Evaluation of the trajectory of recovery following surgically treated acetabular fractures.

Aims: Acetabular fractures are associated with long-term morbidity. Our prospective cohort study sought to understand the recovery trajectory of this injury over five years. Methods: Eligible patients at a level I trauma centre were recruited into a longitudinal registry of surgical acetabular fractures between June 2004 and August 2019. Patient-reported outcome measures (PROMs), including the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS), were recorded at baseline pre-injury recall and six months, one year, two years, and five years postoperatively. Comparative analyses were performed for elementary and associated fracture patterns. The proportion of patients achieving minimal clinically important difference (MCID) was determined. The rate of, and time to, conversion to total hip arthroplasty (THA) was also established. Results: We recruited 251 patients (253 fractures), with a 4:1 male to female ratio and mean age of 46.1 years (SD 16.4). Associated fracture patterns accounted for 56.5% of fractures (n = 143). Trajectory analysis showed all timepoints had significant disability versus baseline, including final follow-up (p < 0.001). Elementary fractures had higher SF-36 PCS at six months (p = 0.023) and one year (p = 0.007) compared to associated fractures, but not at two years (p = 0.135) or five years (p = 0.631). The MCID in SF-36 PCS was observed in 37.3% of patients (69/185) between six months and one year, 26.9% of patients (39/145) between one and two years, and 23.3% of patients (20/86) between two and five years, highlighting the long recovery potential of these injuries. A significant proportion of patients failed to attain the MCID after five years (38.1%; 40/105). Conversion to THA occurred in 13.1% of patients (11/110 elementary and 22/143 associated fractures). Approximately two-thirds of THAs (21/33 patients; 63.6%) were performed within two years of index surgery. Conclusion: Acetabular fractures significantly impact physical function. Recovery trajectory is often elongated beyond one year, with two-thirds of our patients displaying persistent clinically relevant long-term disability.

Effect of humeral rotation on the reliability of radiographic measurements for proximal humerus fractures.

BACKGROUND: There are concerns as to the reliability of proximal humerus radiographic measurements, particularly regarding the rotational position of the humerus when obtaining radiographs. METHODS: Twenty-four patients with proximal humerus fractures fixed surgically with locked plates received postoperative anteroposterior radiographs with the humerus in neutral rotation and in 30° of internal and external rotation. Radiographic measurements for head shaft angle, humeral offset and humeral head height were performed in each humeral rotation position. Intra-class correlation coefficient was used to assess inter-rater and intra-rater reliability. Mean differences (md) in measurements between humeral positions was evaluated using one-way ANOVA. RESULTS: Head shaft angle demonstrated good-to-excellent reliability; the highest estimates for inter-rater reliability (ICC: 0.85; 95% CI: 0.76, 0.94) and intra-rater reliability (ICC: 0.96; 95% CI: 0.93, 0.98) were achieved in neutral rotation. There were significant differences in measurement values between each rotational position, with mean head shaft angle of 133.1° in external rotation, and increasingly valgus measurements in neutral (md: 7.6°; 95% CI: 5.0, 10.3°; p < 0.001) and internal rotation (md: 26.4°; 95% CI: 21.8, 30.9°; p < 0.001). Humeral head height and humeral offset showed good-to-excellent reliability in neutral and external rotation, but poor inter-rater reliability in internal rotation. Humeral head height was significantly greater using internal compared to external rotation (md: 4.5 mm; 95% CI: 1.7, 7.3 mm; p = 0.002). Humeral offset was significantly greater in external compared to internal rotation (md: 4.6 mm; 95% CI: 2.6, 6.6 mm; p < 0.001). CONCLUSIONS: Views of the humerus in neutral rotation and 30° of external rotation displayed superior reliability. Differences in radiographic measurement values, depending on humeral rotation views, can make for problematic correlations with patient outcome measures. Studies assessing radiographic outcomes following proximal humerus fractures should ensure standardized humeral rotation for obtaining anteroposterior shoulder radiographs, with neutral rotation and external rotation views likely yielding the most reliable results. LEVEL OF EVIDENCE: Level IV.

If at first you don't succeed, should you try again? The efficacy of repeated closed reductions of distal radius fractures.

