Factors that influence surgical decision-making for geriatric displaced femoral neck fractures: Bullet Health Analysis (BHA) I : Worldwide Orthopaedic Research Collaboration: Leveraging Big Data (WORLD) I.

PURPOSE: The management of geriatric femoral neck fractures, which includes options like hemiarthroplasty (HA), total hip arthroplasty (THA), and fixation, exhibits regional and healthcare setting variations. However, there is a lack of information on global variations in practice patterns and surgical decision factors for this injury. METHODS: Survey data were collected from April 2020 to June 2023 via Orthobullets Case Studies, a global clinical case collaboration platform hosted on a prominent orthopedic educational website. Collaboratively developed standardized polls, based on the best available evidence and a comprehensive, peer-reviewed, evidence-based item list, were used to capture surgeons' treatment preferences worldwide. Subsequent analyses explored preferences within subspecialties and practice settings. Multivariable regression analysis identified associations between subspecialty, practice type, the likelihood of choosing THA, and the preferred femoral fixation method. RESULTS: Our study encompassed 2595 respondents from 76 countries. Notably, 51.5% of participants (n = 1328; 51.5%, 95% CI 49.6-53.4%) leaned towards THA and 44.9% for HA, while 3.6% favoured surgical fixation. Respondents affiliated with academic institutions and large non-university-affiliated hospitals were 1.74 times more likely to favour THA, and arthroplasty specialists exhibited a 1.77-fold preference for THA. There was a 19-fold variation for cemented femoral fixation between the United Kingdom (UK) and USA with the UK favouring cemented fixation. CONCLUSION: Our study reveals a significant shift towards THA preference for managing geriatric femoral neck fractures, influenced by subspecialty and practice settings. We also observed a pronounced predominance of cement fixation in specific geographic locations. These findings highlight the evolving fracture management landscape, emphasizing the need for standardization and comprehensive understanding across diverse healthcare settings.

What Is the Safe Window from Definitive Fixation to Flap Coverage in Type 3B Open Tibia Fractures? Supporting Plastics and Orthopaedics Alliance in Reducing Trauma Adverse Events (SPARTA).

OBJECTIVES: To delineate whether a "safe" window exists for timing from definitive fixation to definitive soft tissue coverage in the treatment of open tibial diaphyseal fractures requiring flap coverage. DESIGN: International multicenter, retrospective comparative cohort study. PATIENTS/PARTICIPANTS: Three hundred and seventy-three (n = 373) patients who sustained an open tibial shaft fracture requiring flap coverage. METHODS: We evaluated the deep infection rates based on the timing between the definitive fixation and flap coverage. We determined several intervals of time from the day of definitive fixation (regardless of time from injury) and flap coverage. If performed on the same operative setting these were considered day 0. We evaluated coverage after 2 and 5 days from definitive fixation based on time versus infection rate curve inflection points. We adjusted for time to debridement and antibiotics within an hour. MAIN OUTCOME MEASUREMENT: Deep infection after definitive fixation and flap coverage. RESULTS: The mean age of the cohort was 42.4 years (SD = 18.2) and 270 were male (72.4%). The deep infection rate after flap coverage was 20.6% (77/373). Definitive fixation to flap coverage time of up to 2 days was not associated with an increased risk of infection [relative risk (RR) = 1.12; 95% confidence interval, 0.92-1.37; P = 0.26]. There was an increased risk of deep infection for more than 2 days (RR = 1.59) and >5 days (RR = 1.64). CONCLUSION: This study observed a "safe" window of up to 2 days between definitive fixation and flap coverage in open tibial shaft fractures requiring coverage before a statistical increase in risk of deep infection rate occurred. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Carbon fibre reinforced PEEK versus traditional metallic implants for orthopaedic trauma surgery: A systematic review.

