Incidence of Osteoarthritis Diagnosis Within 5 Years of Surgery Was Greater Following Partial Meniscectomy Than Meniscus Repair and/or Anterior Cruciate Ligament Reconstruction.

Purpose: To compare knee osteoarthritis (OA) incidence within 5 years of surgery between 5 common sports medicine procedures: isolated anterior cruciate ligament (ACL) reconstruction, isolated meniscus repair (MR), isolated arthroscopic partial meniscectomy (APM), ACL reconstruction with MR (ACL + MR), and ACL reconstruction with APM (ACL + APM). Methods: The PearlDiver Mariner M157Ortho database was searched. Five cohorts were identified using Current Procedural Terminology (CPT) codes and included those 16 to 60 years old who underwent isolated ACL reconstruction, isolated MR, ACL + MR, isolated APM, or ACL + APM repair. Groups were matched by age, sex, and presence of diagnosis codes for obesity. The incidence of knee OA diagnosis within 5 years of the index procedure was determined for each group, and odds ratios (ORs) were calculated and compared against isolated ACL reconstruction. Results: Each group consisted of 7,672 patients (3,450 females, 4,222 males). A significantly greater proportion of the APM group was diagnosed with knee OA within 5 years of surgery compared to isolated ACL reconstruction (APM = 1,032/7,672 [13.5%] vs ACL = 745/7,672 [9.7%]; P ≤ .001; OR, 1.45; 95% confidence interval [CI], 1.31-1.60). Similarly, a greater proportion of the MR group was diagnosed with OA compared to isolated ACL reconstruction (MR = 826/7,672 [10.7%]; P = .030; OR, 1.12; 95% CI, 1.01-1.25). No differences in OA incidence were noted between the ACL + APM group when compared to isolated ACL reconstruction (P = .81). Patients undergoing ACL + MR demonstrated the lowest OA incidence with reduced odds when compared to isolated ACL reconstruction (ACL + MR = 575/7,672 [7.5%]; P < .001; OR, 0.75; 95% CI, 0.67-0.84). Conclusions: In this analysis using CPT codes, APM was associated with the highest knee OA incidence, and ACL + MR was associated with the lowest OA incidence within 5 years of surgery. Level of Evidence: Level III, retrospective cohort study.

Editorial Commentary: Routine Use of Suture Tape Augmentation for Primary Anterior Cruciate Ligament Reconstruction Surgery Is Not Justified.

High rates of graft failure after primary anterior cruciate ligament reconstruction (ACLR) and the need for revision ACLR continue to be a challenge. Multiple studies demonstrate graft failure rates and the need for revision ACLR in 10% to 15% of young patients participating in pivot sporting activities. Currently, a wide range of strategies to mitigate this is problem being investigated, including extra-articular augmentation (with modified lateral extra-articular tenodesis or anterolateral ligament reconstruction) and intra-articular fixation (that aim for primary anterior cruciate ligament healing or augmentation of an ACLR with suture tape). While the early data on suture tape augmentation of primary ACLR seem optimistic, it does not justify its routine use.

Overexpression of manganese superoxide dismutase mitigates ACL injury-induced muscle atrophy, weakness and oxidative damage.

Oxidative stress has been implicated in the etiology of skeletal muscle weakness following joint injury. We investigated longitudinal patient muscle samples following knee injury (anterior cruciate ligament tear). Following injury, transcriptomic analysis revealed downregulation of mitochondrial metabolism-related gene networks, which were supported by reduced mitochondrial respiratory flux rates. Additionally, enrichment of reactive oxygen species (ROS)-related pathways were upregulated in muscle following knee injury, and further investigation unveiled marked oxidative damage in a progressive manner following injury and surgical reconstruction. We then investigated whether antioxidant protection is effective in preventing muscle atrophy and weakness after knee injury in mice that overexpress Mn-superoxide dismutase (MnSOD+/-). MnSOD+/- mice showed attenuated oxidative damage, atrophy, and muscle weakness compared to wild type littermate controls following ACL transection surgery. Taken together, our results indicate that ROS-related damage is a causative mechanism of muscle dysfunction after knee injury, and that mitochondrial antioxidant protection may hold promise as a therapeutic target to prevent weakness and development of disability.

