The effect of spanning external fixation on entrapped structures in tibial pilon fractures.

PURPOSE: Pilon fractures are often complex injuries involving severe soft tissue injury. Studies have shown pilon fractures may entrap soft tissue structures between fracture fragments. Staged fixation of pilon fractures with spanning external fixation (SEF) is important for soft tissue rest and plays an important role in the management of these injuries. While SEF has been shown to promote soft tissue rest prior to definitive fixation, no studies have shown the effect SEF has on entrapped structures (ES). The purpose of this study was to evaluate how SEF effects ES in pilon fractures. METHODS: A retrospective review of 212 pilon fractures treated at our institution between 2010 and 2022 was performed. Patients with a CT scan pre-SEF and post-SEF met inclusion criteria. CTs were reviewed to characterize ES in pre- and post-SEF imaging. RESULTS: Of the 19 patients with ES identified on CT pre-SEF, seven (36.8%) had full release of ES post-SEF and 12 (63.2%) had no release of ES. The posterior tibial tendon was the most commonly ES and remained entrapped in 62.5% of cases. Only 25% of 43-C3 fractures had release of ES post-SEF, while 100% of 43-C1 and 43-C2 fractures demonstrated complete release of ES post-SEF. CONCLUSION: Entrapped structures in pilon fractures are likely to remain entrapped post-SEF, with only one-third of our cohort demonstrating release. In 43-C3 patterns, if ES are identified on CT pre-SEF, surgeons should consider addressing these either through mini open versus open approaches at the time of SEF as they are likely to remain entrapped post-SEF.

Fracture blisters: predictors for time to definitive fixation in pilon fractures.

PURPOSE: Fracture blisters, a common soft-tissue complication of pilon fractures, are associated with post-operative wound infections, delays in definitive fixation, and alterations in surgical plan. The purpose of this study was to (1) identify the delay in surgery attributable to the presence fracture blisters and (2) investigate the relationship of fracture blisters to comorbidities and fracture severity. METHODS: Patients with pilon fractures at an urban level 1 Trauma center from 2010 to 2021 were identified. The presence or absence of fracture blisters was noted, along with location. Demographic information, time from injury to external fixator placement, and time to definitive open reduction internal fixation (ORIF) were collected. Pilon fractures were classified according to AO/OTA guidelines using CT imaging and plain radiographs. RESULTS: 314 patients with pilon fractures were available for analysis, eighty (25%) of whom were found to have fracture blisters. Patients with fracture blisters had longer time to surgery compared to those without fracture blisters (14.2 days vs 7.9 days, p < 0.001). A greater proportion of patients with fracture blisters had AO/OTA 43C fracture patterns, compared with those without fracture blisters (71.3% vs 53.8%, p = 0.03). Fractures blisters were less likely to be localized over the posterior ankle (12%, p = 0.007). CONCLUSION: The presence of fracture blisters in pilon fractures are associated with significant delays in time to definitive fixation and higher energy fracture patterns. Fracture blisters are less commonly located over the posterior ankle which may support the implementation of a staged posterolateral approach when managing these injures.

Bone Marrow Aspirate Concentrate Augmentation May Accelerate Allograft Ligamentization in Anterior Cruciate Ligament Reconstruction: A Double-Blinded Randomized Controlled Trial.

PURPOSE: To assess the effect of bone marrow aspiration concentrate (BMAC) augmentation on clinical outcomes and magnetic resonance imaging (MRI) findings in anterior cruciate ligament (ACL) reconstruction (ACLR) with bone-patellar tendon-bone (BTB) allografts. METHODS: A double-blinded, randomized controlled trial was conducted on 80 patients undergoing ACL reconstruction using BTB allografts. Patients were randomized to 2 groups: (1) bone marrow aspirate was collected from the iliac crest, concentrated, and approximately 2.5 mL was injected into the BTB allograft, or (2) a small sham incision was made at the iliac crest (control). MRI was performed at 3 months and 9 months postoperatively to determine the signal intensity ratio of the ACL graft. RESULTS: Seventy-three patients were available for follow-up at 1-year postoperatively (36 BMAC, 37 control). International Knee Documentation Committee (IKDC) scores were significantly greater in the BMAC group versus the control at the 9-month postoperative period (81.6 ± 10.5 vs 74.6 ± 14.2, P = .048). There was no significant difference in the proportion of patients who met the minimal clinically important difference for IKDC between the BMAC and control groups at 9 months (89% vs 85%; P = .7). Three months postoperatively, signal intensity ratio of the inferior third of the ACL graft was significantly greater in the BMAC group versus the control group (3.2 ± 2.2 vs 2.1 ± 1.5; P = .02). CONCLUSIONS: Patients who received BMAC augmentation of the BTB allograft during ACL reconstruction demonstrated greater signal intensity scores on MRI at 3 months, suggesting increased metabolic activity and remodeling, and potentially accelerated ligamentization. Additionally, patients in the BMAC group had greater patient-reported outcomes (IKDC) at 9 months postoperatively when compared with those who underwent a standard surgical procedure. There was no significant difference in the proportion of patients who met the minimal clinically important difference for IKDC between the BMAC and control groups at 9 months, suggesting limited clinical significance at this time point. LEVEL OF EVIDENCE: I, randomized control trial.