INTRODUCTION: A repeated closed reduction ("re-reduction") of a displaced distal radius fracture is a common procedure performed to obtain satisfactory alignment and avoid surgery when the initial reduction is deemed unsatisfactory. However, the efficacy of re-reduction is unclear. Compared to a single closed reduction, does a re-reduction of a displaced distal radius fracture: (1) improve radiographic alignment at the time of fracture union and, (2) decrease the rate of operative intervention? MATERIALS AND METHODS: Retrospective cohort analysis of 99 adults aged 20-99 years with extra-articular or minimally displaced intra-articular, dorsally angulated, displaced distal radius fracture with or without an associated ulnar styloid fracture who underwent a re-reduction, compared against 99 adults matched for age and sex who were managed with a single reduction. Exclusion criteria were skeletal immaturity, fracture-dislocation and articular displacement greater than 2 mm. Outcome measures included radiographic alignment at fracture union and rate of surgical intervention. RESULTS: At 6-8 weeks follow-up, the single reduction group had greater radial height (p = 0.045, CI 0.04 to 3.57), and less ulnar variance (p < 0.001, CI - 3.08 to - 1.00) compared to the re-reduction group. Immediately following re-reduction, 49.5% of patients met radiographic non-operative criteria, but by 6-8 weeks follow-up, only 17.5% of patients continued to meet these criteria. Patients in the re-reduction group were treated with surgery 34.3% of the time, compared to 14.1% of the time for patients in the single reduction group (p = 0.001). In patients aged under 65 years, 49.0% of those who underwent a re-reduction were managed with surgery, compared to 21.0% of those who had a single reduction (p = 0.004). CONCLUSION: A re-reduction performed to improve radiographic alignment and avoid surgical management in this subset of distal radius fractures had minimal value. Alternative treatment options should be considered before attempting a re-reduction.

Open Versus Closed Operative Treatment for Tongue-Type Calcaneal Fractures: Case Series and Literature Review.

Because consensus on the optimal surgical treatment of tongue-type calcaneal fractures is lacking, this study aimed to compare outcomes and postoperative complications of open and closed surgical treatment of these fractures. For this cases series, all patients 18 years or older who underwent operative fixation of tongue-type calcaneal fractures at 2 level I trauma centers between 2004 and 2015 were considered eligible for participation. Data on explanatory and outcome variables were collected from medical records based on available follow-up. Additionally, a systematic literature review on surgical treatment of these fractures was conducted. Fifty-six patients (58 tongue-type fractures) were included. Open reduction internal fixation was performed in 33 fractures, and closed reduction internal (percutaneous) fixation was performed in 25. More wound problems and deep infections were observed with open treatment compared with the closed approach: 10 (30%) versus 3 (12%) and 4 (12%) versus 0 (0%) procedures, respectively. In contrast, revision and hardware removal predominated in patients with closed treatments: 4 (16%) versus 1 (3%) and 9 (36%) versus 8 (24%) procedures, respectively. The systematic literature review yielded 10 articles reporting on surgical treatment for tongue-type fractures, all showing relatively good outcomes and low complication rates with no definite advantage for either technique. Both open and closed techniques are suggested as accurate surgical treatment options for tongue-type calcaneal fractures. Surgical treatment should be individualized, considering both fracture and patient characteristics and the treating surgeon's expertise. We recommend attempting closed reduction internal fixation if deemed feasible, with conversion to an open procedure if satisfactory reduction or fixation is unobtainable.

Does Surgical Approach Influence the Risk of Postoperative Infection After Surgical Treatment of Tibial Pilon Fractures?

