Exposure to per- and polyfluoroalkyl substances and alterations in plasma microRNA profiles in children.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans. OBJECTIVE: To investigate associations between PFAS concentrations and miRNA levels in children. METHODS: Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and 64 participants (average age 6.5 years, 39.1% female) from the Rhea study, a mother-child cohort in Greece. PFAS concentrations and miRNA levels were assessed in plasma samples from both studies. Associations between individual PFAS and plasma miRNA levels were examined after adjusting for covariates. Additionally, the cumulative effects of PFAS mixtures were evaluated using an exposure burden score. Ingenuity Pathways Analysis was employed to identify potential disease functions of PFAS-associated miRNAs. RESULTS: Plasma PFAS concentrations were associated with alterations in 475 miRNAs in the Teen-LABs study and 5 miRNAs in the Rhea study (FDR p < 0.1). Specifically, plasma PFAS concentrations were consistently associated with decreased levels of miR-148b-3p and miR-29a-3p in both cohorts. Pathway analysis indicated that PFAS-related miRNAs were linked to numerous chronic disease pathways, including cardiovascular diseases, inflammatory conditions, and carcinogenesis. CONCLUSION: Through miRNA screenings in two independent cohorts, this study identified both known and novel miRNAs associated with PFAS exposure in children. Pathway analysis revealed the involvement of these miRNAs in several cancer and inflammation-related pathways. Further studies are warranted to enhance our understanding of the relationships between PFAS exposure and disease risks, with miRNA emerging as potential biomarkers and/or mediators in these complex pathways.

Environmental pollutant risk factors for worse COVID-19 related clinical outcomes in predominately hispanic and latino populations.

BACKGROUND: Per- and poly-fluorinated compounds (PFAS) and heavy metals constitute two classes of environmental exposures with known immunotoxicant effects. In this pilot study, we aimed to evaluate the impact of exposure to heavy metals and PFAS on COVID-19 severity. We hypothesized that elevated plasma-PFAS concentrations and urinary heavy metal concentrations would be associated with increased odds of ICU admission in COVID-19 hospitalized individuals. METHODS: Using the University of Southern California Clinical Translational Sciences Institute (SC-CTSI) biorepository of hospitalized COVID-19 patients, urinary concentrations of 15 heavy metals and urinary creatinine were measured in n = 101 patients and plasma concentrations of 13 PFAS were measured in n = 126 patients. COVID-19 severity was determined based on whether a patient was admitted to the ICU during hospitalization. Associations of metals and PFAS with ICU admission were assessed using logistic regression models, controlling for age, sex, ethnicity, smoking status, and for metals, urinary dilution. RESULTS: The average age of patients was 55 ± 14.2 years. Among SC-CTSI participants with urinary measurement of heavy metals and blood measures of PFAS, 54.5% (n = 61) and 54.8% (n = 80) were admitted to the ICU, respectively. For heavy metals, we observed higher levels of Cd, Cr, and Cu in ICU patients. The strongest associations were with Cadmium (Cd). After accounting for covariates, each 1 SD increase in Cd resulted in a 2.00 (95% CI: 1.10-3.60; p = 0.03) times higher odds of admission to the ICU. When including only Hispanic or Latino participants, the effect estimates between cadmium and ICU admission remained similar. Results for PFAS were less consistent, with perfluorodecanesulfonic acid (PFDS) exhibiting a positive but non-significant association with ICU admission (Odds ratio, 95% CI: 1.50, 0.97-2.20) and perfluorodecanoic acid (PFDA) exhibiting a negative association with ICU admission (0.53, 0.31-0.88). CONCLUSIONS: This study supports the hypothesis that environmental exposures may impact COVID-19 severity.

Changes in plasma concentrations of per- and Polyfluoroalkyl substances after bariatric surgery in adolescents from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study.

