Operative vs Nonoperative Management of Unstable Medial Malleolus Fractures: A Randomized Clinical Trial.

Importance: Unstable ankle fractures are routinely managed operatively. However, because of soft tissue and implant-related complications, recent literature has reported on the nonoperative management of well-reduced medial malleolus fractures after fibular stabilization, but with limited evidence supporting the routine application. Objective: To assess the superiority of internal fixation of well-reduced (displacement ≤2 mm) medial malleolus fractures compared with nonfixation after fibular stabilization. Design, Setting, and Participants: This superiority, pragmatic, parallel, prospective randomized clinical trial was conducted from October 1, 2017, to August 31, 2021. A total of 154 adult participants (≥16 years) with a closed, unstable bimalleolar or trimalleolar ankle fracture requiring surgery at an academic major trauma center in the UK were assessed. Exclusion criteria included injuries with no medial-sided fracture, open fractures, neurovascular injury, and the inability to comply with follow-up. Data analysis was performed in July 2022 and confirmed in September 2023. Interventions: Once the lateral (and where appropriate, posterior) malleolus had been fixed and satisfactory intraoperative reduction of the medial malleolus fracture was confirmed by the operating surgeon, participants were randomly allocated to fixation (n = 78) or nonfixation (n = 76) of the medial malleolus. Main Outcome and Measure: Olerud-Molander Ankle Score (OMAS) 1 year after randomization (range, 0-100 points, with 0 indicating worst possible outcome and 100 indicating best possible outcome). Results: Among 154 randomized participants (mean [SD] age, 56.5 [16.7] years; 119 [77%] female), 144 (94%) completed the trial. At 1 year, the median OMAS was 80.0 (IQR, 60.0-90.0) in the fixation group compared with 72.5 (IQR, 55.0-90.0) in the nonfixation group (P = .17). Complication rates were comparable. Significantly more patients in the nonfixation group developed a radiographic nonunion (20% vs 0%; P < .001), with 8 of 13 clinically asymptomatic; 1 patient required surgical reintervention for this. Fracture type and reduction quality appeared to influence fracture union and patient outcome. Conclusions and Relevance: In this randomized clinical trial comparing internal fixation of well-reduced medial malleolus fractures with nonfixation, after fibular stabilization, fixation was not superior according to the primary outcome. However, 1 in 5 patients developed a radiographic nonunion after nonfixation, and although the reintervention rate to manage this was low, the future implications are unknown. These results support selective nonfixation of anatomically reduced medial malleolar fractures after fibular stabilization. Trial Registration: ClinicalTrials.gov Identifier: NCT03362229.

Ultrasound assessment of humeral shaft nonunion risk: a feasibility and proof of concept study.

PURPOSE: To determine the feasibility and reliability of ultrasound in the assessment of humeral shaft fracture healing and estimate the accuracy of 6wk ultrasound in predicting nonunion. METHODS: Twelve adults with a non-operatively managed humeral shaft fracture were prospectively recruited and underwent ultrasound scanning at 6wks and 12wks post-injury. Seven blinded observers evaluated sonographic callus appearance to determine intra- and inter-observer reliability. Nonunion prediction accuracy was estimated by comparing images for patients that united (n = 10/12) with those that developed a nonunion (n = 2/12). RESULTS: The mean scan duration was 8 min (5-12) and all patients tolerated the procedure. At 6wks and 12wks, sonographic callus (SC) was present in 11 patients (10 united, one nonunion) and sonographic bridging callus (SBC) in seven (all united). Ultrasound had substantial intra- (weighted kappa: 6wk 0.75; 12wk 0.75) and inter-observer reliability (intraclass correlation coefficient: 6wk 0.60; 12wk 0.76). At 6wks, the absence of SC demonstrated sensitivity 50%, specificity 100%, positive predictive value (PPV) 100% and negative predictive value (NPV) 91% in nonunion prediction (overall accuracy 92%). The absence of SBC demonstrated sensitivity 100%, specificity 70%, PPV 40% and NPV 100% in nonunion prediction (overall accuracy 75%). Of three patients at risk of nonunion (Radiographic Union Score for HUmeral fractures < 8), one had SBC on 6wk ultrasound (that subsequently united) and the others had non-bridging/absent SC (both developed nonunion). CONCLUSIONS: Ultrasound assessment of humeral shaft fracture healing was feasible, reliable and may predict nonunion. Ultrasound could be useful in defining nonunion risk among patients with reduced radiographic callus formation.

