Admission Laboratory Values Accurately Predict In-hospital Mortality: a Retrospective Cohort Study.

BACKGROUND: The greater the severity of illness of a patient, the more likely the patient will have a poor hospital outcome. However, hospital-wide severity of illness scores that are simple, widely available, and not diagnosis-specific are still needed. Laboratory tests could potentially be used as an alternative to estimate severity of illness. OBJECTIVE: To evaluate the ability of hospital laboratory tests, as measures of severity of illness, to predict in-hospital mortality among hospitalized patients, and therefore, their potential as an alternative method to severity of illness risk adjustment. DESIGNS AND PATIENTS: A retrospective cohort study among 38,367 adult non-trauma patients admitted to the University of Maryland Medical Center between November 2015 and November 2017 was performed. Laboratory tests (hemoglobin, platelet count, white blood cell count, urea nitrogen, creatinine, glucose, sodium, potassium, and total bicarbonate (HCO3)) were included when ordered within 24 h from the time of hospital admission. A multivariable logistic regression model to predict in-hospital mortality was constructed using a section of our cohort (n = 21,003). MAIN MEASURES: Model performance was evaluated using the c-statistic and the Hosmer-Lemeshow (HL) test. In addition, a calibration belt was constructed to determine a confidence interval around the calibration curve with the purpose of identifying ranges of miscalibration. KEY RESULTS: Patient age and all laboratory tests predicted mortality with good discrimination (c = 0.79). Patients with abnormal HCO3 levels or leukocyte counts at admission were twice as likely to die during their hospital stay as patients with normal results. A good model calibration and fit were observed (HL = 13.9, p = 0.18). CONCLUSIONS: Admission laboratory tests are able to predict in-hospital mortality with good accuracy, providing an objective and widely accessible approach to severity of illness risk adjustment.

Cytokine requirements for induction of systemic and mucosal CTL after nasal immunization.

Cholera toxin (CT) is frequently used as an experimental adjuvant intranasally for the induction of systemic and mucosal immunity. However, CT is highly reactogenic and not approved for use in humans. To define the cytokine requirements for the nasal activation of the systemic and mucosal immune system, and to design new adjuvants with efficacy similar to CT, we defined the cytokines that were able to replace CT as a nasal adjuvant for the induction of CTL. BALB/c mice were nasally immunized with an HIV immunogen that contains an MHC class I-restricted CTL epitope +/- cytokines and tested for HIV-specific immune responses. We found that combinations of IL-1alpha plus IL-18, IL-1alpha plus IL-12, and IL-1alpha plus IL-12 plus GM-CSF each induced optimal splenocyte anti-HIV CTL responses in immunized mice (range 60-71% peptide-specific (51)Cr release). Peak H-2D(d)-peptide tetramer-binding T cell responses induced by cytokine combinations were up to 5.5% of CD8(+) PBMC. Nasal immunization with HIV immunogen and IL-1alpha, IL-12, and GM-CSF also induced Ag-specific IFN-gamma-secreting cells in the draining cervical lymph node and the lung. The use of IL-1alpha, IL-12, and GM-CSF as nasal adjuvants was associated with an increased expression of MHC class II and B7.1 on nonlymphocytes within the nasal-associated lymphoid tissue/nasal mucosa. Thus, IL-1alpha, IL-12, IL-18, and GM-CSF are critical cytokines for the induction of systemic and mucosal CTL after nasal immunization. Moreover, these cytokines may serve as effective adjuvants for nasal vaccine delivery.

Functional equivalency of B7-1 and B7-2 for costimulating plasmid DNA vaccine-elicited CTL responses.

A costimulatory signal in addition to an Ag-specific stimulus is required for optimal activation of T lymphocytes. CD28, the primary positive costimulatory receptor on T cells, has two identified ligands, B7-1 and B7-2. Whether B7-1 and B7-2 have identical, overlapping, or distinct functions remains unresolved. In this study, we show that mice lacking B7-2 were unable to generate CTL responses following immunization with a plasmid DNA vaccine. The ability of these B7-2-deficient mice to generate CTL responses following plasmid gp120 DNA vaccination was fully reconstituted by coadministering either a plasmid expressing B7-2 or B7-1. Moreover, the ability to generate CTL responses following plasmid DNA vaccination in mice lacking both B7-1 and B7-2 could be reconstituted by administering either plasmid B7-1 or plasmid B7-2 with the vaccine construct. These data demonstrate that either B7-1 or B7-2 administered concurrently with a plasmid DNA vaccine can fully costimulate vaccine-elicited CTL responses. Functional differences between B7-1 and B7-2 observed in vivo therefore may not reflect inherent differences in the interactions of CD28 with these ligands.