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Abstract High-resolution biomacromolecular structure determination is essential to better understand protein function and dynamics. Serial crystallography is an emerging structural biology technique which has fundamental limitations due to either sample volume requirements or immediate access to the competitive X-ray beamtime. Obtaining a high volume of well-diffracting, sufficient-size crystals while mitigating radiation damage remains a critical bottleneck of serial crystallography. As an alternative, we introduce the plate-reader module adapted for using a 72-well Terasaki plate for biomacromolecule structure determination at a convenience of a home X-ray source. We also present the first ambient temperature lysozyme structure determined at the Turkish light source (Turkish DeLight). The complete dataset was collected in 18.5 min with resolution extending to 2.39 Å and 100% completeness. Combined with our previous cryogenic structure (PDB ID: 7Y6A), the ambient temperature structure provides invaluable information about the structural dynamics of the lysozyme. Turkish DeLight provides robust and rapid ambient temperature biomacromolecular structure determination with limited radiation damage.

Introduction: In the Netherlands, most emergency department (ED) patients are referred by a general practitioner (GP) or a hospital specialist. Early risk stratification during telephone referral could allow the physician to assess the severity of the patients' illness in the prehospital setting. We aim to assess the discriminatory value of the acute internal medicine (AIM) physicians' clinical intuition based on telephone referral of ED patients to predict short-term adverse outcomes, and to investigate on which information their predictions are based., Methods: In this prospective study, we included adult ED patients who were referred for internal medicine by a GP or a hospital specialist. Primary outcomes were hospital admission and triage category according to the Manchester Triage System (MTS). Secondary outcome was 31-day mortality. The discriminatory performance of the clinical intuition was assessed using an area under the receiver operating characteristics curve (AUC). To identify which information is important to predict adverse outcomes, we performed univariate regression analysis. Agreement between predicted and observed MTS triage category was assessed using intraclass and Spearman's correlation., Results: We included 333 patients, of whom 172 (51.7%) were referred by a GP, 146 (43.8%) by a hospital specialist, and 12 (3.6%) by another health professional. The AIM physician's clinical intuition showed good discriminatory performance regarding hospital admission (AUC 0.72, 95% CI: 0.66-0.78) and 31-day mortality (AUC 0.73, 95% CI: 0.64-0.81). Univariate regression analysis showed that age ≥65 years and a sense of alarm were significant predictors. The predicted and observed triage category were similar in 45.2%, but in 92.5% the prediction did not deviate by more than one category. Intraclass and Spearman's correlation showed fair agreement between predicted and observed triage category (ICC 0.48, Spearman's 0.29)., Conclusion: Clinical intuition based on relevant information during a telephone referral can be used to accurately predict short-term outcomes, allowing for early risk stratification in the prehospital setting and managing ED patient flow more effectively., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 van Dam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: For most acute conditions, the phase prior to emergency department (ED) arrival is largely unexplored. However, this prehospital phase has proven an important part of the acute care chain (ACC) for specific time-sensitive conditions, such as stroke and myocardial infarction. For patients with undifferentiated complaints, exploration of the prehospital phase of the ACC may also offer a window of opportunity for improvement of care. This study aims to explore the ACC of ED patients with undifferentiated complaints, with specific emphasis on time in ACC and patient experience., Methods: This Dutch prospective observational study, included all adult (≥ 18 years) ED patients with undifferentiated complaints over a 4-week period. We investigated the patients' journey through the ACC, focusing on time in ACC and patient experience. Additionally, a multivariable linear regression analysis was employed to identify factors independently associated with time in ACC., Results: Among the 286 ED patients with undifferentiated complaints, the median symptom duration prior to ED visit was 6 days (IQR 2-10), during which 58.6% of patients had contact with a healthcare provider before referral. General Practitioners (GPs) referred 80.4% of the patients, with the predominant patient journey (51.7%) involving GP referral followed by self-transportation to the ED. The median time in ACC was 5.5 (IQR 4.0-8.4) hours of which 40% was spent before the ED visit. GP referral and referral to pulmonology were associated with a longer time in ACC, while referral during evenings was associated with a shorter time in ACC. Patients scored both quality and duration of the provided care an 8/10., Conclusion: Dutch ED patients with undifferentiated complaints consulted a healthcare provider in over half of the cases before their ED visit. The median time in ACC is 5.5 h of which 40% is spent in the prehospital phase. Those referred by a GP and to pulmonology had a longer, and those in the evening a shorter time in ACC. The acute care journey starts hours before patients arrive at the ED and 6 days of complaints precede this journey. This timeframe could serve as a window of opportunity to optimise care., (© 2024. The Author(s).)

