Mid-regional pro-adrenomedullin as a supplementary tool to clinical parameters in cases of suspicion of infection in the emergency department

Introduction: Mid-regional proadrenomedullin (MR-proADM), a novel biomarker, has recently gained interest particularly with regards to its potential in assisting clinicians\u2019 decision making in patients with suspicion of infection in the emergency department (ED). A group of international experts, with research and experience in MR-proADM applications, produced this review based on their own experience and the currently available literature. Areas covered: The review provides evidence related to MR-proADM as a triaging tool in avoiding unnecessary admissions to hospital and/or inadequate discharge, and identifying patients most at risk of deterioration. It also covers the use of MR-proADM in the context of COVID-19. Moreover, the authors provide a proposal on how to incorporate MR-proADM into patients\u2019 clinical pathways in an ED setting. Expert opinion: The data we have so far on the application of MR-proADM in the ED is promising. Incorporating it into clinical scoring systems may aid the clinician\u2019s decision making and recognizing the \u2018ill looking well\u2019 and the \u2018well looking ill\u2019 sooner. However there are still many gaps in our knowledge especially during the ongoing COVID-19 waves. There is also a need for cost-effectiveness analysis studies especially in the era of increasing cost pressures on health systems globally

Correlations between chest-CT and laboratory parameters in SARS-CoV-2 pneumonia: A single-center study from Italy

To investigate the relationship between damaged lung assessed by chest computed tomography (CT) scan and laboratory biochemical parameters with the aim of finding other diagnostic tools. Patients who underwent chest CT for suspected Corona Virus Disease-2019 (COVID-19) pneumonia at the emergency department admission in the first phase of COVID-19 epidemic in Italy were retrospectively analyzed. Patients with both negative chest CT and absence of the novel coronavirus in nasopharyngeal or oropharyngeal real-time reverse transcriptase polymerase chain reaction (RT-PCR) swabs were excluded from the study. A total of 462 patients with positive CT scans for interstitial pneumonia were included in the study (250 males and 212 females, mean age 57 +/- 17 years, range 18-89). Of these, 344 were positive to RT-PCR test, 118 were negative to double RT-PCR tests. CTs were analyzed for quantification of affected lung volume visually and by dedicated software. Statistical analysis to evaluate the relationship between laboratory analyses and CT patterns and amount of damaged lung related with COVID-19 pneumonia was performed in 2 groups of patients: positive RT-PCR COVID-19 group and negative RT-PCR COVID-19 group, but both with positive CT scans for interstitial pneumonia. Lymphocytopenia, C-reactive protein (CRP), lactate dehydrogenase (LDH), d-dimer, and fibrinogen increased levels occurred in most patients without statistically significant differences between the 2 groups with CT scans suggestive for COVID-19. In fact, in both groups the volume of lung damage was strongly associated with altered laboratory test results, even for patients with negative RT-PCR test. The decreased number of lymphocytes, and the increased levels of CRP, LDH, d-dimer, and fibrinogen levels are associated with SARS-CoV 2 related pneumonia. This may be useful as an additional diagnostic tool in patients with double negative RT-PCR assay and with highly suspected clinic and chest CT features for COVID-19 to isolate patients in a pandemic period

Evaluation of Hepcidin Level in COVID-19 Patients Admitted to the Intensive Care Unit

Coronavirus disease 2019 (COVID-19) presents a clinical spectrum that ranges from a mild condition to critical illness. Patients with critical illness present respiratory failure, septic shock and/or multi-organ failure induced by the so called “cytokine storm”. Inflammatory cytokines affect iron metabolism, mainly inducing the synthesis of hepcidin, a hormone peptide not routinely measured. High levels of hepcidin have been associated with the severity of COVID-19. The aim of this study was to analyze, retrospectively, the levels of hepcidin in a group of COVID-19 patients admitted to the intensive care unit (ICU) of the Policlinico Tor Vergata of Rome, Italy. Thirty-eight patients from November 2020 to May 2021 were enrolled in the study. Based on the clinical outcome, the patients were assigned to two groups: survivors and non-survivors. Moreover, a series of routine laboratory parameters were monitored during the stay of the patients in the ICU and their levels correlated to the outcome. Statistical differences in the level of hepcidin, D-dimer, IL-6, LDH, NLR, neutrophils level, CRP, TNF-α and transferrin were observed between the groups. In particular, hepcidin values showed significantly different median concentrations (88 ng/mL vs. 146 ng/mL) between survivors and non-survivors. In addition, ROC curves analysis revealed sensitivity and specificity values of 74% and 76%, respectively, at a cut-off of 127 (ng/mL), indicating hepcidin as a good biomarker in predicting the severity and mortality of COVID-19 in ICU patients

