Decrease of haemoconcentration reliably detects hydrostatic pulmonary oedema in dyspnoeic patients in the emergency department - a machine learning approach.

BACKGROUND: Haemoglobin variation (ΔHb) induced by fluid transfer through the intestitium has been proposed as a useful tool for detecting hydrostatic pulmonary oedema (HPO). However, its use in the emergency department (ED) setting still needs to be determined. METHODS: In this observational retrospective monocentric study, ED patients admitted for acute dyspnoea were enrolled. Hb values were recorded both at ED presentation (T0) and after 4 to 8 h (T1). ΔHb between T1 and T0 (ΔHbT1-T0) was calculated as absolute and relative value. Two investigators, unaware of Hb values, defined the cause of dyspnoea as HPO and non-HPO. ΔHbT1-T0 ability to detect HPO was evaluated. A machine learning approach was used to develop a predictive tool for HPO, by considering the ability of ΔHb as covariate, together with baseline patient characteristics. RESULTS: Seven-hundred-and-six dyspnoeic patients (203 HPO and 503 non-HPO) were enrolled over 19 months. Hb levels were significantly different between HPO and non-HPO patients both at T0 and T1 (p < 0.001). ΔHbT1-T0 were more pronounced in HPO than non-HPO patients, both as relative (-8.2 [-11.2 to -5.6] vs. 0.6 [-2.1 to 3.3] %) and absolute (-1.0 [-1.4 to -0.8] vs. 0.1 [-0.3 to 0.4] g/dL) values (p < 0.001). A relative ΔHbT1-T0 of -5% detected HPO with an area under the receiver operating characteristic curve (AUROC) of 0.901 [0.896-0.906]. Among the considered models, Gradient Boosting Machine showed excellent predictive ability in identifying HPO patients and was used to create a web-based application. ΔHbT1-T0 was confirmed as the most important covariate for HPO prediction. CONCLUSIONS: ΔHbT1-T0 in patients admitted for acute dyspnoea reliably identifies HPO in the ED setting. The machine learning predictive tool may represent a performing and clinically handy tool for confirming HPO.

SARS-CoV-2 infection risk is higher in vaccinated patients with inflammatory autoimmune diseases or liver transplantation treated with mycophenolate due to an impaired antiviral immune response: results of the extended follow up of the RIVALSA prospective cohort.

Background: A relevant proportion of immunocompromised patients did not reach a detectable seroconversion after a full primary vaccination cycle against SARS-CoV-2. The effect of different immunosuppressants and the potential risks for SARS-CoV-2 infection in these subjects is largely unknown. Methods: Patients from the Rivalsa prospective, observational cohort study with planned anti SARS-CoV-2 third dose mRNA vaccination between October and December 2021 were asked to participate to this follow-up study. Patients were asked about eventual confirmed positivity to SARS-CoV-2 infection within 6 months from the third dose and to undergo a blood draw to evaluate seroconversion status after the additional vaccine shot. Results: 19 out of 114 patients taking part in the survey developed a confirmed SARS-CoV-2 infection; we identified mycophenolate treatment as an independent predictor of an increased risk of infection even after the third vaccine dose (OR: 5.20, 95% CI: 1.70-20.00, p=0.0053). This result is in agreement with the in vitro evidence that MMF impairs both B and T lymphocytes driven immune responses (reduction both in memory B cells producing anti-spike antibodies and in proliferating CD4+ and CD8+ T cells). Conclusions: Immunocompromised patients need an additional vaccine administration to reach a detectable seroconversion, thus fostering a more personalized approach to their clinical management. Moreover, patients undergoing mycophenolate treatment show a specific increased infection risk, with respect to other immunosuppressants thus supporting a closer monitoring of their health status.

COVID-19 Biomarkers at the Crossroad between Patient Stratification and Targeted Therapy: The Role of Validated and Proposed Parameters.