Preoperative Corticosteroid Injections Demonstrate a Temporal and Dose-Dependent Relationship with the Rate of Postoperative Infection Following Total Hip Arthroplasty.

BACKGROUND: Corticosteroid injections (CSI) are commonly used for the treatment of osteoarthritis of the hip. There is concern, however, that these injections may increase the risk of postoperative infection if a subsequent total hip arthroplasty (THA) is performed. The purpose of the present investigation is to determine the relationship between CSI and the risk of periprosthetic joint infection (PJI) and surgical site infections (SSIs) following THA. METHODS: The PearlDiver database was reviewed for patients undergoing THA from 2011 to 2018. Patients with unilateral hip osteoarthritis who received an intra-articular hip CSI prior to ipsilateral THA were matched in a sequential 1:1 fashion based on age, gender, and Charlson Comorbidity Index with THA patients who did not receive an injection in the preoperative period. PJI and SSI within 6 months of the surgical procedure were recorded. Statistical analysis included chi-squared test and multivariate logistic regression. Results were considered significant at P < .05. RESULTS: In total, 29,058 patients underwent a hip CSI within 6 months prior to THA. CSI within 4 months of surgery was associated with a higher incidence of PJI at 6-month follow up (1.6% vs 1.1%, P = .040). An injection within 1 month of surgery corresponded to a higher odds of PJI (odds ratio [OR] 1.97) than an injection 4 months prior to surgery (OR 1.24). Furthermore, the quantity of CSI administered within the 3 months prior to THA demonstrated a dose-dependent relationship, with each subsequent injection increasing odds of PJI (OR 1.45-3.59). A similar relationship was observed for SSI. CONCLUSION: There appears to be both a time and dose-dependent association of hip CSI and PJI following THA. Surgeons should consider delaying elective THA if a CSI has been administered within the 4 months prior to the planned procedure.

Alcohol-dysregulated miR-30a and miR-934 in head and neck squamous cell carcinoma.

BACKGROUND: Alcohol consumption is a well-established risk factor for head and neck squamous cell carcinoma (HNSCC); however, the molecular mechanisms by which alcohol promotes HNSCC pathogenesis and progression remain poorly understood. Our study sought to identify microRNAs that are dysregulated in alcohol-associated HNSCC and investigate their contribution to the malignant phenotype. METHOD: Using RNA-sequencing data from 136 HNSCC patients, we compared the expression levels of 1,046 microRNAs between drinking and non-drinking cohorts. Dysregulated microRNAs were verified by qRT-PCR in normal oral keratinocytes treated with biologically relevant doses of ethanol and acetaldehyde. The most promising microRNA candidates were investigated for their effects on cellular proliferation and invasion, sensitivity to cisplatin, and expression of cancer stem cell genes. Finally, putative target genes were identified and evaluated in vitro to further establish roles for these miRNAs in alcohol-associated HNSCC. RESULTS: From RNA-sequencing analysis we identified 8 miRNAs to be significantly upregulated in alcohol-associated HNSCCs. qRT-PCR experiments determined that among these candidates, miR-30a and miR-934 were the most highly upregulated in vitro by alcohol and acetaldehyde. Overexpression of miR-30a and miR-934 in normal and HNSCC cell lines produced up to a 2-fold increase in cellular proliferation, as well as induction of the anti-apoptotic gene BCL-2. Upon inhibition of these miRNAs, HNSCC cell lines exhibited increased sensitivity to cisplatin and reduced matrigel invasion. miRNA knockdown also indicated direct targeting of several tumor suppressor genes by miR-30a and miR-934. CONCLUSIONS: Alcohol induces the dysregulation of miR-30a and miR-934, which may play crucial roles in HNSCC pathogenesis and progression. Future investigation of the alcohol-mediated pathways effecting these transformations will prove valuable for furthering the understanding and treatment of alcohol-associated HNSCC.

