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1.  Bisected, complex N-glycans and galectins in mouse mammary tumor progression and human breast cancer 
Glycobiology  2013;23(12):1477-1490.
Bisected, complex N-glycans on glycoproteins are generated by the glycosyltransferase MGAT3 and cause reduced cell surface binding of galectins. Previously, we showed that MGAT3 reduces growth factor signaling and retards mammary tumor progression driven by the Polyoma middle T antigen (PyMT) expressed in mammary epithelium under the mouse mammary tumor virus (MMTV) promoter. However, the penetrance of the tumor phenotype became variable in mixed FVB/N and C57BL/6 female mice and we therefore investigated a congenic C57BL/6 Mgat3−/−/MMTV-PyMT model. In the absence of MGAT3, C57BL/6 Mgat3−/−/MMTV-PyMT females exhibited accelerated tumor appearance and increased tumor burden, glucose uptake in tumors and lung metastasis. Nevertheless, activation of extracellular signal-regulated kinase (ERK)1/2 or protein kinase B (AKT) was reduced in ∼20-week C57BL/6 MMTV-PyMT tumors lacking MGAT3. Activation of focal adhesion kinase (FAK), protein tyrosine kinase Src, and p38 mitogen-activated protein kinase were similar to that of controls. All the eight mouse galectin genes were expressed in mammary tumors and tumor epithelial cells (TECs), but galectin-2 and -12 were not detected by western analysis in tumors, and galectin-7 was not detected in 60% of the TEC lines. From microarray data reported for human breast cancers, at least 10 galectin and 7 N-glycan N-acetylglucosaminyl (GlcNAc)-transferase (MGAT) genes are expressed in tumor tissue, and expression often varies significantly between different breast cancer subtypes. Thus, in summary, while MGAT3 and bisected complex N-glycans retard mouse mammary tumor progression, genetic background may modify this effect; identification of key galectins that promote mammary tumor progression in mice is not straightforward because all the eight galectin genes are expressed; and high levels of MGAT3, galectin-4, -8, -10, -13 and -14 transcripts correlate with better relapse-free survival in human breast cancer.
PMCID: PMC3816629  PMID: 24037315
breast cancer; galectins; mammary tumors;  MGAT3; TCGA
2.  The 'Ziran' wrap: reconstruction of critical-sized long bone defects using a fascial autograft and reamer-irrigator-aspirator autograft 
Reconstruction of critical-size bony defects remains a challenge to surgeons despite recent technological advances. Current treatments include distraction osteogenesis, cancellous autograft, induced membranes (Masquelet procedure), polymeric membranes, and titanium-mesh cages filled with bone graft. In this article, the authors presents two cases in which critical-sized defects were reconstructed using a meshed fascial autograft encasing reamer-irrigator-aspirator (RIA) autograft and cancellous allograft. This article will discuss the clinical outcomes of the technique, comparison to other current techniques, and technical insight into the potential biological mechanism.
PMCID: PMC4189609  PMID: 25298784
Critical-sized defect; Stem/progenitor cells; Guided bone regeneration; Periosteum; Reamer-irrigator-aspirator
3.  Reducing mortality in hip fracture patients using a perioperative approach and “Patient- Centered Medical Home” model: a prospective cohort study 
Hip fracture patients experience high morbidity and mortality rates in the first post-operative year after discharge. We compared mortality, utilization, costs, pain and function between two prospective cohorts of hip fracture patients, both managed with identical perioperative protocols and one group subsequently managed via a “Patient-Centered Medical Home” (PCMH) primary care management model.
We analyzed 6 and 12-month outcomes from two matched cohorts of patients who were surgically treated for hip fracture from January 1, 2010 to June 30, 2011 at two hospitals (n = 194). Controls did not receive PCMH and were matched to cases on surgery date, sex, age, and comorbidities. Mortality and healthcare utilization were the primary outcomes studied, with medical costs, quality of life, pain and function at 12 months assessed as secondary outcomes in a subgroup. Survival analysis, regression and Student-t testing were used with p < 0.05 considered significant.
At 6 months, PCMH patients had significantly lower mortality than patients receiving standard care (11% vs. 26%, p < 0.01). At 12 months, a difference persisted (23% vs. 30%, p = 0.12) but was no longer statistically significant. Mean quality of life scores were similar (0.73 vs. 0.76, p = 0.49) and Harris Hip score was slightly improved for PCMH (73 vs. 64, p = 0.04). Mean costs per patient per month were lower for PCMH but not significantly different ($69 vs. $141, p = 0.20 for pharmacy costs; $1212 vs. $1452, p = 0.45 for non-pharmacy costs).