Predictive Value of MR-proADM in the Risk Stratification and in the Adequate Care Setting of COVID-19 Patients Assessed at the Triage of the Emergency Department

In the past two pandemic years, Emergency Departments (ED) have been overrun with COVID-19-suspicious patients. Some data on the role played by laboratory biomarkers in the early risk stratification of COVID-19 patients have been recently published. The aim of this study is to assess the potential role of the new biomarker mid-regional proadrenomedullin (MR-proADM) in stratifying the in-hospital mortality risk of COVID-19 patients at the triage. A further goal of the present study is to evaluate whether MR-proADM together with other biochemical markers could play a key role in assessing the correct care level of these patients. Data from 321 consecutive patients admitted to the triage of the ED with a COVID-19 infection were analyzed. Epidemiological; demographic; clinical; laboratory; and outcome data were assessed. All the biomarkers analyzed showed an important role in predicting mortality. In particular, an increase of MR-proADM level at ED admission was independently associated with a threefold higher risk of IMV. MR-proADM showed greater ROC curves and AUC when compared to other laboratory biomarkers for the primary endpoint such as in-hospital mortality, except for CRP. This study shows that MR-proADM seems to be particularly effective for early predicting mortality and the need of ventilation in COVID-19 patients admitted to the ED

Maladaptive behaviors are linked with inefficient sleep in individuals with developmental disabilities

The purpose of the current study was to assess the relations between nightly sleep patterns and the frequency of daily maladaptive behavior. Antecedent and consequential relations between sleep patterns and behavior were evaluated with time series analysis. Sleep efficiency and maladaptive behavior were determined for 20 female residents of an institutional care facility for adults with developmental disabilities. Daily maladaptive behavioral data and nightly sleep/awake logs were collected for 4 months for each participant. Efficient sleep patterns were significantly associated with lower frequencies of maladaptive behaviors. All lagged cross-correlations 8 days before and 8 days after an evening of sleep were significant. These findings suggested that inefficient sleep was associated with increased maladaptive behaviors and that the lagged associations reflected a chronic but not an acute linkage between sleep and behavior

Identification of COVID-19 patients at risk of hospital admission and mortality: a European multicentre retrospective analysis of mid-regional pro-adrenomedullin

Background: Mid-Regional pro-Adrenomedullin (MR-proADM) is an inflammatory biomarker that improves the prognostic assessment of patients with sepsis, septic shock and organ failure. Previous studies of MR-proADM have primarily focussed on bacterial infections. A limited number of small and monocentric studies have examined MR-proADM as a prognostic factor in patients infected with SARS-CoV-2, however there is need for multicenter validation. An evaluation of its utility in predicting need for hospitalisation in viral infections was also performed. Methods: An observational retrospective analysis of 1861 patients, with SARS-CoV-2 confirmed by RT-qPCR, from 10 hospitals across Europe was performed. Biomarkers, taken upon presentation to Emergency Departments (ED), clinical scores, patient demographics and outcomes were collected. Multiclass random forest classifier models were generated as well as calculation of area under the curve analysis. The primary endpoint was hospital admission with and without death. Results: Patients suitable for safe discharge from Emergency Departments could be identified through an MR-proADM value of ≤ 1.02 nmol/L in combination with a CRP (C-Reactive Protein) of ≤ 20.2 mg/L and age ≤ 64, or in combination with a SOFA (Sequential Organ Failure Assessment) score < 2 if MR-proADM was ≤ 0.83 nmol/L regardless of age. Those at an increased risk of mortality could be identified upon presentation to secondary care with an MR-proADM value of > 0.85 nmol/L, in combination with a SOFA score ≥ 2 and LDH > 720 U/L, or in combination with a CRP > 29.26 mg/L and age ≤ 64, when MR-proADM was > 1.02 nmol/L. Conclusions: This international study suggests that for patients presenting to the ED with confirmed SARS-CoV-2 infection, MR-proADM in combination with age and CRP or with the patient’s SOFA score could identify patients at low risk where outpatient treatment may be safe

Sympathetic Activation and Baroreflex Function during Intradialytic Hypertensive Episodes

