Long-term outcome of alcohol withdrawal seizures.

BACKGROUND AND PURPOSE: Alcohol withdrawal seizures (AWS) are a well-known complication of chronic alcohol abuse, but there is currently little knowledge of their long-term relapse rate and prognosis. The aims of this study were to identify risk factors for AWS recurrence and to study the overall outcome of patients after AWS. METHODS: In this retrospective single-center study, we included patients who were admitted to the Emergency Department after an AWS between January 1, 2013 and August 10, 2021 and for whom an electroencephalogram (EEG) was requested. AWS relapses up until April 29, 2022 were researched. We compared history, treatment with benzodiazepines or antiseizure medications (ASMs), laboratory, EEG and computed tomography findings between patients with AWS relapse (r-AWS) and patients with no AWS relapse (nr-AWS). RESULTS: A total of 199 patients were enrolled (mean age 53 ± 12 years; 78.9% men). AWS relapses occurred in 11% of patients, after a median time of 470.5 days. Brain computed tomography (n = 182) showed pathological findings in 35.7%. Risk factors for relapses were history of previous AWS (p = 0.013), skull fractures (p = 0.004) at the index AWS, and possibly epileptiform EEG abnormalities (p = 0.07). Benzodiazepines or other ASMs, taken before or after the index event, did not differ between the r-AWS and the nr-AWS group. The mortality rate was 2.9%/year of follow-up, which was 13 times higher compared to the general population. Risk factors for death were history of AWS (p < 0.001) and encephalopathic EEG (p = 0.043). CONCLUSIONS: Delayed AWS relapses occur in 11% of patients and are associated with risk factors (previous AWS >24 h apart, skull fractures, and pathological EEG findings) that also increase the epilepsy risk, that is, predisposition for seizures, if not treated. Future prospective studies are mandatory to determine appropriate long-term diagnostic and therapeutic strategies, in order to reduce the risk of relapse and mortality associated with AWS.

Limited Efficacy of Empiric Antibiotics for Pediatric Facial Fractures.

BACKGROUND: Controversies exist regarding the role of perioperative antibiotic use in pediatric craniomaxillofacial fracture repair. PURPOSE: This study aims to identify factors associated with antibiotic prescribing patterns and measures the association between antibiotic exposure and postoperative infections. STUDY DESIGN, SETTING, SAMPLE: In this retrospective cohort study, TriNetX, a research database, was used to gather data on patients under 18 years of age who underwent repair of facial fractures. The records were obtained from 2003 to 2021. Current Procedural Terminology codes for facial fracture procedures were used to identify patients. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: Antibiotic use, defined as a binary categorical variable of whether or not patients received perioperative antibiotics. The secondary predictor variable was timing of antibiotic administration, categorized by pre, intra, and postoperative administration. MAIN OUTCOME VARIABLES: Postoperative infection, determined by International Classification of Diseases, 9th and 10th Revision codes within patient charts. COVARIATES: Covariates included demographic variables such as age, sex, race, ethnicity, geographic location, and fracture characteristics, such as number of fractures and location of fracture. ANALYSES: χ2 analyses were used for categorical variables and two sample t tests for quantitative variables. Multivariable logistic regression was used to evaluate patient infection and antibiotic use with adjustment for covariates. P-values were 2-tailed and statistical significance was defined as P < .05. RESULTS: This cohort included 5,413 patients of which 70.4% were male, 74.4% identified as white, and 83.3% identified as non-Hispanic or Latino. There were no differences in postoperative infections in patients who received antibiotics compared to those who did not (0.9 vs 0.5%, respectively, P = .12). Nevertheless, antibiotic prescriptions have increased over the years. After controlling for relevant covariates, antibiotic use did not decrease the odds of infection (adjusted odds ratio 1.1, 95% CI 0.53 to 2.34, P = .79). There was a significant association between the timing of antibiotic use and infection (P = .044), with increased odds of infection when antibiotics were given postoperatively (adjusted odds ratio 3.8, 95% CI 1.2 to 12.07, P = .023). CONCLUSION AND RELEVANCE: While antibiotic prescriptions have increased over the years, this study demonstrates there is no difference in postoperative infection rates for pediatric patients prescribed antibiotics and those where were not.

