Granulomatosis with polyangiitis-associated acute subglottic stenosis in a 13-year-old boy: a case report.

We present a case of a child with granulomatosis with polyangiitis, admitted with acute respiratory distress attributed to subglottic stenosis. The anesthetic management and potential complications are described.

The impact of HMG-CoA reductase therapy on serum PSA.

BACKGROUND: 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors, otherwise known as statins, inhibit the enzyme that controls the conversion of HMG-CoA to mevalonate, a precursor for cholesterol. Statins may be important to prostate cancer biology by inhibiting cell growth, inflammation, and oxidative stress. The purpose of this study was to assess the influence of statin therapy on serum prostate-specific antigen (PSA) levels. METHODS: The computerized medical records at the University of Rochester Medical Center were used to identify men who filled statin prescriptions between May 31st, 2008 and September 30th, 2008. Men with at least one PSA assay performed within 2 years before and at least one PSA assay performed within 1 year after starting a statin medication were included. The primary endpoint was the change in PSA concentration computed as the difference between PSA levels before and after starting a statin medication. Paired t-tests were used to analyze the mean differences in PSA values. RESULTS: A total of 962 patients were identified. The mean difference in serum PSA level after statin administration was -0.29 ng/ml (-8.04%). Subgroup analyses for mean PSA concentration change before and after statin administration by age group revealed: 50-59 years old (-0.1609, 95% CI: -0.2444, -0.0775, P < 0.0002), 60-69 years old (-0.3393, 95% CI: -0.4641, -0.2145, P < 0.0001), and >70 years old (-0.351, 95% CI: -0.490, -0.212, P < 0.0001). CONCLUSIONS: These observations suggest a statistically significant reduction in serum PSA level that is associated with the onset of statin therapy.

Prostate specific antigen reduction following statin therapy: Mechanism of action and review of the literature.

Prostate specific antigen (PSA) is a serine protease that is exclusively produced in the prostate, and its detection is the only laboratory test available for screening men for prostate cancer (PC). The interpretation of the assay is difficult since it is specific for prostate tissue and cellular growth, but not for PC. Pharmacologic therapy for hyperlipidemia, such as statins, may influence prostate cellular growth and subsequently PSA levels in patients. Dysregulated cellular growth in the prostate is mediated by inhibiting the rate-limiting pathway step in cholesterol synthesis, thereby decreasing isoprenylate intermediates, decreasing cholesterol rich cellular membrane domains, and down-regulating androgen and estrogen receptors. Statins, with variable efficacy, have been previously shown to inhibit cellular inflammation, angiogenesis, proliferation, migration/adhesion, and invasion, while promoting apoptosis in prostate cells by inhibiting the conversion of HMG-CoA to mevalonate. An individual statin's molecular structure, need for enzymatic conversion, bioavailability, and peripheral tissue concentration may partially account for differing properties. By inhibiting prostatic cellular growth and promoting apoptosis, statins may subsequently decrease PSA levels, an effect recently observed in cohorts. There is scientific and clinical evidence supporting the observations that statins are associated with an overall reduction in serum PSA in men, when used for greater than 6 months, and especially when used for greater than 2 years.

Tracheal tear from blunt neck trauma in children: Diagnosis and management.

We describe the management of posterior trachea tears after blunt neck trauma in two children. The first, a 5 year-old boy who fell off his scooter, causing a 1.0cm tear in the membranous cervical trachea, was managed conservatively with 5 days of intubation. The second, a 12 year-old girl who fell on her bicycle, causing a 4.0cm tear in the membranous thoracic trachea, was repaired with thoracoscopic techniques. The presumed mechanism may be expansion of the U-shaped cartilage with tear of the membranous trachea. The size, location, and severity of symptoms dictate the decision about primary repair versus conservative management.

The role of allergy immunotherapy in the treatment of asthma.

