The correction index: setting the standard for recommending operative repair of pectus excavatum.

BACKGROUND: The Haller index, derived from a chest computed tomography scan, remains the standard for determining candidacy for pectus excavatum repair (Haller index≥3.25). However, it has been suggested that this index may not accurately reflect pectus severity in patients with abnormal chest wall morphologies. This study explores a new, more appropriate criteria for recommending repair based on a correction index, while still incorporating the standard set by the Haller index. METHODS: A database of 75 patients with pectus excavatum who received computed tomography scans was compiled. For each patient, a staff radiologist calculated the Haller index, a correction index, and an ideal chest index from the computed tomography image with the greatest sternal depression. A correlation was assessed between all Haller and correction indices and separately for those with standard and nonstandard chest dimensions as assessed by an ideal chest index. RESULTS: There was a modest correlation between the Haller and correction indices measured in this cohort (r=0.79; p<0.0001). When patients with aberrant ideal chest dimensions were removed from analysis, Haller and correction indices showed a stronger correlation (r=0.86; p<0.0001). CONCLUSIONS: The correction index provides an accurate assessment of pectus severity, and by the nature of the measurement, reflects the potential degree of operative repair. The Haller index correlates well with the correction index in pectus patients with standard chest wall dimensions, but is quite discrepant in the nonstandard chest. We recommend operative repair for pectus excavatum with a correction index of 28% or more, because this value correlates with the long-accepted standard (Haller index≥3.25) and this index remains accurate even in nonstandard chest morphologies.

Association of increasing burn severity in mice with delayed mobilization of circulating angiogenic cells.

OBJECTIVE: To perform a systematic exploration of the phenomenon of mobilization of circulating angiogenic cells (CACs) in an animal model. This phenomenon has been observed in patients with cutaneous burn wounds and may be an important mechanism for vasculogenesis in burn wound healing. DESIGN: We used a murine model, in which burn depth can be varied precisely, and a validated culture method for quantifying circulating CACs. SETTING: Michael D. Hendrix Burn Research Center, Baltimore, Maryland. PARTICIPANTS: Male 129S1/SvImJ mice, aged 8 weeks, and 31 patients aged 19-59 years with burn injury on 1% to 64% of the body surface area and evidence of hemodynamic stability. MAIN OUTCOME MEASURES: Burn wound histological features, including immunohistochemistry for blood vessels with CD31 and alpha-smooth muscle actin antibodies, blood flow measured with laser Doppler perfusion imaging, and mobilization of CACs into circulating blood measured with a validated culture technique. RESULTS: Increasing burn depth resulted in a progressive delay in the time to mobilization of circulating CACs and reduced mobilization of CACs. This delay and reduction in CAC mobilization was associated with reduced perfusion and vascularization of the burn wound tissue. Analysis of CACs in the peripheral blood of the human patients, using a similar culture assay, confirmed results previously obtained by flow cytometry, that CAC levels peak early after the burn wound. CONCLUSION: If CAC mobilization and wound perfusion are important determinants of clinical outcome, then strategies designed to augment angiogenic responses may improve outcome in patients with severe burn wounds.

Impaired angiogenesis and mobilization of circulating angiogenic cells in HIF-1alpha heterozygous-null mice after burn wounding.

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that controls vascular responses to hypoxia and ischemia. In this study, mice that were heterozygous (HET) for a null allele at the locus encoding the HIF-1alpha subunit (HET mice) and their wild-type (WT) littermates were subjected to a thermal injury involving 10% of the body surface area. HIF-1alpha protein levels were increased in burn wounds of WT but not of HET mice on day 2. The serum levels of stromal-derived factor 1alpha, which binds to CXCR4, were increased on day 2 in WT but not in HET mice. Circulating angiogenic cells were also increased on day 2 in WT but not in HET mice and included CXCR4(+)Sca1(+) cells. Laser Doppler perfusion imaging demonstrated increased blood flow in burn wounds of WT but not HET mice on day 7. Immunohistochemistry on day 7 revealed a reduced number of CD31(+) vessels at the healing margin of burn wounds in HET as compared with WT mice. Vessel maturation was also impaired in wounds of HET mice as determined by the number of alpha-smooth muscle actin-positive vessels on day 21. The remaining wound area on day 14 was significantly increased in HET mice compared with WT littermates. The percentage of healed wounds on day 14 was significantly decreased in HET mice. These data delineate a signaling pathway by which HIF-1 promotes angiogenesis during burn wound healing.