Do Complexity Measures of Frontal EEG Distinguish Loss of Consciousness in Geriatric Patients Under Anesthesia?

While geriatric patients have a high likelihood of requiring anesthesia, they carry an increased risk for adverse cognitive outcomes from its use. Previous work suggests this could be mitigated by better intraoperative monitoring using indexes defined by several processed electroencephalogram (EEG) measures. Unfortunately, inconsistencies between patients and anesthetic agents in current analysis techniques have limited the adoption of EEG as standard of care. In attempts to identify new analyses that discriminate clinically-relevant anesthesia timepoints, we tested 1/f frequency scaling as well as measures of complexity from nonlinear dynamics. Specifically, we tested whether analyses that characterize time-delayed embeddings, correlation dimension (CD), phase-space geometric analysis, and multiscale entropy (MSE) capture loss-of-consciousness changes in EEG activity. We performed these analyses on EEG activity collected from a traditionally hard-to-monitor patient population: geriatric patients on beta-adrenergic blockade who were anesthetized using a combination of fentanyl and propofol. We compared these analyses to traditional frequency-derived measures to test how well they discriminated EEG states before and after loss of response to verbal stimuli. We found spectral changes similar to those reported previously during loss of response. We also found significant changes in 1/f frequency scaling. Additionally, we found that our phase-space geometric characterization of time-delayed embeddings showed significant differences before and after loss of response, as did measures of MSE. Our results suggest that our new spectral and complexity measures are capable of capturing subtle differences in EEG activity with anesthesia administration-differences which future work may reveal to improve geriatric patient monitoring

Relationship between bacterial diversity, specific urethral bacteria and incident NGU in men who have sex with women

Thesis (Master's)--University of Washington, 2023Background: Nongonococcal urethritis (NGU) is a common syndrome in men that is not well understood. Prior studies have investigated factors associated with prevalent NGU, but factors associated with incident NGU have rarely been examined. We evaluated potential precursors of incident NGU in a group of men who have sex with women (MSW) attending a sexual health clinic in Seattle from August 2014 to July 2018. Methods: We conducted a nested case-control study, evaluating a subset of MSW enrolled in a cohort study designed to investigate the relationship between the male urethral microbiota and NGU. At enrollment and monthly follow-up visits, participants had a clinical examination performed at which they provided a urethral swab specimen for Gram staining and a first-void urine sample. Participants also completed a computer-assisted self-interview (CASI) to assess history of sexually transmitted infections (STIs), sexual behaviors, and other sociobehavioral data at each visit. Case visits were defined as the visit at which an individual had an incident case of NGU. NGU was defined as elevated levels of polymorphonuclear leukocytes (PMNs) when urethral discharge was examined on a Gram-stained slide in the absence of Neisseria gonorrhoeae (GC), with or without symptoms such as painful urination, itching, or urethral discharge, and was considered incident if the participant did not have NGU at the prior monthly visit. We selected the visit when the case was diagnosed with incident NGU, and the preceding visit when they were NGU-negative. Controls were matched to cases on follow-up time for both time points using a 1:1 matching ratio, matching by visit number and interval between visits. Controls were NGU-negative at both matched visits. Nucleic acid amplification testing (NAAT) for GC, Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) was performed on the urine samples using Aptima assays (Hologic, Inc., San Diego, CA). To characterize the urethral microbiota, we applied broad-range 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR) and sequencing to urine samples. We used Fisher’s exact test for comparisons of categorical characteristics and a paired t-test for continuous characteristics. Conditional logistic regression models were used to estimate odds ratios (ORs) for the association of bacterial diversity, as measured by the Shannon Diversity Index (SDI) and species richness, as well as detection of each of four bacterial species (Haemophilus influenzae, Fannyhessea vaginae, Lactobacillus iners, Streptococcus mitis) at the visit prior to diagnosis with incident NGU. Results: The 262 enrolled persons with follow-up data contributed 63 incident NGU events. Although cases and controls did not differ with respect to age, race/ethnicity, or NGU at enrollment, cases had a significantly lower level of education, used condoms less frequently with their most recent sexual partner, and were more likely to have a prior history of NGU and/or CT than controls (p≤0.03 for all). After adjusting for condom use, participants with one-unit higher SDI at the visit prior to NGU diagnosis had 10.29 times the odds of incident NGU (aOR=10.29, 95% CI: 1.49-73.16, p=0.02) compared to participants with a one-unit lower SDI. Similarly, species richness at the visit prior to NGU diagnosis was associated with increased odds of incident NGU (aOR per species = 1.08, 95% CI: 1.001-1.169, p=0.047). In a multivariate model that included all four bacterial species detected at the visit prior to NGU diagnosis, F. vaginae was associated with 29.7 times the odds of incident NGU (aOR=29.68, 95% CI: 1.55-568.26, p=0.02) compared to those without F. vaginae. Neither H. influenzae, L. iners, nor S. mitis were significantly associated with incident NGU, although MSW with S. mitis were somewhat less likely to have incident NGU. Conclusions: Higher SDI, higher species richness, and presence of F. vaginae were significantly associated with higher odds of incident NGU. Future work should involve larger longitudinal studies re-examining these factors’ associations with incident NGU to better understand these relationships and other potential risk factors for the syndrome

