Sex Differences in Quadriceps Atrophy After Anterior Cruciate Ligament Tear.

BACKGROUND: Female athletes lag behind their male counterparts in recovery from anterior cruciate ligament (ACL) injury. Quadriceps muscle size and strength are crucial factors for regaining function after ACL injury, but little is known about how these metrics vary due to biological sex. HYPOTHESIS: Female patients have reduced vastus lateralis fiber cross-sectional area (CSA) and lower quadriceps strength after ACL injury than male patients. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 60 participants with recent ACL tear were evaluated for vastus lateralis muscle fiber CSA, isometric quadriceps peak torque, and quadriceps rate of torque development. Linear mixed models were fit to determine differences across sex and limb for each variable of interest. RESULTS: The female group averaged almost 20% atrophy between limbs (P < 0.01), while the male group averaged just under 4% (P = 0.05). Strength deficits between limbs were comparable between female and male groups. CONCLUSION: Immediately after ACL injury, female patients have greater between-limb differences in muscle fiber CSA but between-limb strength deficits comparable with those of male patients. CLINICAL RELEVANCE: These results indicate that the underpinnings of strength loss differ based on biological sex, and thus individual patients could benefit from a sex-specific treatment approach to ACL injury.

Muscle Fiber Cross-Sectional Area Is Associated With Quadriceps Strength and Rate of Torque Development After ACL Injury.

ABSTRACT: Graham, MC, Thompson, KL, Hawk, GS, Fry, CS, and Noehren, B. Muscle fiber cross-sectional area is associated with quadriceps strength and rate of torque development after ACL injury. J Strength Cond Res 38(6): e273-e279, 2024-The purpose of this study was to investigate the relationship between muscle fiber type-specific properties of the vastus lateralis and quadriceps muscle performance in individuals after an anterior cruciate ligament (ACL) tear. 26 subjects (22.0 ± 5.4 years) were included in this cross-sectional study, and all data were collected before ACL reconstruction. Quadriceps peak torque (QPT) and early (0-100 ms) and late (100-200 ms) rate of torque development (RTD) were obtained from maximal voluntary isometric quadriceps strength testing. Muscle fiber cross-sectional area (fCSA) and percent fiber type distribution (FT%) were evaluated through immunohistochemical analysis of a muscle biopsy. Between-limb differences in fiber characteristics were assessed using paired t-tests (with α-level 0.05). Relationships between fiber-specific properties and quadriceps muscle performance were determined using separate multiple linear regression analyses for ACL-injured and noninjured limbs. There were significant differences in fCSA between ACL-injured and noninjured limbs across all fiber types, but no differences in FT%. Type 1 fCSA, type 2a fCSA, and their interaction effect were the explanatory variables with the strongest relationship to all performance outcomes for the ACL-injured limb. The explanatory variables in the ACL-injured limb had a significant relationship to QPT and late RTD, but not early RTD. These findings suggest that QPT and late RTD are more heavily influenced by fCSA than FT% in ACL-injured limbs. This work serves as a foundation for the development of more specific rehabilitation strategies aimed at improving quadriceps muscle function before ACL reconstruction or for individuals electing nonsurgical management.

Temperature-Dependent Selection of Reaction Pathways, Reactive Species, and Products during Postsynthetic Selenization of Copper Sulfide Nanoparticles.

