Diaphragmatic ultrasound evaluation in acute heart failure: clinical and functional associations.

Heart failure patients often experience respiratory symptoms due to diaphragmatic involvement, but the diaphragmatic motion in heart failure remains understudied. This research aimed to investigate the correlation between ultrasonographically assessed diaphragmatic motion and thickness with cardiac performance indexes in an emergency setting. Seventy-two acutely decompensated heart failure patients and 100 non-heart failure individuals were enrolled. Diaphragmatic motion and thickness were assessed via ultrasound. Cardiac and respiratory parameters were recorded, and regression analysis was performed. Heart failure patients exhibited reduced diaphragmatic motion at total lung capacity compared to controls, and an inverse association was found between motion and heart failure severity (NYHA stage). Diaphragmatic thickness was also higher in heart failure patients at tidal volume and total lung capacity. Notably, diaphragmatic motion inversely correlated with systolic pulmonary artery pressure. The study highlights diaphragmatic dysfunction in acutely decompensated heart failure, with reduced motion and increased thickness. These changes were associated with cardio-respiratory parameters, specifically systolic pulmonary artery pressure. Monitoring diaphragmatic motion via ultrasound may aid in evaluating heart failure severity and prognosis in emergency settings. Additionally, interventions targeting diaphragmatic function could improve heart failure management. Further research is warranted to enhance heart failure management and patient outcomes.

The specialized pro-resolving lipid mediator Protectin D1 affects macrophages differentiation and activity in Adult-onset Still's disease and COVID-19, two hyperinflammatory diseases sharing similar transcriptomic profiles.

Introduction: COVID-19 and autoinflammatory diseases, such as Adult-onset Still's Disease (AOSD), are characterized by hyperinflammation, in which it is observed massive production and uncontrolled secretion of pro-inflammatory cytokines. The specialized pro-resolving lipid mediators (SPMs) family is one the most important processes counteracting hyperinflammation inducing tissue repair and homeostasis restoration. Among SPMs, Protectin D1 (PD1) is able to exert antiviral features, at least in animal models. The aim of this study was to compare the transcriptome of peripheral blood mononuclear cells (PBMCs) from patients with AOSD and COVID-19 and to evaluate the role of PD1 on those diseases, especially in modulating macrophages polarization. Methods: This study enrolled patients with AOSD, COVID-19, and healthy donors HDs, undergoing clinical assessment and blood sample collection. Next-generation deep sequencing was performed to identify differences in PBMCs transcripts profiles. Plasma levels of PD1 were assessed by commercial ELISA kits. Monocyte-derived macrophages were polarized into M1 and M2 phenotypes. We analyzed the effect of PD1 on macrophages differentiation. At 10 days, macrophages were analyzed for surface expression of subtypes markers by flow cytometry. Cytokines production was measured in supernatants by Bio-Plex Assays. Results: In the transcriptomes from AOSD patients and COVID-19 patients, genes involved in inflammation, lipid catabolism, and monocytes activation were specifically dysregulated in AOSD and COVID-19 patients when compared to HDs. Patients affected by COVID-19, hospitalized in intensive care unit (ICU), showed higher levels of PD1 when compared to not-ICU hospitalized patients and HDs (ICU COVID-19 vs not-ICU COVID-19, p= 0.02; HDs vs ICU COVID-19, p= 0.0006). PD1 levels were increased in AOSD patients with SS ≥1 compared to patients with SS=0 (p=0.028) and HDs (p=0.048). In vitro treatment with PD1 of monocytes-derived macrophages from AOSD and COVID-19 patients induced a significant increase of M2 polarization vs control (p<0.05). Furthermore, a significant release of IL-10 and MIP-1ß from M2 macrophages was observed when compared to controls (p<0.05). Discussion: PD1 is able to induce pro-resolutory programs in both AOSD and COVID-19 increasing M2 polarization and inducing their activity. In particular, PD1-treated M2 macrophages from AOSD and COVID-19 patients increased the production of IL-10 and enhanced homeostatic restoration through MIP-1ß production.

Handgrip Strength Test and Bioelectrical Impedance Analysis in SARS-CoV-2 Patients Admitted to Sub-Intensive Unit.