Patients receiving aggressive post-discharge care from a PCMH program showed significant benefits in terms of reduced mortality at 6 months, with similar costs and functional outcomes at 12 months. PCMH was not shown to improve all outcomes studied, but these results suggest that ongoing Medical Home management can have some benefit for patients without negatively impacting function or cost.
PMCID: PMC3914378  PMID: 24490635
Hip fracture; Mortality; Care coordination; Primary care
4.  Outcomes and complication rates of different bone grafting modalities in long bone fracture nonunions: a retrospective cohort study in 182 patients 
Novel bone substitutes have challenged the notion of autologous bone grafting as the ‘gold standard’ for the surgical treatment of fracture nonunions. The present study was designed to test the hypothesis that autologous bone grafting is equivalent to other bone grafting modalities in the management of fracture nonunions of the long bones.
A retrospective review of patients with fracture nonunions included in two prospective databases was performed at two US level 1 trauma centers from January 1, 1998 (center 1) or January 1, 2004 (center 2), respectively, until December 31, 2010 (n = 574). Of these, 182 patients required adjunctive bone grafting and were stratified into the following cohorts: autograft (n = 105), allograft (n = 38), allograft and autograft combined (n = 16), and recombinant human bone morphogenetic protein-2 (rhBMP-2) with or without adjunctive bone grafting (n = 23). The primary outcome parameter was time to union. Secondary outcome parameters consisted of complication rates and the rate of revision procedures and revision bone grafting.
The autograft cohort had a statistically significant shorter time to union (198 ± 172–225 days) compared to allograft (416 ± 290–543 days) and exhibited a trend towards earlier union when compared to allograft/autograft combined (389 ± 159–619 days) or rhBMP-2 (217 ± 158–277 days). Furthermore, the autograft cohort had the lowest rate of surgical revisions (17%) and revision bone grafting (9%), compared to allograft (47% and 32%), allograft/autograft combined (25% and 31%), or rhBMP-2 (27% and 17%). The overall new-onset postoperative infection rate was significantly lower in the autograft group (12.4%), compared to the allograft cohort (26.3%) (P < 0.05).
Autologous bone grafting appears to represent the bone grafting modality of choice with regard to safety and efficiency in the surgical management of long bone fracture nonunions.
PMCID: PMC3847297  PMID: 24016227
Fracture nonunion; Autograft; Allograft; Bone morphogenetic protein
5.  Safe surgical technique for associated acetabular fractures 
Associated acetabular fractures are challenging injuries to manage. The complex surgical approaches and the technical difficulty in achieving anatomical reduction imply that the learning curve to achieve high-quality care of patients with such challenging injuries is extremely steep. This first article in the Journal’s “Safe Surgical Technique” section presents the standard surgical care, in conjunction with intraoperative tips and tricks, for the safe management of all subgroups of associated acetabular fractures.
PMCID: PMC3620582  PMID: 23414782
Acetabular fractures; Safe surgical technique; Acetabular fixation; Patient safety
7.  HLA-DPβ1 Asp84-Lys69 antigen-binding signature predicts event-free survival in childhood B-cell precursor acute lymphoblastic leukaemia: results from the MRC UKALL XI childhood ALL trial 
Blood Cancer Journal  2012;2(7):e80-.
We previously reported that children in the UKALL XI ALL trial with HLA-DP 1 and -DP 3 supertypes had significantly worse event-free survival (EFS) than children with other DP supertypes. As DP 1 and DP 3 share two of four key antigen-binding amino-acid polymorphisms (aspartic acid84–lysine69), we asked whether Asp84-Lys69 or Asp84 alone were independent prognostic indicators in childhood acute lymphoblastic leukemia (ALL). We analysed EFS in 798 UKALL XI patients, stratified by Asp84-Lys69 vs non-Asp84-Lys69, for a median follow-up of 12.5 years. Asp84-Lys69 was associated with a significantly worse EFS than non-Asp84-Lys69 (5-year EFS: Asp84-Lys69: 58.8% (95% CI (confidence of interval): 52.7–64.9%); non-Asp84-Lys69: 67.3% (63.4–71.2%); 2P=0.007). Post-relapse EFS was 10% less in Asp84-Lys69 than non-Asp84-Lys69 patients. EFS was significantly worse (P=0.03) and post-relapse EFS marginally worse (P=0.06) in patients with Asp84 compared with Gly84. These results suggest that Asp84-Lys69 predicted adverse EFS in the context of UKALL XI because of Asp84, and may have influenced post-relapse EFS. We speculate that this may be due to the recruitment of Asp84-Lys69-restricted regulatory T cells in the context of this regimen, leading to the re-emergence of residual disease. However, functional and molecular studies of the prognostic value of this and other HLA molecular signatures in other childhood ALL trials are needed.
