Severity of SARS-CoV-2 infection and albumin levels recorded at the first emergency department evaluation: a multicentre retrospective observational study.

BACKGROUND: The aim of this study was to investigate the association between serum albumin levels in the ED and the severity of SARS-CoV-2 infection. METHODS: This is a retrospective observational study conducted from 15 March 2020 to 5 April 2020 at the EDs of three different hospitals in Italy. Data from 296 patients suffering from COVID-19 consecutively evaluated at EDs at which serum albumin levels were routinely measured on patients' arrival in the ED were analysed. Albumin levels were measured, and whether these levels were associated with the presence of severe SARS-CoV-2 infection or 30-day survival was determined. Generalised estimating equation models were used to assess the relationship between albumin and study outcomes, and restricted cubic spline (RCS) regression was used to plot the adjusted dose-effect relationship for possible clinical confounding factors. RESULTS: The mean albumin level recorded on entry was lower in patients with severe SARS-CoV-2 infection than in those whose infections were not severe (3.5 g/dL (SD 0.3) vs 4 g/dL (SD 0.5)) and in patients who had died at 30 days post-ED arrival compared with those who were alive at this time point (3.3 g/dL (SD 0.3) vs 3.8 g/dL (SD 0.4)). Albumin <3.5 g/dL was an independent risk factor for both severe infection and death at 30 days, with adjusted odd ratios of 2.924 (1.509-5.664) and 2.615 (1.131-6.051), respectively. RCS analysis indicated that there was an adjusted dose-response association between the albumin values recorded on ED and the risk of severe infection and death. CONCLUSION: Albumin levels measured on presentation to the ED may identify patients with SARS-CoV-2 infection in whom inflammatory processes are occurring and serve as a potentially useful marker of disease severity and prognosis.

Rapid antigen test to identify COVID-19 infected patients with and without symptoms admitted to the Emergency Department.

PURPOSE: Early detection of SARS-CoV-2 patients is essential to contain the pandemic and keep the hospital secure. The rapid antigen test seems to be a quick and easy diagnostic test to identify patients infected with SARS-CoV-2. To assess the possible role of the antigen test in the Emergency Department (ED) assessment of potential SARS-CoV-2 infection in both symptomatic and asymptomatic patients. METHODS: Between 1 July 2020 and 10 December 2020, all patients consecutively assessed in the ED for suspected COVID-19 symptoms or who required hospitalisation for a condition not associated with COVID-19 were subjected to a rapid antigen test and RT-PCR swab. The diagnostic accuracy of the antigen test was determined in comparison to the SARS-CoV-2 PCR test using contingency tables. The possible clinical benefit of the antigen test was globally evaluated through decision curve analysis (DCA). RESULTS: A total of 3899 patients were subjected to antigen tests and PCR swabs. The sensitivity, specificity and accuracy of the antigen test were 82.9%, 99.1% and 97.4% (Cohen's K = 0.854, 95% CI 0.826-0.882, p < 0.001), respectively. In symptomatic patients, sensitivity was found to be 89.8%, while in asymptomatic patients, sensitivity was 63.1%. DCA appears to confirm a net clinical benefit for the preliminary use of antigen tests. CONCLUSIONS: The antigen test performed in the ED, though not ideal, can improve the overall identification of infected patients. While it appears to perform well in symptomatic patients, in asymptomatic patients, although it improves their management, it seems not to be definitive.

The ROX index can be a useful tool for the triage evaluation of COVID-19 patients with dyspnoea.

AIM: To assess whether the application of a non-invasive tool, such as ratio of oxygen saturation (ROX) index, during triage can identify patients with COVID-19 at high risk of developing acute respiratory distress syndrome (ARDS). DESIGN: A multi-centre, observational, retrospective study. METHODS: Only COVID-19 positive patients who required an emergency department evaluation for dyspnoea were considered. The primary objective of the study was to compare the ROX value obtained during triage with the medical diagnosis of ARDS and intubation in 72 h of the triage evaluation. The ROX index value was also compared with objective outcomes, such as the pressure of arterial O2 (PaO2 )/fraction of inspired oxygen (FiO2 ) ratio and the lung parenchyma volume involved in COVID-19-related inflammatory processes, based on 3D reconstructions of chest computed tomography (CT). RESULTS: During the study period, from 20 March 2020 until 31 May 2020, a total of 273 patients with confirmed SARS-CoV-2 infection were enrolled. The predictive ability of ROX for the risk of developing ARDS in 72 h after triage evaluation was associated with an area under the receiver operating characteristic (AUROC) of 0.845 (0.797-0.892, p < 0.001), whereas the AUROC value was 0.727 (0.634-0.821, p < 0.001) for the risk of intubation. ROX values were strongly correlated with PaO2 /FiO2 values (r = 0.650, p < 0.001), decreased ROX values were associated with increased percentages of lung involvement based on 3D CT reconstruction (r = -0.371, p < 0.001). CONCLUSION: The ROX index showed a good ability to identify triage patients at high evolutionary risk. Correlations with objective but more invasive indicators (PaO2 /FiO2 and CT) confirmed the important role of ROX in identifying COVID-19 patients with extensive pathological processes. IMPACT: During the difficult triage evaluation of COVID-19 patients, the ROX index can help the nurse to identify the real severity of the patient. The triage systems could integrate the ROX in the rapid patient assessment to stratify patients more accurately.