Clinical knowledge about SARS-CoV-2 infection mechanisms and COVID-19 pathophysiology have enormously increased during the pandemic. Nevertheless, because of the great heterogeneity of disease manifestations, a precise patient stratification at admission is still difficult, thus rendering a rational allocation of limited medical resources as well as a tailored therapeutic approach challenging. To date, many hematologic biomarkers have been validated to support the early triage of SARS-CoV-2-positive patients and to monitor their disease progression. Among them, some indices have proven to be not only predictive parameters, but also direct or indirect pharmacological targets, thus allowing for a more tailored approach to single-patient symptoms, especially in those with severe progressive disease. While many blood test-derived parameters quickly entered routine clinical practice, other circulating biomarkers have been proposed by several researchers who have investigated their reliability in specific patient cohorts. Despite their usefulness in specific contexts as well as their potential interest as therapeutic targets, such experimental markers have not been implemented in routine clinical practice, mainly due to their higher costs and low availability in general hospital settings. This narrative review will present an overview of the most commonly adopted biomarkers in clinical practice and of the most promising ones emerging from specific population studies. Considering that each of the validated markers reflects a specific aspect of COVID-19 evolution, embedding new highly informative markers into routine clinical testing could help not only in early patient stratification, but also in guiding a timely and tailored method of therapeutic intervention.

Decreased Gas6 and sAxl Plasma Levels Are Associated with Hair Loss in COVID-19 Survivors.

Post-acute conditions after coronavirus disease 2019 (COVID-19) are quite common, although the underlying pathogenetic mechanisms leading to these conditions are not yet completely understood. In this prospective observational study, we aimed to test the hypothesis that Growth Arrest-Specific 6 (Gas6) and its soluble receptors, Axl (sAxl) and MerTK (sMer), might be implicated. A total of 263 subjects underwent a structured clinical evaluation one year after their hospital discharge for COVID-19, and they consented to donate a blood sample to measure their circulating Gas6, sAxl, and sMer levels. A total of 98 (37.3%) post-COVID-19 subjects complained of at least one residual physical symptom one year after their hospital discharge. Univariate analysis revealed that sAxl was marginally associated with residual symptoms, but at the level of logistic regression analysis, only the diffusing capacity of the lungs for carbon monoxide (DLCO) (OR 0.98, CI 95%: 0.96-0.99; p = 0.007) and the female sex (OR 2.49, CI 95%: 1.45-4.28; p = 0.001) were independently associated with long-lasting symptoms. A total of 69 (26.2%) subjects had hair loss. At the level of univariate analysis, Gas6, sAxl, DLCO, and the female gender were associated with its development. In a logistic regression analysis model, Gas6 (OR 0.96, CI 95%: 0.92-0.99; p = 0.015) and sAxl (OR 0.98, CI 95%; 0.97-1.0; p = 0.014), along with the female sex (OR 6.58, CI 95%: 3.39-12.78; p = 0.0001), were independent predictors of hair loss. Decreased levels of Gas6 and sAxl were associated with a history of hair loss following COVID-19. This was resolved spontaneously in most patients, although 23.7% complained of persistent hair loss one year after hospital discharge.

Baseline Plasma Osteopontin Protein Elevation Predicts Adverse Outcomes in Hospitalized COVID-19 Patients.

