Cutaneous Wound Healing and the Effects of Cannabidiol.

Cutaneous wounds, both acute and chronic, begin with loss of the integrity, and thus barrier function, of the skin. Surgery and trauma produce acute wounds. There are 22 million surgical procedures per year in the United States alone, based on data from the American College of Surgeons, resulting in a prevalence of 6.67%. Acute traumatic wounds requiring repair total 8 million per year, 2.42% or 24.2 per 1000. The cost of wound care is increasing; it approached USD 100 billion for just Medicare in 2018. This burden for wound care will continue to rise with population aging, the increase in metabolic syndrome, and more elective surgeries. To heal a wound, an orchestrated, evolutionarily conserved, and complex series of events involving cellular and molecular agents at the local and systemic levels are necessary. The principal factors of this important function include elements from the neurological, cardiovascular, immune, nutritional, and endocrine systems. The objectives of this review are to provide clinicians engaged in wound care and basic science researchers interested in wound healing with an updated synopsis from recent publications. We also present data from our primary investigations, testing the hypothesis that cannabidiol can alter cutaneous wound healing and documenting their effects in wild type (C57/BL6) and db/db mice (Type 2 Diabetes Mellitus, T2DM). The focus is on the potential roles of the endocannabinoid system, cannabidiol, and the important immune-regulatory wound cytokine IL-33, a member of the IL-1 family, and connective tissue growth factor, CTGF, due to their roles in both normal and abnormal wound healing. We found an initial delay in the rate of wound closure in B6 mice with CBD, but this difference disappeared with time. CBD decreased IL-33 + cells in B6 by 70% while nearly increasing CTGF + cells in db/db mice by two folds from 18.6% to 38.8% (p < 0.05) using a dorsal wound model. We review the current literature on normal and abnormal wound healing, and document effects of CBD in B6 and db/db dorsal cutaneous wounds. CBD may have some beneficial effects in diabetic wounds. We applied 6-mm circular punch to create standard size full-thickness dorsal wounds in B6 and db/db mice. The experimental group received CBD while the control group got only vehicle. The outcome measures were rate of wound closure, wound cells expressing IL-33 and CTGF, and ILC profiles. In B6, the initial rate of wound closure was slower but there was no delay in the time to final closure, and cells expressing IL-33 was significantly reduced. CTGF + cells were higher in db/bd wounds treated with CBD. These data support the potential use of CBD to improve diabetic cutaneous wound healing.

A Novel Sand Dollar and Staves Technique for Unilateral Lambdoid Craniosynostosis.

BACKGROUND: Unilateral lambdoid synostosis (ULS) is the rarest form of craniosynostosis. Due to the associated cranio-caudal shift seen in ULS, surgical correction is technically challenging from a morphological standpoint. Herein, the authors present a novel "Sand-Dollar and Staves" technique for the repair of ULS. METHODS: A zigzag coronal incision is performed, and an anteriorly-based pericranial flaps are elevated. Prefabricated cutting guides are placed and the calvarium is marked. To treat the flattening on the ipsilateral side, a wedged suturectomy is performed with additional barrel staves. A large circle centered over the bulging on the contralateral side is cut out above the open lambdoid suture. This piece is barrel staved in a radial fashion, leaving the center intact and creating a Sand-Dollar appearance. This disk is then flattened and trimmed. The modified Sand-Dollar is fixed using an absorbable plating system. While gentle pressure is applied to the Sand-Dollar piece as it is being secured, the ipsilateral side demonstrates compensatory filling. Results are evaluated using the Whitaker Classification. RESULTS: Four patients underwent surgical correction with this technique. The procedure was performed at mean age of 11.7 months. The mean operative time was 2.5 hours. Intraoperative blood loss was 50 to 100 ml. Total hospitalization time was 2 to 3 days. No post-operative complications were encountered. Whitaker scores ranged from 1 to 1.5. The mean follow-up was 10 months. CONCLUSION: The Sand-Dollar and Staves procedure is a novel, single-stage approach for the management of ULS with decreased operative time, blood loss, and hospital stay with satisfactory aesthetic outcomes.