Rational design of elaborate, multicomponent nanomaterials is important for the development of many technologies such as optoelectronic devices, photocatalysts, and ion batteries. Combination of metal chalcogenides with different anions, such as in CdS/CdSe structures, is particularly effective for creating heterojunctions with valence band offsets. Seeded growth, often coupled with cation exchange, is commonly used to create various core/shell, dot-in-rod, or multipod geometries. To augment this library of multichalcogenide structures with new geometries, we have developed a method for postsynthetic transformation of copper sulfide nanorods into several different classes of nanoheterostructures containing both copper sulfide and copper selenide. Two distinct temperature-dependent pathways allow us to select from several outcomes-rectangular, faceted Cu2-xS/Cu2-xSe core/shell structures, nanorhombuses with a Cu2-xS core, and triangular deposits of Cu2-xSe or Cu2-x(S,Se) solid solutions. These different outcomes arise due to the evolution of the molecular components in solution. At lower temperatures, slow Cu2-xS dissolution leads to concerted morphology change and Cu2-xSe deposition, while Se-anion exchange dominates at higher temperatures. We present detailed characterization of these Cu2-xS-Cu2-xSe nanoheterostructures by transmission electron microscopy (TEM), powder X-ray diffraction, energy-dispersive X-ray spectroscopy, and scanning TEM-energy-dispersive spectroscopy. Furthermore, we correlate the selenium species present in solution with the roles they play in the temperature dependence of nanoheterostructure formation by comparing the outcomes of the established reaction conditions to use of didecyl diselenide as a transformation precursor.

GDF8 inhibition enhances musculoskeletal recovery and mitigates posttraumatic osteoarthritis following joint injury.

Musculoskeletal disorders contribute substantially to worldwide disability. Anterior cruciate ligament (ACL) tears result in unresolved muscle weakness and posttraumatic osteoarthritis (PTOA). Growth differentiation factor 8 (GDF8) has been implicated in the pathogenesis of musculoskeletal degeneration following ACL injury. We investigated GDF8 levels in ACL-injured human skeletal muscle and serum and tested a humanized monoclonal GDF8 antibody against a placebo in a mouse model of PTOA (surgically induced ACL tear). In patients, muscle GDF8 was predictive of atrophy, weakness, and periarticular bone loss 6 months following surgical ACL reconstruction. In mice, GDF8 antibody administration substantially mitigated muscle atrophy, weakness, and fibrosis. GDF8 antibody treatment rescued the skeletal muscle and articular cartilage transcriptomic response to ACL injury and attenuated PTOA severity and deficits in periarticular bone microarchitecture. Furthermore, GDF8 genetic deletion neutralized musculoskeletal deficits in response to ACL injury. Our findings support an opportunity for rapid targeting of GDF8 to enhance functional musculoskeletal recovery and mitigate the severity of PTOA after injury.

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.

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.

Patients With Depression and/or Anxiety Having Arthroscopic Rotator Cuff Repair Show Decreased Number of Prescriptions and Number of Psychotherapy Sessions in the Year After Surgery.

PURPOSE: To determine whether the utilization of psychological treatments changes after arthroscopic rotator cuff repair (RCR) for patients with preoperative depression and/or anxiety. METHODS: The Truven Healthcare Marketscan database was used to identify patients who underwent arthroscopic RCR between January 2009 and December 2016. We included all patients with diagnosis codes associated with either depression or anxiety before RCR. Patients were excluded if they did not have complete insurance coverage for 1 year before or after surgery, or if they had arthroscopic RCR in the year before the index surgical procedure. We compared the proportion of patients with preoperative depression or anxiety who filled a prescription and had psychotherapy procedural codes in the year before and the year after arthroscopic RCR. RESULTS: A total of 170,406 patients who underwent RCR were identified, of which depression and/or anxiety was found in 46,737 patients (43.7% male). Of the 46,737 patients, 19.6% filled a prescription for a depression/anxiety medication at least once in the year before surgery. Of this subset of patients, 41.5% did not fill a prescription for depression or anxiety medication after surgery, whereas 32.6% continued medication use but demonstrated a median 30-day reduction in the number of days' worth of medication. Similarly, 13.1% of patients were attending psychotherapy sessions preoperatively, but 76.6% of those patients either stopped or reduced the amount of psychotherapy sessions in the year following RCR. CONCLUSIONS: The number of prescriptions and psychotherapy sessions decreased in the year after RCR for patients with preoperative diagnoses of depression and/or anxiety. LEVEL OF EVIDENCE: Level IV, case series.

Effects of foot intensive rehabilitation (FIRE) on clinical outcomes for patients with chronic ankle instability: a randomized controlled trial protocol.

