The Fragility Index is Typically Misinterpreted and of Low Value: Clinical Trials are Designed to be Fragile.

The Fragility Index (FI) is defined as the number of patients whose outcome would need to change to reverse a statistically significant finding to a nonsignificant finding. The FI is nothing more than a repackaging of statistical significance based on the P value, perpetuating the (1) ignoring of results that are "not" statistically significant, (2) treating results that are statistically significant as certain, and (3) distracting from evaluation of clinical significance. A well-designed trial includes a sample size calculation to determine the minimum number of patients required to observe a difference between study groups (if a difference exists). By including this minimum number, clinical trials are designed to be fragile, yet subsequently criticized as such, leading readers to the incorrect conclusion that the studies are flawed. It's time to move past systematic reviews focused on the FI.

Patient Acceptable Symptomatic State and Substantial Clinical Benefit Matter Most to Patients and Must Be Reported Correctly.

Despite a push for a focus on clinical rather than "statistical" significance and an emphasis on reporting of outcome thresholds such as the patient acceptable symptomatic state (PASS) and substantial clinical benefit (SCB), the PASS and SCB are rarely reported and, when reported, are often reported incorrectly. Yet, patients require satisfaction (PASS) as a result of our treatments, and patients desire to improve substantially (SCB). Determining whether patients are satisfied and/or substantially improved is simple . . . just ask them. The questions are known as anchor questions. Obviously, different patients have different PASS and SCB thresholds, and reliance on previously published literature for values of these thresholds can result in error-thus, the anchor questions. And, each patient must be assessed individually. Outcome thresholds are not group-level metrics, and they must be reported as the percentage of individuals who achieve the clinically significant outcome. Certain patients, such as athletes, have high baseline function and may demand maximum outcome improvement. In contrast, the minimal clinically important difference is a less-than-ideal measure; patients do not desire "minimal" improvement. Journals must do a better job of publishing patient-reported outcome measures that matter most to patients: satisfaction and substantial benefit.

The Role of Risk Tolerance in a Patient's Decision to Undergo Total Knee and Hip Arthroplasty.

BACKGROUND: A patient's decision-making process to undergo surgery is crucial for surgeons to understand for patient counseling purposes. Total knee and hip arthroplasty, like any other major surgery, is associated with serious, sometimes life-threatening, complications. Using the results of discrete choice experiments (DCE), we aimed to understand the relationship between a patient's risk tolerance and choosing to undergo surgery in real life. METHODS: This is a retrospective study of prospectively collected DCE results for 142 potential knee or hip arthroplasty clinic patients from October 2021 to March 2022. The DCE presented the patient with two scenarios, each of which was made up of different combinations of attributes and levels. A hierarchal Bayesian model was utilized to obtain a risk score that reflected the risk attributes chosen by each patient. Logistic regressions were then utilized to evaluate the association between a patient's willingness to incur risk and their decision to undergo a total joint arthroplasty (TJA). RESULTS: Out of the 142 patients enrolled in the DCE, 89 (62.3%) underwent a TJA. Risk score (OR [odds ratio] = 2.6, 95% CI [confidence interval] 1.1 to 6.6, P = 0.0400), men (OR = 2.5, 95% CI 1.1 to 5.9, P = 0.0280), and patients who have hip osteoarthritis (OR = 2.4, 95% CI 1.1 to 5.5, P = 0.0360) increased the odds of undergoing arthroplasty, whereas physical function of at least 75% at the initial visit (OR = 0.3, 95% CI 0.1 to 0.7, P = 0.0040) decreased these odds. CONCLUSIONS: We found that a patient's willingness to incur risk, lower baseline physical function, and men were all independently associated with undergoing total knee arthroplasty. We believe that these findings prompt much-needed future studies that focus solely on the relationship between patients inherent risk behavior and surgical and patient-reported outcomes.

Two big bones, one big decision: When to fix bilateral femur fractures.