Prevalence and Predictors of Postoperative Depression and Anxiety After Anterior Cruciate Ligament Reconstruction.

PURPOSE: Preoperative mood disorders influence postoperative outcomes after anterior cruciate ligament (ACL) reconstruction (ACLR), but the prevalence and risk factors associated with postoperative depression/anxiety development remain unknown. The purposes of this study were to quantify the prevalence of postoperative diagnoses of depression or anxiety following ACLR in patients under the age of 25 and assess the interplay between patient sex and ACL reoperation on the prevalence of a depression or anxiety diagnosis following ACLR. METHODS: ACLR patients under the age of 25 years old were identified in the Truven Healthcare Marketscan database. Patients with incomplete coverage +/- one year of the index surgical procedure were excluded. Patients were categorized by the presence of preoperative, postoperative, or no depression/anxiety using the International Classification of Diseases, Ninth Revision (ICD-9) codes. We compared patient demographics and reoperation rates following the index ACLR between the depression and anxiety categories. Additionally, logistic regression was fit to assess the interaction between sex and either ipsilateral or contralateral ACL surgery on postoperative depression/anxiety diagnosis. RESULTS: Of the 42,174 patients, 10.7% had a new depression/anxiety diagnosis after ACLR. Postoperative depression/anxiety was nearly twice as prevalent for females (F: 14.4%, M: 7.6%) despite having similar rates of secondary ACLR (F: 15.5%, M: 13.0%). Those with postoperative depression/anxiety had a considerably greater prevalence of reoperation (18.8%) than those without depression/anxiety (13.7%) and those with pre-existing preoperative depression/anxiety (12.9%). Sex and reoperation were independently associated with postoperative depression/anxiety diagnosis. CONCLUSION: Female sex and secondary ACL surgery are independently associated with an increased prevalence of postoperative depression/anxiety. Nearly one in seven young females are diagnosed with depression/anxiety after ACLR. Similarly, a greater proportion of patients who suffer a secondary ACL surgery are subsequently diagnosed with depression/anxiety. The orthopedic community must be cognizant of the increased risk of postoperative depression/anxiety for females and those who suffer a secondary ACL surgery, and screening for depression/anxiety in these at-risk populations with referrals to mental health professionals may be warranted.

Vitamin D status associates with skeletal muscle loss after anterior cruciate ligament reconstruction.

BACKGROUNDAlthough 25-hydroxyvitamin D [25(OH)D] concentrations of 30 ng/mL or higher are known to reduce injury risk and boost strength, the influence on anterior cruciate ligament reconstruction (ACLR) outcomes remains unexamined. This study aimed to define the vitamin D signaling response to ACLR, assess the relationship between vitamin D status and muscle fiber cross-sectional area (CSA) and bone density outcomes, and discover vitamin D receptor (VDR) targets after ACLR.METHODSTwenty-one young, healthy, physically active participants with recent ACL tears were enrolled (17.8 ± 3.2 years, BMI 26.0 ± 3.5 kg/m2). Data were collected through blood samples, vastus lateralis biopsies, dual energy x-ray bone density measurements, and isokinetic dynamometer measures at baseline, 1 week, 4 months, and 6 months after ACLR. The biopsies facilitated CSA, Western blotting, RNA-seq, and VDR ChIP-seq analyses.RESULTSACLR surgery led to decreased circulating bioactive vitamin D and increased VDR and activating enzyme expression in skeletal muscle 1 week after ACLR. Participants with less than 30 ng/mL 25(OH)D levels (n = 13) displayed more significant quadriceps fiber CSA loss 1 week and 4 months after ACLR than those with 30 ng/mL or higher (n = 8; P < 0.01 for post hoc comparisons; P = 0.041 for time × vitamin D status interaction). RNA-seq and ChIP-seq data integration revealed genes associated with energy metabolism and skeletal muscle recovery, potentially mediating the impact of vitamin D status on ACLR recovery. No difference in bone mineral density losses between groups was observed.CONCLUSIONCorrecting vitamin D status prior to ACLR may aid in preserving skeletal muscle during recovery.FUNDINGNIH grants R01AR072061, R01AR071398-04S1, and K99AR081367.