A Global Evaluation of Surgical Techniques and Results of Unilateral Cleft Lip Repairs.

BACKGROUND: Variations in the clinical presentation of the unilateral cleft lip resulted in numerous surgical repair techniques used around the world. No universally accepted method exists to evaluate aesthetic surgical results. The purpose of this study is to use the Hubli lip grading system, developed by Smile Train, to evaluate the aesthetic results of unilateral cleft lip repairs based on the surgical technique used. METHODS: A retrospective review was conducted of unilateral cleft lip repair operations performed by Smile Train surgeons throughout Africa, Americas, Asia Pacific, and Europe and Middle East between 2014 and 2018. Using the Hubli lip grading criteria, factoring in cleft severity, acceptable outcomes were identified and compared with the surgical technique used. RESULTS: Eight thousand forty-one unilateral cleft lip repairs were reviewed. The majority utilized the rotational advancement technique (n = 5541, 68.9%) with a statistically significant percentage of acceptable outcomes (92.1%), followed by an acceptance rate of 91.9% with variations of the z-plasty technique, 90.5% with the straight-line repair and its variations, and 88.4% using "other" techniques (P < 0.05). The rotational advancement had the highest acceptable outcomes for complete cleft lips (94.7%, P < 0.0001), associated alveolar clefting (94.2%, P < 0.05), and concomitant clefting of the hard and/or soft palate (94.3%, P < 0.05). CONCLUSION: Regardless of surgical technique used, Smile Train surgeons maintain high rates of successful surgical outcomes. Results of our study will help complement and support existing medical infrastructure and training systems Smile Train employs for surgeons working with comprehensive cleft care teams around the world.

Mandibular Distraction in Robin Sequence With Multi-Level Airway Disease: Always Contraindicated?

In patients with Pierre Robin sequence (PRS), understanding the mechanism of airway obstruction and the potential for concurrent airway lesions is important for determining appropriate intervention. When concomitant airway anomalies are present with PRS, mandibular distraction osteogenesis alone is often contraindicated and unsuccessful at alleviating the obstruction, mandating the need for tracheostomy. Herein, the authors present the second-reported case of PRS with concomitant complete tracheal rings and highlight the importance collaborative surgical efforts to avoid tracheostomy. Our patient was born with signs and symptoms of PRS and concomitant complete tracheal rings. At birth, he developed respiratory compromise that was resistant to invasive and noninvasive intervention and was transferred to our care. The severity of his airway compromise necessitated operative intervention. Due to the patient's complex medical condition, avoiding the long-term sequelae of a tracheostomy and performing mandibular distraction was favorable. However, due to his multi-level airway disease, a 2-staged approach was planned: sliding tracheoplasty to release the tracheal rings, followed by mandibular distraction to correct the micrognathia. The patient tolerated both procedures and was successfully distracted and eventually weaned into room air. When managing patients with PRS in the setting of severe respiratory distress, securing the airway and carefully evaluating for concomitant airway anomalies is crucial. Even in the setting of multi-level airway disease where mandibular distraction is typically contraindicated, by directly addressing each anatomic level of airway obstruction, the airway can be safely secured and the resultant consequences of tracheostomy can be avoided. Careful planning with a multidisciplinary team is essential.

Nasal Alar Surface Area Differences After Unilateral Cleft Lip Repair: Long-Term Effects of the Perialar Incision.

BACKGROUND: The Millard rotation-advancement cleft lip repair is the most commonly performed cleft lip repair. An extended perialar incision allows for further advancement of the lateral lip element and improved positioning of the alar base. There is a lack of data evaluating differences in nasal alar growth when the perialar incision is utilized. This study compares the long-term effects of a perialar incision on the alar surface area of unilateral cleft lip patients who underwent a Millard cleft lip repair. METHODS: Thirty-seven patients with a diagnosis of unilateral cleft lip treated with a Millard primary lip repair were studied. A perialar incision was utilized in 16 patients while 21 patients underwent a standard Millard repair. 3dMD facial images were taken at least 10 years after the initial lip repair. Using the patient's non-cleft side as an internal control, the Alar Ratio (AR) was calculated, defined as the cleft alar surface area divided by the non-cleft alar surface area. RESULTS: The AR was significantly greater in the standard Millard repair group compared to the perialar incision group, 0.74 and 0.64 respectively (P = .02). The incomplete cleft population demonstrated a more profound difference between the treatment groups (0.82 and 0.62, respectively). CONCLUSIONS: This study reveals an association between a perialar incision and decreased alar surface area. Long-term follow up results suggest a perialar scar restricts alar growth leading to significant asymmetry between the cleft and non-cleft sides. Therefore, surgical technique must be carefully considered prior to utilizing a perialar incision during unilateral cleft lip repair.