More than three years have passed since the first case, and COVID-19 is still a health concern, with several open issues such as the lack of reliable predictors of a patient's outcome. Osteopontin (OPN) is involved in inflammatory response to infection and in thrombosis driven by chronic inflammation, thus being a potential biomarker for COVID-19. The aim of the study was to evaluate OPN for predicting negative (death or need of ICU admission) or positive (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. We enrolled 133 hospitalized, moderate-to-severe COVID-19 patients in a prospective observational study between January and May 2021. Circulating OPN levels were measured by ELISA at admission and at day 7. The results showed a significant correlation between higher plasma concentrations of OPN at hospital admission and a worsening clinical condition. At multivariate analysis, after correction for demographic (age and gender) and variables of disease severity (NEWS2 and PiO2/FiO2), OPN measured at baseline predicted an adverse prognosis with an odds ratio of 1.01 (C.I. 1.0-1.01). At ROC curve analysis, baseline OPN levels higher than 437 ng/mL predicted a severe disease evolution with 53% sensitivity and 83% specificity (area under the curve 0.649, p = 0.011, likelihood ratio of 1.76, (95% confidence interval (CI): 1.35-2.28)). Our data show that OPN levels determined at the admission to hospital wards might represent a promising biomarker for early stratification of patients' COVID-19 severity. Taken together, these results highlight the involvement of OPN in COVID-19 evolution, especially in dysregulated immune response conditions, and the possible use of OPN measurements as a prognostic tool in COVID-19.

Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial.

As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63-1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70-1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19.

In-Hospital Predictors of Need for Ventilatory Support and Mortality in Chest Trauma: A Multicenter Retrospective Study.

Chest trauma management often requires the use of invasive and non-invasive ventilation. To date, only a few studies investigated the predictors of the need for ventilatory support. Data on 1080 patients with chest trauma managed in two different centers were retrospectively analyzed. Univariate and multivariate analyses were performed to identify the predictors of tracheal intubation (TI), non-invasive mechanical ventilation (NIMV), and mortality. Rib fractures (p = 0.0001) fracture of the scapula, clavicle, or sternum (p = 0.045), hemothorax (p = 0.0035) pulmonary contusion (p = 0.0241), and a high Injury Severity Score (ISS) (p ≤ 0001) emerged as independent predictors of the need of TI. Rib fractures (p = 0.0009) hemothorax (p = 0.0027), pulmonary contusion (p = 0.0160) and a high ISS (p = 0.0001) were independent predictors of NIMV. The center of trauma care (p = 0.0279), age (p < 0.0001) peripheral oxygen saturation in the emergency department (p = 0.0010), ISS (p < 0.0001), and Revised Trauma Score (RTS) (p < 0.0001) were independent predictors of outcome. In conclusion, patients who do not require TI, while mandating ventilatory support with selected types of injuries and severity scores, are more likely to be subjected to NIMV. Trauma team expertise and the level of the trauma center could influence patient outcomes.

May an incidental finding on chest CT be a predictor of access in intensive care unit? Role of hepatic steatosis in patients affected by SARS-CoV-2.

Background: Due to the high prevalence of hepatic steatosis (HS), the aim of the study is to verify the frequency of HS incidentally detected in chest computed tomography (CT) imaging in our population affected by SARS-CoV-2 and to investigate its association with the severity of the infection and outcome in terms of hospitalization. Design and methods: We retrospectively analyzed 500 patients with flu syndrome and clinically suspected of having Sars-CoV-2 infection who underwent unenhanced chest CT and have positive RT-PCR tests for Sars-CoV-2 RNA. Two radiologists both with >5 years of thoracic imaging experience, evaluated the images in consensus, without knowing the RT-PCR results. Liver density was measured by a region of interest (ROI), using a liver attenuation value ≤40 Hounsfield units (HU). Results: On 480 patients, 23.1% (111/480) had an incidental findings of HS on chest CT. The steatosis group, included 83 (74.7%) males and 28 (25.3%) females. Patients with HS were more likely to be hospitalized in the intensive care unit (ICU). On univariate analysis, there is a correlation between probability to be intubate (access in the ICU) and HS: patients with HS are twice as likely to be intubated (OR 2.04, CI 95% 1.11-3.73). Conclusion: Chest CT is an important diagnostic tool for COVID-19 and can provide information about the prognosis of the disease. HS can easily be detected on chest CT taken for the diagnosis of the COVID-19 disease, is an important sign for a poor prognosis and possible predictor of admission in ICU.

