Prognostic value of serial score measurements of the national early warning score, the quick sequential organ failure assessment and the systemic inflammatory response syndrome to predict clinical outcome in early sepsis

BACKGROUND AND IMPORTANCE: Sepsis is a common and potentially lethal syndrome, and early recognition is critical to prevent deterioration. Yet, currently available scores to facilitate recognition of sepsis lack prognostic accuracy. OBJECTIVE: To identify the optimal time-point to determine NEWS, qSOFA and SIRS for the prediction of clinical deterioration in early sepsis and to determine whether the change in these scores over time improves their prognostic accuracy. DESIGN: Post hoc analysis of prospectively collected data. SETTINGS AND PARTICIPANTS: This study was performed in the emergency department (ED) of a tertiary-care teaching hospital. Adult medical patients with (potential) sepsis were included. OUTCOME MEASURES AND ANALYSIS: The primary outcome was clinical deterioration within 72 h after admission, defined as organ failure development, the composite outcome of ICU-admission and death. Secondary outcomes were the composite of ICU-admission/death and a rise in SOFA at least 2. Scores were calculated at the ED with 30-min intervals. ROC analyses were constructed to compare the prognostic accuracy of the scores. RESULTS: In total, 1750 patients were included, of which 360 (20.6%) deteriorated and 79 (4.5%) went to the ICU or died within 72 h. The NEWS at triage (AUC, 0.62; 95% CI, 0.59-0.65) had a higher accuracy than qSOFA (AUC, 0.60; 95% CI, 0.56-0.63) and SIRS (AUC, 0.59; 95% CI, 0.56-0.63) for predicting deterioration. The AUC of the NEWS at 1 h (0.65; 95% CI, 0.63-0.69) and 150 min after triage (0.64; 95% CI, 0.61-0.68) was higher than the AUC of the NEWS at triage. The qSOFA had the highest AUC at 90 min after triage (0.62; 95% CI, 0.58-0.65), whereas the SIRS had the highest AUC at 60 min after triage (0.60; 95% CI, 0.56-0.63); both are not significantly different from triage. The NEWS had a better accuracy to predict ICU-admission/death <72 h compared with qSOFA (AUC difference, 0.092) and SIRS (AUC difference, 0.137). No differences were found for the prediction of a rise in SOFA at least 2 within 72 h between the scores. Patients with the largest improvement in any of the scores were more prone to deteriorate. CONCLUSION: NEWS had a higher prognostic accuracy to predict deterioration compared with SIRS and qSOFA; the highest accuracy was reached at 1 h after triage

CTLA-4 Signaling Regulates the Intensity of Hypersensitivity Responses to Food Antigens, but is Not Decisive in the Induction of Sensitization

Although food allergy has emerged as a major health problem, the mechanisms that are decisive in the development of sensitization to dietary Ag remain largely unknown. CTLA-4 signaling negatively regulates immune activation, and may play a crucial role in preventing induction and/or progression of sensitization to food Ag. To elucidate the role of CTLA-4 signaling in responses to food allergens, a murine model of peanut allergy was used. During oral exposure to peanut protein extract (PPE) together with the mucosal adjuvant cholera toxin (CT), which induces peanut allergy, CTLA-4 ligation was prevented using a CTLA-4 mAb. Additionally, the effect of inhibition of the CTLA-4 pathway on oral exposure to PPE in the absence of CT, which leads to unresponsiveness to peanut Ag, was explored. During sensitization, anti-CTLA-4 treatment considerably enhanced IgE responses to PPE and the peanut allergens, Ara h 1, Ara h 3, and Ara h 6, resulting in elevated mast cell degranulation upon an oral challenge. Remarkably, antagonizing CTLA-4 during exposure to PPE in the absence of CT resulted in significant induction of Th2 cytokines and an elevation in total serum IgE levels, but failed to induce allergen-specific IgE responses and mast cell degranulation upon a PPE challenge. These results indicate that CTLA-4 signaling is not the crucial factor in preventing sensitization to food allergens, but plays a pivotal role in regulating the intensity of a food allergic sensitization response. Furthermore, these data indicate that a profoundly Th2-biased cytokine environment is insufficient to induce allergic responses against dietary Ag

Cohort profile of Acutelines:a large data/biobank of acute and emergency medicine