INTRODUCTION: There is no literature review comparing outcomes of fixation using carbon-fibre-reinforced polyetheretherketone (CFR PEEK) compared to metal implants used in orthopaedic extremity trauma surgery. A systematic review was performed to compare CFR PEEK to metal implants for clinically-important fracture outcomes. METHODS: A search of the online databases of PubMed/Medline, EMBASE and Cochrane Database was conducted. A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A meta-analyses was performed for functional outcomes in proximal humerus fractures converting the score differences to standard mean difference units. GRADE approach was used to determine the level of certainty of the estimates. RESULTS: Two prospective randomised controlled trials and seven comparative observational studies with a total of 431 patients were included. Of the nine studies included, four compared the use of CFR PEEK against metal plates in proximal humerus fractures. Aggregated functional scores across the proximal humerus studies, there was a small signal of better improvement with CFR PEEK (SMD 0.22, 95% CI -0.03 to 0.47, p = 0.08, low certainty). Greater odds of adverse events occurred in the metal group (OR 2.34, 95% CI 0.73 to 7.55, p = 0.15, low certainty). CONCLUSIONS: Low to very low certainty evidence suggests a small improvement in functional recovery with CFR PEEK in proximal humerus fractures. This may be mediated through a small reduction in major adverse events related to fracture healing and stability. There is currently insufficient evidence to support the widespread use of CFR PEEK implants in fracture fixation. LEVEL OF EVIDENCE: Level IV.

Timing of Flap Coverage With Respect to Definitive Fixation in Open Tibia Fractures.

OBJECTIVES: We conducted a large, U.S wide, observational study of type III tibial fractures, with the hypothesis that delays between definitive fixation and flap coverage might be a substantial modifiable risk factor associated with nosocomial wound infection. DESIGN: A retrospective analysis of a multicenter database of open tibial fractures requiring flap coverage. SETTING: Fourteen level-1 trauma centers across the United States. PATIENTS: Two hundred ninety-six (n = 296) consecutive patients with Gustilo III open tibial fractures requiring flap coverage at 14 trauma centers were retrospectively analyzed from a large orthopaedic trauma registry. We collected demographics and the details of surgical care. We investigated the patient, and treatment factors leading to infection, including the time from various points in care to the time of soft-tissue coverage. INTERVENTION: Delay definitive fixation and flap coverage in tibial type III fractures. MAIN OUTCOME MEASUREMENTS: (1) Results of multivariate regression with time from injury to coverage, debridement to coverage, and definitive fixation to coverage in the model, to determine which delay measurement was most associated with infection. (2) A second multivariate model, including other factors in addition to measures of flap delay, to provide the estimate between delay and infection after adjustment for confounding. RESULTS: Of 296 adults (227 M: 69 F) with open Gustilo type III tibial fractures requiring flap coverage, 96 (32.4%) became infected. In the multivariate regression, the time from definitive fixation to flap coverage was most predictive of subsequent wound infection (odds ratio 1.04, 95% confidence interval 1.01 to 1.08, n = 260, P = 0.02) among the time measurements. Temporary internal fixation was not associated with an increased risk of infection in both univariate (P = 0.59) or multivariate analyses (P = 0.60). Flap failure was associated with the highest odds of infection (odds ratio 6.83, 95% confidence interval 3.26 to 14.27, P < 0.001). CONCLUSION: Orthoplastic teams that are dedicated to severe musculoskeletal trauma, that facilitate coordination of definitive fixation and flap coverage, will reduce the infection rates in Gustilo type III tibial fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Definitive Fixation Outcomes of Open Tibial Shaft Fractures: Systematic Review and Network Meta-analysis.