Exposure to per- and poly-fluoroalkyl substances (PFAS) is ubiquitous due to their persistence in the environment and in humans. Extreme weight loss has been shown to influence concentrations of circulating persistent organic pollutants (POPs). Using data from the multi-center perspective Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort, we investigated changes in plasma-PFAS in adolescents after bariatric surgery. Adolescents (Mean age = 17.1 years, SD = 1.5 years) undergoing bariatric surgery were enrolled in the Teen-LABS study. Plasma-PFAS were measured at the time of surgery and then 6-, 12-, and 36 months post-surgery. Linear mixed effect models were used to evaluate longitudinal changes in plasma-PFAS after the time of bariatric surgery. This study included 214 adolescents with severe obesity who had available longitudinal measures of plasma-PFAS and underwent bariatric surgery between 2007 and 2012. Underlying effects related to undergoing bariatric surgery were found to be associated with an initial increase or plateau in concentrations of circulating PFAS up to 6 months after surgery followed by a persistent decline in concentrations of 36 months (p < 0.001 for all plasma-PFAS). Bariatric surgery in adolescents was associated with a decline in circulating PFAS concentrations. Initially following bariatric surgery (0-6 months) concentrations were static followed by decline from 6 to 36 months following surgery. This may have large public health implications as PFAS are known to be associated with numerous metabolic related diseases and the significant reduction in circulating PFAS in individuals who have undergone bariatric surgery may be related to the improvement of such metabolic related diseases following bariatric surgery.

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents. AIM: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD. METHODS: This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study. Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD. Plasma samples were collected during surgery for miRNA profiling. A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform. We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age, sex, race, and other key covariates. Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD. RESULTS: We identified 16 upregulated plasma miRNAs, including miR-193a-5p and miR-193b-5p, and 22 downregulated plasma miRNAs, including miR-1282 and miR-6734-5p, in adolescents with NAFLD. Moreover, 52, 16, 15, and 9 plasma miRNAs were associated with NASH, fibrosis, ballooning degeneration, and lobular inflammation, respectively. Collectively, 16 miRNAs were associated with two or more histological features of NAFLD. Among those miRNAs, miR-411-5p was downregulated in NASH, ballooning, and fibrosis, while miR-122-5p, miR-1343-5p, miR-193a-5p, miR-193b-5p, and miR-7845-5p were consistently and positively associated with all histological features of NAFLD. Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression, while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B. CONCLUSION: Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity. Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.

Per- and polyfluoroalkyl substances, polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers and dysregulation of MicroRNA expression in humans and animals-A systematic review.

BACKGROUND: Persistent organic pollutants (POPs) are chemicals characterized by their environmental persistence. Evidence suggests that exposure to POPs, which is ubiquitous, is associated with microRNA (miRNA) dysregulation. miRNA are key regulators in many physiological processes. It is thus of public health concern to understand the relationships between POPs and miRNA as related to health outcomes. OBJECTIVES: This systematic review evaluated the relationship between widely recognized, intentionally manufactured, POPs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (dichlorodiphenyltrichloroethane [DDT], dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB]), with miRNA expression in both human and animal studies. METHODS: We used PubMed and Embase to systematically search the literature up to September 29th, 2023. Search results for human and animal studies were included if they incorporated at least one POP of interest in relation to at least one miRNA. Data were synthesized to determine the direction and significance of associations between POPs and miRNA. We utilized ingenuity pathway analysis to review disease pathways for miRNA that were associated with POPs. RESULTS: Our search identified 38 eligible studies: 9 in humans and 29 in model organisms. PFAS were associated with decreased expression of miR-19, miR-193b, and miR-92b, as well as increased expression of miR-128, miR-199a-3p, and miR-26b across species. PCBs were associated with increased expression of miR-15a, miR-1537, miR-21, miR-22-3p, miR-223, miR-30b, and miR-34a, as well as decreased expression of miR-130a and let-7b in both humans and animals. Pathway analysis for POP-associated miRNA identified pathways related to carcinogenesis. DISCUSSION: This is the first systematic review of the association of POPs with miRNA in humans and model organisms. Large-scale prospective human studies are warranted to examine the role of miRNA as mediators between POPs and health outcomes.

