ICU prognostication: Time to re-evaluate? Register-based studies on improving prognostication for patients admitted to the intensive care unit (ICU)

Background: ICU prognostication is difficult because of patients’ prior comorbidities and their varied reasons for admission. The model used for ICU prognostication in Sweden is the Simplified Acute Physiology Score 3 (SAPS 3), which uses information gathered within one hour of ICU admission to predict 30-day mortality. Since the SAPS 3 model was introduced, no biomarkers have been added to it to improve its prognostic performance. For comatose patients admitted to the ICU after cardiac arrest, the prognostication performed after 72 h will either result in the continued observation of the patient or the withdrawal of life-sustaining treatment.Purpose: 1) To investigate whether adding the biomarker lactate (study I) or high-sensitivity troponin T (hsTnT) (study II) to SAPS 3 adds prognostic value. 2) To investigate whether using a supervised machine learning algorithm called artificial neural networks (ANNs) can improve the prognostic performance of SAPS 3 (study III). 3) To explore whether ANNs can create reliable predictions for comatose patients at the time of hospital admission (study IV) and during the first three days after ICU admission, with or without promising biomarkers (study V).Methods: 1) To investigate whether the laboratory values of lactate or hsTnT could improve the performance of SAPS 3, we combined patients’ laboratory values on ICU admission at Skåne University Hospital with their SAPS 3 score. 2) Based on all first-time ICU admissions in Sweden from 2009–2017 as retrieved from the Swedish Intensive Care Registry (SIR), we investigated whether ANNs could improve SAPS 3 using the same variables. 3) All out-of-hospital cardiac arrest (OHCA) patients from the Target Temperature Management trial were included for data analysis. Background and prehospital data, along with clinical variables at admission, were used in study IV. Clinical variables from the first three days were used in study V along with different levels of biomarkers defined as clinically accessible (e.g. neuron-specific enolase, or NSE) and research-grade biomarkers (e.g. neurofilament light, or NFL). Patient outcome was the dichotomised Cerebral Performance Category scale (CPC); a CPC of 1–2 was considered a good outcome, and a CPC of 3–5 was considered a poor outcome.Results: 1) Both lactate and hsTnT were independent SAPS 3 predictors for 30-day mortality in the logistic regression model. In a subgroup analysis, the use of lactate improved the area under the receiver operating characteristic curve (AUROC) for cardiac arrest and septic patients, and the use of hsTnT improved the AUROC for septic patients. 2) The overall performance of the SAPS 3 model in Sweden was improved by the use of ANNs. Both the discrimination (AUROC 0.89 vs 0.85, p < 0.001) and the calibration were improved when the two models were compared on a separate test set (n = 36,214). 3) An ANN model outperformed a logistic-regression-based model in predicting poor outcome on hospital admission for OHCA patients. Incorporating biomarkers such as NSE improved the AUROC over the course of the first three days of the ICU stay; when NFL was incorporated, the prognostic performance was excellent from day 1.Conclusion: Lactate and hsTnT probably add prognostic value to SAPS 3 for patients admitted to the ICU with sepsis or after cardiac arrest (lactate only). An ANN model was found to be superior to the SAPS 3 model (Swedish modification) and corrected better for age than SAPS 3. A simplified ANN model with eight variables showed performance similar to that of the SAPS 3 model. For comatose OHCA patients, an ANN model improved the accuracy of the prediction of the long-term neurological outcome at hospital admission. Furthermore, when it used cumulative information from the first three days after ICU admission, an ANN model showed promising prognostic performance on day 3 when it incorporated clinically accessible biomarkers such as NSE, and it showed promising performance on days 1–3 when it incorporated research-grade biomarkers such as NFL

Identification of CD163 as an antiinflammatory receptor for HMGB1-haptoglobin complexes

Secreted by activated cells or passively released by damaged cells, extracellular HMGB1 is a prototypical damage-associated molecular pattern (DAMP) inflammatory mediator. During the course of developing extracorporeal approaches to treating injury and infection, we inadvertently discovered that haptoglobin, the acute phase protein that binds extracellular hemoglobin and targets cellular uptake through CD163, also binds HMGB1. Haptoglobin-HMGB1 complexes elicit the production of antiinflammatory enzymes (heme oxygenase-1) and cytokines (e.g., IL-10) in WT but not in CD163-deficient macrophages. Genetic disruption of haptoglobin or CD163 expression significantly enhances mortality rates in standardized models of intra-abdominal sepsis in mice. Administration of haptoglobin to WT and to haptoglobin gene-deficient animals confers significant protection. These findings reveal a mechanism for haptoglobin modulation of the inflammatory action of HMGB1, with significant implications for developing experimental strategies targeting HMGB1-dependent inflammatory diseases

