondary to restrictive lung disease. Pulmonary hypertension leading to cor pulmonale is the most feared outcome, however mild pulmonary hypertension in adolescent idiopathic scoliosis (AIS) patients has been reported. No study has previously examined changes in the improvement of right heart function following scoliosis surgery. METHODS: Cobb angle, 2D-echo signs of structural heart disease, aortic root dimensions, tricuspid regurgitant jet velocity (TRV), pulmonary function tests (PFTs), arterial blood gas (ABG), and patient demographics reviewed. Right ventricular systolic pressure (RVSP) estimated using Bernoulli equation (4[TRV]2) and right atrial pressure. RVSP ≥36 mmHg is a surrogate marker for pulmonary hypertension. All echocardiograms were read by board certified Pediatric Cardiologists. Logistic regression used to assess for differences in TRV between groups. RESULTS: Mean preoperative RVSP was significantly elevated in AIS patients (26.9 ±â€Š0.49; P < 0.001) compared with controls (17.25 + 0.88). Only 47 (21%) Group 1 patients had elevated preoperative TRV (≥2.8 m/s) versus none in Group 2 (P < 0.001). Additionally, logistic regression showed AIS patients have odds ratio of 3.29 for elevated TRV (P = 0.007)-an indirect measure of pulmonary hypertension. In all Group 3 patients, the cardiac function normalized postoperatively (mean TRV = 2.09 + 0.23; P < 0.001). No association found between Cobb angle, aortic root parameters, or pulmonary function tests. CONCLUSION: This study found 13.9% of patients with adolescent idiopathic scoliosis had elevated TRV while controls had no TRV abnormalities. Additionally, RVSP measurements demonstrated mild pulmonary hypertension in AIS patients. These abnormal values normalized postoperatively, indicating the benefits of scoliosis surgery on cardiac function in adolescent idiopathic scoliosis.Level of Evidence: 3.

Histopathology of osteogenesis imperfecta bone. Supramolecular assessment of cells and matrices in the context of woven and lamellar bone formation using light, polarization and ultrastructural microscopy.

Diaphyseal long bone cortical tissue from 30 patients with lethal perinatal Sillence II and progressively deforming Sillence III osteogenesis imperfecta (OI) has been studied at multiple levels of structural resolution. Interpretation in the context of woven to lamellar bone formation by mesenchymal osteoblasts (MOBLs) and surface osteoblasts (SOBLs) respectively demonstrates lamellar on woven bone synthesis as an obligate self-assembly mechanism and bone synthesis following the normal developmental pattern but showing variable delay in maturation caused by structurally abnormal or insufficient amounts of collagen matrix. The more severe the variant of OI is, the greater the persistence of woven bone and the more immature the structural pattern; the pattern shifts to a structurally stronger lamellar arrangement once a threshold accumulation for an adequate scaffold of woven bone has been reached. Woven bone alone characterizes lethal perinatal variants; variable amounts of woven and lamellar bone occur in progressively deforming variants; and lamellar bone increasingly forms rudimentary and then partially compacted osteons not reaching full compaction. At differing levels of microscopic resolution: lamellar bone is characterized by short, obliquely oriented lamellae with a mosaic appearance in progressively deforming forms; polarization defines tissue conformations and localizes initiation of lamellar formation; ultrastructure of bone forming cells shows markedly dilated rough endoplasmic reticulum (RER) and prominent Golgi bodies with disorganized cisternae and swollen dispersed tubules and vesicles, structural indications of storage disorder/stress responses and mitochondrial swelling in cells with massively dilated RER indicating apoptosis; ultrastructural matrix assessments in woven bone show randomly oriented individual fibrils but also short pericellular bundles of parallel oriented fibrils positioned obliquely and oriented randomly to one another and in lamellar bone show unidirectional fibrils that deviate at slight angles to adjacent bundles and obliquely oriented fibril groups consistent with twisted plywood fibril organization. Histomorphometric indices, designed specifically to document woven and lamellar conformations in normal and OI bone, establish ratios for: i) cell area/total area X 100 indicating the percentage of an area occupied by cells (cellularity index) and ii) total area/number of cells (pericellular matrix domains). Woven bone is more cellular than lamellar bone and OI bone is more cellular than normal bone, but these findings occur in a highly specific fashion with values (high to low) encompassing OI woven, normal woven, OI lamellar and normal lamellar conformations. Conversely, for the total area/number of cells ratio, pericellular matrix accumulations in OI woven are smallest and normal lamellar largest. Since genotype-phenotype correlation is not definitive, interposing histologic/structural analysis allowing for a genotype-histopathologic-phenotype correlation will greatly enhance understanding and clinical management of OI.

Decreased Prescribing of Postoperative Opioids in Pediatric ACL Reconstruction: Treatment Trends at a Single Center.

