Kameron Rezzadeh

Outcomes following polyetheretherketone (PEEK) cranioplasty: Systematic review and meta-analysis

Polyetheretherketone (PEEK) has been used in cranioplasty since the early 2000s. However, there remains limited data that compares its long-term complication rate to autologous grafts and titanium mesh implants. To compare complication and implant failure rates after PEEK, autologous and titanium mesh cranioplasties, the authors of this study conducted a systematic review using the PubMed database. Studies that contained outcome data on complication rates of PEEK cranioplasty patients and studies that compared outcomes of patients who underwent PEEK cranioplasties versus other materials were included in the meta-analysis. Pooled odds ratios using the Mantel-Haenszel method were used for analysis. Fifteen articles, comprised of 183 PEEK cranioplasty patients were included. Of these patients, 15.3% developed post-operative complications and 8.7% experienced implant failure requiring reoperation. Patients who underwent cranioplasties with PEEK implants had 0.130 times the odds of developing post-operative complications (P=0.065) and 0.574 times the odds of implant failure compared to patients with autologous bone graft cranioplasties (P=0.629). Patients who had undergone PEEK cranioplasties had 0.127 times the odds of developing post-op complications (P=0.360) and 0.170 times the odds of implant failure compared to individuals who had undergone titanium mesh cranioplasties (P=0.168). The analysis was severely limited by the paucity in literature. However, there was a trend toward lower post-operative complication rates following PEEK cranioplasty versus autologous grafts, and lower implant failure rates with PEEK versus titanium mesh implants.

The use of negative pressure wound therapy in severe open lower extremity fractures: identifying the association between length of therapy and surgical outcomes

BACKGROUND Negative pressure wound therapy (NPWT) is a widely accepted method of temporary coverage for complex lower extremity wounds before definitive reconstruction. However, the precise role of NPWT in the perioperative management of patients with complicated lower extremity injuries remains unclear. In this study, we examine the effect of NPWT on flap complications and overall outcomes based on timing of soft-tissue reconstruction relative to initial injury and implementation of NPWT. METHODS We retrospectively reviewed the medical records of 32 consecutive patients presenting to a single institution receiving lower extremity reconstruction after Gustilo class IIIB or IIIC open tibial fractures over a 5-y period. Length of hospitalization, number of surgical procedures, flap failure, infection, and nonunion were parameters of interest in this study. RESULTS The incidence of complications in patients treated with NPWT was lower compared with patients who underwent wet-to-dry dressing changes, regardless of when surgery was performed. The highest rate of complications was observed in patients operated on >6 wk after injury and who received wet-to-dry dressing changes wound care. By comparison, those who underwent surgery within 1 wk of injury and who were bridged with NPWT had the lowest rate of complications. CONCLUSIONS The use of NPWT therapy in the perioperative management of patients with open lower extremity fractures reduces complication rates associated with limb salvage surgery. Our results suggest that NPWT can be used as a temporizing measure to optimize patients before flap surgery, effectively lengthening the window of opportunity for definitive reconstruction.

Classification of Newborn Ear Malformations and their Treatment with the EarWell Infant Ear Correction System

Background: A single practice’s treatment protocol and outcomes following molding therapy on newborn ear deformations and malformations with the EarWell Infant Ear Correction System were reviewed. A classification system for grading the severity of constricted ear malformations was created on the basis of anatomical findings. Methods: A retrospective chart/photograph review of a consecutive series of infants treated with the EarWell System from 2011 to 2014 was undertaken. The infants were placed in either deformation or malformation groups. Three classes of malformation were identified. Data regarding treatment induction, duration of treatment, and quality of outcome were collected for all study patients. Results: One hundred seventy-five infant ear malformations and 303 infant ear deformities were treated with the EarWell System. The average age at initiation of treatment was 12 days; the mean duration of treatment was 37 days. An average of six office visits was required. Treated malformations included constricted ears [172 ears (98 percent)] and cryptotia [three ears (2 percent)]. Cup ear (34 ears) was considered a constricted malformation, in contrast to the prominent ear deformity. Constricted ears were assigned to one of three classes, with each subsequent class indicating increasing severity: class I, 77 ears (45 percent); class II, 81 ears (47 percent); and class III, 14 ears (8 percent). Molding therapy with the EarWell System reduced the severity by an average of 1.2 points (p < 0.01). Complications included minor superficial excoriations and abrasions. Conclusion: The EarWell System was shown to be effective in eliminating or reducing the need for surgery in all but the most severe malformations. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Oxy133, a novel osteogenic agent, promotes bone regeneration in an intramembranous bone‐healing model

