Optic Nerve Atrophy in Syndromic Craniosynostosis.

BACKGROUND: Numerous children born with syndromic craniosynostosis will develop visual impairments. Based on the hypothesis that elevations in intracranial pressure might have greater impacts on vision than development, this review sought to ascertain the prevalence of optic nerve atrophy in syndromic craniosynostosis and to look for potential predictive factors. METHODS: The authors conducted a retrospective chart review of all children with syndromic craniosynostosis treated at a single center. RESULTS: Of 442 patients with syndromic craniosynostosis, complete ophthalmologic records were available for 253. Although no instances of optic nerve atrophy were noted among those with Saethre-Chotzen or Muenke syndromes, an overall 14.7 percent prevalence was noted among those with Apert (7.8 percent), Crouzon (27.9 percent), and Pfeiffer syndromes (23.1 percent), with initial diagnoses occurring at a mean age of 10 years. The presence of a Chiari malformation was found to significantly correlate with the subsequent diagnosis of optic nerve atrophy (OR, 3.544; p = 0.002); however, the timing of the first cranial vault procedure, presence of a ventriculoperitoneal shunt, degree of brachycephaly, number of vault expansions, and diagnosis of sleep apnea, did not show significant associations. CONCLUSIONS: A substantial percentage of children with Apert, Crouzon, and Pfeiffer syndromes were found to develop optic nerve atrophy, with a prevalence likely to trend higher with longer follow-up. Chiari malformations were the only significant potential predictor for optic nerve atrophy. With the goal of preventing visual losses, more frequent monitoring for raised intracranial pressure with ophthalmologic evaluations and magnetic resonance imaging measurements of optic nerve sheath diameters should be considered. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

No Opioids after Septorhinoplasty: A Multimodal Analgesic Protocol.

From a public health perspective, nasal surgery accounts for many unused opioids. Patients undergoing septorhinoplasty require few opioids, and efforts to eliminate this need may benefit both patients and the public. METHODS: A multimodal analgesic protocol consisting of 15 components encompassing all phases of care was implemented for 42 patients. RESULTS: Median age and BMI were 34 years and 23, respectively. Most were women (79%), White (79%), primary surgeries (62%), and self-pay (52%). Comorbid conditions were present in 74% of the patients, with anxiety (33%) and depression (21%) being the most common. Septoplasties (67%) and osteotomies (45%) were common. The median operative time was 70 minutes. No patients required opioids in recovery, and median time in recovery was 63 minutes. Ten (24%) patients required an opioid prescription after discharge. In those patients, median time to requirement was 27 hours (range 3-81), and median total requirement was 20 mg morphine equivalents (range 7.5-85). Protocol compliance inversely correlated to opioid use (P = 0.007). Compliance with local and regional anesthetic (20% versus 63%, P = 0.030) as well as ketorolac (70% versus 100%, P = 0.011) was lower in patients who required opioids. Patients who required opioids were less likely to be administered a beta blocker (0% versus 34%, P = 0.041). Pain scores were higher in opioid users on postoperative days 1-5 (P < 0.05). No complications occurred in those requiring opioids, and satisfaction rates were equivalent between groups. CONCLUSION: This protocol allowed us to safely omit opioid prescriptions in 76% of patients following septorhinoplasty, without adverse effects on outcomes or patient satisfaction.

Duraplasty Using Autologous Fascia Lata and Latissimus Dorsi Free Flap for Chronic Cerebrospinal Fluid Leak.

Cerebrospinal fluid (CSF) leak is a common complication after cranial surgery. Therefore, after neurosurgical procedures it is crucial to obtain a dural repair that is complete and watertight. There are many techniques that have been described attempting to achieve this goal. However, there are complicating factors (eg, poor tissue viability, need for future radiation, comorbidities, infection, size of the dural defect, multiple operations) that may require a more comprehensive approach to achieve an optimal healing environment. The authors present a technique that uses a muscle free flap to vascularize an autologous fascia lata graft, preserving the viability of the graft and reinforcing its healing ability.The authors applied this technique to a single patient with chronic CSF leak from poor tissue healing after treatments for recurrent medulloblastoma. After harvesting a fascia lata graft with appropriate size, the graft was sutured into the dural defect in a watertight fashion. A latissimus dorsi muscle free flap was harvested and anastomosed to a saphenous vein Corlett loop/AV fistula to the facial artery. The flap was than sutured to the graft. A drain was left in place and a skin graft was applied to the muscle flap.At 8 months follow-up the patient was able to continue with her treatment and has had a stable repair without leak or breakdown. The authors present an algorithm to facilitate dural repair selection.Duraplasty using autologous fascia lata reinforced with a free muscle flap is an effective technique to control chronic CSF leaks, especially when the dura is poorly vascularized and less viable.

Perioperative Management and Factors Associated With Transfusion in Cranial Vault Reconstruction.