Observation of alumina nanoparticles generated from aqueous solutions of a "flat" aluminum-13 cluster.

Amorphous alumina nanoparticles were synthesized via dynamic processes during the dissolution of aluminum hydroxide by nitric acid, a method commonly used to produce aqueous solutions of aluminum oxide molecular clusters. These particles were characterized by DLS measurements, and corroborated by other solution and solid state analyses. The methods used represent a highly tuneable, facile synthetic pathway that allows for size targeting and scalability for industrial purposes, and provides insight into pH- and temperature-dependent alumina speciation and aggregation.

Comparison of Physical Therapy Utilization and Motion-Related Re-operations Between Isolated Anterior Cruciate Ligament and Multi-Ligament Knee Injuries.

The increased prevalence of postoperative arthrofibrosis after multi-ligament knee injuries (MLKI) compared to isolated anterior cruciate ligament (ACL) injuries has been proposed to be due, in part, to patient factors limiting physical therapy utilization. The purpose of this study was to compare demographic factors, pre- and postoperative physical therapy utilization, and the need for motion-restoring surgery between MLKI and ACL-injured patients. Using the PearlDiver Mariner 151 database, two cohorts matched by age and sex were identified using current procedural terminology (CPT) codes and included those age 16 or greater that underwent isolated ACL (n=3801) vs. MLKI reconstruction (n=3801). The number of pre- and postoperative physical therapy visits was recorded, as was the need for motion-restoring surgery (arthroscopic lysis of adhesions or manipulation under anesthesia). Demographic factors, physical therapy utilization, and the prevalence of motion-restoring surgery were compared between the MLKI and ACL groups using t-tests or chi-square tests, as appropriate. A significantly greater proportion of those with MLKI underwent subsequent motion-restoring surgery (MLKI=412/3081 (13.4%) vs. ACL=84/3081 (2.7%), p<0.001; odds ratio = 5.5 (95% CI: 4.3, 7.0), p<0.0001). Following surgery, less than half of those with MLKI that underwent subsequent motion-restoring surgery attended physical therapy, which was significantly lower than those who did not require motion-restoring surgery (p<0.0001). The prevalence of motion-restoring surgery was significantly greater after MLKI when compared to an isolated ACL injury. While the etiology of arthrofibrosis after MLKI is likely complex, the current results suggest that demographic factors and physical therapy utilization are not solely responsible for the increased risk of arthrofibrosis after MLKI.

Return to Play and Performance After Anterior Cruciate Ligament Reconstruction in the National Women's Soccer League.

Background: The anterior cruciate ligament (ACL) is commonly injured in elite-level female athletes, which usually requires ACL reconstruction (ACLR). Purpose: To analyze return to play (RTP) and changes in performance of players in the National Women's Soccer League (NWSL) after ACLR. Study Design: Descriptive epidemiology study. Methods: NWSL players who sustained an ACL tear and underwent surgery between the 2013 and 2020 seasons were identified by multiple online resources. Players were classified as forwards, defenders, midfielders, and goalkeepers. RTP was assessed according to games played, games started, percentage of minutes played, plus/minus net per 90 minutes (a measure of a player's contribution to their team's performance while on the field), goals scored, and assists. A subanalysis was performed based on the median age at the time of the injury (≤24 vs ≥25 years). Nonparametric testing methods were used throughout the analysis. Results: A total of 30 NWSL athletes were included. Midfielders had the highest percentage of injuries (n = 11; 36.7%), followed by forwards (n = 10; 33.3%). Overall, 27 players returned to the NWSL at a median of 12.1 months (IQR, 10.9-14.3 months), constituting a 90.0% RTP rate. There was a significant decrease in the percentage of minutes played from 1 year before the injury to 1 year after the injury (median, 87.9% [IQR, 80.7%-90.6%] vs 25.1% [IQR, 16.3%-57.2%], respectively; P = .031). Forwards and midfielders had a significant decrease in the number of assists from 1 year before the injury to 1 year after the injury (median, 3.0 [IQR, 1.0-3.0] vs 0.0 [IQR, 0.0-1.0], respectively; P = .037) as well as the number of goals scored when averaging across 2 seasons before the injury to 2 seasons after the injury (median, 3.0 [IQR, 1.5-5.5] vs 1.0 [IQR, 0.5-3.5], respectively; P = .031). On subanalysis, older players started in significantly more games (median, 12.0 [IQR, 3.8-18.5] vs 3.0 [IQR, 0.5-6.0], respectively; P = .048) and had a higher percentage of minutes played (median, 63.0% [IQR, 18.8%-77.3%] vs 14.9% [IQR, 2.0%-21.2%], respectively; P = .046) at 1 year after the injury versus younger players. Conclusion: There was a 90.0% RTP rate after ACLR in the NWSL. Players who returned to the NWSL had a lower percentage of minutes played in their first year after RTP, with older players starting in more games and having a greater percentage of minutes played. Compared with preinjury performance, forwards and midfielders had a significant decrease in the number of assists at 1 year after the injury as well as the number of goals scored at 2 years after the injury.