PMCID: PMC3408639  PMID: 22852049
childhood ALL; HLA-DP supertype; DP molecular signature; event-free survival; relapse
8.  Improved specificity for detection of Mycobacterium bovis in fresh tissues using IS6110 real-time PCR 
Culture of M. bovis from diagnostic specimens is the gold standard for bovine tuberculosis diagnostics in the USA. Detection of M. bovis by PCR in tissue homogenates may provide a simple rapid method to complement bacterial culture. A significant impediment to PCR based assays on tissue homogenates is specificity since mycobacteria other than M. bovis may be associated with the tissues.
Previously published IS6110 based PCR diagnostic assays, along with one developed in house, were tested against environmental mycobacteria commonly isolated from diagnostic tissues submitted to the National Veterinary Services Laboratory. A real-time PCR assay was developed (IS6110_T) that had increased specificity over other IS6110 based assays. Of the 13 non-tuberculous mycobacteria tested with IS6110_T only M. wolinskyi was positive. Thirty M. bovis infected tissue homogenates and 18 control tissues were used to evaluate the potential for the assay as a diagnostic test. In this small sample, IS6110_T detected 20/30 samples from M. bovis infected animals and 0/18 control tissues.
The IS6110_T assay provides a PCR based assay system that is compatible with current diagnostic protocols for the detection of M. bovis in the USA and compliments current testing strategies.
PMCID: PMC3170578  PMID: 21867516
9.  Prevalence of sacral dysmorphia in a prospective trauma population: Implications for a "safe" surgical corridor for sacro-iliac screw placement 
Percutaneous sacro-iliac (SI) screw fixation represents a widely used technique in the management of unstable posterior pelvic ring injuries and sacral fractures. The misplacement of SI-screws under fluoroscopic guidance represents a critical complication for these patients. This study was designed to determine the prevalence of sacral dysmorphia and the radiographic anatomy of surgical S1 and S2 corridors in a representative trauma population.
Prospective observational cohort study on a consecutive series of 344 skeletally mature trauma patients of both genders enrolled between January 1, 2007, to September 30, 2007, at a single academic level 1 trauma center. Inclusion criteria included a pelvic CT scan as part of the initial diagnostic trauma work-up. The prevalence of sacral dysmorphia was determined by plain radiographic pelvic films and CT scan analysis. The anatomy of sacral corridors was analyzed on 3 mm reconstruction sections derived from multislice CT scan, in the axial, coronal, and sagittal plane. "Safe" potential surgical corridors at S1 and S2 were calculated based on these measurements.
Radiographic evidence of sacral dysmorphia was detected in 49 patients (14.5%). The prevalence of sacral dysmorphia was not significantly different between male and female patients (12.2% vs. 19.2%; P = 0.069). In contrast, significant gender-related differences were detected with regard to radiographic analysis of surgical corridors for SI-screw placement, with female trauma patients (n = 99) having significantly narrower corridors at S1 and S2 in all evaluated planes (axial, coronal, sagittal), compared to male counterparts (n = 245; P < 0.01). In addition, the mean S2 body height was higher in dysmorphic compared to normal sacra, albeit without statistical significance (P = 0.06), implying S2 as a safe surgical corridor of choice in patients with sacral dysmorphia.
These findings emphasize a high prevalence of sacral dysmorphia in a representative trauma population and imply a higher risk of SI-screw misplacement in female patients. Preoperative planning for percutaneous SI-screw fixation for unstable pelvic and sacral fractures must include a detailed CT scan analysis to determine the safety of surgical corridors.
