To define which variables upon ICU admission could be related to the presence of coinfection using CHAID (Chi-squared Automatic Interaction Detection) analysis. A secondary analysis from a prospective, multicentre, observational study (2009-2014) in ICU patients with confirmed A(H1N1)pdm09 infection. We assessed the potential of biomarkers and clinical variables upon admission to the ICU for coinfection diagnosis using CHAID analysis. Performance of cut-off points obtained was determined on the basis of the binominal distributions of the true (+) and true (-) results. Of the 972 patients included, 196 (20.3%) had coinfection. Procalcitonin (PCT; ng/mL 2.4 vs. 0.5, p < 0.001), but not C-reactive protein (CRP; mg/dL 25 vs. 38.5; p = 0.62) was higher in patients with coinfection. In CHAID analyses, PCT was the most important variable for coinfection. PCT <0.29 ng/mL showed high sensitivity (Se = 88.2%), low Sp (33.2%) and high negative predictive value (NPV = 91.9%). The absence of shock improved classification capacity. Thus, for PCT <0.29 ng/mL, the Se was 84%, the Sp 43% and an NPV of 94% with a post-test probability of coinfection of only 6%. PCT has a high negative predictive value (94%) and lower PCT levels seems to be a good tool for excluding coinfection, particularly for patients without shock.

BACKGROUND: Despite wide use of noninvasive ventilation (NIV) in several clinical settings, the beneficial effects of NIV in patients with hypoxemic acute respiratory failure (ARF) due to influenza infection remain controversial. The aim of this study was to identify the profile of patients with risk factors for NIV failure using chi-square automatic interaction detection (CHAID) analysis and to determine whether NIV failure is associated with ICU mortality. METHODS: This work was a secondary analysis from prospective and observational multi-center analysis in critically ill subjects admitted to the ICU with ARF due to influenza infection requiring mechanical ventilation. Three groups of subjects were compared: (1) subjects who received NIV immediately after ICU admission for ARF and then failed (NIV failure group); (2) subjects who received NIV immediately after ICU admission for ARF and then succeeded (NIV success group); and (3) subjects who received invasive mechanical ventilation immediately after ICU admission for ARF (invasive mechanical ventilation group). Profiles of subjects with risk factors for NIV failure were obtained using CHAID analysis. RESULTS: Of 1,898 subjects, 806 underwent NIV, and 56.8% of them failed. Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, infiltrates in chest radiograph, and ICU mortality (38.4% vs 6.3%) were higher ( P < .001) in the NIV failure than in the NIV success group. SOFA score was the variable most associated with NIV failure, and 2 cutoffs were determined. Subjects with SOFA ≥ 5 had a higher risk of NIV failure (odds ratio = 3.3, 95% CI 2.4–4.5). ICU mortality was higher in subjects with NIV failure (38.4%) compared with invasive mechanical ventilation subjects (31.3%, P = .018), and NIV failure was associated with increased ICU mortality (odds ratio = 11.4, 95% CI 6.5–20.1). CONCLUSIONS: An automatic and non-subjective algorithm based on CHAID decision-tree analysis can help to define the profile of patients with different risks of NIV failure, which might be a promising tool to assist in clinical decision making to avoid the possible complications associated with NIV failure.

Sonia Alcolea, Rosa Antón, Mercedes Camacho, Marta Soler, Arantzazu Alfranca, Francesc-Xavier Avilés-Jurado, Juan-Miguel Redondo, Miquel Quer, Xavier León, Luis Vila

Head and neck squamous cell carcinoma (HNSCC) is characterized by high rates of mortality and treatment-related morbidity, underscoring the urgent need for innovative and safe treatment strategies and diagnosis practices. Mitochondrial dysfunction is a hallmark of cancer and can lead to the accumulation of tricarboxylic acid cycle intermediates, such as succinate, which function as oncometabolites. In addition to its role in cancer development through epigenetic events, succinate is an extracellular signal transducer that modulates immune response, angiogenesis and cell invasion by activating its cognate receptor SUCNR1. Here, we explored the potential value of the circulating succinate and related genes in HNSCC diagnosis and prognosis. We determined the succinate levels in the serum of 66 pathologically confirmed, untreated patients with HNSCC and 20 healthy controls. We also surveyed the expression of the genes related to succinate metabolism and signaling in tumoral and nontumoral adjacent tissue and in normal mucosa from 50 patients. Finally, we performed immunohistochemical analysis of SUCNR1 in mucosal samples. The results showed that the circulating levels of succinate were higher in patients with HNSCC than in the healthy controls. Additionally, the expression of SUCNR1, HIF-1α, succinate dehydrogenase (SDH) A, and SDHB was higher in the tumor tissue than in the matched normal mucosa. Consistent with this, immunohistochemical analysis revealed an increase in SUCNR1 protein expression in tumoral and nontumoral adjacent tissue. High SUCNR1 and SDHA expression levels were associated with poor locoregional control, and the locoregional recurrence-free survival rate was significantly lower in patients with high SUCNR1 and SDHA expression than in their peers with lower levels (77.1% [95% CI: 48.9–100.0] vs. 16.7% [95% CI: 0.0–44.4], p = 0.018). Thus, the circulating succinate levels are elevated in HNSCC and high SUCNR1/SDHA expression predicts poor locoregional disease-free survival, identifying this oncometabolite as a potentially valuable noninvasive biomarker for HNSCC diagnosis and prognosis.