Hospitalized patients with respiratory failure due to SARS-CoV-2 pneumonia are at increased risk of malnutrition and related mortality. The predictive value of the Mini-Nutritional Assessment short form (MNA-sf®), hand-grip strength (HGS), and bioelectrical impedance analysis (BIA) was determined with respect to in-hospital mortality or endotracheal intubation. The study included 101 patients admitted to a sub-intensive care unit from November 2021 to April 2022. The discriminative capacity of MNA-sf, HGS, and body composition parameters (skeletal mass index and phase angle) was assessed computing the area under the receiver operating characteristic curves (AUC). Analyses were stratified by age groups (<70/70+ years). The MNA-sf alone or in combination with HGS or BIA was not able to reliably predict our outcome. In younger participants, HGS showed a sensitivity of 0.87 and a specificity of 0.54 (AUC: 0.77). In older participants, phase angle (AUC: 0.72) was the best predictor and MNA-sf in combination with HGS had an AUC of 0.66. In our sample, MNA- sf alone, or in combination with HGS and BIA was not useful to predict our outcome in patients with COVID-19 pneumonia. Phase angle and HGS may be useful tools to predict worse outcomes in older and younger patients, respectively.

The similar expression of both ferritin and scavenger receptors activation genes in patients with COVID19 and AOSD support their role in the pathogenesis of these diseases and identify a common mechanism at the basis of the "hyperferritinemic syndromes".

A role for COVID19 in "hyperferritinemic syndromes" has been proposed based on its clinical and serological characteristics and its similarities with AOSD. To better understand the molecular pathways responsible of these similarities, we evaluated in the PBMCs of 4 active AOSD patients, 2 COVID19 patients with ARDS, and 2 HCs the expression of genes associated with iron metabolisms, with monocyte/macrophages activation, and finally with NETs formation.

Incidence and Outcome of Pneumomediastinum in Non-ICU Hospitalized COVID-19 Patients.

OBJECTIVES: Pneumomediastinum (PNM) is a rare complication of mechanical ventilation, but its reported occurrence in patients with acute respiratory distress syndrome secondary to COVID-19 is significant. The objective is to determine the incidence, risk factors, and outcome of PNM in non-ICU hospitalized patients with severe-to-critical COVID-19 pneumonia. DESIGN: Retrospective observational study. SETTING: Population-based, single-setting, tertiary-care level COVID treatment center. PATIENTS: Individuals hospitalized with a diagnosis of COVID-19 pneumonia and severe to critical illness were included. Those hospitalized without respiratory failure, observed for less than 24 hours, or admitted from an ICU were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients underwent a complete clinical assessment and chest CT scan, and were followed up from hospitalization to discharge or death. The outcome was the number of cases of PNM, defined as the presence of free air in the mediastinal tissues diagnosed by chest CT scan, in non-ICU hospitalized patients and the subsequent risk of intubation and mortality. PNM occurred in 48 out of 331 participants. The incidence was 14.5% (95% CI, 10.9-18.8%). A CT-Scan Severity score greater than 15 was positively associated with PNM (odds ratio [OR], 4.09; p = 0.002) and was observed in 35.2% of the participants (95% CI, 26.2-44.9%). Noninvasive ventilation was also positively associated with PNM (OR, 4.46; p = 0.005), but there was no positive association with airway pressures. Fifty patients (15%) were intubated, and 88 (27%) died. Both the risk for intubation and mortality were higher in patients with PNM, with a hazard ratio of 3.72 ( p < 0.001) and 3.27 ( p < 0.001), respectively. CONCLUSIONS: Non-ICU hospitalized patients with COVID-19 have a high incidence of PNM, increasing the risk for intubation and mortality three- to four-fold, particularly in those with extensive lung damage. These findings help define the risk and outcome of PNM in severe-to-critical COVID-19 pneumonia in a non-ICU setting.

Long peripheral cannula in COVID-19 patients: 769 catheter days experience from a semi-intensive respiratory COVID unit.

BACKGROUND: In the daily management of peripheral venous access, the health emergency linked to the COVID-19 pandemic led to re-examining the criteria for choosing, positioning and maintaining the different types of peripheral venous access. OBJECTIVES: This study aimed to observe the dwell time of long peripheral cannula (LPC, also known as mini-midline) in patients affected by COVID 19 related pneumonia. The secondary objective is to study any complications due to mini-midline insertion. MATERIALS AND METHODS: We conducted a prospective observational study on COVID19 patients who arrived at our Semi-Intensive Respiratory Unit from territorial ED between January and April 2021, to whom were positioned an LPC at the time of admission following the SIPUA protocol (Safe Insertion of Peripheral Ultrasound-guided Access). We used Vygon™ Leader-Cath© 18G in polyethylene and 8 cm long catheter. RESULTS: We enrolled 53 consecutive patients, reaching 769 catheter days. The procedure was performed without immediate complications in 37 patients out of 53 (69.8%). In 14 patients (26.4%), we observed a local hematoma (no one led to a failure or early removal of the device) and in two patients (3.7%) was not possible to draw blood. The average catheter dwell time was 14.5 days, from 3 to 41 days. In 42 patients (79.2%), the device was removed at the end of use. In 11 patients out of 53 (20.8%), the device was removed early due to complications: seven accidental removals, one obstruction, two vein thrombosis, and one superficial thrombophlebitis. CONCLUSIONS: The ultrasound-guided implantation of an 18G LPC in COVID19 patients, regardless of the state of their venous heritage, would seem to be an excellent strategy for these patients, reducing the number of venipunctures and CVC implantation, as well as allowing multiple and high pressure (contrast) infusions.

