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1.
Acta Neuropathol ; 138(3): 401-413, 2019 09.
Article in English | MEDLINE | ID: mdl-31183671

ABSTRACT

Cerebral amyloid angiopathy (CAA) consists of beta-amyloid deposition in the walls of the cerebrovasculature and is commonly associated with Alzheimer's disease (AD). However, the association of CAA with repetitive head impacts (RHI) and with chronic traumatic encephalopathy (CTE) is unknown. We evaluated the relationship between RHI from contact sport participation, CTE, and CAA within a group of deceased contact sport athletes (n = 357), a community-based cohort (n = 209), and an AD cohort from Boston University AD Center (n = 241). Unsupervised hierarchal cluster analysis demonstrated a unique cluster (n = 11) with increased CAA in the leptomeningeal vessels compared to the intracortical vessels (p < 0.001) comprised of participants with significantly greater frequencies of CTE (7/11) and history of RHI. Overall, participants with CTE (n = 251) had more prevalent (p < 0.001) and severe (p = 0.010) CAA within the frontal leptomeningeal vessels compared to intracortical vessels. Compared to those with AD, participants with CTE had more severe CAA in frontal than parietal lobes (p < 0.001) and more severe CAA in leptomeningeal than intracortical vessels (p = 0.002). The overall frequency of CAA in participants with CTE was low, and there was no significant association between contact sport participation and the presence of CAA. However, in those with CAA, a history of contact sports was associated with increased CAA severity in the frontal leptomeningeal vessels (OR = 4.01, 95% CI 2.52-6.38, p < 0.001) adjusting for AD, APOE ε4 status, and age. Participants with CAA had increased levels of sulcal tau pathology and decreased levels of the synaptic marker PSD-95 (p's < 0.05), and CAA was a predictor of dementia (OR = 1.75, 95% CI 1.02-2.99, p = 0.043) adjusting for age, sex, and comorbid pathology. Overall, contact sport participation and CTE were associated with more severe frontal and leptomeningeal CAA, and CAA was independently associated with worse pathological and clinical outcomes.


Subject(s)
Athletic Injuries/pathology , Cerebral Amyloid Angiopathy/pathology , Chronic Traumatic Encephalopathy/pathology , Aged , Aged, 80 and over , Athletes , Athletic Injuries/complications , Brain/pathology , Cerebral Amyloid Angiopathy/complications , Chronic Traumatic Encephalopathy/complications , Female , Humans , Male , Sports
2.
Laryngoscope ; 131(5): 1168-1174, 2021 05.
Article in English | MEDLINE | ID: mdl-33034397

ABSTRACT

OBJECTIVES/HYPOTHESIS: Create a competency-based assessment tool for pediatric esophagoscopy with foreign body removal. STUDY DESIGN: Blinded modified Delphi consensus process. SETTING: Tertiary care center. METHODS: A list of 25 potential items was sent via the Research Electronic Data Capture database to 66 expert surgeons who perform pediatric esophagoscopy. In the first round, items were rated as "keep" or "remove" and comments were incorporated. In the second round, experts rated the importance of each item on a seven-point Likert scale. Consensus was determined with a goal of 7 to 25 final items. RESULTS: The response rate was 38/64 (59.4%) in the first round and returned questionnaires were 100% complete. Experts wanted to "keep" all items and 172 comments were incorporated. Twenty-four task-specific and 7 previously-validated global rating items were distributed in the second round, and the response rate was 53/64 (82.8%) with questionnaires returned 97.5% complete. Of the task-specific items, 9 reached consensus, 7 were near consensus, and 8 did not achieve consensus. For global rating items that were previously validated, 6 reached consensus and 1 was near consensus. CONCLUSIONS: It is possible to reach consensus about the important steps involved in rigid esophagoscopy with foreign body removal using a modified Delphi consensus technique. These items can now be considered when evaluating trainees during this procedure. This tool may allow trainees to focus on important steps of the procedure and help training programs standardize how trainees are evaluated. LEVEL OF EVIDENCE: 5. Laryngoscope, 131:1168-1174, 2021.


