ABSTRACT
PURPOSE: The inability to achieve primary fascial closure (PFC) after emergency laparotomy increases the rates of adverse outcomes including fistula formation, incisional hernia, and intraabdominal infection. Hypertonic saline (HTS) infusion improves early PFC rates and decreases time to PFC in patients undergoing damage control laparotomy (DCL) after injury. We hypothesized that in patients undergoing DCL after penetrating abdominal injury, HTS infusion would decrease the time to fascial closure as well as the volume of crystalloid required for resuscitation without inducing clinically relevant acute kidney injury (AKI) or electrolyte derangements. METHODS: We retrospectively analyzed all penetrating abdominal injury patients undergoing DCL within the University of Pennsylvania Health System (January 2015-December 2018). We compared patients who received 3% HTS at 30 mL/h (HTS) to those receiving isotonic fluid (ISO) for resuscitation while the abdominal fascia remained open. Primary outcomes were the rate of early PFC (PFC within 72 h) and time to PFC; secondary outcomes included acute kidney injury, sodium derangement, ventilator-free days, hospital length of stay (LOS), and ICU LOS. Intergroup comparisons occurred by ANOVA and Tukey's comparison, and student's t, and Fischer's exact tests, as appropriate. A Shapiro-Wilk test was performed to determine normality of distribution. RESULTS: Fifty-seven patients underwent DCL after penetrating abdominal injury (ISO n = 41, HTS n = 16). There were no significant intergroup differences in baseline characteristics or injury severity score. Mean time to fascial closure was significantly shorter in HTS (36.37 h ± 14.21 vs 59.05 h ± 50.75, p = 0.02), and the PFC rate was significantly higher in HTS (100% vs 73%, p = 0.01). Mean 24-h fluid and 48-h fluid totals were significantly less in HTS versus ISO (24 h: 5.2L ± 1.7 vs 8.6L ± 2.2, p = 0.01; 48 h: 1.3L ± 1.1 vs 2.6L ± 2.2, p = 0.008). During the first 72 h, peak sodium (Na) concentration (146.2 mEq/L ± 2.94 vs 142.8 mEq/L ± 3.67, p = 0.0017) as well as change in Na from ICU admission (5.1 mEq/L vs 2.3, p = 0.016) were significantly higher in HTS compared to ISO. Patients in the HTS group received significantly more blood in the trauma bay compared to ISO. There were no intergroup differences in intraoperative blood transfusion volume, AKI incidence, change in chloride concentration (â³Cl) from ICU admit, Na to Cl gradient (Na:Cl), initial serum creatinine (Cr), peak post-operative Cr, change in creatinine concentration (â³Cr) from ICU admission, creatinine clearance (CrCl), initial serum potassium (K), peak ICU K, change in K from ICU admission, initial pH, highest or lowest post-operative pH, mean hospital LOS, ICU LOS, and ventilator-free days. CONCLUSIONS: HTS infusion in patients undergoing DCL after penetrating abdominal injury decreases the time to fascial closure and led to 100% early PFC. HTS infusion also decreased resuscitative fluid volume without causing significant AKI or electrolyte derangement. HTS appears to offer a safe and effective fluid management approach in patients who sustain penetrating abdominal injury and DCL to support early PFC without inducing measurable harm. LEVEL OF EVIDENCE: Level III.
