Gregory Goodwin

Intoxication and injury

The relationship between alcohol use and injury severity was investigated in trauma patients admitted to a tertiary referral hospital during a 23-month period. Admission blood alcohol levels (BALs) were obtained on 427 trauma patients, who were stratified into three groups: those with no measurable blood alcohol, those within the legal limit of 100 mg/dL, and those over the legal limit or intoxicated. The no-alcohol group had significantly lower injury severity than the other two groups (p less than 0.001). Even when the BAL was well within the legal limit, injuries suffered by those in the alcohol-positive groups were more severe than those in the no-alcohol group. Confirmatory evidence of the effect of alcohol on injury severity was reflected by a 2.3% mortality in alcohol-negative patients compared with a 13.3% death rate in alcohol-positive patients (p less than 0.0001). To assess the potentially confounding effect of alcohol on injury scoring accuracy, we examined the change in Glasgow Coma Scale (GCS) scores following admission. No significant differences were found when admission GCS values were compared with GCS determinations made 24 hours following admission by separate observers. To correct for any potential bias as a tertiary referral center, repeat analysis with exclusion of transferred patients was done with essentially no change in results. Our data revealed a highly significant relationship between alcohol use, degree of injury, and resource consumption.

Practical evaluation of trauma deaths

The TRISS method of auditing trauma deaths necessitates audit of patients with minor injuries who die of their underlying medical problems. Using an anatomic definition of injury as a criterion for audit, as suggested by Wesson et al. at the Hospital for Sick Children in Toronto, excludes patients with minor injuries but necessitates audit of patients who expired due to systems problems rather than in-hospital patient care. We propose combining the TRISS and Toronto methods in order to identify the deaths truly appropriate for detailed review of hospital care. Fifty-four trauma deaths over a 22-month period were audited and categorized as frankly preventable, potentially salvageable, or nonpreventable. Considering only in-hospital care, the deaths designated as potentially salvageable by audit were likely to be identified by both TRISS and Toronto, while deaths targeted by only one system were more likely to be nonpreventable by audit. The predictive value of this combination of methods (84.6%) was better than Toronto (52.4%) or TRISS (54.5%) using audit results as the standard for comparison. This simple computerized method may serve as a practical and inexpensive method of targeting deaths for in-depth review.

A Case of HDR Syndrome and Ichthyosis: Dual Diagnosis by Whole-Genome Sequencing of Novel Mutations in GATA3 and STS Genes

CONTEXT Atypical presentations of complex multisystem disorders may elude diagnosis based on clinical findings only. Appropriate diagnostic tests may not be available or available tests may not provide appropriate coverage of relevant genomic regions for patients with complex phenotypes. Clinical whole-exome/-genome sequencing is often considered for complex patients lacking a definitive diagnosis. CASE DESCRIPTION A boy who is now 7 years old presented as a newborn with congenital ichthyosis. At 6 weeks of age, he presented with failure to thrive and hypoparathyroidism. At 4 years of age, he was diagnosed with sensorineural hearing loss. Whole-genome sequencing identified novel mutations in GATA3, which causes HDR syndrome (hypoparathyroidism and deafness), and STS, which causes X -linked congenital ichthyosis. CONCLUSION Whole-genome sequencing led to a definitive clinical diagnosis in a case where no other clinical test was available for GATA3, and no sequencing panel would have included both genes because they have disparate phenotypes. This case demonstrates the power of whole-genome (or exome) sequencing for patients with complex clinical presentations involving endocrine abnormalities.

The translocation of inhaled silicon dioxide: An empirically derived compartmental model

Abstract The movement of inhaled silicon dioxide particles was studied by measuring the amounts in alveolar fluid and cells, lung tissue, and lymphoid tissue during the 6 months following short-term aerosol exposure of Fischer 344 rats. A variety of first-order compartmental models were fit to data from nine exposure experiments to identify the most feasible biologic pathways for the transfer of material among these sites and out of the body. A multivariate least-squares approach was used to simultaneously fit the data from several compartments. The results indicate that transfer between alveolar cells and lung tissue occurs in both directions, suggesting that silica can reenter the alveolar space from the lung tissue. This feature has not been included in previously published models. The results also indicate that transfer from lung tissue to the mediastinal lymph nodes and thymus is indirect; there are one or more unidentified extrapulmonary compartments that receive silica from the lung. Rates of transfer among compartments were dependent on mineral type (quartz or cristobalite), heat treatment, and exposure dose. There was no evidence for direct clearance from the alveolar space via the tracheobronchial tract.