Outcomes of Distal Femoral Osteotomy for Valgus Malalignment: A Systematic Review and Meta-analysis of Closing Wedge Versus Opening Wedge Techniques.

BACKGROUND: Valgus knee deformity increases the risk for lateral articular chondral damage, contributing to earlier onset and accelerated progression of osteoarthritis. Distal femoral osteotomy (DFO) unloads the lateral joint compartment and can be performed using closing wedge (CW) or opening wedge (OW) techniques. PURPOSE: To perform a systematic review and meta-analysis for patients with valgus knee deformity undergoing DFO to determine differences in patient-reported outcome measures (PROMs), complications, and survival rates, comparing CW versus OW DFO. STUDY DESIGN: Systematic review, Level of evidence, 4. METHODS: A literature review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines utilizing PubMed, Cochrane Database, Ovid/MEDLINE, and Scopus. Inclusion criteria consisted of studies reporting outcomes in patients undergoing CW or OW DFO for the treatment of valgus knee deformities with symptomatic lateral compartment pathology with a minimum 2-year follow-up. PROMs and complications were analyzed using random-effects modeling to identify differences in outcomes as a function of surgical technique. Long-term survival data, defined as conversion to total knee arthroplasty, were analyzed using a multiple metaregression model as a function of individual study follow-up time points and surgical technique. RESULTS: In total, we included 23 retrospective studies (n = 619 knees), of which 10 studies (n = 271 knees) reported outcomes after CW DFO and 13 studies (n = 348 knees) reported on OW DFO outcomes. Good to excellent clinical outcomes were reported in PROMs when compared with preoperative values with both techniques, while no significant differences between techniques were appreciated on functional Knee Society Scores and Tegner scores. No significant differences were appreciated in the incidence of complications reported in patients undergoing CW (20%) versus OW (33%) DFO (P = .432). Pain requiring hardware removal was the most commonly reported complication in both groups. The survival rate for CW DFO was 81.5% (mean follow-up, 8.8 ± 4.3 years) compared with 90.5% for OW DFO (mean follow-up, 4.5 ± 1.5 years). Multiple metaregression demonstrated that patient follow-up (P < .001) was significantly associated with knee survival, while surgical technique (P = .810) was not a predictor of clinical failure. CONCLUSIONS: Both CW and OW DFO techniques were associated with good to excellent clinical outcomes with no significant differences in PROMs based on technique. Pain requiring hardware removal was the most common complication in both techniques, while long-term survivability was found to be a function of follow-up and not surgical technique. Technique selection should be based on shared patient-physician decision making with an emphasis on surgeon preference and technique familiarity.

Patellar fracture among elite-level European soccer players: 4-year case-control cohort analysis of return to play, re-injury, and player performance.

OBJECTIVES: There is a paucity of literature investigating the relationship between patellar fracture and player performance of professional soccer players following return to play (RTP). Our goal is to determine the rate of RTP, time to RTP, and effect on player performance following patellar fracture. METHODS: Twenty-one elite-level European professional soccer players who sustained a patellar fracture between 1999 and 2018 were identified via a publicly accessible database. Athletes with patellar fracture were matched to controls by age, height, years played in the league, season of injury, and position. Change in performance metrics between one season prior to injury and the following four seasons after injury were compared. RESULTS: Players with patellar fracture were absent for a mean 207.95 ± 135.55 days and 16.81 ± 31.79 games. Fifteen (71%) players returned to play after injury with 67% returning within 1 season after injury. Injured players did not demonstrate significant change in performance metrics at any of the follow-up timepoints compared to control. Subgroup analysis showed that attackers recorded approximately 1200 fewer minutes played per season than pre-injury levels 2 seasons following injury, significantly fewer (p < 0.05) than the control cohort recording similar minutes per season throughout the study period. Midfielders and defenders demonstrated similar fluctuations in performance to the control cohort for both field time and performance metrics (p > 0.05). CONCLUSION: Seventy-one percent of players RTP after patellar fracture with an associated absence of 7 months and 17 missed games. Overall, injured players did not demonstrate a significant decline in performance as demonstrated by games played, total minutes played per season, minutes per game, assists, and goals 1 season after injury. Attackers played fewer minutes during the season of and 2 seasons after the initial injury.