Associations of per- and polyfluoroalkyl substances, polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers with oxidative stress markers: A systematic review and meta-analysis.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs) are intentionally produced persistent organic pollutants (POPs) that are resistant to environmental degradation. Previous in-vitro and in-vivo studies have shown that POPs can induce oxidative stress, which is linked to neurodegenerative diseases, cardiovascular diseases, and cancer. However, findings in epidemiological studies are inconsistent and an evidence synthesis study is lacking to summarize the existing literature and explore research gaps. OBJECTIVE: We evaluated the effects of PFAS, PCBs, OCPs, and PBDEs, on oxidative stress biomarkers in epidemiological studies. METHODS: A literature search was conducted in PubMed, Embase, and Cochrane CENTRAL to identify all published studies related to POPs and oxidative stress up to December 7th, 2022. We included human observational studies reporting at least one exposure to POPs and an oxidative stress biomarker of interest. Random-effects meta-analyses on standardized regression coefficients and effect direction plots with one-tailed sign tests were used for quantitative synthesis. RESULTS: We identified 33 studies on OCPs, 35 on PCBs, 49 on PFAS, and 12 on PBDEs. Meta-analyses revealed significant positive associations of α-HCH with protein carbonyls (0.035 [0.017, 0.054]) and of 4'4-DDE with malondialdehyde (0.121 [0.056, 0.187]), as well as a significant negative association between 2'4-DDE and total antioxidant capacity (TAC) (-0.042 [-0.079, -0.004]), all ß [95%CI]. Sign tests showed a significant positive association between PCBs and malondialdehyde (pone-tailed = 0.03). Additionally, we found significant negative associations of OCPs with acetylcholine esterase (pone-tailed = 0.02) and paraoxonase-1 (pone-tailed = 0.03). However, there were inconsistent associations of OCPs with superoxide dismutase, glutathione peroxidase, and catalase. CONCLUSIONS: Higher levels of OCPs were associated with increased levels of oxidative stress through increased pro-oxidant biomarkers involving protein oxidation, DNA damage, and lipid peroxidation, as well as decreased TAC. These findings have the potential to reveal the underlying mechanisms of POPs toxicity.

Iron Status and Homeostasis Across 2 Competitive Seasons in NCAA Division I Collegiate Cross-Country Runners Residing at Low Altitude.

PURPOSE: Inflammatory cytokines including interleukin-6 can upregulate hepcidin and decrease iron absorption. Endurance exercise is associated with transient increases in cytokines, which may alter the risk of iron deficiency (ID). This study examined whether chronic elevations in basal levels of cytokines and hepcidin were associated with ID in highly trained runners. METHODS: Fifty-four collegiate runners (26 males and 28 females) living at ∼1625 m were recruited from an NCAA Division I cross-country team for this prospective cohort study. Over 2 seasons, fasted, preexercise blood draws were performed in the morning 4 times per season and were analyzed for hemoglobin concentration, ferritin, soluble transferrin receptor (sTfR), hepcidin, and 10 cytokines. Stages of ID were defined using ferritin, sTfR, and hemoglobin concentration. During the study, a registered dietician provided all runners with iron supplements using athletic department-created guidelines. RESULTS: Fifty-seven percent of females and 35% of males exhibited stage 2 ID (ferritin <20 ng/mL or sTfR >29.5 nmol/L) at least once. Cytokines, ferritin, and sTfR exhibited changes through the 2 years, but changes in cytokines were not associated with alterations in hepcidin, ferritin, or sTfR. In males and females, lower ferritin was associated with lower hepcidin (both P < .0001). One female exhibited higher hepcidin and lower iron stores compared with other individuals, suggesting a different etiology of ID. CONCLUSION: ID is common in highly trained collegiate runners. In general, the high prevalence of ID in this population is not associated with alterations in basal hepcidin or cytokine levels.

Exposure to perfluoroalkyl substances and risk of hepatocellular carcinoma in a multiethnic cohort.