Subject(s)
Clinical Competence/standards , Consensus , Esophagoscopy/education , Internship and Residency/standards , Surgeons/standards , Child , Delphi Technique , Esophagoscopes , Esophagoscopy/instrumentation , Esophagus/diagnostic imaging , Esophagus/surgery , Foreign Bodies/diagnosis , Foreign Bodies/surgery , Humans , Surgeons/education , Surgeons/statistics & numerical data , Surveys and Questionnaires/statistics & numerical data
3.
Sci Rep ; 10(1): 2924, 2020 02 19.
Article in English | MEDLINE | ID: mdl-32076055

ABSTRACT

Alzheimer disease (AD) is a chronic neurodegenerative disease with a multitude of contributing genetic factors, many of which are related to inflammation. The apolipoprotein E (APOE) ε4 allele is the most common genetic risk factor for AD and is related to a pro-inflammatory state. To test the hypothesis that microglia and AD-implicated cytokines were differentially associated with AD pathology based on the presence of APOE ε4, we examined the dorsolateral frontal cortex from deceased participants within a community-based aging cohort (n = 154). Cellular density of Iba1, a marker of microglia, was positively associated with tau pathology only in APOE ε4 positive participants (p = 0.001). The cytokines IL-10, IL-13, IL-4, and IL-1α were negatively associated with tau pathology, independent of Aß1-42 levels, only in APOE ε4 negative participants. Overall, the association of mostly anti-inflammatory cytokines with less tau pathology suggests a protective effect in APOE ε4 negative participants. These associations are largely absent in the presence of APOE ε4 where tau pathology was significantly associated with increased microglial cell density. Taken together, these results suggest that APOE ε4 mediates an altered inflammatory response and increased tau pathology independent of Aß1-42 pathology.


Subject(s)
Apolipoprotein E4/genetics , Brain/pathology , Inflammation/genetics , Inflammation/pathology , Aged, 80 and over , Alleles , Amyloid beta-Peptides/metabolism , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Biomarkers/metabolism , Calcium-Binding Proteins/metabolism , Cell Count , Cohort Studies , Cytokines/metabolism , Dementia/pathology , Female , Genotype , Humans , Male , Microfilament Proteins/metabolism , Microglia/metabolism , Microglia/pathology , Models, Biological , tau Proteins/metabolism
4.
Laryngoscope ; 118(3): 517-21, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18091330

ABSTRACT

OBJECTIVE: To describe the cochleovestibular apparatus on computed tomography (CT) imaging in patients with cholesteatoma. We asked whether cochleovestibular anomalies coexist in individuals with cholesteatoma. STUDY DESIGN: Randomized, controlled, prospective measurement. METHODS: A database search yielded 145 children with cholesteatoma: 31 met inclusion criteria by not having sensorineural hearing loss, not having an associated syndrome, and having digitally stored temporal bone CT imaging available. Prospective measurement of 31 individuals (62 ears) with unilateral cholesteatoma and 32 normally hearing nonsyndromic controls (64 ears) was performed by a neuroradiologist blinded to the study objective. Twenty-six temporal bone aspects on axial imaging were evaluated (16 measurement, 10 calculated from measurement). RESULTS: The cholesteatoma group had a larger endolymphatic fossa and vestibular aqueduct, and there was a trend for the lateral semicircular canal vestibule to be smaller as compared with controls. Subgroup analysis revealed a gradient in prevalence of these findings being most common in the congenital cholesteatoma group, intermediate in the acquired cholesteatoma group, and least common in controls. There were no differences in measurements between ears with cholesteatoma and contralateral disease-free temporal bones. CONCLUSIONS: Children with cholesteatoma have abnormal vestibular anatomy. The gradient in prevalence of these findings may suggest a relationship between congenital and acquired cholesteatoma. These may include a generalized temporal bone anomaly that predisposes to cholesteatoma formation, or a third variable such as genetic mutation may predispose to both anomalous cochleovestibular formation and cholesteatoma.


Subject(s)
Abnormalities, Multiple/diagnostic imaging , Cholesteatoma, Middle Ear/complications , Cochlea/abnormalities , Cochlea/diagnostic imaging , Tomography, X-Ray Computed , Vestibule, Labyrinth/abnormalities , Vestibule, Labyrinth/diagnostic imaging , Abnormalities, Multiple/epidemiology , Child , Humans , Prospective Studies , Single-Blind Method
5.
Int J Pediatr Otorhinolaryngol ; 66(3): 227-42, 2002 Dec 02.
Article in English | MEDLINE | ID: mdl-12443811