Return to Play and Player Performance After Foot Fracture in UEFA Soccer Players.

Background: There is a paucity of information on rate and time to return to play (RTP) in elite-level soccer players who have sustained foot fractures. Purpose: To (1) determine the rate and timing of RTP after foot fracture (eg, tarsal, metatarsal, or phalangeal), (2) investigate foot fracture reinjury incidence after RTP, and (3) evaluate performance after foot fracture as compared with matched, uninjured controls. Study Design: Descriptive epidemiology study. Methods: Athletes sustaining foot fractures were identified across the 5 major European soccer leagues (English Premier League, Bundesliga, La Liga, Ligue 1, and Serie A) between 2000 and 2016. Injured athletes were matched to controls (1:1) using demographic characteristics and performance metrics from 1 season before injury. The authors recorded RTP rate, reinjury incidence, player characteristics associated with RTP within 2 seasons of injury, player availability, field time, and performance metrics during the 4 seasons after injury. Results: A total of 192 elite soccer players sustaining a foot fracture were identified; 40 players (20.8%) underwent operative treatment. Athletes missed an average of 69.41 ± 59.43 days and 5.15 ± 23.28 games. In the 4 seasons after injury, 80% of players returned to play, with 72% returning to play within 1 season of injury. Nine players (5%) sustained a subsequent foot fracture. Athletes with a foot fracture demonstrated significantly longer league retention compared with uninjured controls (P < .001). Elite soccer players older than 30 years of age were less likely to RTP (odds ratio, 0.67; P = .002), whereas career experience, field position, and baseline performance showed no significant association with RTP rates. Injured athletes demonstrated similar performance to controls during the 4 years after injury, and there were no position-dependent differences on subgroup analysis. The players who underwent operative treatment had more assists per 90 minutes and more team points per game during the first season after injury compared with athletes treated nonoperatively. Conclusion: Foot fractures in elite soccer players resulted in moderate loss of play time (69.41 days). RTP rates were high at 80%, although players older than 30 years of age were less likely to RTP. On RTP, athletes who sustained a foot fracture maintained performance similar to preinjury levels and to uninjured controls.

Return to Play and Player Performance After Meniscal Tear Among Elite-Level European Soccer Players: A Matched Cohort Analysis of Injuries From 2006 to 2016.

BACKGROUND: Meniscal injuries are extremely common in soccer athletes, and little is known about postrecovery performance. PURPOSE: To (1) identify characteristics associated with return to play (RTP) to the same league level and (2) evaluate long-term effects that injury and management approach may have on player performance. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Using publicly available records, we identified athletes who sustained meniscal tears across the 5 major European soccer leagues (English Premier League, Bundesliga, La Liga, Ligue 1, and Serie A) between 2006 and 2016. Injured athletes were matched to controls 1:2 by demographics and performance. Investigations included rate of RTP to the same league level, reinjury, player characteristics associated with RTP within 2 seasons, long-term availability, field time, and performance metrics standardized to 90 minutes of play during the next 4 seasons. RESULTS: A total of 250 players sustaining meniscal tears were included, of which 106 (42%) received surgical management. Median absence was 57.5 days (interquartile range [IQR], 35-92) or 7 games (IQR, 4-12). Rate of RTP was 70%, and the reinjury rate 5% if a player could RTP. Age greater than 30 years was a negative predictor for RTP (odds ratio [OR], 0.62; P = .002), whereas higher preinjury goals per game (OR, 2.80; P = .04) and surgical management (OR, 1.38; P = .002) were positive predictors for RTP. Surgical management was associated with higher long-term availability (P < .01). As compared with the control, there were no significant differences in field time or performance metrics after RTP, either overall or by player position. As compared with nonoperative management, defenders undergoing surgery demonstrated decreased field time. Attackers and midfielders demonstrated similar field time and performance regardless of management. CONCLUSION: RTP of elite soccer athletes sustaining meniscal tear is contingent on age, preinjury performance, and management approach. Those who RTP to the same league level can be expected to demonstrate equivalent field time, performance, and long-term availability as noninjured athletes.