PMCID: PMC3105956  PMID: 21569232
10.  Severe postpartum disruption of the pelvic ring: report of two cases and review of the literature 
Pelvic dislocations are rare during labor, and the treatment is controversial. We report two cases of young women who sustained postpartum disruption of the pelvic ring: one case is an 8.8 cm wide separation of the pubic symphysis with sacroiliac joint disruption underwent surgical stabilization and the second case with 4.0 cm disruption being treated non-operatively. These cases illustrated of importance of accurate diagnosis, careful physical exam, fully informed consent and specific treatment for this condition.
PMCID: PMC3025835  PMID: 21232102
11.  Acute morbidity and complications of thigh compartment syndrome: A report of 26 cases 
To describe the patient population, etiology, and complications associated with thigh compartment syndrome (TCS). TCS is a rare condition, affecting less than 0.3% of trauma patients, caused by elevated pressure within a constrained fascial space which can result in tissue necrosis, fibrosis, and physical impairment in addition to other complications. Compartment releases performed after irreversible tissue ischemia has developed can lead to severe infection, amputation, and systemic complications including renal insufficiency and death.
This study examines the course of treatment of 23 consecutive patients with 26 thigh compartment syndromes sustained during an eight-year period at two Level 1 trauma centers, each admitting more than 2,000 trauma patients yearly.
Patients developing TCS were young (average 35.4 years) and likely to have a vascular injury on presentation (57.7%). A tense and edematous thigh was the most consistent clinical exam finding leading to compartment release (69.5%). Average time from admission to the operating room was 18 +/- 4.3 hours and 8/23 (34.8%) were noted to have ischemic muscle changes at the time of release. Half of those patients (4/8) developed local complications requiring limb amputations.
TCS is often associated with high energy trauma and is difficult to diagnose in uncooperative, obtunded and multiply injured patients. Vascular injuries are a common underlying cause and require prompt recognition and a multidisciplinary approach including the trauma and orthopaedic surgeons, intensive care team, vascular surgery and interventional radiology. Prompt recognition and treatment of TCS are paramount to avoid the catastrophic acute and long term morbidities.
PMCID: PMC2933643  PMID: 20723263
12.  Bench-to-bedside review: Burn-induced cerebral inflammation – a neglected entity? 
Critical Care  2009;13(3):215.
Severe burn injury remains a major burden on patients and healthcare systems. Following severe burns, the injured tissues mount a local inflammatory response aiming to restore homeostasis. With excessive burn load, the immune response becomes disproportionate and patients may develop an overshooting systemic inflammatory response, compromising multiple physiological barriers in the lung, kidney, liver, and brain. If the blood–brain barrier is breached, systemic inflammatory molecules and phagocytes readily enter the brain and activate sessile cells of the central nervous system. Copious amounts of reactive oxygen species, reactive nitrogen species, proteases, cytokines/chemokines, and complement proteins are being released by these inflammatory cells, resulting in additional neuronal damage and life-threatening cerebral edema. Despite the correlation between cerebral complications in severe burn victims with mortality, burn-induced neuroinflammation continues to fly under the radar as an underestimated entity in the critically ill burn patient. In this paper, we illustrate the molecular events leading to blood–brain barrier breakdown, with a focus on the subsequent neuroinflammatory changes leading to cerebral edema in patients with severe burns.
PMCID: PMC2717412  PMID: 19638180
13.  Cytokines in the systemic inflammatory response syndrome: a review 
Patients subject to major surgery, suffering sepsis, major trauma, or following cardiopulmonary bypass exhibit a systemic inflammatory response.
This inflammatory response involves a complex array of inflammatory polypeptide molecules known as cytokines. It is well accepted that the loss of local control of the release of these cytokines leads to systemic inflammation and potentially deleterious consequences including the Systemic Inflammatory Response Syndrome, Multi-Organ Dysfunction Syndrome, shock and death.
The Medline database was searched for literature on mechanisms involved in the development of SIRS and potential targets for modifying the inflammatory response. We focus on the novel therapy of cytokine adsorption as a promising removal technology.
Accumulating data from human studies and experimental animal models suggests that both pro- and anti- inflammatory cytokines are released following a variety of initiating stimuli including endotoxin release, complement activation, ischaemia reperfusion injury and others.
Pro-and anti-inflammatory cytokines interact in a complex and unpredictable manner to influence the immune system and eventually cause multiple end organ effects. Cytokine adsorption therapy provides a potential solution to improving outcomes following Systemic Inflammatory Response Syndrome.