PURPOSE OF REVIEW: Asthma and allergic rhinitis are two of the most widespread chronic medical conditions. Asthma, a condition which encompasses chronic inflammation of the lower airway resulting in expiratory obstruction, may represent an end phase along the allergic disease spectrum ultimately stemming initially from nasal allergic rhinitis and bronchial hyper-reactivity. The purpose of this review was to evaluate the available published literature over the past 12 months regarding the role of allergy immunotherapy in the treatment of asthma. RECENT FINDINGS: Recent clinical trials, systematic reviews, and meta-analyses have demonstrated that allergen-specific immunotherapy (ASI), especially sublingual immunotherapy for as short as 12 months, may help improve asthma symptoms and reduce medication usage. However, studies have not demonstrated overall improvement in pulmonary function tests despite improvement in symptoms. Barriers to asthmatic patients initiating and maintaining ASI include lack of payment by health insurer, inconvenience, and potentially worsening asthma exacerbations/symptoms for patients with severe disease. SUMMARY: ASI may change the natural course of allergic asthma by reducing the risk of acute respiratory exacerbations and symptoms. Additional studies are necessary to examine whether early treatment of allergy sensitivities with ASI may ultimately prevent the progression to asthma.

Tobacco Smoke Exposure and Eustachian Tube Disorders in US Children and Adolescents.

OBJECTIVES: To describe the association between active, environmental tobacco smoke (ETS) exposure and the prevalence of eustachian tube dysfunction (ETD) in the U.S. pediatric population. STUDY DESIGN: Cross-sectional. SETTING: U.S. representative demographic and audiometric data from the National Health and Nutrition Examination Survey (NHANES);2005-2010. SUBJECTS AND METHODS: The study consisted of 2,977 children aged 12-19 years. ETD was defined as middle ear pressure <100mm H20. ETS was defined as non-active smoking in individuals with serum cotinine over the limit of detection (≥0.015 ng/mL) and <10 ng/mL(N = 1559). RESULTS: The prevalence of ETD was 6.1%. After multivariate adjustment for age, sex, body mass index, education level, ethnicity, or having a cold, sinus problem or earache during the last 24 hours, compared to unexposed children, the odds ratios (95% confidence interval) of ETD for those exposed to ETS ages 12-15 in the first, second and third tertile of cotinine concentrations were, respectively, 1.38 (0.53-3.60), 0.99 (0.53-3.60) and 2.67 (1.12-6.34). Similarly, the odds ratios (95% confidence interval) of ETD for those exposed to ETS ages 16-19 in the first, second and third tertile of cotinine concentrations were, respectively, 1.28 (0.48-3.41), 0.99 (0.40-2.48) and 2.86 (1.19-6.88). CONCLUSION: These data suggest that children and adolescents exposed to high concentrations of ETS may have an increased prevalence of ETD.

Apolipoprotein E Allele and Hearing Thresholds in Older Adults.

BACKGROUND: Whether apolipoprotein E (APOE) E4 allele status which is associated with an increased risk of cognitive decline is also associated with hearing impairment is unknown. METHODS: We studied 1833 men and women enrolled in the Health, Aging and Body Composition study. Regression models adjusted for demographic and cardiovascular risk factors were used to assess the cross-sectional association of APOE-E4 status with individual pure tone hearing thresholds and the 4-frequency pure tone average (0.5-4 kHz) in the better hearing ear. RESULTS: Compared to participants with no APOE-E4 alleles, participants with 1 allele had better thresholds at 4.0 kHz (ß = -2.72 dB, P = .013) and 8.0 kHz (ß = -3.05 kHz, P = .006), and participants with 2 alleles had better hearing thresholds at 1.0 kHz (ß = -8.56 dB, P = .021). CONCLUSION: Our results suggest that APOE-E4 allele status may be marginally associated with better hearing thresholds in older adults.

A standardized regimen of antibiotics prevents infectious complications in skull base surgery.