BACKGROUND: Bleeding is the most common adverse event in patients undergoing cranial vault reconstruction. The authors compare the transfusion rates against a national sample to determine whether the patients experience lower transfusion rates. METHODS: The authors queried the Pediatric National Surgical Quality Improvement Program (Peds-NSQIP) for patients who underwent cranial vault reconstruction (CPT 61559) and compared them to patients who underwent cranial vault reconstruction for sagittal craniosynostosis at Children's Hospital and Medical Center (CHMC) in Omaha, Nebraska. Patients over the age of 24 months were excluded. Binary logistic regression analysis was performed using IBM-SPSS v24.0 to determine factors associated with transfusion at CHMC. RESULTS: Patient demographics, preoperative hematocrit and platelet counts, readmission rates, and reoperation rates did not differ between CHMC (N = 54) and Peds-NSQIP (N = 1320) cohorts. Patients in the CHMC cohort had shorter preincision anesthesia times (47 versus 80 minutes, P < 0.001), shorter operative times (108 versus 175 minutes, P < 0.001), lower transfusion rates (50% versus 73%, P < 0.001), and smaller mean transfusion volumes (16 versus 33 mL/kg, P < 0.001); however mean length of stay was longer (4.1 versus 3.6 days, P < 0.001). Factors independently associated with transfusion at CHMC included preoperative hematocrit (odds ratio [OR] 0.423, P = 0.002), administration of an antifibrinolytic agent (OR 0.004, P = 0.001) and temperature at the time of incision (OR 0.020, P = 0.043). CONCLUSION: Patients at CHMC require less transfused blood and experience low transfusion rates. Preoperative hematocrit, administration of antifibrinolytic agents, and temperature at the time of incision are all modifiable factors associated with perioperative transfusion.

Anterior Cranial Vault Reconstruction With Distraction for Primary and Secondary Craniosynostosis Repair.

Traditional fronto-orbital advancement continues to be a useful operation for correction of craniosynostosis involving the coronal or metopic sutures. Recently, distraction osteogenesis has been used to correct a variety of cranial deformities. Studies have mostly focused on posterior vault distraction due to its simplicity and greater volume gain when compared with anterior vault distraction. However, certain patients are not candidates for posterior distraction due to anterior deformity and need for expansion of the frontal skull. The authors have developed a technique that allows for both reshaping as well as distraction of the anterior cranial vault.This was a retrospective chart review performed between March 2012 and October 2016 at a single institution by a single plastic surgeon. Thirty-nine (39) patients were included in this study. The indications for surgical intervention were signs of increased intracranial pressure or severe anterior skull deformity in the setting of craniosynostosis. The authors reviewed patient characteristics, length of follow-up, number of previous and subsequent surgeries, complications, and rate of relapse.The average age of patients undergoing the procedure was 5.2 years (range 6 months-15 years). Twenty-four (24) patients had 1 previous surgery, 3 had 2 previous surgeries, 1 had 3 previous surgeries, and 11 had no previous surgeries. The average follow-up was 2.5 years (range 6 months-4 years). One patient had a broken activation wire requiring return to the operating room. Three (3) patients (2 Apert and 1 Crouzon) underwent subsequent posterior vault distraction surgery. All patients demonstrated significant improvement in forehead cosmesis.Anterior cranial vault reconstruction with distraction is a safe alternative to traditional cranial vault reconstruction. It can improve forehead shape and position in older children who have had previous surgery as well as patients with severe anterior skull deformity associated with craniosynostosis.

Major Histopathologic Diagnoses of Chronic Wounds.

PURPOSE: To clarify the histopathology of acute osteomyelitis, chronic osteomyelitis, primary vasculitis, and secondary-type vasculitis. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant should be better able to:1. Describe the parameters and significance of this study.2. Identify chronic wound diagnosis and treatment.3. Differentiate the histopathology of osteomyelitis and vasculitis. OBJECTIVE: The presence of a chronic wound can result in significant morbidity/mortality. Understanding the pathological alterations of wound tissue that are refractory to standard wound therapy is essential for effective wound management and healing. The authors describe 4 wound etiologies, specifically, acute osteomyelitis, chronic osteomyelitis, primary vasculitis, and secondary-type vasculitis. SETTING: A tertiary care hospital. DESIGN: A retrospective review of 1392 wound operations performed during a 24-month period at a tertiary care hospital was conducted. Tissue specimens reviewed included soft tissue infections of the lower extremity, sacrum, hip/pelvis, trunk, perineum, and buttocks. MAIN RESULTS: Acute osteomyelitis is defined as bone tissue with a predominance of polymorphonuclear leukocytes, evidence of osteoclast bone resorption with scalloping of the cortical bone edges, and bone detritus. Chronic osteomyelitis is defined as bone tissue with a significant amount of fibrosis surrounding devitalized tissue and heavy infiltration of lymphocytes and plasma cells. Primary-type vasculitis is defined primarily as inflammation and necrosis of blood vessel walls. In cutaneous lesions of granulomatosis with polyangiitis, ulceration with numerous inflammatory granulomas is seen in the papillary dermis. Secondary vasculitis is defined by vessel wall infiltration by inflammatory cells and fibrinoid necrosis of the small vessel wall. CONCLUSIONS: Pathologies of these 4 types of wounds can complicate standard algorithms designed for diagnosis and treatment, and accurate diagnosis through histopathologic analysis can help tailor targeted treatment.

