William Z. Morris

Review of Postoperative Delirium in Geriatric Patients Undergoing Hip Surgery

Postoperative delirium is a serious complication following hip surgery in elderly patients that can adversely affect outcomes in both hip fracture and arthroplasty surgery. Recently, the incidence of hip fracture in the Medicare population was estimated at approximately 500 000 patients per year, with the majority treated surgically. The annual volume of total hip arthroplasty is nearly 450 000 patients and is projected to increase over the next 15 to 20 years. Subsequently, the incidence of postoperative delirium will rise. The incidence of postoperative delirium after hip surgery in the elderly patients ranges between 4% and 53%, and it is identified as the most common surgical complication of older patients. The most common risk factors include advanced age, hip fracture surgery (vs elective hip surgery), and preoperative delirium/cognitive impairment. Exact pathophysiology has not been fully defined. It is hypothesized that imbalances in cortical neurotransmitters or inflammatory cytokine pathway mechanisms contribute to delirium. Development of postoperative delirium is associated with longer hospital stay, increased medical complications, and poorer short-term functional outcome. Patients who develop postoperative delirium are also at increased risk for cognitive decline beyond the acute phase. Following acute care, postoperative delirium is associated with the need for a higher level of care, an additional cost. Management of postoperative delirium centers on prevention and early recognition. Medical prophylaxis has been demonstrated to have limited utility. Utilization of delirium detection methods contributed to early recognition. The most effective means of prevention involved a multidisciplinary team focused on adequate hydration, optimization of analgesia, reduction in polypharmacy, aggressive physiotherapy, and early recognition of the delirium symptoms.

Femoral Version and Tibial Torsion are Not Associated With Hip or Knee Arthritis in a Large Osteological Collection.

Background: Tibial torsion and femoral anteversion are common rotational abnormalities in children, and their courses are most often benign and self-resolving. Although neither usually requires surgical treatment, the decision to perform a derotational osteotomy is usually based on the degree of functional impairment. Neither condition is thought to influence the development of osteoarthritis of the hip or knee; however, to date there have been no large scale studies confirming this. Methods: Tibial torsion and femoral version in 1158 cadaveric tibiae and femora were measured using a camera setup based on previously described radiographic landmarks. Any specimens with obvious traumatic, rheumatic, or metabolic abnormalities were excluded. Degenerative joint disease of the hip and knee were each graded from 0 to 6. Correlations between tibial torsion, femoral version, age, race, and sex with osteoarthritis of the hip and knee joints were evaluated with multiple regression analysis. Results: The mean and SDs of tibial torsion and femoral anteversion were 7.9±8.8 and 11.4±12.0 degrees, respectively. African Americans had significantly increased tibial torsion (5.1±8.7 vs. 9.2±8.5 degrees, P<0.0005) and greater femoral anteversion (14.1±11.9 vs. 10.2±11.8 degrees, P<0.0005) compared with whites. The average grades for hip and knee osteoarthritis were 3.1±1.4 and 2.7±1.4. Using multiple regression analysis neither tibial torsion nor femoral version were independent predictors of hip or knee arthritis (P>0.05 for all). Discussion: This study confirmed previously reported differences in the rotational profiles between races and sexes. However, neither tibial torsion nor femoral anteversion had a significant influence on the development of arthritis of the hip or knee. Clinical Relevance: These results support the practice of treating tibial torsion and femoral anteversion based on the symptomatology of the patient. Parents of asymptomatic children can be reassured that long-term consequences are unlikely.