BACKGROUND: Lateral ankle sprains account for a large proportion of musculoskeletal injuries among civilians and military service members, with up to 40% of patients developing chronic ankle instability (CAI). Although foot function is compromised in patients with CAI, these impairments are not routinely addressed by current standard of care (SOC) rehabilitation protocols, potentially limiting their effectiveness. The purpose of this randomized controlled trial is to determine if a Foot Intensive REhabilitation (FIRE) protocol is more effective compared to SOC rehabilitation for patients with CAI. METHODS: This study will use a three-site, single-blind, randomized controlled trial design with data collected over four data collection points (baseline and post-intervention with 6-, 12-, and 24-month follow-ups) to assess variables related to recurrent injury, sensorimotor function, and self-reported function. A total of 150 CAI patients (50 per site) will be randomly assigned to one of two rehabilitation groups (FIRE or SOC). Rehabilitation will consist of a 6-week intervention composed of supervised and home exercises. Patients assigned to SOC will complete exercises focused on ankle strengthening, balance training, and range of motion, while patients assigned to FIRE will complete a modified SOC program along with additional exercises focused on intrinsic foot muscle activation, dynamic foot stability, and plantar cutaneous stimulation. DISCUSSION: The overall goal of this trial is to compare the effectiveness of a FIRE program versus a SOC program on near- and long-term functional outcomes in patients with CAI. We hypothesize the FIRE program will reduce the occurrence of future ankle sprains and ankle giving way episodes while creating clinically relevant improvements in sensorimotor function and self-reported disability beyond the SOC program alone. This study will also provide longitudinal outcome findings for both FIRE and SOC for up to two years. Enhancing the current SOC for CAI will improve the ability of rehabilitation to reduce subsequent ankle injuries, diminish CAI-related impairments, and improve patient-oriented measures of health, which are critical for the immediate and long-term health of civilians and service members with this condition. Trial Registration Clinicaltrials.gov Registry: NCT #NCT04493645 (7/29/20).

Formation and Transformation of Cu2-xSe1-yTey Nanoparticles Synthesized by Tellurium Anion Exchange of Copper Selenide.

Ion exchange reactions of colloidal nanoparticles post-synthetically modify the composition while maintaining the morphology and crystal structure and therefore are important for tuning properties and producing otherwise inaccessible and/or metastable materials. Reactions involving anion exchange of metal chalcogenides are particularly interesting, as they involve the replacement of the sublattice that defines the structure while also requiring high temperatures that can be disruptive. Here, we show that the tellurium anion exchange of weissite Cu2-xSe nanoparticles using a trioctylphosphine-tellurium complex (TOP═Te) yields weissite Cu2-xSe1-yTey solid solutions, rather than complete exchange to weissite Cu2-xTe, with compositions that are tunable based on the amount of TOP═Te used. Upon storage at room temperature in either solvent or air, tellurium-rich Cu2-xSe1-yTey solid solution nanoparticles transform, over the span of several days, to a selenium-rich Cu2-xSe1-yTey composition. The tellurium that is expelled from the solid solution during this process migrates to the surface and forms a tellurium oxide shell, which correlates with the onset of particle agglomeration due to the change in surface chemistry. Collectively, this study demonstrates tunable composition during tellurium anion exchange of copper selenide nanoparticles along with unusual post-exchange reactivity that transforms the composition, surface chemistry, and colloidal dispersibility due to the apparent metastable nature of the solid solution product.

The T allele of TCF7L2 rs7903146 is associated with decreased glucose tolerance after bed rest in healthy older adults.