CGRP Plasma Levels Correlate with the Clinical Evolution and Prognosis of Hospitalized Acute COVID-19 Patients.

SARS-CoV-2 is the etiological agent of COVID-19, an extremely heterogenous disease that can cause severe respiratory failure and critical illness. To date, reliable biomarkers allowing for early patient stratification according to disease severity are still lacking. Calcitonin gene-related peptide (CGRP) is a vasoactive neuropeptide involved in lung pathophysiology and immune modulation and is poorly investigated in the COVID-19 context. In this observational, prospective cohort study, we investigated the correlation between CGRP and clinical disease evolution in hospitalized moderate to severe COVID-19 patients. Between January and May 2021 (Italian third pandemic wave), 135 consecutive SARS-CoV-2 patients were diagnosed as being eligible for the study. Plasma CGRP level evaluation and routine laboratory tests were performed on blood samples collected at baseline and after 7 days of hospitalization. At baseline, the majority our patients had a moderate to severe clinical presentation, and higher plasma CGRP levels predicted a higher risk of in-hospital negative evolution (odds-ratio OR 2.84 [IQR 1.07-7.51]) and were correlated with pulmonary intravascular coagulopathy (OR 2.92 [IQR 1.19-7.17]). Finally, plasma CGRP levels were also correlated with plasma IP10 levels. Our data support a possible crosstalk between the lung and the neuroimmune axis, highlighting a crucial role for plasma CGRP in sustaining COVID-19-related hyperinflammation.

Ongoing Mycophenolate Treatment Impairs Anti-SARS-CoV-2 Vaccination Response in Patients Affected by Chronic Inflammatory Autoimmune Diseases or Liver Transplantation Recipients: Results of the RIVALSA Prospective Cohort.

Vaccines are the most effective means to prevent the potentially deadly effects of SARS-CoV-2 infection, but not all vaccinated individuals gain the same degree of protection. Patients undergoing chronic immunosuppressive therapy due to autoimmune diseases or liver transplants, for example, may show impaired anti-SARS-CoV-2 antibody response after vaccination. We performed a prospective observational study with parallel arms, aiming to (a) evaluate seroconversion after anti-SARS-CoV-2 mRNA vaccine administration in different subgroups of patients receiving immunosuppressive treatment for rheumatological or autoimmune diseases or to prevent organ rejection after liver transplantation and (b) identify negative predictors of IgG anti-SARS-CoV-2 development. Out of 437 eligible patients, 183 individuals were enrolled at the Rheumatology and Hepatology Tertiary Units of "Maggiore della Carità" University Hospital in Novara: of those, 52 were healthy subjects, while among the remaining 131 patients, 30 had a diagnosis of spondyloarthritis, 25 had autoimmune hepatitis, 10 were liver transplantation recipients, 23 suffered from connective tissue diseases (including 10 cases that overlapped with other diseases), 40 were treated for rheumatoid arthritis, and 5 had vasculitis. Moreover, all patients were receiving chronic immunosuppressive therapy. The immunogenicity of mRNA COVID-19 vaccines was evaluated by measuring IgG anti-SARS-CoV-2 antibody titers before vaccination and after 10, 30, and 90 days since the first dose administration. Of the selected cohort of patients, 24.0% did not develop any detectable anti-SARS-CoV-2 IgG after a complete mRNA-based two doses primary vaccination cycle. At univariate analysis, independent predictors of an absent antibody response to vaccine were a history of liver transplantation (OR 11.5, 95% CI 2.5−53.7, p = 0.0018), the presence of a comorbid active neoplasia (OR 26.4, 95% CI 2.8−252.4, p = 0.0045), and an ongoing immunosuppressive treatment with mycophenolate (MMF) (OR 14.0, 95% CI 3.6−54.9, p = 0.0002) or with calcineurin inhibitors (OR 17.5, 95% CI 3.1−99.0, p = 0.0012). At multivariate analysis, only treatment with MMF (OR 24.8, 95% CI 5.9−103.2, p < 0.0001) and active neoplasia (OR 33.2, 95% CI 5.4−204.1, p = 0.0002) were independent predictors of seroconversion failure. These findings suggest that MMF dose reduction or suspension may be required to optimize vaccine response in these patients.

