ABSTRACT
PURPOSE: The extent of functional impairment after ablative surgery in the orofacial region may be directly reflected in a reduction in Quality of Life. This study intended to compare the patients' perception with an objective functional evaluation of the orofacial system in order to bilaterally distinguish direct influence factors. METHODS: A total of 45 patients were included in this study and were asked to complete the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-30) and the Head and Neck 35 Module (H&N 35). Afterward one independent speech therapist evaluated the patients applying the Frenchay Dysarthria Assessment regarding four main categories: mouth opening, tongue motility, swallowing and intelligibility. Comparisons between groups were performed using Whitney-Mann U-Wilcoxon test and calculating Spearman's rho. RESULTS: Overall the professional assessments by the speech therapists revealed significantly higher scores regarding intelligibility, swallowing and mouth opening when compared to the patients' self-perception. Smaller tumor sizes, no bone resection and local reconstruction techniques led to significantly better functional outcomes, when assessed by speech therapists. Swallowing was perceived significantly better by patients in cases of local reconstruction. CONCLUSIONS: From the professionals' point of view differences were perceived in more items compared to the patients' self-assessments, who widely experienced a more severe functional impairment. Physicians should take this into account when discussing adverse therapy effects with the patients.
Subject(s)
Mouth Neoplasms/surgery , Adult , Aged , Deglutition , Female , Humans , Male , Middle Aged , Mouth Neoplasms/physiopathology , Outcome and Process Assessment, Health Care , Patient Satisfaction , Quality of Life , Plastic Surgery Procedures , Recovery of Function , Self Concept , Speech Intelligibility , Treatment OutcomeABSTRACT
BACKGROUND: Osteonecrosis of the jaw (ONJ) is a rare but serious adverse drug effect linked to long-term and/or high-dose exposure to nitrogen-bisphosphonates (N-BP), the standard of care for the treatment of bone fragility disorders. The mechanism leading to bisphosphonate-associated ONJ (BAONJ) is unclear and optimal treatment strategies are lacking. Recent evidence suggests that BAONJ may be linked to drug-induced immune dysfunction, possibly associated with increased susceptibility to infections in the oral cavity. The objective of this investigation was to comprehensively assess the relationship linking immune function, N-BP exposure, the oral microbiome and ONJ susceptibility. METHODS: Leukocyte gene expression of factors important for immunity, wound healing and barrier function were assessed by real-time quantitative PCR and the oral microbiome was characterized by 454 pyrosequencing of the 16S rRNA gene in 93 subjects stratified by N-BP exposure and a history of ONJ. RESULTS: There were marked differences in the systemic expression of genes regulating immune and barrier functions including RANK (p = 0.007), aryl hydrocarbon receptor (AHR, p < 0.001), and FGF9 (p < 0.001), which were collectively up-regulated in individuals exposed to N-BP without ONJ relative to treatment controls. In contrast, the expression levels of these same genes were significantly down-regulated in those who had experienced BAONJ. Surprisingly, the oral microbiome composition was not directly linked to either BAONJ or N-BP exposure, rather the systemic leukocyte expression levels of RANK, TNFA and AHR each explained 9% (p = 0.04), 12% (p = 0.01), and 7% (p = 0.03) of the oral bacterial beta diversity. CONCLUSIONS: The oral microbiome is unlikely causative of ONJ, rather individuals with BAONJ lacked immune resiliency which impaired their capacity to respond adequately to the immunological stress of N-BP treatment. This may be the common factor linking N-BP and anti-RANK agents to ONJ in at-risk individuals. Preventive and/or therapeutic strategies should target the wound healing deficits present in those with ONJ.
Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/immunology , Bisphosphonate-Associated Osteonecrosis of the Jaw/microbiology , Immunity , Microbiota/immunology , Mouth/microbiology , Aged , Bisphosphonate-Associated Osteonecrosis of the Jaw/genetics , Diphosphonates/adverse effects , Disease Susceptibility/immunology , Disease Susceptibility/microbiology , Female , Gene Expression Regulation , Humans , Leukocytes/metabolism , Male , Microbiota/genetics , Middle Aged , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor Activator of Nuclear Factor-kappa B/metabolism , Receptors, Aryl Hydrocarbon/genetics , Receptors, Aryl Hydrocarbon/metabolism , Wound Healing/geneticsABSTRACT
A lack of sigma(B) activity reduces methicillin resistance in heterogeneous Staphylococcus epidermidis 1057, whereas inactivation of the anti-sigma factor RsbW switched the phenotype to homogeneous expression of resistance. Oxacillin induction of mecA transcription is reduced in a sigma(B)-negative strain. However, mecA is not involved in the switch of expression phenotype.