Comparative Therapeutic Effectiveness of Anticoagulation and Conservative Management in Traumatic Cerebral Venous Sinus Thrombosis.

BACKGROUND: Consensus is currently lacking in the optimal treatment for blunt traumatic cerebral venous sinus thrombosis (tCVST). Anticoagulation (AC) is used for treating spontaneous CVST, but its role in tCVST remains unclear. OBJECTIVE: To investigate the characteristics and outcomes of patients treated with AC compared with patients managed conservatively. METHODS: We retrospectively reviewed patients who presented to a Level 1 trauma center with acute skull fracture after blunt head trauma who underwent dedicated venous imaging. RESULTS: There were 137 of 424 patients (32.3%) presenting with skull fractures with tCVST on venous imaging. Among them, 82 (60%) were treated with AC while 55 (40%) were managed conservatively. Analysis of baseline characteristics demonstrated no significant difference in age, sex, admission Glasgow Coma Scale, admission Injury Severity Score, rates of associated intracranial hemorrhage, or neurosurgical interventions. New or worsening intracranial hemorrhage was seen in 7 patients treated with AC. Patients on AC had significantly lower mortality than non-AC (1% vs 15%; P = .003). There was no difference in the Glasgow Coma Scale or Glasgow Outcome Scale at last clinical follow-up. On follow-up venous imaging, patients treated with AC were more likely to experience full thrombus recanalization than non-AC (54% vs 32%; P = .012), and subsequent multiple regression analysis revealed that treatment with AC was a significant predictor of full thrombus recanalization (odds ratio, 5.18; CI, 1.60-16.81; P = .006). CONCLUSION: Treatment with AC for tCVST due to blunt head trauma may promote higher rates of complete thrombus recanalization when compared with conservative management.

Pre-Operative Antibiotic Agents for Facial Fractures: Is More than One Day Necessary?

Background: Despite a paucity of evidence, patients with facial fractures often receive long courses of pre-operative antibiotic agents. This study compared the effect of a short versus long pre-operative antibiotic course on the development of post-operative head/neck infections in this population. Patients and Methods: All adult patients admitted between January 2010 and May 2015 to a level 1 trauma center with isolated head/neck injuries who underwent surgery for facial fracture(s) were included. Patients with infections prior to surgery were excluded. Our primary analysis compared head/neck infections between patients given a short (≤24 hours) versus long (>24 hours) course of pre-operative antibiotic agents. Bivariate analysis and multivariate logistic regression (MLR) were performed to identify risk factors for head/neck infections. Results: This study included 188 patients; median age was 38.5 years, 83% were male, 81% had blunt injuries, 51.6% had fractures in multiple facial thirds, and 48.9% required intensive care unit (ICU) admission. One hundred twenty-five (66.5%) patients received a short course and 63 (33.5%) received a long course of pre-operative antibiotic agents. Head/neck infections were higher in the long course group (28.6% vs 15.2%; p = 0.034), but median days to infection were similar. Factors associated with head/neck infections included penetrating injury, mandible fracture, involvement of multiple facial thirds, ICU admission, operative time, and receiving a long pre-operative antibiotic course. Multivariable logistic regression found mandible fracture (odds ratio [OR], 2.9; p = 0.01) and ICU admission (OR, 3.3; p = 0.003) to be independent predictors of head/neck infections (area under the curve [AUC] = 0.706), but pre-operative antibiotic course was not. Patients with isolated mandible fractures (n = 42) had higher rates of head/neck infections in the long course group (29.4% vs 4.0%; p = 0.032), despite similar demographics. Conclusion: Long (>24 hours) course of continuous pre-operative antibiotic prophylaxis before surgery for facial fractures did not reduce the development of head/neck infections.

Bone Tissue Engineering in the Growing Calvaria Using Dipyridamole-Coated, Three-Dimensionally-Printed Bioceramic Scaffolds: Construct Optimization and Effects on Cranial Suture Patency.