No Difference in Clinical Outcomes for Arthroscopic Suprapectoral Versus Open Subpectoral Biceps Tenodesis at Midterm Follow-up: A Randomized Prospective Analysis.

BACKGROUND: We have previously reported the 1-year outcomes of arthroscopic suprapectoral biceps tenodesis (ASPBT) versus open subpectoral biceps tenodesis (OSPBT) for the management of long head of the biceps tendon (LHBT) pathology. While patients had similar 1-year biceps muscle strength and pain, longer-term functional outcomes are unknown. PURPOSE: To directly compare clinical outcomes of ASPBT versus OSPBT with interference screw fixation, distal to the bony bicipital groove, at a minimum of 2 years' follow-up. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 85 patients undergoing biceps tenodesis (BT) for LHBT disease were randomized into the ASPBT or OSPBT group. Both techniques utilized polyether ether ketone inference screws for tenodesis fixation. Patients completed American Shoulder and Elbow Surgeons (ASES), Constant subjective, and Single Assessment Numeric Evaluation (SANE) questionnaires preoperatively and again at 6 months, 12 months, and at the final follow-up at a minimum of 24 months. RESULTS: A total of 73 patients (37/42 randomized to ASPBT [88%]; 36/42 randomized to OSPBT [86%]) with a mean age of 50.4 ± 10.3 years and a mean body mass index of 29 ± 7.9 were included in clinical outcome analyses. The mean final follow-up was 2.9 years (ASPBT, 3 years; OSPBT, 2.8 years [range 2-5.2 years]). Comparison of demographic characteristics and intraoperative findings showed no significant differences in age, sex, concomitant procedures, and rotator cuff disease. No statistically significant differences in the ASES (P = .25), Constant subjective (P = .52), and SANE scores (P = .61) were found at the final follow-up. Clinical outcomes scores showed no significant improvement from a mean of 12.6 months to the final follow-up at 34.5 months (ASPBT: ASES, P = .43; Constant, P = .25; SANE, P = .45 vs OSPBT: ASES, P = .65; Constant, P = .78; SANE, P = .70). No patients required revision of BT in either group. CONCLUSION: This study reported a minimum of 2-year follow-up of patients undergoing ASPBT or OSPBT, utilizing the same interference screw technique, for the management of LHBT pathology in the setting of concomitant shoulder procedures. There were no significant differences in patient-reported outcomes and complication rates found at any time point. REGISTRATION: NCT02192073 (ClinicalTrials.gov identifier).

Acromioclavicular Joint Separation in UEFA Soccer Players: A Matched-Cohort Analysis of Return to Play and Player Performance From 1999 to 2018.

BACKGROUND: Acromioclavicular joint (ACJ) separation injuries are uncommon in professional soccer players, threatening future performance and team contributions. Data regarding return to play (RTP) in professional soccer players after ACJ separation are limited. PURPOSE: To determine the rate, time to RTP, and player performance after ACJ separation in soccer players from the top 5 professional European leagues when compared with a retrospective, matched cohort of uninjured players. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Professional soccer players suffering ACJ separation injuries between 1999 and 2018 were identified and were matched to uninjured players (2 controls to 1 injured player) by position, height, age, season year, and length of time played. Information on date of injury, timing to RTP, and player performance metrics (minutes played, games played, goals scored, assists made, and points per game) were collected from transfermarkt.co.uk, uefa.com, fifa.com, official team websites, public injury reports, and press releases. Change in performance metrics for the 4 seasons after the season of injury were based on metrics 1 season before injury. Univariate comparisons were performed using independent 2-group t tests and Wilcoxon rank-sum tests when normality of distributions was violated. RESULTS: A total 59 soccer players with ACJ separation injuries were identified. Mean age at injury was 24.6 ± 5.3 years. Of these, 81% of the players returned to play, with 69% returning within postinjury season 1. Mean time to RTP was 49.8 ± 24.3 days (5.9 ± 4.1 games). Two players suffered recurrent ACJ separation injuries in their professional soccer careers. There were no significant differences between athletes who sustained ACJ injuries versus control athletes in the number of games played, minutes per game per season, goals scored, assists, or points in the 4 seasons after injury. Defenders played fewer minutes and recorded fewer assists during postinjury season 1 when compared with control athletes. CONCLUSION: Of the 59 elite soccer players who sustained ACJ separation injuries during the study period, 81% returned to elite competition. Performance metrics were similar to preinjury levels and matched, uninjured control players.