Background & Aims: Exposure to poly- and perfluoroalkyl substances (PFAS), a class of persistent organic pollutants, is ubiquitous. Animal studies suggest that PFAS may increase risk of fatty liver and hepatocellular carcinoma (HCC) via impacts on hepatic lipid, amino acid, and glucose metabolism, but human data is lacking. We examined associations between PFAS exposure, altered metabolic pathways, and risk of non-viral HCC. Methods: In this nested case-control study, pre-diagnostic plasma PFAS and metabolomics were measured in 50 incident HCC cases and 50 individually matched controls from the Multiethnic Cohort (MEC) study. Cases/controls were matched by age, sex, race, and study area. PFAS exposure and risk of HCC were examined using conditional logistic regression. A metabolome-wide association study and pathway enrichment analysis was performed for PFAS exposure and HCC risk, and key metabolites/metabolic pathways were identified using a meet in the middle approach. Results: High perfluorooctane sulfonic acid (PFOS) levels (90th percentile from NHANES; >55 µg/L) were associated with 4.5-fold increased risk of HCC (odds ratio 4.5, 95% CI 1.2-16.0). Pathway enrichment analysis showed that PFOS exposure was associated with alterations in amino acid and glycan biosynthesis pathways, which were also associated with HCC risk. We identified 4 metabolites linking PFOS exposure with HCC, including glucose, butyric acid (a short-chain fatty acid), α-ketoisovaleric acid (a branched-chain α-keto acid), and 7α-hydroxy-3-oxo-4-cholestenoate (a bile acid), each of which was positively associated with PFOS exposure and risk of HCC. Conclusion: This proof-of-concept analysis shows that exposure to high PFOS levels was associated with increased risk of non-viral HCC, likely via alterations in glucose, amino acid, and bile acid metabolism. Larger studies are needed to confirm these findings. Lay summary: Per- and polyfluoroalkyl substances (PFAS), often referred to as "forever chemicals" because they are difficult to break down and stay in the human body for years, are extremely common and can cause liver damage. In a first of its kind study, we found that exposure to high levels of perfluorooctanesulfonic acid, one of the most common PFAS chemicals, was linked to increased risk of hepatocellular carcinoma in humans. Hepatocellular carcinoma is difficult to treat and is one of the most common forms of liver cancer, and these findings may provide new avenues for helping to prevent this disease.

The importance of lean mass and iron deficiency when comparing hemoglobin mass in male and female athletic groups.

Hemoglobin mass (Hbmass) is important for athletes because it helps determine maximal aerobic power. This study examined how lean mass, iron deficiency (ID), and sex influence Hbmass in athletic and nonathletic groups. NCAA Division I student athletes (21 men, 75 women; altitude: 1,625 m) were recruited from six athletic teams; 14 male and 12 female full-time students (non-varsity athletes) served as control subjects. Hbmass, body composition, and iron homeostasis parameters, including ferritin, soluble transferrin receptor (sTfR), hepcidin, erythroferrone, and 10 inflammatory cytokines, were measured two to four times across a competitive/training season. ID was defined as ferritin < 25 ng/mL. Hbmass was more closely related to lean mass (r2 = 0.90) than body mass (r2 = 0.69, P < 0.01). Compared with female subjects, male subjects had 19.9% higher Hbmass relative to body mass (HbmassBM) but only 7.5% higher Hbmass relative to lean mass (HbmassLEAN) (both P < 0.001). Prevalence of ID was higher in female than male subjects (47% vs. 9%, P < 0.01) but did not vary between groups. HbmassLEAN was 5% lower in ID vs. non-ID female subjects; HbmassBM was not different. ID was associated with lower hepcidin, elevated sTfR, and elevated erythroferrone but not with differences in inflammatory cytokines. Hbmass varied significantly between athletic groups and across sex, but the majority of these differences are explained by differences in lean mass. ID was common in female subjects and was associated with lower HbmassLEAN and hepcidin but not with differences in HbmassBM or inflammatory cytokines. Hbmass relative to lean mass seems advantageous when monitoring iron deficiency.NEW & NOTEWORTHY Differences in hemoglobin mass (Hbmass) between groups and across sex are primarily due to differences in lean mass. Iron deficiency (ID) independently decreases Hbmass; this effect is best characterized with Hbmass relative to lean mass. ID is common in females and is associated with lower hepcidin and elevated erythroferrone but not with differences in inflammatory cytokines. Hbmass relative to lean mass accurately quantifies hematological alterations secondary to iron deficiency.