Leveraging Insurance Claims Data to Identify Risk Factors for Posttraumatic Osteoarthritis After Multiligament Knee Reconstruction.

BACKGROUND: The incidence of subsequent posttraumatic osteoarthritis (OA) diagnosis after surgery and the associated risk factors have been well reported after single-ligament anterior cruciate ligament (ACL) reconstruction; however, to date, the incidence of posttraumatic OA for those who have experienced multiligament knee injury (MLKI) has been reported only in relatively small, single-center studies. PURPOSE: To compare the incidence of OA diagnoses between patients with ACL injury versus patients with MLKI and to identify risk factors for OA diagnosis after MLKI. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study used the PearlDiver Mariner database, which contains insurance claims information on >151 million orthopaedic patients. We identified 2 cohorts for this study by using Current Procedural Terminology codes. The cohorts included patients between the ages of 16 and 60 who underwent either isolated ACL reconstruction (n = 114,282) or MLKI reconstruction (n = 3325) between July 1, 2010, and August 30, 2016. MLKI reconstruction was operationally defined as ACL reconstruction plus concurrent surgical treatment of ≥1 additional ligaments. Demographic factors, concomitant meniscal and cartilage procedures, and subsequent reoperation to restore motion were recorded, as was the incidence of knee OA diagnosis within 5 years of the index surgical procedure. OA incidence and demographic and surgical factors were compared (1) between ACL and MLKI groups and (2) between patients with MLKI either with or without OA diagnosis. RESULTS: A significantly greater proportion of patients with MLKI were diagnosed with knee OA within 5 years of surgery (MLKI = 299/3325 [9.0%] vs ACL = 6955/114,282 [6.1%]; P < .0001) (odds ratio [OR], 1.52; 95% CI, 1.35-1.72; P < .001). Factors associated with increased odds of OA diagnosis after MLKI included age ≥30 years (OR, 5.90), reoperation to restore motion (OR, 2.54), obesity (OR, 1.96), mood disorder diagnoses (OR, 1.85), partial meniscectomy (OR, 1.85), and tobacco use (OR, 1.72). Concomitant meniscal repair was protective against OA diagnosis (OR, 0.06). CONCLUSION: OA incidence was greater after MLKI reconstruction than after isolated ACL reconstruction. Potentially modifiable risk factors for OA after MLKI were identified and include obesity, tobacco use, depression, and the need for motion-restoring surgery.

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy and the role of advanced practice providers and pharmacists.

