Serum CXCL12 levels on hospital admission predict mortality in patients with severe sepsis/septic shock.

OBJECTIVES: We evaluated serum levels of CXCL12 in patients with severe sepsis/septic shock and controls. METHODS: We enrolled 27 patients admitted to our emergency department with severe sepsis/septic shock and 20 healthy controls. Complete blood count, serum levels of CXCL12, C-reactive protein, lactate, Charlson comorbidity index, sequential organ failure score on hospital admission, and inhospital mortality were evaluated at baseline (T0) and after 24 hours (T24). RESULTS: Mean serum levels of CXCL12 were higher in patients with severe sepsis/septic shock than in healthy subjects (3121 vs 1991 pg/mL; P < .001). We also found that patient who survived had lower serum levels of CXCL12 than those who died (2630 vs 3957 pg/mL; P < .001) but still higher than controls (2630 vs 1991 pg/mL; P = .001) on admission. CXCL12 serum levels were higher in patients with serum lactate greater than 4 mmol/L. CONCLUSIONS: Our data suggest a possible role for CXCL12 as a prognostic marker in severe sepsis/septic shock and give background evidence for larger trials to evaluate the pathophysiologic and clinical role of CXCL12 in sepsis, with respect to other markers of inflammation and hypoxia.

The role of lung ultrasound as a frontline diagnostic tool in the era of COVID-19 outbreak.

The diffusion of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) worldwide prompted the World Health Organization to declare the status of pandemic. The molecular diagnosis of SARS-CoV-2 infection is based on the detection of viral RNA on different biological specimens. Unfortunately, the test may require several hours to be performed. In the present study, we evaluated the diagnostic accuracy of lung point-of-care ultrasound (POCUS) for SARS-CoV-2 pneumonia in a cohort of symptomatic patients admitted to one emergency department (ED) in a high-prevalence setting. This retrospective study enrolled all patients who visited one ED with suspected respiratory infection in March 2020. All the patients were tested (usually twice if the first was negative) for SARS-CoV-2 on ED admission. The reference standard was considered positive if at least one specimen was positive. If all the specimens tested negative, the reference was considered negative. Diagnostic accuracy was evaluated using sensitivity, specificity, and positive and negative predictive value. Of the 444 symptomatic patients who were admitted to the ED in the study period, the result of the lung POCUS test was available for 384 (86.5%). The sensitivity of the test was 92.0% (95% CI 88.2-94.9%), and the specificity was 64.9% (95% CI 54.6-74.4%). We observed a prevalence of SARS-CoV-2 infection of 74.7%. In this setting, the positive and negative predicted values were 88.6% (95% CI 84.4-92.0) and 73.3% (95% CI 62.6-82.2%), respectively. Lung POCUS is a sensitive first-line screening tool for ED patients presenting with symptoms suggestive of SARS-CoV-2 infection.

SAA1 is over-expressed in plasma of non small cell lung cancer patients with poor outcome after treatment with epidermal growth factor receptor tyrosine-kinase inhibitors.

It has been shown that a proteomic algorithm based on 8 MALDI TOF MS signals obtained from plasma of NSCLC patients treated with EGFR TKIs, is able to predict patients' clinical outcome. In the current study, we identified the proteins originating 4 out of 8 mass signals in the classification algorithm. Plasma samples collected before the beginning of gefitinib therapy were analyzed by MALDI TOF MS and classified according to the proteomic algorithm in good and poor profiles. Two pools of good and poor classified samples were prepared using MARS and ProteoMiner Protein Enrichment kit before 2DE analysis. Proteins differentially expressed between good and poor 2DE samples were excised from gels and analyzed with MALDI TOF MS and LC MS/MS. The identified proteins were validated by Immunodepletion and Western blot analyses. serum amyloid A protein 1 (SAA1), together with its two truncated forms, was over-expressed in plasma of poor classified patients, and was identified as the protein that generates 4 out of the 8 mass signals composing the proteomic algorithm VeriStrat. SAA levels measured by ELISA in 97 NSCLC patients treated with gefitinib correlated with the clinical outcome of the patients. This article is part of a Special Issue entitled: Integrated omics.

Changes in plasma mass-spectral profile in course of treatment of non-small cell lung cancer patients with epidermal growth factor receptor tyrosine kinase inhibitors.

INTRODUCTION: Our previous study showed that pretreatment serum or plasma Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry may predict clinical outcome of non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In this study, plasma proteomic profiles of NSCLC patients were evaluated in the course of EGFR TKIs therapy. MATERIALS AND METHODS: Plasma samples were collected at baseline, in the course of gefitinib therapy and at treatment withdrawal. Samples were analyzed by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Acquired spectra were classified by the VeriStrat test into "good" and "poor" profiles. The association between VeriStrat classification and progression-free survival (PFS) and overall survival (OS), and types of clinical progression, was analyzed. RESULTS: Plasma samples from 111 NSCLC patients treated with gefitinib were processed. VeriStrat "good" classification at baseline correlated with longer PFS (hazard ratio [HR], 0.54; 95% confidence interval, 0.35-0.83; p = 0.005) and OS (HR, 0.40; 95% confidence interval, 0.26-0.61; p < 0.0001), when compared with VeriStrat "poor." Multivariate analysis confirmed longer PFS (HR, 0.52; p = 0.025) and OS (HR, 0.44; p = 0.001) in patients classified as VeriStrat "good", when VeriStrat was considered as a time-dependent variable. About one-third of baseline "good" classifications had changed to "poor" at the time of treatment withdrawal; progression in these patients was associated with the development of new lesions. CONCLUSIONS: Our findings support the role of VeriStrat in the assistance in treatment selection of NSCLC patients for EGFR TKI therapy and its potential utility in treatment monitoring.