OBJECTIVES/HYPOTHESIS: Craniofacial surgery has been associated with a significant improvement in disease outcome for patients with skull base neoplasms. Despite this improved survival, complications remain considerable. One major source of complications is infectious events. The current study was designed to evaluate a prospectively designed antibiotic regimen and its impact on the incidence and severity of infectious complications. This regimen was compared with a group of historic controls in which antibiotics were administered on an ad hoc basis. The specific objectives/hypothesis were to determine 1) the incidence and severity of infection in a group of patients treated with a nonstandardized antibiotic regimen undergoing craniofacial resection, and 2) whether the use of a prospectively designed, three-drug, broad spectrum antibiotic is associated with a reduced incidence and severity of infections. STUDY DESIGN: A single-arm, prospective antibiotic regimen consisting of ceftazidime, flagyl (metronidazole), and vancomycin (CMV) was compared with a historic control of patients treated with nonstandard antibiotic therapy (nonCMV), all of whom underwent craniofacial resection. Outcome measures focused on incidence of infection, severity of infection, and operative mortality. METHODS: In July 1990, a retrospective review (1973-1990) was performed of craniofacial resection. Beginning in July 1990, a prospective database (1990-2003) has been maintained. Demographics, prior therapy, anatomic site of origin and extent of disease, pathology, standard surgical data, and postoperative therapy were detailed. Antibiotic data were collected from chart review. Complications, focusing on infectious complications, were identified and categorized. Culture results and whether the inciting infection was sensitive or resistant to perioperative antibiotics were noted. Length of hospital stay was tabulated. Disease outcome, including incidence of postoperative mortality, was maintained for each patient. RESULTS: A total of 211 patients underwent craniofacial resection from 1973 to 2003. Major medical comorbidities were present in 53 (25%) patients, and 96 (46%) had prior therapy. The standardized antibiotic therapy (CMV) was used in 90 patients, and the nonstandardized antibiotics (nonCMV) were used in 107 patients. Free flap reconstruction was the sole surgical factor associated with a marked reduction in complications. Infectious wound complications were 11% within the CMV group versus 29% in the nonCMV regimen (P = .002). Moreover, the severity of infections was greatly diminished in the CMV group (P = .0001). With use of a multivariate analysis, the only factor which was predictive of infectious complications was the use of CMV. Patients who received nonCMV antibiotic therapy faced a risk of infection that was 2.5 times higher than those who received CMV. Hospital stay in days and operative mortality were both adversely affected by the use of nonCMV antibiotic therapy. CONCLUSIONS: The data supports the hypothesis that the use of a three-drug, broad spectrum antibiotic regimen in skull base surgery reduces the incidence of infectious complications and appears to reduce operative mortality. Broad spectrum coverage of Gram-positive, Gram-negative, and anaerobic pathogens leads to a marked reduction in infectious complications. Broad spectrum antibiotic coverage avoids many infectious complications and ultimately had a positive impact on patient outcome, quality of life, and, potentially, survival.

Improvement and prevention of asthma with concomitant treatment of allergic rhinitis and allergen-specific therapy.

BACKGROUND: Asthma and allergic rhinitis are 2 of the most prevalent chronic medical diseases. Asthma is estimated to affect 8% of adults and 9% of children, with nearly 300 million people affected worldwide. Poorly controlled allergic rhinitis may be associated with worsening asthma symptoms over time. Various treatments have been proposed in the improvement and prevention of asthma in children and adults with allergic symptoms, which have included pharmacotherapy with antihistamines and topical intranasal corticosteroids, as well as allergen-specific immunotherapy. METHODS: Articles were selected through PubMed and personal knowledge of the authors based on a comprehensive literature review examining whether treatment of allergic rhinitis improves and/or prevents concomitant symptoms of asthma. The largest and highest-quality studies were included in the literature review. The search selection was not standardized. Articles written in a language other than English were excluded. RESULTS: Clinical trials have showed improvement in asthma symptoms with concomitant treatment of allergic rhinitis with antihistamines and topical intranasal corticosteroids, though improvement in objective pulmonary function parameters has not been uniformly demonstrated with antihistamine use alone. There is very strong evidence to suggest that subcutaneous and sublingual immunotherapy may in addition prevent the progression of asthma in high-risk atopic patients by inducing immunological tolerance. CONCLUSION: Traditional pharmacotherapy with antihistamines and topical intranasal steroids has been shown to improve allergic rhinitis symptoms with concomitant allergic asthma; however, only allergen-specific immunotherapy offers long-term control in improving asthma symptoms, exacerbations, and likely ultimate prevention in developing asthma.

Topical intranasal corticosteroids and growth velocity in children: a meta-analysis.