OBJECTIVES: To delineate if there were differences in outcomes between definitive fixation strategies in open tibial shaft fractures. DATA SOURCES: MEDLINE, EMBASE, CENTRAL, and OpenGrey. STUDY SELECTION: Randomized and Quasi-randomized studies analyzing adult patients (>18 years) with open tibial shaft fractures (AO-42), undergoing definitive fixation treatment of any type. DATA EXTRACTION: Data regarding patient demographics, definitive bony/soft-tissue management, irrigation, type of antibiotics, and follow-up. Definitive intervention choices included unreamed intramedullary nailing (UN), reamed intramedullary nailing, plate fixation, multiplanar, and uniplanar external fixation (EF). The primary outcome was unplanned reoperation rate. Cochrane risk of bias tool and Grading of Recommendation Assessment, Development and Evaluation systems were used for quality analysis. DATA SYNTHESIS: A random-effects meta-analysis of head-to-head evidence, followed by a network analysis that modeled direct and indirect data was conducted to provide precise estimates [relative risk (RR) and associated 95% confidence interval (95% CI)]. RESULTS: In open tibial shaft fractures, direct comparison UN showed a lower risk of unplanned reoperation versus EF (RR 0.67, 95% CI 0.43-1.05, P = 0.08, moderate confidence). In Gustilo type III open fractures, the risk reduction with nailing compared with EF was larger (RR 0.61, 95% CI 0.37-1.01, P = 0.05, moderate confidence). UN had a lower reoperation risk compared with reamed intramedullary nailing (RR 0.91, 95% CI 0.58-1.4, P = 0.68, low confidence); however, this was not significant and did not demonstrate a clear advantage. CONCLUSIONS: Intramedullary nailing reduces the risk of unplanned reoperation by a third compared with EF, with a slightly larger reduction in type III open fractures. Future trials should focus on major complication rates and health-related quality of life in high-grade tibial shaft fractures. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

A Reevaluation of the Risk of Infection Based on Time to Debridement in Open Fractures: Results of the GOLIATH Meta-Analysis of Observational Studies and Limited Trial Data.

BACKGROUND: Open fractures are one of the leading causes of disability worldwide. The threshold time to debridement that reduces the infection rate is unclear. METHODS: We searched all available databases to identify observational studies and randomized trials related to open fracture care. We then conducted an extensive meta-analysis of the observational studies, using raw and adjusted estimates, to determine if there was an association between the timing of initial debridement and infection. RESULTS: We identified 84 studies (18,239 patients) for the primary analysis. In unadjusted analyses comparing various "late" time thresholds for debridement versus "early" thresholds, there was an association between timing of debridement and surgical site infection (odds ratio [OR] = 1.29, 95% confidence interval [CI] = 1.11 to 1.49, p < 0.001, I2 = 30%, 84 studies, n = 18,239). For debridement performed between 12 and 24 hours versus earlier than 12 hours, the OR was higher in tibial fractures (OR = 1.37, 95% CI = 1.00 to 1.87, p = 0.05, I2 = 19%, 12 studies, n = 2,065), and even more so in Gustilo type-IIIB tibial fractures (OR = 1.46, 95% CI = 1.13 to 1.89, p = 0.004, I2 = 23%, 12 studies, n = 1,255). An analysis of Gustilo type-III fractures showed a progressive increase in the risk of infection with time. Critical time thresholds included 12 hours (OR = 1.51, 95% CI = 1.28 to 1.78, p < 0.001, I2 = 0%, 16 studies, n = 3,502) and 24 hours (OR = 2.17, 95% CI = 1.73 to 2.72, p < 0.001, I2 = 0%, 29 studies, n = 5,214). CONCLUSIONS: High-grade open fractures demonstrated an increased risk of infection with progressive delay to debridement. LEVEL OF EVIDENCE: Prognostic Level IV. See Instruction for Authors for a complete description of the levels of evidence.