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a severe and potentially life-threatening complication. HSCT-TMA is often underdiagnosed due to multifactorial pathophysiology and a historic lack of standard diagnostic criteria. Identification of the multi-hit hypothesis and the key role of the complement system, particularly the lectin pathway of complement, has led to development of treatments targeting the underlying pathogenesis of HSCT-TMA. Additional research is ongoing to investigate the efficacy and safety of these targeted therapies in patients with HSCT-TMA. Advanced practice providers (APPs; nurse practitioners and physician assistants) and pharmacists are critical members of the multidisciplinary HSCT team and ensure management of patients throughout the continuum of care. Additionally, pharmacists and APPs can improve patient care through medication management of complex regimens; transplant education for patients, staff, and trainees; evidence-based protocol and clinical guideline development; assessment and reporting of transplant-related outcomes; and quality improvement initiatives to improve outcomes. Understanding the presentation, prognosis, pathophysiology, and treatment options for HSCT-TMA can improve each of these efforts. Collaborative practice model for monitoring and care of HSCT-TMA. Advanced practice providers and pharmacists contribute to many aspects of patient care in transplant centers, including medication management for complex regimens; transplant education for patients, staff, and trainees; evidence-based protocol and clinical guideline development; assessment and reporting of transplant-related outcomes; and quality improvement initiatives. HSCT-TMA is a severe and potentially life-threatening complication that is often underdiagnosed. The collaboration of a multidisciplinary team of advanced practice providers, pharmacists, and physicians can optimize recognition, diagnosis, management, and monitoring of patients with HSCT-TMA, thereby improving outcomes for these patients.

Synovial Fluid Inflammatory Profiles did not Differ between Isolated Anterior Cruciate Ligament and Multi-ligament Knee Injuries.

Objective and design: The purpose of this study was to compare synovial concentrations of pro- and anti-inflammatory cytokines between multiple-ligament knee injured (MLKI) and anterior cruciate ligament (ACL)-injured patients. Subjects: 14 patients with MLKI and 10 patients with isolated ACL injury. Methods: Synovial fluid was aspirated from the operative knee at the time of surgery and the concentrations of pro- and anti-inflammatory markers in the synovial fluid were determined. Structures injured, the time between injury and surgery, and demographic factors were collected. Linear regressions were used to determine the association between injury pattern and synovial inflammatory markers when controlling for age, BMI, and time between injury and surgery. Results: When adjusting for group differences in age, BMI and the time between injury and surgery, no group differences were detected (interferon gamma (p = 0.11), interleukin-1beta (IL-1b, p = 0.35), IL-2 (p = 0.28), IL-4 (p = 0.64), IL-6 (p = 0.37), IL-8 (p = 0.54), IL-10 (p = 0.25), IL-12p70 (p = 0.81), IL-13 (p = 0.31), and tumor necrosis factor-alpha (p = 0.90)). Conclusion: Synovial fluid inflammatory markers did not differ between MLKI and isolated ACL injuries. MLKIs have a greater prevalence of postoperative arthrofibrosis when compared to isolated ACL injuries; however, this may be due in part to factors other than the inflammatory status of the joint.

Depressed Protein Synthesis and Anabolic Signaling Potentiate ACL Tear-Resultant Quadriceps Atrophy.

BACKGROUND: Anterior cruciate ligament (ACL) tear (ACLT) leads to protracted quadriceps muscle atrophy. Protein turnover largely dictates muscle size and is highly responsive to injury and loading. Regulation of quadriceps molecular protein synthetic machinery after ACLT has largely been unexplored, limiting development of targeted therapies. PURPOSE: To define the effect of ACLT on (1) the activation of protein synthetic and catabolic signaling within quadriceps biopsy specimens from human participants and (2) the time course of alterations to protein synthesis and its molecular regulation in a mouse ACL injury model. STUDY DESIGN: Descriptive laboratory study. METHODS: Muscle biopsy specimens were obtained from the ACL-injured and noninjured vastus lateralis of young adult humans after an overnight fast (N = 21; mean ± SD, 19 ± 5 years). Mice had their limbs assigned to ACLT or control, and whole quadriceps were collected 6 hours or 1, 3, or 7 days after injury with puromycin injected before tissue collection for assessment of relative protein synthesis. Muscle fiber size and expression and phosphorylation of protein anabolic and catabolic signaling proteins were assessed at the protein and transcript levels (RNA sequencing). RESULTS: Human quadriceps showed reduced phosphorylation of ribosomal protein S6 (-41%) in the ACL-injured limb (P = .008), in addition to elevated phosphorylation of eukaryotic initiation factor 2α (+98%; P = .006), indicative of depressed protein anabolic signaling in the injured limb. No differences in E3 ubiquitin ligase expression were noted. Protein synthesis was lower at 1 day (P = .01 vs control limb) and 3 days (P = .002 vs control limb) after ACLT in mice. Pathway analyses revealed shared molecular alterations between human and mouse quadriceps after ACLT. CONCLUSION: (1) Global protein synthesis and anabolic signaling deficits occur in the quadriceps in response to ACL injury, without notable changes in measured markers of muscle protein catabolism. (2) Importantly, these deficits occur before the onset of significant atrophy, underscoring the need for early intervention. CLINICAL RELEVANCE: These findings suggest that blunted protein anabolism as opposed to increased catabolism likely mediates quadriceps atrophy after ACL injury. Thus, future interventions should aim to restore muscle protein anabolism rapidly after ACLT.