PURPOSE: For polytrauma patients with bilateral femoral shaft fractures (BFSF), there is currently no consensus on the optimal timing of surgery. This study assesses the impact of early (≤ 24 h) versus delayed (>24 h) definitive fixation on clinical outcomes, especially focusing on concomitant versus staged repair. We hypothesized that early definitive fixation leads to lower mortality and morbidity rates. METHODS: The 2017-2020 Trauma Quality Improvement Program was used to identify patients aged ≥16 years with BFSF who underwent definitive fixation. Early definitive fixation (EDF) was defined as fixation of both femoral shaft fractures within 24 h, delayed definitive fixation (DDF) as fixation of both fractures after 24 h, and early staged fixation (ESF) as fixation of one femur within 24 h and the other femur after 24 h. Propensity score matching and multilevel mixed effects regression models were used to compare groups. RESULTS: 1,118 patients were included, of which 62.8% underwent EDF. Following propensity score matching, 279 balanced pairs were formed. EDF was associated with decreased overall morbidity (12.9% vs 22.6%, p = 0.003), lower rate of deep venous thrombosis (2.2% vs 6.5%, p = 0.012), a shorter ICU LOS (5 vs 7 days, p < 0.001) and a shorter hospital LOS (10 vs 15 days, p < 0.001). When compared to DDF, early staged fixation (ESF) was associated with lower rates of ventilator acquired pneumonia (0.0% vs 4.9%, p = 0.007), but a longer ICU LOS (8 vs 6 days, p = 0.004). Using regression analysis, every 24-hour delay to definitive fixation increased the odds of developing complications by 1.05, postoperative LOS by 10 h and total hospital LOS by 27 h. CONCLUSION: Early definitive fixation (≤ 24 h) is preferred over delayed definitive fixation (>24 h) for patients with bilateral femur shaft fractures when accounting for age, sex, injury characteristics, additional fractures and interventions, and hospital level. Although mortality does not differ, overall morbidity and deep venous thrombosis rates, and length of hospital and intensive care unit stay are significantly lower. When early definitive fixation is not possible, early staged repair seems preferable over delayed definitive fixation.

Association Between Severity of Chondrolabral Junction Breakdown and Functional Outcomes After Hip Arthroscopy for Acetabular Labral Tears.

BACKGROUND: Despite focus on surgical preservation of the chondrolabral junction (CLJ), the transition zone between the acetabular cartilage and labrum, the association between severity of CLJ breakdown and functional outcomes after hip arthroscopy remains unexplored. PURPOSE: To assess the influence of CLJ breakdown on patient-reported outcome measures (PROMs) at a 24-month follow-up after hip arthroscopy for symptomatic labral tears. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective review of prospectively collected data was conducted to identify patients ≥18 years of age with a minimum 24-month follow-up who underwent hip arthroscopy by a single surgeon for the treatment of symptomatic labral tears secondary to femoroacetabular impingement. The Beck classification of transition zone cartilage was used to grade CLJ damage; patients with grades 0 to 2 were stratified into the mild CLJ damage cohort, and those with grades 3 and 4 were stratified into the severe CLJ damage cohort. PROMs were collected at baseline and at 3, 6, 12 months, and annually thereafter postoperatively. Linear mixed-effects models were used to compare PROMs. Rates of achieving clinically meaningful thresholds and subsequent surgery rates were also compared. RESULTS: In total, 198 patients met the inclusion criteria, with a mean follow-up of 3.54 ± 1.26 years. A total of 95 patients with severe CLJ damage (mean age, 34.9 ± 10.5 years) were compared with 103 patients with mild CLJ damage (mean age, 38.2 ± 11.9 years). Hip Outcome Score-Activities of Daily Living (HOS-ADL), Non-Arthritic Hip Score (NAHS), and visual analog score for pain were inferior in the severe CLJ group at enrollment and all follow-up time points (P≤ .05). However, patients with severe CLJ breakdown exhibited greater improvements in HOS-ADL and NAHS at the 24-month follow-up and achieved clinically meaningful thresholds at equivalent rates to patients with mild CLJ breakdown. Subsequent surgery rates were 6.8% and 12.6% in patients with mild versus severe CLJ damage, respectively (P = .250). CONCLUSION: Severe CLJ breakdown is associated with increased pain and decreased functional level preoperatively and up to 24 months after hip arthroscopy. Despite this, patients with severe CLJ breakdown experienced greater improvements in functional outcomes at a 24-month follow-up and achieved clinical thresholds at similar rates to patients with mild CLJ damage. Thus, while worse baseline pain and functional levels may indicate severe CLJ breakdown, these patients still benefit substantially from hip arthroscopy.