BACKGROUND: There is no consensus regarding the effects on growth velocity of intranasal topical corticosteroid (ITC) use in children. The objective of this study was to determine whether ITC use reduces growth velocity in children with allergic rhinitis (AR). METHODS: A literature search of the National Center for Biotechnology Information PubMed, EMBASE, SCOPUS, and Cochrane databases from January 1, 1988 to October 7, 2013. The study selection was composed of randomized clinical trials investigating ITC for treatment of AR in children (age <18 years of age) with appropriate controls. Studies must have included interval change in growth as an outcome. Two authors independently extracted data and assessed study quality. Eligible studies were pooled using a random-effects approach. RESULTS: Eight studies with 755 participants from 3 countries provided data for the meta-analysis (knemometry, n =342 participants; stadiometry, n =413 participants). Study duration ranged from 2 to 4 weeks for trials evaluating knemometry outcomes, and 12 months for trials evaluating stadiometry outcomes. Age of participants ranged from 3 to 12 years. The pooled standardized mean difference showed that among studies using knemometry, mean growth was statistically significantly lower among children using ITC vs placebo (-.223 mm/week; 95% confidence interval [CI], -0.429 to -0.017; p < 0.034).The pooled standardized mean difference showed that among studies using stadiometry, there was no significant growth difference among children using ITC vs placebo (-0.053 cm/year; 95% CI, -0.491 to 0.385; p = 0.813). The limitations of this study were the difficulty in predicting longer-term or catch-up growth in children. CONCLUSION: Meta-analytic pooling of trials suggest that short-term ITC for the treatment of AR in children may decrease short-term growth velocity using knemometry; however, the effect on longer-term growth velocity as measured by stadiometry is unclear.

Lead exposure and increased food allergic sensitization in U.S. children and adults.

BACKGROUND: Whether blood lead levels are associated with sensitization to food allergens in adults and children is unclear. Prior studies have shown that exposure to lead is associated with atopic sensitization and modulation of several cytokines (eg, interleukin [IL]-12, IL-10, interferon [IFN]-γ, and IL-4 production) and with T-cell dysregulation and bias toward T helper 2 (Th2) activity. The objective of this work was to assess whether exposure to lead is independently associated with allergic symptoms and sensitizations in a large nationally representative sample of children and adults. METHODS: We studied 2712 children and 4333 adults enrolled in the 2005-2006 cycle of the National Health and Nutritional Examination Surveys (NHANES). Participants were tested for serum-specific immunoglobulin E (IgE) levels to food allergens as well as blood lead levels. Food allergens tested included shrimp, egg, peanut, and milk. Logistic regression models adjusted for demographic factors, body mass index, history of asthma, smoking, housing characteristics, and current exposure to animals in the home, to assess the association of blood lead levels with sensitization to food allergens. RESULTS: Median (interquartile range [IQR]) for serum blood was 0.87 µg/L (0.61 to 1.31) in children and 1.48 µg/L (0.92 to 2.34) in adults. At baseline, 672 (24.7%) of children participants and 719 (16.6%) of adult participants tested positive for increased sensitization to food allergens. A 2-fold increase in blood lead levels in adult participants was associated with increased sensitization to food allergens (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.02 to 1.22). Blood lead was not associated with sensitization to food allergens among pediatric participants (OR, 0.95; 95% CI, 0.82 to 1.10). CONCLUSION: Exposure to lead was associated with increased odds of sensitization to food allergens in adult but not children participants.

Otolaryngological progression of granulomatosis with polyangiitis after systemic treatment with rituximab.

OBJECTIVE: Rituximab is used for the treatment of granulomatosis with polyangiitis (GPA), historically known as Wegener's granulomatosis. However, the otolaryngological progression of GPA after systemic treatment with rituximab (Rituxan) is unclear. We therefore examined the disease sequelae of patients with GPA who were treated with rituximab. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care medical center. SUBJECTS AND METHODS: Patients with a diagnosis of GPA who were treated with rituximab between 2006 and 2012 were included in this study. Systemic and otolaryngological symptomatology, prednisone usage, and procedural interventions following B-cell depletion were analyzed. RESULTS: We identified 11 patients who met our inclusion criteria. The average length of follow-up after treatment with rituximab was 23.5 months. After treatment with rituximab, there was a significant decrease in daily prednisone dose at 3, 12, and 18 months postinfusion (P < .05). However, there was no observed improvement in patients' otolaryngological complaints as measured by the Birmingham Vasculitis Activity Score. Furthermore, patients treated with rituximab underwent numerous otolaryngological interventions during follow-up. Patients with a history of subglottic stenosis (n = 6) underwent an average of 3.40 laryngoscopies and 0.58 dilations per year during rituximab remission, and patients with sinusitis also underwent multiple nasal endoscopies (4.54 per year, n = 9) and nasal debridements (1.34, n = 9). CONCLUSIONS: While rituximab has been shown to be noninferior to cyclophosphamide with respect to remission from systemic GPA, these patients continue to have chronic otolaryngological manifestations of their disease. Otolaryngologists must continue to play a supportive role throughout their maintenance period.

Treatment and outcomes of chronic rhinosinusitis in children with primary ciliary dyskinesia: where is the evidence? A qualitative systematic review.