Evidence-based rationale for treatment of meniscal lesions in athletes.

Meniscal injuries in elite athletes are a common cause of missed game time and even have the potential to be career shortening. In this patient group, care must be paid not only to the pathology, but also to a player's contract status, time in the season, specific demands of his/her sport and position on the field, and future consequences. Successful treatment requires the clinician to understand the player's goals and needs, communicate effectively between all stakeholders, and a have knowledge of the challenges posed by the different types of meniscal tear seen in this population. Paramount is the distinction between injuries to the medial and lateral meniscus. Deficiency of the lateral meniscus, as a result of a tear or a meniscectomy, leads to frequent early problems and inexorably to chondral degeneration thereby affecting an athlete's ability to perform. Therefore, it is strongly recommended to repair the majority of lateral meniscal tears. Medial meniscal tears pose a more challenging treatment dilemma, as the success of partial meniscectomy in achieving reproducible, early return to play must be balanced against the long-term degenerative consequences. Many meniscal tears are correctly treated non-operatively.Level of evidence V.

The Louisiana Amphibian Monitoring Program from 1997 to 2017: Results, analyses, and lessons learned.

To determine trends in either frog distribution or abundance in the State of Louisiana, we reviewed and analyzed frog call data from the Louisiana Amphibian Monitoring Program (LAMP). The data were collected between 1997 and 2017 using North American Amphibian Monitoring Program protocols. Louisiana was divided into three survey regions for administration and analysis: the Florida Parishes, and 2 areas west of the Florida parishes called North and South. Fifty-four routes were surveyed with over 12,792 stops and 1,066 hours of observation. Observers heard 26 species of the 31 species reported to be in Louisiana. Three of the species not heard were natives with ranges that did not overlap with survey routes. The other two species were introduced species, the Rio Grande Chirping Frog (Eleutherodactylus cystignathoides) and the Cuban Treefrog (Osteopilus septentrionalis). Both seem to be limited to urban areas with little to no route coverage. The 15 most commonly occurring species were examined in detail using the percentage of stops at which they observed along a given survey and their call indices. Most species exhibited a multimodal, concave, or convex pattern of abundance over a 15-year period. Among LAMP survey regions, none of the species had synchronous population trends. Only one group of species, winter callers, regularly co-occur. Based on the species lists, the North region could be seen as a subset of the South. However, based on relative abundance, the North was more similar to Florida parishes for both the winter and summer survey runs. Our analyses demonstrate that long-term monitoring (10 years or more) may be necessary to determine population and occupancy trends, and that frog species may have different local demographic patterns across large geographic areas.

Anterior cruciate ligament reconstruction reinitiates an inflammatory and chondrodegenerative process in the knee joint.