The Burden of Spine Fractures in India: A Prospective Multicenter Study.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: The objectives of this study were (1) to determine the characteristics of patients sustaining spinal trauma in India and (2) to explore the association between patient or injury characteristics and outcomes after spinal trauma. METHODS: In affiliation with the ongoing INternational ORthopaedic MUlticentre Study (INORMUS), 192 patients with spinal injuries were recruited during an 8-week period (November 2011 to June 2012) from 14 hospitals in India and followed for 30-days. The primary outcome was a composite of mortality, complications, and reoperation. This was regressed on a set of 13 predictors in a multiple logistic regression model. RESULTS: Most patients were middle-aged (mean age = 51.0 years; median age = 55.5 years; range = 18.0 to 72.0 years), male (60.4%), injured from falls (72.4%), and treated in a private setting (59.9%). Fractures in the lumbar region (51.0%) were most common, followed by thoracic (30.7%) and cervical (18.2%). More than 1 in 5 (21.6%) patients experienced a treatment delay greater than 24 hours, and 36.5% arrived by ambulance. Thirty-day mortality and complication rates were 2.6% and 10.0%, respectively. Care in the public hospital system (odds ratio [OR] = 6.7, 95% CI = 1.1-41.6), chest injury (OR = 11.1, 95% CI = 1.8-66.9), and surgical intervention (OR = 4.8, 95% CI = 1.2-19.6) were independent predictors of major complications. CONCLUSIONS: Treatment in the public health care system, increased severity of injury, and surgical intervention were associated with increased risk of major complications following spinal trauma. The need for a large-scale, prospective, multicenter study taking into account spinal stability and neurologic status is feasible and warranted.

Network Meta-analysis: Users' Guide for Surgeons: Part I - Credibility.

Conventional meta-analyses quantify the relative effectiveness of two interventions based on direct (that is, head-to-head) evidence typically derived from randomized controlled trials (RCTs). For many medical conditions, however, multiple treatment options exist and not all have been compared directly. This issue limits the utility of traditional synthetic techniques such as meta-analyses, since these approaches can only pool and compare evidence across interventions that have been compared directly by source studies. Network meta-analyses (NMA) use direct and indirect comparisons to quantify the relative effectiveness of three or more treatment options. Interpreting the methodologic quality and results of NMAs may be challenging, as they use complex methods that may be unfamiliar to surgeons; yet for these surgeons to use these studies in their practices, they need to be able to determine whether they can trust the results of NMAs. The first judgment of trust requires an assessment of the credibility of the NMA methodology; the second judgment of trust requires a determination of certainty in effect sizes and directions. In this Users' Guide for Surgeons, Part I, we show the application of evaluation criteria for determining the credibility of a NMA through an example pertinent to clinical orthopaedics. In the subsequent article (Part II), we help readers evaluate the level of certainty NMAs can provide in terms of treatment effect sizes and directions.

Network Meta-analysis: Users' Guide for Surgeons: Part II - Certainty.

In the previous article (Network Meta-analysis: Users' Guide for Surgeons-Part I, Credibility), we presented an approach to evaluating the credibility or methodologic rigor of network meta-analyses (NMA), an innovative approach to simultaneously addressing the relative effectiveness of three or more treatment options for a given medical condition or disease state. In the second part of the Users' Guide for Surgeons, we discuss and demonstrate the application of criteria for determining the certainty in effect sizes and directions associated with a given treatment option through an example pertinent to clinical orthopaedics.

Which Surgical Treatment for Open Tibial Shaft Fractures Results in the Fewest Reoperations? A Network Meta-analysis.

