The impact of heterotopic ossification prophylaxis after surgical fixation of acetabular fractures: national treatment patterns and related outcomes.

BACKGROUND: Heterotopic ossification (HO) is a common complication after surgical fixation of acetabular fractures. Numerous strategies have been employed to prevent HO formation, but results are mixed and optimal treatment strategy remains controversial. The purpose of the study was to describe current national heterotopic ossification (HO) prophylaxis patterns among academic trauma centers, determine the association between prophylaxis type and radiographic HO, and identify if heterogeneity in treatment effects exist based on outcome risk strata. METHODS: We used data from a subset of participants enrolled in the Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities (PREPARE) trial. We included only patients with closed AO-type 62 acetabular fractures that were surgically treated via a posterior (Kocher-Langenbeck), combined anterior and posterior, or extensile exposure. PREPARE Clinical Trial Registration Number: NCT03523962 Patient population This cohort study was nested within the Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities (PREPARE) trial. The PREPARE trial is a multicenter cluster-randomized crossover trial evaluating the effectiveness of two alcohol-based pre-operative antiseptic skin solutions. All PREPARE trial clinical centers that enrolled at least one patient with a closed AO-type 62 acetabular fracture were invited to participate in the nested study. RESULTS: 277 patients from 20 level 1 and level 2 trauma centers in the U.S. and Canada were included in this study. 32 patients (12%) received indomethacin prophylaxis, 100 patients (36%) received XRT prophylaxis, and 145 patients (52%) received no prophylaxis. Administration of XRT was associated with a 68% reduction in the adjusted odds of overall HO (OR 0.32, 95% CI, 0.14 - 0.69, p = 0.005). The overall severe HO (Brooker classes III or IV) rate was 8% for the entire cohort; XRT reduced the rate of severe HO in high-risk patients only (p=0.03). CONCLUSION: HO prophylaxis patterns after surgical fixation of acetabular fractures have changed dramatically over the last two decades. Most centers included in this study did not administer HO prophylaxis. XRT was associated with a marked reduction in the rate of overall HO and the rate of severe HO in high-risk patients. Randomized trials are needed to fully elucidate the potential benefit of XRT. PREPARE Clinical Trial Registration Number: NCT03523962.

The novel dopamine D3 receptor antagonist NGB 2904 inhibits cocaine's rewarding effects and cocaine-induced reinstatement of drug-seeking behavior in rats.

Accumulating evidence indicates that dopamine (DA) D(3) receptor antagonists appear highly promising in attenuating cocaine reward and relapse in preclinical models of addiction. In the present study, we investigated the effects of the novel D(3)-selective antagonist NGB 2904 (N-(4-[4-{2,3-dichlorophenyl}-1-piperazinyl]butyl)-3-fluorenylcarboxamide) on cocaine self-administration, cocaine-enhanced brain stimulation reward (BSR), and cocaine-triggered reinstatement of drug-seeking behavior in male Long-Evans rats. We found that: (1) acute intraperitoneal (i.p.) administration of NGB 2904 (0.1-10 mg/kg) failed to alter cocaine self-administration (0.5 mg/kg/infusion) under fixed-ratio 2 (FR2) reinforcement, but 1 or 5 mg/kg NGB 2904 significantly lowered the break-point for cocaine self-administration under progressive-ratio (PR) reinforcement; (2) cocaine (1, 2, and 10 mg/kg) significantly enhanced electrical BSR (decreased brain reward thresholds), while NGB 2904 significantly inhibited the enhancement of BSR elicited by 2 mg/kg, but not 10 mg/kg of cocaine; (3) NGB 2904 alone neither maintained self-administration behavior nor altered brain reward thresholds; and (4) NGB 2904 significantly inhibited cocaine-triggered reinstatement of extinguished drug-seeking behavior, but not sucrose-plus-sucrose-cue-triggered reinstatement of sucrose-seeking behavior. Overall, these data show that the novel D(3)-selective antagonist NGB 2904 attenuates cocaine's rewarding effects as assessed by PR self-administration, BSR, and cocaine-triggered reinstatement of cocaine-seeking behavior. Owing to these properties and to its lack of rewarding effects (as assessed by BSR and by substitution during drug self-administration), NGB 2904 merits further investigation as a potential agent for treatment of cocaine addiction.

Axial strain enhances osteotomy repair with a concomitant increase in connexin43 expression.

The mechanical environment is known to influence fracture healing. We speculated that connexin43 (Cx43) gap junctions, which impact skeletal homeostasis, fracture healing and the osteogenic response to mechanical load, may play a role in mediating the response of the healing bone to mechanical strain. Here, we used an established rat fracture model, which uses a 2 mm osteotomy gap stabilized by an external fixator, to examine the impact of various cyclical axial loading protocols (2%, 10%, and 30% strain) on osteotomy healing. We examined the presence of Cx43 in the osteotomy-healing environment and assessed how mechanical strain modulates Cx43 expression patterns in the callus. We demonstrated that increased cyclical axial strain results in increased radiographic and histologic bone formation. In addition, we show by immunohistochemistry that Cx43 is abundantly expressed in the healing callus, with the expression most robust in samples exposed to increased cyclical axial strain. These data are consistent with the concept that an increase in Cx43 expression by mechanical load may be part of the mechanisms by which mechanical forces enhances fracture healing.

Location of civilian ballistic femoral fracture indicates likelihood of arterial injury.

BACKGROUND: We evaluated whether the location of a ballistic femoral fracture helps predict the presence of arterial injury. We hypothesized that fractures located in the distal third of the femur are associated with a higher rate of arterial injury. METHODS: We conducted a retrospective review of electronic medical records at our level I trauma centre and found 133 consecutive patients with femoral fractures from civilian gunshots from 2002 to 2007, 14 of whom sustained arterial injury. Fracture extent was measured with computerized viewing software and recorded with a standard technique, calculating proximal, distal, and central locations of the fracture as a function of overall length of the bone. Analyses were conducted with Student's t, Chi-squared, and Fisher's exact tests. RESULTS: The location of any fracture line in the distal third of the femur was associated with increased risk of arterial injury (P<0.05). The odds ratio for the presence of arterial injury when the proximal fracture line was in the distal third of the femur was 5.63 (95% confidence interval, 1.7-18.6; P<0.05) and when the distal fracture line was in the distal third of the femur was 6.72 (95% confidence interval, 1.78-25.44; P<0.05). CONCLUSIONS: A fracture line in the distal third of the femur after ballistic injury is six times more likely to be associated with arterial injury and warrants careful evaluation. Our data show that fracture location can help alert clinicians to possible arterial injury after ballistic femoral fracture.

Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI).

Dynamic manganese-enhanced magnetic resonance imaging (MEMRI) detects neuronal activity based on the passage of Mn(2+) into active neurons. Because this mechanism is independent of any hemodynamic response, it is potentially ideal for pharmacological studies and was applied to investigate the acute CNS effects of cocaine in the rat. Dose-dependent, region-specific MEMRI signals were seen mostly in cortical and subcortical mesocorticolimbic structures. To verify the spatial accuracy and physiological mechanisms of MEMRI, neuronal activation following electrical forepaw stimulation revealed somatotopic signal enhancement in the primary and secondary somatosensory cortices, which was blocked by diltiazem, a Ca2+ channel antagonist. These data suggest that MEMRI may serve as a tool for investigating the effects of pharmacological agents and opens an application of MRI to study CNS drug effects at a systems level.