Inpatient populations are at increased risk of hyperglycemia due to factors such as medications, physical inactivity and underlying illness, which increases morbidity and mortality. Unfortunately, clinicians have limited tools available to prospectively identify those at greatest risk. We evaluated the ability of 10 common genetic variants associated with development of type 2 diabetes to predict impaired glucose metabolism. Our research model was a simulated inpatient hospital stay (7 day bed rest protocol, standardized diet, and physical inactivity) in a cohort of healthy older adults (n = 31, 65 ± 8 years) with baseline fasting blood glucose < 100 mg/dL. Participants completed a standard 75 g oral glucose tolerance test (OGTT) at baseline and post-bed rest. Bed rest increased 2-h OGTT blood glucose and insulin independent of genetic variant. In multiple regression modeling, the transcription factor 7-like 2 (TCF7L2) rs7903146 T allele predicted increases in 2-h OGTT blood glucose (p = 0.039). We showed that the TCF7L2 rs7903146 T allele confers risk for loss of glucose tolerance in nondiabetic older adults following 7 days of bed rest.

Mood Disorders Are Associated with Increased Perioperative Opioid Usage and Health Care Costs in Patients Undergoing Knee Cartilage Restoration Procedure.

OBJECTIVE: To identify the prevalence of mood disorder diagnoses in patients undergoing cartilage transplantation procedures and determine the relationship between mood disorders, opioid usage, and postoperative health care costs. DESIGN: Patients with current procedural terminology (CPT) codes for osteochondral autograft transplantation (OAT), osteochondral allograft transplantation (OCA), and autologous chondrocyte implantation (ACI) were identified in the Truven Health Marketscan database (January 2009-September 2014). Patients were grouped based on having a preoperative mood disorder diagnosis (preMDD). Preoperative opioids, postoperative opioids ≥90 days, and health care costs within the year postoperative were compared for those with and without mood disorders. Costs were analyzed, adjusting for preoperative cost, sex, age, and opioid usage, for those with and without mood disorders. RESULTS: A total of 3,682 patients were analyzed (ACI: 690, OAT: 1,294, OCA: 1,698). A quarter of patients had preMDD (ACI: 25.4%, OAT: 20.6%, OCA: 22.7%). Postoperative opioid use was more prevalent in preMDD patients (OAT: 37.1% vs. 24.1%, P < 0.001; OCA: 30.4% vs. 24.8%, P = 0.032; ACI: 33.7% vs. 26.2%, P = 0.070) (odds ratio [OR] ranged from 1.29 to 1.86). First-year postoperative log-transformed costs were significantly greater for preMDD patients (ACI: $7,733 vs. $5,689*, P = 0.012; OAT: $5,221 vs. $3,823*, P < 0.001; OCA: $6,973 vs. $3,992*, P < 0.001; *medians reported). The estimated adjusted first postoperative year cost increase for preMDD OCA patients was 41.7% (P < 0.001) and 28.0% for OAT patients (P = 0.034). There was no statistical difference for ACI patients (P = 0.654). CONCLUSION: Cartilage transplantation patients have a high prevalence of preoperative mood disorders. Opioid use and health care costs were significantly greater for patients with preoperative mood disorder diagnoses. LEVEL OF EVIDENCE: Level III, retrospective therapeutic study.

T1ρ imaging as a non-invasive assessment of collagen remodelling and organization in human skeletal muscle after ligamentous injury.