Baseline Plasma Gas6 Protein Elevation Predicts Adverse Outcomes in Hospitalized COVID-19 Patients.

Reliable biomarkers allowing early patients' stratification for the risk of adverse outcomes in COVID-19 are lacking. Gas6, together with its tyrosine kinase receptors named TAM, is involved in the regulation of immune homeostasis, fibrosis, and thrombosis. Our aim was to evaluate whether Gas6, sAxl, and sMerTK could represent early predictors of disease evolution either towards a negative (death or need of ICU admission) or a positive (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. To this purpose, between January and May 2021 (corresponding to third pandemic wave in Italy), 139 consecutive SARS-CoV-2 positive patients were enrolled in a prospective observational study. Plasma levels of these molecules were measured by ELISA at the time of hospitalization and after 7 and 14 days. We observed that higher plasma Gas6 concentrations at hospital admission were associated with a worsening in clinical conditions while lower sMerTK concentrations at baseline and after 7 days of hospitalization were associated with a more favorable outcome. At multivariate analysis, after correction for demographic and COVID-19 severity variables (NEWS2 and PiO2/FiO2), only Gas6 measured at baseline predicted an adverse prognosis with an odds ratio of 1.03 (C.I. 1.01-10.5). At ROC curve analysis, baseline Gas6 levels higher than 58.0 ng/ml predicted a severe disease evolution with 53.3% sensitivity and 77.6% specificity (area under the curve 0.653, p = 0.01, likelihood ratio of 2.38, IQR: 1.46-3.87). Taken together, these results support the hypothesis that a dysregulation in the Gas6/TAM axis could play a relevant role in modulating the course of COVID-19 and suggest that plasma Gas6 may represent a promising prognostic laboratory parameter for this condition.

Efficacy of Physiotherapy Interventions on Weaning in Mechanically Ventilated Critically Ill Patients: A Systematic Review and Meta-Analysis.

Mechanical ventilation (MV) is currently considered a life-saving intervention. However, growing evidence highlighted that prolonged MV significantly affects functional outcomes and length of stay. In this scenario, controversies are still open about the optimal rehabilitation strategies for improving MV duration in ICU patients. In addition, the efficacy of physiotherapy interventions in critical ill patients without positive history of chronic respiratory conditions is still debated. Therefore, this systematic review of randomized controlled trials (RCTs) with meta-analysis aimed at characterizing the efficacy of a comprehensive physiotherapy intervention in critically ill patients. PubMed, Scopus, and Web of Science databases were systematically searched up to October 22, 2021 to identify RCTs assessing acute patients mechanical ventilated in ICU setting undergoing a rehabilitative intervention. The primary outcomes were MV duration, extubation, and weaning time. The secondary outcomes were weaning successful rate, respiratory function, ICU discharge rate and length of stay. Out of 2503 records, 12 studies were included in the present work. The meta-analysis performed in 6 RCTs showed a significant improvement in terms of MV duration (overall effect size: -3.23 days; 95% CI = -5.79, -0.67, p = 0.01; Z = 2.47) in patients treated with a comprehensive physiotherapy intervention including early mobilization, positioning, airway clearance techniques, lung expansion and respiratory muscle training. The quality assessment underlined 9 studies (75%) of good quality and 3 studies of fair quality according to the PEDro scale. In conclusion, our results provided previously unavailable data about the role of comprehensive physiotherapy intervention in improving MV duration in critical ill patients without chronic respiratory conditions. Further studies are needed to better characterize the optimal combination of rehabilitation strategies enhancing the improvements in critical ill patients without chronic respiratory disorders.