BACKGROUND: Anterior cruciate ligament (ACL) injury is common in the pediatric population. Pain control after ACL reconstruction (ACLR) presents a unique challenge due to age and early rehabilitation needs. Pain management practices are believed to have evolved in recent years to limit unnecessary exposure to risks associated with opioid use in this vulnerable population. PURPOSE: To describe trends in postoperative opioid prescribing and assess factors including obtaining consent for opioid prescribing for minors that may have mitigated excessive prescription of opioids. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This is a retrospective review of a consecutive series of pediatric patients (<18 years) undergoing primary ACLR within an urban academic hospital system over a 5-year period (2014-2018). The study period included the gradual introduction of preoperative consenting for opioid use in minors as mandated by state law in 2016. Patient characteristics, surgical details, presence of a signed consent form to prescribe opioid medications, prescribed postoperative medications, prescriber, and indicators of inadequate pain control were collected. Univariate and multivariate analyses were performed to determine factors associated with reduced postoperative opioid prescribing. RESULTS: This study included 687 patients with a mean age of 15.1 ± 1.9 years, with less than one-third of patients having preoperative consent forms to prescribe opioid medications. Postoperative prescribing trends demonstrated a decline in the number of opioid doses provided and increased utilization of nonopioid medications. Patients who received preoperative opioid counseling and signed a consent form were prescribed fewer opioids and had a smaller number of unscheduled contacts for poorly controlled pain. Univariate analyses identified multiple predictors of the number of opioid doses prescribed postoperatively. Obtaining preoperative consent to prescribe opioids and ambulatory surgery center location were found to be independent predictors of prescribed doses in the multivariate analysis. CONCLUSION: The quantity of opioid medication prescribed for pain management after pediatric ACLR at our institution has declined in recent years. This appears to be, in part, related to state-mandated preoperative counseling about opioid use, signing of a consent form by the parent(s) or guardian(s) to prescribe opioids to minors, and encouragement toward the use of nonopioid medications when possible. Preoperative opioid use discussions in the pediatric population may be useful in reducing opioid overprescription and utilization in this population.

Outcomes of Surgically Treated Chronic Exertional Compartment Syndrome in Runners.

BACKGROUND: Chronic exertional compartment syndrome (CECS) is primarily seen in running athletes. Previous outcomes of surgical treatment with fasciotomy have suggested moderate pain relief, but evidence is lacking regarding postoperative return to running. HYPOTHESIS: Running athletes with limiting symptoms of CECS will show high rates of return to running after fasciotomy. STUDY DESIGN: Case series. LEVEL OF EVIDENCE: Level 4. METHODS: Running athletes treated with fasciotomy for CECS at a single institution were identified using a surgical database and asked to complete a questionnaire designed to assess postoperative pain, activity level, return to running, running distances, overall satisfaction, and rate of revision fasciotomy. RESULTS: A total of 43 runners met the inclusion criteria, and 32 runners completed outcomes questionnaires at a mean postoperative follow-up of 66 months. In total, 27 of these 32 patients (84%) returned to sport(s) after fasciotomy. However, 9 (28%) of these patients pursued nonrunning sports, 5 (16%) due to recurrent pain with running. Of the 18 patients who returned to running sports (56%), the mean weekly running distance decreased postoperatively. Recurrence of symptoms was reported in 6 patients (19%), 4 of whom had returned to running and 2 of whom had been unable to return to sports. All of these 6 patients elected to undergo revision fasciotomy surgery. Twenty-five (78.1%) patients reported being satisfied with their procedure. In the overall cohort, the mean visual analog scale scores for pain during activities/sports decreased from 7.9 preoperatively to 1.7 postoperatively. CONCLUSION: Fasciotomy for CECS in runners may provide significant improvement in pain and satisfaction in over three-quarters of patients and return to sports in 84% of patients. However, only 56% returned to competitive running activity, with a subset (19%) developing recurrent symptoms resulting in revision surgery. CLINICAL RELEVANCE: Fasciotomy has been shown to decrease pain in most patients with CECS. This study provides outcomes in running athletes after fasciotomy for CECS with regard to return to sports, maintenance of sports performance, and rates of revision surgery.

Alternatives to Traditional Cast Immobilization in Pediatric Patients.

Casts are commonly used for fracture management and postoperative immobilization in pediatric patients. However, cast immobilization is not without complications (eg, thermal injuries, pressure sores, infection, and neurovascular injury) and may be associated with additional costs and increased loss of school/work days for cast removal or other complications. The disadvantages of traditional casting can be minimized by alternative management strategies: waterproof casts to facilitate bathing and swimming; a Pavlik harness in infants, a single-leg spica cast, or flexible intramedullary nails to avoid complications with double-leg spica casts for femur fractures; and braces or splints to manage buckle and minimally displaced distal radius fractures, toddler's fractures, and stable foot/ankle fractures.

The impact of rural residence on adult brain cancer survival in the United States.