Dysregulation and fibrosis of the extracellular matrix (ECM) in skeletal muscle is a consequence of injury. Current ECM assessment necessitates muscle biopsies to evaluate alterations to the muscle ECM, which is often not practical in humans. The goal of this study was to evaluate the potential of a magnetic resonance imaging sequence that quantifies T1ρ relaxation time to predict ECM collagen composition and organization. T1ρ imaging was performed and muscle biopsies obtained from the involved and non-involved vastus lateralis muscle on 27 subjects who had an anterior cruciate ligament (ACL) tear. T1ρ times were quantified via monoexponential decay curve fitted to a series of T1ρ-weighted images. Several ECM indices, including collagen content and organization, were obtained using immunohistochemistry and histochemistry in addition to hydroxyproline. Model selection with multiple linear regression was used to evaluate the relationships between T1ρ times and ECM composition. Additionally, the ACL-deficient and healthy limb were compared to determine sensitivity of T1ρ to detect early adaptations in the muscle ECM following injury. We show that T1ρ relaxation time was strongly associated with collagen unfolding (t = 4.093, P = 0.0007) in the ACL-deficient limb, and collagen 1 abundance in the healthy limb (t = 2.75, P = 0.014). In addition, we show that T1ρ relaxation time is significantly longer in the injured limb, coinciding with significant differences in several indices of collagen content and remodelling in the ACL-deficient limb. These results support the use of T1ρ to evaluate ECM composition in skeletal muscle in a non-invasive manner. KEY POINTS: Dysregulation and fibrotic transformation of the skeletal muscle extracellular matrix (ECM) is a common pathology associated with injury and ageing. Studies of the muscle ECM in humans have necessitated the use of biopsies, which are impractical in many settings. Non-invasive MRI T1ρ relaxation time was validated to predict ECM collagen composition and organization with aligned T1ρ imaging and biopsies of the vastus lateralis in the healthy limb and anterior cruciate ligament (ACL)-deficient limb of 27 subjects. T1ρ relaxation time was strongly associated with collagen abundance and unfolding in the ACL-deficient limb, and T1ρ relaxation time was strongly associated with total collagen abundance in the healthy limb. T1ρ relaxation time was significantly longer in the ACL-deficient limb, coinciding with significant increases in several indices of muscle collagen content and remodelling supporting the use of T1ρ to non-invasively evaluate ECM composition and pathology in skeletal muscle.

Psychological Healthcare Burden Lessens After Hip Arthroscopy for Those With Comorbid Depression or Anxiety.

PURPOSE: In this study, we investigated whether patients undergoing arthroscopic treatment of femoral acetabular impingement syndrome (FAIS) seek health care for treatment of comorbid depression and anxiety in the year following hip arthroscopy. METHODS: Using the Truven Health Marketscan database, FAIS patients who underwent hip arthroscopy between January 2009 and December 2016 were identified. Claims related to depression or anxiety filed during the year before surgery were required for inclusion. Using claims for pharmaceutical and psychological therapy treatments for mental health disorders, four groups of patients were analyzed on the basis of preoperative anxiety/depression treatment: medication only, therapy only, medication + therapy, and no treatment. Number of opioid pain prescriptions within 180 days prior to surgery and >90 days after hip arthroscopy were also compared. RESULTS: Depression and anxiety claims were identified in 5,208/14,830 (35.1%) patients. Preoperative treatment for depression and anxiety included medication only (n = 648, 12.4%), therapy only (n = 899, 17.3%), medication + therapy (n = 252, 4.8%), and no treatment (n = 3,409, 65.5%). Of the 900 patients who filled an anxiety/depression-related prescription prior to surgery, 422 (46.9%) patients did not fill a similar prescription in the postoperative year. Of the 1,151 patients receiving anxiety/depression-related therapy prior to surgery, 549 (47.7%) did not receive therapy in the postoperative year. Preoperative opioid prescriptions were filled for 393 patients (60.6%) in medication-only group, 275 (30.6%) in therapy-only group, 156 (61.9%) in medication + therapy group, and 1,059 (31.1%) in the group receiving no treatment. Opioid prescriptions >90 days postoperatively were filled for 330 (50.9%), 225 (25.0%), 120 (47.6%), and 861 (25.3%) patients, respectively. CONCLUSION: Hip arthroscopy for FAIS is associated with a decreased postoperative use of health care resources for the treatment of depression and anxiety. Clinicians should also be aware of the potential interplay between preoperative psychotropic medication use and prolonged opioid use when counseling patients. LEVEL OF EVIDENCE: IV, therapeutic case series.

Male Sex, Western Ontario Shoulder Instability Index Score, and Sport as Predictors of Large Labral Tears of the Shoulder: A Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability Cohort Study.

