Transcriptional time course after rotator cuff repair in 6 month old female rabbits.

Introduction: Rotator cuff tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration, which is not improved upon with surgical repair, highlighting the need to better understand the underlying biology impairing more favorable outcomes. Methods: In this study, we collected supraspinatus muscle tissue from 6 month old female rabbits who had undergone unilateral tenotomy for 8 weeks at 1, 2, 4, or 8 weeks post-repair (n = 4/group). RNA sequencing and enrichment analyses were performed to identify a transcriptional timeline of rotator cuff muscle adaptations and related morphological sequelae. Results: There were differentially expressed (DE) genes at 1 (819 up/210 down), 2 (776/120), and 4 (63/27) weeks post-repair, with none at 8 week post-repair. Of the time points with DE genes, there were 1092 unique DE genes and 442 shared genes, highlighting that there are changing processes in the muscle at each time point. Broadly, 1-week post-repair differentially expressed genes were significantly enriched in pathways of metabolism and energetic activity, binding, and regulation. Many were also significantly enriched at 2 weeks, with the addition of NIF/NF-kappaB signaling, transcription in response to hypoxia, and mRNA stability alongside many additional pathways. There was also a shift in transcriptional activity at 4 weeks post-repair with significantly enriched pathways for lipids, hormones, apoptosis, and cytokine activity, despite an overall decrease in the number of differentially expressed genes. At 8 weeks post-repair there were no DE genes when compared to control. These transcriptional profiles were correlated with the histological findings of increased fat, degeneration, and fibrosis. Specifically, correlated gene sets were enriched for fatty acid metabolism, TGF-B-related, and other pathways. Discussion: This study identifies the timeline of transcriptional changes in muscle after RC repair, which by itself, does not induce a growth/regenerative response as desired. Instead, it is predominately related to metabolism/energetics changes at 1 week post-repair, unclear or asynchronous transcriptional diversity at 2 weeks post-repair, increased adipogenesis at 4 weeks post-repair, and a low transcriptional steady state or a dysregulated stress response at 8 weeks post-repair.

The "Second Hit" of Repair in a Rabbit Model of Chronic Rotator Cuff Tear.

The rabbit supraspinatus is a useful translational model for rotator cuff (RC) repair because it recapitulates muscle atrophy and fat accumulation observed in humans after a chronic tear (the "first hit"). However, a timeline of RC tissue response after repair, especially with regard to recent evidence of muscle degeneration and lack of regeneration, is currently unavailable. Thus, the purpose of this study was to characterize the progression of muscle and fat changes over time after the repair of a chronic RC tear in the rabbit model. Two rounds of experiments were conducted in 2017-2018 and 2019-2020 with N = 18 and 16 skeletally mature New Zealand White rabbits, respectively. Animals underwent left supraspinatus tenotomy with repair 8 weeks later. The unoperated right shoulder served as control. The rabbits were sacrificed at 1-, 2-, 4-, and 8-weeks post-repair for histological and biochemical analysis. Atrophy, measured by fiber cross-sectional area and muscle mass, was greatest around 2 weeks after repair. Active muscle degeneration peaked at the same time, involving 8% of slide areas. There was no significant regeneration at any timepoint. Fat accumulation and fibrosis were significantly increased across all time points compared to contralateral. Statement of Clinical Significance: These results demonstrate model reproducibility and a "second hit" phenomenon of repair-induced muscle atrophy and degeneration which partially recovers after a short time, while increased fat and fibrosis persist.

Corrigendum: Transcriptional Time Course After Rotator Cuff Tear.

[This corrects the article DOI: 10.3389/fphys.2021.707116.].

Supraspinatus muscle architecture and physiology in a rabbit model of tenotomy and repair.