Management of Lisfranc Injuries: A Critical Analysis Review.

¼: There is a spectrum of midtarsal injuries, ranging from mild midfoot sprains to complex Lisfranc fracture-dislocations. ¼: Use of appropriate imaging can reduce patient morbidity, by reducing the number of missed diagnoses and, conversely, avoiding overtreatment. Weight-bearing radiographs are of great value when investigating the so-called subtle Lisfranc injury. ¼: Regardless of the operative strategy, anatomical reduction and stable fixation is a prerequisite for a satisfactory outcome in the management of displaced injuries. ¼: Fixation device removal is less frequently reported after primary arthrodesis compared with open reduction and internal fixation based on 6 published meta-analyses. However, the indications for further surgery are often unclear, and the evidence of the included studies is of typically low quality. Further high-quality prospective randomized trials with robust cost-effectiveness analyses are required in this area. ¼: We have proposed an investigation and treatment algorithm based on the current literature and clinical experience of our trauma center.

Olecranon fractures : current treatment concepts.

Despite being one of the most common injuries around the elbow, the optimal treatment of olecranon fractures is far from established and stimulates debate among both general orthopaedic trauma surgeons and upper limb specialists. It is almost universally accepted that stable non-displaced fractures can be safely treated nonoperatively with minimal specialist input. Internal fixation is recommended for the vast majority of displaced fractures, with a range of techniques and implants to choose from. However, there is concern regarding the complication rates, largely related to symptomatic metalwork resulting in high rates of implant removal. As the number of elderly patients sustaining these injuries increases, we are becoming more aware of the issues associated with fixation in osteoporotic bone and the often fragile soft-tissue envelope in this group. Given this, there is evidence to support an increasing role for nonoperative management in this high-risk demographic group, even in those presenting with displaced and/or multifragmentary fracture patterns. This review summarizes the available literature to date, focusing predominantly on the management techniques and available implants for stable fractures of the olecranon. It also offers some insights into the potential avenues for future research, in the hope of addressing some of the pertinent questions that remain unanswered.Cite this article: Bone Joint J 2023;105-B(2):112-123.

Total knee arthroplasty in patients with severe obesity provides value for money despite increased complications.

AIMS: Access to total knee arthroplasty (TKA) is sometimes restricted for patients with severe obesity (BMI ≥ 40 kg/m2). This study compares the cost per quality-adjusted life year (QALY) associated with TKA in patients with a BMI above and below 40 kg/m2 to examine whether this is supported. METHODS: This single-centre study compared 169 consecutive patients with severe obesity (BMI ≥ 40 kg/m2) (mean age 65.2 years (40 to 87); mean BMI 44.2 kg/m2 (40 to 66); 129/169 female) undergoing unilateral TKA to a propensity score matched (age, sex, preoperative Oxford Knee Score (OKS)) cohort with a BMI < 40 kg/m2 in a 1:1 ratio. Demographic data, comorbidities, and complications to one year were recorded. Preoperative and one-year patient-reported outcome measures (PROMs) were completed: EuroQol five-dimension three-level questionnaire (EQ-5D-3L), OKS, pain, and satisfaction. Using national life expectancy data with obesity correction and the 2020 NHS National Tariff, QALYs (discounted at 3.5%), and direct medical costs accrued over a patient's lifetime, were calculated. Probabilistic sensitivity analysis (PSA) was used to model variation in cost/QALY for each cohort across 1,000 simulations. RESULTS: All PROMs improved significantly (p < 0.05) in both groups without differences between groups. Early complications were higher in BMI ≥ 40 kg/m2: 34/169 versus 52/169 (p = 0.050). A total of 16 (9.5%) patients with a BMI ≥ 40 kg/m2 were readmitted within one year with six reoperations (3.6%) including three (1.2%) revisions for infection. Assuming reduced life expectancy in severe obesity and revision costs, TKA in patients with a BMI ≥ 40 kg/m2 costs a mean of £1,013/QALY (95% confidence interval £678 to 1,409) more over a lifetime than TKA in patients with BMI < 40 kg/m2. In PSA replicates, the maximum cost/QALY was £3,921 in patients with a BMI < 40 kg/m2 and £5,275 in patients with a BMI ≥ 40 kg/m2. CONCLUSION: Higher complication rates following TKA in severely obese patients result in a lifetime cost/QALY that is £1,013 greater than that for patients with BMI < 40 kg/m2, suggesting that TKA remains a cost-effective use of healthcare resources in severely obese patients where the surgeon considers it appropriate. Cite this article: Bone Joint J 2022;104-B(4):452-463.