Return-to-Play Times and Player Performance After Medial Collateral Ligament Injury in Elite-Level European Soccer Players.

BACKGROUND: Participation in elite-level soccer predisposes athletes to injuries of the medial collateral ligament (MCL), resulting in variable durations of time lost from sport. PURPOSE: To (1) determine the rate of return to play (RTP) and timing after MCL injuries, (2) investigate MCL reinjury incidence after RTP, and (3) evaluate the long-term effects of MCL injury on future performance. STUDY DESIGN: Descriptive epidemiology study. METHODS: Using publicly available records, we identified athletes who had sustained MCL injury between 2000 and 2016 across the 5 major European soccer leagues (English Premier League, Bundesliga, La Liga, Ligue 1, and Serie A). Injured athletes were matched to controls using demographic characteristics and performance metrics from the season before injury. We recorded injury severity, RTP rate, reinjury incidence, player characteristics associated with RTP within 2 seasons of injury, player availability, field time, and performance metrics during the 4 seasons after injury. RESULTS: A total of 59 athletes sustained 61 MCL injuries, with 86% (51/59) of injuries classified as moderate to severe and surgical intervention performed in 14% (8/59) of athletes. After injury, athletes missed a median of 33 days (range, 3-259 days) and 4 games (range, 1-30 games). Overall, 71% (42/59) of athletes returned successfully at the same level, with multivariable regression demonstrating no athlete characteristic predictive of RTP. MCL reinjury was reported in 3% (2/59) of athletes. Midfielders demonstrated decreased field time after RTP when compared with controls (P < .05). No significant differences in player performance for any position were identified out to 4 seasons after injury. Injured athletes had a significantly higher rate of long-term retention (P < .001). CONCLUSION: MCL injuries resulted in a median loss of 33 days in elite European soccer athletes, with the majority of injuries treated nonoperatively. RTP remained high, and few athletes experienced reinjury. While midfielders demonstrated a significant decrease in field time after RTP, player performance and long-term retention were not compromised. Future studies are warranted to better understand athlete-specific and external variables predictive of MCL injury and reinjury, while evaluating treatment and rehabilitation protocols to minimize time lost and to optimize athlete safety and health.

Traumatic Leg Fractures in UEFA Football Athletes: A Matched-Cohort Analysis of Return to Play, Reinjury, Player Retention, and Performance Outcomes.

BACKGROUND: The average professional soccer team experiences 1 to 2 traumatic leg fractures per season, with unknown effects on player performance. PURPOSE: To (1) determine the rate and time to return to play (RTP) following leg fracture, (2) investigate the rate of reinjury following RTP, and (3) investigate long-term effects that lower extremity (LE) fracture may have on elite soccer player performance. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Using publicly available records, we identified athletes sustaining a traumatic leg fracture across the 5 major European soccer leagues (English Premier League, Bundesliga, La Liga, Ligue 1, and Serie A) between 2000 and 2016. Athletes with leg fracture (femur, tibia, and/or fibula) were matched 1:2 to controls by demographic characteristics and performance metrics 1 season before the index timepoint. Investigations included the RTP rate, reinjury rate, player characteristics associated with RTP within 2 seasons, long-term player retention, performance metrics during the 4 following seasons, and subgroup analysis by player position. RESULTS: A total of 112 players with LE fracture and 224 controls were identified. Players with LE fractures were absent for a mean of 157 days (range, 24-601 days) and 21 games (range, 2-68 games). The rate of RTP within 1 season was 80%, with 4% experiencing subsequent refracture. Injured players remained active in the league at a higher rate than their uninjured counterparts. As compared with controls, injured athletes played 309 fewer total minutes (P < .05), scored 0.09 more assists per game (P < .01) 1 season after injury, and scored 0.12 more points per game 4 seasons after injury (P < .01). Defenders were most affected by an LE fracture, playing 5.24 fewer games (P < .05), 603 fewer total minutes (P < .01), and recording 0.19 more assists per 90 minutes of play as compared with controls 1 season after injury (P < .001). Attackers and midfielders demonstrated no significant difference in metrics after RTP when compared with controls. CONCLUSION: Most players sustaining an LE fracture returned to elite soccer at the same level after a significant loss of playing time, with a 4% rate of refracture. Player retention was higher for those sustaining an LE fracture versus uninjured controls. Overall, injured players did not experience a decline in performance after recovery from an LE fracture.