Chronic rotator cuff tears can cause severe functional deficits. Addressing the chronic fatty and fibrotic muscle changes is of high clinical interest; however, the architectural and physiological consequences of chronic tear and repair are poorly characterized. We present a detailed architectural and physiological analysis of chronic tear and repair (both over 8 and 16 wk) compared with age-matched control rabbit supraspinatus (SSP) muscles. Using female New Zealand White Rabbits (n = 30, n = 6/group) under 2% isoflurane anesthesia, the SSP was surgically isolated and maximum isometric force was measured at four to six muscle lengths. Architectural analysis was performed, and maximum isometric stress was computed. Whole muscle length-tension curves were generated using architectural measurements to compare experimental physiology to theoretical predictions. Architectural measures are consistent with persistent radial and longitudinal atrophy over time in tenotomy that fails to recover after repair. Maximum isometric force was significantly decreased after 16 wk tenotomy and not significantly improved after repair. Peak isometric force reported here are greater than prior reports of rabbit SSP force after tenotomy. Peak stress was not significantly different between groups and consistent with prior literature of SSP stress. Muscle strain during contraction was significantly decreased after 8 wk of tenotomy and repair, indicating effects of tear and repair on muscle function. The experimental length-tension data were overlaid with predicted curves for each experimental group (generated from structural data), exposing the altered structure-function relationship for tenotomy and repair over time. Data presented here contribute to understanding the physiological implications of disease and repair in the rotator cuff.NEW & NOTEWORTHY We utilize an established method to measure the length-tension relationship for the rabbit supraspinatus in normal, torn, and repaired muscles. We then perform architectural analysis to evaluate structural changes after tear and repair. Although peak isometric force is lower in the tear and repair groups, there are no differences in peak stresses across groups. These findings indicate persistent structural changes (both radial and longitudinal atrophy) and physiological deficiencies (decreased peak force and uncoupling structure-function relationship) after tenotomy that do not significantly recover after repair.

Transcriptional Time Course After Rotator Cuff Tear.

Rotator cuff (RC) tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration in the chronic state, which is not improved with intervention or surgical repair. This highlights the need to better understand the underlying dysfunction in muscle after RC tendon tear. Contemporary studies aimed at understanding muscle pathobiology after RC tear have considered transcriptional data in mice, rats and sheep models at 2-3 time points (1 to 16 weeks post injury). However, none of these studies observed a transition or resurgence of gene expression after the initial acute time points. In this study, we collected rabbit supraspinatus muscle tissue with high temporal resolution (1, 2, 4, 8, and 16 weeks) post-tenotomy (n = 6/group), to determine if unique, time-dependent transcriptional changes occur. RNA sequencing and analyses were performed to identify a transcriptional timeline of RC muscle changes and related morphological sequelae. At 1-week post-tenotomy, the greatest number of differentially expressed genes was observed (1,069 up/873 down) which decreases through 2 (170/133), 4 (86/41), and 8 weeks (16/18), followed by a resurgence and transition of expression at 16 weeks (1,421/293), a behavior which previously has not been captured or reported. Broadly, 1-week post-tenotomy is an acute time point with expected immune system responses, catabolism, and changes in energy metabolism, which continues into 2 weeks with less intensity and greater contribution from mitochondrial effects. Expression shifts at 4 weeks post-tenotomy to fatty acid oxidation, lipolysis, and general upregulation of adipogenesis related genes. The effects of previous weeks' transcriptional dysfunction present themselves at 8 weeks post-tenotomy with enriched DNA damage binding, aggresome activity, extracellular matrix-receptor changes, and significant expression of genes known to induce apoptosis. At 16 weeks post-tenotomy, there is a range of enriched pathways including extracellular matrix constituent binding, mitophagy, neuronal activity, immune response, and more, highlighting the chaotic nature of this time point and possibility of a chronic classification. Transcriptional activity correlated significantly with histological changes and were enriched for biologically relevant pathways such as lipid metabolism. These data provide platform for understanding the biological mechanisms of chronic muscle degeneration after RC tears.

Short-term Revision Risk of Patellofemoral Arthroplasty Is High: An Analysis from Eight Large Arthroplasty Registries.