BACKGROUND: Open tibial shaft fractures are one of the most devastating orthopaedic injuries. Surgical treatment options include reamed or unreamed nailing, plating, Ender nails, Ilizarov fixation, and external fixation. Using a network meta-analysis allows comparison and facilitates pooling of a diverse population of randomized trials across these approaches in ways that a traditional meta-analysis does not. QUESTIONS/PURPOSES: Our aim was to perform a network meta-analysis using evidence from randomized trials on the relative effect of alternative approaches on the risk of unplanned reoperation after open fractures of the tibial diaphysis. Our secondary study endpoints included malunion, deep infection, and superficial infection. METHODS: A network meta-analysis allows for simultaneous consideration of the relative effectiveness of multiple treatment alternatives. To do this on the subject of surgical treatments for open tibial fractures, we began with systematic searches of databases (including EMBASE and MEDLINE) and performed hand searches of orthopaedic journals, bibliographies, abstracts from orthopaedic conferences, and orthopaedic textbooks, for all relevant material published between 1980 and 2013. Two authors independently screened abstracts and manuscripts and extracted the data, three evaluated the risk of bias in individual studies, and two applied Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria to bodies of evidence. We included all randomized and quasirandomized trials comparing two (or more) surgical treatment options for open tibial shaft fractures in predominantly (ie, > 80%) adult patients. We calculated pooled estimates for all direct comparisons and conducted a network meta-analysis combining direct and indirect evidence for all 15 comparisons between six stabilization strategies. Fourteen trials published between 1989 and November 2011 met our inclusion criteria; the trials comprised a total of 1279 patients surgically treated for open tibial shaft fractures. RESULTS: Moderate confidence evidence showed that unreamed nailing may reduce the likelihood of reoperation compared with external fixation (network odds ratio [OR], 0.38; 95% CI, 0.23-0.62; p < 0.05), although not necessarily compared with reamed nailing (direct OR, 0.74; 95% CI, 0.45-1.24; p = 0.25). Only low- or very low-quality evidence informed the primary outcome for other treatment comparisons, such as those involving internal plate fixation, Ilizarov external fixation, and Ender nailing. Method ranking based on reoperation data showed that unreamed nailing had the highest probability of being the best treatment, followed by reamed nailing, external fixation, and plate fixation. CIs around pooled estimates of malunion and infection risk were very wide, and therefore no conclusive results could be made based on these data. CONCLUSION: Current evidence suggests that intramedullary nailing may be superior to other fixation strategies for open tibial shaft fractures. Use of unreamed nails over reamed nails also may be advantageous in the setting of open fractures, but this remains to be confirmed. Unfortunately, these conclusions are based on trials that have had high risk of bias and poor precision. Larger and higher-quality head-to-head randomized controlled trials are required to confirm these conclusions and better inform clinical decision-making. LEVEL OF EVIDENCE: Level I, therapeutic study.

Delayed versus early motion after arthroscopic rotator cuff repair: a meta-analysis.

BACKGROUND: We conducted a meta-analysis of randomized trials to compare delayed vs early motion therapy on function after arthroscopic rotator cuff repair. METHODS: We searched 4 electronic databases (Medline, Embase, Cochrane, and Physiotherapy Evidence Database [PEDro]). The methodologic quality of the included studies was assessed, and the relevant data were extracted. Data were pooled for functional outcomes, rotator cuff tear recurrence, and shoulder range of motion. Complications were reported descriptively. RESULTS: Three level I and 1 level II randomized trials were eligible and included. Pooled analysis revealed no statistically significant differences in American Shoulder and Elbow Surgeons scores between delayed vs early motion rehabilitation (mean difference [MD], 1.4; 95% confidence interval [CI], -1.8 to 4.7; P = .38, I(2) = 34%). The risk of retears after surgery did not differ statistically between treatment groups (risk ratio, 1.01; 95% CI, 0.63-1.64; P = .95). Early passive motion led to a statistically significant, although clinically unimportant, improvement in forward elevation between groups (MD, -1°; 95% CI, -2° to 0°; P = 0.04, I(2) = 0%). There was no difference in external rotation between treatment groups (MD, 1°; 95% CI, -2° to 4°; P = 0.63, I(2) = 0%). None of the included studies identified any cases of postoperative shoulder stiffness. CONCLUSIONS: The current meta-analysis did not identify any significant differences in functional outcomes and relative risks of recurrent tears between delayed and early motion in patients undergoing arthroscopic rotator cuff repairs. A statistically significant difference in forward elevation range of motion was identified; however, this difference is likely clinically unimportant.