Purpose Research in acute care faces many challenges, including enrolment challenges, legal limitations in data sharing, limited funding and lack of singular ownership of the domain of acute care. To overcome these challenges, the Center of Acute Care of the University Medical Center Groningen in the Netherlands, has established a de novo data, image and biobank named ‘Acutelines’.Participants Clinical data, imaging data and biomaterials (ie, blood, urine, faeces, hair) are collected from patients presenting to the emergency department (ED) with a broad range of acute disease presentations. A deferred consent procedure (by proxy) is in place to allow collecting data and biomaterials prior to obtaining written consent. The digital infrastructure used ensures automated capturing of all bed-side monitoring data (ie, vital parameters, electrophysiological waveforms) and securely importing data from other sources, such as the electronic health records of the hospital, ambulance and general practitioner, municipal registration and pharmacy. Data are collected from all included participants during the first 72 hours of their hospitalisation, while follow-up data are collected at 3 months, 1 year, 2 years and 5 years after their ED visit.Findings to date Enrolment of the first participant occurred on 1 September 2020. During the first month, 653 participants were screened for eligibility, of which 180 were approached as potential participants. In total, 151 (84%) provided consent for participation of which 89 participants fulfilled criteria for collection of biomaterials.Future plans The main aim of Acutelines is to facilitate research in acute medicine by providing the framework for novel studies and issuing data, images and biomaterials for future research. The protocol will be extended by connecting with central registries to obtain long-term follow-up data, for which we already request permission from the participant.Trial registration number NCT04615065

Оценка фискальной иллюзии при налогообложении доходов физических лиц

Фискальная иллюзия сама по себе не является негативным явлением, она всего лишь следствие осуществляемой фискальной политики государства. Тем не менее, фискальная иллюзия нарушает представление экономических агентов о масштабах государственного влияния в перераспределении своих доходов и тем самым способствует принятию ими не самых эффективных экономических решений.Фіскальна ілюзія сама по собі не є негативним явищем, вона всього лише слідство здійснюваної фіскальної політики держави. Проте, фіскальна ілюзія порушує уявлення економічних агентів про масштаби державного впливу в перерозподілі своїх доходів і тим самим сприяє ухваленню ними не найефективніших економічних рішень

Injection therapy and denervation procedures for chronic low-back pain: a systematic review

Injection therapy and denervation procedures are commonly used in the management of chronic low-back pain (LBP) despite uncertainty regarding their effectiveness and safety. To provide an evaluation of the current evidence associated with the use of these procedures, a systematic review was performed. Existing systematic reviews were screened, and the Cochrane Back Review Group trial register was searched for randomized controlled trials (RCTs) fulfilling the inclusion criteria. Studies were included if they recruited adults with chronic LBP, evaluated the use of injection therapy or denervation procedures and measured at least one clinically relevant outcome (such as pain or functional status). Two review authors independently assessed studies for eligibility and risk of bias (RoB). A meta-analysis was performed with clinically homogeneous studies, and the GRADE approach was used to determine the quality of evidence. In total, 27 RCTs were included, 14 on injection therapy and 13 on denervation procedures. 18 (66%) of the studies were determined to have a low RoB. Because of clinical heterogeneity, only two comparisons could be pooled. Overall, there is only low to very low quality evidence to support the use of injection therapy and denervation procedures over placebo or other treatments for patients with chronic LBP. However, it cannot be ruled out that in carefully selected patients, some injection therapy or denervation procedures may be of benefit

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms

Contains fulltext : 158967.pdf (publisher's version ) (Open Access)Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Predicting deterioration of patients with early sepsis at the emergency department using continuous heart rate variability analysis: a model-based approach

BACKGROUND: Sepsis is a life-threatening disease with an in-hospital mortality rate of approximately 20%. Physicians at the emergency department (ED) have to estimate the risk of deterioration in the coming hours or days and decide whether the patient should be admitted to the general ward, ICU or can be discharged. Current risk stratification tools are based on measurements of vital parameters at a single timepoint. Here, we performed a time, frequency, and trend analysis on continuous electrocardiograms (ECG) at the ED to try and predict deterioration of septic patients. METHODS: Patients were connected to a mobile bedside monitor that continuously recorded ECG waveforms from triage at the ED up to 48 h. Patients were post-hoc stratified into three groups depending on the development of organ dysfunction: no organ dysfunction, stable organ dysfunction or progressive organ dysfunction (i.e., deterioration). Patients with de novo organ dysfunction and those admitted to the ICU or died were also stratified to the group of progressive organ dysfunction. Heart rate variability (HRV) features over time were compared between the three groups. RESULTS: In total 171 unique ED visits with suspected sepsis were included between January 2017 and December 2018. HRV features were calculated over 5-min time windows and summarized into 3-h intervals for analysis. For each interval, the mean and slope of each feature was calculated. Of all analyzed features, the average of the NN-interval, ultra-low frequency, very low frequency, low frequency and total power were different between the groups at multiple points in time. CONCLUSIONS: We showed that continuous ECG recordings can be automatically analyzed and used to extract HRV features associated with clinical deterioration in sepsis. The predictive accuracy of our current model based on HRV features derived from the ECG only shows the potential of HRV measurements at the ED. Unlike other risk stratification tools employing multiple vital parameters this does not require manual calculation of the score and can be used on continuous data over time. Trial registration The protocol of this study is published by Quinten et al., 2017