Elevated transforming growth factor-beta 1 (TGF-β1) levels in human fracture healing

Introduction

Transforming growth factor-beta 1(TGF-β1) is a regulatory protein, involved in bone fracture healing. Circulating TGF-β1 levels have been reported to be a predictor of delayed bone healing and non-union, suggesting active relationship between tissue and circulating TGF-β1 in fracture healing. The purpose of this study was to analyse TGF-β1 local and serum concentrations in fracture healing to further contribute to the understanding of molecular regulation of fracture healing.

Patients and methods

Serum samples of 113 patients with long bone fractures were collected over a period of 6 months following a standardised time schedule. TGF-β1 serum concentrations were measured using ELISA. Patients were assigned to 2 groups: Group 1 contained 103 patients with physiological healing. Group 2 contained 10 patients with impaired healing. Patients in both groups were matched. One patient of the group 2 had to be excluded because of missing match partner. In addition, fracture haematoma from 11 patients of group 1 was obtained to analyse local TGF-β1 concentrations. 33 volunteers donated serum which served as control.

Results

TGF-β1 serum concentrations increased during the early healing period and were significantly higher in patients with physiological healing compared to controls (P = 0.04). Thereafter, it decreased continuously between weeks 2 and 8 and fell again after week 8. TGF-β1 serum concentrations in patients with physiological healing were significantly higher at week 24 compared to controls (P = 0.05). In non-unions, serum concentrations differed significantly from those of controls at week 6 (P = 0.01). No significant difference in between patients with physiological and impaired fracture healing was observed. Fracture haematoma contained significantly higher TGF-β1 concentrations than peripheral serum of the patients (P = 0.017).

Conclusion

Elevated levels of TGF-β1 in haematoma and in serum after bone fracture especially during the entire healing process indicate its importance for fracture healing.     

Is dopexamine superior to dopamine in the treatment of multiple trauma patients—A prospective, double-blind, randomised study

Background

The goal of this prospective, randomised, double-blind clinical trial study was to assess the effects of dopexamine hydrochloride on organ failure, inflammatory mediators and splanchnic oxygenation in blunt multiple trauma patients at high risk of multiple organ dysfunction syndrome (MODS).

Methods

We performed a prospective randomised controlled trial on 30 consecutive blunt multiple trauma patients with ISS ≥ 16, age 18-60 years and initial blood pressure ≥120 mmHg initially admitted to our level I trauma centre. Patients were randomised to treatment with dopamine (n = 15) or dopexamine (n = 15) for 48 h after admission. Outcome in terms of mortality, MODS, splanchnic perfusion, complications, duration of stay was statistically analysed.

Results

Dopexamine treatment was associated with impaired organ function and an increased duration of ventilation and ICU stay compared with patients who received dopamine treatment. The acute inflammatory response was increased in the Dopexamine group while a decreased pHi and MEGX formation and increased serum lactate levels were measured.

Conclusions

The indication to use dopexamine hydrochloride appears questionable. In the absence of an antiinflammatory effect, dopexamine demonstrated a disadvantageous ICU course in regards to the organ function and the duration of treatment. In addition, a decreased pHi and MEGX formation suggested a deterioration of splanchnic oxygenation.     

Functional outcome of shoulder hemiarthroplasty for fractures: A multicentre analysis

In this multicentre study, data on 102 shoulder hemiarthroplasties for the treatment of fractures were analysed retrospectively with regard to tuberosity healing and functional outcome.

Methods

Clinical outcome was assessed using the constant score (CS) and the American Shoulder and Elbow Score (ASES). The mean follow-up time was 28.1 months. The proportion of patients presenting tuberosity healing was 35.3% (36 out of 102).

Results

Anatomical tuberosity healing has a significant effect on CS, especially for lateral elevation (p = 0.0076), forward elevation (p = 0.0002), power (p = 0.0023) and the ASES (p = 0.017). However, the pain value of the CS was not influenced by tuberosity healing (p = 0.34). In patients with anatomically healed tuberosities, the CS averaged 53.0 points, whereas in the group of patients with non-anatomical tuberosity healing, the score averaged 40.1 points (p = 0.0004).There was an 11-fold increase in tuberosity nonunion in females compared with males (p = 0.0045). Further, nonunion was seen to be associated with advanced age of >70 years (p = 0.037) and the presence of osteoporosis (p = 0.034).

