Platelet-rich plasma enhances rib fracture strength and callus formation in vivo.

BACKGROUND: Rib fractures are a common traumatic injury affecting more than 350,000 patients a year. Early stabilization has shown to be effective in reducing pulmonary complications. Platelet-rich plasma (PRP) is a growth factor-rich blood product known to improve soft tissue and bone healing. We hypothesized that the addition of PRP to a rib fracture site would accelerate callus formation and improve callus strength. METHODS: Platelet-rich plasma was isolated from pooled Lewis rat blood and quantified. Thirty-two Lewis rats underwent fracture of the sixth rib and were treated with 100 µL PRP (1 × 106 platelets/µL) or saline. At 2 weeks, ribs were harvested and underwent a 3-point bend, x-ray, and microcomputed tomography, and callus sections were stained with 4',6-diamidino-2-phenylindole and Alcian blue and picrosirius red. At 6 weeks, ribs were harvested and underwent a 3-point bend test, x-ray, microcomputed tomography, and Alcian blue and picrosirius red staining. RESULTS: At 2 weeks, PRP increased callus diameter (9.3 mm vs. 4.3 mm, p = 0.0002), callus index (4.5 vs. 2.1, p = 0.0002), bone volume/total volume (0.0551 vs. 0.0361, p = 0.0024), cellularization (2,364 vs. 1,196, p < 0.0001), and cartilage (12.12% vs. 3.11%, p = 0.0001) and collagen (6.64% vs. 4.85%, p = 0.0087) content compared with controls. At 6 weeks, PRP increased fracture callus diameter (5.0 mm vs. 4.0 mm, 0.0466), callus index (2.5 vs. 2.0, p = 0.0466), BV/TV (0.0415 vs. 0.0308, p = 0.0358), and higher cartilage (8.21% vs. 3.26%, p < 0.0001) and collagen (37.61% vs. 28.00%, p = 0.0022) content compared with controls. At 6 weeks, PRP samples trended toward improved mechanical characteristics; however, these results did not reach significance (p > 0.05). CONCLUSION: Rib fractures are a common injury, and accelerated stabilization could improve clinical outcomes. Platelet-rich plasma significantly increased callus size, calcium deposition, and cartilage and collagen content at 2 and 6 weeks and trended toward improved strength and toughness on mechanical analysis at 6 weeks compared with controls, although this did not reach significance. These findings suggest that PRP may be a useful adjunct to accelerate and improve fracture healing in high-risk patients.

The impact of hypertonic saline on damage control laparotomy after penetrating abdominal trauma.

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 (△Cl) from ICU admit, Na to Cl gradient (Na:Cl), initial serum creatinine (Cr), peak post-operative Cr, change in creatinine concentration (△Cr) 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.

Enterothecal fistula as a rare cause of adult pneumocephalus and meningitis: a case report.

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.

Early Chemoprophylaxis Against Venous Thromboembolism in Patients With Traumatic Brain Injury.

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.

Platelet-rich plasma enhances mechanical strength of strattice in rat model of ventral hernia repair.

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.

Four Columns of the Thorax: Operative Decision-Making in the Setting of Complete Bony Instability.

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.

Actionable Risk Model for the Development of Surgical Site Infection after Emergency Surgery.

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.

Ultrasound shear wave elastography effectively predicts integrity of ventral hernia repair using acellular dermal matrix augmented with platelet-rich plasma (PRP).

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.

Diagnosis and operative management of a perforated de Garengeot hernia.

INTRODUCTION: A de Garengeot hernia, a femoral hernia containing the appendix, is a difficult diagnosis often made intra-operatively when the hernia sac is opened. It is a rare finding, and complications are more frequent with a de Garengeot hernia. PRESENTATION OF CASE: A 92 year-old female presented to the emergency department (ED) complaining of abdominal pain. A computed tomographic (CT) scan of the abdomen and pelvis demonstrated a hernia anterior to the inguinal ligament without strangulation. Two weeks later the patient returned to the ED with worsening abdominal pain in the right lower quadrant. Repeat CT scan demonstrated a 7×4cm complex fluid collection in the right inguinal region, and the patient was taken to the operating room for exploration. The hernia sac was entered and found to contain the appendix with evidence of distal perforation. The appendix was taken out, and the hernia defect was repaired. The patient tolerated the procedure well. DISCUSSION: Femoral hernias have a high risk of incarceration due to the tightness of the femoral canal (Talini et al. 2015 [4]). Due to anatomic location of the appendix, de Garengeot hernias are most often seen on the right. Incarceration of the appendix is a clear etiology for appendicitis secondary to ischemia. CONCLUSION: Full preoperative workup for a femoral hernia often fails to diagnose the presence of the appendix within the hernia. It is important to have a high clinical suspicion for a de Garengeot's hernia in patients with incarcerated or strangulated right femoral hernias.