Percutaneous Fixation of Posterior Malleolar Fractures in Patients With Unstable Ankle Fractures Treated With a Fibular Intramedullary Nail: A Description of a Technique and Review of Outcomes.

OBJECTIVES: To (1) describe the percutaneous technique used to reduce and fix a posterior malleolar fracture with anteroposterior screws in patients managed with a fibular intramedullary nail, (2) describe the selection of patients to whom this technique can be applied, and (3) report the clinical and patient reported outcome of this intervention. DESIGN: Retrospective review. SETTING: Academic orthopaedic trauma center. PATIENTS: Thirty-two consecutive patients with a mean age of 65 years (range, 39-90) over a thirteen-year period identified from a prospective database. INTERVENTION: Unstable ankle fractures managed surgically with a fibular nail and percutaneous fixation of the posterior malleolar component. MAIN OUTCOME MEASUREMENTS: The primary short-term outcome was complications related to posterior malleolar fracture fixation. The primary mid-term outcome was the Olerud-Molander Ankle Score. Secondary outcomes included the Manchester-Oxford Foot Questionnaire, EuroQol-5D, health, pain, and satisfaction. RESULTS: Thirty of the 32 (94%) posterior malleolar fractures united uneventfully. Postoperative loss of talar reduction occurred in 2 patients (6.3%), which in 1 patient (3.1%) eventually required a hindfoot nail arthrodesis. There were no soft-tissue complications related to the anteroposterior screws or the fibular nail fixation. At a mean follow-up of 3.7 years (range, 1-8), the median Olerud-Molander Ankle Score, Manchester-Oxford Foot Questionnaire, EuroQol-5D, health, pain, and satisfaction scores were 80.0, 23.4, 0.85, 80.0, 85.0, and 87.5, respectively. CONCLUSIONS: Percutaneous ankle fracture fixation with a fibular nail and posterior malleolar screws results in reliable fracture stabilization, good patient outcomes, and high treatment satisfaction. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Acute distal biceps tendon repair using cortical button fixation results in excellent short- and long-term outcomes : a single-centre experience of 102 patients.

AIMS: Acute distal biceps tendon repair reduces fatigue-related pain and minimizes loss of supination of the forearm and strength of flexion of the elbow. We report the short- and long-term outcome following repair using fixation with a cortical button techqniue. METHODS: Between October 2010 and July 2018, 102 patients with a mean age of 43 years (19 to 67), including 101 males, underwent distal biceps tendon repair less than six weeks after the injury, using cortical button fixation. The primary short-term outcome measure was the rate of complications. The primary long-term outcome measure was the abbreviated Disabilities of the Arm, Shoulder and Hand (QuickDASH) score. Secondary outcomes included the Oxford Elbow Score (OES), EuroQol five-dimension three-level score (EQ-5D-3L), satisfaction, and return to function. RESULTS: Eight patients (7.8%) had a major complication and 34 (33.3%) had a minor complication. Major complications included re-rupture (n = 3; 2.9%), unrecovered nerve injury (n = 4; 3.9%), and surgery for heterotopic ossification (n = 1; 1.0%). Three patients (2.9%) overall required further surgery for a complication. Minor complications included neurapraxia (n = 27; 26.5%) and superficial infection (n = 7; 6.9%). A total of 33 nerve injuries occurred in 31 patients (30.4%). At a mean follow-up of five years (1 to 9.8) outcomes were available for 86 patients (84.3%). The median QuickDASH, OES, EQ-5D-3L, and satisfaction scores were 1.2 (IQR 0 to 5.1), 48 (IQR 46 to 48), 0.80 (IQR 0.72 to 1.0), and 100/100 (IQR 90 to 100), respectively. Most patients were able to return to work (81/83, 97.6%) and sport (51/62,82.3%). Unrecovered nerve injury was associated with an inferior outcome according to the QuickDASH (p = 0.005), OES (p = 0.004), EQ-5D-3L (p = 0.010), and satisfaction (p = 0.024). Multiple linear regression analysis identified an unrecovered nerve injury to be strongly associated with an inferior outcome according to the QuickDASH score (p < 0.001), along with infection (p < 0.001), although re-rupture (p = 0.440) and further surgery (p = 0.652) were not. CONCLUSION: Acute distal biceps tendon repair using cortical button fixation was found to result in excellent patient-reported outcomes and health-related quality of life. Although rare, unrecovered nerve injury adversely affects outcome. Cite this article: Bone Joint J 2021;103-B(7):1284-1291.