The "Outside-In" Lesion of Hip Impingement and the "Inside-Out" Lesion of Hip Dysplasia: Two Distinct Patterns of Acetabular Chondral Injury.

BACKGROUND: Femoroacetabular impingement (FAI) and acetabular dysplasia lead to acetabular cartilage damage that commonly results in the chondral flaps seen during hip arthroscopy. PURPOSE: To compare the acetabular chondral flap morphology seen during hip arthroscopy ("outside-in" vs "inside-out") with clinical and radiographic parameters underlying FAI and hip dysplasia. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients who underwent hip arthroscopy by the senior author between 2013 and 2017 with a finding of Outerbridge grade IV acetabular chondral flap were included. Each procedure was retrospectively reviewed on video and chondral flaps were categorized as inside-out or outside-in. An inside-out designation was made for flaps exhibiting an intact chondrolabral junction with a detached sleeve of chondrolabral tissue from the central acetabulum, and an outside-in designation was made for centrally anchored flaps exhibiting a break in the chondrolabral junction. Radiographic markers of hip impingement/dysplasia were noted for each patient during assignment into 1 of 2 radiographic groups: group 1, lateral center edge angle (LCEA) >20 with FAI, and group 2, LCEA ≤20 with or without cam FAI. Associations between chondral flap morphology and clinical diagnosis were tested using a chi-square test. RESULTS: Overall, 95 patients (103 hips) were included (group 1, 78 hips; group 2, 25 hips). Among hips in group 2, 24 had concurrent cam FAI. There was a significant relationship between chondral flap type and radiographic diagnosis (P < .001). Among group 1 hips, 78% exhibited outside-in type chondral flaps, 12% exhibited combined outside-in and inside-out flaps, and 10% exhibited inside-out flaps. Group 2 hips showed 72% inside-out type chondral flaps, 16% combined, and 12% outside-in. Hips exhibiting outside-in type flaps were significantly more likely to be in group 1 (positive predictive value [PPV], 91%; negative predictive value [NPV], 69%). Similarly, hips exhibiting inside-out type flaps were significantly more likely to be in group 2 (PPV, 56%; NPV, 95%). Altogether, 90% of group 1 hips exhibited an outside-in lesion and 88% of group 2 hips exhibited an inside-out lesion. CONCLUSION: Acetabular chondral flap type visualized during hip arthroscopy correlates with radiographic markers of hip impingement and hip instability. Outside-in flaps are highly predictive of FAI, whereas inside-out flaps are highly predictive of acetabular dysplasia.

Effects of Hip Arthroscopy Without a Perineal Post on Venous Blood Flow, Muscle Damage, Peripheral Nerve Conduction, and Perineal Injury: A Prospective Study.

BACKGROUND: Prior reports of hip arthroscopy using a perineal post have established the risks of groin soft tissue injury, sexual dysfunction, and altered lower extremity neurovascular function. These parameters have not been investigated for hip arthroscopy without the use of a perineal post. PURPOSE: To evaluate the effects of postless hip arthroscopy on lower extremity venous blood flow, nerve conduction, muscle tissue damage, and perineal injury. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients between the ages of 18 and 50 years undergoing an elective unilateral or simultaneous bilateral hip arthroscopy were enrolled. Creatine phosphokinase (CPK)-MM levels and D-dimer levels were obtained preoperatively, immediately postoperatively, and 7 to 12 days postoperatively. Bilateral Doppler ultrasonography of the common femoral vein (CFV) and popliteal vein were conducted intraoperatively. Somatosensory evoked potentials (SSEPs) and transcranial motor evoked potentials (TcMEPs) were measured intraoperatively for the lower limbs. Perineal injury was assessed at 7 to 12 days postoperatively. RESULTS: 35 patients underwent a total of 40 hip arthroscopies. No significant differences were found in venous blood flow between the operative and nonoperative legs for either the CFV or popliteal vein. SSEP monitoring of the peroneal nerve showed no significant reduction when traction was applied to the operative leg, 90.8%, compared with final measurement just before it was removed, 72.4% (P = .09). For TcMEPs measured in the muscles outside of the traction boots, no significant changes were seen in the percentage of cases with abnormal measurements throughout the procedure. CPK-MM levels preoperatively, immediately postoperatively, and 7 to 12 days after surgery were on average 112, 190, and 102 IU/L, respectively (normal, <156 IU/L). No significant relationship was found between abnormal venous flow and altered D-dimer levels. No clinical evidence of nerve or vascular injury was encountered, and no groin soft tissue complications were observed during the study period. CONCLUSION: Postless hip arthroscopy is safe, without a notable reduction of venous blood flow or alteration of nerve function in the operative leg. Muscle tissue damage is subclinical, transient, and reduced compared with distraction with a post. No cases of perineal injury were observed during the study period.