Background: Data on hyperglycemia and glucose variability in relation to diabetes mellitus, either known or unknown in ICU-setting in COVID-19, are scarce. We prospectively studied daily glucose variables and mortality in strata of diabetes mellitus and glycosylated hemoglobin among mechanically ventilated COVID-19 patients., Methods: We used linear-mixed effect models in mechanically ventilated COVID-19 patients to investigate mean and maximum difference in glucose concentration per day over time. We compared ICU survivors and non-survivors and tested for effect-modification by pandemic wave 1 and 2, diabetes mellitus, and admission HbA1c., Results: Among 232 mechanically ventilated COVID-19 patients, 21.1% had known diabetes mellitus, whereas 16.9% in wave 2 had unknown diabetes mellitus. Non-survivors had higher mean glucose concentrations (ß 0.62 mmol/l; 95%CI 0.20-1.06; ß 11.2 mg/dl; 95% CI 3.6-19.1; P = 0.004) and higher maximum differences in glucose concentrations per day (ß 0.85 mmol/l; 95%CI 0.37-1.33; ß 15.3; 95%CI 6.7-23.9; P = 0.001). Effect modification by wave, history of diabetes mellitus and admission HbA1c in associations between glucose and survival was not present. Effect of higher mean glucose concentrations was modified by pandemic wave (wave 1 (ß 0.74; 95% CI 0.24-1.23 mmol/l) ; (ß 13.3; 95%CI 4.3-22.1 mg/dl)) vs. (wave 2 (ß 0.37 (95%CI 0.25-0.98) mmol/l) (ß 6.7 (95% ci 4.5-17.6) mg/dl))., Conclusions: Hyperglycemia and glucose variability are associated with mortality in mechanically ventilated COVID-19 patients irrespective of the presence of diabetes mellitus., (© 2023. The Author(s).)

Introduction: Prediction models for identifying emergency department (ED) patients at high risk of poor outcome are often not externally validated. We aimed to perform a head-to-head comparison of the discriminatory performance of several prediction models in a large cohort of ED patients., Methods: In this retrospective study, we selected prediction models that aim to predict poor outcome and we included adult medical ED patients. Primary outcome was 31-day mortality, secondary outcomes were 1-day mortality, 7-day mortality, and a composite endpoint of 31-day mortality and admission to intensive care unit (ICU).The discriminatory performance of the prediction models was assessed using an area under the receiver operating characteristic curve (AUC). Finally, the prediction models with the highest performance to predict 31-day mortality were selected to further examine calibration and appropriate clinical cut-off points., Results: We included 19 prediction models and applied these to 2185 ED patients. Thirty-one-day mortality was 10.6% (231 patients), 1-day mortality was 1.4%, 7-day mortality was 4.4%, and 331 patients (15.1%) met the composite endpoint. The RISE UP and COPE score showed similar and very good discriminatory performance for 31-day mortality (AUC 0.86), 1-day mortality (AUC 0.87), 7-day mortality (AUC 0.86) and for the composite endpoint (AUC 0.81). Both scores were well calibrated. Almost no patients with RISE UP and COPE scores below 5% had an adverse outcome, while those with scores above 20% were at high risk of adverse outcome. Some of the other prediction models (i.e. APACHE II, NEWS, WPSS, MEWS, EWS and SOFA) showed significantly higher discriminatory performance for 1-day and 7-day mortality than for 31-day mortality., Conclusions: Head-to-head validation of 19 prediction models in medical ED patients showed that the RISE UP and COPE score outperformed other models regarding 31-day mortality.