PMCID: PMC3484588  PMID: 23441054
cytokine; systemic; inflammatory response; syndrome; SIRS
14.  Advocating "spine damage control" as a safe and effective treatment modality for unstable thoracolumbar fractures in polytrauma patients: a hypothesis 
The "ideal" timing and modality of fracture fixation for unstable thoracolumbar spine fractures in multiply injured patients remains controversial. The concept of "damage control orthopedics" (DCO), which has evolved globally in the past decade, provides a safe guidance for temporary external fixation of long bone or pelvic fractures in multisystem trauma. In contrast, "damage control" concepts for unstable spine injuries have not been widely implemented, and the scarce literature in the field remains largely anecdotal. The current practice standards are reflected by two distinct positions, either (1) immediate "early total care" or (2) delayed spine fixation after recovery from associated injuries. Both concepts have inherent risks which may contribute to adverse outcome.
Presentation of hypothesis
We hypothesize that the concept of "spine damage control" – consisting of immediate posterior fracture reduction and instrumentation, followed by scheduled 360° completion fusion during a physiological "time-window of opportunity" – will be associated with less complications and improved outcomes of polytrauma patients with unstable thoracolumbar fractures, compared to conventional treatment strategies.
Testing of hypothesis
We propose a prospective multicenter trial on a large cohort of multiply injured patients with an associated unstable thoracolumbar fracture. Patients will be assigned to one of three distinct study arms: (1) Immediate definitive (anterior and/or posterior) fracture fixation within 24 hours of admission; (2) Delayed definitive (anterior and/or posterior) fracture fixation at > 3 days after admission; (3) "Spine damage control" procedure by posterior reduction and instrumentation within 24 hours of admission, followed by anterior 360° completion fusion at > 3 days after admission, if indicated. The primary and secondary endpoints include length of ventilator-free days, length of ICU and hospital stay, mortality, incidence of complications, neurological status and functional recovery.
Implications of hypothesis
A "spine damage control" protocol may save lives and improve outcomes in severely injured patients with associated spine injuries.
PMCID: PMC2686673  PMID: 19432965
16.  Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis 
Critical Care  2009;13(1):R12.
Septic encephalopathy secondary to a breakdown of the blood-brain barrier (BBB) is a known complication of sepsis. However, its pathophysiology remains unclear. The present study investigated the effect of complement C5a blockade in preventing BBB damage and pituitary dysfunction during experimental sepsis.
Using the standardised caecal ligation and puncture (CLP) model, Sprague-Dawley rats were treated with either neutralising anti-C5a antibody or pre-immune immunoglobulin (Ig) G as a placebo. Sham-operated animals served as internal controls.
Placebo-treated septic rats showed severe BBB dysfunction within 24 hours, accompanied by a significant upregulation of pituitary C5a receptor and pro-inflammatory cytokine expression, although gene levels of growth hormone were significantly attenuated. The pathophysiological changes in placebo-treated septic rats were restored by administration of neutralising anti-C5a antibody to the normal levels of BBB and pituitary function seen in the sham-operated group.
Collectively, the neutralisation of C5a greatly ameliorated pathophysiological changes associated with septic encephalopathy, implying a further rationale for the concept of pharmacological C5a inhibition in sepsis.
PMCID: PMC2688129  PMID: 19196477
17.  Absence of the complement regulatory molecule CD59a leads to exacerbated neuropathology after traumatic brain injury in mice 
Complement represents a crucial mediator of neuroinflammation and neurodegeneration after traumatic brain injury. The role of the terminal complement activation pathway, leading to generation of the membrane attack complex (MAC), has not been thoroughly investigated. CD59 is the major regulator of MAC formation and represents an essential protector from homologous cell injury after complement activation in the injured brain.
Mice deleted in the Cd59a gene (CD59a-/-) and wild-type littermates (n = 60) were subjected to focal closed head injury. Sham-operated (n = 60) and normal untreated mice (n = 14) served as negative controls. The posttraumatic neurological impairment was assessed for up to one week after trauma, using a standardized Neurological Severity Score (NSS). The extent of neuronal cell death was determined by serum levels of neuron-specific enolase (NSE) and by staining of brain tissue sections in TUNEL technique. The expression profiles of pro-apoptotic (Fas, FasL, Bax) and anti-apoptotic (Bcl-2) mediators were determined at the gene and protein level by real-time RT-PCR and Western blot, respectively.