Conclusion

In this study, we found that anatomical tuberosity healing around the prosthesis improved functional outcome and range of motion.     

The influence of osteoporosis in femoral fracture healing time

Aim

In order to assess the effect of osteoporosis on healing time, the files of 165 patients with femoral shaft fractures that were treated in our institution with locked-reamed intramedullary nailing were retrospectively reviewed.

Patients and methods

Patients with open fractures, pathological fractures, revision surgery, severe brain injuries and prolonged ITU stay were excluded. In all patients the Singh-index score for osteoporosis and the canal bone ratio (CBR) were assigned. Sixty-six patients fulfilled the inclusion criteria. Patients were divided into two groups; group A (29 patients) consisted of patients over 65 years old with radiological evidence of osteoporosis and group B (37 patients) of patients between 18 and 40 years old with no signs of osteoporosis.

Results

In all group A patients Singh score ≤4 and CBR > 0.50 were assigned, suggesting the presence of osteoporosis, whereas all group B patients were assigned with Singh score ≥5 and CBR < 0.48. Fractures of group A healed in 19.38 ± 5.9 weeks (12-30) and in group B 16.19 ± 5.07 weeks (10-28), P = 0.02.

Conclusions

Fracture healing of nailed femoral diaphyseal fractures is significantly delayed in older osteoporotic patients. Further studies are required to clarify the exact impact of osteoporosis in the whole healing process.     

Leg lengthening using intramedullay skeletal kinetic distractor: Results of 57 consecutive applications

Background

Mechanically activated intramedullary lengthening nails are advantageous over external fixator. However, difficulties with the control of the distraction rate are the main drawbacks, which may in turn cause insufficient bone regenerate.

Patients and methods

A total of 57 lengthening procedures were performed using intramedullary skeletal kinetic distractor (ISKD) nail in 53 patients (femoral = 45 and tibial = 12). Average length gain was 4.3 ± 1.6 cm. The cause of shortening was post-traumatic (n = 33), congenital (n = 20), post-tumour resection (n = 1), cosmetic femoral lengthening (n = 2) and post-correction of distal femoral varus deformity (n = 1).

Results

The desired lengthening was achieved in all patients. The mean follow-up period was 23 ± 12 months. The healing index for patients with normal bone healing was 1.2 ± 0.32 months/cm. Complications in femoral lengthening were superficial wound infection (n = 1), premature consolidation (n = 4) and insufficient bone regenerate (n = 11), while in the tibial lengthening, two developed equinus contractures, one had compartment syndrome following implantation of the nail and one insufficient bone regenerate. Furthermore, nine runaway nails and three non-distracting nails were present in the femoral lengthening. One non-distracting nail responded to manipulation under anaesthesia, one required exchange nailing and accidental acute lengthening of 3 cm took place while manipulating the third nail. Patients with femoral lengthening and those with insufficient regenerate had significantly higher distraction rates (P = 0.006 and 0.003, respectively). Six out of the nine runaway nails developed insufficient bone regenerate. In addition, 10.7-mm tibial ISKD nails were found to have lower rates of runaway nails compared with other used diameters.

Conclusion

We emphasise the rule of distraction rates above 1.5 mm/day in the development of insufficient bone regenerate. Distraction problems with these nails are mostly due to dysfunction within the ratcheting mechanism, which may be related to the diameter of the nail. New designs for mechanically activated nails with a better control mechanism for the distraction rate are required.     

Stepwise approach for nerve sparing without countertraction during robot-assisted radical prostatectomy: technique and outcomes

Background

Although subtle technical variation affects potency preservation during robot-assisted laparoscopic radical prostatectomy (RARP), most prostatectomy studies focus on achieving the optimal anatomic nerve-sparing dissection plane. However, the impact of active assistant/surgeon neurovascular bundle (NVB) countertraction on sexual function outcomes has not been studied or quantified.

Objective

To illustrate technique and compare sexual function outcomes for nerve sparing without (NS-0C) versus with (NS-C) assistant and/or surgeon NVB countertraction.

Design, setting, and participants

This is a retrospective study of 342 NS-0C versus 268 NS-C RARP procedures performed between August 2008 and February 2011.