ABSTRACT
Background: Enterothecal fistulas are pathological connections between the gastrointestinal system and subarachnoid space. These rare fistulas occur mostly in pediatric patients with sacral developmental anomalies. They have yet to be characterized in an adult born without congenital developmental anomaly yet must remain on the differential diagnosis when all other causes of meningitis and pneumocephalus have been ruled out. Good outcomes rely on aggressive multidisciplinary medical and surgical care, which are reviewed in this manuscript. Case Description: A 25-year-old female with history of a sacral giant cell tumor resected via anterior transperitoneal approach followed by posterior L4-pelvis fusion presented with headaches and altered mental status. Imaging revealed that a portion of small bowel had migrated into her resection cavity and created an enterothecal fistula resulting in fecalith within the subarachnoid space and florid meningitis. The patient underwent a small bowel resection for fistula obliteration, and subsequently developed hydrocephalus requiring shunt placement and two suboccipital craniectomies for foramen magnum crowding. Ultimately, her wounds became infected requiring washouts and instrumentation removal. Despite a prolonged hospital course, she made significant recovery and at 10-month following presentation, she is awake, oriented, and able to participate in activities of daily living. Conclusions: This is the first case of meningitis secondary to enterothecal fistula in a patient without a previous congenital sacral anomaly. Operative intervention for fistula obliteration is the primary treatment and should be performed at a tertiary hospital with multidisciplinary capabilities. If recognized quickly and appropriately treated, there is a possibility of good neurological outcome.
ABSTRACT
BACKGROUND: Studying firearm-related mortality is important to reduce preventable firearm death in the US. This study aims to determine the relationship between firearm laws and assault death with firearms. STUDY DESIGN: This ecologic study used public data from the CDC Wide-Ranging Online Data for Epidemiologic Research on decedents age 18 years or older who died from assault with firearms between 2009 and 2018 in all 50 states and Washington, DC. The outcomes were the rate of mortality per 100,000 persons from assault death by firearm used. Exposures of interest included the presence of 7 state firearm laws extracted from the RAND State Firearm Law Database. Welch's t tests were performed to compare mean mortality rate in states with each firearm law to states without each law. RESULTS: There were 114,945 deaths from assault with firearms from 2009 to 2018. States with "stand your ground" laws had a higher assault mortality rate from all firearms and from other/unspecified firearms than states without stand your ground laws (p = 0.026; p = 0.023). States with background checks for private sales of handguns and long guns had a lower assault mortality rate from handguns and rifles, shotguns, and large firearms, respectively, than states without either law (p = 0.019; p = 0.030). CONCLUSIONS: Stand your ground laws are correlated with a higher rate of gun-related assault death, but background checks on private sales are correlated with a lower rate. Future studies should elucidate the specific pathways by which state laws reduce, or fail to reduce, firearm-related assault death.
Subject(s)
Firearms , Wounds, Gunshot , Humans , United States/epidemiology , Adolescent , Wounds, Gunshot/epidemiology , Databases, Factual , Forecasting , HomicideABSTRACT
The use of medical implants continues to grow as the population ages. Biofilm-related implant infection is the leading cause of medical implant failure and remains difficult to diagnose and treat. Recent technologies have enhanced our understanding of the composition and complex functions of microbiota occupying various body site niches. In this review, we leverage data from molecular sequencing technologies to explore how silent changes in microbial communities from various sites can influence the development of biofilm-related infections. Specifically, we address biofilm formation and recent insights of the organisms involved in biofilm-related implant infections; how composition of microbiomes from skin, nasopharyngeal, and nearby tissue can impact biofilm-formation, and infection; the role of the gut microbiome in implant-related biofilm formation; and therapeutic strategies to mitigate implant colonization.
Subject(s)
Microbiota , Staphylococcal Infections , Humans , Biofilms , Postoperative Complications , Prostheses and Implants/adverse effectsABSTRACT
BACKGROUND: There were 23,854 suicides by firearms in 2017 in the US, accounting for 60% of all gun deaths. Studying firearm-related mortalities is vital for reducing preventable gun deaths. This study aims to determine the association between state-level presence of restrictive firearm laws and suicide rates with firearms. STUDY DESIGN: This ecological study used data from the CDC Wide-Ranging Online Data for Epidemiologic Research on decedents older than 18 years who died from intentional self-harm with firearms between 2009 and 2018. Exposures of interest were state-level restrictive firearm laws: background checks on private sales, mandatory waiting periods, and prohibited possession for domestic violence restraining orders or mental health red flags. Outcomes were rates of suicide with firearms per 100,000 persons over the 10-year period within each state. Welch's t -tests compared mean mortality rates in exposed and unexposed states. RESULTS: There were 208,621 deaths from intentional self-harm with firearms from 2009 to 2018. States with background checks, mandatory waiting periods, and prohibited possession were associated with lower suicide rates for all firearm types compared with states without these laws (p < 0.05). Only states with background checks and mandatory waiting periods were associated with lower suicide rates by handguns and large firearms (p < 0.05). CONCLUSION: Background checks and mandatory waiting periods correlated with fewer suicides by all firearms and specific firearm types. This reduction could be due to firearm laws directly preventing people from accessing guns or existing concurrently with other suicide prevention measures. More research should be directed to understanding how firearm laws can help reduce suicide rates.
