Revision rhinoplasty in ethnic patients: pollybeak deformity and persistent bulbous tip.

Pollybeak deformity has been reported as the most common complication of rhinoplasty surgery, occurring in some series in up to 50% of cases. Persistent bulbous tip after initial rhinoplasty is also a common complication; both lead to dissatisfaction with the esthetic result in many patients and are common complaints leading to subsequent revision rhinoplasty. In this retrospective review of 28 cases of revision rhinoplasty in ethnic patients, the most common indication for revision included pollybeak deformity and persistent bulbous tip. A majority of deformities were caused by poor implant selection and placement. Desirable esthetic results were often achieved by removal of existing grafts and replacement with custom-carved silicone implants.

Poor socioeconomic status is associated with delayed femoral fracture fixation in adolescent patients.

INTRODUCTION: Healthcare disparities continue to exist in pediatric orthopedic care. Femur fractures are the most common diaphyseal fracture and the leading cause of pediatric orthopedic hospitalization. Prompt time to surgical fixation of femur fractures is associated with improved outcomes. OBJECTIVE: The objective of this study was to evaluate associations between socioeconomic status and timing of femoral fixation in adolescents on a nationwide level. METHODS: The 2016-2020 National Inpatient Sample (NIS) database was queried using International Classification of Disease, 10th edition (ICD-10) codes for repair of femur fractures. Patients between the ages of 10 and 19 years of age with a principal diagnosis of femur fracture were selected. Patients transferred from outside hospitals were excluded. Baseline demographics and characteristics were described. Patients were categorized as poor socioeconomic status (PSES) if they were classified in the Healthcare Cost and Utilization Project's (HCUP) lowest 50th percentile median income household categories and on Medicaid insurance. The primary outcome studied was timing to femur fixation. Delayed fixation was defined as fixation occurring after 24 h of admission. Secondary outcomes included length of stay (LOS) and discharge disposition. RESULTS: From 2016-2020, 10,715 adolescent patients underwent femur fracture repair throughout the United States. Of those, 765 (7.1 %) underwent late fixation. PSES and non-white race were consistently associated with late fixation, even when controlling for injury severity. Late fixation was associated with decreased rate of routine discharge (p < 0.01), increased LOS (p < 0.01) and increased total charges (p < 0.01). CONCLUSION: Patients of PSES or non-white race were more likely to experience delayed femoral fracture fixation. Delayed fixation led to worse outcomes and increased healthcare resource utilization. Research studying healthcare disparities may provide insight for improved provider education, implicit bias training, and comprehensive standardization of care.

Glucocorticoid receptor and histone deacetylase-2 mediate dexamethasone-induced repression of MUC5AC gene expression.

Airway occlusion in obstructive airway diseases is caused in part by the overproduction of secretory mucin glycoproteins through the up-regulation of mucin (MUC) genes by inflammatory mediators. Some pharmacological agents, including the glucocorticoid dexamethasone (Dex), repress mucin concentrations in lung epithelial cancer cells. Here, we show that Dex reduces the expression of MUC5AC, a major airway mucin gene, in primary differentiated normal human bronchial epithelial (NHBE) cells in a dose-dependent and time-dependent manner, and that the Dex-induced repression is mediated by the glucocorticoid receptor (GR) and two glucocorticoid response elements (GREs) in the MUC5AC promoter. The pre-exposure of cells to RU486, a GR antagonist, and mutations in either the GRE3 or GRE5 cis-sites abolished the Dex-induced repression. Chromatin immunoprecipitation (ChIP) assays showed a rapid temporal recruitment of GR to the GRE3 and GRE5 cis-elements in the MUC5AC promoter in NHBE and in A549 cells. Immunofluorescence showed nuclear colocalization of GR and histone deacetylase-2 (HDAC2) in MUC5AC-expressing NHBE cells. ChIP also showed a rapid temporal recruitment of HDAC2 to the GRE3 and GRE5 cis-elements in the MUC5AC promoter in both cell types. The knockdown of HDAC2 by HDAC2-specific short interfering RNA prevented the Dex-induced repression of MUC5AC in NHBE and A549 cells. These data demonstrate that GR and HDAC2 are recruited to the GRE3 and GRE5 cis-sites in the MUC5AC promoter and mediate the Dex-induced cis repression of MUC5AC gene expression. A better understanding of the mechanisms whereby glucocorticoids repress MUC5AC gene expression may be useful in formulating therapeutic interventions in chronic lung diseases.

IL-8 regulates mucin gene expression at the posttranscriptional level in lung epithelial cells.

Airway inflammation and mucus hypersecretion/overproduction/obstruction are pathophysiological characteristics of cystic fibrosis, asthma, and chronic obstructive pulmonary disease. Up-regulation of airway mucin genes by inflammatory/immune response mediators is one of the major contributors to mucin overproduction. IL-8, a potent proinflammatory mediator and neutrophil chemoattractant, is present at high levels in the airway secretions of such patients. In this study, the effects of IL-8 on expression of two major airway mucin genes, MUC5AC and MUC5B, were evaluated. IL-8 increased the mRNA abundance of both mucin genes in two human respiratory tract-derived cell lines (A549 and NCI-H292) in a time- and concentration-dependent manner. IL-8 also increased MUC5AC and MUC5B mRNA levels in primary normal differentiated human bronchial epithelial cells, with a high concentration of IL-8 required to increase MUC5B mRNA levels. IL-8 did not transcriptionally up-regulate MUC5AC gene expression, but rather increased the stability of the MUC5AC transcript, suggesting regulation at the posttranscriptional level. In addition, IL-8 altered the levels of RNA-binding proteins to specific domains in the 3'-untranslated region of the MUC5AC transcript. Taken together, these data indicate that the IL-8-induced binding of RNA-binding proteins to the 3'-untranslated region of MUC5AC is a potential mechanism for regulating MUC5AC gene expression at the posttranscriptional level, thus suggesting a new role whereby IL-8 sustains mucin gene expression in inflamed airways.

MUC5B Is the predominant mucin glycoprotein in chronic otitis media fluid.

Chronic otitis media (COM), e.g. "glue" ear is characterized by middle ear effusion and conductive hearing loss. Although mucous glycoproteins (mucins), which contribute to increased effusion viscosity, have been analyzed in ear tissue specimens, no studies have been reported that characterize the molecular identity of secreted mucin proteins present in actual middle ear fluid. For this study, effusions from children with COM undergoing myringotomy at Children's National Medical Center, Washington, DC were collected. These were solubilized and gel fractionated, and the protein content was identified using a liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomics approach. Western blot analyses with mucin specific antibodies and densitometry were performed to validate the mass spectrometry findings. LC-MS/MS results identified mucin MUC5B by >26 unique peptides in six of six middle ear effusion samples, whereas mucin MUC5AC was only identified in one of six middle ear effusions. These findings were validated by Western blot performed on the same six and on an additional 11 separate samples where densitometry revealed on average a 6.4-fold increased signal in MUC5B when compared with MUC5AC (p = 0.0009). In summary, although both MUC5AC and MUC5B mucins are detected in middle ear effusions, MUC5B seems to be predominant mucin present in COM secretions.