The Fibular Intramedullary Nail Versus Locking Plate and Lag Screw Fixation in the Management of Unstable Elderly Ankle Fractures: A Cadaveric Biomechanical Comparison.

OBJECTIVES: To compare the biomechanical failure properties of the fibular intramedullary nail with locking plate and lag screw fixation in the management of unstable elderly distal fibular fractures. METHODS: Twelve fresh-frozen cadaveric lower limbs (6 matched-pairs) were studied. A simulated OTA/AO 44-B fracture was created, then randomly allocated within each pair to intramedullary nail or locking plate fixation supplemented with an interfragmentary lag screw. The limbs were secured with the foot rigidly held in 20 degrees of supination, loaded to 700N and subjected to progressive external rotation until failure. RESULTS: The mean specimen age was 86.5 years (61-97). Mean torque to failure was greater in the intramedullary nail group, but did not reach statistical significance (23.5 N·m vs. 21.6 N·m; P = 0.463). The nail failed at a significantly greater angle of rotation compared with plate fixation (66.5 degrees vs. 53.3 degrees; P = 0.046). There was no significant difference between the groups with respect to construct stiffness (P = 0.673) or energy absorbed (P = 0.075). The locking plate specimens failed through plate and screw construct pull off at the implant-bone interface. In contrast, the intramedullary nail specimens failed at the lateral ligament complex, whereas the fracture-implant construct remained intact. CONCLUSION: Intramedullary nailing and locking plate fixation have similar biomechanical characteristics when tested to failure. The benefits of the minimally invasive surgery offered by the intramedullary nail make it an attractive implant in the management of these patients.

Long-Term Outcomes of Fasciotomy for Acute Compartment Syndrome After a Fracture of the Tibial Diaphysis.

OBJECTIVES: To evaluate the short- and long-term patient-reported outcomes of acute compartment syndrome (ACS) complicating a fracture of the tibial diaphysis. DESIGN: A retrospective review. SETTING: Academic orthopaedic trauma center. PATIENTS: We retrospectively identified 559 patients from a trauma database over a 7-year period. Forty-one patients (7.3%) underwent fasciotomies for ACS and were included in the study. A matched cohort of 185 patients who did not develop ACS was used as controls. INTERVENTION: Fasciotomy for ACS. MAIN OUTCOME MEASUREMENTS: The primary short-term outcome measure was the development of complications, including infection, nonunion, and further surgery. The primary long-term outcome measure was the patient-reported EuroQol-5D-3L (EQ-5D). Secondary long-term outcomes included the Oxford Knee Score, the Manchester-Oxford Foot Questionnaire, and satisfaction. RESULTS: There was no significant difference between ACS and non-ACS groups in the overall rate of infection (17% vs. 9.2%, respectively; P = 0.14), deep infection (4.9% vs. 3.8%; P = 0.67), or nonunion (4.9% vs. 7.0%; P = 1.00). There were 206 patients (21 ACS) with long-term outcome data at a mean of 5 years (1-9). There was no significant difference between groups about the EQ-5D (P = 0.81), the Oxford Knee Score (P = 0.24), or the Manchester-Oxford Foot Questionnaire (P = 0.63). Patient satisfaction was reduced in patients who developed ACS (77 vs. 88; P = 0.039). CONCLUSION: These data suggest that when managed with urgent decompressive fasciotomies, ACS does not seem to have a significant impact on the long-term patient-reported outcome although patient satisfaction is reduced. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Medial malleolus: Operative Or Non-operative (MOON) trial protocol - a prospective randomised controlled trial of operative versus non-operative management of associated medial malleolus fractures in unstable fractures of the ankle.