Subject(s)
Firearms , Suicide Prevention , Suicide , Humans , Firearms/legislation & jurisprudence , Suicide/statistics & numerical data , United States/epidemiologyABSTRACT
INTRODUCTION: Timing to start of chemoprophylaxis for venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) remains controversial. We hypothesize that early administration is not associated with increased intracranial hemorrhage. METHODS: A retrospective study of adult patients with TBI following blunt injury was performed. Patients with penetrating brain injury, any moderate/severe organ injury other than the brain, need for craniotomy/craniectomy, death within 24 hours of admission, or progression of bleed on 6 hour follow-up head computed tomography scan were excluded. Patients were divided into early (≤24 hours) and late (>24 hours) cohorts based on time to initiation of chemoprophylaxis. Progression of bleed was the primary outcome. RESULTS: 264 patients were enrolled, 40% of whom were in the early cohort. The average time to VTE prophylaxis initiation was 17 hours and 47 hours in the early and late groups, respectively (P < .0001). There was no difference in progression of bleed (5.6% vs. 7%, P = .67), craniectomy/-craniotomy rate (1.9% vs. 2.5%, P = .81), or VTE rate (0% vs. 2.5%, P = .1). CONCLUSION: Early chemoprophylaxis is not associated with progression of hemorrhage or need for neurosurgical intervention in patients with TBI and a stable head CT 7 hours following injury.
Subject(s)
Anticoagulants/administration & dosage , Brain Injuries, Traumatic/complications , Heparin/administration & dosage , Intracranial Hemorrhages , Venous Thromboembolism/prevention & control , Adult , Brain Injuries, Traumatic/mortality , Chemoprevention , Craniotomy/statistics & numerical data , Disease Progression , Drug Administration Schedule , Factor Xa Inhibitors/administration & dosage , Heparin, Low-Molecular-Weight/administration & dosage , Humans , Intracranial Hemorrhages/diagnostic imaging , Intracranial Hemorrhages/etiology , Middle Aged , Patient Discharge/statistics & numerical data , Pulmonary Embolism/epidemiology , Pulmonary Embolism/prevention & control , Retrospective Studies , Time Factors , Tomography, X-Ray Computed , Venous Thromboembolism/epidemiology , Venous Thromboembolism/mortality , Venous Thrombosis/epidemiology , Venous Thrombosis/prevention & control , Wounds, Nonpenetrating/complicationsABSTRACT
Ventral hernia repair (VHR) with acellular dermal matrix (ADM) has high rates of recurrence that may be improved with allogeneic growth factor augmentation such as amniotic fluid allograft (AFA). We hypothesized that AFA would modulate the host response to improve ADM incorporation in VHR. Lewis rats underwent chronic VHR with porcine ADM alone or with AFA augmentation. Tissue harvested at 3, 14, or 28 days was assessed for region-specific cellularity, and a validated histomorphometric score was generated for tissue incorporation. Expression of pro-inflammatory (Nos1, Tnfα), anti-inflammatory (Arg1, Il-10, Mrc1) and tissue regeneration (Col1a1, Col3a1, Vegf, and alpha actinin-2) genes were quantified using quantitative reverse-transcription polymerase chain reaction. Amniotic fluid allograft treatment caused enhanced vascularization and cellularization translating to increased histomorphometric scores at 14 days, likely mediated by upregulation of pro-regeneration genes throughout the study period and molecular evidence of anti-inflammatory, M2-polarized macrophage phenotype. Collectively, this suggests AFA may have a therapeutic role as a VHR adjunct.