Prognostic Markers in Hospitalized COVID-19 Patients: The Role of IP-10 and C-Reactive Protein.

BACKGROUND: SARS-CoV-2 is responsible for COVID-19, a clinically heterogeneous disease, ranging from being completely asymptomatic to life-threating manifestations. An unmet clinical need is the identification at disease onset or during its course of reliable biomarkers allowing patients' stratification according to disease severity. In this observational prospective cohort study, patients' immunologic and laboratory signatures were analyzed to identify independent predictors of unfavorable (either death or intensive care unit admission need) or favorable (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. METHODS: Between January and May 2021 (third wave of the pandemic), we enrolled 139 consecutive SARS-CoV-2 positive patients hospitalized in Northern Italy to study their immunological and laboratory signatures. Multiplex cytokine, chemokine, and growth factor analysis, along with routine laboratory tests, were performed at baseline and after 7 days of hospital stay. RESULTS: According to their baseline characteristics, the majority of our patients experienced a moderate to severe illness. At multivariate analysis, the only independent predictors of disease evolution were the serum concentrations of IP-10 (at baseline) and of C-reactive protein (CRP) after 7 days of hospitalization. Receiver-operating characteristic (ROC) curve analysis confirmed that baseline IP - 10 > 4271 pg/mL and CRP > 2.3 mg/dL at 7 days predict a worsening in clinical conditions (87% sensitivity, 66% specificity, area under the curve (AUC) 0.772, p < 0.001 and 83% sensitivity, 73% specificity, AUC 0.826, p < 0.001, respectively). CONCLUSIONS: According to our results, baseline IP-10 and CRP after 7 days of hospitalization could be useful in driving clinical decisions tailored to the expected disease trajectory in hospitalized COVID-19 patients.

Genetic Variants of Matrix Metalloproteinase and Sepsis: The Need Speed Study.

Many causal mechanisms in sepsis susceptibility are largely unknown and the functional genetic polymorphisms (GP) of matrix metalloproteinases (MMPs) and their natural tissue inhibitor of MMPs (TIMP1) could play a role in its development. GPs of MMPs and TIMP (namely MMP-1 rs1799750, MMP-3 rs3025058, MMP-8 rs11225395, MMP-9 rs2234681, and TIMP-1 rs4898) have been compared in 1058 patients with suspected sepsis to assess the association with susceptibility and etiology of sepsis. Prevalence of MMP8 rs11225395 G/G genotype was higher in sepsis patients than in those with non-infective Systemic Inflammatory Reaction Syndrome (35.6 vs. 26%, hazard ratio, HR 1.56, 95% C.I. 1.04-2.42, p = 0.032). G/G patients developed less hyperthermia (p = 0.041), even after stratification for disease severity (p = 0.003). Patients carrying the 6A allele in MMP3 rs3025058 had a higher probability of microbiologically-proven sepsis (HR 1.4. 95%C.I. 1.01-1.94, p = 0.044), particularly when due to virus (H.R. 2.14, 95% C.I. 1.06-4.31, p = 0.046), while MMP-1 G/G genotype patients carried a higher risk for intracellular bacteria (Chlamydia, Mycoplasma, and Legionella, H.R. 6.46, 95% C.I. 1.58-26.41, p = 0.003). Neither severity of sepsis at presentation, nor 30-day mortality were influenced by the investigated variants or their haplotype. MMP8 rs11225395 G/G carriers have lower temperature at presentation and a more than 50% increased susceptibility to sepsis. Among patients with sepsis, carriers of MMP1 rs1799750 G/G have an increased susceptibility for intracellular pathogen infections, while virus serology is more often positive in those with the MMP3 rs3025058 A/A genotype.

Are Baseline Levels of Gas6 and Soluble Mer Predictors of Mortality and Organ Damage in Patients with Sepsis? The Need-Speed Trial Database.