Clinically, the brain-injured CD59a-/- mice showed a significantly impaired neurological outcome within 7 days, as determined by a higher NSS, compared to wild-type controls. The NSE serum levels, an indirect marker of neuronal cell death, were significantly elevated in CD59a-/- mice at 4 h and 24 h after trauma, compared to wild-type littermates. At the tissue level, increased neuronal cell death and brain tissue destruction was detected by TUNEL histochemistry in CD59a-/- mice within 24 hours to 7 days after head trauma. The analysis of brain homogenates for potential mediators and regulators of cell death other than the complement MAC (Fas, FasL, Bax, Bcl-2) revealed no difference in gene expression and protein levels between CD59a-/- and wild-type mice.
These data emphasize an important role of CD59 in mediating protection from secondary neuronal cell death and further underscore the key role of the terminal complement pathway in the pathophysiology of traumatic brain injury. The exact mechanisms of complement MAC-induced secondary neuronal cell death after head injury require further investigation.
PMCID: PMC2631471  PMID: 19133139
18.  Pharmacology of Traumatic Brain Injury: Where Is the “Golden Bullet”? 
Molecular Medicine  2008;14(11-12):731-740.
Traumatic brain injury (TBI) represents a major health care problem and a significant socioeconomic challenge worldwide. In the United States alone, approximately 1.5 million patients are affected each year, and the mortality of severe TBI remains as high as 35%–40%. These statistics underline the urgent need for efficient treatment modalities to improve posttraumatic morbidity and mortality. Despite advances in basic and clinical research as well as improved neurological intensive care in recent years, no specific pharmacological therapy for TBI is available that would improve the outcome of these patients. Understanding of the cellular and molecular mechanisms underlying the pathophysiological events after TBI has resulted in the identification of new potential therapeutic targets. Nevertheless, the extrapolation from basic research data to clinical application in TBI patients has invariably failed, and results from prospective clinical trials are disappointing. We review the published prospective clinical trials on pharmacological treatment modalities for TBI patients and outline future promising therapeutic avenues in the field.
PMCID: PMC2527342  PMID: 18769636
19.  Blunt injury to the inferior gluteal artery: case report of a rare "near miss" event 
Traumatic injuries of the inferior gluteal artery are rare, the majority of which are aneurysms due to sharp or blunt trauma. We report the rare case of a "near miss" event of a patient with an acute hemorrhagic mass in the right buttock caused by blunt trauma to the inferior gluteal artery without "hard" clinical signs of vascular injury. Despite the unusual presentation, diffuse injury of the inferior gluteal artery branches was diagnosed by ultrasonography and angiography. This article highlights the importance of considering an arterial injury following blunt trauma to the buttock with subsequent pain and swelling. Appreciation of this rare injury pattern is necessary in order to facilitate rapid diagnosis and appropriate treatment.
PMCID: PMC2585072  PMID: 18959806
20.  Treatment of traumatic forearm bone loss with Ilizarov ring fixation and bone transport 
International Orthopaedics  2006;31(2):165-170.
Bone loss in the forearm results from high-energy trauma or follows non-union with infection. Ilizarov methodology provides stable fixation without implantation of permanent foreign bodies while permitting wrist and elbow movement. We are reporting our experience using distraction osteogenesis in the treatment of traumatic bone loss in the forearm. From 1991 to 2000, 11 consecutive patients with traumatic forearm bone loss were treated with Ilizarov ring fixation. Records were reviewed retrospectively. All patients were contacted 2-10 years after surgery at the Ilizarov Clinic in Lecco, Italy. Eleven atrophic non-unions with bone loss were treated. The time from injury to Ilizarov treatment averaged 2.1 years. Follow-up averaged 6.2 years. The union rate with Ilizarov treatment alone was 64%. Thirty-six percent of the patients were converted to a hypertrophic non-union and underwent compression plating. The overall rate of union was 100%. There were four unplanned reoperations and no refractures, neurovascular injuries or deep infections. Three patients had significant limitations of wrist function. Nine patients described their function as excellent. Ilizarov fixation with bone transport is a viable treatment option for atrophic forearm non-unions with bone loss. Treatment resulted in ablation of infection, healing of atrophic non-unions with minimal complications and early extremity use.