Subject(s)
Acellular Dermis , Amniotic Fluid , Hernia, Ventral , Herniorrhaphy , Surgical Mesh , Animals , Hernia, Ventral/metabolism , Hernia, Ventral/therapy , Rats , Rats, Inbred LewABSTRACT
Platelet rich plasma (PRP) has been shown to improve incorporation and reduce inflammation in ventral hernia repair (VHR) with acellular dermal matrix (ADM). The concentration of platelets in PRP varies in clinical studies and an ideal concentration has yet to be defined. The effects of varied concentrations of PRP on ADM incorporation and inflammatory cell infiltration in a rat model of VHR. We hypothesized that increasing concentration of PRP would lead to improved incorporation, decreased CD8+ and multinucleated giant cell (MNGC) infiltrate. Lewis rats underwent ventral hernia creation and repair 30 days later with porcine non-crosslinked ADM. PRP was applied to the mesh prior to skin closure at concentrations of 1 × 104 plt/µL (PRP-LOW), 1 × 106 plt/µL (PRP-MID), or 1 × 107 plt/µL (PRP-HIGH) and tissue harvested at 2 and 4 weeks. Cellularization, tissue deposition, and mesh thickness using hematoxylin and eosin and Masson's trichrome, and neovascularization was assessed with VVG staining, to establish the relationship of PRP concentration to metrics of incorporation. MNGC and CD8+ T-cell infiltration were quantified to establish the relationship of inflammatory cell infiltration in response to PRP concentration. Lymphocyte infiltration was assessed using immunohistochemical staining for CD8. PRP-HIGH treated had significantly greater tissue deposition at 4 weeks. PRP-MID showed increasing mesh thickness at 2 weeks. Cell infiltration was significantly higher with PRP-HIGH at both 2 and 4 weeks while PRP-LOW showed increased cell infiltration only at 4 weeks. At both time points there was a trend towards a dose dependent response in cell infiltration to PRP concentration. Neovascularization was highest with MID-plt at 2 weeks, yet no significant differences were noted compared to controls. CD8+ cell infiltrate was significantly decreased at 2 and 4 weeks in PRP-LOW and PRP-MID treated groups. PRP at all concentrations significantly decreased MNGC infiltration at 2 weeks while only PRP-HIGH and PRP-MID had significant reductions in MNGC at 4 weeks. Both MNGC and CD8+ cell infiltration demonstrated dose dependent reduction in relation to PRP concentration. Increasing platelet concentrations of PRP correlated with improved incorporation, tissue deposition, and decreased scaffold degradation. These findings were associated with a blunted foreign body response. These findings suggest PRP reduces inflammation which may be beneficial for ADM incorporation in VHR.