Midline Intranasal Dermoid Cyst With Intracranial Extension: Technical Details of a Multidisciplinary Approach to a Rare Condition.

Dermoid cysts are rare, benign neoplasms that develop when ectodermal tissue is ectopically included during neural tube closure. Only 0.7% to 1.8% of dermoid cysts occur intracranially, and these make up only 0.3% of all intracranial tumors. Definitive management of intracranial dermoid cysts is achieved with surgical excision, with the primary goal being removal of the lesion before rupture or infection occurs. The authors report the multidisciplinary management of a 6-month-old patient with a midline intranasal dermoid cyst with intracranial involvement successfully treated with surgical resection. The surgical approach included Neurosurgical access with a bifrontal approach to remove the intracranial portion, then Plastic Surgery accessed and removed the intranasal portion through a transcolumellar and infracartilaginous dissection. The entire cyst was successfully removed without rupture. The patient's postoperative course was without complication.Timely preoperative imaging and diagnosis were crucial to the success of this operation. When considering the possibility of a midline dermoid cyst with intracranial extension, it is essential to obtain proper imaging to distinguish between lesions on the differential diagnosis and to define extent of extension. Once diagnosed, surgical planning requires a multidisciplinary approach. Considerations for the optimal surgical approach to intracranial, intranasal dermoids include maximizing surgical exposure and ensuring an aesthetically pleasing reconstructive outcome.

Cervical Stenosis in Non-Syndromic Pierre Robin Sequence.

Pierre Robin sequence is a triad of micrognathia, glossoptosis, and airway obstruction that has reported associations with numerous birth defects and anomalies including craniocervical pathologies. Given the number of airway assessments and neck manipulations these neonates experience, undetected cervical instability can result in detrimental consequences. The authors present a case of a neonate with non-syndromic Pierre Robin sequence planned for mandibular distraction osteogenesis that developed abnormal motor activity following intubation. The patient was eventually diagnosed with cervical spine stenosis and craniocervical instability after radiologic investigation. This paper demonstrates the significance of preoperative cervical spine evaluation and the importance of maintaining high level of suspicion when performing neck manipulations in those high-risk infants.

The role of indoleamine 2,3 dioxygenase in beneficial effects of stem cells in hind limb ischemia reperfusion injury.

Ischemia-Reperfusion (IR) injury of limb remains a significant clinical problem causing secondary complications and restricting clinical recovery, despite rapid restoration of blood flow and successful surgery. In an attempt to further improve post ischemic tissue repair, we investigated the effect of a local administration of bone marrow derived stem cells (BMDSCs) in the presence or absence of immune-regulatory enzyme, IDO, in a murine model. A whole limb warm ischemia-reperfusion model was developed using IDO sufficient (WT) and deficient (KO) mice with C57/BL6 background. Twenty-four hours after injury, 5 × 105 cells (5×105 cells/200 µL of PBS solution) BMDSCs (Sca1 + cells) were injected intramuscularly while the control group received just the vehicle buffer (PBS). Forty-eight to seventy-two hours after limb BMDSC injection, recovery status including the ratio of intrinsic paw function between affected and normal paws, general mobility, and inflammatory responses were measured using video micrometery, flow cytometry, and immunohistochemistry techniques. Additionally, MRI/MRA studies were performed to further study the inflammatory response between groups and to confirm reconstitution of blood flow after ischemia. For the first time, our data, showed that IDO may potentially represent a partial role in triggering the beneficial effects of BMDSCs in faster recovery and protection against structural changes and cellular damage in a hind limb IR injury setting (P = 0.00058).