OBJECTIVES: To determine whether a particular surgical approach or combination of approaches is a risk factor for infection. DESIGN: Retrospective review. SETTING: Two Level-1 trauma centers. PATIENTS/PARTICIPANTS: Five hundred ninety pilon fractures in 581 patients (66% male) with a median age of 45 years were identified. INTERVENTION: Open reduction internal fixation of pilon fractures. MAIN OUTCOME MEASURES: Postoperative deep surgical site infection and risk factors for postoperative deep infection. RESULTS: The most common primary surgical approach was medial (54%), followed by anterolateral (25%), anteromedial (11%), posterolateral (8%), and posteromedial (2%). A dual approach to the distal tibia was used in 18% of the cases. The overall deep infection rate was 19%. There was no association between primary surgical approach and development of infection (P = 0.19-0.78). Independent risk factors for infection were smoking (hazard ratio, 2.1; P < 0.001) and need for soft tissue coverage (hazard ratio, 6.9; P < 0.001). CONCLUSIONS: Surgical approach does not appear to be a significant risk factor for postoperative infection after open reduction internal fixation of distal tibial pilon fractures. When treating tibial plafond fractures, surgeons should select the approach they feel best addresses the specific fracture pattern. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Is the proximity of external fixator pins to eventual definitive fixation implants related to the risk of deep infection in the staged management of tibial pilon fractures?

INTRODUCTION: In the staged management of tibial pilon fractures, overlap between definitive internal fixation and external fixation pin sites has been investigated as a risk factor for infection with equivocal conclusions. Our aim was to determine if overlap or proximity of definitive internal fixation to external fixation pin sites influences the risk of deep infection. PATIENTS AND METHODS: We reviewed 280 AO/OTA 43B or 43C type distal tibia fractures in 277 patients at two level-one trauma centers. Patients underwent staged management using early temporizing external fixation followed by definitive open reduction and plate fixation. Primary outcome was the association between pin site overlap and the development of deep infection. Secondary outcome was the relationship between development of deep infection and the distance from pin site to definitive fixation. RESULTS: The average duration between external fixation and definitive internal fixation was 14 days. 24% of fractures developed deep infection requiring surgical intervention. There was no association between pin site overlap and the development of deep infection (p = 0.18). There was no relationship between infection and the distance between proximal plate extent and pin site (p = 0.13). DISCUSSION: We identified no association between pin site overlap and the development of deep infection. We suggest that temporizing external fixation pins should be placed so as to obtain optimal stability of the construct with lesser emphasis on aiming to be absolutely outside the zone of future fixation. LEVEL OF EVIDENCE: Level III Therapeutic Retrospective Comparative study.

The willingness of orthopaedic trauma patients in Uganda to accept financial loans following injury.

BACKGROUND: Early access to a monetary loan may mitigate some of the socioeconomic burden associated with surgical treatment and lost wages following injury. The primary objective of this study was to determine the willingness of orthopaedic trauma patients in Uganda to accept a formal financial loan shortly after their time of injury. METHODS: A consecutive sample of adult orthopaedic trauma patients admitted to Uganda's national referral hospital was included in the survey. The primary outcome was the self-reported willingness to accept a financial loan. Secondary outcomes included the preferred loan terms, fracture treatment costs, and the factors associated with loan willingness. RESULTS: Of the 40 respondents (mean age, 40 years; 58% male), the median annual income was $582 United States dollars (USD) (range: $0-$6720). Around 50% reported a willingness to accept a loan with any terms. Patients requested loans with a median principal of $500 USD and a median interest rate of 5% with 12 months to pay back. Patients had received loans with a median principal of $142 USD, an interest rate of 10%, and payback of 6 months. These received loans covered a mean of 63% of the treatment costs. Patients with higher median incomes ($857 USD vs $342 USD) were more willing to accept a loan. CONCLUSION: This study demonstrated a limited interest of orthopaedic trauma patients in Uganda to procure loans through formalized lending. This observed resistance must be overcome in future programs that rely on mechanisms such as conditional cash transfers or microfinancing to improve clinical and socioeconomic outcomes after injury.

Role of North-South Partnership in Trauma Management: Uganda Sustainable Trauma Orthopaedic Program.