BACKGROUND: Patellofemoral arthroplasty (PFA) is one option for the treatment of isolated patellofemoral osteoarthritis, but there are limited data regarding the procedure and results. Because isolated patellofemoral arthritis is relatively uncommon, available case series generally are small, and even within national registries, sample sizes are limited. Combining data from multiple registries may aid in assessing worldwide PFA usage and survivorship. QUESTIONS/PURPOSES: We combined and compared data from multiple large arthroplasty registries worldwide to ask: (1) What proportion of patients undergoing primary knee arthroplasty have PFA? (2) What are the patient and prosthesis characteristics associated with PFA in common practice, as reflected in registries? (3) What is the survivorship free from revision of PFA and what are the reasons for and types of revisions? METHODS: Data were provided by eight registries that are members of the International Society of Arthroplasty Registries (ISAR) who agreed to share aggregate data: Australia, New Zealand, Canada, Sweden, Finland, Norway, the Netherlands, and the United States. De-identified data were obtained for PFA performed from either the beginning of year 2000, or the earliest recorded implantation date after that in each individual registry when PFA data collection commenced, up to December 31, 2016. This included patient demographics, implant use, all-cause revision rate (determined by cumulative percent revision [CPR]), and reasons for and type of revision. RESULTS: During the data collection period, 6784 PFAs were performed in the eight countries. PFAs comprised less than 1% of primary knee replacements in all registries. Patient demographics were comparable in all countries. Patients were generally more likely to be women than men, and the mean age ranged from 50 years to 60 years. All registries showed a high rate of revision for PFA. The 5-year CPR for any reason ranged from 8.0% (95% CI 4.5 to 11.5) in Norway to 18.1% (95% CI 15.5 to 20.7) in the Netherlands. The most common reason for revision across all countries was disease progression (42%, 434 of 1034). Most PFAs (83%, 810 of 980) were revised to a TKA. CONCLUSIONS: The revision risk of PFA in all registries surveyed was more than three times higher than the reported revision risk of TKA at the same times. The survivorship of PFA is similar to that of the no-longer-used procedure of metal-on-metal conventional hip replacement. Although there may be potential functional benefits from PFA, these findings of consistent and alarmingly high rates of revision should create concern, particularly as this procedure is often used in younger patients. LEVEL OF EVIDENCE: Level III, therapeutic study.

National Athletic Trainers' Association Position Statement: Management of Individuals With Patellofemoral Pain.

OBJECTIVE:: To present recommendations for athletic trainers and other health care providers regarding the identification of risk factors for and management of individuals with patellofemoral pain (PFP). BACKGROUND:: Patellofemoral pain is one of the most common knee diagnoses; however, this condition continues to be one of the most challenging to manage. Recent evidence has suggested that certain risk factors may contribute to the development of PFP. Early identification of risk factors may allow clinicians to develop and implement programs aimed at reducing the incidence of this condition. To date, clinicians have used various treatment strategies that have not necessarily benefitted all patients. Suboptimal outcomes may reflect the need to integrate clinical practice with scientific evidence to facilitate clinical decision making. RECOMMENDATIONS:: The recommendations are based on the best available evidence. They are intended to give athletic trainers and other health care professionals a framework for identifying risk factors for and managing patients with PFP.

Editorial Commentary: Got Evidence? What We Really Need Is an Algorithm for Treating Symptomatic Bipartite Patella.

Bipartite patella is an uncommon but potentially troublesome problem for young athletes. Numerous uncontrolled retrospective studies have reported good results after various treatments. What is needed are studies that will guide workup and support treatment decisions based on the condition of the cartilage surfaces of the fragment, presence of pseudoarthrosis, and size and location of the fragment. To support decisions, we need prospective comparative studies, either randomized or, at least, prospective cohort studies that identify patients at the time of presentation, document key decision points, and follow patients to successful resolution of symptoms.

Effect of body mass index on patient outcomes of surgical intervention for the lumbar spine.