Acute abdominal pain in triage: A retrospective observational study of the Manchester triage system's validity.

OBJECTIVE: Roughly 5% to 10% of patients admitted to the emergency department suffer from acute abdominal pain. Triage plays a key role in patient stratification, identifying patients who need prompt treatment versus those who can safely wait. In this regard, the aim of this study was to estimate the performance of the Manchester Triage System in classifying patients with acute abdominal pain. METHODS: A total of 9,851 patients admitted at the Emergency Department of the Merano Hospital with acute abdominal pain were retrospectively enrolled between 1 January 2017 and 30 June 2019. The study was conducted and reported according to the STROBE statement. The sensitivity and specificity of the Manchester Triage System were estimated by verifying the triage classification received by the patients and their survival at seven days or the need for acute surgery within 72 h after emergency department access. RESULTS: Among the patients with acute abdominal pain (median age 50 years), 0.4% died within seven days and 8.9% required surgery within 72 hours. The sensitivity was 44.7% (29.9-61.5), specificity was 95.4% (94.9-95.8), and negative predictive value was 99.7% (99.2-100) in relation to death at seven days. CONCLUSIONS: The Manchester Triage System shows good specificity and negative predictive value. However, its sensitivity was low due to the amount of incorrect triage prediction in patients with high-priority codes (red/orange), suggesting overtriage in relation to seven-day mortality. This may be a protective measure for the patient. In contrast, the need for acute surgery within 72 h was affected by under-triage. RELEVANCE TO CLINICAL PRACTICE: The triage nurse using Manchester Triage System can correctly prioritise the majority of patients with acute abdominal pain, especially in low acuity patients. The Manchester Triage System is safe and does not underestimate the severity of the patients.

Risk factors associated with intracranial bleeding and neurosurgery in patients with mild traumatic brain injury who are receiving direct oral anticoagulants.

BACKGROUND: The established clinical risk factors for post-traumatic intracranial bleeding have not been evaluated in patients receiving DOACs yet. AIM: Evaluating the association between clinic and patient characteristics and post-traumatic intracranial bleeding (ICH) in patients with mild traumatic brain injury (MTBI) and DOACs. METHODS: This is a retrospective observational study conducted on three Emergency Departments. Multivariate analysis provided association in terms of OR with the risk of ICH. The performance of the multivariate model, described in a nomogram, has been tested with discrimination and decision curve analysis. RESULTS: Of 473 DOACs patients with MTBI, 8.5% had post-traumatic ICH. On multivariable analysis, major dynamics (odds ratio [OR] 6.255), post-traumatic amnesia (OR 3.961), post-traumatic loss of consciousness (LOC, OR 7.353), Glasgow Coma Scale (GCS) score < 15 (OR 3.315), post-traumatic headache (OR 4.168) and visible trauma above the clavicles (OR 3.378) were associated with a higher likelihood of ICH. The multivariate model, used for the nomogram construction, showed a good performance (AUC bias corrected with 5000 bootstraps resample 0.78). The DCAs showed a net clinical benefit of the prognostic model. CONCLUSIONS: Clinical risk factors can be used in DOACs patients to better define the risk of post-traumatic ICH.

Estimated plasma volume status (ePVS) could be an easy-to-use clinical tool to determine the risk of sepsis or death in patients with fever.

INTRODUCTION: Capillary permeability can be increased in patients with sepsis. Indirect estimation of plasma volume status (ePVS) could identify more severely ill patients with fever. METHODS: 1502 patients evaluated for fever at the Emergency Department (ED) of Merano General Hospital (Italy) between June 1, 2018 and May 30, 2019. The ePVS value registered on ED admission and derived from complete blood count was considered. Associations between the ePVS value and the two outcomes of the study (30-day mortality and sepsis diagnosis) were studied. RESULTS: Fifty-one of 1502 patients (3.4%) died at 30 days and 5.3% (80/1502) had a diagnosis of sepsis. The median ePVS in patients who died was higher than in those who survived (6.01 dL/g vs 4.49 dL/g, p < .001). In the multivariate analysis, ePVS higher than 4.52 dL/g presented an OR of 2.717 (CI95% 1.103-6.692, p = .020) for 30-day mortality and 1.824 (CI95% 1.055-3.154, p = .030) for the diagnosis of sepsis. ePVS presented a significant improvement in reclassification of the usual evaluation of patients with fever (NRI 21.6% for 30-day mortality and NRI 19.7 for sepsis diagnosis, p < .001). CONCLUSION: The ePVS value was a useful additional predictive tool to assess the severity of illness in patients with fever.