The association between avulsions of the reflected head of the rectus femoris and labral tears: a retrospective study.

BACKGROUND: The aim of this study was to investigate if an association existed between the reflected head of rectus femoris avulsion injuries and labral tears in pediatric patients referred for magnetic resonance arthrography (MRA) or magnetic resonance imaging (MRI) evaluation. METHODS: Electronic medical records of the patients between the ages of 12 and 18 who were treated at the hospitals affiliated by McMaster University between June 2000 and November 2010 with a diagnosis of rectus femoris avulsion injuries were retrospectively identified and analyzed. Patients were included if they had magnetic resonance imaging or MRA images of their hip. RESULTS: Nine patients with avulsion injuries of the rectus femoris muscle were identified. The patient population consisted of 4 females and 5 males (range, 8 to 17 y, mean age 14 y). All injuries occurred during sports activity, which included running and kicking during soccer, skating in hockey, and a squatting exercise. MRA examination of 7 of these patients demonstrated associated labral tears. All patients were initially treated conservatively. Five patients continued to sustain from residual pain in the 9 months after the initial injury. Two of these patients with significant refractory pain were subsequently treated with hip arthroscopy. Intraoperatively, 1 small labral tear and 1 labral avulsion were identified and treated. CONCLUSIONS: This study suggests that there may be an association between avulsion of the reflected head of rectus femoris and labral injuries and that there may be an underlying spectrum of traction injuries. Patients with rectus femoris avulsion injuries with persistent symptoms may be at risk for concurrent traumatic labral tears. LEVEL OF EVIDENCE: Level 4, retrospective case series.

Predictors of nonunion and reoperation in patients with fractures of the tibia: an observational study.

BACKGROUND: Tibial shaft fractures are the most common long bone fracture and are prone to complications such as nonunion requiring reoperations to promote fracture healing. We aimed to determine the fracture characteristics associated with tibial fracture nonunion, and their predictive value on the need for reoperation. We further aimed to evaluate the predictive value of a previously-developed prognostic index of three fracture characteristics on nonunion and reoperation rate. METHODS: We conducted an observational study and developed a risk factor list from previous literature and key informants in the field of orthopaedic surgery, as well as via a sample-to-redundancy strategy. We evaluated 22 potential risk factors for the development of tibial fracture nonunion in 200 tibial fractures. We also evaluated the predictive value of a previously-identified prognostic risk index on secondary intervention and/or reoperation rate. Two individuals independently extracted the data from 200 patient electronic medical records. An independent reviewer assessed the initial x-ray, the post-operative x-ray, and all available sequential x-rays. Regression and chi-square analysis was used to evaluate potential associations. RESULTS: In our cohort of patients, 37 (18.5%) had a nonunion and 27 (13.5%) underwent a reoperation. Patients with a nonunion were 97 times (95% CI 25.8-366.5) more likely to have a reoperation. Multivariable logistic regression revealed that fractures with less than 25% cortical continuity were predictive of nonunion (odds ratio = 4.72; p = 0.02). Such fractures also accounted for all of the reoperations identified in our sample. Furthermore, our data provided preliminary validation of a previous risk index predictive of reoperation that includes the presence of a fracture gap post-fixation, open fracture, and transverse fracture type as variables, with an aggregate of fracture gap and an open fracture yielding patients with the highest risk of developing a nonunion. CONCLUSIONS: We identified a significant association between degree of cortical continuity and the development of a nonunion and risk for reoperation in tibial shaft fractures. In addition, our study supports the predictive value of a previous prognostic index, which inform discussion of prognosis following operative management of tibial fractures.

Anterior cervical discectomy with arthroplasty versus arthrodesis for single-level cervical spondylosis: a systematic review and meta-analysis.

