Pediatric Microsurgery and Free-Tissue Transfer.

Advancements in microsurgery, along with increased microsurgical experience in pediatric patients, have made free-tissue transfer a reliable modality for pediatric bone and soft tissue reconstruction today. Free-tissue transfer is most commonly used in children for the coverage of large or complex defects resulting from traumatic, oncologic, or congenital etiologies. While flap success and complication rates between pediatric and adult populations are similar, special considerations must be taken into account within the pediatric population. In this article, we will describe common indications, technical nuances, and clinical considerations for the management of the pediatric free-tissue transfer patient.

Metabolomic Profiling in Mouse Model of Menopause-Associated Asthma.

Menopause-associated asthma impacts a subset of women, tends to be more severe, and is less responsive to current treatments. We recently developed a model of menopause-associated asthma using 4-Vinylcyclohexene Diepoxide (VCD) and house dust mites (HDM). The goal of this study was to uncover potential biomarkers and drivers of menopause-onset asthma by assessing serum and bronchoalveolar lavage fluid (BALF) samples from mice with and without menopause and HDM challenge by large-scale targeted metabolomics. Female mice were treated with VCD/HDM to model menopause-associated asthma, and serum and BALF samples were processed for large-scale targeted metabolomic assessment. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to examine metabolites of potential biological significance. We identified over 50 individual metabolites, impacting 46 metabolic pathways, in the serum and BALF that were significantly different across the four study groups. In particular, glutamate, GABA, phosphocreatine, and pyroglutamic acid, which are involved in glutamate/glutamine, glutathione, and arginine and proline metabolisms, were significantly impacted in the menopausal HDM-challenged mice. Additionally, several metabolites had significant correlations with total airway resistance including glutamic acid, histamine, uridine, cytosine, cytidine, and acetamide. Using metabolic profiling, we identified metabolites and metabolic pathways that may aid in discriminating potential biomarkers for and drivers of menopause-associated asthma.

ß-Arrestin-biased proteinase-activated receptor-2 antagonist C781 limits allergen-induced airway hyperresponsiveness and inflammation.

BACKGROUND AND PURPOSE: Asthma is a heterogenous disease strongly associated with inflammation that has many different causes and triggers. Current asthma treatments target symptoms such as bronchoconstriction and airway inflammation. Despite recent advances in biological therapies, there remains a need for new classes of therapeutic agents with novel, upstream targets. The proteinase-activated receptor-2 (PAR2) has long been implicated in allergic airway inflammation and asthma and it remains an intriguing target for novel therapies. Here, we describe the actions of C781, a newly developed low MW PAR2 biased antagonist, in vitro and in vivo in the context of acute allergen exposure. EXPERIMENTAL APPROACH: A human bronchial epithelial cell line expressing PAR2 (16HBE14o- cells) was used to evaluate the modulation in vitro, by C781, of physiological responses to PAR2 activation and downstream ß-arrestin/MAPK and Gq/Ca2+ signalling. Acute Alternaria alternata sensitized and challenged mice were used to evaluate C781 as a prophylactically administered modulator of airway hyperresponsiveness, inflammation and mucus overproduction in vivo. KEY RESULTS: C781 reduced in vitro physiological signalling in response to ligand and proteinase activation. C781 effectively antagonized ß-arrestin/MAPK signalling without significant effect on Gq/Ca2+ signalling in vitro. Given prophylactically, C781 modulated airway hyperresponsiveness, airway inflammation and mucus overproduction of the small airways in an acute allergen-challenged mouse model. CONCLUSION AND IMPLICATIONS: Our work demonstrates the first biased PAR2 antagonist for ß-arrestin/MAPK signalling. C781 is efficacious as a prophylactic treatment for allergen-induced airway hyperresponsiveness and inflammation in mice. It exemplifies a key pharmacophore for PAR2 that can be optimized for clinical development.

Robotic Nerve Surgery: Brachial Plexus.