Uganda, as do many low-middle income countries, has an overwhelming volume of orthopaedic trauma injuries. The Uganda Sustainable Trauma Orthopaedic Program (USTOP) is a partnership between the University of British Columbia, McMaster University and Makerere University that was initiated in 2007. The goal of the project is to reduce the disabilities that occur secondary to musculoskeletal trauma in Uganda. USTOP works with local collaborators to build orthopaedic trauma capacity through teaching, innovation, and research. USTOP has maintained a multidisciplinary approach to training, involving colleagues in anesthesia, nursing, rehabilitation, and sterile reprocessing. The project was initiated at the invitation of the Department of Orthopaedics at Makerere University and Mulago Hospital in Kampala. The project is a collaboration between Canadian and Ugandan orthopaedic surgeons and is driven by the needs identified by the Ugandan surgeons. The program has also worked with collaborators to develop several technologies aimed at reducing the cost of providing orthopaedic care without compromising quality. As orthopaedic trauma capacity in Uganda advances, USTOP strives to continually evolve and provide relevant support to colleagues in Uganda to ensure that changes result in sustainable improvements in patient care.

The Socioeconomic Implications of Isolated Tibial and Femoral Fractures from Road Traffic Injuries in Uganda.

BACKGROUND: The purpose of this study was to determine the socioeconomic implications of isolated tibial and femoral fractures caused by road traffic injuries in Uganda. METHODS: This prospective longitudinal study included adult patients who were admitted to Uganda's national referral hospital with an isolated tibial or femoral fracture. The primary outcome was the time to recovery following injury. We assessed recovery using 4 domains: income, employment status, health-related quality of life (HRQoL) recovery, and school attendance of the patients' dependents. RESULTS: The majority of the study participants (83%) were employed, and they were the main income earner for their household (74.0%) at the time of injury, earning a mean annual income of 2,375 U.S. dollars (USD). All of the patients had been admitted with the intention of surgical treatment; however, because of resource constraints, only 56% received operative treatment. By 2 years postinjury, only 63% of the participants had returned to work, and 34% had returned to their previous income level. Overall, the mean monthly income was 62% less than preinjury earnings, and participants had accumulated 1,069 USD in debt since the injury; 41% of the participants had regained HRQoL scores near their baseline, and 62% of school-aged dependents, enrolled at the time of injury, were in school at 2 years postinjury. CONCLUSIONS: At 2 years postinjury, only 12% of our cohort of Ugandan patients who had sustained an isolated tibial or femoral fracture from a road traffic injury had recovered both economically and physically. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

When Surgical Resources are Severely Constrained, Who Receives Care? Determinants of Access to Orthopaedic Trauma Surgery in Uganda.

BACKGROUND: In low- and middle-income countries, the volume of traumatic injuries requiring orthopaedic intervention routinely exceeds the capacity of available surgical resources. The objective of this study was to identify predictors of surgical care for lower extremity fracture patients at a high-demand, resource-limited public hospital in Uganda. METHODS: Skeletally mature patients admitted with the intention of definitive surgical treatment of an isolated tibia or femur fractures to the national referral hospital in Uganda were recruited to participate in this study. Demographic, socioeconomic, and clinical data were collected through participant interviews at the time of injury and 6 months post-injury. Social capital (use of social networks to gain access to surgery), financial leveraging, and ethnicity were also included as variables in this analysis. A probit estimation model was used to identify independent and interactive predictors of surgical treatment. RESULTS: Of the 64 patients included in the final analysis, the majority of participants were male (83%), with a mean age of 40.6, and were injured in a motor vehicle accident (77%). Due to resource constraints, only 58% of participants received surgical care. The use of social capital and femur fractures were identified as significant predictors of receiving surgical treatment, with social capital emerging as the strongest predictor of access to surgery (p < 0.05). CONCLUSION: Limited infrastructure, trained personnel, and surgical supplies rations access to surgical care. In this environment, participants with advantageous social connections were able to self-advocate for surgery where demand for these services greatly exceeded available resources.

Economic loss due to traumatic injury in Uganda: The patient's perspective.

