sodium-oxybate and Neoplasms

To address the impact of underlying immune conditions on the course of septic shock with respect to both mortality and the development of acute infectious and noninfectious complications.. An 8-year (2008-2015) monocenter retrospective study.. A medical ICU in a tertiary care center.. Patients diagnosed for septic shock within the first 48 hours of ICU admission were included. Patients were classified in four subgroups with respect to their immune status: nonimmunocompromised and immunocompromised distributed into hematologic or solid malignancies and nonmalignant immunosuppression. Outcomes were in-hospital death and the development of ischemic and hemorrhagic complications and ICU-acquired infections. The determinants of death and complications were addressed by multivariate competing risk analysis.. None.. Eight hundred one patients were included. Among them, 305 (38%) were immunocompromised, distributed into solid tumors (122), hematologic malignancies (106), and nonmalignant immunosuppression (77). The overall 3-day, in-ICU, and in-hospital mortality rates were 14.1%, 37.3%, and 41.3%, respectively. Patients with solid tumors displayed increased in-hospital mortality (cause-specific hazard, 2.20 [95% CI, 1.64-2.96]; p < 0.001). ICU-acquired infections occurred in 211 of the 3-day survivors (33%). In addition, 95 (11.8%) and 70 (8.7%) patients exhibited severe ischemic or hemorrhagic complications during the ICU stay. There was no association between the immune status and the occurrence of ICU-acquired infections. Nonmalignant immunosuppression and hematologic malignancies were independently associated with increased risks of severe ischemic events (cause-specific hazard, 2.12 [1.14-3.96]; p = 0.02) and hemorrhage (cause-specific hazard, 3.17 [1.41-7.13]; p = 0.005), respectively.. The underlying immune status impacts on the course of septic shock and on the susceptibility to ICU-acquired complications. This emphasizes the complexity of sepsis syndromes in relation with comorbid conditions and raises the question of the relevant endpoints in clinical studies.

Topics: Aged; Aged, 80 and over; Cross Infection; Female; Hospital Mortality; Humans; Immunocompromised Host; Intensive Care Units; Length of Stay; Male; Middle Aged; Multivariate Analysis; Neoplasms; Organ Dysfunction Scores; Retrospective Studies; Risk Factors; Severity of Illness Index; Shock, Septic; Sodium Oxybate; Tertiary Care Centers

Histone deacetylases inhibitors (HDIs) induce growth arrest and apoptosis in a variety of human cancer cells. Sodium butyrate (NaB), a histone deacetylase inhibitor, has been shown to cause a G(1) cell cycle arrest by inducing p21(WAF1/CIP1) in a p53-independent manner. In this report, we present evidence for activation of p53 pathway by NaB and its role in the NaB-mediated growth suppression. Addition of NaB increased the levels of p53 involving a p14(ARF)-dependent post-transcriptional mechanism. NaB induced p53 is functional as it activated p53-specific reporter, induced the level of p21(WAF1/CIP1), inhibited cellular DNA synthesis and induced apoptosis. By using HPV 16 E6 stable transfectants as well as p53 null cancer cells, we show that NaB suppresses the growth of WT p53 containing cells more efficiently. NaB inhibited DNA synthesis to similar extent both in the presence and absence of p53. However, NaB treatment lead to a major G(2)/M arrest of cells in the presence of p53, while cells without wild-type p53 accumulated mainly in G(1) phase of the cell cycle. Furthermore, apoptosis induction by NaB is greatly reduced in the absence of p53. These results suggest that p53 pathway mediates in part growth suppression by NaB and the p53 status may be an important determinant of chemosensitivity in HDI based cancer chemotherapy.

Topics: Apoptosis; Blotting, Western; Bromodeoxyuridine; Cell Cycle Proteins; Cell Division; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p21; DNA; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Flow Cytometry; G1 Phase; G2 Phase; Histone Deacetylase Inhibitors; Humans; Neoplasms; Oncogene Proteins, Viral; Protein Structure, Tertiary; Repressor Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA Processing, Post-Transcriptional; Sodium Oxybate; Transfection; Tumor Suppressor Protein p14ARF; Tumor Suppressor Protein p53

Topics: Adult; Anesthesia; Female; Humans; Hydroxybutyrates; Neoplasms; Pain, Postoperative; Sodium Oxybate