Management of closed brachial plexus injuries has traditionally favored conservative approaches with lengthy intervals between initial injury and surgical reconstruction. The complex anatomy of this region often requires large incisions with extensive dissection. Recently, the use of robotic systems in plastic and reconstructive surgery has been increasing, and robot-assisted brachial plexus reconstruction is a novel application that is currently being explored. Current literature describing this application is primarily comprised of feasibility studies using animal and cadaver models, and literature describing use in human subjects is limited. Advantages demonstrated by these early studies include the reduction of physiologic tremor, 3D visualization of anatomical structures, and ergonomic positioning; this allows for increased surgical dexterity and the ability to perform minimally invasive microsurgical procedures within the confined anatomical spaces of the brachial plexus. Limitations revolve around inadequate instrumentation, large learning curves, and increased costs that restrict the ability to perform these complex microsurgical procedures reliably and efficiently. As companies continue to develop instrumentation specific to robot-assisted microsurgery, more extensive longitudinal studies outlining long-term costs, changes in operating time, and functional outcomes will be required before a conclusion about the utility of these systems in brachial plexus surgery can be made.

Sirenomelia: Review of a Rare Syndrome with Case Report, Review of Anatomy, and Thoughts on Management.

BACKGROUND: Sirenomelia is a rare syndrome in which the infant is born with the legs fused from the pelvis to the feet. Sirenomelia is often fatal in the neonatal period because of multiple other anomalies. The feet may be absent; if present, they are often splayed outward or face backward. There are no case reports of any patient with this syndrome who has been able to walk after separation of the legs. METHODS: The authors report on their patient with sirenomelia who was born with the feet facing backward but otherwise normal-appearing hips and thighs and no other anomalies that would lead to fatality in the near future. After preoperative tissue expansion, the authors performed separation of the legs with through-knee amputations, utilizing a vascularized flap from the lower part of the legs based on the sciatic vessels for coverage of the perineum. There was no need for skin grafts or dermal matrices and the patient was referred to physical therapy after recovery from surgery in an attempt to allow her to ambulate. RESULTS: The patient began to ambulate on her stumps early after surgical repair and is now walking with stubby prostheses. Her other medical issues have remained stable and nonproblematic. CONCLUSIONS: Selected patients with sirenomelia may be able to walk after separation of the legs, depending on the status of other congenital differences as well as the status of the legs when separated. Careful workup with multidisciplinary planning of overall care as well as surgical care is essential.

Arteriovenous Malformations of the Hand: Optimizing Outcomes with Palmar Arch Reconstruction.

BACKGROUND: Arteriovenous malformations are abnormal high-flow vascular anomalies that can greatly alter the structure of surrounding tissues. Treatment of symptomatic hand arteriovenous malformations must address the functional and aesthetic considerations of the hand. Nonsurgical treatment such as embolization continues to be plagued by complications such as digital ischemia and secondary need for amputation. In this study, the authors describe their experience treating hand arteriovenous malformations with wide resection and microsurgical reconstruction of the palmar arch. This technique aims to optimize postoperative function and minimize postoperative complications and recurrence. METHODS: Retrospective review identified five patients who underwent surgical excision of hand arteriovenous malformations performed by two of the senior authors (W.C.P. and M.M.) between 2002 and 2020. Four patients underwent reconstruction of the palmar arch, whereas one patient underwent ray amputation of the involved index finger only. One patient required concurrent free flap for soft-tissue coverage following resection. RESULTS: Mean age at the time of surgery was 34.6 years. After an average follow-up of 2.7 years, there were no postoperative complications, functional deficits, or recurrences. The patient who underwent ray amputation only was postoperatively noted to have pulsatile dorsal veins concerning for a persistent high-flow state, although no recurrent mass was seen at limited 1-year follow-up. CONCLUSIONS: Meticulous surgical excision with microvascular reconstruction is an acceptable technique for management of symptomatic hand arteriovenous malformations. Potential soft-tissue loss does not preclude aggressive resection. Wide excision with palmar arch reconstruction minimizes complications, optimizes functionality, and may prevent ischemia that could otherwise trigger recurrence. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Impact of the Virtual Format on Plastic Surgery Residency and Fellowship Interviews: A National Cross-Sectional Study.