Usefulness of High-Sensitivity Troponin I in Risk Stratification and Final Disposition of Patients with Acute Heart Failure in the Emergency Department: Comparison between HFpEF vs. HFrEF.

Background and Objectives: In patients with acute heart failure (AHF), there is no definite evidence on the relationship between high-sensitivity cardiac troponin (hs-cTnI) and the left ventricular ejection fraction (LVEF) comparing the reduced and preserved EF conditions. Materials and Methods: Between January and April 2022, we retrospectively analyzed the data from 386 patients admitted to the emergency departments (ED) of five hospitals in Rome, Italy, for AHF. The criteria for inclusion were a final diagnosis of AHF; a cardiac ultrasound and hs-cTnI evaluations in the ED; and age > 18 yrs. We excluded patients with acute coronary syndrome (ACS). Based on echocardiography and hs-cTnI evaluations, the patients were grouped for (1) preserved (HFpEF) or (2) reduced LVEF (HFrEF) and a a) negative (within the normal range value) or b) positive (above the normal range value) of hs-cTnI, respectively. Results: There was a significant negative relationship between a positive test for hs-cTnI and LVEF. When compared to the group with a negative hs-cTnI test, the patients with a positive test, both from the HFpEF and HFrEF subgroups, were significantly more likely to have an adverse outcome, such as being admitted to the intensive care unit (ICU) or dying in the ED. Moreover, a reduced ejection fraction was linked with a final disposition to a higher level of care. Conclusions: In patients admitted to the ED for AHF without ACS, there is a negative relationship between hs-cTnI and a reduced LVEF, although a significant percentage of patients with a preserved LVEF also resulted to have high levels of hs-cTnI. In the absence of ACS, hs-cTnI seems to be a reliable biomarker of myocardial injury in AHF in the ED and should be considered as a risk stratification parameter for these subjects regardless of the left ventricular function. Further larger prospective studies are needed to confirm these preliminary data.

Posterior Reversible Encephalopathy Syndrome and brain haemorrhage as COVID-19 complication: a review of the available literature.

BACKGROUND: SARS-CoV-2 infection has been associated with various neurological manifestations. Since patients affected by SARS-CoV-2 infection present coagulation and immune system dysregulation, ischemic or haemorragic stroke is not uncommon, irrespective of respiratory distress. However, the occurrence of focal neurological deficits together with other symptoms like headache, cortical blindness, seizure and altered mental status should prompt the diagnosis of Posterior Reversible Encephalopathy Syndrome (PRES). Antithrombotic treatment, the alteration of endothelial function, and coagulopathy due to COVID-19 and PRES leading to the breakdown of blood-brain barrier may then contribute to the occurrence of a brain haemorrhage. METHODS: We describe the case of a COVID-19 patient who developed bilateral occipital lobe haemorrhages suggestive of haemorrhagic PRES. We then reviewed the available literature about haemorrhagic evolution of PRES in COVID-19. RESULTS: We describe the clinical and radiological features of five COVID-19 patients who developed haemorrhagic PRES. CONCLUSIONS: Coagulopathy and endothelial dysfunction resulting from the massive release of cytokines during the host immune response may be key factors in the pathogenesis of COVID-19-related PRES. Antithrombotic therapy and the leakage of the blood-brain barrier can subsequently increase the risk of haemorrhagic transformation of the lesioned brain tissue. A prompt diagnosis of PRES is mandatory, since the timely interruption/reversal of antithrombotic therapy may be a key determinant for a good prognosis.

COVID-19 sniffer dog experimental training: Which protocol and which implications for reliable sidentification?