Current reconstructive techniques for complex craniofacial osseous defects are challenging and are associated with significant morbidity. Oxysterols are naturally occurring cholesterol oxidation products with osteogenic potential. In this study, we investigated the effects of a novel semi‐synthetic oxysterol, Oxy133, on in vitro osteogenesis and an in vivo intramembranous bone‐healing model. Rabbit bone marrow stromal cells (BMSCs) were treated with either Oxy133 or BMP‐2. Alkaline phosphatase (ALP) activity, expression of osteogenic gene markers and in vitro mineralization were all examined. Next, collagen sponges carrying either Oxy133 or BMP‐2 were used to reconstruct critical‐sized cranial defects in mature rabbits and bone regeneration was assessed. To determine the mechanism of action of Oxy133 both in vitro and in vivo, rabbit BMSCs cultures and collagen sponge/Oxy133 implants were treated with the Hedgehog signalling pathway inhibitor, cyclopamine, and similar outcomes were measured. ALP activity in rabbit BMSCs treated with 1 μm Oxy133 was induced and was significantly higher than in control cells. These results were mitigated in cultures treated with cyclopamine. Expression of osteogenic gene markers and mineralization in BMSCs treated with 1 μm Oxy133 was significantly higher than in control groups. Complete bone regeneration was noted in vivo when cranial defects were treated with Oxy133; healing was incomplete, however, when cyclopamine was added. Collectively, these results demonstrate that Oxy133 has the ability to induce osteogenic differentiation in vitro in rabbit BMSCs and to promote robust bone regeneration in vivo in an animal model of intramembranous bone healing. Copyright

Natural Killer Cells Differentiate Human Adipose-Derived Stem Cells and Modulate Their Adipogenic Potential.

Background: Natural killer cells are thought to represent more than 30 percent of all lymphocytes within the stromal vascular fraction of lipoaspirates. However, their physiologic interaction with adipocytes and their precursors has never been specifically examined. The authors hypothesized that natural killer cells, by means of cytokine secretion, are capable of promoting the differentiation of adipose-derived stem cells. Methods: Human natural killer cells purified from healthy donors’ peripheral blood mononuclear cells were activated with a combination of interleukin-2 and anti-CD16 monoclonal antibody; natural killer cell supernatant was collected. Adipose-derived stem cells isolated from raw human lipoaspirates from healthy patients were treated with growth media, growth media with natural killer cell supernatant, adipogenic media, and adipogenic media with natural killer cells supernatant. Flow cytometric analysis was performed on cells using antibodies against B7H1, CD36, CD44, CD34, CD29, and MHC-1. Adipogenic-related gene expression (PPAR-&ggr;, LPL, GPD-1, and aP2) was assessed. Oil Red O staining was performed as a functional assay of adipocyte differentiation and adipogenesis. Results: Adipose-derived stem cells maintained in growth media with natural killer cell supernatant lost markers of “stemness,” including CD44, CD34, and CD29; and expressed markers of differentiation, including B7H1 and MHC-1. Adipose-derived stem cells treated with natural killer cell supernatant accumulated small amounts of lipid after 10 days of natural killer cell supernatant treatment. Adipose-derived stem cells treated with natural killer cell supernatant showed altered expression of adipogenesis-associated genes compared with cells maintained in growth media. Adipose-derived stem cells maintained in adipogenic media with natural killer cell supernatant accumulated less lipid than those cells in adipogenic media alone. Conclusions: The authors demonstrate that, through secreted factors, natural killer cells are capable of differentiating adipose-derived stem cells. In cells maintained in adipogenic media, treatment with natural killer cell supernatant modulated adipogenic potential.