Subject(s)
Giant Cells/pathology , Platelet-Rich Plasma/metabolism , Surgical Mesh , Acellular Dermis , Animals , CD8-Positive T-Lymphocytes/metabolism , Hernia, Ventral/surgery , Herniorrhaphy , Male , Neovascularization, Physiologic , Rats, Inbred Lew , Tissue Scaffolds/chemistryABSTRACT
Remodeling of the human bony skeleton is constantly occurring with up to 10% annual bone volume turnover from osteoclastic and osteoblastic activity. A shift toward resorption can result in osteoporosis and pathologic fractures, while a shift toward deposition is required after traumatic, or surgical injury. Spinal fusion represents one such state, requiring a substantial regenerative response to immobilize adjacent vertebrae through bony union. Autologous bone grafts were used extensively prior to the advent of advanced therapeutics incorporating exogenous growth factors and biomaterials. Besides cost constraints, these applications have demonstrated patient safety concerns. This study evaluated the regenerative ability of a nanostructured, magnesium-doped, hydroxyapatite/type I collagen scaffold (MHA/Coll) augmented by autologous platelet-rich plasma (PRP) in an orthotopic model of posterolateral lumbar spinal fusion. After bilateral decortication, rabbits received either the scaffold alone (Group 1) or scaffold with PRP (Group 2) to the anatomic right side. Bone regeneration and fusion success compared to internal control were assessed by DynaCT with 3-D reconstruction at 2, 4, and 6 weeks postoperatively followed by comparative osteogenic gene expression and representative histopathology. Both groups formed significantly more new bone volume than control, and Group 2 subjects produced significantly more trabecular and cortical bone than Group 1 subjects. Successful fusion was seen in one Group 1 animal (12.5%) and 6/8 Group 2 animals (75%). This enhanced effect by autologous PRP treatment appears to occur via astounding upregulation of key osteogenic genes. Both groups demonstrated significant gene upregulation compared to vertebral bone controls for all genes. Group 1 averaged 2.21-fold upregulation of RUNX2 gene, 3.20-fold upregulation of SPARC gene, and 3.67-fold upregulation of SPP1 gene. Depending on anatomical subgroup (cranial, mid, caudal scaffold portions), Group 2 had significantly higher average expression of all genes than both control and Group 1-RUNX2 (8.23-19.74 fold), SPARC (18.67-55.44 fold), and SPP1 (46.09-90.65 fold). Our data collectively demonstrate the osteoinductive nature of a nanostructured MHA/Coll scaffold, a beneficial effect of augmentation with autologous PRP, and an ability to achieve clinical fusion when applied together in an orthotopic model. This has implications both for future study and biomedical innovation of bone-forming therapeutics.
ABSTRACT
Background: Infected hernia mesh is a cause of post-operative morbidity. Nitric oxide (NO) plays a key role in the endogenous immune response to infection. We sought to study the efficacy of a NO-releasing mesh against methicillin-resistant Staphylococcus aureus (MRSA). We hypothesized that a NO-releasing polyester mesh would decrease MRSA colonization and proliferation. Materials and Methods: A composite polyester mesh functionalized with N-diazeniumdiolate silica nanoparticles was synthesized and characterized. N-diazeniumdiolate silica parietex composite (NOSi) was inoculated with 104,106, or 108 colony forming units (CFUs) of MRSA and a dose response was quantified in a soy tryptic broth assay. Utilizing a rat model of contaminated hernia repair, implanted mesh was inoculated with MRSA, recovered, and CFUs were quantified. Clinical metrics of erythema, mesh contracture, and adhesion severity were then characterized. Results: Methicillin-resistant Staphylococcus aureus CFUs demonstrated a dose-dependent response to NOSi in vitro. In vivo, quantified CFUs showed a dose-dependent response to NOSi-PCO. Treated rats had fewer severe adhesions, less erythema, and reduced mesh contracture. Conclusions: We demonstrate the efficacy of a NO-releasing mesh to treat MRSA in vitro and in vivo. Creation of a novel class of antimicrobial prosthetics offers new strategies for reconstructing contaminated abdominal wall defects and other procedures that benefit from deploying synthetic prostheses in contaminated environments.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Nanoparticles , Staphylococcal Infections , Animals , Nitric Oxide , Polyesters , Rats , Silicon Dioxide , Staphylococcal Infections/prevention & control , Surgical MeshABSTRACT
Incisional hernia is a common complication of hernia repair despite the development of various synthetic and bio-synthetic repair materials. Poor long-term mechanical strength, leading to high recurrence rates, has limited the use of acellular dermal matrices (ADMs) in ventral hernia repair (VHR). Biologically derived meshes have been an area of increasing interest. Still these materials bring the risk of more aggressive immune response and fibrosis in addition to the mechanical failures suffered by the synthetic materials. Platelet-rich plasma (PRP), a growth-factor-rich autologous blood product, has been shown to improve early neovascularization, tissue deposition, and to decrease the rates of recurrence. Here, we demonstrate that PRP promotes the release of growth factors stromal derived factor (SDF)-1, transforming growth factor-beta, and platelet-derived growth factor in a dose-dependent manner. Additionally, we utilize an aortic ring angiogenesis assay to show that PRP promotes angiogenesis in vitro. A rat model of VHR using StratticeTM ADM demonstrates similar findings in vivo, corresponding with the increased expression of vascular endothelial growth factor and collagen type 1 alpha 1. Finally, we show that the molecular and cellular activity initiated by PRP results in an increased mechanical stiffness of the hernia repair mesh over time. Collectively, these data represent an essential step in demonstrating the utility and the mechanism of platelet-derived plasma in biomaterial-aided wound healing and provide promising preclinical data that suggest such materials may improve surgical outcomes.