INTRODUCTION: Traumatic injury is a growing public health concern globally, and is a major cause of death and disability worldwide. The purpose of this study was to quantify the socioeconomic impact of lower extremity fractures in Uganda. METHODS: All adult patients presenting acutely to Uganda's national referral hospital with a single long bone lower extremity fracture in October 2013 were recruited. Consenting patients were surveyed at admission and again at six-months and 12-months post-injury. The primary outcome was the cumulative 12-month post-injury loss in income. Secondary outcome measures included the change in health-related quality of life (HRQoL) and the injury's effect on school attendance for the patients' dependents. RESULTS: Seventy-four patients were recruited during the study period. Sixty-four (86%) of the patients were available for 12-months of follow-up. Compared to pre-injury earnings, patients lost 88.4% ($1822 USD) of their annual income in the 12-months following their injury. To offset this loss in income, patients borrowed an average of 28% of their pre-injury annual income. Using the EuroQol-5D instrument, the mean HRQoL decreased from 0.91 prior to the injury to 0.39 (p<0.0001) at 12-months post-injury. Ninety-three percent of school-aged dependents missed at least one month of school during their guardian's recovery and only 61% had returned to school by 12-months post-injury. CONCLUSION: This study demonstrates that lower extremity fractures in Uganda had a profound impact on the socioeconomic status of the individuals in our sample population, as well as the socioeconomic health of the family unit.

Racial and ethnic disparities in disease activity in patients with rheumatoid arthritis.

BACKGROUND: Observational studies of patients with rheumatoid arthritis have suggested that racial and ethnic disparities exist for minority populations. We compared disease activity and clinical outcomes across racial and ethnic groups using data from a large, contemporary US registry. METHODS: We analyzed data from 2 time periods (2005-2007 and 2010-2012). The Clinical Disease Activity Index was examined as both a continuous measure and a dichotomous measure of disease activity states. Outcomes were compared in a series of cross-sectional and longitudinal multivariable regression models. RESULTS: For 2005-2007, significant differences of mean disease activity level (P < .001) were observed across racial and ethnic groups. Over the 5-year period, modest improvements in disease activity were observed across all groups, including whites (3.7; 95% confidence interval [CI], 3.2-4.1) compared with African Americans (4.3; 95% CI, 2.7-5.8) and Hispanics (2.7; 95% CI, 1.2-4.3). For 2010-2012, significant differences of mean disease activity level persisted (P < .046) across racial and ethnic groups, ranging from 11.6 (95% CI, 10.4-12.8) in Hispanics to 10.7 (95% CI, 9.6-11.7) in whites. Remission rates remained significantly different across racial/ethnic groups across all models for 2010-2012, ranging from 22.7 (95% CI, 19.5-25.8) in African Americans to 27.4 (95% CI, 24.9-29.8) in whites. CONCLUSIONS: Despite improvements in disease activity across racial and ethnic groups over a 5-year period, disparities persist in disease activity and clinical outcomes for minority groups versus white patients.

Gene expression signatures predictive of early response and outcome in high-risk childhood acute lymphoblastic leukemia: A Children's Oncology Group Study [corrected].

PURPOSE: To identify children with acute lymphoblastic leukemia (ALL) at initial diagnosis who are at risk for inferior response to therapy by using molecular signatures. PATIENTS AND METHODS: Gene expression profiles were generated from bone marrow blasts at initial diagnosis from a cohort of 99 children with National Cancer Institute-defined high-risk ALL who were treated uniformly on the Children's Oncology Group (COG) 1961 study. For prediction of early response, genes that correlated to marrow status on day 7 were identified on a training set and were validated on a test set. An additional signature was correlated with long-term outcome, and the predictive models were validated on three large, independent patient cohorts. Results We identified a 24-probe set signature that was highly predictive of day 7 marrow status on the test set (P = .0061). Pathways were identified that may play a role in early blast regression. We have also identified a 47-probe set signature (which represents 41 unique genes) that was predictive of long-term outcome in our data set as well as three large independent data sets of patients with childhood ALL who were treated on different protocols. However, we did not find sufficient evidence for the added significance of these genes and the derived predictive models when other known prognostic features, such as age, WBC, and karyotype, were included in a multivariate analysis. CONCLUSION: Genes and pathways that play a role in early blast regression may identify patients who may be at risk for inferior responses to treatment. A fully validated predictive gene expression signature was defined for high-risk ALL that provided insight into the biologic mechanisms of treatment failure.

Validation of English and Spanish-language versions of a screening questionnaire for rheumatoid arthritis in an underserved community.