Novel role of PKR in inflammasome activation and HMGB1 release

The inflammasome regulates release of caspase activation-dependent cytokines, including IL-1β, IL-18, and high-mobility group box 1 (HMGB1)1-5. During the course of studying HMGB1 release mechanisms, we discovered an important role of double-stranded RNA dependent protein kinase (PKR) in inflammasome activation. Exposure of macrophages to inflammasome agonists induced PKR autophosphorylation. PKR inactivation by genetic deletion or pharmacological inhibition severely impaired inflammasome activation in response to double-stranded RNA, ATP, monosodium urate, adjuvant aluminum, rotenone, live E. coli, anthrax lethal toxin, DNA transfection, and S. Typhimurium infection. PKR deficiency significantly inhibited the secretion of IL-1beta, IL-18 and HMGB1 in E. coli-induced peritonitis. PKR physically interacts with multiple inflammasome components, including NLR family pyrin domain-containing 3 (NLRP3), NLR family pyrin domain-containing 1 (NLRP1), NLR family CARD domain-containing protein 4 (NLRC4), Absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. PKR autophosphorylation in a cell free system with recombinant NLRP3, ASC and pro-casapse-1 reconstitutes inflammasome activity. These results reveal a critical role of PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation

Novel role of PKR in inflammasome activation and HMGB1 release

The inflammasome regulates release of caspase activation-dependent cytokines, including IL-1β, IL-18, and high-mobility group box 1 (HMGB1)1-5. During the course of studying HMGB1 release mechanisms, we discovered an important role of double-stranded RNA dependent protein kinase (PKR) in inflammasome activation. Exposure of macrophages to inflammasome agonists induced PKR autophosphorylation. PKR inactivation by genetic deletion or pharmacological inhibition severely impaired inflammasome activation in response to double-stranded RNA, ATP, monosodium urate, adjuvant aluminum, rotenone, live E. coli, anthrax lethal toxin, DNA transfection, and S. Typhimurium infection. PKR deficiency significantly inhibited the secretion of IL-1beta, IL-18 and HMGB1 in E. coli-induced peritonitis. PKR physically interacts with multiple inflammasome components, including NLR family pyrin domain-containing 3 (NLRP3), NLR family pyrin domain-containing 1 (NLRP1), NLR family CARD domain-containing protein 4 (NLRC4), Absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. PKR autophosphorylation in a cell free system with recombinant NLRP3, ASC and pro-casapse-1 reconstitutes inflammasome activity. These results reveal a critical role of PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation

On Robust Design in the Conceptual Design Phase - A Qualitative Approach and A Semi-Analytic Approach to Robust Design in the Conceptual Design Phase

One of the most important contributions to quality engineering over the last decades is the concept of robust design and its accomplishment through the use of various experimental methods. However, the prerequisite parameter design in terms of a robust solution principle are seldom discussed and methods that aid robust design in the conceptual design phase are, to our knowledge, few. This article forwards the suggestion to use the principles behind the error transmission formula as a semi-analytic method for evaluation of robustness of concept solutions, prior to entering Taguchi's parameter design stage

Polishandräckningar : en jämförelse mellan Umeå och Skellefteå

Syftet med detta fördjupningsarbete är att få en fördjupad kunskap om polisens samarbete med vårdpersonal. Vi har avgränsat oss till att studera polishandräckningar åt psykavdelningen och tillnyktringsenheten i Skellefteå och Umeå för att se om det finns någonting som går att förbättra. Vi tror inte att det är en tillfällighet att det sker olyckor vid just handräkningsärenden. Vi har efter lite efterforskningar insett att det inte finns så mycket information nedskrivet om hur samarbetet fungerar, utan det mesta är oskrivna rutiner och regler som både vårdpersonalen och poliserna tar förgivet att motparterna vet. Det vi vill belysa är hur polisen och vårdpersonalen samarbetar rent säkerhetsmässigt och hur det kan utvecklas. Vi kommer också lyfta fram de lagar som kan vara relevanta vid olika typer av handräkning och överlämnanden för vård. Men vi nöjer oss med att nämna dessa lagar som bilaga till arbetet