BACKGROUND: There are limited data reporting the outcome of patients with non-operatively managed medial malleolus fractures compared to those treated surgically in the presence of fibular stabilisation for unstable fractures of the ankle. Conservative management could result in fewer complications, reduced surgical time and lower cost. The purpose of this study is to determine if any difference exists in patient reported and surgical outcomes 1 year after surgery between operative and non-operative treatment of medial malleolar fractures in combination with stabilisation of the lateral malleolus. METHODS/DESIGN: This is a single-centre, prospective, randomised controlled trial that aims to randomise 154 participants with an unstable ankle fracture to 'non-fixation' (n = 77) or 'fixation' (n = 77) of an associated well-reduced medial malleolus fracture following fibular stabilisation. The study will include patients ≥ 16 years of age with a closed bimalleolar or trimalleolar ankle fracture who are able to consent, complete questionnaires in the English language, and complete follow-up over a 1-year period. Randomisation will occur intra-operatively when the medial malleolus fracture is deemed 'well-reduced', with 2 mm or less of fluoroscopic displacement. The technique for fixation of both the medial and lateral malleoli is at the discretion of the operating surgeon. Patient-reported, observer-rated, and radiographic assessments will be collected at baseline and then at the following post-operative assessment points: 2 weeks, 6 weeks and 1 year. Postal questionnaire outcome data will be collected at 3 and 6 months. The primary outcome measure will be the Olerud Molander Ankle Score (OMAS) at 1 year following surgery. Secondary outcome measures will include the Manchester-Oxford Foot Questionnaire (MOXFQ), EuroQol-5D (EQ-5D), pain, treatment satisfaction, time to return to activity, operative tourniquet time, and complications. DISCUSSION: There is only one previous randomised trial comparing non-fixation with fixation of associated medial malleolus fractures but that was limited by the lack of baseline patient-reported outcome data and an inferior sample size. This current prospective trial aims to provide high-quality evidence regarding the requirement for medial malleolar fixation in unstable ankle fractures. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03362229 . Registered retrospectively on 5 December 2017.

High Risk of Further Surgery After Radial Head Replacement for Unstable Fractures: Longer-term Outcomes at a Minimum Follow-up of 8 Years.

BACKGROUND: The evidence for treating acute, unreconstructable radial head fractures in unstable elbows with radial head replacement predominantly consists of short- to mid-term follow-up studies with a heterogenous mix of implants and operative techniques. Data on longer-term patient-reported outcomes after radial head replacement is lacking. QUESTIONS/PURPOSES: (1) What proportion of patients undergo revision or implant removal after radial head replacement? (2) At a minimum of 8 years follow-up, what are the patient-reported outcomes (QuickDASH, Oxford Elbow Score, and EuroQol-5D)? (3) What factors are associated with a superior long-term patient-reported outcome, according to the QuickDASH? METHODS: Between September 1994 and September 2010, we surgically treated 157 patients for acute radial head fractures. We excluded patients where the radial head was excised (n = 21), internally fixed (n = 15), or replaced as a secondary procedure after failed internal fixation (n = 2). A total of 119 patients who underwent radial head replacement surgery for an acute unreconstructable fracture were included, with a mean age of 50 years (range 15 to 93 ± 19 years), and 53% of patients (63) were women. All but two implants were uncemented, loose-fitting, monopolar prostheses, of which 86% (102) were metallic and 14% (17) were silastic. Implants were only cemented if they appeared unstable within the proximal radius. Silastic implants were used in the earlier series and replaced by metallic implants starting in 2000. We reviewed electronic records to document postoperative complications and prosthesis revision and removal. A member of the local research team (THC, CDC) who was not previously involved in patient care contacted patients to confirm complications, reoperations and to obtain long-term patient-reported outcomes scores. Nineteen patients had died at the point of outcome score collection. Of the remaining 100 patients, 80 were contacted (67% of total cohort), at a median of 11 years (range 8 to 24 years) after injury. The primary outcome measure was the QuickDASH score. RESULTS: Of 119 patients, 25% (30) underwent reoperation, with three patients undergoing revision and 27 patients undergoing prosthesis removal at a median of 7 months (range 0 to 125 months). Twenty-one of 30 procedures (70%) occurred within 1 year after implantation. Kaplan-Meier survivorship analysis demonstrated a cumulative implant survival rate of 71%. In the 80 patients contacted, the mean QuickDASH score was 13 ± 14, the mean Oxford Elbow Score was 43 ± 6, and the median EuroQol-5D score was 0.8 (-0.3 to 1.0). After controlling for covariates, we found that prothesis revision or removal (p = 0.466) and prosthesis type (p = 0.553) were not associated with patient-reported outcome, according to the QuickDASH. CONCLUSIONS: The management of acute unreconstructable fractures of the radial head in unstable elbow injuries with radial head replacement has a high risk of reoperation. Patients must be counselled regarding this risk of secondary intervention, of which the peak risk appears to be within 1 year after implantation. Despite this, patients report low disability according to the QuickDASH at a minimum follow-up of 8 years. LEVEL OF EVIDENCE: Level IV, therapeutic study.