Soluble tyrosine kinase receptor Mer (sMer) and its ligand Growth arrest-specific protein 6 (Gas6) are predictors of mortality in patients with sepsis. Our aim is to clarify whether their measurement at emergency department (ED) presentation is useful in risk stratification. We re-analyzed data from the Need-Speed trial, evaluating mortality and the presence of organ damage according to baseline levels of sMer and Gas6. 890 patients were eligible; no association with 7- and 30-day mortality was observed for both biomarkers (p > 0.05). sMer and Gas6 levels were significantly higher in acute kidney injury (AKI) patients compared to non-AKI ones (9.8 [4.1-17.8] vs. 7.9 [3.8-12.9] ng/mL and 34.8 [26.4-47.5] vs. 29.8 [22.1-41.6] ng/mL, respectively, for sMer and Gas6), and Gas6 also emerged as an independent AKI predictor (odds ratio (OR) 1.01 [1.00-1.02]). Both sMer and Gas6 independently predicted thrombocytopenia in sepsis patients not treated with anticoagulants (OR 1.01 [1.00-1.02] and 1.04 [1.02-1.06], respectively). Moreover, sMer was an independent predictor of both prothrombin time-international normalized ratio (PT-INR) > 1.4 (OR 1.03 [1.00-1.05]) and sepsis-induced coagulopathy (SIC) (OR 1.05 [1.02-1.07]). An early measurement of the sMer and Gas6 plasma concentration could not predict mortality. However, the biomarkers were associated with AKI, thrombocytopenia, PT-INR derangement and SIC, suggesting a role in predicting sepsis-related organ damage.

The Role of Mid-Regional Proadrenomedullin in the Differential Diagnosis between Culture-Negative and Culture-Positive Sepsis at Emergency Department Admission.

BACKGROUND: The host response in culture-negative sepsis (CnS) has been marginally explored upon emergency department (ED) admission. It would be of paramount importance to create a clinical prediction rule to support the emergency department physician in identifying septic patients who can be treated with antibiotics immediately without waiting time to draw cultures if they are unlikely to provide useful diagnostic information. METHODS: A multivariable logistic regression analysis was applied to identify the independent clinical variables and serum biomarkers of the culture-negative status among 773 undifferentiated septic patients. Those predictors were combined to build a nomogram predictive of CnS. RESULTS: The serum concentrations of six biomarkers, among the eight biomarkers assayed in this study, were significantly lower in the patients with CnS (449) than in those with culture-positive sepsis (324). After correction for co-variates, only mid-regional proadrenomedullin (MR-proADM) was found to be independently correlated with culture-negative status. Absence of diabetes, hemoglobin concentrations, and respiratory source of infection were the other independent clinical variables integrated into the nomogram-its sensitivity and specificity for CnS were 0.80 and 0.79, respectively. CONCLUSIONS: Low concentrations of MR-proADM were independently associated with culture-negative sepsis. Our nomogram, based on the MR-proADM levels, did not predict culture-negative status with reasonable certainty in patients with a definitive diagnosis of sepsis at ED admission.

Neurological emergency at the COVID-19 pandemic: report from a referral hospital in Eastern Piedmont, Italy.

BACKGROUND: The pandemic implied dramatic changes in public health assets. In Italy, some Stroke Units were transformed into sub-intensive COVID-19 Units, making the management of neurological patients demanding. We described how the flow of neurological emergencies was affected by the pandemic impact. METHODS: We analyzed accesses to the Emergency Department (ED) of the "Maggiore della Carità" Hospital, Piedmont, Italy, during a period of 8 months (COVID time; March to May 2020 and October 2020 to February 2021) and analyzed the admissions to the Neurology Unit and the underlying diagnosis. We also evaluated potential changes in the treatment of acute ischemic stroke in the same period. These variables were compared with two equivalent periods of time (2019-2020; 2018-2019). RESULTS: During the COVID time, there was a clear-cut reduction of the total ED accesses compared to NoCOVID times. However, admissions for acute neurological conditions showed a mild but non-significant decrease (6.3%vs.7.3%). The same applied to acute ischemic stroke, which represented the most common condition (47.7%). The proportion of patients who underwent emergent reperfusion therapies remained unchanged. Furthermore, no difference was found in door-to-needle and door-to-groin intervals between COVID time and NoCOVID times. On the contrary, the onset-to-door interval was significantly longer during the COVID time (p value: 0.001). DISCUSSION: While the percentage of admissions following an ED access grew dramatically, those to the Neurology Unit showed overall only a slight non-significant decrease. This finding implicitly reflects the serious and urgent nature of many neurological diseases, compelling people to access EDs at any time.