PMCID: PMC2267575  PMID: 16821011
22.  Femoral artery thrombosis after internal fixation of a transverse acetabular fracture in a patient with osteogenesis imperfecta type I 
Osteogenesis imperfecta is a genetic disorder characterized by increased susceptibility to fractures and vascular injuries due to connective tissue fragility. In this case report, we present a patient with osteogenesis imperfecta type I who sustained a transverse fracture of the right acetabulum while transferring from bed to chair. The fracture was repaired through an ilioinguinal approach. During the surgery, an iatrogenic injury to the femoral artery and vein occurred. This intraoperative complication was salvaged by immediate vascular repair. We discuss the possible causes of iatrogenic vascular injuries in patients with osteogenesis imperfecta. Orthopaedic surgeons should be aware of this potentially devastating complication in this particular patient cohort.
PMCID: PMC2262876  PMID: 18271949
23.  Peroxisome Proliferator-Activated Receptors: “Key” Regulators of Neuroinflammation after Traumatic Brain Injury 
PPAR Research  2008;2008:538141.
Traumatic brain injury is characterized by neuroinflammatory pathological sequelae which contribute to brain edema and delayed neuronal cell death. Until present, no specific pharmacological compound has been found, which attenuates these pathophysiological events and improves the outcome after head injury. Recent experimental studies suggest that targeting peroxisome proliferator-activated receptors (PPARs) may represent a new anti-inflammatory therapeutic concept for traumatic brain injury. PPARs are “key” transcription factors which inhibit NFκB activity and downstream transcription products, such as proinflammatory and proapoptotic cytokines. The present review outlines our current understanding of PPAR-mediated neuroprotective mechanisms in the injured brain and discusses potential future anti-inflammatory strategies for head-injured patients, with an emphasis on the putative beneficial combination therapy of synthetic cannabinoids (e.g., dexanabinol) with PPARα agonists (e.g., fenofibrate).
PMCID: PMC2276625  PMID: 18382619
24.  Repetitive posterior iliac crest autograft harvest resulting in an unstable pelvic fracture and infected non-union: case report and review of the literature 
Fractures of the pelvic ring have been well studied, and the biomechanical relationship between the anterior and posterior elements is an important concept to understand these complex injuries. The vast majority of these injuries are due to trauma. However, in rare circumstances, autogenous bone graft harvesting may lead to an unstable pelvic ring. In this case report, we describe a rare complication in a 70-year old female patient who developed an unstable pelvis and an infected non-union secondary to repeated posterior iliac graft harvest. The orthopaedic surgeon should be aware of this detrimental complication associated with extensive or repeated posterior iliac crest graft harvest.
PMCID: PMC2241775  PMID: 18271999
25.  Bias towards publishing positive results in orthopedic and general surgery: a patient safety issue? 
Research articles reporting positive findings in the fields of orthopedic and general surgery appear to be represented at a considerably higher prevalence in the peer-reviewed literature, compared to published studies on negative or neutral data. This "publication bias" may alter the balance of the available evidence-based literature and may affect patient safety in surgery by depriving important information from unpublished negative studies.
A comprehensive review of all published articles in a defined 7-year period was performed in 12 representative journals in the fields of orthopedic and general surgery. Every article published in all volumes of these journals between January 2000 and December 2006 was reviewed and rated by three investigators. Rating of articles was performed according to a uniform, standardized algorithm. All original articles were stratified into "positive", "negative" or "neutral", depending on the reported results. All non-original papers were excluded from analysis.
A total of 30,197 publications were reviewed over a 7-year time-period. After excluding all non-original articles, a total of 16,397 original papers were included in the final analysis. Of these, 12,251 (74%) articles were found to report positive findings, 2,709 (17%) reported negative results, and 1,437 (9%) were neutral. A similar publication pattern was found among all years and all journals analyzed. Altogether, 91% of all original papers reported significant data (positive or negative), whereas only 9% were neutral studies that did not report any significant findings.
There is a disproportionately high number of articles reporting positive results published in the surgical literature. A bias towards publishing positive data will systematically overestimate the clinical relevance of treatment effects by disregarding important information derived from unpublished negative studies. This "publication bias" remains an area of concern and may affect the quality of care of patients undergoing surgical procedures.
PMCID: PMC2241774  PMID: 18271997

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