Decreasing pelvic incidence is associated with greater risk of cam morphology

Objectives The spinopelvic relationship (including pelvic incidence) has been shown to influence pelvic orientation, but its potential association with femoroacetabular impingement has not been thoroughly explored. The purpose of this study was to prove the hypothesis that decreasing pelvic incidence is associated with increased risk of cam morphology. Methods Two matching cohorts were created from a collection of cadaveric specimens with known pelvic incidences: 50 subjects with the highest pelvic incidence (all subjects > 60°) and 50 subjects with the lowest pelvic incidence (all subjects < 35°). Femoral version, acetabular version, and alpha angles were directly measured from each specimen bilaterally. Cam morphology was defined as alpha angle > 55°. Differences between the two cohorts were analysed with a Student’s t-test and the difference in incidence of cam morphology was assessed using a chi-squared test. The significance level for all tests was set at p < 0.05. Results Cam morphology was identified in 47/100 (47%) femurs in the cohort with pelvic incidence < 35° and in only 25/100 (25%) femurs in the cohort with pelvic incidence > 60° (p = 0.002). The mean alpha angle was also greater in the cohort with pelvic incidence < 35° (mean 53.7°, sd 10.7° versus mean 49.7°, sd 10.6°; p = 0.008). Conclusions Decreased pelvic incidence is associated with development of cam morphology. We propose a novel theory wherein subjects with decreased pelvic incidence compensate during gait (to maintain optimal sagittal balance) through anterior pelvic tilt, creating artificial anterior acetabular overcoverage and recurrent impingement that increases risk for cam morphology. Cite this article: W. Z. Morris, C. A. Fowers, R. T. Yuh, J. J. Gebhart, M. J. Salata, R. W. Liu. Decreasing pelvic incidence is associated with greater risk of cam morphology. Bone Joint Res 2016;5:387–392. DOI: 10.1302/2046-3758.59.BJR-2016-0028.R1.

Capital Femoral Growth Plate Extension Predicts Cam Morphology in a Longitudinal Radiographic Study

BACKGROUND Recent evidence has suggested that cam morphology may be related to alterations in the capital femoral growth plate during adolescence. The purpose of this study was to evaluate the relationship between capital femoral growth plate extension and cam morphology in a longitudinal radiographic study. METHODS We used a historical, longitudinal radiographic collection to identify 96 healthy adolescents (54 boys and 42 girls) with at least 5 consecutive annual radiographs of the left hip including closure of the capital femoral physis. We reviewed 554 anteroposterior radiographs of the left hip to measure the anteroposterior modification of the alpha angle of Nötzli and of the superior epiphyseal extension ratio (EER), measured as the ratio of extension of the capital femoral epiphysis down the femoral neck relative to the diameter of the femoral head. Measurements were made at 3 points in femoral head maturation corresponding to the Oxford bone age (OBA) femoral head stages 5, 6, and 7/8. RESULTS There was a mean increase in the anteroposterior alpha angle (10.7° ± 14.0°) and EER (0.12 ± 0.08) between OBA stages 5 and 7/8, corresponding to maturation and closure of the capital femoral physis. There was a positive correlation between the final anteroposterior alpha angle and both the final EER (r = 0.60) and the change in the EER (r = 0.58). A receiver operating characteristic curve generated to predict an anteroposterior alpha angle of ≥78° through the EER demonstrated an area under the curve of 0.93, indicating that an increasing EER had excellent diagnostic accuracy for predicting concurrent cam morphology. CONCLUSIONS AND CLINICAL RELEVANCE Superior epiphyseal extension was directly and temporally associated with an increase in anteroposterior alpha angle and more cam-like morphology. This alteration in the capital femoral epiphysis occurred immediately before physeal closure (OBA stage 7/8). Given the association of epiphyseal extension with activities that increase shear forces across the physis, we proposed that epiphyseal extension may be an adaptive mechanism to stabilize the physis and prevent slipped capital femoral epiphysis.

Origin of Cam Morphology in Femoroacetabular Impingement

Cam morphology of the proximal femur is an abnormal contour of the femoral head-neck junction present in approximately 15% to 25% of the asymptomatic population, predominantly in males. Alpha angle and femoral head-neck offset ratio are 2 objective measurement tools that define cam morphology. Both primary (idiopathic) and secondary cam deformity develops through distinct mechanisms. The cause of primary (idiopathic) cam morphology remains incompletely understood. Mounting evidence suggests that idiopathic cam morphology develops during adolescence through alterations in the capital femoral epiphysis in response to participation in vigorous sporting activity. While the exact cause of epiphyseal extension has not yet been determined, preliminary evidence suggests that epiphyseal extension may reflect a short-term adaptive response to provide stability to the physis at the long-term cost of the development of cam morphology. Commonly recognized causes of secondary cam deformity include frank slipped capital femoral epiphysis, Legg-Calve-Perthes disease, and deformity after fracture of the proximal femur. Recent studies also support subtle slipped capital femoral epiphysis as a unique and silent cause of a small percentage of subjects previously thought to have idiopathic cam deformity.

Validity and Clinical Consequences of a Rotational Mechanism for Slipped Capital Femoral Epiphysis.