Background: There is growing awareness that sex differences are associated with different patient outcomes in a variety of diseases. Studies investigating the effect of patient sex on sepsis-related mortality remain inconclusive and mainly focus on patients with severe sepsis and septic shock in the intensive care unit. We therefore investigated the association between patient sex and both clinical presentation and 30-day mortality in patients with the whole spectrum of sepsis severity presenting to the emergency department (ED) who were admitted to the hospital., Materials and Methods: In our multi-centre cohort study, we retrospectively investigated adult medical patients with sepsis in the ED. Multivariable analysis was used to evaluate the association between patient sex and all-cause 30-day mortality., Results: Of 2065 patients included, 47.6% were female. Female patients had significantly less comorbidities, lower Sequential Organ Failure Assessment score and abbreviated Mortality Emergency Department Sepsis score, and presented less frequently with thrombocytopenia and fever, compared to males. For both sexes, respiratory tract infections were predominant while female patients more often had urinary tract infections. Females showed lower 30-day mortality (10.1% vs. 13.6%; p  = .016), and in-hospital mortality (8.0% vs. 11.1%; p  = .02) compared to males. However, a multivariable logistic regression model showed that patient sex was not an independent predictor of 30-day mortality (OR 0.90; 95% CI 0.67-1.22; p  = .51)., Conclusions: Females with sepsis presenting to the ED had fewer comorbidities, lower disease severity, less often thrombocytopenia and fever and were more likely to have a urinary tract infection. Females had a lower in-hospital and 30-day mortality compared to males, but sex was not an independent predictor of 30-day mortality. The lower mortality in female patients may be explained by differences in comorbidity and clinical presentation compared to male patients.KEY MESSAGESOnly limited data exist on sex differences in sepsis patients presenting to the emergency department with the whole spectrum of sepsis severity.Female sepsis patients had a lower incidence of comorbidities, less disease severity and a different source of infection, which explains the lower 30-day mortality we found in female patients compared to male patients.We found that sex was not an independent predictor of 30-day mortality; however, the study was probably underpowered to evaluate this outcome definitively.

Introduction: Coronavirus disease 2019 (COVID-19) has a high burden on the healthcare system. Prediction models may assist in triaging patients. We aimed to assess the value of several prediction models in COVID-19 patients in the emergency department (ED)., Methods: In this retrospective study, ED patients with COVID-19 were included. Prediction models were selected based on their feasibility. Primary outcome was 30-day mortality, secondary outcomes were 14-day mortality and a composite outcome of 30-day mortality and admission to medium care unit (MCU) or intensive care unit (ICU). The discriminatory performance of the prediction models was assessed using an area under the receiver operating characteristic curve (AUC)., Results: We included 403 patients. Thirty-day mortality was 23.6%, 14-day mortality was 19.1%, 66 patients (16.4%) were admitted to ICU, 48 patients (11.9%) to MCU, and 152 patients (37.7%) met the composite endpoint. Eleven prediction models were included. The RISE UP score and 4 C mortality scores showed very good discriminatory performance for 30-day mortality (AUC 0.83 and 0.84, 95% CI 0.79-0.88 for both), significantly higher than that of the other models., Conclusion: The RISE UP score and 4 C mortality score can be used to recognise patients at high risk for poor outcome and may assist in guiding decision-making and allocating resources.