Anterior cruciate ligament (ACL) injury leads to a sustained increase in synovial fluid concentrations of inflammatory cytokines and biomarkers of cartilage breakdown. While this has been documented post-injury, it remains unclear whether ACL reconstruction surgery contributes to the inflammatory process and/or cartilage breakdown. This study is a secondary analysis of 14 patients (nine males/five females, mean age = 9, mean BMI = 28) enrolled in an IRB-approved randomized clinical trial. Arthrocentesis was performed at initial presentation (mean = 6 days post-injury), immediately prior to surgery (mean = 23 days post-injury), 1-week post-surgery, and 1-month post-surgery. Enzyme-linked immunosorbant assay kits were used to determine concentrations of carboxy-terminal telopeptides of type II collagen (CTXII), interleukin-6 (IL-6), and IL-1ß in the synovial fluid. The log-transformed IL-1ß was not normally distributed; therefore, changes between time points were evaluated using a non-parametric Kruskal-Wallis one-way ANOVA. IL-1ß concentrations significantly increased from the day of surgery to the first postoperative time point (P ≤ .001) and significantly decreased at the 4-week postoperative visit (P = .03). IL-1ß concentrations at the 4-week postoperative visit remained significantly greater than both preoperative time points (P > .05). IL-6 concentrations at 1-week post-surgery were significantly higher than at initial presentation (P = .013), the day of surgery (P < .001), and 4 weeks after surgery (P = .002). CTX-II concentrations did not differ between the first three-time points (P > .99) but significantly increased at 4 weeks post-surgery (P < .01). ACL reconstruction appears to reinitiate an inflammatory response followed by an increase in markers for cartilage degradation. ACL reconstruction appears to initiate a second "inflammatory hit" resulting in increased chondral breakdown suggesting that post-operative chondroprotection may be needed.

Quadriceps Strength and Kinesiophobia Predict Long-Term Function After ACL Reconstruction: A Cross-Sectional Pilot Study.

BACKGROUND: Many patients live with long-term deficits in knee function after an anterior cruciate ligament reconstruction (ACLR). However, research is inconclusive as to which physical performance measure is most strongly related to long-term patient-reported outcomes after ACLR. HYPOTHESIS: Quadriceps strength would be most strongly associated with patient-reported long-term outcomes after ACLR. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 40 patients (29 female) consented and participated an average of 10.9 years post-ACLR (range, 5-20 years). Patients completed the Lower Extremity Functional Scale (LEFS), the International Knee Documentation Committee (IKDC) Scale, Knee injury and Osteoarthritis Outcome Score Quality of Life (KOOS QoL) and Sport (KOOS Sport) subscales, and the Tampa Scale of Kinesiophobia (TSK-17). Each patient subsequently performed maximal isometric quadriceps contraction, a 60-second single-leg step-down test, and the single-leg single hop and triple hop for distance tests. Multivariate linear and logistic regression models determined how performance testing was associated with each patient-reported outcome when controlling for time since surgery, age, and TSK-17. RESULTS: When controlling for time since surgery, age at the time of consent, and TSK-17 score, maximal isometric quadriceps strength normalized to body weight was the sole physical performance measure associated with IKDC (P < 0.001), KOOS Sport (P = 0.006), KOOS QoL (P = 0.001), and LEFS scores (P < 0.001). Single-leg step-down, single hop, and triple hop did not enter any of the linear regression models (P > 0.20). Additionally, TSK-17 was associated with all patient-reported outcomes (P ≤ 0.01) while time since surgery was not associated with any outcomes (P > 0.05). CONCLUSION: Isometric quadriceps strength and kinesiophobia are significantly associated with long-term patient-reported outcomes after ACLR. CLINICAL RELEVANCE: These results suggest that training to improve quadriceps strength and addressing kinesiophobia in the late stages of recovery from ACLR may improve long-term self-reported function.

DPP8/9 inhibitors activate the CARD8 inflammasome in resting lymphocytes.

Canonical inflammasomes are innate immune signaling platforms that are formed in response to intracellular pathogen-associated signals and trigger caspase-1-dependent pyroptosis. Inflammasome formation and signaling is thought to mainly occur in myeloid cells, and in particular monocytes and macrophages. Here we show that small molecule inhibitors of dipeptidyl peptidases 8 and 9 (DPP8/9), which activate the related CARD8 and NLRP1 inflammasomes, also activate pyroptosis in human and rodent resting lymphocytes. We found that both CD4+ and CD8+ T cells were particularly sensitive to these inhibitors, although the sensitivity of T cells, like macrophages, varied considerably between species. In human T cells, we show that CARD8 mediates DPP8/9 inhibitor-induced pyroptosis. Intriguingly, although activated human T cells express the key proteins known to be required for CARD8-mediated pyroptosis, these cells were completely resistant to DPP8/9 inhibitors. Overall, these data show that resting lymphoid cells can activate at least one inflammasome, revealing additional cell types and states poised to undergo rapid pyroptotic cell death in response to danger-associated signals.