A prospective randomised controlled trial of operative versus non-operative management of fractures of the humeral diaphysis: the HUmeral Shaft Fracture FIXation (HU-FIX) Study protocol.

BACKGROUND: Humeral shaft fractures constitute around 1% of adult fractures in the UK, with an annual incidence of approximately 13 per 100,000 population. Historically, these injuries have been primarily managed non-operatively, with operative fixation reserved for specific indications. Although some recent retrospective studies have suggested there are potential benefits of operative fixation over humeral bracing, there is a deficiency in level 1 evidence to support operative management as the primary treatment for humeral shaft fractures. METHODS/DESIGN: This single-centre prospective randomised controlled trial aims to recruit 70 adult patients with an isolated closed fracture of the humeral diaphysis into one of two treatment arms: operative (n = 35) or non-operative (n = 35). The operative arm will undergo open reduction and internal fixation (ORIF) of the fracture using a standard fixation technique (plate and screws). The non-operative arm will be fitted with a prefabricated humeral brace until fracture union. All patients will be followed up for 1 year post-intervention. The primary outcome measure will be the Disabilities of the Arm, Shoulder and Hand (DASH) score at 3 months post-intervention. Secondary outcome measures will include pain, treatment complications, return to work or sporting activities, shoulder and elbow range of motion, radiographic assessment, EuroQol (EQ-5D) Health Outcome score and 12-item Short Form (SF-12) Health Survey score. A health economic analysis will be performed to compare the cost implications of each treatment strategy. DISCUSSION: This randomised controlled trial will provide level 1 evidence comparing a standard ORIF technique against functional bracing for isolated closed humeral shaft fractures. The investigators hope that the study results will assist surgeons in their decision-making when managing patients with these injuries. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03689335 . Registered on 28 September 2018 (retrospectively).

Selective fixation of the medial malleolus in unstable ankle fractures.

BACKGROUND: Whilst the lateral malleolus appears to be crucial in controlling anatomical reduction of the talus, the role of the medial malleolus is less clear. Medial sided complications including infection, damage to local structures and symptomatic hardware are not without morbidity. This study compares the outcomes of patients with bimalleolar or trimalleolar ankle fractures who underwent fibular nail stabilisation with or without medial malleolar fixation. METHODS: From a prospective single-centre trauma database, we identified 342 patients over a nine-year period who underwent fibular nail insertion to stabilise a bimalleolar or trimalleolar ankle fracture. Isolated lateral malleolar fractures were excluded. Demographic data, clinical outcomes, radiographic evaluation, return to work and sport, and patient reported outcomes, including Olerud-Molander Ankle Score (OMAS), EuroQol-5D (EQ-5D) and Manchester-Oxford Foot Questionnaire (MOXFQ) were collected. RESULTS: This study included 247 patients with a mean age of 66.7 years (range, 25-96 years), of whom 200 were female (81%). Medial malleolar fixation was not performed in 54 cases (22%). There was no significant difference between groups with respect to failure of fixation (p = 0.634) or loss of talar reduction (p = 0.157). No patient required surgery for a symptomatic medial malleolar non-union. Medial sided complications occurred in 32 (16%) of the fixation group, of whom 20 (10%) required further surgery. At a mean mid-term follow-up of 4.8 years (range, 8 months - 9 years) there was no significant difference between the non-fixation and fixation groups with respect to the median OMAS (85 vs 80; p = 0.885) or median EQ-5D (0.80 vs 0.81; p = 0.846). Patient satisfaction was not significantly different between the two groups (85/100 vs 87/100; p = 0.410). CONCLUSION: Non-operative management of the medial malleolar component of an unstable ankle fracture treated with a fibular nail may reduce the rate of post-operative complications without compromising the patient reported outcome.

Open Reduction and Internal Fixation of Distal Tibial Pilon Fractures.