BACKGROUND: The 2020 to 2021 residency and fellowship application cycles were profoundly affected by the introduction of virtual interviews. The authors investigated the impact the virtual format had on plastic surgery residency and fellowship interviews from the perspectives of program directors. METHODS: Surveys were sent to program directors of integrated plastic surgery residency and fellowship programs to ascertain their perspectives regarding the virtual format's impact on residency and fellowship interviews. Program directors were stratified into residency and fellowship cohorts, and comparative analysis was performed. RESULTS: Ninety-two program directors, 28 from integrated plastic surgery residency programs and 64 from fellowship programs, completed our survey (35 percent). Compared to in-person interviews, virtual interviews were reported to be more economical and time efficient by program directors of residency (100 percent and 46 percent, respectively) and fellowship programs (97 percent and 48 percent, respectively). Consequentially, 36 percent and 47 percent of residency and fellowship programs were able to interview more applicants, respectively. Program directors of residency and fellowship programs reported that virtual interviews hindered their ability to assess applicants' fit with the program (75 percent and 63 percent, respectively), personality and communication skills (75 percent and 64 percent, respectively), and commitment to the field, along with their ability to function as a trainee (57 percent and 50 percent, respectively). Overall, 71 percent of program directors of residency and 58 percent of program directors of fellowship programs preferred in-person interviews. The majority of residency (71 percent) and fellowship (56 percent) program directors intend to conduct both in-person and virtual interviews in future application cycles ( p = 0.12). CONCLUSIONS: Despite preferring in-person interviews, program directors intend to host both in-person and virtual interviews in future application cycles. It remains to be seen how virtual interviews will be used moving forward.

The Challenges of Upper Extremity Intramuscular Hemangioma: A Case Study and Systematic Review.

BACKGROUND: Intramuscular hemangiomas are rare, benign vascular tumors, constituting 0.8 percent of all hemangiomas. Upper extremity intramuscular hemangiomas pose diagnostic and therapeutic challenges because of their rarity, invasive nature, and potential for neurovascular involvement. The authors report a comprehensive systematic review of upper extremity intramuscular hemangioma management and a challenging case report. METHODS: A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic databases were used to identify articles describing upper extremity intramuscular hemangiomas through 2019. Patient demographics, clinical presentation, management, complications, and outcomes were reviewed. Based on operative timing, cases were categorized as either "primary" (excision performed at initial diagnosis) or "secondary" (excision performed after failure of conservative treatment). RESULTS: Eighteen articles encompassing 25 patients were included in the authors' systematic review. Of those, 18 underwent primary excision and seven underwent secondary excision. The majority involved the forearm or antecubital region. Complete excision, evaluated by gross examination or pathology, was reported in all primary cases and 71 percent of secondary cases. Primary excisions demonstrated smaller size of mass (19.4 cm 2 versus 165.3 cm 2 ) and superior reported functional outcomes (100 percent versus 33 percent). Complications were reported in 5 percent of the primary excisions compared to 71 percent of the secondary excisions, where one complication was a fatal hematoma. CONCLUSIONS: The literature concerning upper extremity intramuscular hemangioma is limited to mostly case reports and several case series with the potential risk of bias. With careful dissection and microsurgical technique, wide local excision followed by complete reconstruction can be successfully performed at initial diagnosis for upper extremity intramuscular hemangiomas. At early stages, smaller lesion size significantly reduces the risk of functional impairment and complications.

CC16 Deficiency in the Context of Early-Life Mycoplasma pneumoniae Infection Results in Augmented Airway Responses in Adult Mice.

