Implementation of a Cardiogenic Shock Protocol and Data Review Process is Associated With Improved In-Hospital Survival

Background: Despite increasing use of mechanical circulatory support devices (MCS), cardiogenic shock (CS) mortality is persistently high, with worsening outcomes in later stages of CS. Delays in diagnosis and practice variation may contribute to in-hospital mortality. Methods: In June 2018, we devised and implemented a CS protocol at two hospitals from one health system in Portland, OR. The CS protocol was designed to promote early CS recognition, rapid notification of a multi-disciplinary specialty team lead by a heart failure cardiologist, invasive hemodynamic evaluation, and institution of MCS as appropriate. CS was defined by widely accepted clinical and hemodynamic criteria. Patient demographics, disease severity, process metrics, and clinical outcomes were prospectively collected and reviewed monthly by a multi-disciplinary CS task force. M&Ms were conducted routinely to identify improvement opportunities. The task force continually refined data collection, implemented protocol improvements, and educated providers and clinical staff in the emergency department, critical care, intermediate care, and cardiac telemetry units. Education centered on early recognition of CS, protocol for activation, and the time-sensitivity of CS outcomes. Results: From June 1, 2018 to October 1, 2019, identification of CS patients grew from five to 55 patients per month, with 311 total patients identified. Education initially emphasized CS identification and team activation, then expanded to definition of CS stages and hospital-specific protocols. Over 10 months, the CS mortality rate decreased by 30%. Ongoing optimization includes stratifying patients by primary discharge diagnosis, consistently documenting shock stages in the electronic medical record, and refining the transfer process from other hospitals. Conclusions: Implementation of a CS protocol with emphasis on early recognition, hemodynamic assessment, and implementation of MCS is associated with improved survival. Multi-disciplinary education and team engagement in data review are integral to continual process improvement. Character count: 1,818 Clinical Implications: A protocolized, multi-disciplinary approach can improve the outcome of CS

Calcitonin Gene-Related Peptide Partially Reverses Decreased Production of Chemokines KC and MIP-2 Following Murine Sepsis

The secretion of calcitonin gene-related peptide (CGRP) and the chemokines KC and MIP-2 are increased in the animal models of endotoxemic and septic shock. We tested whether CGRP could modulate KC and MIP-2 secretion from different sources of macrophages after murine sepsis induced by cecal ligation and puncture (CLP). Macrophages were obtained from the peritoneal exudate and lung of female BALB/c mice 16 h after CLP and plated in culture with CGRP and/or LPS for 12 h. The results showed that peritoneal macrophage production of the chemokines (KC, MIP-2) and cytokines (TNF-α, IL-6) was markedly decreased in CLP mice. Alveolar macrophages did not display decreased cytokine/chemokines production after CLP. CGRP (0.1 nM–10 nM) partially reversed this decreased production of LPS-induced KC and MIP-2 from peritoneal macrophages. These results suggest that CGRP might be intimately involved in recruitment of neutrophils by promoting local production of the chemokines KC and MIP-2 in murine sepsis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44531/1/10753_2004_Article_376569.pd

Radiation-induced lung injury in vivo: Expression of transforming growth factor—Beta precedes fibrosis

Cytokine release from irradiated cells has been postulated to start soon after irradiation preceding detectable clinical and pathological manifestation of lung injury. The expression of transforming growth factor beta (TGF β ), a fibrogenic and radiation-inducible cytokine, was studied from 1–16 weeks after the 15 and 30 Gray (Gy) of thoracic irradiation to rats. Thoracic irradiation caused an increase in TGF β protein in bronchoalveolar lavage (BAL) fluid peaking at 3–6 weeks as compared to sham-irradiated control rats. Steady state TGF β mRNA expression as shown by whole lung northern blot assay paralleled the TGF β protein expression in BAL fluid. The peak of TGF β protein increase in BAL fluid between 3 and 6 weeks coincided with the initial influx of inflammatory cells in BAL fluid, but preceded histologically discernable pulmonary fibrosis that was not apparent until 8–10 weeks after irradiation. In conclusion, TGF β and mRNA and protein upregulation preceded the radiation-induced pulmonary fibrosis, suggesting a pathogenetic role in the development of radiation fibrosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44516/1/10753_2005_Article_BF01486737.pd

A review of the effects of colour and light on non-image function in humans

This paper reviews current knowledge on non-image-forming aspects of vision. Developments in the last 20 years have included the discovery of a fifth class of human visual pigment (melanopsin), in addition to the three classes of photopsin to be found in the cones and rhodopsin in the rods in the human retina. Melanopsin is found in a small number of retinal ganglion cells which then, in addition to receiving input from rods and cones, are intrinsically photosensitive. These retinal ganglion cells send their input primarily to the hypothalamus, where they help to regulate the circadian system (daily rhythms of sleep patterns, body temperature, heart rate, etc.). The discovery of the anatomical basis of non-image-forming vision has led to a great deal of research into the effects of light on sleep, depression and mood, retinal photodamage and well-being, amongst other factors. Given that recent technological innovations in LED lighting now give us greater control over environmental lighting, it is timely to review the non-visual effects of light in humans in order to inform lighting design in the future

Immunopathologic Alterations in Murine Models of Sepsis of Increasing Severity

We investigated inflammatory and physiologic parameters in sepsis models of increasing lethality induced by cecal ligation and puncture (CLP). Mice received imipenem for antibiotic therapy, and groups were sacrificed at 2, 4, 8, 12, 16, 20, and 24 h after CLP. The severity of sepsis increased with needle puncture size (lethality with 18-gauge puncture [18G], 100%; 21G, 50%; 25G, 5%; sham treatment, 0%). While the temperature (at 12 h) and the activity and diurnal rhythm (at day 4) of the 25G-treated CLP group recovered to normal, the 21G and 18G treatment groups exhibited severe hypothermia along with decreased activities. A direct correlation was also observed between the severity of sepsis and cytokine (interleukin 1β [IL-1β], tumor necrosis factor [TNF], IL-6, and IL-10) concentrations in both the peritoneum and the plasma. There were substantially higher cytokine levels in the more severe CLP models than in the sham-treated one. Peritoneal and plasma TNF levels were always less than 40 pg/ml in all models. None of the cytokines in the septic mice peaked within the first hour, which is in contrast to the results of most endotoxin models. Chemokine (KC and macrophage inflammatory protein 2) profiles also correlated with the severity of sepsis. Except for the chemokines, levels of inflammatory mediators were always higher at the site of inflammation (peritoneum) than in the circulation. Our study demonstrated that sepsis of increasing severity induced increased cytokine levels both within the local environment (peritoneum) and systemically (plasma), which in turn correlated with morbidity and mortality