BACKGROUND: Conflicting findings exist on the effect of obesity on outcomes of lumbar spine surgery; results depend on the diagnosis studied, procedure evaluated, definition of obesity, and specific outcomes measured. The purpose of this retrospective cohort study is to examine the effect of increasing body mass index (BMI) on surgical-related, health-related, and long-term outcomes of lumbar spine surgery in a single representative patient sample. METHODS: Using a surgical registry from an integrated health care system, 8,049 instrumented lumbar spine cases were identified between 1/1/2009 and 09/30/2013. The sample was stratified into five BMI categories. Outcomes of interest included: (I) surgical-related factors and complications; (II) health-related complications; and (III) long-term complications. Mixed linear models, conditional logistic regressions, and survival analysis using a Cox regression model were conducted controlling for surgeon effects. Age, gender, diabetes status, smoking status, admitting diagnosis, and surgical approach were included as covariates. RESULTS: Every 5 kg/m2 increase in BMI was associated with a significant increase in surgical time (7.8 minutes), estimated blood loss (EBL) (36.5 mL), risk of deep infection (OR =1.7 times), and deep vein thrombosis (DVT) (OR =1.5). BMI was not associated with increased incidence of other intraoperative or health-related complications. Rate of re-operation was 1.1 times higher with every 5 kg/m2 increase in BMI, but rate of re-operation due to adjacent segment disease (ASD) was not associated with BMI. CONCLUSIONS: Obesity had an adverse effect on certain surgical-related, health-related and long-term surgical outcomes. The magnitude of this effect increased with increasing levels of obesity, which increases the medical burden associated with obesity.

Statins and hip fracture risk in men: a population-based case-control study.

PURPOSE: To estimate the association between hydroxymethylglutaryl-CoA inhibitor (statin) use and hip fracture. METHODS: We conducted a population-based case-control study. Cases were 6774 male enrollees in a large managed care organization, aged 45 or more years, with an incident hip fracture from 1997 to 2006. Controls without fracture (n = 6774) were matched to cases on age, race, and medical center. Electronic information on pharmaceutical use was used to identify the dispensing of statins from 1991 forward. RESULTS: Overall, 1884 (27.8%) cases and 2150 controls (31.7%) used a statin before index date (matched odds ratio [mOR] = 0.81, 95% confidence interval [CI] = 0.74-0.87). Adjustment for comorbidity burden strengthened the magnitude of the overall association (mOR = 0.68, CI = 0.62-0.74). The adjusted association was similar across age groups but was strongest among men aged 80 years or more (mOR = 0.62, CI = 0.54-0.71) and was most pronounced in African Americans (mOR = 0.43, CI = 0.28-0.64). Greater duration of statin use did not alter the odds ratios. CONCLUSIONS: These data add to the growing evidence of a potential protective effect of statin use on bone health. However, these results need to be replicated in a prospective study that can account for confounding by indication which may explain these findings.

Patellofemoral joint: from instability to arthritis.

Disorders of the patellofemoral joint are commonly seen in musculoskeletal clinics. In recent years, the expansion of imaging techniques, improvements in correlative injury anatomy, and more focused physical examinations have resulted in new knowledge about patellofemoral disorders. To achieve optimal patient outcomes, it is helpful for orthopaedic surgeons who treat knee problems to review the management of patellar dislocations and isolated patellofemoral arthritis, including treatment algorithms.

Injury pathology at the time of anterior cruciate ligament reconstruction associations with self-assessment of knee function.