BACKGROUND: Three-dimensionally-printed bioceramic scaffolds composed of ß-tricalcium phosphate delivering the osteogenic agent dipyridamole can heal critically sized calvarial defects in skeletally mature translational models. However, this construct has yet to be applied to growing craniofacial models. In this study, the authors implanted three-dimensionally-printed bioceramic/dipyridamole scaffolds in a growing calvaria animal model and evaluated bone growth as a function of geometric scaffold design and dipyridamole concentration. Potential adverse effects on the growing suture were also evaluated. METHODS: Bilateral calvarial defects (10 mm) were created in 5-week-old (approximately 1.1 kg) New Zealand White rabbits (n = 16 analyzed). Three-dimensionally-printed bioceramic scaffolds were constructed in quadrant form composed of varying pore dimensions (220, 330, and 500 µm). Each scaffold was coated with collagen and soaked in varying concentrations of dipyridamole (100, 1000, and 10,000 µM). Controls consisted of empty defects. Animals were killed 8 weeks postoperatively. Calvariae were analyzed using micro-computed tomography, three-dimensional reconstruction, and nondecalcified histologic sectioning. RESULTS: Scaffold-induced bone growth was statistically greater than bone growth in empty defects (p = 0.02). Large scaffold pores, 500 µm, coated in 1000 µM dipyridamole yielded the most bone growth and lowest degree of scaffold presence within the defect. Histology showed vascularized woven and lamellar bone along with initial formation of vascular canals within the scaffold lattice. Micro-computed tomographic and histologic analysis revealed patent calvarial sutures without evidence of ectopic bone formation across all dipyridamole concentrations. CONCLUSION: The authors present an effective pediatric bone tissue-engineering scaffold design and dipyridamole concentration that is effective in augmentation of calvarial bone generation while preserving cranial suture patency.

The Efficacy of Hyaluronidase in Early Surgery of Nasal Bone Fracture.

A nasal bone fracture is one of the most common facial injuries and is often treated by closed reduction. Typically, 2 to 3 weeks are needed for patients to return to daily life because the operation is performed after swelling around the fracture site is reduced. This study aimed to investigate that hyaluronidase injection could reduce swelling, perform early operation and return to daily life accelerated.From January 2017 to December 2017, 181 patients with nasal bone fracture were analyzed. 60 patients underwent hyaluronidase injection and massage to reduce edema, then performed surgery within 2 to 4 days. The remaining patients were treated conservatively (massage alone); they then underwent surgery. Ultrasonography was used to measure changes in skin thickness, and the treatment duration, outcome, and patient satisfaction were compared.The duration from injury to surgery was short in the early operation group, and the period of recovery and return to ordinary life was significantly shorter than in the conventional group. The difference in skin thickness after hyaluronidase injection and massage was 0.8 mm in the early operation group; there was no significant difference in the conventional group. There was no statistically significant difference in satisfaction between the 2 groups, but the mean satisfaction was higher in the early operation group.In patients with nasal bone fracture after facial trauma, hyaluronidase injection, and massage led to reduced edema. This might improve patient satisfaction by allowing earlier operation and earlier return to daily life.

Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice.

Bone fractures are associated with considerable morbidity and increased mortality. A major limitation to healing is lack of bone blood flow, which is impaired by physical disruption of intraskeletal and/or periosteal vasculature by the fracture. Thus, pharmacological interventions are needed to improve osseous blood flow, thereby accelerating bone fracture closure. Relaxin is secreted by the ovary and circulates in rodents and humans during pregnancy. Because relaxin might benefit bone fracture healing by stimulating angiogenesis, vasculogenesis (and potentially osteogenesis) through mobilization and activation of bone marrow progenitor cells, and by increasing blood flow via vasodilation, we investigated whether relaxin administration would accelerate closure of a calvarial defect in mice. Whether administered systemically by osmotic pump or locally by collagen scaffolds for ~2 week period after lesioning, relaxin did not accelerate bone healing. Despite implementing relaxin doses that reached plasma concentrations spanning the physiological to supraphysiological range, testing the closure of two different sizes of calvarial lesions, allowing for different intervals of time from instigation of cranial lesion to euthanasia, and investigating mice of different ages, we did not observe a significant benefit of relaxin in bone lesion healing. Nor did we observe stimulation of blood vessel formation in the bone lesion by the hormone. An incidental finding was that relaxin appeared to enhance trabecular bone growth in an uninjured control bone (femur). Although the results of this study were not supportive of a therapeutic benefit for relaxin on calvarial defect closure, future investigation is needed employing different animal species and experimental models of bone fracture.