Blood sampling during nurse triage reduces patient length of stay in the emergency department: A propensity score-weighted, population-based study.

BACKGROUND: Increases in patients' length of stay (LOS) in the emergency department (ED) have led to overcrowding. OBJECTIVES: In this study, the implementation of blood sampling during triage in lower priority level patients was assessed as a possible means to reduce LOS. METHODS: A retrospective study was performed from January 2018 to January 2019. Lower priority level patients who required blood sampling for further diagnosis were considered. Patients who underwent blood sampling during triage evaluation were compared with those who underwent blood sampling after a physician's initial evaluation. RESULTS: During the study period, 15,596 patients were enrolled. LOS was shorter in patients who underwent triage blood sampling, presenting a median value of 154 min in comparison with the 172 min recorded in the control group (p < 0.001). Using a propensity score-matching to control the two groups' differences, LOS remained lower in the triage-sampling group (151 vs. 175 min; p < 0.001). In the adjusted multivariate model, triage blood sampling was found to be an independent factor for a decrease in the LOS, with standardized coefficient ß = 0.857 (0.822-0.894; p < 0.001). CONCLUSIONS: Performing blood sampling during nurse triage can decrease LOS in ED and also reduce ED permanence after a physician's initial evaluation.

Aldosterone and refractory hypertension: a prospective cohort study.

BACKGROUND: Resistant hypertension is common in clinical practice. The aim of our study was to evaluate inappropriate aldosterone activity in causing resistance to antihypertensive therapy. METHODS: Among the patients consecutively evaluated for the first time between 1995 and 2001, we selected all those (n = 157) with an aldosterone-to-renin ratio (ARR) >or=25 (ng/dL)/(ng/mL/h), and plasma aldosterone >or=12 ng/dL. Eight patients with Conn adenoma were excluded from the study. Fifty-eight were diagnosed as idiopathic aldosteronism (IHA), the other 91 patients, who did not meet the criteria for primary aldosteronism, were operatively classified as aldosterone-associated hypertension (AAH). As a control group, we randomly chose 160 patients with essential hypertension and plasma aldosterone <12 ng/dL (EH). Antihypertensive treatment was given in accordance to World Health Organization Guidelines (1999). The study end point was blood pressure (BP) <140/90 mm Hg. RESULTS: During follow-up (22 +/- 2 months), 24 (41.4%) patients with IHA, 35 (38.5%) with AAH, and 72 (54.0%) with EH reached the end point. According to survival analysis, AAH and IHA patients reached the end point in a smaller fraction and in a longer time compared with EH patients, with no difference between IHA and AAH. At the end of follow-up, IHA and AAH patients had higher diastolic BP than EH patients with no difference between IHA and AAH. CONCLUSIONS: Patients with elevated aldosterone plasma levels develop resistant hypertension, even in the absence of clinically diagnosed primary aldosteronism. Their identification will allow a targeted therapy and a more effective BP reduction.

Angiotensin II-induced over-activation of p47phox in fibroblasts from hypertensives: which role in the enhanced ERK1/2 responsiveness to angiotensin II?

BACKGROUND: Fibroblasts are involved in the remodeling of the heart and of the vasculature associated to arterial hypertension, and an abnormal extracellular signal-regulated kinase 1/2 (ERK1/2) activation by angiotensin II (Ang II) plays a pivotal role in this process. However, the intracellular pathways leading to cell hypertrophy and hyperplasia, as well as to collagen production, are still incompletely known. OBJECTIVE: To investigate the role of superoxide anion (O2) and of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase in Ang II-stimulated ERK1/2 over-activation in fibroblasts from hypertensive patients. METHODS: O2 production was measured in skin fibroblasts from hypertensives (HT, n = 11) and from normotensive controls (NT, n = 10) by electron spin resonance technique. ERK1/2 phosphorylation and p47phox NAD(P)H oxidase subunit translocation were measured by western blot. RESULTS: Ang II (1 micromol/l) induced a larger p47phox subunit translocation and increased intracellular O2 production to a larger extent in HT in comparison to NT and this effect was blocked by apocynin, an inhibitor of the NAD(P)H oxidase. Ang II increased ERK1/2 phosphorylation more in HT than in NT. The Ang II-induced ERK1/2 phosphorylation was inhibited by apocynin in a dose-dependent manner in NT, but not in HT. CONCLUSIONS: The chain of cellular events leading to increased ERK1/2 responsiveness to Ang II in hypertension include an exaggerated response of p47phox, NAD(P)H oxidase and O2, but it is partially resistant to apocynin. Therefore, NAD(P)H-dependent reactive oxygen species (ROS) production is not the only determinant of the exaggerated ERK1/2 responsiveness in fibroblasts of hypertensives (HT).

