There is a lack of validated tools to assess potential disease progression and hospitalisation decisions in patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify suitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-65) to fulfil this unmet clinical need. An observational derivation patient cohort validated by an independent secondary analysis across nine EDs. Logistic and Cox regression, area under the receiver operating characteristic (AUROC) and Kaplan-Meier curves were used to assess performance. Disease progression was identified using a composite endpoint of 28-day mortality, ICU admission and hospitalisation > 10 days. One thousand one hundred seventy-five derivation and 896 validation patients were analysed with respective 28-day mortality rates of 7.1% and 5.0%, and hospitalisation rates of 77.9% and 76.2%. MR-proADM showed greatest accuracy in predicting 28-day mortality and hospitalisation requirement across both cohorts. Patient subgroups with high MR-proADM concentrations (≥ 1.54 nmol/L) and low biomarker (PCT < 0.25 ng/mL, lactate < 2.0 mmol/L or CRP < 67 mg/L) or clinical score (SOFA < 2 points, qSOFA < 2 points, NEWS < 4 points or CRB-65 < 2 points) values were characterised by a significantly longer length of hospitalisation (p < 0.001), rate of ICU admission (p < 0.001), elevated mortality risk (e.g. SOFA, qSOFA and NEWS HR [95%CI], 45.5 [10.0–207.6], 23.4 [11.1–49.3] and 32.6 [9.4–113.6], respectively) and a greater number of disease progression events (p < 0.001), compared to similar subgroups with low MR-proADM concentrations (< 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MR-proADM cut-off of < 0.87 nmol/L (15.0% and 16.6%), with decreased readmission rates and no mortalities. In patients presenting to the ED with a suspected infection, the blood biomarker MR-proADM could most accurately identify the likelihood of further disease progression. Incorporation into an early sepsis management protocol may therefore aid rapid decision-making in order to either initiate, escalate or intensify early treatment strategies, or identify patients suitable for safe out-patient treatment.

Objective We examined the effects of the various sleep stages on baroreflex sensitivity (BRS), and heart rate and blood pressure (BP) variability, and tested the hypothesis that there is a different behavior of the baroreflex control of the sinus node in response to hypertensive and hypotensive stimuli and in relation to different cycles of the overnight sleep. Design Polygraphic sleep recordings were performed in 10 healthy males. The BP and the RR interval were continuously recorded during sleep. Methods BRS was calculated by the sequences method. Autoregressive power spectral analysis was used to investigate the RR-interval and BP variabilities. Results During rapid eye movement (REM) sleep BRS significantly increased in response to hypertensive stimuli in comparison with non-rapid eye movement (NREM) sleep and the awake state, whereas it did not change in response to hypotensive stimuli. In the first sleep cycle, BRS significantly increased during NREM in comparison with wakefulness, whereas during REM BRS in response to hypertensive stimuli did not show significant changes as compared with the awake state and/or with NREM. During REM occurring in the sleep cycle before morning awakening, BRS showed a significant increase in response to hypertensive stimuli in comparison with both NREM and the awake state. Conclusions During sleep, arterial baroreflex modulation of the sinus node is different in response to hypotensive and hypertensive stimuli particularly during REM. Furthermore, baroreflex control of the sinus node shows a non-uniform behavior during REM occurring in different nocturnal sleep cycles. These findings suggest that the arterial baroreflex is more effective in buffering the increased sympathetic activation associated with REM at the end of sleep than in the early night.

Background —Analysis of spontaneous fluctuations in systolic arterial pressure (SAP) and pulse interval (PI) reveals the occurrence of sequences of consecutive beats characterized by SAP and PI changing in the same (+PI/+SAP and −PI/−SAP) or opposite (−PI/+SAP and +PI/−SAP) direction. Although the former reflects baroreflex regulatory mechanisms, the physiological meaning of −PI/+SAP and +PI/−SAP is unclear. We tested the hypothesis that −PI/+SAP and +PI/−SAP “nonbaroreflex” sequences represent a phenomenon modulated by the autonomic nervous system reflecting a feed-forward mechanism of cardiovascular regulation. Methods and Results —We studied anesthetized rabbits before and after (1) complete autonomic blockade (guanethidine+propranolol+atropine, n=13; CAB), (2) sympathetic blockade (guanethidine+propranolol, n=15; SB), (3) parasympathetic blockade (atropine, n=16), (4) sinoaortic denervation (n=10; SAD), and (5) controlled respiration (n=10; CR). Nonbaroreflex sequences were defined as ≥3 beats in which SAP and PI of the following beat changed in the opposite direction. CAB reduced the number of nonbaroreflex sequences (19.1±12.3 versus 88.7±36.6, P <0.05), as did SB (25.3±11.7 versus 84.6±23.9, P <0.001) and atropine (11.2±6.8 versus 94.1±32.4, P <0.05). SB concomitantly increased baroreflex sensitivity (1.18±0.11 versus 0.47±0.09 ms/mm Hg, P <0.01). SAD and CR did not significantly affect their occurrence. Conclusions —These results suggest that nonbaroreflex sequences represent the expression of an integrated, neurally mediated, feed-forward type of short-term cardiovascular regulation able to interact dynamically with the feedback mechanisms of baroreflex origin in the control of heart period.