Fibrinolysis in trauma patients: wide variability demonstrated by the Lysis Timer.

Hyperfibrinolysis contributes to the pathophysiology of trauma-induced coagulopathy. At present, systematic administration of tranexamic acid (TXA) is recommended in all patients in the early phase of trauma. However, there is some debate regarding whether TXA is beneficial in all trauma patients. A rapid and accurate tool to diagnose hyperfibrinolysis may be useful for tailoring TXA treatment. We conducted a proof-of-concept study of consecutive adult trauma patients. A first blood sample was obtained at the time of pre-hospital care (T1). Patients received 1 g of TXA after T1. A second sample was obtained on arrival at the emergency unit (T2). We examined coagulation, fibrin and fibrinogen formation and degradation. Fibrinolysis was assessed by determining tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor 1 (PAI-1) activity and global fibrinolysis capacity assay using a device developed by Hyphen BioMed: the Lysis Timer (GFC/LT). The study population consisted of 20 patients (42 ± 21 years, index of severity score 32 ± 21). Both coagulation and fibrinolysis were altered at T1. GFC/LT values exhibited hyperfibrinolysis only in five patients. Principal component analysis carried out at T1 showed two main axes of alteration. The major axis was related to coagulation, altered in all patients, while the second axis was related to fibrinolysis. GFC/LT was mainly influenced by PAI-1 activity while fibrin monomers were related to the severity of trauma. At T2, GFC/LT exhibited the marked effect of TXA on clot lysis time. In conclusion, GFC/LT demonstrated huge variation in the fibrinolytic response to trauma.

Effects of combined menaquinone-4 and PTH1-34 treatment on osetogenesis and angiogenesis in calvarial defect in osteopenic rats.

PURPOSE: The aim of this study was to evaluate the effect of combining human parathyroid hormone (1-34) (PTH1-34; PTH) and menaquinone-4 (MK-4) on calvarial bone defect repair in osteopenic rats. METHODS: Fourteen week olds were subject to craniotomy for the establishment of osteopenic animal models fed through a chronically low-protein diet. After that, critical calvarial defect model was established and all rats were randomly divided into four groups: sham, MK-4, PTH, and PTH + MK-4. The animals received MK-4 (30 mg/kg/day), PTH1-34 (60 µg/kg, three times a week), or PTH1-34 (60 µg/kg, three times a week) plus MK-4 (30 mg/kg/day) for 8 weeks, respectively. Serum γ-carboxylated osteocalcin (Gla-OC) levels, histological and immunofluorescent labeling were employed to evaluate the bone formation and mineralization in calvarial bone defect. In addition, Microfil perfusion, immunohistochemical, and micro-CT suggested enhanced angiogenesis and bone formation in calvarial bone healing. RESULTS: In this study, treatment with either PTH1-34 or MK-4 promoted bone formation and vascular formation in calvarial bone defects compared with the sham group. In addition, combined treatment of PTH1-34 plus MK-4 increased serum level of Gla-OC, improved vascular number and vascular density, and enhanced bone formation in calvarial bone defect in osteopenic conditions as compared with monotherapy. CONCLUSIONS: In summary, this study indicated that PTH1-34 plus MK-4 combination therapy accelerated bone formation and angiogenesis in calvarial bone defects in presence of osteopenia.

Use of an anionic collagen matrix made from bovine intestinal serosa for in vivo repair of cranial defects.

