Safety of Irradiated Homologous Costal Cartilage Graft in Cleft Rhinoplasty.

BACKGROUND: Autologous cartilage grafts have a low risk of infection and extrusion in cleft rhinoplasty. However, harvesting autologous cartilage involves donor-site morbidity and increased time under anesthesia. Irradiated homologous costal cartilage grafts may be an effective alternative. METHODS: A retrospective study was performed on patients with a history of cleft lip who underwent rhinoplasty for cleft nasal deformity at Johns Hopkins Hospital from 2009 to 2018. Patients were excluded if their rhinoplasty did not involve a cartilage graft. RESULTS: One hundred sixty-five cleft rhinoplasties (patient age, 2 to 72 years; 52 percent female) were performed. Median follow-up time was 256 days; 30 percent were revision operations. Ninety-six procedures (58 percent) used irradiated homologous costal cartilage grafts, with the remaining using autologous cartilage. Complications resulted from 18 procedures (11 percent), seven (10 percent) involving autologous cartilage and 11 (12 percent) involving irradiated homologous costal cartilage. Most autologous cartilage complications (86 percent) required operative intervention, versus seven of 11 (64 percent) for irradiated homologous costal cartilage. Complications associated with irradiated homologous costal cartilage included infection (n = 5), warping (n = 2), and extrusion (n = 1), while two patients with autologous cartilage experienced collapse and one each experienced resorption, warping, and hypertrophic donor-site scarring. There was no difference between groups regarding complication rate or complications requiring operative intervention (p = 0.3 and p = 0.5, respectively). CONCLUSIONS: Irradiated homologous costal cartilage grafts are equally safe and effective as autologous cartilage for use in cleft rhinoplasty. These grafts are readily available and eliminate donor-site morbidity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Procedure for Horizontal Transfer of Patient-Derived Xenograft Tumors to Eliminate Corynebacterium bovis.

Human patient-derived xenograft (PDX) tumors, propagated in immunodeficient mice, are rapidly growing in use as a model for cancer research. Horizontal transfer between mice, without in vitro cell culture, allows these tumors to retain many of their unique characteristics from their individual patient of origin. However, the immunodeficient mouse strains used to grow these tumors are susceptible to numerous opportunistic pathogens, including Corynebacterium bovis. At our institution, 2 in vivo tumor banks of PDX tumors had been maintained within nude mouse colonies enzootically infected with C. bovis. Elimination of C. bovis from these colonies required the aseptic harvest and horizontal transfer of tumor tissue between infected and naïve recipient mice without cross-contamination. Out of necessity, we developed a standard operating procedure using enhancements to traditional aseptic surgical technique with concurrent application of both procedural and physical barriers to prevent C. bovis transmission. By using these methods, all 61 unique PDX tumor models were successfully harvested from C. bovis-infected mice and transferred into recipient mice without transmission of infection. Our data demonstrate that, in situations where C. bovis-free colonies can be established and maintained, this procedure can successfully be used to eliminate C. bovis from an in vivo tumor bank of valuable PDX tumors.

Engrafted human cells generate adaptive immune responses to Mycobacterium bovis BCG infection in humanized mice.

BACKGROUND: Currently used mouse models fail to fully reflect human immunity to tuberculosis (TB), which hampers progress in research and vaccine development. Bone marrow-liver-thymus (BLT) mice, generated by engrafting human fetal liver, thymus, and hematopoietic stem cells in severely immunodeficient NOD/SCID/IL-2Rγ(-/-) (NSG) mice, have shown potential to model human immunity to infection. We engrafted HLA-A2-positive fetal tissues into NSG mice transgenically expressing human leukocyte antigen (HLA)-A2.1 (NSG-A2) to generate NSG-A2-BLT mice and characterized their human immune response to Mycobacterium bovis bacillus Calmette-Guerin (BCG) infection to assess the utility of this model for investigating human TB. RESULTS: NSG-A2-BLT mice were infected intravenously with BCG and the immune response of engrafted human immune cells was characterized. After ex vivo antigenic stimulation of splenocytes, interferon (IFN)-γ-producing cells were detected by ELISPOT from infected, but not uninfected NSG-A2-BLT mice. However, the levels of secreted IFN-γ, determined by ELISA, were not significantly elevated by antigenic stimulation. NSG-A2-BLT mice were susceptible to BCG infection as determined by higher lung bacillary load than the non-engrafted control NSG-A2 mice. BCG-infected NSG-A2-BLT mice developed lung lesions composed mostly of human macrophages and few human CD4+ or CD8+ T cells. The lesions did not resemble granulomas typical of human TB. CONCLUSIONS: Engrafted human immune cells in NSG-A2-BLT mice showed partial function of innate and adaptive immune systems culminating in antigen-specific T cell responses to mycobacterial infection. The lack of protection was associated with low IFN-γ levels and limited numbers of T cells recruited to the lesions. The NSG-A2-BLT mouse is capable of mounting a human immune response to M. tuberculosis in vivo but a quantitatively and possibly qualitatively enhanced effector response will be needed to improve the utility of this model for TB research.