ABSTRACT

CONTEXT: There is limited information on the identity and antibiotic susceptibility of bacterial pathogens in children with chronic otitis media whose repeated antibiotic use may place them at increased risk of antibiotic-resistant bacteria. OBJECTIVE: To determine, at myringotomy for tympanostomy tube placement, (1) the prevalence of bacteria, (2) the extent and patterns of antibiotic resistance, and (3) the risk factors associated with the presence and resistant status of pathogens. DESIGN: Prospective, multi-site, cohort study. SETTING AND PATIENTS: Children undergoing myringotomy for tympanostomy tube placement between November 1, 1999 and March 31, 2000 in seven hospitals in Toronto, Ontario, were identified. If fluid was present, aspirates were submitted for bacteriologic testing. A follow-up telephone questionnaire was administered to patient caregivers in order to identify risk factors for the presence of (1) culturable pathogens and (2) resistant pathogens. MAIN OUTCOME MEASURES: The identification and prevalence of bacteria cultured from the middle ears of subjects, and the degree of nonsusceptibility to commonly prescribed antibiotics. RESULTS: Among 601 patients (mean age 3.9 years, 60.7% male), both a telephone interview (n=544) and an ear specimen (n=527) were obtained for 478. Pathogens were found in middle ear effusions of 37% of the children in the study; including at least one 'definite' pathogen in 189 children (31.4%), and a further 32 children (5.3%) with at least one 'possible' pathogen. Definite pathogens included Haemophilus influenzae in 17% of the children, followed by Moraxella catarrhalis (9%) and Streptococcus pneumoniae (6%); ampicillin nonsusceptibility was found in 40, 100 and 24%, respectively. Overall, 123 children (20.5%) were found to have definite pathogens with resistance to ampicillin/penicillin, trimethoprim-sulfamethoxazole, or clarithromycin/erythromycin. Patient characteristics included premature birth and/or long length of stay in the nursery (23%), first infection before the age of 6 months (26%), put to bed with a bottle (28%), household smoker (34%), in out-of-home child care (38%), history of eczema, bronchiolitis and/or asthma (39%), and use of pacifiers (40%). Household characteristics were smoking (34%), married/common law parents (85%), and 60% had completed college or university; in 26% both parents were born outside of Canada; 73% of children were Caucasian. Of the 75% who responded to the question regarding income, 42% had household income over $60,000 (CAN). Risk factors for the presence of a pathogen and for a resistant pathogen in multivariate analysis included younger age, lower maternal education, day care centre attendance, no previous adenoidectomy and bilateral, primarily winter infections as well as amoxicillin use in the previous 6 months. CONCLUSION: Modifiable risk factors for otitis media including household smoking and pacifier use are present in many children undergoing tympanostomy tube placement; child care centre attendees are over-represented. Multiple antibiotic courses were commonly prescribed prior to surgery. H. influenzae and M. catarrhalis are important pathogens and therapy in clinical failures should be directed against them. The 7-valent protein conjugate polysaccharide vaccine (Prevnar) would have covered 73% of the serotypes of S. pneumoniae isolated in this study.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial , Middle Ear Ventilation/methods , Myringoplasty/methods , Otitis Media with Effusion/microbiology , Postoperative Complications/microbiology , Adolescent , Age Distribution , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Cohort Studies , Female , Follow-Up Studies , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/isolation & purification , Humans , Incidence , Infant , Male , Microbial Sensitivity Tests , Middle Ear Ventilation/adverse effects , Myringoplasty/adverse effects , Otitis Media/diagnosis , Otitis Media/microbiology , Otitis Media/surgery , Otitis Media with Effusion/diagnosis , Otitis Media with Effusion/surgery , Prospective Studies , Risk Factors , Sex Distribution
6.
J Otolaryngol ; 35(4): 222-6, 2006 Aug.
Article in English | MEDLINE | ID: mdl-17176796

ABSTRACT

INTRODUCTION: Middle ear reconstruction in children following tympanomastoidectomy for cholesteatoma is commonly limited to a Wullstein type III or IV reconstruction owing to ossicular erosion. The hearing outcomes of this procedure have been unpredictable. Nevertheless, there are children who have remarkably good hearing results despite having extensive and aggressive cholesteatoma surgery and limited reconstruction. METHODS: The current theories of middle ear mechanics following tympanoplasty and ossicular reconstruction are reviewed. In addition, a selective retrospective chart review of pediatric type III and IV tympanoplasty at The Hospital for Sick Children between 1998 and 2003 is presented. RESULTS: Nine patients were reconstructed with a type III (n = 3) or IV (n = 6) tympanoplasty. The mean pre- and postoperative air-bone gaps were 43.6 and 24.9 dB. Speech reception threshold improved from 37.5 to 22.8 dB. The changes were statistically significant (p < .05). CONCLUSIONS: This series of patients demonstrated a statistically significant hearing improvement at long-term follow-up. The improvements are consistent with optimal hearing outcomes predicted by current theories of middle ear mechanics.


Subject(s)
Cholesteatoma, Middle Ear/surgery , Hearing , Tympanoplasty/methods , Audiometry , Child , Female , Humans , Male , Retrospective Studies , Treatment Outcome
7.
J Pediatr Surg ; 40(4): E39-41, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15852263

ABSTRACT

Aspiration of Timothy grass in the airway is a well-recognized cause of bronchiectasis, and management often requires pulmonary resection. The authors describe 2 cases of Timothy grass aspiration with established pulmonary infection that were successfully managed by bronchoscopic removal with subsequent improvement. Every effort should be made to accomplish this goal, and pulmonary resection should be considered a last resort in these cases.