Polymeric biomaterials composed of extracellular matrix components possess osteoconductive capacity that is essential for bone healing. The presence of collagen and the ability to undergo physicochemical modifications render these materials a suitable alternative in bone regenerative therapies. The objective of this study was to evaluate the osteogenic capacity of collagen-based matrices (native and anionic after alkaline hydrolysis) made from bovine intestinal serosa (MBIS). Twenty-five animals underwent surgery to create a cranial defect to be filled with native and anionic collagen matrixes, mmineralized and non mineralized. The animals were killed painlessly 6 weeks after surgery and samples of the wound area were submitted to routine histology and morphometric analysis. In the surgical area there was new bone formation projecting from the margins to the center of the defect. More marked bone neoformation occurred in the anionic matrices groups in such a way that permitted union of the opposite margins of the bone defect. The newly formed bone matrix exhibited good optical density of type I collagen fibers. Immunoexpression of osteocalcin by osteocytes was observed in the newly formed bone. Morphometric analysis showed a greater bone volume in the groups receiving the anionic matrices compared to the native membranes. Mineralization of the biomaterial did not increase its osteoregenerative capacity. In conclusion, the anionic matrix exhibits osteoregenerative capacity and is suitable for bone reconstruction therapies.

Facing the facts on prophylactic antibiotics for facial fractures: 1 day or less.

BACKGROUND: To evaluate the role of initial prophylactic antibiotics on facial fractures, outcomes were compared between a short course (≤24 hours) of antibiotics to those who received an extended course (>24 hours). METHODS: Adults admitted (2010-2015) to a Level I trauma center intensive care unit with at least one facial bone fracture and major injuries isolated to the head and neck were included. Our primary analysis compared infectious complications of the head or neck (H/N infection) between patients given short or extended courses of antibiotic prophylaxis. Multivariate logistic regression and analysis of propensity score matched pairs were performed. RESULTS: A total of 403 patients were included, 85.6% had blunt injuries and 72.7% had their facial fracture managed nonoperatively. The H/N infection rate was 11.2%. Two hundred eighty patients received a short course of antibiotics and 123 patients received an extended course. Median Injury Severity Score was 14 in both groups (p = 0.78). Patients receiving an extended course of antibiotics had higher rates of H/N infection (20.3% vs. 7.1%, p < 0.001). Factors associated with development of H/N infection included younger age, penetrating injury, open fracture, upper face or mandible fracture, fractures in multiple facial thirds, vascular injury, hypertension, and extended antibiotic course. Multivariate logistic regression identified younger age (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.96-1.00; p = 0.02), multiple facial third fractures (OR, 4.9; 95% CI, 2.4-10.2; p < 0.001), and penetrating mechanism (OR, 3.1; 95% CI, 1.5-6.4; p = 0.003) as independent predictors of H/N infection, but not antibiotic duration. Propensity score-matched analysis found no differences in H/N infection between short and extended antibiotic courses (11.4% vs. 12.5%; p = 1.0). Subgroup analyses demonstrated no differences in H/N infection between short or extended antibiotic courses by injury pattern, mechanism, or treatment (operative or nonoperative). CONCLUSION: These results lead us to believe that we should limit antibiotics to 24 hours or less upon admission for facial fractures. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Postoperative CT of the Midfacial Skeleton After Trauma: Review of Normal Appearances and Common Complications.

OBJECTIVE: The objective of this article is to describe the CT appearance of the midfacial skeleton after surgical repair of posttraumatic Le Fort, nasoorbitoethmoidal (NOE), and frontal sinus fractures. Several of the more commonly encountered complications will also be described. CONCLUSION: Surgery after midfacial trauma is aimed at restoring both form and function. Knowledge of the principal tenets of Le Fort, NOE, and frontal sinus fracture repair is vital for radiologists to accurately assess the adequacy of treatment on postoperative CT and provide meaningful reports for the surgeon.

Tuning physical properties and BMP-2 release rates of injectable hydrogel systems for an optimal bone regeneration effect.

For a substance to be used as a drug delivery carrier and tissue inducible material for a target disease, its drug release rate and physical properties should be optimized to facilitate the healing process. We developed multi-tunable hydrogel systems with various physical properties and release behaviors to determine the optimal conditions for bone regeneration. Five injectable poly(phosphazene) hydrogels were developed with different types and amounts of anionic side-chains. The five polymer hydrogels showed considerably different in vitro and in vivo performances for sol-gel phase transition, dissolution/degradation, water uptake, and pore size. Furthermore, bone morphogenetic protein-2 (BMP-2) was loaded into the polymer hydrogels by forming nano-sized ionic-complexes with each polymer. The five types of nanocomplex hydrogels showed completely different BMP-2 release rates. By administering each nanocomplex hydrogel to mouse calvarial, we identified the most adapted nanocomplex hydrogel system for effective bone regeneration. The BMP-2 release rate was the most important factor in effective bone regeneration. Finally, the bone regeneration effect of the optimized hydrogel system was investigated in a critical-sized calvarial defect model.