Case report on the non-operative management of a retrievable inferior vena cava filter perforating the duodenum.

INTRODUCTION: Deep vein thrombosis (DVT) continues to be a significant source of morbidity for surgical patients. Placement of a retrievable inferior vena cava (IVC) filter is used when patients have contraindications to anticoagulation or recurrent pulmonary embolism despite therapeutic anticoagulation. Although retrievable IVC filters are often used, they carry a unique set of risks. PRESENTATION OF CASE: A 67-year-old man presents to the Emergency Room (ER) following large volume melena and complaining of syncope. One year prior, the patient had been diagnosed with Glioblastoma multiforme, for which he underwent a craniotomy with near-total resection of the mass. He subsequently developed a deep vein thrombosis and underwent placement of a retrievable inferior vena cava (IVC) filter. Computerized tomography (CT) and esophagogastroduodenoscopy showed duodenal perforation by the retrievable IVC filter. The filter was successfully retrieved through an endovascular approach. DISCUSSION: Retrievable IVC filter placement is the preferred method of pulmonary embolism prevention in patients with significant risk for bleeding. Duodenal perforation by a retrievable IVC filter is a rare and serious complication. It is usually managed surgically, but can also be managed non-operatively. CONCLUSION: For patients with significant comorbidities or patients who are poor surgical candidates, non-operative management with close monitoring can serve as an initial approach to the patient with a caval enteric perforation secondary to a retrievable IVC filter.

Nanoantibiotics: a new paradigm for the treatment of surgical infection.

Infections following orthopedic device implantations often impose a substantial health burden and result in high medical costs. Currently, preventative methods are often employed following an orthopedic implant to reduce risk of infection; however, contamination of the surgical site can still occur. Although antibiotics have demonstrated a substantial reduction in bacterial growth and maintenance, biofilm formation around the implant can often minimize efficacy of the antibiotic. Recently, nanotechnology has garnered significant interest, resulting in the development of several antibiotic delivery strategies that exhibit extended release and increased efficacy. In this review, treatment methods of orthopedic-device-related infections will be discussed and an overview of antimicrobial-based nanotechnologies will be provided. Specifically, nonmetal-, metal- and oxide-based nanotechnologies, incorporating antibacterial strategies, will be discussed.

Characterization of ventral incisional hernia and repair using shear wave elastography.

BACKGROUND: To assess the integrity of hernia repair, imaging modalities such as computed tomography or ultrasound (US) are commonly used. Neither modality has currently the capacity to simultaneously image the mesh and quantify a prosthetic and surrounding tissue stiffness. In this pilot study, we hypothesize that US shear wave elastography (SWE) can be used to identify a polyester mesh and a biologic graft and to assess their stiffness noninvasively in a rat model of bridging hernia repair. METHODS: Lewis rats underwent hernia creation and repair with Parietex or Strattice at 30 d. After 3 mo, the animals were euthanized, and the Young's Modulus was measured using SWE. Three-dimensional reconstructions of the hernia pre- and post-repair were performed using in-house image processing algorithms. RESULTS: SWE was capable of accurate and real-time assessment and diagnosis of the hernia defects in vivo. Young's Modulus of Parietex meshes and Strattice grafts as estimated from the shear wave elastograms were found to be statistically different from each other (P < 0.05). Accurate three-dimensional reconstructions of the hernia defects pre- and post-repair were generated. CONCLUSIONS: In this study, we demonstrate the feasibility of using US SWE to detect ventral hernias and evaluate mesh repair in vivo. Our results indicate that the presence of a hernia and repair can be reliably visualized by SWE and three dimensionally reconstructed. Thus, this technique may provide both structural and functional information regarding the hernia and the repair.

Platelet-rich plasma: a biomimetic approach to enhancement of surgical wound healing.

Platelets are small anucleate cytoplasmic cell bodies released by megakaryocytes in response to various physiologic triggers. Traditionally thought to be solely involved in the mechanisms of hemostasis, platelets have gained much attention due to their involvement wound healing, immunomodulation, and antiseptic properties. As the field of surgery continues to evolve so does the need for therapies to aid in treating the increasingly complex patients seen. With over 14 million obstetric, musculoskeletal, and urological and gastrointestinal surgeries performed annually, the healing of surgical wounds continues to be of upmost importance to the surgeon and patient. Platelet-rich plasma, or platelet concentrate, has emerged as a possible adjuvant therapy to aid in the healing of surgical wounds and injuries. In this review, we will discuss the wound healing properties of platelet-rich plasma and various surgical applications.

Lost in Translation: The Gap in Scientific Advancements and Clinical Application.

