Cleft palate: a clinical review.

Orofacial clefts, including cleft palates (CP), are one of the most common birth defects. CP have a multiplicity of effects on the individual and society in terms of economic costs, loss of productivity, psychosocial effects, and increased morbidity and mortality at all stages of life. Embryological development of the palate is well delineated, with developments in the last decade regarding the biomolecular processes involved. Etiology is complex, involving a number of genetic and environmental factors. Various techniques can be employed for the repair of CP, depending on whether the cleft is of the primary or secondary palate, the width of the cleft, whether lengthening of the palate is necessary, and with regard to concerns of disruption of midfacial growth. All surgical techniques have the goals of restoring functional speech, swallowing, and aesthetics. A multidisciplinary team is necessary for the long-term pre- and postoperative care of CP patients to handle complications, associated anomalies, and to optimize function and quality of life.

Plastids are major regulators of light signaling in Arabidopsis.

We previously provided evidence that plastid signaling regulates the downstream components of a light signaling network and that this signal integration coordinates chloroplast biogenesis with both the light environment and development by regulating gene expression. We tested these ideas by analyzing light- and plastid-regulated transcriptomes in Arabidopsis (Arabidopsis thaliana). We found that the enrichment of Gene Ontology terms in these transcriptomes is consistent with the integration of light and plastid signaling (1) down-regulating photosynthesis and inducing both repair and stress tolerance in dysfunctional chloroplasts and (2) helping coordinate processes such as growth, the circadian rhythm, and stress responses with the degree of chloroplast function. We then tested whether factors that contribute to this signal integration are also regulated by light and plastid signals by characterizing T-DNA insertion alleles of genes that are regulated by light and plastid signaling and that encode proteins that are annotated as contributing to signaling, transcription, or no known function. We found that a high proportion of these mutant alleles induce chloroplast biogenesis during deetiolation. We quantified the expression of four photosynthesis-related genes in seven of these enhanced deetiolation (end) mutants and found that photosynthesis-related gene expression is attenuated. This attenuation is particularly striking for Photosystem II subunit S expression. We conclude that the integration of light and plastid signaling regulates a number of END genes that help optimize chloroplast function and that at least some END genes affect photosynthesis-related gene expression.

Socioeconomic Status and Rurality Among Patients With Head and Neck Cancer.

OBJECTIVE: Describe the relationship among rurality, socioeconomic status (SES), and patient/tumor characteristics in patients presenting with head and neck cancer. STUDY DESIGN: Retrospective single-institution study. SETTING: Academic tertiary-level medical center. METHODS: Patients with head and neck cancer presenting between 2011 and 2015 were included. Stage at presentation, insurance status, and demographic characteristics were collected. Rurality was measured through Rural-Urban Continuum Codes. SES was measured by SES index scores of the Agency for Healthcare Research and Quality, which incorporate multiple components of SES. Associations among rurality, SES, and patient/tumor characteristics were assessed with univariate and multivariable statistics. All P values were calculated via 2-sided hypotheses. The threshold for statistical significance was set at P < .05. Statistical analyses were conducted with Stata/SE 14 (StataCorp). RESULTS: The study included 266 patients diagnosed with head and neck cancer between 2011 and 2015. Rural residence was associated with lower SES (P < .001). T and N stages were associated with rurality (P = .036 and .050, respectively). Higher educational status was associated with oropharyngeal cancer (P = .005). CONCLUSIONS: Rurality and SES have distinct impacts on patients with head and neck cancer. Specifically, rurality is associated with tumor stage among patients with head and neck cancer. Knowledge of disparities among patients with rural residency may help target interventions to facilitate earlier diagnosis.

Fibroblast levels are increased in chronic rhinosinusitis with nasal polyps and are associated with worse subjective disease severity.

