Accuracy of maxillary positioning using computer-designed and manufactured occlusal splints or patient-specific implants in orthognathic surgery.

OBJECTIVE: To determine the accuracy of maxillary positioning using computer-designed and manufactured occlusal splints or patient-specific implants in orthognathic surgery. MATERIAL AND METHODS: A retrospective analysis of 28 patients that underwent virtually planned orthognathic surgery with maxillary Le Fort I osteotomy either using VSP-generated splints (n = 13) or patient-specific implants (PSI) (n = 15) was conducted. The accuracy and surgical outcome of both techniques were compared by superimposing preoperative surgical planning with postoperative CT scans and measurement of translational and rotational deviation for each patient. RESULTS: The 3D global geometric deviation between the planned position and the postoperative outcome was 0.60 mm (95%-CI 0.46-0.74, range 0.32-1.11 mm) for patients with PSI and 0.86 mm (95%-CI 0.44-1.28, range 0.09-2.60 mm) for patients with surgical splints. Postoperative differences for absolute and signed single linear deviations between planned and postoperative position were a little higher regarding the x-axis and pitch but lower regarding the y- and z-axis as well as yaw and roll for PSI compared to surgical splints. There were no significant differences regarding global geometric deviation, absolute and signed linear deviations in the x-, y-, and z-axis, and rotations (yaw, pitch, and roll) between both groups. CONCLUSIONS: Regarding accuracy for positioning of maxillary segments after Le Fort I osteotomy in orthognathic surgery patient-specific implants and surgical splints provide equivalent high accuracy. CLINICAL RELEVANCE: Patient-specific implants for maxillary positioning and fixation facilitate the concept of splintless orthognathic surgery and can be reliably used in clinical routines.

Treatment Plan and Challenges in Full-Mouth Rehabilitation of a Quadriplegic Patient: A Clinical Report.

Spinal cord injuries lead to physical limitations, and the resulting levels of dependency and emotional distress have devastating consequences on individuals' oral health. A 46-year-old patient with incomplete quadriplegia due to a complicated medical history presented for prosthetic rehabilitation. The patient's ability and tolerance to be treated in the dental chair was assessed. Prosthetic treatment options were discussed considering his dependency on alternating caregivers. The final treatment plan involved restorative treatment, implant-supported crowns, an implant-supported fixed dental prosthesis and, in the upper jaw, an implant-supported overdenture to allow proper oral hygiene. The dental treatment sessions were performed with frequent interruptions in the dental chair, whereas the implants were placed under general anesthesia in the maxillo-facial surgery department. The final treatment plan resulted in a compromise between the prosthetic recommendation and the patient's wish. The decisive factor for choosing an implant-supported overdenture rather than an implant-supported fixed dental prosthesis in the upper jaw was the inability of the patient to maintain adequate hygiene measures by himself and his dependence on the caregivers. This clinical report demonstrates how special care dentistry can improve quality of life, even in people with severe physical and/or mental impairments. We would like to encourage dental professionals to provide high-quality care for patients with disabilities in particular, and this practice is in line with the requirements of the UN convention on the rights of persons with disabilities.

Distinct galactofuranose antigens in the cell wall and culture supernatants as a means to differentiate Fusarium from Aspergillus species.

Detection of carbohydrate antigens is an important means for diagnosis of invasive fungal infections. For diagnosis of systemic Aspergillus infections, galactomannan is commonly used, the core antigenic structure of which consists of chains of several galactofuranose moieties. In this study, we provide evidence that Fusarium produces at least two distinct galactofuranose antigens: Smaller amounts of galactomannan and larger quantities of a novel antigen recognized by the monoclonal antibody AB135-8. In A. fumigatus, only minor amounts of the AB135-8 antigen are found in supernatants and in the apical regions of hyphae. A galactofuranose-deficient A. fumigatus mutant lacks the AB135-8 antigen, which strongly suggests that galactofuranose is an essential constituent of this antigen. Using a combination of AB135-8 and a galactomannan-specific antibody, we were able to unambiguously differentiate A. fumigatus and Fusarium hyphae in immunohistology. Moreover, since Fusarium releases the AB135-8 antigen, it appears to be a promising target antigen for a serological detection of Fusarium infections.

Pre- and Post-Operative Quality of Life in Patients with Osteoradionecrosis of the Jaw.

