Cost-effectiveness of immediate total-body CT in patients with severe trauma (REACT-2 trial).

BACKGROUND: The effect of immediate total-body CT (iTBCT) on health economic aspects in patients with severe trauma is an underreported issue. This study determined the cost-effectiveness of iTBCT compared with conventional radiological imaging with selective CT (standard work-up (STWU)) during the initial trauma evaluation. METHODS: In this multicentre RCT, adult patients with a high suspicion of severe injury were randomized in-hospital to iTBCT or STWU. Hospital healthcare costs were determined for the first 6 months after the injury. The probability of iTBCT being cost-effective was calculated for various levels of willingness-to-pay per extra patient alive. RESULTS: A total of 928 Dutch patients with complete clinical follow-up were included. Mean costs of hospital care were €25 809 (95 per cent bias-corrected and accelerated (bca) c.i. €22 617 to €29 137) for the iTBCT group and €26 155 (€23 050 to €29 344) for the STWU group, a difference per patient in favour of iTBCT of €346 (€4987 to €4328) (P = 0.876). Proportions of patients alive at 6 months were not different. The proportion of patients alive without serious morbidity was 61.6 per cent in the iTBCT group versus 66.7 per cent in the STWU group (difference -5.1 per cent; P = 0.104). The probability of iTBCT being cost-effective in keeping patients alive remained below 0.56 for the whole group, but was higher in patients with multiple trauma (0.8-0.9) and in those with traumatic brain injury (more than 0.9). CONCLUSION: Economically, from a hospital healthcare provider perspective, iTBCT should be the diagnostic strategy of first choice in patients with multiple trauma or traumatic brain injury.

Management of critical-sized bone defects in the treatment of fracture-related infection: a systematic review and pooled analysis.

PURPOSE: This systematic review determined the reported treatment strategies, their individual success rates, and other outcome parameters in the management of critical-sized bone defects in fracture-related infection (FRI) patients between 1990 and 2018. METHODS: A systematic literature search on treatment and outcome of critical-sized bone defects in FRI was performed. Treatment strategies identified were, autologous cancellous grafts, autologous cancellous grafts combined with local antibiotics, the induced membrane technique, vascularized grafts, Ilizarov bone transport, and bone transport combined with local antibiotics. Outcomes were bone healing and infection eradication after primary surgical protocol and recurrence of FRI and amputations at the end of study period. RESULTS: Fifty studies were included, describing 1530 patients, the tibia was affected in 82%. Mean age was 40 years (range 6-80), with predominantly male subjects (79%). Mean duration of infection was 17 months (range 1-624) and mean follow-up 51 months (range 6-126). After initial protocolized treatment, FRI was cured in 83% (95% CI 79-87) of all cases, increasing to 94% (95% CI 92-96) at the end of each individual study. Recurrence of infection was seen in 8% (95% CI 6-11) and amputation in 3% (95% CI 2-3). Final outcomes overlapped across treatment strategies. CONCLUSION: Results should be interpreted with caution due to the retrospective and observational design of most studies, the lack of clear classification systems, incomplete data reports, potential underreporting of adverse outcomes, and heterogeneity in patient series. A consensus on classification, treatment protocols, and outcome is needed to improve reliability of future studies.

Open reduction and internal fixation versus closed reduction and percutaneous fixation in the treatment of Bennett fractures: A systematic review.