Local pulsatile PTH delivery regenerates bone defects via enhanced bone remodeling in a cell-free scaffold.

Parathyroid hormone (PTH) is currently the only FDA-approved anabolic drug to treat osteoporosis, and is systemically administered through daily injections. A new local pulsatile PTH delivery device was developed from biodegradable polymers to expand the application of PTH from systemic treatment to spatially controlled local bone defect regeneration in this work. This is the first time that local pulsatile PTH delivery has been demonstrated to promote bone regeneration via enhanced bone remodeling. The biodegradable delivery device was designed to locally deliver PTH in a preprogrammed pulsatile manner. The PTH delivery was utilized to facilitate the regeneration of a bone defect spatially defined with a cell-free biomimetic nanofibrous (NF) scaffold. The local pulsatile PTH delivery (daily pulse for 21 days) not only promoted the regeneration of a critical-sized bone defect with negligible systemic side effects in a mouse model, but also advantageously achieved higher quality regenerated bone than the standard systemic PTH injection. These results demonstrate a promising and novel pulsatile PTH delivery device for spatially defined local bone regeneration.

Repair of rat cranial bone defect by using bone morphogenetic protein-2-related peptide combined with microspheres composed of polylactic acid/polyglycolic acid copolymer and chitosan.

The effects of the transplanted bone morphogenetic protein-2 (BMP2) -related peptide P24 and rhBMP2 combined with poly(lactic-co-glycolic acid) (PLGA)/chitosan (CS) microspheres were investigated in promoting the repair of rat cranial bone defect. Forty white rats were selected and equally divided into four groups (group A: 1 µg of rhBMP2/PLGA/CS composite; group B: 3 mg of P24/PLGA/CS composite; group C: 0.5 µg of rhBMP2 + 1.5 mg of P24/PLGA/CS composite; group D: blank PLGA/CS material), and rat cranial bone defect models with a diameter of 5 mm were established. The materials were transplanted to the cranial bone defects. The animals were sacrificed on weeks 6 and 12 post-operation. Radiographic examinations (x-ray imaging and 3D CT scanning) and histological evaluations were performed. The repaired areas of cranial bone defects were measured, and the osteogenetic abilities of various materials were compared. Cranial histology, imaging, and repaired area measurements showed that the osteogenetic effects at two time points (weeks 6 and 12) in group C were better than those in groups A and B. The effects in groups A and B were similar. Group D achieved the worst repair effect of cranial bone defects, where a large number of fibrous connective tissues were observed. The PLGA/CS composite microspheres loaded with rhBMP2 and P24 had optimal concrescence and could mutually increase their osteogenesis capability. rhBMP2 + P24/PLGA/CS composite is a novel material for bone defect repair with stable activity to induce bone formation.

Bone regeneration induced by an in situ gel-forming poloxamine, bone morphogenetic protein-2 system.

The aim of this study was to confirm previously shown, in vitro osteogenic induction by the Tetronics T908 and T1307 in a critical-size, rat calvaria defect. In vivo, the osteogenic activity of the hydrogels was comparable to in vitro, but less pronounced. However, similar to in vitro, the system was strongly potentiated by incorporating 6.5 microg of bone morphogenetic protein-2 in solution or pre-encapsulated in poly(lactic-co-glycolic) acid microspheres. These two systems extended the in vivo release of bone morphogenetic protein-2, determined with 125I- bone morphogenetic protein-2, for one and two additional weeks, respectively, time enough to fill approximately 40% and 90% of the defect with well-organized bone. Furthermore, the structural characteristics of Tetronic hydrogels together with their biocompatibility, injectability, and adaptability to multiple defect sizes and shapes suggest their role as new, potential bone morphogenetic protein-2 delivery, low-cost scaffolds for minor as well as critical bone defects.

The role of postoperative prophylactic antibiotics in the treatment of facial fractures: a randomised, double-blind, placebo-controlled pilot clinical study. Part 3: Le Fort and zygomatic fractures in 94 patients.