Effectiveness and feasibility of smoking counselling: a randomized controlled trial in an Italian emergency department.

BACKGROUND: 5A's counselling is recommended for screening and treating patients with smoking addiction. The emergency department (ED) setting might be a suitable environment for conducting interventions for smoking cessation. The present study aims to determine the feasibility and effectiveness on smoking cessation of 5A's counselling administered to ED patients by nurses. METHODS: Parallel group randomized trial assessing 5A's counselling for smoking cessation vs. usual care at a University Hospital in the North of Italy. The primary end-point was prevalence of tobacco-free patients. The secondary outcomes at 6- and 12-month follow-up were (i) consecutive past 30-day smoking abstinence; (ii) past 7-day 50%, or more, decrease in daily tobacco consumption over baseline; and (iii) number of attempts to quit smoking. RESULTS: A total of 480 patients were randomized to intervention (n = 262) or usual care (n = 218). Intention to treat analysis displayed no differences in primary and secondary outcomes between groups. A slight but not statistically significant enhancement in cessation was recorded in the intervention group [relative risk (RR) = 1.04, 95% confidence interval (CI) = 0.58-1.87] at 6 months, whereas a reversed observation at 12 months (RR = 0.86, 95% CI = 0.50-1.47). Similar results were obtained for the secondary outcomes. Per protocol analysis increased the size of the results. Of the 126 smokers receiving counselling, 18 were visited and treated at the local smoking cessation centre, with 12 of them successfully completing the treatment. CONCLUSION: The results of this study indicate that the ED is not a suited environment for 5A's counselling.

Mycotic infection prevalence among patients undergoing bronchoalveolar lavage with search of SARS-CoV-2 after two negative nasopharyngeal swabs.

The evidence that severe coronavirus disease 2019 (COVID-19) is a risk factor for development of mycotic respiratory infection with an increased mortality is rising. Immunosuppressed are among the most susceptible patients andAspergillusspecies is the most feared superinfection. In this study we evaluated mycotic isolation prevalence on bronchoalveolar lavage (BAL) of patients who underwent bronchoscopy in search of severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA. Moreover, we described the clinical characteristics and main outcomes of these patients. We included 118 patients, 35.9% of them were immunosuppressed for different reasons: in 23.7% we isolated SARS-CoV-2 RNA, in 33.1% we identified at least one mycotic agent and both in 15.4%. On BAL we observed in three casesAspergillusspp, in six casesPneumocystisand in 32Candidaspp. The prevalence of significant mold infection was 29.3% and 70.7% of cases were false positive or clinically irrelevant infections. In-hospital mortality of patients with fungal infection was 15.3%. The most frequent computed tomography (CT) pattern, evaluated with the Radiological Society of North America consensus statement, among patients with a mycotic pulmonary infection was the atypical one (p< 0.0001). Mycotic isolation on BAL may be interpreted as an innocent bystander, but its identification could influence the prognosis of patients, especially in those who need invasive investigations during the COVID-19 pandemic; BAL plays a fundamental role in resolving clinical complex cases, especially in immunosuppressed patients independently from radiological features, without limiting its role in ruling out SARS-CoV-2 infection.