PURPOSE: Open reduction and internal fixation (ORIF) of Bennett fractures is increasingly preferred over closed reduction and percutaneous fixation (CRIF) in an attempt to prevent the development of post-traumatic arthrosis. The aim of this systematic review was to determine whether the preference for ORIF is justified based on the available literature regarding functional outcome and complications after surgery. METHODS: A systematic review was performed in Medline, Embase, Cochrane CENTRAL, Web of science, and Google scholar. Duplicates were removed and title and abstract were screened after which full text articles were analysed. The reference lists of selected articles were screened for additional relevant studies. Study characteristics were recorded and methodological qualities were assessed after which data was extracted from the included articles. The Eaton-Littler score for post-traumatic arthrosis (primary outcome) on follow-up X-rays was used as primary outcome. Secondary outcomes were Grip strength, Pinch strength, persistent pain, fixation failure, functional impairment, infection and surgery time. RESULTS: Ten studies were included; three retrospective comparative studies and seven retrospective case series. Of the 215 patients in these studies, 138 had been treated using an open technique and 77 by a closed percutaneous technique. The pooled rate of post-traumatic arthrosis was 57.5% (26.6-85.5) in the ORIF group versus 26.1% (3.9-59.0) in the CRIF group. Mean surgical operation time was 71.9 min for ORIF and 30.2 min for percutaneous patients. Fixation failure was significantly more often seen in the ORIF patients, 8.2% (0.7-22.8) vs. 2.9% (0.8-9.1), Risk Ratio 1.132 (0.01-176.745); p = 0.048. Infection was only seen in 5 CRIF patients. Persistent pain was seen in 32.9% (0.6-83.1) in ORIF patients versus 22.3% (8.1-41.1) in the CRIF patients. The pooled means Grip strength was 48.3 kg (95% CI; 39.7-56.9) versus 43.4 kg (95% CI; 22.9-63.8) for ORIF and CRPF, respectively. Functional impairment was similar between the two groups, 1.4% (0.1-4.4) vs 1.8% (0.1-5.7) respectively. CONCLUSION: The analysed data do not confirm ORIF to prevent post-traumatic arthrosis, secondly more fixation failure and pain was seen in the ORIF group. The pooled data show percutaneous fixation to be preferable over ORIF in the surgical treatment of Bennett fractures.

Bennett's fracture: Comparative study between open and closed surgical techniques.

The aim of this study was to assess long-term outcomes of surgically treated Bennett fractures, while comparing open reduction and internal fixation (ORIF) with closed reduction and percutaneous fixation (CRPF). Patients treated between 1994 and 2010 were assessed retrospectively during an outpatient visit using a validated questionnaire (i.e. DASH, pain assessed through VAS), sensory testing, grip- and pinch-strength and radiographic analysis for post-traumatic arthritis. Fifty patients were included. Mean follow-up was 10 years. Mean age at trauma was 34 years. ORIF was used in 35 patients. CRPF was used in 15 patients. No differences in grip- and pinch-strength were found. Re-operations were needed in five ORIF-treated patients. Higher Pain Scores (VAS) were seen in the ORIF-treated patients. No correlation was found between surgical technique and functional outcomes. A persistent step-off or gap larger than 2 mm after surgical fixation was significantly correlated with post-traumatic arthritis at 10 years' follow-up. The need to perform ORIF for anatomical reduction seems to be less important in preventing post-traumatic arthritis as a persistent step-off or gap of more than 2 mm was found to be significantly correlated with the development of post-traumatic arthritis. Secondly, both techniques lead to good functional outcomes, although persistent pain was seen in the ORIF-treated patients. Bennett fractures can therefore be safely treated with CRPF when the persistent step-off and gap after fixation do not exceed 2 mm. LEVEL OF EVIDENCE: Therapeutic study, Level III.

Insights into treatment and outcome of fracture-related infection: a systematic literature review.