BACKGROUND: Fibroblasts are implicated in tissue remodeling and recruitment of inflammatory cells in chronic rhinosinusitis (CRS). Populations of fibroblasts remain unquantified in CRS subtypes. The objectives of this study were to measure fibroblast populations in subtypes of CRS, and to investigate the association between fibroblasts and disease severity. METHODS: Patients undergoing endoscopic sinus surgery (ESS) for CRS were prospectively enrolled from January 2011 to December 2014. Control subjects included patients undergoing endoscopic surgery for non-inflammatory conditions such as cerebrospinal fluid leak repair or non-hormone-secreting pituitary tumors. Patients completed 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaires prior to surgery. Blood and tissue biopsies were taken during surgery. Percent of sinonasal fibroblasts was determined via flow cytometry by selecting fibroblast-specific protein (FSP)-positive and Mucin 1 (MUC1)-negative cells. RESULTS: A total of 69 patients were enrolled: control (n = 24), CRS without nasal polyps (CRSsNP) (n = 13), CRS with nasal polyps (CRSwNP) (n = 22), and allergic fungal rhinosinusitis (AFRS) (n = 10). Patients with CRSwNP had significantly more fibroblasts than both control (p < 0.001) and CRSsNP (p < 0.01). Patients with AFRS had the most fibroblasts when compared to control (p < 0.0001), CRSsNP (p < 0.0001), and CRSwNP (p < 0.05). Atopy and asthma were not associated with increased fibroblasts in CRSwNP (p = 0.21, p = 0.26, respectively). Increased fibroblasts correlated with subjective disease severity as measured by SNOT-22 for CRSwNP (p = 0.003) and AFRS (p = 0.048). CONCLUSION: Sinonasal fibroblasts are increased in CRSwNP and AFRS compared to control and CRSsNP. Increased fibroblasts correlated with worse quality of life in CRSwNP and AFRS.

Predictors of 30-day morbidity and mortality in transnasal microscopic pituitary tumor excision.

BACKGROUND: There is a lack of population-based, multi-institutional analyses of factors associated with morbidity and mortality following pituitary tumor excision. METHODS: The American College of Surgeons National Surgical Quality Improvement Project files were used to compile information on patients that had undergone transnasal microscopic pituitary tumor resection from 2006 to 2012. Patient demographics, comorbidities, operative characteristics, and morbidity and mortality in the 30 days following surgery were included. Multivariate logistic regression was used for categorical variables and multivariate linear regression was used for continuous variables to evaluate factors leading to adverse events. RESULTS: A total of 658 patients were included, of which 58 (8.81%) experienced a complication, reoperation or death in the 30 days following surgery. The most common complications were reoperation (3.37%), followed by unplanned reintubation (1.99%), urinary tract infection (1.68%), and transfusion (1.68%). Predictors of any complication, reoperation, or death include preoperative sepsis (odds ratio [OR] = 7.596) and lower preoperative serum albumin (OR = 6.667). Younger age predicted surgical complications (OR = 1.105). Predictors of medical complications include higher body mass index (OR = 1.112), chronic steroid use (OR = 6.568), preoperative sepsis (OR = 15.297), and lower preoperative serum hematocrit (OR = 1.225). Predictors of increased total length of hospital stay were older age (ß = 0.146), higher body mass index (ß = 0.188), chronic steroid use (ß = 0.142), preoperative sepsis (ß = 0.489), and lower preoperative serum albumin (ß = -0.213). CONCLUSION: Although adverse events following pituitary tumor excision are low, awareness of factors associated with morbidity and mortality in the early postoperative period may allow for improved patient monitoring and outcomes.

Protecting the airway and the physician: Aspects of litigation arising from tracheotomy.

BACKGROUND: In recent decades, medical malpractice costs have increased and have led to a change in the way physicians practice medicine. Tracheotomies are cases in which complications have a high risk of morbidity and mortality and the potential for litigation. METHODS: The Westlaw legal database was used to gather data on 43 jury verdicts and settlements from 1987 to 2013. Various factors included outcome, defendant specialty, and the reason for litigation. RESULTS: Median settlements were $500,000 and median verdict awards were $2,000,000. Postoperative negligence was alleged most often (81%) followed by intraoperative negligence (27.9%) and permanent injury (18.6%). Otolaryngologists were named as defendants most often (25.6%), with nurses named second most often. Pediatric cases had significantly higher awards and were more often named in favor of the plaintiff. CONCLUSION: An awareness of tracheotomy malpractice litigation has the potential to both help physicians avoid future litigation and improve patient safety.

Multi-institutional study of risk factors for perioperative morbidity following transnasal endoscopic pituitary adenoma surgery.