Increased Prevalence of Femoroacetabular Impingement in Patients With Proximal Hamstring Tendon Injuries.

PURPOSE: To determine the prevalence of clinically diagnosed femoroacetabular impingement (FAI) in a consecutive series of patients presenting with proximal hamstring tendon injury and to correlate this with pelvic anatomic factors. METHODS: The prevalence of clinically symptomatic cam-, pincer-, and mixed-type and overall FAI was calculated among a consecutive series of patients presenting to a hip preservation clinic with a confirmed clinical and radiographic diagnosis of proximal hamstring tendon injury between 2012 and 2017. The presence of a cam lesion was determined by an alpha angle > 50° on radiographs and computed tomography radial sequences of the head-neck junction and a femoral head-neck offset ratio < 0.18. Clinical diagnoses of osseous impingement were determined according to accepted pathomorphologic signs and measurements. A diagnosis of FAI was confirmed by imaging findings of acetabular overcoverage for pincer-type FAI and the presence of an anterior or lateral cam lesion for cam-type FAI. RESULTS: Overall, 120 hips in 97 patients (mean age, 45 years) were included in this study. A clinical diagnosis of FAI was noted in 70.8% of hips (pincer-type 9.2%, cam-type 40.8%, mixed-type 20.8%), an approximate 2- to 7-fold increased prevalence in comparison with the general population from prior studies. CONCLUSIONS: The prevalence of FAI is high in patients with symptomatic proximal hamstring tendon pathology. Because FAI results in restriction of hip range of motion and altered pelvic tilt, future studies are warranted to investigate whether the presence of FAI acts as a predisposing factor for injury to the hamstring muscle complex. LEVEL OF EVIDENCE: Level IV, case series.

Combined Lateral Osseolabral Coverage Is Normal in Hips With Acetabular Dysplasia.

PURPOSE: To compare the lateral osseolabral coverage between groups of patients with different degrees of acetabular bony coverage using a magnetic resonance imaging parameter known as the combined lateral center-edge angle (cLCEA). METHODS: The cLCEA was measured among a consecutive series of patients presenting to a dedicated hip preservation surgeon with a magnetic resonance imaging scan. The cLCEA was measured using a coronal T1 or proton density image and was defined as the angle subtended by (1) a line through the center of the femoral head and orthogonal to the transverse line passing through the teardrops of both hips and (2) an oblique line drawn from the center of the femoral head to the free edge of the lateral acetabular labrum. The average difference between the lateral center-edge angle (LCEA) and the cLCEA was calculated and compared between groups based on acetabular bony coverage: dysplasia (LCEA <20°), borderline dysplasia (LCEA 20°-24.9°), normal coverage (LCEA 25°-39.9°), and overcoverage (LCEA ≥40°). RESULTS: In total, 341 patients (386 hips) were included. There were no significant differences in cLCEA between hips with normal acetabular coverage and dysplasia (P = .10) or borderline dysplasia (P = .46). Despite the large difference in mean LCEA between dysplasia (14.8° ± 3.9°) and acetabular overcoverage (43.1° ± 2.8°), the mean cLCEA values exhibited only a modest difference (44.7° ± 4.9° vs 52.7° ± 4.5°, respectively). Concordantly, hips with dysplasia exhibited the largest difference between mean LCEA and cLCEA (delta = 29.9° ± 4.7°) and hips with acetabular overcoverage had the smallest difference between measures (9.6° ± 5.2°). CONCLUSIONS: With decreasing acetabular bony coverage, there is increasing labral size such that the total osseolabral coverage, measured by the combined LCEA, remains equivalent between hips with normal acetabular coverage versus dysplasia. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Standardizing the Prearthritic Hip Joint Space Width: An Analysis of 994 Hips.