OBJECTIVE: To evaluate the association of preoperative Knee Injury and Osteoarthritis Outcome Score (KOOS) and structural injuries reported at the time of anterior cruciate ligament reconstruction (ACLR). DESIGN: Cross-sectional study. SETTING: Three medical centers in California. PARTICIPANTS: Primary ACLRs (N = 636) performed between January 2009 and June 2010. INDEPENDENT VARIABLES: The 5 KOOS subscales: pain, other symptoms, activities of daily living (ADL), function in sport and recreation (Sport/Rec), and quality of life (QoL). MAIN OUTCOME MEASURES: Associated injuries (cartilage, medial meniscus, lateral meniscus, other ligaments), identified at the time of ACLR. RESULTS: Sixty-eight percent of the cohort was male and the median age was 26 years. No gender differences in KOOS were observed. No KOOS differences were observed by race, except in Sport/Rec. Younger patients reported higher KOOS. Pain and ADL scores were not associated with any concurrent injury. A 10-point increase in KOOS symptoms subscale was associated with 22% higher likelihood of isolated ACL, 13% lower likelihood of medial meniscus injury, and 10% lower likelihood of lateral meniscus. A 10-point increase in the KOOS Sport/Rec subscale score was associated with 8% higher likelihood of isolated ACL and 9% lower likelihood of medial meniscus injury. A 10-point increase in the KOOS QoL subscale was associated with 15% lower likelihood of medial meniscus injury. CONCLUSIONS: Weak associations between the symptoms, Sports/Rec, and QoL subscales and structural injuries at ACLR were observed. The KOOS and its subscales are not useful as indicators of the pattern or severity of preoperative injury of patients presenting for ACLR.

The impact of pre-operative weight loss on incidence of surgical site infection and readmission rates after total joint arthroplasty.

This study characterized a cohort of obese total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients (1/1/2008-12/31/2010) and evaluated whether a clinically significant amount of pre-operative weight loss (5% decrease in body weight) is associated with a decreased risk of surgical site infections (SSI) and readmissions post-surgery. 10,718 TKAs and 4066 THAs were identified. During the one year pre-TKA 7.6% of patients gained weight, 12.4% lost weight, and 79.9% remained the same. In the one year pre-THA, 6.3% of patients gained weight, 18.0% lost weight, and 75.7% remained the same. In TKAs and THAs, after adjusting for covariates, the risk of SSI and readmission was not significantly different in the patients who gained or lost weight pre-operatively compared to those who remained the same.

Medial patellofemoral ligament (MPFL) reconstruction for the treatment of patellofemoral instability.

Patellofemoral instability can be a disabling problem. Numerous techniques are employed for its treatment. Medial patellofemoral ligament (MPFL) reconstruction in combination with other procedures has been explored by many orthopedic surgeons. The purpose of the study was to determine the effectiveness of isolated MPFL reconstruction in treating the symptoms associated with patellofemoral instability, preventing recurrence of patella dislocation, and returning patients to preinjury level of activity. This is a case series study. We conducted a clinical follow-up study on 56 knees (49 patients) after MPFL reconstruction for recurrent patellar instability with a mean follow-up of 4.3 years (range, 1.1-6.8). A single MPFL reconstruction technique was performed in all cases. Patient outcomes were evaluated using: International Knee Documentation Committee (IKDC) subjective knee form, Tegner activity score, functional hop test, and radiographs. Mean age at time of surgery was 24 years old (range, 13-49). Females comprised 75% of the sample. Mean interval from injury to surgery was 7.2 ± 8.6 years (range, 51 days-37 years). At follow-up, there were no recurrent dislocations reported, patella subluxation in 6 (11%) cases, and radiographic degenerative changes were none to mild in all patients. The series mean IKDC scores at follow-up was 76.3 ± 19.2 (range, 30-99), and Tegner activity scores were 5.6 ± 2.5. MPFL reconstruction is an option for treating the symptoms of patellar instability, preventing recurrent dislocation, and returning patients near to their preinjury level of activity. The level of evidence is IV.

Do patients lose weight after joint arthroplasty surgery? A systematic review.

BACKGROUND: The ability of patients with a total joint arthroplasty (TJA) to lose weight after surgery has been investigated in a few studies with inconsistent results. QUESTIONS/PURPOSES: We asked: (1) What is the quality of evidence of current published literature on postoperative weight trends for patients who have had a TJA? (2) Do patients lose any weight after TJA? (3) Do patients lose a clinically meaningful amount of weight after TJA? METHODS: We conducted a systematic review of PubMed and the Cochrane Library. Studies were summarized according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement. Studies were reviewed for quality of evidence and limitations according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Twelve studies were identified, one case-cohort study and 11 case series. Most studies were from single-surgeon or single-hospital series. Five studies included THAs and TKAs, four only THAs, and three only TKAs. We determined study type, level of evidence, inclusion criteria, procedures, proportion of patients who changed weight, body composition assessment, time of composition assessment, statistical analysis performed, and subgroup analysis conducted. RESULTS: Owing to the observational nature of the studies and the serious limitations identified, all were considered very low quality according to GRADE criteria. Studies reported 14% to 49% of patients had some weight loss at least 1 year postoperatively. CONCLUSIONS: We found no conclusive evidence that weight or body composition increases, decreases, or remains the same after TJA.