The aim of our study was to evaluate the prognostic value of MR-proADM and PCT levels in febrile patients in the ED in comparison with a disease severity index score, the APACHE II score. We also evaluated the ability of MR-proADM and PCT to predict hospitalization.

Serum albumin levels are strongly associated with the morbidity, prognosis, and mortality rates of patients with hypoalbuminemia, which is a frequent problem during hospitalization. An observational retrospective study was carried out to analyze changes in albumin levels in hospitalized patients at the “Fondazione Policlinico Tor Vergata—PTV” in 2018. The prevalence of preexisting hypoalbuminemia at the time of discharge from hospital was investigated using a sample of 9428 patients. Information was collected from the discharge files recorded in the central informatics system of the hospital. Analysis of albumin levels at admission and at discharge was conducted by classes of albuminemia and then stratified by age. At the time of admission, hypoalbuminemia was found to be present in more than half of the sample, with no sex differences. The serum albumin level tended to decrease with age, with pathologic levels appearing from 50 years and progressive worsening thereafter. The condition of marked and mild hypoalbuminemia was more prevalent in patients over 65 years of age. Our findings suggest that hypoalbuminemia should be considered a dangerous condition in itself and a serious public health problem. We aimed to emphasize the role of albumin as useful marker of the in-hospital malnutrition and frailty, to be integrated in the routinely assessment of patients for reconsidering ad hoc healthcare pathways after discharge from hospital, especially when dealing with fragile populations.

(i) evaluate the performance of MR-pro-ADM in reflecting the outcome and risk for CAP patients in the emergency department, and (ii) compare the prognostic performance of MR-pro-ADM with that of clinical scores PSI and CURB65. Observational prospective, single-center study in patients with suspected community acquired pneumonia (CAP). Eighty one patients underwent full clinical and laboratory assessment as by protocol, and were followed up a 28 days. Primary endpoints measured were: death, death at 14 days, non-invasive mechanical ventilation (NIMV), endotracheal intubation (EI), ICU admission, overall hospital stay >10 days, emergency department stay >4 days. The discriminative performance of MR-pro-ADM and clinical scores was assessed by AUROC analysis. The distribution for MR-pro-ADM followed an upward trend, increasing with the increase of both PSI (p<0.001) and CURB65 (p10 days and DE stay >4 days, compared to the PSI and CURB (though difference not statistically significant). For each endpoint measured, the best thresholds values for Mr-pro-ADM were: 1.6 (specificity 76.5%; sensitivity 77.8%) for death; 2.5 (specificity 88.9%; sensitivity 80.0%) for death at 14 days; 1.5 (specificity 77.0%; sensitivity 87.5%) for NIMV; 2.4 (specificity 88.7%; sensitivity 83.3%) for endotracheal intubation; 0.9 (specificity 53.5%; sensitivity 70.6%) for DE stay greater than 4 days; 1.9 (specificity 82.1%; sensitivity 55.3%) for hospital stay greater than 10 days. The AUC for the combination of MR-pro-ADM and PSI was 81.29% [63.41%–99.17%], but not in a statistically significant manner compared to the AUCs of the single predictors. Conversely, the AUC for the combination of MR-pro-ADM and CURB65 was 87.58% [75.54%–99.62%], which was significantly greater than the AUC of CURB65 (p = 0.047) or PSI (p = 0.017) alone. The present study confirms that assessment of MR-pro-ADM levels in CAP patients in addition to CURB scores increases the prognostic accuracy of CURB alone and may help rule out discrepancies arising from flawed clinical severity classification. With particular reference to patients scoring in the upper classes of CURB and PSI, MR-pro-ADM values provided additional information towards a better risk stratification of those patients. In particular, our results pointed towards two MR-pro-ADM threshold values that appear to predict with a good degree of accuracy the patient's need for non-invasive mechanical ventilation, endotracheal intubation, or intensive care. This aspect, however, deserves further investigation.