PURPOSE: To identify factors predictive of a large labral tear at the time of shoulder instability surgery. METHODS: As part of the Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability cohort, patients undergoing open or arthroscopic shoulder instability surgery for a labral tear were evaluated. Patients with >270° tears were defined as having large labral tears. To build a predictive logistic regression model for large tears, the Feasible Solutions Algorithm was used to add significant interaction effects. RESULTS: After applying exclusion criteria, 1235 patients were available for analysis. There were 222 females (18.0%) and 1013 males (82.0%) in the cohort, with an average age of 24.7 years (range 12 to 66). The prevalence of large tears was 4.6% (n = 57), with the average tear size being 141.9°. Males accounted for significantly more of the large tears seen in the cohort (94.7%, P = .01). Racquet sports (P = .01), swimming (P = .02), softball (P = .05), skiing (P = .04), and golf (P = .04) were all associated with large labral tears, as was a higher Western Ontario Shoulder Instability Index (WOSI; P = .01). Age, race, history of dislocation, and injury during sport were not associated with having a larger tear. Using our predictive logistic regression model for large tears, patients with a larger body mass index (BMI) who played contact sports were also more likely to have large tears (P = .007). CONCLUSIONS: Multiple factors were identified as being associated with large labral tears at the time of surgery, including male sex, preoperative WOSI score, and participation in certain sports including racquet sports, softball, skiing, swimming, and golf. LEVEL OF EVIDENCE: I, prognostic study.

Feasibility as a mechanism for model identification and validation.

As new technologies permit the generation of hitherto unprecedented volumes of data (e.g. genome-wide association study data), researchers struggle to keep up with the added complexity and time commitment required for its analysis. For this reason, model selection commonly relies on machine learning and data-reduction techniques, which tend to afford models with obscure interpretations. Even in cases with straightforward explanatory variables, the so-called 'best' model produced by a given model-selection technique may fail to capture information of vital importance to the domain-specific questions at hand. Herein we propose a new concept for model selection, feasibility, for use in identifying multiple models that are in some sense optimal and may unite to provide a wider range of information relevant to the topic of interest, including (but not limited to) interaction terms. We further provide an R package and associated Shiny Applications for use in identifying or validating feasible models, the performance of which we demonstrate on both simulated and real-life data.

Heart Failure in Humans Reduces Contractile Force in Myocardium From Both Ventricles.

This study measured how heart failure affects the contractile properties of the human myocardium from the left and right ventricles. The data showed that maximum force and maximum power were reduced by approximately 30% in multicellular preparations from both ventricles, possibly because of ventricular remodeling (e.g., cellular disarray and/or excess fibrosis). Heart failure increased the calcium (Ca2+) sensitivity of contraction in both ventricles, but the effect was bigger in right ventricular samples. The changes in Ca2+ sensitivity were associated with ventricle-specific changes in the phosphorylation of troponin I, which indicated that adrenergic stimulation might induce different effects in the left and right ventricles.

Increased Health Care Costs and Opioid Use in Patients with Anxiety and Depression Undergoing Rotator Cuff Repair.

PURPOSE: To (1) quantify the prevalence of mood disorders in patients undergoing arthroscopic rotator cuff repair (RCR) by use of a large claims database and (2) compare opioid use and medical costs in the year before and the year after RCR between patients with and without comorbid mood disorders. METHODS: A large claims database was queried to identify patients who underwent arthroscopic RCR (Current Procedural Terminology code 29827) between October 2010 and December 2015. All patients were then screened for insurance claims relating to either anxiety or depression. We compared net costs and opioid use both 1 year preoperatively and 1 year postoperatively between patients with and without mood disorders by use of an analysis of covariance. RESULTS: A total of 170,329 patients (97,427 male patients [57.2%] and 72,902 female patients [42.8%]) undergoing arthroscopic RCR were identified. Of the 170,329 patients, 46,737 (27.4%) had comorbid anxiety or depression, and after adjustment for preoperative cost, sex, age, and both preoperative and postoperative opioid use, the 1-year postoperative cost was 7.05% higher for those with a preoperative mood disorder than for those without a mood disorder. In addition, opioid use both in the 180 days prior to surgery (36.7% vs 26.9%) and more than 90 days after surgery (33.0% vs 27.2%) was substantially greater in the group with comorbid depression or anxiety. CONCLUSIONS: In patients with comorbid mood disorders, opioid use and health care costs were increased both preoperatively and postoperatively. The increased cost in this patient population is estimated at $62.3 million annually. In an effort to provide high-quality, value-based care, treatment strategies should be developed to identify these patients preoperatively and provide the appropriate resources needed to improve the probability of a successful surgical outcome. LEVEL OF EVIDENCE: Level III, retrospective, comparative therapeutic study.