Disaggregation of Medical Research Data Reveals Outcome Differences in Demographic Groups and Presents Opportunity to Improve Patient Care.

Disaggregation, in the medical literature, means separation into demographic groups. This results in an opportunity to discover differences in outcomes by group, which could improve future treatments and provide outcome data, by group, that could be included in future systematic reviews. In research, the term disaggregation is most often used in reference to addressing inequities. We support the Sex and Gender Equity Research (SAGER) guidelines and encourage authors to examine how sex and gender are taken into account in their study and ensure adequate representation by sex and gender. (We respect that not all studies can or are designed to capture data by sex and gender, and that gender is "complex" and "fluid.") Disaggregation is encouraged, when possible, for other demographic variables allowing evaluation of all marginalized (as well as nonmarginalized) populations, so that we can better care for patients.

Variations in the Anatomic Morphology of the Scapular Spine and Implications on Fracture After Reverse Shoulder Arthroplasty.

INTRODUCTION: This study evaluates the role of anatomic scapular morphology in acromion and scapular spine fracture (SSAF) risk after reverse shoulder arthroplasty (RSA). METHODS: Twelve scapular measurements were captured based on pilot study data, including scapular width measurements at the acromion (Z1), middle of the scapular spine (Z2), and medial to the first major angulation (Z3). Measurements were applied to 3D-CT scans from patients who sustained SSAF after RSA (SSAF group) and compared with those who did not (control group). Measurements were done by four investigators, and the intraclass correlation coefficient was calculated. Regression analysis determined trends in fracture incidence. RESULTS: One hundred forty-nine patients from two separate surgeons (J.L., A.M.) were matched by age and surgical indication of whom 51 sustained SSAF after reverse shoulder arthroplasty. Average ages for the SSAF and control cohorts were 78.6 and 72.1 years, respectively. Among the SSAF group, 15 were Levy type I, 26 Levy type II, and 10 Levy type 3 fractures. The intraclass correlation coefficient of Z1, Z2, and Z3 measurements was excellent (0.92, 0.92, and 0.94, respectively). Zone 1 and 3 measurements for the control group were 18.6 ± 3.7 mm and 3.2 ± 1.0 mm, respectively, compared with 22.5 ± 5.9 mm and 2.0 ± 0.70 mm in the SSAF group, respectively. The fracture group trended toward larger Z1 and smaller Z3 measurements. The average scapular spine proportion (SSP), Z1/Z3, was significantly greater in the control 6.20 ± 1.80 versus (12.60 ± 6.30; P < 0.05). Regression analysis showed a scapular spine proportion of ≤5 was associated with a fracture risk <5%, whereas an SSP of 9.2 correlated with a 50% fracture risk. DISCUSSION: Patients with a thicker acromions (Z1) and thinner medial scapular spines (Z3) have increased fracture risk. Understanding anatomic scapular morphology may allow for better identification of high-risk patients preoperatively.

Biologic Adjuvants to Rotator Cuff Repairs Induce Anti-inflammatory Macrophage 2 Polarization and Reduce Inflammatory Macrophage 1 Polarization In Vitro.