Studies have shown that club cell secretory protein (CC16) plays important protective roles in the lungs, yet its complete biological functions are unclear. We devised a translational mouse model in order to investigate the impact of early life infections, in the context of CC16 deficiency, on lung function in adult mice. CC16 sufficient (WT) and deficient (CC16-/-) mice were infected with Mycoplasma pneumoniae (Mp) as weanlings and assessed as adults (early life infection model; ELIM) and compared to adult mice infected for only 3 days (adult infection model; AIM). CC16-/- Mp-infected mice had significantly increased airway hyperresponsiveness (AHR) in both models compared to WT mice. However, CC16-/- mice infected in early life (ELIM) displayed significantly increased AHR compared to CC16-/- mice infected in adulthood (AIM). In stark contrast, lung function in ELIM WT mice returned to levels similar to saline-treated controls. While WT mice cleared Mp infection in the ELIM, CC16-/- mice remained colonized with Mp throughout the model, which likely contributed to increased airway remodeling and persistence of Muc5ac expression. When CC16-/- mouse tracheal epithelial cells (MTECs) were infected with Mp, increased Mp colonization and collagen gene expression were also detected compared to WT cells, suggesting that CC16 plays a protective role during Mp infection, in part through epithelial-driven host defense mechanisms.

Free latissimus dorsi flap for upper extremity reconstruction in a 9-month-old.

Successful outcomes for free tissue transfer are well-documented in pediatric patients but less so in infants. Challenges with infants are unique and include implications of prolonged anesthetic exposure. We present a 9-month-old female who underwent a free latissimus dorsi flap to reconstruct a congenital upper extremity lesion threatening limb development.

Two-Stage Treatment of a Large Premaxillary Defect.

ABSTRACT: Bilateral cleft lip and palate (CLP) patients commonly require surgical management to treat maxillary hypoplasia following the primary repair. Rarer is the CLP patient who also presents with a missing premaxillary segment. Here the authors present the case of a 19-year-old female with a history of bilateral CLP who demonstrated significant maxillary hypoplasia in addition to a large premaxillary defect. To correct this deformity, LeFort I advancement with fibular reconstruction of the maxilla and dental implant placement was performed as a single surgical procedure. The authors discuss the advantages of undergoing this single-staged operation. By utilizing virtual surgical planning (VSP) and incorporating a multidisciplinary team within the operating room, the patient was able to successfully undergo maxillary reconstruction and dental implant placement in a single operation.

Operative Pediatric Hand Infections: A Retrospective Review.

BACKGROUND: Infections in the pediatric population are a less well studied topic in hand surgery. Crucial aspects of the management of pediatric hand infections differ from adults, though much of current treatment is generalized from adult care. This study evaluates our clinical experience with regards to the epidemiology, management, and outcomes of pediatric hand infections requiring operative intervention. METHODS: A 7-year retrospective chart review was performed of all pediatric patients who required operative intervention for hand infections at Texas Children's Hospital. Clinical information was collected and analyzed, including demographics, infection characteristics, management, and outcomes. RESULTS: Fifty-seven patients met the inclusion criteria for our study over the 7-year period. Of these, 7% (n=4) had a pre-existing diagnosis of diabetes mellitus, and 5% (n=3) had a recent history of upper extremity infections. The most common infection was a discrete abscess, whereas urgent/emergent conditions represented 25% (n=14) of infections. Radiographic changes consistent with osteomyelitis were present in over one-quarter of patients (n=13, 23%). The median length of hospital stay was 3 days (95% confidence interval: 3.05-5.05) and the most common pathogen was Staphylococcus aureus (n=33, 58%), with slightly more being methicillin sensitive (MSSA) than resistant (MRSA) (n=19, 33% vs. n=14, 25%). The incidence of reoperation was 12.5% (n=7). CONCLUSIONS: Hand infections are a common problem in the pediatric population. Cases tend to be associated with accidental trauma and discrete abscesses colonized by MSSA/MRSA. The vast majority of cases require only one operation and a short course of wound care before discharge. LEVEL OF EVIDENCE: Level IV-therapeutic study.

Recurrent brachial artery aneurysm repair in a child managed with Gore-Tex conduit reinforcement.