Subject(s)
Bronchoscopy/methods , Foreign Bodies/surgery , Phleum , Bronchiectasis/etiology , Child , Humans , Infant , Lung/pathology , Male , Pneumonia/etiology
8.
J Otolaryngol ; 33(3): 145-50, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15841990

ABSTRACT

OBJECTIVE: The purpose of this article is to review the cases of bilateral cholesteatomas in a tertiary care pediatric otolaryngology department. We compare the presenting signs and symptoms and timing of ipsilateral and contralateral cholesteatomas and the initial audiometric findings. METHODS: Retrospective chart review. SETTING: Department of Otolaryngology, The Hospital for Sick Children, Toronto, ON. RESULTS: Twenty-two patients with bilateral cholesteatomas were accrued. Nine patients had bilateral congenital cholesteatomas and presented at a substantially younger age than those with acquired disease (average of 5 years, 9 months vs 11 years). Sixteen of the 22 patients were initially diagnosed with bilateral cholesteatomas. The majority of the remaining patients had evidence on initial assessment of contralateral middle ear disease. A particular subset of patients with severe disease requiring numerous bilateral revision surgeries was also identified. These patients also underwent revision surgery after a substantially shorter follow-up period. CONCLUSIONS: Bilateral cholesteatomas in the pediatric population are extremely rare. Bilateral congenital cholesteatomas are more common in males, whereas bilateral acquired cholesteatomas are more common in females. The outcome is generally poor. A small subset with particularly aggressive disease requires many more bilateral revision surgeries at an earlier period when compared with the remainder of the group.


Subject(s)
Cholesteatoma, Middle Ear/epidemiology , Adolescent , Age Factors , Audiometry , Child , Child, Preschool , Cholesteatoma, Middle Ear/congenital , Cholesteatoma, Middle Ear/surgery , Female , Follow-Up Studies , Humans , Male , Ontario/epidemiology , Otitis Media/epidemiology , Reoperation/statistics & numerical data , Retrospective Studies , Sex Factors , Treatment Outcome
9.
J Pediatr Surg ; 37(1): E1, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11782010

ABSTRACT

In August 1996, a 7-year-old boy was crushed from behind into the steering wheel of a go-cart, suffering a tear of his right innominate artery into the aortic arch, a 2-inch tear of the posterior trachea into left main bronchus, and 2 4-inch tears in the esophagus. These were all repaired on cardiopulmonary bypass through a sternotomy; a Gor-tex (W. L. Gore and Associates, Flagstaff, AZ) graft was required for the arterial repair. His recovery was complicated by a midesophageal stricture and a nearby fistula to the left main bronchus, which caused frequent lung infections and 12 hospital admissions over 2(1/2) years. During this time he had his stricture dilated 5 times and resected twice, his fistula surgically closed twice and glued 4 times, and an antireflux procedure, pyloroplasty, and gastrostomy for his persistent gastroesophageal reflux. He also had 2 esophageal stents placed; the first (titanium) lasted 4 months and the second (SILASTIC(R) [Dow Corning, Midland, MI]) 1 year later lasted 9 months, solving both the stricture and fistula problems and spontaneously passing through and out of his gastrointestinal tract. Throughout this recovery time, his nutrition was maintained mostly by gastrostomy feeding, supplemented by total parenteral nutrition and oral feeding when able. After 2(1/2) years of treatment, all has returned to normal, and he has remained well for the last 2(1/2) years (April 2001). He still is on Omeprazole.


Subject(s)
Aorta, Thoracic/injuries , Esophagus/injuries , Multiple Trauma/surgery , Trachea/injuries , Wounds, Nonpenetrating/surgery , Accidents, Traffic , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/surgery , Brachiocephalic Trunk/diagnostic imaging , Brachiocephalic Trunk/injuries , Brachiocephalic Trunk/surgery , Bronchi/injuries , Bronchi/surgery , Child , Dilatation , Esophageal Stenosis/therapy , Esophagus/diagnostic imaging , Esophagus/surgery , Gastroesophageal Reflux/etiology , Gastroesophageal Reflux/surgery , Humans , Male , Multiple Trauma/diagnostic imaging , Off-Road Motor Vehicles , Postoperative Complications/therapy , Radiography , Trachea/diagnostic imaging , Trachea/surgery , Wounds, Nonpenetrating/diagnostic imaging , Wounds, Nonpenetrating/etiology
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