Surgical procedure

RARP.

Measurements

We used the Expanded Prostate Cancer Index Composite (EPIC) sexual function and potency scores, estimated blood loss (EBL), operative time, and positive surgical margin (PSM).

Results and limitations

In unadjusted analysis, men undergoing NS-0C versus NS-C were older, had worse baseline sexual function, higher biopsy and pathologic Gleason grade, and higher preoperative prostate-specific antigen (PSA) levels (all p ≤ 0.023). However, NS-0C versus NS-C was associated with higher 5-mo sexual function scores (20 vs 10; p < 0.001), and this difference was accentuated for bilateral intrafascial nerve sparing in preoperatively potent men (35.8 vs 16.6; p < 0.001). Similarly, 5-mo potency for preoperatively potent men was better with bilateral intrafascial NS-0C versus NS-C (45.0% vs 28.4%; p = 0.039). However, no difference in sexual function or potency was observed at 12 mo. In adjusted analyses, NS-0C versus NS-C was associated with improved 5-mo sexual function (parameter estimate: 10.90; standard error: 2.16; p < 0.001) and potency (odds ratio: 1.69; 95% confidence interval, 1.01-2.83; p = 0.046). NS-0C versus NS-WC was associated with shorter operative times (p = 0.001) and higher EBL (p = 0.001); however, there were no significant differences in PSM. Limitations include the retrospective, single-surgeon study design and smaller numbers for 12-mo comparison.

Conclusions

Reliance on countertraction to facilitate dissecting NVB away from the prostate leads to neuropraxia and delayed recovery of sexual function and potency. Subtle technical modification to dissect the prostate away from the NVB without countertraction enables earlier return of sexual function and potency.     

International phase III trial of liprotamase efficacy and safety in pancreatic-insufficient cystic fibrosis patients

Background

Most cystic fibrosis (CF) patients have exocrine pancreatic insufficiency (EPI) and need supplementation with pancreatic enzyme replacement therapy (PERT). Liprotamase, a novel non-porcine PERT containing highly purified biotechnology-derived lipase, protease, and amylase, has successfully undergone initial efficacy and safety testing.

Methods

In this international phase III parallel-group, randomized-withdrawal, double-blind placebo-controlled trial, CF patients with EPI 7 years and older, including nutritionally and functionally compromised individuals, underwent baseline testing for coefficients of fat and nitrogen absorption (CFA and CNA) and stool weight and frequency while off PERT. After an open-label treatment period with liprotamase, subjects were randomized 1:1 to one liprotamase or placebo capsule taken with 3 meals and 2 snacks per day. The dose was fixed and increases were not allowed. The same measurements were obtained again after treatment with double-blind study drug or placebo.

Results

138 subjects were randomized. The adjusted least squares mean (LSM) difference between the treatment and placebo groups for change in CFA was 15.1% (p = 0.001) for the subgroup with baseline CFA < 40%, 8.6% (p = 0.006) for subjects with baseline CFA ≥ 40%, and 10.6% (p < 0.001) for the overall intent-to-treat population. Similar results were seen for change in CNA. Stool weight was significantly decreased although not stool frequency. Liprotamase was well tolerated with no safety concerns identified.

Conclusions

In a CF patient population reflective of that encountered in clinical practice, this trial demonstrated that liprotamase at a fixed dose of one capsule per meal or snack (5 capsules per day) was well tolerated and significantly increased fat absorption as measured by improvement in CFA, significantly increased protein absorption as measured by improvement in CNA, and significantly decreased stool weight.     

Effects of rapid distraction rate on new bone formation during mandibular distraction osteogenesis in goats

Objective

Distraction osteogenesis typically requires a long treatment period, which can lead to bone and soft-tissue infection and considerable patient discomfort. Use of a rapid distraction rate in craniofacial distraction osteogenesis to shorten the distraction period is possible owing to the unique characteristics of craniofacial bones, including an abundant blood supply and rapid bone healing compared with long bones. The effects of using a rapid distraction rate in the treatment of craniofacial deformities are currently unclear, however. The objective of this study was to investigate the effects of a rapid distraction rate on new bone formation during mandibular distraction osteogenesis in goats.