Alcohol and hepatitis virus-dysregulated lncRNAs as potential biomarkers for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths because of frequent late detection and poor therapeutic outcomes, necessitating the need to identify effective biomarkers for early diagnosis and new therapeutic targets for effective treatment. Long noncoding RNAs (lncRNAs) have emerged as promising molecular markers for diagnosis and treatment. Through analysis of patient samples from The Cancer Genome Atlas database, we identified putative lncRNAs dysregulated in HCC and by its risk factors, hepatitis infection and alcohol consumption. We identified 184 lncRNAs dysregulated in HCC tumors versus paired normal samples, 53 lncRNAs dysregulated in alcohol-drinking patients with hepatitis B, and 5, 456 lncRNAs dysregulated in patients with hepatitis infection. A panel of these candidate lncRNAs' expressions correlated significantly with patient survival, clinical variables, and known genomic alteration in HCC. Two most significantly dysregulated lncRNAs in our computational analysis, lnc-CFP-1:1 and lnc-CD164L2-1:1, were validated in vitro to be dysregulated by alcohol. Our findings suggest that lncRNAs dysregulated by different etiologies of HCC serve as potential disease markers and can be further investigated to develop personalized prevention, diagnosis, and treatment strategies.

Alcohol-dysregulated microRNAs in hepatitis B virus-related hepatocellular carcinoma.

Alcohol consumption and chronic hepatitis B virus (HBV) infection are two well-established risk factors for Hepatocellular carcinoma (HCC); however, there remains a limited understanding of the molecular pathway behind the pathogenesis and progression behind HCC, and how alcohol promotes carcinogenesis in the context of HBV+ HCC. Using next-generation sequencing data from 130 HCC patients and 50 normal liver tissues, we identified a panel of microRNAs that are significantly dysregulated by alcohol consumption in HBV+ patients. In particular, two microRNAs, miR-944 and miR-223-3p, showed remarkable correlation with clinical indication and genomic alterations. We confirmed the dysregulation of these two microRNAs in liver cell lines treated by alcohol and acetaldehyde, and showed that manipulation of miR-223-3p and miR-944 expression induces significant changes in cellular proliferation, sensitivity to doxorubicin, and the expression of both direct-binding and downstream mRNA targets. Together, the results of this study suggest that alcohol consumption in HBV+ HCCs regulates microRNAs that likely play previously uncharacterized roles in the alcohol-associated carcinogenesis of HCC, and future studies of these microRNAs may be valuable for furthering the understanding and treatment of alcohol and HBV-associated HCC.

Smoking status regulates a novel panel of PIWI-interacting RNAs in head and neck squamous cell carcinoma.

OBJECTIVE: Smoking remains a primary etiological factor in head and neck squamous cell carcinoma (HNSCC). Given that non-coding RNAs (ncRNAs), including PIWI-interacting RNAs (piRNAs), have emerged as mediators of initiation and progression in head and neck malignancies, we undertook a global study of piRNA expression patterns in smoking-associated HNSCC. MATERIALS AND METHODS: Using RNA-sequencing data from 256 current smoker and lifelong nonsmoker samples in The Cancer Genome Atlas (TCGA), we analyzed the differential expression patterns of 27,127 piRNAs across patient cohorts stratified by tobacco use, with HPV16 status and tumor status taken into account. We correlated their expression to clinical characteristics and to smoking-induced alterations of PIWI proteins, the functional counterparts of piRNAs. Finally, we correlated our identified piRNAs and PIWI proteins to known chromosomal aberrations in HNSCC to understand their wider-ranging genomic effects. RESULTS AND CONCLUSION: Our analyses implicated a 13-member piRNA panel in smoking-related HNSCC, among which NONHSAT123636 and NONHSAT113708 associated with tumor stage, NONHSAT067200 with patient survival, and NONHSAT081250 with smoking-altered PIWIL1 protein expression. 6 piRNAs as well as PIWIL1 correlated with genomic alterations common to HNSCC, including TP53 mutation, TP53-3p co-occurrence, and 3q26, 8q24, and 11q13 amplification. Collectively, our findings provide novel insights into the etiology-specific piRNA landscape of smoking-induced HNSCC.