Objective: To mitigate the burden of COVID-19 on the healthcare system, information on the prognosis of the disease is needed. The recently developed Risk Stratification in the Emergency Department in Acutely ill Older Patients (RISE UP) score has very good discriminatory value for short-term mortality in older patients in the emergency department (ED). It consists of six readily available items. We hypothesised that the RISE UP score could have discriminatory value for 30-day mortality in ED patients with COVID-19., Design: Retrospective analysis., Setting: Two EDs of the Zuyderland Medical Centre, secondary care hospital in the Netherlands., Participants: The study sample consisted of 642 adult ED patients diagnosed with COVID-19 between 3 March and until 25 May 2020. Inclusion criteria were (1) admission to the hospital with symptoms suggestive of COVID-19 and (2) positive result of the PCR or (very) high suspicion of COVID-19 according to the chest CT scan., Outcome: Primary outcome was 30-day mortality, secondary outcome was a composite of 30-day mortality and admission to intensive care unit (ICU)., Results: Within 30 days after presentation, 167 patients (26.0%) died and 102 patients (15.9%) were admitted to ICU. The RISE UP score showed good discriminatory value for 30-day mortality (area under the receiver operating characteristic curve (AUC) 0.77, 95% CI 0.73 to 0.81) and for the composite outcome (AUC 0.72, 95% CI 0.68 to 0.76). Patients with RISE UP scores below 10% (n=121) had favourable outcome (zero deaths and six ICU admissions), while those with scores above 30% (n=221) were at high risk of adverse outcome (46.6% mortality and 19.0% ICU admissions)., Conclusion: The RISE UP score is an accurate prognostic model for adverse outcome in ED patients with COVID-19. It can be used to identify patients at risk of short-term adverse outcome and may help guide decision-making and allocating healthcare resources., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare: no support from any organisation for the submitted work, no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Older emergency department (ED) patients are at high risk of mortality, and it is important to predict which patients are at highest risk. Biomarkers such as lactate, high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), D-dimer and procalcitonin may be able to identify those at risk. We aimed to assess the discriminatory value of these biomarkers for 30-day mortality and other adverse outcomes., Design: Prospective cohort study. On arrival of patients, five biomarkers were measured. Area under the curves (AUCs) and interval likelihood ratios (LRs) were calculated to investigate the discriminatory value of the biomarkers., Setting: ED in the Netherlands., Participants: Older (≥65 years) medical ED patients, referred for internal medicine or gastroenterology., Primary and Secondary Outcome Measures: 30-day mortality was the primary outcome measure, while other adverse outcomes (intensive care unit/medium care unit admission, prolonged length of hospital stay, loss of independent living and unplanned readmission) were the composite secondary outcome measure., Results: The median age of the 450 included patients was 79 years (IQR 73-85). In total, 51 (11.3%) patients died within 30 days. The AUCs of all biomarkers for prediction of mortality were sufficient to good, with the highest AUC of 0.73 for hs-cTnT and NT-proBNP. Only for the highest lactate values, the LR was high enough (29.0) to be applicable for clinical decision making, but this applied to a minority of patients. The AUC for the composite secondary outcome (intensive and medium care admission, length of hospital stay >7 days, loss of independent living and unplanned readmission within 30 days) was lower, ranging between 0.58 and 0.67., Conclusions: Although all five biomarkers predict 30-day mortality in older medical ED patients, their individual discriminatory value was not high enough to contribute to clinical decision making., Trial Registration Number: NCT02946398; Results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Older emergency department (ED) patients often have complex problems and severe illnesses with a high risk of adverse outcomes. It is likely that these older patients are troubled with concerns, which might reflect their preferences and needs concerning medical care. However, data regarding this topic are lacking., Methods: This study is a sub study of a prospective, multicenter, observational cohort study among older medical ED patients (≥65 years). Patients or their caregivers were asked about their illness-related concerns during the first stage of the ED visit using a questionnaire. All concerns were categorized into 10 categories, and differences between patients and caregivers, and between age groups were analyzed. Odds Ratios were calculated to determine the