Effects of angiotensin II and insulin on ERK1/2 activation in fibroblasts from hypertensive patients.

BACKGROUND: Insulin resistance, a frequent finding in hypertensive patients, leads to accelerated cardiovascular damage. It has been suggested that a crosstalk between angiotensin II and insulin signaling pathways may provoke insulin resistance, and may contribute to the development of cardiovascular damage. To identify a common pathophysiologic pathway between metabolic disorders and cardiovascular remodeling, we investigated the effect of angiotensin II and insulin on extracellular signal regulated kinases 1 and 2 (ERK1/2), isoforms of mitogen-activated protein kinases (MAPK) involved in cellular proliferation and extracellular matrix deposition. METHODS: Skin fibroblasts from normotensive subjects, insulin sensitive hypertensive subjects, and insulin resistant hypertensive subjects were cultured and used after four passages. The ERK1/2 expression and phosphorylation were measured by Western blot using specific antibodies, respectively anti-ERK1/2 and anti-pERK1/2. Expression of AT1 receptor for angiotensin II was determined by reverse transcriptase-polymerase chain reaction in real time. RESULTS: The ERK1/2 were similarly expressed in skin fibroblasts from all groups; ERK1/2 phosporylation evoked by angiotensin II was significantly higher in fibroblasts from hypertensive patients in comparison to normotensive subjects, but the increase was observed only in insulin resistant hypertensive subjects. The effect of insulin on ERK1/2 phosphorylation was not significantly different in the three groups. Treatment with the combination of insulin and angiotensin II increased ERK1/2 phosphorylation to a greater extent in comparison to the single agonists in normotensive subjects and in insulin sensitive but not in insulin resistant hypertensive subjects. CONCLUSIONS: Angiotensin II stimulated ERK1/2 activation is increased in insulin resistant hypertensive subjects, and it may play a role in the pathogenesis of insulin resistance and accelerated cardiovascular damage.

Abnormal regulation of G protein alpha(i2) subunit in skin fibroblasts from insulin-resistant hypertensive individuals.

BACKGROUND: Studies in experimental animals and human cells have demonstrated increased intracellular calcium (Ca(i2) signalling and Galphai signal transduction associated with hypertension. We have recently shown that angiotensin II-induced mobilization of Ca(i2) is enhanced in fibroblasts from hypertensive individuals in comparison with that in normotensive individuals and that it is blunted by insulin and pertussis toxin in insulin-sensitive, but not in insulin-resistant, patients. This suggests that G(i)-mediated signal transduction is reduced in insulin-resistant hypertension. OBJECTIVE: To investigate the expression and regulation of Galpha(i2) subunit in insulin-sensitive and insulin-resistant hypertensive individuals. METHODS: G protein alpha(i2) subunit mRNA was measured in cultured skin fibroblasts from patients with insulin-sensitive and insulin-resistant hypertension, by real-time reverse transcriptase polymerase chain reaction. We also investigated the effects of short-term exposure to fetal calf serum, angiotensin II and insulin, alone and in combination, on the expression of Galpha(i2) in vitro. Spectrofluorophotometric measurement of free Cai was performed in monolayers of 24 h serum-deprived cells in basal conditions and after exposure to angiotensin II, with and without pre-incubation with insulin. RESULTS: Expression of Galpha(i2) was significantly greater in fibroblasts from hypertensive individuals than in normotensive individuals and the increase was unrelated to age and body mass. The difference was largely accounted for by greater values in insulin-sensitive than in insulin-resistant hypertensive individuals. In fibroblasts from those with insulin-sensitive hypertension, angiotensin II and insulin were additive to fetal calf serum in increasing the expression of Galpha(i2). In these patients, insulin blunted the angiotensin-II induced Cai transient. In contrast, in those with insulin-resistant hypertension, Galpha(i2) was lower and unresponsive to angiotensin II and insulin. Finally, in fibroblasts from insulin-resistant patients, insulin was unable to reduce the angiotensin II-induced Cai peak. CONCLUSIONS: A subnormal Galpha(i2)-mediated signal transduction may be involved in the pathogenesis of cellular insulin resistance in hypertension. This novel Galpha(i2)-mediated signal transduction associated with insulin sensitivity in fibroblasts may help to control excessive angiotensin II signalling.