BACKGROUND: The goal of this study was to identify preoperative risk factors associated with increased perioperative morbidity after endoscopic pituitary surgery. METHODS: A retrospective review of patients undergoing endoscopic pituitary adenoma surgery between 2002 and 2014 at 6 international centers was performed. Standard demographic and comorbidity data, as well as information regarding tumor extent and treatment were collected. Logistic regression was used to examine risk factors for the following 30-day outcomes: systemic complications, intracranial complications, postoperative cerebrospinal fluid (CSF) leaks, length of hospital stay, readmission, and reoperation. RESULTS: Data was collected on 982 patients with a mean age of 52 years. The median body mass index (BMI) for all patients was 30.9 kg/m(2) with 56% female. The median hospital stay was 5 days and 23.8% of patients suffered a postoperative adverse event. Systemic complications occurred in 3.2% of patients and intraventricular extension was a risk factor (odds ratio [OR] 8.9). Intracranial complications occurred in 7.3% of patients and risk factors included previous radiation (OR 8.6) and intraventricular extension (OR 7.9). Reoperation occurred in 6.5% of patients and intraventricular extension (OR 7.3) and age (<40 years, OR 3.5; 40 to 64 years, OR 3.2) were risk factors. Postoperative CSF leaks occurred in 5.5% of patients and risk factors included female gender (OR 2.4), BMI ≥ 30 (OR 2.1), age (<40 years, OR 5.3; 40 to 64 years, OR, 7.9), and intraventricular extension (OR, 9.5). CONCLUSION: Postoperative endoscopic pituitary adenoma surgery complications are associated with tumors with intraventricular extension, preoperative radiation, as well as common patient comorbidities. Identification of these factors may permit implementation of strategies to reduce postoperative complications.

Vitamin D for the treatment of respiratory diseases: is it the end or just the beginning?

A large number of human, animal and in vitro studies have suggested that vitamin D3 (VD3) plays a critical role in inflammatory airway diseases such as asthma, chronic rhinosinusitis, and allergic rhinitis. VD3 acts upon a broad range of immune cells involved in the pathogenesis of these diseases including T-cells, dendritic cells (DCs), macrophages, and B-cells. In addition, VD3 can also regulate the functions of a number of non-immune cells including epithelial cells, fibroblasts, and smooth muscle cells. Given that VD3 has known effects on the immune system, it seems logical that supplementation with VD3 would prove efficacious in the treatment of these three diseases. While many studies, most of which are observational, have suggested that VD3 deficiency is associated with more severe disease, VD3 supplementation trials in humans have resulted in varied outcomes in terms of efficacy. In this review article we will discuss the role of VD3 in these three commonly associated respiratory diseases. We will explore the literature describing associations of VD3 deficiency with patient outcomes, cells in the respiratory microenvironment susceptible to VD3 regulation, conflicting results of VD3 supplementation trials, and potential gaps in our knowledge that may be limiting the widespread use of VD3 for the treatment of respiratory diseases such asthma, chronic rhinosinusitis and allergic rhinitis. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

Hockey-related facial injuries: a population-based analysis.

OBJECTIVES/HYPOTHESIS: Recognition of the potentially severe sequelae arising from inadequate facial protection has facilitated sustained efforts to increase the use of protective visors in recent decades. Our objective was to characterize nationwide trends among patients presenting to emergency departments (ED) for facial injuries sustained while playing ice hockey. METHODS: The National Electronic Injury Surveillance System was searched for hockey-related facial injuries, with analysis for incidence; age and gender; and specific injury diagnoses, mechanisms, and facial locations. RESULTS: There were an estimated 93,444 ED visits for hockey-related facial injuries from 2003 to 2012. The number of annual ED visits declined by 43.8% from 2003 to 2012. A total of 90.6% of patients were male; and the peak age of injury was 17 years. Lacerations were the most common form of facial injury (81.5% of patients) across all age groups. Contusions/abrasions and fractures followed in frequency, with fractures increasing with advancing age. CONCLUSIONS: The overall incidence of ED visits due to facial injuries from ice hockey has significantly decreased over the last decade, concurrent with increased societal use of facial protective equipment. Nonetheless, facial hockey injuries facilitate a significant number of ED visits among both adults and children; thus, the knowledge of demographic-specific trends described in this analysis is relevant for physicians involved in the management of facial trauma. These findings reinforce the need to educate individuals who play hockey about the importance of appropriate facial protection.

Volumetric computed tomography analysis of the olfactory cleft in patients with chronic rhinosinusitis.