PURPOSE: To examine the effect of various biologic adjuvants on the polarization of macrophages in an in vitro model for rotator cuff tears. METHODS: Tissue was harvested from 6 patients undergoing arthroscopic rotator cuff repair. An in vitro model of the supraspinatus and subacromial bursa was created and treated with control, platelet-rich plasma (PRP), autologous activated serum (AAS), or a combination of PRP+AAS. The effect of treatment on macrophage polarization between M1 proinflammatory macrophages or M2 anti-inflammatory macrophages was measured using gene expression, protein expression, flow cytometry, and nitric oxide production. RESULTS: Tendon and bursa treated with PRP, AAS, and PRP+AAS significantly decreased the gene expression of M1 markers interleukin (IL)-12 and tumor necrosis factor-alpha while significantly increasing the expression of M2 markers arginase, IL-10, and transforming growth factor-ß (P < .05) compared with treatment with control. Enzyme-linked immunosorbent assay analysis of protein production demonstrated that, compared with control, coculture treated with PRP, AAS, and PRP+AAS significantly decreased markers of M1-macrophages (IL-6, IL-12, and tumor necrosis factor-alpha) while significantly increasing the expression of markers of M2-macrophages (arginase, IL-10, and transforming growth factor-beta) (P < .05). Flow cytometry analysis of surface markers demonstrated that compared with control, tendon and bursa treated with PRP, AAS, and PRP+AAS significantly decreased markers of M1-macrophages (CD80, CD86, CD64, CD16) while significantly increasing the expression of markers of M2-macrophages (CD163 and CD206) (P < .05). Treatment of the coculture with PRP, AAS, and PRP+AAS consistently demonstrated a decrease in nitric oxide production (P < .05) compared with control. AAS and PRP+AAS demonstrated an increased macrophage shift to M2 compared with PRP alone, whereas there was not as uniform of a shift when comparing PRP+AAS with AAS alone. CONCLUSIONS: In an in vitro model of rotator cuff tears, the treatment of supraspinatus tendon and subacromial bursa with PRP, AAS, and PRP+AAS demonstrated an increase in markers of anti-inflammatory M2-macrophages and a concomitant decrease in markers of proinflammatory M1-macrophages. AAS and PRP+AAS contributed to a large shift to macrophage polarization to the anti-inflammatory M2 compared with PRP. CLINICAL RELEVANCE: The mechanism of biologic adjuvant effects on the rotator cuff remains poorly understood. This study suggests that they may contribute to polarization of macrophages for their proinflammatory (M1) state to the anti-inflammatory (M2) state.

Clinical and radiologic outcomes of posterior column extension, pedicle subtraction, and vertebral column resection osteotomies in adult chin on chest deformity: A systematic review.

Background: Chin-on-chest deformity is a rare and severely disabling condition characterized by kyphotic deformity in the cervicothoracic spine. To treat this deformity, various osteotomy techniques were described. Methods: A comprehensive literature search of biomedical databases including MEDLINE (via PubMed), Scopus (via Elsevier), Embase (via Elsevier), and Cochrane Library in English from 1/1/1990 to 3/31/2022 was conducted using a combination of text and Medical Subject Headings (MeSH). Results: The final analysis included 16 studies. All the studies were assigned a level of evidence of four. Except for two articles, all of the articles were non-comparative studies. A total of 288 patients were included in this review. Of the 288 patients, 107 underwent posterior column extension osteotomy (PCEO), 108 underwent pedicle subtraction osteotomy (PSO), and 33 underwent vertebral column resection osteotomy (VCRO). The most common osteotomy level in fifteen of the studies was C7/T1. The studies included in this review described several techniques for cervical sagittal balance correction. The range of preoperative and postoperative visual analogue scale (VAS) scores was 5.5-8.6 to 1.7-4.91, respectively. The range of preoperative and postoperative neck disability index (NDI) was 34.2-65.4 to 22.1-51.3, respectively. The most common complications were upper extremity paresthesia and hand numbness through the C8 dermatome distribution. Conclusions: Corrective osteotomies provide satisfactory results in patients with chin-on-chest deformity; however, the quality of the included studies limits the evidence.

Current Concepts in Management of Acromioclavicular Joint Injury.