Patient Susceptibility & Technical Factors Associated with PersistentDiaphragmatic Paralysis after Interscalene Nerve Block

Background and objectives: Interscalene nerve blocks (ISB) have been associated with the rare complication of persistent diaphragmatic paralysis. Little is known regarding patient susceptibility or technical factors that may contribute to the development of this debilitating adverse reaction. Methods: An observational study was performed between 2009 and 2014 to compare two groups of patients who received ISB for upper extremity surgery. Patient demographic factors, co-morbidities, and technical aspects of the nerve block were reviewed and compared in two groups: 50 consecutive patients receiving ISB without consequence at a university-based hospital and affiliated outpatient surgery center (Group I); 29 patients with persistent diaphragmatic paralysis after ISB evaluated and treated at a tertiary referral center (Group II). We analyzed the following patient factors between groups: age, sex, BMI, laterality, history of peripheral or diabetic neuropathy, prior nerve blocks, and underlying cervical spondylosis. An assessment of technical aspects of the nerve block was also performed. Results: In Group I there was 26 females and 24 males with an average age of 55, whereas in Group II there were 4 females and 25 males with an average age of 58. There was no significant difference between groups for BMI (mean=36 vs. 30) or laterality (Left=38% vs. 31%), however there were a significantly higher proportion of males in Group II (p<0.01). No difference was demonstrated between groups for peripheral or diabetic neuropathy, whereas prior ipsilateral blocks and cervical spondylosis were significantly more prevalent in Group II (p<0.01 & p<0.01, respectively). In Group I, 86% of patients received blocks performed with either nerve stimulator (64%) or ultrasound (22%) guidance, and 10% using both modalities. This contrasts to 79% of patients in Group II whose blocks were performed using either nerve stimulator (24%) or ultrasound (55%) guidance, and 6% in combination. Conclusion: Both patient factors and technical aspects of ISB may impact occurrence of persistent diaphragmatic paralysis. Use of ultrasound and nerve stimulator guidance can improve accuracy and reduce associated tissue inflammation, and there should be a redoubling of efforts to ensure technical expertise with these modalities in clinical practice.

Development of chemotactic smart scaffold for use in tissue regeneration.

Background: Regenerative medicine aims to obviate the need for autologous grafting through the use of bioengineered constructs that combine stem cells, growth factors, and biocompatible vehicles. Human mesenchymal stem cells and vascular endothelial growth factor (VEGF) have both shown promise for use in this context, the former because of their pluripotent capacity and the latter because of its chemotactic activity. The authors harnessed the regenerative potential of human mesenchymal stem cells and VEGF to develop a chemotactic scaffold for use in tissue engineering. Methods: Human mesenchymal stem cells were transduced with human VEGF via lentivirus particles to secrete VEGF. The chemotactic activity of the VEGF-transduced stem cells was evaluated via a trans-well assay. Migration through semipermeable membranes was significantly greater in chambers filled with medium conditioned by VEGF-transduced cells. VEGF-transduced cells were then seeded on apatite-coated poly(lactic-co-glycolic acid) scaffolds, thereby creating the Smart Scaffold. To determine in vivo angiogenesis, the Smart Scaffolds were implanted into subcutaneous pockets in the backs of nude mice. Results: Significantly larger numbers of capillaries were observed in the Smart Scaffold compared with control implants on immunohistologic studies. For the chemotactic in vivo study, human mesenchymal stem cells tagged with a fluorescent dye (1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide) were injected intravenously via tail vein after the subcutaneous implantation of the Smart Scaffolds. In vivo fluorescent imaging revealed that fluorescent dye–tagged human mesenchymal stem cells successfully accumulated within the Smart Scaffolds. Conclusion: These observations suggest that VEGF may play a vital role in the design of clinically relevant tissue regeneration graft substitutes through its angiogenic effects and ability to chemoattract mesenchymal stem cells.