INTRODUCTION: Standardized guidelines for treatment of fracture-related infection (FRI) are lacking. Worldwide many treatment protocols are used with variable success rates. Awareness on the need of standardized, evidence-based guidelines has increased in recent years. This systematic literature review gives an overview of available diagnostic criteria, classifications, treatment protocols, and related outcome measurements for surgically treated FRI patients. METHODS: A comprehensive search was performed in all scientific literature since 1990. Studies in English that described surgical patient series for treatment of FRI were included. Data were collected on diagnostic criteria for FRI, classifications used, surgical treatments, follow-up protocols, and overall outcome. A systematic review was performed according to the PRISMA statement. Proportions and weighted means were calculated. RESULTS: The search yielded 2051 studies. Ninety-three studies were suitable for inclusion, describing 3701 patients (3711 fractures) with complex FRI. The population consisted predominantly of male patients (77%), with the tibia being the most commonly affected bone (64%), and a mean of three previous operations per patient. Forty-three (46%) studies described FRI at one specific location. Only one study (1%) used a standardized definition for infection. A total of nine different classifications were used to guide treatment protocols, of which Cierny and Mader was used most often (36%). Eighteen (19%) studies used a one-stage, 50 (54%) a two-stage, and seven (8%) a three-stage surgical treatment protocol. Ten studies (11%) used mixed protocols. Antibiotic protocols varied widely between studies. A multidisciplinary approach was mentioned in only 12 (13%) studies. CONCLUSIONS: This extensive literature review shows a lack of standardized guidelines with respect to diagnosis and treatment of FRI, which mimics the situation for prosthetic joint infection identified many years ago. Internationally accepted guidelines are urgently required to improve the quality of care for patients suffering from this significant complication.

Systematic review and pooled analysis of the rate of carpal tunnel syndrome after prophylactic carpal tunnel release in patients with a distal radius fracture.

The aim of this study was to determine the rate of carpal tunnel syndrome (CTS) in patients with a volar plated distal radius fracture (DRF), with or without prophylactic carpal tunnel release (CTR). The PubMed database was searched for studies reporting on CTS in patients with a DRF fixed by a volar plate. Selected patients were those who underwent prophylactic CTR versus patients who did not. Pooled rates of CTS were calculated using inverse - variance weighting assuming a random effects model. Tests for heterogeneity were applied. In this study, 172 patients in the CTR group and 1839 patients in the non-CTR group were included. The pooled rate for CTS in the CTR group was 28.1% (95% CI: 11.8% to 48.2%) while it was 4.4% (95% CI: 3.1% to 6.0%) in the non-CTR group. CTR is of no prophylactic value for postoperative CTS in volar plated DRF patients.

Total medical costs of treating femoral neck fracture patients with hemi- or total hip arthroplasty: a cost analysis of a multicenter prospective study.

UNLABELLED: The aim of this study was to determine the total medical costs for treating displaced femoral neck fractures with hemi- or total hip arthroplasty in fit elderly patients. The mean total costs per patient at 2 years of follow-up were €26,399. These results contribute to cost awareness. INTRODUCTION: The absolute number of hip fractures is rising and increases the already significant burden on society. The aim of this study was to determine the mean total medical costs per patient for treating displaced femoral neck fractures with hemi- or total hip arthroplasty in fit elderly patients. METHODS: The population was the Dutch sample of an international randomized controlled trial consisting of femoral neck fracture patients treated with hemi- or total hip arthroplasty. Patient data and health care utilization were prospectively collected during a total follow-up period of 2 years. Costs were separated into costs for hospital care during primary stay, hospital costs for clinical follow-up, and costs generated outside the hospital during rehabilitation. Multiple imputations were used to account for missing data. RESULTS: Data of 141 participants (mean age 81 years) were included in the analysis. The 2-year mortality rate was 19 %. The mean total cost per patient after 10 weeks of follow-up was €15,216. After 1 and 2 years of follow-up the mean total costs were €23,869 and €26,399, respectively. Rehabilitation was the main cost determinant, and accounted for 46 % of total costs. Primary hospital admission days accounted for 22 % of the total costs, index surgery for 11 %, and physical therapy for 7 %. CONCLUSIONS: The main cost determinants for hemi- or total hip arthroplasty after treatment of displaced femoral neck fractures (€26,399 per patient until 2 years) were rehabilitation and nursing homes. Most of the costs were made in the first year. Reducing costs after hip fracture surgery should focus on improving the duration and efficiency of the rehabilitation phase.

Full regeneration of segmental bone defects using porous titanium implants loaded with BMP-2 containing fibrin gels.