OBJECTIVE: Questionnaires to screen for rheumatoid arthritis (RA) have been tested in groups that were primarily well educated and Caucasian. We sought to validate the RA questions of the Connective Tissue Disease Screening Questionnaire (CSQ) in ethnic minorities in an underserved community, and to test a Spanish-language version. METHODS: The Spanish-language version was developed by 2 native speakers. Consecutive English-speaking or Spanish-speaking patients in a community-based rheumatology practice completed the questionnaire. Diagnoses were confirmed by medical record review. Sensitivity and specificity of the questionnaire for a diagnosis of RA were computed for each language version, using 2 groups as controls: patients with noninflammatory conditions, and participants recruited from the community. RESULTS: The English-language version was tested in 53 patients with RA (79% ethnic minorities; mean education level 11.3 yrs), 85 rheumatology controls with noninflammatory conditions, and 82 community controls. Using 3 positive responses as indicating a positive screening test, the sensitivity of the questionnaire was 0.77, the specificity based on rheumatology controls was 0.45, and the specificity based on community controls was 0.94. The Spanish-language version was tested in 55 patients with RA (mean education level 7.8 yrs), 149 rheumatology controls, and 88 community controls. The sensitivity of the Spanish-language version was 0.87, with specificities of 0.60 and 0.97 using the rheumatology controls and community controls, respectively. CONCLUSION: The sensitivity of the English-language version of the RA questions of the CSQ was lower in this study than in other cohorts, reflecting differences in the performance of the questions in different ethnic or socioeconomic groups. The Spanish-language version demonstrated good sensitivity, and both had excellent specificity when tested in community controls.

Clinical significance of colonoscopic findings associated with colonic thickening on computed tomography: is colonoscopy warranted when thickening is detected?

GOAL: To determine the utility of colonoscopy in the management of patients with abdominal pain found to have colonic thickening on computed tomography (CT). BACKGROUND: CT is often used in the investigation of abdominal pain. Clinical guidelines regarding colonoscopy when colonic wall thickening is reported at CT are lacking. STUDY: From July 2000 to April 2004, the abdominal CT reports of all patients at a major teaching hospital who were investigated for abdominal pain were reviewed. Cases were selected if any colonic wall thickening was reported. Patients were excluded if they had a previously diagnosed gastrointestinal condition, or if they had not undergone colonoscopy within 30 days of the abnormal CT. Clinical, endoscopic, and pathologic data were extracted from the medical records of all eligible patients. RESULTS: One hundred seven cases were identified. Of these, 8 (7.4%) had colorectal adenocarcinoma. In 10 patients (9.3%), a new diagnosis of inflammatory bowel disease (IBD) was made. Sixteen (15.0%) had findings consistent with infectious colitis, 39 (36.4%) ischemic colitis, and 6 patients (5.6%) had miscellaneous findings possibly responsible for the colonic thickening (diverticulitis, appendicitis, proctitis, and melanosis coli). In 28 patients (26.1%), no abnormality was found that could explain the CT finding. Of those diagnosed with colorectal carcinoma or IBD, only 4 of the 18 patients (28%) presented with evidence of gastrointestinal bleeding or anemia. CONCLUSIONS: On the basis of the rate of new diagnoses of colorectal carcinoma and IBD, we recommend colonoscopy be performed after clinical evaluation in patients with abdominal pain and colonic thickening on CT.

Does delay matter? The restoration of objectively measured shoulder strength and patient-oriented outcome after immediate fixation versus delayed reconstruction of displaced midshaft fractures of the clavicle.

