Percutaneous Drainage of Pediatric Pulmonary Abscesses: An Effective Therapy.

INTRODUCTION: Pulmonary abscess is a complication of lung infection with localized necrosis and purulent cavity formation. Pulmonary abscesses are typically managed using antibiotic therapy with anatomic surgical resection reserved as a rescue. Percutaneous drainage is considered relatively contraindicated in some centers due to perceived risk of bronchopleural fistula. However, drain placement has been frequently employed at our institution. The purpose of this study was to review and describe our longitudinal experience. METHODS: Medical records of children diagnosed with lung abscess and treated with percutaneous drainage from 2005 through 2023 were reviewed. Patient clinical parameters, follow-up imaging, and clinical outcomes were evaluated. RESULTS: Percutaneous drainage (n = 24) or aspiration alone (n = 4) under imaging guidance was performed by interventional radiologists for 28 children with lung abscesses. A single catheter (8-12 Fr) was deployed in the pulmonary abscess cavity and remained for a median of 6 days (IQR: 6-8 days). The median hospital stay was 10 days (IQR: 8.8-14.8 days). The technical success rate for percutaneous drainage or aspiration of primary pulmonary abscesses was 100% (26/26). Two children were later diagnosed with secondarily infected congenital pulmonary airway malformations that were both successfully drained and ultimately surgically resected. The abscess cavities resolved in all patients and catheters were removed upon clinical, radiographic, and laboratory improvement. Complications included the presence of two bronchopleural fistula, both of which were treated with immediate pleural drain placement. CONCLUSION: Percutaneous drainage of pulmonary abscesses is an effective therapeutic option in children and can be considered alongside antibiotics as part of the initial treatment for pulmonary abscesses. Bronchopleural fistula can occur, but at a lower frequency than previously reported. LEVEL OF EVIDENCE: Level V.

The impact of age and sex on the inflammatory response during bone fracture healing.

Inflammation is thought to be dysregulated with age leading to impaired bone fracture healing. However, broad analyses of inflammatory processes during homeostatic bone aging and during repair are lacking. Here, we assessed changes in inflammatory cell and cytokine profiles in circulation and in bone tissue to identify age- and sex-dependent differences during homeostasis and repair. During homeostatic aging, male mice demonstrated accumulation of CD4+ helper T cells and CD8+ cytotoxic T cells within bone while both pro-inflammatory "M1" and anti-inflammatory "M2" macrophage numbers decreased. Female mice saw no age-associated changes in immune-cell population in homeostatic bone. Concentrations of IL-1ß, IL-9, IFNγ, and CCL3/MIP-1α increased with age in both male and female mice, whereas concentrations of IL-2, TNFα, TNFR1, IL-4, and IL-10 increased only in female mice - thus we termed these "age-accumulated" cytokines. There were no notable changes in immune cell populations nor cytokines within circulation during aging. Sex-dependent analysis demonstrated slight changes in immune cell and cytokine levels within bone and circulation, which were lost upon fracture injury. Fracture in young male mice caused a sharp decrease in number of M1 macrophages; however, this was not seen in aged male mice nor in female mice of any age. Injury itself induced a decrease in the number of CD8+ T cells within the local tissue of aged male and of female mice but not of young mice. Cytokine analysis of fractured mice revealed that age-accumulated cytokines quickly dissipated after fracture injury, and did not re-accumulate in newly regenerated tissue. Conversely, CXCL1/KC-GRO, CXCL2/MIP-2, IL-6, and CCL2/MCP-1 acted as "fracture response" cytokines: increasing sharply after fracture, eventually returning to baseline. Collectively, we classify measured cytokines into three groups: (1) age-accumulated cytokines, (2) female-specific age-accumulated cytokines, and (3) fracture response cytokines. These inflammatory molecules represent potential points of intervention to improve fracture healing outcome.

Receptor Tyrosine Kinase EPHA2 Drives Epidermal Differentiation through Regulation of EGFR Signaling.

Intricate signaling systems are required to maintain homeostasis and promote differentiation in the epidermis. Receptor tyrosine kinases are central in orchestrating these systems in epidermal keratinocytes. In particular, EPHA2 and EGFR transduce distinct signals to dictate keratinocyte fate, yet how these cell communication networks are integrated has not been investigated. Our work shows that loss of EPHA2 impairs keratinocyte stratification, differentiation, and barrier function. To determine the mechanism of this dysfunction, we drew from our proteomics data of potential EPHA2 interacting proteins. We identified EGFR as a high-ranking EPHA2 interactor and subsequently validated this interaction. We found that when EPHA2 is reduced, EGFR activation and downstream signaling are intensified and sustained. Evidence indicates that prolonged SRC association contributes to the increase in EGFR signaling. We show that hyperactive EGFR signaling underlies the differentiation defect caused by EPHA2 knockdown because EGFR inhibition restores differentiation in EPHA2-deficient 3-dimensional skin organoids. Our data implicate a mechanism whereby EPHA2 restrains EGFR signaling, allowing for fine tuning in the processes of terminal differentiation and barrier formation. Taken together, we purport that crosstalk between receptor tyrosine kinases EPHA2 and EGFR is critical for epidermal differentiation.

Evaluating the Biomechanical Integrity of Various Constructs Utilized for First Metatarsophalangeal Joint Arthrodesis: A Systematic Review.