The evolution of medicine and medical technology hinges on the successful translation of basic science research from the bench to clinical implementation at the bedside. Out of the increasing need to facilitate the transfer of scientific knowledge to patients, translational research has emerged. Significant leaps in improving global health, such as antibiotics, vaccinations, and cancer therapies, have all seen successes under this paradigm, yet today, it has become increasingly difficult to realize this ideal scenario. As hospital revenue demand increases, and financial support declines, clinician-protected research time has been limited. Researchers, likewise, have been forced to abandon time- and resource-consuming translational research to focus on publication-generating work to maintain funding and professional advancement. Compared to the surge in scientific innovation and new fields of science, realization of transformational scientific findings in device development and materials sciences has significantly lagged behind. Herein, we describe: how the current scientific paradigm struggles in the new health-care landscape; the obstacles met by translational researchers; and solutions, both public and private, to overcoming those obstacles. We must rethink the old dogma of academia and reinvent the traditional pathways of research in order to truly impact the health-care arena and ultimately those that matter most: the patient.

An unusual presentation of congenital intestinal malrotation in a nonagenarian.

INTRODUCTION: Appendicitis is a common surgical pathology with many clinical presentations. Diagnosis can be challenging if there is an alteration to the normal position of anatomical structures and their relationships. CASE PRESENTATION: In this case, we report an unusual presentation of congenital intestinal malrotation in a nonagenarian presenting with generalized abdominal pain and lactic acidosis found to have perforated appendicitis. The patient was admitted to the Hospitalist service for abdominal pain and misdiagnosed with bowel obstruction secondary to previous "operation". After further review of imaging malrotation with internal hernia was suggested. The patient was taken emergently to the operating room and found to have perforated and gangrenous appendix in the midabdomen. An appendectomy was performed and patient was ultimately discharged home in good condition on postoperative day four. DISCUSSION: Malrotation of the intestines is a developmental variant that occurs when normal fetal rotation of the intestines around the superior mesenteric artery and their peritoneal fixation fails to occur. Presentation typically occurs during infancy and diagnosis in an elderly patient is exceedingly rare. Operative intervention is often required as it is commonly associated with lactic acidosis or peritonitis. CONCLUSIONS: Malrotation can go undiagnosed well into elderly life and can present with unusual signs and symptoms. CT is very helpful in aiding the diagnosis but itself can be misleading.

Enhanced osteogenic potential of mesenchymal stem cells from cortical bone: a comparative analysis.

INTRODUCTION: Mesenchymal stem cells (MSCs) hold great promise for regenerative therapies in the musculoskeletal system. Although MSCs from bone marrow (BM-MSCs) and adipose tissue (AD-MSCs) have been extensively characterized, there is still debate as to the ideal source of MSCs for tissue-engineering applications in bone repair. METHODS: MSCs were isolated from cortical bone fragments (CBF-MSCs) obtained from patients undergoing laminectomy, selected by fluorescence-activated cell sorting analysis, and tested for their potential to undergo mesodermic differentiation. CBF-MSCs were then compared with BM-MSCs and AD-MSCs for their colony-forming unit capability and osteogenic potential in both normoxia and hypoxia. After 2 and 4 weeks in inducing media, differentiation was assessed qualitatively and quantitatively by the evaluation of alkaline phosphatase (ALP) expression and mineral deposition (Von Kossa staining). Transcriptional activity of osteoblastogenesis-associated genes (Alp, RUNX2, Spp1, and Bglap) was also analyzed. RESULTS: The cortical fraction of the bone contains a subset of cells positive for MSC-associated markers and capable of tri-lineage differentiation. The hypoxic conditions were generally more effective in inducing osteogenesis for the three cell lines. However, at 2 and 4 weeks, greater calcium deposition and ALP expression were observed in both hypoxic and normoxic conditions in CBF-MSCs compared with AD- and BM-MSCs. These functional observations were further corroborated by gene expression analysis, which showed a significant upregulation of Bglap, Alp, and Spp1, with a 22.50 (±4.55)-, 46.56 (±7.4)-, 71.46 (±4.16)-fold increase compared with their uninduced counterparts. CONCLUSIONS: This novel population of MSCs retains a greater biosynthetic activity in vitro, which was found increased in hypoxic conditions. The present study demonstrates that quantitative differences between MSCs retrieved from bone marrow, adipose, and the cortical portion of the bone with respect to their osteogenic potential exist and suggests the cortical bone as suitable candidate to use for orthopedic tissue engineering and regenerative medicine.

Biology of aortic aneurysms and dissections.

The biology of aortic aneurysm and dissection has evolved to where we now understand the genetic implications of changes in extracellular matrix proteins, smooth muscle cells, and growth factors and how they affect aortic wall homeostasis. These predeterminants are influenced by smoking, hypertension, and atherosclerosis, and the result in an inflammatory response coupled to an accelerated proteolytic cascade that disrupts both elastin and collagen in the aortic wall.