Outcome after surgical treatment for nonunion and malunion of midshaft displaced clavicle fractures has generally been described as favorable and equal to results of acute repair. This assumption has been based on subjective criteria, however, and no direct comparison is available in the literature. This study used objective measurements of limb function to compare outcome in patients who underwent delayed operative intervention for nonunion and malunion with the outcome of patients who underwent immediate open reduction and internal fixation after displaced clavicle fracture. All patients had sustained completely displaced, closed, isolated midshaft clavicle fractures, of whom 15 had undergone acute open reduction and internal fixation with a compression plate at a mean of 0.6 months after injury (acute group). Another 15 patients had undergone delayed reconstruction with open reduction, bone grafting, and compression plate fixation for nonunion or malunion a mean of 63 months after injury (delayed group). The 2 groups were similar in age, gender, original fracture characteristics, and mechanism of injury. Complete assessment included standard history and physical examination, the Disabilities of the Arm, Shoulder and Hand (DASH) score and Constant Shoulder Score, subjective rating of outcome satisfaction, and objective muscle strength testing using a previously validated and published protocol on the Baltimore Therapeutic Equipment (BTE) work simulator. There were no significant differences between acute fixation and delayed reconstruction groups with regard to strength of shoulder flexion (acute, 94%; delayed, 93%; P = .82), shoulder abduction (acute, 97%; delayed, 97%; P = .92), external rotation (acute, 97%; delayed, 90%; P = .11), or internal rotation (acute, 98%; delayed, 96%; P = .55). Constant scores in the acute group were superior (acute, 95; delayed, 89; P = .02), but differences in DASH scores were not significant (acute, 3.0; delayed, 7.2; P = .15). Shoulder flexion muscle endurance was significantly decreased in the delayed group (acute, 109%; delayed, 80%; P = .05). Differences in muscle endurance in other planes were not significantly different (abduction endurance: acute, 107%; delayed, 81%; P = .24). Both groups rated their satisfaction with the procedure as excellent. Late reconstruction of nonunion and malunion after displaced midshaft fractures of the clavicle is a reliable and reproducible procedure that results in restoration of objective muscle strength similar to that seen with immediate fixation; however, there are subtle decreases in endurance strength and outcome compared with acute fracture repair. This information should not be used to justify primary operative repair in isolation but is useful in decision-making when counseling patients with displaced midshaft fractures of the clavicle.

Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: a Children's Oncology Group study.

Outcome for children with childhood acute lymphoblastic leukemia (ALL) who relapse is poor. To gain insight into the mechanisms of relapse, we analyzed gene-expression profiles in 35 matched diagnosis/relapse pairs as well as 60 uniformly treated children at relapse using the Affymetrix platform. Matched-pair analyses revealed significant differences in the expression of genes involved in cell-cycle regulation, DNA repair, and apoptosis between diagnostic and early-relapse samples. Many of these pathways have been implicated in tumorigenesis previously and are attractive targets for intervention strategies. In contrast, no common pattern of changes was observed among late-relapse pairs. Early-relapse samples were more likely to be similar to their respective diagnostic sample while we noted greater divergence in gene-expression patterns among late-relapse pairs. Comparison of expression profiles of early- versus late-relapse samples indicated that early-relapse clones were characterized by overexpression of biologic pathways associated with cell-cycle regulation. These results suggest that early-relapse results from the emergence of a related clone, characterized by the up-regulation of genes mediating cell proliferation. In contrast, late relapse appears to be mediated by diverse pathways.

Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction.

To determine whether gene expression profiling could improve risk classification and outcome prediction in older acute myeloid leukemia (AML) patients, expression profiles were obtained in pretreatment leukemic samples from 170 patients whose median age was 65 years. Unsupervised clustering methods were used to classify patients into 6 cluster groups (designated A to F) that varied significantly in rates of resistant disease (RD; P < .001), complete response (CR; P = .023), and disease-free survival (DFS; P = .023). Cluster A (n = 24), dominated by NPM1 mutations (78%), normal karyotypes (75%), and genes associated with signaling and apoptosis, had the best DFS (27%) and overall survival (OS; 25% at 5 years). Patients in clusters B (n = 22) and C (n = 31) had the worst OS (5% and 6%, respectively); cluster B was distinguished by the highest rate of RD (77%) and multidrug resistant gene expression (ABCG2, MDR1). Cluster D was characterized by a "proliferative" gene signature with the highest proportion of detectable cytogenetic abnormalities (76%; including 83% of all favorable and 34% of unfavorable karyotypes). Cluster F (n = 33) was dominated by monocytic leukemias (97% of cases), also showing increased NPM1 mutations (61%). These gene expression signatures provide insights into novel groups of AML not predicted by traditional studies that impact prognosis and potential therapy.