BACKGROUND: Commonly used computed tomography (CT) staging systems for chronic rhinosinusitis (CRS) focus on the sinuses and do not quantify disease in the olfactory cleft. The goal of the current study was to determine whether precise measurements of olfactory cleft opacification better correlate with olfaction in patients with CRS. METHODS: Olfaction was assessed using the 40-item Smell Identification Test (SIT-40) before and after sinus surgery in adult patients. Olfactory cleft opacification was quantified precisely using three-dimensional (3D), computerized volumetric analysis, as well as via semiquantitative Likert scale estimations at predetermined anatomic sites. Sinus opacification was also quantified using the Lund-Mackay staging system. RESULTS: The overall cohort (n = 199) included 89 (44.7%) patients with CRS with nasal polyposis (CRSwNP) and 110 (55.3%) with CRS without nasal polyposis (CRSsNP). The olfactory cleft opacified volume correlated with objective olfaction as determined by the SIT-40 (Spearman's rank correlation coefficient [Rs ] = -0.461; p < 0.001). The correlation was significantly stronger in the CRSwNP subgroup (Rs = -0.573; p < 0.001), whereas no appreciable correlation was found in the CRSsNP group (Rs = -0.141; p = 0.141). Correlations between sinus-specific Lund-Mackay CT scoring and SIT-40 scores were weaker in the CRSwNP (Rs = -0.377; p < 0.001) subgroup but stronger in the CRSsNP (Rs = -0.225; p = 0.018) group when compared to olfactory cleft correlations. Greater intraclass correlations (ICCs) were found between quantitative volumetric measures of olfactory cleft opacification (ICC = 0.844; p < 0.001) as compared with semiquantitative Likert grading (ICC = 0.627; p < 0.001). CONCLUSION: Quantitative measures of olfactory cleft opacification correlate with objective olfaction, with the strongest correlations seen in patients with nasal polyps.

Recent randomized controlled trials in otolaryngology.

OBJECTIVE: To assess recent trends in the prevalence and quality of reporting of randomized controlled trials (RCTs) in 4 otolaryngology journals. STUDY DESIGN: Methodology and reporting analysis. SETTING: Randomized controlled trials in 4 otolaryngology journals. SUBJECTS AND METHODS: All RCTs published from 2011 to 2013 in 4 major otolaryngology journals were examined for characteristics of study design, quality of design and reporting, and funding. RESULTS: Of 5279 articles published in 4 leading otolaryngology journals from 2011 to 2013, 189 (3.3%) were RCTs. The majority of RCTs were clinical studies (86%), with the largest proportion consisting of sinonasal topics (31%). Most interventions were medical (46%), followed by surgical (38%) and mixed (16%). In terms of quality, randomization method was reported in 54% of RCTs, blinding in 33%, and adverse events in 65%. Intention-to-treat analysis was used in 32%; P values were reported in 87% and confidence intervals in 10%. Research funding was most often absent or not reported (55%), followed by not-for-profit (25%). CONCLUSIONS: Based on review of 4 otolaryngology journals, RCTs are still a small proportion of all published studies in the field of otolaryngology. There seem to be trends toward improvement in quality of design and reporting of RCTs, although many quality features remain suboptimal. Practitioners both designing and interpreting RCTs should critically evaluate RCTs for quality.

Superoxide dismutase reduces the inflammatory response to Aspergillus and Alternaria in human sinonasal epithelial cells derived from patients with chronic rhinosinusitis.