Remifentanil and Nitrous Oxide Anesthesia Produces a Unique Pattern of EEG Activity During Loss and Recovery of Response

Nitrous oxide (N2O) and remifentanil (remi) are used along with other anesthetic and adjuvant agents for routine surgical anesthesia, yet the electroencephalogram (EEG) changes produced by this combination are poorly described. N2O administered alone produces EEG spectral characteristics that are distinct from most hypnotics. Furthermore, EEG frequency-derived trends before and after clinically relevant time points vary depending on N2O concentration. Remifentanil typically increases low frequency and decreases high frequency activity in the EEG, but how it influences N2O’s EEG effect is not known. Previous attempts to characterize EEG signals of patients anesthetized with N2O using frequency-derived measures have shown conflicts and inconsistencies. Thus, in addition to determining the spectral characteristics of this unique combination, we also test whether a newly proposed characterization of time-delayed embeddings of the EEG signal tracks loss and recovery of consciousness significantly at clinically relevant time points. We retrospectively investigated the effects of remi and N2O on EEG signals recorded from 32 surgical patients receiving anesthesia for elective abdominal surgeries. Remifentanil and N2O (66%) were co-administered during the procedures. Patients were tested for loss and recovery of response (ROR) to verbal stimuli after induction and upon cessation of anesthesia, respectively. We found that the addition of remifentanil to N2O anesthesia improves the ability of traditional frequency-derived measures, including the Bispectral Index (BIS), to discriminate between loss and ROR. Finally, we found that a novel analysis of EEG using nonlinear dynamics showed more significant differences between states than most spectral measures

Do Complexity Measures of Frontal EEG Distinguish Loss of Consciousness in Geriatric Patients Under Anesthesia?

While geriatric patients have a high likelihood of requiring anesthesia, they carry an increased risk for adverse cognitive outcomes from its use. Previous work suggests this could be mitigated by better intraoperative monitoring using indexes defined by several processed electroencephalogram (EEG) measures. Unfortunately, inconsistencies between patients and anesthetic agents in current analysis techniques have limited the adoption of EEG as standard of care. In attempts to identify new analyses that discriminate clinically-relevant anesthesia timepoints, we tested 1/f frequency scaling as well as measures of complexity from nonlinear dynamics. Specifically, we tested whether analyses that characterize time-delayed embeddings, correlation dimension (CD), phase-space geometric analysis, and multiscale entropy (MSE) capture loss-of-consciousness changes in EEG activity. We performed these analyses on EEG activity collected from a traditionally hard-to-monitor patient population: geriatric patients on beta-adrenergic blockade who were anesthetized using a combination of fentanyl and propofol. We compared these analyses to traditional frequency-derived measures to test how well they discriminated EEG states before and after loss of response to verbal stimuli. We found spectral changes similar to those reported previously during loss of response. We also found significant changes in 1/f frequency scaling. Additionally, we found that our phase-space geometric characterization of time-delayed embeddings showed significant differences before and after loss of response, as did measures of MSE. Our results suggest that our new spectral and complexity measures are capable of capturing subtle differences in EEG activity with anesthesia administration-differences which future work may reveal to improve geriatric patient monitoring

Malaria-associated L-arginine deficiency induces mast cell-associated disruption to intestinal barrier defenses against nontyphoidal Salmonella bacteremia.

Coinfection with malaria and nontyphoidal Salmonella serotypes (NTS) can cause life-threatening bacteremia in humans. Coinfection with malaria is a recognized risk factor for invasive NTS, suggesting that malaria impairs intestinal barrier function. Here, we investigated mechanisms and strategies for prevention of coinfection pathology in a mouse model. Our findings reveal that malarial-parasite-infected mice, like humans, develop L-arginine deficiency, which is associated with intestinal mastocytosis, elevated levels of histamine, and enhanced intestinal permeability. Prevention or reversal of L-arginine deficiency blunts mastocytosis in ileal villi as well as bacterial translocation, measured as numbers of mesenteric lymph node CFU of noninvasive Escherichia coli Nissle and Salmonella enterica serotype Typhimurium, the latter of which is naturally invasive in mice. Dietary supplementation of malarial-parasite-infected mice with L-arginine or L-citrulline reduced levels of ileal transcripts encoding interleukin-4 (IL-4), a key mediator of intestinal mastocytosis and macromolecular permeability. Supplementation with L-citrulline also enhanced epithelial adherens and tight junctions in the ilea of coinfected mice. These data suggest that increasing L-arginine bioavailability via oral supplementation can ameliorate malaria-induced intestinal pathology, providing a basis for testing nutritional interventions to reduce malaria-associated mortality in humans