Validation of Thermal Imaging and the ALT-70 Prediction Model to Differentiate Cellulitis From Pseudocellulitis.

Importance: Cellulitis is misdiagnosed in up to 30% of cases due to mimic conditions termed pseudocellulitis. The resulting overuse of antibiotics is a threat to patient safety and public health. Surface thermal imaging and the ALT-70 (asymmetry, leukocytosis, tachycardia, and age ≥70 years) prediction model have been proposed as tools to help differentiate cellulitis from pseudocellulitis. Objectives: To validate differences in skin surface temperatures between patients with cellulitis and patients with pseudocellulitis, assess the optimal temperature measure and cut point for differentiating cellulitis from pseudocellulitis, and compare the performance of skin surface temperature and the ALT-70 prediction model in differentiating cellulitis from pseudocellulitis. Design, Setting, and Participants: This prospective diagnostic validation study was conducted among patients who presented to the emergency department with acute dermatologic lower extremity symptoms from October 11, 2018, through March 11, 2020. Statistical analysis was performed from July 2020 to March 2021 with additional work conducted in September 2023. Main Outcomes and Measures: Temperature measures for affected and unaffected skin were obtained. Cellulitis vs pseudocellulitis was assessed by a 6-physician, independent consensus review. Differences in temperature measures were compared using the t test. Logistic regression was used to identify the temperature measure and associated cut point with the optimal performance for discriminating between cellulitis and pseudocellulitis. Diagnostic performance characteristics for the ALT-70 prediction model, surface skin temperature, and both combined were also assessed. Results: The final sample included 204 participants (mean [SD] age, 56.6 [16.5] years; 121 men [59.3%]), 92 (45.1%) of whom had a consensus diagnosis of cellulitis. There were statistically significant differences in all skin surface temperature measures (mean temperature, maximum temperature, and gradients) between cellulitis and pseudocellulitis. The maximum temperature of the affected limb for patients with cellulitis was 33.2 °C compared with 31.2 °C for those with pseudocellulitis (difference, 2.0 °C [95% CI, 1.3-2.7 °C]; P < .001). The maximum temperature was the optimal temperature measure with a cut point of 31.2 °C in the affected skin, yielding a mean (SD) negative predictive value of 93.5% (4.7%) and a sensitivity of 96.8% (2.3%). The sensitivity of all 3 measures remained above 90%, while specificity varied considerably (ALT-70, 22.0% [95% CI, 15.8%-28.1%]; maximum temperature of the affected limb, 38.4% [95% CI, 31.7%-45.1%]; combination measure, 53.9% [95% CI, 46.5%-61.2%]). Conclusions and Relevance: In this large diagnostic validation study, significant differences in skin surface temperature measures were observed between cases of cellulitis and cases of pseudocellulitis. Thermal imaging and the ALT-70 both demonstrated high sensitivity, but specificity was improved by combining the 2 measures. These findings support the potential of thermal imaging, alone or in combination with the ALT-70 prediction model, as a diagnostic adjunct that may reduce overdiagnosis of cellulitis.

Common gamma chain-signaling cytokines promote proliferation of T-cell acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: The identification of signals critical for the pathophysiology of T-cell acute lymphoblastic leukemia (T-ALL) should contribute to the development of novel, more effective therapeutic strategies. Common gamma-chain signaling cytokines (gammac-cytokines) - interleukins 2, 4, 7, 9 and 15 - differentially regulate T-cell development, survival, proliferation and differentiation. Although studies exist on some individual cytokines, no comprehensive analysis of the effects of the Zc-cytokine family on malignant T cells has been reported. Here, we examined the effect of Zc-cytokines on T-ALL proliferation. DESIGN AND METHODS: Primary leukemic cells were collected at diagnosis from the blood or bone marrow of children with T-ALL. The cells were immunophenotyped and classified according to maturation stage. Proliferative responses to gammac-cytokines were assessed by 3H-thymidine incorporation. RESULTS: All gammac-cytokines promoted proliferation of primary T-ALL cells. Interleukin (IL)-7 was the cytokine that most frequently induced leukemic cell proliferation and promoted the most robust responses. IL-4 preferentially stimulated proliferation of samples with a more mature immunophenotype, whereas CD1a-positive cortical T-ALL cells were less responsive to IL-9. Finally, combinations of two Zc-cytokines showed synergistic or additive proliferative effects. INTERPRETATION AND CONCLUSIONS: This study indicates that all the gammac-cytokines tested can stimulate proliferation of leukemic T cells and suggests that synergistic effects may occur in vivo. We present the first demonstration that IL-9 and IL-15 can provide a proliferative signal to T-ALL cells. Importantly, our results support the hypothesis that IL-7 may function as a critical regulator of T-ALL and that its activity may be potentiated by other Zc-cytokines.