Regeneration of load-bearing segmental bone defects is a major challenge in trauma and orthopaedic surgery. The ideal bone graft substitute is a biomaterial that provides immediate mechanical stability, while stimulating bone regeneration to completely bridge defects over a short period. Therefore, selective laser melted porous titanium, designed and fine-tuned to tolerate full load-bearing, was filled with a physiologically concentrated fibrin gel loaded with bone morphogenetic protein-2 (BMP-2). This biomaterial was used to graft critical-sized segmental femoral bone defects in rats. As a control, porous titanium implants were either left empty or filled with a fibrin gels without BMP-2. We evaluated bone regeneration, bone quality and mechanical strength of grafted femora using in vivo and ex vivo µCT scanning, histology, and torsion testing. This biomaterial completely regenerated and bridged the critical-sized bone defects within eight weeks. After twelve weeks, femora were anatomically re-shaped and revealed open medullary cavities. More importantly, new bone was formed throughout the entire porous titanium implants and grafted femora regained more than their innate mechanical stability: torsional strength exceeded twice their original strength. In conclusion, combining porous titanium implants with a physiologically concentrated fibrin gels loaded with BMP-2 improved bone regeneration in load-bearing segmental defects. This material combination now awaits its evaluation in larger animal models to show its suitability for grafting load-bearing defects in trauma and orthopaedic surgery.

The societal costs of femoral neck fracture patients treated with internal fixation.

SUMMARY: The study rationale was to provide a detailed overview of the costs for femoral neck fracture treatment with internal fixation in the Netherlands. Mean total costs per patient at 2-years follow-up were 19,425. Costs were higher for older, less healthy patients. Results are comparable to internationally published costs. INTRODUCTION: The aim of this study was to provide a detailed overview of the cost and healthcare consumption of patients treated for a hip fracture with internal fixation. A secondary aim was to compare costs of patients who underwent a revision surgery with patients who did not. METHODS: The study was performed alongside the Dutch sample of an international randomized controlled trial, concerning femoral neck fracture patients treated with internal fixation. Patient characteristics and healthcare consumption were collected. Total follow-up was 2 years. A societal perspective was adopted. Costs included hospital costs during primary stay and follow-up, and costs related to rehabilitation and changes in living situation. Costs were compared between non-revision surgery patients, implant removal patients, and revision arthroplasty patients. RESULTS: A total of 248 patients were included (mean age 71 years). Mean total costs per patient at 2-years follow-up were 19,425. In the non-revision surgery patients total costs were 17,405 (N = 137), in the implant removal patients 10,066 (N = 38), and in the revision arthroplasty patients 26,733 (N = 67). The main contributing costs were related to the primary surgery, admission days, physical therapy, and revision surgeries. CONCLUSIONS: The main determinant was the costs of admission to a rehabilitation center/nursing home. Costs were specifically high in elderly with comorbidity, who were less independent pre-fracture, and have a longer admission to the hospital and/or a nursing home. Costs were also higher in revision surgery patients. The 2-years follow-up costs in our study were comparable to published costs in other Western societies.

Risk of infection and sepsis in severely injured patients related to single nucleotide polymorphisms in the lectin pathway.