Patient and surgeon characteristics associated with primary anterior cruciate ligament reconstruction graft selection.

BACKGROUND: It has been suggested that a surgeon's experience and training are the most important factors associated with graft selection, but no studies have qualified this association. Graft usage prevalence has not been described for large anterior cruciate ligament reconstruction (ACLR) populations in the United States. PURPOSE: To describe the prevalence of graft usage in a large community-based practice and evaluate the association of patient, surgeon, and site characteristics with choice of primary ACLR graft. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Primary ACLRs performed between February 2005 and June 2010 were selected for the study. A community-based ligament registry was used to identify cases and variables used for analysis. Graft choice (any allograft, hamstring autograft, and bone-patellar tendon-bone [BPTB] autograft) was compared by patient characteristics and surgeon and site characteristics. Associations between independent variables and graft choice were evaluated using a polychotomous regression model. RESULTS: Of the 9849 patients included in the study, 64% were male, and overall median age was 28 years. Of these, 2796 (28.4%) received BPTB autografts, 3013 (30.6%) received hamstring autografts, and 4040 (41.0%) received allografts. The prevalence of graft source by patients' gender, race, age, body mass index (BMI), as well as surgeons' fellowship training status, average volume, and site volume were significantly different (all P < .001). Adjusted models showed that patients' gender (P < .001), race (P = .018), age (P < .001), BMI (P < .001), as well as surgeons' fellowship training status (P < .001), average volume (P < .001), and site volume (P < .001) are associated with graft selection. Older and female patients with lower BMI were more likely to receive allografts and hamstring autografts than BPTB autografts. Cases performed by non-fellowship-trained surgeons, lower volume sites, and/or lower volume surgeons were also more likely to be performed with allografts or hamstring autografts than BPTB autografts. CONCLUSION: Gender, age, race, as well as facility and surgeon characteristics such as volume and location are associated with ACL graft choices.

A treatment algorithm for primary patellar dislocations.

CONTEXT: Primary patellar dislocation continues to be a common problem facing clinicians today. These injuries are associated with significant morbidity and a substantial recurrence rate. Myriad operative and nonoperative options have been described to treat these injuries, although the evidence-based literature is sparse. EVIDENCE ACQUISITION: PubMed was searched from 1970-2010 to identify publications on patellar dislocations, including clinical presentation, natural history, radiographic workup, and treatment. RESULTS: The initial workup of a patella dislocation includes a history, physical examination, and radiographs. If there is evidence of a displaced osteochondral fragment or hemarthrosis, then magnetic resonance imaging should be obtained. The treatment of first-time patella dislocators has been controversial, and no study has demonstrated a clear benefit to early operative intervention. CONCLUSION: First-time patellar dislocations should be treated conservatively unless there is evidence of a displaced osteochondral fragment.

Rehabilitation of the knee after medial patellofemoral ligament reconstruction.

The principles of rehabilitation after medial patellofemoral ligament reconstruction are similar to those guiding rehabilitation after other ligamentous reconstructions of the knee, such as anterior cruciate ligament (ACL). The key features are to address pain control, range of motion (ROM), quadriceps strengthening, and proximal lower limb control. Return of full ROM, pain control, and protected weight bearing are stressed in the early phases of recovery. Progression of strength training and return to functional activities follow lines of evidence regarding graft necrosis, remodeling, and tunnel ingrowth, which are most commonly associated with ACL reconstruction.