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.

The Novel Monoclonal IgG1-Antibody AB90-E8 as a Diagnostic Tool to Rapidly Distinguish Aspergillus fumigatus from Other Human Pathogenic Aspergillus Species.

In most cases, invasive aspergillosis (IA) is caused by A. fumigatus, though infections with other Aspergillus spp. with lower susceptibilities to amphotericin B (AmB) gain ground. A. terreus, for instance, is the second leading cause of IA in humans and of serious concern because of its high propensity to disseminate and its in vitro and in vivo resistance to AmB. An early differentiation between A. fumigatus and non-A. fumigatus infections could swiftly recognize a potentially ineffective treatment with AmB and lead to the lifesaving change to a more appropriate drug regime in high-risk patients. In this study, we present the characteristics of the monoclonal IgG1-antibody AB90-E8 that specifically recognizes a surface antigen of A. fumigatus and the closely related, but not human pathogenic A. fischeri. We show immunostainings on fresh frozen sections as well as on incipient mycelium picked from agar plates with tweezers or by using the expeditious tape mount technique. All three methods have a time advantage over the common procedures currently used in the routine diagnosis of IA and outline the potential of AB90-E8 as a rapid diagnostic tool.

Recent Advances, Systemic Therapy, and Molecular Targets in Adenoid Cystic Carcinoma of the Head and Neck.

With an incidence of 3-4.5 cases per million, adenoid cystic carcinoma (ACC) of the head and neck is one of the most common tumors of the parotid and sublingual salivary glands. In the clinical course, ACC is shown to have an aggressive long-term behavior, which leads to the fact that radical surgical resection of the tumor with tumor-free margins remains the "gold standard" in treating ACC. Particle radiation therapy and systemic molecular biological approaches offer new treatment options. However, risk factors for the formation and prognosis of ACC have not yet been clearly identified. The aim of the present review was to investigate long-term experience of diagnosis and treatment as well as risk and prognostic factors for occurrence and outcome of ACC.

Lymph nodal recurrence in levels IV and V in oral squamous cell carcinoma after neck dissection.

BACKGROUND: The aim of the study was to determine the risk of lymph node recurrence in levels IV and V after tumour resection and neck dissection of level I-III and level I-V. METHODS: Data from 228 patients suffering from OSCC were analysed retrospectively. Patients with level I-III neck dissection were compared to those with level I-V neck dissection in terms of number and location of nodal recurrence. The incidence of level IV-V recurrence in patients who had received level I-III neck dissection was compared with that of patients who had received level I-V neck dissection. The incidence of level IV-V recurrence was also compared between patients with pN0 and pN+ necks. RESULTS: Overall, 19 patients developed metastases. Only in two cases appeared nodal recurrence in levels IV or V. There was no statistically significant difference between both groups. CONCLUSIONS: Neck dissection of levels I-III seems to be sufficient treatment in cases of unsuspicious lymph nodes in levels IV and V, even in cases of positive nodes in levels I-III if adjuvant radiation therapy is applied. However, 5-year-disease free survival rate is lower in patients with nodal metastases in levels IV and V than in patients with metastases located in levels I-III.

Functional Orthodontic Treatment of Mandibular Condyle Fractures in Children and Adolescent Patients: An MRI Follow-Up.

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.

Dental management before radiotherapy of the head and neck region: 4-year single-center experience.

OBJECTIVE: To review our experience with a standardized dental management approach in patients with planned radiotherapy of the head and neck region based on preradiation and follow-up data. MATERIAL AND METHODS: Records of patients who underwent radiotherapy between June 2016 and November 2020 were reviewed. Data on dental findings and therapeutic recommendations were extracted from a prospectively managed database. Hospital records were used to obtain follow-up data. RESULTS: Two hundred eighty-one patient records were identified. After the exclusion of 81 patients because of incomplete data, 200 patients were included in the study. Dental findings relevant to radiotherapy were found in 144 cases (72.0%). Teeth extractions were recommended in 112 (56.0%) patients. Follow-up data were available for 172 (86.0%) patients (mean follow-up: 16.8 ± 10.7 months). Radiodermatitis was the most frequently observed sequela of radiotherapy (42.4%), followed by dysphagia (38.4%) and stomatitis (36.6%). Osteoradionecrosis was observed in only 2.3% of the patients. CONCLUSION: Dental findings relevant to planned radiotherapy were frequent and in many cases resulted in recommendations for teeth extraction. Based on our standardized dental management protocol, we observed low rates of late oral complications after radiotherapy of the head and neck region.