The aim of this study was to evaluate the difference between the effect of a 5-day and a 1-day postoperative course of antibiotics on the incidence of infection after midfacial fractures. A total of 98 patients with displaced Le Fort or zygomatic fractures that required operation were randomly assigned into 2 groups, both of which were given amoxicillin/clavulanic acid 1.2g intravenously every 8h from the time of admission until 24h postoperatively. The 5-day group was then given amoxicillin/clavulanic acid 625 mg orally 8-hourly for another 4 days. The 1-day group was given placebo orally at the same time points. Patients were followed up 1, 2, 4, 6, and 12 weeks, and 6 months, postoperatively. The development of an infection of the wound was the primary end point. Ninety-four of the 98 patients completed the study. Two of the 45 patients in the 5-day group (4%) and 2/49 in the 1-day group (4%) developed postoperative wound infections. One in each group had a purulent infection, while the others had only wound breakdown. Two patients of the 5-day group and one in the 1-day group developed rashes on the trunk. There were no significant differences in the incidence of infection or side effects between the groups. In midfacial fractures a 1-day course of antibiotics postoperatively is as effective in preventing infective complications as a 5-day regimen.

Low-dose bone morphogenetic protein-2/stromal cell-derived factor-1ß cotherapy induces bone regeneration in critical-size rat calvarial defects.

Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1/CXCL12) is involved in bone formation, though underlying molecular mechanisms remain to be fully elucidated. Also, contributions of SDF-1ß, the second most abundant splice variant, as an osteogenic mediator remain obscure. We have shown that SDF-1ß enhances osteogenesis by regulating bone morphogenetic protein-2 (BMP-2) signaling in vitro. Here we investigate the dose-dependent contribution of SDF-1ß to suboptimal BMP-2-induced local bone formation; that is, a dose that alone would be too low to significantly induce bone formation. We utilized a critical-size rat calvarial defect model and tested the hypotheses that SDF-1ß potentiates BMP-2 osteoinduction and that blocking SDF-1 signaling reduces the osteogenic potential of BMP-2 in vivo. In preliminary studies, radiographic analysis at 4 weeks postsurgery revealed a dose-dependent relationship in BMP-2-induced new bone formation. We then found that codelivery of SDF-1ß potentiates suboptimal BMP-2 (0.5 µg) osteoinduction in a dose-dependent order, reaching comparable levels to the optimal BMP-2 dose (5.0 µg) without apparent adverse effects. Blocking the CXC chemokine receptor 4 (CXCR4)/SDF-1 signaling axis using AMD3100 attenuated the osteoinductive potential of the optimal BMP-2 dose, confirmed by qualitative histologic analysis. In conclusion, SDF-1ß provides potent synergistic effects that support BMP-induced local bone formation and thus appears a suitable candidate for optimization of bone augmentation using significantly lower amounts of BMP-2 in spine, orthopedic, and craniofacial settings.

The innovative application of a novel bone adhesive for facial fracture osteosynthesis-in vitro and in vivo results.

This study evaluates a novel adhesive fixation technique to affix cortical bone fragments to osteosynthesis plates using common PMMA cement. This technique utilizes a new amphiphilic bone bonding agent adhering with both hydrophilic bone and hydrophobic PMMA cement. After in vitro biomechanical testing of the bonding strength with explanted bovine and rabbit calvarian bone samples, osteosynthesis plates with screw holes of 1.3 and 1.5 mm were placed on the cranial bone of New Zealand white rabbits and the bond strength of these plates was determined through tension tests. In vitro bond strengths of 19.8-26.5 MPa were obtained. Control samples, prepared without a bone bonding agent, exhibited bone bonding strengths <0.2 MPa. In vivo respective bond strengths at the cranium of the white rabbits were 2.5-4.1 MPa 2 weeks post surgery and 1.9-2.5 MPa 12 weeks after implantation. This new innovative fixation method can be envisioned for cases in which conventional fixation techniques of screws and plates are insufficient or not possible due to the bone or trauma conditions. The observed bonding strengths support implementing this technique in nonload bearing regions, such as the central midface or frontal sinus, facilitating immobilization until bone reunion is complete.