Subject(s)
Hernia, Ventral/surgery , Herniorrhaphy , Platelet-Rich Plasma/chemistry , Animals , Biomechanical Phenomena , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cross-Linking Reagents/pharmacology , Dermis/drug effects , Disease Models, Animal , Intercellular Signaling Peptides and Proteins/pharmacology , Male , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Microvessels/drug effects , Myofibroblasts/cytology , Myofibroblasts/drug effects , Rats, Inbred Lew , Swine , Wound Healing/drug effectsABSTRACT
Thoracic skeletal injury is a common outcome of motor vehicle accidents. Skeletal reconstruction is guided by anatomic and physiologic variables dictated by the injury complex. Here we describe a report of a patient who sustained complex trauma to the thorax leading to complete thoracic dissociation. Clinical and operative decision-making is discussed to inform the reader of a proposed ordered protocol and considerations for operative intervention and reconstruction.
Subject(s)
Accidents, Traffic , Decision Making , Ribs/injuries , Sternum/injuries , Thoracic Injuries/diagnosis , Thoracoplasty/methods , Aged , Humans , Imaging, Three-Dimensional , Male , Radiography, Thoracic , Ribs/diagnostic imaging , Ribs/surgery , Sternum/diagnostic imaging , Sternum/surgery , Thoracic Injuries/surgery , Tomography, X-Ray ComputedABSTRACT
Background: Surgical site infections (SSIs) increase mortality and the economic burden associated with emergency surgery (ES). A reliable and sensitive scoring system to predict SSIs can help guide clinician assessment and patient counseling of post-operative SSI risk. We hypothesized that after quantifying the ES post-operative SSI incidence, readily abstractable parameters can be used to develop an actionable risk stratification scheme. Patients and Methods: We reviewed retrospectively all patients who underwent ES operations at an urban academic hospital system (2005-2013). Comorbidities and operative characteristics were abstracted from the electronic health record (EHR) with a primary outcome of post-operative SSIs. Risk of SSI was calculated using logistic regression modeling and validated using bootstrapping techniques. Beta-coefficients were calculated to correlate risk. A simplified clinical risk assessment tool was derived by assigning point values to the rounded ß-coefficients. Results: A total of 4,783 patients with a 13.2% incidence of post-operative SSIs were identified. The strongest risk factors associated with SSIs included acute intestinal ischemia, weight loss, intestinal perforation, trauma-related laparotomy, radiation exposure, previous gastrointestinal surgery, and peritonitis. The assessment tool defined three patient groups based on SSI risk. Post-operative SSI incidence in high-risk patients (34%; score = 6-10) exceeded that of medium- (11.1%; score = 3-5) and low-risk patients (1.5%; score = 1-2) (C statistic = 0.802). Patients with a risk score ≥10 points evidenced the highest post-operative SSI risk (71.9%). Conclusion: Pre-operative identification of ES patient risk for post-operative SSI may inform pre-operative patient counseling and operative planning if the proposed procedure includes medical device implantation. A clinically relevant seven-factor risk stratification model such as this empirically derived one may be suitable to incorporate into the EHR as a decision-support tool.