Intra-articular fractures of the distal end of the tibia, more commonly referred to as pilon fractures, account for approximately 5% to 7% of all tibial fractures1,2. Type-C fractures present a unique surgical challenge: a total articular fracture contained within a vulnerable soft-tissue envelope. Treatment options include internal fixation3, external fixation with or without limited internal fixation4, and primary ankle arthrodesis2. The management, and particularly the timing, of surgery is often dictated by the patient's general state of health, soft-tissue condition, and fracture comminution as well as the experience of the surgeon. The surgical goals are to reconstruct the articular surface of the plafond, restore limb alignment, and protect the soft-tissue envelope. Since the publication of the seminal paper by Sirkin et al.5 in 1999, it has become orthopaedic orthodoxy to stage the surgery of pilon fractures, adopting a so-called span, scan, and plan approach. We more commonly operate early, and in a recently published retrospective review of 102 type-C pilon fractures in 99 patients, 73 patients (73 fractures; 71.6%) underwent primary internal fixation6. Outcomes were equivalent to the results of a staged protocol: 36 complications in 28 patients (28 fractures; 27.5%), with superficial (n = 9) and deep (n = 9) infection being the most common. Forty-one fractures (40.2%) required at least 1 additional operation, with removal of symptomatic metalwork being the primary indication (n = 30). No patient required an amputation. At a mean follow-up of 6 years, both the mean Foot and Ankle Disability Index (FADI) and mean Foot and Ankle Outcome Score (FAOS) were 76 (range, 0 to 100). Median patient satisfaction was 7 of 10. The results demonstrated a satisfactory outcome following primary internal fixation in appropriately selected patients. This instructional video outlines the surgical technique used. The key steps of the procedure are (1) preoperative planning with assessment of imaging and soft tissues; (2) application of a thigh tourniquet and placement of the patient predominantly in the supine position, unless the fracture configuration requires a prone position; (3) intraoperative use of a spanning external fixator; (4) careful exposure of the distal end of the tibia, dictated by the fracture configuration, with the anterolateral, anteromedial, and direct medial approaches most commonly used, elevating full-thickness tissue flaps wherever possible; (5) fracture reduction and fixation through a joint arthrotomy and fracture windows, allowing visualization of the articular margins, followed by initial Kirschner wire stabilization and definitive lag screw fixation; (6) application of a low-profile, locking or nonlocking plate in either buttress or bridging mode, joining the articular-metaphyseal block to the distal tibial diaphysis; (7) fixation of an associated fibular fracture, typically with intramedullary nailing and removal of the external fixator; (8) layered closure according to surgeon preference; and (9) postoperative protocol, consisting of a removable orthosis with a strict non-weight-bearing restriction for up to 3 months.

Optimizing Long-Term Outcomes and Avoiding Failure With the Fibula Intramedullary Nail.

OBJECTIVES: To identify risk factors for fixation failure, report patient outcomes, and advise on modifications to the surgical technique for fibula nail stabilization of unstable ankle fractures. DESIGN: Retrospective review. SETTING: Academic orthopaedic trauma unit. PATIENTS: All 342 patients were identified retrospectively from a prospectively collected single-center trauma database over a 9-year period. INTERVENTION: Unstable ankle fractures managed surgically with a fibula nail. MAIN OUTCOME MEASUREMENTS: The primary short-term outcome was failure, defined as any case that required revision surgery because of an inadequate mechanical construct. The mid-term outcomes included the Olerud-Molander Ankle Score and the Manchester-Oxford Foot Questionnaire. RESULTS: Twenty failures occurred (6%), of which 7 (2%) were due to device failure and 13 (4%) due to surgeon error. Of the surgeon errors, 8 consisted of inappropriate weight-bearing after syndesmotic diastasis, and 5 were due to inadequate fracture reduction or poor nail placement. Proximal locking screw (PLS) pull-out was the cause of all device failures. Positioning the PLS >20 mm above the plafond significantly increased failure risk (P = 0.003). At a mean follow-up of 5.1 years (range, 8 months-8 years) the median Olerud-Molander Ankle Score and Manchester-Oxford Foot Questionnaire were 80 (interquartile range, 45) and 10.94 (interquartile range, 44.00), respectively. Patient outcome was not negatively affected by the requirement for revision surgery. CONCLUSIONS: The fibula nail offers secure fixation and good patient-reported outcomes for unstable ankle fractures. Appropriate postoperative management and surgical technique, including careful placement of the PLS, is essential to minimize construct failure risk. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Prognostic and biological significance of the proangiogenic factor EGFL7 in acute myeloid leukemia.