BACKGROUND: Consensus on treatment of chronic rhinosinusitis (CRS) in children with primary ciliary dyskinesia (PCD) is limited. We sought to synthesize the best available evidence pertaining to treatment and outcomes of CRS in children with PCD. METHODS: This work is a systematic review of PubMed and EMBASE for studies pertaining to treatment and outcomes of CRS in children with PCD in a 20-year period. Two reviewers independently extracted information on study design, setting, medical or surgical therapy for CRS, and treatment outcomes. RESULTS: Twelve studies from 8 countries were included for analysis: (3 retrospective cohorts, 2 prospective cohorts, 2 cross-sectional, 1 case series, and 4 case reports). The number of patients with PCD ranged from 1 to 78. Medical treatment included oral antibiotics, intranasal steroids, and oral steroids. Surgical treatment was mentioned in 8 studies, with endoscopic sinus surgery (ESS) described in 3 of 8. Outcome measures were rarely defined but included the 20-item Sino-Nasal Outcome Test (SNOT-20) questionnaire (1/12), symptom questionnaire (1/12), decreased recurrent pneumonia (1/12), and subjective report of CRS symptoms. No randomized, controlled, or long-term prospective cohort studies were identified, and no study employed a disease-specific, pediatric-validated instrument to measure outcomes of therapy. CONCLUSION: There is a paucity of evidence pertaining to CRS treatment or outcomes in children with PCD. Given the rare prevalence of PCD and the insufficient evidence pertaining to treatment effectiveness for CRS, we propose an international, multicenter database to prospectively track data pertaining to diagnosis, treatment, and outcomes of CRS for children with PCD. This effort would encourage implementation of validated and standardized outcome measures.

Measuring quality of life in dysphonic patients: a systematic review of content development in patient-reported outcomes measures.

To review existing patient reported outcomes measures (PROMs) used in dysphonic populations to assess the procedures used in their development and the extent to which these meet current development standards for content generation and psychometric evaluation. The study is a systematic review. A systematic review of Medline, Cumulative Index to Nursing & Allied Health, and Health and Psychosocial Instruments databases was completed using voice, quality of life, and PROMs as keywords. We identified all patient or parent-reported questionnaires measuring quality of life associated with voice disorders from the review findings. Questionnaires were appraised for adherence to international guidelines for the development and evaluation of PROMs as outlined by the Scientific Advisory Committee of the Medical Outcome Trust. Nine PROMs fulfilled the inclusion criteria. The quality of these questionnaires was variable with regard to instrument development and none met all of the current, recommended criteria. Of the nine questionnaires, the Voice Symptom Scale underwent the most rigorous development process. Furthermore, many instruments have been augmented to allow for proxy administration, failing to address quality of life-related issues specific to the target population. Instrument development is often overlooked when attempting to quantify patient reported outcomes in dysphonic patients. Careful instrument development procedures are required to ensure that PROMs are valid, reliable, and responsive. Our review suggests that the deficits in psychometric properties of the current voice-related PROMs may be, at least in part, due to deficits in the development process. Furthermore, these data suggest the potential utility of a novel PROM adhering to rigorous international standards to better ensure that clinicians appreciate the variables most relevant to patients with voice disorders and address some of the psychometric shortcomings of the currently used questionnaires.

Correlation between functional MRI and voice improvement following Type I thyroplasty in unilateral vocal fold paralysis--a case study.

The objectives of this study are to describe central nervous system modulation associated with voice improvement following Type I thyroplasty in a patient with glottic insufficiency secondary to unilateral vocal fold paralysis. Serial functional magnetic resonance imaging scans were performed before as well as one and six months after thyroplasty. Paradigms consisting of four voice production tasks and a motor control task were completed. Volumes of activation within regions activated during each task were measured. Acoustic and aerodynamic measures were also obtained. A widespread network of neural activations was shown for all tasks. Differences in volumes of activation 1-month postsurgery positively correlated with acoustic and aerodynamic improvements. Sixth months following medialization, lesser volumes of activation were observed in all regions. Prior to this session, however, the patient's mediastinal disease progressed, leading to a significant deterioration in voice. Functional differences between patient brain maps yield new information about the central nervous system's ability to reorganize sensorimotor representations associated with voice improvement following Type I thyroplasty in a patient with glottic insufficiency secondary to unilateral vocal fold paralysis (UVFP).