Subject(s)
Digestive System Surgical Procedures , Surgical Wound Infection , Humans , Incidence , Retrospective Studies , Risk Factors , Surgical Wound Infection/epidemiologyABSTRACT
The recurrence of ventral hernias continues to be a problem faced by surgeons, in spite of efforts toward implementing novel repair techniques and utilizing different materials to promote healing. Cadaveric acellular dermal matrices (Alloderm) have shown some promise in numerous surgical subspecialties, but these meshes still suffer from subsequent failure and necessitation of re-intervention. Here, it is demonstrated that the addition of platelet rich plasma to Alloderm meshes temporally modulates both the innate and cytotoxic inflammatory responses to the implanted material. This results in decreased inflammatory cytokine production at early time points, decreased matrix metalloproteinase expression, and decreased CD8+ T cell infiltration. Collectively, these immune effects result in a healing phenotype that is free from mesh thinning and characterized by increased material stiffness.
Subject(s)
Acellular Dermis , Biocompatible Materials , Collagen , Platelet-Rich Plasma , Rats, Inbred Lew , Surgical Mesh , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Collagen/chemistry , Collagen/immunology , Hernia, Ventral/immunology , Hernia, Ventral/surgery , Male , Platelet-Rich Plasma/chemistry , Platelet-Rich Plasma/immunology , RatsABSTRACT
The animal model of infection following ventral hernia repair (VHR) has previously been utilized in exploring treatments and innovative therapies, such as implantation of biologic mesh imbedded with various anti-bacterial properties. The rat model has been utilized most commonly, but prior work has failed to recreate an adequately clinically representative model of infection following VHR. Additionally, there is lack of standardization of mesh infection severity across existing literature. Therefore, the aim of this paper is to describe the creation of a clinically representative VHR infection model utilizing an index procedure where a hernia defect is created followed by a VHR using biologic mesh and subsequent infectious agent inoculation. Additionally, we describe the development of a standardization index to quantify severity of mesh infection: the Mesh Infection Severity Index (MISI).â¢Our protocol involves two procedures, an index procedure where a hernia model is created, and a subsequent procedure where an infectious inoculant is introduced.â¢We describe the MISI, a standardization tool we hope will allow for ease of cross-institutional data assessment.â¢In summary, our protocol not only serves as a more clinically representative animal model, but also includes a novel metric to standardize mesh infection severity.
ABSTRACT
Bone morphogenetic protein-2 (BMP-2) has been demonstrated to be one of the most vital osteogenic factors for bone augmentation. However, its uncontrolled administration has been associated with catastrophic side effects, which compromised its clinical use. To overcome these limitations, we aimed at developing a safer controlled and sustained release of BMP-2, utilizing poly(lactic-co-glycolic acid)-multistage vector composite microspheres (PLGA-MSV). The loading and release of BMP-2 from PLGA-MSV and its osteogenic potential in vitro and in vivo was evaluated. BMP-2 in vitro release kinetics was assessed by ELISA assay. It was found that PLGA-MSV achieved a longer and sustained release of BMP-2. Cell cytotoxicity and differentiation were evaluated in vitro by MTT and alkaline phosphatase (ALP) activity assays, respectively, with rat mesenchymal stem cells. The MTT results confirmed that PLGA-MSVs were not toxic to cells. ALP test demonstrated that the bioactivity of BMP-2 released from the PLGA-MSV was preserved, as it allowed for the osteogenic differentiation of rat mesenchymal stem cells, in vitro. The biocompatible, biodegradable, and osteogenic PLGA-MSVs system could be an ideal candidate for the safe use of BMP-2 in orthopedic tissue engineering applications.
