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Objectives: Sterile and infectious critical illnesses often result in vasoplegic shock and a robust systemic inflammatory response that are similar in presentation. The innate immune system is at the center of the response to both infectious and traumatic insults. Damage-associated molecular patterns are small molecules that are released from stressed or dying cells. Damage-associated molecular patterns activate pattern recognition receptors and coordinate the leading edge of the innate immune response. This review introduces the concept of damage-associated molecular patterns and how they activate a systemic inflammatory response, specifically in trauma, neurologic injury, and infection. It also explores how, when carried to extremes, damage-associated molecular patterns may even perpetuate multisystem organ failure., Data Sources: Basic and clinical studies were obtained from a PubMed search through August 2017., Study Selection: Articles considered include original articles, review articles, and conference proceedings., Data Extraction: An analysis of scientific, peer-reviewed data was performed. High quality preclinical and clinical studies adjudicated by the authors were included and summarized., Data Synthesis: Pattern recognition receptors respond to damage-associated molecular patterns and then activate inflammatory pathways. Damage-associated molecular patterns have been linked to the recruitment of sentinel leukocytes and the initiation of the inflammatory cascade. Damage-associated molecular patterns have been linked to many conditions in critical care illnesses. Preclinical models have added insight into how they may mediate distant organ dysfunction., Conclusions: Damage-associated molecular pattern activation and release is an important research for intensive care practitioners. It will add to our understanding of the phase and state of the innate immune response to an insult. Early work is encouraging. However, only with improved understanding of damage-associated molecular pattern activation and function, we can perhaps hope to target damage-associated molecular patterns as diagnostic and/or therapeutic modalities in the future.

Purpose of Review: Latent tuberculosis infection (LTBI) may affect over two billion individuals and serves as a potential reservoir for future active tuberculosis. The identification and treatment of LTBI in those at highest risk for progression is an essential part of tuberculosis control., Recent Findings: Interferon-γ release assays are increasingly used for targeted testing and diagnosis of latent disease. The performance of these immunodiagnostic tests has been studied in various groups and may be better than the tuberculin skin test in certain populations. Ongoing research is focused on new biomarkers that may diagnose LTBI or predict progression to active tuberculosis. Isoniazid preventive treatment is effective at reducing risk of active disease, but length of treatment and potential side-effects limit patient acceptance and compliance. Rifamycin-based regimens are increasingly studied as a shorter and perhaps less toxic alternative for preventive therapy., Summary: Identification of those with LTBI is important as it allows treatment of those at highest risk of progression to active disease and thus decreases the overall burden of tuberculosis. The development of new immunodiagnostics may further improve identification of those at risk and alternative medication regimens may increase compliance with and efficacy of preventive therapy.

Objectives: There is considerable discussion regarding "success" rates for laparoscopic antireflux surgery (LARS). We hypothesized that, in part, this was a reflection of the outcome variables used. We, therefore, defined 8 specific variables (within 3 categories) and assessed outcomes for each in a large cohort of patients., Methods: Four hundred patients (208 women; median age 52 years old) who underwent LARS at the University of Washington from 1993 to 2008 were given a comprehensive questionnaire to assess various aspects of their outcomes from LARS. In addition, we analyzed all functional studies and all endoscopies performed in these patients in our institution, whether the patients had symptoms or not, and compared the findings to all available preoperative values., Results: The median follow-up was 92 (6-175) months., Conclusions: The success or failure of LARS cannot be defined in a single domain. A comprehensive analysis of outcomes requires categorization that includes symptom response, side-effects, patient's perception and objective measurement of acid exposure, mucosal integrity, and the need for additional medical or surgical treatment. Only then can patients and physicians better understand the role of LARS and make informed decisions.

Background: Use of remifentanil during general anesthesia for cesarean delivery has been described, but its maternal and neonatal effects have not been investigated by a controlled study., Methods: In a randomized, double-blind, controlled study, patients undergoing elective cesarean delivery received an intravenous bolus of 1 microg/kg remifentanil (n = 20) or saline (n = 20) immediately before induction of general anesthesia. The authors compared maternal hemodynamic changes and neonatal condition and measured plasma concentrations of remifentanil., Results: The maximum increase in systolic arterial pressure from baseline after induction was smaller in the remifentanil group (median, 9 [range, -17 to 31] mmHg) compared with the control group (42 [6-73] mmHg, median difference, 33 mmHg; 95% confidence interval of difference, 23-45 mmHg; P < 0.0001). Maximum recorded values were smaller in the remifentanil group compared with the control group for systolic and mean arterial pressure and maternal heart rate. Apgar scores and time to sustained respiration were similar between groups. Two neonates in the remifentanil group were considered clinically depressed at birth and were given a single dose of naloxone. Remifentanil crossed the placenta with an umbilical venous/maternal arterial concentration ratio of 0.73 (SD, 0.17) and an umbilical arterial/umbilical venous concentration ratio of 0.60 (0.23)., Conclusions: A single bolus of 1 microg/kg remifentanil effectively attenuated hemodynamic changes after induction and tracheal intubation. However, remifentanil crosses the placenta and may cause mild neonatal depression and thus should be used for clear maternal indications when adequate facilities for neonatal resuscitation are available.

The expression of endothelin-1-like immunoreactivity in astrocytes of the human brain was investigated by the avidin-biotin-peroxidase complex method in post mortem material. A marked immunoreaction was present in reactive astrocytes around infarcts, lacunes, traumatic injuries, the lesions of progressive multifocal leuco-encephalopathy and in the cerebral cortex and white matter of Alzheimer's disease. The brains of patients who had neither history nor signs of cerebral disease exhibited only occasional immunoreactive astrocytes. A hypothesis is presented that endothelin-1 may be released from reactive astrocytes in many organic diseases of the human brain with considerable pathogenic consequences. It is known from experimental investigations that endothelin-1 may for instance cause severe vasoconstriction resulting in cell injury and that it may act as a growth factor for glial cells.