Background: The management of acromioclavicular joint injuries requires a thorough understanding of the anatomy and biomechanics of the joint, as well as knowledge of the pertinent physical exam findings and classification to determine an appropriate treatment approach, whether operative or nonoperative. In this article, we present a narrative review of the current state of understanding surrounding these issues. Although there are a large number of options for operative intervention, we additionally present our experience with anatomic coracoclavicular ligament reconstruction (ACCR) with imbrication of the deltoid fascia. Methods: A retrospective review of prospectively collected data on a total of 45 patients who had undergone ACCR between 2003 and 2016 were collected. Results: We found that improvements were seen in American Shoulder and Elbow Surgeons Score (ASES) (53 ± 19 to 81 ± 23), Simple Shoulder Test (SST) (6 ± 3 to 12 ± 13), Constant-Murley (CM) (60 ± 18 to 92 ± 8), and Rowe (67 ± 14 to 89 ± 11) and the mean post-operative SANE score was 86 ± 17. Conclusions: ACCR has the advantage of addressing both horizontal and vertical stability with good outcomes.

Editorial Commentary: The Difficulties of Assessing Return to Play and Return to Performance After Ulnar Collateral Ligament Reconstruction.

Ulnar collateral ligament (UCL) tears have moved from a career-ending injury to one in which success is almost expected from reconstruction. In reality, however, success from a UCL reconstruction is not guaranteed. As we have attempted to assess the true success rate of UCL reconstructions, we have also learned the difficulties of this assessment. Rates of return to sport after UCL reconstruction vary by level of play, the primary or revision status of the repair, along with the specific surgical techniques performed, the chronicity of the tear, the rehabilitation protocols associated with the surgery, and more. Return to sport is difficult to assess, as high school, collegiate, and even professional careers can be variable and there are no standard definitions of "returning to play." These variables also affect our assessments of performance after UCL reconstruction. Decisions for UCL reconstructions and appropriate counseling of patients regarding the likelihood of success currently remain an individual process.

Novel 3D MRI-based volumetric assessment of rotator cuff musculature demonstrates stronger correlation with preoperative functional status when compared to the Goutallier grading scheme.

BACKGROUND: The Goutallier classification (GC) is used to assess fatty atrophy in rotator cuff (RC) tears, yet limitations exist. A battery of 3-dimensional (3D) magnetic resonance imaging (MRI) volumetric scores (VSs) was developed to provide comprehensive characterization of RC pathology. The purposes of this study were to (1) describe the correlation between GC and VSs for supraspinatus changes in RC tears, (2) characterize the chronicity of RC tears using a battery of 12 VS measurements, and (3) compare GC and VSs to determine which method most closely corresponds with preoperative patient-reported outcome measures (PROMs). METHODS: Preoperative shoulder MRIs were reviewed after arthroscopic RC repair. Preoperative GC stage and Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF) and pain interference (PI) scores were collected. The battery of VSs included fat infiltration (FIS), muscle size (MSS), and relative volume contribution (RCS) for each RC muscle. Backward linear regression was performed to compare GC stage with preoperative PROMIS PF and PI to determine which VS measurement most closely correlated with preoperative PROMs. RESULTS: Eighty-two patients underwent RC repair (mean age 55 ± 8.2 years, 63% male, 68% GC stage ≤1). In evaluation of the supraspinatus, there was a moderate positive correlation between GC and FIS (r = 0.459, P < .001); strong negative correlations were observed between MSS (r = -0.800, P < .001) and RCS (r = -0.745, P < .001) when compared to GC. A negligible linear correlation was observed between GC and preoperative PROMIS PF (r = -0.106, P = .343) and PI (r = -0.071, P = .528). On multivariate analysis, subscapularis MSS (ß >0, P = .064) was a positive predictor and subscapularis FIS (ß <0, P = .137), teres minor MSS (ß <0, P = .141), and FIS (ß <0, P = .070) were negative predictors of preoperative PF (r = 0.343, P = .044); in contrast, supraspinatus MSS (ß >0, P = .009) and FIS (ß >0, P = .073), teres minor FIS (ß >0, P = .072), and subscapularis FIS (ß >0, P = .065) were positive predictors of preoperative PI (r = 0.410, P = .006). CONCLUSION: Although the criterion standard in evaluation of RC pathology, GC demonstrated negligible correlation with preoperative functional disability. Alternatively, a battery of 3D VSs showed strong correlation with GC through a quantitative, comprehensive evaluation of the RC unit including several moderate predictors of preoperative functional disability.