BACKGROUND: Infectious complications remain a serious threat to patients with multiple trauma. Susceptibility and response to infection is, in part, heritable. The lectin pathway plays a major role in innate immunity. The aim of this study was to assess whether single nucleotide polymorphisms (SNPs) in three key genes within the lectin pathway affect susceptibility to infectious complications in severely injured patients. METHODS: A prospective cohort of severely injured patients admitted to a level I trauma centre between January 2008 and April 2011 were genotyped for SNPs in MBL2 (mannose-binding lectin 2), MASP2 (MBL-associated serine protease 2) and FCN2 (ficolin 2). Association of genotype with prevalence of positive culture findings and infection was tested by χ(2) and logistic regression analysis. RESULTS: A total of 219 patients were included, of whom 112 (51·1 per cent) developed a positive culture from sputum, wounds, blood or urine. A systemic inflammatory response syndrome (SIRS) developed in 139 patients (63·5 per cent), sepsis in 79 (36·1 per cent) and septic shock in 37 (16·9 per cent). Patients with a MBL2 exon 1 variant allele were more prone to positive wound cultures (odds ratio (OR) 2·51, 95 per cent confidence interval 1·12 to 5·62; P = 0·025). A MASP2 Y371D DD genotype predisposed to SIRS (OR 4·78, 1·06 to 21·59; P = 0·042) and septic shock (OR 2·53, 1·12 to 4·33; P = 0·003). A FCN2 A258S AS genotype predisposed to positive wound cultures (OR 3·37, 1·45 to 7·85; P = 0·005) and septic shock (OR 2·18, 1·30 to 4·78; P = 0·011). CONCLUSION: Severely injured patients with SNPs in MBL2, MASP2 Y371D and FCN2 A258S of the lectin pathway of complement activation are significantly more susceptible to positive culture findings, and to infectious complications, SIRS and septic shock than patients with a wildtype genotype.

Immediate thoracotomy for penetrating injuries: ten years' experience at a Dutch level I trauma center.

BACKGROUND: An emergency department thoracotomy (EDT) or an emergency thoracotomy (ET) in the operating theater are both beneficial in selected patients following thoracic penetrating injuries. Since outcome-descriptive European studies are lacking, the aim of this retrospective study was to evaluate ten years of experience at a Dutch level I trauma center. METHOD: Data on patients who underwent an immediate thoracotomy after sustaining a penetrating thoracic injury between October 2000 and January 2011 were collected from the trauma registry and hospital files. Descriptive and univariate analyses were performed. RESULTS: Among 56 patients, 12 underwent an EDT and 44 an ET. Forty-six patients sustained one or multiple stab wounds, versus ten with one or multiple gunshot wounds. Patients who had undergone an EDT had a lower GCS (p < 0.001), lower pre-hospital RTS and hospital triage RTS (p < 0.001 and p = 0.009, respectively), and a lower SBP (p = 0.038). A witnessed loss of signs of life generally occurred in EDT patients and was accompanied by 100 % mortality. Survival following EDT was 25 %, which was significantly lower than in the ET group (75 %; p = 0.002). Survivors had lower ISS (p = 0.011), lower rates of pre-hospital (p = 0.031) and hospital (p = 0.003) hemodynamic instability, and a lower prevalence of concomitant abdominal injury (p = 0.002). CONCLUSION: The overall survival rate in our study was 64 %. The outcome of immediate thoracotomy performed in this level I trauma center was similar to those obtained in high-incidence regions like the US and South Africa. This suggests that trauma units where immediate thoracotomies are not part of the daily routine can achieve similar results, if properly trained.

Determinants of outcome in operatively and non-operatively treated Weber-B ankle fractures.

INTRODUCTION: Treatment of ankle fractures is often based on fracture type and surgeon's individual judgment. Literature concerning the treatment options and outcome are dated and frequently contradicting. The aim of this study was to determine the clinical and functional outcome after AO-Weber B-type ankle fractures in operatively and conservatively treated patients and to determine which factors influenced outcome. PATIENTS AND METHODS: A retrospective cohort study in patients with a AO-Weber B-type ankle fracture. Patient, fracture and treatment characteristics were recorded. Clinical and functional outcome was measured using the Olerud-Molander Ankle Score (OMAS), the American Orthopaedic Foot and Ankle Society ankle-hindfoot score (AOFAS) and a Visual Analog Score (VAS) for overall satisfaction (range 0-10). RESULTS: Eighty-two patients were treated conservatively and 103 underwent operative treatment. The majority was female. Most conservatively treated fractures were AO-Weber B1.1 type fractures. Fractures with fibular displacement (mainly AO type B1.2 and Lauge-Hansen type SER-4) were predominantly treated operatively. The outcome scores in the non-operative group were OMAS 93, AOFAS 98, and VAS 8. Outcome in this group was independently negatively affected by age, affected side, BMI, fibular displacement, and duration of plaster immobilization. In the surgically treated group, the OMAS, AOFAS, and VAS scores were 90, 97, and 8, respectively, with outcome negatively influenced by duration of plaster immobilization. CONCLUSION: Treatment selection based upon stability and surgeon's judgment led to overall good clinical outcome in both treatment groups. Reducing the cast immobilization period may further improve outcome.

