Multivariate Analysis of Predictive Factors for the Severity in Stable Patients with Severe Injury Mechanism

PURPOSE: For determining the prognosis of critically injured patients, transporting patients to medical facilities capable of providing proper assessment and management, running rapid assessment and making rapid decisions, and providing aggressive resuscitation is vital. Considering the high mortality and morbidity rates in critically injured patients, various studies have been conducted in efforts to reduce those rates. However, studies related to diagnostic factors for predicting severity in critically injured patients are still lacking. Furthermore, patients showing stable vital signs and alert mental status, who are injured via a severe trauma mechanism, may be at a risk of not receiving rapid assessment and management. Thus, this study investigates diagnostic factors, including physical examination and laboratory results, that may help predict severity in trauma patients injured via a severe trauma mechanism, but showing stable vital signs. METHODS: From March 2010 to December 2011, all trauma patients who fit into a diagnostic category that activated a major trauma team in CHA Bundang Medical Center were analyzed retrospectively. The retrospective analysis was based on prospective medical records completed at the time of arrival in the emergency department and on sequential laboratory test results. PASW statistics 18(SPSS Inc., Chicago, IL, USA) was used for the statistical analysis. Patients with relatively stable vital signs and alert mental status were selected based on a revised trauma score of more than 7 points. The final diagnosis of major trauma was made based on an injury severity score of greater than 16 points. Diagnostic variables include systolic blood pressure and respiratory rate, glasgow coma scale, initial result from focused abdominal sonography for trauma, and laboratory results from blood tests and urine analyses. To confirm the true significance of the measured values, we applied the Kolmogorov-Smirnov one sample test and the Shapiro-Wilk test. When significance was confirmed, the Student's t-test was used for comparison; when significance was not confirmed, the Mann-Whitney u-test was used. The results of focused abdominal sonography for trauma (FAST) and factors of urine analysis were analyzed using the Chi-square test or Fisher's exact test. Variables with statistical significance were selected as prognostics factors, and they were analyzed using a multivariate logistics regression model. RESULTS: A total of 269 patients activated the major trauma team. Excluding 91 patients who scored a revised trauma score of less than 7 points, 178 patients were subdivided by injury severity score to determine the final major trauma patients. Twenty-one(21) patients from 106 major trauma patients and 9 patients from 72 minor trauma patients were also excluded due to missing medical records or untested blood and urine analysis. The investigated variables with p-values less than 0.05 include the glasgow coma scale, respiratory rate, white blood cell count (WBC), serum AST and ALT, serum creatinine, blood in spot urine, and protein in spot urine. These variables could, thus, be prognostic factors in major trauma patients. A multivariate logistics regression analysis on those 8 variables showed the respiratory rate (p=0.034), WBC (p=0.005) and blood in spot urine (p=0.041) to be independent prognostic factors for predicting the clinical course of major trauma patients. CONCLUSION: In trauma patients injured via a severe trauma mechanism, but showing stable vital signs and alert mental status, the respiratory rate, WBC count and blood in the urine can be used as predictable factors for severity. Using those laboratory results, rapid assessment of major trauma patients may shorten the time to diagnosis and the time for management.

Molecular Approach for Distal Renal Tubular Acidosis Associated AE1 Mutations.

The molecular approaches to distal renal tubular acidosis (dRTA) associated AE1 mutations lead us to understand the genetic and pathophysiological aspects of the acidification defects. An unanticipated high value of the urine-blood (U-B) PCO(2) after NaHCO(3) loading observed in a case of dRTA and southeast Asian ovalocytosis (SAO) might be from a mistarget of the AE1 to the luminal membrane of type A intercalated cells. The mutations of the AE1 gene resulted in SAO and also affected renal acidification function. Notwithstanding, after the NH4Cl loading in 20 individuals with SAO, the acidification in the distal nephron was normal. The presence of both SAO and G701D mutations of AE1 gene would explain the abnormal urinary acidification in the patients with the compound heterozogosity. In terms of the effect of the mutations on trafficking of AE1, truncated kidney isoform (kAE1) of wild-type showed a 'dominant-positive effect' in rescuing the recessive mutant kAE1 (S773P or G701D) trafficking to the plasma membrane, in contrast with the dominant mutant kAE1 (R589H) resulting in a 'dominant-negative effect' when heterodimerized with the wild-type kAE1. It is notable that the dominant mutants kAE1 (R901X or G609R) expression in MDCK cells clearly results in aberrant surface expression with some mutant protein appearing at the apical membrane. These might result in net bicarbonate secretion and increasing U-B PCO(2) in the distal nephron. The molecular physiological and genetic approaches have permitted identification of the molecular defects, predominantly in transporter proteins, and should in turn prompt development of novel therapeutic strategies.

Molecular Approach for Distal Renal Tubular Acidosis Associated AE1 Mutations

The molecular approaches to distal renal tubular acidosis (dRTA) associated AE1 mutations lead us to understand the genetic and pathophysiological aspects of the acidification defects. An unanticipated high value of the urine-blood (U-B) PCO2 after NaHCO3 loading observed in a case of dRTA and southeast Asian ovalocytosis (SAO) might be from a mistarget of the AE1 to the luminal membrane of type A intercalated cells. The mutations of the AE1 gene resulted in SAO and also affected renal acidification function. Notwithstanding, after the NH4Cl loading in 20 individuals with SAO, the acidification in the distal nephron was normal. The presence of both SAO and G701D mutations of AE1 gene would explain the abnormal urinary acidification in the patients with the compound heterozogosity. In terms of the effect of the mutations on trafficking of AE1, truncated kidney isoform (kAE1) of wild-type showed a 'dominant-positive effect' in rescuing the recessive mutant kAE1 (S773P or G701D) trafficking to the plasma membrane, in contrast with the dominant mutant kAE1 (R589H) resulting in a 'dominant-negative effect' when heterodimerized with the wild-type kAE1. It is notable that the dominant mutants kAE1 (R901X or G609R) expression in MDCK cells clearly results in aberrant surface expression with some mutant protein appearing at the apical membrane. These might result in net bicarbonate secretion and increasing U-B PCO2 in the distal nephron. The molecular physiological and genetic approaches have permitted identification of the molecular defects, predominantly in transporter proteins, and should in turn prompt development of novel therapeutic strategies.