association of the concerns for different adverse outcomes., Results: Most of the 594 included patients (or their caregivers) were concerned (88%) about some aspects of their illness or their need for medical care. The most often reported concerns were about the severity of disease (43.6%), functional decline (9.4%) and dying (5.6%). Caregivers were more frequently concerned than patients (p<0.001) especially regarding the severity of disease (50.5 vs 39.6%, p = 0.016) and cognitive decline (10.8 vs. 0.3%, p <0.001). We found no difference between age groups. The concern about dying was associated with 30-day mortality (OR 2.89; 95%CI: 1.24-6.70) and the composite endpoint (intensive- or medium care admission, length of hospital stay >7 days, loss of independent living and unplanned readmission within 30 days) (OR 2.32; 95%CI: 1.12-4.82). In addition, unspecified concerns were associated with mortality (OR 1.88; 95%CI: 1.09-3.22)., Conclusion: The majority of older patients and especially their caregivers are concerned about their medical condition or need for medical care when they visit the ED. These concerns are associated with adverse outcomes and most likely reflect their needs regarding medical care. More attention should be paid to these concerns because they may offer opportunities to reduce anxiety and provide care that is adjusted to their needs., Trial Registration: This study was registered on clinicalTriagls.gov (NCT02946398)., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Early differentiation between emergency department (ED) patients with and without corona virus disease (COVID-19) is very important. Chest CT scan may be helpful in early diagnosing of COVID-19. We investigated the diagnostic accuracy of CT using RT-PCR for SARS-CoV-2 as reference standard and investigated reasons for discordant results between the two tests., Methods: In this prospective single centre study in the Netherlands, all adult symptomatic ED patients had both a CT scan and a RT-PCR upon arrival at the ED. CT results were compared with PCR test(s). Diagnostic accuracy was calculated. Discordant results were investigated using discharge diagnoses., Results: Between March 13th and March 24th 2020, 193 symptomatic ED patients were included. In total, 43.0% of patients had a positive PCR and 56.5% a positive CT, resulting in a sensitivity of 89.2%, specificity 68.2%, likelihood ratio (LR)+ 2.81 and LR- 0.16. Sensitivity was higher in patients with high risk pneumonia (CURB-65 score ≥3; n = 17, 100%) and with sepsis (SOFA score ≥2; n = 137, 95.5%). Of the 35 patients (31.8%) with a suspicious CT and a negative RT-PCR, 9 had another respiratory viral pathogen, and in 7 patients, COVID-19 was considered likely. One of nine patients with a non-suspicious CT and a positive PCR had developed symptoms within 48 hours before scanning., Discussion: The accuracy of chest CT in symptomatic ED patients is high, but used as a single diagnostic test, CT can not safely diagnose or exclude COVID-19. However, CT can be used as a quick tool to categorize patients into "probably positive" and "probably negative" cohorts., Competing Interests: The authors have declared that no competing interests exist.

Background/objectives: Currently, accurate clinical models that predict short-term mortality in older (≥ 65 years) emergency department (ED) patients are lacking. We aimed to develop and validate a prediction model for 30-day mortality in older ED patients that is easy to apply using variables that are readily available and reliably retrievable during the short phase of an ED stay., Methods: Prospective multi-centre cohort study in older medical ED patients. The model was derived through logistic regression analyses, externally validated and compared with other well-known prediction models (Identification of Seniors at Risk (ISAR), ISAR-Hospitalised Patients, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Modified Early Warning Score (MEWS))., Results: Within 30 days after presentation, 66 (10.9%) of 603 patients in the derivation cohort and 105 (13.3%) of 792 patients in the validation cohort died. The newly developed model included 6 predictors: age, ≥2 abnormal vital signs, serum albumin, blood urea nitrogen, lactate dehydrogenase, and bilirubin. The discriminatory value of the model for mortality was very good with an AUC of 0.84 in the derivation and 0.83 in the validation cohort. The final model was excellently calibrated (Hosmer-Lemeshow p-value 0.89). The discriminatory value of the model was significantly higher than that of the four risk stratification scores (highest AUC of 0.69 for ISAR score, p-value 0.007)., Conclusion: We developed and externally validated an accurate and simplified prediction model for 30-day mortality in older ED patients. This model may be useful to identify patients at risk of short-term mortality and to apply personalised