Background: Recent anatomic data supports a mechanism for slipped capital femoral epiphysis (SCFE) where the metaphysis rotates on the epiphysis through the eccentrically located epiphyseal tubercle as a pivot. The validity of such a mechanism and its clinical consequences have not been well investigated. Methods: This cadaveric study defined the normal location of the calcar ridge line in 100 paired femora and compared them with 11 SCFE specimens, and with 25 immature femora where the metaphysis was rotated 30, 60, and 90 degrees on the epiphysis to model progressive SCFE. Coronal, sagittal, and axial plane deformity were measured on the rotational model to define the characteristic deformity caused by rotation, and lateral epiphyseal foramina stretch was measured to quantify the protective effect of an eccentric pivot. Results: The posterior displacement of the fovea with respect to the calcar ridge line was 1±5 mm for the controls, versus 23±10 mm for the SCFE specimens (P<0.0005), and posterior displacement increased with incremental rotation in the rotational model (P<0.0005). The rotational model found minimal varus deformity, but substantial extension and retroversion, with deformities of 0±5, −16±12, and −38±9 degrees, respectively, at 90 degrees of rotation. The eccentric pivot mitigated lateral epiphyseal vessel stretch by 55% to 70%. Conclusions: This study provides strong anatomic support for a rotational mechanism for stable SCFE. When the metaphysis is rotated on the epiphysis acutely, minimal varus deformity is created, while substantial retroversion occurs. As this rotation occurs the eccentric pivot protects the lateral epiphyseal vessels, and likely accounts for the low rate of avascular necrosis observed in stable SCFE. Clinical Relevance: If SCFE is treated in an open manner then the presence of a chronic rotational deformity should be considered. When planning osteotomies for deformity after a stable SCFE, any suspected varus component should be carefully investigated as it may represent retroversion deformity brought into view by external rotation posturing of the leg.

Increased and decreased pelvic incidence, sagittal facet joint orientations are associated with lumbar spine osteoarthritis in a large cadaveric collection

PurposeDegenerative joint disease of the lumbar spine is a pervasive problem in healthcare; however, its aetiology and risk factors remain poorly defined. There have been recent attempts to correlate the anatomic parameters of facet angle and pelvic incidence with spine osteoarthritis, although data remains limited. The purpose of this experiment was to determine how age, gender, race, facet angle, tropism, and pelvic incidence correlate to facet joint osteoarthritis in the lumbar spine.MethodsA total of 576 cadaveric lumbar spines were obtained. Using validated techniques, facet angle, tropism, and pelvic incidence were measured. Osteoarthritis of the lumbar spines was graded from 0-4 at each level. Correlations between osteoarthritis and age, gender, facet angle, tropism, and pelvic incidence were evaluated with regression analysis.ResultsFacet angle became more coronally oriented, and facet tropism increased from L1-L2 to L5-S1. Arthritis was highest at the L4-L5 joint (2.2 ± 1.1), compared to the L5-S1 (2.1 ± 1.1), L3-L4 (1.9 ± 1.1), L2-L3 (1.5 ± 1.0) and L1-L2 (1.0 ± 1.0) joints (p < 0.001). Age was the strongest predictor of arthritis at all levels (standardized betas 0.342 through 0.494, p < 0.001). Correlations between gender, race and osteoarthritis were not significant at any level. A decreased facet angle was predictive of increased arthritis at each joint level (standardized betas –0.091 through –0.153, p < 0.05 for all). Tropism was a predictor of increased arthritis at caudal levels. Pelvic incidence was a predictor of increased arthritis at L3-L4 (standardized beta 0.080, p = 0.02), L4-L5 (standardized beta 0.081,p = 0.02), and L5-S1 (standardized beta 0.100, p = 0.01).ConclusionsFacet arthritis was correlated with a more sagittal orientation of the facet joints, increased tropism, and perturbations of pelvic incidence.

