Outcomes of tympanostomy tube placement in children with Down syndrome--a retrospective review.

OBJECTIVES: Tympanostomy tubes are commonly used for treatment of chronic otitis media with effusion (COME) or recurrent acute otitis media (RAOM) in patients with Down syndrome, but hearing outcomes in this population have been mixed, and complications appear to be common. We aim to characterize outcomes and complications associated with tympanostomy tube placement in this population. METHODS: Retrospective review. All patients with Down syndrome presenting to a tertiary academic pediatric otolaryngology practice over a ten year period from 2002 to 2012 who received tympanostomy tubes for COME, RAOM, or hearing loss were reviewed. RESULTS: Long term follow up data was obtained in 102 patients, with average follow up 4.7 years. COME was the primary indication for tube placement in 100/102 (98%). Less than half of these patients (44%) initially failed their newborn hearing screen. Post operative hearing was found to be normal or near normal for the better hearing ear in 85/99 (85.9%), and normal to near normal in bilateral ears in 71/99 (71%). A majority (63.7%) of patients required two or more sets of tubes during the follow up period. Long term complications were common and were significantly increased if the patient required three or more sets of tubes, including chronic perforation (36.6% vs 8.2%, p<0.001), atelectasis (29.3% vs 1.6%, p<0.0001), and cholesteatoma (14.6% vs 0%, p=0.003). CONCLUSIONS: COME is a frequent problem in Down syndrome, and the majority of patients will require two or more sets of tubes during their childhood and achieve normal postoperative hearing. Long term complications of otitis media appear to be more common in this population and appear to correlate with increasing number of tubes placed. More investigation is required to determine optimal treatment strategies for COME in patients with Down syndrome.

Role of chronic lymphocytic thyroiditis in central node metastasis of papillary thyroid carcinoma.

OBJECTIVE: (1) To investigate the role of chronic lymphocytic thyroiditis (CLT) in central node metastasis of papillary thyroid carcinoma (PTC) and (2) to evaluate the presence of chronic lymphocytic thyroiditis according to PTC-specific molecular markers. STUDY DESIGN: Historical cohort study. SETTING: Academic medical center. SUBJECTS AND METHODS: All patients who underwent total thyroidectomy with central neck dissection for PTC at Oregon Health & Science University between 2005 and 2010 were screened for the presence of CLT and reviewed for clinical prognostic factors. Patients with inadequate central neck dissections were excluded. Molecular markers for PTC were analyzed on archived tumor samples. RESULTS: A total of 139 patients met selection criteria. The rate of CLT was 43.8%. The rate of central node positivity was 63%. Presence of CLT was associated with a significantly lower proportion of central node metastases (49% vs 74%, P = .003) and angiolymphatic invasion (31% vs 15%, P = .03). There was no significant difference in mean age, tumor size, and extracapsular extension. Molecular genotyping did not reveal a significant difference in the types of mutations found in both groups. CONCLUSION: The data indicate a lower incidence of central compartment lymph node metastasis in those with CLT in this patient population, suggesting a potential protective role in tumor spread. The equal distribution of tumor mutations between the carcinomas with and without evidence of CLT argues against a mutation-specific antigen as the immunologic stimulus. Further research is needed to characterize the role of autoimmunity in thyroid cancer.

ILPIP, a novel anti-apoptotic protein that enhances XIAP-mediated activation of JNK1 and protection against apoptosis.

We have previously described a new aspect of the Inhibitor of Apoptosis (IAP) family of proteins anti-apoptotic activity that involves the TAK1/JNK1 signal transduction pathway (1,2). Our findings suggest the existence of a novel mechanism that regulates the anti-apoptotic activity of IAPs that is separate from caspase inhibition but instead involves TAK1-mediated activation of JNK1. In a search for proteins involved in the XIAP/TAK1/JNK1 signaling pathway we isolated by yeast two-hybrid screening a novel X chromosome-linked IAP (XIAP)-interacting protein that we called ILPIP (hILP-Interacting Protein). Whereas ILPIP moderately activates JNK family members when expressed alone, it strongly enhances XIAP-mediated activation of JNK1, JNK2, and JNK3. The expression of a catalytically inactive mutant of TAK1 blocked XIAP/ILPIP synergistic activation of JNK1 thereby implicating TAK1 in this signaling pathway. ILPIP moderately protects against interleukin-1beta converting enzyme- or Fas-induced apoptosis and significantly potentiates the anti-apoptotic activity of XIAP. In vivo co-precipitation experiments show that both ILPIP and XIAP interact with TAK1 and tumor necrosis factor receptor-associated factor 6. Finally, expression of ILPIP did not affect the ability of XIAP to inhibit caspase activation, further supporting the idea that XIAP protection against apoptosis is achieved by two separate mechanisms: one requiring JNK1 activation and a second involving caspase inhibition.