medical care., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to disclose., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Older patients (≥65 years old) experience high rates of adverse outcomes after an emergency department (ED) visit. Reliable tools to predict adverse outcomes in this population are lacking. This manuscript comprises a study protocol for the Risk Stratification in the Emergency Department in Acutely Ill Older Patients (RISE UP) study that aims to identify predictors of adverse outcome (including triage- and risk stratification scores) and intends to design a feasible prediction model for older patients that can be used in the ED., Methods: The RISE UP study is a prospective observational multicentre cohort study in older (≥65 years of age) ED patients treated by internists or gastroenterologists in Zuyderland Medical Centre and Maastricht University Medical Centre+ in the Netherlands. After obtaining informed consent, patients characteristics, vital signs, functional status and routine laboratory tests will be retrieved. In addition, disease perception questionnaires will be filled out by patients or their caregivers and clinical impression questionnaires by nurses and physicians. Moreover, both arterial and venous blood samples will be taken in order to determine additional biomarkers. The discriminatory value of triage- and risk stratification scores, clinical impression scores and laboratory tests will be evaluated. Univariable logistic regression will be used to identify predictors of adverse outcomes. With these data we intend to develop a clinical prediction model for 30-day mortality using multivariable logistic regression. This model will be validated in an external cohort. Our primary endpoint is 30-day all-cause mortality. The secondary (composite) endpoint consist of 30-day mortality, length of hospital stay, admission to intensive- or medium care units, readmission and loss of independent living. Patients will be followed up for at least 30 days and, if possible, for one year., Discussion: In this study, we will retrieve a broad range of data concerning adverse outcomes in older patients visiting the ED with medical problems. We intend to develop a clinical tool for identification of older patients at risk of adverse outcomes that is feasible for use in the ED, in order to improve clinical decision making and medical care., Trial Registration: Retrospectively registered on clinicaltrials.gov ( NCT02946398 ; 9/20/2016).

Background: Older emergency department (ED) patients are at risk for adverse outcomes, however, it is hard to predict these. We aimed to assess the discriminatory value of clinical intuition, operationalized as disease perception, self-rated health and first clinical impression, including the 30-day surprise question (SQ: "Would I be surprised if this patient died in the next 30 days" of patients, nurses and physicians. Endpoints used to evaluate the discriminatory value of clinical intuition were short-term (30-day) mortality and other adverse outcomes (intensive/medium care admission, prolonged length of hospital stay, loss of independent living or 30-day readmission)., Methods: In this prospective, multicentre cohort study, older medical patients (≥65 years), nurses and physicians filled in scores regarding severity of illness and their concerns (i.e. disease perception and clinical impression scores) immediately after arrival of the patient in the ED. In addition, patients filled in a self-rated health score and nurses and physicians answered the SQ. Area under the curves (AUCs) of receiver operating characteristics (ROCs) were calculated., Results: The median age of the 602 included patients was 79 years and 86.7% were community dwelling. Within 30 days, 66 (11.0%) patients died and 263 (43.7%) patients met the composite endpoint. The severity of concern score of both nurses and physicians yielded the highest AUCs for 30-day mortality (for both 0.75; 95%CI 0.68-0.81). AUCs for the severity of illness score and SQ of nurses and physicians ranged from 0.71 to 0.74 while those for the disease perception and self-rated health of patients ranged from 0.64 to 0.69. The discriminatory value of the scores for the composite endpoint was lower (AUCs ranging from 0.60 to 0.67). We used scores that have not been previously validated which could influence their generalisability., Conclusion: Clinical intuition,-disease perception, self-rated health and first clinical impression-documented at an early stage after arrival in the ED, is a useful clinical tool to predict mortality and other adverse outcomes in older ED patients. Highest discriminatory values were found for the nurses' and physicians' severity of concern score. Intuition may be helpful for the implementation of personalised medical care in the future., Competing Interests: The authors have declared that no competing interests exist.