ABSTRACT
Achieving bone fracture union after trauma represents a major challenge for the orthopedic surgeon. Fracture non-healing has a multifactorial etiology and there are many risk factors for non-fusion. Environmental factors such as wound contamination, infection, and open fractures can contribute to non-healing, as can patient specific factors such as poor vascular status and improper immunologic response to fracture. Nitric oxide (NO) is a small, neutral, hydrophobic, highly reactive free radical that can diffuse across local cell membranes and exert paracrine functions in the vascular wall. This molecule plays a role in many biologic pathways, and participates in wound healing through decontamination, mediating inflammation, angiogenesis, and tissue remodeling. Additionally, NO is thought to play a role in fighting wound infection by mitigating growth of both Gram negative and Gram positive pathogens. Herein, we discuss recent developments in NO delivery mechanisms and potential implications for patients with bone fractures. NO donors are functional groups that store and release NO, independent of the enzymatic actions of NOS. Donor molecules include organic nitrates/nitrites, metal-NO complexes, and low molecular weight NO donors such as NONOates. Numerous advancements have also been made in developing mechanisms for localized nanomaterial delivery of nitric oxide to bone. NO-releasing aerogels, sol- gel derived nanomaterials, dendrimers, NO-releasing micelles, and core cross linked star (CCS) polymers are all discussed as potential avenues of NO delivery to bone. As a further target for improved fracture healing, 3d bone scaffolds have been developed to include potential for nanoparticulated NO release. These advancements are discussed in detail, and their potential therapeutic advantages are explored. This review aims to provide valuable insight for translational researchers who wish to improve the armamentarium of the feature trauma surgeon through use of NO mediated augmentation of bone healing.
ABSTRACT
Prosthetic contamination and biofilm formation continue to plague implanted materials. With increasing resistance to traditional antibiotic regimens, alternative approaches to preventing bacterial adhesion and biofilm formation have focused on the physiochemical properties of the prosthetics. Roughness, topography, hydrophobicity, porosity, charge, stiffness, and surface area all influence the processes of adhesion and colonization leading to biofilm formation. In this review, we discuss the physiochemical properties of solid and porous prosthetic materials that influence biofilm formation at the nanometric scale.
Subject(s)
Bacteria/growth & development , Biofilms/growth & development , Chemical Phenomena , Nanomedicine/methods , Prostheses and Implants/microbiology , Surface Properties , HumansABSTRACT
BACKGROUND: Complications of ventral hernia repair (VHR) may be investigated by computed tomography or ultrasound (US) but neither modality gives a quantifiable metric of repair quality short of identifying hernia recurrence. Platelet-rich plasma (PRP), a growth factor-rich autologous blood product, has been shown to improve incorporation of native tissue with bioprosthetics. In this study, we investigate the effect of PRP on the incorporation and mechanical integrity of a non-crosslinked porcine acellular dermal matrix (pADM) in a rodent model of VHR and the correlative ability of ultrasound shear wave elastography (US-SWE) to assess repair quality. METHODS: PRP was isolated from whole blood of Lewis rats. Twenty-eight Lewis rats underwent chronic VHR using either pADM alone or augmented with autologous PRP prior to non-invasive imaging assessment and specimen harvest at either 3 or 6 months. US-SWE was performed to estimate the Young's modulus prior to histological assessment and data from PRP-treated rodents were compared to controls. RESULTS: Implanted pADM was easily distinguishable by US-SWE imaging in all cases analyzed in this study. The mean Young's modulus measured was 1.78 times and 2.54 times higher in PRP-treated samples versus control at 3-month and 6-month time points respectively (p < 0.05). At 3 months, qualitative and quantitative histology revealed decreased inflammation and improved incorporation in PRP-treated samples along the implant/abdominal wall interface. At 6 months, the PRP cohort had no hernia recurrence and preserved ADM integrity from immunologic degradation, while all control animals suffered hernia recurrence (4/6) or extreme ADM thinning (2/6). CONCLUSION: This study confirms both the efficacy of PRP in augmenting VHR using pADM, as well as the reliability of US-SWE to non-invasively predict the quality of VHR. Although further human studies are necessary, this work supports PRP use to improve VHR outcomes and US-SWE potential for bedside non-invasive hernia characterization.