The introduction of trained sniffer dogs for COVID-19 detection could be an opportunity, as previously described for other diseases. Dogs could be trained to detect volatile organic compounds (VOCs), the whiff of COVID-19. Dogs involved in the study were three, one male and two females from different breeds, Black German Shepherd, German Shepherd, and Dutch Shepherd. The training was performed using sweat samples from SARS-CoV2 positive patients and from SARS-Cov2 free patients admitted at the University Hospital Campus Bio-medico of Rome. Gauze with sweat was collected in a glass jar with a metal top and put in metal boxes used for dog training. The dog training protocol was performed in two phases: the olfactory conditioning and the olfactory discrimination research. The training planning was focused on the switch moment for the sniffer dog, the moment when the dog was able to identify VOCs specific for COVID-19. At this time, the dog was able to identify VOCs specific for COVID-19 with significant reliability, in terms of the number of correct versus incorrect (p < 0.0001) reporting. In conclusion, this protocol could provide a useful tool for sniffer dogs' training and their introduction in a mass screening context. It could be cheaper and faster than a conventional testing method.

High value of mid-regional proadrenomedullin in COVID-19: A marker of widespread endothelial damage, disease severity, and mortality.

The widespread endothelial damage due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to a disruption of the adrenomedullin (ADM) system responsible for vascular leakage, increased inflammatory status, and microvascular alteration with multi-organs dysfunction. The aim of this study was to evaluate the role of mid-regional proadrenomedullin (MR-proADM) as a marker of SARS-CoV2 related widespread endothelial damage, clinically identified by organs damage, disease severity and mortality. Patients with SARS-CoV-2 infection has been prospectively enrolled and demographic characteristic, clinical and laboratory data has been evaluated. In the overall population, 58% developed acute respiratory distress syndrome (ARDS), 23.3% of patients died, 6.5% acute cardiac injury, 1.4% of patients developed acute ischemic stroke, 21.2% acute kidney injury, 11.8% acute liver damage, and 5.4% septic shock. The best MR-proADM cut-off values for ARDS development and mortality prediction were 3.04 and 2 nmol/L, respectively. Patients presenting with MR-proADM values ≥2 nmol/L showed a significantly higher mortality risk. In conclusion, MR-proADM values ≥2 nmol/L identify those patients with high mortality risk related to a multiorgan dysfunction syndrome. These patients must be carefully evaluated and considered for an intensive therapeutic approach.

Comparison between white blood cell count, procalcitonin and C reactive protein as diagnostic and prognostic biomarkers of infection or sepsis in patients presenting to emergency department.

BACKGROUND: Procalcitonin (PCT) is currently the most studied infection biomarker and its blood levels seem to mirror the severity of illness and outcome. PCT is widely used together with other biomarkers, such as white blood cells (WBC) count and C reactive protein (CRP), in order to guide antibiotic therapy. This study aimed to verify the diagnostic and prognostic power of WBC, CRP and PCT in patients with suspected infection in emergency department (ED). METHODS: A total of 513 patients presenting to the ED with signs/symptoms of local infections or sepsis were enrolled. APACHEII score and in-hospital death were recorded. Patients were subdivided into quartiles by age, and the biomarkers were measured at baseline. Receiver operating characteristics (ROC) curves for evaluating diagnostic and prognostic role of PCT, CRP and WBC were calculated for each variable alone and combined. RESULTS: When compared each other for PCT, CRP, and WBC there was no significant difference between the four subgroups. A direct correlation between PCT and WBC was found in the II, III, and IV quartiles (the highest correlation, r=0.34, p<0.0003). PCT alone or when combined with WBC showed the best diagnostic and prognostic power at ROC analysis. CONCLUSIONS: Our data demonstrate that WBC, but more CRP and PCT are reliable diagnostic and prognostic biomarkers, when considered in combination and with severity clinical score. PCT confirms its stronger usefulness as a diagnostic marker of sepsis. A multi-diagnostic tools approach is fundamental to perform a correct and rapid diagnosis of infection and sepsis in ED.

Thirty and ninety days mortality predictive value of admission and in-hospital procalcitonin and mid-regional pro-adrenomedullin testing in patients with dyspnea. Results from the VERyfing DYspnea trial.