Micrometastatic drug screening platform shows heterogeneous response to MAP chemotherapy in osteosarcoma cell lines

Background Approximately 80% of patients with osteosarcoma harbor subclinical pulmonary micrometastases at diagnosis. Conventional chemotherapy includes methotrexate, doxorubicin, and cisplatin (MAP); however, this regimen and thus overall survival (60%-70%) have remained largely unchanged for 30 years. It therefore is necessary to identify novel therapeutics targeting the metastatic progression of osteosarcoma. Questions/purposes This laboratory study explored application of osteosarcoma spheroids (sarcospheres) for drug screening with the following purposes: (1) to characterize sarcosphere size; (2) to establish accurate measurement of sarcosphere growth; (3) to confirm sarcosphere uniformity; and (4) to apply the platform to evaluate MAP chemotherapy. Methods Sarcospheres were first characterized to establish accurate measurement of sarcosphere growth and uniform production. The refined platform then was applied to evaluate MAP chemotherapy to validate its use in drug screening. Sarcospheres were generated from highly metastatic human cell lines (143B, MG-63.3, and LM7) by centrifugation to form three-dimensional aggregates modeling micrometastases. Sarcospheres were matured for 24 hours and then incubated with or without drug from Days 0 to 2. Size was assessed by diameter and volume using brightfield microscopy. Growth was measured by volume and resazurin reduction in viable cells. Sarcosphere uniformity was assessed by diameter and resazurin reduction at Day 0 and the Z’ factor, a measure of assay suitability for high-throughput screening, was calculated at Day 2. Sarcospheres were treated with individual MAP agents (0 to 1000 &mgr;mol/L) to determine concentrations at which 50% of growth from Days 0 to 2 was inhibited (GIC50). Cell lines resistant to MAP in sarcospheres were treated in monolayer for comparison. Results Sarcosphere diameter and growth from Days 0 to 2 were quantitatively dependent on the number of cells seeded and the cell line used. Accurate measurement of growth occurred after resazurin incubation for 6 hours, without EDTA-mediated permeabilization, and was correlated with the number of cells seeded and sarcosphere volume for 143B (Spearman’s r: 0.98; p < 0.001), MG-63.3 (0.99; p < 0.001), and LM7 (0.98; p < 0.001). Sarcospheres met established criteria for screening applications as mean Z′ factors were greater than 0.5 for all cell lines. Response to MAP therapy was cell line-dependent, because MG-63.3 and LM7 sarcospheres exhibited greater than 2000-fold resistance to methotrexate (GIC50 = 88 ± 36 &mgr;mol/L and 174 ± 16 &mgr;mol/L, respectively) compared with the 143B cell line (GIC50 = 0.04 ± 0.01 &mgr;mol/L; p < 0.001 for MG-63.3 and LM7). MG-63.3 monolayers were more sensitive to methotrexate (GIC50 = 0.01 ± 0.01 &mgr;mol/L; p < 0.001) than MG-63.3 sarcospheres, whereas LM7 monolayers remained chemoresistent (GIC50 not reached). Conclusions This study developed and validated a drug screening platform for progression of osteosarcoma micrometastases. It also highlights heterogeneity among osteosarcoma cell lines. These findings appear to reflect known patient-to-patient heterogeneity and underscore the importance of evaluating multiple tumor models when testing drugs for the treatment of osteosarcoma. Clinical Relevance The described approach is a promising starting point for drug screening in osteosarcoma because it is tailored to evaluate micrometastatic disease. A reliable and rapid method to identify novel therapeutics is critical to improve stagnant outcomes for patients with osteosarcoma.

Low Pelvic Incidence Is Associated With Proximal Junctional Kyphosis in Patients Treated With Growing Rods.

Study Design. Retrospective review of a prospectively collected pediatric orthopedic spine database. Objective. To investigate whether pelvic incidence (PI) changes during growing rod treatment and to report the effects of PI, if any, on complications during treatment. Summary of Background Data. Growing rods have been demonstrated to correct spinal deformity in early onset scoliosis while allowing for spinal growth. There has been little investigation into the potential effects, if any, of abnormal PI on complications, especially proximal junctional kyphosis (PJK). Methods. We retrospectively reviewed clinical and surgical data from our prospectively collected pediatric orthopedic spine database. Our final cohort of 48 patients had at least one lateral radiograph throughout the course of treatment containing the femoral heads and sacral endplate, and a minimum follow-up of 2 years. Defined failures were identified prospectively. Radiographs were measured for PI and development of PJK. Results. Mean age at initial treatment was 6.9 years (range 2.8–10.8 yr), with 35 females and 13 males. The mean length of follow-up was 8.1 years (range 2.0–22.1 yr). No statistical change in PI was observed throughout this study (P = 0.655). Development of any failure as well as total number of failures was associated with younger age at initial treatment (P < 0.0005 for both). Development of PJK was associated with younger age at initial treatment (P = 0.030), female sex (P = 0.002), and lower mean PI (P = 0.042). Conclusion. PI remains constant throughout growth and the course of treatment with growing rods. Low PI was associated with increased PJK. When using growing rods in early onset scoliosis patients with decreased PI, increased attention should be paid to sagittal plane balance in an attempt to avoid PJK. Level of Evidence: 4

Capital Femoral Epiphyseal Extension May Confer Physeal Stability in Slipped Capital Femoral Epiphysis.