Methods

Sixteen goats were randomly divided into four groups consisting of four goats each. In Groups A, B, and C, the right mandible of each goat was distracted at a rate of 0.8 mm/d, 1.6 mm/d, and 2.0 mm/d, respectively; Group D was the control group and did not undergo distraction. Six weeks after the conclusion of distraction, bone densitometry and three-point bending testing were performed in all groups.

Results

The mean bone density value of goats in Group A was significantly higher than those of all the other groups (p < 0.05), and the mean bone density value of goats in Group C was significantly lower than those of all the other groups (p < 0.05). The mean curve slope, peak stress, bending modulus, and energy to failure values of Groups A, B, and C were all significantly lower than those of the control group (p < 0.05). As the distraction rate increased, the curve slope and peak stress values gradually declined (p < 0.05).

Conclusions

Use of a rapid distraction rate in mandibular distraction osteogenesis may have detrimental effects on the quality of new bone, despite the abundant blood supply of craniofacial bones.     

Randomized controlled single center study comparing a polyhexanide containing bio-cellulose dressing with silver sulfadiazine cream in partial-thickness dermal burns

Objective

A prospective, randomized, controlled single center study was designed to evaluate clinical efficacy of a polyhexanide containing bio-cellulose dressing (group B) compared to a silver-sulfadiazine cream (group A) in sixty partial-thickness burn patients.

Patients and methods

Local ethics committee approval was obtained and patients consented. Parameters were: pain reduction (VAS), healing time and wound bed condition, comparing day 0 (start) versus day 14 (end), as well as, ease of dressing use and treatment costs.

Results

All completed the study (n = 30/n = 30) and were included in the ITT analysis, with a total of 72 burns (group A: n = 38, group B: n = 34). We noted no differences in healing time. Pain reduction was significantly faster and better in group B (p < 0.01). There were fewer dressing changes in group B, compared to group A. Ease of use for the bio-cellulose dressing was rated better compared to group A. In group B, € 95.20 was saved for a 10 day treatment period, compared to group A.

Conclusion

Group B demonstrated a better and faster pain reduction in the treated partial-thickness burns, compared to group A. The results indicate the polyhexanide containing bio-cellulose dressing to be a safe and cost effective treatment for partial-thickness burns.     

Development of electronic software for the management of trauma patients on the orthopaedic unit

Introduction

Continuity of patient care is an essential prerequisite for the successful running of a trauma surgery service. This is becoming increasingly difficult because of the new working arrangements of junior doctors. Handover is now central to ensure continuity of care following shift change over.The purpose of this study was to compare the quality of information handed over using the traditional ad hoc method of a handover sheet versus a web-based electronic software programme. It was hoped that through improved quality of handover the new system would have a positive impact on clinical care, risk and time management.

Methods

Data was prospectively collected and analyzed using the SPSS 14^® statistical package. The handover data of 350 patients using a paper-based system was compared to the data of 357 cases using the web-based system. Key data included basic demographic data, responsible surgeon, location of patient, injury site including site, whether fractures were open or closed, concomitant injuries and the treatment plan. A survey was conducted amongst health care providers to assess the impact of the new software.

Results

With the introduction of the electronic handover system, patients with missing demographic data reduced from 35.1% to 0.8% (p < 0.0001) and missing patient location from 18.6% to 3.6% (p < 0.0001). Missing consultant information and missing diagnosis dropped from 12.9% to 2.0% (p < 0.0001) and from 11.7% to 0.8% (p < 0.0001), respectively. The missing information regarding side and anatomical site of the injury was reduced from 31.4% to 0.8% (p < 0.0001) and from 13.7% to 1.1% (p < 0.0001), respectively. In 96.6% of paper ad hoc handovers it was not stated whether the injury was ‘closed’ or ‘open’, whereas in the electronic group this information was evident in all 357 patients (p < 0.0001). A treatment plan was included only in 52.3% of paper handovers compared to 94.7% (p < 0.0001) of electronic handovers. A survey revealed 96% of members of the trauma team felt an improvement of handover since the introduction of the software, and 94% of members were satisfied with the software.

Conclusions

The findings of our study show that the use of web-based electronic software is effective in facilitating and improving the quality of information passed during handover. Structured software also aids in improving work flow amongst the trauma team. We argue that an improvement in the quality of handover is an improvement in clinical practice.