Citations

Cysts of the vallecula are rare, accounting for 10.5% to 20.1% of all laryngeal cysts. Vallecular cysts may present with diverse symptoms affecting the voice, airway, and swallowing. We describe the evaluation and treatment of a 70-year-old woman who presented with dysphagia caused by large bilateral vallecular cysts.

Abstract Multiple myeloma (MM) is a cancer of the plasma cells in the bone marrow. Although rare, MM is a deadly form of cancer with a 5 year survival rate of only 37%. African Americans (AA) are twice as likely to be diagnosed with and die from MM as compared to European Americans (EA). Socioeconomic factors may contribute to this disparity, however, biological factors may also be an influence. We have identified somatic copy number alterations in MM as a part of the Multiple Myeloma Genomics Initiative by profiling 250 MM tumors using array-based comparative genomic hybridization (aCGH). Using this cohort, we identified 16 African American and 180 European American patients using a MMRC database that indicated the racial demographics of each patient. To determine if somatic alterations may play a role in the disparity in incidence and/or severity of MM in AA, we compared the frequency of specific chromosomal aberrations in genes and genomic regions found to be involved in progression and poor outcome. The number of events of occurring was calculated and a univariate analysis was conducted using the Fisher's exact test. P-values were used to determine statistical significance. Results revealed significant differences for chromosome 1 p alterations. Specifically, homozygous deletion at the p18 locus at 1 p occurred in 12.5% (2/16) of tumors from AA patients and 2.8% (5/180) of EA patient tumors (p = 0.045). Further stratification of tumors by hyperdiploid or non-hyperdiploid status revealed significant differences in p18 homozygous deletion. Homozygous deletion of p18 was found in 25% (2/8) of AA patients and only 1.2% (1/83) of EA patients with non-hyperdiploid tumors (p=3.2 × 10-4). A nominally significant difference among non-hyperdiploid patients was also present for overall 1 p deletion, which was observed in 2/8 (25%) of AA non-hyperdiploid tumors and 33/83 (40%) of EA with non-hyperdiploid tumors (p=0.05). No differences were observed for 1 p deletion or p18 homozygous deletion among hyperdiploid tumors between AA and EA patients. We then combined our AA dataset with an independent dataset of 8 AA MM patients generated at the Mayo Clinic, Scottsdale AZ and repeated the analysis. Interestingly, very little or no aberrations were found in the dataset from the Mayo Clinic, however, differences of p18 homozygous deletion and 16q deletion among AA and EA remained statistically significant. To determine the correlation between hemizygous and biallelic loss of p18 and poor prognosis we used the 70 gene signature (Shaughnessy, et al., 2007) as a surrogate to identify patients with poor prognosis within the Multiple Myeloma Genomics Initiative dataset. Genomic identification of significant targets in cancer (GISTIC) was used (Beroukhim et al., 2007) to identify regions of aberrant copy number that were over-represented among samples. A relationship between poor prognosis and biallelic loss was found to be statistically significant (p = 0002) while samples with hemizygous loss showed no relationship (p = 0.57). Although the size of the current AA cohort is small, these results suggest that homozygous deletions at the p18 locus may be more common among African American MM patients with non-hyperdiploid tumors which may help to explain the disparity in AA patients with MM. Array CGH is currently being conducted on an additional 40 tumors from AA MM patients for a more robust analysis. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B64.

ABSTRACTObjectives:Variation in the prevalence of eosinophilic gastrointestinal diseases in different geographical regions has not been extensively studied. The aim of the present study was to define the regional and national prevalence of eosinophilic gastrointestinal diseases, and differences in practice approaches.Patients and Methods:We administered a survey electronically to members of the American College of Gastroenterology, the American Academy of Allergy, Asthma, and Immunology, and the North American Society Pediatric Gastroenterology, Hepatology, and Nutrition. Questions pertained to the number and proportion of patients seen with eosinophilic gastroenteritis or colitis and eosinophilic esophagitis (EoE), and methods used to diagnose and treat these conditions.Results:A total of 1836 physicians responded from 10,874 requests (17% response). Extrapolating responses from our US sample, we estimated an overall prevalence of 52 and 28/100,000 for EoE and eosinophilic gastroenteritis or colitis. The patient burden of EoE is higher in urban (0.58) and suburban (0.44) compared with rural settings (0.36, P < 0.0065), observations consistent with other allergic disorders. There was also increased prevalence in northeast region when calculated by prevalence per 100,000. There was considerable variability in criteria and initial treatment options used to diagnose EoE. Only one‐third of respondents reported using diagnostic criteria proposed in a 2007 consensus document. Seventy‐one and 35% of respondents reported treating some patients with EoE with a food elimination or elemental diet, respectively.Conclusions:EoE is diagnosed more often in northeastern states and urban areas. There is considerable variability in diagnostic criteria and initial treatment approach supporting the need for additional clinical trials and consensus development.