OBJECTIVE: To estimate the effectiveness of anterior cervical discectomy with arthroplasty (ACDA) compared to anterior cervical discectomy with fusion (ACDF) for patient-important outcomes for single-level cervical spondylosis. DATA SOURCES: Electronic databases (MEDLINE, EMBASE, Cochrane Register for Randomized Controlled Trials, BIOSIS and LILACS), archives of spine meetings and bibliographies of relevant articles. STUDY SELECTION: We included RCTs of ACDF versus ACDA in adult patients with single-level cervical spondylosis reporting at least one of the following outcomes: functionality, neurological success, neck pain, arm pain, quality of life, surgery for adjacent level degeneration (ALD), reoperation and dysphonia/dysphagia. We used no language restrictions. We performed title and abstract screening and full text screening independently and in duplicate. DATA SYNTHESIS: We used random-effects model to pool data using mean difference (MD) for continuous outcomes and relative risk (RR) for dichotomous outcomes. We used GRADE to evaluate the quality of evidence for each outcome. RESULTS: Of 2804 citations, 9 articles reporting on 9 trials (1778 participants) were eligible. ACDA is associated with a clinically significant lower incidence of neurologic failure (RR = 0.53, 95% CI = 0.37-0.75, p = 0.0004) and improvement in the Neck pain visual analogue scale (VAS) (MD = 6.56, 95% CI = 3.22-9.90, p = 0.0001; Minimal clinically important difference (MCID) = 2.5. ACDA is associated with a statistically but not clinically significant improvement in Arm pain VAS and SF-36 physical component summary. ACDA is associated with non-statistically significant higher improvement in the Neck Disability Index Score and lower incidence of ALD requiring surgery, reoperation, and dysphagia/dysphonia. CONCLUSIONS: There is no strong evidence to support the routine use of ACDA over ACDF in single-level cervical spondylosis. Current trials lack long-term data required to assess safety as well as surgery for ALD. We suggest that ACDA in patients with single level cervical spondylosis is an option although its benefits and indication over ACDF remain in question.

Future perspectives: the need for large clinical trials.

Fragility fractures represent a growing problem with large economic and patient burdens that are likely to increase as the population ages. The elderly patient with osteopenic bone presents a unique surgical challenge with appreciable risks associated with each surgical treatment option. As demonstrated in this supplement, the current evidence suggests that the best surgical treatment options for patients with fragility fractures remains largely unknown. Additional evidence, from large clinical trials, is required before definitive treatment recommendations can be made in many cases. In this article, we review the example of the femoral neck fracture to illustrate this point.

Polymorphisms of multidrug resistance gene (MDR1) and cyclosporine absorption in de novo renal transplant patients.

BACKGROUND: Several single nucleotide polymorphisms (SNPs) in the multidrug resistance (MDR1) gene may play a role in the interindividual variation of cyclosporine A (CsA) absorption in renal transplant patients. METHODS: An analysis of CsA absorption measured by the dose- and weight-adjusted 4 hr area under the time-concentration curve, AUC(0-4)/mg doseCsA/kg, was conducted on day 3 after transplantation, in 69 de novo renal transplant patients who were genotyped for MDR1 SNPs. Follow-up pharmacogenomic analysis at 1 month posttransplant was performed utilizing dose- and weight-adjusted 2-hour postdose CsA concentration (C2). RESULTS: AUC(0-4)/mg doseCsA/kg was significantly higher (P=0.024) in (C/C)3435 individuals than in a grouped population of (C/T)3435 and (T/T)3435 patients on postoperative day 3. G2677T variants were not significantly correlated with CsA absorption (P=0.084). The number of C3435-G2677 haplotypes was the best predictor of CsA exposure. At 1 month posttransplant, no correlation was seen between MDR1 SNPs and CsA exposure. The frequency of wild-type variants for C3435T and G2677T were 61% and 77.6%, respectively. SNPs at G2677T and C3435T loci were found to be in linkage disequilibrium. CONCLUSIONS: MDR1 polymorphisms are associated with differences in CsA exposure only in the first posttransplant week.