INTRODUCTION: Mid-regional pro-atrial natriuretic peptide (MR-proANP), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) demonstrated usefulness for management of emergency department patients with dyspnea. METHODS: To evaluate in patients with dyspnea, the prognostic value for 30 and 90 days mortality and readmission of PCT, MR-proADM, and MR-proANP, a multicenter prospective study was performed evaluating biomarkers at admission, 24 and 72 hours after admission. Based on final diagnosis, patients were divided into acute heart failure (AHF), primary lung diseases, or both (AHF + NO AHF). RESULTS: Five hundred one patients were enrolled. Procalcitonin and MR-proADM values at admission and at 72 hours were significantly (P < .001) predictive for 30-day mortality: baseline PCT with an area under the curve (AUC) of 0.70 and PCT at 72 hours with an AUC of 0.61; baseline MR-proADM with an AUC of 0.62 and MR-proADM at 72 hours with an AUC of 0.68. As for 90-day mortality, both PCT and MR-proADM baseline and 72 hours values showed a significant (P < .0001) predictive ability: baseline PCT with an AUC of 0.73 and 72 hours PCT with an AUC of 0.64; baseline MR-proADM with an AUC of 0.66 and 72 hours MR-proADM with an AUC of 0.71. In AHF, group biomarkers predicted rehospitalization and mortality at 90 days, whereas in AHF + NO AHF group, they predict mortality at 30 and 90 days. CONCLUSIONS: In patients admitted for dyspnea, assessment of PCT plus MR-proADM improves risk stratification and management. Combined use of biomarkers is able to predict in the total cohort both rehospitalization and death at 30 and 90 days.

Opinion paper on innovative approach of biomarkers for infectious diseases and sepsis management in the emergency department.

Sepsis is a leading healthcare problem, accounting for the vast majority of fatal events in critically ill patients. Beyond early diagnosis and appropriate treatment, this condition requires a multifaceted approach for monitoring the severity, the potential organ failure as well as the risk of death. Monitoring of the efficacy of treatment is also a major issue in the emergency department (ED). The assessment of critically ill conditions and the prognosis of patients with sepsis is currently based on some scoring systems, which are, however, inefficient to provide definite clues about organ failure and prognosis in general. The discretionary and appropriate use of some selected biomarkers such as procalcitonin, inducible protein 10 (IP10), Group IV phospholipase A2 type II (PLA2 II), neutrophil gelatinase-associated lipocalin (NGAL), natriuretic peptides, mature adrenomedullin (ADM), mid-regional pro-adrenomedullin (MR-proADM), copeptin, thrombopoietin, Mer receptor and even red blood cell distribution width (RDW) represent thereby an appealing perspective in the diagnosis and management of patients with sepsis. Nevertheless, at the moment, it is not still clear if it is better to use a multimarkers approach or if a single, most appropriate, biomarker exists. This collective opinion paper is aimed at providing an overview about the potential clinical usefulness of some innovative biomarkers of sepsis in its diagnosis and prognosis, but also in the treatment management of the disease. This manuscript represents a synopsis of the lectures of Third Italian GREAT Network Congress, that was hold in Rome, 15-19 October 2012.

Utility of Procalcitonin (PCT) and Mid regional pro-Adrenomedullin (MR-proADM) in risk stratification of critically ill febrile patients in Emergency Department (ED). A comparison with APACHE II score.

BACKGROUND: 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. METHODS: This was an observational, multicentric study. We enrolled 128 patients referred to the ED with high fever and a suspicion of severe infection such as sepsis, lower respiratory tract infections, urinary tract infections, gastrointestinal infections, soft tissue infections, central nervous system infections, or osteomyelitis. The APACHE II score was calculated for each patient. RESULTS: MR-proADM median values in controls were 0.5 nmol/l as compared with 0.85 nmol/l in patients (P < 0.0001), while PCT values in controls were 0.06 ng/ml versus 0.56 ng/ml in patients (P < 0.0001). In all patients there was a statistically significant stepwise increase in MR-proADM levels in accordance with PCT values (P < 0.0001). MR-proADM and PCT levels were significantly increased in accordance with the Apache II quartiles (P < 0.0001 and P = 0.0012 respectively).In the respiratory infections, urinary infections, and sepsis-septic shock groups we found a correlation between the Apache II and MR-proADM respectively and MR-proADM and PCT respectively. We evaluated the ability of MR-proADM and PCT to predict hospitalization in patients admitted to our emergency departments complaining of fever. MR-proADM alone had an AUC of 0.694, while PCT alone had an AUC of 0.763. The combined use of PCT and MR-proADM instead showed an AUC of 0.79. CONCLUSIONS: The present study highlights the way in which MR-proADM and PCT may be helpful to the febrile patient's care in the ED. Our data support the prognostic role of MR-proADM and PCT in that setting, as demonstrated by the correlation with the APACHE II score. The combined use of the two biomarkers can predict a subsequent hospitalization of febrile patients. The rational use of these two molecules could lead to several advantages, such as faster diagnosis, more accurate risk stratification, and optimization of the treatment, with consequent benefit to the patient and considerably reduced costs.