High-sensitivity troponin T is an important independent predictor in addition to the Simplified Acute Physiology Score for short-term ICU mortality, particularly in patients with sepsis

Purpose: Elevated cardiac troponin levels have been shown to be associated with a poor prognosis under some intensive care conditions. This study investigated whether inclusion of high-sensitivity troponin T (hsTnT) increased the prognostic accuracy of the Simplified Acute Physiology Score (SAPS 3) for general intensive care unit (ICU) patients, cardiac arrest patients, or patients with a non-cardiac arrest diagnosis. Materials and methods: We performed a single-center cohort study of ICU patients with an hsTnT measurement on ICU admission at a tertiary university hospital between February 2010 and June 2017. Results: Of 4185 first-time admissions, 856 patients (20.5%) had hsTnT evaluated at ICU admission. Factoring in ICU admission hsTnT values increased the ability of SAPS 3 to accurately predict 30-day mortality (odds ratio 1.27, 95% confidence interval: 1.15–1.41, p 10%. Conclusion: Addition of hsTnT evaluation to SAPS 3 enhances the predictive capability of this model in relation to mortality. In sepsis, the hsTnT level may be an important prognostic marker

Kockens kunskaper : Vad tycker krögare och lärare att en nybliven kock ska kunna?

    I skolans styrdokument talas det om kunskaper som en kock ska ha efter avslutad utbildning. Syftet är att undersöka vilka kunskaper som en blivande kock från det treåriga HR-programmet bör inneha efter avslutad gymnasieutbildning. För att genomföra denna undersökning har vi använt oss av en enkätundersökning med fyra efterföljande intervjuer. Det skickades ut en webbaserad enkät till 76 yrkeslärare och till 65 krögare. Resultatet visar att det är den praktiska kunskapen och den sociala förmågan som är det viktigaste. Den kunskapskategori som fått flest markeringar är "stort matintresse", andra som fått många är "bra social förmåga", "ansvarstagande", "planeringsförmåga" och "arbeta ekonomiskt". Man kan se detta som färdigheter och förtrogenhet som erhållits genom praktiskt arbete. Slutsatsen är att skolan tillsammans med branschen mer bör fokusera på att hitta former för hur teori och praktik kan bygga upp färdigheter och förtrogenhet. Enligt krögarna och lärarna bör skolan prioritera "grunder och grundmatlagning" i undervisningen. I framtiden ska kockarna vara "flexibla", kunna "sund och hälsosam matlagning" samt vara kunniga inom området "hygien och miljöarbete" enligt undersökningen

Sulphur recirculation for high temperature corrosion and dioxin abatement in Waste-to-Energy boilers

Sulphur Recirculation is a new patented technology for reducing high temperature boiler corrosion and dioxin formation in Waste-to-Energy plants. SO2 is separated from a tail end wet scrubber using H2O2, producing a 15-25wt% H2SO4 solution, which is injected into the boiler producing SO2, thus creating a sulphur loop. The recirculated sulphur will increase the gas concentration of SO2 in the boiler and decrease the Cl/S ratio of the deposits and ashes, thus producing a less corrosive environment for the superheaters. Furthermore, the lower chlorine content of the boiler deposits also significantly decreased the dioxin formation rates as well as dioxin emissions. Sulphur Recirculation was initially demonstrated in pilot plant tests as well as full-scale tests at a Waste to Energy plant in G\uf6teborg (Sweden) during nearly two months of operation. Babcock &amp; Wilcox V\uf8lund AB in Sweden has installed their Sulphur Recirculation technology in one of the two Waste-to Energy lines at Maabjerg Energy Center (MEC) in Denmark in order to combat high temperature corrosion and dioxin formation. This is the first commercial installation and it has been operating since mid-October 2016. Sulphur Recirculation decreased the high temperature corrosion rates of the superheaters in this full-scale installation by approximately 50%, which may increase green electricity production from combustion of biomass and waste in the future. Furthermore, the dioxin gas concentrations decreased by 72%. Sulphur Recirculation almost entirely decreased the need for costly road transports of effluent sulphate water for the Sulphur Recirculation line, since most sulphur from the waste now ends up in the ashes instead of creating a surplus dilute Na2SO4 solution. The sulphur content of the waste varies with time, which may create periods of sulphur surplus and deficit respectively. Most of these variations are being evened out by a storage vessel for H2SO4. These variations may facilitate a small market of waste sulphuric acid between plants in the future