Usefulness of Findings by Multimodality Imaging to Stratify Risk of Major Adverse Cardiac Events After Sepsis at 1 and 12 months.

Cardiovascular complications are reported in up to 30% of sepsis survivors. Currently, there is limited evidence to guide cardiovascular risk stratification of septic patients. We propose the use of left ventricular ejection fraction (LVEF) and coronary artery calcification (CAC) on nongated computed tomography (CT) scans to identify septic patients at highest risk for major adverse cardiovascular events (MACE). We retrospectively reviewed 517 adult patients with sepsis, elevated troponin levels, nongated CT scans that visualized the coronaries, and an echocardiogram. Patients were stratified into 4 groups based on the LVEF and presence or absence of CAC. Using the CAC negative/LVEF ≥ 50% as a control, we compared MACE and all-cause mortality outcomes across the patient groups. At 30 days, 39 patients (7.5%) experienced MACE and 166 patients (32%) died. Patients with no CAC and LVEF ≥ 50% experienced no MACE at 30 days or 1 year. Among patients with EF < 50%, CAC positive or negative patients were statistically more likely to experience a MACE event at 30 days (p < 0.001 for both groups). After 30 days, a further 6 patients (1.2%) experienced MACE and 66 (12.7%) patients died within the first year. Patients with CAC positive/LVEF < 50% experienced the highest rates of MACE at 1 year (p < 0.001). In conclusion, the combination of LVEF on echocardiography and CAC on nongated CT scans provides a powerful risk stratification tool for predicting cardiovascular events in septic patients.

Depression and Anxiety Are Associated With Increased Health Care Costs and Opioid Use for Patients With Femoroacetabular Impingement Undergoing Hip Arthroscopy: Analysis of a Claims Database.

PURPOSE: To determine if opioid use and health care costs in the year before and following hip arthroscopy for femoroacetabular impingement (FAI) differ between those with or without depression or anxiety. METHODS: Using the Truven Health Marketscan database, FAI patients who underwent hip arthroscopy between October 2010 and December 2015 were identified (Current Procedural Terminology codes 29914 [femoroplasty], 29915 [acetabuloplasty], and/or 29916 [labral repair]). Patients were excluded if they had incomplete coverage for 1 year either before or following surgery. The number of patients with 1 or more claims related to depression or anxiety during the year before surgery was quantified (International Statistical Classification Diseases and Related Health-9 codes 296, 298, 300, 309, 311). Health care costs in the year before and following hip arthroscopy were compared between those with or without depression or anxiety. We also compared the number of patients in each group who filled a narcotic pain prescription within 180 days before surgery as well as >60 or >90 days after hip arthroscopy. RESULTS: Depression or anxiety claims were seen in 5,208/14,830 patients (35.1%) before surgery. A significantly greater proportion of those with preoperative depression or anxiety filled opioid-related prescriptions in the 6 months before surgery (36.2% vs 25.6%, P < .0001) and both >60 days (31.3% vs 24.7%, P < .0001) and >90 days after surgery (29.5% vs 23.4%, P < .0001). The group with preoperative depression or anxiety had significantly greater health care costs both before ($8,775 vs $5,674, P < .0001) and following surgery ($5,287 vs $3,908, P < .0001). CONCLUSIONS: Both before and following hip arthroscopy, opioid use and health care costs were significantly greater for FAI patients with comorbid depression or anxiety. LEVEL OF EVIDENCE: Level III, retrospective comparative therapeutic study.