Aspergillus fumigatus is a ubiquitous mold that can cause severe infections in immunocompromised patients, typically manifesting as invasive pulmonary aspergillosis (IPA). Adaptive and innate immune cells that respond to A. fumigatus are present in the endogenous repertoire of patients with IPA but are infrequent and cannot be consistently isolated and expanded for adoptive immunotherapy. Therefore, we gene-engineered A. fumigatus –specific chimeric antigen receptor (Af-CAR) T cells and demonstrate their ability to confer antifungal reactivity in preclinical models in vitro and in vivo. We generated a CAR targeting domain AB90-E8 that recognizes a conserved protein antigen in the cell wall of A. fumigatus hyphae. T cells expressing the Af-CAR recognized A. fumigatus strains and clinical isolates and exerted a direct antifungal effect against A. fumigatus hyphae. In particular, CD8 ⁺ Af-CAR T cells released perforin and granzyme B and damaged A. fumigatus hyphae. CD8 ⁺ and CD4 ⁺ Af-CAR T cells produced cytokines that activated macrophages to potentiate the antifungal effect. In an in vivo model of IPA in immunodeficient mice, CD8 ⁺ Af-CAR T cells localized to the site of infection, engaged innate immune cells, and reduced fungal burden in the lung. Adoptive transfer of CD8 ⁺ Af-CAR T cells conferred greater antifungal efficacy compared to CD4 ⁺ Af-CAR T cells and an improvement in overall survival. Together, our study illustrates the potential of gene-engineered T cells to treat aggressive infectious diseases that are difficult to control with conventional antimicrobial therapy and support the clinical development of Af-CAR T cell therapy to treat IPA.

Background: The purpose of this study was to retrospectively evaluate and follow up a conservative treatment approach with functional orthodontic appliances for the management of mandibular condyle fractures in children and adolescent patients. Methods: Between 2020 and 2022, the treatment records of patients with mandibular condyle fractures receiving a functional orthodontic treatment (FOT) were evaluated. In addition to the clinical and functional findings, magnetic resonance images of the mandibular condyles and surrounding structures were assessed. Results: Out of 61 patients, 8 met the inclusion criteria. The follow-up examination records showed no functional limitations. In 75% of cases, mild midline deviations persisted (mean 1.1 mm) without significant alterations to the occlusal relationships. Magnetic resonance imaging (MRI) showed the remodeling of the condyles and the restitution of the ramus heights, even in dislocated and displaced fractures. In three cases, a partial displacement of the articular disc was observed at the follow-up. No differences in the remodeling patterns were noted depending on age, sex, or fracture location. Conclusions: A FOT led to favorable functional and morphologic outcomes, supporting the concept of a conservative functional approach in children and adolescent patients. Functional adjunctive therapy should be considered in the conservative treatment of mandibular condyle fractures in growing patients.

The aim of this study was to analyze the spectrum of Candida manifestations in the orofacial region to address the lack of comprehensive data in the diverse pediatric population. This retrospective study included all positive Candida findings in patients aged 0–18 years treated between 2014 and 2023 at a university maxillofacial department in Germany and evaluated associated risk profiles, comorbidities and species distributions. Candida infection sites included oral mucosa, dental abscesses and otitis media. Candida was more frequent in children with pre-existing conditions, particularly immunosuppression, neuromuscular disorders and facial deformities. Tympanostomy tubes and recent antibiotic use were significant risk factors for Candida in otitis media. Whereas in dental abscesses, Candida had a significant proportion independent of prior antibiotic use. Non-albicans subspecies, particularly Candida parapsilosis, were notably more prevalent in the middle ear compared to oral and dental infections. Candida manifests in various forms in the orofacial region, with different characteristics and species distributions. Further investigations are needed to better understand the role of Candida as a symptom or a contributor to an underlying condition.

Osteoradionecrosis of the jaw (ORNJ) is a feared complication following radiation therapy performed for oncological treatment of head and neck cancers (HNC). To date, there is no clear evidence regarding the impact of surgical treatment of ORNJ on the quality of life (QoL) of affected patients. However, understanding the significance of the surgical treatment approach and its effects on QoL is an essential factor in the decision-making process for optimal, individualized therapy. In this prospective clinical study, QoL was assessed in relation to health related QoL (HRQoL) and oral health related QoL (OHQoL) before and after surgical treatment of ORNJ using standardized questionnaires (EORTC QLQ-C30, QLQ-HN35, OHIP-14). The overall QoL scores as well as individual domains of the collected scales regarding functional and symptom-related complaints were statistically analyzed. Subgroups concerning age, gender, different risk factors and type of ORNJ therapy were compared using Kruskal Wallis test. In addition, clinical and demographic patient data were collected and analyzed. QoL improvement correlated with the type of surgical ORNJ and the length of hospitalization. Better QoL scores were achieved post-operatively regarding different symptoms like pain, swallowing and mouth opening. Long-term effects of radiation therapy remained visibly restrictive to QoL and worsen over time.

In recent years, there has been a growing number of adult orthodontic patients with periodontal disease. The progression of periodontal disease is well-linked to oxidative stress (OS). Nevertheless, the impact of OS on orthodontic tooth movement (OTM) is not fully clarified. Therefore, we applied an OS in vitro-model utilizing H₂O₂ to study its effect on tension-induced mechanotransduction in human osteoblasts (hOBs). Experimental parameters were established based on cell viability and proliferation. Apoptosis detection was based on caspase-3/7 activity. Gene expression related to bone-remodeling (RUNX2, P2RX7, TNFRSF11B/OPG), inflammation (CXCL8/IL8, IL6, PTRGS2/COX2), autophagy (MAP1LC3A/LC3, BECN1), and apoptosis (CASP3, CASP8) was analyzed by RT-qPCR. IL6 and PGE2 secretion were determined by ELISA. Tension increased the expression of PTRGS2/COX2 in all groups, especially after stimulation with higher H₂O₂ concentration. This corresponds also to the measured PGE2 concentrations. CXCL8/IL8 was upregulated in all groups. Cells subjected to tension alone showed a general upregulation of osteogenic differentiation-related genes; however, pre-stimulation with OS did not induce significant changes especially towards downregulation. MAP1LC3A/LC3, BECN1 and CASP8 were generally upregulated in cells without OS pre-stimulation. Our results suggest that OS might have considerable impacts on cellular behavior during OTM.