BACKGROUND: The mechanisms of intradialytic increases in blood pressure are not well defined. The present study was undertaken to assess the role of autonomic nervous system activation during intradialytic hypertensive episodes. METHODOLOGY/PRINCIPAL FINDINGS: Continuous interbeat intervals (IBI) and systolic blood pressure (SBP) were monitored during hemodialysis in 108 chronic patients. Intradialytic hypertensive episodes defined as a period of at least 10 mmHg increase in SBP between the beginning and the end of a dialysis session or hypertension resistant to ultrafiltration occurring during or immediately after the dialysis procedure, were detected in 62 out of 113 hemodialysis sessions. SBP variability, IBI variability and baroreceptor sensitivity (BRS) in the low (LF) and high (HF) frequency ranges were assessed using the complex demodulation technique (CDM). Intradialytic hypertensive episodes were associated with an increased (n = 45) or decreased (n = 17) heart rate. The maximal blood pressure was similar in both groups. In patients with increased heart rate the increase in blood pressure was associated with marked increases in SBP and IBI variability, with suppressed BRS indices and enhanced sympatho-vagal balance. In contrast, in those with decreased heart rate, there were no significant changes in the above parameters. End-of-dialysis blood pressure in all sessions associated with hypertensive episode was significantly higher than in those without such episodes. In logistic regression analysis, predialysis BRS in the low frequency range was found to be the main predictor of intradialytic hypertension. CONCLUSION/SIGNIFICANCE: Our data point to sympathetic overactivity with feed-forward blood pressure enhancement as an important mechanism of intradialytic hypertension in a significant proportion of patients. The triggers of increased sympathetic activity during hemodialysis remain to be determined. Intradialytic hypertensive episodes are associated with higher end-of-dialysis blood pressure, suggesting that intradialytic hypertension may play a role in generation of interdialytic hypertension

Cardiovascular control and stabilization via inclination and mobilization during bed rest

Cardiovascular deconditioning has long been recognized as a characteristic of the physiological adaptation to long-term bed rest in patients. The process is thought to contribute to orthostatic intolerance and enhance secondary complications in a significant way. Mobilization is a cost-effective and simple method to maintain the cardiovascular parameters (i.e., blood pressure, heart rate) stable, counter orthostatic intolerance and reduce the risk of secondary problems in patients during long-term immobilization. The aim of this project is to control the cardiovascular parameters such as heart rate and blood pressure of bed rest patients via automated leg mobilization and body tilting. In a first step, a nonlinear model predictive control strategy was designed and evaluated on five healthy subjects and 11 bed rest patients. In a next step, a clinically feasible study was conducted on two patients. The mean values differed on average less than 1 bpm from the predetermined heart rate and less than 2.5 mmHg from the desired blood pressure values. These results of the feasibility study are promising, although heterogeneous disease etiologies and individual medication strongly influence the mechanically induced reactions. The long-term goal is an automation of the control of physiological signals and the mobilization of bed rest patients in an early phase of the rehabilitation process. Therefore, this new approach could help to strengthen the cardiovascular system and prevent secondary health problems arising from long-term bed rest

Positive and Negative Feedback Mechanisms in the Neural Regulation of Cardiovascular Function in Healthy and Spinal Cord–Injured Humans

Background —We tested the hypothesis that in humans, hypertension/tachycardia and hypotension/bradycardia nonbaroreflex sequences that occur within spontaneous arterial pressure (AP) and R-R interval fluctuations are an expression of positive feedback mechanisms neurally regulating the cardiovascular system. Methods and Results —We studied 15 spinal cord–injured (SCI) subjects (8 tetraplegics and 7 paraplegics) and 8 healthy subjects. The occurrence of nonbaroreflex (NBseq) and baroreflex (Bseq) sequences, ie, hypertension-bradycardia and hypotension-tachycardia sequences, was assessed during rest and head-up tilt (HUT). The ratio between Bseq and NBseq (B/NB ratio) was also calculated. In resting conditions, the occurrence of NBseq was significantly lower ( P <0.05) in tetraplegics (7.9±1.5) than in paraplegics (16.2±3.2) and normal subjects (19.0±3.5), whereas the occurrence of Bseq was not significantly different between the 3 groups (38.6±11.9 versus 45.4±6.0 versus 47.0±11.9). In tetraplegics, the B/NB ratio showed a marked, significant decrease (from 8.4±4.2 to 1.9±0.8, P <0.05) in response to HUT, whereas in normal subjects, it showed a significant increase (from 3.5±0.7 to 9.4±2.7, P <0.05). In paraplegics, the B/NB ratio did not change significantly in response to HUT (from 4.5±1.6 to 4.8±1.1). Conclusions —Our data suggest that nonbaroreflex sequences occur in humans and might represent the expression of an integrated, neurally mediated, feed-forward type of short-term cardiovascular regulation that is able to interact dynamically with feedback mechanisms of baroreflex origin