BACKGROUND: Aspergillus fumigatus and Alternaria alternata are ubiquitous environmental fungal allergens that can exacerbate airway inflammation and contribute to the disease process in patients with chronic rhinosinusitis (CRS). These antigens have been shown to induce human sinonasal epithelial cells (HSNECs) to promote a proinflammatory response, but what is unclear is a means by which to reduce these effects. Inhaled pathogens can induce HSNECs to produce reactive oxygen species (ROS) that trigger cytokine production. OBJECTIVE: This study aimed to determine whether the free radical scavenger superoxide dismutase (SOD) could reduce HSNEC-derived inflammation, as measured by interleukin (IL)-6 and IL-8 production, in response to Aspergillus or Alternaria exposure. METHODS: Sinus tissue explants were collected at the time of surgery from control patients (n = 7) and patients with CRS with nasal polyps (CRSwNP) (n = 9). HSNECs were cultured from the explants and treated with Aspergillus, Alternaria, and SOD for 24 hours. Cell supernatants and lysates were collected, and IL-6 and IL-8 concentrations were measured using enzyme-linked immunosorbent assay. RESULTS: In control and CRSwNP HSNECs, Aspergillus and Alternaria both increased cytokine production (p < 0.05), as measured by IL-6 and IL-8 concentration. SOD treatment reduced the inflammatory response to fungal antigen exposure from CRSwNP HSNECs but not control HSNECs. In CRSwNP patients, SOD significantly decreased IL-6 and IL-8 production after Alternaria exposure and IL-8 after Aspergillus exposure (p < 0.05). CONCLUSIONS: When HSNECs from CRSwNP patients are treated with SOD concurrently with Aspergillus or Alternaria, SOD treatment decreases the fungal antigen-induced inflammatory response. The ability to attenuate inflammation induced by common fungal allergens with SOD treatment could provide a novel therapeutic or preventative approach for patients with CRS or other allergic inflammatory airway diseases.

Vitamin D3 as a novel regulator of basic fibroblast growth factor in chronic rhinosinusitis with nasal polyposis.

BACKGROUND: The immunopathogenesis of chronic rhinosinusitis (CRS) is largely unknown, but it is thought that different inflammatory profiles are responsible for the different CRS subtypes. 25-Hydroxyvitamin-D (25-VD3) has been shown to alter inflammatory mediators in other disease processes and 25-VD3 deficiency is associated with CRS with nasal polyps (CRSwNP), but it is unknown if 25-VD3 levels impact local inflammation in CRS. This study investigated the correlation between plasma 25-VD3 and sinonasal mucus monocyte chemoattractant protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted (RANTES), and basic fibroblast growth factor (bFGF) levels in patients with CRS. METHODS: Study subjects undergoing endoscopic sinus surgery (ESS) for CRS were prospectively enrolled from January 2012 to August 2014. Control subjects included patients undergoing ESS for noninflammatory pathology. Blood and sinonasal mucus were collected at the time of ESS. Plasma 25-VD3 was measured by enzyme-linked immunosorbent assay (ELISA) and mucus levels of MCP-1, RANTES, and bFGF by cytometric bead array (CBA). RESULTS: A total of 57 patients were enrolled and categorized as CRS without nasal polyps (CRSsNP) (n = 31), CRSwNP (n = 14), and controls (n = 12). No significant correlation was found between MCP-1 and 25-VD3. There was a significant negative correlation between 25-VD3 and RANTES (r = -0.612; p = 0.026) and bFGF (r = -0.578; p = 0.039) in CRSwNP patients; however, there was no significant correlation in CRSsNP patients. CONCLUSION: This data suggests that 25-VD3 may play a role in regulation of RANTES and bFGF expression in CRSwNP. This may occur through regulation of NP fibroblasts or other immune cells. Further investigation is warranted to better elucidate the role of RANTES, bFGF, and 25-VD3 in CRSwNP.

Levamisole-adulterated cocaine induced skin necrosis of nose, ears, and extremities: Case report.

Levamisole is an immunomodulatory and antihelminthic drug, previously removed from the United States market, and now estimated to be present in the vast majority of cocaine distributed in the United States. Levamisole-adulterated cocaine (LAC) exposure can result in neutropenia, thrombocytopenia, and vasculitis with a predilection for subsites of the face. The objective of this review is to increase awareness among otolaryngologists of the manifestations of LAC exposure. We present the case of a 33-year-old woman with a history of cocaine use, consulted for purpuric, necrotic lesions of the nose, cheeks, and ears, with accompanying leukopenia, thrombocytopenia, and positive antineutrophil cytoplasmic antibodies (ANCA). The effects of levamisole are immune mediated, with antibodies directed against neutrophils causing neutropenia, and vasculitis caused by antibody deposition or secondary to induction of antiphospholipid antibodies causing thrombosis. LAC exposure can be differentiated from other similar appearing pathologies by evaluating serology for specific ANCA. The most important treatment is cessation of cocaine use, which most often results in complete resolution of symptoms. Awareness of the presentation, complications, and treatment of LAC exposure may be especially important for otolaryngologists, who may be one of the firsts to evaluate an affected patient.