The strict limit in proliferative potential of normal human somatic cells - a process known as replicative senescence - is highly relevant to the immune system, because clonal expansion is fundamental to adaptive immunity. CD8(+) T cells that undergo extensive rounds of antigen-driven proliferation in cell culture invariably reach the end stage of replicative senescence, characterized by irreversible cell-cycle arrest and a critically short telomere length. Cultures of senescent CD8(+) T cells also show resistance to apoptosis, permanent loss of CD28 expression, altered cytokine profiles, reduced ability to respond to stress, and various functional changes. Cells with similar characteristics accumulate during normal aging as well as in younger persons infected with human immunodeficiency virus, suggesting that the process of replicative senescence is not an artifact of cell culture but is also occurring in vivo. Interestingly, in elderly persons, the presence of high proportions of CD8(+) T cells with characteristics of replicative senescence is correlated with reduced antibody responses to vaccines as well as with osteoporotic fractures. CD8(+)CD28(-) T cells also accumulate in patients with certain types of cancer. The emerging picture is that senescent CD8(+) T cells may modulate both immune and non-immune functions, contributing not only to reduced anti-viral immunity but also to diverse age-related pathologies.
Background: The goal of preoperative fasting is to prevent pulmonary aspiration during general anesthesia. Fasting times are often prolonged leading to patient discomfort and risk for adverse events. This retrospective quality improvement survey evaluated effective nil-per-os (NPO) times and causes for prolonged NPO times with the aim to suggest improvement strategies by a newly founded fasting task force.Methods: Data from all electronic anesthesia records from 2019 at our institution were reviewed for fasting times. Our NPO instructions follow American Society of Anesthesiology guidelines and are calculated based on the patient’s arrival time (90 min before OR time). Primary outcome was the effective NPO time for clear liquids, secondary outcomes were incidence of delays and the parental compliance with the NPO instructions. Data are presented as median (interquartile range).Results: 9,625 cases were included in the analysis. NPO time was documented in 72.1% with a median effective NPO time of 7:13 h (7:36). OR in room times were documented in 72.8%, 2,075 (29.5%; median time 0:10 h [0:21]) were earlier and 4,939 (70.5%; median time 0:29 h [0:54]) were later than scheduled. Parental NPO compliance showed a median deviation for clear liquid intake of 0:55 h (8:30).Conclusions: This study revealed that effective NPO times were longer than current ASA guidelines. Contributing causes include case delays and parental non-compliance to NPO instructions. Thus, task force recommendations include change NPO instruction calculations to scheduled OR time versus arrival time, and encourage parents to give their child clear liquids at the instructed time.
Learning Objectives: Lactate is a biomarker that is followed to assess inadequate perfusion in patients with severe sepsis and septic shock. In many clinical laboratories a normal lactate level is < 2.0 -2.2 mmol/L depending on the assay. The liver is the main organ of lactate clearance. Patients with end-state liver disease (ESLD) are presumed to have significant impairment in lactate clearance. However, we find no evidence in the literature demonstrating that these patients have baseline elevated lactate levels. We sought to determine the relationship between measured whole blood lactate and Model for End-Stage Liver Disease (MELD) score in patients with ESLD undergoing orthotopic liver or combined liver and kidney transplants. Methods: A retrospective chart review and analysis was performed with the first intraoperative measured whole blood lactate level and calculated MELD score of 344 patients undergoing either orthotopic liver transplant or combined orthotopic liver and kidney transplant at . These patients had documented ESLD and were without active infection, severe sepsis or septic shock. The UCSF Committee for Human Research study approved the study. The relationship between MELD scores and elevated lactate (>2.0 mmol/L) was analyzed by logistic regression and receiver operating characteristic (ROC) curves. Results: MELD score was significantly related to elevated lactate (P<0.0001) with an area under the ROC curve of 0.76 (95% CI 0.70 to 0.82), when utilizing a lactate level >2.0 mmol/L as a threshold for abnormal lactate. For MELD scores < 10, 10-19, 20-29, 30-34, and ≥ 35, the percentage of patients that had an elevated lactate were 13.5%, 9.6%, 15.9%, 30.4%, and 54.8% respectively. Conclusions: Higher baseline lactate levels are an important consideration for patients with ESLD who develop severe sepsis or septic shock. In ESLD patients, a mildly elevated lactate may represent end-organ dysfunction rather than inadequate perfusion, and therefore a false positive for diagnostic criteria for sepsis.
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