Accuracy of an expanded early warning score for patients in general and trauma surgery wards.

BACKGROUND: Early warning scores (EWS) may aid the prediction of major adverse events in hospitalized patients. Recently, an expanded EWS was introduced in the Netherlands. The aim of this study was to assess the relationship between this EWS and the occurrence of major adverse clinical events during hospitalization of patients admitted to a general and trauma surgery ward. METHODS: This was a prospective cohort study of consecutive patients admitted to the general and trauma surgery ward of a university medical centre (March-September 2009). Follow-up was limited to the time the patient was hospitalized. Logistic regression analysis was used to assess the relationship between the EWS and the occurrence of the composite endpoint consisting of death, reanimation, unexpected intensive care unit admission, emergency surgery and severe complications. Performance of the EWS was analysed using sensitivity, specificity, predictive values and receiver operating characteristic (ROC) curves. RESULTS: A total of 572 patients were included. During a median follow-up of 4 days, 46 patients (8.0 per cent) reached the composite endpoint (two deaths, two reanimations, 17 intensive care unit admissions, 44 severe complications, one emergency operation). An EWS of at least 3, adjusted for baseline American Society of Anesthesiology classification, was associated with a significantly higher risk of reaching the composite endpoint (odds ratio 11·3, 95 per cent confidence interval (c.i.) 5·5 to 22·9). The area under the ROC curve was 0·87 (95 per cent c.i. 0·81 to 0·93). When considering an EWS of at least 3 to be a positive test result, sensitivity was 74 per cent and specificity was 82 per cent. CONCLUSION: An EWS of 3 or more is an independent predictor of major adverse events in patients admitted to a general and trauma surgery ward.

Increased rates of wound complications with locking plates in distal fibular fractures.

INTRODUCTION: There is a growing use of locking compression plates in fracture surgery. The current study was undertaken to investigate the wound complication rates of locking versus non-locking plates in distal fibular fractures. PATIENTS AND METHODS: During a 6-year study period all consecutive, closed distal fibular fractures treated with either a locking or a non-locking plate were included and retrospectively analysed for complication related to the fibula. RESULTS: A total of 165 patients received a one-third tubular plate and 40 patients were treated with a locking plate. The two groups were comparable with respect to patient characteristics (age, gender, smokers and diabetics), injury characteristics (affected side, fracture dislocations, number of fractured malleoli and classification) and operation characteristics (surgical delay and duration, use of a tourniquet and plate length). The wound complication rate was 5.5% in the conventional plating group, and 17.5% in the locking plate group (p=0.019). This difference was largely due to an increase in major complications, for which removal of the plate was necessary (p=0.008). CONCLUSION: There is a significant increase in wound complications in distal fibular fractures treated with a locking compression plate. In light of the current study, we would caution against the application of the currently used locking compression plates in the treatment of distal fibular fractures.

Comparison of three different pelvic circumferential compression devices: a biomechanical cadaver study.