A comprehensive study of smoking-specific microRNA alterations in head and neck squamous cell carcinoma.

OBJECTIVE: While tobacco smoking is a well-known risk factor for head and neck squamous cell carcinoma (HNSCC), the molecular mechanisms underlying tobacco-induced HNSCC remain unclear. This study sought to comprehensively identify microRNA (miRNA) alterations and evaluate their clinical relevance in smoking-induced HNSCC pathogenesis and progression. MATERIALS AND METHODS: Using small RNA-sequencing data and clinical data from 145 HNSCC patients, we performed a series of differential expression and correlation analyses to identify a panel of tobacco-dysregulated miRNAs associated with key clinical characteristics in HNSCC. We then examined the expression patterns of these miRNAs in normal epithelial cell lines following exposure to cigarette smoke extract. RESULTS: Our analyses revealed distinct panels of miRNAs to be dysregulated with smoking status and associated with additional clinical features, including tumor stage, metastasis, anatomic site, and patient survival. The differential expression of key miRNAs, including miR-101, miR-181b, miR-486, and miR-1301, was verified in cigarette-treated epithelial cell lines, suggesting their potential roles in the early development of smoking-related HNSCCs. CONCLUSION: Specific alterations in miRNA expression may be traced to tobacco use and are associated with important HNSCC clinical characteristics. Future studies of these miRNAs may be valuable for furthering the understanding and targeted treatment of smoking-associated HNSCC.

Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines.

OBJECTIVES: Evaluate the cytotoxicity and genotoxicity of short- and long-term e-cigarette vapor exposure on a panel of normal epithelial and head and neck squamous cell carcinoma (HNSCC) cell lines. MATERIALS AND METHODS: HaCaT, UMSCC10B, and HN30 were treated with nicotine-containing and nicotine-free vapor extract from two popular e-cigarette brands for periods ranging from 48 h to 8 weeks. Cytotoxicity was assessed using Annexin V flow cytometric analysis, trypan blue exclusion, and clonogenic assays. Genotoxicity in the form of DNA strand breaks was quantified using the neutral comet assay and γ-H2AX immunostaining. RESULTS: E-cigarette-exposed cells showed significantly reduced cell viability and clonogenic survival, along with increased rates of apoptosis and necrosis, regardless of e-cigarette vapor nicotine content. They also exhibited significantly increased comet tail length and accumulation of γ-H2AX foci, demonstrating increased DNA strand breaks. CONCLUSION: E-cigarette vapor, both with and without nicotine, is cytotoxic to epithelial cell lines and is a DNA strand break-inducing agent. Further assessment of the potential carcinogenic effects of e-cigarette vapor is urgently needed.

The non-coding landscape of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease marked by frequent recurrence and metastasis and stagnant survival rates. To enhance molecular knowledge of HNSCC and define a non-coding RNA (ncRNA) landscape of the disease, we profiled the transcriptome-wide dysregulation of long non-coding RNA (lncRNA), microRNA (miRNA), and PIWI-interacting RNA (piRNA) using RNA-sequencing data from 422 HNSCC patients in The Cancer Genome Atlas (TCGA). 307 non-coding transcripts differentially expressed in HNSCC were significantly correlated with patient survival, and associated with mutations in TP53, CDKN2A, CASP8, PRDM9, and FBXW7 and copy number variations in chromosomes 3, 5, 7, and 18. We also observed widespread ncRNA correlation to concurrent TP53 and chromosome 3p loss, a compelling predictor of poor prognosis in HNSCCs. Three selected ncRNAs were additionally associated with tumor stage, HPV status, and other clinical characteristics, and modulation of their expression in vitro reveals differential regulation of genes involved in epithelial-mesenchymal transition and apoptotic response. This comprehensive characterization of the HNSCC non-coding transcriptome introduces new layers of understanding for the disease, and nominates a novel panel of transcripts with potential utility as prognostic markers or therapeutic targets.