Treatment After Anterior Cruciate Ligament Injury: Panther Symposium ACL Treatment Consensus Group.

Treatment strategies for anterior cruciate ligament (ACL) injuries continue to evolve. Evidence supporting best-practice guidelines for the management of ACL injury is to a large extent based on studies with low-level evidence. An international consensus group of experts was convened to collaboratively advance toward consensus opinions regarding the best available evidence on operative versus nonoperative treatment for ACL injury. The purpose of this study was to report the consensus statements on operative versus nonoperative treatment of ACL injuries developed at the ACL Consensus Meeting Panther Symposium 2019. There were 66 international experts on the management of ACL injuries, representing 18 countries, who were convened and participated in a process based on the Delphi method of achieving consensus. Proposed consensus statements were drafted by the scientific organizing committee and session chairs for the 3 working groups. Panel participants reviewed preliminary statements before the meeting and provided initial agreement and comments on the statement via online survey. During the meeting, discussion and debate occurred for each statement, after which a final vote was then held. Ultimately, 80% agreement was defined a priori as consensus. A total of 11 of 13 statements on operative versus nonoperative treatment of ACL injury reached consensus during the symposium. Overall, 9 statements achieved unanimous support, 2 reached strong consensus, 1 did not achieve consensus, and 1 was removed because of redundancy in the information provided. In highly active patients engaged in jumping, cutting, and pivoting sports, early anatomic ACL reconstruction is recommended because of the high risk of secondary meniscal and cartilage injuries with delayed surgery, although a period of progressive rehabilitation to resolve impairments and improve neuromuscular function is recommended. For patients who seek to return to straight-plane activities, nonoperative treatment with structured, progressive rehabilitation is an acceptable treatment option. However, with persistent functional instability, or when episodes of giving way occur, anatomic ACL reconstruction is indicated. The consensus statements derived from international leaders in the field will assist clinicians in deciding between operative and nonoperative treatment with patients after an ACL injury.

Evolution of Atomic-Level Structure in Sub-10 Nanometer Iron Oxide Nanocrystals: Influence on Cation Occupancy and Growth Rates.

Spinel iron oxide nanocrystals (NCs) have been reported to have atomic-level core and surface structural features that differ from those of the bulk material. Recent advances in a continuous growth synthesis of metal oxide NCs make it possible to prepare a series of NCs with subnanometer control of size with diameters below 10 nm that are well-suited for investigating size-dependent structure and reactivity. Here, we study the evolution of size-dependent structure in spinel iron oxide and determine how nanoscale structure influences the growth of NCs. We synthesized spinel iron oxide NCs via a continuous growth method that permits layer-by-layer control of size in order to monitor nanoscale structure over 16 core sizes between 3 and 10 nm. X-ray total scattering data were collected and analyzed with pair distribution function (PDF) analysis in order to refine quantitative structural features including cation occupancies that could be used to detect changes both in the oxidation state and the presence of tetrahedrally coordinated cation vacancies in the NCs. We find that the average iron oxidation state increases as core diameters decrease from 8 down to 3 nm. The trend in iron oxidation state can be explained by the oxidation of surface layers in the NCs. For samples exposed to air for several weeks, oxidation appears to cease when a volume equivalent to that of an ∼1.3 nm shell is converted to the more oxidized maghemite. The number of tetrahedrally coordinated cation vacancies also increases as the NC core size decreases. The correlation between the number of these vacancies and the faster growth for smaller NCs suggests that these reactive vacancies may be responsible for the rapid growth observed for nanocrystals with diameters smaller than 8 nm.