The first metatarsophalangeal (MTP) joint is a frequently loaded joint, handling loads up to 90% of bodyweight. First MTP arthrodesis is a frequently performed procedure designed to improve pain in patients with degenerative MTP joint disease. There are a wide variety of fixation constructs for this procedure without consensus on the most effective method. The purpose of this study was to compare the biomechanical integrity of various constructs utilized for first MTP arthrodesis. A systematic review of the literature was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, CINAHL, MEDLINE, and Web of Science databases were searched from inception to 18 June 2023. Articles discussing the biomechanics of first MTP arthrodesis constructs were included. A total of 168 articles were retrieved. A total of 20 articles involving 446 cadaveric and synthetic bone constructs were included in the final review. Of the six articles comparing dorsal plating with compression screws to crossed interfragmentary screws, five found that dorsal plating had significantly higher stiffness. All three studies assessing shape-memory staples found them to be significantly less stable than crossed screws or dorsal plates alone. Both studies evaluating fully threaded screws found them to be stronger than crossed cancellous screws. Wedge resections have been shown to be 10 times stronger than standard planar or conical excision. Dorsal plating with compression screws is the gold standard for MTP arthrodesis. However, more research into newer methods such as fully threaded screws and wedge resections with an increased focus on translation to clinical outcomes is needed.

Metal Hypersensitivity Following Total Ankle Arthroplasty: Case Series and Literature Review.

Metal hypersensitivity following total ankle arthroplasty (TAA) is an underreported complication that can manifest as dermal, systematic, and orthopaedic-specific symptoms. It is critical to recognize that metal hypersensitivity is a diagnosis of exclusion; only after all other potential sources of failure, such as loosening or infection are ruled out, can this diagnosis be considered. Aside from imaging and common laboratory analysis, skin patch testing, leukocyte migration inhibition test (LMIT), and lymphocyte transformation test (LTT) are the testing options available for metal allergy. With regards to management of metal hypersensitivity, nonoperative modalities involving topical dermatological management are generally preferred. Severe cases of metal allergy may necessitate operative management consisting of explantation of the implant and either revision TAA with a custom hypoallergenic implant or conversion to an ankle fusion. We present 3 cases of presumed metal hypersensitivity following TAA. In all 3 cases, other forms of TAA failure were carefully ruled out. One patient underwent explantation and conversion to hypoallergenic implant, 1 patient underwent explantation and ankle arthrodesis with hypoallergenic hardware, and 1 patient elected for conservative care. In patients who underwent explantation and conversion to hypoallergenic hardware, no further symptoms associated with metal allergy were noted. Additional research is necessary to improve diagnostic accuracy of metal allergy and make treatment options more effective and accessible.Level of Evidence: Retrospective case series, IV.

Early Outcomes of Combined Total Ankle Total Talus Replacement Using a 3D-Printed Talus Component With Hindfoot Arthrodesis.

Late-stage talar avascular necrosis (AVN) results in devascularization of the talus with osteonecrosis and subchondral collapse. A combined total ankle and total talus replacement (TATTR) with hindfoot arthrodesis may be utilized for end-stage talar AVN with tibiotalar and hindfoot joint arthritis. The purpose of this study is to evaluate the short-term outcomes of combined TATTR with hindfoot arthrodesis. Patients who underwent a combined TATTR or TTR with a hindfoot arthrodesis (subtalar with or without talonavicular arthrodesis) from 2016 to 2020 were retrospectively reviewed. Patient demographics, comorbidities, and surgical data were collected. Outcomes included the Visual Analog Scale (VAS) scores, range of motion, radiographic parameters, union rates, and complications. A total of 18 patients were reviewed. Nine patients were included with an average of 19.4 months follow-up. Significant postoperative improvements were observed in VAS scores (P < .001), ankle plantarflexion (P = .04), talocalcaneal height (P = .03), and tibiotalar alignment (P = .02). All patients achieved a successful union of their subtalar and talonavicular joints arthrodesis. There was one reoperation for a persistent varus ankle deformity. This is the first study to evaluate the clinical outcomes, radiographic outcomes, and union rate in combined TATTR with hindfoot arthrodesis. The early results demonstrated significant clinical improvement with 100% hindfoot union rate and no prosthetic failure.Level of Evidence: IV.

The role of Meteorin-like in skeletal development and bone fracture healing.

Meteorin-like protein (Metrnl), homologous to the initially identified neurotrophic factor Meteorin, is a secreted, multifunctional protein. Here we used mouse models to investigate Metrnl's role in skeletal development and bone fracture healing. During development Metrnl was expressed in the perichondrium and primary ossification center. In neonates, single cell RNA-seq of diaphyseal bone demonstrated strongest expression of Metrnl transcript by osteoblasts. In vitro, Metrnl was osteoinductive, increasing osteoblast differentiation and mineralization in tissue culture models. In vivo, loss of Metrnl expression resulted in no change in skeletal metrics in utero, at birth, or during postnatal growth. Six-week-old Metrnl-null mice displayed similar body length, body weight, tibial length, femoral length, BV/TV, trabecular number, trabecular thickness, and cortical thickness as littermate controls. In 4-month-old mice, lack of Metrnl expression did not change structural stiffness, ultimate force, or energy to fracture of femora under 3-point-bending. Last, we investigated the role of Metrnl in bone fracture healing. Metrnl expression increased in response to tibial injury, however, loss of Metrnl expression did not affect the amount of bone deposited within the healing tissue nor did it change the structural parameters of healing tissue. This work identifies Metrnl as a dispensable molecule for skeletal development. However, the osteoinductive capabilities of Metrnl may be utilized to modulate osteoblast differentiation in cell-based orthopedic therapies.