Epithelial growth factor-like 7 (EGFL7) is a protein that is secreted by endothelial cells and plays an important role in angiogenesis. Although EGFL7 is aberrantly overexpressed in solid tumors, its role in leukemia has not been evaluated. Here, we report that levels of both EGFL7 mRNA and EGFL7 protein are increased in blasts of patients with acute myeloid leukemia (AML) compared with normal bone marrow cells. High EGFL7 mRNA expression associates with lower complete remission rates, and shorter event-free and overall survival in older (age ≥60 y) and younger (age <60 y) patients with cytogenetically normal AML. We further show that AML blasts secrete EGFL7 protein and that higher levels of EGFL7 protein are found in the sera from AML patients than in sera from healthy controls. Treatment of patient AML blasts with recombinant EGFL7 in vitro leads to increases in leukemic blast cell growth and levels of phosphorylated AKT. EGFL7 blockade with an anti-EGFL7 antibody reduced the growth potential and viability of AML cells. Our findings demonstrate that increased EGFL7 expression and secretion is an autocrine mechanism supporting growth of leukemic blasts in patients with AML.

Expression and prognostic impact of lncRNAs in acute myeloid leukemia.

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides, located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. LncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis, and cell cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged ≥60 y) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. An independent set of 71 untreated older patients with CN-AML was used to validate the outcome scores using RNA sequencing. Distinctive lncRNA profiles were found associated with selected mutations, such as internal tandem duplications in the FLT3 gene (FLT3-ITD) and mutations in the NPM1, CEBPA, IDH2, ASXL1, and RUNX1 genes. Using the lncRNAs most associated with event-free survival in a training cohort of 148 older patients with CN-AML, we derived a lncRNA score composed of 48 lncRNAs. Patients with an unfavorable compared with favorable lncRNA score had a lower complete response (CR) rate [P < 0.001, odds ratio = 0.14, 54% vs. 89%], shorter disease-free survival (DFS) [P < 0.001, hazard ratio (HR) = 2.88] and overall survival (OS) (P < 0.001, HR = 2.95). The validation set analyses confirmed these results (CR, P = 0.03; DFS, P = 0.009; OS, P = 0.009). Multivariable analyses for CR, DFS, and OS identified the lncRNA score as an independent marker for outcome. In conclusion, lncRNA expression in AML is closely associated with recurrent mutations. A small subset of lncRNAs is correlated strongly with treatment response and survival.

A multicenter phase I/II study of obatoclax mesylate administered as a 3- or 24-hour infusion in older patients with previously untreated acute myeloid leukemia.

PURPOSE: An open-label phase I/II study of single-agent obatoclax determined a maximum tolerated dose (MTD) and schedule, safety, and efficacy in older patients (≥ 70 yr) with untreated acute myeloid leukemia (AML). EXPERIMENTAL DESIGN: Phase I evaluated the safety of obatoclax infused for 3 hours on 3 consecutive days (3 h × 3 d) in 2-week cycles. Initial obatoclax dose was 30 mg/day (3 h × 3 d; n = 3). Obatoclax was increased to 45 mg/day (3 h × 3 d) if ≤ 1 patient had a dose-limiting toxicity (DLT) and decreased to 20 mg/day (3 h × 3 d) if DLT occurred in ≥ 2 patients. In the phase II study, 12 patients were randomized to receive obatoclax at the dose identified during phase I (3 h × 3 d) or 60 mg/day administered by continuous infusion over 24 hours for 3 days (24 h × 3 d) to determine the morphologic complete response rate. RESULTS: In phase I, two of three patients receiving obatoclax 30 mg/day (3 h × 3 d) experienced grade 3 neurologic DLTs (confusion, ataxia, and somnolence). Obatoclax was decreased to 20 mg/day (3 h × 3 d). In phase II, no clinically relevant safety differences were observed between the 20 mg/day (3 h × 3 d; n = 7) and 60 mg/day (24 h × 3 d; n = 5) arms. Neurologic and psychiatric adverse events were most common and were generally transient and reversible. Complete response was not achieved in any patient. CONCLUSIONS: Obatoclax 20 mg/day was the MTD (3 h × 3 d) in older patients with AML. In the schedules tested, single-agent obatoclax was not associated with an objective response. Evaluation in additional subgroups or in combination with other chemotherapy modalities may be considered for future study. TRIAL REGISTRATION: ClinicalTrials.gov NCT00684918.