BACKGROUND Factors including obesity and morphologic parameters around the hip that increase physeal stress are associated with an increased risk of slipped capital femoral epiphysis (SCFE). Recent evidence suggests that superior epiphyseal extension may confer stability to the physis and help protect against SCFE. The purpose of this study is to investigate the relationship between epiphyseal extension and SCFE using an age-matched and sex-matched cohort study. METHODS We generated 2 separate cohorts for comparison: 89 patients with unilateral SCFE and 89 healthy subjects with no evidence of hip disease or deformity. We utilized the anterior-posterior and lateral films of the hip to measure the Southwick angle and the epiphyseal extension ratio (EER), defined as the ratio of extension of the capital femoral epiphysis down the femoral neck relative to the diameter of the femoral head. We then compared these measurements between cohorts and in subgroup analysis based on slip stability and whether subjects progressed to a contralateral slip. RESULTS The SCFE cohort demonstrated a decreased superior epiphyseal extension ratio compared with control (superior EER 0.71 vs. 0.68, P=0.002). There was also a significant downward trend in superior EER from the control subjects (0.71±0.07) to the stable slips (0.69±0.06) to the unstable slips (0.65±0.04) with an overall difference between the groups (P=0.001). Eighteen of 44 (41%) subjects with unilateral stable slips and at least 6 months of follow-up went on to develop SCFE of the contralateral limb. The subjects who developed contralateral slips were younger (11.6±1.2 vs. 12.7±1.4 y, P=0.008); however, there was no difference in superior or anterior epiphyseal extension (P=0.75 and 0.23, respectively). There was no significant linear correlation between Southwick angle and superior or anterior EER (r=0.13 and 0.17, respectively, P>0.05 for both). CONCLUSIONS Increasing capital femoral epiphyseal extension may confer physeal stability in the setting of SCFE. We propose that this epiphyseal extension reflects an adaptive response to limit physeal stress and reduce the risk for progression to SCFE. LEVEL OF EVIDENCE Level III-prognostic study.BACKGROUND Factors including obesity and morphologic parameters around the hip that increase physeal stress are associated with an increased risk of slipped capital femoral epiphysis (SCFE). Recent evidence suggests that superior epiphyseal extension may confer stability to the physis and help protect against SCFE. The purpose of this study is to investigate the relationship between epiphyseal extension and SCFE using an age-matched and sex-matched cohort study. METHODS We generated 2 separate cohorts for comparison: 89 patients with unilateral SCFE and 89 healthy subjects with no evidence of hip disease or deformity. We utilized the anterior-posterior and lateral films of the hip to measure the Southwick angle and the epiphyseal extension ratio (EER), defined as the ratio of extension of the capital femoral epiphysis down the femoral neck relative to the diameter of the femoral head. We then compared these measurements between cohorts and in subgroup analysis based on slip stability and whether subjects progressed to a contralateral slip. RESULTS The SCFE cohort demonstrated a decreased superior epiphyseal extension ratio compared with control (superior EER 0.71 vs. 0.68, P=0.002). There was also a significant downward trend in superior EER from the control subjects (0.71±0.07) to the stable slips (0.69±0.06) to the unstable slips (0.65±0.04) with an overall difference between the groups (P=0.001). Eighteen of 44 (41%) subjects with unilateral stable slips and at least 6 months of follow-up went on to develop SCFE of the contralateral limb. The subjects who developed contralateral slips were younger (11.6±1.2 vs. 12.7±1.4 y, P=0.008); however, there was no difference in superior or anterior epiphyseal extension (P=0.75 and 0.23, respectively). There was no significant linear correlation between Southwick angle and superior or anterior EER (r=0.13 and 0.17, respectively, P>0.05 for both). CONCLUSIONS Increasing capital femoral epiphyseal extension may confer physeal stability in the setting of SCFE. We propose that this epiphyseal extension reflects an adaptive response to limit physeal stress and reduce the risk for progression to SCFE. LEVEL OF EVIDENCE Level III-prognostic study.