CAR T cells targeting Aspergillus fumigatus are effective at treating invasive pulmonary aspergillosis in preclinical models.

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.

Tape mount immunostaining: a versatile method for immunofluorescence analysis of fungi.

AIM: Immunofluorescence microscopy is a powerful technique to detect surface antigens and study their distribution. Analysis of fungi is often hampered by their weak adherence to glass. We therefore established a novel immunofluorescence staining method to overcome this problem. MATERIALS & METHODS: Fungal material from colonies is bound to adhesive tape and stained with antibodies. RESULTS: The obtained samples had very good optical quality, showing low unspecific background staining and allowing analysis by confocal laser scanning microscopy. We have exemplified applying the new method to study the distribution of galactomannan on conidiophores of Aspergillus fumigatus and of ß-glucans on Malassezia pachydermatis. CONCLUSION: Tape mount immunostaining facilitates analysis of fungal surface molecules and provides a base for expeditious diagnostic procedures.

The RNA Chaperone Hfq Is Essential for Virulence and Modulates the Expression of Four Adhesins in Yersinia enterocolitica.

In Enterobacteriaceae, the RNA chaperone Hfq mediates the interaction of small RNAs with target mRNAs, thereby modulating transcript stability and translation. This post-transcriptional control helps bacteria adapt quickly to changing environmental conditions. Our previous mutational analysis showed that Hfq is involved in metabolism and stress survival in the enteropathogen Yersinia enterocolitica. In this study we demonstrate that Hfq is essential for virulence in mice and influences production of surface pathogenicity factors, in particular lipopolysaccharide and adhesins mediating interaction with host tissue. Hfq inhibited the production of Ail, the Ail-like protein OmpX and the MyfA pilin post-transcriptionally. In contrast Hfq promoted production of two major autotransporter adhesins YadA and InvA. While protein secretion in vitro was not affected, hfq mutants exhibited decreased protein translocation by the type III secretion system into host cells, consistent with decreased production of YadA and InvA. The influence of Hfq on YadA resulted from a complex interplay of transcriptional, post-transcriptional and likely post-translational effects. Hfq regulated invA by modulating the expression of the transcriptional regulators rovA, phoP and ompR. Therefore, Hfq is a global coordinator of surface virulence determinants in Y. enterocolitica suggesting that it constitutes an attractive target for developing new antimicrobial strategies.

The RNA chaperone Hfq impacts growth, metabolism and production of virulence factors in Yersinia enterocolitica.

To adapt to changes in environmental conditions, bacteria regulate their gene expression at the transcriptional but also at the post-transcriptional level, e.g. by small RNAs (sRNAs) which modulate mRNA stability and translation. The conserved RNA chaperone Hfq mediates the interaction of many sRNAs with their target mRNAs, thereby playing a global role in fine-tuning protein production. In this study, we investigated the significance of Hfq for the enteropathogen Yersina enterocolitica serotype O:8. Hfq facilitated optimal growth in complex and minimal media. Our comparative protein analysis of parental and hfq-negative strains suggested that Hfq promotes lipid metabolism and transport, cell redox homeostasis, mRNA translation and ATP synthesis, and negatively affects carbon and nitrogen metabolism, transport of siderophore and peptides and tRNA synthesis. Accordingly, biochemical tests indicated that Hfq represses ornithine decarboxylase activity, indole production and utilization of glucose, mannitol, inositol and 1,2-propanediol. Moreover, Hfq repressed production of the siderophore yersiniabactin and its outer membrane receptor FyuA. In contrast, hfq mutants exhibited reduced urease production. Finally, strains lacking hfq were more susceptible to acidic pH and oxidative stress. Unlike previous reports in other Gram-negative bacteria, Hfq was dispensable for type III secretion encoded by the virulence plasmid. Using a chromosomally encoded FLAG-tagged Hfq, we observed increased production of Hfq-FLAG in late exponential and stationary phases. Overall, Hfq has a profound effect on metabolism, resistance to stress and modulates the production of two virulence factors in Y. enterocolitica, namely urease and yersiniabactin.