PURPOSE: The purposes of this study were (1) to define a normal prearthritic hip joint space width (JSW) in symptomatic and asymptomatic patients with various degrees of acetabular coverage based on the lateral center edge angle (LCEA) and (2) to determine predictors of JSW using patient-specific variables. METHODS: In a consecutive series of patients presenting to a hip preservation clinic between July 2012 and April 2016, a standard weight-bearing anteroposterior pelvic view was obtained. JSW was defined as the distance between the bony contour of the acetabular rim and femoral head in 2 locations (lateral and medial weight-bearing zone). Hips with severe anatomic deformity, a Tönnis grade >0, or a lateral or medial JSW <2.5 mm were excluded. A linear mixed model analysis was performed in order to determine which variables (age, sex, side, height, weight, symptomatic/asymptomatic, LCEA, and clinical diagnosis) were significantly related to JSW. RESULTS: A total of 994 hips were included. LCEA was found to be a significant predictor of both the lateral and medial JSW, with a decreased JSW associated with increasing degrees of acetabular bony coverage (P < .02). A mean 0.9 mm (20%) difference in medial JSW was found between patients with frank dysplasia (LCEA <20°) compared with those with pincer-type FAI (LCEA ≥40°). There was no difference between symptomatic and asymptomatic hips, either for lateral (asymptomatic: 4.51 ± 0.83 mm; symptomatic: 4.52 ± 0.85 mm; P = .58) or medial JSW (asymptomatic: 4.02 ± 0.96 mm; symptomatic: 3.97 ± 0.84 mm; P = .49). CONCLUSIONS: The LCEA is a significant predictor of hip JSW, with the mean JSW decreasing with increasing degrees of acetabular bony coverage. Joint space is not a major factor in symptomatology in adults with prearthritic hip pain. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Quadriceps Tendon Autograft for Primary Anterior Cruciate Ligament Reconstruction: A Systematic Review of Comparative Studies With Minimum 2-Year Follow-Up.

PURPOSE: To systematically review the literature in an effort to compare outcomes of patients undergoing primary anterior cruciate ligament reconstruction (ACLR) with a quadriceps tendon (QT) autograft versus a bone-patellar tendon-bone (BPTB) or hamstring tendon (HT) autograft. METHODS: A systematic review was performed by searching PubMed, the Cochrane Library, and Embase to locate studies (Level of Evidence I-III) comparing the clinical outcomes of the QT autograft versus the BPTB or HT autograft in patients undergoing primary ACLR. Patients were evaluated based on graft failure rate, examination of knee laxity, and patient-reported outcome scores. RESULTS: Eight studies (1 Level II, 7 Level III) were identified that met inclusion criteria, including a total of 368 patients undergoing primary ACLR with a QT autograft, 225 with a BPTB autograft, and 150 with an HT autograft. The average follow-up duration for all patients was 2.9 years. Overall, 2.8% of patients (17/603) experienced graft failure. Within the studies that compared the QT versus BPTB autograft, no study found a significant difference in graft failure rate between groups, and the odds ratio for graft failure between QT and BPTB was found to be 1.58 (95% confidence interval: 0.49-5.07; P = .44). Within the studies that compared graft failure rate between the QT and HT autograft, none found significant differences between groups, although a meta-analysis was not performed because of a low number of trials. Two studies found significantly greater postoperative knee laxity in HT patients compared with QT patients (P < .05), although there were no significant differences found in laxity measurements between QT and BPTB patients. CONCLUSIONS: Patients undergoing primary ACLR with either a QT, BPTB, or HT autograft can all be expected to experience improvement in clinical outcomes. QT patients experienced less knee laxity postoperatively compared with HT patients, although no significant differences were found in graft failure rate between groups. LEVEL OF EVIDENCE: Level III, systematic review of Level II and III studies.