High-frequency oscillations (HFOs) have been observed in animal and human intracranial recordings during both normal and aberrant brain states. It has been proposed that the relationship between subclasses of these oscillations can be used to identify epileptic brain. Studies of HFOs in epilepsy have been hampered by selection bias arising primarily out of the need to reduce the volume of data so that clinicians can manually review it. In this study, we introduce an algorithm for detecting and classifying these signals automatically and demonstrate the tractability of analyzing a data set of unprecedented size, over 31,000 channel-hours of intracranial electroencephalographic (iEEG) recordings from micro- and macroelectrodes in humans. Using an unsupervised approach that does not presuppose a specific number of clusters in the data, we show direct evidence for the existence of distinct classes of transient oscillations within the 100- to 500-Hz frequency range in a population of nine neocortical epilepsy patients and two controls. The number of classes we find, four (three plus one putative artifact class), is consistent with prior studies that identify “ripple” and “fast ripple” oscillations using human-intensive methods and, additionally, identifies a less examined class of mixed-frequency events.

Abstract Rationale Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies. Objectives To determine the frequency and outcome of ALI development in patients at risk and validate a lung injury prediction score (LIPS). Methods In this prospective multicenter observational cohort study, predisposing conditions and risk modifiers predictive of ALI development were identified from routine clinical data available during initial evaluation. The discrimination of the model was assessed with area under receiver operating curve (AUC). The risk of death from ALI was determined after adjustment for severity of illness and predisposing conditions. Measurements and Main Results Twenty-two hospitals enrolled 5,584 patients at risk. ALI developed a median of 2 (interquartile range 1–4) days after initial evaluation in 377 (6.8%; 148 ALI-only, 229 adult respiratory distress syndrome) patients. The frequency of ALI varied according to predisposing conditions (from 3% in pancreatitis to 26% after smoke inhalation). LIPS discriminated patients who developed ALI from those who did not with an AUC of 0.80 (95% confidence interval, 0.78–0.82). When adjusted for severity of illness and predisposing conditions, development of ALI increased the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9–5.7). Conclusions ALI occurrence varies according to predisposing conditions and carries an independently poor prognosis. Using routinely available clinical data, LIPS identifies patients at high risk for ALI early in the course of their illness. This model will alert clinicians about the risk of ALI and facilitate testing and implementation of ALI prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT00889772).

Sudden unexpected death in epilepsy is the sudden, unexplained, unexpected death of an individual with epilepsy in which postmortem examination does not reveal an anatomic or toxicologic cause of death. Patients with congenital long QT syndrome and catecholaminergic polymorphic ventricular tachycardia have been frequently initially diagnosed with epilepsy. A cardiac channel molecular autopsy of the common long QT syndrome and catecholaminergic polymorphic ventricular tachycardia-susceptibility genes was performed on an archived necropsy specimen from an 8-year-old victim of sudden unexpected death in epilepsy. A novel, sporadic missense mutation in exon 104 of the RYR2-encoded ryanodine receptor/calcium release channel (c. 14806G>A, p.Gly4936Arg) was discovered. This mutation was absent in >600 reference alleles including both parents, involved a highly conserved amino acid, and localized to a key structure-function domain. To our knowledge, this is the first postmortem molecular diagnosis of catecholaminergic polymorphic ventricular tachycardia in a patient with sudden unexpected death in epilepsy.