Pediatric nonaortic arterial aneurysms are uncommon diagnoses and can be affiliated with underlying conditions, which include neurofibromatosis I, Ehlers-Danlos type IV syndrome, Kawasaki disease, Marfan syndrome, and Loeys-Dietz, polyarteritis nodosa, as well as Klippel-Trenauny syndrome. The standard of care has been early surgical excision and arterial reconstruction when indicated. This report details a case of recurrent brachial artery aneurysm in a 2-year-old boy despite multiple attempts at excision and reconstruction. Such recurrences were seen as rapidly as 3 months postoperatively. Ultimately, a Gore-Tex conduit was used to reinforce a reversed saphenous vein graft repair. There has been no evidence of recurrent disease during the 18-month follow-up period.

The Medial Femoral Condyle Flap in the Pediatric Patient.

BACKGROUND: The use of free flaps from the medial femoral condyle has grown in popularity and is now a workhorse in the reconstruction of skeletal defects. The utility of this technique has not yet been described for the pediatric patient population. The authors present their series of pediatric patients who underwent surgery using a medial femoral condyle free flap or a variant thereof in skeletal reconstruction and demonstrate the efficacy of this technique in this population. METHODS: A multi-institutional retrospective review of patients aged 18 years or younger who required a medial femoral condyle flap for skeletal reconstruction was undertaken. Operative technique, radiographs, and clinical outcomes were recorded. A novel technique (Innocenti) was used to avoid the distal femoral physis in which a Kirschner wire was placed under fluoroscopic guidance just proximal to the growth plate. RESULTS: Thirteen patients met inclusion criteria, with an average age of 14.7 years (range, 7 to 18 years) and mean follow-up of 28 months (range, 3 to 120 months). Six were skeletally immature at the time of medial femoral condyle harvest, with the last patient having organic bone disease, putting her at risk for pathologic fracture. All 13 patients achieved bony union, and no patients suffered pathologic fractures or physeal injuries; no patients developed length discrepancies. CONCLUSIONS: The authors present the first series of corticocancellous medial femoral condyle free flaps in the pediatric population along with a novel technique to avoid injury to the physis in skeletally immature patients. This technique is effective for a variety of skeletal defects or nonunions and is safe for growing patients without causing physeal arrest or growth disturbance. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Genetic variation in surfactant protein-A2 alters responses to ozone.

BACKGROUND: Increased exposure to Ozone (O3) is associated with adverse health effects in individuals afflicted with respiratory diseases. Surfactant protein-A (SP-A), encoded by SP-A1 and SP-A2, is the largest protein component in pulmonary surfactant and is functionally impaired by O3-oxidation. OBJECTIVE: We used humanized SP-A2 transgenic mice with allelic variation corresponding to a glutamine (Q) to lysine (K) amino acid substitution at position 223 in the lectin domain to determine the impact of this genetic variation in regards to O3 exposure. METHODS: Mice were exposed to 2ppm O3 or Filtered Air (FA) for 3 hours and 24 hrs post-challenge pulmonary function tests and other parameters associated with inflammation were assessed in the bronchoalveolar lavage (BAL) fluid and lung tissue. Additionally, mouse tracheal epithelial cells were cultured and TEER measurements recorded for each genotype to determine baseline epithelial integrity. RESULTS: Compared to FA, O3 exposure led to significantly increased sensitivity to methacholine challenge in all groups of mice. SP-A2 223Q variant mice were significantly protected from O3-induced AHR compared to SP-A-/- and SP-A2 223K mice. Neutrophilia was observed in all genotypes of mice post O3-exposure, however, SP-A2 223Q mice had a significantly lower percentage of neutrophils compared to SP-A-/- mice. Albumin levels in BAL were unchanged in O3-exposed SP-A2 223Q mice compared to their FA controls, while levels were significantly increased in all other genotypes of O3-exposed mice. SP-A 223Q MTECS has significant higher TEER values than all other genotypes, and WT MTECS has significantly higher TEER than the SP-A KO and SP-A 223K MTECS. SIGNIFICANCE: Taken together, our study suggests that expression of a glutamine (Q) as position 223 in SP-A2, as opposed to expression of lysine (K), is more protective in acute exposures to ozone and results in attenuated O3-induced AHR, neutrophilia, and vascular permeability.

Autologous Osteoligamentous Reconstruction of Scaphoid Proximal Pole With Metatarsal Head and Collateral Ligament: Cadaver Anatomic Description of Novel Surgical Technique.