Hip Distraction Without a Perineal Post: A Prospective Study of 1000 Hip Arthroscopy Cases.

BACKGROUND: Hip arthroscopy has traditionally been performed with a perineal post, resulting in various groin-related complications, including pudendal nerve neurapraxias, vaginal tears, and scrotal necrosis. PURPOSE: To assess the safety of a technique for hip distraction without the use of a perineal post. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We prospectively analyzed a consecutive cohort of 1000 hips presenting to a dedicated hip preservation clinic; all patients had hip pain and were subsequently treated with hip arthroscopy. Demographic variables, hip pathology, and lateral center edge angle were recorded for each case. In the operating room, the patient's feet were placed in traction boots in a specifically designed distraction setup, and the operative table was placed in varying degrees of Trendelenburg. With this technique, enough resistance is created by gravity and friction between the patient's body and the bed to allow for successful hip distraction without the need for a perineal post. In a subset of 309 hips (n = 281 patients), the degrees of Trendelenburg as well as the distraction force were analyzed. RESULTS: The mean ± SD Trendelenburg angle used among the subset of 309 hips was 11° ± 2°. The mean initial distraction force necessary was 90 ± 28 lb, which decreased to 65 ± 24 lb by 30 minutes after traction initiation ( P < .0001). The most important variables in determining initial force for this cohort of patients were, in order of magnitude, sex ( P < .0001), weight ( P < .0001), and lateral center edge angle ( P < .01). No groin-related complications occurred among the entire cohort of patients, including soft tissue or nerve-related complications. The rate of deep venous thrombosis was 2 in 1000. CONCLUSION: The use of the Trendelenburg position and a specially designed distraction setup during hip arthroscopy allows for safe hip distraction without a perineal post, thereby eliminating groin-related soft tissue and nerve complications. Certain patient variables can be used to estimate the required distraction force and inclination angle with this method.

The Iliofemoral Line: A Radiographic Sign of Acetabular Dysplasia in the Adult Hip.

BACKGROUND: Several radiographic parameters utilized for the diagnosis of acetabular dysplasia in adults suffer from poor reproducibility and reliability. PURPOSE: To define and validate a novel radiographic parameter (the iliofemoral line [IFL]) for the detection of frank and borderline hip dysplasia and to compare the sensitivity and specificity of this radiographic marker to those of previously validated qualitative parameters. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: A consecutive cohort of 222 adult patients (436 hips) undergoing hip preservation surgery was included. The IFL, which extends from the lateral femoral neck through the inner cortical lip of the iliac crest, intersects the femoral head in cases of dysplasia. Percent medialization of the IFL was defined as the horizontal distance of the exposed femoral head lateral to the IFL, relative to the horizontal femoral head width at the center of the femoral head. RESULTS: Percent medialization of the IFL was strongly correlated to the lateral center edge angle ( P < .0001). Values of percent medialization ranging from 15% to 22% predicted the presence of borderline hip dysplasia with a sensitivity of 62% and specificity of 89%, while values exceeding 22% predicted the presence of frank acetabular dysplasia with a sensitivity of 77% and specificity of 94%. By comparison, abnormality of the Shenton line demonstrated a sensitivity of 3.7% and specificity of 97% for the detection of borderline dysplasia and a sensitivity of 16% and specificity of 99% for the detection of frank acetabular dysplasia. Compared with the Shenton line, percent medialization of the IFL was significantly more sensitive for the detection of both borderline and frank acetabular dysplasia (both P < .0001). The intraobserver and interobserver reproducibility of the horizontal difference outside the IFL were 0.99 and 0.96, respectively. CONCLUSION: Percent medialization of the IFL is a reliable and accurate radiographic marker of frank acetabular dysplasia and, to a lesser extent, borderline dysplasia. The use of this radiographic parameter as an additional tool may enable the earlier detection of borderline and frank hip dysplasia in young adults presenting with hip pain.