BACKGROUND: Pelvic circumferential compression devices are designed to stabilize the pelvic ring and reduce the volume of the pelvis following trauma. It is uncertain whether pelvic circumferential compression devices can be safely applied for all types of pelvic fractures because the effects of the devices on the reduction of fracture fragments are unknown. The aim of this study was to compare the effects of circumferential compression devices on the dynamic realignment and final reduction of the pelvic fractures as a measure of the quality of reduction. METHODS: Three circumferential compression devices were evaluated: the Pelvic Binder, the SAM Sling, and the T-POD. In sixteen cadavers, four fracture types were generated according to the Tile classification system. Infrared retroreflective markers were fixed in the different fracture fragments of each pelvis. The circumferential compression device was applied sequentially in a randomized order with gradually increasing forces applied. Fracture fragment movement was studied with use of a three-dimensional infrared video system. Dynamic realignment and final reduction of the fracture fragments during closure of the circumferential compression devices were determined. A factorial repeated-measures analysis of variance with pairwise post hoc comparisons was performed to analyze the differences in pulling force between the circumferential compression devices. RESULTS: In the partially stable and unstable (Tile type-B and C) pelvic fractures, all circumferential compression devices accomplished closure of the pelvic ring and consequently reduced the pelvic volume. No adverse fracture displacement (>5 mm) was observed in these fracture types. The required pulling force to attain complete reduction at the symphysis pubis varied substantially among the three different circumferential compression devices, with a mean (and standard error of the mean) of 43 ± 7 N for the T-POD, 60 ± 9 N for the Pelvic Binder, and 112 ± 10 N for the SAM Sling. CONCLUSIONS: The Pelvic Binder, SAM Sling, and T-POD provided sufficient reduction in partially stable and unstable (Tile type-B1 and C) pelvic fractures. No undesirable overreduction was noted. The pulling force that was needed to attain complete reduction of the fracture parts varied significantly among the three devices, with the T-POD requiring the lowest pulling force for fracture reduction.

Demographics and outcome of metatarsal fractures.

INTRODUCTION: Although metatarsal fractures are amongst the most common injuries of the foot, this is the first study on outcome after metatarsal fractures. METHOD: All consecutive patients with metatarsal fractures treated between January 2006 and September 2008 were re-evaluated. Patients aged 16 to 75 were sent a questionnaire consisting of the American Orthopaedic Foot Ankle Society midfoot score and a Visual Analogue Scale (VAS) for patient satisfaction. RESULTS: Four-hundred metatarsal fractures were identified in 322 patients. The fifth metatarsal was involved in more than 50% of patients. Most fractures were caused by an inversion injury or fall from height (75%). Out of 247 patients between 16 and 75 years, a total of 166 patients (67.2%) returned the questionnaire with a median follow-up of 33 months. All patients were treated conservatively. The median AOFAS score was 100 points (P(25)-P(75), 87-100), the median VAS was 9 points (P(25)-P(75), 8-10). The AOFAS and VAS scores correlated negatively with the body mass index (BMI) (R (s) = -0.409 and -0.305; p < 0.001). Patients with diabetes reported lower VAS (p = 0.010) and AOFAS scores (p = 0.020). Females reported a lower AOFAS score (p = 0.034). An increase in dislocation (>2 mm) resulted in a decrease in VAS score (p = 0.017). Multivariable analysis indicated that the VAS score was significantly affected by BMI and dislocation >2 mm (p = 0.013). The AOFAS score was affected by BMI (p = 0.011). CONCLUSION: This is the first investigation using two validated outcome scoring systems to determine functional outcome in metatarsal fractures. Overall outcome in metatarsal fractures is high, as almost all fractures healed without complaints at 33 months. Outcome is dependent on BMI, diabetes, gender, and dislocation at the fracture site.

Cost-effectiveness and quality-of-life analysis of physician-staffed helicopter emergency medical services.

BACKGROUND: The long-term health outcomes and costs of helicopter emergency medical services (HEMS) assistance remain uncertain. The aim of this study was to investigate the cost-effectiveness of HEMS assistance compared with emergency medical services (EMS). METHODS: A prospective cohort study was performed at a level I trauma centre. Quality-of-life measurements were obtained at 2 years after trauma, using the EuroQol-Five Dimensions (EQ-5D) as generic measure to determine health status. Health outcomes and costs were combined into costs per quality-adjusted life year (QALY). RESULTS: The study population receiving HEMS assistance was more severely injured than that receiving EMS assistance only. Over the 4-year study interval, HEMS assistance saved a total of 29 additional lives. No statistically significant differences in quality of life were found between assistance with HEMS or with EMS. Two years after trauma the mean EQ-5D utility score was 0.70 versus 0.71 respectively. The incremental cost-effectiveness ratio for HEMS versus EMS was 28,327 Euro per QALY. The sensitivity analysis showed a cost-effectiveness ratio between 16,000 and 62,000 Euro. CONCLUSION: In the Netherlands, the costs of HEMS assistance per QALY remain below the acceptance threshold. HEMS should therefore be considered as cost effective.