Recommended Requirements and Essential Elements for Proper Reporting of the Use of Artificial Intelligence Machine Learning Tools in Biomedical Research and Scientific Publications.

Essential elements required for proper use of artificial intelligence machine learning tools in biomedical research and scientific publications include (1) explanation justifying why a machine learning approach contributes to the purpose of the study; (2) description of the adequacy of the data (input) to produce the desired results (output); (3) details of the algorithmic (i.e., computational) approach including methods for organizing the data (preprocessing); the machine learning computational algorithm(s) assessed; on what data the models were trained; the presence of bias and efforts to mitigate these effects; and the methods for quantifying the variables (features) most influential in determining the results (e.g., Shapley values); (4) description of methods, and reporting of results, quantitating performance in terms of both model accuracy and model calibration (level of confidence in the model's predictions); (5) availability of the programming code (including a link to the code when available-ideally, the code should be available); (6) discussion of model internal validation (results applicable and sensitive to the population investigated and data on which the model was trained) and external validation (were the results investigated as to whether they are generalizable to different populations? If not, consideration of this limitation and discussion of plans for external validation, i.e., next steps). As biomedical research submissions using artificial intelligence technology increase, these requirements could facilitate purposeful use and comprehensive methodological reporting.

Editorial Commentary: Regression Modeling and Nomograms in Biomedical Research Are Valuable Decision-Making Tools When Externally Validated and Well Maintained.

The mathematical formulas underpinning biostatistical modeling in medical research can be complicated. Nomograms are pictoral tools showing a graphical solution of a formula in which all variables in the formula can be read off the diagram. Nomograms can be used to simplify the calculation of risk of recurrence of injuries or disease. Although nomograms can be valuable, external validation is required (of all models) to ensure accuracy outside of the original population, because variation in patient populations, activities, and risk behaviors outside of the patient data used in the original analysis may deteriorate model performance (external validity). A model also needs to be maintained over time to ensure continued accuracy as populations and activities change. A model that fails to keep up will eventually have its accuracy and clinical utility fade. An externally validated, well-maintained model can be a valuable tool for patient counseling and decision-making.

Editorial Commentary: Ceiling Effects Are a Limitation of Frequently Used Patient-Reported Outcomes Measures Used to Assess Shoulder Function: Appropriate Selection of Shoulder Patient-Reported Outcomes Measures Is Required-Especially in Athletes.

Ceiling effects (CEs) are a major limitation of frequently used patient-reported outcomes measures (PROMs) in the assessment of shoulder function. It is generally considered that a CE may be present when the best possible score for a given PROM is achieved by at least 15% of the study population. When a CE occurs, it typically indicates that the scoring criteria are relatively easy and therefore may not reliably capture greater levels of patient function. This is a particular problem with the use of activities of daily living-oriented PROMs in the evaluation of athletic patients because they can still score highly, despite limitations in athletic shoulder function. When a CE is present, it can result in failure to determine the true efficacy of a procedure, limited responsiveness to change, and furthermore if a subsequent comparison of 2 groups of patients is undertaken, it may produce similar results despite meaningful differences between them. It is important to recognize that CEs are common and have important consequences but that careful selection of PROMs adapted to the characteristics of the study population and the specific research question can help to mitigate these issues.

Editorial Commentary: Utility of Patient-Reported Outcome Threshold Scores to Estimate Patient Satisfaction: 'Let's Ask the Patient!'

The reporting and analysis of patient-reported outcome measures have come a long way. Since the concept of the minimally clinically important difference was first introduced in 1989, threshold scores have grown to include substantial clinical benefit and patient acceptable symptomatic state (PASS). The initial motivation for developing these thresholds was rooted in separating clinical significance from statistical. These thresholds provide insight into the relationship between scores on patient-reported outcome measures (PROM) and patient-reported improvement and satisfaction. It follows that in order to evaluate PROM scores, the best method for deriving the threshold typically uses an anchor-based methodology, i.e., "ask the patient." Specifically, patients are asked how much change they've experienced and whether they consider their current state to be satisfactory. The responses to these questions are compared with the scores on PROMs to find outcome thresholds that best separate patients who reported no improvement from those who reported minimal improvement, substantial improvement, and satisfaction with their current state of health (PASS). The PASS is of particular importance as it speaks to what arguably matters most to patients-a satisfactory state of health. Finally, viewing the PASS from the perspective of variation from study to study rather than as a uniform classifier is needed to make use of the growing number of papers reporting these thresholds. Examining differences in PASS values across papers can provide insight into how well PROM scores reflect patient satisfaction in different settings.