Clinical application of growth factors and cytokines in wound healing.

Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous growth factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various growth factors in the clinical management of nonhealing wounds (e.g., pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted an online search of Medline/PubMed and critically analyzed the literature regarding the role of growth factors and cytokines in the management of these wounds. We focused on currently approved therapies, emerging therapies, and future research possibilities. In this review, we discuss four growth factors and cytokines currently being used on and off label for the healing of wounds. These include granulocyte-macrophage colony-stimulating factor, platelet-derived growth factor, vascular endothelial growth factor, and basic fibroblast growth factor. While the clinical results of using growth factors and cytokines are encouraging, many studies involved a small sample size and are disparate in measured endpoints. Therefore, further research is required to provide definitive evidence of efficacy.

Attenuation of the transforming growth factor beta-signaling pathway in chronic venous ulcers.

Transforming growth factor beta (TGFbeta) is important in inflammation, angiogenesis, reepithelialization and connective tissue regeneration during wound healing. We analyzed components of TGFbeta signaling pathway in biopsies from 10 patients with nonhealing venous ulcers (VUs). Using comparative genomics of transcriptional profiles of VUs and TGFbeta-treated keratinocytes, we found deregulation of TGFbeta target genes in VUs. Using quantitative polymerase chain reaction (qPCR) and immunohistochemical analysis, we found suppression of TGFbeta RI, TGFbeta RII and TGFbeta RIII, and complete absence of phosphorylated Smad2 (pSmad2) in VU epidermis. In contrast, pSmad2 was induced in the cells of the migrating epithelial tongue of acute wounds. TGFbeta-inducible transcription factors (GADD45beta , ATF3 and ZFP36L1) were suppressed in VUs. Likewise, genes suppressed by TGFbeta (FABP5, CSTA and S100A8) were induced in nonhealing VUs. An inhibitor of Smad signaling, Smad7 was also downregulated in VUs. We conclude that TGFbeta signaling is functionally blocked in VUs by downregulation of TGFbeta receptors and attenuation of Smad signaling resulting in deregulation of TGFbeta target genes and consequent hyperproliferation. These data suggest that application of exogenous TGFbeta may not be a beneficial treatment for VUs.

Surgical pathology to describe the clinical margin of debridement of chronic wounds using a wound electronic medical record.

BACKGROUND: Chronic wounds, including diabetic foot ulcers (DFU), pressure ulcers (PU), and venous ulcers (VU) result from multiple physiologic impairments. Operative debridement is a mainstay of treatment to remove nonviable tissue and to stimulate wound healing. Unlike tumor resection, however, operative wound specimens are not routinely sent for pathology. The objective of this study was to describe the pathology present in chronic wounds. STUDY DESIGN: Pathology reports of the skin edge and wound base from 397 initial debridements in 336 consecutive patients with chronic wounds were retrospectively reviewed. All data were entered and stored in a Wound Electronic Medical Record. Pathology data were extracted from the Wound Electronic Medical Record, coded, and quantified. RESULTS: Up to 15 distinct histopathologic findings across 7 tissue types were observed after review of pathology reports from chronic wounds. Specifically, the pathology of epidermis revealed hyperkeratosis: 66% in DFUs, 31% in PUs, and 29% in VUs. Dermal pathology revealed fibrosis in 49% of DFUs, 30% of PUs, and 15% of VUs. Wound bed pathology revealed necrosis in the subcutaneous tissue in 67% of DFUs, 55% of PUs, and 19% of VUs. Fibrosis was reported in between 19% and 52% of all wound types. Acute osteomyelitis was present in 39% of DFUs, 33% of PUs, and 29% of VUs. CONCLUSIONS: This observational study of the histopathology of initial surgical debridement of chronic wounds revealed a wide range of findings across multiple tissue levels. Although certain findings such as osteomyelitis and gangrene have been shown to directly relate to impaired wound healing and amputation, other findings require additional investigation. To rigorously define a margin of debridement, a prospective study relating histopathology and clinical outcomes such as healing rates and amputation is needed.

Growth factors and cytokines in wound healing.

Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous growth factors, cytokines and chemokines. Of particular importance is the epidermal growth factor (EGF) family, transforming growth factor beta (TGF-beta) family, fibroblast growth factor (FGF) family, vascular endothelial growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), interleukin (IL) family, and tumor necrosis factor-alpha family. Currently, patients are treated by three growth factors: PDGF-BB, bFGF, and GM-CSF. Only PDGF-BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other growth factors may soon be available to patients. This review will focus on the specific roles of these growth factors and cytokines during the wound healing process.