Background: Historically, scaphoid nonunion has been surgically treated with vascularized bone graft taken from multiple different anatomic sites. However, none of these grafts fully recapitulate the unique osteoligamentous anatomy of the proximal pole of the scaphoid and the attachment of the scapholunate ligament (SLIL). We studied the anatomy of the vascularized second metatarsal head with its lateral collateral ligament as a potential novel treatment of proximal pole scaphoid nonunion with collapse. Methods: Scaphoids and second metatarsal heads were harvested from bilateral upper and lower extremities of 18 fresh frozen cadavers (10 male, 8 female) for a total of 36 scaphoids and 36 second metatarsal heads. The ipsilateral second metatarsal head was harvested with its lateral collateral ligament and its blood supply from the second dorsal metatarsal artery (SDMA). Measurements of the scaphoid, the SLIL, the second metatarsal head, and lateral collateral ligaments were compared to matched limbs from the same cadaver. Results: The anatomic dimensions of the second metatarsal head with its lateral collateral ligament are similar to the scaphoid proximal pole and the SLIL in matched cadaveric specimen. Conclusions: This anatomic cadaver study reveals that the second metatarsal head with its associated lateral collateral ligament is a well-matched donor to reconstruct the proximal pole of the scaphoid and SLIL. This anatomic similarity may be well suited to treat nonunion of the scaphoid proximal pole with or without avascular necrosis with simultaneous reconstruction of the SLIL. The authors describe a technique of vascularized reconstruction of the osteoligamentous proximal pole of the scaphoid with its attached SLIL utilizing autologous second metatarsal head with its attached lateral collateral ligament. Based on this cadaver study, this technique merits consideration.

The Epidemiology of Operative Pediatric Hand Trauma: A Retrospective Chart Review.

Background: Hand injuries are common in the pediatric population with a wide spectrum of morbidity that can occur. Simple injuries are distinguished from complex injuries by the number of fingers/systems that are involved. The epidemiology of simple and complex operative hand trauma in the pediatric population has not yet been defined. Methods: A retrospective review was performed of all pediatric patients requiring operative intervention for hand trauma at a major children's hospital over a 3-year period (2015-2017). Data pertaining to demographics, mechanism, severity, type of surgery, and other factors related to hand trauma were then analyzed and interpreted. Results: Three hundred seventy-one pediatric hand injuries over a 3-year period required surgical intervention, with 19.2% being classified as complex. The average patient age was 11.0 years. A total of 68.7% of patients were men. Bony injuries made up 86.3% of simple injuries, with the proximal phalanx being the most commonly fractured bone. Complex injuries occurred more frequently in men and required a greater number of surgeries (1.6 vs 1.0). Of the complex injuries, only major injuries (severity score >100) required a significantly greater number of surgeries. Major hand injuries were mostly caused by motorized vehicles and required a significantly greater number of surgeries (3.8), compared with other causes of injuries. Conclusions: Operative hand injuries occur along a spectrum of morbidity in the pediatric population. While most of the injuries are simple and require only 1 procedure, more complex injuries can also occur and deserve a higher level of care and attention.

Reconstruction of a Portion of the Articular Surface of the Distal Radius With a Vascularized Osteochondral Graft From the Proximal Phalanx of the Great Toe.

Distal radius fractures are among the most common injuries to the upper extremity and have a bimodal distribution in younger male patients and older women. Young men suffer from high-energy injuries and older women from fragility fractures. Approximately 50% of these are intra-articular. Timely and appropriate treatment usually will lead to an acceptable outcome, but loss of congruity of the articular surface remains a difficult problem to manage. We report here on the case of a 16-year-old boy with malunion of the radial articular surface with lack of motion and pain. He was managed by replacing the displaced and damaged segment of the radial articular surface with a vascularized osteochondral graft from the proximal phalanx of the great toe. This matched the shape of this portion of the radius quite well, and he has had improvements in motion and pain in the 10 months since that time. The donor site has not caused him any difficulty to date.