Editorial Commentary: The Statistical Fragility Index of Medical Trials Is Low By Design: Critical Evaluation of Confidence Intervals Is Required.

The Fragility Index (FI) provides the number of patients whose outcome would need to have changed for the results of a clinical trial to no longer be statistically significant. Although it's a well-intended and easily interpreted metric, its calculation is based on reversing a significant finding and therefore its interpretation is only relevant in the domain of statistical significance. Its interpretation is only relevant in the domain of statistical significance. A well-designed clinical trial includes an a priori sample size calculation that aims to find the bare minimum of patients needed to obtain statistical significance. Such trials are fragile by design! Examining the robustness of clinical trials requires an estimation of uncertainty, rather than a misconstrued, dichotomous focus on statistical significance. Confidence intervals (CIs) provide a range of values that are compatible with a study's data and help determine the precision of results and the compatibility of the data with different hypotheses. The width of the CI speaks to the precision of the results, and the extent to which the values contained within have potential to be clinically important. Finally, one should not assume that a large FI indicates robust findings. Poorly executed trials are prone to bias, leading to large effects, and therefore, small P values, and a large FI. Let's move our future focus from the FI toward the CI.

Editorial Commentary: The Minimal Clinically Important Difference Is Less Important Than It Sounds: Patients Seek to Achieve Substantial Clinical Benefits and Not Minimally Perceptible Improvements When They Undergo Arthroscopic Surgery.

The minimal clinically important difference (MCID) is a frequently reported metric for describing within-patient improvement in patient-reported outcome measures (PROMs). It was originally defined by Jaeschke et al. as "the smallest difference in score in the domain of interest which patients perceive as beneficial and which would mandate, in the absence of troublesome side effects and excessive cost, a change in the patient's management." The latter part of this statement is often omitted, and this results in a loss of the originally intended value through lack of sufficient clinical importance to change management. Other pitfalls in the use of the MCID include that they are population- and condition-specific. As such, MCIDs lack external validity and cannot easily be extrapolated from one study to another. Furthermore, broadly different values can be obtained depending on the calculation method used. This makes the MCID an unhelpful metric when seeking to understand the true efficacy of a given intervention. The Food and Drug Administration recommends anchor-based methodologies (which take into account patient perception), over distribution-based methods (which are purely statistical and do not account for clinical meaningfulness to patients). Regardless, it should be noted that even anchor-based methodologies are susceptible to statistical bias, and measures are apt to be influenced by the regression to mean phenomena, where the value of the preintervention scores and their relationship to postintervention scores can bias estimates of the MCID. Finally, when using MCIDs, one must consider that they are a low bar. This means that patients do not undergo treatment to achieve minimally perceptible clinical improvements; instead, they undergo treatment with the hope of achieving substantial clinical benefit or a patient acceptable symptom state, and so these are more appropriate individual-level metrics to consider when evaluating clinically meaningful outcomes of treatment.

Postoperative Radiographic Outcomes Following Primary Open Coracoid Transfer (Bristow-Latarjet) Vary in Definition, Classification, and Imaging Modality: A Systematic Review.