Prognostic significance of molecular-cytogenetic abnormalities in pediatric T-ALL is not explained by immunophenotypic differences.

Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is characterized by chromosomal rearrangements possibly enforcing arrest at specific development stages. We studied the relationship between molecular-cytogenetic abnormalities and T-cell development stage to investigate whether arrest at specific stages can explain the prognostic significance of specific abnormalities. We extensively studied 72 pediatric T-ALL cases for genetic abnormalities and expression of transcription factors, NOTCH1 mutations and expression of specific CD markers. HOX11 cases were CD1 positive consistent with a cortical stage, but as 4/5 cases lacked cytoplasmatic-beta expression, developmental arrest may precede beta-selection. HOX11L2 was especially confined to immature and pre-AB developmental stages, but 3/17 HOX11L2 mature cases were restricted to the gammadelta-lineage. TAL1 rearrangements were restricted to the alphabeta-lineage with most cases being TCR-alphabeta positive. NOTCH1 mutations were present in all molecular-cytogenetic subgroups without restriction to a specific developmental stage. CALM-AF10 was associated with early relapse. TAL1 or HOX11L2 rearrangements were associated with trends to good and poor outcomes, respectively. Also cases with high vs low TAL1 expression levels demonstrated a trend toward good outcome. Most cases with lower TAL1 levels were HOX11L2 or CALM-AF10 positive. NOTCH1 mutations did not predict for outcome. Classification into T-cell developmental subgroups was not predictive for outcome.

Metabolic gene polymorphism frequencies in control populations.

Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1, NAT2, GSTP, and EPHX) in the human population were determined. Major and significant differences in these frequencies were observed between Caucasians (n = 12,525), Asians (n = 2,136), and Africans and African Americans (n = 996), and some, but much less, heterogeneity was observed within Caucasian populations from different countries. No differences in allele frequencies were seen by age, sex, or type of controls (hospital patients versus population controls). No examples of linkage disequilibrium between the different loci were detected based on comparison of observed and expected frequencies for combinations of specific alleles.

Immunohistochemical localization of glutathione S-transferase alpha and pi in human esophageal squamous epithelium, Barrett's epithelium and carcinoma.

High tissue levels of glutathione S-transferases (GSTs), a family of detoxification enzymes, are inversely correlated with cancer risk in the human gastrointestinal tract. Patients with Barrett's esophagus, wherein squamous epithelium is replaced by columnar epithelium, have an increased risk for developing esophageal adenocarcinoma. Biochemical analyses revealed that Barrett's epithelium contains lower levels of GST enzyme activity as well as some GST isoforms, as compared with squamous epithelium. So far, little information on the immunohistochemical distribution of the GST alpha and pi isoforms in normal squamous epithelium, in Barrett's metaplastic epithelium or in adeno- and squamous cell carcinomas of the esophagus is available. Tissues were fixed in formalin and embedded in paraffin. Three 4 microm thick sections were used for hematoxylin and eosin staining and for immunostaining with antibodies against GST alpha and pi. GST alpha and pi were seen in normal squamous epithelium (0% and 75%, respectively), Barrett's epithelium (75% and 100%), adenocarcinoma (25% and 100) and squamous cell carcinoma (27% and 91%). Staining was mainly cytoplasmic, though some nuclear staining with the GST pi antibody was apparent. The varying expression of GST alpha and pi in normal and (pre)neoplastic esophagus may have consequences for the treatment of these diseases and may contribute to an understanding of the development of these esophageal disorders.