Pediatric variants of the transolecranon fracture dislocation: recognition and tension band fixation: report of 3 cases

Anterior transolecranon fracture dislocation of the elbow is relatively uncommon in children. We reviewed the experience over the past 5 years at our institution in treating this injury to identify pediatric variants and outline a rational treatment strategy. We found 2 pediatric variants to the injury pattern and determined that tension band constructs can successfully be used to treat certain pediatric transolecranon fracture dislocations. The pediatric variants identified in this report are fracture dislocations with associated medial epicondyle fracture and radial neck fracture. We recommend a heightened vigilance in looking for a fracture through the ulna when an anterior dislocation is present, as physeal injuries can be challenging to see on plain radiographs.     

Mesenchymal stem cell transplantation to promote bone healing

An overall decline in the availability of osteogenic precursor cells and growth factors in the bone marrow microenvironment have been associated with impaired bone formation and osteopenia in humans. The objective of the current study was to determine if transplantation of mesenchymal stromal cells (MSC) from a healthy, young donor mouse into an osteopenic recipient mouse could enhance osseointegration of a femoral implant. MSC harvested from normal young adult mice differentiated into bone forming osteoblasts when cultured on implant grade titanium surfaces ex vivo and promoted bone formation around titanium-coated rods implanted in the femoral canal of osteopenic recipient mice. Micro computed tomographic imaging and histological analyses showed more, better quality, bone in the femur that received the MSC transplant compared with the contra-lateral control femur that received carrier alone. These results provide pre-clinical evidence that MSC transplantation promotes peri-implant bone regeneration and suggest the approach could be used in a clinical setting to enhance bone regeneration and healing in patients with poor quality bone.     

Bilateral differences in gait mechanics following total ankle replacement: A two year longitudinal study

Background

Following total ankle replacement (TAR) patients demonstrate improvements in gait. The purpose of this study was to assess the changes in gait symmetry from a pre-operative assessment through two years following TAR.

Methods

Seventy-eight patients who received a primary TAR and had no contralateral pain were examined. Three-dimensional joint mechanics and ground reaction forces were collected during seven walking trials pre-operatively, and 1 and 2-years post-operatively. Data was analyzed using a 2 × 3 repeated measures ANOVA to determine significant differences between limbs and across time points (α = 0.05).

Findings

Walking speed improved from pre-operative to each post-operative time point (P < .001; ES = 1.5). Peak dorsiflexion was not changed across time or between sides, however, the dorsiflexion angle at heel strike was increased on the nonsurgical side (P = 0.049; ES = 0.32). Peak plantar flexion moment (P < .001; ES = .80), stance (P < .001; ES = .29) and step time (P < .001; ES = .41) were improved from pre-op to 1 year post-surgery on the surgical side. Step (P < .001; ES = 1.2) and stride length (P < .001; ES = 1.2) demonstrated improvements across all time points, while the weight acceptance (P < .001; ES = .27) and propulsion ground reaction forces (P < .001; ES = .22) showed improvements between pre-op and 1 year post-op.

Interpretation

The results of the study indicate that the patients are able to walk faster and demonstrate an improvement in gait symmetry; however, this improvement does not return the patient to a symmetric walking pattern by 2 years post-TAR.     

The immunological axis in heart failure: importance of the leukocyte differential

The important role of the immune system and inflammation in the pathophysiology of heart failure (HF) is becoming increasingly appreciated. We have reviewed the prognostic significance of under-recognized aspects of the leukocyte differential in HF, including lymphocytes, monocytes, eosinophils and mast cells. Studies to date evaluating lymphocyte counts in both chronic and hospitalized HF patients have consistently shown worse prognosis associated with low lymphocyte counts, despite widely heterogeneous study designs. Limited data suggest elevations in monocyte-derived cytokines and serum monocyte count may be predictive of poor outcomes in HF. Further data are required to better define the relationship between eosinophils, mast cells and HF. Leukocyte differentials are widely available, simple, inexpensive and appear to have independent prognostic significance, beyond traditional risk factors. Enhanced sympathetic activation and increased circulating cytokine levels (particularly tumor necrosis factor) have been implicated in the variability of leukocyte subpopulations. To date, immune-modulators targeting these mediators have been largely unsuccessful in improving cardiovascular outcomes in HF. Given the potential role of the immunological axis in HF, there may be an unmet need for novel therapeutic agents that can safely and effectively ameliorate these leukocyte derangements and perhaps improve the unacceptably high event rate in this population. Variations in leukocyte differentials may identify a high-risk subset of patients that may benefit from tailored immune therapies.     

The Effect of Ticagrelor on the Metabolism of Midazolam in Healthy Volunteers

Background

In vitro studies have demonstrated that ticagrelor, an oral antiplatelet agent, is a substrate, activator, and inhibitor of cytochrome P450 (CYP) 3A. Thus, potential CYP3A-mediated drug–drug interactions may occur.

Objectives

The goal of this article was to report study results on the effect of ticagrelor on the pharmacokinetics of oral midazolam (oral midazolam study) and oral versus intravenous (IV) midazolam (oral/IV midazolam study). Secondary objectives included assessing the effect of midazolam on ticagrelor pharmacokinetic parameters, and the safety and tolerability of ticagrelor/midazolam coadministration.

Methods

Two randomized crossover studies were conducted in healthy volunteers (n = 28 in each) with ticagrelor and midazolam. In the first study, volunteers received oral ticagrelor (400 mg daily) or placebo for 6 days, then oral midazolam (7.5 mg). The second study regimen was a single dose of ticagrelor 270 mg, then ticagrelor 180 mg BID for 6 days with a single oral (7.5 mg) or IV (2.5 mg) dose of midazolam.

Results

After oral midazolam administration, ticagrelor significantly reduced the AUC_0–∞ of midazolam (30%–32%) and 4-hydroxymidazolam (42%–47%) but not 1-hydroxymidazolam. After administration of IV midazolam, ticagrelor reduced the AUC_0–∞ of midazolam (12%) and 4-hydroxymidazolam (23%) but not 1-hydroxymidazolam.

Conclusions

These results indicate that ticagrelor can weakly activate the metabolism of midazolam to its major 1′-hydroxy metabolite, and at the same time, seems to weakly inhibit midazolam 4′-hydroxylation. Furthermore, ticagrelor affects both hepatic and intestinal CYP3A activity.     

An audit of blood component therapy in a Canadian general teaching hospital.

As part of a quality assurance program a retrospective audit of transfusion practices for packed red blood cells, fresh frozen plasma and albumin was undertaken with predetermined criteria in a general teaching hospital. Of 520 transfusion episodes with 1218 units of packed red blood cells given to 297 patients 88% were considered appropriate; of 106 episodes with 405 units of fresh frozen plasma given to 83 patients 90% were deemed appropriate; and of 187 episodes with 320 units of albumin given to 99 patients 64% were considered appropriate. The results of this audit, when compared with those of other surveys of blood use in a similar population, suggest that pretransfusion approval of requested components would reduce the number of inappropriate transfusions.