PURPOSE: To analyze radiographic outcomes by conventional radiography, computed tomography (CT), or both and complication rates of open coracoid transfer at a minimum of 12-months follow-up. METHODS: A literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using PubMed, Medline (Ovid), and EMBASE library databases. Inclusion criteria were clinical studies reporting on open Latarjet as the primary surgical procedure(revision coracoid transfer after failed prior stabilization excluded) with postoperative radiographic outcomes at a minimum mean 1-year follow-up. Patient demographics, type of postoperative imaging modality, and radiographic outcomes and complications including graft union, osteoarthritis, and osteolysis were systematically reviewed. Data were summarized as ranges of reported values for each outcome metric. Each radiographic outcome was graphically represented in a Forest plot with point estimates of the incidence of radiographic outcomes with corresponding 95% confidence intervals and I2. RESULTS: Thirty-three studies met inclusion criteria, with a total of 1,456 shoulders. The most common postoperative imaging modality was plain radiography only (n = 848 [58.2%]), both CT and radiography (n = 287 [19.7%]), and CT only (n = 321 [22.1%]). Overall, the reported graft union rate ranged from 75% to 100%, of which 79.8% (n = 395) were detected on plain radiography. The most common reported postoperative radiographic complications after the open coracoid transfer were osteoarthritis (range, 0%-100%, pooled mean 28%), graft osteolysis (range, 0%-100%, pooled mean 30%), nonunion (range, 0%-32%, pooled mean 5.1%), malpositioned graft (range, 0%-75%, pooled mean 14.75%), hardware issues (range, 0%-9.1%, pooled mean 5%), and bone block fracture (range, 0%-8%, pooled mean 2.1%). Graft healing was achieved in a majority of cases (range, 75%-100%). CONCLUSION: Postoperative radiographic outcomes after open coracoid transfer vary greatly in definition, classification, and imaging modality of choice. Greater consistency in postoperative radiographic outcomes is essential to evaluate graft healing, osteolysis, and nonunion. LEVEL OF EVIDENCE: Level IV, systematic review of Level III-IV studies.

Human Rotator Cuff Tears Reveal an Age-Dependent Increase in Markers of Cellular Senescence and Selective Removal of Senescent Cells With Dasatinib + Quercetin Increases Genetic Expression of COL1A1 In Vitro.

PURPOSE: To quantify cellular senescence in supraspinatus tendon and subacromial bursa of humans with rotator cuff tears and to investigate the in vitro efficacy of the senolytic dasatinib + quercetin (D+Q) to eliminate senescent cells and alter tenogenic differentiation. METHODS: Tissue was harvested from 41 patients (mean age, 62 years) undergoing arthroscopic rotator cuff repairs. In part 1 (n = 35), senescence was quantified using immunohistochemistry and gene expression for senescent cell markers (p16 and p21) and the senescence-associated secretory phenotype (SASP) (interleukin [IL] 6, IL-8, matrix metalloproteinase [MMP] 3, monocyte chemoattractant protein [MCP] 1). Senescence was compared between patients <60 and ≥60 years old. In part 2 (n = 6) , an in vitro model of rotator cuff tears was treated with D+Q or control. D+Q, a chemotherapeutic and plant flavanol, respectively, kill senescent cells. Gene expression analysis assessed the ability of D+Q to kill senescent cells and alter markers of tenogenic differentiation. RESULTS: Part 1 revealed an age-dependent significant increase in the relative expression of p21, IL-6, and IL-8 in tendon and p21, p16, IL-6, IL-8, and MMP-3 in bursa (P < .05). A significant increase was seen in immunohistochemical staining of bursa p21 (P = .028). In part 2, D+Q significantly decreased expression of p21, IL-6, and IL-8 in tendon and p21 and IL-8 in bursa (P < .05). Enzyme-linked immunosorbent assay analysis showed decreased release of the SASP (IL-6, MMP-3, MCP-1; P = .002, P = .024, P < .001, respectively). Tendon (P = .022) and bursa (P = .027) treated with D+Q increased the expression of COL1A1. CONCLUSIONS: While there was an age-dependent increase in markers of cellular senescence, this relationship was not consistently seen across all markers and tissues. Dasatinib + quercetin had moderate efficacy in decreasing senescence in these tissues and increasing COL1A1 expression. CLINICAL RELEVANCE: This study reveals that cellular senescence may be a therapeutic target to alter the biological aging of rotator cuffs and identifies D+Q as a potential therapy.