PURPOSE: Rural/urban disparities in brain cancer survival have been reported. However, disparities by cancer type or in the United States as a whole remain poorly understood. Using the Surveillance, Epidemiology, and End Results (SEER) 18 registries database, we examined brain cancer survival by rural/urban residence defined by Rural-Urban Continuum Codes (RUCCs). METHODS: We obtained data from SEER 18 registries for individuals aged 20 years and older with a first primary malignant brain cancer from 2001 to 2011. Rural/urban residence at diagnosis was defined using both metropolitan/non-metropolitan county classifications and individual RUCC categories. We used Cox proportional hazards regression to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between rural/urban residence and brain cancer survival. RESULTS: Among 37,581 cancer cases, 77.9% were non-Hispanic White, 56.5% were male, and 88.7% lived in a metropolitan county. Brain cancer patients living in the most rural counties had a significant increased risk of cancer death compared to those living in the most urban counties (HR 1.15; 95% CI 1.01-1.31). Those living in non-metropolitan counties had a similar risk of cancer death compared to those living in metropolitan counties (HR 1.01; 95% CI 0.97-1.06). Effect modification was observed overall by cancer type, with non-specified oligodendroglioma (HR 1.35; 95% CI 1.01-1.81) showing the greatest effect. CONCLUSION: After adjusting for confounding factors, our results suggest that rural residence has a modest effect on brain cancer survival, and that this disparity may vary by cancer type. Future research should explore differences in treatment strategies between rural and urban brain cancer patients.

Detection of prostate specific antigen and salivary amylase in vaginal swabs using SERATEC® immunochromatographic assays.

Immunochromatographic assays are used by crime laboratories to conduct simple and quick analyses of bodily fluids. These streamlined tests are ideal for decreasing the sexual assault kit backlog in the United States. A large-scale analysis of the frequency of positive results of amylase and prostate specific antigen (PSA) endogenously found in the vaginal cavity was conducted using the SERATEC PSA Semiquant and Amylase tests. Vaginal swabs were self-collected by participants after 7-10 days of no oral contact or male ejaculation. In this study of 50 participants, 98% were negative for PSA and 92% were negative for amylase. Positive results were confirmed to contain no exogenous DNA by male-specific quantitation, short tandem repeat (STR) typing, and Y-STR typing. These results can be used by crime laboratories to help guide interpretation of immunochromatographic test results from vaginal swabs and aid in decision-making in downstream DNA testing.

National Trends in the Surgical Management of Lumbar Spinal Stenosis in Adult Spinal Deformity Patients.

STUDY DESIGN: This is a retrospective analysis of national administrative hospital data. OBJECTIVE: This study examines national trends in the surgical management of lumbar spinal stenosis (LSS) in patients with and without coexisting scoliosis between 2010 and 2014. The study also examines revision rates for LSS procedures. SUMMARY OF BACKGROUND DATA: There is wide variability in the surgical management of patients with LSS, with and without coexisting spinal deformity. METHODS: Data were obtained from the Healthcare Cost and Utilization Project's National Inpatient Sample Database. International Classification of Diseases 9th revision- Clinical Modification codes were used to identify all patients with a primary diagnosis of lumbar spinal stenosis. These patients were divided into two groups: 1) LSS alone and 2) LSS with coexisting scoliosis. The two groups were examined for one of three surgical outcomes: 1) decompression alone (discectomy, laminectomy), 2) simple fusion, and 3) complex fusion (>three vertebrae or 360° fusion). The groups were then further examined for revision operations. National Inpatient Sample discharge weights were applied where relevant. RESULTS: In 2014 national estimates of discharged patients indicated 76,275 patients with a primary diagnosis of LSS (population rate, 23.9; in the elderly (65+) the age-adjusted population rate was 95.4). Of these patients, 88.5% were managed through primary surgery (34.6% decompression, 47.2% simple fusion, 5.7% complex fusion). Between 2010 and 2014, the percentage of decompression decreased from 47.5% to 34.6%, the percent of simple fusion increased from 35.3% to 47.2%, and the percent of complex fusion increased from 5.7% to 7.1% (P < 0.01). In patients with coexisting scoliosis, lumbar spinal stenosis was predominantly managed by simple fusion and complex fusion (15.5% decompression, 51.9% simple fusion, 27.3% complex fusion, in 2014). Revision rates were highest among patients without scoliosis managed with complex fusion (15.8% in 2014) compared with patients with scoliosis (8.8% in 2014). Patients with scoliosis who underwent decompression only had revision rates of 1.7% and 0.62% in 2010 and 2014, respectively. CONCLUSION: We observed a leveling-off of the rate of operation for patients with a primary diagnosis of LSS at around 88%. There was an increase in the rate of fusion and a decrease in the rate of decompression across all patient groups. We report no difference in revision rates between patients with and without scoliosis, except in those undergoing a complex fusion. LEVEL OF EVIDENCE: 3.